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a 47-year - old man with poorly controlled type 2 diabetes sought care at the royal darwin hospital in the tropical north of the northern territory of australia in january 2011 after several weeks of increasing lethargy and 1 week of fevers and cough . he was patient 692 in the darwin prospective melioidosis study ( 4 ) , which is approved by the human research ethics committee of the northern territory department of health and the menzies school of health research ( approval 02/38 ) . the patient s chest radiograph ( figure 1 , panel a ) showed patchy pneumonia in the right lung and a large soft - tissue mass on the left side of the chest . a computed tomography scan ( figure 1 , panel b ) confirmed the mass to be a 7-cm 6-cm loculated fluid collection in the anterior mediastinum contiguous with patchy bilateral pneumonia and associated with multiple enlarged mediastinal lymph nodes and a pericardial effusion . the patient required initial management in the intensive care unit for his pneumonia , severe sepsis , and ketoacidosis . he received 45 days of intravenous antimicrobial drugs ( meropenem for 11 days , followed by ceftazidime for 34 days ) in conjunction with oral trimethoprim / sulfamethoxazole . after discharge , he received 15 subsequent weeks of eradication therapy with trimethoprim / sulfamethoxazole . at follow up clinical studies of a patient with melioidosis , royal darwin hospital , darwin , northern territory , australia . a ) chest radiograph shows a soft - tissue mass associated with the left side of the mediastinum and obscuring the aortic arch . b ) chest computed tomography scan shows a large loculated mass in the anterior mediastinum ; the mass is contiguous with multiple enlarged mediastinal lymph nodes and with pulmonary consolidation . the unusual finding of extensive mediastinal disease raised the possibility that the patient had inhalational melioidosis . the patient described sitting most days outside his urban accommodation on an elevated and exposed mowed grassy area that overlooks ground sloping downhill to a rocky open drain , an environment that prompted the potential for targeted air sampling . the site was visited and environmental samples taken 6 weeks after the patient s hospital admission . during the sampling , squally rain showers occurred , accompanied by wind blowing up the hill and the drain flowing swiftly . each air collection entailed passing 1,000 l of air ( 50 l / min for 20 min ) through a portable microbiologic air sampler ( md8 airport ; sartorius stedim , dandenong , victoria , australia ) with a disposable gelatin filter ( 3.0 m ) for sample collection . the air sampler was placed on a tripod at 1.0 m elevation above ground level and was protected by a secured , angled overhead umbrella to prevent direct rain contact . after each air sampling , the gelatin filter was placed in 30 ml of modified ashdown selective broth and incubated at 37c , with the broth supernatant plated onto ashdown agar after 2 and 7 days ( 3 ) . sterile water ( 20 ml ) was added to 20 g soil and shaken at 220 rpm for 48 h at 37c . after the soil samples were removed from the shaker and left to stand for 12 h , 10 ml of supernatant was placed in 30 ml of modified ashdown selective broth and incubated at 37c ; the broth supernatant was plated onto ashdown agar after 2 and 7 days . suspected b. pseudomallei colonies were confirmed by using the b. pseudomallei specific tts1 real - time pcr , described previously ( 5 ) . b. pseudomallei was cultured from 1 of the 2 air samples and 1 of the 3 soil samples . multilocus - sequence typing , completed by using standard methods ( 6 ) , confirmed that 2 isolates from each of the positive air and soil samples and the isolate from the patient s blood culture were all sequence type ( st ) 562 . to further resolve the relatedness of st562 isolates , pcr - based , multilocus variable - number tandem - repeat analysis of 4 loci ( mlva-4 ) was performed as described ( 7 ) on the 4 environmental isolates , the patient s blood culture isolate , and isolates from 13 other patients in the darwin prospective study whose melioidosis was caused by st562 b. pseudomallei . mlva-4 categorized the 18 st562 isolates into 3 distinct types : 55 ( n = 7 ) , 71 ( n = 8) , and 168 ( n = 3 ) . the isolate from patient 692 , all 4 environmental isolates , and isolates from 2 of the 13 other patients were mlva-4 type 55 . to further define the relatedness of st562 isolates , whole - genome sequencing was performed on 17 of the 18 st562 isolates for which mlva-4 results were available ; to reduce duplication and cost , 1 of the 2 b. pseudomallei isolates from air samples was not sequenced because it was clonal with the other air sample . genomic dna was extracted by using the qiagen dneasy blood and tissue kit ( qiagen , chadstone , victoria , australia ) , as described ( 7 ) . ( gasan - dong , seoul , south korea ) by using hiseq 2000 ( illumina , san diego , ca , usa ) . genome analysis was performed with spandx version 2.3 ( 8) by using the st562 strain mshr4388 from the mlst database ( http://bpseudomallei.mlst.net/ ) as the reference genome . whole - genome identification of single nucleotide polymorphisms ( snps ) , followed by phylogenetic reconstruction by using maximum parsimony in paup 4.0b10 ( 9 ) , showed that all st562 isolates were closely related ; only 26 snps were observed among all 17 genomes ( figure 2 ) . the air isolate ( added to the mlst database as mshr46817 ) and the 2 soil isolates ( mshr4681 and mshr4682 ) obtained from the environment outside the residence of patient 692 were identical by whole - genome sequencing and differed from the blood culture isolate of patient 692 ( mshr4515 ) by only 3 snps . these genetic similarities support the epidemiologic link between the air and soil b. pseudomallei and the patient s infection . whole - genome core orthologous single - nucleotide polymorphism ( snp ) phylogeny of sequence type 562 burkholderia pseudomallei isolates from a patient with melioidosis and from environmental sampling at the patient s residence , darwin , northern territory , australia . mshr4515 ( mlst database identifier , http://bpseudomallei.mlst.net/ ) was a blood culture isolate from the index patient , identified as patient ( p ) 692 ( p692 , arrow ) . analysis of isolates from 13 other patients with sequence type 562 are also shown ( identifiers begin with p ) . comparison of data for nps and for multilocus variable - number tandem - repeat analysis of 4 loci ( mlva-4 ) types ( shown in parentheses ) supports the hypothesis that p692 was infected from environmental b. pseudomallei at his residence . consistency index = 1 . epidemiologic data from australia , singapore , and taiwan support the hypothesis that inhalation may replace inoculation as the predominant route of b. pseudomallei transmission during severe weather events ( e.g. , tropical monsoonal storms , cyclones , and typhoons ) ( 1012 ) . similar clinical distinctions between percutaneous and inhalational infections are observed for anthrax , plague , and tularemia ( 4 ) . animal studies have also shown the potential importance of aerosol inhalation of b. pseudomallei with high lethality ( 13,14 ) . inhalational melioidosis is supported by the increasing recognition from computed tomography scanning that enlarged mediastinal lymph nodes are not uncommon in patients with severe melioidosis pneumonia ( 4,10 ) . nevertheless , no direct evidence exists to confirm occurrence of inhalation of b. pseudomallei in melioidosis - endemic regions . a recent report from taiwan documented an air sampling technique that uses a filtration real - time quantitative pcr method to quantify ambient b. pseudomallei dna ; high positive rates were found during typhoons ( 12 ) . b. pseudomallei was recovered from air samples taken outside the residence of a patient with clinical features consistent with inhalational melioidosis . whole - genome sequencing linked the environmental b. pseudomallei to an isolate from the patient s blood culture . these data provide evidence of aerosolization of b. pseudomallei during stormy conditions in an endemic location and strong circumstantial evidence for inhalation of b. pseudomallei . the proportion of melioidosis cases resulting from inhalation rather than percutaneous inoculation or ingestion requires further study and is likely to vary substantially by location and season .

the frequency with which melioidosis results from inhalation rather than percutaneous inoculation or ingestion is unknown . we recovered burkholderia pseudomallei from air samples at the residence of a patient with presumptive inhalational melioidosis and used whole - genome sequencing to link the environmental bacteria to b. pseudomallei recovered from the patient .

our patient was an 8-month - old male child of indian origin and the first issue of a nonconsanguineous marriage . he presented to our center with the complaints of cough , cold , progressively increasing breathlessness , and refusal to feed over the past 3 days . past history was elicited that the child was a full - term baby weighing 2.4 kg . his important clinical course is summarized in table 1 . on presentation to us , he had tachycardia ( 160 beats per minute ) , tachypnea ( 64 breaths per minute ) , capillary refill time of 3 s , and blood pressure of 76/60 mmhg in the right arm supine position . the child had increased work of breathing , as evidenced by the subcostal and intercostal retractions . cardiac examination revealed a pansystolic murmur ( grade iii ) , in the third and fourth intercostal spaces . his weight , length , and head circumference were below the third percentile for his age ( weight 3.5 kg , length 61 cm , head circumference 37 cm ) . he had narrow and upslanting palpebral fissures , epicanthal folds , and prominent ears [ figure 1 ] . past clinical course of the patient hgt = hemoglucotest ; pcv = packed cell volume ; cbc = complete blood count ; tlc = total leucocyte counts ; dlc = differential leucocyte count ; anc = absolute neutrophil count ; alc = absolute lymphocyte count ; crp = c - reactive protein ; tof = tetralogy of fallot ; ps = pulmonary stenosis ; vsd = ventricular septal defect ; * dose of the iv calcium 2cc / kg / dose , tds for 3 days facial profile of the child . note the narrow and upslanting palpebral fissures , epicanthal folds , and prominent ears q1 : name some hereditary and nonhereditary conditions in which the facial dysmorphisms associated with the underlying heart disease can give a clue to the etiology of the condition . ans . : table 2 elaborates the conditions in which facial dysmorphisms associated with underlying heart disease can give a clue to the etiology of the condition . conditions in which facial dysmorphisms are associated with a heart disease ecd = endocardial cushion defect ; asd = atrial septal defect ; pda = patent ductus arteriosus ; ar = aortic regurgitation ; mr = mitral regurgitation ; cad = coronary artery disease ; as = aortic stenosis ; pa = pulmonary artery ; dgs = digeorge syndrome case details ( continued ) : in view of the association of conotruncal cardiac anomaly , hypocalcemia with hypoparathyroidism [ table 1 ] in the infantile period , and typical dysmorphic facies , we were prompted to suspect digeorge syndrome ( dgs ) . : dgs is a 22q11.2 microdeletion syndrome , associated with the classic triad of conotruncal cardiac anomalies , hypoplastic thymus ( resulting in immunodeficiencies ) , and hypoplasia of the parathyroid glands ( resulting in hypoparathyroidism and hypocalcemia ) . the other synonyms for dgs are 22q11.2 deletion syndrome ( preferred terminology ) , velocardiofacial syndrome , conotruncal anomaly face syndrome , sedlackova syndrome , and cayler cardiofacial syndrome . in less than 1% of all patients with dgs , there is complete athymia , resulting in severe combined immunodeficiency ( scid ) . this is called complete dgs ; the remaining 99% are partial dgs , having some thymic function preserved . in our patient , repeated blood investigations failed to show lymphopenia [ table 1 ] . detailed immunological tests could not be carried out in our patient . with a worldwide prevalence of between 1/2000 and 1/4000 live births , the actual prevalence may be higher due to high clinical expressivity , accounting for underrecognition . : dgs is caused due to the deletion of the genes in the digeorge chromosomal region ( dgcr ) on chromosome 22q11.2 , secondary to a nonallelic meiotic recombination during spermatogenesis or oogenesis . a great percentage ( 93% ) of the probands have a de novo deletion of 22q11.2 , while some ( 7% ) inherit the 22q11.2 deletion from a parent in an autosomal dominant fashion . rarely , less than 1% of the individuals with dgs have chromosomal rearrangements , such as a translocation between chromosome 22 and another autosome , involving 22q11.2 . ? ans . : the clinical features of dgs [ table 3 ] , are exceedingly variable , with over 190 features described in the literature , involving almost every organ system thus underlining the need for sensitization among physicians and surgeons from all specialties . of note , no phenotype occurs in 100% of the patients , as the penetrance of each clinical feature is diverse . thus , one should be wary of excluding differential of dgs solely on the basis of absence of a particular feature . the presence of congenital heart disease ( chd ; especially conotruncal anomalies ) , neonatal hypocalcemia ( with hypoparathyroidism ) , and palatal defects can usually be picked up in the neonatal period , and should serve as red flags for early diagnosis . authorities in this subject recommend that , given the high frequency of dgs among individuals with conotruncal anomalies , newborns with these heart anomalies should be routinely screened with fluorescence in situ hybridization ( fish ) for 22q11.2 deletion , once other causes ( down syndrome , trisomy 13 ) have been ruled out . other pointers for this condition , such as dysmorphisms , intellectual disability , and psychiatric disorders may appear only years later , often delaying the diagnosis . an emerging area of great interest is the high predilection of psychotic disorders ( including schizophrenia and bipolar disorders ) in adolescents and adults with dgs ( 25 times higher than the general population ) . other than serving as a reminder to psychiatrists , this also underlines that pediatricians and geneticists dealing with dgs / suspected dgs should diligently excavate the psychiatric history of the pedigree in detail , along with the other relevant particulars . clinical features of digeorge syndrome scid = severe combined immunodeficiency ; chd = congenital heart disease ; jra = juvenile rheumatoid arthritis case details ( continued ) : in view of suspected dgs , fish was performed using tuple1 probes on 200 interphase nuclei and 7 metaphases of the cultured blood . all the cells analyzed showed a heterozygous deletion in the 22q11.2 region [ figures 2a and b ] . presence of two green signals ( control arsa probe , locus 22q13 ) one orange signal ( tuple1 , locus 22q11.2 ) denotes hemizygous deletion in the 22q11.2 region ( b ) fish image of the patient : metaphase cell , each cell has two chromatids . presence of two pairs of green signals ( control arsa probe , locus 22q13 ) and only one pair of orange signals ( tuple1 locus 22q11.2 ) denotes hemizygous deletion in the 22q11.2 region q5 : what is the diagnostic modality for digeorge syndrome ? : the most regularly and widely used diagnostic test for detecting the 22q11.2 deletion is fish using probes for the commonly deleted region . however , around 5% of the cases may require more sophisticated and costlier methods such as multiplex ligation - dependent probe amplification ( mlpa ) and array comparative genomic hybridization ( acgh ) to detect the underlying genetic aberration . the presence of a chd in association with one or more of the following should serve as an important red flag for considering an underlying chromosomal imbalance as the possible genetic etiology : growth failure , intellectual disability , other malformations affecting a second organ , multiple anomalies , and dysmorphic features . in such cases , when the conventional karyotype fails to pick up the underlying genetic condition , an acgh can lead to increased detection of the underlying causal chromosomal imbalance . the major advantage of this acgh technique is its increased resolution , which surpasses that of conventional karyotyping by at least fivefold . in an excellent study by breckpot et al . , 150 children with an underlying chd and one or more of the red flags mentioned above were subjected to acgh , after a genetic diagnosis could not be reached despite a conventional karyotype and ruling out well - defined genetic disorders . of these 150 children , 24 ( 17.3% ) were detected as having an underlying copy number variation ( cnv ) , that is , a deletion or duplication , as responsible for their syndromic chd , as detected by acgh . some examples of the cnvs detected in this study include 1p36 deletion , 1q21.1 duplication , 8q deletion , 14q32 deletion , and 16p13.3 duplication . acgh can also diagnose , among many other cnv conditions , williams syndrome and some cases of charge syndrome . case details ( continued ) : on admission in our center , the child had leukocytosis ( total leukocyte count = 32 10/l ) and radiological evidence of bronchopneumonia . however , the child 's condition worsened on day 9 , due to congestive cardiac failure precipitated by the infection . in spite of ionotropic support and mechanical ventilation , the child timely diagnosis of this condition can alert the treating physician about the possibility of the associated comorbities known to occur with this disease . acute management in neonates and during infancy is mainly focused on the evaluation and treatment of hypocalcemia and the underlying chd as in our case . proactive prevention of the secondary complications and a watchful system - wise surveillance plan can go a long way in ensuring a healthy life for most of these individuals [ table 4 ] . however , the lack of centers performing thymic transplantation in india and the immunosuppression following the transplant make that a difficult option . prevention of secondary complications and the system - wise surveillance in patients with digeorge syndrome case details ( continued ) : the parents were offered genetic counseling , the main focus being on the future risk of recurrence , as our patient was the first issue . ans . : following the detection of 22q11.2 deletion in the proband , it is of vital importance to screen both the parents for the same ( using fish or mlpa ) in order to ascertain the origin of the deletion , sporadic or inherited . if either parent is detected with the deletion , then the risk of recurrence in the next pregnancy is 50% irrespective of the sex of the child ( autosomal dominant inheritance ) . however , if the parents of an individual with 22q11.2ds have normal studies , the risk of recurrence in the subsequent pregnancy is low , though greater than that of the general population . this is due to the possibility of germline or low - level somatic mosaicism in the parents . report retrospectively detecting 30 relatives of probands having a deletion in the 22q 11.2 region , following a diagnosis in the proband . of note , only 32% of the adults and 55% of the children in this case series ever had any major medical problems warranting care . thus , the absence of obvious clinical features should not be a reason to exclude the screening for the 22q11.2 deletion in the parents , if their child has been proven to carry the same . unfortunately , in our case the parents were unwilling to investigate themselves further . in the scenario of one child having dgs , prenatal testing by fish or mlpa can be offered in the next pregnancy , using fetal cells obtained by chorionic villus sampling ( 10 - 13 weeks of gestation ) or amniotic fluid analysis ( 15 - 18 weeks of gestation . ) in pregnancies without any family history of the disorder , the sonographic markers that should prompt one to request for prenatal diagnosis are : chd ( especially conotruncal anomalies ) and/or cleft lip and/or cleft palate , congenital diaphragmatic hernia , umbilical or inguinal hernia , tracheoesophageal fistula / esophageal atresia / laryngeal atresia , polydactyly , craniosynostosis , polymicrogyria , and renal anomalies . the prognosis for patients with dgs depends mainly on whether the dgs is partial or complete and on the severity of the underlying cardiac defect . most children with complete dgs who do not undergo a thymic transplant usually die in infancy . in contrast , the overall mortality rate in children with partial dgs is reported to be < 10% , most of them due to the underlying heart disease . however , if the child with an underlying heart disease has a successful repair , then the prognosis may be much better , the majority of the immunological problems settling with time . the endocrinological problems , too , do not tend to be devastating , most of them being treatable . learning disabilities , speech issues , and psychiatric manifestations respond well if remedial and supportive therapy is begun early . dgs is the most common microdeletion syndrome , with a notoriety of being clinically varied . timely diagnosis aids better management , more holistic counseling , and the opportunity for prenatal diagnosis in a subsequent pregnancy . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . this research received no specific grant from any funding agency in the public , commercial , or not - for - profit sectors . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . this research received no specific grant from any funding agency in the public , commercial , or not - for - profit sectors .

our patient presented with congenital heart disease ( chd : tetralogy of fallot ) , hypocalcemia , hypoparathyroidism , and facial dysmorphisms . suspecting digeorge syndrome ( dgs ) , a fluorescence in situ hybridization ( fish ) analysis for 22q11.2 deletion was made . the child had a hemizygous deletion in the 22q11.2 region , diagnostic of dgs . unfortunately , the patient succumbed to the heart disease . dgs is the most common microdeletion syndrome , and probably underrecognized due to the varied manifestations . this case stresses the importance of a detailed physical examination and a high index of suspicion for diagnosing this genetic condition . timely diagnosis can help manage and monitor these patients better and also offer prenatal diagnosis in the next pregnancy .

the ovaries are the most common sites affected , but endometriosis can also involve the gastrointestinal tract , urinary tract , chest , and soft tissues . endometriosis of the chest is uncommon , and the diagnosis is usually established on clinical grounds . endometrial tissue may involve the pleura by migrating from the peritoneal cavity to the pleural cavity through diaphragmatic defects or via microembolization . pleuritic chest pain , pneumothorax , pleural effusions , or cyclic haemoptysis can occur with pulmonary involvement [ 35 ] . a 35-year - old female presented with episodes of a right chest pain approximately 3 - 4 days in a month and resolved spontaneously . her primary care physician had treated her with antibiotics empirically throughout the four months . during the last episode of chest pain , the patient described having a pain not resolving with analgesics combination . the patient did not have any exacerbating factors , fevers , dyspnoea , haemoptysis , weight loss , and gastrointestinal complaints . the patient 's medical history was unremarkable , and she specifically denied a history of trauma and cardiopulmonary disease . she had spent 4 months in seaside town and had also worked at a seafood restaurant . her physical examination was within normal limits , except minimal pain in the right - sided lower chest and tenderness of the left lower abdominal quadrant . routine laboratory tests and tumor markers ( afp , cea , ca 15 - 3 , ca 19 - 9 ) were within normal limits but increased serum level of ca-125 level ( 53.7 u / ml , normal value : 035 u / ml ) . her chest radiography showed a closed right - sided costophrenic angle and minimal pleural effusion without evidence of pneumonia ( figure 1(a ) ) . chest computed , tomography ( ct ) scans were performed 6 days after the onset of menstruation , and these did not demonstrate pleural effusion or any abnormality ( figure 1(b ) ) . a percutane thoracal punction ( no abnormalities were noted on histopathologic examination ) was done because she denied thoracoscopic examination . pelvic endometriosis was considered a possible diagnosis according to the results of us and mr of the abdomen . pelvic us revealed a left adnexal semisolid mass , with a thick wall and septa , measuring 71 61 cm ( figure 1(c ) ) . mr imaging evaluated a left adnexal mass in 67 57 mm diameter with , high - signalintensity areas on t1- ( figures 2(a ) and 2(b ) ) and t2-weighted ( figures 2(c ) and 2(d ) ) images . in addition , dynamic signal range was not narrowed with fat - suppressed sequence , and heterogeneous pattern was found on postcontrast series . therefore , based on imaging characteristics immature teratoma , endothermal sinus tumor , and germ cell tumor must be considered primarily . at exploratory laparotomy , a transverse incision was performed , and a 6 cm mass was found just behind the uterus , as well as adhesions between the mass and the adjacent tissues . the patient needed sharp dissection and underwent adhesiolysis with left - sided salpingo - oophorectomy . rest of endometriotic focuses on uterus , pouch of douglas , and other peritoneal surfaces were destroyed with electro - coagulation . macroscopic appearance showed multiple irregular hemorrhagic foci and chocolate cysts ( figure 3 ) . the postoperative recovery was uneventful , and the patient was discharged on the third post - operative day . leuprolide acetate ( lucrin 3.75 mg ; abbott australasia , kurnell , nsw , australia ) was used to achieve endometrial atrophy for six months after surgery . medical treatment was continued with a cyclic low - dose combined oral contraceptive ( yasmin ; bayer healthcare pharmaceuticals inc . , one year of regular followup , there was no evidence of recurrent pleural effusion , chest pain , and abdominal complaints . the endometrial cells implant on serosal surfaces into the peritoneal cavity and transport to the thorax through diaphragmatic defects and lymphatic or vascular channels . thoracal endometriosis , depending on the extent and tissue affected , can produce pleuritic chest pain , pleural effusion , hemothorax , and pneumothorax . the physical manifestations are variable , with some patients being asymptomatic and others having disabling chest or pelvic pain , adnexal masses , or unusually signs . in our patient , periodic episodes of symptoms concurrent with menstruation led to the suspicion of a relationship between these conditions . the peak incidence for pelvic endometriosis occurred between 24 and 29 years , whereas the peak incidence for thoracal involvement was between 30 and 34 years . in a series of 110 patients with thoracal endometriosis , pneumothorax , hemothorax , hemoptysis , and pulmonary nodules the right hemithorax was involved in more than 90% of all manifestations except for nodules . regardless of pathophysiology , thoracal endometriosis is generally associated with coexistent pelvic endometriosis and usually occurs 5 years after the diagnosis of pelvic endometriosis . however , most women with endometriosis have normal or nonspecific results from physical examinations , and laparoscopy is necessary for the definitive diagnosis . for the definite confirmation of presence of endometrial tissue ct - guided percutaneous transthoracic needle biopsy or thoracoscopic tissue biopsy we only able to perform thoracal ct and abdominal mr imaging in present case , because our patient denied a thoracoscopic examination . the us appearance of pelvic endometriosis exhibits diffuse low - level internal echoes , hypoechoic focal lesion , and rarely , may be anechoic , mimicking a functional ovarian cyst . patel et al . found that wall thickness is not a differentiating feature between endometriomas and other ovarian masses . using ct , endometriosis of the lung parenchyma mr imaging has been shown to have greater specificity for the diagnosis of abdominal endometriomas . . lesions with degenerated blood products , including concentrated protein , appear with high - signalintensity areas on t1- and t2-weighted images . in our case , t1-weighted mr image showed a multilocular high - signalintensity mass on the left ovary , and highness in signal intensity remained in t2-weighted image . a common feature of an endometrioma , shading , is present when a cyst that is hyperintense on a t1-weighted image becomes hypointense on a t2-weighted image . this shading reflects the chronic nature of an endometrioma and helps differentiate it from other blood - containing lesions except hemorrhagic corpus luteum cysts , which do not exhibit shading on t2-weighted images . other lesions that appear with high - signalintensity on t1-weighted images include dermoids , mucinous cystic tumors , and hemorrhagic masses . treatment for thoracal endometriosis can be medical for chest pain and effusion or surgical , depending on the severity of urgent and elective symptoms . medical treatment is one of the choices of treatment to relieve cyclic pain in endometriosis . multiple pharmacologic agents in use include combined oral contraceptives , danazol , gn - rh agonists and progestins . in our patient , medical treatment with a gn - rh agonist , which was continued with a cyclic low - dose definitive surgery includes hysterectomy and oophorectomy and is usually reserved for women with intractable pain . the conservative surgery , including left - sided oophorectomy , was performed to our patient . in our patient , , we did not establish pleural endometriosis cytologically but the monthly chest pain associated with endometrioma of the ovary supported extrapelvic lesion , clinically .

chest pain is a rare sign of thoracal endometriosis associated with endometrioma of the tubo - ovarian endometrioma . we report the case periodic episodes of chest pain concurrent with menstruation in a 35-year - old female , in which ovarian endometrioma was diagnosed and left - sided oophorectomy was performed . after surgery , patient underwent medical treatment which included a gn - rh agonist and a combined oral contraceptive . in the follow - up period , there was no evidence of chest pain .

collapsing glomerulopathy has been recognized as a form of focal segmental glomerulosclerosis characterized by collapse of the glomerular capillary tuft and proliferation of the visceral epithelial cells . most cases have been seen in patients with hiv infection , but since 1986 an association with several non - hiv - related conditions has also been reported [ 13 ] . indeed , as early as in 1999 , one center reported that as many as two - thirds of cases of collapsing glomerulopathy ( collapsing gn ) were non - hiv - related ; labeled as collapsing idiopathic gn . it is now known that collapsing gn may occur in association with viruses ( parvovirus b19 , cytomegalovirus ( cmv ) , htlv-1 and hcv ) , bacteria ( tuberculosis ) , parasites ( leishmaniasis ) , febrile illness , drugs ( interferon alpha , pamidronate ) , autoimmune diseases , malignancy ( acute monoblastic leukemia , multiple myeloma , hemophagocytic syndrome ) , post - transplantation and certain genetic causes . a previously healthy 21-year - old african - american woman presented with a 4-day history of malaise , fever , nausea , vomiting , anorexia and left - sided abdominal pain . kg / m , had a temperature of 38.9c ( 102f ) , pulse rate of 100 bpm , respiratory rate of 22 per minute and blood pressure of 110/70 mmhg . the spleen was markedly enlarged and there was tenderness over the left upper abdominal quadrant . initial laboratory tests were significant for a normocytic normochromic anemia [ hemoglobin 5.8 g / dl ( 58 g / l ) ] , thrombocytopenia ( platelet count 103 000 cells/l ) and a lymphocyte count of 4400 cells/l ( normal 12003400 cells/l ) . ct scan of the abdomen ( without intravenous contrast ) revealed massive splenomegaly and hypodensities suggestive of infarcts . autoimmune workup including serum antinuclear antibodies , antineutrophil cytoplasmic antibodies , complements , antiphospholipid antibodies , serum and urine protein electrophoresis with immunofixation were normal . testing for lymphoproliferative diseases revealed normal flow cytometry , absent jak 2 mutation , no bcr / abl gene translocation and unremarkable bone marrow biopsy . infectious workup was negative for human immunodeficiency virus ( hiv ) 1 and 2 serology , and hiv rna by polymerase chain reaction ( pcr ) . hepatitis b and c serologies , urine histoplasma antigen , serum rapid plasma reagin and parvovirus b19 were negative . barr virus ( ebv ) dna and viremia ( as assessed by qualitative pcr methods ) was reported as positive on day 9 . subsequent testing for ebv - specific antibodies revealed positive igm vca ( viral capsid antigen ) titers ( > 1:10 ) and positive igg vca on day 10 . on admission , urinalysis showed specific gravity of 1.019 , 1 + dipstick proteinuria , 5 red blood cells , and 15 white blood cells per high power field magnification ( hpf ) , no cellular casts and sterile urine culture . no previous baseline values were available for comparison . at the time of renal consultation on day 10 of admission , serum creatinine had increased to 133 mol / l ( 1.5 mg / dl ) 24 h after administration of intravenous contrast for a repeat ct scan of the abdomen . repeat urinalysis revealed a specific gravity of 1.036 , 4 + dipstick proteinuria , 5 red blood cells and 215 white blood cells per hpf , sterile urine culture and a spot urine protein to creatinine ratio of 23 , confirmed on two separate occasions . g / l ( 3.2 g / dl ) , and total cholesterol had increased to 4.8 mmol / l ( 185 mg / dl ) from a baseline 2.2 mmol / l ( 85 mg / dl ) . renal biopsy was performed on day 15 to characterize the new - onset nephrotic syndrome as the patient had now also developed anasarca . it revealed collapse of the glomerular capillary tuft , visceral epithelial cell proliferation and vacuolization consistent with collapsing glomerulopathy ( figure 1 ) , alongside with evidence of recovering acute tubular necrosis . in situ 1.collapse of glomerular tuft ( a ) along with visceral epithelial cell proliferation and vacuolization ( b ) on pas ( periodic acid - schiff ) and jones stain . collapse of glomerular tuft ( a ) along with visceral epithelial cell proliferation and vacuolization ( b ) on pas ( periodic acid - schiff ) and jones stain . on day 18 , a therapeutic splenectomy was performed because of unremitting abdominal pain and radiologic evidence of capsular rupture . splenic tissue examination showed multifocal infarction , capsular rupture and confirmed the presence of ebv - encoded rna ( eber ) by in situ hybridization ( figure 2 ) . serum creatinine returned to a baseline of 53 mol / l ( 0.6 mg / dl ) on day 20 . follow - up ebv serology on day 21 revealed positive igg ebna ( epstein barr nuclear antigen ) titers . subsequent follow - up over the next few months showed improving proteinuria , urine sediment and serum albumin levels . at the last clinic visit ( 11 months after illness onset ) , serum creatinine was 53 g / l ( 3.9 g / dl ) , urine sediment had 1 red blood cell and 1 white blood cell per hpf , and proteinuria had lowered to < 1 g / g of creatinine in the urine . the patient continues to be conservatively managed with up - titration of raas blockade and is being closely monitored by the clinic . here we report an association between collapsing glomerulopathy and an acute ebv syndrome , manifesting itself clinically as nephrotic syndrome with massive proteinuria , hypoalbuminemia , anasarca and hypercholesterolemia . the reversible rise in creatinine was most likely due to contrast - induced acute kidney injury , also demonstrated on renal biopsy . evidence of renal involvement is reported in 316% of patients with acute infectious mononucleosis [ 6 , 7 ] . nephrotic syndrome in acute infectious mononucleosis was first published in 1963 in a case in which kidney biopsy was inconclusive . glomerular lesions have included membranous nephropathy [ 10 , 11 ] , mesangial focal proliferative disease with cellular crescents , minimal - change disease [ 13 , 14 ] and vasculitic lesions such as polyarteritis nodosa . to our knowledge , this is the first report of collapsing glomerulopathy . ebv predominantly infects b lymphocytes , the producers of immunoglobulin through specific ebv / c3d receptors on b cells . a viral glycoprotein , gp350 , bears sequence homology to the c3 complement fragment c3d . one of the main reservoirs of ebv is the nasopharyngeal mucosa , where epithelial cells endocytose circulating polymeric iga - ebv immune complexes by specific receptors and transport them to the luminal surface . ebv infection seems to represent equilibrium between viral replication in vivo and the host 's immune removal of the virus , and disease occurs when there is an imbalance in the host immunity . it could be related to an uptake of immunoglobulin ebv complexes by glomerular visceral and parietal epithelial cells similar to that in the nasopharyngeal mucosa . have shown localization of parvovirus b19 dna ( another viral cause of collapsing gn ) in glomerular parietal and visceral epithelial cells . another study suggested a causative role of ebv infection in the pathogenesis of interstitial nephritis . ebv dna has been detected in renal tissue in iga nephropathy , membranous nephropathy and focal / segmental lesions ; and is quantitatively greater in subgroups with mesangial injury , fibrinogen deposits and immunoglobulin deposits , suggesting a causative role . other studies have also reported transformation of b cells by ebv to produce more iga than igg , especially in iga nephropathy , and the same iga1 subtype that was produced by transformed b cells was found deposited in the glomerular mesangium [ 22 , 23 ] . in our patient , this may have been due to a low viral copy number or to the focal nature of the infection . differences in the detection techniques applying pcr and southern blot to the extracted dna may have also contributed to the absence of ebv detection in renal tissue . however , there was a significant association of acute ebv viremia and collapsing gn in our patient . as the acute phase of the infection cleared , proteinuria gradually improved , but persisted , suggesting the possibility of secondary autonomous phase of podocyte loss .

a 21-year - old woman presenting with acute epstein barr virus ( ebv ) infection ( infectious mononucleosis ) was noted to have renal involvement . she had proteinuria , leukocyturia and microscopic hematuria , and 10 days after admission became nephrotic ( 23 g of protein per g of creatinine ) . renal biopsy revealed glomerular tuft collapse , visceral epithelial cell proliferation and vacuolization consistent with collapsing glomerulopathy . she had only transient deterioration in renal function , attributed to contrast nephropathy , but after recovery remained proteinuric . renal disease is well described in ebv infection , but collapsing glomerulopathy has not been reported previously .

the use of oocyte freezing for fertility preservation is becoming more widely practiced.1 although there is evidence that the success rates of oocyte cryopreservation and subsequent thaw cycles appear to approach that of a fresh in vitro fertilization ( ivf ) cycle ( coupled with reports of numerous live births ) , oocyte cryopreservation is still not considered mainstream , but has become a more accepted option for cancer patients.2 despite the controversy surrounding embryo biopsy for aneuploidy assessment ( preimplantation genetic screening [ pgs ] ) , recent advances such as trophectoderm biopsy and array comparative genomic hybridization ( a - cgh ) have provided more support for its continued and expanded use . as more patients are choosing oocyte cryopreservation for fertility preservation , and as more evidence accumulates that aneuploidy screening lowers miscarriage rates and improves implantation rates , it is likely the combination of oocyte cryopreservation and pgs will be utilized in the future.3,4 we report a successful live birth from previously vitrified oocytes from a known donor , which were thawed , fertilized , cultured to blastocyst , underwent trophectoderm biopsy , and refrozen awaiting analysis of ploidy by a - cgh . a 31-year - old with a history of two miscarriages requested pgs due to our decreased loss rates in patients with recurrent pregnancy loss utilizing pgs compared to those not using pgs.3,4 the patient was in a same - sex relationship and had failed several intrauterine inseminations and two ivf cycles using donor sperm ( donor karyotype known to be 46 , xy ) in the past . one miscarriage occurred after an insemination ( chromosomes not tested ) and one after an ivf cycle , which was found to be 45 , x. the patient was found to have uterine lining issues , including asherman s syndrome , but due to her schedule , she requested to undergo ovarian stimulation with oocyte retrieval and cryopreserve her oocytes . at the time , we felt that our oocyte thaw pregnancy rates were greater than or equal to our frozen embryo transfer pregnancy rates , and after much discussion , the patient felt most comfortable cryopreserving her oocytes over embryos with donor sperm . her plan was to address her endometrial lining issues when her schedule permitted , which would then be followed by fertilization , embryo biopsy , and an embryo transfer . ovarian stimulation for her third cycle was achieved by a combination of injectable recombinant follicle - stimulating hormone ( follistim ; organon , orange , nj , usa ) and human menopausal gonadotropin ( menopur ; ferring , suffern , ny , usa ) . an ovulation trigger of human chorionic gonadotropin ( 10,000 iu ) was administered when her two lead follicles were 18 mm , and an ultrasound - guided transvaginal oocyte retrieval was performed 3436 hours later . oocytes were frozen by both vitrification ( n = 11 ) and slow freeze ( n = 7 ) by our previously published methods , and thawed by the same methods.1,5 the oocytes were thawed 2 months later and placed in human tubal fluid media ( irvine scientific , irvine , ca , usa ) , supplemented with 6% plasmanate ( 5% usp plasma protein fraction [ human ] ; bayer , elkhart , in , usa ) , and overlaid with sage mineral oil ( cooper surgical co. , trumbull , ct , usa ) . thirteen mature oocytes survived the thaw ( 12/15 m2 frozen and one mi developed into an m2 upon thaw ) . fertilization was documented 18 hours after insemination by the presence of two pronuclei ( 2pn ) ; this patient had twelve 2pns ( seven from vitrification and five from slow freeze ) , leading to a 92% fertilization rate . on day 3 , a hole was made in the zona pellucida using a cronus laser ( research instruments , falmouth , uk ) on a nikon inverted te-2000 microscope ( nikon corporation , tokyo , japan ) using cronus software to allow hatching in all twelve embryos . resultant embryos were cultured for 5 days , but the embryos were all morulas or cleavage - stage embryos and not suitable on day 5 for biopsy ; therefore , they were cultured to day 6 . on day 6 , five ( three from vitrification and two from slow - freeze ) of her embryos underwent trophectoderm biopsy and were vitrified a second time . vitrification was performed according to the kuwayama vitrification method with cryolocks and using an irvine scientific vitrification system , which contains dimethyl sulfoxide and ethylene glycol.6 the biopsied cells were placed in eppendorf tubes , frozen in dry ice , and then transported to reprogenetics for pgs analysis once all of the biopsies were performed . this analysis was performed using the method described in gutirrez - mateo et al7 without modification . oocytes were frozen by both vitrification ( n = 11 ) and slow freeze ( n = 7 ) by our previously published methods , and thawed by the same methods.1,5 the oocytes were thawed 2 months later and placed in human tubal fluid media ( irvine scientific , irvine , ca , usa ) , supplemented with 6% plasmanate ( 5% usp plasma protein fraction [ human ] ; bayer , elkhart , in , usa ) , and overlaid with sage mineral oil ( cooper surgical co. , trumbull , ct , usa ) . thirteen mature oocytes survived the thaw ( 12/15 m2 frozen and one mi developed into an m2 upon thaw ) . fertilization was documented 18 hours after insemination by the presence of two pronuclei ( 2pn ) ; this patient had twelve 2pns ( seven from vitrification and five from slow freeze ) , leading to a 92% fertilization rate . on day 3 , a hole was made in the zona pellucida using a cronus laser ( research instruments , falmouth , uk ) on a nikon inverted te-2000 microscope ( nikon corporation , tokyo , japan ) using cronus software to allow hatching in all twelve embryos . resultant embryos were cultured for 5 days , but the embryos were all morulas or cleavage - stage embryos and not suitable on day 5 for biopsy ; therefore , they were cultured to day 6 . on day 6 , five ( three from vitrification and two from slow - freeze ) of her embryos underwent trophectoderm biopsy and were vitrified a second time . vitrification was performed according to the kuwayama vitrification method with cryolocks and using an irvine scientific vitrification system , which contains dimethyl sulfoxide and ethylene glycol.6 the biopsied cells were placed in eppendorf tubes , frozen in dry ice , and then transported to reprogenetics for pgs analysis once all of the biopsies were performed . this analysis was performed using the method described in gutirrez - mateo et al7 without modification . overall , the patient underwent three operative hysteroscopies with lysis of adhesions followed by uterine balloon catheter by three different skilled physicians without improvement in her uterine lining . ultimately , the patient decided to transfer the euploid embryos into her partner who had a normal lining . the thaw cycle utilized sequential oral estradiol supplemented by intramuscular progesterone after the endometrial stripe achieved a ring pattern and was 11 mm in the first thaw cycle and 9 mm in the second thaw cycle . an appropriately timed ultrasound guided embryo transfer was performed of euploid blastocysts . in the first embryo transfer cycle , two euploid embryos ( 35bb , 6bc ) the second attempt with a single euploid embryo ( 35bc ) resulted in a pregnancy . the couple went on to deliver a viable 8-pound , normal male infant ( confirming a - cgh results ) at 38 weeks gestation via normal spontaneous vaginal delivery . as more oocytes are frozen for fertility preservation before cancer treatment or electively , there will be increasing instances where preimplantation genetic diagnosis ( pgd ) or pgs will be indicated or requested after thawing . as more recessive genes are identified , more patients will be candidates for single gene pgd . in addition , as more cancer - causing genes are identified , cancer survivors who utilized fertility preservation will request pgd to avoid inheritance of these genes . the evolving literature on 24 chromosome screening already shows that the miscarriage rate is lower and the implantation rate is higher than ivf cycles without pgs ( and equivalent to donor oocyte unscreened embryos ) , suggesting the possibility of routine aneuploidy assessment prior to embryo transfer.4,8,9 in either case , more patients will electively request the utilization of these techniques for their previously cryopreserved oocytes . this case report demonstrates proof of a concept that it is possible to perform pgd or pgs on embryos derived from previously cryopreserved oocytes .

our objective is to describe a successful live birth from oocyte vitrification followed by thaw , fertilization , blastocyst culture , trophectoderm biopsy , vitrification , and subsequent thaw . fifteen mature oocytes were frozen from a patient with uterine factor infertility . thirteen oocytes survived the thaw , and five underwent trophectoderm biopsy and were refrozen . three euploid embryos were obtained . a single euploid embryo was transferred in the second thaw cycle to a known recipient leading to the delivery of a normal male infant . this case report is proof of the concept that preimplantation screening and diagnosis is an option for fertility preservation patients .

since the original description of the disease by alois alzheimer , memory difficulties are considered the initial and the most prominent and typical symptom of alzheimer 's disease . more recently , the detection of elderly subjects with mild cognitive impairment and a high risk of progression to alzheimer 's disease also relies on the presence of memory complaints , and , in proposed revised criteria for prodromal ad , like the dubois criteria , the report by patients or informants of memory decline remains part of the core diagnostic features . memory complaints thus represent an important symptom in clinical practice . on the other hand , in fact , not only elderly but also young subjects may have an unfavourable opinion about their memory capabilities . using a formal scale , the subjective memory complaints scale ( smc ; ) , as much as 75.9% of people report at least minor complaints when answering to the first general question do you have any complaints concerning your memory ? ( smc1 ) . the significance and clinical implications of the frequent report of memory difficulties in the community setting are not clear . in a meta - analysis , the presence of memory complaints was more frequent in cognitively impaired than in cognitively normal elderly subjects . a systematic review concluded that the subjective memory complaints appear to be associated with depressive symptoms and personality traits and may predict future cognitive decline . a recent study found that self perceived memory complaints are an independent predictor of dementia . in the present study , we analysed the severity and type of memory difficulties presented by patients who look for medical help in a memory clinic or hospital outpatient setting , as compared to the memory difficulties that subjects in the community report when specifically asked for . the same instrument , the subjective memory complaints scale , was applied in both samples . we tested the hypothesis that some types of memory complaints would be selectively reported by subjects in the clinical setting . the objective was to identify the memory complaints most prone to raise concern from the patients and their families and bring them to clinical care . subjects with cognitive complaints older than 50 years referred for neuropsychological evaluation at the laboratory of language studies , santa maria hospital , and a memory clinic , both in lisbon . controls were volunteers older than 50 years attending a health itinerant unit that aims to screen and promote general health , a blood donor centre , a leisure centre for retired people , and a senior citizens college and university , all in the area of lisbon . presence of dementia ( criteria of the american psychiatric association , dsm - iv - tr ) , or mmse score below the education - adjusted cutoff , neurological disorders ( stroke , tumors , significant head trauma , and epilepsy ) , psychiatric conditions ( including major depression ) , or uncontrolled medical illness ( hypertension , metabolic , endocrine , toxic , and infectious diseases ) able to interfere with cognition , psychoactive medications with possible influence on cognition , chronic alcohol or drug abuse , sensory deficits likely to interfere with assessment , and nonnative portuguese speakers . all participants gave their informed consent . a semi - structured interview recorded clinical information , present and past medical conditions , psychiatric and neurological history , medication , social and familial status . the mini - mental state examination ( mmse ; participants with mmse below education - adjusted values for the portuguese population were excluded ( < 23 for less than 11 years of education , participants were assessed with the subjective memory complaints scale ( smc ; [ 5 , 12 ] ) . they were required to answer 10 individual items concerning difficulties in daily - life memory tasks , with total scores ranging from 0 ( absence of complaints ) to 21 ( maximal complaints score ) . the smc was always applied at the end of the clinical interview . for the assessment of depressive symptoms the geriatric depression scale ( gds ; [ 13 , 14 ] ) was used . differences in the total smc scores among the different community settings were tested with one - way anova . comparison of demographic and neuropsychological data between the participants in the community and in the clinical setting was done using student 's t test on quantitative variables and the fisher 's exact test on the nominal variable . comparison of the smc items and the smc total score between participants in the community and in the clinical setting was performed with the mann - whitney u test . eta - squared values were calculated for the individual smc items to explain the total smc score with ancova , controlling for depression score and education years . the 95% confidence intervals for eta - squared values were obtained by nonparametric bootstrap sampling ( k = 1000 ) using the boot library in the r system software ( v. 12.2.1 , r development core team ) . eight - hundred and seventy - one nondemented subjects older than 50 years were included in the study , 581 recruited in the community , and 290 in the clinical setting . participants in the clinical setting were more educated , had slightly lower mmse scores , and presented more depressive symptoms than the participants in the community ( table 1 ) . all participants in the clinical setting had complaints at least in one smc item , and 20 ( 3.4% ) participants in the community reported no memory complaints ( total smc score = 0 ) . since no differences in the total smc scores were found among the different community settings ( health itinerant unit , blood donor centre , leisure centre for retired people , and senior citizens college and university ) , the results from community participants were pooled together . participants in the clinical setting had a higher total smc score [ 10.3 4.2 ( 121 ) ] than those in the community [ 5.1 3.0 ( 015 ) ] ( figure 1 ) , and this held true for almost all types of memory complaints ( table 2 ) . the only exception was the smc7 item , did you ever lose your way in neighbourhood ? few subjects reporting this difficulty , both in the clinical setting ( 4.8% ) and in the community ( 3.1% ) . analysing the weight of the different types of complaints to the global smc score in the two groups , we found that smc3 , do you ever forget names of family members or friends ? contributed to only 11% of the total score variance in the community sample , and as much as 18% of the total score variance in the clinical sample ( as shown in figure 2 , the 95% confidence intervals for the eta - squared values of smc3 are separated ) . this was the item that contributed most to the total smc score variance in the clinical group . in contrast , smc1 , which a general question about memory complaints , smc6 , do you ever have difficulties in finding particular words ? , and smc 8 , do you think more slowly than you used to ? elderly patients who seek for medical help in a memory clinic or hospital outpatient setting reported more prominent memory difficulties as compared to the subjects in the community . nevertheless , only 20 community participants reported to be completely free from memory difficulties ( i.e. , to say , had 0 in the smc total score ) . the participants in the clinical setting scored higher in almost all smc items , reflecting more problems in different types of memory complaints . the exception was item smc7 , about being lost in the neighbourhood , to which few participants answered positively , as found in previous studies . difficulties in spatial orientation in known places may well reflect the beginning of a dementing disorder like alzheimer 's disease . in a recent study , the complaining of difficulties on finding one 's way around familiar streets was highly associated with objective cognitive impairment . the hypothesis advanced in the present work , that some types of memory complaints would be selectively reported by nondemented elderly subjects in the clinical setting , as compared to the community , was confirmed . forgetting names of family members or friends contributed more strongly to the global subjective memory complaints in the clinical setting . this memory difficulty is probably perceived as particularly worrisome , or more likely to impact on close interpersonal relationships . it is interesting that it is not just the problem with names that is involved because subjects in the clinical setting did not report more difficulties in finding particular words ( item 6 ) . the trouble with such a trivial task as remembering proper names of close people appears particularly disturbing . it is interesting that the neuronal basis for processing familiar proper nouns is different from other names and quite widespread , involving both cerebral hemispheres . the perception of this type of memory complaint as worrisome is certainly justified since 20% percent of patients with early alzheimer 's disease report forgetting the names of relatives . factors other than the memory complaints themselves may of course influence whether elderly people seek for clinical help or not . the clinical participants were more educated , possibly with more awareness of the implications of memory problems and an easier access to clinical care . they also had more depressive symptoms , which could indeed drive their concern about memory problems . an association between depressive symptoms and reporting of memory complaints has been consistently found ( see , for instance , [ 18 , 19 ] ) . a recent study , comparing patients in a memory clinic and non - help - seekers , found that beliefs about memory , as well as the presence of a close relative with dementia , were associated with the decision to seek help . it must be recognized that in the present study the evaluation of memory complaints was based on a single scale , the subjective memory complaints scale . although this scale has items considered representative of common memory complaints , the results may not necessarily be generalizable to other instruments of memory complaints evaluation . in conclusion , the clinical diagnosis of mild cognitive impairment relies on the presence of memory complaints in subjects who seek for medical help . the present study suggests that both the global severity of memory complaints and the type of memory difficulties reported , particularly forgetting names of family members or friends , are associated with the clinical setting . further research should clarify the reasons why some elderly people seek for medical help , and others do not , since important consequences for the screening of early cognitive decline in the community may ensue .

diagnosis of mild cognitive impairment relies on the presence of memory complaints . however , memory complaints are very frequent in healthy people . the objective of this study was to determine the severity and type of memory difficulties presented by elderly patients who seek for clinical help , as compared to the memory difficulties reported by subjects in the community . assessment of subjective memory complaints was done with the subjective memory complaints scale ( smc ) . the mini - mental state examination was used for general cognitive evaluation and the geriatric depression scale for the assessment of depressive symptoms . eight - hundred and seventy - one nondemented subjects older than 50 years were included . participants in the clinical setting had a higher total smc score ( 10.3 4.2 ) than those in the community ( 5.1 3.0 ) . item 3 of the smc , do you ever forget names of family members or friends ? contributed significantly more to the variance of the total smc score in the clinical sample ( 18% ) as compared to the community sample ( 11% ) . forgetting names of family members or friends plays an important role in subjective memory complaints in the clinical setting . this symptom is possibly perceived as particularly worrisome and likely drives people to seek for clinical help .

a total of 100 dentate dental students of which 50 males and 50 females aged between 20 and 25 years were randomly selected as representative of the young adult group . the selected students had no restorations in the anterior teeth and had not received orthodontic treatment . the clinical research study was conducted after explaining the student subjects in their own language along with a signed written consent approved by the institutional ethical committee . an impression of each student 's maxillary dentition was made with irreversible hydrocolloid impression material of 50 male and 50 female subjects to obtain study casts poured with dental plaster . additional duplicated sectional study casts were obtained to aid in identification and classification of the palatal form . a standardized procedure was adopted to obtain digital photograph of the maxillary central incisors , the maxillary dental arch from the study casts [ figures 1 and 2 ] and the palatal contour from the duplicated sectional casts using nikon coolpix digital camera ( s3400 ; nikon corp . the photographs were then transferred to a computer ( windows pc , microsoft ) having image editing software ( photoshop 6.0 adobe , nikon corp . japan ) to obtain individual photographic tracing printouts of the tooth form , arch form and the palatal form for evaluation by visual method . frontal photograph of the maxillary incisor teeth occlusal photograph of the maxillary dental arch the tooth form was determined on the right maxillary central incisor tooth by an outline tracing made around the buccal surface of the tooth , which corresponded to the mesial and distal contours , the incisal edge and the cervical margin . the photographic printouts of the tracing had a diagram of perpendicular lines that was placed on the tooth form outline tracing [ figure 3 ] and the tooth in each quadrant was classified visually according to william 's as follows : square incisor tooth - mesial and distal proximal surfaces are parallel for at least half of the cervicoincisal length of the crownovoid incisor tooth - mesial and distal proximal surfaces are biconvextapering incisor tooth - mesial and distal proximal surfaces converge from incisal to cervical . square incisor tooth - mesial and distal proximal surfaces are parallel for at least half of the cervicoincisal length of the crown ovoid incisor tooth - mesial and distal proximal surfaces are biconvex tapering incisor tooth - mesial and distal proximal surfaces converge from incisal to cervical . tracing printout of the maxillary incisor tooth form one of the three basic tooth forms ( square , ovoid or tapering ) was classified to a tooth only if that form predominated in at least 75% of the outline tracing print ( three quadrants ) . if one of the basic form predominated in at least 50% of the outline tracing print ( two quadrants ) , the tooth form should be classified as a combination tooth form . the arch form was determined on the maxillary arch by an outline tracing made around the arch corresponding to the incisal edges of the incisors , canine cusp tips , buccal cusps tips of premolars and molars . the photographic printouts [ figure 4 ] of the tracing were used to classify the arch form visually as square , ovoid or tapering . tracing printout of the maxillary arch form the palatal form was determined by a contour tracing made along the surface of the maxillary cast with a deep midpoint marked along the mid palatal suture that joins the palatal cusps of two selected premolar or molar teeth . the photographic printouts [ figure 5 ] of the tracing were used to classify the palatal form visually as u - shaped , v - shaped or shallow . tracing printout of the palatal form six prosthodontists with more than 5 years of experience classified the photographic outline tracings of the tooth , arch and palatal forms visually based on the instructions obtained before evaluation . the means of prosthodontists evaluation were considered and statistically analyzed using chi - square test for distribution differences and results were tabulated . the following results were tabulated : the combination tooth form 44% predominated in males followed by square 28% , ovoid 14% and tapering 14% tooth forms when compared with the ovoid tooth form 36% predominated in females , followed by combination 32% , square 24% and tapering 8% tooth forms [ table 1 ] . the = 6.759 was found to be not significant with a p = 0.080 . descriptive statistics for comparison of predominant maxillary central incisor tooth form in males and females of saudi population the ovoid arch form 42% predominated in males followed by tapering 36% and square 22% arch forms when compared with the square arch form 44% predominated in females followed by ovoid 40% and tapering 16% arch forms [ table 2 ] . descriptive statistics for comparison of predominant maxillary arch form in males and females of saudi population the u - shaped and v - shaped palatal forms 46% respectively predominated in males followed by shallow palatal form 8% when compared with the u - shaped palatal form 74% predominated in females followed by v - shaped 14% and shallow 12% palatal forms [ table 3 ] . the = 12.20 was found to be significant with a p = 0.002 . the size and form of the maxillary anterior teeth are important to not only dental , but also facial esthetics . the most influential factors contributing to a harmonious anterior dentition are the size , shape , and arrangement of the maxillary anterior teeth , particularly the maxillary central incisors as viewed from the front . according to the glossary of prosthodontics terms ( gpt 8) the outline form as viewed in any selected plane or / and other contours of an anterior tooth . in the present study , outline form of the maxillary right central incisor tooth was considered to classify according to williams method of classification of tooth forms into square , ovoid , tapering or combination tooth forms . the dentulous arch form of an individual will remain the same even after becoming an edentulous arch and that the edentulous arch remains fairly constant in the absence of surgical intervention . boucher is of the same opinion that the original form of the dental arch is maintained even after the removal of natural teeth . the arch form is defined according to gpt 8 as the geometric shape of the dental arch when viewed in the horizontal plane ( square , tapering , ovoid , etc . ) . in 1932 , chuck classified the arch forms as tapered , ovoid and square for the first time which can also be expressed as narrow , normal and wide respectively . in the present study , the maxillary arch form was classified as square , ovoid and tapering arch forms . the form of the palatal vault or depth of the hard palate gives an idea about the original form of the dental arch before removal of the natural teeth and resorption of the residual ridge . the palatal vault is defined according to gpt 8 as the deepest and most superior part of the palate or the curvature of the palate . the palatal vault is classified as low palate , medium palate and high / deep palate , which can also be expressed as shallow / flat palate , u - shaped palate and v - shaped palate respectively . in this study , the palatal form or palatal shape was classified as u - shaped , v - shaped or shallow palatal forms . the predominant tooth form for males in the present study was combination tooth form 44% followed by square 28% , ovoid 14% and tapering 14% tooth forms . the value was lesser when compared with the previous study being combination tooth form 58% , followed by square 22% , tapering 13% and ovoid 8% tooth forms . the predominant tooth form for females in the present study was ovoid tooth form 36% followed by combination 32% , square 24% and tapering 8% tooth forms . this was in correlation with the previous study being ovoid teeth for females but the value was higher and not in correlation when compared with the previous study being predominant combination tooth form 51% , followed by square 22% , ovoid 15% and tapering 12% tooth forms . the predominant arch form for males in the present study was ovoid arch form 42% followed by tapering 36% and square 22% arch forms . the value was lesser when compared with the previous study being ovoid arch form 66.7% followed by tapering 33.3% arch forms . the value was not in correlation when compared with the previous study being predominant narrow ( tapering ) arch form 13.5% followed by flat 10.5% , wide ( square ) 10.3% , pointed 8.3% and mid ( ovoid ) 7% arch forms . the value was lesser when compared with the previous study being ovoid arch form 55.1% , followed by tapering 54.2% and square 42% arch forms . the value was higher and not in correlation when compared with the previous study being predominant square arch form 35.33% , followed by ovoid 34.67% and tapering 30% arch forms . the predominant arch form for females in the present study was square arch form 44% , followed by ovoid 40% and tapering 16% arch forms . the value was lesser when compared with the previous study being square arch form 58% , followed by tapering 45.8% and ovoid 44.9% arch forms . the value was not in correlation when compared with the previous study being predominant narrow ( tapering ) arch form 17.4% , followed by wide ( square ) 13.6% , pointed 9.3% , flat 7.8% , and mid ( ovoid ) 2.3% arch forms . the value was higher when compared with the previous study being square arch form 36.67% followed by ovoid 33.33% and tapering 30% arch forms . the predominant palatal form for males in the present study was both u and v shaped palatal forms 46% respectively , followed by shallow 8% palatal form . this was in correlation with the previous study that the palatal depth is significantly higher in males . the predominant palatal form for females in the present study was u - shaped palatal form 74% followed by v - shaped 14% and shallow 12% palatal forms . this was in correlation with the previous study that the palatal depth significantly is not higher in females . the palatal form value in the present study for both males and females combined was higher and not in correlation when compared with the previous study based on qualitative method of palatal depth assessment being predominant low palate ( shallow ) 51.4% followed by medium palate ( u - shaped ) 43.2% and high palate ( v - shaped ) 5.4% palatal forms but the value was higher and in correlation when compared with quantitative method of palatal depth assessment being predominant medium palate ( u - shaped ) 55.4% followed by high palate ( v - shaped ) 39.2% and low palate ( shallow ) 5.4% palatal forms . within the limitations of the saudi population group studied , the following inferences may be drawn : the predominant tooth form was combination tooth in males and ovoid tooth in femalesthe predominant arch form was ovoid arch in males and square arch in femalesthe predominant palatal form was both u and v shaped ( medium and deep palates ) in males , and only u - shaped ( medium palate ) in femalesexcept for the tooth form , there was a significant difference with arch and palatal form among males and females of the population group studied . the predominant tooth form was combination tooth in males and ovoid tooth in females the predominant arch form was ovoid arch in males and square arch in females the predominant palatal form was both u and v shaped ( medium and deep palates ) in males , and only u - shaped ( medium palate ) in females except for the tooth form , there was a significant difference with arch and palatal form among males and females of the population group studied . thus during selection and arrangement of artificial teeth for edentulous saudi patients , the dentist and the laboratory technician will require basic tooth forms ( square , ovoid and tapering ) along with combination tooth forms . individual patient 's preferences during the selection and arrangement of anterior teeth should also be considered to increase the success rate of fixed and removable dental prosthetic treatment . however

aims : to determine various tooth form , arch form , and palatal form with gender identification between males and females of the saudi population.materials and methods : irreversible hydrocolloid impressions were made of the maxillary teeth of 100 dentate male and female subjects to obtain study casts . a standardized procedure was adopted to photograph the maxillary dental arches and the maxillary central incisors on the study casts taken from each subject . the outline form of tooth , arch , and palatal form were determined using a standardized method . the average of six prosthodontist 's evaluation was considered who classified the outline tracings visually . the statistical analysis was performed using chi - square and results tabulated.results:the predominant tooth is combination form in males and ovoid form in females , the predominant arch is ovoid form in males and square form in females and the predominant palatal form are both u and v shaped in males and u - shaped in females.conclusion:except for the tooth form there was a significant difference with arch and palatal form among males and females of the population group studied . the determined tooth , arch and palatal forms are useful in selection and arrangement of artificial teeth among saudi edentulous population group . generalizing from the study is questionable as the sample size is small . further studies should be conducted in a larger sample to confirm the study results

bronchogenic cysts are not uncommon in either children or adults . in children , they comprise approximately 6% of all mediastinal masses . their presentation can range from an asymptomatic incidental finding to sudden respiratory distress . video - assisted thoracoscopy was utilized to remove a bronchogenic cyst that was densely adherent to the adjacent esophagus in a child . the chest tube was removed on postoperative day 1 , and the patient was discharged on postoperative day 2 . an esophagogram obtained 2 weeks after surgery was normal , and the patient 's preoperative symptoms had not returned . bronchogenic cysts should be considered in the differential diagnoses for mediastinal masses at any age . given their benign nature . they may become symptomatic due to esophageal compression as they increase in size or from development of infection . we report the case of a 9-year - old female with a symptomatic bronchogenic cyst , undiagnosed since the age of 2 years , who underwent successful thoracoscopic excision . a 9-year - old girl was first seen at the age of 2 years for cough and fever in the emergency room . a chest x - ray was obtained at that time , which was interpreted as normal . nonetheless , the patient was diagnosed with pneumonia , given a prescription for antibiotics , and released . subsequent to this , she presented several more times each year with similar complaints and with identical posteroanterior ( pa ) chest x - ray findings , resulting in several hospital admissions . her examination revealed no abnormalities , and her laboratory work was within normal limits at the time of her presentation to the pediatric surgery service . repeat chest x - rays were obtained ( figure 1 ) as well as a computed tomography ( ct ) scan of the chest ( figure 2 ) . it revealed a well - circumscribed cyst in the right chest measuring approximately 3x4 cm directly adjacent to the esophagus in the midthoracic region . it was unilocular and homogenous and did not appear to communicate with the esophagus or any neural structures . given these findings , the diagnosis of either an esophageal duplication cyst or bronchogenic cyst was entertained . a thoracoscopic approach was utilized to evaluate and remove the mass ( figure 3 ) . the medial aspect of the cyst was intimately involved with the muscular wall of the esophagus for several centimeters . a harmonic scalpel was used to separate the cyst , which was filled with a white mucoid material , from the esophagus . a small portion of the cyst wall was left in place to avoid perforation of the esophagus . the chest tube drainage was negligible , and it was removed on postoperative day one . she was seen at follow - up 2 weeks after surgery where a normal barium esophagogram ( figure 4 ) was obtained , and her preoperative symptoms were completely resolved . bronchogenic cysts are embryological remnants that are isolated from the normal development of the foregut . on rare occasions they may be found incidentally on a radiographic study or once symptoms are produced as a result of compression or infection . if communication with the airways occurs , an air - fluid level is usually present . histologically , they are lined with ciliated columnar epithelium and can contain cartilage and bronchial glands . accepted treatment is excision because of concern about continued growth and subsequent compression of surrounding structures , the risk of infection , and the unlikely but reported possibility of malignant degeneration . bronchogenic cysts comprise approximately 6% of all mediastinal masses in children , while foregut cysts as a group account for 15% . traditionally , open thoracotomy has been the method by which these cysts have been removed . even with increasingly sophisticated radiographic and percutaneous techniques , an exact diagnosis is often uncertain , and the unequivocal diagnosis must be made surgically . thoracoscopy offers both a minimally invasive diagnostic modality and also a highly successful method of definitive therapy for patients with bronchogenic cysts . although many case reports exist regarding bronchogenic cysts and their minimally invasive treatments , reports of precious few series have been published regarding their thoracoscopic excision . in 1993 , hazelrigg published a series of seven bronchogenic cysts removed thoracoscopically with favorable results . martinod et al reported a series of 20 cases of bronchogenic cysts in adults , of which they successfully removed 13 thoracoscopically . their reasons for conversion were bleeding in 2 cases and dense adhesions to surrounding vital structures in 5 . in 5 cases , thoracoscopy was performed on 22 children , 15 of which were found to have bronchogeni ccysts . of these merry et al reported in their series of 8 foregut duplications 1 recurrence with incomplete excision 1 year after surgery . two other reports of recurrence have been reported , , but so have several reporting successful obliteration of the mucosal lining with good results . reported complications in these articles include the following : bronchial / tracheal laceration ( both repaired endoscopically ) , , recurrence , esophageal injury , pneumothorax , , vascular injury . bronchogenic cysts are not uncommon and , as this case illustrates , can be easily misdiagnosed . subtle findings , as on this patient 's chest x - ray taken at 2 years of age , are overlooked if one fails to consider cystic mediastinal masses in the differential diagnosis . we assert that thoracoscopy is a safe and effective method to deal with bronchogenic cysts and involves considerably less morbidity than thoracotomy does . as experience with thoracoscopy improves , so too will its acceptance as a superior alternative to thoracotomy in most cases of bronchogenic cysts .

background : bronchogenic cysts are not uncommon in either children or adults . in children , they comprise approximately 6% of all mediastinal masses . their presentation can range from an asymptomatic incidental finding to sudden respiratory distress.case report : video - assisted thoracoscopy was utilized to remove a bronchogenic cyst that was densely adherent to the adjacent esophagus in a child . this was accomplished with a harmonic scalpel . the chest tube was removed on postoperative day 1 , and the patient was discharged on postoperative day 2 . an esophagogram obtained 2 weeks after surgery was normal , and the patient 's preoperative symptoms had not returned.conclusions:bronchogenic cysts should be considered in the differential diagnoses for mediastinal masses at any age . given their benign nature , thoracoscopy offers an excellent alternative to open thoracotomy for their removal .

early recognition of rupture - prone atherosclerotic lesions in patients with high - graded carotid artery stenosis is an important clinical issue to prevent ischemic stroke [ 15 ] . various pathophysiological mechanisms are responsible for the plaque progression and vulnerability such as degradation of extracellular matrix components especially by matrix metalloproteinases ( mmps ) , intensified inflammatory reaction , and neovascularisation [ 3 , 57 ] . thus , mmps and inflammatory factors might also serve as possible markers for patients with unstable high - graded carotid artery stenosis [ 2 , 816 ] . however , the data that have been achieved up to date are not consistent . some studies investigated patients with symptomatic versus asymptomatic carotid stenosis or patients with or without emboli [ 12 , 1417 ] . furthermore , only very few investigations evaluated the usefulness of multiple biomarkers to predict rupture - prone atherosclerotic lesions [ 2 , 17 , 20 , 21 ] . the aim of this work was the comparison of results of multiple analyses of various relevant biomarkers in patients with stable versus unstable carotid plaques and in individuals with or without neurological symptoms to evaluate whether multiple - score evaluation is superior to the analysis of single factors . the retrospective study consisted of 110 consecutive patients with high - grade carotid artery stenosis > 70% ( determined by ultrasound ) , intended for carotid endarterectomy ( cea ) . all patients underwent a detailed neurological examination by a neurologist , and the carotid plaques were analysed by means of histology to divide the study subjects into four groups : ( 1 ) asymptomatic patients with stable plaques ( n = 25 ) ; ( 2 ) asymptomatic patients with unstable plaques ( n = 36 ) ; ( 3 ) symptomatic patients with stable plaques ( n = 13 ) ; ( 4 ) symptomatic patients with unstable plaques ( n = 36 ) . the study was performed according to the guidelines of the world medical association declaration of helsinki . the excised carotid plaques were fixed in formalin , separated into segments of 3 - 4 mm , and embedded in paraffin . from each segment sections of 2 - 3 m were prepared and routinely stained with hematoxylin / eosin ( he ) and elastin van gieson ( evg ) to assess the morphological and histological features of each plaque . stained specimens were analysed by light microscopy from two independent and experienced investigators blinded for the study groups . in accordance with our own expertise and the study of rothwell and redgrave [ 18 , 19 ] , appropriate selection into stable or unstable plaques was performed . primary antibodies against following antigens were used : cd68 ( macrophages / monocytes ; dako ) , cd45 ( inflammatory infiltrates ; novocastra , uk ) , smooth muscle cell actin ( dako , hamburg , germany ) , and factor viii ( endothelial cells ; dako ) . mmps and timps were quantified in serum samples using elisa assays from r&d system ( quantikine human mmps and timps kit ; wiesbaden - nordenstadt , germany ) according to the manufacture 's protocols . the colour development was determined by multiplate reader mithras lb940 ( berthold technologies , bad herrenalb , germany ) at 450 nm with correction at 570 nm . inflammatory markers were analysed using cytometric bead array ( bd biosciences , san jose , ca , usa ) . fibrinogen activity was determined by the clauss method ( dade behring , schwalbach , germany ) . the hscrp ( high sensitivity crp ) was determined by elisa assay ( life diagnostics ; west chester , pa , usa . additional clinical blood parameters were measured in laboratories of our clinical chemistry . one - way anova test was applied for comparison between the groups . correlations between the single factors were quantified by spearman 's rank correlation coefficient . receiver operating characteristics ( roc ) analysis was applied to evaluate the optimal positive and negative predictive value of each prognostic marker and their combinations . delong and clarke - pearson approach was used to compare roc curves to provide the best statistical evidence . all statistical comparisons were performed two sided in sense of an exploratory data analysis using p < 0.05 , p < 0.01 , and p < 0.001 as level of significance . all groups were well matched , without any significant differences with regard to patient epidemiology , associated diseases , or medication . the average age of the study population was 69 years ( range 59 to 79 ) . the majority of patients had hypertension ( > 87% ) and about one - third suffered under accompanying coronary heart disease . all patients with the exception of one individual received asa or clopidogrel , and more than half of the study subjects were on statins . significant differences between the groups were observed only for mmp-1 , -7 , -9 , and timp-1 . ( p = 0.047 , 0.005 , 0.028 , and 0.044 , resp . ) . tendency was observed also for mmp-8 ; the difference was , however , not statistically significant . in many cases , increased level of various inflammatory factors was found in the group of symptomatic patients with unstable carotid plaques . however , again the values were not statistically different . regarding causal relationships between the individual factors analysed in our study , we performed correlation analysis between mmps , timps , and all the inflammatory factors tested in blood of the patient cohort ( table 3 ) . most correlations were found between individual mmps and timps : the levels of mmp-1 correlated significantly with mmp-7 and timp-1 ( p < 0.001 and p < 0.05 , resp . ) , mmp-2 with timp-2 ( p < 0.001 ) , mm-3 with mmp-7 ( p < 0.05 ) , mmp-7 with timp-1 ( p < 0.001 ) , mmp-8 with mmp-9 and timp-1 ( p < 0.001 and p < 0.05 , resp . ) , and timp-1 with timp-2 ( p < 0.001 ) . furthermore , significant correlations were observed between some inflammatory factors and mmps : il-1 correlated with mmp-9 ( p < 0.05 ) , il-6 with mmp-7 and -8 ( p < 0.001 and p < 0.01 , resp . ) , and il-12 with mmp-2 ( p < 0.01 ) ; the amount of leukocytes was related to mmp-8 and -9 ( p < 0.01 and p < 0.001 , resp . ) and fibrinogen to mmp-7 , -8 , and -9 ( p < 0.05 and p < 0.001 , resp . ) . to evaluate whether the individual factors and their appropriate combination in blood of the study patients can be associated with carotid plaque instability or neurological symptoms , roc curve was designed accordingly . furthermore , multiple analysis was performed to assess the validity of biomarkers to further improve the predictability . in accordance with the above - described analyses between the study groups , only factors with significant differences were involved in the roc curve analysis : mmp-1 , -7 , -9 , and timp-1 . the area under curve ( auc ) and the predictive values are summarised in table 4 . the cutoffs were selected by using delong and clarke - pearson approach to provide the best statistical evidence . all patients with biomarker values higher than the ascertained cutoff points were considered as individuals with neurological symptoms or as patients with unstable plaques . furthermore , multiple roc analysis was performed for all possible combinations of the above - described biomarkers . regarding neurological symptoms , the positive predictive value ( ppv ) was quite low with around 50% for the single factors and increased over 60% by their appropriate combination . in contrast , the negative predictive value ( npv ) was significantly higher with curtly under 70% for the individual biomarkers and achieving up to 80% for the factor grouping . with regard to the maximal ppv , combination of mmp-7 and timp-1 achieved the highest value of 65.1% . on the contrary to the neurological symptoms , ppv for patients with vulnerable plaques was markedly higher with 7679% for the single factor analysis . their grouping led to an increase for up to 86.4% using combined analysis with mmp-1 , -7 , and -9 . biomarkers for prevention of stroke are promising diagnostic tool in medical praxis . due to the heterogeneity of the atherosclerotic lesions , however , single marker will never be sufficient for reliable prediction of patients at increased risk of stroke . furthermore , the values of the biomarkers and the cutoff value at risk can markedly alternate between the individual patients . so far only few studies have evaluated the usefulness of multiple biomarkers and their overall association with neurological symptoms or plaque vulnerability , especially concerning unstable carotid lesions . from the various mmps , their inhibitors , and the inflammatory factors analysed in this study , serum levels of mmp-1 , -7 , -9 , and timp-1 all these factors were already described being involved in the degradation of extracellular matrix [ 5 , 7 , 10 , 11 , 24 , 25 ] . thus , they could reliably reflect unstable carotid plaques in patients at risk of stroke . interestingly , different biomarkers can be related either to neurological symptoms or to plaque instability [ 2 , 17 ] . this is an important issue , because many researchers often equate neurological symptoms with plaque vulnerability . only 1520% of all ischemic strokes account for atherosclerotic carotid stenosis [ 5 , 26 ] . therefore , prevention of stroke on the basis of biomarker evaluation in the blood of the concerned patients should be related to plaque vulnerability . this is the reason for the discrepancy between the individual biomarker in our study related either to neurological symptoms or carotid plaque stability . from our point of view , the markers that show significant differences between patients with stable versus unstable plaques are of higher value compared to biomarkers corresponding with symptoms . this was also the reason why we have combined neurological symptoms and plaque vulnerability together . in contrast , mmp-9 seemed to be related mainly to the neurological symptoms ( table 2 ) . regarding inflammatory factors , increased levels of tnf- and il-6 were associated with plaque instability , il-10 only in the group of symptomatic patients with unstable plaques . high sensitive crp appeared to be more related to neurological symptoms than to plaque instability and fibrinogen for both . again , these data confirm the pathophysiological differences between patient symptomatic and plaque vulnerability [ 2 , 17 ] . nevertheless , our data demonstrated that whether the symptoms are caused by unstable carotid plaques or atherosclerotic changes in other vessels can also have common features that can be reflected in the blood of patients at risk of stroke . this assumption was further confirmed by the correlation analysis of the individual factors ( table 3 ) . interestingly , independent of neurological symptom or plaque instability , no statistically significant differences between patients with stable and unstable lesions were observed for mmp-2 as described in some former studies [ 1315 ] . the reason for these discrepancies is that we have characterised the plaques in accordance with redgrave and rothwell [ 18 , 19 ] , looking effectively for the true unstable plaques . in contrast , the early studies graded the plaques according to aha classification , assuming atherosclerotic lesion type v as stable , type vi as unstable . but patients with carotid lesions of type vi ( plaques with thrombotic deposits and haemorrhage ) with thick fibrous cap can still be considered as stable . and plaques of type v with thin fibrous cup under 200 m over a large necrotic core can be considered as unstable . regarding inflammatory factors , no significant differences were observed between the groups , even if some tendencies have been observed , especially for tnf- , il-6 , il-10 , crp , and fibrinogen . however , it is to consider that our patients had already an advanced stage of carotid artery stenosis > 70% and almost all of them were hypertensive . so , the level of many of the inflammatory factors in blood of our patients was already increased , compared to healthy individuals . so , inflammatory factors may correlate with advanced carotid stenosis , are , however , not specific enough to detect vulnerable plaques [ 25 , 27 ] . the main goal of the study was to evaluate whether combination of relevant biomarkers of advanced carotid lesions might be better associated with neurological symptoms or plaque vulnerability compared with single biomarkers . interestingly , high positive prediction could be associated with plaque vulnerability for up to 86% compared to only 65% regarding patient symptomatic . in contrast , negative prediction was high for the clinical symptoms with up to 80% , but the factor grouping did not significantly improve the npv for patients with unstable plaques , which was in the most cases between 50 and 60% , considering patients incorrectly as individuals at risk . so , if the level of one of them is increased , the others are increased as well ( see also table 3 ) . the combination of such biomarkers , however , does not necessarily lead to an increased predictivity over the analysis of single factors . to establish a set of relevant biomarkers for more reliable diagnosis of stroke , independent markers are necessary to improve the overall sensitivity and especially specificity . still , our data demonstrate that the use of more than one biomarker better correlates with the clinical findings and seems therefore to be superior to the analysis of single factors . these results further confirm our assumption that multivariate analyses of relevant biomarkers are necessary to reduce the risk of inaccurate diagnosis . in summary , we evaluated various predictive biomarkers and their combinations in patients with advanced carotid stenosis in order to improve the concordance with clinical findings such as neurological symptoms or / and unstable plaques . further experiments , especially large prospective clinical studies , are necessary to evaluate the relevance of such biomarkers . in addition , the proper cutoff values have to be accurately interpreted and carefully reevaluated before they can be used in clinical praxis for , for example , reliable prevention of patients at increased risk of stroke .

early recognition of vulnerable patients is an important issue for stroke prevention . in our study , a multiscore analysis of various biomarkers was performed to evaluate its superiority over the analysis of single factors . study subjects ( n = 110 ) were divided into four groups : asymptomatic patients with stable ( n = 25 ) and unstable ( n = 36 ) plaques and symptomatic patients with stable ( n = 13 ) and unstable ( n = 36 ) plaques . serum levels of mmp-1 , -2 , -3 , -7 , -8 , -9 , timp-1 , -2 , tnf- , il-1b , and il-6 , -8 , -10 , -12 were measured . multi - score analysis was performed using multiple receiver operating characteristics ( roc ) and determination of appropriate cutoff values . significant differences between the groups were observed for mmp-1 , -7 , -9 and timp-1 in serum of the study subjects ( p < 0.05 ) . multiple biomarker analysis led to a significant increase in the auc ( area under curve ) . in case of plaque instability , positive predictive value ( ppv ) for up to 86.4% could be correctly associated with vulnerable plaques . thus , multiscore analysis might be preferable than the use of single biomarkers .

knowledge of the anatomical variations of the axillary region has become more relevant with increasing surgeries of this region for breast cancer , reconstruction procedures and axillary by - pass . lager 's arch or the axillary arch ( aa ) is the best - known variant structure in the axilla . it is a muscular or fibromuscular slip of varying dimensions , extending from the latissimus dorsi ( ld ) muscle about the middle of the posterior axillary fold , and crosses over the neurovascular structures , to join the under surface of the tendon of the pectoralis major , the coracobrachialis , or the fascia over the bicepsbrachii [ 1 , 2 ] . a 60-year - old female presented to our breast clinic with a left breast lump sized 3 2.5 cm incidentally felt since 3 months . it was gradually increasing in size and was not associated with any other breast complaints . she was evaluated with mammography that suggested a birads 3 lesion at 12 oclock position . subsequently , her metastatic work - up included abdominal pelvic ultrasound , chest computed tomography and bone scan . intra - operatively , during the axillary lymph node dissection , we encountered an unusual muscle slip crossing the axilla from the ld muscle to the posterior surface of the pectoralis major muscle anterior to the axillary vein . all neurovascular structures and lymphoid tissue were lying posterior to this abnormal muscle ( fig . 1 ) . figure 1:aa muscle extending from ld muscle to under surface of pectoralis major tendon in the left axilla crossing over axillary neurovascular structures ( in view ) . aa , axillary arch ; pm , pectoralis major ; ld , latissimus dorsi muscle ; av , axillary vein ; tnb , thoracodorsal neurovascular bundle ; ltn , long thoracic nerve . aa muscle extending from ld muscle to under surface of pectoralis major tendon in the left axilla crossing over axillary neurovascular structures ( in view ) . aa , axillary arch ; pm , pectoralis major ; ld , latissimus dorsi muscle ; av , axillary vein ; tnb , thoracodorsal neurovascular bundle ; ltn , long thoracic nerve . the lymph nodes lateral and beneath the arch were successfully dissected , and the arch itself was left undisturbed . the procedure was uneventful , and the patient had a good post - operative recovery . on follow - up , 21 months after surgery , the patient was alive and free of known disease . however , it was karl langer in 1846 who gave a more accurate description of this variant , so thereafter , it was named after him [ 24 ] . throughout the literature , several terms have been used to describe the muscular variant running from the ld muscle towards the pectoralis major muscle : aa muscle , axillopectoral muscle and also their translations in different languages . in the following text , the anatomical description of the aa is variable among authors . according to testu 's classification ( 1884 ) , the complete aa extended between the ld and the tendon of the pectoralis major near its insertion on the humerus ; the incomplete one extended from the ld to the axillary fascia , biceps brachii muscle , coracobrachialis muscle , the distal end of the bicipital groove and the inferior edge of pectoralis minor muscle or coracoid process . the case we encountered was of unilateral complete aa . according to many anatomic texts , however , it has been recognized in only 0.25% during axillary surgical procedures [ 1 , 2 , 4 , 5 ] . the difference in surgical and anatomical incidence reflects a failure of reporting or identification during surgery . also , this discrepancy may be attributed to the specific aim of cadaveric studies to identify such anatomic anomalies . this should be kept in mind as it can be confused with axillary lymphadenopathy or soft tissue tumour [ 1 , 3 ] . aa can act as entrapment site for the neurovascular bundle during some arm movements causing circulatory deficiency , chronic pain and paraesthesia . simple division of the arch is curative in such cases [ 2 , 5 ] . jelev , through his extensive work , introduced a new definition of clinical aa as a variant muscular structure in the axilla that is a possible entrapment site for the nerves and vessels . , the existence of a superficial or deep aa could be suspected according to the vessels or nerves mostly affected . it can positively correlate its presence with neurovascular entrapment symptoms . also , it can assess its anatomic relations [ 1 , 5 ] . the surgical significance of the aa is 2-fold : ( i ) it may hide some axillary nodes , and ( ii ) it may mislead the dissection into a supra axillary plane . a group of lateral axillary nodes may be concealed under the aa while crossing over the axillary vein . missing these nodes during axillary node dissection imposes a risk for local recurrence in patients with breast cancer and melanoma . this also can lead to inaccurate staging , which in turn could negatively affect adjuvant and systemic therapy decisions for breast cancer . this may lead the surgeon to dissect in a plane above the axillary vein increasing the risk of injury to the axillary artery and brachial plexus . during sentinel node biopsy , the aa can pose difficulty as it stretches in the hyper abducted position shifting the nodes higher . in order to clearly identify , the anatomic landmarks the arch can be divided at the level of the axillary vein . furthermore , some authors suggest division of the arch in all cases to prevent possible post - operative axillary vein compression and associated lymphoedema [ 3 , 4 ] . in our case , there was no added morbidity related to dissection of nodes beneath and lateral to the arch . the presence of the aa may precipitate lymphoedema in cases where ld myocutaneous flap is used for breast reconstruction . for this reason , the aa should be divided if there is a possibility of a ld flap being required in the future . as in our case , most reported clinical cases describing the aa have been identified during axillary surgical procedures [ 2 , 4 ] . it can cause confusion during routine axillary surgery for breast cancer , which can both affect procedure safety and misguide further treatment decisions [ 3 , 4 ] .

langer 's arch is the best - known anatomic variant of definite surgical implication in the region of the axilla . this rare anomaly is a muscular slip extending from the latissimus dorsi ( ld ) muscle to the tendons , muscles or fasciae around the superior part of the humerus . in this report , we present a rare case of left axillary arch . during modified radical mastectomy for breast cancer , we encountered an abnormal muscle slip crossing the axilla from the ld muscle to the posterior surface of the pectoralis major muscle anterior to the neurovascular structures . preoperative knowledge is essential to identify such unusual anomaly and avoid potential complications both intra- and postoperatively .

a 63-year - old woman presented with sudden onset vertigo and was diagnosed with an acute infarction in the left cerebellum on october 17 , 2015 . on the brain magnetic resonance imaging ( mri ) , an acute infarction was observed in the territory of the left superior cerebellar artery ( sca ) ( fig . magnetic resonance angiography showed a mild irregularity in both proximal vas and an occlusion in the left sca ( fig . the sca was completely recanalized , and there was no definite abnormality in both vas . incidentally , we observed an unopacified streaming at the level of c5 during the selective catheter angiography of the left va originated from the left subclavian artery ( fig . the medial limb of the left va arising from the aortic arch could be found on the selective catheter angiography , which was not observed on the mra . the dominant , lateral limb of the left va was originated from the left subclavian artery ( fig . 2a , b ) and the small , medial limb was originated directly from the aortic arch between the left common carotid artery and the left subclavian artery ( fig . a right - to - left shunt was suspected on the transcranial doppler using an agitated saline solution with blood . a pulmonary arteriovenous malformation ( avm ) in the right lung was detected by transesophageal echocardiography and chest computed tomography . with an elevated level of d - dimer with 421 ng / ml , the pulmonary avm was suspected as a source of embolus causing an acute cerebellar infarction . the left va arising from the aortic arch is the third most common pattern of aortic arch branching with an incidence of 2.4 - 5.8% . however , the duplicated origin of the va is quite rare and the majority cases were found incidentally . we reported a patient with duplicated origin of the left va , and it could be suspected when an unopacified streaming was observed during the selective catheter angiography of the dominant va limb arising from left subclavian artery . it could be potentially misdiagnosed as an arterial dissection , if the possibility of duplicated origin of the va was not considered . in a previous literature , 26 cases with duplicated origin of the va were reported before 1998 and have been summarized in detail . since 1998 , we found 15 additional cases with duplicated origin of the va , including three patients with bilateral duplicated origin of vas ( table 1 ) . overall , 24 patients had a duplicated origin of the left va , including our case , and 21 patients had a duplicated origin of the right va . among them , three patients had a bilateral duplicated origin of vas . the medial limb directly from the aorta and the lateral limb from the subclavian artery was the most common pattern of the duplicated left va ( 21 of 24 , 87.5% ) . two patients had origins of both limbs in the subclavian arteries . and only one patient had origins of both limbs in the aortic arch . contrast to the left side , the duplicated limbs arising from the ipsilateral subclavian artery was the most common pattern in the right side ( 18 of 21 , 85.7% ) . and there was no available data about the origins of the duplicated va in one patient . embryologically , the va is formed by the longitudinal anastomoses between the cervical intersegmental arteries . and the connections of the intersegmental arteries to the dorsal aorta eventually regress , except the seventh intersegmental artery , which develops into the proximal subclavian artery containing an origin of the va . the left va originated from the left subclavian artery and enters the sixth transverse foramen . the variation of an aortic origin of the left va results from degeneration of the connection with the seventh intersegmental artery and a persistence of a higher intersegmental artery . in this situation , the va commonly enters the f ifth transverse foramen . likewise , persistence of the left fourth or fifth cervical intersegmental arteries and the normal origin from the seventh intersegmental artery result in a duplicated origin of the left va ( fig . the left fourth or fifth intersegmental arteries originate from the aorta between the left common carotid artery and left subclavian artery . in contrast to the left side , duplicated origins of the right va are usually arising from the right subclavian or brachiocephalic artery when the fourth or fifth cervical intersegmental artery is persistent . first , the right seventh cervical intersegmental artery is originated from the descending aorta distal to the left subclavian artery . second , the right fourth or fifth cervical intersegmental artery is originated from the ascending aorta , and the right subclavian artery is originated from the descending aorta distal to the left subclavian artery . the majority of previous cases and our case had no clinical implication from the duplicated origin of the va , although it has been suggested that the duplicated origin of the va might be a predisposing factor for certain cerebrovascular pathologies , such as aneurysm or dissection . to take hypothetical example , it could be the other route for an interventional procedure for the posterior circulation or the potential collateral channel in case of a proximal , extracranial va occlusion . for all that the duplicated origin of the va may have in the clinical implication mentioned above , there should be more evidence supporting the hypothesis that the rare variation of the va could be related to a pathologic condition or therapeutic intervention . in conclusion , the duplicated origin of the va is rare , but then it is a good example to explain the embryological development of the va . while it could be a false negative on the contrast enhanced mra , we could incidentally find the duplicated origin of the left va on selective catheter angiography by recognizing the unopacifed streaming in the original path of the va .

the duplicated origin of vertebral artery ( va ) is a very rare condition . it could be easily misdiagnosed as an arterial dissection on selective catheter angiography , especially in a patient with acute cerebellar infarction of unknown etiology . we report a patient with an acute cerebellar infarction and duplicated origin of the left va , which was found during the selective catheter angiography .

the potential of comparative effectiveness research ( cer ) for dealing with practical clinical questions , enhancing the quality and effectiveness of care , and personalizing evidence - based care , is clear.1 yet cer strains the current clinical research paradigm because of its emphasis on assessing effectiveness in typical care delivery settings , its requirement for very large study populations to study effectiveness heterogeneity , and , often , its need for treatments to be allocated by randomization . in july 2012 , the patient - centered outcomes research institute ( pcori ) convened a national multi - stakeholder workshop to advance the use of electronic health data in cer.2 building on research networks that include among others , the hmo research network , the agency for healthcare research and quality ( ahrq ) american recovery and reinvestment act ( arra ) investments in data networks , the us centers for disease prevention and control ( cdc ) vaccine safety data link , the food and drug administration 's ( fda ) mini - sentinel , the national institutes of health ( nih ) health care systems research collaboratory , two components of a national research infrastructure emerged.38 these comprise clinical data research networks ( cdrns ) based on the electronic health records and other electronic sources of very large populations receiving healthcare within integrated or networked delivery systems9 and patient - powered research networks ( pprns ) built by communities of motivated patients , forming partnerships with researchers.10 cdrn and pprn brief communications included in this special focus issue provide further information about these networks . in december 2013 , pcori 's board of governors funded 11 cdrns and 18 pprns for a period of 18 months starting in march 2014 that together form pcornet ( http://www.pcornet.org ) . each cdrn is committed to building a large patient cohort with comprehensive , longitudinal electronic clinical data ; developing policies for data standardization , shared governance , efficient use of clinical information for multicenter studies , stringent attention to data security and patient privacy , and robust , scalable centralized research support tools ; and building the capacity to participate successfully in multi - network randomized trials and observational studies . each cdrn is a collaboration of health systems that include among others academic health centers , community hospitals , health plans , inpatient and outpatient hospitals and providers , federally qualified health centers , veterans administration clinics , pediatric hospitals and providers , integrated delivery systems , private electronic health record companies , and a regional health information exchange ( table 1 ) . clinical data research networks each pprn consists of patients , caregivers , or families , who are linked by the experience of a shared condition ( table 2 ) . an important commitment of these patient - based networks is to collect and curate data from at least 80% of their membership . the pprns are also expected to expand the number of patients in their network ; to collect standardized patient data ; and , when necessary , for the purposes of research , engage patients to participate in interventional research and in building , using , and governing their networks . the organizational set - up of pprns is diverse , as exemplified by the number of different partnership models that link patient foundations and associations with academic research centers . the cdrns and pprns are geographically diverse , with patients in 50 states ( figure 1 ) . patient powered research networks map of clinical data research networks ( cdrn ) and patient - powered research networks ( pprn ) across the usa . a coordinating center co - led by the harvard pilgrim health care institute and duke university ( contract awarded in september 2013 ) provides technical and logistical expertise and assistance to awardees . it has established 11 task forces ( figure 2 ) , whose members are nominated from the cdrns and pprns and whose role is to develop policies , operations , and products to support the development of pcornet . a steering committee , subject to the oversight of pcori , guides members of pcornet and advises pcori leadership ( figure 2 ) . final approval of all policies , activities , and recommendations resides with the pcori leadership . ahrq , agency for healthcare research and quality ; aspe , assistant secretary for planning and evaluation ; cdc , us centers for disease prevention and control ; cms , centers for medicare and medicaid services ; fda , food and drug administration ; nih , national institutes of health ; onc , office of the national coordinator for health information technology ; pcori , patient - centered outcomes research institute . pcornet is being developed as a distributed research network ( drn ) that facilitates multi - site , observational and interventional research across the cdrns , pprns , and other interested contributors , while minimizing the transfer of individual - level clinical data outside of the system where care is received . pcornet 's unique vision is to create a network that supports the cdrn and pprn internal network development while creating a mechanism to facilitate research across these networks . advantages of conducting research across multiple networks of pcornet comprise greater sample size and power , the ability to study effects of practice pattern and treatment variation , the inclusion of diverse populations , and the possibility of supporting analyses that assess heterogeneity of treatment effect . the distributed network will enable research studies to be conducted , while allowing each participating organization to maintain physical and operational control over their data . this structure lowers institutional barriers to participation and ensures availability of local experts who can interpret the data.11 12 the data standards , security and network infrastructure ( dssni ) task force will identify minimal data standards and technical specifications for data standardization across cdrns and pprns and develop an approach to cross - network querying that meets the security , patient privacy , institutional confidentiality , and governance needs of the network participants.13 the distributed querying approach allows simple and complex analyses to be executed behind institutional firewalls , thereby eliminating or minimizing the release of protected health information . instead , only the minimum information needed to answer a specific question is transferred to the person making a request . increasingly , even complex multi - site analyses can be accomplished without transfer of private health information by use of privacy preserving regression techniques.14 15 as part of their pcornet participation , each cdrn will develop an analyzable research dataset ( to be specified by the dssni task force ) that supports complex distributed analyses . after 18 months , this dataset should contain data on one million patients and the cdrn will be able to regularly complete queries against the dataset using the secure pcornet drn tools . an example of the type of observational studies that might be supported by the drn is a comparison of the outcomes of ischemic and hemorrhagic stroke in adults with atrial fibrillation who are new users of dabigatran or warfarin.16 the pcornet drn tools will be developed by input from the relevant task forces , including dssni , governance , and data privacy during the first 18-month phase of funding ( starting march 2014 ) . the dssni task force will develop a pcornet common data model ( cdm ) to support the development of analyzable research datasets that will permit efficient distributed analyses . the pprns aim in 18 months to have the ability to build a standardized clinical database with relevant clinical and patient - reported outcomes data from at least 80% of their membership . overall , implementation of the pcornet drn networking and querying capabilities will prioritize rapid development , testing , use , and feedback learning cycles . this process will enable experimentation in networking approaches , demonstrate approaches to secure network operations , and identify potential barriers as early as possible . over the 18-month funding phase , each cdrn and pprn will develop effective patient - engagement strategies at the level of their networks . these strategies will involve ensuring that patients have a central role in collecting data for the generation of new knowledge for patients with their condition , as well as in participating in the governance of the network , prioritizing research questions , and disseminating results.10 at the cdrn level , patient engagement strategies require developing approaches to inform patients who are members of the systems of the existence and function of the research network , to involve patients in generating research questions , and in including patients in the governance associated with the development and uses of the network.9 rapidly building a new national resource to facilitate large - scale , patient - centered cer will face a number of technical , regulatory , and organizational challenges . technical challenges , first , include successfully completing the capture of relevant longitudinal clinical data , a requirement for all cer studies . since most electronic health record systems typically do not have information on care provided outside their health system , both cdrns and pprns will need to explore approaches to dealing with this problem.17 second , in order to achieve multi - institutional querying , pcornet will have to deal with data harmonization.18 this will require understanding the context in which the data were collected , the various clinical and other terminologies in use , and changes in local systems and national standards ( such as those associated with the centers for medicare and medicaid 's meaningful use regulation ) that affect the data . this should be done without requiring a change in the way the routine medical care data are collected , and will require data harmonization.19 20 pcornet has chosen to develop a cdm , derived from the mini - sentinel cdm to enable efficient cross - networking querying.21 third , the collection , harmonization , and use of a wide range of potential patient - reported data ( eg , personal and family medical histories , use of remote monitoring devices , etc ) for research is a nascent field,22 yet promises to empower patients to provide data that more fully describe their experience of , and preferences for , the treatment and management of their condition . in the absence of a standardized ontology or lexicon for a large number of these data elements , the ability to routinely include this information in analyzable research datasets will be explored in this first phase of pcornet 's development but will probably occur fully in later phases . in addition to technical challenges , pcornet will need to examine ethical and regulatory oversight . many patients , advocates , and researchers describe the research oversight system as cumbersome , inefficient , and expensive.2325 pcornet will need to deal with problems associated with the design of appropriate clinical studies , informing prospective participants , and obtaining permissions in a manner that protects human rights while supporting the acknowledged need for more research to provide patients and clinical decision - makers with more reliable evidence.26 areas of interest that pcornet will explore through its task forces include central institutional review boards or internet - facilitated shared review systems , and , centralized support for enrolling subjects and obtaining their consent . because of the scale and complexity of the types of research envisaged , pcornet will be challenged to develop streamlined approaches to the structure and function of the network and its projects while maintaining sound ethics and regulatory compliance . pcornet will be faced with the organizational challenges associated with the rapid development of a national resource with a heterogeneous group of cdrns and pprns of varying size , populations served , health systems included and many other characteristics . although this diversity among awardees was both predictable and desirable , one area in which the diversity of networks was quickly apparent was the divergent approaches used for data management . nevertheless , each cdrn and pprn will be challenged with balancing the demands of their local networks , research cultures , and areas of particular expertise with the requirements of participating in a national research resource . this will require them to agree rapidly on a common approach to data interoperability and to the conduct of joint analyses . pcornet 's success and long - term sustainability will also depend on communicating with health system leaders and providing them with evidence of the benefits of conducting high - quality , efficient research as part of the routine delivery of care . securing the commitment of delivery systems leaders , health system administrators , and clinicians will require considerable strategy and effort by all pcornet stakeholders . finally , and importantly , pcornet is committed to supporting patient engagement across the networks and will need to deal with the challenges of successfully supporting a variety of governance structures that fully ensure that patients are involved in setting policies for pcornet and for their own networks , determining strategic direction , and prioritizing research questions.27 the pcornet drn will be open to external data and research affiliates willing to participate in research studies alongside the pcori - funded cdrns and pprns . of particular note , pcornet 's distributed networking platform is shared by the fda mini - sentinel program , the nih health care systems research collaboratory and other networks such as the hmo research network.3 6 7 any organization that is part of these networks can make itself visible to the others and choose to receive queries from any of them . pcori 's vision is for the pcornet drn to be available for use by researchers not directly affiliated with pcornet cdrns and pprns through collaborative arrangements . the proposed governance models and mechanisms for these types of collaboration will be developed during the initial 18-month funding phase , which started in march 2014 . the first phase of building pcornet will span 18 months . at the end of this time , we hope that a functional research network that can support both observational and interventional research will have emerged . we also expect a new model for efficiency and affordability in clinical research , made possible both by investments in , and use of , this evolving data infrastructure , and the involvement of host healthcare systems , clinicians , and patients together with researchers . although pcornet will need to continue to grow and improve its data resources and capabilities , a measure of success will be the willingness of external research funders , both public and private , to fund research studies using pcornet .

the patient - centered outcomes research institute ( pcori ) has launched pcornet , a major initiative to support an effective , sustainable national research infrastructure that will advance the use of electronic health data in comparative effectiveness research ( cer ) and other types of research . in december 2013 , pcori 's board of governors funded 11 clinical data research networks ( cdrns ) and 18 patient - powered research networks ( pprns ) for a period of 18 months . cdrns are based on the electronic health records and other electronic sources of very large populations receiving healthcare within integrated or networked delivery systems . pprns are built primarily by communities of motivated patients , forming partnerships with researchers . these patients intend to participate in clinical research , by generating questions , sharing data , volunteering for interventional trials , and interpreting and disseminating results . rapidly building a new national resource to facilitate a large - scale , patient - centered cer is associated with a number of technical , regulatory , and organizational challenges , which are described here .

appendiceal neuroendocrine tumours ( nets ) are the commonest tumours of the appendix and may be found in 0.30.9% of all appendicectomy samples . about 6% of these share mixed histologic features of bot mucinous glandular and neuroendocrine differentiation and other names have been used in the literature for this type of tumour , such as adenocarcinoid , mucinous carcinoid , crypt cell carcinoma , and mucin - producing net . the tumour is thought to arise from pluripotent intestinal epithelial crypt - base stem cells . the term goblet cell carcinoid was first coined in 1974 by subbuswamy et al . and is still accepted by the current who classification . the median age of presentation is in the 5th decade with a second peak in the 7th decade without any sex predilection . patients with gccs are usually diagnosed incidentally following a surgical presentation ( e.g. appendicitis , bowel obstruction / perforation or abdominal pain ) [ 5 , 6 ] . there is only one published report of lung metastasis to date , but it was retrospectively considered as an adenocarcinoma rather than a gcc . it was previously considered unusual to have lung metastases ; however , the general literature on gcc is small . here , we present the first histologically proven lung metastasis from a typical gcc . a 44-year - old woman with a long - standing history of lower abdominal pain was initially referred to the gynaecology department for an ultrasonography of the abdomen / pelvis arranged by her local practitioner . levels of serum ca 125 and ca 19 - 9 were raised at that time and the patient underwent a bilateral oophorectomy and salpingectomy . histology showed both ovaries massively infiltrated by mucin - positive tumour nests admixed with scattered synaptophysin-/chromogranin - positive neuroendocrine cells . the proliferation fraction with mib1 immunostain was < 5% . these features were interpreted as metastasis from a primary appendiceal gcc . on the basis of these findings , the patient was referred to our neuroendocrine tumour unit where the possibility of further surgery ( appendicectomy and right hemicolectomy ) was discussed . at the time of referral , the patient had fully recovered from her recent surgery and was asymptomatic . in order to assess the disease status , we arranged for the patient to have a triple phase contrast ct of the chest , abdomen , and pelvis as well as functional imaging including indium-111 pentetreotide scinitigraphy ( octreoscan ) and fdg - pet . the ct scan demonstrated a malignant - looking right lung hilar lesion which measured 4.0 1.8 cm ( fig . 1 ) and also multiple intra - abdominal lymph nodes measuring up to 1 cm . fdg - pet demonstrated low - to - moderate avidity in the noted hilar lesion and there was no fdg uptake elsewhere ( fig . 2 ) . serum chromogranin a was normal , whilst the serum levels of ca 19 - 9 and ca 125 were elevated at 4,405 iu / ml ( normal : 037 iu / ml ) and 205 iu / ml ( normal : < 30 iu / ml ) , respectively . the possibility of a separate lung pathology was considered and the lung lesion was biopsied bronchoscopically . 3 ) and similar features to those of the ovarian metastases . following discussion in the multidisciplinary team meeting , a decision not to undergo further surgical intervention was taken and the patient was referred to the oncology team for systemic chemotherapy . a pretherapy contrast ct showed interlobular interstitial / septal thickening within the right lung ( fig . systemic chemotherapy was initiated with a combination of folinic acid , 5-fluorouracil , and oxaliplatin ( folfox ) . the patient received 11 cycles of palliative folfox in total , which was eventually stopped due to symptomatic deterioration . further ct imaging at that time showed an unchanged lung lesion ; however , the patient had new bony lesions , widespread peritoneal disease , pleural effusions , and ascites . a second - line chemotherapy regimen was considered but not given due to the patient 's poor performance status . she was discharged at the local hospice where she died 11 months after the initial diagnosis . appendiceal gccs usually behave more aggressively than conventional appendiceal nets . according to a suggested classification and on the basis of tumour cell differentiation and ki67 , gccs typical gcc and adenocarcinomas ex - gcc of either signet ring cell type or poorly differentiated adenocarcinoma type . as soon as the histopathological diagnosis is confirmed , according to recent guidelines , patients with gccs are usually offered further prophylactic surgery usually right hemicolectomy and/or bilateral salpingo - oophorectomy . in contrast to the common appendiceal carcinoids , gcc run an aggressive course and quite often metastasize . gcc metastases have also been reported in the liver , ribs , vertebrae , and prostate , whilst in one case gcc cells were found in the pleural fluid as well . debulking surgery with adjuvant intraperitoneal chemotherapy may improve survival in some patients with disseminated disease [ 2 , 6 , 12 , 13 ] . distant metastases occur in 1020% of all patients at presentation , and the most common sites include the ovaries , peritoneum , and liver . kanthan et al . reported a histologically proven case of a gcc metastasizing to the lung in a 60-year - old male . however , in that case , as well as in all cases of metastatic gccs in our previously reported series , the ki67 proliferation index was > 20% and the tumours , according to the new gcc classification , were poorly differentiated adenocarcinoma type. in our case , the ki67 proliferation index was surprisingly low ( < 5% ) , and therefore this is the first case in the literature with a lung metastasis from a typical gcc . the normal levels of chromogranin a and the absence of uptake in octreoscan in our patient , despite advanced disease , confirm our previous findings about the limited values of octreoscan in gcc in contrast to other metastatic appendiceal or midgut carcinoids . in gccs , according to our previous observation , fdg - pet seems to be a very good imaging modality for assessment of disease extent . in our patient , it showed uptake in the right hilar mass . the absence of uptake in the abdominal lymph nodes may have been due to their small size . fdg - pet , in general , seems to be more sensitive than octreoscan in net and high - grade tumour patients . in our case , the fact that fdg - pet showed uptake in the lung lesion , despite the absence of a high proliferation index , probably reflects the aggressiveness of gccs . in patients with advanced gcc , systemic chemotherapy is considered , although there is no well - established chemotherapy regimen for these patients . this case demonstrates the supra - diaphragmatic metastatic potential of gccs even in those patients with a low - grade histology . the overall 5-year survival for gcc ranges between 4075% and depends on the tumour stage at presentation . enets guidelines recommend lifelong screening for synchronous or metachronous malignancies . a comparable follow - up , we would recommend consideration of a contrast ct of the chest , abdomen , and pelvis for all patients with a gcc tumour regardless of histological grade because of their potential to metastasize to distant sites , including the lungs . in case of indeterminate findings , fdg - pet seems to be helpful and , if still in doubt , a guided biopsy of the suspicious lesion may be required to confirm the diagnosis .

goblet cell carcinoid tumours are often considered a subset of appendiceal neuroendocrine tumours which behave more aggressively . they usually metastasize through transcoelomic / peritoneal invasion and common sites include the ovaries , peritoneum , and liver . metastases may have goblet cell carcinoid , signet ring cell carcinoma or classic carcinoid histology . we report the first case in the literature of a patient with a goblet cell carcinoid with lung metastasis , which was associated with unfavourable outcome .

blunt trauma of the abdominal wall can lead to a traumatic abdominal wall hernia ( tawh ) . defined tawh as the herniation through disrupted musculature and fascia associated with adequate trauma , without skin penetration , and no evidence of a prior hernia defect at the site of injury . although this type of hernia is unusual , it has been described in some reviews [ 27 ] . two reviews studied tawh , especially in the lumbar position [ 8 , 9 ] . the increased abdominal pressure and shearing forces likely cause disruption of the abdominal wall muscles and fasciae . we describe the history and imaging of a patient with a traumatic abdominal wall hernia and the operative treatment . a 59-year - old male sustained a fall from a height of 9 m onto a pile of steel bars , landing on his right flank . upon arrival of helicopter emergency medical services , the patient was alert and complained of pain in the abdomen . an advanced trauma life support ( atls ) survey revealed a right - sided pneumothorax , which was treated with a chest tube . after this intervention , the patient was respiratorily and haemodynamically stable and transported to the emergency department . upon arrival , the initial assessment according to the atls protocol was performed without any new findings according to the a , b , c and d approaches . during the secondary survey , inspection revealed a large swelling at the right side of the abdomen , with abrasions of the overlying skin ( fig . 1 ) . focussed assessment with sonography for trauma identified the presence of free intraperitoneal fluid around the spleen . 1patient after blunt abdominal trauma with swelling of the right hemi - abdomen patient after blunt abdominal trauma with swelling of the right hemi - abdomen in addition , a computed tomography ( ct ) scan of the abdomen showed a traumatic hernia of the right lateral abdomen , with protrusion of bowel and laceration of the spleen ( fig . 2 ) . the patient was transported to the operating theatre , and exploration of the abdomen through a median incision revealed a transverse rupture of the total abdominal wall , including rectus muscle and external , transverse and internal abdominal muscles , with a length of 30 cm from the midline to the vertebral column on the right side ( fig . 3 ) . the small bowel , ascending colon and the right lobe of the liver were herniated due to this defect . a non - vital part of the small bowel ( 10 cm ) was resected , and haemorrhages from the mesentery and spleen were treated . this anatomical reconstruction was reinforced with an intra - abdominal polyester composite mesh ( parietex ) with at least 4 cm overlap and fixed with sutures and taggers . after closure of the linea alba , the overstretched median fascia below the umbilicus was protected by an absorbable polyglactin mesh ( vicryl ) . post - operatively , the patient developed superficial skin necrosis in the area of the abdominal wall with deglovement , which healed by secondary intention assisted by a vacuum assisted closure system . a ct scan of the abdomen 4 months after the operation showed the anatomical reconstruction of the right abdominal wall with the use of an intra - abdominal mesh fixed with taggers ( fig . 4 ) . 2preoperative abdominal computed tomography ( ct ) scan demonstrating three ruptured muscle layers on the right sidefig . 3intra - operative picture of the right inner abdominal wall with rupture of all muscle layers . . 1 parietal peritoneum , 2 rupture of abdominal muscle layers , 3 liverfig . 4post - operative abdominal ct scan demonstrating anatomical restoration of the right abdominal wall with the use of an intra - abdominal mesh fixated with taggers preoperative abdominal computed tomography ( ct ) scan demonstrating three ruptured muscle layers on the right side intra - operative picture of the right inner abdominal wall with rupture of all muscle layers . . 1 parietal peritoneum , 2 rupture of abdominal muscle layers , 3 liver post - operative abdominal ct scan demonstrating anatomical restoration of the right abdominal wall with the use of an intra - abdominal mesh fixated with taggers our patient sustained a high - energy trauma caused by a fall from a large height . this trauma gave rise to the tawh and associated devascularisation of the small bowel , necessitating bowel resection . low energy trauma can lead to smaller tawhs , which can easily be missed on physical evaluation . handlebar injury is an example of a low energy trauma that can lead to tawh [ 2 , 11 , 12 ] . the diagnosis of a tawh on physical examination can be difficult ; because of its rare occurrence , a diagnosis of tawh is not often considered . the tawh was not diagnosed by physical examination , and the very tender right hemi - abdomen was thought to be associated with intra - abdominal lesions . because life - threatening intra - abdominal injuries can occur after high - energy trauma , a ct scan should be used as a diagnostic method . the ct scan in this case led to the diagnosis of tawh after careful examination of the abdominal wall and also to multiple haematomas in the mesentery and a spleen laceration . the strong shear forces had split the three layers of the lateral abdominal wall and the peritoneum . with the routine use of ct scans after blunt trauma tawh can be operated on by an incision overlying the defect , but in this case , a midline exploratory laparotomy was necessary for the associated intra - abdominal injuries . in addition , because of the associated intra - abdominal injuries , delayed exploration of the tawh was not a treatment option in our case . we combined the primary closure in the anatomical layers with an intraperitoneal mesh because the fascia was stretched out by the trauma and the hernia was very large . we used a composite mesh because the inner side was in direct contact with the bowels . in a recent review of the open treatment of incisional hernia , also , in a recent retrospective study of 206 open sublay mesh repairs with intraperitoneal placement of a composite mesh , the infection rate was 10.2% in a 9.5-year period . in our case , resection of a small bowel section could have increased the risk of a mesh infection . the high infection rate has to be weighed against the risk of recurrence . in a series of eight acutely repaired tawhs without mesh , three developed a recurrent hernia after 8 months . in another series of seven acute repairs of tawhs , thus , the acute repair of a large tawh should not be underestimated because of the associated injuries and the risk of a recurrence .

although blunt abdominal trauma is frequent , traumatic abdominal wall hernias ( tawh ) are rare . we describe a large tawh with associated intra - abdominal lesions that were caused by high - energy trauma . the diagnosis was missed by clinical examination but was subsequently revealed by a computed tomography ( ct ) scan . repair consisted of an open anatomical reconstruction of the abdominal wall layers with reinforcement by an intraperitoneal composite mesh . the patient recovered well and the results of a post - operative ct scan are presented .

sheehan 's syndrome ( ss ) is one of the commonest causes of hypopituitarism in underdeveloped and developing countries . it occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage.[13 ] although a small percentage of patients with ss may present as abrupt onset acute hypopituitarism immediately after delivery , most patients have a mild disease and go undiagnosed and untreated for years together.[46 ] the spectrum of clinical presentation of ss is extremely varied and ranges from non - specific complaints such as weakness , fatigue , and anemia to severe pituitary insufficiency resulting in coma and death . as in other types of hypopituitarism , other associations include anemia , pancytopenia , and cardiac abnormalities like cardiomyopathy.[810 ] ss presenting as acute kidney injury ( aki ) is rare . only few cases have been reported in the literature and most are precipitated by rhabdomyolysis.[1113 ] we report a case of aki in a middle- aged female with ss who recovered dramatically after being started on intravenous steroids and volume replacement . our case suggests that besides hypothyroid myopathy leading to rhabdomyolysis and consequently compromised renal function and aki , chronic adrenal insufficiency can also predispose to the risk of aki . a 56-year - old woman was referred to our hospital with a 45 day history of nausea , two episodes of vomiting , and few episodes of loose motions , followed by oliguria at home . she denied any history of fever , dysentery , abdominal pain , trauma , muscle pain , or change in color of urine . she also denied history of any drug intake . on enquiring , the patient gave history of longstanding ill health in the form of generalized weakness , easy fatigability , cold intolerance , constipation , hair loss , and weight gain starting after her last child birth some 22 years back . last delivery was a full - term normal delivery conducted by a local midwife at her home . she denied any history of profuse bleeding or blood transfusion during her last peripartum period . however , she had lactation failure and had menstrual cycles for a few months before complete cessation of menses after her last delivery . physical examination revealed an ill - looking , dehydrated patient with pulse of 54 beats/ minute , blood pressure of 90/60 mm hg without any postural drop , respiratory rate of 18/ minute , and oral temperature of 97.6f ( 36.4c ) . the patient had mild pallor , dry tongue , coarse and dry skin with non - pitting edema of the lower extremities . hypopigmented area was seen around right nasal orifice and there was loss of lateral eyebrows . central nervous system examination revealed slow mentation in the form of delayed response to verbal commands . examination of motor system did not reveal any focal neurodeficit , but deep tendon jerks were markedly delayed . kidney function test was deranged with initial urea of 71 mg / dl ( normal value 2040 mg / dl ) and serum creatinine of 4.5 mg / dl ( normal value 0.51.5 mg / dl ) . muscle enzymes were slightly elevated with creatine phosphokinase ( cpk ) being 168 1u / l ( normal value 1070 arterial blood gas and electrolyte analysis revealed ph of 7.31 , pco2 of 27 mm hg , bicarbonate of 13 mmol / l , serum sodium 130 mmol / l , and potassium of 3.6 mmol / l . chest x - ray was normal and 12-lead ecg revealed sinus bradycardia with low - voltage qrs complex . routine urine examination revealed pus cells 45 , rbcs 23 , absent albumin and casts . renal ultrasound revealed relatively small - sized kidneys ( right 8.5 3.2 cm , left 8.7 3.4 cm ) with increased echogenicity , with maintained corticomedullary differentiation bilaterally . the diagnosis of panhypopituitarism most likely secondary to ss associated with acute renal failure was made on the basis of her past medical history of failure to lactate post her last child birth with gradual cessation of menses , peripheral signs and symptoms of hypothyroidism , and abnormal biochemical and hormone profile . basal anterior pituitary hormones and serial kidney function tests during admission the patient was given intravenous fluids in the form of dextrose normal saline with close monitoring of urine output , replacement therapy in the form of intravenous hydrocortisone 50 mg intravenously 6 hourly , and levothyroxine given orally at a starting dose of 50 mcg/ day . on repeating renal function tests and other biochemical tests , there was dramatic improvement in serial renal function parameters . with improvement in the general condition of the patient , intravenous antibiotics were stopped in view of absence of fever and negative septic screen . she was shifted to oral prednisolone 5 mg twice daily , while levothyroxine was continued at a dose of 50 mcg / day . she was discharged on the same medication on 10th day of admission and was advised to taper prednisolone to 5 mg/ day after 2 weeks . four weeks after discharge , the patient had general sense of well - being with better appetite and renal function had normalized with creatinine 0.64 mg/ dl and serum urea 23 mg / dl . the patient was subjected to magnetic resonance imaging ( mri ) brain with sellar and parasellar focus which revealed empty sella with normal rest of the brain parenchyma [ figure 1 ] . mri pituitary sagittal view showing pituitary fossa filled with cerebrospinal fluid and stalk touching the base of pituitary floor ; features suggestive of empty sella the present report describes a 56-year - old woman with ss who presented with acute renal insufficiency owing to depletion of intravascular volume secondary to gastroenteritis . the chronic hypocortisol state has increased the predisposition to renal injury which was precipitated by mild acute gastroenteritis . ss , first described by hl sheehan in 1937 , classically refers to postpartum hypopituitarism due to pituitary necrosis occurring during severe hypotension or shock secondary to massive bleeding at or just after delivery . the frequency of ss has gradually decreased especially in developed countries , as a result of improved obstetric care including treatment of hemodynamic complications with rapid blood transfusion and/or intravenous fluid replacement . it , however , continues to be the most common cause of hypopituitarism in underdeveloped and developing countries . enlarged pituitary volume , small sellar size , prothrombotic nature of pregnancy , and autoimmunity have been suggested to play a role in the pathogenesis of ss in women who suffer from severe postpartum hemorrhage . on the other hand , the spectrum of clinical presentation of ss is quite variable and ranges from non - specific symptoms such as weakness , fatigue , and anemia to severe pituitary insufficiency resulting in coma and death . clinical manifestations of ss may change from one patient to another , as hormonal deficiency varies from loss of one trophic hormone to classical panhypopituitarism.[157 ] failure of postpartum lactation is the most consistent feature of patients with ss and failure of regaining menstrual flow postpartum is the most common symptom of ss . despite the failure to menstruate , gonadotrophin reserve may still be preserved in some patients and these patients can even conceive spontaneously . another important clinical presentation in ss is related to secondary hypothyroidism and patients may present with weight gain , cold intolerance , tiredness , aches and pains , and muscle disorders ranging from elevation of muscle enzymes to frank rhabdomyolysis and renal failure.[1113 ] our patient also had severe central hypothyroidism as was evident from history , examination , and hormone tests . adrenal insufficiency in ss can be catastrophic and can range from non - specific complaints to hypotension , sallow skin , and severe adrenal crisis , particularly under stressful conditions such as infection . only few cases have been reported in which aki was caused by rhabdomyolysis.[1113 ] aki has been defined as rapid decline in kidney function , as measured by rising serum creatinine or decline in urine output ( oligo / anuria ) . introduced by acute kidney injury network , specific criteria exist for diagnosing aki . our case presented with rapid deterioration of renal function in the form of oliguria together with rise in serum creatinine , thus meeting the criteria for aki . although , as stated earlier , aki can occur in ss , hypothyroid myopathy is the most common etiological factor.[1113 ] hypothyroid myopathy is usually manifested by delayed relaxation of tendon reflexes , muscle stiffness , proximal muscle weakness , myalgia , muscle cramps , and occasional elevated muscle enzymes , however , rhabdomyolysis is rare . rhabdomyolysis can occur spontaneously or is precipitated by hypoxemia , hypotension , sepsis , or vigorous exercise . the exact cause of rhabdomyolysis in hypothyroidism is unclear , but both impaired glycogenolysis and oxidative mitochondrial metabolism have been implicated.[1113 ] although our patient had subtle features of hypothyroid myopathy as revealed by history , examination , and lab evaluation , there was no evidence of rhabdomyolysis . the most probable cause of aki in our patient was chronic hypocortisolemia as renal function in our patient rapidly improved after initiation of intravenous hydrocortisone ; an association between adrenal insufficiency and disturbed renal function has been demonstrated repeatedly . a study was done by christine waterhouse and henry keutmenn in 1947 , in which kidney function of 13 patients with adrenal insufficiency was studied . it was concluded that there is reduction in effective vascular bed in the kidney , resulting in decreased renal plasma flow with concomitant decrease in the rate of glomerular filtration . besides , it has been found that cortisol has major effects on hemodynamics and absence of cortisol causes decrease in cardiac index with an inadequate response of systemic vascular resistance to maintain the mean arterial pressure . in summary , a middle - aged woman with ss presented with aki which reversed completely with conservative management including glucocorticoids .

sheehan 's syndrome occurs as a result of ischemic pituitary necrosis secondary to severe postpartum bleeding . it is one of the most common causes of hypopituitarism , characterized by variable clinical presentation . acute kidney injury occurs rarely in sheehan 's syndrome and most of the cases have been found to be precipitated by rhabdomyolysis . we here present a case of sheehan 's syndrome with acute kidney injury where theprecipitating cause was chronic hypocortisolemia . we believe this is the first reported case of sheehan 's syndrome in which acute kidney injury was precipitated by adrenal insufficiency .

it has been proved previously that thp-1 cells can differentiate into macrophages following treatment with 100 nm phorbol 12-myristate 13-acetate ( pma ) for 72 h and macrophages can transform into foam cells by incubation in the presence of 50 g / ml oxidized low - density lipoprotein ( ox - ldl ) for 48 h. therefore , thp-1 macrophage - derived foam cells have been used as a model system for investigating the possible molecular mechanisms that ox - ldl influences foam cell development , which represents a promising therapeutic strategy for atherosclerosis . evidence showed that ox - ldl played a significant role in the initiation and progression of atherosclerosis . the previous study revealed that an elevated level of ox - ldl was one of the major risk factors for atherosclerosis . after differentiation , intimal macrophages intake ox - ldl via scavenger receptors , thereby transforming into foam cells . to gain a molecular understanding of the mechanism by which ox - ldl transforms the macrophages into foam cells , we generated thp-1 macrophage - derived foam cells by ox - ldl treatment . long noncoding rnas ( lncrnas ) are nonprotein coding transcribed rna molecules consisting of more than 200 nucleotides . an increasing number of studies have revealed that lncrnas have a variety of important functions , including their role in transcription , splicing , translation , nuclear factor trafficking , imprinting , genome rearrangement , and chromatin modification , . studies have shown that aberrant lncrna expression is associated with a variety of human diseases such as cardiovascular diseases and cancer , . thus , a better understanding of the roles of lncrna in atherosclerosis will advance us to find a promising strategy for regulating lipid metabolism balance . to identify the genes that are regulated by ox - ldl , we isolated total rna from 6 independent samples of thp-1 macrophages cultured in the presence or absence of 50 g / ml of ox - ldl in serum - free rpmi 1640 medium containing 0.3% bsa for 48 h using trizol ( invitrogen life technologies ) . total rna from each sample was quantified by the nanodrop nd-1000 and rna integrity was assessed by standard denaturing agarose gel electrophoresis ( fig . the sample preparation and microarray hybridization were performed based on the manufacturer 's standard protocols with minor modifications . briefly , mrna was purified from 1 g total rna after removal of rrna ( mrna - only eukaryotic mrna isolation kit , epicentre ) . then , each sample was amplified and transcribed into fluorescent crna along the entire length of the transcripts without 3 bias utilizing a random priming method . the labeled crnas were hybridized onto the human lncrna array v2.0 ( 8 60 k , arraystar ) . after having washed the slides , the arrays were scanned by the agilent scanner g2505b . agilent feature extraction software ( version 10.7.3.1 ) was used to analyze acquired array images . all microarray data were submitted to the gene expression omnibus ( accession number gse54039 ) . agilent feature extraction software ( version 10.7.3.1 ) was used to analyze acquired array images . quantile normalization and subsequent data processing were performed using the genespring gx v11.5.1 software package ( agilent technologies ) . after quantile normalization of the raw data , lncrnas and mrnas that at least 1 out of 6 samples have flags in present or marginal ( all target values ) were chosen for further data analysis . differentially expressed lncrnas and mrnas with statistical significance were identified through volcano plot filtering . pathway analysis and go analysis were applied to determine the roles of these differentially expressed mrnas played in these biological pathways or go terms . finally , hierarchical clustering was performed to show the distinguishable lncrna and mrna expression pattern among samples . to explore possible changes in rna expression during macrophage formation , we performed microarray analysis of thp-1 macrophages and thp-1 macrophage - derived foam cells using the arraystar probe dataset , which included 24,748 lncrnas and 24,420 coding transcripts . lncrna and mrna expression profiles from thp-1 macrophages ( 3 samples ) and thp-1 macrophage - derived foam cells ( 3 samples ) were produced using the arraystar human lncrna array v2.0 platform . scatter plots of normalized signal values in lncrnas and mrnas are shown in fig . 2a and b. differently expressed probe sets were identified based on student 's t - test for paired samples ' normalized expression values using the following cutoff : absolute fold change value larger than 3 and p value less than 0.01 . by using a 3 fold change as a cut - off , p - value 0.01 , 100 lncrnas and 63 mrnas were differentially expressed between thp-1 macrophage versus thp-1 macrophage - derived foam cells . it has been proved previously that thp-1 cells can differentiate into macrophages following treatment with 100 nm phorbol 12-myristate 13-acetate ( pma ) for 72 h and macrophages can transform into foam cells by incubation in the presence of 50 g / ml oxidized low - density lipoprotein ( ox - ldl ) for 48 h. therefore , thp-1 macrophage - derived foam cells have been used as a model system for investigating the possible molecular mechanisms that ox - ldl influences foam cell development , which represents a promising therapeutic strategy for atherosclerosis . evidence showed that ox - ldl played a significant role in the initiation and progression of atherosclerosis . the previous study revealed that an elevated level of ox - ldl was one of the major risk factors for atherosclerosis . after differentiation , intimal macrophages intake ox - ldl via scavenger receptors , thereby transforming into foam cells . to gain a molecular understanding of the mechanism by which ox - ldl transforms the macrophages into foam cells , we generated thp-1 macrophage - derived foam cells by ox - ldl treatment . long noncoding rnas ( lncrnas ) are nonprotein coding transcribed rna molecules consisting of more than 200 nucleotides . an increasing number of studies have revealed that lncrnas have a variety of important functions , including their role in transcription , splicing , translation , nuclear factor trafficking , imprinting , genome rearrangement , and chromatin modification , . studies have shown that aberrant lncrna expression is associated with a variety of human diseases such as cardiovascular diseases and cancer , . thus , a better understanding of the roles of lncrna in atherosclerosis will advance us to find a promising strategy for regulating lipid metabolism balance . to identify the genes that are regulated by ox - ldl , we isolated total rna from 6 independent samples of thp-1 macrophages cultured in the presence or absence of 50 g / ml of ox - ldl in serum - free rpmi 1640 medium containing 0.3% bsa for 48 h using trizol ( invitrogen life technologies ) . total rna from each sample was quantified by the nanodrop nd-1000 and rna integrity was assessed by standard denaturing agarose gel electrophoresis ( fig . the sample preparation and microarray hybridization were performed based on the manufacturer 's standard protocols with minor modifications . briefly , mrna was purified from 1 g total rna after removal of rrna ( mrna - only eukaryotic mrna isolation kit , epicentre ) . then , each sample was amplified and transcribed into fluorescent crna along the entire length of the transcripts without 3 bias utilizing a random priming method . the labeled crnas were hybridized onto the human lncrna array v2.0 ( 8 60 k , arraystar ) . after having washed the slides , the arrays were scanned by the agilent scanner g2505b . agilent feature extraction software ( version 10.7.3.1 ) was used to analyze acquired array images . all microarray data were submitted to the gene expression omnibus ( accession number gse54039 ) . agilent feature extraction software ( version 10.7.3.1 ) was used to analyze acquired array images . quantile normalization and subsequent data processing were performed using the genespring gx v11.5.1 software package ( agilent technologies ) . after quantile normalization of the raw data , lncrnas and mrnas that at least 1 out of 6 samples have flags in present or marginal ( all target values ) were chosen for further data analysis . differentially expressed lncrnas and mrnas with statistical significance were identified through volcano plot filtering . pathway analysis and go analysis were applied to determine the roles of these differentially expressed mrnas played in these biological pathways or go terms . finally , hierarchical clustering was performed to show the distinguishable lncrna and mrna expression pattern among samples . to explore possible changes in rna expression during macrophage formation , we performed microarray analysis of thp-1 macrophages and thp-1 macrophage - derived foam cells using the arraystar probe dataset , which included 24,748 lncrnas and 24,420 coding transcripts . lncrna and mrna expression profiles from thp-1 macrophages ( 3 samples ) and thp-1 macrophage - derived foam cells ( 3 samples ) were produced using the arraystar human lncrna array v2.0 platform . scatter plots of normalized signal values in lncrnas and mrnas are shown in fig . 2a and b. differently expressed probe sets were identified based on student 's t - test for paired samples ' normalized expression values using the following cutoff : absolute fold change value larger than 3 and p value less than 0.01 . by using a 3 fold change as a cut - off , p - value 0.01 , 100 lncrnas and 63 mrnas were differentially expressed between thp-1 macrophage versus thp-1 macrophage - derived foam cells . we described here a dataset composed of microarray expression profiling of ox - ldl - responsive genes . with this dataset , we were able to demonstrate a large number of ox - ldl - responsive lncrna and mrna , which advance us to further investigate their relationships and functions in foam cell formation and atherosclerosis progression . we believe that this dataset would be particularly valuable for investigating the cellular processes associated with lipid metabolism balance and the underlying molecular mechanisms . for example , we revealed that ox - ldl could significantly promote lincrna - dynlrb2 - 2 expression , which upregulated atp - binding cassette transporter a1 ( abca1 ) expression through g protein - coupled receptor 119 ( gpr119 ) . in addition , lincrna - dynlrb2 - 2 and gpr119 promoted abca1-mediated cholesterol efflux from thp-1 macrophage - derived foam cells , and inhibited inflammatory responses . moreover , we paid particular attention to rp5 - 833a20.1 as it is a key lncrna in our study of regulation of cholesterol homeostasis and inflammatory reaction . we found that lncrna rp5 - 833a20.1 was located in intron 2 of the nuclear factor i / a ( nfia ) gene and had an opposite transcription direction to that of nfia through the ucsc genome browser . in addition , we demonstrated that rp5 - 833a20.1 could inhibit nfia expression by promoting mir-382 - 5p expression . this finding sheds new light on the interplay between lncrna and atherosclerosis , and suggests that lncrna may become a promising strategy for regulating lipid metabolism balance .

atherosclerosis has a high incidence and is harmful to human health . an elevated level of oxidized low - density lipoprotein ( ox - ldl ) is one of the major risk factors for atherosclerosis . during atherogenesis progression , circulating monocytes adhere to the intima and differentiate into macrophages . after differentiation , intimal macrophages intake ox - ldl via scavenger receptors , thereby transforming into foam cells . foam cell formation due to excessive accumulation of cholesterol by macrophages is a pathological hallmark of atherosclerosis . to gain a molecular understanding of the effect of ox - ldl in atherosclerosis development , we conducted a genome - wide analysis of the ox - ldl - induced macrophage transformation by microarray gene expression profiling . here we describe in details the contents and quality controls for the gene expression and related results associated with the data uploaded to gene expression omnibus ( accession number gse54039 ) .

malignant lymphoma is a heterogeneous group of diseases with a wide spectrum of histological subtypes . traditionally , malignant lymphomas have been divided into hodgkin lymphomas and non - hodgkin lymphomas . more than 40 subgroups are defined ; both indolent and aggressive variants exist , and a wide range of treatment is used . the danish national lymphoma registry ( lyfo ) was established in 1982 , covering the western part of denmark ( jutland and funen ) , including patients with non - hodgkin lymphoma . in 1998 , the lyfo aims to register the clinical and paraclinical characteristics of patients diagnosed with malignant lymphoma in denmark . the lyfo aims to monitor the clinical course of the disease as well as to monitor and improve the quality of treatment nationwide by benchmarking departments and patient risk groups . the lyfo includes all patients diagnosed with malignant lymphoma in denmark , referred to one of the ten departments of hematology . patients with cutaneous lymphomas , some hiv+-associated lymphomas , and some lymphomas where treatment is futile are not referred to hematological departments and hence not registered in the lyfo . patients diagnosed and treated outside of denmark are not registered ; according to the database registration , it is two patients per year . patients who relapse where the initial lymphoma diagnosis was prior to start of the registry in that region are not registered . by the end of 2014 , ~23,000 patients were registered since 1982 . since it is a national quality database , all departments of hematology are obligated to register patients in the lyfo at the time of diagnosis , at the end of first - line treatment , at relapse , and at the end of follow - up or death . standardized forms are used to collect data on lymphoma patients ( table 1 ) . since 2005 , the registration is submitted electronically through a secure internet - based database system , and all information is saved electronically . for each patient , four forms are available in a consecutive manner ( figure 1 ) . at the time of diagnosis the department responsible for the treatment initiation and evaluation has the obligation to enter the form . the diagnosis is coded according to the who classification of tumours of haematopoietic and lymphoid tissues.1 since a minor subset has a discordant diagnose , this is also registered . ann arbor stage , b - symptoms , largest tumor diameter , eastern cooperative oncology group performance status , concomitant neoplastic diseases , and treatment strategy are required in the form . in addition to a number of laboratory test results ( table 1 ) , information of each nodal and extranodal involvement sites is required . the treatment form consists of detailed information on the first - line treatment : chemotherapy regimens , treatment with monoclonal antibodies , radiotherapy , radioimmunotherapy , major surgery , and date and type of eventually autologous stem - cell therapy . a response assessment is required and has been adjusted to the different versions of the international response criteria for malignant lymphoma.2 furthermore , toxicity assessment is recorded for patients experiencing toxicity grades iii and iv.3 in the case of clinical or histologically confirmed relapse or refractory disease , defined as progression within 3 months after termination of first - line treatment , a relapse form is requested . this form is also completed for all patients who were initially observed without need of treatment . the relapse form requires date of relapse , lymphoma histology at relapse , treatment information of second - line treatment , and response assessment identical to the treatment form . a follow - up form is requested at death or termination of outpatient follow - up . this form includes information on vital status , date of follow - up or death , and disease remission status . the four schemes in the database are merged to an analyzable dataset , where new data fields are derived from the entered values in the schemes . this process utilizes calculation of a number of prognostic indexes such as the international prognostic index ( ipi)4 and the follicular lymphoma international prognostic index5 and a number of nodal and extranodal sites , in addition to calculation of both result and process quality indicators . result quality indicators are mortality 30 and 180 days after diagnosis for patients receiving treatment , response to first - line treatment and kaplan - meier survival estimates 1 , 3 , and 5 years after the time of diagnosis . the process quality indicators include time from diagnosis to start of treatment , fulfillment of entered data used in the international prognostic index , and the inclusion rate in clinical trials . to ensure high registry completeness , the lyfo is cross - referenced with the danish national patient registry and the national pathology registry . since all patients with a hospital admission , both as inpatient and outpatient , are registered in the danish national patient registry with diagnosis and date of contact , all patients referred to a hematological department are identified by this cross - reference.6 departments can instantly retrieve lists of patients with missing registration in the database , both at time of diagnosis and time of an eventual relapse . all departments register in the lyfo and fulfill the demand of coverage of at least 90% . the department responsible for the treatment initiation and evaluation has the obligation to enter the form . the diagnosis is coded according to the who classification of tumours of haematopoietic and lymphoid tissues.1 since a minor subset has a discordant diagnose , this is also registered . ann arbor stage , b - symptoms , largest tumor diameter , eastern cooperative oncology group performance status , concomitant neoplastic diseases , and treatment strategy are required in the form . in addition to a number of laboratory test results ( table 1 ) , information of each nodal and extranodal involvement sites is required . the treatment form consists of detailed information on the first - line treatment : chemotherapy regimens , treatment with monoclonal antibodies , radiotherapy , radioimmunotherapy , major surgery , and date and type of eventually autologous stem - cell therapy . a response assessment is required and has been adjusted to the different versions of the international response criteria for malignant lymphoma.2 furthermore , toxicity assessment is recorded for patients experiencing toxicity grades iii and iv.3 in the case of clinical or histologically confirmed relapse or refractory disease , defined as progression within 3 months after termination of first - line treatment , a relapse form is requested . this form is also completed for all patients who were initially observed without need of treatment . the relapse form requires date of relapse , lymphoma histology at relapse , treatment information of second - line treatment , and response assessment identical to the treatment form . a follow - up form is requested at death or termination of outpatient follow - up . this form includes information on vital status , date of follow - up or death , and disease remission status . the four schemes in the database are merged to an analyzable dataset , where new data fields are derived from the entered values in the schemes . this process utilizes calculation of a number of prognostic indexes such as the international prognostic index ( ipi)4 and the follicular lymphoma international prognostic index5 and a number of nodal and extranodal sites , in addition to calculation of both result and process quality indicators . result quality indicators are mortality 30 and 180 days after diagnosis for patients receiving treatment , response to first - line treatment and kaplan - meier survival estimates 1 , 3 , and 5 years after the time of diagnosis . the process quality indicators include time from diagnosis to start of treatment , fulfillment of entered data used in the international prognostic index , and the inclusion rate in clinical trials . to ensure high registry completeness , the lyfo is cross - referenced with the danish national patient registry and the national pathology registry . since all patients with a hospital admission , both as inpatient and outpatient , are registered in the danish national patient registry with diagnosis and date of contact , all patients referred to a hematological department are identified by this cross - reference.6 departments can instantly retrieve lists of patients with missing registration in the database , both at time of diagnosis and time of an eventual relapse . all departments register in the lyfo and fulfill the demand of coverage of at least 90% . in addition to the follow - up form , which is completed at the time of termination of outpatient follow - up or death , whichever occurs first , a linkage to the danish civil registration system secures that date of death is available.7 thereby , no patient is lost to follow - up . data from the lyfo has for decades been used for both clinical epidemiological research and for monitoring the treatment of lymphoma patients in denmark.8 the danish lymphoma group , who runs the database , publishes annually a report based on data from the lyfo in collaboration with registry support center of epidemiology and biostatistics ( east).9 the quality indicators are presented for each department by year together with comments from clinicians and epidemiologists . the reports have shown improved 180 days mortality for patients with diffuse large b - cell lymphoma ( dlbcl ) , improving from 12% to 10% during the past 4 years . the annual report is publically available and is used by both clinicians and for administrative purposes . in case of one department having significant worse outcome than the others , the administrative staff will examine the numbers and differences and draw the clinicians attention to the differences in order to standardize treatment and outcome . as an example , the survival for patients with dlbcl was significantly lower in two out of ten departments in 20012007 . the survival has increased , but is now at the same level for all departments due to publication of the survival results ( figure 2 ) . a substantial number of papers originated from the lyfo have been published in the past decade in international journals , and collaboration with other national databases has resulted in unique publications.913 in 2014 , a publication of mantle cell lymphoma showed male sex to be an independent negative prognostic factor , and that both rituximab and autologous stem - cell transplant were independently associated with better outcome.11 a study on routine imaging in the follow - up setting after treatment for dlbcl compared the widespread use of routine imaging in denmark with the more restrictive use in sweden . no impact was found on survival , and the study concludes that routine imaging for dlbcl in the first complete remission is not recommended.13 data quality in the lyfo has recently been measured through a validation process , and the data quality and coverage was found to be very high with positive predictive values for individual variables ranging from 87% to 100% using individual medical records as reference and a registration completeness of 94.9% using danish national patient registry ( dnpr ) as reference.14,15 health care professionals ( eg , medical doctors , study nurses ) report to the database , and consent is not required from patients due to the danish legislation . registration in the lyfo is approved by the national board of health and the danish data protection agency ( 2006 - 54 - 2093 ) . a data entry manual is publically available , and training is performed locally . prior to submission of a form , an internal validation of the data fields is performed and the clinician has to clarify open issues ( eg , date of diagnosis , lymphoma subtype ) before submission of the form can be performed . funding from the danish regions allows the maintenance and development of the database and the database office . registry support center of epidemiology and biostatistics east is responsible for it support as well as statistical and epidemiological support . the lyfo is a nationwide registry , established in 1982 , with extensive information on all lymphoma patients treated at a department of hematology in denmark . the database is used for quality assurance , clinical epidemiological research , and administrative purposes .

aim of databasethe danish national lymphoma registry ( lyfo ) was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in denmark.study populationthe lyfo database was established in 1982 as a seminational database including all lymphoma patients referred to the departments of hematology . the database became nationwide on january 1 , 2000.main variablesthe main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation . up to four forms are completed for each patient : a primary registration form , a treatment form , a relapse form , and a follow - up form . variables are used to calculate six result quality indicators ( mortality 30 and 180 days after diagnosis , response to first - line treatment , and survival estimates 1 , 3 , and 5 years after the time of diagnosis ) , and three process quality indicators ( time from diagnosis until the start of treatment , the presence of relevant diagnostic markers , and inclusion rate in clinical protocols).descriptive dataapproximately 23,000 patients were registered in the period 19822014 with a median age of 65 years ( range : 16100 years ) and a male / female ratio of 1.23:1 . patients can be registered with any of 42 different subtypes according to the world health organization classifications.conclusionlyfo is a nationwide database for all lymphoma patients in denmark and includes detailed information . this information is used for both epidemiological research and clinical follow - up as well as for administrative purposes .

a prospective clinical trial was conducted on a consecutive series of the patients with primary io overaction or secondary overaction due to superior oblique palsy . institutional review board approval was obtained and signed informed consent was obtained from all participants in accordance with the declaration of helsinki . exclusion criteria included presence of dvd , history of simultaneous or previous strabismus and/or ocular surgery , inadequate follow up , and concurrent conditions that might influence results such as eyelid anomalies and orbital disease . the patients who did not cooperate enough for taking measurements were also excluded such as small children and the patients with low vision who could not fixate properly . all patients received a thorough ophthalmic examination 1 day before surgery and 3 months thereafter . overaction of io was determined as overelevation in adduction and graded by a scale ranging from 0 to + 4 . output measurements were consisted of pf , margin reflex distance ( mrd ) 12 , lower lid function ( llf ) , hertel value , and lower lid crease ( llc ) . pf was measured by assessing the distance between the upper and lower eyelid margin at the point that bisected the light reflex on the cornea . mrd-1 represented the distance from the corneal light reflex to the upper eyelid margin whereas mrd-2 represented the distance to lower eyelid margin . llf was assessed by measuring eyelid excursion from extreme upgaze to extreme downgaze while holding the head still . hertel mirror exophthalmometer was used to measure the protrusion of the glob from the lateral orbital rim . all the stable measurements were taken by a handheld ruler while the patient sitting upright and fixating with that eye to a penlight held at 50 cm in front of the patient . all preoperative and postoperative measurements were always performed by the same examiner , who did not know the details of patients . to increase the reliability of the measurements , all were taken twice and the average value used , if there was any inconsistency a third measurement was considered . the hyperdeviation was measured with prism and cover test or with krimsky test if corrected visual acuity was inadequate for prism and cover test . all preoperative and postoperative examinations and measurements were made by the same observer , who was not masked to the data . all surgeries were done using a similar technique which was first described by elliot and nankin . in this original procedure , io was sutured just anterior to the insertion of the inferior rectus muscle ; however , we sutured the io posterior to the inferior rectus insertion . in brief , a lid speculum was inserted and the globe was maximally elevated and adducted . polyglactin 6 - 0 sutures were placed in the io near its insertion , with locking bites on either edge . then , the muscle was freed and the anterior arm of the suture was placed posterior to the temporal edge of the inferior rectus muscle insertion . the posterior arm was placed temporally and posteriorly within 23 mm [ fig . 1 ] . hence , the new direction of the io insertion was also different from the original procedure of elliot and nankin . in original technique , the new io insertion should be just anterior but parallel to the inferior rectus insertion . the anterior arm of disinserted inferior oblique muscle placed 12 mm posterior to lateral edge of inferior rectus insertion . the posterior arm was placed temporally and posteriorly within 23 mm to anterior arm the differences of the collected data were calculated for statistical significance using the wilcoxon test . all surgeries were done using a similar technique which was first described by elliot and nankin . in this original procedure , io was sutured just anterior to the insertion of the inferior rectus muscle ; however , we sutured the io posterior to the inferior rectus insertion . in brief , a lid speculum was inserted and the globe was maximally elevated and adducted . polyglactin 6 - 0 sutures were placed in the io near its insertion , with locking bites on either edge . then , the muscle was freed and the anterior arm of the suture was placed posterior to the temporal edge of the inferior rectus muscle insertion . the posterior arm was placed temporally and posteriorly within 23 mm [ fig . 1 ] . hence , the new direction of the io insertion was also different from the original procedure of elliot and nankin . in original technique , the new io insertion should be just anterior but parallel to the inferior rectus insertion . the anterior arm of disinserted inferior oblique muscle placed 12 mm posterior to lateral edge of inferior rectus insertion . the differences of the collected data were calculated for statistical significance using the wilcoxon test . a total of 19 eyes of 16 consecutive patients who met the criteria were included . the mean age of the patients was 8.7 7.1 years , with a range of 223 years . seven eyes ( 36.8% ) of 4 cases had primary io overaction , while 12 eyes ( 63.2% ) of 12 cases had secondary overaction due to superior oblique palsy . the surgery was performed unilaterally for one case with bilateral asymmetric primary io overaction because this case had severe amblyopia in that eye . the median preoperative grade of io overaction was 3.5 ( ranging from 3 to 4 ) , which decreased to 0 ( ranging from 0 to 2 ) ( p < 0.05 ) 3 months postoperatively . all of the eyes underwent anterior transposition of io placed 12 mm posterior to inferior rectus insertion . the mean preoperative hypertropia in the primary position was 14.1 5.9 prism diopters ( pds ) and the mean postoperative hypertropia was 2.4 4.5 pd at the 3-month follow - up visit ( p = 0.005 ) . demographic and operative data for patients who underwent anterior transposition of the inferior oblique the mean preoperative pf was 10.2 1.3 mm in which no change was observed and it was 10.2 0.9 mm postoperatively ( p = 0.79 ) . the mean preoperative mrd-1 was 4.7 0.7 mm , which decreased postoperatively to 4.2 0.6 mm ( p = 0.08 ) . the mean preoperative mrd-2 was 5.6 0.8 mm , which increased postoperatively to 5.8 0.5 mm ( p = 0.25 ) . the mean preoperative hertel value was 15.4 2.2 mm which decreased postoperatively to 15.0 2.8 mm ( p = 0.48 ) . the mean preoperative llf was 5.4 1.4 mm , which increased postoperatively to 5.6 1.2 mm ( p = 0.21 ) . the mean preoperative llc was 4.6 1.2 mm which decreased postoperatively to 4.4 1.3 mm ( p = 0.41 ) [ table 2 ] . preoperative and postoperative values of output measures abnormal head posture was observed in 12 patients and all of them had unilateral superior oblique palsy . the abnormal head posture was not noticable in 7 ( 58.3% ) of these patients and the angle of head tilt reduced in 5 patients ( 41.7% ) at the 3-month postoperative visit . within the orbit , a complex musculofibroelastic structure suspends the globe , interrelates with the eyelids , and other orbital elements . the capsulopalpebral fascia which is analogs to the levator aponeurosis in the upper lid is a major component of lower lid retractors . it originates from the belly of the inferior rectus muscle ; there are firm adhesions between capsulopalpebral fascia and inferior rectus . the capsulopalpebral fascia splits open and forms a anterior layer and a posterior layer which wrapping around the io . any procedure on io as well as anterior transposition surgery might have effect on lower lid retractors and therefore might influence lower lid configuration and functioning . anterior transposition of the inferior io , introduced by elliott and nankin , was highly effective in the treatment of dvd , primary inferior io overaction and secondary overaction due to superior oblique palsy . we also observed clinically and statistically significant decrease in the preoperative hypertropia after this procedure and 68.4% of the patients achieved a hypertropia of 5 pd or less postoperatively . anterior transposition has been shown to work in part by converting the io from an elevator to a depressor of the globe because the neurovascular bundle became a new origin for the temporal portion of the io . elliott and nankin also found that anterior transposition of io was advantageous when compared to standard recession surgery and also was devoid of difficulties and complications related to reinserting the muscle . graded anterior transposition to reduce the complication of limited elevation . in this procedure , the amount of anterior transposition was titrated to the amount of io overaction . farvardin et al . , reported combined resection and anterior transposition of io in the treatment of io overaction secondary to superior oblique palsy with successful results . fard described anterior and nasal transposition of io for the treatment of dvd associated with io overaction . limitation of elevation in abduction and/or adduction and hypotropia in primary position are known complications of anterior transposition surgery of io . functionally , less significant complications such as pf alteration , pf asymmetry , lower lid fullness , were noted in a few study . in the present study , we prospectively evaluated the alteration of the pf , lower lid contour , and function parameters with anterior transposition of the inferior io surgery . for this purpose , the pf , mrd-1 , mrd-2 , hertel value , llf , and llc were evaluated however , none of them revealed significant change postoperatively ( p > 0.05 ) . comparable to our results , no postoperative pf asymmetry has been reported by goldchmit et al . , after io anterior transposition in patients with unilateral io overaction . in their technique , the disinserted io was sutured adjacent to the lateral end of inferior rectus insertion bunched with one suture . they noted slight lower lid curvature deformity on forced upgaze in four of ten patients . farvardin and nazarpoor have observed mild fullness in 25% of the patients with superior oblique palsy following anterior transposition surgery in which the disinserted io was sutured just anterior to the lateral of inferior rectus insertion . however , they did not reported any elevation of lower lid on upgaze in their patients . however , kushner has mentioned that anterior transposition of the inferior io caused a narrowing of the pf and this could be cosmetically noticeable . he compared postoperative pf of patients who underwent io transposition surgery with control group who underwent standard recession without transposition . in this work , the outcomes of transposition surgery were evaluated in two separate groups in first group the io was placed at the level of inferior rectus insertion and in second group the io was placed 2 mm anterior to inferior rectus insertion . compared with the control both groups showed significant decrease in pf and gonzlez and cinciripini reported elevation deficiency , elevation of lower lid on upgaze and reduced inferior scleral show in the eyes following anterior transposition in which io reinserted 3 mm posterior from the limbus in the line of lateral edge of inferior rectus insertion . they speculated that the reason for lower lid elevation to be the advancement of the capsulopalpebral fascia extending to inferior rectus . some studies have reported that io transposition of 1 mm or more anterior to the inferior rectus muscle insertion as well as the lateral spreading of the posterior fibers more than 2 mm at the new insertion are risk factors for complications of this surgery such as anti - elevation syndrome and hypotropia . the lower lid elevation and fullness in lower lid on upgaze also noted more in this augmented anteriorization procedures . kushner demonstrated that if the posterior fibers of io are inserted more distant from the lateral extremity of the inferior rectus insertion , the effect on limitation of elevation would be greater , because these new fibers become more stretched . those cases can not be compared with ours because we performed anteriorization surgery in which io was placed posterior to the lateral end of the inferior rectus insertion thus , the posterior fibers had minor anteriorization . postoperatively no significant change on lower lid configuration and function parameters were observed in our patients . the small sample size and the parameters depending on patients cooperation such as pf , llf are main limitations of this study . we tried to overcome this issue by including only cooperative patients and using the average of two compatible measurements . due to close anatomic relationship of io with lower lid retractors , it is rational to expect an alteration of lower lid configuration and functioning with io surgery . in this study , we did not observe any significant effect on lower lid parameters with io anterior transposition in which we placed the io posterior to inferior rectus insertion . however , the alteration of these parameters might be more noticeable particularly in patients with greater degrees of anterior transpositions in which io placed anterior to inferior rectus insertion . placing the io posterior to the inferior rectus insertion avoiding further anterior transposition may enable successful surgical outcomes without any effect on eyelid configuration and functioning . further observations should also be done on a larger number of patients to confirm the effect of io anterior transposition on the eyelid tissues .

purpose : to evaluate the alteration of lower lid configuration and function with anterior transposition surgery of the inferior oblique ( io ) muscle.patients and methods : a prospective clinical trial was conducted on a consecutive series of patients underwent anterior transposition of the io as a sole operation . all patients received a thorough ophthalmic examination 1 day before and 3 months after surgery . output parameters were consisted of palpebral fissure , margin reflex distance 12 , lower lid function , hertel value , and lower lid crease . the differences of the collected data were calculated for statistical significance by using the wilcoxon test.results:a total of 19 eyes of 16 consecutive patients were included . the median preoperative grade of io overaction was 3.5 ( ranging from 3 to 4 ) , which decreased to 0 ( ranging from 0 to 2 ) postoperatively ( p < 0.05 ) . no significant change was observed in all parameters 3 months postoperatively ( p > 0.05).conclusion : in this study , no significant effect on lower lid configuration and function was observed following io anterior transposition in which the disinserted muscle was placed posterior to inferior rectus insertion .

idiopathic macular epiretinal membrane ( ierm ) is a relatively common disorder , with an incidence reaching 12% in those older than 70 years . on one hand , ierm seems to begin with microfractures in the inner retina after posterior vitreous detachment , while , on the other hand , it seems to occur when the external layer of the posterior vitreous cortex remains attached to the macula . ierm can vary from a single layer to a thick , multilayer fibrocellular proliferation shrinking the retinal surface . although patients with ierm can be asymptomatic at the beginning , they may complain of various degree of visual symptoms : distortion of lines ( metamorphopsia ) , decreased visual acuity , macropsia , micropsia , and monocular diplopia . in symptomatic patients , the surgical removal of the epiretinal membranes with pars plana vitrectomy ( ppv ) is the gold standard surgical procedure [ 3 , 4 ] . , it could be advisable to remove ilm to reduce erm recurrence by eliminating the scaffold for the proliferation of fibrocellular tissue . on the contrary , liu et al . reported that ilm + erm peeling compared to erm peeling alone , achieved better best - corrected visual acuity ( bcva ) 12 months after surgery but not after 18 months , showing that a longer follow - up would be advisable . quality of life , contrast , and color sensitivity are becoming useful parameters in the workup of patients affected by ierm , together with visual acuity and retinal morphology . microperimetry provides information on foveal fixation , macular sensitivity , and depth of central macular defects and is gaining interest in the assessment of various retinal diseases [ 612 ] . microperimetry , before and after ierm surgery , can help the surgeon in evaluating which kind of patients could benefit from surgery and what could be their prognosis . moreover , thanks to the autotracking system that corrects involuntary eye movements and the possibility to do follow - up examinations , it allows a greater reliability and reproducibility of the tests than automated perimetry [ 13 , 14 ] . long - term follow - up is a useful tool to evaluate the effectiveness of a treatment , especially when a total consensus about the timing of a surgical procedure is still not available . aim of the study was to investigate the potential recovery of retinal functions assessing the microperimetric outcomes in patients affected by ierm and cataract who underwent 25-gauge ppv with ilm peeling combined with phacoemulsification and intraocular lens ( iol ) implantation in a long - term follow - up . this interventional open label study has been approved by the local institutional ethics committee and review board and registered on clinicaltrials.gov ( number nct01771939 ) . the research adhered to the tenets of the declaration of helsinki and written informed consent was obtained from all patients before participation in the study . from october 2009 to july 2010 , 30 eyes of 30 consecutive patients affected by idiopathic epiretinal membranes and various degree of cataract were recruited for the study . inclusion criteria were ierm clinical finding , macular thickness > 250 m as measured by spectral - domain oct ( sd - oct , rtvue 100 , optovue , fremont , ca ) , presence of metamorphopsia at the amsler grid chart , and a visual acuity loss of 2 snellen lines in the last six months . exclusion criteria were glaucoma , corneal or lens opacities that precluded an acceptable retinal visualization , ocular axial length > 25 mm ( measured with a - scan biometry ) , epiretinal membrane secondary to trauma or vascular diseases , any macular degeneration , diabetic retinopathy , and/or previous ophthalmic surgery . all patients underwent a routine ophthalmic examination ( before and at 1 , 7 , 30 , 90 , 180 , and 360 days after surgery ) including slit - lamp biomicroscopy , bcva with the early treatment diabetic retinopathy study ( etdrs ) score at 4 meters , dilated fundus examination , and intraocular pressure measurement using goldmann tonometry . oct examination calculating central retinal thickness ( crt ) in the central mm using the macular map 5 5 mm ( mm5 ) and microperimetry with the mp1 ( nidek technologies , padova , italy ) were performed before surgery and at 90 , 180 , and 360 days after surgery . patients were called back to our center four years after the intervention to assess long - term functional and morphological outcomes . an expert vitreoretinal surgeon ( mdv ) performed all surgical procedures . after the insertion of three 25-gauge cannulas , through a 2.75 mm clear - cornea incision , phacoemulsification of the lens was performed . a foldable intraocular lens ( iol ) akreos ao ( bausch and lomb , rochester , the core vitrectomy was performed with the accurus machine 25 g+ ( alcon laboratories , fort worth , tx , usa ) . the posterior hyaloid membrane , if not spontaneously detached , was dyed with micronized triamcinolone acetonide ( ivt , bioos , italy ) , separated by aspiration , and removed . after the extension of vitrectomy to the ora serrata the membraneblue - dual dye ( dorc , zuidland , netherlands ) was used in order to peel the erm and the ilm within the vascular arcades , with a 25-gauge micro forceps ( alcon laboratories ) . a second stain with membraneblue - dual dye was applied to check whether the ilm peeling was completed . an accurate inspection of the peripheral retina and the photocoagulation of eventual retinal holes , tears , or rhegmatogenous degenerations was followed by the exchange of the balanced salt solution ( bss ) with filtered air and cannulas removal . tobramycin 0.3% and dexamethasone 0.1% eye drops were prescribed 3 times a day for a month after surgery . patient sat in front of the mp1 with the head carefully aligned in the chin rest and against the forehead strap . all subjects underwent the exam under dim light conditions with dilated pupil in the study eye . stimulus size was goldmann iii white spot , with a stimulus duration of 200 ms . threshold strategy was hfa 4 - 2 , and background luminance was 1.27 cd / m ( 4 asb ) . stimulus attenuation ranged from 0 db that represents the instrument 's maximum stimulus luminance to 20 db that represents the minimum stimulus luminance . the automatic eye tracker was used to compensate eye movements and to calculate horizontal and vertical shifts relative to a reference frame during the examination . the recorded fixation points were classified into three categories for fixation stability analysis ( stable , relatively unstable , and unstable ) . fixation was regarded as stable if more than 75% of the fixation points were inside the 2 diameter circle , as relatively unstable if < 75% were inside the 2 diameter circle but more than 75% inside the 4 diameter circle , and as unstable if < 75% were inside the 4 diameter circle . mean sensitivity ( ms ) , mean defect ( md ) , and the total number of absolute scotoma locations ( points with a threshold value of 0 db ) in the 10 central area were evaluated . mean retinal sensitivity is the arithmetic mean of all the measured absolute thresholds expressed in db ; mean retinal defect is the arithmetic mean of all local defects , including the values above the upper limits ( expressed in db ) . secondary outcomes were the changes in bcva , crt , fixation stability at 2 and 4 , and frequency of microscotomas in the 10 area . statistical analysis was carried out with analyse - it statistical software for microsoft excel ( version 2.26 ; analyse - it software , leeds , uk ) . differences in bcva , crt , and microperimetry values before and after surgery were determined with the wilcoxon signed - ranks tests . all patients completed the 1-year follow - up visit , whereas 23 of them ( 76.6% ) completed the 4-year follow - up . 7 patients were unable to attend the last follow - up visit : 3 had moved to another city , 2 were unable to come to our center , and 2 of them died . in the 23 patients who completed the 4-year follow - up , no significant differences at all study visits no significant intraoperative complications were recorded . in one case ( 3.3% ) , a laser photocoagulation was required due to a little iatrogenic hole beyond the vascular arcades , without consequences for the macular function or the visual acuity . 19 patients ( 63% ) developed posterior lens capsule opacity and underwent yag laser capsulotomy before follow - up exams . preoperative mean visual acuity significantly improved ( p < 0.01 ) after surgery at both 1 and 4 years . the highest gain in mean visual acuity was documented at 4 years although no significant differences were found between 1 year and 4 years ( p = 0.08 ) . compared to baseline , at one and 4 years , 16/30 ( 53.3% ) and 15/23 patients ( 65.2% ) presented a gain in visual acuity > 2 etdrs lines , respectively . mean bcva change was of 3.1 etdrs lines at one year and 3.3 etdrs lines at 4 years . preoperative mean crt significantly changed ( p < 0.01 ) after surgery at both 1 and 4 years . baseline mean value was 381.22 69.86 m , while at one and four years 293.71 47.66 m and 280.74 39.57 m were , respectively , measured . in one patient , the crt increased ( 31 m at one year and 18 m at 4 years ) probably due to preoperative borderline crt value ( 252 m ) . no significant changes were observed in mean crt values between 1 and 4 years ( p = 0.08 ) . significant differences ( p < 0.01 ) were found between preoperative and postoperative data at one and four years for both mean retinal sensitivity and mean defect ( figure 1 ) . at baseline , one year , and four years the mean retinal sensitivity in the 10 central area was 10.48 4.17 db , 12.33 3.66 db , and 14.18 3.46 db , respectively . at baseline , one year , and four years the mean retinal defect in the 10 central area was 9.18 4.40 db , 7.49 3.31 db , and 4.66 2.85 db , respectively . significant differences were found in ms and md between one and four years after surgery ( p < 0.001 ) . no significant differences in fixation stability in the central 2 and 4 were found at all visits . surgical approach in symptomatic patients with ierm showed good results in terms of visual acuity and retinal function recovery with minimal surgical complications and no recurrence of pathology . the application of dyes during vitreoretinal surgery improved visualization of erm and the vitreoretinal interface . the toxic effect of dyes used during the peeling can not be excluded . however , trypan blue and brilliant blue g used in this study are recognized safe staining agents with no or minimal toxic effects on retina at the concentrations used . when patients present a certain degree of cataract , the association of ppv with cataract surgery enables a better visualization of the retina . moreover , ppv in phakic eyes determines a progression of nuclear sclerosis , and , after vitreoretinal surgery , phacoemulsification is more difficult and with a greater rate of complications [ 16 , 17 ] . our patients showed a significant and early improvement of functional outcomes and a reduction of crt at oct , as reported in the literature [ 1820 ] . although after ierm surgery bcva continues to improve up to 2 years , best values are reached at about 1 year , in accordance with our findings , as no changes have been detected between 1 and 4 years [ 2123 ] . as observed by ripandelli et al . in patients who underwent ilm peeling , in our study the number of microscotomas in the 10 analyzed area improved after surgery , although not significantly . with a steady fixation stability over time , ms and md interestingly increased between 1 and 4 years , demonstrating a significant dissociation between bcva and retinal sensitivity , as has already been demonstrated in other retinal pathologies , underlying the microperimetry capability to detect even subtle changes in patients ' quality of life . as in our study combined surgery was performed in all cases , it was impossible to determine if the immediate postoperative outcome improvements were completely associated with the ierm removal or with cataract extraction or both . on the other hand , the double procedure removed an important potential confounding factor in the evaluation of the outcomes after surgery . this study has some limitations : the small sample size analyzed might have influenced the power of the study , the incomplete follow - up of some patients ( only 67% at four years ) , and the absence of a quantification of metamorphopsia ( e.g. , m - chart ) providing another quality of life parameter . in conclusion , microperimetry proved an effective diagnostic tool in evaluating subtle changes in retinal function , undetectable with a visual acuity exam . long - term follow - up after vitreoretinal surgery would be advised to reveal changes in retinal sensitivity affecting patients quality of life . the use of high definition imaging techniques to analyze further aspects of this pathology such as correlation between long - term anatomical changes and microperimetric data are recommended .

purpose . to investigate retinal function using microperimetry in patients affected by idiopathic epiretinal membrane ( ierm ) and cataract who underwent combined surgery : 4-year follow - up . design . prospective , interventional case series . methods . 30 eyes of 30 consecutive patients with ierm and age - related cataract underwent 25-gauge vitrectomy and cataract surgery . at baseline , 90 and 180 days , and 1 and 4 years , we examined retinal mean sensitivity ( ms ) , retinal mean defect ( md ) , fixation stability , and frequency of microscotomas using mp1 microperimetry . best - corrected visual acuity ( bcva ) and central retinal thickness ( crt ) using a spectral domain optical coherence tomography ( sd - oct ) were also performed . results . all patients completed 1-year follow - up , while 23 patients reached last follow - up . baseline ms and md ( 10.48 4.17 and 9.18 4.40 db ) significantly changed at one year ( 12.33 3.66 and 7.49 3.31 db , p < 0.01 ) , at four years ( 14.18 3.46 and 4.66 2.85 , p < 0.01 ) , and between one and four years ( p < 0.01 ) after surgery . compared to baseline , crt and bcva significantly changed at one year and remained stable at four years . no variations were observed in fixation stability and frequency of microscotomas compared to baseline . conclusions . long - term follow - up using microperimetry seems useful to evaluate patients after ierm surgery : retinal sensitivity changes even when bcva and crt remain stable .

a cross - sectional , questionnaire - based survey was conducted among internship students attending the department of community and preventive dentistry in faculty of dentistry , benghazi , libya , between july and october 2012 . surveying new dental graduates is a popular method used to assess their competencies at the time of graduation ( 10 , 11 ) . recently the number of dentists has dramatically increased in libya with around 350 new dentists expected every year and thirty trainers are anticipated at the department of community and preventive dentistry on a monthly basis . a total of 125 internship students were invited to participate in this survey , of which 108 participants had completed information on all the variables selected for analysis ( 75% ) . this research has been conducted in full accordance with the world medical association declaration of helsinki . a self - administrated questionnaire was used to collect data , which was distributed in - person on the last day of the training month and collected the next day . the participants were asked to provide information on their demographics ( sex and age ) and their performance in the final academic year ( acceptable , good , very good , and excellent ) . information that could identify the participant 's identity was not requested , so that participants are encouraged to provide truthful information . a three point likert scale ( agree , not sure , disagree ) of nine qualities of preventive dentistry was used to assess the attitudes towards preventive dentistry . the qualities of preventive dentistry were : scientific , valuable , essential , useful , reputable , attractive , easy , and beneficial ( 12).yes or no questions were used to assess the perceived competence of providing preventive dental care . the interns were asked whether or not they felt themselves competent in performing the following preventive dental practices : advice to quit smoking , dietary counselling , topical application of fluoride , placement of sealant in the molars , oral hygiene instructions / oral health education , and caries risk assessment . the questionnaire was piloted for clearance and understanding among a group of 15 internship students . data were analysed using the statistical software spss , version 21.0 ( armonk , ny : ibm corp . ) . information regarding the participants grades in the final year was recoded into acceptable and good for those who have good , very good , or excellent . frequencies and percentages were used to participants responses to attitude statements and perceived competence questions . chi - square test was employed to test the differences in frequencies between the participants according to their gender and academic grade in the final year , in terms of positive attitude and perceived competence . data from 108 libyan dental graduates were analysed for this study , out of which 64% of them were females and 42.1% of them passed the final year with grade : acceptable . table 1 shows the percentage of participants who were positive towards the different qualities of preventive dentistry . the most acknowledged aspects of preventive dentistry were being useful and essential to the community ( 95.4 and 90.8% , respectively ) . on the other hand less than half of the participants thought of preventive dentistry as reputable , attractive , or beneficial ( 22.2 , 29.6 , and 39.8% , respectively ) . comparison of attitudes by participants sex and final year grades revealed no statistically significant differences between the study 's subgroups . percentages of students with positive attitudes towards preventive dentistry chi - squared test was used to compare study subgroups . the percentages of participants who perceived themselves competent in performing preventive dental practices are presented in table 2 . while the proficiency in providing oral hygiene instructions was expressed by most of the participants ( 95.4% ) , topical fluoride application , diagnosis of initial caries , and pit and fissure sealants were the least grasped skills ( 12.0 , 22.2 , and 25.0% , respectively ) . females were more confident than males in practicing the skills of diagnosing initial dental caries and applying pit and fissure sealant ( p=0.043 and 0.01 , respectively ) . similarly , a larger number of participants who have had grade good or higher considered themselves competent in performing preventive resin restoration , and pit and fissure sealant procedures ( p=0.022 and 0.004 , respectively ) . percentages of students who perceived themselves competent in practising preventive dentistry chi - squared test was used to compare study subgroups this study shows that the currently implemented training programme in community and preventive dentistry in benghazi dental school does not adequately prepare dentists to fulfil their role in providing a prevention - oriented dental service . the findings of this study are in accordance with other studies regarding the role of dental education in preventive dentistry ( 13 , 14 ) , all of which have blamed undergraduate curricula for inadequate preparation of dentists . the attitude of dental practitioners towards preventive dentistry is an important factor that can influence their decision to apply preventive dental care ( 9 ) and may potentially affect their ability to motivate patients to receive preventive care measures ( 15 ) . in our study , although the majority of dental graduates appreciated the merits of preventive dentistry at the community level , it was considered less reputable , attractive , and beneficial to the dentists . these results mirror previous finding among iranian senior dental students and dental practitioners ( 12 , 16 ) . they might be attributed to the low monetary income from the provision of preventive dental care which may reduce the practitioners interest in providing such care . previous research has shown that dentists refrain from providing preventive care because of insufficient payment ( 17 , 18 ) . moreover , a recently published systematic review has concluded that despite the questionable quality of the included reports , the evidence that emerged seems to indicate that further education and training coupled with a fairer pay scheme would be a reasonable approach to change the balance in favour of the provision of dental caries preventive measures by dentists ( 19 ) . the reported attitude in this study could be a reflection of the nature of dental services , which has long been focusing on restorative treatment or tooth extraction for the management of existing disease despite the fact that most oral diseases are highly preventable ( 18 , 20 , 21 ) . however , further research is needed to understand how such an attitude has been adopted . it is interesting to note that , unlike previous research in this area in which females were more positive towards preventive dentistry than males ( 12 , 16 ) , the gender difference of our study participants did not appear to influence attitudes towards preventive dentistry . similarly , no statistically significant differences were observed in attitudes when compared by participants academic performance . however , socioeconomic background may explain the different results found in this study compared to other groups of dental graduates . apart from oral hygiene instructions , the majority of the participants in this study do not feel themselves competent in applying preventive dental care . these findings are inconsistent with previous reports in this field . according to american dental education association ( adea ) in 2008 , most of the senior students consider themselves prepared to provide preventive dental care ( 22 ) . holmes et al . surveyed the graduated alumina and found them particularly competent in treatment and prevention of dental caries ( 23 ) . another study among mongolian dental students has reported that 6894% were at least quite competent in practicing preventive dentistry ( 24 ) . considering the shortage of teaching staff available for both lecturing and clinical training in preventive dentistry , as well as limited facilities and the huge number of dental students ( over 300 in a building meant to host maximum of 50 ) , this finding could be a result of the obvious discrepancy between the resources and student numbers which has led to insufficient education and training in preventive dentistry . previous research has shown that low priority of preventive dentistry in dental education is perceived by dentists as a major barrier to the provision of preventive dental care ( 15 ) . another possible explanation could be that students are not interested in learning clinical skills related to preventive dentistry . this study shows that the majority of participants do not consider preventive dentistry attractive , reputable , or beneficial for dentists . in addition , comparison by sex and academic performance in the final year shows that females and those with high academic grades are more likely to rank themselves as competent in applying preventive measures . this result could be affected by a larger number of female participants , but previous reports have shown that females were more positive about preventive dentistry than their male peers ( 12 , 16 ) . knowledge and attitude are considered factors that can predispose to action . however , dental practice is not all about science ; additional cultural , social , and financial elements can affect the provision of preventive measures ( 25 ) . in the light of recommended shift from surgical intervention to the cost - effective prevention efforts ( 26 ) , the present study 's findings concerning dental students in such developing country are especially noteworthy . the dental education community and stakeholders in academic institutions are required to take immediate as well as long - term actions to supply the community with dental professionals who have the necessary attitude and competence to meet the oral health needs of the public . adoption of more effective education and training strategies , continuing education programmes , and re - assessment of undergraduate curriculum contents , as well as teaching strategies would help improve the current situation . first , the findings of this study are based on a self - reported questionnaire , which , as in any other similar research , may be biased by faking the responses and social desirability by the participants . second , this study was based on a relatively small convenience sample from benghazi and hence may not represent libya as a whole . the timing of this study , during the summer when there were no undergraduates , could be considered as a third limitation because during this period , dental trainers undertake more training hours than any other time in the year . on the other hand , conducting the study during this period could be an advantage as the training hours were similar for all the participants . further research is needed to explore in - depth opinions of dental students regarding the facilitators and barriers of training in preventive dentistry as well as their view of future careers . a qualitative approach using observation of clinical training as well as content analysis of dental curriculum and its goals and structure this study highlighted that the currently implemented undergraduate education programme in benghazi dental school does not provide dentists with the required attitude and skills to fulfil their role in providing preventive - oriented health services . more efforts are required to tackle this problem and to provide more effective undergraduate education , as well as continuing dental education programmes . the authors have not received any funding or benefits from industry or elsewhere to conduct this study .

backgrounda previous study has shown that dental practitioners in benghazi believed that the less prevention - oriented education system is one of the barriers to applying preventive dentistry.objectiveto assess attitudes and perceived competence of the dental graduates in benghazi towards prevention and early management of dental caries.methodsa cross - sectional , questionnaire - based survey was conducted among internship students attending the department of community and preventive dentistry in faculty of dentistry , benghazi , libya . the participants were asked to provide demographic information , to respond to statements about their attitudes towards preventive dentistry , and to answer questions regarding their perceived competence in applying preventive dentistry procedures.resultsdata from 108 libyan dental graduates were analysed for this study , of which 64% of them were females and 42.1% of them passed their final year with grade : acceptable . the most acknowledged aspects of preventive dentistry were being useful and essential to the community ( 95.4 and 90.8% , respectively ) . the percentage of participants expressing a proficiency in providing oral hygiene instructions was the highest ( 95.4% ) . there were differences between study subgroups in their perceived competence of preventive dental practices by gender and academic performance ( p0.05).conclusionthis study highlighted that the currently implemented undergraduate education programme in benghazi dental school does not provide dentists with the required attitude and skills to fulfil their role in providing preventive - oriented health services .

diabetes mellitus type 2 ( dm2 ) is a disease often related to poor lifestyle choices resulting in hyperglycemia ; it affects nearly 10% of the entire us population , including more than 25% of seniors . conventional medicine views dm2 as a chronic , irreversible disease and focuses on disease management utilizing insulin - sensitizing agents , such as biguanides , and oral hypoglycemic agents , such as sulfonylureas . naturopathic approaches for dm2 focus on disease management utilizing motivational interviewing to empower patients to make dietary and lifestyle changes , while employing both conventional and natural agents , such as chromium and gymnema sylvestre , for their insulin sensitizing - effect . although both conventional and naturopathic physicians often recommend dietary and lifestyle modification in the treatment of dm2 , there is a stark difference in the amount of time spent consulting with the patient on the dietary recommendations and the frequency of follow - up visits that allows for more compliance via patient support , empowerment , and education with naturopathic physicians . previous studies have shown that lifestyle modification is superior to metformin at restoring normoglycemia in patients who were at high risk for diabetes . the following case reflects these findings and demonstrates the need for focusing treatment and prevention of diabetes on lifestyle modification while utilizing both natural and conventional treatments to improve clinical outcomes . a 56-year - old caucasian male presented with a diagnoses of hypertension , hyperlipidemia , and fatty liver disease . his 30-year history of hypertension was linked to anxiety , and he was currently employed in a high - stress job . past medical interventions included carvedilol ( 6.25 mg ) and lisinopril / hydrochlorothiazide ( 20/12.5 mg ) , both of which he voluntarily stopped using approximately 6 months before starting naturopathic treatment . blood pressure at time of intake was 173/96 mm hg . prior to seeking naturopathic treatment , the patient had been told by conventional doctors to decrease alcohol consumption and to improve diet and exercise , but he was unable to make these lifestyle changes . metformin and db-7 nutritional supplement ( figure 1 ) were both used to manage dm2 by improving insulin sensitization . to attempt reversal of dm2 , weight loss via diet and liver and gallbladder cleansing via cholagogue herbs in addition , motivational interviewing was used to empower the patient to move away from a standard american diet high in processed foods , alcohol , and sugar , to a whole - foods , high - vegetable diet with a maximum of 20 g per day net grain carbohydrates , which was crucial for proper glucose control . each visit with the naturopathic physician typically lasted approximately 1 hour . at the initial visit , the physician spent 20 minutes explaining the diet and provided a handout with the complete guidelines , resources , and recipe information . at each follow - up visit , a period of 10 minutes was spent discussing diet , exercise practices , and goals . the physician had the patient complete a 7-day diet diary and glucograph upon initiating the diet ; the patient measured his blood glucose level on waking , 1.5 hours after each meal , and before bed . this intervention was designed to help the patient understand the effects of various foods on his blood sugar and allowed for personal accountability to occur . in addition to dietary recommendations , the patient was encouraged to increase exercise to 20 to 30 minutes per day . supplementation included db-7 nutritional supplement ( rx vitamins inc , elmsford , new york ; 1 capsule 3 times daily with meals ) , opti lipotropic herbal supplement ( eclectic institute , sandy , oregon ; 2 capsules twice daily ) , alpha lipoic acid ( 300 mg / d ) , lypo - spheric vitamin c : ( livon labs , henderson , nevada ; 1000 mg twice daily ) , and rauwolfia tincture ( 10 drops 2 - 3 times / d ) ( see figure 1 for ingredient lists ) . laboratory testing was done at the onset of treatment and following 3 months , 7 months , and 10 months of treatment . figures 2a and 2b demonstrate the levels of dm2 markers of fasting glucose and glycated hemoglobin ( hba1c ) , respectively . after 7 months of treatment , the patient 's fasting glucose went from 168 mg / dl to 97 mg / dl and hba1c went from 7.7% to 5.0% . at the 7-month mark , the patient no longer met diagnostic criteria for dm2 , so both the db-7 and metformin were discontinued while the patient continued the diet and lifestyle recommendations . as shown in figure 2b , after 3 months without taking both db-7 and metformin , the patient 's hba1c remained within the normal range and slightly improved from 5.0% to 4.7% . figure 4 demonstrates the improvement of his fasting lipid profile during the first 7 months of treatment . the total cholesterol decreased from 249 mg / dl to 196 mg / dl ; triglycerides decreased from 219 mg / dl to 76 mg / dl ; and low - density lipoprotein ( ldl ) decreased from 153 mg / dl to 104 mg / dl . the most significant improvement in his lipids was demonstrated by the dramatic decrease in triglycerides , which was likely directly related to his changes in dietary carbohydrate intake . figure 5 shows a timeline illustrating the treatment alongside the laboratory results during the 10 months of treatment . fasting glucose and hemoglobin a1c ( hba1c ) results over the treatment period . figure 2a illustrates the patient 's fasting glucose levels ( mg / dl ) over a 7-month period . figure 2b illustrates the patient 's hba1c levels ( percentage ) over a 10-month period . this figure illustrates the patient 's alanine aminotransferase ( alt ) and aspartate aminotransferase ( ast ) levels ( iu / l ) over a 7-month period . the patient had a 10-year history of fatty liver disease with elevated liver enzymes previous to starting treatment . this figure illustrates the patient 's total cholesterol , triglycerides , and low - density lipoprotein ( ldl ) levels ( iu / l ) over a 7-month period . timeline of treatment recommendations , clinical findings , and lab results over the 10-month treatment period . lab values followed by indicate values that meet diagnostic criteria for dm2 ( fasting glucose and hba1c ) , hyperlipidemia ( tot . abbreviations : alt , alanine aminotransferase ; ast , aspartate aminotransferase ; fast gluc , fasting glucose ; hba1c , hemoglobin a1c ; tot . chol , total cholesterol ; ldl , low - density lipoprotein ; trigly , triglycerides ; vldl , very low - density lipoprotein . this case documents the results of an integrative approach to the treatment of dm2 using a short - term course of herbal and nutritional supplementation and metformin in conjunction with a long - term implementation of a low - carbohydrate diet and regular exercise . the patient was able to reverse the diagnosis of dm2 during treatment as his biological markers fell well within the normal range for the last 3 months of treatment . when approaching a patient with dm2 , naturopathic physicians typically focus on treating the whole person through diet , exercise , and insulin - sensitizing and antioxidant supplementation . dietary changes are often difficult for the patient to implement , so the physician practiced docere or to teach , 1 of the 6 main philosophies of naturopathic doctors , by taking the necessary time to educate and motivate the patient toward proper dietary practices . the amount of time the naturopathic physician spent with the patient was approximately 60 minutes per visit , which is up to 5 times longer than conventional doctors . by employing motivational interviewing strategies , the naturopathic physician was able to inspire the patient to become an active participant in his health improvement . through the interview process , the physician and patient were able to explore the patient 's motivations for drinking , which revolved around a difficulty with dealing with work - related stress . the physician was able to discuss the risks vs benefits with the patient of continued drinking vs stopping in terms of his diabetes but also with regard to his previously diagnosed fatty liver disease . one of the central themes of motivational interviewing is that if patients make the case for positive life change , they are more likely to follow through , and this was apparently the case here . patient empowerment and self - responsibility must be further studied , as they may be the most important aspects of successfully reversing chronic disease . the alpha lipoic acid and lypospheric vitamin c may have contributed to insulin sensitization , which along with exercise and low - carbohydrate foods helped facilitate the patient 's weight loss . these substances are also antiinflammatory , which is paramount in effectively treating diabetes since systemic inflammation is a major contributor to excess weight gain and leads to micro- and macrovascular complications . for this patient , utilizing frequent follow - up and laboratory testing helped support the lifestyle changes needed to improve his dm2 . the improvements in liver function tests were most likely due to consuming less alcohol and may have been supported by the low - carbohydrate , whole - foods diet and the opti lipotropic and vitamin c supplements . proper liver functioning is key to proper glucose control via glycogen storage , gluconeogenesis , and glycogenolysis . by addressing liver function through diet and lifestyle changes , supported by dietary supplementation , this case study focused on a low - carbohydrate , whole - foods diet to improve dm2 , which is supported by previous research . in comparison , various diets for treating dm2 including the mediterranean and low - fat vegan diets have also been shown to have efficacy . previous research has shown that reversal of dm2 is possible with dietary modifications , although 1 study used a 600 kcal / day diet , which would be very difficult for most patients to follow . we believe this case report documents that less intensive dietary changes can be recommended to patients with good clinical results as long as adequate follow - up and accountability are established and maintained throughout treatment . the significance of lifestyle modifications including diet and exercise is well documented by figure 2 and figure 5 , which show that the patient 's hba1c continued to improve after pharmaceutical and nutritional supplementation were discontinued . this has enormous consequences for health economics , preventive health strategy , and health policy . in conclusion , we believe that conventional practice management guidelines for dm2 should be adjusted to shift the emphasis of treatment from medication to lifestyle modifications via motivational interviewing and patient education .

this case report demonstrates a successful approach to managing patients with type 2 diabetes mellitus ( dm2 ) . botanical herbs ( including gymnema sylvestre ) and nutrients ( including alpha lipoic acid and chromium ) were used alongside metformin to help improve insulin sensitization ; however , the greatest emphasis of treatment for this patient centered on a low - carbohydrate , whole - foods diet and regular exercise that shifted the focus to the patient 's role in controlling their disease . research on dm2 often focuses on improving drug efficacy while diet and lifestyle are generally overlooked as both a preventive and curative tool . during the 7 months of treatment , the patient 's hemoglobin a1c and fasting glucose significantly decreased to within normal ranges and both cholesterol and liver enzyme markers normalized . a significant body of evidence already exists advocating for disease management using various diets , including mediterranean , low - carb , and low - fat vegan diets ; however , no clear dietary standards have been established . this study supports the use of naturopathic medicine as well as dietary and lifestyle changes to develop the most efficacious approach for the treatment of dm2 .

during the past three decades , fertility preservation has become an important issue in cancer patients management . survival rates have improved dramatically in childhood cancers and also in young women who undergo cancer treatment , leading to long term cancer survivors who are affected by iatrogenic infertility and premature ovarian insuffiency . abdominal radiotherapy , total body irradiation , and chemotherapy regimens all lead to ovarian damage consequently leading to infertility . though disease remission is the first goal of cancer treatment , greater attention is being focused on the delayed effects of cancer treatment and towards safeguarding future fertility . survival rates per thawed embryo range between 35 - 90% , implantation rates between 8 - 30% and cumulative pregnancy rates > 60% . oocyte cryostorage is considered as an important tool for fertility preservation as no surgery is required and minimally invasive ovarian stimulation protocols are available . there are certain challenges faced in breast and endometrial cancer patients as conventional ovarian hyperstimulation regimens in in vitro fertilization ( ivf ) cycles result in estradiol levels which may be 10 fold higher than peak estradiol levels seen in natural cycles , and thus may not be recommended in breast cancer patients. even though tamoxifen results in peak estradiol levels , it can block the effect of supraphysiological level on breast tissue and inhibits the growth of breast tumors by competitive antagonism of estrogen at its receptor site . endometrial cancer patients can not be given tamoxifen for ovarian stimulation since it has a stimulatory effect on endometrium , for such patients aromatase inhibitors can be used for ovarian stimulation , in vitro fertilization ( ivf ) and embryo cryopreservation . aromatase inhibitors have shown to benefit in ovulation induction alone or in combination with follicle stimulating hormone ( fsh ) . mature and immature oocyte cryopreservation : since embryo cryopreservation may not be an option for single women , freezing of mature and immature oocytes can be considered instead . however , early results with oocyte cryopreservation have been disappointing with low survival , fertilization and pregnancy rates after ivf of thawed oocytes . survival and fertilization rates of frozen - thawed mature oocytes varied between 25 - 95% . review of recent data revealed a mean survival rate of 47% , mean fertilization rate of 52.5% , and a mean pregnancy rate per thawed oocyte of 1.52% . cryostorage induced injuries on human oocytes include ice crystal formation , osmotic stress and toxicity of cryoprotectant agents , zona pellucida cracking , mitochondrial shrinkage and alterations in microfilaments . the main consequences of freezing / thawing procedures involve organelle displacement , mitochondrial disruption , vacuolization of the cytoplasm , loss of spindle cell polarity with predisposition to an altered chromosomal alignment . cryobiology aims at minimizing these harmful effects and two well - established laboratory protocols have been proposed . the slow freezing protocol and the vitrification protocol . selection of candidates for fertility preservation is crucial in order to offer the best suitable technique for each patient . the procedure should be safe , having a good chance of oocyte retrieval and a minimal risk of growth of the preexisting neoplasm . it should also be quick so that there is no delay in initiation of cancer therapy . oocyte cryopreservation is the best technique to preserve fertility of women without an established partner and may be preferable to ovarian tissue freezing since it obviates the need of surgery . storage of oocytes in women above the age of 40 years results in a very poor chance to get a pregnancy in the future . besides age , factors such as antral follicle count , hormonal levels like follicle stimulating hormone ( fsh ) and anti - mullerian hormone ( amh ) need to be considered . the procedure involves a controlled ovarian hyperstimulation with exogenous gonadotrophins that lead to supraphysiological and high levels of serum estradiol . type and stage of neoplastic disease and patients overall health status influence the feasibility and selection of protocols of ovarian stimulation . this procedure may not be suitable for prepubertal girls since their hypothalamic , pituitary , ovarian axis is not fully developed . ovarain cortex ablation and cryostorage with subsequent autografting is an option available to prepubertal girls , however it is still experimental with limited results . the growing body of literature shows encouraging results of oocyte in vitro maturation ( ivm ) followed by vitrification for cryostorage . this option consists in the possibility of retrieving immature oocytes from unstimulated preantral follicles , which are arrested in the prophase of first meiotic division . the technique is safe and effective for all oncological patients as no hormonal stimulation is needed and is not limited by any time restriction . the effectiveness of the procedure appears to be higher when immature oocytes are first matured in vitro and then frozen . some data also suggest that immature oocytes could be less sensitive to cryodamage than mature oocytes since their nuclear apparatus was not fully developed and after thawing could be matured in vitro to metaphase ii . cryopreservation of immature oocytes should be considered in oncological patients who can not undergo hormonal stimulation with high peak estradiol concentrations . slow freezing and rapid thawing was the first cryostorage protocol adopted for oocytes in ivf laboratories and was originally introduced with the aim to preserve supernumerary embryos obtained from assisted reproduction procedures . it is considered the gold standard technique for oocyte cryopreservation for years with survival rates of 60 - 80% . however , few authors have observed a detrimental effect of high sucrose concentration on oocyte cytoplasm organelles and have proposed alternate freezing techniques and timing schedules . clinical reports on slow freezing show a pregnancy rate ranging between 13 - 20% ( pregnancy / embryo transfer ) and implantation rates still low in comparison to those in fresh cycles . grifo and noyes compared slow freezing to vitrification on sibling oocytes showing similar results in terms of survival , but higher fertilization and blastocyst formation rates using the former . the scientific basis of vitrification consists in the ultrarapid freezing of cells , whose intra- and extracellular environment turns into a glassy like state . vitrfication combines two different biophysical processes : a preliminary equilibration step , in which oocytes are exposed to low concentrations of cryoprotectants to allow water outflow , and a subsequent vitrification phase in which cells undergo a high osmotic gradient that completes cell dehydration . in this condition , the oocytes can be directly merged into liquid nitrogen and then subsequently stored . the cryoprotectants used during vitrification are the same as slow freezing such as ethylene glycol ( eg ) , sucrose , 1,2 propanediol ( proh ) and dimethyl sulphoxide ( dmso ) but are more concentrated . successful vitrification occurs when samples are loaded in a minimal fluid volume and then frozen / thawed at an extremely fast rate ( 1500 - 2000c ) . although no cross contamination between liquid nitrogen and stored oocytes have been reported to date , closed systems may provide a safer and more effective vitrification procedure . oocyte spindle repolymerization occurs within an hour of warming suggesting that the ultrastructure of these gametes is better preserved by vitrification than slow freezing and metabolomic profiling of vitrified oocytes is comparable to fresh eggs . data on the clinical use of vitrified eggs in routine ivf show that pregnancy rates can be comparable to those achieved with fresh oocytes . studies which have compared vitrification and slow freezing have reported implantation and pregnancy rates higher with vitrification but the number of observed cases have been very low . though significant improvements have been achieved in the clinical effectiveness of oocyte freezing and thawing techniques , further studies need to be done to establish an optimum protocol for oocyte storage so that maximum women can be benefitted .

preservation of fertility is an important issue in the management of young cancer patients . though embryo cryostorage is a well - established procedure , it can only be availed by couples . recent studies have indicated increasing success rates with mature and immature oocyte cryopreservation . cryostorage induces injuries on the human oocytes which can be minimized by slow freezing and vitrification . selection of candiidates is crucial so that the most suitable technique can be offered without any delay in initiation of cancer therapy . factors affecting suitability are age of patient , assessment of ovarian reserve , hormonal status and type and stage of neoplastic disease . encouraging results have been obtained with oocyte in vitro maturation ( ivm ) followed by vitrification for cryostorage . data on the use of vitrified eggs in routine in vitro fertilization ( ivf ) show that pregnancy rates can be comparable to those achieved with fresh oocytes .

neurofibromatosis type 1 ( nf1 ) or von recklinghausen 's disease is an autosomal dominant disorder , the cardinal feature of which is the development of multiple peripheral nerve sheath tumors called neurofibromas . other characteristics include pigmentory changes in the skin , skeletal anomalies , and learning disabilities . it is well - known that malignant tumors of the nervous system , such as malignant peripheral nerve sheath tumors , gliomas , or astrocytomas , often co - exist with nf1 or nf2 . malignant tumors unrelated to nervous system rarely co - exist with neurofibromatosis 1 or 2 , and most of such reports were cases with malignant lymphoma . there are only few cases of chronic myeloid leukemia co - existing with nf1 reported . in pediatric patients , a 40-year - old indian man presented with pain and fullness in left hypochondrium . on palpation , a huge splenomegaly was detected . total leukocyte count was more than 1.5 lac / mm . the differential count was , myeloblast and promeylocyte - 8% , myelocyte and metamyelocyte - 50% , band forms and neutrophils - 30% , basophils - 8% , and lymphocytes - 4% [ figure 1 ] . considering all these features in peripheral blood smear along with presence of splenomegaly , a diagnosis of chronic myeloid leukemia ( chronic phase ) was given . peripheral smear showing features of chronic myeloid leukemia ( leishman stain , 1000 ) patient also complained of presence of a huge mass in his lower back region . the mass was present since 15 - 20 years , which was of smaller size initially , but it has grown rapidly to reach the present size in last 6 months . he had multiple caf - au - lait spots and small swellings over trunk and limbs . on examination , the tumor was arising in lower lumbar region of back and extending up to gluteal region . grossly , the tumor measured 30 cm 12 cm 10 cm with overlying skin flap showing black discoloration . cut surface showed a whitish , firm , glistening mass with a cyst of 9 cm diameter containing hemorrhagic fluid [ figure 3 ] . sections were taken from representative areas , processed , and stained with hematoxyline and eosin for histological diagnosis . tumor mass in lower lumbar region with a caf - au - lait spot in overlying skin cut surface of tumor showing whitish , firm glistening areas and a large cyst containing hemorrhagic fluid microscopically , tumor was composed of spindle cells having short , fusiform , and rounded nuclei with inapparent cytoplasm and sheets of laminated bodies i.e. , wagner - meissner corpuscles [ figure 4 ] in a fine fibrillary collagenous matrix . the tumor also infiltrated subcutaneous fat and encircled the adnexal structures without compressing them [ figure 5 ] . the diagnosis of diffuse neurofibroma was made on the basis of these classical histological features . photomicrograph of wagner - meissner corpuscles in a fine fibrillary collagenous matrix ( h and e , 400 ) photomicrograph of tumor mass showing features of diffuse neurofibroma ( h and e , 40 ) in view of presence of multiple caf - au - lait spots and swellings all over the body , excisional biopsy of two more swellings was done , the histology of which showed classical features of usual type of neurofibroma . however , mutational analysis of nf-1 gene and fish analysis for bcr / abl translocation ( philadelphia chromosome ) for chronic myeloid leukemia ( cml ) could not be done , as these facilities are not available in our center . this patient is alive and without any recurrence at 1-year of follow - up after treatment . neurofibromatosis is divided broadly into 3 categories : ( a ) von recklinghausen 's neurofibromatosis or nf-1 , ( b ) bilateral acoustic neuroma ( nf-2 ) , and ( c ) all other neurofibromatosis , including alternate or atypical forms of the disease . it is an autosomal dominant inherited disorder with a high rate of penetrance affecting about 1 in 4000 people . neurofibromatosis type 1 has been recognized as a clinical entity for more than a century , but it is only since the nf1 gene was identified in 1990 that we have begun to understand the pathophysiology of the disorder . it is clear that nf1 has tumor suppressor function , which is involved in the formation of neurofibromas , and that it also has other important functions in the pathogenesis of non - tumor manifestations . the nf1 gene is located on the proximal long arm of chromosome 17 and is thought to be a kind of tumor suppressor gene . neurofibromin - a product of the nf1 gene - has an important role in the activation of ras protein and in controlling the proliferation and differentiation of cells . , people with nf1 are at increased risk for the development of malignancies such as leukemia , rhabdomyosarcoma , optic glioma , and brain tumors . however , the relationship of nf1 with cml has not been clarified . as per a recent report published of a adult ghanaian patient of nf1 developing cml , the authors have kept the possibility of a synergistic action between the absence of neurofibromin and the presence of the tyrosine kinase activity of the bcr / abl gene in the development of cml in these patients . there were 21 central nervous system malignancies , 6 peripheral nervous sarcomas , and 57 other cancers or sarcomas . in addition to pnsts and sarcomas , individuals with nf1 are also at higher risk for developing hematological malignancies like lymphoma , multiple myeloma , acute myeloid leukemia , chronic lymphoid leukemia , juvenile chronic myelomonocytic leukemia , and myelodysplastic syndrome . the triple association of leukemia , xanthomatous skin lesions , and neurofibromatosis 1 was first described by royer , et al . in 1958 . most of the leukemias in this study were of the juvenile chronic myelogenous type ( jcml ) . jang , et al . described a 7-year - old male child with xanthoma , nf 1 , and chronic myelomonocytic leukemia with positive family history of nf1 in mother . they suggested that the presence of xanthomas and nf1 in a young child should raise awareness of the possible development of jcml , especially in patients with family history of nf1 . reported an increased proportion of non - lymphocytic leukemia among children with nf1 and leukemia . siller , et al . conducted a population - based study and found an increased relative risk of chronic myelomonocytic leukemia , acute lymphoblastic leukemia , and non - hodgkin 's lymphoma in nf1 population . juvenile xanthogranuloma ( jxg ) , cutaneous nodules consisting of histiocytes , is found with increased frequency in children with nf1 and also has been correlated with risk of chronic myelogenous leukemia ( jcml ) in the general population . review of literature shows that most of such cases reported are in children with nf1 and jcml . however , to date , there has been only one case reported to the best of our knowledge of an adult patient with nf1 developing cml . hence , our case is a second rare case in literature showing association of nf1 and cml in an adult patient . leukemic cells from nf1 patients have loss of heterozygosity for nf1 gene , but do not have activating ras mutations in contrast with many non - nf1-associated myeloid malignancies . increased levels of ras - gtp are found in the nf1-associated leukemias , and the leukemic cells show hypersensitivity to gm - csf and other cytokines . malignancy is an important component of nf1 phenotype and one of the few life - threatening complications . furthermore , the natural history of malignancy in patients of nf1 is often different from that of similar tumor types in the general population . early diagnosis is particularly problematic since tumors usually arise from pre - existing benign lesions , and individuals with nf1 are accustomed to having lesions , for which they do not seek care . our patient responded to chemotherapy and doing well without any relapse in 1-year follow - up . it is recommended that thorough clinical examination at diagnosis and during routine follow - up should be done . although malignancies are rare in nf1 , there is an increased incidence of sarcomas and leukemias , especially in childhood . when malignancies are detected , nf1 patients should be evaluated and treated in the same manner as other patients . as nf1 patients also have an increased incidence of second malignancies , they must have long - term follow - up . the association of nf - i with hematolymphoid malignancies is known most of the cases reported jcml in children . however only one case of nf - i developing cml in adult is reported till date

neurofibromatosis type 1 ( nf1 ) represents a major risk factor for development of malignancies , particularly malignant peripheral nerve sheath tumors ( mpnst ) , optic gliomas , other gliomas , and leukemia . we report an unusual case of chronic myeloid leukemia ( cml ) , developed in a patient of nf1 . a 40-year - old indian male , clinically manifesting nf1 since his childhood , presented with huge splenomegaly . patient also had a large tumor mass arising in a caf - au - lait spot on lower back with rapid growth in last 6 months . excision of this tumor was done , and it turned out to be a diffuse neurofibroma histologically . peripheral smear was also done in view of splenomegaly , which showed features of chronic myeloid leukemia . cml rarely co - exists with nf1 , and there are a very few reports of such cases . it is important to be aware of the possibility that not only the malignant change in benign pnst is more common in these patients , but also other malignancies like cns tumors and hematolymphoid neoplasm do occur with increased frequency .

the female child is six - years - old and comes from fortaleza in the state of ceara in brazil . initial symptoms began six months ago and included fever , asthenia , and weight loss . tests findings include : cbc : normochromic and very microcytic anemia ( hb : 7.1 g ) , leucopenia ( 3,300 wbc ) , and thrombopenia ( 70,000 platelets / mm ) ; esr : 77 mm for first hour ; serology of leishmaniasis : positive ( 1/1600 using immunofluorescence and 5 archs in electrosyneresis ) ; bone marrow biopsy : the medulla is rich , but no leishmania are seen . the patient is given a meglumine antimoniate treatment with increasing doses reaching 60 mg / kg / day after three days . transient hepatic cytolysis emerges with alanine transaminasi ( alt ) and aspartate aminotransferase ( ast ) 1.5 times above upper normal limit . according to the world health organization , leishmaniasis is a poverty - related disease whose public health impact has been , until recently , grossly underestimated . the disease is caused by protozoan parasites belonging to the genus leishmania that are transmitted by the bite of a phlebotomine sandfly . there are approximately two million new cases each year 1.5 million of cutaneous leishmaniasis and 500,000 of visceral leishmaniasis or kala - azar . kala - azar is endemic to south america , east africa , the mediterranean basin , the middle east , india , and china . the cardinal sign of kala - azar is an anarchic type of fever resisting all forms of treatment . the disease always yields splenomegaly and is thought by many to produce the largest spleens in parasitology . contrary to adult manifestations , cutaneous signs such as erythematous , hyper- or hypopigmented papules and nodules of various sizes are rare in children . although not performed in the case reported , protein immunoelectrophoresis reveals hypergammaglobulinemia with an igg peak in patients with kala - azar . serological tests , which are useful for the diagnosis of kala - azar , include elisa ( enzyme linked immunosorbent assay ) , direct agglutination test ( dat ) , indirect fluorescent antibody test ( ifat ) , and the rk39 dipstick test . elisa is widely performed , particularly in epidemiological studies , because it is very simple . anemia secondary to kala - azar is aregenerative because of bone medullar parasitic invasion . even without direct evidence of leishmania , this child s poor health condition coupled with the epidemiological , clinical , and biological presentations called for immediate treatment . in brazil , side - effects of this case s treatment drug of choice , meglumine antimoniate , include the following : i ) intolerance that usually appears after the first injections and consists of fever , chills , cough , myalgia , and/or skin rash . treatment discontinuation is mandatory if such intolerance occurs ; ii ) intoxication resulting in fever , cough , skin rash , polyneuritis , hepatitis , cardiac , and renal signs . alternative treatments for kala - azar include sodium stibogluconate , amphotericin b , liposomal amphotericin b , pentamidine , and paromycin . the cardinal sign of kala - azar is an anarchic type of fever resisting all forms of treatment . the disease always yields splenomegaly and is thought by many to produce the largest spleens in parasitology . contrary to adult manifestations , cutaneous signs such as erythematous , hyper- or hypopigmented papules and nodules of various sizes are rare in children . although not performed in the case reported , protein immunoelectrophoresis reveals hypergammaglobulinemia with an igg peak in patients with kala - azar . serological tests , which are useful for the diagnosis of kala - azar , include elisa ( enzyme linked immunosorbent assay ) , direct agglutination test ( dat ) , indirect fluorescent antibody test ( ifat ) , and the rk39 dipstick test . elisa is widely performed , particularly in epidemiological studies , because it is very simple . anemia secondary to kala - azar is aregenerative because of bone medullar parasitic invasion . even without direct evidence of leishmania , this child s poor health condition coupled with the epidemiological , clinical , and biological presentations called for immediate treatment . in brazil , the etiological agent of kala - azar is leishmania donovani . without treatment , side - effects of this case s treatment drug of choice , meglumine antimoniate , include the following : i ) intolerance that usually appears after the first injections and consists of fever , chills , cough , myalgia , and/or skin rash . treatment discontinuation is mandatory if such intolerance occurs ; ii ) intoxication resulting in fever , cough , skin rash , polyneuritis , hepatitis , cardiac , and renal signs . alternative treatments for kala - azar include sodium stibogluconate , amphotericin b , liposomal amphotericin b , pentamidine , and paromycin .

we report the case of a six - year - old brazilian girl referred for splenomegaly who first presented with fever , asthenia , and weight loss . geographical location , clinical exam , and blood laboratories suggested kala - azar . serology confirmed kala - azar diagnosis , but direct evidence of the parasites was not made . a treatment by meglumine antimoniate is given under hospital surveillance for two weeks . thereupon , the patient is asymptomatic and all tests are normal .

paragangliomas are tumors that originate from extra - adrenal medullary neural crest derivatives . most of them are located in the head and neck , but can be found in various body sites , including the thoracic cavity , abdomen , pelvis , and bladder . periampullary cancers include adenocarcinomas arising from the pancreas , ampulla of vater , duodenum or distal common bile duct . we report the case of a patient who had a retroperitoneal paraganglioma manifested as an abdominal mass with concurrent periampullary carcinoma ; it is the first report of such a concurrency . an 81-year - old woman with fit physiologic condition , was admitted to our institution in isfahan , iran , in 2012 , because she experienced progressive abdominal fullness and dull epigastric pain for a few months . her blood pressure and heart rate were within normal limits and liver enzymes including serum glutamic oxaloacetic transaminase ( sgot ) , serum glutamic - pyruvic transaminase ( sgpt ) , alkaline phosphatase and gamma glutamyl transferase showed increased values . bilirubin level , carcinoembryonic antigen and cancer antigen 19 - 9 levels were within normal limits . in the abdominal examination a large mass on upper paramedian , left side was touched . a computed tomography ( ct ) scan of the abdomen demonstrated a large retroperitoneal solid - cystic mass and significant dilation of gallbladder , intra and extra hepatic and pancreatic ducts [ figure 1 ] . abdominal ct revealed large retroperitoneal mass magnetic resonance cholangiopancreatography of the patient showed large solid - cystic tumor anterior to left psoas muscle and left kidney , inferior to pancreatic tail . it showed either , complete obstruction of main distal pancreatic duct and distal common bile duct ( cbd ) [ figure 2 ] . mrcp revealed biliary tract dilation the patient underwent endoscopic retrograde cholangiopancreatography ( ercp ) , which revealed a tumoral papilla ( 2 cm 2 cm 1 cm ) and biopsy was taken . she was planned for surgery with frozen section examination of abdominal mass . at the time of surgery , an encapsulated , hypervascular mass ( approximately 13 cm 10 cm 4 cm ) was observed in her retroperitoneal area with the central degeneration and hemorrhage and was subsequently excised [ figure 3 ] . large abdominal mass excised pathological analysis of the mass on frozen section showed a cellular lesion with probability of malignancy , without any sign of metastatic carcinoma . , the abdominal mass revealed an encapsulated tumor ; the tumor cells were arranged in sheets , large nests and organoid patterns , and contained mild pleomorphic nuclei with low mitotic activity [ figure 4 ] . the neoplasm was histologically benign , with no evidence of invasion , compatible with a paragangliom . after three months from patient 's surgery , her treatment has been completed and patient seems to be healthy . pheochromocytomas and extra - adrenal paragangliomas are very rare tumors that arise from the neural crest tissue . these tumors are functional in more than half of cases , and patients commonly present with symptoms , such as palpitation , headache , and sweating that are related to excess catecholamine secretion . about 70% of sympathetic paragangliomas are intra - abdominal , usually found in the perinephric and paraaortic spaces . the non - secretory type most commonly presents as an abdominal pain or mass ; a large proportion of these tumors are incidentally discovered in normotensive patients during imaging evaluation for other reasons . they are commonly located in the para - aortic region and they may be confused with other retroperitoneal tumors , especially pancreatic tumors . magnetic resonance imaging ( mri ) scintigraphy with 123-i labeled meta - iodo - benzyl - guanidinemibg offers superior specificity than ct and mri imaging . besides the use of imaging studies for diagnosing paragangliomas , assessment of the plasma normetanephrine level or of the metanephrine and catecholamine levels via 24 h urine collection can help physicians make the actual diagnosis . in our patient 's case , diagnosing the paraganglioma before surgery was not clear ; so , we did not analyze the relevant serum marker . a definitive diagnosis can be made only by histology and there are no histologic criteria to distinguish between benign and malignant tumors . only the appearance of distant metastases , metastases at a site where paraganglionic tissue is not usually found or local recurrence can confirm that the tumor is cancerous . however , total excision is the basis of curative treatment because these tumors are potentially malignant . the precise origin of a periampullary adenocarcinoma is often difficult to determine even with standardized histopathologic evaluation , particularly if the tumor is large and involves more than one potential site of origin . tumor destruction of normal periampullary anatomy , and presence of epithelial dysplasia in more than a single periampullary compartment , occurs frequently . however , in our case , according to early detection , the precise site of the neoplasm was clear . surgeons in treating patients with these tumors have favored an aggressive method of resection to benefit these patients with better prognosis . although the perioperative outcomes for these tumors are similar , the long - term survival has traditionally varied . it is unknown why outcome varies for adenocarcinomas arising from anatomic sites in such close proximity . of the 242 patients with resected periampullary adenocarcinoma , 149 ( 62% ) were pancreatic primaries , 46 ( 19% ) arose in the ampulla , 30 ( 12% ) were in distal bile duct , and 17 ( 7% ) were duodenal cancers . the tumor - specific 5 year actual survival rates were 15% for pancreatic , 39% for ampullary , 27% for distal bile duct , and 59% for duodenal cancers . among patients with periampullary adenocarcinoma treated by pancreaticoduodenectomy , developments in the broad field of molecular genetics may allow for earlier detection of periampullary neoplasms , perhaps using gene - based diagnostic testing of easily accessible clinical specimens such as blood , duodenal juice or stool . furthermore , progress in adjuvant therapies , maybe incorporating new combinations of chemotherapy , radiation therapy , and immunotherapy , would result in improvements in disease - free and overall survival rates . in conclusion , concurrent duodenal cancer and a retroperitoneal paragangliomas is an in experienced event in the clinic and pathologic fields and it makes pre - operative diagnosis of such masses difficult or even impossible , especially when the paraganglioma is non - functional .

paragangliomas are tumors that originate from extra - adrenal medullary neural crest derivatives . they are rarely located in retroperitoneal space . these tumors are often discovered incidentally during imaging studies performed for other reasons . periampullary cancers include adenocarcinomas arising from the pancreas , ampulla of vater , duodenum or distal common bile duct . the exact site of origin of periampullary tumors is often difficult to ascertain pre - operatively . we report the case of a patient who had a retroperitoneal non - functional paraganglioma , concurrent with periampullary adenocarcinoma . an 81-year - old woman was admitted with progressive abdominal fullness . there was an upper paramedian , left sided , large , palpable mass on the physical examination . laboratory investigations showed an increase in liver enzyme levels . on abdominal computed tomography the patient found to have a large retroperitoneal mass and dilation in biliary tract , which was confirmed by magnetic resonance cholangiopancreatography . she had a tumoral papi in endoscopic retrograde cholangiopancreatography . which biopsy revealed adenocarcinoma . she underwent surgery for excision of abdominal mass and pancreaticoduodenectomy . and pathologic study showed paraganglioma . this is the first ever reported case of concurrent paraganglioma and periampullary adenocarcinoma .

a 75-year - old female was referred to our clinic with bilateral adrenal masses that were detected incidentally by lumbar spine magnetic resonance imaging ( mri ) for evaluation of radiating flank pain . she presented with a high blood glucose level that had been controlled with medical treatment for 10 years . she had undergone surgery for a compressive fracture of the lumbar spine 3 months previously . a contrast - enhanced computer tomography ( ct ) scan was performed and revealed a left adrenal mass with inhomogeneous enhancement after application of contrast medium ( 4018 mm ) ( fig . 1a and 1b ) . on axial mri , the bilateral adrenal masses had high - signal intensity on t1- and t2-weighted images and a heterogeneous enhancement pattern ( left , 4819 mm ; right , 2923 mm ) ( fig . for evaluation of other malignant lesion or metastases , a 2[(18)f]fluoro-2-deoxyglucose ( fdg)-positron emission tomography ( pet ) scan was performed and showed an intense fdg accumulation in the bilateral adrenal masses without abnormal fdg uptake in extra - adrenal regions ( left , 3820 mm ; right , 3528 mm ) ( fig . the macroscopic findings were as follows : left adrenal tumor , 1614 mm ; and right adrenal tumor , 3915 mm . the adrenal masses reveal marked nuclear pleomorphism with compact eosinophilic cytoplasm , numerous mitoses , and necrosis . the adrenal masses were graded according to the weiss criteria ( 0 - 9 ) with a score of 5 microscopically ( fig . neoplastic involvement of the adrenal gland may result from primary tumors originating from the adrenal cortex of the adrenal medulla . primary malignant tumors originating from the adrenal gland include adrenocortical carcinomas , primary adrenal lymphomas , and malignant pheochromocytomas . any primary cancer can spread to the adrenal glands ; lymphomas , lung cancer , melanomas , leukemia , renal carcinoma , and ovarian carcinoma account for the majority of adrenal metastases . adrenocortical carcinoma increases with tumor size to 25/100,000 ( median diameter > 6 cm ) . in contrast to our patient , many patients with adrenocortical carcinomas present with clinical symptoms of endocrine excess . indeed , hormone - functioning tumors account for 26% to 94% of adrenocortical carcinomas . most patients with adrenocortical carcinomas are diagnosed at an advanced stage of disease with large primary tumors ( median tumor size at diagnosis , > 10 cm ) and invasion to adjacent organs . the main clinical symptoms , such as abdominal discomfort or back pain , are related to the mass effect of a large tumor . all adrenal tumors detected have to be diagnosed for malignancy potential and hormonal activity to render timely and curative treatment . imaging studies using ct , mri , and fdg - pet to demonstrate adrenal mass size and appearance have been used to distinguish between benign and malignant lesions . differentiation between malignant and benign adrenal lesions can be performed by using 18-fdg - pet with > 95% accuracy . in particular , 18-fdg - pet plays an important role in evaluating treatment response and residual masses . in general , surgery involving adrenal tumors should be considered in patients with functioning cortical tumors and clinical symptoms . regarding nonfunctioning tumors , recommendations regarding treatment mainly refer to the tumor size . in general , clinically silent lesions <3 cm without any criteria of malignancy are not resected and should be followed closely by ct or mri scans every 6 or 12 months . the indications for an adrenalectomy are a definitive or presumed diagnosis of primary adrenocortical carcinoma and circumstances technically obstructive to a minimally invasive approach . in the case of any intraoperative features of malignancy , conversion to an open approach should be performed to enable extensive radical compartment resection . in our case , the differentiation between benign and malignant adrenal lesions is based on macroscopic and microscopic features . the weiss score is the most widely used classification for microscopic characteristics suggestive of a malignant tumor . three or more histologic criteria are necessary to establish the diagnosis of adrenal carcinoma . in our case , marked nuclear atypia , frequent mitoses ( 8 - 10/10 high power fields ) , vascular and capsular invasion , and necrosis were found .

a 75-year - old female visited our hospital with bilateral adrenal masses that were detected incidentally during lumbar spine magnetic resonance imaging ( mri ) for the evaluation of radiating flank pain . consecutive computed tomography and mri revealed bilateral adrenal masses with no evidence of lymph node enlargement or local invasion ; 2[(18)f]fluoro-2-deoxyglucose ( fdg)-positron emission tomography showed an intense fdg accumulation in both adrenal glands without abnormal fdg uptake in extra - adrenal regions . the laboratory test results were within normal ranges . we performed a bilateral adrenalectomy . the pathologic diagnosis of both adrenal masses was consistent with adrenocortical carcinoma . the patient recovered well with no complications .

a 61-year - old male was admitted to our hospital for evaluation of melena of several days duration . he had a history of an acute myocardial infarction six years ago . abdominal computed tomography revealed diffuse concentric wall thickening of the stomach , suggesting advanced cancer , with enlargement of multiple lymph nodes ( the largest one was 2.8 cm in size and located along the gastric body of the lesser curvature directly abutting or focally invading the primary wall thickening ) . the mucosa revealed an ill - defined ulcerative mass ( 32.5 cm ) on the anterior wall of the body , which involved the entire thickness of the stomach . a white - gray , solid , firm mural mass ( 2.82.3 cm ) was present which abutted the ulcerative mass ( fig . an abutting mural mass was located in the proper muscle layer consisting of vaguely whirling benign spindle cells with a peripheral lymphoid cuff ( fig . 3 ) and glial fibrillary acidic protein ( gfap ) , but negative for c - kit , cd34 , smooth muscle actin , desmin , and calretinin . gastric adenocarcinomas account for approximately 95% of all malignant gastric tumors.8 gastric adenocarcinomas may co - exist with synchronous tumors of a different histologic type,2 specifically , gastric adenocarcinomas co - exist most commonly with lymphomas and less commonly with carcinoid tumors.2 the synchronous occurrence of adenocarcinomas and mesenchymal tumors is uncommon in the stomach . the majority of synchronous gastric epithelial and mesenchymal tumors are adenocarcinomas and gists,1 and only 22 cases of synchronous gastric adenocarcinomas and gists have been reported.1 - 7 moreover , co - existence of adenocarcinomas and schwannomas in the stomach is extremely rare and only one case has been previously reported.1 schwannomas are rare in the stomach , occurring with a frequency similar to leiomyomas.9 schwannomas are benign neoplasms displaying schwann cell differentiation.10 these tumors form intramural masses 2 - 10 cm in size1 and most involve the submucosa and muscularis propria.10 schwannomas can present in a manner similar to gists including gross features.9 histologically , the typical features of schwannomas included a relatively circumscribed mass , often partly surrounded by patches of lymphoid infiltration . schwannomas are composed of variably organized tumor cells , often arranged in a microtrabecular pattern in a collagenous background . focal nuclear atypia is common , but mitotic activity only exceeds 5 per 50 high power fields in exceptional cases.9 immunohistochemically , gastric schwannomas are positive for s100 protein and usually gfap , but negative for c - kit and cd34.9 lesions classified as gastric schwannomas differ from conventional somatic soft tissue schwannomas histologically by having peripheral lymphoid cuffs lacking a fibrous capsule and rarely showing degenerative changes.10 nuclear palisading is uncommon in gastric schwannomas.11 gastric schwannomas lack alterations in the nf2 gene , which are found in many sporadic conventional schwannomas from other sites , and do not express calretinin.10 the differential diagnosis of the spindle cell lesion in our case includes schwannomas , gists , and smooth muscle tumors . schwannomas can be distinguished from gists because gists typically show c - kit and cd34 labeling and lack s100 protein expression.9,10 moreover , gists do not have an inflammatory cuff,10 which is a peculiar feature of gastric schwannomas . smooth muscle tumors do not have a lymphoid cuff and express smooth muscle markers including desmin , actin , and calponin , which differ from schwannomas.10 our case can be differentiated from neurofibroma , another type of peripheral nerve sheath tumor , because the tumor cells showed uniform intense immunostaining for s100 protein . in our case , the mural mass consisted of benign spindle cells , which were diffusely and strongly positive for s100 protein and gfap , but negative for c - kit , cd34 , smooth muscle actin , and desmin . with characteristic histologic and immunohistochemical findings , the spindle cell lesion was diagnosed as a gastric schwannoma . in most of the reported cases of synchronous gastric adenocarcinomas and gists , gastric adenocarcinomas coexisted with gist in a different part of the stomach , and the pre - operative biopsy fragments showed adenocarcinomas only and gists were detected in following laparotomy and examination of the resected specimens.2 however , tumor cells of different histologic types rarely coexist in the same location , and form a collision tumor in the stomach.2,5,12,13 one case previously mentioned the synchronous occurrence of a primary adenocarcinoma and schwannoma of the stomach that presented as two separate masses . in our case , however , a schwannoma was detected on the pre - operative computed tomography and thought to be an enlarged lymph node near the main mass . the surgical specimen revealed that the main mass , an advanced mucinous adenocarcinoma , was present adjacent to the mural mass , a schwannoma , and the carcinoma cells focally infiltrated into the schwannoma . therefore , the present case is a collision tumor of a schwannoma and adenocarcinoma occurring in the stomach . the simultaneous finding of epithelial and stromal gastric tumors raises the questions of whether or not such an occurrence is a simple incidental association or the two lesions are connected by a causal relationship . coincidence alone could easily account for such an association , particularly in countries that exhibit a high incidence of gastric cancer.2 in one retrospective study , gastric adenocarcinomas were shown to harbor a synchronous gist with an incidence of 0.25% ( 5/2,010 cases).14 in another study involving incidental gastric gists , microscopic gists had an incidence of 35 of 100 stomachs ( 35%).15 therefore , it is possible that gastric adenocarcinomas and schwannomas of the present case can simply co - exist in the same stomach because of the high incidence of gastric cancer in korea . the possibility that gene mutations might underlie tumor predisposition in patients harboring a double gastric neoplasia can not be theoretically discarded . an interesting hypothesis is that a single carcinogenic agent might interact with two neighboring tissues , inducing the development of tumors of different histologic types in the same organ.2 experimental evidences for this possibility are as follows : first , n - methyl - n'-nitro - n - nitrosoguanidine induces the development of gastric adenocarcinomas in rats , but , when combined with agents that alter gastric mucosal barrier , leiomyosarcomas develop in conjunction with epithelial tumors . second , whereas administration of 9,10-dimethyl-1,2-benzanthracene ( dmba ) alone induces the development of adenocarcinoma , treatment with dmba and cellophane plate causes the induction of gastric sarcoma.2 rare examples of collision tumors consisting of a gastric adenocarcinoma and a primary gist also suggest that these two types of tumors occur in response to a single carcinogenic agent.8 although there are no reports of same carcinogenic agent inducing gastric adenocarcinoma and schwannoma , our case might support that possibility , because carcinoma cells focally infiltrated and intermingled with the schwannoma forming a collision tumor . irrespective of the origin , the co - existence of gastric mesenchymal tumors with epithelial tumors has increased in recent years . therefore , in any case of a gist or gastrointestinal adenocarcinoma , the surgeon should be alert to a possible co - existing tumor with a different histologic origin.16 herein we report the first case of a collision tumor consisting of an adenocarcinoma and schwannoma in the stomach , which raises the question that a single carcinogenic agent might interact with two neighboring tissues resulting in two types of tumors .

the simultaneous occurrence of an adenocarcinoma and schwannoma is extremely rare in the stomach , and only one such case has been previously reported , which presented as two separate masses . indeed , the collision of these tumors has never been reported . we report the case of a 61-year - old male patient who was diagnosed with the synchronous development of a schwannoma and advanced mucinous adenocarcinoma of the stomach , in which the carcinoma cells focally invaded the schwannoma .

the achilles tendon is the thickest and strongest tendon in the human body . like any other tendon in the body achilles tendon ruptures are increasing in frequency due to an overall increase in athletic activity , especially in men in their thirties and forties . about 18 out of 100,000 humans rupture their achilles tendon each year , depending on the social environment . acute ruptures of the achilles tendon occur most often in men in the third and fourth decades of life who intermittently participate in athletic activity . 1(a ) and ( b)intra - operative view of ruptured achilles tendon ( a ) and ( b)intra - operative view of ruptured achilles tendon the spectrum of achilles tendon ruptures includes both acute and chronic injuries . treatment options include operative repair with postoperative immobilization , operative repair with accelerated rehabilitation using early weight bearing , as well as non - operative treatment . clinical evaluations of non - operative treatment have demonstrated a re - rupture rate of 1030% . other drawbacks of non - operative treatment include decreased plantar flexion and decreased endurance when compared to surgically repaired tendons . some reports , however , suggest that the results of non - operative management are equivalent to operative repair [ 46 ] . several current studies favor operative repair via open or percutaneous techniques in younger , active patients who wish to return to pre - injury activities [ 7 , 8 ] . in addition , re - rupture is less in surgically repaired achilles tendons . complications of operative repair include infection and poor wound healing . ultimately , decision - making regarding the treatment options relies on many factors including patient age , chronicity of the tear , functional demand , medical comorbidities , and patient expectations . the achilles tendon is composed of tendinous fibers contributed by the gastrocnemius and soleus muscles . the blood supply to the achilles tendon has three principle sources : the musculotendinous junction , the osseous insertion , and multiple vessels in the mesotenon . injection studies using computer assisted imaging show a reduction in the number and the mean relative area of mesotenal vessels in the mid - section of the tendon . similarly , the number of intratendinous vessels is fewest 4 cm from the calcaneal insertion . diagnosis of an acute achilles tendon rupture can usually be made by history and physical examination alone . mri or ultrasound can be helpful in cases of suspected rupture for pre - operative planning , but is usually unnecessary . the patient will often describe abrupt severe pain over the tendon with an activity requiring forceful plantar flexion such as while playing tennis . pop or have the sensation of being hit in the back of the heel . physical examination signs that suggest achilles tendon rupture include weakness of plantar flexion and a palpable defect over the posterior calf . a thompson test is performed by squeezing the calf and observing motion at the foot . with an intact tendon with a rupture , plantar flexion does not occur with squeezing the calf ( fig . note lack of plantar flexion with squeezing of the calf demonstrating a ruptured achilles tendon normal thompson s test . note lack of plantar flexion with squeezing of the calf demonstrating a ruptured achilles tendon controversy regarding operative versus non - operative treatment focuses on re - rupture rates and wound complications related to surgery . khan et al . compared the results of all randomized trials comparing surgical and conservative management in a meta - analysis . results gave a pooled re - rupture rate of 3.5% in the operatively treated group and 12.6% in the non - operative group . complications such as adhesions , altered sensation , and wound infection , however , were more common in operatively treated patients with 34.1% in the operative group versus 2.1% in the non - operative group [ 6 , 13 , 14 ] . in a large prospective study of 196 consecutive patients with acute achilles tendon ruptures that were treated with 8 weeks of casting and immediate postoperative weightbearing , the re - rupture frequency was 7% . this is only slightly higher than most results in operatively treated groups [ 24 , 6 , 15 ] . due to the similar percentage of re - rupture between most studies advocating surgery and their promising results with non - operative management , ingvar et al . question the necessity for surgical repair of achilles tendons , with all of its risks and high cost . in 1977 , this technique involves passing a suture through small stab wounds above and below the tendon tear . the original article reported on 18 patients with only two minor complications . prospectively studied 134 percutaneous repairs and found a rerupture rate and return to pre injury activities comparable to open procedures . percutaneous repair has the added benefit of being done under local anesthesia without a tourniquet . . showed no significant difference between open compared to percutaneously repaired tendons , but a significantly higher rate of wound infection in the open group compared to the percutaneous group . historically , patients were immobilized in a rigid cast for at least 46 weeks to allow for presumed tendon healing . current trends , however , favor minimizing postoperative immobilization and focus on early weightbearing with excellent results . in a rat model of tendon were able to show that physical activity speeds up tendon healing as compared to plaster immobilization . this suggests that that there may be some stimulatory effect of mechanical loading on tendon healing . in a clinical prospective study with full postoperative weight bearing in a controlled ankle motion walker accompanied by active stretching , jacob and paterson showed few minor complications , high patient satisfaction , and no re - ruptures . patients with both acute and chronic tears repaired with an open technique did equally well under this treatment protocol . in their meta - analysis of randomized trials comparing early postoperative weightbearing with cast immobilization , suchak et al . found no difference in re - rupture rates and more excellent rated subjective patient responses . patients preferred the early function protocol with a mobile cast for multiple reasons including a decrease in leg edema , the ability to bear weight , and easier and faster ability to obtain normal gait after removal of the cast . divided their treatment groups into three sections based on the number of days between achilles tendon rupture and surgery : acute tears ( < 7 days ) , sub chronic tears ( > 7 days but < 4 weeks ) , and chronic tears ( > 4 weeks ) . all patients resumed their normal activities within 100 days of operative repair , regardless of time until surgery . thus , according to this study , there does not appear to be an advantage of early operative repair over delayed surgical treatment . the main concern to prolonged treatment delay after achilles tendon rupture is weakness of plantar flexion . controversy regarding operative versus non - operative treatment focuses on re - rupture rates and wound complications related to surgery . khan et al . compared the results of all randomized trials comparing surgical and conservative management in a meta - analysis . results gave a pooled re - rupture rate of 3.5% in the operatively treated group and 12.6% in the non - operative group . complications such as adhesions , altered sensation , and wound infection , however , were more common in operatively treated patients with 34.1% in the operative group versus 2.1% in the non - operative group [ 6 , 13 , 14 ] . in a large prospective study of 196 consecutive patients with acute achilles tendon ruptures that were treated with 8 weeks of casting and immediate postoperative weightbearing , the re - rupture frequency was 7% . this is only slightly higher than most results in operatively treated groups [ 24 , 6 , 15 ] . due to the similar percentage of re - rupture between most studies advocating surgery and their promising results with non - operative management , ingvar et al . question the necessity for surgical repair of achilles tendons , with all of its risks and high cost . this technique involves passing a suture through small stab wounds above and below the tendon tear . the original article reported on 18 patients with only two minor complications . prospectively studied 134 percutaneous repairs and found a rerupture rate and return to pre injury activities comparable to open procedures . complications included complete and partial reruptures , sural neuritis , and superficial wound infection . percutaneous repair has the added benefit of being done under local anesthesia without a tourniquet . . showed no significant difference between open compared to percutaneously repaired tendons , but a significantly higher rate of wound infection in the open group compared to the percutaneous group . historically , patients were immobilized in a rigid cast for at least 46 weeks to allow for presumed tendon healing . current trends , however , favor minimizing postoperative immobilization and focus on early weightbearing with excellent results . in a rat model of tendon rupture using wheel running for early tendon motion , bring et al . were able to show that physical activity speeds up tendon healing as compared to plaster immobilization . this suggests that that there may be some stimulatory effect of mechanical loading on tendon healing . in a clinical prospective study with full postoperative weight bearing in a controlled ankle motion walker accompanied by active stretching , jacob and paterson showed few minor complications , high patient satisfaction , and no re - ruptures . patients with both acute and chronic tears repaired with an open technique did equally well under this treatment protocol . in their meta - analysis of randomized trials comparing early postoperative weightbearing with cast immobilization , suchak et al . found no difference in re - rupture rates and more excellent rated subjective patient responses . patients preferred the early function protocol with a mobile cast for multiple reasons including a decrease in leg edema , the ability to bear weight , and easier and faster ability to obtain normal gait after removal of the cast . sorrenti et al . divided their treatment groups into three sections based on the number of days between achilles tendon rupture and surgery : acute tears ( < 7 days ) , sub chronic tears ( > 7 days but < 4 weeks ) , and chronic tears ( > 4 weeks ) . all patients resumed their normal activities within 100 days of operative repair , regardless of time until surgery . thus , according to this study , there does not appear to be an advantage of early operative repair over delayed surgical treatment . the main concern to prolonged treatment delay after achilles tendon rupture is weakness of plantar flexion . many authors advocate surgical repair , mostly citing decreased re - rupture rates and improved functional outcome . no studies show a clear advantage to early surgical intervention over delayed repair . waiting for surgical repair for longer than 1 month may show worse functional results postoperatively . non - operative treatment has shown similar re - rupture rates as compared to surgically repaired tendons . any patient undergoing achilles tendon repair should understand the inherent risks of an invasive procedure including bleeding , infection , and pain at the surgical site . in our practice , we offer surgical repair of the ruptured achilles tendon for those patients who wish to return to an active lifestyle . while for many years , patients were rigidly immobilized for 68 weeks postoperatively , new studies have shown excellent results with early weightbearing , and this is quickly becoming the standard of care amongst many physicians .

the achilles tendon is the strongest and thickest tendon in the human body . like any other tendon in the body , however , it is susceptible to rupture . many surgeons advocate early operative repair of the ruptured achilles tendon , citing decreased re - rupture rates and improved functional outcome . waiting for surgical repair for longer than one month may lead to inferior functional results postoperatively . non - operative treatment has higher re - rupture rates as compared to surgically repaired tendons , but may be the treatment of choice in some patients . while for many years , patients were rigidly immobilized in a non - weightbearing cast for 68 weeks postoperatively , newer studies have shown excellent results with early weightbearing , and this is quickly becoming the standard of care amongst many physicians .

pressure exerted by the growing uterus may cause herniation of abdominal organs such as stomach , spleen , intestine , etc . , into the thoracic cavity through a defect in the diaphragm . this defect may be inherent to the diaphragm or caused by rupture of it . presentation of this rare condition mimics pneumothorax and tension pneumothorax , though the management is entirely different . a 28-year - old primigravida , at 31 weeks of gestation and no other co - morbidity , had an acute onset of upper abdominal pain and recurrent vomiting for one day . her blood investigations were normal , except for a raised total leukocyte count ( 16,800/l ) . her chest x - ray revealed left hydropneumothorax with mediastinal shift to the right [ figure 1 ] . she was having hypoxemia , dyspnoea , tachycardia , even on rest , with aggravation in supine position . intercostal drain ( icd ) was placed in the left 5 intercostals space , in mid - axillary line [ figure 2 ] . ct scan and mri could not be done as patient was not able to lie down and the family expressed unwillingness to expose the patient to further radiations . differential diagnosis of left pulmonary bulla , left pulmonary cyst , and tension gastrothorax were made . multiple attempts for placement of nasogastric tube were made but failed , as the patient was very uncooperative and did not tolerate removal of the oxygen supply . patient and family were counselled about the need for urgent delivery of the baby by caesarean section . she was given two doses of betamethasone 12 mg , 24 hours apart . patient was not allowed to take food through the mouth and was feed through the parenteral route . patient was intubated with single lumen endotracheal tube after rapid sequence induction and ventilated with pressure control mode . after closure of uterus and good uterine contraction , abdominal cavity was explored along with the diaphragm . there was herniation of stomach , spleen , and part of colon into the left hemithorax , due to rupture of left hemidiaphragm . left lung was fully inflated and an implantable cardioverter defibrillator ( icd ) placed before closure of the thorax . patient was shifted to the ward in a stable condition on the fourth day after the operation . chest x - ray of a 28-year - old pregnant female shows herniation of the stomach into the left hemithorax ( horizontal arrow ) , with air fluid level ( vertical inverted arrow ) and mediastinal shift to the right side ( arrow head ) . left tension gastrothorax with left intercostal drain . chest x - ray of a 28-year - old pregnant female shows herniation of the stomach into the left hemithorax ( vertical arrow ) , with intercostal drain ( horizontal arrow ) and mediastinal shift to the right side ( arrow head ) . herniation of stomach with or without other intra - abdominal organs into the chest is called gastrothorax . subsequent distension of the stomach or intestine in the chest may cause respiratory distress , mediastinal shift , and hemodynamic compromise leading to tension gastrothorax . this increased iap can force the intra - abdominal content into the chest through a defect in the diaphragm . rupture of the diaphragm without a history of trauma is rare and can lead to lethal complication in pregnancy . there is very little data regarding the incidence of gastrothorax and tension gastrothorax associated with pregnancy . also , it is very difficult to establish the diagnosis of diaphragmatic rupture . the former presents as nausea , vomiting , and abdominal distension and the latter manifests as palpitations , dyspnoea , cough , or chest pain . the variety of symptoms , rarity of the condition , and absence of trauma make the diagnosis of diaphragmatic rupture difficult . tension gastrothorax can even be misdiagnosed as tension pneumothorax or hydropneumothorax with subsequent placement of icd . the first chest x - ray of our patient showed an air fluid level [ figure 1 ] so an icd was placed [ figure 2 ] . the definitive treatment for tension gastrothorax is repair of the defect , but emergent decompression with a nasogastric tube ( ngt ) may be required . as the patient was extremely dyspnoeic , uncooperative , and period of gestation was more than 32 weeks , we decided to perform elective lscs after steroid therapy . all the preparations for thoracotomy were completed before caesarean section . to prevent any further complications , we decided to perform thoracotomy and repair the diaphragm rupture , after uterine closure . . a high index of suspicion of the possibility of tension gastrothorax should be present when pregnant patients present with respiratory distress and hemodynamic instability along with a typical chest x - ray .

gastrothorax is characterized by herniation of the stomach and other abdominal contents into the thoracic cavity either through the oesophageal hiatus or ruptured diaphragm . when gastrothorax causes pulmonary and hemodynamic compromise , due to compression of lungs and mediastinal structures , it is named as tension gastrothorax . diagnosis of tension gastrothorax is often complicated during late pregnancy , because of unusual presentation , altered physiology , absence of trauma , hesitation about radiation exposure , and rarity of the condition . we report a case of a patient , in her 32nd week of pregnancy , who presented with left tension gastrothorax . lower segment caesarean section was planned after steroid therapy , with all the preparations for thoracotomy . intra - operatively , stomach , spleen , and colon were found herniated in the left hemithorax , through a ruptured left hemidiaphragm . thoracotomy was done immediately after caesarean section , with reduction of herniated contents and repair of the defect in the diaphragm . the patient and her baby were discharged in stable condition 2 weeks after thoracotomy .

anaphylaxis is an acute life - threatening systemic reaction that requires quick diagnosis and correct management to save the patient . although it is a rare intraoperative complication , most drugs used in the perioperative period can lead to anaphylaxis . the incidence of anaphylaxis during anaesthesia has been estimated between 1 in 10,000 and 1 in 20,000 . ninety percent of the anaphylactic reactions occur at the time of induction of anaesthesia . nowadays , propofol is the most widely used drug not only for induction of anaesthesia but also for sedation in various settings short surgical procedures under total intravenous anaesthesia , intensive care settings and paediatric procedures . propofol ( 2 , 6 di - isopropylphenol ) is currently formulated in a lipid vehicle containing soya bean oil , egg lecithin and glycerol . 1.2% of the cases of perioperative anaphylaxis in france have been reported to be caused by propofol . anaphylactic shock has also been reported in the european literature after first exposure to propofol . we also report a case of anaphylaxis to propofol ( diprivan , 1% formulation in 10% soyabean oil containing disodium edetate glycerol and egg lecithin ) after first exposure at the time of induction of anaesthesia . a 56 year - old male patient , asa i , weighing 64 kg , diagnosed as having right renal mass , was scheduled for elective laparoscopic nephrectomy . he had no past history of allergy to drugs and his physical examination and investigations ( blood investigations , chest x - ray and electrocardiogram ) were all within normal limits . on arrival in the operation theatre , his non - invasive blood pressure was 120/80 mmhg , heart rate was 78/min and spo2 100% on room air were recorded . after insertion of an 18 g intravenous cannula in the dorsum of the hand , inj . magnamycin ( sulbactam and cefoperazone ) 1 g diluted in 10 ml of normal saline was injected slowly over 10 min and injection amikacin sulphate 500 mg was given intravenous over 15 min in 100 ml normal saline . because of some technical reasons there was a delay of 45 min before the induction of anaesthesia . during this time , the patient was haemodynamically stable with pulse of 7075/min and bp 120/70 mmhg . at induction , fentanyl citrate 100 mg , propofol 80 mg and vecuronium bromide 6 mg was given to aid intubation . during the time positive - pressure ventilation was being given , the blood pressure dropped to 60/30 mmhg with tachycardia of 130150 beats / min . the intravenous fluid infusion rate was increased and ephedrine 3 mg , repeated twice , was given intravenous . the trachea was intubated and the patient was ventilated with 100% o2 . thereafter , a cutaneous rash was visible all over the body and the patient 's lips , eyes , ears and hands appeared swollen and edematous . injection adrenaline 0.2 mg intravenous bolus , trendelenberg position , intravenous crystalloids 22.5 l over the next 2 h and injection hydrocortisone 200 mg intravenous were given . during this time , his systolic blood pressure was between 40 and 60 mmhg and diastolic blood pressure was 2540 mmhg , even after a repeat dose of intravenous adrenaline 0.2 mg . because the blood pressure was not responding , adrenaline infusion 0.05 mg / kg / min was started . after about 1.5 h , the patient 's condition started improving and he became hemodynamically stable . the patient was mechanically ventilated till the blood pressure stabilized to 100/60 mmhg and pulse rate to 100/min . we confirmed absence of edema in the oral cavity , uvula and epiglottis by larygoscopic examination . when the patient was fully awake and there was sufficient leak around the deflated cuff , the trachea was extubated after 3 h with cook 's airway exchanger in trachea , which was subsequently removed after a few hours [ figure 1 ] . patient after extubation with evident swelling over the ear lobule , periorbital tissues and lips the surgery was postponed . the patient was kept under observation for 24 h in the post post - anaesthesia care unit and discharged home after 48 h. blood samples for plasma levels of lge antibody were sent and the reported value was 350 ng / ml ( normal reference value in our lab is less than 50 ng / ml ) . the skin test included skin prick test and intradermal test using saline as negative control and histamine as positive control . the prick test was performed on the anterior aspect of the forearm using a drop of undiluted propofol , vecuronium , amikacin , magnamycin , 10% intralipid and diluted fentanyl ( 1 in 10 dilution ) . the intradermal test was then performed on the other forearm by injection of 0.020.05 ml of the diluted drugs in saline starting with a dilution of 1 in 1000 progressing to a dilution of 1 in 10 . the intradermal test of propofol showed a positive response at 1 in 1000 dilution thus confirming our suspicion of anaphylaxis to propofol . this time , injection thiopentone sodium was used for induction instead of propofol while all other drugs were the same as that used for induction during the first time . the surgery and anaesthesia were uneventful [ figure 2 ] and the patient was discharged after 3 days . our suspicion of anaphylaxis was based on the presence of cutaneous rash all over the body , oedema over the face and upper limbs and severe hypotension not responding initially to intermittent doses of adrenaline . serological testing for confirmation of anaphylactic reaction includes measurement of mast cell tryptase levels immediately after the event , 1 h later and 24 h later . detection of the presence of ige antibodies by the radioallergosorbent test ( rast ) measures the presence of specific ige antibodies in the serum that bind to a disc coupled with the specific drug . rast is highly specific , but sensitivity is low for most of the drugs . because there is no facility for measuring mast cell tryptase level and drug drug - specific ige levels at our centre , we could not measure them . although total ige levels were raised significantly , this does not confirm anaphylaxis as drug - specific ige levels could not be measured and , therefore , we went ahead with skin tests that are more specific than measuring ige levels . ideally , the skin test should be performed 46 weeks after the event because of the risk of a false negative result . in our case , because of the semiemergent nature of case ( renal tumour ) , it compelled us to carry out the test earlier . the patient and the surgeon were very keen to have the tumour removed at the earliest . if necessary , the skin test can be performed earlier , but if the results are negative , they require subsequent confirmation . the skin prick test is easier and less traumatic to perform , but the intradermal test is more sensitive than the skin prick test ; it carries a higher risk of inducing a false positive reaction and is more likely to cause systemic reactions . the detection of drug causing anaphylaxis is difficult because , at induction , multiple drugs are administered . this patient was not exposed to latex and thus it was ruled out as a cause of anaphylaxis . anaphylaxis due to propofol is rare ; it has two potential allergenic molecules the di - isopropyl side chain and phenol . propofol when given in an oil water emulsion equivalent to 10% intralipid provides 1.82.4 g / kg of intravenous lipids daily , which is within the range used in parentral nutrition . therefore , the immunological test with 10% intralipid is carried out to rule out the lipid solvent as the allergenic molecule . many patients who develop anaphylaxis after first exposure may do so because of sensitivity to the di - isopropyl radical that is found in many dermatological products and lipid formulations . thus , history of prior use of parenteral nutrition with intralipids and sensitivity to dermatological products is important . our patient had no history of allergies , but his anaphylactic reaction shows that sensitization can occur in normal persons who might have been exposed to phenolic group in the past . laxenaire in 1992 reported 14 cases of anaphylaxis to propofol , oscar in 1992 reported a case of anaphylaxis after the third exposure to propofol , nishiyama and hanaoka in 2001 reported a case of propofol induced bronchoconstriction and mcncill in 2008 reported that 28% ( 14 ) cases had sensitization to propofol when he evaluated 50 patients with clinical episodes of anaesthesia - associated anaphylaxis . most episodes of anaphylaxis usually respond to treatment with a single dose of epinephrine , but some cases who do not respond to single or intermittent doses may need epinephrine infusion as in our case . there are reports of use of pure -agonists and even vasopressin in refractory cases . although cardiovascular symptoms and bronchospasm are more frequent manifestations in ige - dependent reactions , absence of respiratory symptoms as in our patient does not preclude the diagnosis of anaphylaxis . the severity of clinical symptoms , positive skin prick test , intradermal test to propofol and absence of hypersensitivity during the second surgery when propofol was omitted definitely points to propofol as the causative agent . every patient with a suspected anaphylactic reaction during anaesthesia should be investigated to determine the allergic nature of the reaction and to identify the responsible drug with the aim of providing safe and documented advice for future administration of anaesthetic drugs .

although propofol is one of the most commonly used drugs for induction of anaesthesia , it is not devoid of anaphylactic potential . early detection of any suspected anaphylactic reaction during anaesthesia , prompt management , identification of the offending agent and prevention of exposure to the offending agent in the future is the responsibility of the anaesthesiologist . this is a case report of anaphylaxis to propofol at the induction of anaesthesia in a previously non - allergic 56 year - old man , planned to undergo laparoscopic nephrectomy , who responded to epinephrine infusion .

among the mechanical thrombectomy devices used for cases of acute ischemic stroke , the solitaire stent ( ev3 , plymouth , mn , usa ) is one of the mostly used and reported device recently due to its fully retrievable and self - expandable property2,7 ) . however , mechanical thrombectomy using the solitaire stent is not always successful , and unexpected self - detachment is possible during the retrieval of the stent through severely tortuous or atherosclerotic vessels4 ) . we recently experienced the self - detachment of a solitaire stent and failed to recanalize the occlusion with endovascular method . then , we performed surgical removal of the stent in order to rescue the patient and elucidate the reason why the self - detachment occurred . based on the operative findings , the stent was likely to fail to pass the acutely angled and circumferentially calcified internal carotid artery ( ica ) segment , and it finally detached inadvertently at the tortuous segment . a 78-year - old female presented with left hemiparesis ( 2/5 ) at four hours from onset of symptoms . she was taking oral anticoagulation medication ( warfarin 2 mg daily ) due to atrial fibrillation . the computed tomography ( ct ) brain scan was normal , magnetic resonance imaging ( mri ) showed acute infarction in diffusion weighted mri and diffusion and perfusion mismatch ( fig . 2a ) . in our practice , forced suction thrombectomy with the penumbra reperfusion catheter ( penumbra , alameda , ca , usa ) is usually first undertaken to recanalize large vessel occlusion3 ) , and if failure occurs , solitaire stent assisted thrombectomy is then performed . under local anesthesia , forced suction thrombectomy with the 041 f penumbra reperfusion catheter was performed . following two attempts of forced suction thrombectomy , a 10 mm sized visible clot was retrieved , and the ica was fully recanalized . however , a distal m1 segment occlusion remained ( fig . we switched to solitaire ab stent assisted thrombectomy after failure of the remained occlusion with previous technique . after confirming the location of the occlusion via distal angiography with a prowler selector plus microcatheter ( cordis neurovascular , miami lakes , fl , usa ) , a solitaire stent 420 was deployed into the m1 and m2 segments through the occlusion site for the purpose of temporary opening and thrombus removal we waited several minutes , then , the stent was carefully retrieved after partial withdrawal into the prowler microcatheter under applying negative pressure through the guiding catheter . during the passage of the distal ica and siphon , so , the endovascular neurosurgeon reinforced to retrieve the stent , meanwhile , the stent was detached unexpectedly . following angiography revealed that the detached stent was located from cavernous segment to communicating segment of the ica , and partial radiolucent area was contained within the distal part of the stent , which suggested the thrombus was captured at the area ( fig . 2c ) . then , we tried to remove the detached stent using micro - snare and to open the occlusion with another attempt of forced suction thrombectomy , but failed to achieve recanalization with endovascular means . after declaration of endovascular failure , we first verified no significant increase in infarction size using repeated diffusion weighted image mri . the time spent on the endovascular procedure was 1 hour , and the time from the declaration of endovascular failure to the induction of general anesthesia in an operating room was 50 minutes . the patient underwent an extended superciliary approach as canvassed in a previous report by the present authors6 ) . we first created a supraorbital craniotomy , and dissection of the proximal sylvian fissure revealed an intracranial ica that was diffusely atherosclerotic and occluded with the solitaire stent harboring the embolus ( fig . a part of superior wall of the ica that was not atherosclerotic and contained the distal part of the stent was chosen for arteriotomy . the neurovascular surgeon first pulled the stent carefully but failed to remove , which was probably caused by some strut of the stent engaging a part of calcified lumen , then reinforced the pulling force resulted in successful removal of the stent finally . the stent grabbed the main thrombi at distal part of the stent and both proximal and distal markers of the stent were preserved ( fig . the patient 's neurological deficits improved , and the modified rankin scale score was 2 at three months after surgery . based on the operative findings , the stent grabbed the main thrombi but was likely to fail to pass the acutely angled and circumferentially calcified ica segment , and it finally detached inadvertently at the tortuous segment . notably , bone window images of the baseline ct scan corresponded to the operative findings and showed severe and circumferential calcification at the supraclinoid ica ( arrow , fig . among several mechanical thrombectomy techniques and devices , the solitaire ( self - expandable and fully retrievable ) stent has several benefits , including possible immediate reperfusion in most patients after stent deployment and short procedure time . . however , the recanalization rate of solitaire stent assisted thrombectomy can not be 100% , and although rare , complications involving the stent are also possible . the present case is an example of a complication , reported elsewhere , involving the inadvertent detachment of the solitaire stent4 ) . in our case , we performed surgical removal of the stent including the thrombi grabbed within the stent , and we elucidated the reason why the inadvertent detachment occurred . based on our experience , the detachable property , the most powerful benefit of the solitaire , can harbor some risks in limited circumstances . if patients have anatomic features involving severely tortuous and acutely angled vessels coupled with circumferential calcification , some attention regarding difficult retrieval is required to prevent unexpected detachment . it is notable that a baseline ct scan could have a potential role in anticipating this complication under those circumstances . in the present case , the surgical findings of a tortuous ica with circumferential calcification corresponded to bone window images of the baseline ct scan ( fig . a baseline ct scan usually precedes an intraarterial procedure to screen for hemorrhagic stroke and/or intravenous rt - pa ; therefore , we can easily obtain additional information related to the severity of preexisting atherosclerosis in a large artery . also , if the findings are like the present case , more cautious retrieval is required to perform the solitaire stent assisted technique and using another technique including forced suction thrombecotmy or intra - arterial chemical thrombolysis is also able to be considered . first , self - detachment of solitaire stent can be caused by other reasons , for example , stent grabbed unusually large amount of thrombi and/or the problems of stent itself including the characteristics of detach zone or production process error . second , ica calcification is highly prevalent and can occur more than 50% on the ct scan1 ) , therefore , the findings in this case can be regarded as additional information for minimizing the chance of such drastic complication if circumferential ica calcifications coupled with severe tortuosity . this study presents a case of inadvertent self - detachment of a solitaire ab stent during mechanical thrombectomy involving a vessel with severe circumferential arteriosclerosis coupled with tortuous anatomy . based upon our experience , some caution is required regarding difficult retrieval to prevent unexpected detachment in such circumstances . additionally , we suggest that bone window images of a baseline ct scan can play a role in terms of anticipating difficult stent retrieval before the procedure .

we recently experienced self - detachment of the solitaire stent during mechanical thrombectomy of acute ischemic stroke . then , we tried to remove the detached stent and to recanalize the occlusion , but failed with endovascular means . the following diffusion weighted image mri revealed no significant increase in infarction size , therefore , we performed surgical removal of the stent to rescue the patient and to elucidate the reason why the self - detachment occurred . based upon the operative findings , the stent grabbed the main thrombi but inadvertently detached at a severely tortuous , acutely angled , and circumferentially calcified segment of the internal carotid artery . postoperative angiography demonstrated complete recanalization of the internal carotid artery . the patient 's neurological deficits gradually improved , and the modified rankin scale score was 2 at three months after surgery . in the retrospective case review , bone window images of the baseline computed tomography ( ct ) scan corresponded to the operative findings . according to this finding , we hypothesized that bone window images of a baseline ct scan can play a role in terms of anticipating difficult stent retrieval before the procedure .

musa acuminata ( banana ) is one of the most important fruit crops of world as well as of india . banana could be considered poor man 's apple , and it is the cheapest among all other fruits in the country . the pathogen is soil - borne and remains viable up to several years and cause 20%80% loss of banana . several disease management strategies can be used such as crop rotation , burning infected plants or plant parts , and application of carbendazim . methods mentioned have limited success , and the application of synthetic fungicides may result in undesirable effects on the environment . an alternative to above strategies for managing fusarium wilt is the use of biological control . biocontrol agent can be a beneficial organism ( live or dead ) or its part such as cell wall , protein , and oligosaccharides . while using live organisms as a biocontrol agent , appropriate conditions for maintaining it should be strictly followed . nevertheless , if part of the organism such as cell wall , protein , oligosaccharide , or attenuated / killed organism is used then strict conditions are not required . plants , humans , and animals give instantaneous response to the pathogen or its part . animals and humans produce antibodies against pathogen or vaccine , similarly plants response to pathogen attack by producing pr - proteins , defense - related enzymes , plantibodies , and phytoalexins . study of pr - proteins or defense - related enzymes are key to any plant disease resistance mechanism . farmers in gujarat , india purchase tissue culture plants every year for sowing in the fields with the expectations of getting high production and high profit . foc being soil borne may enter the plant and cause disease anytime after sowing and affects fruit production . if plants are immunized , that is , accumulation of defense - related enzymes occurs before the attack of pathogen then the pathogen can be successfully warded off , and loss can be minimized . elicitor used here is acting as a vaccine ( derived from the dead fungus ) to protect the plant . the aim of the present study was to compare the interaction of dead and live pathogen with banana plants ( grand naine variety ) . grand naine is a large fruit yielding dwarf cavendish variety with height of 6.5 to 7.5 ft introduced to india from israel remains choice of farmers as the bunches of banana fruits can be harvested within twelve to thirteen months from the date of planting . the plant response was documented using several marker enzymes to analyze whether the plant could differentiate the signals from dead and live pathogen . another important aim was to check if the response generated using dead pathogen was sufficient to ward off the forced inoculated live pathogen . cubense ( foc ) from fusarial wilt infected banana plants was maintained on potato dextrose agar ( pda ) at 27c . for liquid culture of fungus , 8-mm agar plug of 3 - 4 w k old culture was inoculated in potato dextrose broth ( pdb ) and incubated at 27c for 21 day on pdb . the media with mycelium was autoclaved at 121c for 20 minutes , crushed intensely in grinder , and was used as dead fungi for treatment . two months old banana ( grand naine variety ) plantlets were procured from gujarat state fertilizers and chemicals ( gsfc ) , baroda , gujarat . plant roots of grand naine variety were exposed without damaging them by carefully removing the surrounding soil . dead and live fungus suspensions were prepared by mixing 1 g of dead fungus and live fungus per liter of distilled water . per plant , 1 ml of dead and live pathogen suspension was administered against control plants treated with 1 ml of distilled water in exposed root region . after treatment , changes in levels of defense - related enzymes in leaves were assayed after each successive day till seventh day [ 4 , 5 ] . leaves were excised up to seven days at regular interval of 24 h for estimation of defense related enzymes , namely , pox , ppo , -1,3 glucanase , chitinase , and total phenolics from both control and treated plants . experiments were repeated twice under similar conditions with different sets of plants , and all the analyses were performed in triplicates . ppo , -1,3 glucanase , chitinase , and total phenolics assays were done as described by meena et al . . to ensure the induction of resistance , plant roots treated with dead pathogen was exposed to spore suspension of foc ( 10 spores / ml ) where plants treated with distil water was used as control and exposed to same quantity of spore suspension as experimental . the aim of this study was to investigate interaction of dead and live pathogen , fusarium oxysporum f.sp . cubense a causative agent of panama disease , with banana plants ( grand naine ) . interaction was determined using accumulation of several defense related enzymes , namely , pox , ppo , -1,3 glucanase , chitinase , and total phenolics as markers for induction of defense . hypothesis was that plants could differentiate signals from dead and live pathogen and in response to signals from dead pathogen , it can induce defense enzymes , which could protect plants upon subsequent exposure to pathogen . pox activity induced earlier in dead and live pathogen treated plants and retained elevated levels compared to control plants . pox activity increased 4- and 2.5-fold in dead and live fungus treated plants , respectively . highest pox activity in plant treated with dead and live pathogen was observed on 6th and 7th day , respectively ( figure 1 ) . comprehensible difference in ppo activity was observed on treatment of dead and live pathogen . with live fungus interaction , plants showed to induce 3-fold ppo activity from first day onward , reached highest level on 4th day , and thereafter reached near basal . however , dead fungus treatment failed to mount significant induction in ppo activity for initial five days of interaction followed by 2- and 3-fold induction in ppo activity on 6th and 7th days , respectively compared to control plants ( figure 2 ) . interaction of dead and live fungus with banana plants resulted in induction of -1,3 glucanase activities from 1st day onward . up to five days , pattern of -1,3 glucanase activity was very similar in both treatments . from the 5th day onward , -1,3 glucanase activities stabilized at 2- to 2.5- fold higher levels in live fungus interaction as compared to control . in case of dead fungus interaction , gradual increase in -1,3 glucanase activity was observed from 5th day onward with highest increase 3.5-fold on 7th day as compared to control ( figure 3 ) . chitinase activity induced from 1st day in banana plants treated with dead and live pathogenic fungus . figure 4 showed stiff rise ( 10-fold ) in chitinase activity on 2nd and 3rd day followed by rapid fall and retention of about 1.5 fold chitinase activity in banana treated with live fungus compared to control plants . whereas , in dead fungus treated plants , chitinase activity increased twofold on 1st day followed by gradual increase up to 4-fold on 7th day . in dead fungus treated plants , total phenolics content gradually increased and reached to maximum on 7th day ( 2-fold ) . whereas in live fungus treated plants , total phenolics content increased on 3rd day followed by sharp decline to reach basal level as compared to control plants ( figure 5 ) . control plants and plants treated with dead pathogen were forced inoculated with the live fungal spores and observed for the development of symptoms . in control plants , the characteristic symptoms of fusarial wilt were observed in the first week after forced inoculation followed by aggravation of disease condition after 15 days . however , no symptoms of fusarium wilt were observed even after two months after forced inoculation in plants treated with dead pathogen . in the present study , analysis of plants response towards dead and live pathogenic strain was carried out using induction of several key marker enzymes associated with plant defense mechanism . development of effective , durable , economic , and environmentally sound strategies for the control of crop diseases could be possible through an improved understanding of the interactions between plants and pathogenic agents . the ability of a pathogen to produce a disease in a host plant is usually the exception , not the rule . this is because plants have an innate ability to recognize potential invading pathogens and to set up successful defenses . on the other hand , successful pathogens produce diseases because they are capable to evade detection or suppress host defense mechanisms , or both . when plants are challenged by a pathogen , early local defense reactions and delayed , systemic responses get activated in order to counteract the pathogen attack . among the early local responses , the hypersensitive response ( hr ) leads to a local programmed cell death in order to deprive the pathogens of their nutrition base . later on , the plant can develop systemic acquired resistance ( sar ) leading to resistance throughout the whole plant in an unspecific manner towards a broad spectrum of pathogens . in case of sar , signal is transmitted from infected tissue in the whole plant for induction of overall defense gene expression . this demonstrates that signal perception in initial pathogen recognition and signal transduction to initiate further defense responses is essential for plants to counteract phytopathogens . some defenses are constitutive , such as various pre - formed antimicrobial compounds , whereas others activated by pathogen recognition . recognition process includes product of a dominant or semidominant resistance r gene present in the plant and the corresponding dominant avirulence ( avr ) factor encoded by or derived from the pathogen . recognition of avr factor by host plant starts one or more signal transduction pathways that activate several of plant 's defenses , thus compromising ability of pathogen to colonize plant [ 11 , 12 ] . in the present study , interaction of banana plants with dead and live pathogen resulted in induction of pox activity . as dead pathogen was capable to generate initial recognition signals ; however , it can not counter the plant response , which leads to induction of pox activity more than live fungus . peroxidases are a well - known class of pr proteins and induced in host plant tissues by pathogen infection . they belong to pr - protein 9 subfamily and are expressed to limit cellular spreading of infection through establishment of structural barriers or generation of highly toxic environments by massively producing ros and rns . peroxidase activity or peroxidase gene expression in higher plants is , indeed , induced by fungi , bacteria , viruses , and viroids . cross - linking of the phenolic monomers in oxidative coupling of lignin subunits has been associated with peroxidase using h2o2 as oxidant . one significant event in plant defense reactions is oxidative burst , a common early response of host plant cells to pathogen attack and elicitor treatment . our results showed increase in pox activity in dead fungus treated as well as fungus treated plants as compared to control . this result indicates that elicitor slowly increases level of lignin formation , suberization , and hypersensitive response . other enzymes , ppos are a group of copper containing enzymes that catalyze oxidation of hydroxy phenols to their quinone derivatives , which have antimicrobial activity . because of its reaction products and wound inducibility , ppo plays a role in defense against plant pathogens . plant immediately respond to pathogen so there is immediate rise in ppo indicating immediate synthesis of antimicrobials to ward off pathogen . in elicitor treated plant ppo activity increases slowly day by day indicating that plant has got stimuli to increase ppo . in case of live pathogen interaction , there was immediate response by plants increasing ppo 5-fold on the first day , which starts decreasing from the 6th day indicating multiplication of fungus in the plant system . however , dead pathogen completely fails to mount this response , which strongly suggests that plants are capable to differentiate signals from live and dead pathogen . increase in ppo activity was reported in banana roots treated with foc - derived elicitors by thakker et al . . marked increase in ppo activity was observed in banana roots treated with psuedomonas fluorescens against fusarial wilt . -1,3 glucan and chitin , polymer of n - acetylglucosamine ( nag ) are major cell wall components of many fungi . since -1,3 glucanase and chitinases have been shown to be capable of attacking cell wall of fungal pathogens , these enzymes have been proposed as direct defense enzymes of plants . we observed an increase in chitinase and -1,3 glucanase activity indicating plants ready mechanism to ward off pathogen by directly degrading the pathogen cell wall and in turn protecting the plant . in our previous study , we found antifusaric activity of elicitor induced -1,3 glucanase that showed swelling of mycelia after one hour incubation of pathogen with purified elicitor . endochitinase purified from barley was capable of inhibiting the growth of trichoderma rescei , alternaria alternate and neurospora crassa . in addition , mauch et al . reported that in combination , chitinase and -1,3 glucanase act synergistically to inhibit fungal growth . phenolic acids are involved in phytoalexin accumulation , biosynthesis of lignin , and formation of structural barrier , and play a main role in the resistance against pathogen . marked accumulation of phenolics was observed on the 3rd third day in fungus treated plants indicating the plants sensitivity to pathogen , and it attempt to protect itself by the formation of structural barriers . further , from the 4th day activity decreases showing successful multiplication and establishment of pathogen by overcoming structural barriers formed by plants . in dead pathogen - treated plants , we found slow increase in phenolics activity indicating ability to recognize dead pathogen as some foreign body , but it is not multiplying ; therefore , it will not break structural barrier . marked accumulation of phenols leading to suppression of fusarial wilt was observed in tomato plants . similar results were observed in banana plants in vitro condition . when tomato plants were treated with catechol , marked accumulation of phenols anna and dubery investigated that subfraction of cell - wall bound phenolics , ester - bound phenolics , glycoside bound phenolics , and free phenolics increased 6.3- , 4.2- , 3.0- , and 2.3-folds , respectively , upon induction . in plants treated with dead pathogen , a forced inoculation of live pathogen was performed to assess induced plant 's ability to ward off pathogen . interestingly no symptoms of fusarial wilt were observed in these plants even though pathogen was in close proximity . the present study strongly supports the view of preparation of plant vaccines for combating devastating disease like fusarium wilt of banana . dead pathogen preparation was not only successful in mounting defense response but also in protecting plants upon subsequent infections . therefore , it could be potential candidate for plant vaccine preparation to combat panama disease .

the aim of the present study was to scrutinize the response of banana ( grand naine variety ) plants when interacting with dead or live pathogen , fusarium oxysporum f.sp . cubense , a causative agent of panama disease . response of plants was evaluated in terms of induction of defense - related marker enzyme activity , namely , peroxidase ( pox ) , polyphenol oxidase ( ppo ) , -1,3 glucanase , chitinase , and phenolics . plant 's interaction with live pathogen resulted in early induction of defense to restrain penetration as well as antimicrobial productions . however , pathogen overcame the defense of plant and caused disease . interaction with dead pathogen resulted in escalating defense response in plants . later on plants inoculated with dead pathogen showed resistance to even forced inoculation of live pathogen . results obtained in the present study suggest that dead pathogen was able to mount defense response in plants and provide resistance to panama disease upon subsequent exposure . therefore , preparation from dead pathogen could be a potential candidate as a biocontrol agent or plant vaccine to combat panama disease .

acute pancreatitis ( ap ) is a pathology with acute inflammatory manifestations , and constitutes around 3% of all inpatient cases of abdominal pain ( 1 ) . all prevalence and incidence values of ap are based on hospital records and their accuracy is influenced by data collection methods , etiological and diagnostic approaches and social - demographic factors . descriptive incidence ranges from 5 , 4/100,000 per year in england ( 3 , 4 ) , to 15/100,000 per year in germany ( 5 ) , to 79.8 80 /100 000 per year in the u.s ( 6 , 7 , 8) . in countries where ap data are available was 9.4/100,000 from 1968 to 1980 , but it has been found a steep growth in 31 , 8/100,000 between 1985 - 1995 ( 5 , 9 ) . a similar increase is observed in other countries as well , such as england , denmark , sweden , finland , germany and the netherlands . recent studies show that the incidence of ap has increased during the last years ( 10 ) . the increase of incidence in northern european countries like finland and the netherlands is related to the increase of excessive alcohol consumption ( 11 ) , but on the other hand it might be linked with better discernibility due to better and faster diagnostic methods . distribution of ap etiology consists of 48% gallstones - related , 21% alcohol - related , 18% idiopathic and 57% other etiologies . this disparity is due to higher excessive alcohol consumption prevalence among males and because the distribution of gallstones - related ap is similar in males and females ( 5 , 6 ) . mortality rates of ap are , on average 1.3/100,000 ( 3 , 9 , 10 ) ; 55%65% of patients develop mild ap , 20%30% necrosis of the pancreas and 25% severe ap with complications ( 13 , 14 ) . there is a lack of data and publications regarding ap and incidence rates . in our daily practice , it has been found that the hospital admissions with the diagnosis of ap have increased . our study is intended to describe the epidemiological situation of ap among albanians patients , as well as to obtain data on incidence rates , etiology and severity of the disease . this is a retrospective study based on clinical records and patient admissions during an 8 year period 2005 - 2012 in the uhc mother theresa in tirana . mother theresa is a tertiary health care institution and serves as a reference for acute pancreatitis , as all cases are referred to this center from all corners of albania . patients with ap are admitted at the gastroenterology service , surgery service and intensive care unit depending on their situation at the moment of hospital admission . data collected included age , gender , symptoms , alcohol and drug consumption , coexisting diseases and pathologies . nearly all the patient had an ultrasonography on admission and during hospitalization , ct scans and/or magnetic resonance image ( mri ) when possible . ap was diagnosed if there were persistent clinical data for ap ( abdominal pain , nausea and vomiting ) , and elevated serum amylases levels 3 times over the normal values ( reference values of amylase lower than 110 iu / i ) . in those cases where amylasemia levels were not elevated , the diagnosis was based on clinical examination and imaging findings on ultrasonography and ct scan . ap diagnosis was determined only if at least two of the below listed criteria were present : acute pain or sensitivity in the epigastric regionelevation of amylase level 3 times over the normal values in blood or in the ascitic fluid ( if ascites present)imaging data of the pancreatic gland that suggest appatients with recurrent ap and chronic ap were not included in the study . acute pain or sensitivity in the epigastric region elevation of amylase level 3 times over the normal values in blood or in the ascitic fluid ( if ascites present ) imaging data of the pancreatic gland that suggest ap patients with recurrent ap and chronic ap were not included in the study . classification of acute pancreatitis was determined by : ( 1 ) etiology ( gallstones , alcohol , hyper - triglyceridemia , hypercalcemia , traumatic , autoimmune , viral etc . ) and by ( 2 ) severity ( mild to moderate and severe ap ) based on atlanta classification and ranson criteria . statistical package for social sciences , version 15.0 , chicago , illinois ( spss ) was used for analysis of the collected data . out of 1428 patients included in the beginning of the study based on their files , only 964 patients fulfilled the inclusion criteria of the ap during the years 2005 - 2012 . the total average age was 54.50 years 16.93 , range 2 - 104 years old . among 964 patients , 377 or 39.1% were females and 587 or 60.9% males . figure 1 shows the incidence of ap during the years 2005 - 2012 as well as the incidence of ap in females and males during these years . there is a steady increase in incidence rates of ap from 2005 to 2007 . incidence rates increase after 2008 and lower in 2010 with slight fluctuations . from 2010 to 2012 according to gender , incidence among males is generally stable , but among females there is a tendency of growth from 2010 to 2012 , almost doubled . incidence of acute pancreatitis between 2005 and 2012 , by sex ( per 100,000 ) incidence rates of ap in albania range from 3 , 6 5 , 64 new cases per 100,000 inhabitants , per year . incidence of ap is calculated based on data from our study and population data from the national institute of statistics of albania ( instat , census 2011 ) ( 16 ) . the distribution of ap cases by residence was 782 cases or 81.1% were residents of urban areas and 182 cases or 18.9% of rural areas . according to instat , the resident population in urban areas was 53.5 per cent , while 46.5 per cent of the population was living in rural areas . based on the risk factors , we have classified patients with ap as biliary , alcoholic , hypertriglyceridemic and other etiology , including viral , trauma , autoimmune and idiopathic causes . distribution of ap by risk factors and gender . out of 964 cases with ap , 382 ( 39.6% ) of them reported alcohol consumption , which was greater compared with other etiological risk factors . in 362 patients ( 37.6% ) we identified gallstones as a risk factor , hypertriglyceridemia in 19 patients ( 2.0% ) and other etiologic factors in 201 patients ( 20.8% ) . in males , alcoholic etiology is the most common cause of ap ( 382 out of 587 male patients or 65.07% had alcoholic ap ) , and the gallstones are more frequent in females ( 308 or 81.69% out of 377 female patients ) . our results show that females develop more biliary pancreatitis , while men develop alcoholic pancreatitis and this is statistically significant ( kendall s tau - b r = 0.473 , p < 0,001 ) . in albania , males are distinctively more heavy drinkers compared to females , and this difference is expressed in the table 1 ; actually we have no females identified to be alcohol consumer . mean age of patients with biliary etiology was 62 14 , while the mean age of patients with alcoholic etiology was 51 14 ( p < 0 , 05 ) . mean age of female patients with biliary etiology was 59 17 , while the mean age of male patients with biliary etiology was 62 13 . males with alcoholic pancreatitis have younger age than females with biliary etiology who develop pancreatitis at an older age . during the study period , 690 cases ( 71.57% ) have been classified with mild or moderate ap . 274 patients ( 28.42% ) have been determined to have a severe manifestation of the disease , table 2 . the incidence of ap ranges from 10 to 80 new cases/100,000 inhabitants worldwide , but in most european studies , it has a much narrower range from 20 to 30 new cases/100,000/year ( 18 ) , higher than the results of our study . although several european studies have shown a significant increase in the incidence over the last 20 years , our study showed a slight increasing trend over an eight year period ( 19 , 20 , and 21 ) . our study has also shown a pattern in the incidence of ap with regards to the etiology . the incidence of alcohol ap seems to be almost steady , with slight fluctuations over the years . on the other hand , , the general impression is that we see more alcoholic than biliary pancreatitis , but our data do not support our impression . most of the studies have demonstrated that specific etiologic factors dominate within a certain region of the country . for example , a higher proportion of cases with alcoholic ap were found in the grampian and highland region of scotland ( 22 ) . the different distribution of afore mentioned etiologies is not entirely clear but can be explained by the difference in alcohol consumption and the incidence of gallstone ap between north and south europe . continental europe has a particularly high incidence of alcoholic pancreatitis , not only because of high alcohol consumption per capita , but also due to the fact that alcoholic beverages in this climate contain a high percentage of alcohol , and as such may have a stronger toxic effect on the pancreas ( 25 ) . a reasonable explanation of this epidemiologic situation might be that the incidence of alcoholic ap is steady because but most of our alcoholic ap cases have developed severe ap , and mild to moderate cases are not recovering at the hospital , as the symptoms of the disease are mild . according to the albanian demographic and health survey of 2008 - 09 , 16 . 3% of men aged 15 - 49 are heavy drinkers and a sharp increase is observed among the group age of 35 - 49 from 19.5 in 24 . this might be because of the better diagnosis and discernibility of the gallstones and improved diagnosis of the biliary tree during the last years . during the last years it has been demonstrated that increased prevalence of gallstones and gallbladder disease in the obese patients is accompanied with an increasing incidence of acute pancreatitis in those patients , and this might be another reason ( 23 ) and data from adhs show an increasing prevalence of overweight and obesity during the last two decades ( 17 ) . the frequency of alcohol and biliary etiology varies between sexes , but without significant ( p>0.05 ) and as we would expect , significantly more women than man had biliary ap , and more man than women suffered considerably from alcohol - induced ap . men develop alcoholic ap at a younger age 51 14 years , while females develop biliary pancreatitis at an older age 59 17 years , and this is statistically significant ( p<0.05 ) in our analysis , there were 19 patients ( 2% ) with hypertriglyceridemia as the etiologic cause of ap . according to the literature , it is assumed that hypertriglyceridemia is the cause of ap in 4% of cases , and we are relatively close to this figure ( 19 , 24 ) . we have identified a virus as the etiological factor for ap , one of them was a two year old baby boy . these data are in agreement with other epidemiological studies , especially with the results published in our neighboring countries , italy , greece and croatia , even that the incidence rates are lower ( 25 ) . the incidence of acute pancreatitis in albania varies from 3.6 to 5.64 new cases per 100,000 inhabitants , which is lower than the incidence of pancreatitis in the region , but with an increasing trend . the majority of cases have an alcoholic etiology ( 39.6% ) and the young age of male patients .

background : acute pancreatitis ( ap ) is an inflammatory pathology with large regional variations in incidence and etiologyaim : the aim of the study was to provide a description of the epidemiologic situation of ap in albanian population , regarding incidence , etiology and severity of the diseasemethods : we have studied all the files of all patients with acute pancreatitis admitted at the uhc mother theresa during an eight year period ( 2005 - 2012).the results : we had 964 admissions with the diagnosis acute pancreatitis , making an incidence of 5.64 per 100 000 inhabitants per year . mean age of patients was 54.5 16.93 years old . among risk factors , alcohol consumption was found in 382 patients ( 39.6% ) , gallstone in 362 patients ( 37.6% ) , and others in 220 patients ( 22.8%).conclusion : the incidence of acute pancreatitis in albania ranges from 3.6 5.64 new cases per 100 000 inhabitants per year , with an increasing trend during the last years . the incidence of ap among females almost doubles during 2005 - 2012 . alcohol consumption is the predominating etiologic factor among young males .

we selected and analyzed three melanoma - related tissue types ( prms , lnms and mbms ) and normal melanocytes ( mncs ) representing the melanoma progression to mbm . first , the conventionally accepted normal controls for melanoma are short - term cultured mnc cells . second , due to the small size of prm and mbm lesions , tissue availability is usually very limited . our study focused on dna methylation , which was analyzed for all the samples ( n = 40 ; gse44661 ) . to evaluate the potential transcriptional impact of dna methylation changes on mbm - development , rna expression was also assessed in metastatic melanomas and mncs ( n = 22 ; gse44660 ) . to exclude the influence of snps or allele cnv on dna methylation analysis , genome - wide snp analysis was performed on metastatic melanomas ( n = 16 ; gse44019 ) . this study included three human mncs isolated from normal skin ( life technologies , carlsbad , ca ) , four paraffin - embedded archival tissue ( peat ) prms obtained from ajcc stage ii melanoma patients , seventeen lnms ( peat and cultured cells ) obtained from ajcc stage iii melanoma patients and sixteen mbms ( peat and cultured cells ) obtained from ajcc stage iv melanoma patients . importantly , lnms were classified based on disease - free survival ( dfs ) into good ( n = 10 ; dfs>5 yr ) and poor ( n = 7 ; dfs<2 yr ) prognosis groups ( table 1 ) . melanoma patients were included in the study under protocols approved by providence saint john 's health center / jwci joint institutional review board and western institutional review board and the sydney local health district , rpah zone , human ethics review committee . informed consent was obtained from all subjects and the experiments were performed according to the principles set out in the wma declaration of helsinki and the nih belmont report . tissue specimens were coded according to hipaa recommendations to ensure the confidentiality of the patients . dna methylation assays were performed using illumina humanmethylation450 ( hm450k ) beadchip following the manufacturer 's protocol ( illumina , san diego , ca ) . the chips were scanned with illumina iscan microarray scanner ( illumina ) , and the data was extracted using the r package methylumi on bioconductor . the methylation levels were reported as a -value [ = intensity of the methylated allele/(intensity of the unmethylated allele + intensity of the methylated allele ) ] , and calculated using the signal intensity value for each cpg site . genotyping of dna from melanoma specimens was performed using affymetrix genome - wide human snp array 6.0 by following the manufacturer 's recommendations ( affymetrix , santa clara , ca ) . the genotype calls of each specimen were determined by the birdseed 2.0 genotype calling algorithm included in the affymetrix genotyping console 4.0 . quality control ( qc ) of arrays was conducted using the contrast quality control ( cqc ) algorithm , with a minimal call rate of > 95% . copy number ( cn ) analysis was performed using regional gc correction and default software settings . cn segments were reported with an hmm algorithm using the default cn map in genotyping console 4.0 ( toronto dgv map ) . total rna was analyzed by genechip human exon st array 1.0 ( huex 1.0 ) following the manufacturer 's protocol ( affymetrix ) . data were analyzed in expression console 1.1 software ( affymetrix ) using the core transcript set and employing the robust multi - array average algorithm ( rma ) for background correction and normalization of data . as we described , dna methylation data was filtered to exclude probes associated with snps , regions with commonly occurring cnv and sex chromosomes . additionally , after background correction , probes with no significant difference from the background noise ( p > candidate cpg sites with differential methylation among study groups were validated as functional by seeking statistical differences in rna expression . in this data in brief article , we described in detail the contents of the dataset associated with the study published by marzese and colleagues in the human molecular genetics journal in 2014 . this multiplatform analysis offers the opportunity of identifying genetic and epigenetic alterations that can be used as potential theranostic biomarkers for melanoma progression to mbm .

melanoma has a high tendency to metastasize to brain tissue . the understanding about the molecular alterations of early - stage melanoma progression to brain metastasis ( mbm ) is very limited . identifying mbm - specific genomic and epigenomic alterations is a key initial step in understanding its aggressive nature and identifying specific novel druggable targets . here , we describe a multi - platform dataset generated with different stages of melanoma progression to mbm . this data includes genome - wide dna methylation ( illumina hm450k beadchip ) , gene expression ( affymetrix huex 1.0 st array ) , single nucleotide polymorphisms ( snps ) and copy number variation ( cnv ; affymetrix snp 6.0 array ) analyses of melanocyte cells ( mncs ) , primary melanoma tumors ( prms ) , lymph node metastases ( lnms ) and mbms . the analysis of this data has been reported in our recently published study ( marzese et al . , 2014 ) .

the demand for esthetic restorations in dentistry has increased over the past few years . since resin composites were first developed , many efforts have been made to improve the clinical behavior of these restorative materials . although both organic and inorganic phases might influence the material behavior , the filler particle features and rate are the most important factors affecting the mechanical properties of resin composites . adequate polymerization could be considered a crucial factor in obtaining good clinical performance , particularly in stress - bearing areas . an insufficient curing degree affects the resin composite 's chemical properties such as water absorption , wear resistance , and strength , as well as the elution of possible irritant , allergic , or toxic components from the material . factors such as the filler particle size , polymeric matrix , and radiant exposure generated by the light source can influence the degree of conversion of resin composites , and thereby influence their mechanical properties . the degree of monomer conversion of resin composites can be measured using different testing techniques , either directly or indirectly . among the indirect methods , surface hardness testing has been used in many studies because it has been shown to be a good indicator of the degree of conversion . surface hardness can be measured on the upper and lower surfaces of disk - shaped specimens with a given thickness . this method is used to measure the relative hardness , which is considered a good indicator for degree of conversion . the filler particles features and rate are the most important factors related to improvement of the mechanical properties of resin composites . resin composites have been classified according to their filler particle size as hybrid ( 0.5 - 3 mm ) , microhybrid ( 0.4 - 1 mm ) , and microfilled ( 0.04 - 0.4 mm ) . more recently , the nanocomposites have been introduced , materials presenting high initial polishing ability combined with superior polish and gloss retention . the degree of cure of visible light activated dental resins is also strictly dependent on the characteristics of curing lights . a curing light intensity output depends on many factors ( light guide , condition of the bulb , battery power ) ; the mechanical properties of the resin composites are determined by total energy irradiation , which is clearly related to irradiation time chosen by the operator . also , the distance of the light from the resin composite is a crucial factor . light - emitting diode ( led ) curing lights have recently become very popular since they have a number of advantages over the conventional halogen units . hardness has been used to predict the wear resistance of a material and its ability to abrade or be abraded by opposing tooth structures . to define depth of cure based on top and bottom hardness measurements , it is common to calculate the ratio of bottom / top hardness and give an arbitrary minimum value for this ratio in order to consider the bottom surface as adequately cured ; values of 0.80 and 0.85 manufacturers of dental resins give recommendations about depth of cure as they relate to light activation . the most common indication is the use of a specific light intensity and exposure time which is able to cure a 2 mm thickness of the material . actually , in clinical practice , it is often difficult to make 2 mm regular increments , especially in cavities with irregular depth or in the presence of undercuts , where light intensity could be shielded by dental tissues . the current in vitro study focused on vickers microhardness ( vk ) of six commercial resin composites : the influence of polymerization time of 20 and 40 s and depths of cure of 2 and 3 mm was evaluated . six resin composites ( shade a2 ) were selected in accordance with their type of filler particles : three microhybrid composites ( filtek silorane , esthet.x , kalore ) , two nanohybrid composites ( grandio and ceram.x mono ) , and a nanofilled resin composite ( filtek supreme xt ) . the properties of the materials used are shown in table 1 . the chosen resin composites were light activated with an led unit , celalux ii ( voco , cuxhaven , germany ) . a standard light polymerization mode was used for each material at 1000 mw/ cm intensity for 20 and 40 s. the hardness testing methodology used to assess the effectiveness of cure was based upon that used by yap and seneviratne . samples were prepared by placing the material into a stainless steel mold ( 7 mm , h 2 - 3 mm ) , placed on a dark opaque paper background covered with a polyester matrix strip . the mold was filled with the resin composite and a second polyester matrix strip was placed on the top of the filled mold . a glass slide was pressed against the upper polyester film to extrude the excess resin composite and to form a flat surface . the distal end of the light guide ( diameter 10 mm ) was placed against the surface of the matrix strip and positioned concentrically with the cavity in the mold ; the material was then light - cured from the top . the cordless curing unit was maintained at full charge before use , and irradiance was monitored periodically using a radiometer ( led radiometer , kerr , orange , ca , usa ) . after polymerization , the samples were stored for 24 h in complete darkness at 37c and 100% humidity before performing the vickers hardness test . the vk of the surface was determined with a microhardness tester ( zwick - roell durometer , zhv1/2 micro - vickers , italy ) using a vickers diamond indenter and a 200 g load applied for 15 s. five vk readings were recorded for each sample surface ( top and bottom ) ; hardness measurements were not taken at more than 4 mm from the specimen center to avoid any possible effect of the mold on polymerization . for a given specimen , the five hardness values for each surface were averaged and reported as a single value . the mean vickers hardness and hardness ratio of the specimens were calculated and tabulated using the formula : hardness ratio = vk of bottom surface / vk of top surface . materials and manufacturers mean vickers hardness and hardness ratio of 2 mm specimens of the composite resins were evaluated after polymerization for 20 and 40 s. mean vickers hardness and hardness ratio at 2 mm and 3 mm depth of the composite resins were compared choosing a polymerization time of 40 s for all the specimens . differences in the averaged values amongst the groups were analyzed by analysis of variance ( anova ) test and tukey 's honestly significant difference ( hsd ) post hoc test . mean vickers hardness and hardness ratio of 2 mm specimens of the composite resins were evaluated after polymerization for 20 and 40 s. mean vickers hardness and hardness ratio at 2 mm and 3 mm depth of the composite resins were compared choosing a polymerization time of 40 s for all the specimens . differences in the averaged values amongst the groups were analyzed by analysis of variance ( anova ) test and tukey 's honestly significant difference ( hsd ) post hoc test . the mean vickers hardness at 2 mm depth of top and bottom surfaces associated with the 20 and 40 s polymerization modes is shown in table 2 . hardness ratio values for the two groups are reported in table 3 . among the materials tested , only grandio ( voco ) showed a non - significant statistical difference ( p > 0.05 ) in hardness values on both up and down sides and for 20 and 40 s polymerization time . mean vickers hardness of top and bottom surfaces at 2 mm depth with 20 and 40 s polymerization time periods hardness ratio at 2 mm depth recorded after 20 and 40 s polymerization time periods the mean vk of top and bottom surfaces and hardness ratio at 2 and 3 mm depth associated with the 40 s polymerization mode is shown in table 4 . mean vickers hardness of top and bottom surfaces with 2 and 3 mm depth of cure hardness ratio recorded with 2-and 3-mm depth of cure the mean vickers hardness at 2 mm depth of top and bottom surfaces associated with the 20 and 40 s polymerization modes is shown in table 2 . hardness ratio values for the two groups are reported in table 3 . among the materials tested , only grandio ( voco ) showed a non - significant statistical difference ( p > 0.05 ) in hardness values on both up and down sides and for 20 and 40 s polymerization time . mean vickers hardness of top and bottom surfaces at 2 mm depth with 20 and 40 s polymerization time periods hardness ratio at 2 mm depth recorded after 20 and 40 s polymerization time periods the mean vk of top and bottom surfaces and hardness ratio at 2 and 3 mm depth associated with the 40 s polymerization mode is shown in table 4 . mean vickers hardness of top and bottom surfaces with 2 and 3 mm depth of cure hardness ratio recorded with 2-and 3-mm depth of cure resin composites are widely used in restorative dentistry and specifically in posterior restorations , putting the material under constant masticatory stresses . one of the most important parameters involved in resin composites resistance to stress is depth of cure . the effectiveness of cure depends on the filler particle type , size , and quantity , and on the parameters ( intensity , time , and polymerization modes ) of the light source . the optimal degree of curing throughout the bulk of a visible light - activated dental resin composite is acknowledged to be important to the clinical success of a resin composite restoration . unfortunately , the dentist has no means of monitoring the cure of the resin surfaces not directly exposed to the curing light . . stated that one brand of composite in flowable , hybrid , and packable formulations did not achieve a 2 mm depth of cure with a 20 s light exposure . these data suggested that a 2-mm build - up layering technique may not result in adequate curing of the bottom layer for such a wide range of materials ; manufacturers need to provide quantitative information about degree of conversion at specific activation time periods and light intensities for their entire range of resin materials and shades so that the dentist can devise a placement technique that will ensure adequate cure of the bulk of a restoration . these findings are in disagreement with some studies which have shown that 2-mm increments are well polymerized . concluded that the bottom - to - top surface microhardness ratios of a composite resin can not be an accurate reflection of bottom - to - top degree of conversion ; bottom - to - top microhardness and degree of conversion were independent of composite composition . in the present study , two related aspects of resin composites polymerization were compared : polymerization time of 20 and 40 s and depth of cure at 2 and 3 mm depth . in the first part of the experimentation , 2-mm - thick composite specimens were used as they ensured uniform and maximum polymerization . the degree to which light - activated composites polymerize is proportional to the amount of light intensity to which they are exposed . ideally , the degree of polymerization of the composite should be the same throughout its depth and the hardness ratio should be very close or equal to 1 . as light passes through the composite , the light intensity is greatly reduced due to light scattering , thus decreasing the effectiveness of cure at the bottom surface . it was suggested that hardness ratio should be greater than 0.8% for light - activated composites to be adequately polymerized . among the materials tested , only grandio ( voco ) showed a non - significant statistical difference ( p > 0.05 ) in hardness values on both up and down sides and for 20 and 40 s polymerization time . comparing the two polymerization time periods , grandio , filtek silorane , and filtek supreme xt gave no statistical difference ( p > 0.05 ) between 20 and 40 s polymerization time periods on both sides . amaris , esthet.x hd , ceram.x mono gave statistically different values ( p < 0.05 ) between 20 and 40 s polymerization time periods on both sides . these results depend on the total amount of energy reaching the composite layer and on chemical composition of the composites . regarding hardness ratio , all the materials provided values within the limit of 0.8 , although only for ceram.x mono the value recorded coincided with the above - mentioned limit . hardness ratio values were not increased by increasing the polymerization time for grandio , amaris , filtek silorane , and filtek supreme xt ; on the contrary , for esthet.x hd and ceram.x mono , hardness ratio increased by increasing the polymerization time . this means that for these materials , the mechanical properties will be affected by polymerization time . pires , et al . found that the top surface hardness of composites was less independent on light intensity than the bottom surface . the top surface is actually receiving the maximum energy from the curing light . at the top surface it has also been established that even relatively low - intensity lights can cure the resin matrix to an extent almost equal to when high - intensity lights are used . the general lack of significance between 20 and 40 s polymerization time periods in top vickers hardness found in this study corroborates the above - mentioned studies . at the top surface , sufficient light energy reaches the photoinitiator , thus starting the polymerization reaction . at the bottom surface , a significant difference in vk was observed , depending on their chemical composition , but hardness ratio values were not affected by these differences . regarding the properties of the composite resins , the results were generally dependent on the material evaluated , especially with regard to filler features . moraes , et al . suggested that no trend toward the size or shape of fillers affected hardness ; grandio , for instance , presented the highest top and bottom vk values , probably because of its large particles and the highest filler content . supreme xt showed significantly higher hardness values than esthet.x hd , filtek silorane , and ceram.x mono , which were all conceived for posterior restorations . except for ceram.x , which was very sensible to polymerization time , the materials tested provided very good performances both at 20 and 40 s polymerization time periods . the good values recorded for grandio and filtek supreme xt are probably due to the presence of tegdma in the resin , which reduces the resin viscosity and increases the reactivity of the monomers . analyzing the second part of the experiment , for all the materials tested , there was not a statistical difference ( p > 0.05 ) in hardness values on the up side ( irradiation side ) with 2 and 3-mm thickness . a statistically significant difference ( p < 0.001 ) was recorded on the opposite side for all the composite resins . despite this sharp reduction in hardness values for 3 mm thickness , the hardness ratio values were higher than 0.8 for all the materials tested . these findings provided useful hints about clinical practice : the polymerization of a 3-mm composite resin increment for 40 s achieved a sufficient hardness ratio value for all the materials tested . among the materials tested , the nanofilled and the nanohybrid resin composites are very versatile and rather insensible to thickness variations . miicrohybrid composites , instead , have features different from one another : filtek supreme xt showed little variation with increasing depth of cure , while amaris and esthet.x hd provided a sharp reduction in hardness values with increasing depth of cure .

background : adequate polymerization of resin composites could be considered as a crucial factor in obtaining good clinical performance , particularly in stress - bearing areas . an insufficient curing degree affects the resin composite 's chemical properties the current in vitro study evaluated the influence of polymerization time and depth of cure of six commercial resin composites by vickers microhardness ( vk).materials and methods : six resin composites were selected : three microhybrid ( esthet.x hd , amaris , filtek silorane ) , two nanohybrid ( grandio , ceram.x mono ) , and one nanofilled ( filtek supreme xt ) . the vk of the surface was determined by a microhardness tester using a vickers diamond indenter and a 200 g load applied for 15 s. the bottom to top mean vk ratio was calculated using the formula : hardness ratio = vk of bottom surface / vk of top surface . vickers hardness values of test materials during exposure time of 20 and 40 s and depths of cure of 2 and 3 mm were determined and compared . data were analyzed using analysis of variance ( anova ) test.results:for all the tested materials and with all the exposure time periods , hardness ratio was higher than the minimum value indicated in literature ( 0.8 ) . exposure time and depth of cure did not affect hardness ratio values for filtek silorane , grandio , and filtek supreme xt.conclusion:among the materials tested , the nanofilled and the nanohybrid resin composites were rather insensible to thickness variations . miicrohybrid composites , instead , had features different from one another .

familial adenomatous polyposis ( fap ) is an autosomal dominant inherited disease that dictates development of colorectal adenocarcinoma in virtually all affected individuals by the age of 50 , unless prophylactic proctocolectomy is performed timely . even after this mutilating surgery , patients bear a significantly increased risk of duodenal adenocarcinoma ( 412% lifetime incidence ) and a risk of small bowel carcinoma 13 times greater than that of the general population . early diagnosis of fap and proctocolectomy allow extended survival , and concomitance with other diseases may appear as a clinical challenge . crohn 's disease ( cd ) is a chronic inflammatory bowel disease of unknown etiology that can affect any segment of the digestive tract . immunosuppressants and immunomodulators such as anti - tumor necrosis factor ( anti - tnf ) agents are the mainstay of therapy for inducing and maintaining remission in moderate to severe disease . despite advances in medical therapy , the majority of patients will need at least one surgery during their life , and issues such as permanent stoma or short bowel syndrome are not out of the horizon . the case we report illustrates the extremely rare association of fap and cd in the same patient , with obvious challenges in diagnosis , management and cancer surveillance . a 29-year - old man presents with bloody diarrhea , progressive asthenia and weight loss ( 8% of his usual weight in 6 months ) . physical examination was unremarkable and laboratory tests showed iron deficiency anemia ( hemoglobin 8.5 g / dl , mean corpuscular volume 72 fl , serum iron 8 g / dl and serum ferritin 5 ng / ml ) . the patient was followed in our family cancer risk clinic because he belonged to a family with fap . at the age of 16 prophylactic proctocolectomy with j - ileal pouch and ileo - anal anastomosis was performed when he was 26 years old and he maintained sphincteric tone with good continence and about 4 bowel movements per day . annual physical examination , laboratory screening and endoscopic evaluation of the pouch was performed as well as upper gastrointestinal endoscopy as dictated by the spigelman score ( last upper gastrointestinal endoscopy performed 3 months before symptoms ) . one year before bloody diarrhea and weight loss were noted , multiple ulcers were seen on a routine pouch evaluation . at that time he was completely asymptomatic , hemoglobin levels were normal , and he mentioned a 7-day course of nonsteroidal anti - inflammatory drugs for dental pain . investigation consisted of upper gastrointestinal endoscopy with findings of mild esophagitis and duodenal polyposis ( spigelman ii ) , and pouch endoscopy showed no abnormal features . small bowel capsule endoscopy showed multiple deep ulcers , some of them > 2 cm long , and a hyperemic and congestive surrounding mucosa ( fig . 1 ) . ileoscopy up to 60 cm from the anal verge was performed and multiple biopsies were taken from the ulcerated surface ( fig . 2 ) . histology showed ulceration , regenerative changes , inflammation with lymphoid follicle formation and numerous polymorphonuclear cells infiltrating the submucosa . mri enterography showed no abnormal findings other than mucosal uptake in the jejunum and ileum . we considered him to be a high - risk patient as he was a young smoker , with severe small bowel involvement from cd including the upper gastrointestinal tract ( jejunum ) , already submitted to small bowel surgery ( ileal pouch ) . after the mandatory viral serology tests and latent tuberculosis screening , 60 mg of oral prednisolone was started , with slow tapering during 12 weeks , while azathioprine was escalated up to 2.5 mg / kg . one year after diagnosis of cd the patient is symptom - free , has gained back 8 kg and has a normal hemoglobin level with replenished iron reserve . the prevalence of fap in portugal is thought to be around 1/7,500 and that of cd is 1/1,667 . assuming that there is no causal relation between fap and cd , . nevertheless , there are to our knowledge three case reports of concomitant fap and cd [ 1 , 2 , 3 ] . the association of fap and cd raises many concerns that we will try to discuss below . if cd is known before surgery for fap , the most important aspect is to completely assess the small bowel before surgery , in order to decide whether it is wise to proceed to proctocolectomy with ileal pouch . this should be done by ct or mri enterography and capsule endoscopy if no stenotic segments are described . a patient with cd may need small bowel surgery during his lifetime , and concerns about short bowel syndrome could make an ileostomy more advisable . we think that surgical decisions must be made on a case to case basis , taking into account cd risk features , namely young age at presentation , smoker status , phenotype , upper or extensive small bowel affection and difficulty to achieve and maintain remission with medical therapy . decisions must be shared with the surgeon and obviously with the patient , as permanent stoma means a serious quality of life impairment . if the cd diagnosis is only made intraoperatively , ileostomy would be the best option at least until cd is properly characterized . in the case described above , cd was diagnosed many years after fap had been discovered and 2 years after prophylactic proctocolectomy with j - ileal pouch had been performed . this sequence of events makes the need to medically control cd vital in order to avoid further small bowel surgery . family cancer risk clinics may represent a biased setting , as annual clinical evaluations and routine pouchoscopy offer the opportunity to diagnose otherwise subclinical disease . in these cases , cd with ileal involvement can be mistaken for pouchitis , with a delay in diagnosis , although it is known that pouchitis is very rare when the surgery is performed for fap , and the threshold for alternative diagnosis should be low . fap is a hereditary high penetrance disease , with an autosomal dominant pattern , that dictates an increased cancer risk . even after prophylactic proctocolectomy , fap patients have an increased risk of extracolonic malignancy , namely duodenal cancer ( 412% lifetime risk ) , thyroid cancer ( 23% lifetime risk ) and medulloblastoma ( < 1% lifetime risk ) . the risk of small bowel cancer is also increased , although this disease remains rare . immunosuppression with azathioprine is considered the standard medical therapy for maintaining remission in moderate to severe cd . thiopurine analogues have been used in cd for more than 40 years . up to date it is known that there is a 4-fold increase in the risk of lymphoma in patients treated with azathioprine and a 5-fold increase in the risk of nonmelanoma skin cancer . there is no association between thiopurine analogues and fap - related cancers , namely small bowel cancer risk increase . in fact , thiopurines might even reduce the risk of colorectal cancer , as recently described in patients with inflammatory bowel disease , possibly by reducing inflammation . considering that carcinogenesis through apc loss is the most common pathway to sporadic colorectal cancer and that the cumulative experience with thiopurines has never shown an increase in the risk for this malignancy , we feel there is no reason to exclude this therapeutic option in fap patients . another option to induce and maintain remission in these patients is immunomodulation with anti - tnf agents , but the risk of malignancy with these newer agents remains an unanswered issue . few conditions increase this risk , including both fap and cd . small bowel cancer ( distal to the ligament of treitz ) has rarely been reported in fap patients and current guidelines state that there is no evidence supporting routine surveillance . further studies are needed to know whether routine video capsule or mri enterography are justified . the cumulative risk of small bowel adenocarcinoma seems to be around 2.2% at 25 years of disease , with ileal predominance . it can only be speculated whether small bowel cancer risk is cumulative , synergistic or decreased in patients with both fap and cd . it seems reasonable to try to reduce ongoing inflammation with medical therapy for cd and to have a low threshold to investigate unclear complaints . we feel there is no reason to adopt a routine screening protocol with enterography or enteroscopy . if cd is known before surgery for fap , the most important aspect is to completely assess the small bowel before surgery , in order to decide whether it is wise to proceed to proctocolectomy with ileal pouch . this should be done by ct or mri enterography and capsule endoscopy if no stenotic segments are described . a patient with cd may need small bowel surgery during his lifetime , and concerns about short bowel syndrome could make an ileostomy more advisable . we think that surgical decisions must be made on a case to case basis , taking into account cd risk features , namely young age at presentation , smoker status , phenotype , upper or extensive small bowel affection and difficulty to achieve and maintain remission with medical therapy . decisions must be shared with the surgeon and obviously with the patient , as permanent stoma means a serious quality of life impairment . if the cd diagnosis is only made intraoperatively , ileostomy would be the best option at least until cd is properly characterized . in the case described above , cd was diagnosed many years after fap had been discovered and 2 years after prophylactic proctocolectomy with j - ileal pouch had been performed . this sequence of events makes the need to medically control cd vital in order to avoid further small bowel surgery . family cancer risk clinics may represent a biased setting , as annual clinical evaluations and routine pouchoscopy offer the opportunity to diagnose otherwise subclinical disease . in these cases , cd with ileal involvement can be mistaken for pouchitis , with a delay in diagnosis , although it is known that pouchitis is very rare when the surgery is performed for fap , and the threshold for alternative diagnosis should be low . fap is a hereditary high penetrance disease , with an autosomal dominant pattern , that dictates an increased cancer risk . even after prophylactic proctocolectomy , fap patients have an increased risk of extracolonic malignancy , namely duodenal cancer ( 412% lifetime risk ) , thyroid cancer ( 23% lifetime risk ) and medulloblastoma ( < 1% lifetime risk ) . the risk of small bowel cancer is also increased , although this disease remains rare . immunosuppression with azathioprine is considered the standard medical therapy for maintaining remission in moderate to severe cd . thiopurine analogues have been used in cd for more than 40 years . up to date it is known that there is a 4-fold increase in the risk of lymphoma in patients treated with azathioprine and a 5-fold increase in the risk of nonmelanoma skin cancer . there is no association between thiopurine analogues and fap - related cancers , namely small bowel cancer risk increase . in fact , thiopurines might even reduce the risk of colorectal cancer , as recently described in patients with inflammatory bowel disease , possibly by reducing inflammation . considering that carcinogenesis through apc loss is the most common pathway to sporadic colorectal cancer and that the cumulative experience with thiopurines has never shown an increase in the risk for this malignancy , we feel there is no reason to exclude this therapeutic option in fap patients . another option to induce and maintain remission in these patients is immunomodulation with anti - tnf agents , but the risk of malignancy with these newer agents remains an unanswered issue . few conditions increase this risk , including both fap and cd . small bowel cancer ( distal to the ligament of treitz ) has rarely been reported in fap patients and current guidelines state that there is no evidence supporting routine surveillance . further studies are needed to know whether routine video capsule or mri enterography are justified . on the other hand , the cumulative risk of small bowel adenocarcinoma seems to be around 2.2% at 25 years of disease , with ileal predominance . the risk is thought to be related to disease extension and duration . it can only be speculated whether small bowel cancer risk is cumulative , synergistic or decreased in patients with both fap and cd . it seems reasonable to try to reduce ongoing inflammation with medical therapy for cd and to have a low threshold to investigate unclear complaints . we feel there is no reason to adopt a routine screening protocol with enterography or enteroscopy .

familial adenomatous polyposis ( fap ) and crohn 's disease ( cd ) are two entities with no known etiologic or physiopathogenic relation . the rarity of the former makes the coincidence of both diagnoses in one patient very unlikely . nevertheless , management in such cases can be puzzling as surgical options must be considered , and immunosuppression / immunomodulation is set in a territory of accelerated carcinogenesis . we report the case of a 29-year - old male with a diagnosis of fap since adolescence , already submitted to prophylactic proctocolectomy , presenting with anemia and bloody diarrhea , revealing small bowel cd . this case allows for a rich discussion of the clinical dilemmas presenting when fap and cd are diagnosed in the same patient and for a deep analysis of the concerns inherent to the available therapeutic options .

fistulae between the upper respiratory and gastrointestinal tracts are uncommon in adults . whereas developmental anomaly is the commonest cause in infancy and childhood , the etiology in adults is most frequently secondary to an esophageal malignancy . we report two cases of esophagobronchial fistulae one secondary to chronic chest tuberculosis and the other secondary to a squamous cell carcinoma of the upper esophagus diagnosed by multi - detector computed tomography ( mdct ) . traditionally , fluoroscopy with oral contrast swallow examination has been the mainstay radiological investigation for the diagnosis of these fistulae . however , it can be an inconvenient study with need for multiple projections to adequately demonstrate the fistula and its course . also , being a luminal study , the cause of the fistula is not adequately evaluated . use of the various post - processing features like thick maximum intensity projections ( mips ) and volume rendering techniques ( vrts ) enables better detection and depiction of these fistulae . use of virtual endoscopy also guides the clinician for the conventional endoscopy which would be needed for biopsy and treatment . a 15-year - old male presented with cough , mucopurulent expectoration , and dyspnea since 3 months . this finding of swallow cough sequence has been referred to as ono 's sign . a chest radiograph revealed complete opacification of the right hemithorax with volume loss suggesting complete collapse of the right lung with mediastinal shift to the right [ figure 1 ] . a plain and intravenous contrast - enhanced ct study with oral contrast swallow was performed on a 128-slice mdct scanner ( siemens somatom definition as , erlangen , germany ) . the study revealed complete collapse of the right lung with irregular dilated ectatic bronchi in the right lower lobe [ figure 2 ] . there was stenosis and diffuse narrowing of the right mainstem bronchus with nodularity of the mucosa seen best on the virtual bronchoscopy [ figure 3 ] . an air - filled tract was noted extending from one of the right lower lobar bronchi toward the posterior mediastinum with ill - defined soft tissue around it . the possibility of an esophagobronchial fistula was suspected , and we did a ct oral contrast swallow study to detect it . oral contrast swallow study performed with the patient in right decubitus position using diluted non - ionic iodinated contrast medium ( 1:20 dilution of iohexol with normal saline ) . it depicted the site and the fistula tract between the right lateral wall of the esophagus and one of the ectactic bronchi in the right lower lobe of the lung . thick mip images and vrt processing demonstrated the fistula site and tract [ figures 4 and 5 ] . these imaging findings led us to conclude that these changes were most likely the sequelae of chronic tuberculosis . histology of the lung specimen revealed distorted bronchioles with diffuse and focal dense infiltration by mononuclear cells and giant cells . frontal chest radiograph reveals severe volume loss and complete opacifi cation of the right hemithorax with ipsilateral tracheal and mediastinal shift . branching tubular radiolucencies are noted in the right lower zone representing bronchiectasis ( encircled area ) axial ( a ) and coronal ( b ) ct of the chest in lung window shows complete collapse of the right lung with shift of of the heart and the mediastinum to the right . dilated irregular fluid bronchi are seen in the right lower lobe ( thin black arrows ) with few having air - fluid levels within ( thick black arrow ) coronal ct of the chest in lung window ( a ) demonstrates narrowing of the right mainstem bronchus ( thick black arrow ) . a virtual bronchoscopy images ( b ) revealing stenotic orifice of the right mainstem bronchus with mucosal nodularity near the carina thick maximum intensity projection ( mip ) image of the ct contrast swallow study demonstrating the esophagus pulled to the right and opacification by oral contrast of the fistula tract between the esophagus and the dilated right lower lobe bronchi volume rendering technique ( vrt ) images- frontal ( a ) and lateral ( b ) projections derived from post - processing of the contrast swallow examination demonstrating the fistula ( arrowheads ) between the right lateral aspect of the pulled esophagus and the right lower lobar bronchus with opacifi cation of the bronchial tree a 65-year - old male presented with progressive dysphagia to solids over the past 2 months . an ultrasound of the neck revealed few enlarged lymph nodes which on fine needle aspiration ( fna ) revealed neoplastic squamous cells . a plain and intravenous contrast - enhanced ct study with ct oral contrast swallow was performed . there was a loss of fat plane between the esophagus and the carina , left mainstem bronchus , and aorta . a defect was seen in the posterior wall of the proximal left mainstem bronchus suggesting formation of a fistula with the esophagus [ figure 6 ] . a ct oral contrast swallow study performed in prone position with diluted non - ionic contrast ( 1:20 dilution of iohexol in normal saline ) revealed a small fistula tract between the esophagus and the proximal left mainstem bronchus just distal to the carina [ figure 7 ] . post - processing of this contrast swallow study with volume rendering depicted the fistulous communication in 3d [ figure 8 ] . axial contrast enhanced ct ( a ) at a level just beyond the carina demonstrates defect in the posterior wall of the proximal left mainstem bronchus ( thick white arrow ) . a virtual bronchoscopy image ( b ) shows the site of the fistula opening ( thin white arrow ) oral contrast ct swallow- axial ct performed with patient in prone position shows the fistula tract ( white arrow ) opacifi ed by the diluted oral contrast volume rendering technique ( vrt ) images- frontal ( a ) and lateral ( b ) projections derived from post - processing of the contrast swallow examination show the fistula tract between the esophagus and the proximal left mainstem bronchus a 15-year - old male presented with cough , mucopurulent expectoration , and dyspnea since 3 months . this finding of swallow cough sequence has been referred to as ono 's sign . a chest radiograph revealed complete opacification of the right hemithorax with volume loss suggesting complete collapse of the right lung with mediastinal shift to the right [ figure 1 ] . a plain and intravenous contrast - enhanced ct study with oral contrast swallow was performed on a 128-slice mdct scanner ( siemens somatom definition as , erlangen , germany ) . the study revealed complete collapse of the right lung with irregular dilated ectatic bronchi in the right lower lobe [ figure 2 ] . there was stenosis and diffuse narrowing of the right mainstem bronchus with nodularity of the mucosa seen best on the virtual bronchoscopy [ figure 3 ] . an air - filled tract was noted extending from one of the right lower lobar bronchi toward the posterior mediastinum with ill - defined soft tissue around it . the possibility of an esophagobronchial fistula was suspected , and we did a ct oral contrast swallow study to detect it . oral contrast swallow study performed with the patient in right decubitus position using diluted non - ionic iodinated contrast medium ( 1:20 dilution of iohexol with normal saline ) . it depicted the site and the fistula tract between the right lateral wall of the esophagus and one of the ectactic bronchi in the right lower lobe of the lung . thick mip images and vrt processing demonstrated the fistula site and tract [ figures 4 and 5 ] . these imaging findings led us to conclude that these changes were most likely the sequelae of chronic tuberculosis . histology of the lung specimen revealed distorted bronchioles with diffuse and focal dense infiltration by mononuclear cells and giant cells . frontal chest radiograph reveals severe volume loss and complete opacifi cation of the right hemithorax with ipsilateral tracheal and mediastinal shift . branching tubular radiolucencies are noted in the right lower zone representing bronchiectasis ( encircled area ) axial ( a ) and coronal ( b ) ct of the chest in lung window shows complete collapse of the right lung with shift of of the heart and the mediastinum to the right . dilated irregular fluid bronchi are seen in the right lower lobe ( thin black arrows ) with few having air - fluid levels within ( thick black arrow ) coronal ct of the chest in lung window ( a ) demonstrates narrowing of the right mainstem bronchus ( thick black arrow ) . a virtual bronchoscopy images ( b ) revealing stenotic orifice of the right mainstem bronchus with mucosal nodularity near the carina thick maximum intensity projection ( mip ) image of the ct contrast swallow study demonstrating the esophagus pulled to the right and opacification by oral contrast of the fistula tract between the esophagus and the dilated right lower lobe bronchi volume rendering technique ( vrt ) images- frontal ( a ) and lateral ( b ) projections derived from post - processing of the contrast swallow examination demonstrating the fistula ( arrowheads ) between the right lateral aspect of the pulled esophagus and the right lower lobar bronchus with opacifi cation of the bronchial tree a 65-year - old male presented with progressive dysphagia to solids over the past 2 months . an ultrasound of the neck revealed few enlarged lymph nodes which on fine needle aspiration ( fna ) revealed neoplastic squamous cells . a plain and intravenous contrast - enhanced ct study with ct oral contrast swallow was performed . there was a loss of fat plane between the esophagus and the carina , left mainstem bronchus , and aorta . a defect was seen in the posterior wall of the proximal left mainstem bronchus suggesting formation of a fistula with the esophagus [ figure 6 ] . a ct oral contrast swallow study performed in prone position with diluted non - ionic contrast ( 1:20 dilution of iohexol in normal saline ) revealed a small fistula tract between the esophagus and the proximal left mainstem bronchus just distal to the carina [ figure 7 ] . post - processing of this contrast swallow study with volume rendering depicted the fistulous communication in 3d [ figure 8 ] . axial contrast enhanced ct ( a ) at a level just beyond the carina demonstrates defect in the posterior wall of the proximal left mainstem bronchus ( thick white arrow ) . a virtual bronchoscopy image ( b ) shows the site of the fistula opening ( thin white arrow ) oral contrast ct swallow- axial ct performed with patient in prone position shows the fistula tract ( white arrow ) opacifi ed by the diluted oral contrast volume rendering technique ( vrt ) images- frontal ( a ) and lateral ( b ) projections derived from post - processing of the contrast swallow examination show the fistula tract between the esophagus and the proximal left mainstem bronchus esophagobronchial fistulae are uncommon and difficult to diagnose . in the elderly , they are most frequently seen with an intrathoracic malignancy and are most commonly associated with malignancy of the esophagus . in a large case series , subsequent ulceration and necrosis of the malignant tissue leads to tissue breakdown and fistula formation . non - malignant causes are infrequent and include trauma ( blunt , penetrating , or iatrogenic ) , chronic inflammation ( chronic infections like tuberculosis and histoplasmosis , crohn 's disease ) , late presentation of a congenital fistula , and rarely poisoning . over the years , iatrogenic trauma has become a commoner cause for such fistulae compared to infections . tuberculosis as a cause for these fistulae has been infrequently reported in the western literature . however , in the indian subcontinent where the incidence of tuberculosis is high , chest tuberculosis should be high in the list of differentials when a non - malignant fistula is encountered . in nonmalignant conditions , traumatic bronchial or tracheal wall necrosis or necrotizing inflammation is responsible for the fistulization . fluoroscopic oral contrast swallow examination with barium is the initial investigation of choice for evaluation of dysphagia and suspected fistulae , even though endoscopy is needed for definite evaluation . if esophageal perforation is suspected , an iodinated contrast medium should be used as barium extravasation can lead to mediastinitis . if there is no frank leak seen , then barium can be given as it produces better radiographic quality being of higher density than iodine . if respiratory fistula is suspected , barium still may be used as small quantity of barium in the tracheobronchial tree is harmless . however , ionic iodinated contrast medium should not be used as they can cause chemical pneumonitis and only non - ionic iodinated contrast medium should be used in such cases . the best initial agent to use in both these scenarios of perforation or fistula is a non - ionic iodinated contrast agent . fluoroscopy allows for dynamic evaluation of esophageal motility as well as evaluation of its lumen . even though barium swallow fluoroscopy examination has the advantage of being a real - time study , fistula tracts may not always be detected . if detected , depiction of the three - dimensional course of the fistula may be difficult in spite of use of multiple projections . also , being a luminal study , it would fail to show changes in the wall of the esophagus and in the mediastinum that are shown accurately by ct . no large case series has been published about its efficacy in adult fistulae , but few case reports have highlighted its role . the patient should be given a mouthful bolus of the preparation and asked to swallow it promptly on instruction to do so . since the oral and pharyngeal phases of deglutition take no more than 2 seconds , the acquisition can be triggered immediately after the instruction to the patient to swallow has been given . the patient position may be changed to better opacify the fistula tract as we used prone and right decubitus positions in our cases to better opacify the fistula tracts . a recent study demonstrated that ct contrast swallow was better tolerated and more sensitive than fluoroscopy at detecting post - esophagectomy anastomotic leaks . post - processing these studies with maximum - intensity projection and with volume rendering allows a three - dimensional evaluation of the fistula tract . supplementing oral contrast swallow to the chest ct protocol in cases where fistulae are suspected can improve the diagnostic ability of ct and also better demonstrate these fistulae .

we report two cases of esophagobronchial fistulae diagnosed by multi - detector computed tomography ( mdct ) oral contrast swallow examination . it is helpful to supplement the ct study with an oral contrast swallow as it aids in confirmation of a suspected fistula and also demonstrates the fistula tract better . we present the clinical details and the imaging findings on mdct of two cases of esophagobronchial fistulae one secondary to chronic chest tuberculosis and the other secondary to a squamous cell carcinoma of the upper esophagus followed by discussion of the etiology , pathogenesis , and imaging of these fistulae .

suicide has been recognized as a major public health problem affecting all nations in general and low- and middle - income countries in particular . it has an adverse impact on individuals , families , communities , and on society as a whole . the who mental health action plan 2013 2020 foregrounds the prevention of suicide and has included indicators that measure progress . . however , part perceptions , which highlight particular correlates , argue for specific solutions while ignoring others , are partial responses to a complex , multidimensional problem . psychiatry continues to focus on the individual when the need is for a change in contexts , environments , and populations . suicide , behavior , is a final common pathway for a variety of factors : predisposing , precipitating , and perpetuating causes . nevertheless , each of the risk factors and condition associated with suicide is neither necessary nor sufficient for suicide . while interventions have shown a reduction in method - specific or site - specific rates , there is no firm evidence to suggest an overall reduction in suicide . a national strategy encompassing diverse approaches needs to be in place to achieve any degree of success . medicalizing suicide or reducing it to a psychiatric label will prove inadequate for reducing population rates . the poor health status of populations in the poorest countries is related to chronic poverty working through a lack of basic needs and access to health services , social discrimination , economic insecurity , and political exclusion . suicide is also associated with many of these sociodemographic , cultural , and economic correlates and demands comprehensive population - based strategies . many of the risk factors associated with suicide require a social security net provided by the state . without a social security net many vulnerable individual face significant socioeconomic distress , which can easily propel them toward the option of suicide . the egalitarian society promised in the indian constitution requires the provision of basic needs such as clean water , nutrition , housing , health care , education , and employment . in addition , it should provide gender justice and protect against social exclusion . without such public health approaches , suicide prevention would remain on paper with the medical and psychiatric approaches currently advocated completely inadequate for the task of reducing suicide rates . multidimensional problems like suicide require large - scale public health interventions to reduce suicide rates of populations . many risk factors associated with suicide are neither necessary nor sufficient for death making the search for single and direct solutions impossible . nevertheless , experts tend to identify causal mechanisms operating in a minority of suicides and suggest single and simplistic solutions to manage the complex individual and social phenomenon of suicide . comprehensive solutions demand a package of macroeconomic policies that reduce the impact of free - markets , schemes which meet basic human needs and rights , psychosocial interventions that organize local support within communities , an essential pesticide list that excludes lethal compounds , gender justice , universal primary health care , legal and social protection for the vulnerable and increasing awareness and education through mass media .

recent studies from india have challenged the fact that the majority of the people who die by suicide have severe mental illness ; they have demonstrated its frequent links to environmental stress , social , cultural , economic , and political correlates . suicide , a complex phenomenon , is a final common pathway for a variety of causal etiologies . nevertheless , psychiatry continues to argue for curative solutions based on the reductionistic biomedical model , rather than support public health measures to manage the larger sociocultural , economic , and political context . while psychiatry and curative medicine help many people in distress , specific mental health interventions are unlikely to impact secular trends in the rates of suicide . the reduction of population rates of suicide requires a range of public health measures .

between 20 and 30,000 men die each year from prostate cancer . for a vast majority of these men , death comes after progression through androgen withdrawal and taxotere chemotherapy . before the arrival of jevtana , zytiga and provenge , the median survival after taxotere was roughly 12 months . these three new drugs each have published median survivals of less than 18 months [ 2 , 3 , 4 ] . studies have shown that androgen receptor overexpression is present in many prostate cancers after taxotere . after the use of fda - approved drugs , there is a fairly long list of drugs where phase ii results suggest possible clinical utility and this includes 5-flurouracil , doxorubicin , platinum - based drugs , methotrexate , and etoposide . however , there has been no reliable way to identify which of these drugs might have the greatest chance at success . for most of these drugs , the genes that influence response are known and gene expression profiling offers promise as a means to select agents with the greatest chance of success . in this case report , we present a patient who had failed lhrh agonist , pure antiandrogen , taxotere and doxorubicin . molecular profiling showed androgen receptor overexpression and treatment with ketoconazole , estrogen and leukine was associated with a dramatic response in measurable disease . this patient was diagnosed with prostate cancer in august of 2000 . in september of 2000 the specimen showed bilateral capsular penetration , but the seminal vesicles and margins were negative . his first post - operative psa was 0.4 ng / ml in december of 2000 . at that time , ct scan done in march 2001 showed a 2.8 1.8 cm left external iliac lymph node . he was given neoadjuvant zoladex and casodex followed by external beam radiation between may and july of 2001 . again , ct scan showed an enlarged left iliac lymph node . by september of 2002 he was then placed on a clinical protocol that combined taxotere and doxorubicin with hormonal therapy . he had a dramatic psa response with his psa dropping from 5 to 0.1 ng / ml . the ct scan showed the lymph node had decreased to 1.3 1.2 cm . again , off hormonal therapy , his psa resumed its one - month doubling time . at this point , he entered a short remission with an undetectable psa and negative staging studies until he recurred in july of 2006 with an increasing psa and a 1.4 1.7 cm lymph node again in his left pelvis . this time this resulted in a psa that dropped to 0.04 ng / ml . by may of 2008 , his psa again started to increase and a left perirectal node was found at a previously radiated site . at this point , intermittent hormonal therapy was recommended . by march 2010 , he had recurred with a psa doubling time of 3 months while on hormonal therapy . he was placed on a clinical trial testing mdv3100 , where he was randomized to the placebo arm . by march of 2011 , he had a 2.2 1.7 6.1 cm mass at the bifurcation of the aorta . while he had a psa of only 0.45 ng / ml , ct scan showed a large pelvic mass . the surgical specimen from may 2010 was analyzed with target now ( caris life sciences , phoenix , ariz . the staining intensity by immunohistochemistry was 3 + in 80% of cells and ar at the mrna level was overexpressed 2.9-fold over control tissue as determined by gene expression . estrogen and progesterone receptor levels were also tested but they were found to be negative . based on the molecular profiling results in march 11 , 2011 , he was started on a combination of ketoconazole , estradiol and leukine . ketoconazole was initiated at 200 mg every 8 h and escalated to patient tolerance , which was 600 mg every 8 h. vivelle dot transdermal estradiol patches 0.1 mg / day were used . we had him place 4 new patches on each day and these were replaced after 3 days . leukine was started at 250 mcg per day , but escalated to 500 mcg per day based on patient tolerance . testosterone levels remained undetectable at less than 15 ng / dl . by august 2011 , ct scans showed dramatic resolution of one pelvic mass , partial resolution of the second lesion and a psa nadir of 0.06 ng / ml ( fig . taxotere is the standard initial chemotherapy after failure of androgen withdrawal and is associated with median survivals between 16 and 19 months . cabazitaxel is the standard second - line chemotherapy agent and it is associated with median survivals of 15 months as compared to just over 12 months for the control group . interestingly , in patients who have failed taxotere , tumor specimens often show overexpression of the androgen receptor . recent studies demonstrate the so - called castration - resistant tumors are still dependent on androgen receptor signaling . various molecular mechanisms ( e.g. , androgen receptor gene amplification , overexpression , or mutations , enhanced ar signal transduction ) have been reported in castration - resistant prostate cancers . these molecular mechanisms allow the androgen receptor to be activated at castrate levels of testosterone . this has been confirmed in a series of laboratory experiments where prostate cancer cell lines have been developed that grow well at 1/100 to 1/1,000 the normal testosterone concentration . overexpression of the androgen receptor is one of the more common mechanisms involved in this adaptation to low androgen levels . androgen receptor tyrosine phosphorylation has also been shown to facilitate androgen receptor function at low testosterone levels . these findings have led to a search for better means of reducing serum testosterone levels or blocking the androgen receptor . abiraterone , a 17 -hydroxylase / c17,20 lyase ( cyp17a1 ) receptor antagonist , is the first drug approved to address this problem . abiraterone is very effective at inhibiting synthesis of testosterone as serum levels of this hormone become undetectable . this drug was fda - approved for post - taxotere patients based on a survival extension of 3.9 months . at the time this patient started second - line treatment in march 2011 , the fda had not yet approved abiraterone . for this reason , we chose to use ketoconazole , an older drug reported to decrease androgen synthesis . in addition to inhibiting 17 -hydroxylase / c17,20 lyase , ketoconazole also inhibits a wide range of other microsomal enzymes and hence , lacks the specificity of abiraterone . this lack of specificity on the part of ketoconazole makes it a much difficult drug to use clinically unlike abiraterone . we elected to add leukine to the treatment program based on reports of synergy between ketoconazole and leukine . investigators at university of california san francisco reported a 75% response to this combination in patients who had failed androgen withdrawal . finally , we added transdermal estradiol because estradiol is also reported to decrease serum testosterone . in summary , this patient had failed extensive treatment with hormonal therapy as well as treatment with taxotere / doxorubicin . while he was clinically hormone refractory , his cancer overexpressed androgen receptor and he has had radiologic response of his cancer after 5 months on second - line hormonal therapy . molecular profiling was successful in predicting response to second - line hormonal therapy in this heavily pretreated patient . charles e. myers is funded to participate in a clinical trial funded by caris life sciences to evaluate the role of molecular profiling in the management of advanced prostate cancer patients .

after taxotere fails , treatment options for metastatic prostate cancer are limited . the three drugs with fda approval in this setting , jevtana , provenge and zytiga , are associated with median survivals of less than 2 years . in part , the impact on survival is the result of low response rates , indicating a significant proportion of patients exhibiting de novo resistance to these agents . an alternate approach is to let treatment selection be governed by gene expression profiling so that the treatment is tailored to the specific patient . here , we report a case of metastatic prostate cancer with a dramatic response to treatment selected based on molecular profiling . this patient had failed lhrh agonist , bicalutamide , taxotere , and doxorubicin . molecular profiling showed overexpression of the androgen receptor and he had a dramatic response of measurable disease to second - line hormonal therapy with ketoconazole , estrogen and leukine .

the introduction of next - generation sequencing technologies has had a tremendous impact on all areas of biology dealing with genomic information , from population genetics to comparative genomics , including the plant sciences . this impact is expected to grow exponentially as technical advances are continuously increasing the length and quality of sequenced dna fragments while decreasing the cost of the process . the throughput of current ultra - high - throughput sequencing ( uhts ) equipment has already reached several giga base pairs per run , which means that complex multicellular organisms with an average - sized genome , such as the model plant arabidopsis thaliana ( arabidopsis ) , can be sequenced at reasonable coverage and cost . to reliably assemble whole genome sequences from the short reads generated by uhts , a well - defined this is the case for arabidopsis , which was one of the immediate candidate organisms for resequencing projects . indeed , a few studies have already focused on comparative analysis of divergent arabidopsis genomes to characterize the extent of intraspecific genome variation with respect to the columbia-0 ( col-0 ) reference accession . sufficient funding permitting , these initial studies are just the prelude to the ambitious 1001 genomes project , which aims to resequence divergent arabidopsis accessions by the hundreds . in a pilot study , ossowski et al . resequenced the genome of col-0 , revealing more than 2000 homozygous single nucleotide polymorphisms ( snps ) and insertions and deletions ( indels ) that represent potential errors in the original annotation or spontaneous mutations ( see below ) . moreover , they analyzed the genome of two divergent strains and found that each of them carries more than 800,000 snps and 80,000 short indels . longer indels were difficult to assess from the short reads by simple re - mapping to the reference genome . however , a de novo assembly approach allowed the authors to identify some larger structural variants by starting from reads that flanked regions characterized by low coverage . using an alternative , combinatorial approach , santuari et al . evaluated the genome - wide abundance of large - scale deletions in four arabidopsis strains sequenced at moderate coverage the authors demonstrated that the intersection of signal intensities from tiling array hybridizations with uhts read coverage accurately detects larger deletions . hundreds of major deletions were observed , which frequently affect gene function . among them , transposable elements were found to be overrepresented , suggesting that the majority of genomic rearrangements identified result from the activity of mobile elements . individual deletions were frequently observed in two or more of the accessions examined , suggesting that variation in gene content partly reflects a common history of deletion events . in summary , the characterization of only a limited number of divergent arabidopsis genomes has already identified an unexpected degree of structural diversity that significantly affects gene content and function ( figure 1 ) . although the majority of those polymorphisms supposedly originated in the wild , recent studies have highlighted the dynamics of the evolutionary process over merely a few generations , as exemplified in another pioneering publication by ossowski et al . . in this paper , the authors used next - generation sequencing to evaluate the rate and accumulation of spontaneous mutations across several generations . they analyzed five col-0 lines that had been maintained for 30 generations and found a mutation per site rate equaling 7 10 base pairs per generation . thus , arabidopsis geneticists are confronted with the finding that mutant lines and reference backgrounds might be more disparate than suspected . in practice , this should not pose a major problem as most mutations observed are essentially neutral . however , another study analyzing structural genome variation over several inbred generations subjected to stress treatment found major , stress - induced structural variation that could significantly affect phenotype . although purely array - based and thus not ultimately conclusive , if confirmed by uhts , these findings might force us to rethink our notions of genome stability . a region on arabidopsis chromosome 4 of approximately 68 kilo base pairs ( kb ) contains a series of receptor - like protein kinase - related proteins in col-0 , but shows a clear lack of read coverage in the eilenberg-0 ( eil-0 ) strain ( top ) , as depicted by the grey bars , and significant decrease in coverage for the other strains in the diagram . a closer look reveals that a major number of reads mapped to this region are probably mis - mapped and thus misleading due to very low mapping quality . overall , this picture indicates a series of large scale deletions comprising at least 15 genes that are present in the col-0 strain , represented by the brx-2 mutant obtained from a col-0 background , but missing in all four other strains . as this perspective is written , it is already likely to be superseded by ongoing technological progress , which should soon permit routine identification of structural genome variants . for instance , using paired - end sequencing it is already possible to follow the movements of transposons , which are highlighted as mis - mappings of the two ends of a sequenced fragment on the reference genome . beyond hardware improvements already several tools have been developed to detect inter- and intra - chromosomal rearrangements . the read length provided by the current versions of most uhts platforms coupled with different insert size libraries will ultimately make it feasible to move from analysis that is focused on read mapping onto a reference genome towards a reference - free , de novo assembly approach . this is critical to overcome the intrinsic limitations dictated by relying on a single reference sequence . the collection of high - quality scaffolds and contigs from divergent arabidopsis accessions could be used to define genomic regions that may have accumulated a degree of divergence that would prevent their accurate elucidation by classical mapping approaches ( figure 2 ) . in particular , in the case of duplicated or partially conserved regions , the assembly itself is limited by the highly repetitive content of these sequences . the integration of data from the reference mapping with assembled scaffolds will help to reconstruct specific regions that would otherwise be hard to decipher using either mapping or assembly alone . de novo assembly algorithms that take into account the read mapping position on the reference sequence are already being developed , such as locas or the recent columbus algorithm implemented in velvet . notably , these tools can also assemble genomes from low coverage data , further decreasing costs . another important challenge in analyzing these data this will probably be driven by increasingly advanced and intuitive genome browsers , such as the recent version of ensembl plants or genomemapper . the aop3 gene , involved in glucosinolate biosynthesis and thus pathogen defense , appears to be duplicated in an exact copy in the eilenberg-0 ( eil-0 ) accession , as indicated by homozygous single nucelotide polymorphisms depicted with colored vertical lines . breakpoints are genomic regions where both ends of a fragment sequenced with the paired - end library are mapped on the reference genome at a distance that is significantly different from the insert size of the library , suggesting structural rearrangements . here , the reads supporting breakpoints are shown in different colors , with each color representing the chromosome where the other end of the fragment is located . following these reads , it is possible to reconstruct where the second copy of aop3 is located , which appears to be 10 kilo base pairs downstream of its original locus , immediately downstream of the aop2 locus in col-0 . every day lab approaches , such as mutant mapping , one might ask : why should we generate these data ? clearly , one of the greatest promises lies in their integration into genome - wide association studies , which would enable us to move from assessing the qualitative and quantitative effects of a single locus towards identifying and evaluating the systemic effects of multiple genes involved in a trait of interest [ 18 - 20 ] . the genome sequences of specific parental accessions would also greatly accelerate standard quantitative genetics approaches , such as quantitative trait locus analysis of recombinant inbred lines . maybe most importantly , sequencing hundreds of strains , as proposed by the 1001 genomes project , will not only indicate which genes are divergent , missing , or not functional with respect to the col-0 reference sequence in a given accession , but will also lead to the discovery of genes that are present in the worldwide arabidopsis population ( but absent from col-0 ) . without this dark matter of the arabidopsis genome , defining the full gene complement of the species and gaining a complete understanding of the ecological - evolutionary and developmental history of this plant can not be attained .

ultra - high - throughput sequencing ( uhts ) techniques are evolving rapidly and may soon become an affordable and routine tool for sequencing plant dna , even in smaller plant biology labs . here we review recent insights into intraspecific genome variation gained from uhts , which offers a glimpse of the rather unexpected levels of structural variability among arabidopsis thaliana accessions . the challenges that will need to be addressed to efficiently assemble and exploit this information are also discussed .

however , in the setting of appendicitis with abscess or phlegmon , initial non - operative management has been shown to be safe and effective.[13 ] the treatment of appendicitis with phlegmon has been debated for more than 100 years . conservative treatment is an established practice , but the necessity of interval appendectomy remains controversial . advocates of interval appendectomy propose that appendectomy prevents recurrence and gives definitive treatment.[46 ] appendectomy can also provide a definitive diagnosis , and may sometimes reveal an unexpected malignancy . however , another group of surgeons who oppose this policy[79 ] point out that the rate of recurrent appendicitis is around 620% , and that the complication rate of interval appendectomy is not low ( 919% ) . the aim of this study was to determine the risk of recurrent appendicitis following initial non - operative treatment for appendicitis , and evaluate factors associated with recurrence . our hypothesis was that the risk of recurrent appendicitis is low and that interval appendectomy is not routinely indicated . patients who received conservative treatment for appendicitis with lump formation were prospectively studied from june 2006 to june 2008 . baseline investigations viz complete blood count , liver function and kidney function was done in every patient . computed tomography ( ct ) was done in every patient for confirmation of diagnosis . every patient was treated with intravenous fluids , antibiotics ( third generation cephalosporin , amikacin and metronidazole ) . patients were followed up in outpatient department monthly for three months , bimonthly for another six months , and six monthly thereafter . if signs of recurrent appendicitis appeared ( such as right lower quadrant pain , or tenderness with or without fever ) , ct was repeated and appendectomy was performed if recurrent appendicitis was confirmed . data was collected and analyzed statistically using spss software . a total of 763 patients with acute appendicitis were treated from june 2006 to june 2008 . out of them 220 ( 28.8% ) patients presented with lump formation . high rate of lump formation was because of late referral and due to poor health care facilities available in our state . seven patients in this group ( 3.2% ) were operated in the index admission as they did not respond to conservative treatment . mean follow up was 32 months . out of the total ; 115 of them were men and 98 were women . most of the patients had classical history of pain , starting at the umbilicus then radiating to the right iliac region . most of the patients ( 79.8% ) had history of anorexia but nausea and vomiting was found in only 23.4% of patients . all the patients had a lump palpable in the right iliac region on clinical examination . there was no clinical difference in the primary clinical presentation between the cases that later developed recurrence and the patients who did not had recurrence [ table 2 ] . clinical presentation of patients of appendicitis with lump formation clinical presentation of patients who later had recurrence among 213 patients , 28 ( 13.1% ) had recurrent appendicitis on follow - up and they were operated for the same . all these patients had recurrences within six months of the primary treatment [ figure 1 ] . lump formation after acute appendicitis is as a result of walled off perforation of appendix . lump can be an inflammatory mass consisting of inflamed appendix , adjacent viscera , and greater omentum or a pus containing appendiceal mass . although management of acute appendicitis is primarily surgical , management of appendicitis with lump is controversial for more than a century now . mcpherson and kinmonth reported that non - operative management of appendicitis with tumor formation achieved a 76% success rate and 0.8% mortality rate . currently , conservative treatment of appendicitis with lump formation is the preferred one . the success rate of conservative treatment of appendicitis with tumor formation ranges from 76% to 97% . ct- or ultrasound - guided drainage of an appendix abscess has made surgical drainage less common . however , some surgeons still advocate early surgical intervention instead of conservative approach , although this approach has been criticized because of possibility of spread of previously localized infection , injury to surrounding structures , and overall higher complication rate . after successful conservative treatment the morbidity of interval appendectomy ranges from 3.4% to 19%[4611151921 ] which can be compared to the reported incidence of recurrent appendicitis after conservative treatment of an appendix mass that ranges from 0% to 20%.[4681012 ] the danger of recurrence is reported to be greatest during the first 6 months after the initial episode and minimal after 2 years . lai et al . , also suggested that routine elective appendectomy can be safely omitted in more than80% of patients . , in their studies also support the practice of nonsurgical treatment without interval appendectomy in patients with appendiceal abscess or phlegmon . the risk of recurrence is low , which does not motivate routine interval appendectomy after initial conservative treatment .

background : interval appendectomy after acute appendicitis with lump formation ( phlegmon ) remains controversial . we conducted this study to determine the risk of recurrent appendicitis following initial non - operative treatment for appendicitis , and evaluate factors associated with recurrence . secondarily , we evaluate the efficacy of interval appendectomy versus no appendectomy.materials and methods : patients who received conservative treatment for appendicitis with lump formation were prospectively studied from june 2006 to june 2008 . these patients were followed for recurrence of appendicitis.results:of 763 patients with acute appendicitis some 220 patients had lump formation ( 28.8% ) . median age was 28 years . conservative treatment was successful in 213 ( 96.8% ) patients . the rate of recurrence was 13.1% , all occurring within six months after the index admission . mean follow - up was 2618 months.conclusion:conservative treatment of appendicitis with lump formation is efficient and the recurrence rate is low . routine interval appendectomy after initial conservative treatment for lump formation is not a cost - effective intervention and not recommended .

it has previously been shown that fibromyalgia patients differ from other widespread pain patients in that fibromyalgia patients are more likely to perceive a much greater degree of difficulty both in understanding the cause of their pain and in explaining the cause of their pain to others . this was concluded after utilization of the understand pain scale and the explain pain scale . that is , subjects were asked to indicate on a likert scale the degree to which they understand the cause of their pain ( the reason they have pain ) ( the understand pain scale ) and the degree to which they can explain the cause of their pain ( the reason they have pain ) to others ( the explain pain scale ) . using these scales and controlling for age , gender , and duration of pain , fibromyalgia subjects had higher scores than comparator groups , which included whiplash - associated disorder , tendinitis / bursitis , and osteoarthritis . although a handful of rheumatoid arthritis subjects were included in this study , they were few , and to date there is no further validation of the understand pain scale and explain pain scale , in patients with painful disorders . on the other hand , the pain beliefs and perceptions inventory has had a much more detailed study of its construct [ 2 , 3 ] . specific items of this inventory comprise the mysteriousness construct , asking subjects specifically about the extent to which they agree with the statements : no one 's been able to tell me exactly why i 'm in pain , i do not know enough about my pain , and i can not figure out why i 'm in pain . as depression , anxiety , and perceived injustice have high correlations with pain in both fibromyalgia and rheumatoid arthritis patients , a comparison of the mysteriousness scores in these two groups necessitates controlling for these confounders . rheumatoid arthritis is useful as a comparator group for fibromyalgia cohorts [ 1 , 57 ] , in part because rheumatoid arthritis sufferers share many of the same symptoms , especially widespread pain and fatigue . at the same time that is , fibromyalgia has a controversial nature that presents a challenge for both patients and physicians [ 811 ] . it is possible that this issue and the controversial nature of fibromyalgia contribute to this sense of mysteriousness or lack of understanding expressed by sufferers . some researchers have invoked explanations such as central sensitization or viral syndrome [ 12 , 13 ] , while others regard fibromyalgia as a psychocultural illness . while there are controversies in rheumatoid arthritis , this extreme spectrum of polar views does not exist . this polarity may in part help to explain the difficulties that fibromyalgia patients have in understanding or explaining their suffering to others . fibromyalgia patients have remarked that the fact that the medical community can not agree on the nature of fibromyalgia and can not resolve the controversies makes it very difficult for fibromyalgia patients to know what to believe about their illness . the purpose of this study was therefore to quantify the degree to which fibromyalgia patients perceive mysteriousness in the cause of their pain and to compare this to the perceptions of rheumatoid arthritis patients . the subjects are those described in a previous study that has been part of a larger effort to determine the clinical utility of various questionnaires in the care of fibromyalgia patients . these subjects were recruited from two adult rheumatology practices in edmonton , alberta , canada , serving a catchment area of 1.5 million population . the subject groups consist of consecutive patients presenting with a confirmed diagnosis of rheumatoid arthritis via the 1987 american college of rheumatology criteria ( ra group ) and the other group with a diagnosis of fibromyalgia via the 2010 modified american college of rheumatology criteria ( fm group ) . the authors reviewed the charts of all consecutively seen subjects who had a confirmed diagnosis of either rheumatoid arthritis or fibromyalgia . exclusion criteria included the following : being unable to read english ; having lower than grade 8 level education ; having suspected or known malignancy , or other serious illness ; and having both fibromyalgia and rheumatoid arthritis . from january 2013 , the authors had been , as part of clinical care , routinely asking chronic pain patients , including rheumatoid arthritis and fibromyalgia patients to complete various instruments in an effort to determine their utility in practice . as part of a practice audit , the charts of rheumatoid arthritis and fibromyalgia patients were reviewed until may , and data gathered regarding age , gender , and assessment responses ( see below ) . thus , no data was then available on duration of condition , comorbidities , history of trauma , litigation or compensation status , psychiatric diagnoses , disability status , or treatment . subjects were asked to specify , on average , how much pain they had because of their condition over the past week . they circled a number between 0 and 10 , with 0 being labelled as no pain and 10 being labelled as worst pain imaginable . the injustice experiences questionnaire ( ieq ) was used , as described by sullivan et al . subjects were asked to rate the frequency with which they experienced each of 12 pain - related thoughts on a 5-point scale , ranging from 0 ( never ) to 4 ( all the time ) . examples of items include the following : most people do not understand how severe my condition is , my life will never be the same , i am suffering because of someone else 's negligence , and it all seems so unfair . the maximum score ( maximal perceived injustice ) is 48 and the minimum is zero . the scale can be further divided and scored along two factors : blame / unfairness and severity / irreparability of loss . the questionnaire instructions were modified to include the phrase injury / illness , as the original questionnaire referred only to injury , which would not be appropriate in this sample . the hospital anxiety and depression scale ( hads ) was originally developed by zigmond and snaith to determine the levels of anxiety and depression that a patient is experiencing . the hads is a fourteen - item scale ( seven of the items relate to anxiety and seven relate to depression ) . subjects rate the severity of depression or anxiety symptoms on a scale of 03 ( 3 being most severe ) and receive a score on each of the depression and anxiety scales of 021 . this was assessed using items 1 , 4 , 8 , and 14 from the pain beliefs and perceptions inventory . we did not include the full pain beliefs and perceptions inventory so as not to overburden subjects in this pilot study . instead , four statements from the pain beliefs and perceptions inventory were presented to each subject with a likert scale ranging comprised of strongly disagree ( 2 ) , disagree ( 1 ) , agree ( 1 ) , and strongly agree ( 2 ) . the more positive the total , the more mysteriousness the subject perceives in regard to their pain . initially , all data records were reviewed in order to ascertain if any data issues , such as missing data , outliers , or out of range values , existed within the data set . subjects with missing diagnosis or data were removed from analysis along with subjects diagnosed with both fibromyalgia and rheumatoid arthritis . after data cleaning , the subjects were divided into two groups ( ra group and fm group ) as the main variable . the mean age , gender distribution , and mean scores of the assessments were calculated for each group . inferential statistics were then used to determine whether subjects in the two diagnostic groups had significantly different scores on the mystery scale items . this was done univariately using t - tests and after adjusting for potential confounders ( sex , age , pain , hads depression , hads anxiety , and perceived injustice ) using ancova . adjusted mean scores were determined by estimating marginal means for the diagnosis variable after entering potential confounders into the ancova model . we also examined the adjusted association between diagnostic group and mystery scale scores using multivariable linear regression . our final models were built in a blocked fashion by initially entering diagnostic category into the model and then entering other variables simultaneously using a stepwise strategy ( p - to - enter 0.05 ; p - to - remove 0.10 ) . however , we had a fixed sample from our practice audit , which limited the sample size . considering the number of subjects in the study sample previously reported to be 64 rheumatoid arthritis subjects and 62 fibromyalgia subjects , we have calculated that , given a standard deviation in mystery scale scores of 5.5 ( observed for the two groups combined ) , we had an 80% power to detect an absolute difference of 2.8 in the total mystery scale scores between groups . 9 subjects were excluded ( 6 because of lack of english language skills , 1 because of malignancy , and 3 because of having both ra and fm ) . of these , an additional 12 were excluded from analysis because of significant missing data . thus , a total of 126 subjects ( 64 ra and 62 fm ) had complete data available for analysis . the gender distribution , mean age , and unadjusted assessment scores are shown in table 1 . the fm group had a greater percentage of female subjects , more severe pain , more severe anxiety , more severe depression , and a higher perception of injustice . in unadjusted analysis , as shown in table 1 , the fm group also had a higher mean mystery scale scores . that is , the unadjusted mean for the fm group mystery scale score was 2.9 , indicating that they were more likely to agree that their pain was not understood or had greater mysteriousness . in contrast , the ra group had an unadjusted mean mystery scale score of 4.5 . this indicates that they tended to disagree with the notion of having mysteriousness to their pain . after adjustments by sequentially adding the confounders of age and sex , pain , hads depression , hads anxiety , and perceived injustice , a significant difference remains between groups . that is , the adjusted mean for the fm group mystery scale score was 1.6 and the ra group had an unadjusted mean mystery scale score of 3.4 . this indicates again that the fm group supported the notion of having a mysteriousness concerning their pain when compared to the ra group . this study of a referred cohort of subjects with either fibromyalgia or rheumatoid arthritis shows that fibromyalgia patients are much more likely than rheumatoid arthritis patients to endorse the belief that they have a degree of mysteriousness concerning their pain . this remains the case even after adjusting for confounders that included severity of pain , for example . the results of this study are in agreement with a previous study using novel understand pain and explain pain scales , suggesting that understanding or explaining pain is perceived to be more difficult in fibromyalgia sufferers . a narrative approach to understanding fibromyalgia patients affirms that both the wide array of symptoms in fibromyalgia and the variability in the illness course make it an illness difficult for patients themselves to understand and even more difficult to explain to others [ 10 , 11 ] . fibromyalgia patients have long been described as having a disorder that lacks face - validity . the cause of their illness remains controversial despite an extensive number of therapies and considerable progress in pain research , specifically as it pertains to fibromyalgia [ 6 , 2127 ] . the feeling or implication that one 's symptoms , especially pain , are described as medically unexplained is of concern to patients , to the point of being offensive . fibromyalgia patients report a wide array of symptoms , frequent fluctuation in the presence and severity of symptoms , and unpredictable exacerbations [ 2831 ] . labelling the condition fibromyalgia , in itself , patients have indicated exactly that while the diagnosis may confer some legitimacy , it does not improve their understanding of their own illness , nor help them explain their illness to others [ 32 , 33 ] , nor does the label appear to assist or comfort physicians . what the current study confirms is that this mysteriousness or lack of understanding around fibromyalgia persists even if one controls for other factors , like pain severity , anxiety , depression , and a sense of injustice . first , the psychometrics of the mystery scale score used without the remainder of the pain beliefs and perceptions inventory are not known . further study may be required to ascertain the reproducibility , reliability , and validity of using selected items from this inventory in various settings , adding the other constructs of this inventory as confounders in the analysis . the questionnaires we used , however , were part of a practice audit and assessment . they were thus used in a way that , through brevity , would be most applicable in the clinical setting . in terms of selection bias , these subjects were from two clinics . there may be a selection bias in this group that affected their sense of mysteriousness because they were indeed a referral sample , possibly with more severe pain , or seeking more explanation . we did not track the scores used to confirm the fm diagnosis via the modified 2010 acr criteria , which may have told us how severe these patients were in terms of polysymptomatic distress . still , we did adjust for illness severity to an extent , in that we adjusted for pain , depression , and anxiety . this could explain why fibromyalgia patients have difficulty understanding their pain , but narrative and other qualitative studies of fibromyalgia patients clearly indicate that fibromyalgia patients are very much capable of logically and earnestly processing their illness and suffering : despite this , they find their illness often inexplicable [ 10 , 11 ] . cognitive dysfunction is frequently reported in other widespread pain subjects who do not have fibromyalgia , as well ; yet , this does not prevent them from holding the belief that they understand the cause of their pain and can readily explain it to others . the question remains as to what to do with the knowledge that fibromyalgia patients perceive a greater perception of mysteriousness to their pain . to the extent that this mysteriousness might contribute to their distress , future studies could examine whether encouraging patients not to seek explanations ( but rather solutions ) for their pain may help their condition . as far off as such studies may be , the mystery scale may be used to inform both clinical practice and research efforts . it may also be that there is no solution to this problem because the research literature is the problem . the mysteriousness of pain perceived by fibromyalgia patients may simply be a reasonable reflection of the polarity reported by researchers holding divergent views on the topic .

objectives . to compare the mysteriousness scores of the pain beliefs and perceptions inventory in fibromyalgia . methods . two cohorts of patients , one with fibromyalgia ( fm ) and one with rheumatoid arthritis ( ra ) , completed the mystery scale component of the pain beliefs and perceptions inventory to determine whether subjects in the two diagnostic groups had significantly different scores on the mystery scale . results . a total of 126 subjects ( 64 fm , 62 ra ) completed all questionnaires . the fm group had a greater percentage of female subjects , more severe pain , more severe anxiety , more severe depression , and a higher perceived injustice score . when the ra and fm group scores for the mystery scale were adjusted for age , sex , pain severity , hads scores , and perceived injustice scores , the fm group still had a higher mystery scale score . discussion . fibromyalgia is associated with a higher level of perception of mysteriousness in the pain beliefs and perceptions inventory than is seen with rheumatoid arthritis . this difference appears to be independent of levels of pain , depression , anxiety , and perceived injustice . this sense of mysteriousness may reflect a lack of understanding of pain in fibromyalgia as previously reported and may be an area to be addressed in therapy .

amyand 's hernia is an extremely rare condition in which the inguinal hernia sac contains the appendix . this unusual situation is estimated to occur in approximately one percent of adult inguinal hernia cases . we describe a case of acute appendicitis in the inguinal hernia sac with an incarceration in the external ring ; this led to distal appendicitis even though the appendix had a healthy body and base . our report includes a review of the literature and further evaluation of predisposing factors in this case . an 85-year - old - male arrived at our hospital in 2006 presenting a right groin mass . his history included hypertension , coronary artery disease , and transient infarction accident , of which all were receiving regular medical treatment . additionally , he had recently experienced urinary frequency and nocturia . a right groin mass had been protruding for 1 month prior to hospital admission , which increased in size when standing and before stool passage , but decreased in size after stool passage or lying down . the patient was scheduled for elective surgery . the oblique conventional incision between external and internal rings swelling and induration protruded outside the external ring toward the scrotum , leaving a mark on the vermiform organ ( fig . the body and base of the appendix was healthy and a moderate amount of clear ascites was found in the hernial sac . the distal portion of the appendix was attached to the distal portion of the hernial sac , which lay outside the external ring of the right groin . the mobilized cecum and ascending colon were far away from the paracolic space , apparently sliding until occupying the neck of the hernial sac . the patient 's postoperative condition was uneventful and he was discharged on the next day . he was followed up at our opd one week later and the right groin looked good . pathology revealed an acute suppurative appendicitis with mixed inflammatory cells in the appendiceal wall , presenting many eosinophils and small foci of granulomatous lesion ( fig . this rare condition was named after the first surgeon to perform appendectomy , claudius amyand , an english surgeon of the 18th century who first described a case of acute appendicitis in a hernial sac in an 11-year - old child . the first appendectomy ever to be performed in the usa , more than a century later , was also a case of amyand 's hernia in which an abscess with gangrenous appendicitis was found inside the hernial sac . the incidence of amyand 's hernia is estimated to occur in approximately one percent of adult inguinal hernia repair cases . acute appendicitis occurs much less frequently , and perforated appendix and periappendicular abscess formation within an inguinal hernia sac is an extremely rare clinical entity . ryan presented 11 of 8,692 cases of acute appendicitis occurring in external hernia of all forms . reviewed seven cases of acute appendicitis in a series of external hernia ( three inguinal ) collected in 8 years . a detailed description of the historical background and the management of amyand 's hernia was presented by r. hutchinson in 1993 . other investigators have infrequently presented case reports and literature reviews [ 7 , 8 ] . the incidence of acute appendicitis occurring in a hernial sac varies between the 0.13% reported by ryan et al . in 1937 and the 1% reported by carey in 1967 . more recently , c. d'alia and his colleagues reported their unique case of acute appendicitis within the hernial sac in 1,341 inguinal hernia operations performed over 13 years in messina university hospital in 2003 . most reported cases of amyand 's hernia have occurred in the right inguinal region and only a few reported cases have occurred in the left inguinal region [ 8 , 11 ] . the present case , diagnosed during surgery , is the first case of amyand 's hernia in our hospital , a 40-year - old district hospital with 800 beds . acute appendicitis only occurred over the tip of the appendix located outside the external ring . the blood supply was affected by the narrowed external ring and distal appendicitis developed subsequently . the body and base of the appendix appeared to be healthy ; the wide base of the hernial sac in the internal ring caused the vermiform organ to have a strange appearance . neither turbid ascites nor pus formation was found inside the hernial sac , making an excellent prognosis . we preferred to perform the repair via the traditional procedure ( bassini 's method ) to prevent the possibility of infection by the insertion of a foreign body ( mesh ) . treatment procedures have been well discussed in many recent case reports , including mesh hernioplasty , endoscopic hernioplasty or the traditional method of hernioplasty , although controversy still exists . sharma et al . briefly discussed the management of amyand 's hernia among 18 patients in a 15-year period , including appendectomy followed by bassini 's repair , mesh hernioplasty after reduction of a normal appendix , and bassini 's hernia repair plus a lower midline laparotomy for pelvic washout . discussions in recent reports emphasized the incidence and management of amyand 's hernia , highlighting the rarity and causes of the abnormality . abu - dalu and urca have suggested that the appendix becomes more vulnerable to trauma in amyand 's hernia and is ultimately retained by adhesions . its blood supply may subsequently be cut off or significantly reduced , resulting in inflammation and bacterial overgrowth . contraction of the abdominal muscles and other sudden increases in intra - abdominal pressure may cause compression of the appendix , resulting in further inflammation . apart from the above opinions , we found a mobilized cecum and ascending colon in our case , allowing facile advancement of the appendix into the hernial sac . the tip of the appendix proceeded through the narrowed external ring and incarceration developed , followed by adhesion and non - reducibility of the segment . the cecum was pulled close to the internal ring . the congenital anomaly ( mobilized ascending colon and cecum ) is considered to be a predisposing factor for developing amyand 's hernia . in addition , our pathology revealed many eosinophils in the inflamed appendix . most often , the stained white cell differential in acute appendicitis is neutrophil - predominant . the situation may be the result of an incarceration but no strangulation of the distal appendix for one week ( prolonged reduction of blood supply without complete interruption ) , leading to a subacute inflammation of the organ . computed tomography scans may be useful in diagnosis , but are typically not performed routinely . we did not order abdominal ct scanning for our patient because he did not present as an emergency and strangulation was not considered during the preoperative period . differential diagnosis should include strangulated hernia , strangulated omentocele , richter 's hernia , testicular tumor with hemorrhage , acute hydrocele , inguinal adenitis , and epidydimitis . the treatment for hernial appendicitis is appendectomy through the herniotomy with primary hernia repair using the same incision . only lyass et al . reported a delayed wound closure due to a retroperitoneal abscess secondary to the appendicular inflammation . mesh is not suggested in the contaminated abdominal wall defects because of greater risk of wound infection and appendiceal stump fistula . laparoscopic reduction of amyand 's hernia has been described previously [ 15 , 16 ] . amyand 's hernia is a rare condition that has been frequently diagnosed accidentally during a hernioplasty , and especially an incarcerated inguinal hernia diagnosed in the emergency room . it is closely linked to peritoneal spread of the septic process and may be life - threatening , with an incidence of mortality varying between 14 and 30% [ 9 , 17 , 18 ] ; mortality risk is most likely associated with perforated appendix with or without periappendicular abscess formation , or even peritonitis . consequently , our recommendation is that acute appendicitis should be considered as a potential cause for increasing morbidity in patients with incarcerated hernias . awareness of this clinical entity would be useful in the preoperative evaluation of patients with non - reducible or incarcerated inguinal hernias .

amyand 's hernia is an extremely rare condition in which the appendix is positioned in the inguinal hernia sac . acute appendicitis is much less common in this situation and few reports are found in the literature . we report a case of acute appendicitis with the tip of the appendix incarcerated outside the external ring of the right groin . a mobilized cecum and ascending colon were noticed during surgery . we conducted a review of the literature , emphasizing possible causes and suggesting a predisposing factor for the condition .

the relation between orthodontic force application and dental pulp tissue has been the subject of studies in the recent years . however , there is no conclusive evidence on the effect of orthodontic forces on pulpal tissue , and therefore , the issue has been studied for many years in human . reported that light continuous forces have little or no effect on dental pulp . on the other hand , the reaction of dental pulp to orthodontic forces has been reported to vary from mild hyperemia to complete necrosis in the literature . type of the force application , duration and dimension of the force , age of the patients , and size of the apical foramen are among the contributory factors . furthermore , higher incidence of irreversible pulpal reactions is usually expected in teeth with complete root formation . the aim of the present study was to evaluate histologic changes of dental pulp of human premolars in response to intrusive forces and to compare pulpal changes in patients of two different age ranges ( adults vs. adolescents ) . furthermore , early ( after 7 days ) and delayed ( after 30 days ) response of the pulp is assessed . this study was approved by the regional ethics committee on research of mashhad university university of medical sciences . a written informed consent form was signed by all participants before start of the study . patients with a history of systemic disease , probing depth of more than 3 mm in upper premolars , marginal bone resorption , and anti - inflammatory drug application during the last month was excluded from the study . furthermore , premolars with incomplete apical root formation , caries , restorations , and endodontic treatment were left out . the patients were classified into two groups according to their age : adolescent of 1318-year - old ( n = 11 ) and adults of 2532-year - old ( n = 11 ) . for each subject , one randomly selected maxillary premolar was loaded with intrusive force . the contralateral premolar was not subjected to mechanical loading and served as control tooth . orthodontic bands with triple buccal tubes were cemented onto the maxillary first molars . to avoid tipping and extrusion of molars , first molars were connected with a 1 mm stainless steel palatal bar into a rigid unit . orthodontic brackets ( 0.018 0.022 standard edgewise ; dentaurum , germany ) were bonded in the center of the buccal surface of the first and second upper premolar of the test side . a stainless steel wire ( 0.016 0.22 , dentaurum , germany ) was inserted into the molar tube and second premolar bracket to improve the anchorage . a cantilever spring ( 0.16 0.22 stainless steel , dent aurum , germany ) was fabricated for each patient to generate intrusive force . the spring was positioned 3 mm above the slot of the bracket of the first premolar in the passive state and was ligated to the bracket of the test tooth , with the use of wire ligature [ figure 1 ] . intraoral view of the cantilever spring for application of intrusive force to upper first premolar . ( a ) passive , ( b ) active position , ( c ) transpalatal arch cemented to avoid extrusion and tipping of the first molar . the magnitude of the intrusive force for every experimental tooth was approximately 15 g. in both groups of adults and adolescents , 6 pairs of teeth were extracted after 7 days , whereas the other 5 pairs were extracted after 30 days . after extraction , the tip of each root was cut with a bur to facilitate fixation . the teeth were fixed in 10% formalin for one week and were then immersed in decalcifying solution including 5 ml pure nitric acid , 5 ml pure formalin , and 90 ml 95% alcohol for 710 days immediately after removal . serial sections ( 45 m thick ) were cut longitudinally and stained with hematoxylin and eosin dye . the specimens were examined by an expert pathologist under a light microscope ( leica , exwave had , model number : ssc - dc58ap ) . the studied histological changes were as follows : degree of inflammation was determined by counting inflammatory cells by high magnification field ( 400 ) . each high magnification field corresponds to 0.1 mm none = 01 cell per field , mild = 25 cells per field , moderate = 615 cells per field , severe = more than 15 cells per fieldtype of inflammation : acute - chronic - nonefibrous tissue formation ( mild to severe)necrosis ( none , partial , complete)disruption of odontoblastic layerodontoblastic aspiration into dentinal tubulesvascular dilationresorption of cementum or dentin . degree of inflammation was determined by counting inflammatory cells by high magnification field ( 400 ) . each high magnification field corresponds to 0.1 mm none = 01 cell per field , mild = 25 cells per field , moderate = 615 cells per field , severe = more than 15 cells per field type of inflammation : acute - chronic - none fibrous tissue formation ( mild to severe ) necrosis ( none , partial , complete ) disruption of odontoblastic layer odontoblastic aspiration into dentinal tubules resorption of cementum or dentin . statistical analysis was performed using statistical package for the social sciences ( version 16.0 , spss inc , chicago , ill , usa ) . frequency distribution of the histologic parameters in the studied groups is shown in tables 13 and figures 1 , 2 . there was not a significant difference between the test and control teeth during the 7 days and 1 month test period in adolescents and adults . furthermore , there was not a significant difference between the test teeth after 7 days compared to 1 month in the adolescents and adults . whitney u - test revealed that there was a significant difference between adolescents and adults after 1 month regarding degree of inflammation ( p = 0.032 ) , and type of inflammation ( p = 0.032 ) in the test teeth . frequency distribution according to degree of inflammation , fibrous tissue formation , vascular dilation , and odontoblastic layer disruption in the studied groups in adolescents frequency distribution according to degree of inflammation , fibrous tissue formation , vascular dilation , and odontoblastic layer disruption in the studied groups in adult patients frequency distribution of aspiration of odontoblasts into dentinal tubules , as well as resorption of dentin or cement in adolescents and adult patients ( a ) fibrous tissue formation in the dental pulp . however , 2 teeth ( 33.3% ) in the test group and also 1 tooth ( 16.6% ) in the control group showed chronic inflammation after 7 days in the adolescents . in the adult group , chronic inflammation was observed in 4 teeth ( 66.6% ) in the intrusive group and 2 teeth ( 40% ) in the control group after 7 days . similarly , after 1 month , 4 teeth ( 80% ) and 2 teeth ( 40% ) showed signs of chronic inflammation in the intrusive and control group , respectively . some studies have reported significant pulpal reactions to orthodontic tooth movement , yet there is not conclusive evidence on the relation between orthodontic forces and pulpal alterations . some studies have demonstrated that most of the pulpal changes are associated with intrusive forces compared to other orthodontic movements . in the present study , pulpal reactions to orthodontic forces were investigated 7 days and 1 month after force application to study both the immediate and the late pulpal responses . some pulpal reactions to intrusive forces have been reported to occur as early as 3 days after force application in ramzanzadeh 's study . in present study , mild inflammation was observed in adolescents only after 1 month of force application . in contrast , cases with moderate and severe inflammation were found among the adult patients after 7 days . this result is in line with our findings . on the other hand , we found a significant difference in the amount of chronic inflammation between the adolescents and adults this emphasizes the importance of applying lighter forces with suitable intervals in the adult patients . some studies have demonstrated that hemodynamic changes are the first observable signs after orthodontic movements . some studies have reported a considerable decrease of pulpal blood flow after intrusion , whereas kvinnsland et al . have demonstrated an increase or no change . in the present study , we did not find a significant difference in vascular dilation between adolescents and adults after 7 days and 1 month of intrusion . we found no fibrous tissue formation after 7 days and 1 month of intrusion in adolescents . however , there were some cases with mild ( 33.2% ) and moderate ( 16.6% ) fibrous tissue after 1 week . nevertheless , the difference between the adolescents and adults and also between the control and intrusive groups was not significant . distribution of collagen fiber changes according to the age , fibers gradually change into fibrotic bundles . these changes usually occur in response to external stimuli such as caries or enamel attrition . since the studied teeth in the present study was completely intact , it seems that the observed difference between the adolescents and adults is related to the age of patients , albeit not statistically significant . similarly , ramazanzadeh et al . reported no significant difference between their intrusive and control group regarding fibrous tissue formation . aspiration of odontoblasts into dentinal tubules has been demonstrated as pulpal reactions to external stimuli in several studies . found odontoblasts aspiration in 1 case ( 10% ) after 3 days and also 3 weeks of intrusion . probable trauma to the teeth during extraction or before the study in the adult group can be mentioned as possible causes of this finding . in the current study , we did not find a significant difference in disruption of odontoblastic layer between the studied groups . in contrast , ramazanzadeh et al . reported more cases with odontoblastic layer disruption in the intrusive group compared to controls . similar to the results of ramazanzadeh 's study , we did not find a significant difference in resorption of dentin or cement between the studied groups . it seems that some reactions of pulpal tissue including disruption of odontoblasts , aspiration of odontoblasts into dentinal tubules , and resorption of dentin or cement occur with a considerable delay in adults compared to the adolescent group . according to graber et al . , lag phase before tooth movement takes usually longer time in adults compared to younger patients . the delayed reactions of pulp in the adult group in comparison to adults might be associated with longer lag phase in these patients . the 1-month period used in this experiment corresponds to the usual interval between consultations of orthodontic treatment and is sufficient for a tooth to move and complete its cycle of bone formation and resorption provided that the orthodontic forces are optimal . on the other hand , immediate response to orthodontic forced has been shown to occur as early as 3 days . furthermore , some studies have found some pulpal changes 7 days after orthodontic force application . thus , we decided to investigate immediate pulpal reactions to force application after 7 days . the results of the present study should be interpreted with caution due to the limited number of cases in each group . mild orthodontic intrusive force application in closed apex teeth causes no significant histological changes in adolescents and adults . however , it seems that inflammatory - related histological pulpal changes are more severe in adults after one month of intrusion . this emphasizes the importance of applying mild orthodontic forces with adequate rest intervals in older individuals . the authors of this manuscript declare that they have no conflicts of interest , real or perceived , financial or nonfinancial in this article . the authors of this manuscript declare that they have no conflicts of interest , real or perceived , financial or nonfinancial in this article .

background : there is no conclusive evidence on the effect of orthodontic force application on dental pulp tissue . the aim of this study was to compare early and delayed histological effects of intrusive forces on dental pulp of adolescents and adults.materials and methods : patients referred to the department of orthodontics of mashhad university of medical sciences participated in this study . they were assigned to adult ( 2532-year - old ) and adolescent ( 1318-year - old ) groups . a cantilever spring made of 16 22 steel wire was used to apply intrusive force to upper first premolars ( 11 teeth in adolescents and 11 teeth in adults ) and the opposing teeth were considered as control group . in each group , 6 pairs of teeth were extracted after one week , and the remaining 5 pairs were extracted after one month of intrusion . histologic changes were compared between the control and intrusive groups and also between the adults and adolescents after 7 days and 1 month . statistical analysis was performed using statistical package for the social sciences and wilcoxon and mann whitney u - tests . p 0.05 was set as statistically significant.results:significant difference was not found in any histological parameters between intrusive and control groups 1 week and 1 month after intrusion in adolescents and adults ( p > 0.05 ) . one month after intrusion , inflammatory cell response intensity ( p = 0.032 ) and frequency of chronic inflammation ( p = 0.032 ) were significantly higher in adults compared to adolescents.conclusion:mild intrusive force in closed apex teeth causes no significant histologic changes in adolescents and adults . however , it seems that inflammatory - related histologic pulpal changes are more severe in adults after one month of intrusion .

seaweeds are key ecological factors in shallow marine areas forming the base of the trophic web and structuring ecosystems especially on consolidated substrata . hence , the pharmaceutical and the cosmetics industries have a special interest in algae as sources of specific molecules [ 14 ] . also , several works have investigated their value in human and animal nutrition [ 58 ] . among the algae - derived compounds , polyunsaturated fatty acids are especially important as they act as antioxidant agents involved in many physiological processes [ 9 , 10 ] . the studies to determine the fatty acids profiles started some years before and many of them focused on the use of these compounds as biomarkers for chemotaxonomy , though their concentration may be susceptible to environmental interference [ 1114 ] . some of the main important factors that influence the algae fatty acid concentration are the temperature , [ 15 , 16 ] , types of habitat [ 15 , 17 ] , and presence of metals and pollutants [ 12 , 13 , 18 ] . although less common , other approaches using fatty acids have explored the effects of industrial effluents and environmental variables on the amount and quality of fatty acids produced [ 19 , 20 ] and their role in food assimilation by herbivorous invertebrates . fernando de noronha archipelago is an isolated group of islands formed by relatively recent volcanic processes . the islands are located approximately 350 km off the northeastern brazilian coast and are part of pernambuco state . the archipelago was established as a marine protected area since 1988 , and its marine flora is composed of 128 taxa , including 44 species of chlorophyta , 62 of rhodophyta , and 22 of phaeophyta . the most abundant benthic algae groups found in the archipelago are represented by the families dictyotaceae and sargassaceae . other seaweeds also commonly found are the green algae caulerpa verticillata and red algae galaxaura spp . [ 23 , 24 ] . as part of a broader research project aimed to study chemical compounds of seaweeds from fernando de noronha , herein is provided baseline information on the fatty acids produced by eleven species commonly found in the archipelago . samples were collected between february and march 2006 at two sites of the main island , caieiras beach ( 35018.8s , 322357.3w ) and sueste bay ( 3521.2s , 322519.7w ) . research permit from the brazilian environmental agency ( ibama ) to collect algae was registered under number 050/2006 . seaweeds were randomly collected by hand by uprooting the whole plant , which were placed in labeled plastic bags , frozen , and sent to the laboratory . the algae were identified , cleaned from epiphytes , animals , and sediment , washed with distilled water , and in an oven at 40c dried for seven days . ten milliliters ( 10 ml ) of dichloromethane ( j. t. baker , phillipsburg , nj , usa ) were added to 1 g ( dried weight ) of each species of algae and submitted to ultrasonic bath for 30 minutes . this procedure was repeated three times and the total extract was concentrated on nitrogen gas . subsequently , 2.0 ml of 1.0 m sodium methoxide were added to the extract and shaken occasionally during five minutes at 65c . after cooling the extract , 1.0 ml of water and three samples of 1.0 ml of chloroform ( j. t. baker , phillipsburg , nj , usa ) was added to each sample , shaken for one minute , and centrifuged at 3000 rpm , or 1612.8 g , to extract methyl esters of the fatty acids . the chloroform phase ( 3.0 ml ) , was removed and nitrogen gas was used to evaporate the solvent . samples were suspended in 1.0 ml ethyl acetate ( j. t. baker , phillipsburg , nj , usa ) , and sodium sulphate anhydrous ( sigma inc . , st . samples were analyzed through gc - ms ( gas chromatography coupled to mass spectrometer detector ) in a shimadzu qp2010 with ionization source of 70 ev and fragmentation by electronic ionization ( ei ) . the volume of 1.0 l for each sample was injected at 220c in a dbwax column ( 30 m 0.25 mm 0.25 m ) . the analysis occurred with 1-minute sample time in the splitless mode , a column flow of 1.3 ml min , a linear velocity of 41.4 cm s , and scan between m / z 40 and m / z 500 . oven 's temperature started with 50c , increasing to 20c min until 200c , kept in this temperature for 5 minutes , then increased to 5c min until 230c and kept in this temperature for 30 minutes . for identification of compounds , the peaks were compared with some standards and always consulting the libraries wiley version no . 7 and nist version nos . the gc - ms analysis had excellent resolution , and the characteristics of the detected unsaturated and saturated fatty acids are given in tables 2 and 3 . the eleven species have myristic acid ( 14 : 0 ) , pentadecanoic acid ( 15 : 0 ) , palmitic acid ( 16 : 0 ) , stearic acid ( 18 : 0 ) , oleic acid ( 18 : 1 , n ) , linoleic acid ( 18 : 2 ) , arachidonic acid ( 20 : 4 ) , and eicosapentaenoic acid ( 20 : 5 ) . the major compounds were hexadecanoic acid methyl ester and phytol , which were detected in all samples analyzed . other apolar compounds , mainly alcohols , were also identified and are provided in table 4 . the only seaweed in which 20 : 0 fatty acid was absent was the green algae , c. verticillata , and the acid 17 : 0 was absent in only one red algae . there were problems in isomer identification while conducting tentative taxonomic analysis , especially in double and triple bonds of c16 and c18 fatty acids , due to great similarity in retention time and in the molecular fragmentation in mass spectrum . few differences were observed in the production of fatty acids by brown , green , and red algae . also , as only one species of green seaweed was analyzed , this prevents further taxonomic comparisons with brown and red algae . in spite of the fact that gc - ms is a highly efficient and sensitive method of analysis , it was unable to precisely determine which of the polyunsaturated fatty acids with 16 or 18 atoms of carbon was present in each species . other apolar compounds detected had a more restrict distribution among species , and although most of them were detected in only one species , it was not possible to use them as chemotaxonomy markers , that is , phytol or loliolide . moreover , the fatty acids referred to as chemotaxonomic agents in previous investigations [ 14 , 17 ] did not allow discerning brown , green , and red algae in the present study . fernando de noronha is an area subjected to low levels of pollution because it is a marine protected area where anthropic activities are controlled . hence , it would be interesting to compare the fatty acid profiles obtained in this study with the ones from coastal areas of the main land near of the archipelago region that has different degrees of pollution . fatty acid profiles or other algae species , which are widely distributed and resistant to environmental changes , might be compared to the profiles of specimens collected in areas subjected to agrotoxics , solvents , and metals , as already done by tewari et al . with mercury . in addition , the baseline information obtained may also be applicable to a long - term ongoing research focusing on the sea urchins , which are important grazers in the archipelago , in order to determine possible relationships between the algae species consumed and their assimilation efficiency by those invertebrates . the methodology used allowed determining the fatty acid profile of eleven seaweed species from fernando de noronha archipelago . as no specificity was found in the presence of a particular set of fatty acids , these compounds could not be used as taxonomic indicators in this case .

hyphenated techniques of gas chromatography coupled to mass spectrometer were used to determine fatty acids in eleven species of seaweeds from fernando de noronha archipelago . the main compounds detected in all studied species were the alcohol phytol and the fatty acids 14 : 0 ; 15 : 0 ; 16 : 0 ; 18 : 0 ; 18 : 1 n9 ; 18 : 2 9,12 ; 20 : 4 ; 20 : 5 . these fatty acids are commonly found in seaweeds present in warm regions . thus , we found no specificity in the presence of a particular set of fatty acids and the studied species indicating that they are not useful as taxonomic indicators . however , they could be used in a comparative study with algae found in polluted area because many of the studied seaweeds are widespread and fernando de noronha has low human influence .

simple bone cysts ( sbcs ) are benign bone tumors that traditionally present in the first 2 decades of life . the cysts have a predilection to occur in males more frequently than in females ( 3:1 ) . the most common site of sbcs is the humerus ( 59% ) , followed by the femur ( 25% ) and the calcaneus ( 6% ) . alternative therapeutic options for sbcs have included steroid injections , autologous bone marrow injection , open curettage and bone grafting , various methods of cyst decompression , the use of calcium phosphate and calcium sulfate , and cannulated screws . however , treatment of sbcs remains controversial because of the cure rate and the invasiveness of surgery . although most sbcs resolve by the time the patient reaches skeletal maturity , it has been reported that patient age and the location of the cyst within the physis are predictors of successful treatment . the purpose of the present study was to evaluate the treatment of sbcs using a cannulated hydroxyapatite ( ha ) pin ( figure 1 ) that can decompress continuously and does not require further surgery for implant removal unlike cannulated screws . cannulated hydroxyapatite pin ( outside diameter 8 mm , inside diameter 3 mm ) . between 1989 and 2014 , ha pins ( kobayashi medical , tokyo , japan ) insertion was performed as the first operation on all cases of sbc that required surgery . of the 43 patients that underwent ha pins insertion , 35 were males and 8 were females , with a mean age of 12.1 years ( range , 522 years ) . the sbcs were located in the calcaneus in 23 , the humerus in 15 , the femur in 3 , and the pelvis in 2 cases ( table 1 ) . in all patients , minimal fenestration ( diameter , 8 mm ) was performed in the cyst wall , and then curettage was done . after that , multiple drill holes were made in the cyst wall with a k - wire to establish a connection to healthy bone marrow , followed by insertion of the ha pin . healing period , recurrence and healing rates , and risk factors for recurrence were evaluated . fisher exact test was performed to examine the risk factors for sbc recurrence , such as sex , age , cyst sites , and distance from the physis statistical analyses were performed using ibm spss statistics software , version 19 ( ibm spss , armonk , ny ) . healing was achieved without intervention in 38 patients after a mean of 6.4 months ( range , 112 ) ( figures 2 and 3 ) . two patients had persistent small residual cysts , which had no changes after 1 year at the latest follow - up . there were 5 patients with recurrences ( humerus 4 , femur 1 ) , which were cured by curettage and artificial bone grafting in expectation of adding mechanical strength ( figure 4 ) . all patients with sbcs of the calcaneus were healed after a mean of 5.0 months ( range , 110 months ) . fisher exact test , age < 10 years , site involving the humerus , and contact with the growth plate were significantly associated with sbc recurrence ( p < 0.05 ) ( table 2 ) . ( a ) an ha pin has been inserted into the cyst cavity after curettage and drilling . ( d ) recurrence of the cyst occurred in part of the proximal artificial bone 23 months after reoperation . ( e ) sixteen months after the third operation , the cyst has completely healed . in the present study , cannulation using an ha pin was found to be a useful technique for sbcs , particularly calcaneal cysts , because it is a minimally invasive procedure with a high cure rate . strategies for treatment of sbcs have evolved over a long time . currently , management methods include observation , injections of steroid or bone marrow or demineralized bone matrix , decompression using a cannulated pin and screw , and combined surgical techniques . however , management of sbcs remains controversial because of their healing rate and the invasiveness of treatment . spontaneous healing occurs in < 10% of patients with an sbc as a result of traumatic decompression by a pathological fracture . steroid injection was proposed by scaglietti et al in 1979 ; they reported a high healing rate after steroid injection . however , subsequent studies reported a lower healing rate for steroid injection , only 41% to 63% . the injection of bone marrow alone or in combination with demineralized bone matrix has been proposed to have a good healing rate of 43% to 69% . on the other hand , the gold standard procedure has been considered for many years to be curettage with removal of the cyst membrane and bone grafting . decompression of sbcs can be achieved using needles or implants , such as intramedullary nails , kirchner wires , and cannulated screws or pins . decompression using intramedullary nails provided healing rates of almost 70% , with recurrence rates of < 10% . however they do not need to be removed and have osteoconductive properties that may stimulate healing . in the present study , the healing rate was 88.2% , which was satisfactory compared with the healing rate by the methods mentioned earlier . cho et al , rougraff et al , and glanzmann and campos reported that it took 9 to 16 months to achieve remodeling . in the present study , age was reported to be a reliable predictor , with children > 10 years of age having a higher rate of cyst healing than those < 10 years . nonetheless , in a more recent study however , in the present study , age < 10 years and location in the humerus were associated with a significantly higher recurrence rate . alternatively , haidar et al reported that a lesion located < 2 cm from the growth plate may be a risk factor for recurrence . in the present study , a significantly higher recurrence rate was found for patients with a lesion contacting the physis . as the reason for this , we speculate that the proximal humerus in the young , due to its rapid growth , may have a likelihood of venous obstruction leading to the formation of cysts . the limitation of the present study is the absence of a comparative group or a randomized comparison . moreover , the number of patients enrolled was relatively small , and thus the statistical power of the study was weak , the present study suggests that cannulation using ha pins for sbcs is a useful technique , particularly for calcaneal cysts , because it is a minimally invasive procedure with a high cure rate . age < 10 years , site in the humerus , and contact with the growth plate were significant risk factors for sbc recurrence .

abstractsimple bone cysts ( sbcs ) are benign bone tumors . however , the treatment of sbcs remains controversial because of their healing rate and the invasiveness of surgery . the purpose of the present study was to evaluate the treatment of sbcs using a cannulated hydroxyapatite ( ha ) pin.a total of 43 patients ( 35 males , 8 females ; mean age 12.1 years ; age range , 522 years ) with sbcs were treated with continuous decompression by inserting ceramic ha pins between 1989 and 2014 . the sbcs were located in the calcaneus in 23 , the humerus in 15 , the femur in 3 , and the pelvis in 2 cases . in all patients , minimal fenestration of the cyst wall and curettage and multiple drilling in the cyst wall were performed , followed by insertion of the ha pin . the mean follow - up period was 26.6 months . operating time , healing period , risk factors for recurrence , and the cure rate were evaluated.healing was achieved without intervention in 38 patients after a mean of 6.4 months . two patients had persistent small residual cysts , which had no changes after 1 year at the latest follow - up . there were 5 patients with recurrences ( humerus 4 , femur 1 ) , who were cured by curettage and artificial bone grafting . the final healing rate by cannulation only using an ha pin was 88.2% . on fisher exact test , age , site of sbcs , and distance from the physis were found to be significantly associated with sbc recurrence ( p < 0.05).in the present study , cannulation using an ha pin for sbcs was found to be a useful technique , particularly for calcaneal cysts , because it is a minimally invasive procedure with a high cure rate . in patients < 10 years , involvement of the humerus and contact with the growth plate were significant risk factors for sbc recurrence .

metastasis to the skin from an internal malignancy is rare . to date , most of the data regarding frequency has been obtained from autopsy series where the frequency of skin metastasis has ranged from 0.7% to 10.4%1 - 3 ) . when cutaneous metastasis appears as the first sign of a primary cancer , the internal malignancy should be identified . however , most skin metastasis manifest at end stage disease of the primary cancer or during treatment . here we describe a case of acral metastasis from ampullary carcinoma and review the related literature . a 71-year - old korean man was admitted to our hospital with epigastric pain and general weakness . the blood chemistry revealed hgb 12.5 g / dl , bilirubin 1.3 mg / dl , alp 1879 u / l and ggt 89 u / l . tumor markers were ca19 - 9 8.5 u / ml , cea 8.5 ng / ml and ca-125 7.46 u / ml which were within normal limits . the patient 's abdominal computed tomography ( ct ) showed a mass , with contrast enhancement , at the ampulla of vater and dilatation of the bile duct as well as the main pancreatic duct ( figure 1a ) . his duodenoscopy showed a reddish protruding tumor mass at the ampulla of vater ( figure 1b ) . the endoscopic ultrasonography demonstrated a hypoechoic mass at the ampulla of vater without any invasion into the duodenal muscularis propria layer , or pancreatic parenchyma ; the mass measured 2525 mm in size . the endoscopic biopsy of the tumor showed a well - differentiated adenocarcinoma ( figure 3a ) . the patient underwent pylorus preserving pancreatico - duodenectomy ; the resection margins were intact histologically . the results of the microscopic examination along with dissection of six lymph nodes confirmed that the lymph nodes did not have any tumor cells . invasion of the lymphatic and venous systems were not found histologically ; however , focal invasion of the common bile duct was observed . twenty - seven months after surgery , he revisited our hospital because of painful erythematous swelling of the left thumb and the distal phalanx of the right middle finger ( figure 2 ) . physical examination showed that the patient had a firm , hard , painful swelling that measured 3 cm in diameter on the affected fingers . skin biopsy from the right middle finger revealed a well - differentiated adenocarcinoma ( figure 3b ) . in order to confirm that this lesion originated from the primary ampullary carcinoma . and to exclude that this lesion was from other primary sites , immunohistochemical staining was performed with cytokeratin 7 ( ck 7 ) , cytokeratin 20 ( ck 20 ) , mucin 1 ( muc 1 ) , mucin 2 ( muc 2 ) , thyroid transcription factor-1 ( ttf-1 ) , prostate specific antigen ( psa ) against the ampullary tumor and skin biopsy specimen . both tissues were not stained with the ttf-1 , psa , muc 2 , ck 20 ; however , they stained positive with muc 1 and ck 7 ( figure 3c - f ) . the negative result for ttf-1 and the bone scan showed metastasis at the first , third and ninth thoracic spine and fifth left rib ; however , no metastasis to the finger bones was observed . he refused to undergo further treatment , and died eight months after the diagnosis of cutaneous metastases . the incidence of cutaneous metastases is associated with the type of primary tumor and the patients ' gender . in their report , brownstein and helwig4 ) found that the lung is the most common primary site of carcinoma in men while the breast is the most common primary site of carcinoma in women . although both pancreatic and biliary adenocarcinoma usually metastasize to the lymph nodes , liver and peritoneum , cutaneous metastasis is rare . therefore , common sites of skin metastasis are the head , chest6 ) , and abdomen , but metastasis to the fingers is rare7 ) . generally , cutaneous metastases are classified into three groups according to their appearance : nodular , inflammatory and sclerodermoid metastatic lesions4 ) . they must be distinguished from acute suppurative inflammation , osteomyelitis , acute paronychia , foreign body granuloma , infectious hematoma , as well as tuberculosis . based on the fact that this patient had problems with his fingers as a result of gardening work , initially his finger lesion was misdiagnosed as a foreign body granuloma caused by thorns . however , the biopsy of the inflammatory lesion revealed adenocarcinoma . ampullary carcinomas have two different types of histopathologic morphology ; most tumors exhibit an intestinal morphology resembling primary adenocarcinomas of the colon and rectum , whereas a minority have pancreaticobiliary features similar to adenocarcinoma of pancreas or distal bile duct8 ) . periampullary tumors represent a spectrum of disease with intestinal - type tumors ( duodenal and most ampullary ) at the biologically favorable end and the pancreaticobiliary type tumors with an unfavorable prognosis9 ) . because the two subtypes have different outcomes , it is necessary to identify the appropriate classification . the positive results found for both ck 20 and muc 2 classified the tumor in the case presented here as an intestinal type , while the positive results for both ck 7 and muc 1 classified it as a pancreatobiliary type10 - 12 ) . because of the positive ck 7 and muc 1 , the ampullary tumor was thought to be classified as a pancreatobiliary type tumor with an unfavorable prognosis . the recognition of metastatic disease to the skin is important for the following two reasons . first , a cutaneous metastasis may be present before there are clinical signs of an internal malignancy . second , if a cutaneous metastasis is present , a skin biopsy may help confirm a suspected diagnosis of cancer suggested by findings from other organs which may be much more difficult to biopsy . the results of the skin biopsy may help clinicians focus on the likely location of the primary tumor . the causes of skin metastasis are as follows : direct invasion from underlying structures , extension through the lymphatics , embolization by the lymphatics and blood vessels and accidental seeding at surgery13 ) . although the patient in our case had an early stage tumor , he manifested the cutaneous metastasis only twenty - seven months after complete surgical resection of the tumor . we suggest that the leading cause of the cutaneous metastasis might have been embolization through the lymphatics and blood vessels . however , most cases have been reported to appear at the end stage14 ) ; therefore , it is generally associated with a poor prognosis . in addition , the majority of cancer patients who show skin metastasis are over 50 years of age and most die within a few months after the metastasis is identified1 , 2 ) . our patient had extensive metastases including abdominal and bone metastases at the time the skin lesions were found . this distant spread illustrates that the cancer cells may reach many sites of the body via the blood stream and the lymphatic system . although a tumor with cutaneous metastases is unlikely to respond to systemic therapy , local radiotherapy may be indicated for relief of symptoms . on rare occasions , surgical excision of cutaneous metastases may be indicated . in this case , because the patient did not want to receive further treatment , he died eight months after the diagnosis of cutaneous metastasis . it is important to be alert to the possibility that skin metastasis , in distal parts of the extremities , may result from extensive metastasis . in addition , immunohistochemical staining for ck and muc may be helpful for prediction of prognosis of ampullary carcinoma .

although skin metastasis from a malignant tumor of an internal organ usually occurs at an advanced disease stage , there has been no prior report of a cutaneous acral metastasis from ampullary carcinoma to date . we report a 71-year old male patient with cutaneous metastasis from an ampullary adenocarcinoma . the patient had a history of pylorus preserving pancreaticoduodenectomy for carcinoma of the ampulla of vater two years prior to presentation . physical examination revealed ill - defined , painful and hard erythematous nodules at the left thumb and distal phalanx of the right middle finger . the computed tomography scan showed low density masses in the retroperitoneum ; the histological examination of a nodule from the right middle finger showed a metastatic adenocarcinoma . this case illustrates that cutaneous metastasis from ampullary carcinoma has a poor prognosis .

clinical wnv patients , confirmed by immunoglobulin m elisa and identified through local surveillance in the houston metropolitan area from 2002 through 2004 , were invited to participate in a study to determine long - term clinical sequelae . no patient was denied participation on the basis of age , sex , race , or ethnicity . excluded patients included those who were residing outside of the houston area , deceased , or lost to follow - up . this study was reviewed and approved by the university of texas health science center institutional review board ( hsc - sph-03039 ) . initial interviews were conducted after hospitalization , and follow - up interviews were conducted every 6 months until the patient reported being back to pre - wnv infection functioning . for the 1-year follow - up , interviews were conducted during each december at the end of transmission season . interviews were mainly conducted over the telephone , but a small proportion were conducted in person . in all of these interviews , a higher than expected proportion of patients reported depression immediately after their illness . to better assess this quantitatively , we incorporated the center for epidemiologic studies depression ( ces - d ) scale ( 6 ) into both initial and follow - up interviews . the tool is composed of 20 questions focused on self - report of depressive moods and behavioral changes experienced by the patient during 1 week . 1 ) < 15 , the patient is not experiencing depression ; 2 ) 1521 , the patient may be experiencing mild - to - moderate depression ; 3 ) > 2260 , the patient may be experiencing major depression . in addition to the objective measurement using the ces - d scale , we also asked patients if they were experiencing depression since their illness and if they had a previous history of depression , with yes / no responses elicited . barthel index scores were used to quantitatively evaluate level of physical functioning and disability in patients ; a score of 100 points indicated no physical disability . because patients also commonly reported a change in personality immediately after wnv infection , we assessed this finding subjectively and asked those reporting a change to describe what they were experiencing . data were analyzed by using ncss statistical software ( kaysville , ut , usa ) . with the kruskal - wallis 1-way analysis of variance on ranks , we analyzed ces - d scores and wnv outcome ; ces - d scores and sex , age , and depression ( ces - d score of > 15 ) ; and physical functioning ( barthel index ) and depression . a total of 65 patients were interviewed ; 38 ( 58% ) cases had encephalitis when initially evaluated , 19 ( 29% ) had meningitis , and 8 ( 12% ) had fever . most patients were white , non - hispanic ( 80% ) , followed by black ( 11% ) and white , hispanic ( 9% ) . one year after infection with wnv , 26 patients reported experiencing depression . of these , 6 reported a history of depression before infection . of the 20 patients considered to have new - onset depression , 13 ( 65% ) had a clinical diagnosis of wnv encephalitis ( table ) , and 10 ( 50% ) were male . the mean ces - d scores for those who reported no depression was 5.5 ( range 019 ) compared with a mean score of 22 ( range 044 ) for those who reported depression . there was no statistical difference in ces - d scores between those who had encephalitis and those who had meningitis or fever ( p = 0.19 ) or between those with west nile neuroinvasive disease ( encephalitis or meningitis ) compared with those with fever ( p = 0.55 ) . on the basis of ces - d scores for those self - reporting depression since their illness with wnv , 5 ( 25% ) patients were classified by ces - d as not depressed , 6 ( 30% ) were classified as having mild - to - moderate depression , and 9 ( 45% ) were classified as having major depression . of the 39 patients who self - reported that they had not had depression since their wnv illness , 4 had a ces - d score of > 15 . no statistically significant associations were found between loss of physical functioning ( barthel index scores < 100 ; p = 0.39 ) , sex ( p = 0.89 ) , or age ( p = 0.47 ) and depression ( ces - d scores of > 15 ) . * wnv , west nile virus ; ces - d , center for epidemiological studies depression . seven ( 35% ) patients reported taking antidepressants for their symptoms ; 4 of these patients reported at least some improvement . ces - d scores of 6 of these 7 patients were > 15 ; 4 showed evidence of major depression . two patients reported seeing a counselor for depression , including 1 who was also taking antidepressants . both patients reported that the counseling was helpful ; however , based on their ces - d scores , both were classified as having major depression at the time of the interview . personality changes were reported subjectively among 29 ( 45% ) of the 65 patients ( table ) ; 18 ( 62% ) of these were in patients who had encephalitis , and 16 ( 55% ) of these patients were male . when asked to describe their personality change , 19 patients ( 66% ) reported an increase in anger ( being short - tempered and irritable ) ; 8 patients ( 28% ) reported being less social ; 3 patients ( 10% ) reported increased sensitivity ; and 1 patient ( 3% ) reported feelings of hopelessness . depression and personality changes after wnv infection have been briefly observed in previous studies ( 4,5 ) ; however , this study is the first known to objectively evaluate this outcome . as evidenced by subjective and objective measurements , depression is an important outcome in patients with a clinical diagnosis of wnv infection : indeed , 75% of those reporting no previous history of depression had high ces - d scores . understanding the pathology of this outcome and determining whether the depression is situational ( a result of prolonged recovery ) or caused by chemical changes in the brain related to inflammation are critical . depression and personality changes in humans have been previously reported as a neuropsychiatric consequence of lyme disease , nipah virus , tickborne encephalitis virus , and saint louis encephalitis virus infections ( 710 ) . after the encephalitis lethargica pandemic from 1917 to 1926 , depression , mania , and obsessive - compulsive disorder were observed in postencephalitis patients ( 11 ) . these observations led to the understanding of the role of the basal ganglia in mood , personality , and obsessional syndromes . in a mouse model experiment , infection of the brain with venezuelan equine encephalitis virus resulted in a serotonin presynaptic deficit and postsynaptic hyperreactivity of the serotonin system ( 12 ) . inflammation of the brain can result in an alteration in the neurotransmitter serotonin , which may lead to the development of mood disorders ( 13 ) . capuron et al . identified a significant proportion of patients in whom depression developed after cytokine therapy for cancer . the neurotoxic inflammation induced by cytokines resulted in decreased levels of tryptophan , the amino acid precursor for serotonin . this decrease was positively correlated with the development and severity of depressive symptoms in patients . the long - term clinical sequelae of wnv neuroinvasive disease need to be further defined . by understanding potential outcomes and determining whether certain interventions such as physical therapy , counseling , and antidepressant drug therapy can improve recovery physicians should note that depression and personality changes could be important neuropsychiatric consequences in patients with clinical wnv infection .

previous reports have noted depression after west nile virus ( wnv ) infection . we further measured this outcome and found that 31% of patients reported new - onset depression and 75% of these had center for epidemiologic studies depression scores indicative of mild - to - severe depression . physicians should be aware of neuropsychiatric consequences of wnv in patients .

keeping this in view , during the mid-1980s the government of india decided to assess the extent of yaws problem in the country8 . based on the data so obtained , the government took the initiative to renew its efforts to eradicate yaws based on the premise that yaws eradication can not only alleviate the suffering of the tribal populations but also assist in bringing them out of economic deprivation9 . moreover , since women and children are at particularly high risk , the disease has a negative impact on reproductive and general health and on nutritional status as well . several other factors helped india decide to launch the eradication programme , including - ( i ) epidemiological : there is no extra - human reservoir of infection and the disease is endemic only in limited albeit difficult and hard to reach areas ; ( ii ) technological : simple diagnostic tests and effective low cost treatments are available ; the use of a single intra - muscular injection of long - acting benzathine penicillin to cases and their contacts can cure the disease and interrupt transmission ; ( iii ) historical : the disease was almost eradicated during the 1950s ; and ( iv ) perhaps most importantly , the government of india was convinced that eradication of yaws was an attainable goal and was committed to achieve the goal10 . india launched an anti - yaws campaign in 1952 with assistance from who and unicef . from 1952 to 1964 , the campaign detected and treated about 200 thousand cases in four states , namely orissa ( now odisha ) , andhra pradesh , maharashtra and madhya pradesh5 . the prevalence of yaws declined from 14.4 to 1.1 per cent in odisha , from 5.6 to 0.3 per cent in andhra pradesh , and 5.5 to 1.4 per cent in the bastar district of madhya pradesh . the active yaws eradication efforts were gradually abandoned in the country and the strategy changed from active case finding and treatment to passive surveillance as part of general health services . it is ironic that yaws control was left for general health services to take care of , in the very areas where there were virtually no health care services existing in the first place . unsurprisingly , as a result the disease began to re - emerge in the late 1970s11 . in 1986 , the national institute of communicable diseases ( nicd ) , encouraged by the success of smallpox eradication during the 1970s and progress being made in eradication of guinea worm disease in the country during the early 1980s , organized a meeting to develop a strategy for yaws eradication9 . the strategy agreed to in the consultation consisted of ( i ) active search for and treatment of infectious cases , and ( ii ) health education and social mobilization in the community . cases were to be treated with long - acting benzathine penicillin , thereby rendering them non - infectious ; simultaneously , the family contacts given penicillin shots as prophylaxis . in cases sensitive to penicillin , tetracycline or erythromycin was recommended for a period of 15 days . more recently , studies have shown the efficacy of single - dose azithromycin for treatment of yaws in children12 . the strategy was first piloted in koraput district in odisha during 1996 - 1997 to ascertain the feasibility of its implementation as a part of the programme . subsequently , based on positive feedback from the pilot studies , the national programme was extended to four more states , namely andhra pradesh , gujarat , madhya pradesh and maharashtra . by 1999 , the programme was expanded to all 51 districts in 10 states where yaws cases were reported in the past ( fig . active case search operations were carried out by multipurpose workers and community level functionaries , who visited house - to - house carrying a coloured disease recognition card and other health education materials looking for yaws cases . the treatment consisted of penicillin injections ( 1.2 million units for those above 10 years and 0.6 million units for children below 10 yr ) , preceded by testing for sensitivity to penicillin . the active search and treatment operations were carried out at 6-monthly intervals before and after monsoon seasons . in addition to active search , cases which were routinely diagnosed at health centres were also treated and their contacts given prophylaxis . through active case search and routine reporting , the programme detected and treated about 7000 infectious cases and their contacts . the strategy was highly effective , as the number of yaws cases detected in the country started declining rapidly ; from 3571 cases in 1996 to 664 in 2000 ( a reduction of more than 80% ) and only 46 three years later6 . the last case was diagnosed and treated in mayurbhanj district , odisha in 2003613 ( fig . 3 ) , thereby achieving the interim goal of yaws elimination set by the programme ( no yaws case status ) in 200414 . at the recommendation of the task force , the government of india on september 19 , 2006 formally declared having achieved yaws elimination6 . to move from yaws elimination to eradication , defined by the programme as absence of new cases for a continuous period of three years , supported by data indicating absence of transmission through serological surveys among children , a road map was developed based on consensus building among yaws experts in the country10 . the road map consisted of three new activities : ( i ) serological surveys among children between one and five years of age to assess cessation of community transmission of yaws , ( ii ) rumour reporting and verification , and ( iii ) institution of cash reward for anyone reporting a yaws case , in addition to the information and communication activities and active search for cases which were continued on yearly basis . many rumours of possible yaws cases were verified as non - yaws over the next five years . and , no one came forward to receive the cash award . during the 2009 - 2011 period , serological surveys were carried out among randomly selected children using rapid plasma reagin ( rpr ) test with treponema pallidum haemagglutination assay ( tpha ) for confirmation . of the 18,217 children surveyed in the erstwhile yaws villages , no serological evidence of yaws infection was found ( jain sk , personal communication ) . simulteneously , for comparison purposes , 39319 children in non - yaws villages were tested and none were found positive , collectively indicating cessation of yaws transmission in the community and in the country as a whole ( jain sk , personal communication ) . while the overall programme was planned , implemented and coordinated by nicd ( now called national centre for disease control or ncdc ) , the programme performance at the field level was evaluated by an independent set of experts through appraisal missions . at the highest level , the programme was monitored by a task force under the chairmanship of the director general of health services , government of india . since 2000 , six such independent appraisal missions were fielded ; the last and sixth mission consisting of 16 teams was undertaken during may and june 2014 and visited 16 districts in 10 states ( jain sk , personal communication ) . the single key factor responsible for the success was the sustained effort of health care workers on the frontline , supported by programme staff , working under trying field conditions , in the affected areas . the most important among those were as follows : first , yaws is immensely amenable to eradication due to a number of favourable factors - there is no animal reservoir ; only a few localized foci of infection remain ; a single intra - muscular injection of long - acting penicillin completely cures the disease ; and the diagnosis of yaws can be done clinically with minimum training of staff and through community education . however , efforts must be continued until the last case is diagnosed , treated , and cured . second , to achieve the goal of yaws eradication , not only is a high level of political commitment needed but must be sustained over time so that the programme achieves its ultimate goal of eradication . for the field operations , human resources and logistic support were provided by the state governments while the government of india , besides policy support , ensured funding support for supplies , training , search operations , and for monitoring missions and feedback . third , partnership among various sectors and stakeholders engaged in the programme was essential for success . besides the health directorate , other sectors namely department of tribal welfare and other institutions such as panchayati raj , education , forest , etc . they visited the field at regular intervals for verification of the progress being made to ensure that yaws cases are no longer existing and that community transmission is interrupted , even at the risk of their personal safety and security . fourth , the programme was implemented through the existing health care delivery system of the state health directorates . successful programme implementation was facilitated by a target oriented campaign , provision of supportive supervision during field activities , improved communication from the field to ncdc , and regular review meetings of state programme officers to review progress and share lessons learnt . finally and most importantly , the success of the programme could be attributed to a technically sound strategy which proved effective in trying field conditions . the programme was primarily funded by the government out of its own resources and as a part of its national 5-year plan , with additional technical and financial support from the who . the achievement of yaws eradication in india is an excellent example of a triumph of public health over a disease which still afflicts many populations in remote areas in africa and asia . the indian experience clearly shows that with commitment and renewed efforts , the disease can be eradicated from all those countries of the world where yaws is still prevalent . programmes such as these can go beyond health and play a role in enhancing the socio - economic conditions of people long neglected from policy point of view15 . as stated above , the eradication campaign in india was conceived with the idea of not only alleviating the suffering of the poor , predominantly tribal population , but also with a view that the programme could contribute to the economic empowerment of remote areas and work as an entry point for primary health care for people living in these areas . the anecdotal information is available ( jain sk , personal communication ) to suggest that yaws eradication has brought about considerable improvements in the lives of tribal people , and has been instrumental in stimulating productivity and economic growth in these otherwise impoverished and so - called backward areas of the country . with improvements in living conditions , sanitation , and health and nutritional levels , the eradication programme is contributing towards poverty reduction among neglected populations living in hard to reach areas .

yaws , a non - venereal treponematosis , affecting primarily the tribal populations , has been considered historically as one of the most neglected tropical diseases in the world . in 1996 , india piloted an initiative to eradicate yaws based on a strategy consisting of active case finding through house - to - house search and treatment of cases and their contacts with long acting penicillin . thereafter , the campaign implemented in all 51 endemic districts in 10 states of the country led to the achievement of a yaws - free status in 2004 . in the post - elimination phase , surveillance activities accompanied by serological surveys were continued in the erstwhile endemic districts . these surveys carried out among children between the age of 1 - 5 yr , further confirmed the absence of community transmission in the country . the experience of india demonstrates that yaws can be eradicated in all endemic countries of africa and asia , provided that political commitment can be mobilized and community level activities sustained until the goal is achieved .

a 49-year - old man with a history of sick sinus syndrome presented with quadriplegia and ophthalmoplegia . brain magnetic resonance imaging ( mri ) and an angiography examination , which were performed a day after quadriplegia , revealed acute brain infarction in the bilateral midbrain , right median thalamus , and superior cerebellum associated with the distal basilar artery occlusion . it is also unclear whether the mechanism of symptomatic bruxism is identical with that of idiopathic sleep bruxism . it has been shown that rhythmic jaw movement is generated by a neuronal activation in the brainstem of animals.7 rhythmic firing of interneurons in the pontine reticular formation ( prf ) and a connection between the oral motor nuclei and the prf have been observed.7 - 10 rodents move their jaws continuously and cows ruminate throughout the day . however , the activity of the generator is so weak that the release from high cortical inhibition during normal sleep may not be sufficient to cause bruxism . thus , the release phenomenon due to sleep and other factors such as dental problems , smoking , alcohol , and the coma state6 may cause bruxism . in our case , bilateral midbrain infarction may have caused the interruption of higher cortical inhibition and damaged the dentato - rubro - olivary pathway . although higher cortical inhibition is interrupted , the brainstem generator may not be sufficient to cause bruxism . additional damage to the dentato - rubro - olivary pathway may cause bilateral olivary hypertrophy , which can stimulate the prf . because no connection between the oral motor nuclei and the inferior olivary nuclei has been observed in animal study , we do not think that the hypertrophied olivary nucleus directly stimulates the motor nucleus in the brainstem.8 instead , hyperactive bilateral prfs may cause bruxism . pollack and cwik have reported bruxism after cerebellar hemorrhage,5 which may also be related to the damage to the dentato - rubro - olivary pathway . unlike palatal myoclonus , bruxism requires bilateral harmonic rhythmic contraction and relaxation of involved muscles . since the neurons in the prf project to both the trigeminal motor nuclei,8 the prf may induce the contraction of one side and relaxation of the opposite side . on the other hand , the normal side can influence both we suspect that this is a reason why bruxism is very rare in patients with brainstem infraction . in conclusion , furthermore , we suggest that the human bruxism generator may be located in the prf . large bilateral midbrain lesions that interrupt cortical inhibition seem to produce bilateral olivary hypertrophy , resulting in bruxism in the presence of the intact pontine generator .

delayed - onset continuous bruxism due to brain stem infarction has not yet been reported . a 49-year old man presented with quadriplegia and ophthalmoplegia . brain mri showed acute infarction in the bilateral midbrain , right thalamus and the superior cerebellum . one month later , the patient developed bruxism which persisted during sleep . a palatal myoclonus was not observed . follow up mri taken 4 months later showed bilateral olivary hypertrophy . we suggest that the patient 's bruxism may be related to the olivary hypertrophy . the bruxism generator may be located in the pontine - reticular - formation ( prf ) . bilateral large midbrain lesions interrupting the cortical inhibition may have produced bilateral olivary hypertrophy , which could stimulate the prf , producing continuous bruxism .

according to the world health organization ( who ) classification , odontogenic tumors are considered to be tumors of the odontogenic mesenchyme , with or without the presence of odontogenic epithelium . myxomas of head and neck are divided into two forms : i ) deriving from facial bone which has also been subdivided into osteogenic myxoma and odontogenic myxoma ; ii ) deriving from soft tissue which originate from perioral soft tissues , parotid glands , ears and larynx . patients may also complain of malocclusion , loss of tooth and palatal swelling . from a histological aspect , odontogenic myxomas include spindle like cells , star shaped cells with elonged cytoplasms and , in some cases , small masses of inactive odontogenic epithelium . radiographically , the tumors present as unilocular or multilocular radiolucent lesions . the lesions usually have well - defined borders and are described as honeycombed or soap bubble shaped . differential diagnosis must be made with ameloblastoma dentiginous cysts , fibrous dysplasia , osteosarcoma , chondrosarcoma and odontogenic fibroma . although local trauma has been thought to be the cause , the etiology is unknown . there are high recurrence rates after surgical excision . therefore , wide local excision is mandatory for treatment . in this case report we discuss these tumors with examples from literature because they are very unusual in childhood and have high recurrence rates . the patient was a 9-year old girl presenting with swelling on the right facial region . physical examination of the patient revealed that the mass had obliterated the right nasolabial groove and caused swelling of the right facial region . the computerized tomography ( ct ) examination revealed that the mass was originating from the right maxillar bone and the maxillary sinus antrum was filled by the tumor . medial and anterior wall of the sinus was displaced because of the growing mass ( figures 1 and 2 ) . an incisional biopsy was made through the nasolabial groove and was reported to be odontogenic myxoma . surgical removal of the mass including wide periincisional tissue was performed via a right superior gingivo - buccal incision . during the operation it was seen that the mass was white in color , completely encapsulated and was completely filling the sinus antrum . the anterior wall of the maxillary sinus was thinned , partially destructed and pushed anteriorly . figure 1axial tomographic image of the myxoma showing obliteration of the right maxillary sinus and bone destruction with finger like projections into maxilla . axial tomographic image of the myxoma showing obliteration of the right maxillary sinus and bone destruction with finger like projections into maxilla . figure 2coronal tomographic images of the myxoma showing obliteration of the right maxillary sinus and bone destruction with finger like projections into maxilla . coronal tomographic images of the myxoma showing obliteration of the right maxillary sinus and bone destruction with finger like projections into maxilla . the patient was followed up for two years and there has been no evidence of recurrence . histological examination of both masses removed during the two surgical interventions revealed hypocellular tumoral tissues with myxoid stromas and scattered stellate fusiform cells with hyperchromatic nuclei ( figures 3 and 4 ) . figure 3hypocellular tumoral tissue with myxoid stroma and scattered stellate and fusiform cells with hyperchromatic nuclei ( hematoxylin & eosin , 200 ) . hypocellular tumoral tissue with myxoid stroma and scattered stellate and fusiform cells with hyperchromatic nuclei ( hematoxylin & eosin , 200 ) . figure 4tumor tissue showing the same morphology in every field including the bone trabeculae ( hematoxylin & eosin , 200 ) . tumor tissue showing the same morphology in every field including the bone trabeculae ( hematoxylin & eosin , 200 ) . thoma and goldman separated myxomas of the mandible and maxilla from other myxomas . in 1948 , stout redefined the histological criteria for myxomas as benign neoplasms of mesenchymal origin . ghosh et al . defined only 10 osseous myxomas in a review of 8723 primary bone tumors ; 6 in the mandible and 4 in the maxilla . although it is claimed that maxilla and mandible are equally involved , others noted a more frequent involvement of the mandible . however , there is a theory that they arise from odontogenic mesenchyme , especially from the molar and premolar region of the maxilla . stromas of myxomas are hypocellular and they include mucopolysaccharides , hyaluronic acid , and chondroitin sulfate molecules . these substances are thought to be the cause of the locally aggressive behavior of the myxomas . histologically , these tumors may be confused with myxoid degeneration , malignant nerve sheath tumors and myxoid chondrosarcoma . enucleation is performed for protecting the facial growth centers and this approach prevents facial asymmetry . it is suggested that enucleation may be performed in small tumors , but recurrence rates are higher than partial maxillectomy . therefore , wide surgical excision and close follow up is mandatory in osseous myxomas . in our patient , recurrence was confirmed four months after the operation and partial maxillectomy had to be performed . recurrence rates are high and a long follow - up period over years is essential after treatment for patients with these tumors .

myxomas are mostly seen in the 2th and 3rd decades . they rarely occur in childhood and maxillofacial region is rarely involved . the recurrence incidence is high . we report this unusual case occurring in a 9-year - old girl in the maxillofacial region and recurrence four months after initial treatment .

a 66-year - old woman with sjgren syndrome presented with a 5-year history of bilateral shoulder pain that was significantly worse on the right than the left side . the pain was reported to be constant in nature but worse at night , and completely prohibited activities above shoulder height . examination of the right shoulder revealed a globally restricted range of movement at the glenohumeral joint . treatment with copeland resurfacing hemiarthroplasty was performed in june 2007 through an anterosuperior ( mackenzie ) approach . . 1 interrupted pds ( polydioxanone ) sutures were used for reattachment of the anterior border of the osteo - periosteal sleeve to the acromion . the sutures were placed transosseously through the acromium on one side and through the deltoid fascia , incorporating an osteo - periosteal sleeve , on the other [ figure 2 ] . preoperative radiograph demonstrating severe osteoarthritis radiograph taken in the immediate postoperative period showing a copeland resurfacing hemiarthroplasty passive elevation past 90 could be achieved on the first postoperative day . a shoulder immobilizer was worn for 3 weeks and the patient was instructed to avoid active elevation . the patient had returned to aerobics and table tennis by the 4 postoperative month , at which point increased pain in the shoulder was reported . at the end of the 1 postoperative year , significant impingement symptoms were reported and x - rays demonstrated a new bony spur on the anteroinferior edge of the acromion [ figure 3 ] . an ultrasound scan showed a bony spur indenting the supraspinatus , but there was no accompanying cuff tear . the pain continued to worsen and diagnostic arthroscopy was performed in july 2009 , which confirmed the presence of the spur at the anteroinferior edge of the acromion and excluded the presence of significant glenoid arthrosis or adhesions as contributing factors to the patient 's symptoms . radiograph at 1 year showing new bony spur on the inferior surface of the acromion appearance following arthroscopic resection of the spur the mackenzie anterosuperior approach has been popularized for several types of shoulder arthroplasties . in this approach the anterior deltoid is commonly reflected with an osteo - priosteal sleeve . we postulate that the bony spur responsible for the impingement symptoms in our patient was formed by malunion of the osteo - periosteal sleeve . at the time of arthroscopy , a sharp spur of bone of the same size and shape as the osteo - periosteal sleeve was found to be united in the correct position on the anterior acromion but , from its shape , it had apparently rotated 90 from the original orientation . the onset of symptomatic impingement along with new x - ray findings at 4 months postoperatively is consistent with rotation of the fragment during healing following the patient 's return to sporting activity . full resolution of the patient 's symptoms following resection of the spur also supports this conclusion . intra - articular factors are the most common reasons for postoperative pain following copeland resurfacing hemiarthroplasty and are due to the nonanatomical shape of the prosthesis , which does not accurately recreate the original shape of the humeral head . as our patient was initially pain free with good shoulder function , we carried out other investigations , including diagnostic arthroscopy , to look for other causes for her pain preoperative investigation to establish the diagnosis of subacromial impingement could include an injection of local anesthetic under aseptic technique into the subacromial space . immediate pain relief would be convincing evidence of the existence of subacromial impingement . to the best of our knowledge , this is the first report of formation of an acromial spur following the mackenzie approach . complications of the copeland resurfacing hemiarthroplasty have been reported as infection , aseptic loosening , periprosthetic humeral fracture , and osteolysis . subacromial impingement has been reported in patients after this procedure and the symptoms have necessitated subacromial decompression , but this has not previously been reported to be associated with a malunited osteo - periosteal sleeve . nonunion ( or fibrous union ) has been reported by previous authors following surgical access using the mackenzie approach but they did not report symptomatic subacromial impingement . in our patient , simple arthroscopic excision of the bony spur proved curative . this case has altered our practice , as we have now abandoned the osteoperiosteal sleeve technique and instead opt for subperiosteal dissection of the anterior deltoid . we conclude that the cause for the delayed , severe impingement symptoms in this patient following successful copeland resurfacing hemiarthroplasty was malunion of the osteo - periosteal sleeve that was made as part of the mackenzie approach . all symptoms resolved following arthroscopic resection of the spur .

we report the case of a patient with end - stage osteoarthritis who received a successful copeland resurfacing hemiarthroplasty through a mackenzie anterosuperior approach , which involves taking the anterior portion of the deltoid attachment from the acromion along with an osteo - periosteal sleeve . the patient went on to develop severe subacromial impingement symptoms 4 months postoperatively . x - rays revealed a large anteroinferior acromial osteophyte that had not been present preoperatively and was deemed to represent a malunited osteo - periosteal sleeve from the mackenzie approach .

myofibroblasts are derived from fibroblasts , and exist in various tissues such as normal connective tissues , granulation tissue and reactives inflammatory tissues . a low - grade myofibroblastic sarcoma ( lgms ) is a rare malignant tumor with myofibroblastic differentiation , and just a few cases have been reported in the oral and maxillofacial region . here , we describe a patient with lgms of the palate , and bibliographic considerations are reviewed . a 73-year - old man was referred by his general dental practitioner to the department of oral and maxillofacial surgery ( kochi university , kochi , japan ) regarding a tumor on the palate that had developed over a couple of months . physical examination revealed an elastic hard , 10 mm10 mm mass on the posterior border of the palate . an excisional biopsy of the palatal mass was performed , and microscopic examination revealed infiltrative spindle tumor cells surrounded by a fibrous capsule . the tumor cells had round - shaped or spindle nuclei , and the cytoplasm was eosinophilic . there were few mitotic cells , however , and atypical cells with large nuclei were observed ( figure 2 ) . immunohistochemistry revealed that most spindle cells were immunoreactive for muscle - specific actin ( hhf35 ) , and focally for -smooth muscle actin ( -sma ) and mib-1 ( figure 3 ) , in contrast , immunostaining for other markers , such as cd34 , cd68 , desmin , epithelial membrane antigen ( ema ) , s-100 protein , cytokeratin ( ae1/ae3 ) , and p53 was not observed ( table 1 ) . the patient was disease - free at the last examination , 2 years postoperatively ( figure 4 ) . myofibroblasts are mesenchymal spindle cells that are first observed in the granulation tissue of healing wounds , and play a role in the production of contractile force . myofibroblasts exist under various reactive conditions , including reparative granulation tissue , granulomas , inflammatory pseudotumors , and various benign and malignant soft tissue tumors . lgms used to be a controversial neoplasm , but has been reclassified as a distinct entity in the newly published world health organization classification of soft tissue tumors . however , intermediate- and high - grade myofibroblastic sarcomas were also documented in the literature . high - grade ( pleomorphic ) myofibroblastic sarcomas were described as pleomorphic sarcomas composed of atypical spindle , polygonal and giant cells showing the ultrastructural features of myofibroblastic differentiation and numerous mitotic figures . the tumor cells have a scanty to moderate amount of eosinophilic or amphophilic cytoplasm and fusiform nuclei with mild nuclear pleomorphism and a low mitotic rate . immunohistochemically , myofibroblastic sarcoma is immunopositive for vimentin , sma , muscle - specific actin , calponin and fibronectin , rarely immunopositive for desmin , and immunonegative for laminin and type iv collagen . lgms is easily confused with myofibroblasts composed of nodular fasciitis because of their morphological similarity and overlapping immunophenotype . in addition to nodular fasciitis , lgms is differentiated from leiomyosarcoma , malignant fibrous histiocytoma , inflammatory myofibroblastic tumor and fibromatosis . leiomyosarcoma has a well - delineated pushing margin and show longitudinally fibrillary cytoplasm and cigar - shaped vesicular nuclei with paranuclear vacuolation . malignant fibrous histiocytoma shows anaplasia and multinucleated giant cells and marked cytological pleomorphism and nuclear atypia . fibromatosis is characterized by fibroblasts and myofibroblasts in parallel alignment , but cytologic atypia and nuclear pleomorphism are absent . the specimen from our case was immunopositive for sma and muscle - specific actin , and was immunonegative for ema , s-100 , ae1/ae3 and cd34 . histologically , infiltrative spindle tumor cells showed a myofibroblastic differentiation , and there were several atypical cells . based on these findings lgms mainly occurs in adults , and most frequently affects the deep soft tissues of the oral cavity ( especially the tongue ) , limbs , trunk , or abdominal and pelvic cavities . the head and neck region , including the oral cavity , is the preferred location for lgms ; however , only few cases were reported of lgms occurring in the oral and maxillofacial region . in the literature , there are 38 cases of lgms in the oro - maxillofacial region , including our case ( table 2 ) . the average age was 40.7 years ( range : 285 years , median : 41 years ) , and the male to female ratio was 43 . the tongue was the most preferred site , followed by the maxilla and palate , mandible , nasal / paranasal cavity and deep tissue spaces including the parapharyngeal space . rr was 21.4% when tumor size was less than 3 cm , whereas that of over 3-cm tumor was 46.2% . as lgms is associated with little symptoms , early detection may be difficult when tumors are in deep tissues , such as nasal cavity , paranasal sinus , jawbone and masticatory space , resulting high rr . lgms may cause focal recurrences and metastasis , and it has a relatively indolent course . radiotherapy or chemotherapy are not established treatments , and the importance of surgery is emphasized .

low - grade myofibroblastic sarcoma ( lgms ) is a rare , malignant tumor with myofibroblastic differentiation . despite it being classified as a distinct entity by the world health organization , a few cases were reported in the oral and maxillofacial region . here , a lgms developed on the palate of a 73-year - old man who presented with a 1-cm tumor on the posterior border of the palate . based on the histological and immunohistochemical features , a diagnosis of lgms was established . the tumor was resected , and no recurrence was observed over 2 years . although the tongue is the most preferred site for lgms , it may occur in any region of the oral cavity .

the most common species in sub - saharan africa is plasmodium falciparum which is the most dangerous of the four human malaria parasites . it is one of the leading causes of morbidity and mortality in developing countries like nigeria , with adverse effects seen more in children under 5 years and pregnant women the result of this study may provide data that will improve maternal and neonatal outcome and aid the achievement of the millennium development goals of 4 and 5 . this cross - sectional study was carried out in the labor ward of the federal medical center , owerri , between december 2013 to may 2014 . the parturients that fulfilled the criteria a questionnaire was administered by the researcher to get the biodata of the women and other information about malaria control strategies which included the use of ipt , use of insecticide - treated net ( itn ) , or both . while in labor , peripheral blood was collected from the mother into an ethylenediaminetetraacetic acid bottle for malaria parasitemia and a smear was made from blood taken from the placental tissue postdelivery . the newborn was weighed and examined . as used in the study by sowunmi et al.,1 the fetal surface of the placenta was inserted through the whole thickness of the placenta at its thickest point to measure its thickness . the needle was then withdrawn , and the approximate thickness of the placenta was determined . the needle was reinserted at the same point such that its tip was at a level approximately below half the depth of the estimated placental thickness . the tip of the needle at this position was located in the maternal half of the placenta.2 blood was aspirated at this point . they were sent to the laboratory where the researcher with the assistance of the hospital laboratory scientist stained the smears with freshly prepared 20% giemsa stain maintained at a ph of 7.2 for 15 min . the neonates were seen 10 days postpartum for the assessment of peripheral blood plasmodium parasitemia data collected were sorted out , coded , and imputed into spss version 16.0 statistical package 16 ( spss , inc . frequency tables , charts , and graphs were used to represent relevant variables and observed patterns . the prevalence of placental parasitemia was determined by the proportion of placentae with parasites to overall sample of placentae . the relationship between placental parasitemia and average neonatal birth weight was tested using chi - square . this method was also used to investigate the association between the use of malarial preventive measures ( mpms ) , maternal peripheral blood parasitemia , and occurrence of placental parasitemia . all analyses were done at 5% level of significance with p < 0.05 considered statistically significant . data collected were sorted out , coded , and imputed into spss version 16.0 statistical package 16 ( spss , inc . , 2007 , chicago ) . frequency tables , charts , and graphs were used to represent relevant variables and observed patterns . the prevalence of placental parasitemia was determined by the proportion of placentae with parasites to overall sample of placentae . the relationship between placental parasitemia and average neonatal birth weight this method was also used to investigate the association between the use of malarial preventive measures ( mpms ) , maternal peripheral blood parasitemia , and occurrence of placental parasitemia . all analyses were done at 5% level of significance with p < 0.05 considered statistically significant . one hundred and eighty mother / baby pairs were studied . ninety ( 50% ) of participants were aged 25 - 29 years , with a mean age of 27.1 5.4 years . one hundred and fourteen ( 63.3% ) were resident in urban areas , and 132 ( 73.3% ) of women received antenatal care at federal medical centre , owerri [ table 1 ] . sociodemographic and obstetric characteristics of the mothers table 2 shows that the mean birth weight of babies with no placental parasitemia ( 3.420 0.2 kg ) was significantly higher than that of their counterparts with placental parasitemia , 2.971 1.1 kg ( z - test = 17.96 , p 0.0001 ) . women with affected placentae were found to have babies weighing approximately 449 g less than those with unaffected plancentae . mean birth weight and placental parasitemia figure 1 shows the relationship between placental parasite count and average birth weight . the y - axis represents absolute number of affected respondents and weight in kilogram while weight in kilograms is shown on the x axis there was a consistent fall in birth weight with increasing placental parasitemia which was significant ( p = 0.0294 ) . in table 3 , it was shown that those who had not used any form of mpm in pregnancy ( = 56.07 , df = 1 , p 0.0001 ) have a significantly higher placental parasitemia when compared with their counterparts . moreover , those who had not used ipt in pregnancy ( 49.2% ) ( = 12.214 , df = 2 , p = 0.0004 ) and those who did not use itn at all times ( 46.2% ) or never ( 34.3% ) had significantly higher placental parasitemia than their counterparts , p < 0.05 . relationship between the use of malaria preventive measures and parasitemia table 4 revealed that the average birth weight of neonates with placental parasitemia in mothers who used ipt only ( t = 2.22 , p = 0.005 ) and ipt + itn ( t = 7.91 , p 0.0001 ) was significantly higher than those who did not use any form of malaria prevention in pregnancy ( t = 4.69 , p 0.0001 ) . no significant difference in weight was found among those who used itn only ( t = 0.95 , p = 0.200 ) . method of preventing malaria and average birth weight table 5 shows the occurrence of fever with the use of malaria preventive measures . participants who had only one dose of ipt during pregnancy ( 75.0% ) had a higher prevalence of fever than their counterparts who had two or three doses during pregnancy . this difference was statistically significant ( = 17.911 , df = 2 , p 0.0001 ) . occurrence of fever with the use of malaria preventive measures figure 2 shows that a large proportion of the participants reported unavailability of the nets , 60 ( 56.6% ) as the reason for noncompliance followed by ignorance of its use , 33 ( 31.1% ) . this value was comparable to that of 28.2% noted in the gambia3 and 21.5% in cameroun4 but much lower than values of 52.2% and 68.3% given by ojiezeh et al.5 and umeh et al . in the south west nigeria and enugu , respectively.6 the difference in values noted may be due to the difference in endemicity and malaria preventive practices . to prevent the consequences of malaria in pregnancy , the world health organization ( who ) recommends effective case management , use of insecticide - treated bed nets , and intermittent presumptive treatment ( ipt ) with sulpfadoxine - pyrimethamine ( sp).7 intermittent presumptive strategy has been recommended by the who since the early 2000s and has been adopted by most african countries including nigeria . it consists of the administration of two doses of sp under supervision at least 1 month apart from the second trimester of pregnancy . this may be extended to at least three times where human immunodeficiency virus seroprevalence is > 10%.8 placental malaria occurs as a result of sequestration of parasites in the placenta which interferes with nutrient transport to the fetus . the presence of parasites in the placenta was found to be associated with reduced birth weight of 449 g in this study ( 2971 vs. 3420 g ) . this was similar to results noted by steketee et al.9 this is however different from findings in the studies by rulisa et al.,10 anagnos et al.,11 and shulman and dorman,12 which showed no association between low birth weight and placental parasitemia . this study was prospective and done among a homogenous group of primigravidae which removed the bias of parity which may have been responsible for the different results obtained . the results of studies have shown that patients without placental parasitemia had larger babies weighing about 105382 g more than those with parasitemia.131415 findings in this study were similar to those of others which show that birth weights were more in nonparasitized placentae with the affected neonates weighing an average of 449 g less . this weight disparity was more prevalent among neonates of mothers with higher levels of third - trimester maternal peripheral parasitemia . this may be related to the severity of late acute infestations . as this study did not differentiate acute and chronic infections , the above preventive measures against malaria in pregnancy remain the priority intervention method to protect the fetus and neonate against its adverse effects.161718 the who recommended three - pronged strategic frameworks in the areas of stable malaria transmission in sub - saharan africa : ipt , itn , and case management of malaria illness still remains the gold standard.17 the association between the use of malaria preventive measures and placental parasitemia with low birth weight is clear . parturients who failed to use itn or receive ipt are more likely to deliver smaller babies as was seen in this study . showed the reduced risk for primigravida but not in higher parities , and with each dose of sp mean birth weight increased by 220 g.8 only 74 ( 41.1% ) of the respondents used itn consistently . this was surprising as majority of the women attended antenatal care in a tertiary center where these nets ideally should have been readily available . the low prevalence of placental parasitemia among parturients that used malaria preventive measures observed in this study ( 7.2% ) was similar to that documented by inyang - etoh et al.19 ( 10.6% ) . the study by umeh et al . however showed no difference in parasitemia levels between treatment and control groups.6 in this study , it was observed that 20% of the respondents were offered ipt in the clinics as was documented in the case notes but did not take it . directly observed therapy ( dot ) for the administration of this medication is not offered in our center . the reason for noncompliance may have been due to diverse reasons including side effect profile , lack of funds for the purchase of the drug , and poor attitude to antenatal drug use . primigravidae with placental or maternal peripheral parasitemia are more likely to deliver babies with reduced average birth weight . a scheme to introduce intermittent presumptive treatment in the hospital , making itn readily available , and improving the girl child education

background : despite the global efforts made to eradicate malaria , it continues to be a significant cause of morbidity and mortality in both neonates and the parturients . this study was done to determine the relationship between placental parasitemia , average neonatal birth weight and the relationship between the use of malaria preventive measures and the occurrence of placental parasitemia with the aim to improving maternal and neonatal outcome.patients and methods : this cross - sectional study was done at the labor ward unit of the federal medical center , owerri , from december 2013 to may 2014 . it involved one hundred and eighty primigravidae and baby pairs recruited consecutively . thick and thin blood films were made from maternal peripheral blood and placenta . the babies were examined and weighed immediately after delivery.results:most of the participants had only one dose of intermittent preventive therapy ( 75% ) with statistically significant higher level of fever episodes ( p < 0.0001 ) . forty participants ( 58.0% ) did not use any form of malaria preventive measure in pregnancy ( p < 0.0001 ) and had a significantly higher placental parasitemia when compared with their counterparts . average birth weight of neonates with placental parasitemia in mothers who used intermittent presumptive therapy ( ipt ) only ( t = 2.22 , p = 0.005 ) , and ipt + insecticide - treated net ( itn ) ( t = 7.91 , p 0.000 ) was significantly higher than those who did not use any form of malaria prevention in pregnancy ( t = 4.69 , p 0.0001).conclusion : primigravidae with placental or maternal peripheral parasitemia who failed to use malaria preventive measures delivered babies with reduced average birth weight . a scheme aimed at making itn readily available , and improving the girl child education is highly recommended .

the first cases of in vitro and in vivo chloroquine resistance in burkina faso were seen in 1983 and 1988 , respectively , and reported clinical failure rates after use of chloroquine for treatment of uncomplicated malaria in children were already around 5% in the early 1990s . more recently , the clinical failure rate of chloroquine in pre - school children was shown to be around 10% in western burkina faso . these findings have led to the conclusion that chloroquine still remains sufficiently effective after many years of resistance occurrence in this part of west africa . little information exists on the dynamics of resistance development towards pyrimethamine - sulfadoxine , the usual second - line treatment choice in african countries with moderate chloroquine resistance . in burkina faso , only very low parasitological and clinical failure rates during use of have been reported in the past . the efficacy of pyrimethamine - sulfadoxine in a rural area of north - western burkina faso is reported . the study took place in six representative villages of the research area of the centre de recherche en sant de nouna ( crsn ) in north - western burkina faso . the nouna area is a dry orchard savanna , populated mainly by subsistence farmers of different ethnic groups . the study was nested into an ongoing insecticide - treated bed net ( itn ) study . all itn cohort children from the six villages visited during a cross - sectional survey in october 2002 were enrolled if they fulfilled the following inclusion criteria : age > 6 months , falciparum malaria ( 37.5c axillary temperature + 2.000 plasmodium falciparum parasites/l blood in the absence of another obvious fever cause ) , absence of antimalarial treatment during previous two weeks , informed oral consent . all study children received a fully supervised single - drug treatment with 1/2 tablet fansidar ( 12.5 mg pyrimethamine plus 250 mg sulfadoxine ) , taken from the essential drug stock of nouna health district . enrolled children were seen daily by village - based field staff over a 14-day period and , in case of fever ( 37.5c axillary temperature ) , blood films were taken . systematic blood slides were taken from all study children on day 0 , 3 , 7 and 14 . blood films were examined by two experienced laboratory technicians of the crsn . for the evaluation of treatment outcome , a modified definition of the who protocol for assessment of therapeutic efficacy of anti - malarial drugs in areas with intense transmission was used . early treatment failure ( etf ) was defined as development of severe malaria on days 13 or axillary temperature 37.5c on day 3 in the presence of parasitaemia , and late treatment failure ( ltf ) as development of severe malaria and/or axillary temperature 37.5c on days 414 in the presence of parasitaemia without previously meeting the criteria of etf . late parasitological failure ( lpf ) was defined as the presence of parasitaemia on day 7 and/or day 14 . approval for the study was granted by the ethical committee of the heidelberg university medical school and the ministry of health in burkina faso . of 357 cohort children seen during the survey , 40 children ( 11% ) were febrile and of those only 4 children had no detectable malaria parasitaemia . overall , 28 children met the inclusion criteria and were enrolled into the study . at baseline , the mean age of these study children was 23 months ( range 932 ) , 17/28 ( 61% ) were male , the mean temperature was 38.1c ( range 37.539.9 ) , and the mean weight was 9.5 kg ( range 5.512.9 ) . the median baseline number of p. falciparum trophozoites was 13.100/l ( range 2.000177.000 ) , and 9/28 ( 32% ) study children had p. falciparum gametocytes on day 0 . no etf was observed and only one ltf occurred in a 26 months old and 10.0 kg weighing male child , who had fever ( 38.7c ) and a low - grade parasitaemia ( 50/l ) on day 14 . in addition , 7/28 ( 25% ) study children still had measurable parasitaemia on day 3 ( 50475/l ) without fever , and 4/28 ( 14% ) study children had a lpf with low - grade parasitaemias ( 75250/l ) , two on day 7 and two on day 14 ( all male ) . on day 7 and/or day 14 , p. falciparum gametozytes were seen in 19/28 ( 68% ) of study children . the findings from this study confirm the still very low level of resistance to pyrimethamine - sulfadoxine in west africa [ 2,7 - 9 ] . the likely reason for the continued efficacy of pyrimethamine - sulfadoxine is the low level of drug pressure in these areas , where the large majority of malaria cases is still treated with chloroquine . these findings justify continued use of pyrimethamine - sulfadoxine for malaria second - line treatment in burkina faso , as in most of west africa . however , the question of which drug or drug combination should be the successor of chloroquine for malaria first - line treatment once this has reached unacceptable high failure rates remains largely unsolved for the poor malaria - endemic countries in sub - saharan africa ( ssa ) . although , with regard to its still high efficacy , pyrimethamine - sulfadoxine would be a promising candidate for replacing chloroquine in west africa , resistance is predicted to occur rapidly when the drug is used alone . artemisinin combination therapy ( act ) is now recommended by the world health organization as a first - line treatment for malaria , but these combinations are comparably very expensive and their use in malaria control programmes will thus not be possible in many countries of ssa without sustainable external support . the combination of amodiaquine and pyrimethamine - sulfadoxine has recently been shown to be even more effective than act , and this combination has now been chosen as a pragmatic interim solution by some countries of ssa . finally , the implications on the long - term effectiveness of intermittent pyrimethamine - sulfadoxine preventive treatment during pregnancy need to be taken seriously into consideration when using pyrimethamine - sulfadoxine as a first - line malaria therapy regimens in ssa . he was responsible for the design of the study , drafted the manuscript and made all necessary corrections . bk was responsible for the overall organisation in burkina faso and contributed to data analysis . the study was funded by the deutsche forschungsgemeinschaft ( sfb 544 , control of tropical infectious diseases ) .

the efficacy of pyrimethamine - sulfadoxine in the treatment of uncomplicated falciparum malaria in young children of a malaria holoendemic area in rural burkina faso is reported . of 28 children treated with a standard single dose of pyrimethamine - sulfadoxine and followed - up over 14 days , only one late treatment failure and four late parasitological failures were observed , all with low - grade parasitaemia . in this area of very restricted use of pyrimethamine - sulfadoxine , the drug appears to be still sufficiently effective in the treatment of malaria . these findings provide further evidence for the justification of continued use of pyrimethamine - sulfadoxine as a second - line treatment for malaria in burkina faso .

injuries range from mild respiratory complaints , phytodermatitis , irritant contact dermatitis , and allergic contact dermatitis to toxin - induced injuries and mechanical damage . tulipalin a induced phytotoxicity , also tulip fingers and alstroemeria dermatitis , is a common occupational allergy in floral workers exposed to tulip and alstroemeria cultivars . tulipalin a ( a - methylene - g - butyrolactone ) and its parent compound tuliposide a ( a - methylene - g - hydroxybutyric acid ) are concentrated in the outer layers of the plant bulbs and the pistils . in the plant , they are protective antibiotics exerting a fungicidal effect in flower bulbs . they were assigned to category b : solid - based indication for contact allergenic effects , because there is evidence of contact allergenic effects in animals and humans as well as induction of cross reactions in humans . they can also be considered skin sensitizers because under the globally harmonized system for classification and labeling of chemicals ( ghs ) , a human skin sensitizer is a substance that will induce an allergic response following skin contact . tulip fingers and alstroemeria dermatitis , the latter in particular due to the popularity of the inexpensive alstroemeria in lower cost floral arrangements , should be considered as a differential diagnosis in cases of unresolved dermatitis in floral workers . in this article we highlight the importance of comprehensive patient histories in a case of tulipalin a induced phytotoxicity misdiagnosed as a tinea manuum infection in an individual with suspected occupational fungal exposure and a review of the relevant scientific literature necessary to evaluate risk factors for the disease . an immunocompetent 30-year - old female , was referred for a medical examination to assess persistent unresolved tinea manuum , possibly related to occupational fungal exposure . the patient complained of little bumps on the dorsal surface of her right index finger around the distal interphalangeal joint . the bumps erupted across the dorsal surface of her right hand between digits # 1 and # 2 , progressed up to her wrists , popped , dried , and flaked off the residual skin . all physical examination outcomes were normal with the exception of lichenification and peeling of multiple fingers , including the palmar and dorsal surface , ulcers on several fingertips of each hand , pain , and discoloration of hands . apart from the ongoing issue with her hands , the patient 's medical history was unremarkable . the patient was initially diagnosed with tinea manis and prescribed a lengthy course of prescription antifungal treatment in 2010 after a nail culture indicated yeast , later identified as cryptococcus . tinea manis is unlikely , given the absence of the characteristic ring - like pattern . the presence of a cryptococcus species was likely a skin contaminant as it is unlikely that she would have an infection since the vast majority of cryptococcal infections occur in immunocompromised individuals . the lesions seem to worsen over time , and then get better . over time , the skin on her finger pads has thinned greatly . she has resorted to wearing a band - aid over her right index finger tip because it is continuously tender and depigmented . at night , the dorsal surfaces of her fingers seem to itch a great deal with no relief . the patient was instructed not to wear gloves at work because the gloves reportedly trap the patient mentioned that she works a great deal with the ornamental plant and flower alstroemeria , which has a moderate literature database detailing cases of persistent allergic contact dermatitis in florists . as previously noted , the causative allergen is known as tulipalin a ( -methylene--butyrolactone ) . the glycoside and its parent compound are named for the tulip bulbs from which they were originally derived . there is also a moderate literature database describing tulip fingers , an allergic contact dermatitis found in tulip workers primarily in the netherlands . interestingly , areas of depigmentation often follow the characteristic lesions that are similar to the initial bumps that this patient reported at the first visit . the patient was instructed to wear nitrile gloves at work , as her condition is not a fungal problem . she should not wear vinyl gloves , as the causative allergen crosses every type of common gloves except nitrile . she was referred to a dermatologist who may elect to take a skin biopsy and/or perform patch testing . diagnosis of tulipalin a induced phytotoxicity requires patch testing with the routine true test , as well as a number of plant extracts including : sesquiterpene lactone mix 0.1% , parthenolide 0.1% , 2,6-ditert - butyl - p - cresol 2% , and at least one preparation of tulipalin a. first described as tulip fingers in the european tulip industry , tulipalin a induced phytotoxicity results in severe dermatitis . similar phytotoxicity , termed alstroemeria dermatitis , has been described in florists who use alstroemeria . it is a common occupational complaint in floral workers who handle alstoemeria and tulip cultivars . the toxin is most concentrated in the flower bulbs and stems , although smaller amounts may be found in other parts of the plant . manifestations of phototoxicity include pruritus and edema in the fingers and along the palmar surface of the hand . paronychia is commonly seen along with nail splitting and ulceration of the nail bed in more severe cases . typically , a sensitized individual will develop acute symptoms 12 - 24 h after any subsequent exposures . patch testing is used to demonstrate contact with the allergenic tulipaside a. given the occupational history of this patient , a diagnosis of tulipalin a phytotoxicity is far more appropriate than tinea manis or cryptococcus . follow - up with a dermatologist for skin biopsy and/or patch testing with true test is recommended .

tulipalin a induced phytotoxicity is a persistent allergic contact dermatitides documented in floral workers exposed to alstroemeria and its cultivars.[1 ] the causative allergen is tulipalin a , a toxic glycoside named for the tulip bulbs from which it was first isolated.[2 ] the condition is characterized by fissured acropulpitis , often accompanied by hyperpigmentation , onychorrhexis , and paronychia . more of the volar surface may be affected in sensitized florists . dermatitis and paronychia are extremely common conditions and diagnostic errors may occur . a thorough patient history , in conjunction with confirmatory patch testing with a bulb sliver and tuliposide a exposure , can prevent misdiagnosis . we report a case of tulipalin a induced phytotoxicity misdiagnosed as an unresolved tinea manuum infection in a patient evaluated for occupational exposure .

charcot postulated that neuropathic joints were caused by an abnormality of blood flow due to denervation : denervation will also be expressed by changes in the circulation or nutrition if it involves , in addition , nerve fibers which are vasomotor or trophic ( translation ) ( 1 ) . in addition , charcot recognized the role of acute inflammation : the joints were inflamed , red and rather painful , similar to exacerbations of subacute rheumatoid arthritis ( translation ) ( 3 ) . nearly 150 years later , researchers have found molecular evidence to support charcot 's observation of acute inflammation . indeed , it is the uncontrolled inflammation that results in the final common pathway for decreased bone density in cn : osteoclast osteoblast imbalance . under normal circumstances , bone undergoes a constant remodeling process , with an intricate homeostasis between bone resorption by osteoclasts and bone formation by osteoblasts . gough and colleagues proved that excessive osteoclastic activity occurs in patients with acute cn ( 4 ) . they studied four groups : patients with acute cn , chronic cn , diabetic controls , and non - diabetic controls . using radioimmunoassay of blood samples from the dorsal venous arch , this group of researchers found a statistically significant increase in the pyridinoline cross - linked carboxy - terminal telopeptide domain of type 1 collagen , which is indicative of osteoclast activity , in the acute cn group ( p < 0.0001 ) . a similar increase in osteoblast precursors , carboxy - terminal propeptide of type 1 collagen was not found , indicating a higher concentration of osteoclasts than osteoblasts . in addition , the patients with acute cn showed a significant increase in levels of alkaline phosphatase , a marker of bone turnover . the role of inflammation in upsetting osteoclast osteoblast homeostasis was investigated by baumhauer et al . the investigators stained 20 surgical bone specimens of charcot patients with hematoxylin and eosin ( h&e ) , interleukin-1 ( il-1 ) antibody , tumor necrosis factor ( tnf ) alpha antibody , and interleukin-6 ( il-6 ) antibody . these inflammatory cytokines lead to bone resorption by promoting osteoclast recruitment , proliferation , and differentiation . osteoclasts demonstrated a moderate pattern of staining for tnf - alpha and il-1 , and a diffuse pattern of staining for il-6 . these results suggest that osteoclasts express inflammatory cytokines during the acute and reparative phases of cn . staining also showed the presence of excessive numbers of multinucleated osteoclasts in lacunae surrounded by lamellar bone . uccioli and colleagues further elucidated the role of inflammation in the charcot process as they characterized the cytokine phenotype of monocytes in patients with acute cn ( 6 ) . they studied three groups : patients with acute cn , diabetic patients with neuropathy , and normal control subjects . in patients with acute cn , they found monocytes expressing increased amounts of the proinflammatory cytokines tnf - alpha , il-1 beta , and il-6 as well as decreased amounts of the anti - inflammatory cytokines il-4 and il-10 . furthermore , monocytes from acute cn subjects had a marked increase in the percentage of positive cells and intensity of expression of the costimulatory surface molecules cd40 , cd80 , and cd86 . in contrast , there was no statistically significant difference in these surface molecules among the diabetic control and healthy control groups ( p > 0.05 ) . the inability to end the cycle of aggressive inflammation that is so characteristic of cn was explained by a resistance to monocyte apoptosis conferred by il-1 beta and tnf - alpha . the results of this study stimulate one to consider anti - tnf - alpha therapy as a potential treatment for cn . the presence of proinflammatory cytokines alone does not account for the entire influx of osteoclasts in cn . receptor activator of nuclear factor - kappa b ligand ( rankl ) has been studied extensively for its role in activating osteoclasts in diabetic cn . rankl is an important mediator of osteoclastogenesis and is essential in osteoclast formation and modulation ( fig . jeffcoate suggested that disruption of the rankl / opg pathway is responsible for both vascular smooth muscle calcification and the osteopenia seen in cn ( 7 ) . three years later , mabilleau and colleagues performed an elegant study that demonstrated the role of rankl in cn and also suggested that there may be a rankl - independent pathway ( 8) . osteoclast formation was assessed in peripheral blood samples from nine diabetic charcot patients , eight age - matched diabetic controls , and eight age - matched non - diabetic control patients . three isolates were obtained : one in the presence of macrophage - colony stimulating factor ( m - csf ) alone , one in the presence of m - csf and rankl , and one containing m - csf , rankl , and opg . they found a statistically significant increase in the formation of osteoclasts in diabetic charcot patients when compared with diabetic control and non - diabetic control patients ( p = 0.008 ) in cultures with m - csf alone . percentage of area bone resorption in charcot patients was four times higher than in healthy controls ( p = 0.005 ) and 2.9 times higher than in diabetic controls ( p = 0.008 ) . the addition of rankl to the cultures yielded a significant increase in osteoclastic resorption in the charcot group when compared with the diabetic and healthy control groups ( p < 0.0001 ) . finally , the addition of opg caused a greater decrease in resorption in the diabetic and healthy control groups than in the charcot group , implicating that there is a rankl - independent pathway of bony destruction in cn . the authors of this study suggest that the increased levels of circulating proinflammatory cytokines , tnf - alpha , il-6 , and il-8 induce osteoclast formation independent of rankl . indeed , inflammation is the final common pathway in the pathogenesis of cn . the role of rankl in charcot neuroarthropathy . to attempt to address the osteoclast osteoblast imbalance , there has been research to evaluate the use of bisphosphonates in cn . performed a level 1 study of 20 patients in which the treatment group received 70 mg of alendronate once weekly , and the control group received placebo ( 9 ) . both groups were prescribed standard off - loading methods . while these researchers found significant reductions in hydroxyproline and serum c - terminal telopeptide of type 1 collagen ( ictp ) , markers of bone turnover , they did not report differences in the resolution of clinical symptoms . they did , however , demonstrate a reduction in the serum levels of insulin - like growth factor 1 ( igf-1 ) in the treatment group . this finding prompted the same group of researchers to study the relationship between igf-1 , neuropathy , inflammation , and the rankl system ( 10 ) . bisphosphonates may decrease igf-1 and help regulate rankl , but their clinical efficacy remains to be proven . how is the expression of rankl increased in patients with cn ? aside from the supposition that inflammation itself induces rankl , there is research that supports a lack of negative - feedback mechanisms in patients with diabetes . peripheral and autonomic neuropathy can minimize the release of the neuropeptide calcitonin gene - related peptide ( cgrp ) , which antagonizes the expression of rankl . associated with blood vessels , cgrp is produced in the hypothalamus and found in the periosteum and bone marrow . experiments utilizing fractures in rat femora demonstrated that cgrp increases at the site of the fracture gap , suggesting that neuropeptides play an active role in bone remodeling ( 12 ) . with a lack of cgrp la fontaine and colleagues substantiated the cgrp hypothesis with their study in 2008 ( 13 ) . they performed immunohistological studies in bone samples of three groups : diabetic patients without neuropathy , diabetic patients with neuropathy , and diabetic patients with stage 2 or 3 cn . samples of bone were collected during reconstructive operations , and patients with history of ulceration , osteomyelitis , or end - stage renal disease were excluded . they found a trend toward significance in comparing cgrp expression , with the charcot group having the least amount of cgrp . additionally , these researchers looked at the relative amounts of endothelial nitric oxide synthase ( enos ) , an isoenzyme that regulates nitric oxide production . immunohistochemical studies found a statistically significant decrease in enos in the charcot bone compared with the other two groups ( p = 0.008 ) ; thus , lack of enos is another breakdown in the negative - feedback mechanisms that are normally in place for osteoclast modulation and proliferation . another mechanism by which rankl , and thus osteoclast function , is increased is by accumulation of advanced glycation end products ( ages ) . the formation of ages is driven by hyperglycemia and primarily affects collagen in tissues with the slowest turnover , such as cortical bone ( 14 ) . ages have been found to increase rankl activation as well as induce osteoblast apoptosis ( 15 ) . in patients with diabetes , there is increased formation of ages but a lack of a receptor for ages ( rage ) . witzke and colleagues designed a cross - sectional study in which they enrolled 80 male subjects : 30 healthy controls , 30 diabetic patients without charcot , and 20 diabetic patients with stage-2 cn ( 14 ) . they found a significant reduction in calcaneal stiffness in the patients with cn ( p < 0.01 ) . in all subjects , there was a positive correlation between calcaneal bone stiffness and rage concentration , indicating that rage is protective against osteoclastic resorption . cn patients had rage values that were 86% lower than control subjects and 50% lower than diabetics without cn ( p < 0.05 ) . in addition , these researchers found an elevated level of osteocalcin , a marker of bone turnover , in cn patients . in summary , there was a linear relationship between impaired age defense ( lack of rage ) , increased bone turnover , and reduced bone stiffness . this study suggests compelling evidence that drugs that increase rage levels , such as ace - inhibitors , statins , and glitazones , may be useful in preventing or suppressing cn . with an increasing prevalence of diabetes , there will be a rising incidence of cn , along with a higher rate of the associated devastating foot and ankle complications . the exact pathogenesis of cn remains elusive ; however , it is known that sensory and autonomic neuropathy are prerequisite to begin the process of uncontrolled inflammation through proinflammatory cytokines tnf - alpha and interleukins , unchecked activation of rankl , and the resulting imbalance of osteoclasts and osteoblasts ( 16 ) . elevated glucose levels form ages , and the lack of rage leads to an increase in rankl . these mechanisms that have been implicated in the pathogenesis of cn are the targets of therapeutic agents , including bisphosphonates , anti - tnf therapy , ace - inhibitors , statins , and glitazones . the authors have received no funding or benefits from industry to conduct this literature review .

the pathogenesis of charcot neuroarthropathy ( cn ) has been poorly understood by clinicians and scientists alike . current researchers have made progress toward understanding the cause of cn and possible treatment options . the authors review the current literature on the pathogenesis of this debilitating disorder and attempt to explain the roles of inflammation , bone metabolism , and advanced glycation end products .

thus , vision loss is a major medical , economic , safety , and social issue affecting millions of persons worldwide . neurodegenerative diseases of the retina involve progressive and irreversible loss of retinal neurons , their connections and supporting glia , thereby leading to impaired visual function . major neurodegenerative eye diseases include glaucoma and age - related macular degeneration . despite being major causes of disability , limited effective therapeutic methods for treating these neurodegenerative eye diseases exist which , at best , slow down the neurodegenerative progression . until now , no therapeutic option has been proven to successfully reverse or cure vision loss from these neurodegenerative eye diseases , especially glaucoma . although glaucoma is a group of aetiologically heterogeneous optic neuropathies , all glaucomas are associated with dysfunction and the eventual death of retinal ganglion cells ( rgcs ) , resulting in degeneration of optic nerve and ultimately loss of vision . therefore , preserving the rgcs and the optic nerve , both structurally and functionally , is vital for the treatment and possible cure of glaucoma and other neurodegenerative eye diseases . however , similar to other central nervous system ( cns ) tracts in mammals , the injured optic nerve has very limited regenerative capacity due to the weak intrinsic capacity of adult neurons to reactivate a growth program after injury and the presence of an inhibitory neuronal tissue environment in the adult cns . in order to slow the progressive decline in visual function caused by neurodegenerative eye diseases or even restore vision function , a lot of effort has been devoted toward three major avenues of engagement : cell based therapy , neuro - regeneration and neuro - rejuvenation , which will be discussed in detail later . a better understanding of these approaches will provide insight into the cure of neurodegenerative eye diseases and bring hope to those patients who suffer from vision loss . three general approaches have been commonly suggested to overcome the barrier of neuronal repair in the ocular system ( figure 1 ) . one approach involves introducing stem cells into the degenerating retina to replace dead neuronal cells . alternatively , the retinal neuronal growth program might be stimulated in adult neurons , allowing them to overcome the inhibitory environment and grow new dendrites and axon often termed neuro - regeneration . and last , we propose what we believe to be the most promising and practical approach : enhancing the function of existing rgcs with established visual neuropathways which we term neuro - rejuvenation stem cell therapies function as paracrine - mediated treatments with trophic factors ( black symbols ) secreted from transplanted cells ( blue cells ) protecting injured retinal ganglion cells ( rgc , red cells ) . however , most of injected cells remain in the vitreous cavity and do not or poorly integrate into existing neuronal circuits . neuro - regeneration involves stimulating intrinsic growth programs in adult neurons to overcome inhibitory environmental cues in the cns . the injured optic nerve can be stimulated to produce new axonal fibers which migrate incorrectly toward the retina and toward wrong targets . the green newly formed axon ends in an ipsilateral tract which is supposed to join the contralateral tract ( solid green dots ) . neuro - rejuvenation enhances the function of existing rgcs with established neuropathways by stimulating the creation of super rgcs . increased neuronal activity and communication among the existing rgcs can enhance signal to noise ratios and retinal ganglion cell function and neuronal survival . most current ocular cell transplantation treatments function as paracrine - mediated therapies in which retinal cell - derived trophic factors protect injured endogenous retinal neurons ( i.e. , retinal pigmented epithelium cell transplantation ; figure 1 ) . however , a successful stem cell treatment for neurodegenerative eye diseases must include not only the replacement of degenerated neurons , but also the correct restoration of neural circuits in a one - to - one correspondence . one major hindrance to successful retinal stem cell transplantation is that differentiation of stem cells into retinal neurons from transplanted stem cells has not been widely achieved in vivo , much less restoring a correct neural circuity . for example , rgc cell death protection and neurite growth , induced by bone mesenchymal stem cells ( bmscs ) , were reported to be mediated by platelet - derived growth factor ( pdgf ) , nerve growth factor ( ngf ) , brain - derived neurotrophic factor ( bdnf ) and neurotrophin-3 ( nt-3 ) ( mead et al . transplantation of bmscs into the vitreous cavity after optic nerve transection demonstrated no evidence of their differentiation into mature retinal neurons and bmscs remained static in the vitreous instead of integrating into the rgc layer . transplanted cells that do not integrate into the retina can not communicate with existing neural circuits and have only relatively short lifespans without cell to cell contact or cellular adherence . thus , the beneficial effect of transplanted stem cells is unlikely to be long lasting , if any . embryonic stem cells ( escs ) , which can successfully express mature rgc markers after intravitreal injection into n - methyl - d - aspartic acid ( nmda ) damaged retinas ( aoki et al . , 2008 ) , are also potential candidates for stem cell therapy . however , only a small percentage of transplanted escs appear to integrate into the rgc layer . most escs appear to form abnormal structures , including teratomas and multi - rgc layers , and no visual evoked potentials ( veps ) were detected in nmda - exposed animals after escs transplantation treatment suggesting transplanted escs are few or unable to produce any electrical signals upon intravitreal injection . in addition , transplanting escs are not equivalent to transplanting differentiated adult retinal cells for cellular transplantation and replacement . aside from the physical barriers of transplanting retinal cells , a major and critical challenge that needs to be addressed with stem cell therapy is the altered retinal system caused by the degenerative neuronal disease ( cuenca et al . , changes to the resting state of the damaged retina may exist , which would affect the function of transplanted cells and the existing cells . for example , the ocular system has immune privilege which can be compromised in disease states . an important aspect of cellular transplantation into the eye that needs to be taken into serious consideration is the possibility of immune rejection and the development of sight threatening uveitis . transplanted stem cells may also differentiate into unpredictable phenotypes under disease states , unlike phenotypes characterized in vitro , and may express abnormal cytokine profiles when surrounded by different retinal cell types unlike the uniform cell types observed in vitro under laboratory and non - physiological conditions . also , uncontrolled cell growth and migration within the cns neuropil and possible oncogenesis ( due to the loss of normal growth and regulatory pathways in stem cells ) possible challenges for stem cell therapy the protection and/or restoration of vision loss in neurodegenerative eye diseases . the injured optic nerve , in glaucoma patients for example , can not intrinsically regenerate ( quigley , 1999 ) . the lack of adequate stimulation and growth responses by adult neurons to overcome inhibitory molecules in the cns tissue are the important impediments to axonal regrowth . overstimulating the retinal growth program may overcome this barrier and alleviate the decline toward retinal cell death signals . two key pathways have been identified to be able to promote significant axonal growth in vivo . upregulation of ciliary neurotrophic factor ( cntf ) or activation of downstream signal transducer and activator of transcription 3 ( stat3 ) in adult rgcs after injury was sufficient to promote robust axonal regeneration in vivo ( muller et al . , 2007 ; pernet et al . , 2013b ) . both molecular approaches elicited long - distance growth of injured optic nerves , near or up to the optic chiasm . the effect of upregulated cntf can be further enhanced by the elevation of cyclic amp ( camp ) ( cui et al . , 2003 ) . deletion of the suppressor of cytokine signaling ( socs)3 , which is involved in the negative feedback loop of stat3 activation , was also able to achieve comparable extent of axonal growth ( smith et al . mammalian target of rapamycin ( mtor ) is a central regulator of growth in all cell types . deletion of two upstream repressors - phosphatase and tensin homolog ( pten ) and tuberous sclerosis ( tsc)1/2 - selectively in retinal ganglion cells after optic nerve crush strongly stimulated axonal regeneration up to 4 mm ( park et al . synergistic treatment that inducing controlled inflammatory response in the eye , when combined with elevation of intracellular camp and deletion of the gene encoding pten enabled rgcs to regenerate axons to the full length of the optic nerve in mature mice ; even a rare subset of axons managed to enter the brain ( kurimoto et al . however , under such high level of local growth stimulation , massive axonal sprouts formed and grew randomly in a dense plexus that covered the inner surface of the retina and blood vessels ( pernet et al . , 2013a ) . unfortunately , an unexpected regeneration pattern was also observed in the injured optic nerve : the return of many new fibers toward the retina and pronounced axonal misrouting at the optic chiasm ( figure 1 ) . in the stat3 group , 40% of axons showed u - turns , and this was also observed in co - activation of mtor and stat3 ( pernet et al . more than half of all fibers joined the ipsilateral tract in the pten and socs3 double - knock out mice , whereas the percentage should be lower than 5% in normal mice ( luo et al . , 2013 ) . vision function recovery requires re - innervation of the correct corresponding region in the occipital cortex by the appropriate types of retinal axons . even if some of the few regenerated fibers extended beyond the chiasm and terminated in the vicinity of the closest target , it is still doubtful that they will reach the correct target ( luo et al . , 2013 ) ( figure 1 ) . vision would be much worse if connections are made to a wrong target and present a false image similar to cell phones with the wrong ip addresses communicating with the wrong cell towers . compared to the other two approaches for restoring vision , neuro - rejuvenation is the most practical and most accessible approach to preserve and enhance vision by taking advantage of existing neuronal connections to produce an enhanced true image , protect retinal ganglion cells through elevated intrinsic activity which enhances signal to noise ratios , and enhance retinal ganglion cell function ( figure 1 ) . instead of focusing on rescuing dying retinal neurons or replacing them with transplanted neurons , the existing dysfunctional and healthy neurons and neuronal networks are the main therapeutic target . one major technical barrier to neuronal transplantation is the lack of the correct neuronal circuitry through each of the relays ( i.e. , superior colliculus , lateral geniculate nucleus , occipital cortex ) , to produce a real image versus many bright spots that do not correspond to an image , but only to the location of the transplanted cells assuming they can even make connections as far as the optic chiasm . neuro - rejuvenation is based upon the concept that electrical activity is essential for neuronal survival and axonal growth . trans - corneal electrical stimulation ( tes ) promotes both axonal regeneration and survival of rgcs after optic nerve crush ( tagami et al . , 2009 ) . axon regeneration mediated by insulin - like growth factor ( igf-1 ) receptors can be blocked by igf-1 receptor antagonists . furthermore , visual evoked potential ( vep ) amplitudes impaired by optic nerve crush can be increased by tes stimulation , indicating functional visual recovery ( miyake et al . , 2007 ) . however , compared to traditional electrical stimulation which causes unintended side effects or even may be detrimental to neighboring cells , optogenetic stimulation has significant advantages , such as cell - specific targeting and excellent spatiotemporal resolution reaching millisecond - timescales of activation . optogenetics combines the use of genetic and optical techniques to modulate activity in targeted cells or tissues . by genetically introducing wavelength - specific modular light - gated ion channels and pumps to targeted neurons , optogenetics offers a noninvasive method of excitation and suppression in existing correctly neuronally linked excitable cells and tissues in vivo . recently , different groups have achieved neuronal protection and axonal regeneration by optogenetic stimulation under various conditions , which offers a promising and practical approach to protect vision loss in neurodegenerative eye diseases , not through cell replacement , but by enhancing the function of existing neuronal cells . subcellular calcium release by ryanodine receptor ( ryr ) is required for neuronal regeneration in c. elegans and this can be enhanced by optogenetic stimulation ( sun et al . , 2014 ) . damaged neurons were depolarized by the activation of channelrhodopsin-2 ( chr2 ) , resulting in calcium influx via l - type voltage gated calcium channels ( vgccs ) . the increased calcium flux triggered additional calcium concentration elevation from the endoplasmic reticulum via ryr channels , effectively amplifying the innate calcium signal to enhance axonal regeneration . optogenetic stimulation has also been shown to successfully promote nerve growth in dorsal root ganglion ( drg ) cell cultures , which is attributed to the increased secretion of ngf and bdnf ( park et al . , 2015 ) . this was verified by the directional bias in the outgrowth of wild - type drgs in the presence of stimulated chr2-drgs . recently , optically - induced neuronal activity has been demonstrated to sufficiently promote functional motor axon regeneration in vivo . thy1-chr2-yfp transgenic mice , in which a subset of motor neurons expresses chr2 , received blue light stimulation immediately prior to transection and surgical repair of the sciatic nerve . compared to animals without blue light stimulation , mice that received optogenetic stimulation had significantly more chr2 + axons successfully re - innervated , more reformation of neuromuscular junctions , more moto - neurons that can be retrograde labeled by cholera toxin subunit b , and restored evoked muscle electromyography ( emg ) activity ( m responses ) one month after injury to the gastrocnemius muscle ( ward et al . , 2016 ) . novel therapeutic approaches to neurodegenerative eye diseases , which cause serious medical , economic and social issues , are very much needed . thus , far , the three treatment strategies are stem cell transplantation , neuro - regeneration and neuro - rejuvenation , which have all attracted much attention . compared to stem cell therapy , in which transplanted cells have uncertain cell fates and a challenging integration into neuronal circuits , and neuro - regeneration , which faces challenges of reaching the correct neuronal destinations , neuro - rejuvenation provides us with a more promising and practical approach by taking advantage of existing rgcs and neuronal networks . instead of introducing new cells into the retina or stimulating those dying retinal neurons , neuro - rejuvenation focuses on existing cells , by enhancing their intrinsic functional capacity , allowing existing neuronal cells to aid their sick partners , and strengthening existing connections to increase existing signal - to - noise ratios . a deeper understanding of neuro - rejuvenation will shed light on the treatment of neurodegenerative eye diseases and bring hope to those patients who suffer from vision loss .

neurodegenerative eye diseases , such as glaucoma , cause irreversible vision loss in millions of patients worldwide , creating serious medical , economic and social issues . like other mammalian central nervous system tracts , optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non - permissive to regeneration . any axonal damage also triggers a vicious cycle of retinal ganglion cell ( rgc ) death . exploring methods that can enhance rgcs survival and promote axonal regeneration will not only enable vision restoration for millions of patients , but also shed light on the treatment of other neurodegenerative diseases . in this review article , we will go through three current approaches to cure neurodegenerative eye diseases , including cell based therapy , neuro - regeneration and neuro - rejuvenation .

the klippel - trenaunay syndrome is a rare mesodermal abnormality characterized by a triad of vascular nevus , varicose veins , and soft tissue and bony hypertrophy of limb.1 ) klippel - trenaunay syndrome can be diagnosed on the basis of any two of these three features.2 ) clinical presentation of klippel - trenaunay syndrome has wide spectrum from asymptomatic state to potentially life - threatening complications , such as hypercoagulability , deep vein thrombosis and pulmonary thromboembolism ( pte).1 ) the hypercoagulability may be attributed to stagnation of blood within the disordered , enlarged venous blood vessels , which can lead to the continuous formation of thrombi , resulting in recurrent pte.1 ) venous thromboembolism has been reported to occur in 8 - 22% of klippel - trenaunay syndrome patient population.3 ) over 30 cases on klippel - trenaunay syndrome - associated pte have been reported.3)45)6)7)8 ) also , compromised vascular integrity increases risk of thrombus formation of the cerebral aneurysm and stroke in patients with klippel - trenaunay syndrome.9 ) here , we report a rare case of klippel - trenaunay syndrome with unruptured basilar tip aneurysm , complicated by acute submassive pte treated successfully with intravenous thrombolytic therapy . a 48-year - old female presented to the emergency department in our hospital with complaints of severe dyspnea ( new york heart association iii - vi functional class ) and anterior chest discomfort of two days duration . she had a history of hypertension and took amlodipine besylate 5 mg and atenolol 50 mg daily for antihypertensive medication . twenty days prior to visit , she had complained of visual impairment and had been diagnosed with compressive optic neuropathy associated with unruptured basilar tip small aneurysm with a diameter of 6 mm detected by enhanced computed tomography ( ct ) scan of the brain ( fig . she had refused further management for the aneurysm . on this arrival to emergency department , the patient 's blood pressure was 147/94 mm hg , heart rate was 70 beats / min , respiratory rate was 28 breaths / min , and temperature was 36.4. the room air oxygen saturation was 88% . physical examination revealed large varicose veins on the lateral aspect of right lower limb and hypertrophy of left big toe ( fig . 2 ) . she reported that these varicose veins had been first noticed in early infancy . a diagnosis of klippel - trenaunay syndrome was made on the basis of the history and physical examination result . an electrocardiogram demonstrated diffuse t wave inversions in the precordial leads with s1q3t3 pattern ( fig . 3 ) . laboratory investigations revealed d - dimer level 8.94 g / ml ( reference range : 0 - 0.5 g / ml ) ; n - terminal prohormone of brain natriuretic peptide , 7376 pg / ml ( 0 - 125 pg / ml ) ; troponin i , 0.12 ng / ml ( 0 - 1.0 ng / ml ) ; creatine kinase - myocardial band , 2.0 ng / ml ( 0 - 4.9 ng / ml ) ; myoglobin , 23.9 ng / ml ( 0 - 107 ng / ml ) ; and high - sensitivity c - reactive protein ( crp ) , 15.4 mg / l ( 0 - 8.0 mg / l ) . arterial blood gas analysis at an inspired oxygen fraction of 0.5 results were as follows : ph 7.47 ; partial pressure of co2 , 36.0 mm hg ; partial pressure of o2 , 55.2 mm hg ; plasma bicarbonate concentration , 25.6 mmol / l ; and o2 saturation , 89.7% . bedside transthoracic echocardiography ( tte ) revealed flattening of the interventricular septum [ d - shaped left ventricle ( lv ) ] and severely dilated right ventricle ( rv ) with poor systolic function ( tricuspid annular plane systolic excursion = 8 mm & rv fractional area change = 24.1% ) and severe pulmonary hypertension ( estimated pulmonary artery systolic pressure = 112 mm hg ) . the rv apex was hyperkinetic and the free wall segment was akinetic , a finding consistent with mcconnell 's sign ( fig . 4 ) . acute pte was highly suspected and enhanced ct scan of the chest confirmed thromboemboli of the both main pulmonary artery branches ( fig . 5 ) . with a diagnosis of acute submassive pte with intermediate - high risk category in klippel - trenaunay syndrome , she was admitted in intensive care unit for close monitoring and detection of haemodynamic decompensation and anticoagulation with low molecular weight heparin ( enoxaparin ) was immediately administered . one day after admission , she became progressively more tachypneic , hypoxemic and systolic blood pressure ( sbp ) dropped to 90 mm hg from 140 mm hg despite of heparin therapy . the vital signs were the following : blood pressure was 90/60 mm hg , heart rate was 80 beats / min , respiratory rate was 31 breaths / min . although she had an unruptured cerebral aneurysm , rescue reperfusion therapy was determined to be performed and she received intravenous thrombolytic therapy with tissue plasminogen activator ( tenecteplase ) , which brought rapid improvement of oxygenation and shortness of breath and normalization of blood pressure . on the fourth day after thrombolysis , repeated tte showed significant improvement of the rv function ( fig . venous doppler studies and enhanced ct venography of the lower extremity performed on the third day after thrombolysis did not reveal evidence of deep venous thrombosis . additional investigation of inherited thrombophilias did not reveal underlying prothrombotic abnormalities of the coagulation system ( antithrombin iii , protein c and s , antibodies for lupus anticoagulants and antiphospholipid ) . she continued to improve clinically and was discharged home on oral warfarin therapy after 15-day hospital course of treatment . follow - up enhanced ct scan of the chest obtained 2 month after discharge revealed complete resolution of thrombi of pulmonary arteries ( fig . a follow - up tte obtained 2 years after discharge demonstrated normal dimension and systolic function of rv and disappearance of the d - shaped lv with complete resolution of mcconnell 's sign and mild pulmonary hypertension ( estimated pulmonary systolic pressure = 50 mm hg ) ( fig . 4 ) . considering high risk of recurrent pte , she continued indefinite oral anticoagulation with compression stockings and was asymptomatic during the 3-year follow - up after that episode without any evidence of recurrent pte or bleeding complications . here we report a rare case of klippel - trenaunay syndrome with classic triads of vascular nevus , varicose veins and soft tissue hypertrophy . the patient developed acute submassive pte and was treated successfully with thrombolytic and anticoagulation therapy . although a few cases of klippel - trenaunay syndrome complicated with pseudo - kaposi 's sarcoma,10 ) bladder hemangioma,11 ) sigmoid varix,12 ) lymphangioma circumscriptum13 ) have reported in korea , case of klippel - trenaunay syndrome complicated with acute thromboembolism has not been reported to date and to the best of our knowledge , this is the first reported case in korea . peculiarly , intracranial aneurysm is very rare in klippel - trenaunay syndrome with only several cases published to date.9 ) this case illustrates the importance of careful history taking and detailed clinical examination for clue to the underlying cause and the diagnosis of pte which is often incorrectly diagnosed leading to high morbidity and mortality . although varicose veins and soft tissue hypertrophy are very bizarre findings , these can be missed if careful history and physical examination are not taken . the venous stasis in vascular malformations of lower limbs in klippel - trenaunay syndrome increases the chance of thrombus formation and pte.1)4 ) due to the continuous formation of thrombi , recurrent thromboembolic complications are common in klippel - trenaunay syndrome patients and lifelong anticoagulation therapy should be considered in the case of a first deep vein thrombosis or pte.1)5 ) this case demonstrated echocardiographic evidence of rv dysfunction , that is , submassive pte . the decision to administer a thrombolytic agent in addition to heparin anticoagulation in patients with submassive pte requires individualized assessment of the balance of benefits versus risk.14 ) current guidelines recommend risk - adjusted management strategies in acute pte and anticoagulation is initially recommended in patients with intermediate - high risk category ( right ventricular dysfunction detected on echocardiography and elevated n - terminal prohormone of brain natriuretic peptide level as our case ) and close monitoring is recommended in these cases to permit early detection of hemodynamic decompensation and the need for initiation of rescue reperfusion therapy.15 ) the definition of hemodynamic decompensation is 1 ) need for cpr , 2 ) sbp < 90 mm hg for 15 minutes , 3 ) drop in sbp by 40 mm hg for 15 minutes with findings of end organ hypoperfusion ( as our case ) , or 4 ) need for catecholamines to maintain organ perfusion and sbp > 90 mm hg , including dopamine infused at > 5 mcg / kg / min.16 ) therefore , we thought that our case became hemodynamically decompensated and she needed initiation of rescue thrombolytic therapy . although this case had unruptured basilar tip aneurysms , there is no evidence of an increased risk of intracranial hemorrhage in patients with pre - existing unruptured cerebral aneurysms who are given thrombolytic therapy.17)18 ) thrombolytic therapy was safely administered to our patient , which demonstrated significant clinical improvement without any major bleeding events . although the patient was regularly followed - up with oral anticoagulation ( in optimal international normalized ratio range ) and remained asymptomatic after discharge , mild pulmonary hypertension still persisted on follow - up echocardiogram performed two years after thrombolytic therapy . the possibility of chronic thromboembolic pulmonary hypertension ( cteph ) , a rare long - term complication after pte , must be considered for the cause of pulmonary hypertension . the reported cumulative incidence of cteph was 0.1 - 9.1% within the first two years after a symptomatic pte event.15 ) recurrent thromboembolic complications are also common in klippel - trenaunay syndrome patients despite anticoagulation.1 ) ventilation - perfusion lung scanning may be used to differentiate cteph from other causes of pulmonary hypertension.15 ) chest ct scan is used widely for diagnosis of cteph.15 ) in conclusion , the present case demonstrated a rare and first reported case of klippel - trenaunay syndrome with unruptured intracranial aneurysm complicated with acute submassive pte treated successfully with thrombolytic and anticoagulation therapy . physicians should be aware of this potentially life - threatening existence and pay particular attention to the physical findings to make the correct diagnosis .

klippel - trenaunay syndrome is a rare congenital mesodermal abnormality characterized by varicose veins , cutaneous hemangiomas , soft tissue and bony hypertrophy of limb . potential complications such as deep venous thrombosis and pulmonary thromboembolism have not been reported in korea to date . we demonstrate the case of a 48-year - old woman with klippel - trenaunay syndrome with extensive varicose veins on right lower limb , hypertrophy of left big toe and basilar artery tip aneurysm , complicated with acute submassive pulmonary thromboembolism treated successfully with intravenous thrombolytic therapy .

deep cerebral venous thrombosis is an uncommon but often fatal disease , which can result in possible stroke , coma , and local neuropathies , with a mortality rate of 8 - 14%.1)6 ) however , most patients , exhibit mild symptoms , such as headache or papilledema due to increased intracranial pressure.4 ) of these phenomena , occurrence of the deep cerebral venous thrombosis is more uncommon.1,4 ) the lesions of deep venous origin tend to be bilateral , and spread to the adjacent basal ganglia and other white matter regions from both sides of the thalamus.2)3 ) thus , cases involving unilateral deep venous thrombosis at the thalamus are rarely reported.7)12 ) this study reports on a case in which a unilateral thrombosis at the internal cerebral vein caused reversible changes of an edema in the unilateral thalamus region . a 36-year - old female patient presented with dysarthria and right - sided hemiparesis . the patient had suffered a spell of nausea , vomiting , and headache two years before admission . findings on brain computed tomography ( ct ) , and a cerebrospinal fluid ( csf ) examination during the time showed no abnormal findings . the same symptoms recurred one week before admission , however , brain magnetic resonance imaging ( mri ) showed no abnormal findings ( fig . one week later , she was admitted again due to newly - developed dysarthria and hemiparesis of her right side . a t2 fluid attenuated inversion recovery ( flair ) imaging study of brain mri at this time showed left thalamic high signal intensity , suggesting edema ( fig . an mri susceptibility weighted image ( swi ) showed occlusions of the left internal cerebral vein and thalamostriate vein due to the thrombosis ( fig . digital subtraction angiography ( dsa ) revealed a venous occlusion of the left internal cerebral vein and thalamostriate vein ( fig . 1d ) . low molecular weight heparin ( lmwh ) was administered subcutaneously 60 mg twice per day for one week without replacing lmwh to warfarin , and the dysarthria and right hemiparesis subsided completely . findings on ct angiography one week after symptom onset revealed the left internal cerebral vein and the thalamostriate vein had regained normal blood flow ( fig . the headache subsided over a period of several months , and a t2 flair image of the brain mri taken two months after the initial symptoms showed disappearance of pre - existing edema of the thalamus . thrombosis of the cerebral veins is an uncommon disease , which arises from various causes , including infection , connective tissue disease , anemia , inflammatory bowel diseases , and trauma.11 ) women are afflicted three times more often than men.6 ) cerebral vein thrombosis often affects young pregnant or puerperal women , and those who are taking oral contraceptives or have coagulopathic disorders.1 ) when a superficial cerebral vein thrombosis occurs , the thrombosis shows slow progression , and the majority of patients complain of headache . symptoms can also appear suddenly , and can be mistaken for subarachnoid hemorrhage.5 ) as for cardiac arrhythmial thrombosis , it tends to occur in the bilateral thalamic region , and may result in delirium , amnesia , and mutism.9 ) cerebral vein thrombosis arises from either of two mechanisms , one being an ischemic nerve injury following venous edema caused by a thrombosis , and the other being an intracranial hypertension due to the decrease of csf absorption following a venous occlusion.14 ) in our patient , nausea and headache were followed by dysarthria and unilateral nerve palsy . the cause of nausea and headache appeared to be intracranial hypertension and neurologic deficit appeared to be ischemic nerve injury due to venous edema . due to its non - specific symptoms , cerebral vein thrombosis can be easily over - looked . because venous paths do not match with arterial paths , venous infarctions can not be easily localized with symptoms . thus , suspicion of cerebral vein thrombosis in high - risk patients is very important , and adequate radiologic study is needed.13 ) a diagnosis can be made with an abnormal signal on mri , and confirmation of loss of blood flow on mra.8 ) as for a thrombosis on the internal cerebral vein , the thalamus is bilaterally affected , causing vascular edema of parenchyma , which can induce hemorrhage or infarction . a vascular edema or infarction is hyperintense upon t2 of the mri , and hypointense upon t1 imaging . a thrombosis at a deep cerebral vein , like our patient 's finding , showed hyperintensity on t2 flair , and a loss of flow signal intensity through an swi.2)3 ) based on these radiological findings , our patient was confirmed as having a thrombosis of the left internal cerebral vein and left thalamic edema . other than the mri , a cerebral angiography , which can show a more precise vascular stature , can also be utilized . we were able to confirm the accurate location of the thrombosis of our patient using the mri and dsa . when the patient 's neurologic status suggests imminent brain herniation , emergency treatment is needed . intravenous mannitol and sometimes decompressive craniotomy may be required.15 ) other than immediate treatment for acute exacerbation , the general antithrombotic treatment using heparin is used for reperfusion of a thrombotic occluded vein or sinus . as reported by pfefferkorn et al . , of 32 patients with deep cerebral vein thrombosis , all patients were treated with dose - adjusted intravenous heparin ( activated partial thromboplastin time ( aptt ) 60 - 100 sec ) or lmwh . eight patients ( 25% ) showed rapid deterioration to coma over a period of 6 - 48 hours.10 ) our patient received subcutaneous administration of 60 mg of lmwh twice per day without replacing lmwh to warfarin , and neurological symptoms showed improvement . urokinase or endovascular thrombolysis can also be considered for patients who show no improvement with this conventional treatment.10 ) the outcome of deep cerebral vein thrombosis varies greatly , from complete recovery to death . as for our patient , compared to superficial cerebral venous thrombosis , deep cerebral venous thrombosis has a higher tendency to leave permanent neurologic symptoms and to show more rapid progression.3 ) prognosis of unilateral deep cerebral vein thrombosis is better than that of bilateral thrombosis . according to one report thrombosis of the cerebral veins is an uncommon disease , which arises from various causes , including infection , connective tissue disease , anemia , inflammatory bowel diseases , and trauma.11 ) women are afflicted three times more often than men.6 ) cerebral vein thrombosis often affects young pregnant or puerperal women , and those who are taking oral contraceptives or have coagulopathic disorders.1 ) when a superficial cerebral vein thrombosis occurs , the thrombosis shows slow progression , and the majority of patients complain of headache . symptoms can also appear suddenly , and can be mistaken for subarachnoid hemorrhage.5 ) as for cardiac arrhythmial thrombosis , it tends to occur in the bilateral thalamic region , and may result in delirium , amnesia , and mutism.9 ) cerebral vein thrombosis arises from either of two mechanisms , one being an ischemic nerve injury following venous edema caused by a thrombosis , and the other being an intracranial hypertension due to the decrease of csf absorption following a venous occlusion.14 ) in our patient , nausea and headache were followed by dysarthria and unilateral nerve palsy . the cause of nausea and headache appeared to be intracranial hypertension and neurologic deficit appeared to be ischemic nerve injury due to venous edema . due to its non - specific symptoms , cerebral vein thrombosis can be easily over - looked . because venous paths do not match with arterial paths , venous infarctions can not be easily localized with symptoms . thus , suspicion of cerebral vein thrombosis in high - risk patients is very important , and adequate radiologic study is needed.13 ) a diagnosis can be made with an abnormal signal on mri , and confirmation of loss of blood flow on mra.8 ) as for a thrombosis on the internal cerebral vein , the thalamus is bilaterally affected , causing vascular edema of parenchyma , which can induce hemorrhage or infarction . a vascular edema or infarction is hyperintense upon t2 of the mri , and hypointense upon t1 imaging . a thrombosis at a deep cerebral vein , like our patient 's finding , showed hyperintensity on t2 flair , and a loss of flow signal intensity through an swi.2)3 ) based on these radiological findings , our patient was confirmed as having a thrombosis of the left internal cerebral vein and left thalamic edema . other than the mri , a cerebral angiography , which can show a more precise vascular stature , can also be utilized . we were able to confirm the accurate location of the thrombosis of our patient using the mri and dsa . when the patient 's neurologic status suggests imminent brain herniation , emergency treatment is needed . intravenous mannitol and sometimes decompressive craniotomy may be required.15 ) other than immediate treatment for acute exacerbation , the general antithrombotic treatment using heparin is used for reperfusion of a thrombotic occluded vein or sinus . as reported by pfefferkorn et al . , of 32 patients with deep cerebral vein thrombosis , all patients were treated with dose - adjusted intravenous heparin ( activated partial thromboplastin time ( aptt ) 60 - 100 sec ) or lmwh . eight patients ( 25% ) showed rapid deterioration to coma over a period of 6 - 48 hours.10 ) our patient received subcutaneous administration of 60 mg of lmwh twice per day without replacing lmwh to warfarin , and neurological symptoms showed improvement . urokinase or endovascular thrombolysis can also be considered for patients who show no improvement with this conventional treatment.10 ) the outcome of deep cerebral vein thrombosis varies greatly , from complete recovery to death . as for our patient , neurological symptoms disappeared completely after treatment , and previous lesions were no longer seen . compared to superficial cerebral venous thrombosis , deep cerebral venous thrombosis has a higher tendency to leave permanent neurologic symptoms and to show more rapid progression.3 ) prognosis of unilateral deep cerebral vein thrombosis is better than that of bilateral thrombosis . according to one report , a patient with a unilateral thrombosis showed complete recovery from neurologic symptoms.7)12 ) due to its lack of specific symptoms , unilateral deep cerebral vein thrombosis is an uncommon disease that can be misdiagnosed . , due to the fact a unilateral lesion shows better prognosis than a bilateral one , a quick diagnosis and treatment are needed . due to the small volume of patients in previously reported studies , more research into the pathology and natural course of a unilateral deep cerebral vein thrombosis through treatment of more patients

symptoms of deep cerebral vein thrombosis ( dcvt ) are variable and nonspecific . radiologic findings are essential for the diagnoses . in the majority of cases of deep internal cerebral venous thrombosis , the thalamus is affected bilaterally , and venous hypertension by thrombosis causes parenchymal edema or venous infarction and may sometimes cause venous hemorrhage . intravenous injections of mannitol can be administered or decompressive craniectomy can be performed for reduction of intracranial pressure . the objectives of antithrombotic treatment in dcvt include recanalization of the sinus or vein , and prevention of propagation of the thrombus . herein , the authors report dcvt which was successfully treated by low molecular weight heparin .

the use of adrenocorticotrophic hormone ( acth ) has been established since the 1950s and 1960s and was widely used in the treatment of childhood nephrosis . acth was attractive in this group due to reduced growth stunting due to less adrenal suppression than traditional exogenous steroids . the use of synthetic acth has declined in recent decades , due to the injectable route of administration and the emergence of oral steroids preparations such as prednisolone which are cheap , and widely available . novel therapy due to an incidental finding by swedish researchers , berg et al . in their research into the lipid - lowering effects of acth in 14 patients with idiopathic membranous nephropathy ( mn ) . this finding was surprising as steroid monotherapy was shown to have no role in the treatment of idiopathic mn [ 3 , 4 ] . a treatment regime of slow - release acth was given in the form of synacthen depot at a maximal dose of 1 mg twice weekly for 211 months . they proceeded to administer this to an uncontrolled case series of 23 patients with nephrosis due to a variety of diagnoses . all patients had a significant response to therapy . a randomized pilot trial carried out by ponticelli et al . directly compared the use of methylprednisolone plus a cytotoxic agent versus synthetic acth in idiopathic mn . they used primary outcome measure as cumulative number of remissions as a first event and concluded that most patients with idiopathic mn responded to either treatment , and that there was a significant decrease in proteinuria with both treatments , without either being more effective . a further retrospective study in the united states evaluated the initial use of acth gel in 21 patients with nephrotic syndrome of different histopathologies . they found that 11 of 21 patients achieved either complete or partial remission with at least 6 months of follow - up . while these data are encouraging , caution must be taken in interpretation of the data due to the limitations of observational studies . hp acthar gel is a proprietary mixture isolated from porcine pituitary extracts , the main component of which is acth139 . it is available in north america and administered subcutaneously . in europe , a shortened , synthetic acth analogue , known as tetrocosactide , consisting of the first 24 amino acids of the original hormone is available in depo form and licensed for intramuscular use in testing for adrenocortical insufficiency . we use the unlicensed subcutaneous route to allow self - administration which has shown to be well tolerated . the longer chained acthar gel is the only acth analogue licenced in the usa for use in nephrotic syndrome . it had been presumed that both forms were equally effective in treatment of nephrotic syndrome . there is currently no head - to - head evidence to compare the two formulations . the side effects are similar to exogenous steroids but on the whole the treatment is well tolerated with most adverse effects settling off therapy . serious allergic reactions are rare and reported in the literature when acth is used in allergic conditions . the commonest reason for drug discontinuation in our experience is exacerbation of fluid overload and non - adherence to self - injection . acth is a peptide hormone of the melanocortins group , which has an affinity to five melanocortin receptors ( mc1r - mc5r ) found throughout the body . acth is cleaved to -msh , but these two proteins have different properties , with acth being the only peptide that binds to the mc2r melanocortin receptor in the adrenal cortex , responsible for the instigation of steroidogenesis . as steroid therapy alone has not been proven to be an effective therapy to induce remission or delay end - stage renal disease for idiopathic mn [ 2 , 3 ] , it is proposed that there may be other mechanisms of action . acth and -msh have both been proposed to have a potent anti - inflammatory and immune modulating response . kidney - specific effects of -msh have protected against acute kidney injury in rodents with ischaemia reperfusion by reducing inflammatory cell recruitments and infiltration into injury sites . acth may work directly on the podocyte to reduce proteinuria , reduce oxidative stress and improve glomerular morphology . furthermore , acth may have a direct architectural effect on podocytes by decreasing nf-b activity . acth has been shown to have a stronger affinity than -msh for mc3r receptors , located on macrophages , which suppress inflammatory response . dyslipidaemia has long been shown to have an important role in the progression of nephrotic syndrome , with lipid - lowering agents proven to improve proteinuria in randomized , controlled trials of patients with idiopathic mn . furthermore , reduced levels of apolipoprotein j is a cause of proteinuric glomerulonephropathy , including mn and focal segmental glomerulosclerosis ( fsgs ) . acth directly regulates hepatic lipoprotein metabolism , modifying apolipoprotein metabolism , restoring levels of certain lipoproteins , such as lipoprotein j and e . these increased circulating lipoproteins may neutralize the activity of circulating permeability factors , such as in fsgs , thereby inducing remission of proteinuria . further studies have shown that apolipoprotein j may actually competitively bind to the megalin receptor in the podocyte , preventing components of complement binding , reducing glomerular injury [ 16 , 18 ] . the full picture is that a combination of all the above factors is responsible for the effectiveness of acth therapy in nephrotic syndrome particularly when other therapies have failed . what is understood is there is increasing evidence to show that acth can be as effective as more established therapies for nephrotic syndrome , and further study and research is warranted into the field .

there has been a re - emergence of interest in adrenocorticotropic hormone ( acth ) in patients with resistant nephrotic syndrome . we describe a patient with severe nephrosis and advanced chronic kidney disease with idiopathic membranous nephropathy resistant to conventional immunosuppressive therapies that achieved lasting remission with acth therapy . we explore the literature showing the extra renoprotective effects which might explain the response of proteinuric renal diseases to this treatment .

ultrasound has been widely used for rapid assessment of critical illness and is regarded as a visual stethoscope . there are few reports on the diagnosis of intracranial lesions by ultrasound in icu patients . here we present a multiple trauma patient who had undergone craniectomy and in whom recurrent intraventricular hemorrhage was rapidly detected by ultrasound . a 29-year - old man was transferred from a local hospital 9 hours after a 5-meter fall . his glascow coma score ( gcs ) was 4 and both pupils were unequal in size . the diagnosis was severe cerebral contusion and subdural hemotoma in the left temporal and parietal lobe , bilateral lung contusion and left clavicle fracture . he received an urgent decompressive craniectomy and evacuation of hematoma , and was then admitted to the emergency icu . in the following days , his condition improved and his gcs reached 8 , although this suddenly decreased to 6 on day 12 . bedside ultrasound was performed instantly and showed acute intraventricular hemorrhage ( ivh ) , which was confirmed by subsequent computed tomography ( ct ) ( figure 1 ) . bedside ultrasound and a head ct scan were arranged immediately , both showing recurrence of ivh ( figure 1 ) . the family refused further treatment and he then became brain dead ( figure 1 ) . computed tomography and ultrasound images of the head in a multiple trauma patient with craniectomy and recurrent intraventricular hemorrhage . ( a , b ) head computed tomography ( ct ) before craniectomy showing severe cerebral contusion and the deformed left lateral ventricle . ( c , d ) head ct on the fi rst day post - craniectomy showing the absence of the skull and the normal left lateral ventricle . ( e ) ultrasound image corresponding to the ct scan shown in ( d ) ; ( f ) the normal doppler pattern of the left middle cerebral artery ( lmca ) . ( g - i ) head ct and ultrasound images after the fi rst intraventricular hemorrhage ( ivh ) : ( g , h ) hematocele in both lateral ventricles ; ( i ) slightly abnormal doppler pattern of the lmca . ( j - l ) head ct and ultrasound images after the second ivh : ( j , k ) both enlarged lateral ventricles with hematocele compared with ( g ) ; ( l ) reverse blood fl ow during the diastolic period of lmca . the absence of the skull may facilitate the ultrasound to detect the brain , and intracranial morphological abnormal signs such as dislocation of the midline , intracerebral hematomas , size of lateral ventricular and hydrocephalus may be clearly displayed on the screen . this rapid and non - invasive method can complement the results of ct and may help to reduce delays in surgical management . caricato and colleagues found that ultrasound in patients with decompressive craniectomy was as effective as ct to evaluate intracerebral disorders . in this multiple trauma patient , ivh happened twice after the craniectomy and was immediately identified by ultrasound . meanwhile , ultrasound may detect the characteristics of cerebral blood flow , which helps to assess intracranial pressure and cerebral perfusion pressure . ct : computed tomography ; gcs : glascow coma score ; ivh : intraventricular hemorrhage .

ultrasound may be a useful tool to evaluate intracranial abnormalities in critically ill patients undergoing decompressive craniectomy . we present a multiple trauma patient who had undergone craniectomy and in whom recurrent intraventricular hemorrhage and patterns of cerebral blood flow were rapidly detected by ultrasound .

cystic lymphangiomas are unusual nonmalignant lesions , which result from failure of lymphatic channels to communicate with the main lymphatic system during embryological development . these lesions are mostly seen in the head and neck region . in addition , these lesions are lined with a single layer of endothelium like any vascular lesion . the lesions are located anywhere in the body with the abdomen being an uncommon location . cystic lymphangiomas of the colon are uncommon , with the potential to grow to a large size . these lesions have been increasingly reported lately with more colonoscopies being performed in the current era for various indications . in this current situation , it becomes imperative for general physicians and gastroenterologists to know how to manage these lesions . various imaging modalities including computed tomography , magnetic resonance imaging , and , more recently , endoscopic ultrasound , are being used to diagnose and assess the extent of lesions prior to therapeutic intervention . conventionally , endoscopic removal has been done for smaller - sized lesions , while larger ones are commonly treated with surgical interventions . however , based on the clinical presentation and locations , various treatment options including minimally invasive and open surgical interventions are being employed . our case exemplifies that with the advancement of therapeutic endoscopy , larger lesions can be successfully removed with endoscopic interventions . a 69-year - old male was referred to the gastroenterology clinic for screening colonoscopy . upon the initial interview , he denied abdominal pain , nausea , vomiting , or change in bowel habit . his medical comorbidities included bronchial asthma , hypertension , type ii diabetes mellitus , and gout . on a further interview his family history was noncontributory for any gastrointestinal malignancies . at the time of the initial visit , his vital signs were within normal limits . laboratory parameters showed a hemoglobin level of 12.6 g / dl , hematocrit 39.3% , white blood cell count of 7.3 k/l and platelets of 218 k/l . his blood urea nitrogen and creatinine were 24 mg / dl and 2 mg / dl , respectively . biopsies of the lesion were done , which were nondiagnostic . given the large size of the lesion and the inconclusive biopsy , we decided to proceed with repeat colonoscopy . although no immediate bleeding was noted , prophylactic endoscopic hemoclips were deployed at the site to close the defect and to prevent delayed bleeding . histopathological examination showed polypoid colonic tissue with markedly dilated spaces , lined by a single layer of thin endothelial cells predominantly in the submucosa with overlying normal colonic mucosa , consistent with cystic lymphangioma of the colon ( fig . lymphangiomas are uncommon , benign tumors arising from lymphatics involving various parts of the body . the most common location is usually the head and neck , with 5% of all lesions occurring in the abdominal cavity and with the colon also being one of the reported locations . the symptomatology spectrum ranges from asymptomatic presentation detected on routine colonoscopy to bleeding and alteration in bowel habit or pain . colonic cystic lymphangiomas appear as smooth sessile or pedunculated lesions noted on white light endoscopy . biopsy with cold forceps may not be yielding given the submucosal location of the lesion as in our case . the literature also suggests a role of endoscopic ultrasound in the diagnosis , where these lesions appear as anechoic , septate , and submucosal . there is also a school of thought that if the typical endosonography confirms the diagnosis of cystic lymphangioma based on the characteristic features , these lesions may not need treatment . given that larger lesions have the propensity to lead to acute complications , endoscopic or surgical treatment should generally be considered . endoscopic removal of lesions described in the literature so far has been done for lesions ranging to a maximum measurement of 23.5 cm . use of a ligating device for removal and unroofing are among the various techniques described for the successful removal of smaller lesions . although cystic lymphangiomas of the colon are among the uncommon , benign tumors of the colon , the increase in the reported incidence may parallel the increased use of routine screening colonoscopy . in this setting , we believe that gastroenterologists should be aware of such differentials , workup , and management options . we herein report a case of colonic cystic lymphangioma of a size of 5 cm that was successfully managed by endoloop endoscopic resection . previously , endoscopic resection has been attempted for smaller lesions , and so far , we are not aware of such gigantic lesions being removed endoscopically . endoscopic therapy is associated with less morbidity , lower healthcare costs , and better utilization of resources . operative intervention is still the option for lesions that can not be removed endoscopically and for lesions that present with acute gastroenterological complications . our case opens doors to an undiscovered option of potential endoscopic intervention for these larger colonic lesions . all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research board , bronx lebanon hospital center , bronx , ny , usa .

cystic lymphangiomas are benign colonic neoplasms arising from the submucosa . traditionally , endoscopic resection has been described for smaller lesions , while surgery is reserved for larger symptomatic lesions . we present a case of a 69-year - old asymptomatic individual noted to have a cystic lymphangioma of the colon measuring 5 cm , which was successfully removed with endoloop endoscopic resection without any complications .

our patient presented with accelerated silicosis starting as gradually progressive shortness of breath for about 1 year , progressing to chronic type 1 respiratory failure . this was followed by development of full blown mctd , with combined features of rheumatoid arthritis , scleroderma and systemic lupus erythematosus with severe arthritis , myositis and joint contractures . this was a case report of a 32-year - old stone crusher presented with gradually progressive breathlessness , initially on exertion and later , also at rest for 1 year . at the same time , he also noticed raynaud 's phenomenon involving the fingers and toes . over the next 6 months , he developed a gradual binding down of the skin over the dorsa of hands , forearms , face and leg . the patient also had severe joint pains predominantly involving all joints of the hands , including the wrist joint and the knees bilaterally . patient had been working as a stone crusher for the past 6 years . on examination , the patient had diffuse hyperpigmentation , visible respiratory distress with a respiratory rate of 34/min with mild pallor . arterial blood gas analysis revealed type 1 respiratory failure with pao2- 54 mmhg , ph - 7.38 , paco2- 38 mmhg . testing for immune markers revealed antinuclear antibody ( ana ) positive-9 ( if assay ) , anti - double stranded - deoxyribonucleic acid positive , anti - scl70 igg antibody positive 86 u / l , anti - u1 ribonucleoprotein ( rnp ) antibodies positive in high titers , anti - cyclic citrullinated peptide and rheumatoid factor positive . contrast enhanced computed tomography of the chest was suggestive of diffuse intra and interlobular septal thickening with fibrosis and randomly situated nodules [ figure 1 ] . transbronchial lung biopsy was compatible with silicosis and revealed focal interstitial fibrosis interspersed with pigment laden macrophages and refractile material . low dose prednisonolone ( 20 mg od ) was given in view of the arthritis . methotrexate at a dose of 25 mg weekly was also started along with proton pump inhibitors and physiotherapy . his hypoxia has also improved on therapy , but he continues to be on supplemental oxygen . some patients have features of more than one rheumatic disease and thus do not fit into traditional classification . patients with combination of clinical finding similar to those of systemic lupus erythematosus , progressive systemic sclerosis , polymyositis , rheumatoid arthritis and with unusually high titers of circulating ana with specificity for nuclear rnp are considered to have mctd . hypotheses implicating modified self - antigens and/or infectious agents in the pathogenesis of mctd have been advanced , but none have been proven yet . crystalline silica ( quartz ) particles less than 1 are the most pathogenic in silicosis . this constitutes a permanent stimulus for the fibroblasts , which increase their production of collagen leading to cutaneous sclerosis , vascular occlusion and pulmonary fibrosis , which explains the myriad clinical features of scleroderma and mctd .

silica exposure has been implicated with the development of various connective tissue diseases . we report a case of 32-year - old stone crusher who developed silicosis with mixed connective tissue disorder ( mctd ) 6 years after exposure to silica . this association of silicosis with mctd has never been reported from the indian subcontinent , although the problem of this pneumoconiosis remains rampant . this rare association urges us to report this case .

patients with known diabetes , hba1c > 6.5% ( 48 mmol / mol ) , previous small intestinal surgery , or evidence of acute or chronic pancreatitis were excluded . in this prospective , double - blind , crossover study performed on consecutive days , patients were randomly assigned to receive either the intervention ( gip at 2 pmol / kg min ) or control ( intravenous [ iv ] 0.9% saline ) in addition to iv glp-1 at 1.2 pmol / kg min . patients were fasted for 6 h , and exogenous insulin was ceased 3 h prior to each study . synthetic gip and glp-1 ( bachem , weil am rhein , germany ) were reconstituted in 0.9% saline by the royal adelaide hospital pharmacy , which undertook computer generated randomization . study solutions were administered via low absorbance tubing . between t60 and t420 , a mixed liquid nutrient ( ensure plus ; abbott nutrition ) was infused into the small intestine at 1.5 kcal / min ( 5 ) . this study protocol was approved by the research ethics committee of the royal adelaide hospital with informed consent obtained from patients next of kin . the protocol was registered with the australian new zealand clinical trials registry ( actrn12611000735954 ) . blood glucose concentrations were measured immediately using a blood gas analyzer ( abl800 flex ; radiometer ) . serum insulin was measured by elisa , while plasma glucagon , gip , and glp-1 were measured using radioimmunoassays . data are presented as mean sd or median ( range ) as appropriate . as data for inferential analysis were normally distributed , comparisons were made using the student paired t test . because the islet cell effects of gip are glucose - dependent ( 6,7 ) , the effect of gip in the subgroup of patients in whom peak blood glucose concentrations were > 10 mmol / l was also assessed . patients with known diabetes , hba1c > 6.5% ( 48 mmol / mol ) , previous small intestinal surgery , or evidence of acute or chronic pancreatitis were excluded . in this prospective , double - blind , crossover study performed on consecutive days , patients were randomly assigned to receive either the intervention ( gip at 2 pmol / kg min ) or control ( intravenous [ iv ] 0.9% saline ) in addition to iv glp-1 at 1.2 pmol / kg min . patients were fasted for 6 h , and exogenous insulin was ceased 3 h prior to each study . synthetic gip and glp-1 ( bachem , weil am rhein , germany ) were reconstituted in 0.9% saline by the royal adelaide hospital pharmacy , which undertook computer generated randomization . study solutions were administered via low absorbance tubing . between t60 and t420 , a mixed liquid nutrient ( ensure plus ; abbott nutrition ) this study protocol was approved by the research ethics committee of the royal adelaide hospital with informed consent obtained from patients next of kin . the protocol was registered with the australian new zealand clinical trials registry ( actrn12611000735954 ) . blood glucose concentrations were measured immediately using a blood gas analyzer ( abl800 flex ; radiometer ) . serum insulin was measured by elisa , while plasma glucagon , gip , and glp-1 were measured using radioimmunoassays . data are presented as mean sd or median ( range ) as appropriate . as data for inferential analysis were normally distributed , comparisons were made using the student paired t test . because the islet cell effects of gip are glucose - dependent ( 6,7 ) , the effect of gip in the subgroup of patients in whom peak blood glucose concentrations were > 10 mmol / l was also assessed . twenty patients ( age 52 16 years ; sex : 12 male ; hba1c : 5.7% [ range 4.86.5% ] , 39 [ 2948 ) ] mmol / mol ; acute physiology and chronic health evaluation ii score : 17 [ 930 ] ; days in icu when studied : 6 [ 215 ] days ; admission diagnostic group : sepsis , 9 ; trauma , 7 ; asthma , 2 ; neurological , 2 ) were studied . baseline blood glucose concentrations were similar on both days ( p = 0.38 ) . in nine patients , the peak blood glucose was > 10 mmol / l at least on one study day . gip had no effect on fasting , peak , or overall glycemic response in either the entire cohort ( fig . 1a ) or the group with glycemic excursions > 10 mmol / l ( fig . effects of the coinfusion of gip and glp-1 ( open circles ) when compared with glp-1 alone ( filled squares ) . a : peak ( p = 0.43 ) and overall glycemic response to nutrient infusion ( p = 0.34 ) were similar . b : overall glycemia in the subgroup ( p = 0.55 ) of patients with excursions > 10 mmol / l was comparable ( n = 9 ) . data are mean sd . area under the curve calculated using the trapezoidal rule . comparisons using paired student t tests ; n = 20 for all except the subgroup described . gip had no effect on fasting or overall insulin concentrations in either the entire cohort ( fig . 1c ) or the subgroup of patients with glycemic excursions > 10 mmol / l ( p = 0.96 ) . the addition of gip led to a minor increase in glucagon before nutrient was given ( t60 : 152 93 vs. 145 113 pg / ml ; p = 0.03 ) , but there was no difference at the end of the infusion ( p = 0.55 ) . overall , glucagon responses to the infusion were also comparable regardless of gip administration ( fig . there was no difference in the glucagon response between the 2 days in patients with glycemic excursions > 10 mmol / l ( p = 0.38 ) . baseline gip and glp-1 concentrations were similar on both days ( p = 0.79 and 0.35 , respectively ) . while there was a sustained twofold rise above fasting plasma gip concentrations in response to intraduodenal nutrient during the control infusion ( p < 0.001 ) , gip concentrations were fourfold greater during gip infusion ( p < 0.001 ) . on both days , glp-1 concentrations increased 40% in response to glp-1 infusions , with the addition of gip having no effect on plasma glp-1 concentrations ( p = 0.88 ) . baseline blood glucose concentrations were similar on both days ( p = 0.38 ) . in nine patients , the peak blood glucose was > 10 mmol / l at least on one study day . gip had no effect on fasting , peak , or overall glycemic response in either the entire cohort ( fig . 1a ) or the group with glycemic excursions > 10 mmol / l ( fig . effects of the coinfusion of gip and glp-1 ( open circles ) when compared with glp-1 alone ( filled squares ) . a : peak ( p = 0.43 ) and overall glycemic response to nutrient infusion ( p = 0.34 ) were similar . b : overall glycemia in the subgroup ( p = 0.55 ) of patients with excursions > 10 mmol / l was comparable ( n = 9 ) . comparisons using paired student t tests ; n = 20 for all except the subgroup described . gip had no effect on fasting or overall insulin concentrations in either the entire cohort ( fig . 1c ) or the subgroup of patients with glycemic excursions > 10 mmol / l ( p = 0.96 ) . the addition of gip led to a minor increase in glucagon before nutrient was given ( t60 : 152 93 vs. 145 113 pg / ml ; p = 0.03 ) , but there was no difference at the end of the infusion ( p = 0.55 ) . overall , glucagon responses to the infusion were also comparable regardless of gip administration ( fig . there was no difference in the glucagon response between the 2 days in patients with glycemic excursions baseline gip and glp-1 concentrations were similar on both days ( p = 0.79 and 0.35 , respectively ) . while there was a sustained twofold rise above fasting plasma gip concentrations in response to intraduodenal nutrient during the control infusion ( p < 0.001 ) , gip concentrations were fourfold greater during gip infusion ( p < 0.001 ) . on both days , glp-1 concentrations increased 40% in response to glp-1 infusions , with the addition of gip having no effect on plasma glp-1 concentrations ( p = 0.88 ) . this study indicates that iv administration of gip to glp-1 does not lower blood glucose concentrations in the critically ill more than exogenous glp-1 alone . in keeping with this , the addition of gip does not affect insulin or suppress glucagon response to enteral nutrient . while these observations are at variance with the outcome of studies performed in healthy volunteers ( 3,4 ) , they are consistent with the reported effects of concurrent administration of glp-1 and gip in patients with type 2 diabetes ( 4,8 ) . we have reported that glp-1 at 1.2 pmol / kg min attenuates , but does not abolish , the glycemic response to enteral nutrition in critically ill patients with and without type 2 diabetes ( 5,9,10 ) . while this is the first report on the effects of gip in the critically ill , in healthy volunteers , the coinfusion of gip at doses > 1 pmol / kg min is additive to the insulinotropic effect of glp-1 ( 3,4 ) . we confirmed that gip concentrations reached pharmacological levels , so it appears unlikely that the negative outcome of our study reflects an insufficient dose of gip . the reason gip failed to lower glucose concentrations may relate to antecedent glycemic control , as the insulinotropic effect of gip is markedly attenuated in various conditions associated with chronic hyperglycemia , such as latent autoimmune diabetes , chronic pancreatitis , and monogenic diabetes ( 11,12 ) . moreover , in vivo , hyperglycemia acutely reduces the expression of gip receptors on -cells , providing a plausible explanation as to why even pharmacological concentrations of gip are not insulinotropic during chronic hyperglycemia ( 13 ) . ( 14 ) recently reported that the insulinotropic property of gip increased several - fold following 4 weeks of near - normal glycemia in patients with type 2 diabetes . these data and ours indicate that the response of the -cell to pharmacological doses of gip is acutely susceptible to the effects of antecedent glycemia . in both healthy humans and patients with pre - existing hyperglycemia and hyperglucagonemia , exogenous gip is reportedly glucagonotropic , which would counteract any insulinotropic effect ( 6,8,11,15 ) . however , we observed a modest glucagontropic effect during fasting ( t60 ) , which is unlikely to be of clinical significance . we can not exclude the possibility that gip alone lowers glycemia in the critically ill compared with placebo . our cohort was relatively small and heterogeneous , and the exposure to exogenous gip was relatively short ( 7 h ) . it therefore remains possible , albeit intuitively unlikely , that an insulinotropic effect would be apparent during more prolonged gip exposure . in conclusion , this study indicates that the addition of gip to exogenous glp-1 does not yield any additional glucose - lowering effect , nor potentiate insulin secretion , in critically ill patients . the implication is that the insulinotropic capacity of gip , unlike glp-1 , is diminished in critically ill patients with hyperglycemia , as is the case in patients with type 2 diabetes .

objectiveglucose - dependent insulinotropic polypeptide ( gip ) and glucagon - like peptide-1 ( glp-1 ) have additive insulinotropic effects when coadministered in health . we aimed to determine whether gip confers additional glucose lowering to that of glp-1 in the critically ill.research design and methodstwenty mechanically ventilated critically ill patients without known diabetes were studied in a prospective , randomized , double - blind , crossover fashion on 2 consecutive days . between t0 and t420 minutes , glp-1 ( 1.2 pmol / kg min1 ) was infused intravenously with either gip ( 2 pmol / kg min1 ) or 0.9% saline . between t60 and t420 minutes , nutrient liquid was infused into the small intestine at 1.5 kcal / min.resultsadding gip did not alter blood glucose or insulin responses to small intestinal nutrient . gip increased glucagon concentrations slightly before nutrient delivery ( p = 0.03 ) , but not thereafter.conclusionsthe addition of gip to glp-1 does not result in additional glucose - lowering or insulinotropic effects in critically ill patients with acute - onset hyperglycemia .

blood samples were collected from 1,938 suspected case - patients from the 3 states ; serum was separated and transported to the laboratory on wet ice . immunoglobulin m ( igm ) antibodies to chikv ( igm anti - chik ) and dengue virus ( igm anti - dengue ) ( 8) were assayed by igm capture elisa . for chikv elisa , brain suspensions from mice infected with chikv were the source of antigen , and monoclonal antibodies were the source of antibodies ( 9 ) . dengue / chikv igm antibodies and negative control human sera were included for respective tests . approval for use of mice for antigen preparation was obtained from the institutional ethical committee according to national guidelines . immunofluorescence assay ( ifa ) was used to detect the virus in cell culture and in crushed heads of adult mosquitoes ( 10 ) . a patient with the following was confirmed as having chikv infection : acute onset of moderate - to - high fever with joint pain of varying severity ; negative test results for malaria , typhoid , and tuberculosis ; and positive results for igm anti - chikv antibodies , seroconversion , or chikv isolation . we studied chikv isolates obtained during current investigations and viruses isolated during earlier epidemics in india ( 19632000 ) ( table 1 ) . rna was isolated by using qiaamp viral rna mini kit ( qiagen , hilden , germany ) according to the manufacturer 's instructions . superscript ii ( invitrogen , carlsbad , ca , usa ) was used for reverse transcription ( 42c for 1 h ) . specific primers that produced a 472-bp fragment ( ns4 gene ) were f1 5 gay gci tay yti gay atg gti gai gg 3 and r1 5 kyt cyt cig trt gyt tig tic cigg 3 ( 11 ) . the second set of primers that amplified a 294-bp product of e1 gene were chik / e1-s 5 tac cca ttc atg tgg ggc 3 and chik / e1-c 5 gcc ttt gta cac cac gatt 3 ( 12 ) . cycling conditions were 1 cycle at 94c for 5 min ; then 35 cycles each of 94c ( 1 min ) , 50c ( 1 min ) , and 68c ( 1.5 min ) ; followed by final extension of 7 min at 68c . the pcr products were purified by using qiaquick pcr purification kit ( qiagen ) and sequenced by using bigdye terminator cycle sequencing ready reaction kit ( applied biosystems , foster city , ca , usa ) and an automatic sequencer ( abi prism 3100 genetic analyzer , applied biosystems ) . the phylogenic status of the chikv isolates was assessed with the software mega 3.1 ( 13 ) , kimura 2-parameter distance , and neighbor - joining algorithm . the reliability of different phylogenic groupings was evaluated with the bootstrap test ( 1,000 bootstrap replications ) available in mega . acute onset of moderate - to - high fever in association with body ache , backache , and headache was recorded . joint pain of varying severity occurred within 2 days of onset of fever and , in decreasing order of affliction , involved knees , ankles , wrists , hands , and feet . inflammation of joints and transient macular rash on earlobes , neck , trunk , and upper extremities were reported for a few patients . all ages and both sexes were affected ; significantly more cases occurred in persons aged > 15 years ( 299 [ 89.8% ] of 333 , p<0.001 ) . cases were reported from 11 of 23 districts in andhra pradesh , 15 of 27 in karnataka , and 16 of 35 in maharashtra ( figure 1 ) . chikv , chikungunya virus ; igm , immunoglobulin m. state governments of andhra pradesh , karnataka , and maharashtra have declared outbreaks of chikv . by mid - april , the declared numbers of fever cases associated with this outbreak were > 25,000 in andhra pradesh , > 65,000 in maharashtra , and > 36,000 in karnataka . aegypti was reasonably high in most of the localities ; adult household indexes and breteau indexes , respectively , were 1060 and 1375 in andhra pradesh , 2070 and 40200 in karnataka , and 1030 and 3050 in maharashtra . aegypti populations in affected areas and 23 isolations or detections of chikv from adult mosquitoes indicate that this species is the main vector in india . earlier outbreaks in india were mainly restricted to large cities ; in contrast , the current outbreak is predominantly rural . the finding of antibodies to dengue virus in 0.9% to 9.9% of patients and to chikv and dengue virus in 0.4% to 4.3% of patients indicates that these viruses cocirculate in the area . nine patients whose acute - phase serum sample was negative had anti - chikv igm in the early convalescent - phase sample , collected during the second week of illness . ns4-based phylogenic analysis identified the yawat isolate ( 2000 ) from maharashtra as central / east african genotype , not asian genotype as reported earlier ( 14 ) . phylogenic analyses based on ns4 ( figure 2a ) and e1 regions ( figure 2b ) yielded identical results . the indian viruses isolated from 1963 through 1973 belonged to the asian genotype , whereas the current isolates from the 3 indian states and the yawat isolate belonged to the central / east african genotype . within the asian genotype , all older isolates ( india 19631973 and thailand 19621978 ) clustered together , whereas later isolates from the philippines ( 1985 ) , indonesia ( 1985 ) , thailand ( 1988 , 1995 , 1996 ) , and malaysia ( 1998 ) formed a distinct cluster . the sequence from reunion islands , which represents a recent outbreak of the disease ( genbank accession no . percentage nucleotide identity within earlier ( 19631973 ) and recent ( 20052006 ) indian isolates was 99.71% 0.16% and 99.94% 0.05% , respectively , whereas percentage nucleotide identity between these isolates was 96.11% 1.09% . the 20052006 indian isolates were 98.61% 0.6% and 98.95% 0.57% identical with the reunion and yawat isolates , respectively . phylogenic analyses of partial ns4 ( 456 nt , panel a ) and e1 ( 294 nt , panel b ) . the following sequences were obtained from genbank database : e1 , ross ( af490259 ) ; s27africa ( nc-004162 ) ; tanz53 ( af192905 ) ; africa76 ( af192903 ) ; congo1 ( ay549583 ) ; congo2 ( ay549581 ) ; congo3 ( ay549579 ) ; uganda82 ( af192907 ) ; thai95 ( af192897 ) ; thai96 ( af192900 ) ; thai88 ( af192896 ) ; thai62 ( af192908 ) ; thai75 ( af192898 ) ; thai78 ( af192899 ) ; philip85 ( af192895 ) ; indon85 ( af192894 ) ; malay98a ( af394210 ) ; malay98b ( af394211 ) ; seneg83a ( ay726732 ) ; ony - ug96 ( af079456 ) ; reuni06 ( dq443544 ) ; seneg83b ( af192892 ) ; niger64 ( af192893 ) ; seneg66 ( af192891 ) ; ns1 , uk / s27 ( af345888 ) ; ross ( af490259 ) ; s27africa ( nc-004162 ) ; seneg83a ( ay726732 ) ; ony - ug96 ( af079456 ) ; and reuni06 ( dq443544 ) . o'nyong - nyong virus ( af079456 ) was used as an outgroup . this report confirms chikv as the causative agent for large outbreaks of fever with arthralgia and arthritis in 3 indian states . the current epidemic is caused by central / east african genotype of chikv . that the yawat isolate is grouped with central / east african genotype suggests that this genotype had been introduced > 5 years before the current outbreaks . in this context , determining the genotype of currently circulating strains in southeast asia and understanding the modes of transportation of this strain in india and the conditions favoring such large outbreaks would be worthwhile .

chikungunya fever is reported in india after 32 years . immunoglobulin m antibodies and virus isolation confirmed the cause . phylogenic analysis based on partial sequences of ns4 and e1 genes showed that all earlier isolates ( 19631973 ) were asian genotype , whereas the current and yawat ( 2000 ) isolates were african genotype .

histoplasmosis classically presents as opportunistic mycosis caused by the intracellular dimorphic fungus histoplasma capsulatum and is frequently associated with hiv infection and other immunocompromised states . in india , histoplasmosis is prevalent in the gangetic delta . we report a rare case of cutaneous histoplasmosis in a hiv seronegative patient from west bengal , india . a 28-year - married female from kolkata , presented at dermatology outpatient department ( opd ) of a hospital with history of nodulo - ulcerative lesions accompanied with extensive inflammation over left antero - lateral neck and chest for last 10 months . close examination revealed pale white to pink nodules , painless papules , ulcerated plaques , and few crusted lesions [ figure 1 ] . areas of skin were visible amidst the lesions and also over neck and anterior shoulder . pale white to pink nodules , papules , ulcerated plaques , and few crusted lesions over left antero - lateral neck and chest there was neither any history of fever , nor travelling abroad or to other places in india . however , she gave a history of irregular treatment with antibiotics for last 3 months , for the same . on extensive discussion with the patient , we found that patient was carrying with herself a histopathological report by a private laboratory , mentioning the diagnosis as histoplasmosis . also , the patient was taking oral itraconazole ( past 1 week ) and mentioned that lesions have started to heal after taking itraconazole . the anxious patient had somehow lost faith in ongoing treatment and attended our institution in search of alternative opinion and rapid recovery . on examination patient was seronegative for hiv and , flow cytometry for cd4 count was within normal limit . for microbiological assessment , swabs and scrapings were taken from surface of lesion for staining and bacterial and fungal culture . scrapings from the surface of the lesions were also sent for histopathological assessment . though the bacterial and fungal cultures showed no growth , histopathological examination revealed periodic acid - schiff ( pas ) positive multiple tiny intracellular round to oval yeast forms , few surrounded with halo ; suggestive of histoplasmosis [ figure 2 ] . multiple tiny intracellular round to oval yeast forms , few surrounded with halo in dermis , 400 pas stain three main clinical manifestations of histoplasmosis are pulmonary , progressive disseminated and chronic cavitory forms : all may be accompanied with skin lesions , or rarely , the disease manifests as pch . pch in immunocompetent individuals itself is very rare , with hardly three case reports , and can present with nodules , ulcers and abscesses . confirmation of etiology in our case is credited to histopathology and good response to the approved antifungal itraconazole . absence of lymphadenopathy and hepatosplenomegaly , normoglycemic status , a normal hemogram and renal biochemical parameters and a normal chest x - ray , rule out systemic involvement . puckering of skin amidst the area of involvement was probably due to healing of inflamed and ulcerated lesions following administration of itraconazole . the probable route of infection may be through direct inoculation of spores through skin with splinter injury or thorn pricks . cutaneous presentation without any systemic involvement , florid inflammation and ulceration , normal cd4 count , hiv seronegative status of the patient and prompt response to appropriate treatment are the notable features of our case . the differential diagnosis of nodulo - ulcerative lesions should include skin and lymphocutaneous malignancies and other systemic mycoses . though histoplasmosis is reported to be endemic in west bengal , there are no reports of primary cutaneous histoplasmosis accompanied with extensive inflammation in hiv seronegative individual from west bengal , till date . in our case , early diagnosis and accurate treatment would have relieved the patient of morbid stress much earlier .

a patient presented with multiple nodulo - ulcerative lesions over neck and chest . lymphadenopathy and systemic involvement were absent . patient was seronegative for hiv . there was no history of local injury and no history of travel . histopathological findings were consistent with histoplasmosis . diagnosis of primary cutaneous histoplasmosis was made . we highlight this case owing to its rare and atypical presentation , in an attempt to promote clinical and micro - pathological awareness regarding such occurrences .

many different surgical procedures have been described , and tension - free repair using a prosthetic mesh became the mainstay of herniorrhaphy . therefore , laparoscopic transabdominal preperitoneal ( tapp ) and totally extraperitoneal ( tep ) techniques are frequently preferred . when comparing the two techniques , tapp is easier to learn and may be associated with a shorter learning curve . recent studies have been focused to minimise further the invasiveness of laparoscopy by reducing the number of incisions and the port size . in this way , pain and complications associated with incisions single - incision laparoscopic surgery ( sils ) was developed with the aim of reducing the invasiveness of conventional laparoscopy , and has been successfully performed by many surgeons . the aim of this retrospective study was to evaluate the safety and feasibility of a single - incision approach for laparoscopic tapp repair of the inguinal hernia . patients older than 18 years of age who underwent tapp or sils - tapp between december 2012 and january 2015 in the department of surgery of a university research hospital were included in this retrospective study . the study has been performed in accordance with the ethical standards laid down in the declaration of helsinki . after the patients were informed about the surgical procedure and potential complications of the surgery , written informed consents were obtained from all the participants . the data included age , gender , body mass index ( bmi ) , operative time ( placement of ports to skin closure ) , american society of anesthesiologists ( asa ) classification score , length of hospital stay ( defined as operation day to discharge day from the hospital ) , visual analogue scale ( vas ) score 24 h after the surgery , operative complications , and short - term and long - term outcomes that were obtained from hospital charts and office records . patients with complicating diseases resulting in asa classification score iv , contraindications to laparoscopic surgery such as previous laparotomy or huge chronic scrotal hernia were also excluded from the study . all operations were performed by the same surgeon ( h.y . ) who had experience in single - port surgery . after standard preoperative preparation , a single intravenous dose of antibiotic prophylaxis ( cefazolin 1 g ) was administered before induction , and all the patients underwent surgery under general anaesthesia . a similar surgical technique through a single umbilical port with conventional instruments was followed to perform sils - tapp repair . a standard postoperative analgesic protocol was followed with intravenous petidine hydrochloride 50 mg after operation , intravenous paracetamol 500 mg every 6 h and tenoxicam 20 mg twice a day . patients were asked to rate their pain in the range of 0 ( no pain ) to 10 ( most pain ) that most closely expressed their level of postoperative pain . the patient was placed in a supine position on the operating table and the surgeon stood on the opposite side of the hernia . the first 10-mm trocar ( versaport plus , covidien , mansfield , ma , usa ) was introduced through the umbilicus with open technique . additionally , two 10-mm and 5-mm ports were placed on the right and left sides of the camera port . the 10-mm port was used to introduce the mesh and a 30-mm curved needle for peritoneal suturing . the peritoneal cavity was insufflated with co2 to a pressure of 12 mmhg , and a 30 laparoscope ( karl storz , germany ) was inserted . the patient was placed in a trendelenburg position with the hernia site rotated up to allow slipping of the bowel . the peritoneum was incised using hook electrocautery from the upper edge of the inguinal floor toward the median umblical ligament , and the preperitoneal plane was developed with sharp and blunt dissections . a 10 15 cm - sized polypropylene mesh ( surgipro mesh , covidien , ma , usa ) was introduced through the 10-mm trocar , placed over the inguinal floor . all potential hernia areas were covered with meshes such as hesselbach 's triangle , inguinal ring , and femoral ring . the mesh was tacked to the transversus abdominis , iliopubic tract , and cooper ligament using absorbable tackers ( absorbatack , covidien , usa ) . sils - tapp was performed with a similar technique to the standard tapp repair through a single umbilical port . the sils - port ( covidien corp , mansfield , ma , usa ) was introduced through a single 2.0 - 3.0 cm transverse transumbilical skin and facial incision [ figure 1 ] . after creation of pneumoperitoneum at pressure of 12 mmhg , two 5-mm working ports and a 10-mm camera port was inserted [ figure 2a ] . a mesh was placed , and the peritoneum was closed with standard laparoscopic instruments or tackers . after releasing the pneumoperitoneum , the umbilical fascia was routinely closed with polypropylene loop suture ( surgipro ii , tyco , usa ) and the skin was sutured with 4 - 0 absorbable intradermic sutures ( monocryl , ethicon , usa ) . a 3-cm skin and facial incision was performed ( a ) to insert the sils port ( b ) two working ports and a camera port were inserted to the abdomen ( a ) , the peritoneum incised from the upper edge of the inguinal floor ( b ) the peritoneum was separated from epigastric vessels and the vas deferens the evaluation of patient data was performed by using statistical package for the social sciences ( spss ) version 18.0 program ( ssps , inc . , chicago , il , usa ) . continuous variables were presented as mean standard deviation and categorical variables as the number ( % ) . categorical variables were compared using the chi - square test and fisher 's exact test . a p level of < 0.05 was accepted as statistically significant . the patient was placed in a supine position on the operating table and the surgeon stood on the opposite side of the hernia . the first 10-mm trocar ( versaport plus , covidien , mansfield , ma , usa ) was introduced through the umbilicus with open technique . additionally , two 10-mm and 5-mm ports were placed on the right and left sides of the camera port . the 10-mm port was used to introduce the mesh and a 30-mm curved needle for peritoneal suturing . the peritoneal cavity was insufflated with co2 to a pressure of 12 mmhg , and a 30 laparoscope ( karl storz , germany ) was inserted . the patient was placed in a trendelenburg position with the hernia site rotated up to allow slipping of the bowel . the peritoneum was incised using hook electrocautery from the upper edge of the inguinal floor toward the median umblical ligament , and the preperitoneal plane was developed with sharp and blunt dissections . a 10 15 cm - sized polypropylene mesh ( surgipro mesh , covidien , ma , usa ) was introduced through the 10-mm trocar , placed over the inguinal floor . all potential hernia areas were covered with meshes such as hesselbach 's triangle , inguinal ring , and femoral ring . the mesh was tacked to the transversus abdominis , iliopubic tract , and cooper ligament using absorbable tackers ( absorbatack , covidien , usa ) . sils - tapp was performed with a similar technique to the standard tapp repair through a single umbilical port . the sils - port ( covidien corp , mansfield , ma , usa ) was introduced through a single 2.0 - 3.0 cm transverse transumbilical skin and facial incision [ figure 1 ] . after creation of pneumoperitoneum at pressure of 12 mmhg , two 5-mm working ports and a 10-mm camera port was inserted [ figure 2a ] . a mesh was placed , and the peritoneum was closed with standard laparoscopic instruments or tackers . after releasing the pneumoperitoneum , the umbilical fascia was routinely closed with polypropylene loop suture ( surgipro ii , tyco , usa ) and the skin was sutured with 4 - 0 absorbable intradermic sutures ( monocryl , ethicon , usa ) . a 3-cm skin and facial incision was performed ( a ) to insert the sils port ( b ) two working ports and a camera port were inserted to the abdomen ( a ) , the peritoneum incised from the upper edge of the inguinal floor ( b ) the peritoneum was separated from epigastric vessels and the vas deferens the evaluation of patient data was performed by using statistical package for the social sciences ( spss ) version 18.0 program ( ssps , inc . , continuous variables were presented as mean standard deviation and categorical variables as the number ( % ) . categorical variables were compared using the chi - square test and fisher 's exact test . a p level of < 0.05 was accepted as statistically significant . in total , 148 patients underwent laparoscopic inguinal hernia repair . of the 148 patients , the mean follow - up period was 15.4 3.8 months for patients who underwent tapp and 14.8 3.6 months for patients who underwent sils - tapp . there was a statistically significant difference between the two groups regarding age : the mean age of the patients was 57.1 12.4 years in the tapp group and 50.7 10.1 years in the sils - tapp group . the groups were also similar in terms of gender , nyhus classification , asa classification , and follow - up time . all sils - tapp procedures were completed successfully without conversion to tapp or open repair , and no additional port was required in both groups . there were no differences in operative time , length of hospital stay and vas scores of patients 24 h after the operation . the mean operative time was 36.8 8.7 min in the tapp group and 38.7 9.2 min in the sils - tapp group . no intraoperative major complications were observed such as vessel , intestine , or bladder injury . the first control examination was performed 2 weeks after the operation to record the short - term complications for all patients . every 2 months , telephone surveys were conducted to investigate the patients ' complaints related to surgery . one patient in each group had a complaint of pain for longer than 3 months . several small seroma and hematomas were reported in both groups , and all of them were resolved with conservative treatment . long - term complications such as mesh infection and recurrence were not detected in both the groups . three patients ( 5.0% ) in the sils - tapp group experienced port site hernia ( psh ) . two of the patients were obese ( bmi : 33.7 kg / m and 34.1 kg / m ) , diabetic , and male . the other psh had occured in 52-year - old female patient with chronic obstructive pulmonary disease . all of the pshs were confirmed by ultrasound , and elective mesh hernioplasty was performed . preoperative patients ' characteristics comparison of the operative time , length of hospital stay and vas scores comparison of the intraoperative , short - term and long - term postoperative complications sils is developed in an attempt to minimize the abdominal wall trauma by reducing the number of ports . the most important advantage of sils has been reported as the improvement in cosmetic results . one of the important results of this study is that the sils - tapp is associated with high psh rate when compared with tapp . however , in the short - term and long - term complication rates , and pain scores showed no difference with surgical technique . in this study , we have evaluated conventional three - port tapp and single - incision tapp repair with respect to perioperative events and postoperative outcomes . but there was a limitation of this study , namely , the choice of surgical technique to be used was based on patients ' demands . however , the bigger umbilical incision to accommodate the sils port should not be underestimated . several studies have very low incidence of psh but the current follow - up period of patients who underwent sils is limited . reported a psh rate of 2.9% in a study of 211 patients that included appendectomy , cholecystectomy , nissen fundoplication , sleeve gastrectomy , gastric banding , colectomy and gastrojejunostomy . authors were recommended to extend the duration of the follow - up period to 2 - 3 years to determine the true risk of incisional hernias . the prospective study of christoffersen et al . demontrated the incisional hernia rate to be similar with a long - term follow - up period of median 4 years . it is known that the incisional hernia rate is significantly higher in patients with comorbidities such as diabetes mellitus , obesity and chronic obstructive pulmonary disease . in our sils - tapp group , therefore , the bigger umbilical incision is not a single factor for incisional hernia ; the patient selection seems to be a cornerstone of decreasing the risk of psh . in a majority of the studies , sils groups have a longer operative time because of the proximity of the instruments with limited triangulation and limited motion of the laparoscope . the problem of clashing of instruments was partially offset by using articulating dissector , grasper and shear . the learning curve with conventional instruments is not very long , and after the first 10 - 20 cases the training process was almost completed . the surgeons who are at the learning curve period for sils should select uncomplicated patients with lower bmi . in fact , obesity is not a contraindication for sils technique . patients with bmi of 40 kg / m or higher underwent sils procedures in our clinic without any major complication . therefore , the operative time of the groups were found to be similar in our study . the analysis of patient demographics demonstrated that patients undergoing sils - tapp were significantly younger than patients undergoing tapp . among younger people in the experienced laparoscopic surgery centers , sils - tapp inguinal hernia repair is a feasible and safe technique with remarkable cosmesis , and comparable postoperative pain scores although the single umbilical incision may also lead to an incisional hernia risk to patients . with careful patient selection , sils - tapp prospective randomized studies with long - term follow - up are necessary to evaluate the true psh rates , and potential benefits associated with these approaches .

background : laparoscopic surgery has been a frequently performed method for inguinal hernia repair . studies have demonstrated that the laparoscopic transabdominal preperitoneal ( tapp ) approach is an appropriate choice for inguinal hernia repair . single - incision laparoscopic surgery ( sils ) was developed to improve the cosmetic effects of conventional laparoscopy . the aim of this study was to evaluate the safety and feasibility of sils - tapp compared with tapp technique.materials and methods : a total of 148 patients who underwent tapp or sils - tapp in our surgery clinic between december 2012 and january 2015 were enrolled . data including patient demographics , hernia characteristics , operative time , intraoperative and postoperative complications , length of hospital stay and recurrence rate were retrospectively collected.results:in total , 60 sils - tapp and 88 tapp procedures were performed in the study period . the two groups were similar in terms of gender , type of hernia , and american society of anesthesiologists ( asa ) classification score . the patients in the sils - tapp group were younger when compared the tapp group . port site hernia ( psh ) rate was significantly high in the sils - tapp group , and all pshs were recorded in patients with severe comorbidities . the mean operative time has no significant difference in two groups . all sils procedures were completed successfully without conversion to conventional laparoscopy or open repair . no intraoperative complication was recorded . there was no recurrence during the mean follow - up period of 15.2 3.8 months.conclusion:sils tapp for inguinal hernia repair seems to be a feasible , safe method , and is comparable with tapp technique . however , randomized trials are required to evaluate long - term clinical outcomes .

fractures of the distal radius represent one - sixth of all fractures treated in emergency department.1 closed reduction and cast immobilization has been the mainstay of treatment of these fractures , but invariably it results in malunion , poor functional and cosmetic outcome.2 restoration and maintenance of anatomy correlates well with function . it adversely affects wrist motion and hand function by interfering with the mechanical advantage of the extrinsic hand musculature.35 in many cases there is weakness of handgrip and return to preinjury activity level becomes impossible . percutaneous k - wire fixation provides additional stability and is one of the earliest forms of internal fixation.810 depalma described ulno - radial pinning drilled at 45 angle , 4 cm proximal to ulnar styloid . kapandji11 described double intrafocal pinning into the fracture surface and rayhack12 described ulno - radial pinning with fixation of distal radioulnar joint . ruch et al15 and many others described open reduction and internal fixation of distal radius fracture . doi et al . recommended it for comminuted intra - articular fractures.16 most of the work done with percutaneous pinning emphasizes that there is significant residual stiffness of the hand and wrist.1718 the acute palmarflexed position of the wrist during the postoperative immobilization period was blamed as the main reason for stiffness.19 this study was conducted to examine the functional outcome of non comminuted extra - articular distal end radius fractures treated with closed reduction and percutaneous k - wire fixation with immobilization in neutral position of the wrist and early physiotherapy . thirty two consecutive patients with extra - articular distal radius fractures were prospectively enrolled for the study between january 2006 and march 2010 . the mean age of patients was 41.4 years ( range 18 - 70 years ) . in 21 patients , all patients with intra- articular distal radius fractures , comminuted distal end radius fractures , presenting later than 2 weeks of injury , patients in whom ulnar shaft was not intact , polytrauma patients , patients with open fractures and patients with open fractures were excluded . out of the 32 patients enrolled for the study , none of them were lost to follow - up . the mode of trauma was a simple fall on the outstretched hand in 21 patients and a sports - related injury in 11 patients . fractures were classified according to the ao classification , using the preoperative anteroposterior and lateral roentgenogram [ figure 1 ] . ( a ) preoperative anteroposterior view and ( b ) preoperative lateral view of the ao type a2 fracture closed reduction of the fracture was achieved by longitudinal traction and direct pressure over the displaced fragment under anesthesia . hyperextension or flexion an assistant held the wrist with fracture in the reduced position , the first k - wire of 1.5 - 2.0 mm was inserted from the dorsolateral aspect of the distal radius fragment across the fracture and into the proximal fragment under image intensifier guidance . a second k - wire was passed from the dorsomedial aspect of the distal fragment across the fracture into the proximal fragment . after checking the stability of the fracture under image intensifier , if required , a third k - wire was passed from dorsolateral aspect from distal to proximal fragment . k - wires were bent at a right angle and cut short outside the skin for easy removal . a sterile dressing including sponge padding was applied to prevent skin irritation . with the wrist in the neutral position , patients were discharged 24 hours post surgery after ensuring good distal circulation of fingers . at 3 weeks follow - up , x - rays were taken , both in the anteroposterior and lateral planes to check the position of the fracture . the slab was removed and active finger , wrist exercises and forearm pronation and supination exercises were started . wrist physiotherapy and handgrip exercises were continued for another 2 to 4 weeks [ figure 2 ] . post - operative anteroposterior and lateral views showing good reduction , k - wires in situ and back slab results were evaluated clinically and radiologically at 6 months using sarmiento 's modification of lindstrom criteria20 [ table 1 ] and by the sarmiento et al , modification of the demerit point system of gartland and werley21 ( described below ) [ table 2 ] . sarmiento 's modification of lindstrom criteria20 demerit point system of gartland & werley with sarmiento et al modification ( functional evaluation)21 closed reduction of the fracture was achieved by longitudinal traction and direct pressure over the displaced fragment under anesthesia . as an assistant held the wrist with fracture in the reduced position , the first k - wire of 1.5 - 2.0 mm was inserted from the dorsolateral aspect of the distal radius fragment across the fracture and into the proximal fragment under image intensifier guidance . a second k - wire was passed from the dorsomedial aspect of the distal fragment across the fracture into the proximal fragment . after checking the stability of the fracture under image intensifier , if required , a third k - wire was passed from dorsolateral aspect from distal to proximal fragment . k - wires were bent at a right angle and cut short outside the skin for easy removal . a sterile dressing including sponge padding was applied to prevent skin irritation . with the wrist in the neutral position , patients were discharged 24 hours post surgery after ensuring good distal circulation of fingers . at 3 weeks follow - up , x - rays were taken , both in the anteroposterior and lateral planes to check the position of the fracture . the slab was removed and active finger , wrist exercises and forearm pronation and supination exercises were started . wrist physiotherapy and handgrip exercises were continued for another 2 to 4 weeks [ figure 2 ] . post - operative anteroposterior and lateral views showing good reduction , k - wires in situ and back slab results were evaluated clinically and radiologically at 6 months using sarmiento 's modification of lindstrom criteria20 [ table 1 ] and by the sarmiento et al , modification of the demerit point system of gartland and werley21 ( described below ) [ table 2 ] . sarmiento 's modification of lindstrom criteria20 demerit point system of gartland & werley with sarmiento et al modification ( functional evaluation)21 all fractures healed . restoration of anatomy was excellent in 21 patients ( 65.63% ) and 9 patients ( 28.13% ) had a good anatomical outcome while 2 ( 6.25% ) had fair results . preoperative radiographic assessment showed that the average radial height was 2.56 mm ( range 14 mm ) and volar tilt was -12.31 ( range 8 to -18 ) . assessment of postoperative radiographs revealed that the average radial height was 10.44 mm ( range 8 - 14 mm ) and volar tilt was 11.13 ( range 8 - 16 ) on the immediate postoperative x - rays . at the time of pin removal at 6 weeks , radial height was 9.34 mm ( range 5 - 13 mm ) and volar tilt 10.03 ( range 4 - 16 ) . the radial height was 7.53 mm ( range 2 - 12 mm ) and volar tilt 8.56 ( range -2 26 patients ( 81.25% ) had excellent hand function [ figures 3 and 4 ] ; 4 patients ( 12.5% ) had good results ; 2 patients ( 6.25% ) who had residual displacement and joint stiffness had a fair outcome [ tables 3 and 4 ] . clinical photographs at 6 months followup showing ( a ) dorsiflexion at the wrist ( b ) palmar flexion at the wrist clinical photographs at 6 months followup showing ( a ) radial deviation of the wrist ( b ) ulnar deviation of the wrist results based on sarmiento 's modification of lindstrom criteria results based on demerit point system of gartland & werley with sarmiento et al modification pin loosening was encountered in 13 cases . pin tract infection ( n=2 ) , malunion in ( n=2 ) , joint stiffness ( n=2 ) , reduced grip strength ( n=2 ) and paresthesia in the distribution of superficial radial nerve ( n=1 ) were the other complications observed . post - traumatic arthritis of wrist , subluxation of distal radio - ulnar joint and penetration of vessel were not seen . . the importance of anatomic reduction has been demonstrated by clinical studies as well as by laboratory assessment of force and stress studies.2223 in fractures with articular displacement greater than 2 mm , radial shortening greater than 5 mm or dorsal angulation greater than 20 , suboptimal results have been reported in previously published studies.21 accurate reduction of the fracture is the first step in the treatment of distal radial fractures . the most common traditional method is closed reduction and cast immobilization , but this often fails to prevent early radial collapse and is associated with a high risk of malunion , joint stiffness and painful wrist . hence , this method is for low - demand elderly patients.2425 external fixators can maintain radial length and radial inclination by ligamentotaxis , but can not effectively maintain palmar tilt.26 also complication rates as high as 60% have been reported with the use of external fixators.27 these mainly include pin loosening , pin tract infection , reflex sympathetic dystrophy , radial sensory neuritis and delayed union . thus , external fixators are better avoided in noncomminuted extra - articular distal radial fractures.28 open reduction and internal fixation15 and arthroscopic reduction16 techniques should be reserved for partial and complex intra - articular distal radius fractures . percutaneous pinning with k - wires was first recommended by green29 as a simple and inexpensive procedure . most studies attribute poor results of this technique to radial shortening , wrist stiffness and reflex sympathetic dystrophy.1718 the authors are of the view that wrist stiffness and reflex sympathetic dystrophy occur because of the palmar - flexed position of the wrist in which postoperative immobilization of the fracture is done . prolonged immobilization of the wrist for greater than 3 weeks increases the magnitude of the problem . hence we developed our protocol for the treatment of extra - articular distal radius fractures . fracture reduction was achieved by longitudinal traction and direct pressure over the displaced fragment followed by percutaneous pinning . instead of circumferential cast , dorso - radial plaster of paris slab was applied in neutral position of the wrist . we did not encounter reflex sympathetic dystrophy while 2 cases had wrist stiffness which required mobilization exercises under the supervision of physiotherapist . radial shortening remains the main displacement in distal end radius fractures , especially intra - articular and comminuted fractures.30 in our opinion , percutaneous pinning maintains radial length adequately in extra - articular distal radial fractures . two cases in our series had pin tract infection , but this was superficial and did not necessitate early removal of the pins . the infection subsided with removal of the pins at 6 weeks in both the cases . these 2 patients also had malunion with significant radial shortening , wrist joint stiffness and reduced grip strength . the functional result obtained in these patients at the end of follow - up period was fair . loosening of one of the k - wires was observed in 13 cases at the time of removal of the pins , but it did not jeopardize the fracture alignment . this can be avoided by using a limited incision for lateral pin insertion . in conclusion , percutaneous pinning and immobilization of the fracture with wrist immobilized in neutral position for 3 weeks and early physiotherapy is a simple procedure for extra - articular noncomminuted distal radius fractures . it provides anatomic fracture reduction and fixation and allows earlier rehabilitation without jeopardizing the fracture alignment .

background : various treatment modalities have been described for the treatment of extra - articular distal radius fractures each with its own merits and demerits . most of the work done with percutaneous pinning has shown a significant residual stiffness of the hand and wrist . our technique involves percutaneous pinning of the fracture and immobilization in neutral position of the wrist for three weeks . this study 's aim was to examine the functional outcome of percutaneous k - wiring of these extra - articular distal radius fractures with immobilization in neutral position of the wrist.materials and methods : this is a prospective study of 32 patients aged between 18 and 70 years with extra - articular distal radius fracture . patients were treated with closed reduction and percutaneous pinning using two or three k - wires . a below- elbow plaster of paris dorsoradial slab was applied in neutral position of the wrist for 3 weeks . at the end of 3 weeks , the slab was removed and wrist physiotherapy started . the radiographs were taken postoperatively , at 3 weeks , 6 weeks and 6 months . the functional evaluation of the patients was done at 6 months follow - up . we used sarmiento 's modification of lindstrom criteria and gartland and werley 's criteria for evaluation of results.results:excellent to good results were seen in 93.75% of the cases while 6.25% had fair results . the complications observed were pin loosening ( n=13 ) , pin tract infection ( n=2 ) , malunion ( n=2 ) , wrist joint stiffness ( n=2 ) , reduced grip strength ( n=2 ) and injury to the superficial radial nerve ( n=1).conclusion : percutaneous pinning followed by immobilization of the wrist in neutral position is a simple and effective method to maintain reduction and prevent stiffness of wrist and hand .

dpp-4 inhibitors prolong the activity of incretin peptides , glucagon - like peptide-1 ( glp-1 ) , and glucose - dependent insulinotropic polypeptide ( gip ) , which stimulate glucose - dependent insulin secretion and inhibit glucagon secretion . glp-1 action is thought to be the main glucose - lowering effect of dpp-4 inhibitors because the gip receptor is downregulated under the hyperglycemic condition . because the receptor for glp-1 has been shown to exist on various cells , including hepatocytes , dpp-4 inhibitors may have pleiotropic effects independent of lowering plasma glucose level and stimulating insulin secretion . non - alcoholic fatty liver disease ( nafld ) describes a disease with excessive deposition of fat within the liver and includes a broad spectrum of liver diseases ranging from simple fatty liver to non - alcoholic steatohepatitis ( nash ) and cirrhosis . nafld is more prevalent and more severe in patients with type 2 diabetes , and is associated by increased mortality rates . because liver function is extremely important for glucose metabolism , nafld moreover , a recent study revealed that nafld was associated with increased prevalence of diabetic macroangiopathy and coronary heart disease in elderly japanese patients with type 2 diabetes . therefore , it is no less important to maintain the liver function in diabetic patients than in their nondiabetic counterparts . recently , several clinical studies have shown that glp-1 receptor agonists reduced fat deposition in the liver and improved liver function independently of body weight loss in type 2 diabetes . these findings suggest that activation of glp-1 signaling in the liver has beneficial effects on nafld and that dpp-4 inhibitors may also affect liver function . however , the impact of improving liver function by dpp-4 inhibitors is still unknown . therefore , in this study we examined the effects of dpp-4 inhibitors on liver function in patients with type 2 diabetes . the inclusion criteria are shown in figure 1 . according to the records of our hospital , a total of 459 patients with type 2 diabetes were prescribed dpp-4 inhibitors from september to november 2012 . we excluded the patients with glucocorticoid use ( n=56 ) , hepatitis b or c , and other diseases that might affect liver function and diabetes status ( n=114 ) . we also excluded patients who were not followed - up at our hospital ( n=31 ) or for whom we could not define when dpp-4 inhibitors were initially prescribed ( n=34 ) . demographic and biochemical parameters at the initial date of dpp-4 inhibitors prescription were collected and body weight , parameters of liver function [ aspartate transaminase ( ast ) , alanine transaminase ( alt ) , and gamma - glutamyl transpeptidase ( gtp ) ] , and hemoglobin a1c ( hba1c ) were followed up to 6 months . the numbers of patients who were prescribed sitagliptin , alogliptin , and vildagliptin were 155 , 37 , and 32 , respectively . this study was retrospective in design , approved by the ethics review board of shimane university faculty of medicine , and complied with the helsinki declaration . all biochemical markers were measured by standard methods at the clinical laboratory in shimane university hospital . hba1c was determined by high - performance liquid chromatography and was calculated according to the national glycohemoglobin standardization program ( ngsp ) . statistical significance between the patients with and without liver injury was determined using the t - test and test . statistical significance between baseline versus 1 , 3 , and 6 months was determined using the wilcoxon signed rank test . all analyses were performed using the statview ( abacus concepts , berkeley , ca ) statistical computer program . the inclusion criteria are shown in figure 1 . according to the records of our hospital , a total of 459 patients with type 2 diabetes were prescribed dpp-4 inhibitors from september to november 2012 . we excluded the patients with glucocorticoid use ( n=56 ) , hepatitis b or c , and other diseases that might affect liver function and diabetes status ( n=114 ) . we also excluded patients who were not followed - up at our hospital ( n=31 ) or for whom we could not define when dpp-4 inhibitors were initially prescribed ( n=34 ) . demographic and biochemical parameters at the initial date of dpp-4 inhibitors prescription were collected and body weight , parameters of liver function [ aspartate transaminase ( ast ) , alanine transaminase ( alt ) , and gamma - glutamyl transpeptidase ( gtp ) ] , and hemoglobin a1c ( hba1c ) were followed up to 6 months . the numbers of patients who were prescribed sitagliptin , alogliptin , and vildagliptin were 155 , 37 , and 32 , respectively . this study was retrospective in design , approved by the ethics review board of shimane university faculty of medicine , and complied with the helsinki declaration . all biochemical markers were measured by standard methods at the clinical laboratory in shimane university hospital . hba1c was determined by high - performance liquid chromatography and was calculated according to the national glycohemoglobin standardization program ( ngsp ) . statistical significance between the patients with and without liver injury was determined using the t - test and test . statistical significance between baseline versus 1 , 3 , and 6 months all analyses were performed using the statview ( abacus concepts , berkeley , ca ) statistical computer program . forty - four patients ( 19.6% ) had liver dysfunction defined by ast or alt above the normal level of 40 u / l . the levels of ast , alt , and gtp were significantly higher in the patients with liver dysfunction than those without it , while hba1c levels and dpp-4 inhibitors were not different . chronological changes in body weight , ast , alt , gtp , and hba1c are shown in table 2 . in all subjects , hba1c levels were significantly decreased for up to 6 months , but body weight and the parameters of liver function were not changed . in the patients with liver dysfunction , hba1c , ast , and alt were significantly decreased for up to 6 months , whereas body weight and gtp were not changed . the mean changes of ast and alt at 6 months were 6.2 u / l [ 95% confidence interval ( ci ) 10.9 to 1.4 , p=0.012 ] and 11.9 u / l ( 95%ci 19.5 to 4.2 , p=0.003 ) , respectively . when changes in ast and alt levels were compared among sitagliptin , alogliptin , and vildagliptin , there was no significant difference ( data not shown ) . in contrast , ast or alt levels were not changed in the patients without liver dysfunction , although hba1c levels were significantly decreased in the same manner as in the patients with liver dysfunction . to find which parameters predict the reduction of ast and alt , the correlation of percent changes in ast and alt at 6 months with baseline characteristics was examined ( table 3 ) . percent changes in ast and alt were significantly and inversely correlated with baseline ast and alt levels , but they were not correlated with age , body mass index , gtp , or hba1c . forty - four patients ( 19.6% ) had liver dysfunction defined by ast or alt above the normal level of 40 u / l . the levels of ast , alt , and gtp were significantly higher in the patients with liver dysfunction than those without it , while hba1c levels and dpp-4 inhibitors were not different . chronological changes in body weight , ast , alt , gtp , and hba1c are shown in table 2 . in all subjects , hba1c levels were significantly decreased for up to 6 months , but body weight and the parameters of liver function were not changed . in the patients with liver dysfunction , hba1c , ast , and alt were significantly decreased for up to 6 months , whereas body weight and gtp were not changed . the mean changes of ast and alt at 6 months were 6.2 u / l [ 95% confidence interval ( ci ) 10.9 to 1.4 , p=0.012 ] and 11.9 u / l ( 95%ci 19.5 to 4.2 , p=0.003 ) , respectively . when changes in ast and alt levels were compared among sitagliptin , alogliptin , and vildagliptin , there was no significant difference ( data not shown ) . in contrast , ast or alt levels were not changed in the patients without liver dysfunction , although hba1c levels were significantly decreased in the same manner as in the patients with liver dysfunction . to find which parameters predict the reduction of ast and alt , the correlation of percent changes in ast and alt at 6 months with baseline characteristics was examined ( table 3 ) . percent changes in ast and alt were significantly and inversely correlated with baseline ast and alt levels , but they were not correlated with age , body mass index , gtp , or hba1c . in this study , we found that dpp-4 inhibitors significantly reduced ast and alt levels in the type 2 diabetes patients with liver dysfunction , but they did not affect liver function in those without liver dysfunction . the liver injury of the subjects enrolled in the analysis might have been caused by nafld because we excluded subjects who had hepatitis b or c. furthermore , the baseline and subsequent data showed that the patients with liver dysfunction were obese compared to those without liver dysfunction . in addition , gtp levels were not changed , suggesting that the improvement of ast and alt was not caused by restriction of alcohol abuse . these findings also support that nafld caused the abnormality of ast and alt levels in our subjects . most recently , iwasaki et al . reported for the first time that liver function was improved by 4-month treatment with sitagliptin in type 2 diabetes patients with nafld diagnosed by ultrasonography . examined paired liver biopsies in 15 diabetic patients with nash and reported that a significant reduction of nash scores was observed after 1-year treatment with sitagliptin , and that these effects were accompanied by significant decreases in body mass index , ast , and alt levels . moreover , we found that the changes in ast and alt by dpp-4 inhibitors were independent of hba1c level and body weight . thus , dpp-4 inhibitors have a desirable effect on liver function independent of diabetes status . the pleiotropic effects of incretin - related therapies have recently attracted widespread attention because the receptor for glp-1 is reported to be expressed in various tissues . although glp-1 has a great potential for treatment of type 2 diabetes , its half - life is extremely short because glp-1 is rapidly inactivated by dpp-4 . it has recently been shown that the receptor for glp-1 exists in human hepatocytes and administration of glp-1 analogue directly reduced triglyceride stores compared with control - treated cells in the absence of insulin . moreover , several clinical studies showed that glp-1 receptor agonists improved abnormal liver function and hepatic steatosis . on the other hand , it is reported that dpp-4 is ubiquitously expressed , and that dpp-4 inhibitors have direct effects independent of incretin activity . for example , in vitro and in vivo studies showed that a dpp-4 inhibitor , alogliptin , directly inhibited macrophage migration via suppressing adenosine deaminase on the cell in the absence of incretin signals . a recent study demonstrated that dpp-4 was locally expressed in the liver and that hepatic dpp-4 expression was significantly greater in nafld patients than in healthy subjects . these findings suggest that inhibition of local dpp-4 activity in the liver may be important for the treatment of nafld . taken together , these findings suggest that dpp-4 inhibitors improve liver function via increasing glp-1 activity , as well as directly inhibiting local dpp-4 activity in the liver . in our study , the effects of dpp-4 inhibitors on the changes in ast and alt were independent of hba1c levels , suggesting that dpp-4 inhibitors have pleiotropic effects on liver function , not only in experimental studies , but also in clinical settings . however , there appear to be no studies examining effects of increasing glp-1 activity and inhibiting hepatic dpp-4 activity by dpp-4 inhibitors on liver function in patients with nafld . further studies are necessary to understand the mechanism for improving liver function of nafld by dpp-4 inhibitors . the present study showed that dpp-4 inhibitors improved the abnormality of ast and alt , and that percent changes in ast and alt were inversely associated with baseline ast and alt levels . in addition , the effects of dpp-4 inhibitors on changes in ast and alt were independent of hba1c and body weight . these findings suggest that dpp-4 inhibitors are clinically useful for patients with type 2 diabetes accompanied by liver dysfunction based on fatty liver , and that dpp-4 inhibitors affect liver function regardless of diabetic status and obesity . moreover , in this study , dpp-4 inhibitors significantly reduced hba1c levels even in the patients with liver dysfunction . liver function is quite important for glucose metabolism because the liver is one of the most important target organs of insulin to decrease plasma glucose level . therefore , dpp-4 inhibitors may be more useful for type 2 diabetes patients with nafld than those without it . however , our study is limited because it is retrospective and based on the database of our hospital . also , other supportive data such as ultrasonography and liver biopsy were not available in this study .

backgrounddipeptidyl peptidase-4 ( dpp-4 ) inhibitors might have pleiotropic effects because receptors for incretin exist in various tissues , including liver . we examined whether dpp-4 inhibitors affect liver function in patients with type 2 diabetes.material/methodsa retrospective review of 459 patients with type 2 diabetes who were prescribed dpp-4 inhibitors was performed . after exclusion of patients with hepatitis b or c , steroid use , and other diseases that might affect liver function and diabetes status , 224 patients were included in the analysis.resultsforty-four patients ( 19.6% ) with liver injury defined by aspartate transaminase ( ast ) or alanine transaminase ( alt ) over the normal level of 40 u / l . in the patients with liver injury , ast and alt were significantly decreased after 6 months from the first date of dpp-4 prescription , with mean changes of 6.2 u / l [ 95% confidence interval ( ci ) 10.9 to 1.4 , p=0.012 ] and of 11.9 u / l ( 95%ci 19.5 to 4.2 , p=0.003 ) , respectively . percent changes in ast were significantly and negatively correlated with baseline ast and alt ( r=0.27 , p<0.001 and r=0.23 , p=0.002 , respectively ) , and percent changes in alt were also negatively correlated with them ( r=0.23 , p=0.001 and r=0.27 , p<0.001 , respectively).conclusionsdpp-4 inhibitors improved liver dysfunction in patients with type 2 diabetes .

gallstones and their sequelae cause considerable morbidity , mortality , and healthcare costs around the world . although laparoscopic cholecystectomy is highly effective , the health care costs of the procedure vary widely by institution and according to technical practices of surgeons . further savings should accrue when an uncomplicated cholecystectomy is performed in a free - standing ambulatory surgery center ( asc ) , since the fixed costs of ascs are less than those of full - service hospitals . however , a single complication can eliminate the gains of most frugal decision - making . convenience and cost savings are the primary reasons why ascs have become popular with patients and surgeons . the typical asc provides admission , surgical services , and recovery facilities in a geographically concentrated area . the ideal ambulatory center also provides overnight stay capability in the event of late afternoon operation or excessive nausea . for the surgeon , the asc operating schedule is less apt to be altered by emergencies compared to a full - service hospital . essential outcomes for successful laparoscopic cholecystectomy in the asc include completion of the operation without complication and discharge on the same day or the following morning in the event of overnight stay . before considering cholecystectomy in the asc , we reviewed our database of 1750 patients having laparoscopic cholecystectomies in a hospital setting . empirical criteria for possible ambulatory operation included the following : a ) age < 65 years , b ) low risk for common bile duct ( cbd ) stones , as defined by normal liver enzymes and common bile duct diameter of 5 mm or less , c ) elective operation , d ) absence of major medical problems , and e ) no previous upper abdominal operations . thirty - five percent ( 605/1750 ) of the hospitalized patients met these strict criteria for potential ambulatory center cholecystectomy ; furthermore , 98% of those selected patients were discharged on the same day or else the next morning after operation . only one patient ( 0.2% , 1/605 ) was converted to an open procedure ; another was explored 30 hours postoperatively with hemorrhage from the liver bed . based on the analysis of our own data , we felt that laparoscopic cholecystectomy could be offered to selected patients in a free - standing asc that had overnight stay . selection criteria for the ideal patient for ambulatory cholecystectomy were outlined in the preceding paragraphs ( table 1 ) . however , some patients with mild abnormalities of either enzymes or common duct diameter were selected for operation in the asc . for example , an elevation in serum alutamate oxalacetate transaminase ( sgot ) in an obese patient with a 3 mm cbd diameter and a single large gallstone is most likely related to a fatty liver rather than to a cbd stone . in addition , a mild dilatation of the cbd ( 5.5 mm ) would be expected in a 50 year old with a contracted and nonfunctioning gallbladder filled with stones . ideal patient for asc . data from the first 100 laparoscopic cholecystectomies from the asc were accumulated prospectively from january 1997 to november 1998 . for comparative purposes , a similar database was accumulated concurrently on 218 hospitalized patients , who either did not meet our criteria or their insurer 's pre - certification for ambulatory center procedures . lasers , bipolar electrosurgery , and ultrasonic dissectors were not utilized as they all increase costs and operating times without any other discernible benefits for performing cholecystectomy . ( for example , the use of the ultrasonic dissector is associated with a facility charge of over $ 1000 . ) total operating room time , surgeon operating time , time of discharge , and complications were recorded . while efforts were made to perform the procedures in the morning to facilitate same - day discharge , anesthetic practices varied with 12 different anesthesiologists but included short - term anesthetics with pre - emptive treatment of pain and nausea . the time of discharge was dictated by the patient 's return of gi function and level of discomfort . early follow - up appointments were scheduled , but patients were given the option of either coming to the office or calling in to report an excellent recovery . the one exception was a 62-year - old lady in whom the gallbladder was found to be severely scarred with a thickened wall suggesting malignancy . the laparoscopic exam was aborted before major dissection was initiated , and she was transferred to a hospital where an open cholecystectomy was performed later that same day ( no malignancy ) . there were no conversions to open operations , no transfusions , and no biliary or bowel complications . with the exception of the patient listed above same - day discharge was accomplished in 74 patients , and the remaining 25 patients were discharged the next morning . some of the overnight stays were related to psychological conditioning and social factors ( children at home , personal preference , etc . ) telephone follow - up on the day after discharge was accomplished in all patients ; 60% of patients elected to have their follow - up office visit by telephone rather than in person . the mean operating time was 29.1 minutes ( standard deviation 13.7 ) with total use of the room averaging 56.2 minutes ( standard deviation 12.3 ) . the tabulated total facility costs for routinely disposable items ( including instruments , gowns , sutures , metal clips , suction tubing , and adhesive bandages was $ 98 . during the same period , 218 laparoscopic cholecystectomies were attempted in the hospital , and the conversion to open operation occurred in 1.4% ( table 2 ) . since medicare does not allow the performance of cholecystectomy in a free - standing center in mississippi , all medicare patients were treated in the hospital . while some other non - medicare cholecystectomies were performed in the hospital by direction of the insurer , the majority were admitted because of acute complications of cholelithiasis . twelve of the first 100 patients had mild abnormalities of liver enzymes that were judged acceptable for the asc . none of the operative cholangiograms in the patients performed in the ambulatory care center showed common bile duct stones . in the same period , operative cholangiograms and laparoscopic cbd explorations were performed in 39% and 6% of the hospitalized patients , respectively . as would be expected , the hospitalized patients were older and had more complex disease as reflected by a greater need for operative cholangiograms , cbd exploration , and a longer hospital stay ( table 2 ) . in the group of patients in whom operative cholangiograms were not obtained ( 214 of 318 patients ) , there were no bile leaks , duct injuries , or subsequent clinical evidence of missed common duct stones . the current fixed facility charge for laparoscopic cholecystectomy in the ambulatory center is $ 2990 . the charge for most hospitalized patients in neighboring hospitals is variable but exceeds $ 4000 . cost - control systems with global pricing and capitated care have changed the payment scheme for surgical services . with reimbursement ambulatory surgical centers , offering fewer services than hospitals , enjoy lower fixed costs , which should lead to lower costs for selected procedures such as laparoscopic cholecystectomy . prerequisites include an experienced surgeon with a track record of few complications . a dedicated laparoscopy team must be well trained and provided with a caseload adequate to maintain proficiency . as outlined in this study , patient selection should limit the need for conversion to laparotomy or more advanced laparoscopic procedures . conversion to open operation is appropriate in some circumstances and can be associated with discharge within 24 hours in selected patients . however , numerous studies previously have shown the cost - savings of reusable over disposable instruments . the operating room times reported herein compare favorably to all previously reported studies , supporting the position that excellent reusable instruments do not prolong operating times . the veress needle has been completely abandoned in favor of a rapid , open insertion of a blunt cannula under laparoscopic vision . the reusable clip applier does extend the operation by about 20 seconds ( compared to the disposable multiclip applier ) but with a cost savings of about $ 150 and no other alteration in outcome . the enthusiastic support of the surgeon and surgical staff is essential for a smooth transition to reusable instruments . suggestions that morbidity of cholecystectomy is reduced by using 2 or 3 mm instruments have not yet been documented by shorter recovery periods . the author 's preference is to use two 10 mm and two 5 mm cannulas . the gallbladder is extracted through the epigastric 10 mm port site as a time - saving maneuver but also because there is a distinctly lower infection and hernia rate in the epigastric port site compared to the umbilicus . the 5 mm instruments are considerably more sturdy than their smaller counterparts , and the cosmetic differences between a 5 and 3 mm incision are arguably quite small . the use of routine versus selective operative cholangiograms has been a matter of debate since inception , and consensus remains incomplete . whenever there is a question regarding anatomy or suspicion of cbd stones , dynamic flourocholangiograms are extremely important . the facility charge of $ 2990 is currently one of the lowest reported charges in the united states . in traverso 's fairly exhaustive study , the costs of laparoscopic cholecystectomy in a hospital setting was estimated to be $ 2,180 , of which $ 595 was for disposable instruments . our total cost of routinely disposable items was only $ 98 , which included all instruments , gowns , gloves and adhesive bandages . our shorter operating times are explained by factors such as patient selection , the selective use of operative cholangiograms and , perhaps , a fairly major interest in best uses of electrosurgery . however , traverso pointed out that shorter or times lead to true cost savings only when total staffing costs are reduced for the day or else when demand elasticity provides another case to increase output . the asc is a more malleable entity than a full - service hospital for predicting staffing needs and limiting costs . the cost - saving practices reported herein have not led to any discernible reduction in outcome for any patient . while the concept of outpatient cholecystectomy is gaining momentum , broader implementation of outlined practices , such as the use of reusable instruments , has been relatively slow since the incentive for change is variable and indirect . however , the importance of risk - management issues is heightened when patient recuperation occurs in an outpatient setting . corporate leaders and insurers have an unexploited opportunity , a vested interest , and responsibility to offer cost - responsible educational programs for their surgeons and staff . the ambulatory surgical center provides a low - cost environment for low - risk procedures . with appropriate selection of patients , coordination of the operating team , and experience of the surgeon , laparoscopic cholecystectomy can be safely performed in the free - standing ambulatory surgical center .

background and objectives : keys to economic survival in an era of decreasing reimbursement include controlling costs and avoiding complications . in an effort to reduce costs , laparoscopic cholecystectomy has been performed with same - day discharge from a hospital setting . the free - standing ambulatory surgery center offers even greater cost savings if safety can be assured . facility charges , surgical technique and instrument selection influence the costs of the procedure.methods:a database was accumulated prospectively on the first 100 laparoscopic cholecystectomies performed in a free - standing ambulatory surgery center to assess costs , logistical constraints , and safety.results:laparoscopic cholecystectomies were accomplished in 99 of 100 patients . one patient was suspected of having cancer during laparoscopy and was transferred to a nearby hospital for open cholecystectomy . there were no other postoperative hospitalizations for complications . the fixed facility charge for the procedure was $ 2990 , and the total costs for all routinely disposable items ( gowns , gloves , instruments , and adhesive bandages was $ 98 . the mean or time was 29 minutes ( standard deviation 13.7).conclusions : the free - standing ambulatory surgery center is an appropriate facility for an experienced operating team to perform laparoscopic cholecystectomy in selected patients . the surgeon 's selection of appropriate energy sources and instruments is essential to complete the operation in a most cost - effective manner .

the prevalence of cardiovascular disease ( cvd ) in rural india is 7.4% , and in urban india , it is 11% . the incidence of ischaemic heart disease ( ihd ) and coronary heart disease ( chd ) is steadily increasing in the indian subcontinent . according to world health report 2002 this number will represent 54.1% of all cvd deaths in the age group of 3069 years . although many studies have been carried out in urban populations , very few studies have examined the etiologic factors in rural indian populations . ihd is a progressive disease arising when the supply of oxygen in the myocardium is compromised by impeded blood flow in the coronary vasculature caused by luminal occlusion . the pathogenesis of atherosclerosis involves damage to the capillary endothelium caused by various factors including oxidized low - density lipoprotein ( ldl ) [ 3 , 4 ] . muscular hypertrophy is caused by elaboration of local elaboration of growth factors from surrounding macrophages which are primed by free radicals . free radicals are chemical species that can be considered as fragments of molecules possessing unpaired electrons . they are generally very reactive , and they are produced continuously in cells either as by - products of metabolism or during phagocytosis . the major types of free radicals found in biological systems are reactive oxygen species ( ros ) and reactive nitrogen species ( rns ) . they are generated by absorption of radiant energy , endogenous oxidative reactions , enzymatic metabolism of exogenous chemicals , and generation of free radicals in pathogenic conditions . the present study was planned and conducted to evaluate the role of oxidative stress in patients with cvd patients from populations of the nilgiris , south india , and the role of antioxidants in patients with ihd patients and to assess the classical risk factors associated with the oxidative stress related to cvd . an open randomized control study was conducted at the government district headquarters hospital , ootacamund , nilgiris district , tamil nadu , india , over 10 months . a total of 72 patients with cvd and 12 healthy volunteers were screened for the study . college of pharmacy , ootacamund , and the study was performed according to the recommendations of the declaration of helsinki . the study was conducted on patients ( 3180 years ) suffering from cvd , such as , ihd , myocardial infarction ( mi ) or unstable angina ( ua ) , who were admitted in the intensive cardiac care unit ( iccu)/intensive care unit ( icu ) of the government district headquarters , ootacamund . ihd patients with chronic diseases such as diabetes and hypertension and those who had suffered strokes were excluded . forty - seven patients in the 3180 year age group and 10 healthy volunteers in the 3140 year age group were included in the intervention and control groups , respectively . the subjects or their guardians were interviewed for 1520 minutes , and their demographic details were collected . the demographic details included primary patient information ( such as name , age , and sex ) , socioeconomic status and food habituation . after enrolment as a study participants , the history was collected through a structured enrolment form , the medical records ( case history of patients ) which included the age , gender , in - patient number , socioeconomic status , social habits , past medical , and surgical history . the blood samples were centrifuged at 3000 rpm for 20 minutes , and the serum was separated and stored at 20c until analysis . the levels of enzymic ( superoxide dismutase ( sod ) and catalase ( cat ) ) and nonenzymic ( ascorbic acid ) antioxidants and predictor of lipid peroxidation as measured by the thiobarbituric acid species ( tbars ) in the serum were determined . flow diagram of requirement and allocation of participants and analysis of the data are given in figure 1 . significant difference between groups was determined using one - way anova followed by the bonferroni test . a p value less than 0.05 was considered as significant . the greatest number of subjects was in the 6170 year group ( 20of which 13 were males and 7 were females ) and 5160 year group ( 16of which 9 were males and 7 were females ) . in all , there were 33 male subjects ( 58% ) and 24 female subjects ( 42% ) in the intervention group ( table 1 ) . in our study , of the 47 patients , 33 were workers with an average monthly income of rs.600 . in the intervention group , 26 male subjects out of 30 and 7 female subjects out of 17 were workers by occupation . this may be due to their habits , such as heavy smoking and having a high alcohol intake and high consumption of animal fat . in the control group , most of the male subjects in the intervention group were nonvegetarians , smokers , and alcoholics ( table 2 ) . the levels of enzymic and nonenzymic antioxidants of the patients with cvd were evaluated after the initial symptomatic management was done . the mean value of sod levels in healthy participants was found to be 2.15 0.01 units / minute / mg protein . in patients with cvd , a significant reduction ( p < 0.001 ) in sod levels the sod levels observed in patients with ihd , mi , and ua were 1.05 0.01 , 1.54 0.01 and 1.86 0.01 , units / minute / mg protein , respectively ( table 3 ) . the mean value of catalase in healthy participants was found to be 19.33 0.81 moles of h2o2 consumed / minute / mg protein . in patients with cvd , a significant reduction ( p < 0.001 ) in the catalase values was observed compared with healthy control participants . the catalase levels observed in patients with ihd , mi , and ua were 6.01 0.45 , 6.73 0.14 , and 6.28 0.08 moles of h2o2 consumed / minute / mg protein , respectively . the normal mean value of ascorbic acid was found to be 139.20 10.08 mg / dl . in patients with cvd , a significant reduction ( p < 0.001 ) in the ascorbic acid values was observed when compared with the control participants . the ascorbic acid levels observed in patients with ihd , mi , and ua were 66.60 17.32 , 57.92 10.17 , and 71.90 9.73 mg / dl , respectively . the estimated level of antioxidants in the intervention group was lower than that in the control group . the results of the present investigation suggest that the lowered level of antioxidants may be a result of the oxidative stress of the disease . individual comparisons of ascorbic acid levels showed that the differences between smoker versus nonsmokers , alcoholics versus nonalcoholics and vegetarians versus nonvegetarians were not statistically significant ( tables 4 , 5 , and 6 ) . the normal mean value of tbars was found to be 68.70 6.73 moles of malondialdehyde / dl serum . increased levels of tbars were observed in subjects with ihd , mi , and ua , but the results were not statistically significant . the increased tbars levels may be a result of the oxidant stress of the disease . individual comparisons of the tbars level between smokers versus nonsmokers , alcoholics , versus nonalcoholics and vegetarians versus non - vegetarians showed that the differences were not statistically significant ( tables 4 , 5 , and 6 ) . to evaluate the oxidative stress and antioxidant status in patients with cvd in a rural indian population , a cross - sectional study was carried out in which an intervention group consisting of 47 patients with cvd was compared with 10 healthy volunteers . the demographic data showed a higher incidence of ihd in males compared with females of the same age group . the lower incidence in menopausal and postmenopausal females is probably due to the protective effect of estrogens . the presence of other comorbid factors may be responsible for the oxidant damage caused due to smoking and diabetes . earlier studies have suggested that , in both men and women , diabetes , age , and plasma cholesterol levels were independent predictors of ihd mortality . the prevalence of ihd and relative mortality risk associated with several risk factors ( age , marital status , education , cigarette smoking , systolic blood pressure , cholesterol , fasting plasma glucose , and obesity ) differ with sex [ 13 , 14 ] . when the mean values of the serum enzymes were compared , a marked decrease in the levels of sod and catalase was found , whereas the level of tbars , indicating lipid peroxidation , was markedly increased . evaluation of the serum values in various demographic subsets of the population was performed , and the greatest changes were found in smokers , followed by nonvegetarians , suggesting that smoking has an important role in causing oxidant stress . free radicals , cytokines , nitric oxide ( no ) , and antioxidants play a major role in both atherosclerosis and myocardial damage and preservation . in the present study , it was found that rural people from the nilgiris admitted with ihd , mi , and ua had increased tbars levels and reduced sod , catalase , and ascorbic acid levels . previous studies have demonstrated the biological relevance of the antioxidant defence system to myocardial infarction . chandra et al . ( 1994 ) demonstrated that there were elevated superoxide anion , malonyldialdehyde , and glutathione reductase levels and reduced superoxide dismutase and catalase levels in unstable angina and acute myocardial infarction cases . gupta and chari ( 2006 ) measured the levels of proxidants and antioxidants in patients with ihd and type ii diabetes mellitus . significantly increased levels of malondialdehyde and decreased levels of superoxide dismutase , glutathione peroxidase , and vitamin c were found in diabetics without complications and nondiabetics with ihd compared with control subjects . the levels of sod , catalase , and ascorbic acid were shown to be lower and the tbars level was shown to be higher in patients from rural india with ihd , mi , and unstable angina . risk factors such as age , being male , smoking , alcohol consumption , a nonvegetarian diet , and occupation played an important role in the genesis of oxidative stress , which is one of the causes of cvd . it is concluded on the basis of the present study that free radicals are implicated in the etiology of cvd and that enzymatic antioxidants , sod , and catalase have a major role in preventing cellular oxidative damage .

objective . the objective of this work was to study the risk factors of ischaemic heart disease ( ihd ) in rural populations of the nilgiris , south india , with stress on the various social habits and oxidant stress . methods . a total of 72 patients with cardiovascular disease ( cvd ) and 12 healthy volunteers were screened . forty - seven patients with cvd ( intervention group ) and 10 healthy volunteers ( control group ) were randomly selected for the study . written informed consent was obtained from all the participants , and their demographic details were collected . a 6 ml blood sample was collected from each of the participants , and the serum was separated in the samples . the levels of enzymic ( superoxide dismutase , catalase ) and nonenzymic antioxidants ( ascorbic acid ) in the plasma were determined biochemically . the level of thiobarbituric acid species ( tbars ) , which is a predictor of lipid peroxidation , was measured . results . the participants of the study were stratified as according to demographic and social variables . the values of all the antioxidants and tbars were statistically compared . significantly reduced antioxidant levels and increased tbars levels were found in the intervention group compared with the control group . the results suggest that the lowered antioxidant level may be a result of the oxidant stress of the disease . statistically significant differences were not found in the antioxidant and tbars levels when comparing smokers versus nonsmokers , alcoholics versus nonalcoholics , and vegetarians versus nonvegetarians . conclusion . the major causes of cvd amongst the rural populations of the nilgiris , south india , are preventable causes such as smoking and high fat intake , all of which cause oxidative stress , as seen in our study through various serum markers .

this retrospective review was conducted through a medical record search to identify all patients with a diagnosis of nmo or transverse myelitis admitted from the emergency department at johns hopkins hospital . patients were included in this study if they had a history of nmo as defined by the 2006 clinical diagnostic criteria , were admitted to the hospital between 2009 and 2015 , and presented with an acute exacerbation defined as new or worsening neurologic symptoms in the setting of a presumed relapse . workup for all patients included neurologic examination , mri at the time of admission , and hematologic and urine studies . demographic information , data on signs , symptoms , workup on admission , and information on final diagnosis were aggregated . two distinct nmo cohorts were subsequently described : one group consisting of patients diagnosed with true relapses and the other with pseudorelapses . the gold standard for a relapse in this study was defined as a clinical exacerbation presenting with new or worsening symptoms with a change on neurologic examination that correlated with a new or enhancing mri lesion . the gold standard for a pseudorelapse in this study was defined as a clinical exacerbation with similar symptoms and signs , but the mri was negative for a new or enhancing lesion and there was an alternative cause for the symptoms that , when treated , resulted in the improvement of neurologic symptoms . these gold standard definitions for relapse and pseudorelapse do not encompass the full spectrum of nmo spectrum disorder ( nmosd ) disease in practice . the purpose for including only cases that met these strict criteria is to identify early clinical and objective measures that could definitively exclude a pseudorelapse . the motor examination was scored as no change ( none ) , a 1-point change in the medical research council ( mrc ) motor scale ( mild ) , a 2-point mrc change ( moderate ) , or 3 + change ( severe ) . mris were obtained by using either 1.5- or 3-tesla scanners : philips healthcare ( best , the netherlands ) , ge healthcare ( milwaukee , wi ) , and siemens ( erlangen , germany ) . diffusion - weighted imaging and t1-weighted , data analysis was performed using graphpad prism statistical software ( graphpad software , la jolla , ca ) to compare differences between the 2 cohorts ( see table e-1 at neurology.org/nn ) . the fisher exact probability test was used to test statistical significance in race , sex , urinary tract infection ( uti ) , weakness , numbness , bowel / bladder symptoms , and vision complaints on admission . seventy - four individual hospital admissions met criteria for inclusion , 57 of which met gold standard criteria for true relapses and 17 met the criteria for pseudorelapses . the average age at presentation in the true relapse cohort was 41.2 years ( range 378 ) and was 37.7 years ( range 371 ) in the pseudorelapse cohort ( table 1 ) . the sex distribution was skewed toward female in both groups , with a female to male ratio of 13:5 and 12:3 in the relapse and pseudorelapse cohorts , respectively . there was also a higher proportion of african american patients overall , with 56% of the relapse cohort and 53% of the pseudorelapse cohort , reflecting the nmosd patient population in baltimore , md . of the patients who presented with true relapses , 75% had a positive anti demographics of the neuromyelitis optica cohorts of the 57 hospital admissions for true relapses , 64% demonstrated upper and/or lower extremity weakness ( table 2 ) ; 53% of the 17 admissions for pseudorelapses also had documented weakness compared to prior baseline . of note , more than half of all true relapses were graded as mild with only a 1-point worsening in the mrc score ( table 2 ) . numbness or worsening sensory loss was recorded in 52% of true relapse patients and 24% of pseudorelapse patients , which was not different . twenty - one percent of true relapse and 41% of pseudorelapse admissions presented with bowel and/or bladder symptoms , including urinary incontinence and increased frequency and urgency . thirty percent of relapse and 35% of pseudorelapse admissions had documented utis . in sum , there were no differences in the following between the 2 groups : age at presentation , sex , race , uti , white blood cell count , weakness , numbness , and bowel / bladder symptoms ( table 3 ) . clinical presentations of the neuromyelitis optica cohorts the only difference found between the groups at presentation was unilateral or bilateral worsening of visual acuity , both by symptomatic presentation and visual acuity examination , consistent with an acute optic neuritis . the prevalence of visual symptoms was notably different between the 2 cohorts ; 41% of true relapse admissions vs 12% of pseudorelapse admissions presented with complaints of changes in visual acuity ( p = 0.039 , table 2 ) . neither of the 2 subjects in the pseudorelapse group presenting with visual complaints had detectable changes on visual acuity testing or any other ophthalmologic finding . of the 24 patients with true optic neuritis relapses presenting with visual complaints , all had ophthalmologic findings on examination , and all but one had reduced visual acuity compared to baseline . among admissions with true relapses , 93% were treated with a course of steroids and 30% required plasma exchange . among patients with pseudorelapses who were ultimately determined to have an alternative , noninflammatory etiology for their worsening neurologic symptoms , 35% were initially treated with a course of high - dose steroids . the most common cause of pseudorelapses included infections , hyperglycemia , pancreatitis , hypomagnesemia , lupus , dysautonomia , medication withdrawal , medication overuse , and conversion disorder . for patients with true relapses , defined as an inflammatory attack of the cns causing neurologic dysfunction , delaying or deferring immunosuppressive treatment may result in permanent damage and increasing disability . however , unnecessarily immunosuppressing patients with nmo presenting with pseudorelapses can worsen metabolic syndromes , contribute to long - term steroid toxicity , and accrue costly , and avoidable , medical expenses . therefore , correctly distinguishing between true relapses and pseudorelapses in patients with nmo with new or worsening symptoms can significantly change their long - term medical and neurologic outcome . in this analysis , we found that worsening visual acuity is a sensitive biomarker of a true relapse of acute optic neuritis in patients with nmo . while inflamed optic nerves in multiple sclerosis are susceptible to uhthoff phenomenon and other metabolic abnormalities early in the first 2 months of the recovery period , our data support the observation that worsening visual acuity sustained for more than 24 hours is more concerning for a true relapse . in contrast , loss of motor function in patients with nmo is not a sensitive marker for a true relapse . pseudorelapses and true relapses were equally likely to present with worsening weakness with no threshold for severity of motor dysfunction that rules out pseudorelapses . numbness just failed to reach statistical significance , which may have been attributable to a small sample size . therefore , we conclude that for patients with nmo presenting with symptoms and signs of a transverse myelitis relapse , an mri is necessary to rule out a pseudorelapse . first , data collection for this retrospective study was based on extraction of relevant patient information from electronic medical records . second , selection bias is present because johns hopkins hospital is a tertiary nmo referral center ; however , this bias applies to both the relapse and pseudorelapse groups . third , our definition of a true relapse based on mri evidence may be too restrictive as we did not look for other evidence of inflammation such as spinal fluid pleocytosis , in all pseudorelapse cases . and finally , our study is limited in sample size because of the rarity of nmosd and the number of nmosd relapses and pseudorelapses that met our strict gold standard criteria . r.a.k . : contributed to the design and conceptualization of the study , analysis and interpretation of the data , and drafting of the manuscript . m.a.m . : contributed to the design and conceptualization of the study , analysis and interpretation of the data , and drafting of the manuscript . m.l . : contributed to the design and conceptualization of the study , analysis and interpretation of the data , and drafting of the manuscript . m. levy served on the scientific advisory board for asterias , chugai , alexion , is an editorial board member for multiple sclerosis and related disorders , holds a patent for an aquaporin-4 sequence that elicits pathogenic t cell response in an animal model of neuromyelitis optica , consulted for guidepoint global , gerson lehrman group , cowen group , received research support from viropharma / shire , acorda , apopharma and sanofi , genzyme , alnylam , alexion , terumo bct , ninds , guthy - jackson charitable foundation .

objective : the purpose of this study was to review cases of neuromyelitis optica spectrum disorder ( nmosd ) relapses and pseudorelapses to identify early features that differentiate between them at onset of symptoms.methods:this was a retrospective analysis of 74 hospitalizations of patients with nmosd who were admitted to the johns hopkins hospital for workup and treatment of a presumed relapse . standard workup included mri and blood and urine testing for metabolic and infectious etiologies . the gold standard for a relapse was defined as new or worsening symptoms and a change in neurologic examination correlating with a new or enhancing mri lesion . a pseudorelapse was a clinical exacerbation with similar symptoms and signs but the mri was negative , and workup identified an alternative cause for the symptoms that , when treated , resulted in the improvement of neurologic symptoms . factors considered to be early predictors of relapses vs pseudorelapses were analyzed using the fisher test.results:among 74 nmosd hospitalizations for presumed relapse , 57 were confirmed relapses while 17 had a negative mri and an identifiable cause of pseudorelapse . the most common causes of pseudorelapse were infection , pain , and dysautonomia . the only early predictor that reliably differentiated relapse from pseudorelapse among this nmosd patient population was vision loss ( p = 0.039 ) . race , sex , presentations of weakness , numbness , and bowel / bladder dysfunction , white blood cell count , and urinary tract infection were not different among patients with relapses vs pseudorelapses.conclusions:vision loss in nmosd is strongly suggestive of a true relapse vs a pseudorelapse . pseudorelapses localized to the spinal cord in patients with previous myelitis presented similarly to true relapses and could only be ruled out by a negative mri .

fine needle aspiration cytology ( fnac ) has been applied routinely as a useful and indispensable method to diagnose thyroid lesions . however , it is still quite difficult to establish a precise diagnosis of follicular lesions of the thyroid preoperatively by cytology . the present study was undertaken to analyse the usefulness of quantitative estimations of various cytological nuclear features in specimens obtained by preoperative fnac that were confirmed by histopathological examination . the study was conducted on 36 patients who presented to the surgical outpatient department with thyroid lesions . all 36 cases were subjected to fine needle aspiration ( fna ) and tissue sections were obtained subsequently . a concise clinical history , examination , and details of relevant investigations were also obtained . these were helpful in reaching a probable clinical diagnosis as well as in cytohistological evaluation and formulations of the pathological diagnosis . the data included 10 cases each of adenomatoid goiter , follicular neoplasm , papillary carcinoma , 4 cases of medullary carcinoma and 2 cases of anaplastic carcinoma . their ages ranged from 28 to 50 years ( average 45 years ) , and there were nine females and one male . the stained smears were examined with a standard microscope connected to a computerised video system and analyzed with image analyzer proplus v software . using 200 magnifications , three to five fields of vision were sampled randomly and a minimum of 10 nuclei per case were measured automatically and calculated . overlapping of the cells , oddly shaped nuclei and degenerative cells were excluded from the study . the mean nuclear area and the mean nuclear perimeter [ figure 1 ] were measured by the calculations of pixels corresponding to the nuclei for the evaluation of the nuclear size in each case . to determine the variation in shape , the circular rate and the largest to the smallest dimension ratio of the nuclei ( ls ratio ) were calculated [ figure 2 ] . in a round circle , if the object is elliptical , the circular rate becomes < 1 ; in contrast , the ls ratio is higher than 1 . the coefficient of variation of the nuclear area ( nacv ) was calculated by expressing the variation in size in an individual case . statistical differences were determined by the analysis of variance ( anova ) test , both within the group and in between the groups . aspirate showing thyroid follicular epithelial cells highlighting nuclear perimeter ( h and e , 200 ) aspirate showing thyroid follicular epithelial cells highlighting the largest to smallest ( l / s ) ratio ( h and e , 200 ) the study examined 10 cases each of adenomatoid goiter , follicular neoplasm , papillary carcinoma , 4 cases of medullary carcinoma and 2 cases of anaplastic carcinoma . all clinical data , including the patient 's age , gender and tumor size , revealed no statistically significant difference among the five groups . among the parameters for the quantitative morphometrics of nuclei , the mean nuclear diameter and the perimeter were higher in anaplastic carcinomas and were the least for follicular neoplasms . the circular rate was significantly higher in the group with adenomatous goiter than with follicular neoplasm ( p < 0.05 ) . the adenomatous goiter patients had a higher ls ratio than the patients with follicular neoplasm ( p < 0.05 ) . the nacv value was 44.24 7.76% in adenomatous goiter , 24.02 4.11% in follicular neoplasm and 66.17 13.88% in papillary carcinoma which showed significant differences between all the groups ( p < 0.0001 ) . the data of the nuclear parameters are shown in tables 2 and 3 and figures 36 . clinical characteristics of patients chart depicting nuclear area among variants ( ag adenomatoid goiter ; fn follicular neoplasm ; pc papillary carcinoma ; mc medullary carcinoma ; ac anaplastic carcinoma ) chart depicting perimeter among variants ( ag adenomatoid goiter ; fn follicular neoplasm ; pc papillary carcinoma ; mc medullary carcinoma ; ac anaplastic carcinoma ) chart depicting circular rate among variants ( ag adenomatoid goiter ; fn follicular neoplasm ; pc papillary carcinoma ) chart depicting ( l / s ) largest to smallest ratio among variants ( ag adenomatoid goiter ; fn follicular neoplasm ; pc papillary carcinoma ; mc medullary carcinoma ; ac anaplastic carcinoma ) however , it is difficult to establish a precise diagnosis of follicular lesions of thyroid preoperatively by cytology . the potential significance of this technique is to distinguish between benign , borderline and malignant lesions , for objective grading of invasive tumors , prediction of prognosis and therapeutic response . morphometry has been described for more than a century because the histological characteristics of normal and abnormal cells have been used as a measure of prognosis and as a way of predicting the cause of the disease . while adaptation of quantitative morphometric analysis as a clinical tool has been discussed in the literature for over 30 years , the usefulness of this approach has helped in cytological grading of breast lesions , but has not yet received widespread acceptance in thyroid lesions owing to limited references and subjectivity.[16 ] rajesh et al . studied histopathologically proven 19 cases of lobular carcinoma , 30 cases of ductal carcinoma , 10 cases of borderline lesions and 20 cases of benign breast lesions . anova showed that morphometric data may be useful in distinguishing invasive lobular carcinoma from infiltrating ductal carcinoma on cytological smears . however , data were not helpful in distinguishing benign and borderline lesions from invasive lobular carcinoma . nuclear area ( na ) and nacv were compared with prognostic factors and this analysis reflected the chemosensitivity and the risk of recurrence . there are studies where morphometry has been applied to other organs like nasopharynx , skin , urinary bladder and colon . in our study , we evaluated 10 cases each of adenomatoid goiter , follicular neoplasm , papillary carcinoma , 4 cases of medullary carcinoma and 2 cases of anaplastic carcinoma . the circular rate was significantly higher in the group with adenomatous goiter than with follicular neoplasm . also reported that nuclear features were not helpful in differentiation of follicular carcinomas from adenomas . nagashima et al . also evaluated variation in nuclear size by using nacv which showed significant differences among follicular carcinomas , adenomas and adenomatous goiters . in our study , the circular rate was higher in papillary carcinoma when compared to medullary carcinoma , which was not documented in any of the studies . fernandez - lopez et al . evaluated in their study , the prognostic value of the colorectal cancer in 90 patients . it was noticed that the patients with greater nuclear diameters also had a significant poor prognosis than the patients with cells of smaller diameter . this study asserted that the variations could be related to the survival of these patients . analyzed nuclear parameters like nuclear area , axis minor , diameter minor , radius minor , perimeter area in oligodendroglioma and found it to be statistically significant with regard to grading of oligodendrogliomas . studies including larger series of cases investigating detailed nuclear morphometric analysis of subtypes of thyroid carcinoma with longer periods of observation are required in order to demonstrate the association between clinical outcome and morphometric parameters and in order to standardize the morphometric method by giving a suitable cut - off value of nacv in thyroid lesions . when correctly applied with appropriate cutoffs , morphometry can help in preoperative assessment and may act as an adjunct to morphological features in thyroid lesions .

aim : to evaluate the cytomorphometric features in fine needle aspiration cytology ( fnac ) of thyroid lesions.materials and methods : fnac of 36 thyroid cases was reviewed . the study included 10 cases each of follicular lesion , adenomatous goiter , papillary carcinoma , 4 cases of medullary carcinoma and 2 cases of anaplastic carcinoma . their ages ranged from 28 to 50 years , and there were nine females and one male . morphometric analysis was done on aspiration smears from 36 thyroid lesions . hematoxylin and eosin stained smears were examined using image analyzer proplus v software . morphological parameters measured included mean nuclear diameter , mean nuclear perimeter , mean nuclear area , circular rate , largest to smallest dimension ratio ( ls ratio ) and coefficient of variation of nuclear area ( nacv).statistical analysis : statistical evaluation was carried out using the analysis of variance ( anova ) test for the five variables , both within the group and in between the groups . the result was considered significant when p < 0.05.results:the follicular carcinomas had higher ls ratio than patients with adenomatous goiters . mean nuclear diameter and the mean nuclear perimeter were higher in anaplastic carcinomas when compared to other subtypes and were the least for follicular neoplasms.conclusion:when correctly applied , quantitative estimation of cytological nuclear features can play an important role in preoperative assessment and can complement morphological features in thyroid lesions .

double dislocations of the thumb joints have only been reported on four previous occasions , in all cases reported to date , the joints have dislocated dorsally . we present the case of a 26-year - old male patient with simultaneous volar dislocations of the carpometacarpal and metacarpophalangeal joints of the thumb . there was delayed operative treatment of this injury with ligament reconstruction and stabilization of the metacarpophalangeal joint . this rare case provides a mechanism to this type of injury , highlights the importance of initial , and repeated clinical and radiographic review , highlights the soft tissue component to this injury , and demonstrates how even delayed treatment can result in a good functional outcome . the thumb joints are vital to the co - ordinated , multidirectional and precise movements of the hand . the thumb is positioned in a perpendicular plane to the other fingers , with the saddle - shaped carpometacarpal ( cmc ) joint providing six different planes of movement . the metacarpophalangeal ( mcp ) joint of the thumb is more like an interphalangeal articulation with movements restricted to one plane . dislocations of joints in the hand are relatively common ; however multiple dislocations of the thumb joints have been rarely described [ 1 - 6 ] . these dislocations involve high - energy axial loading injuries to the thumb , and can also be associated with fractures and ligament disruption . stiffness and pain after injuries to these joints can result in significant impact on activities of daily living . there have been four other reports of double dislocations of the thumb in the literature . our report of simultaneous volar dislocations of both of these joints is the first to be described . a 26-year - old right - handed male horse - trainer injured his right hand while riding , as he raised his arm to protect himself from a low branch . he presented to the accident and emergency department with a painful and obviously deformed right thumb . this was a closed isolated injury , and he had no neurological or vascular deficit of the affected thumb . there was also a fracture of the volar aspect of the base of the first metacarpal , which appeared to be an avulsion - type ( fig . 1 ) . ap and lateral radiographs of the initial injury under local anaesthesia block , the two dislocations were reduced with longitudinal traction , and the thumb was immobilized in a bennett s cast . upon review in fracture clinic one week later , the position of the cmc joint was excellent , but there was slight radial translation at the mcp joint ( fig . the patient declined operative intervention at this stage , and was maintained in his thumb cast . the patient failed to attend subsequent clinic appointments , but was reviewed again four weeks after the injury . unfortunately in the interim , the patient had attended a minor injuries department and had his cast changed ( without a new x - ray ) after soiling it while at work . at this stage the cmc joint was again well reduced , but there was approximately 30 degrees of radial angulation of the proximal phalanx at the mcp joint ( fig . a dorsal approach was taken over the mcp joint in order to examine both collateral ligaments . the radial collateral ligament was intact but the ulnar collateral ligament was completely ruptured , with disruption of the capsule extending around to the dorsal aspect of the joint . the ulnar collateral was repaired by tying the ligamentous attachments from the metacarpal , to mitek ( de puy mitek , warsaw , in , usa ) sutures anchored into the proximal phalanx . finally the mcp joint was temporarily immobilized with a kirschner ( k ) wire ( fig . ap and lateral radiographs one week post - operatively post - operatively the patient continued to work with horses , despite advice to the contrary . the kirschner wire was removed three weeks post - operatively due to a superficial pin site infection , which was successfully treated with systemic oral antibiotics ( amoxicillin / clavulanic acid ) . the patient was working and able to perform most of his manual tasks , although he complained of weakened grip strength . he was found to have considerable stiffness at the 1st mcp joint , with range of movement limited from 0 to 30 degrees at 12 months the patient was pain free without restriction of function , and although he could fully extend his mcp joint , he could only flex to 50 degrees only ( compared to 90 degrees on the contralateral side ) . double dislocations of thumb joints are rare , there are only six previous reports of concurrent dislocations of the cmc and mcp of the thumb , and of these only one report also includes an associated fracture at the base of the thumb . interestingly , in the other case reports , both the cmc and mcp dislocated dorsally . the accepted mechanism of this injury is a longitudinally directed force with hyperextension at the mcp , and slight flexion at the cmc joint . when questioned he described gripping the reins with hands together , and then raising both arms above his head for protection just prior to impact . this would cause his wrists to be flexed and radially deviated , with thumb metacarpals extended , and phalanges flexed . the authors feel that a longitudinally directed force with the thumb in this position would account for this unique injury . in all of the previous reports , the cmc joint was unstable and required operative stabilization ; with k - wires in four cases , and ligament reconstruction ( eaton s procedure ) in two cases [ 1 - 6 ] . in two of these case reports , the radial collateral ligament of the mcp joint was unstable , and in another the ulnar collateral ligament was unstable . all of these ligaments required repair , with additional k - wire fixation in one of these cases [ 2 - 6 ] . in their report of concurrent cmc and mcp joint dislocations , drosos et al categorize mcp joint dislocations as simple ( reducible with a closed technique ) and complex ( irreducible with closed technique , requiring open reduction ) . it has been postulated that the energy required to produce double dislocations causes more ligamentous damage , and hence greater instability that either injury on its own . four weeks after the injury , the cmc joint of our patient was still in a good position , and although the lateral view of the mcp showed no subluxation / dislocation , the antero - posterior view of the mcp joint showed further radial angulation . even though there was slight translation at the mcp joint at the one - week review , we were forced to opt for conservative management because the patient declined operative intervention . certainly we did no harm by delayed operative fixation until three weeks later . in the case described by ibrahim and noor , the patient had both cmc and mcp joints dislocated for five weeks before operative repair was performed ; the cmc joint was stabilized with a sole k - wire , and at the mcp joint a k - wire plus radial collateral ligament repair . farzan et al , report a case of a volar dislocated cmc which presented 3 months after the initial injury , due to pain and an inability to pinch and perform opposition . this required open reduction , reconstruction with eaton s procedure , k - wire stabilization , and a thumb spica for six weeks . at four month follow up thumb opposition was possible and pain - free , pinch and grip were near normal compared to the contra - lateral side , and the global reduction in thumb movement was only 10 degrees . this injury can be treated non - operatively if assessed accurately at presentation , with close follow up . marcotte and trzeciak , described a case of cmc and mcp dislocations , which were stable after closed reduction , with only slight laxity of the ulnar collateral ligament . although the option of surgical stabilization was discussed , the joints remained anatomically reduced for the 5 weeks the patient remained in a cast . the patient continued to have clinical and radiological follow up monthly , for 3 months to confirm the joints remained reduced . at 2 year follow up , the thumb was pain free , stable , with a good range of movement and no evidence of arthritis . in our report , the patient was followed up for one year , similar follow up to the other reports . moore et al followed up their patient for 9 years , with no evidence of arthritis or instability . however , gerard et al , did report degenerative changes in the cmc and mcp joints in a patient with double dislocations . given the severity of this injury , it is certainly conceivable that these patients would develop symptomatic degenerative changes in the long term . our literature review suggests there are many options for the treating this injury : operative or conservative treatment ; treating both joints as separate injuries or together ; and ligamentous repair and/or k - wire fixation . the key to these decisions seems to rest at the initial clinic review after successful reduction . if instability can be assessed here and operative or nonoperative decisions made , then management can be tailored accordingly . furthermore these injuries need weekly radiographic follow up if conservative treatment is opted for , so that any further subluxation or dislocation is highlighted early . although the patient opted for initial conservative management , and even with delayed operative stabilization of one joint , the patient had a good functional outcome . double dislocation of cmc and mcp joints of the thumb is rare entity ; however it behaves similar to isolated injuries .

introduction : multiple dislocations of joints in the hand are rare . double dislocations of the thumb joints have only been reported on four previous occasions , in all cases reported to date , the joints have dislocated dorsally.case report : we present the case of a 26-year - old male patient with simultaneous volar dislocations of the carpometacarpal and metacarpophalangeal joints of the thumb . there was delayed operative treatment of this injury with ligament reconstruction and stabilization of the metacarpophalangeal joint.conclusions:this rare case provides a mechanism to this type of injury , highlights the importance of initial , and repeated clinical and radiographic review , highlights the soft tissue component to this injury , and demonstrates how even delayed treatment can result in a good functional outcome .

murine or endemic typhus is caused by rickettsia typhi , formerly r. mooseri ( 1 ) . classic murine typhus is a zoonosis maintained in rats ( rattus rattus and rattus norvergicus ) and transmitted to humans through damaged skin by infected feces from the oriental rat flea ( xenopsylla cheopis ) ( 2 ) . new patterns of disease ( murine typhus - like disease ) have been described in recent years , and a new species of rickettsia ( r. felis ) that causes a similar clinical picture has been identified ( 13 ) . new modes of infection have been identified , including infection through inhalation of flea feces and transmission by different types of fleas ( ctenophtephalis felis ) and from different reservoirs ( e.g. , dog , cat , and opossum ) . murine typhus occurs worldwide , particularly in warm and humid climates ( 1 ) . in spain , two seroepidemiologic surveys , in salamanca and madrid ( central / western spain ) , yielded seroprevalence rates of 12.8% and 68% , respectively , in the general population ( 4,5 ) . , murine typhus is an important cause of fever of intermediate duration ( 6 ) , and in canary islands , 10 autochthonous cases have been reported from tenerife ( 7 ) . for this reason , we include serologic testing for r. typhi in the evaluation of patients with fever of intermediate duration . adult ( > 14 years of age ) in- and outpatients at the hospital universitario insular of las palmas with a serologic diagnosis of murine typhus during december 1 , 2000 , through july 30 , 2002 , were included in our study . a case was defined by an immunoglobulin ( ig ) m titer > 1 : 40 , or a fourfold or higher increase in igg titers against r. typhi by direct immunofluorescence test in 8 weeks ( biomeriux , france ) , or both . antibodies against other agents that may cause a fever of intermediate duration ( e.g. , coxiella burnetii , r. conorii , leptospira sp . , twenty - two patients ( 21 men , 1 woman ) , with a mean age of 28 years ( range 14 to 76 years ) , were included . murine typhus was more frequent in summer ( figure 1 ) . no case aggregation was observed . all patients reported contact with animals ( 13 with dogs , 6 with horses , 5 with goats , 2 with cats , and 1 with camels ) . all patients had a high fever ( mean 39.3c ) during a mean of 10 days ( range 7 to 20 days ) . a light maculopapular , nonpurpuric rash , with rather centripetal distribution , was a frequent finding ( 68.2% ) . for most patients , leukocyte counts were normal , mild leukopenia was detected in two patients , and mild leukocytosis in four patients . ten case - patients ( 45% ) had thrombocytopenia . in most patients ( 89.5% ) , the erythrocyte sedimentation rate was high ( 11 mm to 83 mm ) , and the activated partial thromboplastin time ( aptt ) was prolonged in six patients . aminotransferase elevation , usually four times above normal , was found frequently ; two patients had normal values . the plasma blood urea nitrogen was elevated ; plasma creatinine was above normal in three cases ( 13% ) . in 19 cases ( 87% ) , alterations were found in the urinalysis . fifteen patients had proteinuria and microhematuria with or without leukocyturia and granular casts , with a negative nitrite reaction . in two patients , eight patients fulfilled both diagnostic criteria ( igm > 1:40 plus seroconversion ) , eight patients had initial igm elevation , and six seroconverted without igm increase . fifty percent of the patients had serologic evidence of past infection with c. burnetii ( 12/22 ) or r. conorii ( 3/22 ) and , in one case , of co - infection with c. burnetii . patient 6 was admitted with acute respiratory failure , lung infiltrates , and acute renal failure ( plasma creatinine 2.8% mg ) , microhematuria , and leukocyturia . intravenous fluids , doxycycline , ciprofloxacin , and methylprednisolone ( 1 g ) were administered , and the patient rapidly improved . patient 16 had a dry cough and acute renal failure ( plasma creatinine 2.7% mg ) and later become disoriented . a cranial contrast computed tomography scan was normal , and cerebrospinal fluid ( csf ) showed mononuclear pleocytosis ( 90 cells/l ) , protein 70 mg / dl , and normal glucose . finally , patient 21 had a progressive meningeal syndrome , csf showed mononuclear pleocytosis ( 19 cells/l ) , increased protein ( 49 mg / dl ) , and normal glucose . fever of intermediate duration has been defined by others in spain as fever of 7 to 28 days without localizing signs ( i.e. , respiratory , digestive , urinary , or neurologic ) , plus the absence of diagnostic clues after a complete evaluation ( 6 ) . a few diseases can account for most cases of this type of fever ( mainly q fever , brucellosis , boutonneuse fever , leptospirosis , mononucleosic syndromes , and murine typhus ) . in our area , therefore , in the meantime , identifying clinical data for empirical treatment is important . in our study , the number of cases per year is 12 , higher than that in other areas of spain ( 6 ) , israel ( 8) , or the united states ( 9,10 ) , with higher rate in summer . all patients had direct contact with animals as reported by others ( 9,10 ) ; dogs were the most frequently cited animal ( 9,10 ) . the clinical features in our study are similar to those reported by others ( 6,913 ) with respect to those most frequent symptoms ( fever , headache , and arthromyalgia ) ( table 1 ) . the incidence of rash is similar to that reported by bernabeu ( 6 ) and whiteford ( 9 ) and higher than that in other series . reports of insect bites were more frequent in our study than studies from other areas ( bernabeu and silpapojakul ) , but more insect bites were reported from a texas study ( 9 ) . the laboratory findings in our study are similar to findings in other studies , although its relative frequency is variable ( table 2 ) . the frequency of anemia varies from 1% to 69% , leukopenia from 4% to 40% , and thrombocytopenia from 3% to 60% ( 6,911 ) . while 80% of the patients with q fever in our area have a prolonged aptt , 27% of the patients with murine typhus displayed this abnormal coagulation test . an elevation of aminotransferases in the range of viral hepatitis was common , but hyperbilirubinemia is exceptional and usually associated with alcoholism , co - infection , or glucose-6-phosphate dehydrogenase deficiency . tx , texas ; esr , erythrocyte sedimentation rate ; aptt , activated partial thromboplastin time ; bun , blood urea nitrogen ; ldh , lactate dehydrogenase ; ast , aspartate aminotransferase ; alt , alanine aminotransferase ; ggt , gamma glutamic transferase . three patients had acute renal failure , and 87% had some abnormality in the urinalysis , mainly microhematuria . these data are in sharp contrast with the low incidence of urinary alterations found in other studies . some broad studies ( 6,9,10 ) do not report urinary abnormalities in murine typhus , though dumler et al . ( 13 ) reported microhematuria or proteinuria in 28% of their patients . in a study specifically focused on renal involvement in murine typhus , shaked et al . observed urinary abnormalities in 5 of 27 patients studied ( 8) to the best of our knowledge , 11 cases of acute renal failure have been related to r. typhi ( 9,11,14,15 ) . in general , our severe cases accounted for 13% ( one renopulmonary syndrome , one encephalitis , and one meningitis with renal failure ) . in summary , in canary islands , incidence of murine typhus seem to be higher , patients more frequently report contact with dogs , the frequency of complicated cases is higher , and the incidence of renal involvement is higher . these data define a clinical picture of murine typhus that is somewhat different for the canary islands . these differences could be attributed to age ( infantile versus adult series ) , mode of transmission or infection , or different strains of r. typhi . the diagnostic methodology was indirect , so cross - reaction with other rickettsiae can not be excluded ( 11 ) . moreover , in our area , dogs are frequently parasitized by the flea of cats , a well - known vector for r. felis ( 3 ) . finally , detecting urinary abnormalities in the setting of fever of intermediate duration , especially if associated with skin rash , thrombocytopenia , or hypertransaminasemia , in our geographic area is strongly suggestive of murine typhus .

murine typhus and murine - thypus - like disease are reemerging infectious diseases . in canary islands ( spain ) , a rather distinct clinical pattern characterized by higher incidence of complications , especially renal damage ( including acute failure and urinalysis abnormalities ) , is apparent and highly suggestive . it could be related to different strains of rickettsia typhi or other cross - reactive species .

fallopian tube prolapse after hysterectomy into the vaginal vault is a rare occurrence , although failure to recognized this has lead to its under reporting . since the first description of this condition by piozzi in 1902 , fewer than 100 cases have been reported so far , the majority following vaginal hysterectomy probably due to non closure of the vault and the pelvic peritoneum . it accounts for cumulative incidence of 0.5% with vaginal hysterectomy and 0.06% following abdominal hysterectomy . a 35-year - old , presented with symptoms of watery discharge per vaginum , lower abdominal pain , and dyspareunia of 1 month duration . she had undergone total abdominal hysterectomy with left salpingo - oophorecomy with right cystectomy 20 months back . per speculum examination revealed a polypoidal , strawberry colored growth 1.5 cm 1.5 cm , at the vaginal vault . histopathology revealed ciliated columnar lining polypoidal projections and papillae resembling tubal plicae , lamina propria showed chronic inflammatory cells along with few smooth muscle bundles clinching the diagnosis of prolapsed fallopian tube [ figures 1 and 2 ] . microphotograph showing fallopian tubal epithelium thrown into papillary folds , lamina propria showing congested blood vessels and dense chronic inflammatory infiltrate along with few smooth muscle bundles . ( h and e 10 ) microphotograph showing fallopian tube lining of pseudostratified ciliated columnar epithelium ( h and e 40 ) tubal prolapsed is seen commonly after vaginal hysterectomy as compared to abdominal hysterectomy and rarely following interposition and colpotomy . the first two cases to occur after abdominal hysterectomy were described in 1955 by funnel et al . the exact incident of fallopian tube prolapse is difficult to estimate since few cases may resolve before detection . the median age of presentation is 29 years ( range from 17 to 40 years ) . predisposing factors include postoperative fever , hematoma formation , poor physical state of the woman , insufficient vaginal preparation preoperatively , difficult surgical procedure , failure to achieve adequate hemostasis , failure to close vaginal cuff , profuse postoperative drainage vaginally and use of intraperitoneal vaginal drains and packs . the presentation can be soon after hysterectomy as early as 2 months , or up to 8 years afterwards . the diagnosis of ftb should be suspected when a red granular polypoidal mass is seen at the vaginal cuff protruding into the vagina after hysterectomy . the differential diagnosis includes , proliferative granulation tissue related to surgery , granuloma not related to surgery , malignant lesion and endometriosis . the easy passage of probe into the lumen of the tube will aid establishing the diagnosis . differential diagnosis on microscopy includes cysts of mesonephric and paramesonephric duct , vaginal adenosis , endometrosis , primary and metastatic adenocarcinoma . it can be misdiagnosed as malignancy as vaginal vault is not the site for columnar cells . the technique of management varies from partial vaginal excision to total vaginal excision to combined abdominal and vaginal approaches . while total vaginal salphingectomy may be sufficient to annul the chances of recurrence where adhesion and concomitant pelvic pathology is anticipated , a combined vaginal and laparoscopic approach is preferable . prevention of tubal prolapse can be achieved by suturing the adnexae high in the pelvis at abdominal hysterectomy , and the incidence decreased if the pelvic peritoneum is closed and the vault not drained . awareness of this complication will provoke more efficient referral and prevent inadequate treatment which prolong the patient 's distress .

fallopian tube prolapse into the vaginal vault is a rare complication after hysterectomy with adnexal preservation . it can occur following vaginal and abdominal hysterectomy , and rarely following interposition and colpotomy . histopathology is the only means of definitive diagnosis . prevention of tubal prolapse can be achieved by suturing the adnexae high in the pelvis at abdominal hysterectomy , and the incidence decreases if the pelvic peritoneum is closed properly .

since the first description by cabriolus in 1550 , few cases of urachal sinuses have been reported in literature . various types of remnants have been described and urachal sinus is the little common variety . diagnosis remains challenging due to the rarity of this lesion and the nonspecific nature of its symptomatology . a 22-year - old male patient , with no relevant past medical history , presented with a three days history of fever , abdominal pain , and umbilical discharge without digestive nor urinary symptoms . physical examination revealed an initial temperature of 38.9c , purulent umbilical discharge with erythema , and tender umbilical mass ( figure 1 ) . laboratory tests revealed marked leucocytosis of 24,000/mm and elevated c - reactive protein ( 42 mg / l ) . computed tomography scan confirmed the diagnosis of infected urachal sinus showing a heterogeneous collection with calculus and gas formation communicating with the umbilicus ( figures 2(a ) and 2(b ) ) . two days after apyrexia , cystoscopy and excision of the infected urachal sinus were performed simultaneously . an infraumbilical midline incision was used to excise the sinus and fibrous tract ( figure 3 ) . the urachus is a vestigial remnant of at least two embryonic structures : the cloaca , and the allantois . the tubular urachus normally involutes before birth , remaining as a fibrous cord between the transversalis fascia anteriorly and the peritoneum posteriorly and attaches the umbilicus to the bladder dome . histologically , it presents with 3 layers : an innermost layer of modified transitional epithelium similar to the urothelium , a middle layer of fibro - connective tissue , and an outermost layer of smooth muscle continuing the detrusor [ 1 , 3 ] . usually presenting in early childhood , urachal anomalies occur in a 2 : 1 male to female ratio with 2% ratio reported in adults . there are five types of urachal abnormalities : ( 1 ) patent urachus , in which the entire tubular structure fails to close ( 50% ) ; ( 2 ) urachal cyst , in which both ends of the canal close leaving an open central portion ( 30% ) ; ( 3 ) urachal sinus , which drains proximally into the umbilicus ( 15% ) ; ( 4 ) vesicourachal diverticulum , where the distal communication to the bladder persists ( 35% ) ; and ( 5 ) alternating sinus , which can drain to either bladder or umbilicus [ 4 , 5 ] . the commonly cultured microorganisms from the pus are escherichia coli , enterococcus faecium , proteus , streptococcus viridans and fusobacterium [ 4 , 5 ] . in our case , the clinical signs and symptoms are nonspecific , as urachal sinus is largely asymptomatic until they become infected . however , the presence of the triad of symptoms including a tender midline infraumbilical mass , umbilical discharge and sepsis should arouse suspicion of urachal sinus . differential diagnosis of this condition includes anomalies of the vitelline ducts ( such as meckel 's diverticulum ) , patent omphalomesenteric duct , infected umbilical vessel , appendicitis , or omphalitis . ultrasonography could help in establishing the diagnosis in 77% of patients . in our case , ultrasonography was not specific and computed tomography scan was used to confirm the diagnosis and analyse the connection to surrounding structures . urachal sinus can be complicated by stone and gaseous formation as was seen in our patient . other reported complications include rupture into the peritoneal cavity leading to peritonitis , uracho - colonic fistula , and neoplastic transformation . the risk of urachal malignancy in adults is high and the prognosis is poor . although the innermost layer of the urachus is mainly transitional cell , adenocarcinoma ( mostly mucinous ) is the predominant histological type . noninfected urachal sinus are usually removed in a single - step radical excision of the remnant which removes the entire lesion with or without a bladder cuff via open or laparoscopic surgical approach . this intervention is performed to ovoid recurrence following simple drainage and to prevent developing malignant transformation . in case of infection , a single - stage procedure backed with appropriate antibiotic therapy or 2-stage procedure involving initial incision and drainage , followed by later excision of the urachal remnant are adopted with uneventful postoperative course . presentation is atypical ; therefore , a high index of suspicion is required in order to achieve a diagnosis . ultrasound and computed tomography scan confirm the diagnosis and analyses the surrounding anatomical connections . an antibiotic regimen according to bacterial sensitivity is recommended prior to the surgical intervention . in order to prevent recurrence and malignant transformation , complete surgical excision with or without a bladder cuff is the standard treatment .

urachal affections are rare . their variable ways of presentation may represent a diagnostic challenge . urachal sinuses are a rare type of these abnormalities . they are usually incidental findings and remain asymptomatic unless a complication ( most commonly the infection ) occurs . infection of the urachal sinus would clinically present as purulent umbilical discharge , abdominal pain , and periumbilical mass . we report herein a case of infected urachal sinus in male adult . the diagnosis was suspected clinically and confirmed with ultrasonography and computed tomography scan . a preoperative cysto - fibroscopy showed normal aspect of the bladder and excluded sinus communication . an initial broad spectrum antibiotic therapy followed by complete excision of the sinus and fibrous tract without cuff of bladder has been therefore performed . the postoperative course was uneventful . no recurrence was observed after 18 months of followup . histological examination did not reveal any sign of malignancy .

chlamydia trachomatis ( c. trachomatis ) is an obligate intracellular human pathogen which is responsible for the most reported bacterial sexually transmitted disease worldwide . genital chlamydial infection has been identified as a major public health and there is an estimated annual incidence of around 92 million cases of chlamydial infections in the world ( 1 ) . although , infection with this organism can be asymptomatic in up to 80% of women ( 2 ) , it may give rise to urethral syndrome , salpingitis , pelvic inflammatory disease ( pid ) , tubal factor infertility and chronic pel vic pain ( 3 ) . infection of the female reproductive tract with c. trachomatis is one of the leading global causes of tubal factor infertility ( 4 ) , and leading causes of female factor infertility . in order to reduce the rate of pid and prevent development of reproductive sequelae , early diagnosis and treatment of chlamydial infection can be of great importance ( 5 ) . since the prevalence of chlamydial diseases is on the rise , development of sensitive , specific , and rapid methods to diagnose this infections cell culture , cytological tests for the detection of cytoplasmic inclusion bodies , direct immunofluorescence ( dfa ) , enzyme - linked immunosorbent assay ( elisa ) , dna hybridization techniques and polymerase chain reaction ( pcr ) are several laboratory methods which are used for the diagnosis of c. trachomatis ( 6 ) . studies indicate that pcr has a sensitivity of 97% to 100% and a specificity of 98% for detecting c. trachomatis . the sensitivity and specificity of cell culture are 85% and 100% , respectively ( 7 , 8) . therefore , cell culture is the gold standard for the diagnosis of c. trachomatis . in this study , we used a nucleic acid amplification method ( pcr ) to detect and evaluate the prevalence of c. trachomatis infection in woman with tubal infertility using cytobrush and cervical swab samples . we recruited 51 women with tubal factor infertility , confirmed by laparos - copy and hysterosalpingography , attending avicenna infertility clinic in tehran , iran between january 2010 and january 2011 . patients were 1948 years old ( mean 33.3sd years ) and their age at first intercourse was 23.57.2 ranging from ( 1043 years ) . swab and cytobrush samples were placed in pbs and 2sp ( sucrose - phosphate ) transport media , respectively , and were sent to laboratory under suitable protective ( 4c ) condition . dna was extracted from cervical swabs using dna extraction kit ( qiagen , germany ) according to the manufacturer 's instructions . primers for amplification of orf8 gene were : forward 5-ctaggcgtttgtactccgtca-3 and reverse 5-tcctcaggagtttatgcact-3. after setting up , pcr was performed . the amplification program consisted of a first cycle of a 5 min denaturation at 94c , followed by 37 cycles , each lasting 40 s at 94c , 45 s at 61.6c , and 89 s , at 72c , with a final extension for 5 min at 72c . the volume of each pcr tube was 50 l containing 5 l dna , 25 mmol mgcl2 , 25 mmol dn tp , 1 mmol forward and reverse primers and 1.5 unit taq polymerase . the amplified pcr product ( 5 l ) was analysed by electrophoresis on 1.5% w / v agarose gel containing 0.5 g / ml of ethidium bromide . cytobrush samples were used for isolation of c. trachomatis in cycloheximide treated mccoy cell monolayer , which was grown on cover slip cultures in 12well plates using rpmi supplement with 10% fetal bovine serum ( fbs ) , 2 mm l - glutamine and antibiotics . after vigorous vortexing , 200 l of each cytobrush specimen was inoculated on the cells . the plates were centrifuged for 1 hr ( 1500 g , 30c ) and after replacement of medium , they were incubated at 37c for 4872 hr the monolyers were fixed in methanol and inclusion bodies were detected by giemsa staining . chi square ( ) , fisher 's exact test , and independent t - test , were used for significance analysis . a p - value smaller than 0.05 was regarded as statistically significant . we recruited 51 women with tubal factor infertility , confirmed by laparos - copy and hysterosalpingography , attending avicenna infertility clinic in tehran , iran between january 2010 and january 2011 . patients were 1948 years old ( mean 33.3sd years ) and their age at first intercourse was 23.57.2 ranging from ( 1043 years ) . swab and cytobrush samples were placed in pbs and 2sp ( sucrose - phosphate ) transport media , respectively , and were sent to laboratory under suitable protective ( 4c ) condition . dna was extracted from cervical swabs using dna extraction kit ( qiagen , germany ) according to the manufacturer 's instructions . primers for amplification of orf8 gene were : forward 5-ctaggcgtttgtactccgtca-3 and reverse 5-tcctcaggagtttatgcact-3. after setting up , pcr was performed . the amplification program consisted of a first cycle of a 5 min denaturation at 94c , followed by 37 cycles , each lasting 40 s at 94c , 45 s at 61.6c , and 89 s , at 72c , with a final extension for 5 min at 72c . the volume of each pcr tube was 50 l containing 5 l dna , 25 mmol mgcl2 , 25 mmol dn tp , 1 mmol forward and reverse primers and 1.5 unit taq polymerase . the amplified pcr product ( 5 l ) was analysed by electrophoresis on 1.5% w / v agarose gel containing 0.5 g / ml of ethidium bromide . cytobrush samples were used for isolation of c. trachomatis in cycloheximide treated mccoy cell monolayer , which was grown on cover slip cultures in 12well plates using rpmi supplement with 10% fetal bovine serum ( fbs ) , 2 mm l - glutamine and antibiotics . after vigorous vortexing , 200 l of each cytobrush specimen was inoculated on the cells . the plates were centrifuged for 1 hr ( 1500 g , 30c ) and after replacement of medium , they were incubated at 37c for 4872 hr the monolyers were fixed in methanol and inclusion bodies were detected by giemsa staining . chi square ( ) , fisher 's exact test , and independent t - test , were used for significance analysis . a p - value smaller than 0.05 was regarded as statistically significant . fifty - one infertile women who had failed to have children after one year of intercourse without contraception were enrolled in this study . about 67.4% of the aptients had a history of vaginal infection ; 86.0% had primary infertility , and 64.7% were infertile for more that five years . we amplified a fragment with a length of 200 bp during pcr and visualized it on 1.5% agarose gel ( figure 1 ) . lane 1 , dna size markers ; lane 2 - 5 , positive patients for c. trachomatis ; lane 6 , positive control ; lane 7 , negative control maccoy cell line ; a : before inoculation of specimen ; b : after inoculation and c : after gimsa staining according to the result presented in table 1 , of 51 samples , 6 ( 11.7% ) were positive by pcr and 2 ( 3.9% ) by cell culture ( table 1 ) . pcr and cell culture results in tfi patients the mean age at first intercourse was 30.679.89 and 22.726.45 in positive and negative pcrs , respectively , ( p < 0.05 ) . moreover , a significant relation was seen between the age at first intercourse and the risk of infection ( p < 0.05 ) . about 18.8% of patients with an infertility duration less than 5 years versus 9.1% of those with an infertility duration more than 5 years had positive pcr results ( p < 0.05 ) , while such a relation was not observed for cell culture . t - test showed no significant relationship between the patients age and c. trachomatis infection , but the possibility of infection increased significantly with increased age of marriage ( p < 0.05 ) . infertility duration had a certain correlation with pcr results but it was not significant ( p = 0.056 ) and showed no relationship with results obtained from cell culture . chi - squarea and fisher 's exact test were used to evaluate the relationship between symptoms of genital infections with pcr and culture results . none of the symptoms such as genital discharge , dysuria , genital itching or pelvic showed any significant association with the infection ( table 2 ) . genital chlamydial infection , caused by the sexually transmitted bacterium c. trachomatis , is currently the most prevalent sexually transmitted infection throughout the world ( 1 ) . c. trachomatis is among the most common microorganisms interfering with female fertility and is considered the most important cause of tubal obstruction and pid ( 9 ) . therefore , screening and treatment of chlamydial infection in order to reduce its transmission and prevent pid and its long - term sequelae including infertility , chronic pain , pid and ectopic pregnancy are of great value . about 10% to 20% of female infertility although c. trachomatis infection will effectively clear in most women , but infection persists in some and may ascend to the upper genital tract and increase the risk of tubal factor subfertility ( 10 ) . in the current study , we evaluated women with tubal factor infertility for c. trachomatis infection by pcr and cell culture . based on several investigations , prevalence of c. trachomatis infection varies with the population under study and the type and sensitivity of the detection methods used . for example , the prevalence of chlamydial dna in fresh tissue specimens from 14 women with tubal factor infertility was investigated in uk . c. trachomatis dna was detected in 43% of these patients ( 11 ) . the prevalence was 12% in our study , which is comparable with the results of other studies carried out in iran , suggesting the lower incidence of this infection in our community . assessment of c. trachomatis infection in iranian women with cervicitis was done earlier by direct fluorescent antibody ( dfa ) and pcr techniques . about 15.5% of 142 samples were positive for chlamydia based on pcr results , while dfa results showed a 14.1% positivity ( 12 ) . these data are comparable with pcr results of the current study , although the values had been higher for cell culture . of 110 indian women with primary and secondary infertilities , c. trachomatis was detected in 25 ( 22.72% ) cases by cell culture method ( 13 ) , while we detected the organisms this way in only 4% of the cases . this difference could be due to different sample sizes and populations and perhaps better cell - culture techniques used in their study . endocervical swabs from 109 women attending gynecology and infertility clinics in gaza were analyzed using pcr and enzyme immunoassay techniques . the results showed that overall prevalence rate of c. trachomatis to be 20.2% ( 14 ) . in another study , the rate of c. trachomatis infection evaluated by pcr was 27.2% and 18.9% in asymptomatic and symptomatic women , respectively ( 15 ) . in the present study we used pcr and cell culture techniques to detect c. trachomatis in cervical swabs and cytobrush specimens . based on pcr results , the prevalence of c. trachomatis in the study population was 12% , while cell culture detected the organism in only 4% of the cases . in agreement with several other studies , our results showed that pcr is more sensitive than cell culture in detecting chlamydial infections . although culture was earlier considered the gold standard , its sensitivity is as low as 75% to 85% even in expert laboratories and it takes 3 to 6 days to complete ( 16 ) . but nucleic acid amplification methods , such as pcr , have high sensitivity and specificity and the results could be obtained within a short time . furthermore in this method specimens will be stable during transport and can be subjected to delays between collection and processing without significant loss of sensitivity ( 17 ) . since undetected and untreated chlamydial infections may lead to many reproductive sequelae , such as infertility , the results of the current study suggest that all infertile women should referred to infertility clinics and be screened for c. trachomatis in our community .

background chlamydia trachomatis is the most reported bacterial sexually transmitted disease , especially among young women worldwide . the aim of this study was comparison the prevalence of chlamydia trachomatis infection in woman with tubal infertility by means of pcr and cell culture techniques.methodsfifty-one women with confirmed tfi were enrolled in this study in ( avicenna infertility clinic ) between january 2010 and january 2011 . cervical swab and cytobrush specimens were collected from each patient by gynecologists and sent to laboratory in transport media . detection of chlamydia trachomatis in samples was performed using pcr and bacteria culture in maccoy cell line . the data were analyzed by fisher 's exact test and independent t - test . statistical significance was established at a p - value < 0.05.resultsa significant relation was observed between increased the age of first intercourse and chlamydial infection . six ( 11.7% ) samples had positive pcr result , whereas cell culture results were positive in only 2 ( 3.9% ) samples . a significant relation was also identified between the duration of infertility and infection ( p < 0.05 ) by pcr versus cell culture method.conclusionthe results showed that pcr is a rapid method , compared to cell culture for detecting chlamydial organism . it also became clear that the age at first intercourse is important to predict the likelihood of chlamydia trachomatis .

aesthetics and color of the teeth are reflection of systemic health . several intrinsic and the extrinsic factors can influence tooth color . while intrinsic discoloration of the tooth may be caused following trauma , loss of vitality , endodontic treatment , and restorative procedures apart from known local and systemic factors . extrinsic tooth stains occur due to poor tooth brushing techniques , smoking , dietary intake of tannin - rich foods , excess use of chlorhexidine mouth wash , and/or consumption of metal salts . many techniques have been evolved for the purpose of managing discolored non - vital tooth . amongst these techniques , inside / outside bleaching technique is an effective and conservative treatment option compared to placing restorations . in this technique , bleaching is carried out within the tooth and on the outside of the tooth simultaneously . here a 30-year - old female patient reported to the institution with a complaint of discolored upper front tooth and desired the discolored tooth be treated [ figure 1 ] . on examination , intra oral periapical radiograph with maxillary left central incisor revealed a complete root canal obturation without periapical pathology . patient was explained about the bleaching procedure and consented for the inside and outside in - office power bleaching therapy to correct discolored tooth . discolored maxillary left central incisor tooth using rubber dam , the tooth to be bleached was isolated and cleaned with pumice and the shade was recorded [ figure 2 ] . the obturated material was removed from the tooth up to 2 mm below the gingival margin . 1 mm glass ionomer cement ( type 1 , gc corporation , singapore ) was placed over the gutta - percha . using 37% phosphoric acid , pulp chamber was etched for 30 - 60 s , washed and dried , which resulted in the opening of dentinal tubules . following this , 38% hydrogen peroxide ( pola office ultradent , usa ) , bleaching agent was mixed into thick paste and placed immediately in the pulp chamber and on the external labial surface of the tooth [ figure 3 ] . after 10 - 15 min , the tooth was cleansed and the residue bleach inside was removed with water using a high suction unit . tooth shade was evaluated , which matched with adjacent tooth and satisfactory results were achieved [ figure 4 ] . the access and the partially empty pulp chamber were restored using tooth colored composite resin . internal and external bleaching in progress guma barrier applied for external bleaching post bleaching appearance of the discolored teeth using rubber dam , the tooth to be bleached was isolated and cleaned with pumice and the shade was recorded [ figure 2 ] . the obturated material was removed from the tooth up to 2 mm below the gingival margin . 1 mm glass ionomer cement ( type 1 , gc corporation , singapore ) was placed over the gutta - percha . using 37% phosphoric acid , pulp chamber was etched for 30 - 60 s , washed and dried , which resulted in the opening of dentinal tubules . following this , 38% hydrogen peroxide ( pola office ultradent , usa ) , bleaching agent was mixed into thick paste and placed immediately in the pulp chamber and on the external labial surface of the tooth [ figure 3 ] . after 10 - 15 min , the tooth was cleansed and the residue bleach inside was removed with water using a high suction unit . tooth shade was evaluated , which matched with adjacent tooth and satisfactory results were achieved [ figure 4 ] . the access and the partially empty pulp chamber were restored using tooth colored composite resin . internal and external bleaching in progress guma barrier applied for external bleaching post bleaching appearance of the discolored teeth different options are used in the treatment of discolored endodontically treated anterior tooth . in - office , the bleach has many advantages over the conventional options and is especially , useful in treating the crown and intrinsic discoloration of the tooth . the in - office bleach , which was used in this patient , is discussed here . for a tooth that had discolored following de - vitalization , bleaching is preferable to the crown placement when the tooth is relatively intact . in vitro studies suggested that it is the bulk of the remaining tooth structure rather than the dowel that provides strength and resistance to fracture of the endodontically treated tooth . a previous study reported no significant difference in the success rate achieved between anterior non - vital teeth with and without crowns . trabert et al . also concluded no appreciable difference in the resistance to fracture between untreated anterior teeth and endodontically treated anterior teeth . further despite small proximal restorations , most pulp less anterior teeth with sound coronal tooth structure can be conservatively restored with the lingual composite restoration . interestingly , there was no advantage in reinforcement by cementing posts in endodontically treated anterior teeth . in contrast placement of a dowel and crown in such a tooth is likely to weaken rather than strengthening it . for instance , intact endodontically treated anterior teeth with natural crowns demonstrate greater strength against fracture than teeth built - up with pin retained amalgam cores or cast gold dowel cores . further central incisors were three times more resistant to fracture than the teeth , which were restored with dowel core and crowns . it may mask the discoloration , but also may undergo fracture , debonding , and marginal leakage . however , it requires tooth preparation and is irreversible . considering the above reasons in - office the major advantage of this approach is ( 1 ) it is more conservative ( 2 ) more effective in stain removal and ( 3 ) significantly improves the appearance of tooth color . hence , in - office bleaching should be the most commonly adapted method by the dentist as it provides complete control on the process throughout treatment . moreover , in - office bleaching is usually a rapid process and the results are evident even after a single intervention . nevertheless , many of the patients prefer this bleaching approach by the dental professional because it requires less active participation on their part . pola office ultradent xtra boost containing 38% hydrogen peroxide chemically activated without light and heat was used in the current procedure . hydrogen peroxide releases oxygen that breaks down conjugated bonds associated with the stains into a single bond , which in turn can be washed out with water and hence effectively removes the stains . the use of light in bleaching had no demonstrable benefit over the chemically activated tooth whitening system . anterior tooth trauma , with or without fracture / s may or may not involve the pulp . the amount of tooth structure destroyed , location of the fracture and the severities of discolorations are considered while selecting a type of treatment , a type of restorative material and kind of tooth preparation . when anterior tooth is discolored and non - vital , but is structurally intact , it should be preferentially endodontically treated with the minimal access cavity opening and using inside and outside bleach . this approach is minimally invasive than complete ceramic , ceramic fused to metal , or veneers , which removes substantial amount of tooth structure , leading to irreversible damage , and are expensive . the type of intrinsic stain can play a significant part in the ultimate outcome of tooth bleaching , and choice of treatment depends on clinical experience and judgment of dentist in context of patient 's circumstances .

intrinsic discoloration of a non - vital permanent incisor tooth due to trauma may have a significant esthetic and social impact on children and adolescents . treatment options for discolored non - vital teeth are bleaching , crowns or veneers . however , this restorative crown or veneer approach has a significant drawback of being an invasive technique . intervention should be minimal destruction of tooth structure and should not compromise future restorative options . the advantage bleaching over crown is that it offers simple conservative approach in removal of stain and whitening discolored teeth without damaging tooth structure .

liposarcoma is the most common of the soft tissue sarcomas encountered in adulthood . liposarcomas are generally found in the extremities , retroperitoneum , and in inguinal lesions . the clinical characteristics of liposarcomas closely reflect their pleomorphic histologies , and the large size lesions are more common in the retroperitoneum [ 2 , 3 ] . herein , we report a case of a dedifferentiated liposarcoma that weighed 8.5 kg for which fish analysis contributed to the diagnosis . a 47-year - old woman was admitted to the nagoya city university hospital , nagoya , japan , complaining of an abdominal swelling that had been present for the past 12 months . no other disorders , including any tumor markers , were detected . a computed tomography scan ( ct ) showed two masses in the retroperitoneum , one of which was 26 15 29 cm and enhanced slightly , and the right kidney was involved and pushed aside . the other mass was walnut - sized tumor adjacent to the large one , and mostly of low density . magnetic resonance imaging ( mri ) revealed the giant tumor was t1-low intensity and t2-high intensity , but the small tumor was t1-high intensity , with a changed low signal in fat suppression ( figure 1 ) . this indicated that the small tumor was mainly fat - containing , and the giant tumor appeared to be mainly composed of mucinous tissue . under general anesthesia , the tumor was well circumscribed and encapsulated and weighed 8.5 kg ( figure 2 ) . the small one was yellowish , and histopathologically , they were mainly composed of fat cells that varied in size , that is , mature - appearing adipose tissue with scattered lipoblasts exhibiting large hyperchromatic nuclei . immunohistochemical analysis revealed that the cells were strongly stained by s-100 protein which is a marker for fat ( figure 3 ) . therefore , this small tumor was diagnosed as a well - differentiated liposarcoma . on the other hand , giant tumor was white and , histopathologically , mainly contained abundant mucinous mesenchyme and filled with atypical spindle cells . there was extensive in - depth invasion into the renal parenchyma , but the surgical margin was negative . according to immunohistochemical analysis , the poorly differentiated tumor cells had no expression of several mesenchymal markers containing s-100 protein . therefore , a comorbid malignant fibrous histiocytoma ( mfh ) , or other myxoid tumor could not be ruled out . consequently , we focused attention on fish analysis , using specific probes for the mdm2 gene ( figure 3 ) . the amplification of mdm2 gene was detected in the nuclei of both small and giant tumors . thus , a definitive diagnosis was made of the two tumors as a dedifferentiated liposarcoma . the patient was strictly observed without adjuvant therapy . during the last follow - up investigation , performed 12 months after surgical intervention , the patientbecame well with no clinical or radiological signs of recurrence . they are currently classified into five groups : myxoid liposarcomas , well - differentiated liposarcomas , round cell liposarcomas , pleomorphic liposarcomas , and dedifferentiated liposarcomas . dedifferentiated liposarcomas are characterized by the coexistence of well - differentiated and poorly differentiated , nonlipogenic areas in a portion of the same tumor or in the primary tumor and the recurrent tumor . however , in this case , the two tumors were clearly divided and expression of s-100 protein was not detected in the poorly differentiated component . therefore , we could not rule out the coexistence of a well - differentiated liposarcoma and mfh . dedifferentiated liposarcomas have been a challenge to distinguish from other high - grade sarcomas , and some reports have described that most of mfh developing in the retroperitoneum are dedifferentiated liposarcomas [ 5 , 6 ] . recently , well - differentiated liposarcoma / atypical lipomatous tumors and dedifferentiated liposarcomas have been shown by cytogenetics to harbor ring and giant marker chromosomes consisting of amplicons of the 12q1315 region , resulting in amplification of several genes , including most notably mdm2 . in addition , the prognosis of lipomatous tumors has been recently clarified on the basis of the genetic background . there is little precise information as to the effectiveness of various therapies , but radical excision is the treatment of choice for liposarcomas , especially in dedifferentiated liposarcomas expressing the mdm2 gene . some reports described postoperative radiation as a valuable adjuvant to surgical therapy , especially for the myxoid type , but the efficacy remains to be established . , this case represents the second largest primary retroperitoneal dedifferentiated liposarcoma that has been reported in the english literature . complementary molecular testing may refine the therapeutic strategy and result in avoiding ineffective adjuvant therapy .

surgical resection was performed on a 47-year - old woman for a retroperitoneal mass that weighed 8.5 kg . histological examination revealed a myxoid sarcomatous tumor . because diagnosis could not be determined by immunohistochemistry , attention was focused on mdm2 ( murine double minute ) gene amplification by fluorescence in situ hybridization ( fish ) analysis . the tumor was finally determined to be a dedifferentiated liposarcoma . we experienced a case of a giant retroperitoneal dedifferentiated liposarcoma . fish analysis was useful for the diagnosis and determination of the therapeutic strategy .

peripheral arterial disease and venous disease often coexist and they have common risk factors . if virchow s triad is accepted as a basis for the development of venous thrombosis , peripheral vascular disease has a number of characteristics which are likely to promote venous thrombosis . first , compared to normal subjects , blood flow increased to a lesser extent in patients with peripheral arterial disease during exercise and reactive hyperemia . second , there is an increased concentration of metabolites such as complement c3 and c5 , free oxygen radicals and lipid peroxides produced in relation to distal tissue ischaemia which , at least in vitro , upregulate the procoagulant properties of the vascular endothelium . with the use of color duplex ultrasound scanning , veins may be identified and their dimensions may be measured . by analyzing the spectrum of the doppler signal , the velocity can be estimated . to find out how peripheral arterial disease influences deep venous flow in the lower limbs , we undertook a prospective controlled study examining velocity flow in the popliteal vein with color duplex ultrasound scanning . thirty - one subjects who had chronic peripheral arterial disease ( 24 men and 7 women ) , were recruited for the study : 19 complained of claudication alone , 18 suffered from rest pain and 21 had gangrene . twenty - three control subjects ( 16 men and 7 women ) without peripheral arterial disease of similar age who were awaiting general surgical procedures were also invited to take part in the study . the presence or absence of peripheral arterial disease was confirmed by the history of the disease and measurement of the ankle - brachial index ( abi ) . patients with deep venous thrombosis , chronic venous insufficiency as well as incompressibility of the leg arteries detected while measuring the abi were excluded . the equipment used was a diasonics ultrasound , coupled with 4mhz transmitted frequency for doppler measurements . venous blood flow velocity was estimated by the ultrasound scanner as time averaged peak velocity . the popliteal vein was chosen as the target for the ultrasound measurements because the anatomical position makes it an easy target for ultrasound examination . in all patients and control subjects a mean of three measurements of the venous flow velocity was recorded , and the average was calculated , at rest . then , a 20 cm wide femoral blood pressure cuff was placed around the thigh and inflated 50 mmhg above the systolic blood pressure for 5 minutes . after the cuff was released , the maximum venous flow velocity were recorded during 60 seconds . this test is flow mediated dilatation or reactive hyperemia . written informed consent was obtained from all participants . statistical analysis . measurements form the patient and control groups were compared with the mann - whitney test . linear correlation analysis was used , and the result was expressed as pearson s correlation coefficient to determine the relationship between paired variables . resting popliteal venous flow velocity did not show a significant difference between subjects with peripheral arterial disease 9.5015.616 cm / sec ( 3.121.6 95%ci 7.83311.169 ) and controls 9.2707.858 cm / sec ( 1.845.7 95%ci 7.30711.233 ) ; p=0.621 , but in limbs with an abi less than 0.9 venous flow velocity was significantly higher 16.55719.656 ( 2.952.5 95%ci 1.62234.736 ) than in limbs with an abi of 0.9 or more 12.6735.792 ( 3.124.7 95%ci 9.4615.81 ) ; p=0.001 . venous flow velocity appeared to be greater among younger subjects , and decreased in elderly subjects ( p=0.042 ) ( figure 1 ) interestingly , resting venous flow velocity appeared to be greater among subjects without dyslipidemia 10.0428.26 cm / sec versus 9.63510.177 in those with dyslipidemia , although this difference did not quite reach statistical significance ( p=0.057 ) . furthermore , among patients with peripheral arterial disease there was a negative correlation between dyslipidemia and resting popliteal vein flow velocity ( p=0.049 ) . during reactive hyperemia venous flow velocity increased in all subjects , but to a significantly lesser extent in subjects with peripheral arterial disease : 9.5325.665 ( 7.0719.643 95%ci 2.321.1 ) versus controls 10.5594.696 ( 2.711.953 95%ci 10.55918.1 ) p=0.007 . the degree of this velocity showed significant positive correlation with ankle - brachial index ( p=0.001 ) . venous flow in reactive hyperemia conditions was not statistically influenced in diabetic subjects and in those with dyslipidemia ( p=0.251 versus p=0.908 ) . this study documents the change in venous flow in peripheral arterial disease there are conflicting reports regarding the relationship between deep venous disease and peripheral arterial disease in the lower limbs . we chose the popliteal vein as a representative area for both anatomic and technical reasons . our observations indicate that the deep veins of the lower limb constrict in response to ischemia and the deep venous flow increased . the degree of this constriction is related to the severity of the peripheral arterial disease . during reactive hyperemia , when the hypoxia was augmented by the preceding arterial occlusion , the venous flow increased . healthy endothelium produces a wide range of factors that regulate vascular tone , adhesion of circulating blood cells to the vessel wall , thrombus formation , smooth muscle cell proliferation , and vessel wall inflammation , which is the key mechanism of the thrombosis process . one of the most important functions of the endothelium is its effect on the vascular tone . consequently , some humoral factor related to tissue ischemia must be involved in producing this venoconstriction . perhaps there are change in the endothelial production of nitric oxide or endothelins , which may be responsible for the contraction of the vascular smooth muscle . venous flow velocity decreases with age , which may be attributable in part to decreased nitric oxide release and to diminished smooth muscle cell responsiveness in older subjects . we also observed an increase in resting venous flow velocity among subjects with peripheral vascular disease that was dependent on the severity of the disease . the correlation between ankle - brachial index and venous flow velocity was significant in subjects with peripheral arterial disease . during reactive hyperemia venous flow velocity increases to a lesser extent in subjects with peripheral arterial disease as compared to subjects . reduced venous flow has long been considered to be an important factor in the development of venous thrombosis . it is likely that increased venous flow velocity , resulting from venoconstriction , has an important protective role for the development of deep venous thrombosis . as the activity of the coagulation system is also increased , it is surprising that deep vein thrombosis does not have a higher incidence . future studies as well as investigation of blood coagulation are necessary to show the link bretween peripheral arterial disease and the venous disorder .

aimthis prospective study was undertaken to determine how peripheral atherosclerotic disease influences the flow in the deep veins of the leg.material and methodthirty one subjects with peripheral atherosclerotic disease and 23 age matched control subjects were studied . the popliteal vein flow velocity was measured at rest and during reactive hyperemia by means of color duplex ultrasound scanning . patient age , ankle - brachial index ( abi ) and the presence of risk factors for venous thrombosis were also recorded.resultsthere was a negative correlation between the ankle - brachial index and venous flow velocity among subjects with peripheral arterial disease ( p=0.001 ) . there was a negative correlation between dyslipidemia and resting venous flow velocity ( p=0.049 ) . during reactive hyperemia , venous flow velocity increased less in subjects with peripheral arterial disease than it did in control subjects ( p=0.007 ) . the subjects with dyslipidemia showed no changes in venous flow velocity in reactive hyperemia measurements ( p=0.908).conclusionincreasing the venous flow velocity in peripheral arterial disease , may confer some protection against the deep venous thrombosis .

rice ( oryza sativa ) was the first crop species selected for whole genome sequencing because of its relatively small genome size ( 1 ) and its global importance in food production ( 2 , 3 ) . draft genome sequences for rice were first produced in 2002 ( 4 , 5 ) , followed by a map - based , nearly complete genome sequence ( 6 ) , and culminating in the release of a high - quality genome assembly with gene annotation ( 7 ) . the high - quality reference genome has enabled high - density genotyping ( 8 , 9 ) and resequencing of over 3000 additional rice varieties ( 10 , 11 ) . the availability of genomic and high - density genotyping data will be of tremendous value for rice genetics and breeding . however , due to the size and structure of the datasets , working with these data is challenging for many field and bench scientists . approaches such as genome - wide association mapping can reveal significant phenotype associations with particular snps . from those significantly associated snps , some of the next investigative steps include : browsing the surrounding genomic region to look for likely candidate genes , examining potential functional consequences of an snp within in a gene , and determining if the snp is near a molecular marker that has been previously reported to be associated with the same or a related phenotype . most of the current rice genetics literature has only older molecular marker technologies as genomic position reference points . these are primarily simple sequence repeat ( ssr ) markers ( 12 , 13 ) . ssrs are still in use in many laboratories because of their high levels of polymorphism because certain ssrs are known to be linked to traits of interest , such as marker rm190 at the waxy gene ( 14 ) , which controls starch content , and because they can provide fast results and are more flexible in comparison to large snp sets that are pre - defined . most ssr markers in rice were developed before the complete genome sequence became available , and their positions on the current pseudomolecules are not reported . determining the positions of the ssr markers can be done by blast ( 15 ) but primer sequences do not always match uniquely or perfectly . to address this , we have developed a pipeline to map ssr primer sequences to the pseudomolecule sequence that uses a stepwise relaxation in match stringency , and incorporates a series of rules for declaring a match for primer pairs that uses distance and orientation . a number of other genomic databases exist for rice including gramene ( http://gramene.org ) ( 16 ) , oryzabase ( 17 ) and snp - seek ( 10 ) . these databases focus on comparative genomics , diversity data , gene annotation or mutant collection resources . ricebase is unique in that it specifically includes ssrs as a track and has a focus on breeding and genetics and closes some critical gaps linking the latest resources with historical genetic knowledge . the ricebase database inherits its model , view and controller architecture from the sol genomics network ( sgn ) ( 18 ) . the model consists of dbix::class - based perl modules to manipulate data in a relational database schema . the schema includes the community developed chado natural diversity module ( 19 ) as well as several local schemas . all code is publicly available on github ( http://github.com/solgenomics/sgn ) with ricebase specific modifications available at ( http://github.com/solgenomics/ricebase ) . jbrowse is a javascript - based genome browser that is scrollable , zoomable and supports the simultaneous display of multiple data types along the genome as tracks , such as gene annotations , sequence variants and other features . ricebase has pre - loaded gene annotations ( 7 ) , a 700 000 snp dataset across 413 diverse accessions ( 8) , a 20 million snp dataset across 3000 accessions ( 10 ) , and over 17 000 ssr markers . to determine the positions of the ssr markers , a pipeline was developed using blast and perl scripts ( supplementary materials ) . to allow for imperfect matches , primer pairs are concatenated for a single blast search . for each ssr primer pair , the ssr search begins with a blast expect ( e ) value of 0.1 , and if no primer is found , the search is repeated at a lower stringency with e values of 0.1 , 1 , 10 , 100 and 1000 . hits found at the specified threshold are rejected if multiple loci are found , the primer pairs align in the incorrect orientation , or if the predicted amplicon exceeds a size threshold ( 500 bp ) . in addition , the genomic locations of the primer pairs are checked for correct orientation and expected distance apart . collections of publically available ssr primer sequences were obtained from the gramene database ( http://archive.gramene.org/markers/microsat/ ) . the reference genomes included the irgsp 1.0 assembly ( 7 ) of nipponbare , a temperate japonica oryza sativa variety , the indica oryza sativa variety 93 - 11 ( 5 ) and the related wild species o. rufipogon , o. nivara , o. glaberrima , o. barthii , o. glumaepatula , o. longistaminata , o. meridionalis , o. punctate and o. brachyantha obtained from ftp://ftp.gramene.org/pub/gramene/current_release/data/fasta/ ( 21 ) . the ssr names , primer sequences and genomic positions were used to generate generic feature format version 3 ( gff3 ) files for display as tracks in jbrowse . each ssr name and position a published capillary electrophoresis dataset of 421 diverse rice accessions ( 22 ) , estimated ssr amplicon sizes for 36 of the markers also were loaded in the relational database . pedigrees of rice accessions included in the rice diversity panel 1 ( rdp1 ) ssr dataset ( 22 ) were obtained from the genetic stocks oryza ( gsor ) collection ( http://www.ars.usda.gov/gsor ) . relationships between accessions are represented in the database as stock properties with controlled vocabulary terms to indicate the female and male parent . ssr primers from a commonly used set of 1947 ( 13 ) and the exhaustive gramene set of 19 480 were mapped to two o. sativa assembled reference genomes and nine genomes of wild relatives . nipponbare irgsp 1.0 assembly 92.9 and 91.2% of the ssrs could be unambiguously located for the mccouch et al.s ( 13 ) and gramene sets , respectively ( table 1 ) . the primary reason for inability to determine genome positions for ssrs was predicted amplicons at multiple locations . it is common for multiple amplicons to be observed for ssr markers and bands outside of expected size ranges are often ignored in allele calling . as expected the number of located ssrs decreased within the wild species as the genetic distance from o. sativa increased ( 23 ) . table 1.number of ssr markers from the complete gramene collection and published mccouch 2002 collection mapped to the temperate japonica nipponbare rice reference sequence , the indica rice cultivar 93 - 11 , and 9 oryza wild relatives.referencegramenemccouch et al . brachyantha5024144564581489 number of ssr markers from the complete gramene collection and published mccouch 2002 collection mapped to the temperate japonica nipponbare rice reference sequence , the indica rice cultivar 93 - 11 , and 9 oryza wild relatives . the predicted amplicon sizes , in base pairs , for each ssr primer pair were calculated based on the nipponbare reference and compared with published estimate band sizes in nipponbare with capillary electrophoresis . out of 39 markers , slight deviations from the expected band sizes were seen for all but three of the ssrs with a maximum of an 8-bp difference ( figure 1 ) . there was no strong correlation between fragment length and deviation of predicted and capillary electrophoresis estimated band sizes ( r = 0.15 ) ( supplementary figure s1 ) . figure 1.distribution of differences between the estimated amplicon size using capillary electrophoresis and the sequence - determined amplicon sizes for cv nipponbare . distribution of differences between the estimated amplicon size using capillary electrophoresis and the sequence - determined amplicon sizes for cv nipponbare . genome browser tracks , generated using the ssr marker positions on the rice pseudomolecules , allow users to view the ssr markers in the surrounding context of annotated genes and snps ( figure 2 ) . the gene annotation track and the snp track can be used to find snps residing in coding regions , and clicking on the snp displays the predicted effect ( synonymous , non - synonymous , stop - codon , frameshift , etc . ) . clicking on an ssr marker in the genome browser brings up information on primer sequences and amplicon size in the reference genome . figure 2.screenshot showing the genome browser displaying the ssr marker rm190 and surrounding context of genes and snps . screenshot showing the genome browser displaying the ssr marker rm190 and surrounding context of genes and snps . additional information about each ssr marker is stored in the relational database and markers are searchable through the website menu . the marker detail page shows the chromosome and location of the marker on the sequence map ( numerically and using a clickable diagram ) and measured band ( amplicon ) sizes in particular accessions when available ( figure 3 ) . clicking on the map diagram brings up a comparative map viewer highlighting the selected marker and providing an interface to compare the current map with other sequence - based or genetic maps ( figure 4 ) . when band size information is available for a marker , the assayed accessions are clickable to be directed to the corresponding stock ( accession ) detail page . the stock detail page may contain synonyms for the accession , images , phenotypic data , related accessions , pedigree and descendants . the pedigree and descendants are displayed as an interactive scalable vector graphics where clicking on any displayed accession will take the user to the corresponding accession s stock detail page ( figure 5 ) . the combination of a pedigree search and genetic marker assay data enable users to search for progenitors or descendants of a line and determine if they do or do not share an allele state at a particular genetic marker . figure 3.allele ( band size ) data by accession for an ssr marker . figure 4.comparative map viewer aligning the sequence - based maps of the gramene ssr set ( left ) and the mccouch 2002 set ( right ) . figure 5.pedigree and descendent display : a , pedigree of cultivar cypress and b , descendants of the cultivar comparative map viewer aligning the sequence - based maps of the gramene ssr set ( left ) and the mccouch 2002 set ( right ) . pedigree and descendent display : a , pedigree of cultivar cypress and b , descendants of the cultivar rexoro as displayed on the accession detail view . the development of a fully automated pipeline for determining pseudomolecule assembly positions of ssrs will be useful to overlay marker information on additional de novo assemblies of other rice accessions or other species as they become available . this will help maintain a connection between the latest genomic discoveries and the extensive body of ( largely ssr - based ) rice genetics literature . with the results of this pipeline , ricebase distinguishes itself from other genomic databases for rice such as gramene , rice genome annotation project and the 3000 genome project by providing continuity from past and current marker technologies to whole genome resequencing data . fine mapping / positional cloning research often requires new markers to be designed near or between pairs of existing markers . using the browser , new markers may be developed near an existing marker using snp information and even gene annotation to potentially capture functional polymorphisms . having a common coordinate system based on pseudomolecule position combined with the ability to browse the genomic context will ease the transition of ssrs to snps . additional snp or other marker data may be added as tracks to the database in the future , or users may overlay their own tracks on the browser . this will ease the transition for users when working across different genotyping platforms . the inclusion of pedigree information , along with molecular marker assay data , presents the possibility of tracing the transmission of particular allele states through a series of crosses . this information may be also used for quality control to detect events where the observed allele state is not possible or highly unlikely given the allele states of the parents or accessions in the pedigree . the integration of pedigrees and breeding records is a unique feature of ricebase among the existing rice genomics databases . with a relational database of genetic markers in rice , there is now an opportunity to include additional user curated information for each marker . any type of metadata may be attached to a genetic marker , such as experimental validation , inclusion in a genotyping project , or multiplexing protocols . users may wish to record phenotypes associated with a particular genetic marker ( or allele states of that marker ) and supporting literature . establishment of a user curated resource that contains a collection of markers tightly linked to genes of interest with known phenotypic effects may help researchers pool their collective knowledge to facilitate gene discovery and accelerate rice breeding through marker assisted selection .

ricebase ( http://ricebase.org ) is an integrative genomic database for rice ( oryza sativa ) with an emphasis on combining datasets in a way that maintains the key links between past and current genetic studies . ricebase includes dna sequence data , gene annotations , nucleotide variation data and molecular marker fragment size data . rice research has benefited from early adoption and extensive use of simple sequence repeat ( ssr ) markers ; however , the majority of rice ssr markers were developed prior to the latest rice pseudomolecule assembly . interpretation of new research using snps in the context of literature citing ssrs requires a common coordinate system . a new pipeline , using a stepwise relaxation of stringency , was used to map ssr primers onto the latest rice pseudomolecule assembly . the ssr markers and experimentally assayed amplicon sizes are presented in a relational database with a web - based front end , and are available as a track loaded in a genome browser with links connecting the browser and database . the combined capabilities of ricebase link genetic markers , genome context , allele states across rice germplasm and potentially user curated phenotypic interpretations as a community resource for genetic discovery and breeding in rice .

the first survey , intended to clarify the rift valley fever epidemiologic situation on the island , was undertaken in the mtsangamouji area ( northern part of mayotte ) . it examined samples from 29 illegally introduced goats and 79 cattle born on the island and living near the goats . among the 29 goats , competitive igg elisa found igg against rvfv in 4 goats that had been introduced illegally during november 2007april 2008 ( 13 ) , and igm - capture elisa found igm against rvfv in 2 goats ( 14 ) , suggesting recent infection . among the 79 cattle , igg against rvfv was found in 29 ( 37% ) and igm against rvfv was found in 3 ( 4% ) . these data led us to conduct the second survey , a retrospective study on the whole island to define the geographic distribution of the infection and to trace back the period of introduction . this survey analyzed 301 cattle serum samples collected during june 2007may 2008 on 104 farms in 17 districts . exposure to rvfv was indicated by competitive igg elisa detection of rvfv - specific antibodies . positive results were found for 32 samples from cattle in 9 districts ( table ) . the overall apparent rvfv seroprevalence of 10.6% ( 95% ci 7%14% ) was supported by the high specificity of the elisa ( 14 ) . the 32 positive samples came from cattle distributed all over the island ( figure 2 , panel a ) . herds ) and , in parentheses , by animal in infected municipalities ( no . infected / total no . ) . b ) status of goat herds sampled for longitudinal serologic study , mayotte , 20082009 . because rvfv circulation had been confirmed as early as 20072008 in mayotte , a third cross - sectional and retrospective study was conducted to trace previous virus circulation . the 120130 samples that had been collected from cattle since 2004 were randomly selected every year over a 4-year period and analyzed by igg elisa ; results were confirmed by neutralization tests ( 15 ) . these results helped evaluate rvfv circulation on mayotte island before the 20072008 outbreak on the eastern africa mainland . in 2004 , a total of 29 of 130 cattle had igg against rvfv ; thus , seroprevalence was high ( 22.66% ) . in 2005 , seroprevalence rates fell ; igg against rvfv was found in only 4 of the 130 , suggesting low levels of rvfv circulation . in 2006 and 2007 , seroprevalence increased ; igg against rvfv was found in 16 of 130 and 39 of 126 cattle , reaching seroprevalence rates of 12.31% and 30.95% for 2006 and 2007 , respectively . specific igm against rvfv was not detectable during this cross - sectional and retrospective study . the fourth survey , intended to evaluate the recent virus dynamics in mayotte , was a longitudinal serologic survey of goat farms . in june 2008 , a total of 13 goat farms were selected and all 272 animals were screened for antibodies against rvfv . of the 13 farms , 8 had seropositive animals ( herd prevalence 62% , 95% ci 35%88% ) ( figure 2 , panel b ) . the 5 farms with seronegative goats ( total 70 goats ) were included in the longitudinal study . during august 2008august 2009 , the seronegative goats were sampled every 68 weeks . only 1 goat , located in bouyouni and sampled in february 2009 , had seroconverted and was confirmed igm positive for rvfv . the 4 serologic surveys conducted in mayotte revealed medium to high rates of rvfv prevalence all over the island . the high rates obtained with the first survey in the mtsangamouji area suggest that illegal animal movements from the comoros are a likely source for rvfv introduction onto mayotte . after a low seroprevalence rate in 2005 , the increased seroprevalence rates for 2006 and 2007 suggest that the virus had recirculated or had been newly introduced . it is unclear why relatively high circulation of rvfv in mayotte and an increased rate of seroprevalence to 22% did not result in detectable clinical cases in animals while rift valley fever was diagnosed for humans with brain disorders ( 11 ) . this finding might be because the density of susceptible animals on the island was high enough to support virus circulation but too low to support waves of epidemic abortion and death . these study findings , coupled with epidemics in eastern africa , illustrate the risk for introduction of infectious agents from the african mainland to mayotte or other comoros islands . entomologic studies need to be conducted to identify all potential vector species on the island and to better understand the ecologic and climatic factors that favor rvfv dissemination . the ecologic factors in favor of rift valley fever outbreaks might be comparable between mayotte , the other comoros islands , madagascar , and the eastern african mainland ( kenya , tanzania , and mozambique ) but need to be looked at more closely . in mayotte , an entomologic surveillance program is being developed to help define the distribution of potential vectors in association with virus circulation and provide better understanding of disease spread mechanisms . these data highlight the need for extensive studies to determine rvfv distribution and to evaluate the effect of rift valley fever on the susceptible livestock populations .

rift valley fever threatens human and animal health . after a human case was confirmed in comoros in 2007 , 4 serosurveys among ruminants in mayotte suggested that rift valley fever virus had been circulating at low levels since 2004 , although no clinical cases occurred in animals . entomologic and ecologic studies will help determine outbreak potential .

since it was first performed in 1984 by galibert and deramond ( 1 ) , percutaneous vertebroplasty has become widely accepted as a minimally invasive procedure for the treatment of osteoporotic vertebral fractures and osteolytic malignant vertebral tumors . however , more complications associated with percutaneous vertebroplasty have been reported over time with increasing performance of this procedure . among the various complications , the most serious is embolization of polymethylmethacrylate ( pmma ) mixture , a commonly used cement material , in the pulmonary arteries ( 2 , 3 ) . in most cases , however , this event is asymptomatic . thus , radiologists have a greater chance of encountering cement emboli in postoperative patients undergoing chest ct for some unrelated reason ( 4 ) . although postoperative chest radiography is performed to detect bone cement , the diagnosis of bone cement emboli is usually made with a chest ct ( 5 ) . typical ct findings include the presence of multiple tubular or branching dense opacities located along the course of the pulmonary arteries . however , dense opacified blood during contrast injection may mask the high - density bone cement emboli in some cases , and determining the functional significance of the emboli is not possible . recently , ct pulmonary angiography ( ctpa ) with dual energy or spectral imaging mode was introduced to detect pulmonary thromboemboli and consequent perfusion defects in patients with dyspnea of unknown etiology , and , promisingly , it has been reported to result in significant improvements in the diagnostic performance of ctpa ( 6 , 7 , 8) . we performed ctpa with spectral mode in a patient with dyspnea and describe the ct findings of bone cement embolism with special emphasis on the potential benefits of the spectral imaging mode . to our knowledge , this is the first report to describe spectral ct angiographic findings in a patient with pulmonary bone cement embolism . she had undergone seven previous vertebroplasties at another hospital for the treatment of the compression fractures due to severe osteoporosis , with a bone mineral density t - score of -3.4 . on arrival , her blood pressure was 80/50 mm hg ; however , blood gas analysis revealed normal oxygenation status . a chest radiograph showed multiple tubular , radiopaque lesions corresponding to the course of the pulmonary vascular structures . ctpa was then performed using gemstone spectral imaging ( gsi ) to obtain spectral ct images by fast kv switching , which allows for virtual monochromatic images at different kv levels from 40 to 140 kev and the creation of material density images . an axial maximal intensity projection image using 140 kvp revealed radiopaque emboli of variable sizes and shapes in the lobar , segmental , and subsegmental pulmonary arteries of the right upper , middle , and both lower lobes ( fig . additionally , images with a mediastinal setting demonstrated the origin of the leak by showing cement in right laterovertebral vein at the level of the third and fifth lumbar vertebral bodies , draining into the inferior vena cava and right common iliac vein . a small amount of asymptomatic cement leakage in the epidural space of the fifth to the eighth thoracic , first lumbar , and third lumbar vertebrae and a needle tract at the sixth thoracic vertebral level there was no characteristic finding of pulmonary infarction , such as pleural - based truncated consolidation or ground - glass opacities . iodine maps were created using the gsi software ( aw gemstone spectral imaging , ge medical systems , milwaukee , wi , usa ) . an axial iodine material density image at the same level shown in figure 1a more clearly demonstrated the smaller segmental and subsegmental emboli and the corresponding decrease in the parenchymal iodine content ( fig . these images also showed the under - perfused areas in the right middle lobe and lingular division of the left upper lobe that correlated with the embolic - occluded pulmonary arterial vascular territory ( fig . 1d ) , which was not visible on the monochromatic ctpa image for morphological assessment of the pulmonary artery ( fig . 1e , f ) for material separation showed that the pulmonary emboli and bone cement in the vertebral body were similar in composition . however , the cortical bone , bone cement in the vertebral body , and iodine being assessed in this patient were different in composition from one another , although all of them showed high attenuation similarly on the monochromatic image . after administration of inotropics , the patient 's blood pressure normalized , and she was transferred to another community hospital for further anticoagulation treatment . although percutaneous vertebroplasty is considered to be a minimally invasive procedure , many local and systemic complications can occur . cement leakage is the most frequent complication after percutaneous vertebroplasty caused by injecting pmma mixture ( approximately 90% mma and 10% barium sulfate ) when it is still too liquid in state or by applying too much pressure while injecting the material ( 2 ) . although there is a high prevalence of extravertebral cement leakage into the surrounding venous plexus after vertebroplasty , only a small percentage of cement leakage leads to pulmonary embolism ( 3 ) . the present case showed that the cement leaked into the right laterovertebral veins and was drained by the inferior vena cava via which the cement migrated to the pulmonary arteries . traditional imaging tools for the diagnosis of pulmonary embolism include invasive pulmonary angiography , nuclear ventilation / perfusion scans , and , more recently , ctpa . although chest radiography can be used as a screening tool , ctpa is widely accepted as the standard for the diagnosis of pulmonary embolism by direct visualization of emboli within a pulmonary artery ( 5 ) . however , while ctpa is known to be highly accurate for the detecting thromboemboli in the central pulmonary vessels , its sensitivity decreases near the periphery , where the vessels are smaller and there is a higher chance of motion artifacts caused by breathing . the ct detectability of subsegmental pulmonary thrombi is variable , with a sensitivity ranging from 37 to 96% ( 9 ) . furthermore , while multidetector ct ( mdct ) technology has better spatial resolution and a lower scan time than those of traditional diagnostic tools , the lack of functional data obtained from ct often requires the use of additional nuclear imaging studies to visualize perfusion defects , especially with chronic smaller emboli ( 9 ) . the ongoing evolution in mdct technology has resulted in dual - source , dual - energy ct or single - source spectral ct with rapid tube voltage switching , which allow for iodine mapping of the lung field on post - contrast ct studies and the detection of decreased iodine content ( perfusion defects ) distal to obstructive clots ( 6 , 7 , 8) . initial studies evaluated the diagnostic accuracy of the perfusion map generated using dual - energy ct and spectral ct imaging and showed promising results for the detection of blood clots . in those studies , the detection performance of blood clots , especially in smaller segmental and subsegmental arteries , could be improved not by direct visualization of clots but rather with simultaneous evaluation of iodine perfusion maps ( 6 ) . however , in contrast to those studies , spectral ct imaging in the present case improved the direct visualization of tiny radiopaque cement materials in smaller segmental and peripheral subsegmental arterial branches that were masked by iodinated contrast materials in the pulmonary arteries ( fig . 1a , c ) . furthermore , as shown in figure 1e and f , spectral imaging allowed for the creation of material decomposition images , which may provide additional information on the material composition , based on the attenuation physics ( 8) . this enabled estimating the different compositions of high - density materials , including iodinated contrast , bone , and cement , using material separation and spectral scatter plots . we believe that this may help to overcome the limitations associated with using only hounsfield units and morphology to differentiate materials . in this case , the positions of the emboli in the pulmonary arteries and cement in the vertebral bodies overlapped each other on the gsi scatter plots and the histograms , suggesting that these two materials have identical or similar compositions , and that the pulmonary emboli originated from cement material in the vertebral body . thus , we believe that spectral imaging may be useful in patients with both bone cement embolism as well as " classic " thromboembolism , although further studies involving more cases are needed . furthermore , spectral imaging may have potential benefits for the early diagnosis of minor small , peripheral emboli to guide a follow - up plan in asymptomatic patients . the indications for treatment in this setting have not been studied fully . in previous reports , most patients with asymptomatic cement embolism remained untreated . in symptomatic patients , however , anticoagulation therapy was started immediately to prevent further thrombus formation although there are no data supporting the value of preventive anticoagulation ( 4 ) . in conclusion , we performed pulmonary cta in a patient with bone cement embolism using the spectral imaging mode . spectral imaging allowed for better detection of smaller emboli even in the peripheral pulmonary arteries , as well as evaluation of parenchymal perfusion by assessing the parenchymal iodine content in addition to angiographic information . furthermore , we believe that the use of the material decomposition technique with spectral ct may help to compensate for the drawbacks of using only hounsfield units in differentiating materials with similar ct densities .

we report a case of pulmonary bone cement embolism in a female who presented with dyspnea following multiple sessions of vertebroplasty . she underwent spectral ct pulmonary angiography and the diagnosis was made based on enhanced visualization of radiopaque cement material in the pulmonary arteries and a corresponding decrease in the parenchymal iodine content . here , we describe the ct angiography findings of bone cement embolism with special emphasis on the potential benefits of spectral imaging , providing additional information on the material composition .

primary intraosseous meningioma is a very rare benign tumor , mainly originating from the cranial bones , and is also found in the skin , nasopharnyx or neck [ 1 , 2 ] . this tumor can be clinically and radiologically confused with metastatic cancer and other malignant bone tumors . only one case report has dealt with f - fluorodeoxyglucose ( f - fdg ) positron emission tomography / computed tomography ( pet / ct ) in a primary intraosseous meningioma of the calvarium showing high f - fdg uptake . we present a case of primary benign intraosseous meningioma of the sphenoid bone that was confused with malignancy on f - fdg pet / ct . a 44-year - old female patient who had a protruding right eye and headache came to our hospital for further evaluation . contrast - enhanced mri showed a large , heterogeneously well - enhancing soft tissue mass in the right sphenoid bone destroying the right greater and lesser wing of the sphenoid bone , replacing bone marrow and involving the right orbital roof with invasion of the right supraorbital muscle complex and right lateral rectus muscle , which suggested a malignancy ( fig . 1 ) . pet / ct was performed using a discovery ste scanner ( ge healthcare , milwaukee , wi , usa ) 60 min after the intravenous injection of 370 mbq f - fdg . pet / ct showed a large hypermetabolic mass involving the right retrobulbar area and right sphenoid bone with a maximum standardized uptake value ( suvmax ) of 9.1 . however , no significant abnormal f - fdg uptake suggesting a malignancy was found in other sites ( fig . 2 ) . the histophathologic examination by an incisional biopsy of the right orbital mass showed who grade i meningioma . the final diagnosis was primary benign intraosseous who grade i transitional meningioma ( fig . 3 ) . after surgery , the patient was clinically followed up for 6 months without evidence of recurrence.fig . axial ( a ) and coronal ( b ) t2-weighted images show a hyperintense lesion in the right sphenoid bone with invasion of the right supraorbital muscle complex and right lateral rectus muscle . axial ( c ) and coronal ( d ) gadolinium - enhanced t1-weighted images show a large , heterogeneously well - enhancing soft tissue mass in the right sphenoid bone destroying the right greater and lesser wing of the sphenoid bonefig . 2ct ( a ) , transaxial pet ( b ) and fused transverse ( c ) and coronal ( d ) pet / ct images show a hypermetabolic lesion involving the right sphenoid bone and right retrobular area ( suvmax = 9.1)fig . 3pathological specimen after surgery shows that the tumor is composed of a mixture of meningothlieal ( a ) and fibrous ( b ) types of meningioma , which suggests transitional meningioma . a nested aggregate of epithelioid cells , compatible with meningothelial meningioma ( h&e , 200 ) . b however , most of the tumor is composed of spindle cells and interspersed collagen bundles , consistent with fibrous meningioma . ( h&e , 400 ) mri images of the patient . axial ( a ) and coronal ( b ) t2-weighted images show a hyperintense lesion in the right sphenoid bone with invasion of the right supraorbital muscle complex and right lateral rectus muscle . axial ( c ) and coronal ( d ) gadolinium - enhanced t1-weighted images show a large , heterogeneously well - enhancing soft tissue mass in the right sphenoid bone destroying the right greater and lesser wing of the sphenoid bone ct ( a ) , transaxial pet ( b ) and fused transverse ( c ) and coronal ( d ) pet / ct images show a hypermetabolic lesion involving the right sphenoid bone and right retrobular area ( suvmax = 9.1 ) pathological specimen after surgery shows that the tumor is composed of a mixture of meningothlieal ( a ) and fibrous ( b ) types of meningioma , which suggests transitional meningioma . a nested aggregate of epithelioid cells , compatible with meningothelial meningioma ( h&e , 200 ) . b however , most of the tumor is composed of spindle cells and interspersed collagen bundles , consistent with fibrous meningioma . because meninges originate from mesenchymal cells , meningioma could theoretically develop in any site where mesenchymal multipotent precursor cells exist . some researchers thought that extradural meningioma originated from ectopic arachnoid cap cells or ectopic meningocytes in the cranial sutures during molding at birth . extradural meningioma that arises from the skull has been referred to as intraosseous , intradiploic or calvarial meningioma . the skull base and convex diploe are two major sites for primary intraosseous meningioma [ 9 , 10 ] . primary intrasosseous meningioma on the sphenoid bone corresponds to 1520 % of all cranial meinigiomas . usually primary osseous meningiomas have been shown to be benign and slow growing . however , the possibility of malignant transformation in the primary intrasosseous meningioma is higher than that in the intracranial meningioma [ 2 , 6 ] . primary intraosseous meningioma in the sphenoid bone can involve the adjacent orbit and cavernous sinus . however , other histologic subtypes include fibroblastic , chordoid , transitional , psammomatous , microcytic and even atypical , malignant meningiomas . who grade i meningiomas such as meningothelial , fibroblastic , transitional , psammomatous and microcytic meningiomas are classified as a benign tumors [ 12 , 13 ] . the histologic subtype in our case was a transitional meningioma . on simple skull radiographs , primary intraosseous meningioma can show either osteoblastic or osteolytic features . t2-weighted images usually show hyperintense features . several previous studies dealt with nuclear medicine imaging in primary osseous meningioma . this tumor had high tc - diphosphate , tc - medronate and in - pentetreotide uptake . on the contrary , the tc - pertechnetate scan was negative [ 15 , 16 ] . recently f - fdg pet / ct has been widely used for tumorous conditions for the differential diagnosis including intracranial meningiomas . in usual dural meniogiomas , who grade 2 or 3 meningioma shows higher f - fdg uptake than who grade 1 , which suggests that f - fdg uptake in intracranial meningiomas reflects tumor aggressiveness [ 13 , 17 ] . until now , only one case of primary intraosseous meningioma of the convex diploe detected by f - fdg pet / ct has been reported . this case showed a hypermetabolic lesion in the right parietal meningothelial meningioma that mimicked a metastasis in a patient with bladder cancer . our study was the second reported case of pet / ct findings of primary intraosseous meningioma and first case of primary intraosseous meningioma of the sphenoid bone and transitional type along with a description of the suvmax . in our case , the hypermetabolic lesion involving the right sphenoid bone and right retrobulbar area was bone - destructive and showed high f - fdg uptake with a suvmax of 9.1 . therefore , it was considered a malignancy such as a metastatic carcinoma or lymphoma at the time of initial interpretation . however , the final pathological diagnosis was benign who grade i transitional meningioma . thus , our case suggested that it is difficult to differentiate primary intraosseous meningioma from other malignant tumors by f - fdg uptake . although it was not clear why the primary benign intraosseous meningioma had high f - fdg uptake , some benign intracranial meningiomas have been reported to have high f - fdg uptake . in addition , our case suggested that f - fdg uptake might not be associated with tumor grade and aggressiveness in intraosseous meningioma , unlike intracranial meningioma . in summary , our case demonstrates that primary benign intraosseous meningioma shows high f - fdg uptake and bone destruction mimicking a malignancy . although rare , primary intraosseous meningioma should be considered one of the false positives for the differential diagnosis of bone lesions detected by f - fdg pet / ct .

we present a case of primary benign intraosseous meningioma in the sphenoid bone mimicking malignancy . a 44-year - old female patient who had a protruding right eye and headache came to our hospital . mri showed a large , destructive , heterogeneously well - enhancing soft tissue mass in the right sphenoid bone suggesting malignancy . 18f - fdg pet / ct showed a hypermetabolic mass in the same site with an suvmax of 9.1 the pathological diagnosis by surgery revealed that this tumor was a who grade i transitional meningioma . this case suggests that primary benign intraosseous meningioma may show high 18f - fdg uptake mimicking a malignancy .

. it may be of open variety caused by primary neurulation failure , leading to neural tissue getting exposed without skin covering and usually associated with external discharge of cerebrospinal fluid , while another being closed category is caused by faulty secondary neurulation and in resultant defect , the neural tissue being not exposed and usually covered with intact skin . the anterior and posterior neuropore used to close in the last , so these sites are most likely to remain vulnerable for occurrence of such congenital defects . occurrence of lipomyelomeningocele with type ii split cord malformation , low - lying tethered cord with anomaly of cervical vertebrae fusion in the form of block klippel feil syndrome and sacral agenesis plays a challenge to the clinician in the search and early diagnosis for multiple neural tube defects , and further , management of such cases also possesses challenge to the neurosurgical , urologist , orthopedician , and rehabilitatory team . a 23-year - old male presented with low backache for the last 2-years , with a history of surgery for repair of lumbosacral lipomeningocoele at the age of 1 year . he was asymptomatic after surgery for almost 20-years , and later on , he noticed wasting and weakness of lower limbs associated with difficulty in walking ; however , he had no bowel or bladder disturbances . clinical examination revealed an healthy male , wasting of bilateral calf muscle , and power of grade 4/5 at bilateral hip , knee , and ankle joints and rest of the neurological examination were essentially within normal limits . x - ray of the lumbosacral spine revealed the presence of spina bifida with agenesis of lower sacral and coccygeal segments [ figure 1 ] . x - ray of the cervical spine showed fusion of c2 and c3 spinous process [ figure 2 ] , and lumbosacral spine magnetic resonance imaging sagittal section , t1-weighted image showed the presence of the low - lying conus lying at the l4 vertebra level with tethering with lipoma and associated agenesis of the lower sacral and coccygeal segments [ figure 3 ] . x - ray lumbar spine , anteroposterior view showing spina bifida with partial sacral agenesis x - ray cervical spine , lateral view showing c2-c3 block vertebrae magnetic resonance imaging , t2-weighted image showing low - lying tethered cord at l4 vertebra with sacral agenesis t2-weighted coronal section magnetic resonance image revealed type ii split cord malformation with split extending from d11 vertebrae to l4 vertebrae [ figures 4 and 5 ] . he underwent surgical repair of lipomyelomeningocele with the resection of residual lipoma ; conus was freed and reconstructed , with meticulous dural closure being carried out . in the postoperative period , he had temporary mild worsening in the neurological status , which recovered over next 2 months ; however , wasting of calf muscles was still persisting at the last follow - up at 2-years , following the second surgery . magnetic resonance imaging lumbosacral spine , axial section , t1-weighted image showing conus tethering at the previous surgical exploration site magnetic resonance imaging axial section , t2-weighted image showing presence of type - ii split cord malformation with two neural tubes lying in the single dural sheath neural tube defects are congenital development anomaly and commonly observed at these potential sites , which includes posterior and anterior neuropore , as these sites used to close in the last during the embryonic life and remain most vulnerable for congenital defect . divergent views are existing regarding etiogenesis of multiple neural tube defects , and two most important theories are postulated . another theory is multiple neural tube defect closure theory , which was postulated by van allen et al . in 1993 , described , and advocated five sites of initiation for the neural tube closure process and the multiple tube defect commonly used to occur at the these collision sites of neural tube closure and as such can produce a spectrum of combinations of associated developmental anomaly , which are developing simultaneously in an individual . the occurrence of two or more meningomyelocele , or meningocele in combination with encephaloceles or even triple meningoceles , can be lying dispersed along the entire neuraxis ; however , such occurrence of two or three defects combinations occurring along the entire vertebral axis is extremely rare although reported in the form of isolated case reports . authors observed simultaneous occurrence of pentad of congenital defects , spread along the whole spinal axis , not reported previously , who presented with tethered cord in the literature , the current case report represents the first case of its kind . exact mechanism of dichotomy about the age of onset clinical presentation is still debated being symptomatic either in the infancy age or later life . as majority may get symptomatic in infancy or early childhood , a few cases only get symptomatic in adult age . the spectrum of amount of the traction applied on the conus is incriminated to be related to the age of onset of clinical manifestation . in those cases , who have thick filum terminale or very firm causing tethering and severely stretched conus , it leads to early onset of neurological disturbances even appearing in infancy or toddler age . while lesser degree of tethering may cause only minimal or nonprogressive neurological deficits in childhood , making subclinical in childhood until aggravated factors however , other postulates hypothesized that the mechanism of late onset of tethered cord syndrome is due to progression of tightening of conus ; as a child grows older , the cumulative effect of repeated cord traction over many years , during natural movement of spine , could ultimately leads to the to development of the conus injury . reported direct trauma to the back can precipitate the neurological deficit manifestations by causing deformation of the remaining merely functioning neuronal elements of the involved stretched cord . reported neurological dysfunction in patient with tethered cord correlating well with the anoxia of mitochondria , which is energy powerhouse within the conus developmental stenosis of lower spinal cord and disc prolapse are also other known precipitate factors . the closed spinal dysraphism with lipoma called as lipomyeloschisis and it can be of lipomyelomeningocele or lipomyelocele when associated with meningomyelocele or myelocele . lipomyelocele is one of the more common than lipomyelomeningocele , usually presents as a fatty subcutaneous mass and commonly located in the thoracolumbar spinal region . with the growth of spinal canal , lipomas cause distortion of nerve roots attached to the lipoma , leading to neurological deficits . posterior spinal defect is commonly observed in these patients , which is covered with skin and shows interspersed lipomatous tissue . the interface of neural placode - lipoma junction lies inside or just at dural edge within the spinal canal in the lipomyelocele , while in the lipomyelomeningocele , it lies outside the spinal canal with resultant enlargement of anterior subarachnoid space . it can clearly delineate posterior spinal elements defect with the presence of intact skin cover and interspersed lipomatous tissue . in lipomyelocele , the lipoma - neural placed interface lies within the spinal canal or at its edge while in lipomyelomeningocele it lies outside the spinal canal due to enlargement of subarachnoid space and commonly associated with low lying conus . clinically , it may present with low backache , weakness of both lower limbs , foot deformity , spinal deformity , or failure of sphincter control of bowel and urinary bladder ; these can lead to significant progressive disability and psychological trauma to the patients as well as family and associated economic loss to the society . the diagnosis of based on high degree of clinical suspicion and findings of various neuroimaging modalities includes x - ray and mri to evaluate the whole spine is must to exclude other associated lesion . however , management includes surgical detethering with careful intradural dissection of lipoma to avoid fresh neurological deficit and meticulous dural and wound closure . however , any case who had associated with sacral agenesis is another indicator for imaging screening of the entire spine . early diagnosis and prompt surgical management can be helpful in at least halting neurological deterioration , and some cases may get neurological improvement with almost negligible surgical complication rate . authors analyzed 147 cases , having spinal lipomas , out of which 93 had conus lipomas , 26 had filum lipomas , and remaining 28 had only lipomeningomyelocele . management of such cases was challenging , especially in the groups of the patients with no neurological deficits . the neurological deficits were observed in the older age group patients in comparison to those neurologically intact were relatively younger . authors also reported a rare occurrence of thoracic myelocystocele associated with multiple neural tube defects including presence of type-1 split cord malformation with low - lying tethered conus , dorsal syringomyelia in the dorsal region along with the presence of sacral agenesis , who underwent successful surgical repair . in a few cases , spinal dysraphism may have additional presence of two or multiple neural tube defect located at far from conus region along the spinal axis , so screening of the whole spine is highly imperative to look for the search for the presence of additional defect and accordingly surgical planning should be tailor made with aim to improve the neurological outcome and providing proper care in the future as many of additional anomaly currently might be asymptomatic , may get symptomatic later on , warranting neurosurgical therapeutic intervention . hence , authors advise that mri screening of the whole spine is highly essential along with screening of craniovertebral junction and scout film of brain to exclude hydrocephalus for holistic management planning of spinal dysraphism cases . hence , high degree of clinical suspicion of existence of multiple defects , detailed clinical evaluation and appropriate neuroimaging is prerequisite for proper diagnosis of such rare multiple neural tube closure defects .

neural tube defects are congenital development anomaly of the central nervous system and usually have relatively more predilection to affect at anterior and posterior neuropore embryological development sites , so usually one or two defects are commonly encountered . however , occurrence of simultaneous multiple neural tube defects is very rare , presence of constellation of five neural defects is extremely rare , and all defects add up together to produce gross neurological deficit . we present an interesting case of a 23-year - old male who presented with history of lower backache and noticed wasting and weakness of lower limbs associated with difficulty in walking for the last 2 years but had no associated sphincter disturbances . he was operated for lumbosacral lipomeningocoele repair at the age of 1 year . he was asymptomatic , following the first surgical intervention . at the current admission , he underwent re - exploration of surgical wound with surgical repair although suffered mild - temporary neurological worsening in the immediate postoperative period . imaging feature and management of such rare constellation of five embryological anomalies and its significance and brief literature are discussed .

the term work - related musculoskeletal disorders ( wmsds ) refers to msds that are made worse or longer lasting by work conditions . dentists are among the workers who are more often susceptible to msds ; their work includes risk factors that may lead to many pathologies such as tendinitis , synovitis , tenosynovitis , and bursitis . occupational diseases have not only physical , psychological , and social consequences , but also economic and security impacts when they reach a level of severity that directly affects work capacity , causing absences and early retirement . dental surgeons often can not avoid prolonged static postures . even in optimal seated postures , more than one - half of the muscles of the body this may result in damaging physiological changes that can lead to back , neck , or shoulder pain or msds . if regularly occurring pain or discomfort is ignored , the cumulative physiological damage can lead to an injury ( macro change ) or a career - ending disability . it is generally agreed that the physical posture of the operator should be such that all the muscles are in a relaxed , well - balanced , and neutral position . a thorough understanding of the underlying physiological mechanism leading to these problems is necessary to develop and implement a comprehensive approach to minimize the risk of work - related injury . in dentistry , bad working habits and repetitive tasks such as scaling , root planning , and uncomfortable physical postures contribute greatly to msds , stress , and loss of productivity . the key objective for clinicians is to find a position that allows them to achieve optimum access , visibility , comfort , and control at all times . the objectives of this pilot study wereto identify the msds in terms of perception of pain and stiffness experienced by dental surgeons due to the rigors of dental work , to determine the prevailing working environment with particular reference to dental work station in relation to msds , and to find the association between pain and stiffness experienced by dental surgeons and selected socio - demographic variables . the study was conducted on 30 graduated dental surgeons having working experience of 1 year or more , post graduates , and faculty members of various specialties at yenepoya dental college hospital , mangalore . the subjects were selected randomly from the hospital and they were given closed - ended questionnaire to find out perception of pain and stiffness experienced in the past 6 months . a written consent was obtained from all the participants on a voluntary basis and ethical clearance to conduct the study was obtained from yenepoya university ethical committee . the tools ( dental workstation observation check list- closed - ended questionnaire ) , was developed specifically for the study purpose by modifying the ergonomics recommendations for dental programs from indian health service , and musculoskeletal disorders rating scale . the check list was validated by seven experts in the subject and the modifications suggested were implemented , and reliability was established on 20 subjects . the same was pre - tested on 5 subjects . inter - rater reliability was tested for the dental workstation observation check list by using pearson product - moment correlation coefficient ( pmcc ) : ( r = 0.672 ) , reliability for musculoskeletal disorders rating scale ( pain and stiffness ) was tested by using cronbach 's alpha : frequency of pain alpha ( 0.7933 ) , frequency of stiffness alpha ( 0.7282 ) and intensity of pain dental workstation observation check list manual material handlingphysical energy demandsinstrumentsenvironmentother musculoskeletal demands manual material handling physical energy demands other musculoskeletal demands musculoskeletal disorders rating scale socio - demographic proforma - age , gender , field of dental practice , years in profession , average working hours per day , average workdays per week , average patients treated per day , height and weight.pain and stiffness - frequency of pain , stiffness and intensity of pain . statistical significance was accepted for p < 0.05 . socio - demographic proforma - age , gender , field of dental practice , years in profession , average working hours per day , average workdays per week , average patients treated per day , height and weight . pain and stiffness - frequency of pain , stiffness and intensity of pain . musculoskeletal disorder rating scale is a self - administered scale consisting of socio - demographic proforma and pain and stiffness . pain and stiffness was divided into frequency of pain , frequency of stiffness , which has three components ( always , sometimes , and never ) , and intensity of pain which was assessed by 010 numeric pain rating scale ( 0 : no pain ; 13 : mild pain ; 46 : moderate pain ; 710 : severe pain ) . the data on msds in terms of pain and stiffness are presented in table 1 . ( 6.6% ) in the case of shoulder and sometimes in the case of back and neck , which formed 83.3 and 70% , respectively . with respect to the frequency of stiffness among dental surgeons while performing their professional duties , it was observed that only 3.3% had knee pain always and a majority number of dentists observed pain sometimes in the back , ( 73.3% ) followed by shoulder pain ( 46.7% ) and neck pain ( 33.3% ) . description of musculoskeletal disorders in terms of perception of pain and stiffness among dental surgeons ( n = 30 ) in the case of intensity of pain , it was observed that 23.3% had severe pain in the back followed by shoulder pain ( 13.3% ) and 66.7% had moderate pain in the back followed by neck pain ( 33.3% ) , whereas 46.7% had mild pain in the ankle , followed by 40% reporting pain in the back , wrist , and hand . findings of the prevailing working environment in terms of the quality of dental work station [ figure 1 ] revealed that all the ( 100% ) dental surgeons had to twist at the waist , and bend at the waist to handle the instruments and to achieve postures involving sustained muscle contraction of upper limb . similarly , 96.7% required frequent bending in the neck and 90% required frequent bending in the shoulder joint . further , the study also reveals that about 86.7% of dental surgeons were unable to change position while performing their work and 83.3% had to frequently bend their elbow joints , continuously monitoring the work , and the same percentage of surgeons were using finger pinch grip . 80% of the dental surgeons had to reach a distance greater than 20 inches to perform the work and all these activities make the job of the dental surgeon a bit difficult and thus affect their musculoskeletal health . description of prevailing working environment ( dental work station ) ( n = 30 ) the association between frequency of pain and the selected socio - demographic variables presented in table 2 shows that there was a statistically significant association between patients treated per day and pain in the hip / thigh ( p = 0.024 ) experienced by the treating dental surgeons , and similarly , there was a significant association between the frequency of pain in the hip / thigh and knee and the height of the of dental surgeons ( p = 0.037 ) . all the remaining variables like gender , age , working hours per day , and weight had no significant association with the frequency of pain in neck , back , shoulder , elbow , wrist , hand and ankle / foot . association between frequency of pain , frequency of stiffness , intensity of pain , and the selected sociodemographic variables ( n = 30 ) the association between frequency of stiffness and the selected socio - demographic variables is presented in table 2 , which shows that there was a statistically significant association between age and stiffness in the neck ( p = 0.030 ) and hip / thigh ( p = 0.031 ) . similarly , there was a significant association between working hours per day and stiffness in the hand ( p = 0.018 ) and a significant association was found between patients treated per day and stiffness in the wrist ( p = 0.048 ) . also , there was a significant association between the height of the dental surgeon and the stiffness in the wrist joint ( p = 0.045 ) . frequency of stiffness in back , shoulder , elbow , knee , and ankle / foot was independent of gender and weight . the association between intensity of pain and the selected socio - demographic variables depicted in table 2 shows that there was a statistically significant association between patients treated per day and the intensity of pain in the back ( p = 0.018 ) , and similarly , there was a significant association between the weight of the dental surgeon and the intensity of the pain in the neck ( p = 0.033 ) . intensity of pain in shoulder , elbow , wrist , hand , hip / thigh , knee , and ankle / foot was independent of gender , age , working hours per day , and height . dental surgeons are normally included within the group of professionals at risk of suffering from msds due to prolonged awkward or forced postures at work and failure to adopt preventive measures . the present study found that most of the dental surgeons had some kind of musculoskeletal pain and stiffness while performing their professional work in the last 6 months . the onset of modern dentistry , as evidenced by four - handed dentistry , has made the major part of the dentist tasks purely sedentary in nature . karwaski et al . reported that the symptoms are a product of many risk factors including prolonged static postures , repetitive movements , and poor positioning . ratzen , on the other hand , linked musculoskeletal pain occurrence in the dentists to the frequent assumption of static postures , which usually requires more than 50% of the body 's muscles to contract to hold the body motion less , while resisting gravity . the static forces resulting from these postures have been shown to be much more tasking than dynamic forces . repeated prolonged static postures are thought to initiate a series of events that could account for pain , injuries , or career - ending problems seen in msds . reported that all dental specialties show a high occurrence of msds , but with variations in frequency and locations . in this study , we found that frequency of pain varies with the number of patients treated per day in the area of hip / thigh and with the height of the dentists in case of hip / thigh and knee joints . according to some studies , , we found that the frequency of stiffness varies with the age in case of neck and hip / thigh , while it varies with working hours per day in case of hand , and with number of patients treated and height of the dental surgeon in case of wrist . the intensity of pain varies with the patients treated per day in case of back and with the weight of the dental surgeon in case of neck . repetitive movements and prolonged body postures can be expected to cause muscle damage as well as ligament and joint injuries . in our study , we observed that majority of the dental surgeons had bad postures while performing their professional work . bernard found that 48% of workers had work - related neck disorders , 42% had work - related back disorders and 37% had work - related shoulder disorders . contrary to this , our study showed that 73.3% had work - related neck disorders , 86.6% had work - related back disorders , and 20.6% had work - related shoulder disorders . yamalik reported that age , gender , and perceived general health status are strongly associated with chronic complaints and seeking medical care . elderly people , women , and those who experience poor general health also report more chronic complaints . back pain has been reported to be more associated with sickness absence than neck and shoulder pain . symptoms such as carpal tunnel syndrome ( cts ) , ulnar nerve entrapment , pronator syndrome , tendonitis , tenosynovitis , thoracic outlet syndrome , and rotator cuff tendonitis may occur among all dental personnel . to sum up , dentists report a high prevalence of various types of work - related musculoskeletal symptoms and most are perceived symptoms from the neck , shoulders , and lower back . the present study reveals back pain as the most common complaint of the dental surgeons under study , followed by neck pain and ankle / foot pain . most studies consistently report that back pain is the most common musculoskeletal complaint among the dental surgeons.[2024 ] within the limitationsofthe study , msd is a significant occupational health problem among the dental surgeons . the study revealed that various socio - demographic variables contributed to the msds experienced by the dental surgeons . however , the number of patients attended per day by the dental surgeons vis - - vis pain experienced in the back , wrist , and hip / thigh was significant . however , an interventional study is needed to decrease the prevalence of msds among the dental surgeons .

aim : to describe the work - related musculoskeletal disorders among on - job dental surgeons.objectives:to identify the musculoskeletal disorders in terms of perception of pain and stiffness experienced by the dental surgeons due to the rigors of dental work , to determine the prevailing working environment with particular reference to dental work station in relation to musculoskeletal disorders , and to find the association between pain and stiffness experienced by the dental surgeons and the selected socio - demographic variables.materials and methods : the study was conducted on 30 graduated dental surgeons having a work experience of 1 year or more , post graduates and faculty members of various specialties at yenepoya dental college hospital , mangalore . the subjects were selected randomly from the hospital and they were given closed - ended questionnaire to find out perception of pain and stiffness experienced in the past 6 months . the observation of the working environment was done by walk - through observational survey.results:the study showed that 6.6% dental surgeons always experienced shoulder pain , while 83.3% dental surgeons sometimes experienced back pain and 70% sometimes experienced neck pain . majority of the dental surgeons ( 73.3% ) experienced stiffness in the back and 23.3% experienced severe pain in their neck . it was observed that the number of patients attended per day by the dental surgeons had a significant association ( p = 0.024 ) with the pain they experienced in their hip / thigh region . the frequency of pain experienced by the dental surgeons in the hip / thigh and knee joints also showed a significant association ( p = 0.037 ) with the height of the dental surgeons.conclusion:the study revealed that various socio - demographic variables contributed to the musculoskeletal disorders experienced by the dental surgeons . however , the number of patients attended per day by the dental surgeons vis - - vis pain experienced in the back , wrist , and hip / thigh was significant .

in 1932 , crohn , ginzburg and oppenheimer first presented the clinical and pathologic features of a new disease which affected the terminal ileum . they described the disease as granulomatous inflammation associated with thickening of the bowel wall , and called the condition terminal ileitis . it later became apparent , however , that any region of the gastrointestinal fract from the mouth to the anus could be affected , so its name was changed from regional ileitis to regional enteritis or crohn s disease . interest in this disease has increased recently , because its incidence and prevalence have greatly increased in western countries since the beginning of the sixties . the disease is characterized by its insidious onset with diarrhea , intermittent abdominal pain , general malaise , loss of weight and anemia ; by its indolent , prolonged and variable course ; by its diversity of clinical features ; by its perianal and sytemic complications ; and its remarkable tendency to recur after resection of the involved intestine . crohn s disease is quite rare in korea . it is not well understood why the disorder is rare in korea , but diarrhea of uncertain etiology and intestinal tuberculosis are common among koreans , and there is a possibility that the true incidence of crohn s disease have been masked . the subjects were 45 patients with crohn s disease , including 23 cases at the author s of the hospital , that had been reported in korea during the period of 34 years from 1852 to 1985 . nearly all of the cases were diagnosed having crohn disease after surgical intervention and subsequent pathologic exam of the resected specimens because they had initially appeared to have apparent surgical problems such as colon cancer , intestinal perforation , intestinal obstruction or acute appendicitis . on a retrospective basis , 45 patients were reviewed and the following details were recorded : sex , age of onset , site of macroscopic disease at diagnosis , the frequency of clinical symptoms and signs , the incidence of perianal disease , the incidence of extraintestinal manifestations , and the list of presumptive diagnosis on initial evaluation . and , we also compared the results of our patient population with representative experiences reported in the medical literatures . the total number of the patients was only 45 , and of the 45 patients , 25 were males . the male to female ratio was 1.3 to 1 with a slight preponderace to male . 1 ) ranged from 8 to 72 years , and the mean age was 35.5 . the disease was relatively uncommon before the age of ten , and the peak incidence occurred in the 3rd , 4th and 5th decades and declined therafter . nearly one third had the disease diagnosed before their 30th birthday , two thirds between their 20th and 50th birthday , and three fourths before their 50th birthday . the patients with crohn s disease were divided into those with small bowel disease alone , those with ileocolitis , those with disease involving only the colon and the rectum . nearly 60 per cent of the patients had macrosocpic disease confined to the ileum , and the ileum was involved in more than 75 per cent of the patients . the colon was also involved in one third of the patients , and in only 20 per cent of the cases is the colon affected without concomitant small bowel disease , illustrating the diffuse nature of the disorder . it appears that the vast majority of small and large bowel diseases mainly involve the ileum , cecum and ascending colon . two patients had macroscopic diseases confined to the rectum , two to the sigmoid , and one to the descending colon . table 2 shows representative experience reported in the medical literatures , and of our patient population . the proportion of patients with small bowel , small and large bowel , and large bowel disease at diagnosis shows a significantly greater portion of patients with distal small bowel involvement compared with the patients studied by other authors . there was a corresponding significant reduction in the proportion of patients with macroscopic colonic disease at diagnosis . comparison of the anatomic distribution of lesions of crohn s disease in different centers is shown in table 3 . it is worthy of notice that the anatomic distribution of lesions of crohn s disease in our patients is quite similar to that observed by dr . the proportion of the patients with macroscopic disease confined to large bowel alone was only 15.6 per cent . the most common symptom observed was abdominal pain , occurring in 89 per cent of the patients . nonspecific symptoms such as anorexia , indigestion , weight loss were observed in one fourth of the patients . table 5 shows the frequency of clinical signs according to the location of the disease . abdominal mass was palpable in more than half the cases , which made it difficult to differentiate crohn s disease from cancer of colon , especially from the one with predominant infiltration of the bowel wall and secondary ulcer formation . the frequency of perianal disease was also low in our patients , occurring in 11 per cent . extraintestinal findings and their relationship to disease sites are shown in table 7 . in our series of 45 patients , only three patients presented with symptoms of arthritis . other extraintestinal manifestations such as skin lesions , hepatobiliary manifestations , renal complications , eye complications were not observed at all . table 8 shows the list of diagnosis which had been originally made on initial evaluation . only 7 out of 45 patients had been presumed to have crohn s disease from the onset . two fifths of the patients had been diagnosed colon cancer , because abdominal mass had been palpable in the majority of these patients . ten patients had been initially thought to have intestinal tuberculosis , and two patients who had been presumed to have acute appendicitis turned out to have crohn s disease after surgical intervention . it is now known that there are highly varying difference in the reported incidence of inflammatory bowel disease throughout the world and there are no areas which careful search has found to be free of these disorders . hahn and choi in our hospital reported 23 cases of crohn s disease . a review of the literature shows another 22 cases were reported in korea by 1985 . so the total number of the patients with crohn s disease that had been reported in korea during the period of 34 years from 1952 to 1985 only 45 . it is not well understood why the disorder is so rare in korea , but there is a possibility that the true incidence of crohn s disease would have been masked because of confusion with intestinal tuberculosis and diarrhea of uncertain etiology which are quite common in korea . table 9 is a list of illnesses that could potentially be considered in the differential diagnosis of crohn s disease in korea . when , as is often the case , the disease begins abruptly with an apparantly transient episode of diarrhea , abdominal cramps and fever , the physician is likely to pass this initial episode off as salmonella infection which is quite endemic in korea . during the early , acute phase of the illness , crohn s disease tuberculous involvement of bowel and peritoneum remains a major medical problem in korea , and it is extremely difficult to differentiate intestinal tuberoulosis from crohn s disease because the two disease share cardinal features , including diarrhea , abdominal pain , fever , weight loss , and radiologic demonstration of ileocecal involvement , with x - ray findings of intramural swelling , stricture and fistulas . amebiasis , which is still common in korea , may be difficult to differentiate from crohn s disease , especially when localized to terminal ileum and cecum causing a chronic intramural lesion . because the abdominal mass is palpable in more than half the cases , it is difficult to make a differential diagnosis of crohn s disease from colon cancer , particularly if the latter lesion predominantly infiltrates the bowel wall and associated with secondary ulcer formation , which sometimes causes sinus tracts and fistulas into bowel or bladder . the ratio of male to female patients was 1.3:1 ( 25 males and 20 females ) . the age at diagnosis of the patients did not show a typical bimodal distribution which had been observed in other series . a review of the literature shows that there has been considerable change in the anatomic distribution of crohn s disease over the past 50 years , and the proportion of patients with small bowel , small and large bowel , and large bowel disease at diagnosis shows recently a significantly greater proportion of patients with large bowel involvement at diagnosis . there was a corresponding significant reduction in the proportion of patients with macroscopic ileal disease at diagnosis . it is quite interesting to find the anatomic distribution of lesions of crohn s disease in our patients is similar to that observed by dr . the literature shows that the symptoms of diarrhea is one of cardinal features of crohn s disease and is present in virtually all patients . but , in our patients group , diarrhea was observed in only 13 per cent of the patients . the exact reason why the symptom was rarely observed in the crohn s disease in korea is not well understood , but there is a possibility that crohn s disease presenting diarrhea as its chief clinical manifestation has been overlooked , because diarrhea of uncertain etiology is still prevalent in korea , masking the true incidence of crohn s disease . an abdominal mass was palpable in more than half the cases , which made it difficult to differentiate crohn s disease from colon cancers . over 40 per cent of the patients had been presumed to have colon cancer on initial evaluation , and that is one of the reasons why most cases in korea have been reported by surgeons . intestinal obstruction was observed in 11 per cent of the patients , and the frequency of the lesion was quite lower than those reported by other authors . the frequency of occurrence and detection of perianal disease is known to vary with their classification and the care of the examination , and it has also been shown that perianal disease is more common in crohn s disease and one half with crohn s colitis develop symptomatic perianal or perirectal fistulas . the overall incidence of perianal disease in our patients was only 11 per cent , and it is suggested that low incidence of perianal disease might be due to small percentage of the disases with macroscopic involvement of large bowel . it is now known that systemic manifestations develop in crohn s disease , particularly in those individuals who have colonic involvement , about as often as they occur in ulcerative colitis . extraintestinal manifestations also appear to occur more frequently among patients with perianal disease . in our series of 45 patients , only three patients presented symptoms of arthritis , and other extraintestinal manifestations such as skin lesions , hepatobiliary manifestations , renal complications , eye complications were not observed at all . in conclusion , crohn s disease is a quite rare disease among koreans , so it may be that this review on inflammatory bowel disease can not be given in statistically meaningful terms , and it would be better to accept the results of the data as a simple indication of the existence of crohn s disease among korean people .

crohn s disease is a rare disease in korea , and only 45 cases have been reported during a 34 year from 1952 to 1985.the male to female ratio was about 1.3 to 1 with a slight preponderance of males . the age at diagnosis ranged from 8 to 72 ( mean 35.5 ) years , and the peak incidence occurred in the 3rd , 4th and 5th decades and declined thereafter.more than two thirds of the cases had a grossly demonstrable lesion involving the small bowel including the terminal ileum . the proportion of the patients with macroscopic disease confined to the large bowel alone was only 15 per cent.abdominal pain was common presenting in 89 per cent of the patients , while such symptoms as fever , hematochezia and diarrhea were not common . abdominal mass was palpable in more than half the cases , which made it difficult to differentiate crohn s disease from cancer of the colon , especially from the one with a predominant infiltration of the bowel wall and a secondary ulcer formation . that is one of the reasons why most cases in korea have been reported by surgeons.a wide variety of complications were present , of which small bowel obstruction was the most common . other complications were free perforation , malnutrition , fistula formation , hemorrhage and abscess formation in decreasing order.the incidence of symptomatic perianal diseas was only 11 per cent , and this might be due to the small proportion of the disesase confined to large bowel.extraintestinal manifestations were also rare , and only three patients presented the symptoms of arthritis . other systemic features such as liver disease , skin lesions , eye complicaitons were absent .

there has been an ongoing debate in several countries on who is not qualified to learn and practice cosmetic and aesthetic procedures . many professional societies representing a diverse group of specialists often claim competence in a particular cosmetic or aesthetic procedure and project it as their exclusive domain and try to restrict other specialists from other streams to learn it , do it and master it . this is a seemingly never - ending debate , and the professional societies often have biased views due to conflicting interests . the regulatory bodies have been unable to decide on such issues , as aesthetic medicine and surgery is a relatively new field which at present is poorly defined , high in demand and not an independent speciality with a dedicated postgraduate course . aesthetic medicine and surgery is gaining rapid significance as the society at large has given up the myth of inner beauty since the 1980s and allowed open and uninhibited discussions on physical beauty . the biological anthropologist karl grammer found that symmetrical scorpion flies attract more mates than asymmetrical ones . in humans , it has been observed that even young infants look more frequently at beautiful faces and beautiful children are less likely to get punishment in school . appreciation of beauty is one of the conserved traits in the animal kingdom [ figure 1a ] . the author was attracted towards the beauty of these flowers , so was the insect . dermatologic aesthetic surgery international league congresses are so successful because they engage different specialists on a single platform to create a high - standard scientific programme . the picture shows some of the indian colleagues during a social event of the dermatologic aesthetic surgery international league congress - 2016 in dubai quantum physicist david deutsch introduced the concept of objective beauty . he emphasised that beauty exists outside cultural fads or sexual selection and it is as objective as the laws of mathematics and physics . people from south africa and austria judged the same japanese women as beautiful suggesting that beauty is defined on similar lines across cultures . populations as diverse as the members of hazda tribe of africa , who are not exposed to the external world and europeans , judged the more average faces of hazda tribe as attractive suggesting that the cross - cultural similarity of beautiful traits is not due to the effect of western media and ideals . extreme ( non - average ) genotypes are more likely to possess genes that are detrimental to an individual than those with more average genotypes . thus attraction to averageness ( close resemblance to the majority of other faces within a population ) is also explained by theory that beauty is associated with biological fitness . , there is a great demand and huge market for the so - called fairness creams which reflect the strong desire of people to turn the dark colour of their skin fairer or close to the global averages . on the other hand , many light skin - coloured populations in the west try to tan their skin by exposing to sun or ultraviolet rays to make their skin darker ( closer to the global averages ) even at the risk of exaggerated photoageing and skin cancers at a later age . though the basis of beauty is explained by biology research has shown that attractive people are judged as being more trustworthy as compared to the not - so - attractive ones . the author ( sg ) introduces the concept of aesthetic socialism ; according to this , those who are not so beautiful or those who have lost their beauty because of disease , trauma or ageing should have an opportunity to achieve or regain attractiveness by enhancing or restoring their beauty by modifying dimensions , proportions and complexion to bring them closer to the population averages so that they can enjoy social privileges which a naturally beautiful person enjoys . aesthetic medicine and surgery can help achieving this by interdisciplinary cooperation and interaction to devise strategies to enhance or restore beauty . karl grammar has done extensive work on the anthropological , biological and evolutionary basis of beauty . he identified eight pillars of beauty ( the author has added two more i.e. the body shape and physical fitness ) . table 1 suggests how inter - disciplinary cooperation is necessary to achieve the aesthetic socialism . the pillars of beauty and how experts from different specialities can work together to enhance or restore beauty when it is lost or missing and achieve the goal of aesthetic socialism by giving everyone a chance to look beautiful and thus enjoy sociocultural advantages modern medicine , as a whole , and aesthetic medicine and surgery , in particular , is rapidly becoming a part of the profit - making industry . when we adopt the models of market for medicine , we are exposed to both the strengths and pitfalls of the market . we are living in a globalised world which allows open competition in the market ; those who provide quality services and products will survive . minimally invasive aesthetic medicine and surgery is among high - demand , high - profit and low - risk ventures and attracts a large number of specialists from different specialities . this upwards trend of inter - specialty aesthetic care is likely to continue for several more years until it slows down due to saturation of the market . for example , the number of cosmetic procedures in the united states has increased from 10 million procedures in the year 2005 to close to 16 million procedures in 2014 , this amounts to an enormous growth of 60% . the american society of plastic surgeons report indicates 759% increase in the use of botulinum toxin type a , 274% increase in soft - tissue fillers , 14% increase in chemical peel and 52% increase in laser hair removal between 2000 and 2015 in the united states . this includes a period of economic recession which affected other industries but did not affect the growth of cosmetic procedures . hassan ghaladari jokingly said in his lecture during the dermatologic aesthetic surgery international league ( dasil ) congress in 2016 at dubai that people may die hungry but they do nt want to die ugly. thus , the insecurities of specialists regarding the loss of market to another specialty to another specialty are excessive and unnecessary . rather professional societies should focus on strengthening the training opportunities for their members to improve the quality of aesthetic services and place them in a comfortable position in the aesthetic industry . the training opportunities to interested specialists will continue to grow to meet the increasing demand of cosmetic procedures . as the open market principles are applicable to aesthetics , different specialties and specialists would seek and attempt to legitimise their claim on this field . on the other hand , beauticians and unqualified workers will also try to put forward their claim on quasi - medical cosmetic procedures in an attempt to capture the market . this may become a challenge in countries where regulatory bodies are not so effective . in such countries , they will capture a significant share of the minimally invasive aesthetics market as services provided by them will be economical as compared to qualified physicians . it is an excellent platform where experts and specialists of various specialties who have common interests in aesthetic and dermatologic surgery come together to exchange knowledge and interact [ figure 1b ] . just have a look at their membership categories below ; it does not discriminate between specialties : fellow member : a physician or surgeon , either allopathic or osteopathic , in good standing within the individual 's country and is certified or credentialed by the country 's or regional accrediting agencyassociate member : a physician or surgeon , either allopathic or osteopathic , in good standing within the individual 's country and who is eligible to be credentialed by the country or geographical accrediting agencyfellow - in - training : an individual currently engaged in post - residency or postgraduate study : graduate of an allopathic or osteopathic school who is studying in specialty - focused trainingaffiliate : a non - graduate of either an allopathic or osteopathic medical school who is actively engaged in the study and training of either dermatologic or aesthetic surgery or is employed supporting this practice environmentretired : a person who is no longer in active practice or employment , who has reached a predefined age but still wants involvement with the dasil . fellow member : a physician or surgeon , either allopathic or osteopathic , in good standing within the individual 's country and is certified or credentialed by the country 's or regional accrediting agency associate member : a physician or surgeon , either allopathic or osteopathic , in good standing within the individual 's country and who is eligible to be credentialed by the country or geographical accrediting agency fellow - in - training : an individual currently engaged in post - residency or postgraduate study : graduate of an allopathic or osteopathic school who is studying in specialty - focused training affiliate : a non - graduate of either an allopathic or osteopathic medical school who is actively engaged in the study and training of either dermatologic or aesthetic surgery or is employed supporting this practice environment retired : a person who is no longer in active practice or employment , who has reached a predefined age but still wants involvement with the dasil . for a professional society to grow and expand , it has to breach the narrow boundaries of nationality , specialty , gender , age , etc . , the association of cutaneous surgeons ( i ) ( acs[i ] ) can take the lead from the dasil . some suggested steps which acs(i ) can take for its members are as follows : take initiatives to include cosmetic , aesthetic and dermatologic minimally invasive procedures in postgraduate training curriculum of dermatologyform an alliance with different specialities to ensure holistic advancement in the field of cosmetic and aesthetic surgeries in india . this will ensure exchange of knowledge and will facilitate learning of acs(i ) members from the best of the expertsincrease learning opportunities for its members through multidisciplinary conferences , workshops , hands - on training courses and fellowships . however , in the second phase , acs(i ) should involve experts from other specialties and use modern techniques in imparting training and providing fellowships to its members [ figure 2 ] . this will be mutually beneficial.let us stop worrying about the loss of patient population to another specialty . there are 10,000 dermatologists in india for a population of 1.3 billion , out of whom , only less than a quarter practice cosmetic and aesthetic surgeries . this means , on an average , one cosmetic dermatologist is catering to the aesthetic needs a population of about 500,000 people . the demand and supply deficit will continue to remain high . take initiatives to include cosmetic , aesthetic and dermatologic minimally invasive procedures in postgraduate training curriculum of dermatology form an alliance with different specialities to ensure holistic advancement in the field of cosmetic and aesthetic surgeries in india this will ensure exchange of knowledge and will facilitate learning of acs(i ) members from the best of the experts increase learning opportunities for its members through multidisciplinary conferences , workshops , hands - on training courses and fellowships . however , in the second phase , acs(i ) should involve experts from other specialties and use modern techniques in imparting training and providing fellowships to its members [ figure 2 ] . there are 10,000 dermatologists in india for a population of 1.3 billion , out of whom , only less than a quarter practice cosmetic and aesthetic surgeries . this means , on an average , one cosmetic dermatologist is catering to the aesthetic needs a population of about 500,000 people . milind naik , an oculoplastic surgeon from hyderabad , india , had organised a three - dimensional video workshop for the association of cutaneous surgeons ( i ) members , mostly dermatologists , during the association of cutaneous surgeons ( i ) north zone workshop on november 13 , 2016 , in new delhi . interdisciplinary interaction and exchange of knowledge along with the use of modern technologies for training and teaching are the need of the hour about 1 centuries ago , charles darwin introduced his famous theory of evolution . according to his theory , struggle and violence however , subsequently , with further advancement of science , we came to the realisation that cooperative interaction among organisms and their environment is a far more important factor in evolutionary advancement than competitive struggle . the cooperation among the members of hunter - gatherer homo sapiens gave them an evolutionary edge and thus supremacy over other species . the countries such as the united states which have opened their door to scientists and technocrats from all over the world have achieved more prosperity and technological advancement . as an association , we should follow the same model if we wish to evolve in the current socio - cultural - economic scenario with the rapidly increasing demand of cosmetic and aesthetic procedures [ figure 2 ] . in the introduction , the author said aesthetic and cosmetic surgery is no one 's domain , he ends this viewpoint by saying aesthetic and cosmetic surgery should be everyone 's domain ( i.e. everyone , in allied specialities who is trained in aesthetics ) , till such time it is an independent specialty with a dedicated post - graduate course .

the rise of aesthetics in medicine has resulted from society 's acknowledgement of the importance of physical beauty . this has led to an emerging conflict between allied specialties . the author introduces the concept of aesthetic socialism according to which everyone should have an opportunity to enhance or restore the beauty where it is missing or when it is lost due to disease , trauma or ageing . however , there are multiple aspects of aesthetics , which can not be addressed by a single specialty , therefore author recommends interdisciplinary cooperation rather than conflict to achieve aesthetic socialism .

medical practitioners commonly advice their patients who are on antiplatelet therapy to either stop or alter their medications prior to surgical procedures due to fear of excessive and uncontrolled bleeding . it is a proven fact that aspirin causes increased risk of intraoperative as well as postoperative bleeding and also increased risk of thromboembolic events such as myocardial infraction and cerebrovascular accidents if the drug is continued . thrombotic and thromboembolic occlusion of blood vessels is the main cause of ischemic events in heart , lungs , and brain . in case of blood vessel injury , primary mechanism arrests early bleeding as a result of platelet plug formation . the secondary hemostasis phase is mediated by a complex cascade of clotting factors which helps in the formation of fibrin clot . in recent years , lot of research has been done and progress has been made in the field of antiplatelet agents and anticoagulants . even though a number of antiplatelet and anticoagulant agents have been developed , aspirin and warfarin remain the standard drugs of choice . development of aspirin dates back to 1897 and is considered as one of the safest and cheapest drugs worldwide . a general practitioner lawrence craven prescribed low - dose aspirin ( baby aspirin ) to his 400 patients and none of them developed myocardial infraction . this was probably the first time in medical history where aspirin was used to prevent myocardial infarction . the antithrombotic effect of aspirin is mediated by irreversible inhibition of cyclooxygenase activity in platelets . thromboxane a2 is a potent platelet stimulant which leads to degranulation of platelet and platelet aggregation . aspirin inhibits cyclooxygenase enzyme and decreases the level of platelet stimulant thromboxane a2 , thus increasing the bleeding time . this is the important reason for a medical practitioner to stop aspirin 3 - 7 days prior to any invasive surgery . the purpose of this study was to investigate the influence of aspirin on post - extraction bleeding . patients who were on aspirin therapy , aged between 50 and 65 years , and who had to undergo tooth extraction for endodontic reason with no mobility were selected for the study . patients on warfarin , non - steroidal anti - inflammatory drugs , heparin , steroids , or suffering from blood disorders and diabetes were excluded from the study . informed consent was obtained from the patients and the ethical committee clearance was also obtained . two hundred patients including both males and females whose teeth were indicated for extraction were included in the study . group a patients continued to receive aspirin preoperatively , while group b patients were asked to stop aspirin 7 days prior to extraction after consultation with the physician . bleeding time ( white and lee technique ) and clotting time ( ivy 's technique ) were calculated . after atraumatic extraction ( forceps method ) was performed , the bleeding time was recorded . chi - square test was used to evaluate the relative frequencies of patients in both groups . after applying chi - square test , the mean bleeding time was calculated as 2.1 0.52 min in the patients who discontinued baby aspirin ( group b ) 7 days prior to extraction . bleeding time of group a patients who continued aspirin through the entire study was found to be 3.8 0.75 min . this difference was statistically significant ( p = 0.002 ) [ table 1 and graph 1 ] . although there was significant increase in the bleeding time of group a patients , it should be noted that the bleeding time of both the groups was within normal limits . clotting time of group b patients was 3.8 0.75 min and group a patients was 4.7 0.52 min , which were also within the normal limits ( normal range according to ivy 's method : 3 - 5 min ) . mean bleeding time and mean clotting time ( in minutes ) of group a and group b patients historically , aspirin was used as an anti - inflammatory , analgesic , and antipyretic drug for a short period of disease activity . in 1950 , lawrence craven reported for the first time its long - term use to prevent myocardial infarction . antiplatelet activity of aspirin occurs at doses ranging from as low as 40 mg / day to 320 mg / day . doses above 320 mg / day decrease the effectiveness of aspirin as an antiplatelet agent due to inhibition of prostacyclin production . however , recent clinical trial indicates that 160 mg / day is optimal for antiplatelet action . in emergencies where urgent antithrombotic action is required , a loading dose of 300 mg is advocated . usually , in the united states , daily dose of 81 mg , 160 mg , or 325 mg is prescribed , while in europe and other countries , daily dose of 75 mg , 150 mg , or 300 mg is prescribed . risk of continuing aspirin therapy prior to surgery is that with the alteration of platelet function , longer time period is required to stop bleeding from a surgical site . collet et al . stated that in patients on aspirin , the average risk of bleeding increases 1.5-fold . at the same time , there is a risk of stopping aspirin prior to surgery , which leads to a potential risk of rebound of thromboembolic vascular events . on stopping aspirin , thromboxane a2 activity increases to a greater extent with decrease in fibrinolytic activity . anderson et al . showed the existence of biological platelet rebound phenomenon on interruption of aspirin therapy . approximately 20% of these episodes are fatal and another 40% can lead to permanent disability . practitioners who advocate the stoppage of aspirin have been debating among themselves regarding the time limit to stop aspirin . according to literature the effect lasts for 7 - 10 days which is the life span of platelets . sonksen et al . , in their study comprising 52 healthy individuals , reported that it is not recommended to withdraw aspirin for more than 5 days . wahl et al . advocated that aspirin should be discontinued for 3 days only , as after 3 days of interruption of aspirin , sufficient number of newer platelets would be present in the circulation for hemostasis . some studies have shown that there is always an increased risk of bleeding in patients continuing aspirin . however , if the aspirin therapy is discontinued , there is increased risk of thromboembolic events which can be fatal , but none of these have been reported in dental literature . mentioned in their article that there is scarcity of literature regarding dental surgeries involving patients on aspirin medication . little et al . reported that unless the bleeding time is increased above 20 min , aspirin - affected platelets would not cause significant bleeding complication . canigral et al . conducted a research involving surgical extraction in patients on antithrombotic therapy . in 92% cases , gaspar et al . advocated that ambulatory oral surgical procedures can be performed in patients without discontinuing the use of aspirin . a recent recommendation from the american heart association and american college of cardiology is either continuing aspirin or clopidogrel therapy for minor oral surgical procedures in patients with coronary artery stents or delay the treatment until prescribed regimen is complicated . the present study demonstrated that there was significant increase in the bleeding time in both the groups , but it was not difficult to stop the bleeding in any case . although the bleeding time increased in group a patients , it still remained within the normal range , regardless of whether the patients continued or discontinued their aspirin therapy . conducted a study with 17 patients randomized to aspirin and 19 to placebo and found no differences in the bleeding outcomes for patients on aspirin . this finding suggested that there was no need to discontinue aspirin prior to any ambulatory oral surgical procedure . adchariyapetch compared the postoperative bleeding in subjects who stopped taking aspirin and those who continued taking aspirin for 7 days prior to extraction . matocha concluded in his study that the risk of bleeding after dental extraction is minimal in the patients with aspirin therapy and did not exceed 0.2 - 2.3% murphy et al . concluded in their survey that 86% of the dental practitioners who advised patients to stop taking antiplatelet drugs prior to dental extraction did so with the consultation of the patients physicians , and found that the protocol followed by the physicians and dentists was not based on the current recommendations and guidelines . concluded that the risk of stopping antiplatelet therapy and predisposing the patient to thromboembolic events overweighed the minimal risk of bleeding from dental procedures . wahl reported in his study that of 950 patients receiving anticoagulation therapy , only 12 required ( < 1.3% ) more than local measures to stop the bleeding . he concluded that while discontinuation of anticoagulation therapy has been a common practice , bleeding after dental surgery is rarely life threatening . thus , it can be concluded based on dental and medical literature that if a practitioner wishes to discontinue the aspirin therapy , it should not exceed more than 3 days . risk of stopping antiplatelet therapy and predisposing the patient to thromboembolic events overweighs the minimal risk of bleeding from dental procedures . although there was increase in bleeding time in the present study , it was not beyond the normal range . hence , it can be concluded that low dose of aspirin should not be discontinued prior to dental extractions , as it predisposes the patient to unwanted thromboembolic events .

aim : the aim of the study was to evaluate the influence of aspirin on post - extraction bleeding in a clinical setup.materials and methods : two hundred patients aged between 50 and 65 years who were indicated for dental extraction for endodontic reason were selected from the outpatient department of oral and maxillofacial surgery . the patients were randomly divided into aspirin continuing group ( group a ) and aspirin discontinuing group ( group b ) . after checking all the vital signs , the extractions were carried out . bleeding time and clotting time were recorded for evaluation by chi - square test.results:chi-square test revealed that the bleeding time increased ( 3.8 0.75 ) in group a patients continued with the aspirin therapy where as group b discontinued aspirin . similarly , the clotting time increased in group b patients and decreased in group a patients . but in both the groups , bleeding and clotting time remained within normal limits.conclusion:reviewing most of the dental and medical literature , it can be concluded that there is absolutely no need to discontinue antiplatelet therapy for any ambulatory dental procedure , and even if the practitioner wishes to discontinue , it should not be for more than 3 daaq2ys . this is also stated in the guidelines of the american heart association .

infective endocarditis ( ie ) is a severe acquired heart disease , which is frequently observed in kawasaki disease , neonates and infants suffering from severe infections , as well as children with a correction of congenital heart disease ( chd ) at a younger age . although antibacterial therapy is the current mainstay for ie management , surgical intervention has been adopted in some patients , especially for those who have a vegetation . disintegration and/or falling of a vegetation is the most frequently observed severe complications in ie ; it may block downstream arteries in pulmonary or systematic circulation based on its location , resulting in paralysis or sudden death . here , we report a rare ie case with a complication of pulmonary artery dissection ( pad ) following the detachment of vegetation , which was successfully treated with surgical intervention . to our best knowledge , this is first case of pad complication in an ie patient . this study was approved by the ethics committee of west china second university hospital of sichuan university . a 10-year - old female child experienced cough and fever ( > 38c ) for > 10 days , with a progressive exertional dyspnea was admitted to our hospital . the echocardiography revealed a patent ductus arteriosis ( pda , 5 mm shunting duct ) and a vegetation on the left side of pulmonary artery trunk ( 10 5 mm ) , which moved with the heart beating . in addition , pulmonary valvular regurgitation and pericardial effusion have also been identified ( figure 1a ) . the bacterial and fungal culture showed negative results , presumably owing to antibacterial treatment before admission . upon reviewing previous records in addition , the rheumatoid factor test was positive and ct scan revealed severe pneumonia . according to the duke criteria , the patient was diagnosed as ie , meeting 1 primary diagnostic criterion ( vegetation in pulmonary trunk ) and 3 secondary diagnostic criteria ( fever , essential heart disease , and positive rheumatoid factor ) . ( a ) the presence of a vegetation in pulmonary artery upon admission to hospital . ( b ) the dissection of pulmonary artery after the falling of the vegetation . based on the positive result for s aureus from the previous blood bacterial culture , vancomycin ( 1 g / day ) and cefoperazone ( 4 g / day ) echocardiography showed the pre - existing pda , reduction of pericardial effusion , and smaller size of vegetation on pulmonary artery trunk ( 7 3 mm ) . taken together , the treatment was proper and effective . surprisingly , the patient had a sudden attack of sustained and crushing right chest pain , orthopnea with increasing respiratory rate ( > 60/min ) , and high fever . the emergency echocardiography revealed the detachment of vegetation , which presumably entered the second or third sectional pulmonary arteries . despite of negative results for blood bacterial culture , the antibacterial regimen was amended as vancomycin ( 1 g / day ) plus meropenem ( 1.5 g / day ) based on our empirical success in managing patient with septic embolism . on the next day , the repeated echocardiography revealed the dissection of pulmonary artery with a newly formed aneurysm with a size of 25 18 mm ( figure 1b ) . chest x - ray revealed a large prominence of pulmonary artery truck when compared to previous examination ( figure 2a and b ) . the contrast - enhanced ct scan indicated that the pulmonary artery dissection originated from the site where the former vegetation located ( figure 2c ) . considering the risk of aneurysm rupture , because there was no evidence of pulmonary artery hypertension and the size of aneurysm was < 50 mm , the replacement of pulmonary artery and the insertion of endovascular stent - graft were not recommended by surgeons . instead , the direct repair of aneurysm and closure of pda with suture were carried out under general anesthesia and standard extracorporeal circulation . following pericardiotomy , the dilated aneurysm on pulmonary artery was exposed . under mild hypothermia , cardiopulmonary bypass was conducted with aortic and bicaval cannulations . after cardiopulmonary bypass was established , the main pulmonary artery was dissected carefully to expose the lesion site of the pad . it was found that aneurysm had a size of 28 20 mm and its orifice ( the dissecting site , on the left side of the pulmonary artery trunk ) located on the opposite side of the pda opening ( right side of the pulmonary artery trunk ) . the dissected left wall of pulmonary artery trunk was reconstructed followed by the closure of pda with suture . echocardiography on 8th postoperative day revealed normal cardiac function and a smooth pulmonary artery lumen . patient was discharged on the 10th postoperative day . the chest x - ray and ct scan . ( b ) x - ray shows the significant increase in prominence of pulmonary artery segment . there are < 100 reported cases of pad in the literature , and most of them were found in autopsies for individuals with a sudden death . although pad has a very high mortality rate , no consensus has been reached on how to prevent the formation of pad . the primary pulmonary hypertension or secondary to chd are considered as the major cause of pad . vascular inflammatory disease , aorto - pulmonary fistulas , connective tissue disease , and catheter - induced vessel wall injury are also considered to be potential risk factors . to our knowledge , the present study is the first report of a pulmonary artery dissection associated with ie . regarding the formation of vegetation and pad in this patient the abnormal hydrodynamics from the pda shunting might cause the injury on the wall of pulmonary artery trunk and facilitate bacterial colonization . we speculate that the bacterial growth formed a vegetation and subsequently developed into severe ie . following the 3-week antibacterial treatment , the vegetation shirked and disintegrated . unfortunately , the falling of vegetation remainder resulted in the embolization of the sectional pulmonary arteries . despite the patient survived this severe complication , the vegetation attaching site might be further damaged by the shearing stress from the shunting blood and resulted in a dissection . in summary , pda might initially facilitate the formation of bacterial vegetation , and the focal lesion from bacteria weakened the pulmonary arty wall . in the meantime , pda might also contribute to the development of pad after the falling of vegetation . this case suggested that pad could occur in the absence of pulmonary hypertension if a pda is present in ie patient . in the past decades , extensive studies have been conducted on the treatment of ie , and several guidelines have been established and proved to be effective . according to the standard regimen , the antibacterial therapy should be started as soon as the ie is diagnosed and should be given continuously for at least 4 week . during such long duration of treatment , recently , surgical intervention has been considered as the second option for ie patient who have an indication . the surgical removal of vegetation , repair of injured cardiovascular wall , and correction of abnormal structure greatly decrease the risk of complications and improve the prognosis . however , it is still controversial when the best time for such an operation is . based on our experience with the present case , we propose to conduct the operation at a earlier time for ie patients with a vegetation in pulmonary artery when the following conditions are observed during antibacterial treatment : ( 1 ) normal body temperature , ( 2 ) negative results for multiple bacterial cultures , ( 3 ) reduction of vegetation size , ( 4 ) decrease in adhesion and/or increase of vegetation movement , ( 5 ) reduction of pericardial effusion , and ( 6 ) evidence of pulmonary hypertension . the earlier surgical intervention may be able to prevent the development of severe complication , such as pad . of course , in addition to these considerations , the final regimen should be determined by overall surgical risk for specific individuals . the present study is the first report of pad associated with ie and pda without the presence of pulmonary artery hypertension . because of timely surgical intervention , the patient survived pad and recovered . from this case , we learned that the surgical intervention should be considered at an early time ( after the infection is fully controlled ) for ie patients who have a vegetation in pulmonary artery and pda .

abstractpulmonary artery dissection ( pad ) is a rare condition with high mortality and has not been reported in patient with infective endocarditis ( ie ) . here , we report the first case of such patient who experienced pda and survived after surgical intervention.a 10-year - old female child was diagnosed as ie with a patent ductus arteriosis ( pda ) and a vegetation on the left side of pulmonary artery trunk ( 10 5 mm2 ) . following 3-week antibacterial treatment , the body temperature of patient returned to normal , and the size of vegetation reduced ( 7 3 mm2 ) . however , the patient had a sudden attack of sustained and crushing right chest pain , orthopnea with increasing respiratory rate ( > 60/min ) , and acute high fever . echocardiography revealed the detachment of vegetation on the first day and dissection of pulmonary artery on the next day . the patient received immediate surgical intervention . it was found that aneurysm had a size of 28 20 mm2 and its orifice ( the dissecting site ) located on the opposite side of the pda opening ( right side of the pulmonary artery trunk ) . the dissected left wall of pulmonary artery trunk was reconstructed followed by the closure of pda with suture . the patient recovered uneventfully.from this case , we learned that the surgical intervention should be considered at an early time for ie patients who have a vegetation in pulmonary artery and pda . after the infection is under control , the earlier surgery may prevent severe complications .

individuals with refractory epilepsy are investigated for surgical candidacy using noninvasive techniques such as functional magnetic resonance imaging ( fmri ) and functional near infrared spectroscopy ( fnirs ) for presurgical assessment of language lateralization . however , the clinical value of these techniques is still unclear , especially in the pediatric population . this case study describes the repeated use of pre- and postsurgical fmri and simultaneous functional near infrared spectroscopy and electroencephalography ( fnirs eeg ) for language localization in a boy with refractory epilepsy who underwent multiple resective surgeries for a left temporal lobe tumor . seizure onset occurred at 5 years with drug - resistant focal dyscognitive seizures occurring three to four times a day . his seizures involved a loss of consciousness for 20 to 45 s accompanied by automatisms . his mri revealed changes compatible with a neuroglial tumor located in the left temporal lobe including wernicke 's area . at 6 years old , the patient underwent a presurgical assessment followed by a first resection of the tumor . a second presurgical assessment was performed and led to a second resection of an enlarged tumor at age 10 . initial pre- and postsurgical cognitive assessments revealed normal intellectual functioning with attention and executive deficits as well as a moderate to severe receptive and expressive dysphasia . more specifically , language assessment revealed a poor lexical access and difficulties of phonological awareness and for the understanding of complex instructions . at 6 and 10 years old , the patient underwent presurgical assessments for language lateralization and localization including fnirs eeg and fmri while he performed expressive and receptive language tasks . at 11 years old , a postneurosurgical fmri was performed for language investigation . the expressive language task consisted of a categorical verbal fluency task ( e.g. , name as many animals as possible ) . both tasks were done alternatively with rest periods . combined with fnirs ( imagent , iss ; 11 detectors , 46 sources ( 690/830 nm ) ) , eeg ( 19 electrodes ) simultaneous eeg was not possible during fmri ( simens , germany ; 1.5 t ) because of technical constraints . significant hemodynamic changes in regions of interest ( rois : broca 's area or brodmann 's areas 44 and 45 and wernicke 's areas or brodmann 's areas 22 , 39 , and 40 , and right homologous regions ) were identified by computing a two - tailed paired t - test ( fnirs ) and t statistic ( fmri ) of a general linear model analysis on hemodynamic responses . for language lateralization , significant ( p < 0.05 ) hemodynamic changes in the left ( lh ) and right ( rh ) hemisphere rois associated with each language task , compared with rest periods , were used to calculate a lateralization index ( li ) . the li was calculated on mean around the peak ( 5 s ) of activations measured in the rois ( broca 's area for expressive language ; wernicke 's area for receptive language ) . the li was calculated using the following formula : ( ( lh rh ) / ( lh + rh ) ) . the li values range between 1 and 1 , with a value between 1 and 0.26 , indicating right hemisphere dominance , and between 0.26 and 1 , indicating left language lateralization , and with a value close to zero ( 0.25 to 0.25 ) revealing a bilateral distribution . at 6 years old , the first presurgical fnirs showed left hemisphere dominance for expressive language ( li = 0.5 ) , with a significant activation in broca 's area ( fig . the receptive language was not assessed because of time limitation . to validate fnirs results , the fmri showed left hemisphere dominance for receptive language ( li = 0.3 ) but inconclusive results for expressive language . at 10 years old , a second presurgical fnirs showed right hemisphere dominance for both expressive and receptive language ( li = 0.5 and 0.3 , respectively , fig . conversely , fmri showed left hemisphere lateralization for receptive language ( li = 0.3 ) and inconclusive results for expressive language . a postsurgical fmri performed at 11 years old , while the patient was seizure - free , showed right hemisphere dominance for receptive language ( li = 0.3 ) , confirming the second presurgical fnirs findings . this case study illustrates the potential for fnirs to contribute favorably to the localization of language functions in children with epilepsy and cognitive or behavioral problems . to verify whether the child correctly understands the instructions and performs the task properly during recordings , it is essential that expressive language tasks are performed aloud , therefore generating muscle and articulatory movement artifacts , which are less tolerated by fmri . conversely , fnirs has no major restrictions on movements , making it suitable for investigations in young children with behavioral disorders . as in this 6-year - old boy , it is not always possible to obtain conclusive results using fmri because of movement constraint and the intimidating environment . consequently , multiple scans may be required and are associated with significant costs . as for receptive language tasks , the intimidating noise associated with the scanner makes it more difficult for listeners to entirely hear the auditory stimuli , subsequently disengaging the participants from performing the task , especially in a pediatric population . in contrast , fnirs has no major ambient noise , which allows participants to clearly hear stimuli , thus providing better language localization . another advantage of fnirs over fmri is that an experimenter is always present during the acquisition to ensure that the child adequately performs the tasks ; this approach provides a more child - friendly recording session . at 10 years old since eeg was not simultaneously acquired with fmri data , it could not be excluded that left hemisphere activation found during the language task could be related to epileptic discharges occurring during the acquisition and not to a specific language response . the eeg acquired simultaneously with fnirs allowed us to exclude epileptic discharges from the analyses , providing more reliable language localization . moreover , these results were supported by stable language functions found after the second left temporal resection and by the postsurgical fmri showing right hemisphere language dominance while the patient was seizure - free . therefore , the use of simultaneous eeg during fnirs or fmri data acquisition provides important information , especially in patients with temporal lobe epilepsy , considering that epileptic activity may interfere with language localization . in the present case , the first presurgical fnirs revealed a typical left hemisphere language lateralization whereas the one performed prior to the second resection showed atypical right language representation and brain reorganization , which is probably reflecting a compensatory mechanism supported by brain plasticity . it has been reported that the damage associated with epilepsy stimulates the brain either to activate preexisting connections to the dormant functional language areas or to recruit new areas in the right hemisphere to compensate for the altered left hemisphere language centers . for instance , an fmri study investigating language patterns in 34 children with epilepsy aged from 7 to 18 years performing a verbal fluency task revealed a reorganization of the language network that was significantly influenced by both age of onset and duration of epilepsy . in fact , early onset and a longer duration of the epilepsy are factors that increase the probability of cerebral language reorganization . in this young patient , we found evidence for interhemispheric language reorganization after his first resection using fnirs , thus confirming that fnirs is a sensitive tool in the localization of language network reorganization related to epilepsy . overall , this case report highlights the clinical value of fnirs in the presurgical assessment of young patients with epilepsy and its potential advantages over fmri . to conclude , fnirs is a promising technique , which may serve to determine language localization or to investigate atypical language representations in young patients with epilepsy .

as part of a presurgical investigation for a resection of a tumor located in the left temporal brain region , we evaluated pre- and postsurgical language lateralization in a right - handed boy with refractory epilepsy . in this study , we compared functional near infrared spectroscopy ( fnirs ) results obtained while the participant performed expressive and receptive language tasks with those obtained using functional magnetic resonance imaging ( fmri ) . this case study illustrates the potential for nirs to contribute favorably to the localization of language functions in children with epilepsy and cognitive or behavioral problems and its potential advantages over fmri in presurgical assessment . moreover , it suggests that fnirs is sensitive in localizing an atypical language network or potential brain reorganization related to epilepsy in young patients .

an important goal of community ecology is to illuminate the processes governing the assembly and coexistence of species ( hardy , 2008 ) . because phenotypes are not randomly distributed with respect to phylogeny , we should expect a direct link to exist between the evolutionary relatedness of organisms in a community , the characters they possess , and the ecological processes that determine their distribution and abundance ( kraft et al . , 2007 ) . a phylogenetic perspective that recognizes the dual role of evolutionary history in generating species diversity and in shaping phenotypes may provide insight into the relative importance of different processes affecting species coexistence and community assembly ( whitfeld et al . , 2012 ) . nowadays , evolutionary ecologists are increasingly combining phylogenetic data with distributional and ecological data to assess how and why communities of species differ from random expectations for evolutionary and ecological relatedness ( emerson and gillespie , 2008 ) . community composition at any point in time is the result of past immigration , speciation and extinction , together with associated interactions that vary according to the sequence of assembly and/or disturbance ( emerson and gillespie , 2008 ) . numerous processes contribute to the assembly of communities ( kraft et al . , 2007 ) . environmental filters can select for the species that possess phenotypes necessary for survival and successful reproduction resulting in a community of species that share a similar phenotype ( webb et al . , by contrast , competition among different species leads to that related traits show evenness ( eiserhardt et al . , the likelihood that a pathogen can infect two plant species decreases continuously with the phylogenetic distance between the plants which tend to yield patterns of over - dispersion ( gilbert and webb , 2007 ) . facilitation derived from related species sharing pollinators is predicted to yield communities with phenotypically similar species ( sargent and ackerly , 2008 ) . nurse species facilitate distantly related species and increase phylogenetic diversity ( valiente - banuet and verdu , 2007 ) . abiotic factors , which include high air temperature , low relative humidity , low water , low nutrient availability , act as environmental filters selecting for species with tolerant traits in arid areas ( rajaniemi et al . , 2012 ) . , along with the variation in the type and gradient of limiting factor , community structure does not remain the same . on the contrary , similar communities , whose constituent species have a close genetic relationship , may experience smaller differentiated ecological processes . here , we chose different calligonum communities as research subjects which grow in active sand dunes and stabilized sand fields . we address two critical questions : 1 ) whether differences exist in the community structure in terms of phylogeny and phenotype among sibling communities ? 2 ) what kind of link exists among traits , phylogenetic relationships and environmental conditions of these communities ? calligonum linnaeus is a genus in the family polygonaceae with 35 species across the mediterranean sea region , asia and north africa ( wu et al . , 2003 ) . based primarily on fruit morphology and anatomy , calligonum species were divided into four sections , including sect . a representative of each section was selected as the comparison target , including c. calliphysa , c. ebi - nuricum , c. klementzii , and c. rubicundum . we consulted the plant specimens collected in several units of chinese academy of sciences including institute of botany , cold and arid regions environmental and engineering research institute , xinjiang institute of ecology and geography , kunming institute of botany , jiangsu institute of botany , the northwest institute of plateau biology , and northwest a&f university , lanzhou university , inner mongolia university , inner mongolia agricultural university , xinjiang university , xinjiang agricultural university . according to the distribution of each species , we randomly placed three quadrats in each plot and computed the number of each species in each quadrat . plant voucher specimens were deposited in the specimen museum of xinjiang institute of ecology and geography . we obtained the state of relatively stable traits ( smaller intraspecific variation ) from flora of china and flora xinjiangensis . plant traits are encoded according to supplementary table 1 , which shows the characters and character states scored for plant morphology . in total 16 characters 9 characters were scored as binary and the remaining characters were scored as multi - state characters . we used phylomatic version 3 web service ( http://phylodiversity.net/phylomatic/ ) to construct a phylogeny for the species list , using the stored tree r20120829 ( phylomatic tree r20120829 for plants ) . phylogenetic distance between species should ideally be proportional to divergence time ( blomberg and garland , 2002 ) . we approximated divergence times in phylocom 4.2 using the branch length adjustment ( bladj ) function . when conducting analysis of phylogenetic community composition , communities with fewer species can cause large errors . therefore , community collection in accordance with the constructive species was used as analysis objects . we used the function pcd in the r package picante to calculate phylogenetic community dissimilarity ( pcd ) that is partitioned into a nonphylogenetic component that reflects shared species between communities and a phylogenetic component that reflects the evolutionary relationships among nonshared species ( ives and helmus , 2010 ) , and subsequently used the function hclust in the r package stats to implement hierarchical cluster analysis . phylogenetic community structure was quantified as the net relatedness index ( nri ) , which is based on the mean phylogenetic distance ( mpd ) between taxa in an observed sample compared to random draws from the species pool ( webb et al . , 2002 ) . nri expresses the deviation of the mean pairwise distance from random in a given community , and positive nri indicates phylogenetic clustering , while negative nri indicates evenness . significance of the nri values is assessed by comparing the observed mpd value with the expected mpd value based on the null distribution of the 999 random assemblages . the species pool was all species found in the 22 plots . in this study , we calculated measures of trait diversity within communities in a manner analogous to the methods we used to calculate phylogenetic diversity by substituting a trait distance matrix for the phylogenetic distance matrix . calligonum linnaeus is a genus in the family polygonaceae with 35 species across the mediterranean sea region , asia and north africa ( wu et al . , 2003 ) . based primarily on fruit morphology and anatomy , calligonum species were divided into four sections , including sect . a representative of each section was selected as the comparison target , including c. calliphysa , c. ebi - nuricum , c. klementzii , and c. rubicundum . we consulted the plant specimens collected in several units of chinese academy of sciences including institute of botany , cold and arid regions environmental and engineering research institute , xinjiang institute of ecology and geography , kunming institute of botany , jiangsu institute of botany , the northwest institute of plateau biology , and northwest a&f university , lanzhou university , inner mongolia university , inner mongolia agricultural university , xinjiang university , xinjiang agricultural university . according to the distribution of each species , we randomly placed three quadrats in each plot and computed the number of each species in each quadrat . plant voucher specimens were deposited in the specimen museum of xinjiang institute of ecology and geography . we obtained the state of relatively stable traits ( smaller intraspecific variation ) from flora of china and flora xinjiangensis . plant traits are encoded according to supplementary table 1 , which shows the characters and character states scored for plant morphology . in total 16 characters 9 characters were scored as binary and the remaining characters were scored as multi - state characters . we used phylomatic version 3 web service ( http://phylodiversity.net/phylomatic/ ) to construct a phylogeny for the species list , using the stored tree r20120829 ( phylomatic tree r20120829 for plants ) . phylogenetic distance between species should ideally be proportional to divergence time ( blomberg and garland , 2002 ) . we approximated divergence times in phylocom 4.2 using the branch length adjustment ( bladj ) function . when conducting analysis of phylogenetic community composition , communities with fewer species can cause large errors . therefore , community collection in accordance with the constructive species was used as analysis objects . we used the function pcd in the r package picante to calculate phylogenetic community dissimilarity ( pcd ) that is partitioned into a nonphylogenetic component that reflects shared species between communities and a phylogenetic component that reflects the evolutionary relationships among nonshared species ( ives and helmus , 2010 ) , and subsequently used the function hclust in the r package stats to implement hierarchical cluster analysis . phylogenetic community structure was quantified as the net relatedness index ( nri ) , which is based on the mean phylogenetic distance ( mpd ) between taxa in an observed sample compared to random draws from the species pool ( webb et al . , 2002 ) . nri expresses the deviation of the mean pairwise distance from random in a given community , and positive nri indicates phylogenetic clustering , while negative nri indicates evenness . significance of the nri values is assessed by comparing the observed mpd value with the expected mpd value based on the null distribution of the 999 random assemblages . the species pool was all species found in the 22 plots . in this study , we calculated measures of trait diversity within communities in a manner analogous to the methods we used to calculate phylogenetic diversity by substituting a trait distance matrix for the phylogenetic distance matrix . the largest plant families in calligonum communities are amaranthaceae ( 24 species ) and asteraceae ( 11 species ) . the number of taxa in c. rubicundum community was highest among 4 kinds of communities at different levels of family , genera and species . phylogenetic relationships of co - occurring species in calligonum community were shown in figure 2(fig . according to the results returned by pairwise dissimilarity in phylogenetic community composition , hierarchical cluster analysis was carried out and shown by figure 3(fig . 3 ) . c. rubicundum community showed a larger dissimilarity in phylogenetic community composition with other communities . c. calliphysa and c. klementzii showed the highest similarity , due to a larger number of shared species between communities ( 10 species ) . the nri was significant negative value in c. rubicundum community , and became positive values in the other three communities . the results indicated that species that co - occurred in c. rubicundum community have greater phylogenetic evenness compared to species in other communities . that is to say , co - occurring plants were more distantly related than expected by chance in c. rubicundum community ( nri < 0 ) . trait ses ( mpd ) represents the standardized effect size of trait diversity by measuring trait dissimilarity among co - occurring species . these metrics of all communities but c. rubicundum community were below 0 , and trait diversity was lower than expected ( figure 5(fig . 5 ) ) . the statistical test demonstrated that trait diversities within c. ebi - nuricum and c. klementzii communities were significantly different from randomization . the results indicated that co - occurring plants had similar traits , and this pattern of trait clustering was stronger in c. ebi - nuricum and c. klementzii communities . the pattern of trait diversity was similar to the pattern we saw for phylogenetic diversity . phylogenetic data provide a historical framework to quantify evolutionary and ecological patterns and infer evolutionary and ecological processes ( emerson and gillespie , 2008 ) . for example , pattern of phylogenetic clustering was generally considered to result from ( 1 ) difficulty in dispersing to some habitats or , ( 2 ) environmental filtering for a conserved niche . in this study , c. rubicundum community was distinguished from other three communities in phylogenetic community composition , and the latter in community structure displayed as phylogenetic clustering . in addition , to test for community assembly processes we need to quantify both the trait evolution and the phylogenetic structure of the community ( pausas and verdu , 2010 ) . our results showed that phenotypic pattern of these traits are identical with phylogenetic community structure among different communities . thus , there were differences in the community structure in terms of phylogeny and phenotype among sibling communities and gives an affirmative answer to question 1 . when species enter a community , species possessing the necessary traits to complete their life cycle within that habitat are retained by ecological processes controlling community assembly . in other words , environmental conditions impose absolute bounds on the phenotype space ( lovette and hochachka , 2006 ) . thenceforth , the competition as an important factor drives competitive exclusion or niche differentiation of similar traits related to competition . other literature reports that total salt content and ph values of soil are significantly different among communities , and all but c. rubicundum communities have distinct degrees of salinization and alkalization ( tan et al . , 2009 ) . compared with the c. rubicundum community , trait diversity was lower than expected in the other three communities and similar to the pattern we saw for phylogenetic diversity . therefore , we can infer that species of these communities are under more intense selection pressure and evolution of traits is conservative . there were more than expected annuals in c. ebi - nuricum and c. klementzii community , and we guessed that it is an environmental filtering to directional selection under stressful conditions . there was a definite relationship that environmental conditions limit phylogenetic diversity and trait diversity within communities . in order to potentially restore the ecosystem functioning of desert plant communities , understanding how ecological process affects community composition is an essential prerequisite . in this study , we compared the community structure of similar communities in order to illuminate the influence of environmental variability governing the assembly and coexistence of species . based on the similarity between the pattern of trait diversity and the pattern of phylogenetic diversity , we inferred that the evolution of traits is conservative and species of all but c. rubicundum communities are under more intense selection pressure . this work was supported by the national natural science foundation of china ( grant no 31100150 ) and the west light talents cultivation program of chinese academy of sciences ( xbbs 201202 ) .

since phylogenetic data provide the evolutionary history of the species and traits are the result of adaptation to the environmental conditions , joint analysis of these two aspects and ecological data may illuminate that how ecological processes affect the evolution of species and assembly of communities . in this study , we compared the community structure of sibling communities in order to illuminate the influence of environmental variability . we chose different calligonum communities as research subjects which grow in active sand dunes and stabilized sand fields . our results show that species which co - occurred in c. rubicundum community have greater phylogenetic evenness compared to species in other communities where co - occurring plants had similar traits . soil variability might legitimately explain this result . based on the similarity between the pattern of trait diversity and the pattern of phylogenetic diversity , we inferred that the evolution of traits is conservative and species of all but c. rubicundum communities are under more intense selection pressure .

although angiotensin ( ang ) ii has been reported to have proinflammatory and oxidative effects , little is known about the correlation between ang ii and reactive oxygen species ( ros ) in polymorphonuclear leukocytes ( pmls ) . activation of the renin - angiotensin system and increased production of ang ii are implicated in the pathogenesis of hypertension , atherosclerosis , and cardiac hypertrophy . ang ii acts through high - affinity cell surface receptors , which are linked to pathways classically associated with g - protein - coupled and tyrosine - kinase - mediated responses . ang ii type 1 ( at1 ) receptors for ang ii have also been found in circulating neutrophils and human circulating pmls ; furthermore , ang ii - induced cell activation has been reported [ 5 , 6 ] . one major mechanism through which ang ii induces pathological effects pmls ros production participates in host defense by killing bacteria , but can also damage host tissues and play an important role in disease pathogenesis . nitric oxide ( no ) regulates important functions of pmls , including chemotaxis , adhesion , aggregation , apoptosis , and pmn - mediated bacterial killing or tissue damage . it has been reported that rat pmls constitutively express neural no synthase ( nnos ) mrna and nnos protein and exhibited spontaneous basal release of low concentrations of nitrate and nitrite anions . the presence of nnos and inos in rat peripheral pmls has been well documented [ 7 , 9 ] . no is an important mediator in a wide range of physiological and pathophysiological processes involving ros . no and superoxide have opposing effects on vascular tone , reacting and negating one another . ros induced by ang ii may be involved in endothelial dysfunction through inactivation of endothelium - derived no . there are several controversial reports regarding the effect of ang ii on pmls function [ 5 , 11 ] . reported that neutrophils are highly responsive to ang ii in the context of ( o2 ) production . to elucidate the role of ang ii in pmls ros production , we examined hydrogen peroxide ( h2o2 ) , one of the ros , and no production in at1a receptor knockout ( at1ko ) mice . eight - week - old male wild type ( n = 6 ) , and ang ii type 1a receptor knockout ( at1ko ) mice ( n = 4 ) from the same genetic background were used . all mice were maintained on a 12-hour light/12-hour dark cycle and fed normal mouse chow . animal care and the experimental procedure were performed in accordance with kansai medical university animal care facility guidelines and the national research council guidelines . 2 7-dichlorofluorescein diacetate ( dcfh - da ) was purchased from eastman kodak ( rochester , ny ) ; phorbol myristate acetate ( pma ) was purchased from sigma chemical ( st . louis , mo ) ; diaminofluorescein-2 diacetate ( daf-2/da ) was purchased from daiichi pure chemical ( tokyo , japan ) ; edta 4na and magnesium - free dulbecco 's phosphate - buffered saline ( pbs ) were purchased from wako pure chemical industries ( osaka , japan ) . pbs containing 5 mm glucose and 0.1% gelatin is denoted as pbsg . anti - gr-1 antibody was purchased from miltenyi biotec ( aubum , ca ) . staphylococcus aureus , strain atcc 25923 ( kindly supplied from shionogi pharmaceutical co. , osaka , japan ) , was cultured for 18h in tryptic soy broth ( difco , detroit , mi , usa ) at 37c . the bacteria were heat - killed at 60c for 30min , washed three times with normal saline , and labeled with a 5% solution of pi ( sigma ) in normal saline for 30min at room temperature in the dark . the fluorescent bacteria were washed three times with normal saline and suspended in pbs containing 5 mm glucose . the bacterial density was adjusted to the absorbance value of 2.50 at 620 nm with an uv - visible recording spectrophotometer 240 ( shimadzu , kyoto , japan ) . the number of bacteria at this density was about 2.4 10 colony - forming units / ml . pi - labeled s. aureus ( pis ) were opsonized with pooled human ab serum ( gemini bio - products , woodland , ca , usa ) for 30 min at 37c and prepared for phagocytic assay . briefly , 850 l of heat - killed bacterial suspension originating from s. aureus was added to 100 l of whole blood and 50 l of 10 m diaminofluorescein-2 diacetate ( daf-2/da ) ( 25 m ) in pbsg in each plastic tube . the tubes were incubated with rotational agitation for 90 min at 37c in an incubator , then 1.0 ml of 3 mm edta was added to terminate phagocytosis and prevent bacteria from adhering to the pmls membranes . in order to study pmls h2o2 production , 2 7-dichlorofluorescein diacetate ( dcfh - da ) was used to monitor a nadph oxidase - mediated oxidative burst in pmls . the measurement of h2o2 production by pmls following phagocytosis was described previously . a mixture of 100 l of heparinized whole blood , 200 l of dcfh - da in phosphate - buffered saline pbsg ( pbs containing 5 mm glucose and 0.1% gelatin ) , and 700 l of propidium iodide ( pi)-labeled s. aureus suspension ( 1.7 10 colony - forming units / ml ) was incubated with rotational agitation for 30 min at 37c in a shaking water bath , and then 1.0 ml of 3 mm edta was added to terminate phagocytosis . erythrocytes were then removed by hypotonic lysis for 60 s. finally , after centrifugation , each cell pellet was resuspended in 1.0 ml of 3 mm edta in pbsg and prepared for flow cytometry . a mixture of 100 l of heparinized whole blood , 200 l of dcfh - da ( 10 m ) in pbsg and 10 l of pma ( 25 g / ml ) was prepared in a plastic tube . the tube was incubated with rotational agitation for 30 min at 37c in a shaking water bath . c57bl/6 mice ( arb group ; n = 6 ) were administrated for 2 weeks at1 receptor blocker ( arb ) , losartan ( 100 mg / l drinking water ) . two weeks before euthanasia , all animals were subcutaneously implanted with alzet osmotic minipumps ( model 1002 ; durect corporation , cupertino , ca ) under isoflurane anesthesia . in the ang ii and saline groups , 6 mice received ang ii ( 1000 ng / min per kg ) and 6 were infused with saline , respectively . at the end of the incubation period , erythrocytes were first hypotonically lyzed for 60 s. after centrifugation , each cell pellet was resuspended in 0.5 ml pbsg or edta - mixed pbsg . single color fluorescence staining was analyzed using a cytofluorometer ( epics xl ii , beckman coulter co. , hialeah , fl ) with an argon - ion laser ( wavelength 488 nm ) with system ii software . mean fluorescence intensity was determined after gating for granulocytes by their forward and side scatter characteristics . gain and amplitude settings were determined according to blood samples from the same subject , allowing for establishment of reference gates for leukocyte identification . quantitative values for phagocytosis and hydrogen peroxide production were estimated according to mean pi and dcfh - da fluorescence / cell , respectively . further , the statistically significant differences among the groups were determined by subjecting the data to one way analysis of variance ( anova ) with diet as the main effect , followed by inspection of all differences between pairs of means by tukey 's test . we measured no production from c57bl/6 wild type mice ( control group ; n = 6 ) , losartan treated mice ( arb group ; n = 6 ) , and at1ko mice ( at1ko group ; n = 4 ) . no production in the at1ko group , both at baseline and following phagocytosis stimulation , was observed but lower than in the control group ( figure 1 ) . no production after phagocytosis stimulation was lower in arb group compared to control group , although the difference did not reach statistical significance . basal h2o2 production in the at1ko group was low ( figures 2(a ) and 2(b ) ) . after s. aureus phagocytosis or pma stimulation , at1ko mice could produce equivalent amounts of h2o2 compared to control mice ( figures 2(a ) and 2(b ) ) . next , to determine if ang ii affected the production of h2o2 , we tested the model mice infused ang ii for 2 weeks by osmotic pump ( ang ii group ) . h2o2 production stimulated by pma or phagocytosis did not differ between the ang ii and saline groups ( figures 3(a ) and 3(b ) ) . no production in the at1ko group , both at baseline and following phagocytosis stimulation , was lower than the control group . this result showed that at1a pathway plays a significant role in no production from pmls . the presence of nnos and inos in rat peripheral pmls has been well documented [ 7 , 9 , 14 ] . inos produces large amount of no , it could be therefore important armor to intruders during phagocytosis . only a small percentage of at1ko mice survive to weaning compared to wild type mice because of inflammatory problem as well as lower blood pressure or renal malfunction . no production after phagocytosis was lower in arb group compared to control group . in arb group , at1 receptor was partially blocked in vivo and no production was decreased . at1a receptor plays a significant role in mediating no production after phagocytosis stimulation . a large number of studies have demonstrated that at ii is involved in key events of the inflammatory process . phagocyte nadph oxidase or respiratory burst oxidase is a well - characterized reactive oxygen species - generating system that catalyzes the 1-electron reduction of oxygen to superoxide radical ( o2 ) . ang ii highly stimulates endogeneous and extracellular ( o2 ) production in human neutrophils , consistent with the translocation to the cell membrane of the cytosolic components of nadph oxidase . ang ii acts through binding to specific cellular receptors , of which at1 and at2 are the best characterized . at1 receptors mediate many important cardiovascular responses , such as vasoconstriction , vascular , and cardiac remodeling . in mouse aortic rings , ang ii increases aortic protein levels of nadph oxidase component with increased ( o2 ) production . after exposure to ang ii , the elevation of superoxide production occurs through at1 receptor mediated activation in nadph oxidase of the coronary arterioles , renal cortices , and human umbilical vein endothelial cells . in addition , our results show that pmls exposed to ang ii for 2 weeks had no effects on h2o2 production after pma or phagocytosis stimulation . it has been hypothesized that activation of the at2-receptor may be antagonistic to at1-receptor activation . at2 receptor may play a counter - regulatory protective role mediated by bradykinin and no . there are several controversial reports regarding the effect of ang ii on pmls function [ 5 , 11 ] . reported that neutrophils are highly responsive to ang ii in the context of ( o2 ) production . however most evidence suggests that assembly of nadph oxidase onto cell membranes is initiated by rac-1 , which is activated by ang ii binding to at1 receptor . this study demonstrated for the first time that at1a receptor is not essential for h2o2 production from pmls . in conclusion , we have demonstrated that at1a pathway plays a significant role in no production from pmls .

background . although angiotensin ii ( ang ii ) has inflammatory effects , little is known about its role in polymorphonuclear leucocytes ( pmls ) . to elucidate the role of ang ii in pmls ros production , we examined hydrogen peroxide ( h2o2 ) , one of the ros , and no production in at1a receptor knockout ( at1ko ) mice . methods and results . pmls were analyzed from ang ii type 1a receptor knockout mice ( at1ko ) and c57bl/6 wild type mice . using flow cytometry , we studied hydrogen peroxide ( h2o2 ) production from pmls after staphylococcus aureus phagocytosis or phorbol myristate acetate ( pma ) stimulation . nitric oxide ( no ) production in the at1ko was low at basal and after phagocytosis . in the at1ko , basal h2o2 production was low . after pma or phagocytosis stimulation , however , h2o2 production was comparable to wild type mice . next we studied the h2o2 production in c57bl/6 mice exposed to ang ii or saline . h2o2 production stimulated by pma or phagocytosis did not differ between the two groups . conclusions . at1a pathway is not necessary for pmls h2o2 production but for no production . there was a compensatory pathway for h2o2 production other than the at1a receptor .

the knowledge of variation of upper abdominal vessels is very useful for surgeons , nephrologists , endocrinologists , and radiologists . . the renal veins may be more than one in number may receive abnormal tributaries or may have variant relations . the renal arteries also may vary in their number , point of entry into the kidney , source of origin , and distribution . they normally arise from abdominal aorta ( aa ) ; however , they may arise from the celiac trunk or renal arteries . however , their distribution to the stomach is very rare . we report here multiple variations associated with the upper abdominal vessels and discuss their radiological and surgical importance . during the dissection classes of the abdomen for undergraduate medical students , we observed multiple vascular variations in the upper part of the abdomen of an adult male cadaver . further , the aa , inferior vena cava ( ivc ) , and the major vessels in the vicinity of the kidney were dissected . ivc was cut and reflected downward along with the renal veins to display the variant renal arteries . duplication of the right renal vein : both the right renal veins drained into the ivc [ figure 1]partial duplication of the left renal vein ( lrv ) : the lrv formed by the confluence of two renal veins emerging from the left kidney ( lk ) . upper renal vein received the left suprarenal and testicular veins [ figure 2]duplication of the right renal artery : upper right renal artery entered the kidney through the hilum . it gave origin to the right inferior phrenic artery ( ipa ) and right lower suprarenal artery at a distance of 3 mm from its origin . the lower right renal artery arose from the anterior surface of the aorta and entered the kidney through the hilum [ figure 3]duplication of the left renal artery : upper left renal artery gave a polar branch to the lk which entered the kidney near the upper pole . after the onset of the polar artery , distally , the upper left renal artery divided again into two branches , which entered the kidney through the hilum . lower left renal artery crossed between the two divisions of lrv and entered the kidney through the hilum [ figure 4]the left ipa arose from the aa at the level of origin of superior mesenteric artery , apart from supplying diaphragm ; it gave a reasonably large branch to the fundus of the stomach . the stomach had its usual blood supply in addition to this gastric branch [ figure 2]the right kidney was over rotated so that its hilum was directed posteriorly [ figure 1 ] . duplication of the right renal vein : both the right renal veins drained into the ivc [ figure 1 ] partial duplication of the left renal vein ( lrv ) : the lrv formed by the confluence of two renal veins emerging from the left kidney ( lk ) . upper renal vein received the left suprarenal and testicular veins [ figure 2 ] duplication of the right renal artery : upper right renal artery entered the kidney through the hilum . it gave origin to the right inferior phrenic artery ( ipa ) and right lower suprarenal artery at a distance of 3 mm from its origin . the lower right renal artery arose from the anterior surface of the aorta and entered the kidney through the hilum [ figure 3 ] duplication of the left renal artery : upper left renal artery gave a polar branch to the lk which entered the kidney near the upper pole . after the onset of the polar artery , distally , the upper left renal artery divided again into two branches , which entered the kidney through the hilum . lower left renal artery crossed between the two divisions of lrv and entered the kidney through the hilum [ figure 4 ] the left ipa arose from the aa at the level of origin of superior mesenteric artery , apart from supplying diaphragm ; it gave a reasonably large branch to the fundus of the stomach . the stomach had its usual blood supply in addition to this gastric branch [ figure 2 ] the right kidney was over rotated so that its hilum was directed posteriorly [ figure 1 ] . duplication of the right renal vein with upper ( 1 ) and lower ( 2 ) right renal veins can be seen ( aa = abdominal aorta , ivc = inferior vena cava , lrv = left renal vein ) . upper division ( 1 ) of the left renal vein receiving the left testicular vein and left suprarenal vein can be seen ( aa = abdominal aorta , gb = gastric branches of left inferior phrenic artery , ira = left inferior renal artery , ivc = inferior vena cava , ipa = left inferior phrenic artery , lk = left kidney , lsg = left suprarenal gland , lsv = left suprarenal vein , pb = phrenic branches of left inferior phrenic artery ) . upper ( 1 ) and lower ( 2 ) right renal arteries can be seen ( aa = abdominal aorta , ivc = inferior vena cava ( reflected down ) , ripa = right inferior phrenic artery , risa = right inferior suprarenal artery , rsg = right suprarenal gland ) . upper ( 1 ) and lower ( 2 ) left renal arteries can be seen ( aa = abdominal aorta , ct = celiac trunk , ivc = inferior vena cava ( reflected down ) , ipa = left inferior phrenic artery , lrv = left renal vein , pa = polar artery arising from left upper renal artery , rra = right renal arteries , sma = superior mesenteric artery ) . their relations with the aorta and the neighboring structures also may show variations . in a study by zhu et al . , variations of renal veins was found in 24.7% of cases . in this study , the variations of lrv were seen in 19.2% , and variations of right renal vein were seen in 1.7% of cases . even in another study by ballesteros et al . , the lrv variations were more common ( 21.1% ) than the right renal vein variations ( 0.64% ) . nayak et al . have reported the presence of retropelvic tributary for the lrv . in the current case angiography study , inar and trkvatan have found renal arterial variations in 31.3% cases . in this study , 22.2% patients had two , 7.5% had three , 1.4% had four , and 0.2% had five renal arteries . in a study by saldarriaga et al . , additional renal arteries were found in 22.3% of cases . additional renal arteries were more common on the left side ( 32.0% ) compared to the right ( 23.3% ) in a study by satyapal et al . gulas et al . , have reported that the prevalence of accessory renal arteries is low in south east asian countries than the western countries . according to their study , it fluctuates from 4% in malaysian to 61.5% in brazilians . in a study on kidney donors by munnusamy et al . , 51% of donors had variations in the renal artery , and 13% each had accessory renal arteries on the right and left sides . in a ct scan study by johnson et al . about 23.5% patients had accessory arteries on the left , and 17.9% had them on the right side . mao and li have reported the origin of the accessory renal artery from the testicular artery . the ipa usually arises from the aa , just after the entry of the aorta into the abdomen . it supplies the undersurface of the diaphragm , the peritoneum covering it and also the suprarenal gland . to the best of our knowledge , this type of variations has not been reported earlier . during early development , as the development proceeds , the kidney rotates along its vertical axis in medial direction so that the hilum faces medially . if the rotation is less , the hilum faces anteriorly and if it is more , the hilum faces posteriorly . thorough knowledge of renal vascular variations is required during renal transplant surgeries to avoid iatrogenic bleeding . the knowledge is also useful to radiologists in the interpretation of the ct scan and images of magnetic resonance imaging . additional renal vessels and posteriorly placed hilum of the right kidney in the current case makes the case more interesting and important because this can lead to the compression of the renal vessels at the hilum . thorough knowledge of renal vascular variations is required during renal transplant surgeries to avoid iatrogenic bleeding . the knowledge is also useful to radiologists in the interpretation of the ct scan and images of magnetic resonance imaging . additional renal vessels and posteriorly placed hilum of the right kidney in the current case makes the case more interesting and important because this can lead to the compression of the renal vessels at the hilum . knowledge of concurrent variations of renal vessels , ipa , and the position of hilum of kidney makes this case unique . the case may be of special interest to surgeons , radiologists , nephrologists , and endocrinologists .

introduction : knowledge of vascular variations near the kidney is of importance to many clinical disciplines such as nephrologists , radiologists , gastroenterologists , and general surgeons . variant branches of the abdominal aorta and renal arteries are the victims of iatrogenic bleeding during surgery . we found multiple vascular variations in the upper part of the abdomen during our dissection classes.methods:during the dissection classes of the abdomen for undergraduate medical students , we observed multiple vascular variations in the abdomen of an adult male cadaver . the vessels and surrounding viscera were cleaned using dissection instruments . variations observed were photographed.results:the right kidney had its hilum directed posteriorly . there were two right renal veins and a partially doubled left renal vein ( lrv ) . the left suprarenal and gonadal veins drained into the upper lrv . there were two right renal arteries . upper right renal artery gave origin to the right inferior phrenic and middle suprarenal arteries . there were two renal arteries on the left side also . the left upper renal artery gave a polar branch to the left kidney and divided into two branches before entering the kidney . the left inferior phrenic artery ( ipa ) gave two gastric branches to the fundus of the stomach.conclusions:the variations noted by us are of tremendous surgical application . the variant vessels might get damaged during surgical procedures if the surgeons are not aware of these variations . the most important among the variations reported here is the gastric branch of the ipa , which has not been reported yet .

the reported incidence of inguinal hernia in those younger than 18 years old varies from 0.8 - 4.4% . males are more likely to have hernia with 3:1 - 10:1 ratio . approximately 6 % of females present with bilateral inguinal hernia . although there is variability in the way pediatric surgeons perform some of the technical aspects of inguinal herniotomy , we know of no technique that describes a single suprapubic incision to repair bilateral inguinal hernia in girls . ladd and gross original description of pediatric hernia repairs likely result from evolving techniques , experiences , and analysis of outcomes that suite the local community , population , or surgeon . the specific technique described in this manuscript was adopted to fill a need for its local community by local surgeons in gaza , but is applicable to the wider pediatric surgical population . we are describing a new approach for bilateral inguinal hernia repair in female children through a small 1 - 1.5 cm transverse suprapubic midline incision . approval from the administrative review board committee ( irb equivalent ) was obtained for this retrospective chart review . the new approach was performed on 99 consecutive female children aged 12 years or younger with bilateral inguinal hernias at a single institution at the european gaza hospital , gaza , palestinian territories between january 2005 and april 2012 . informed consent was obtained from the parents after explaining the goals , benefits , risks , and alternatives for this approach . all patients had a pre - operative clinical diagnosis of bilateral inguinal hernia based on history and physical exam . no radiologic procedures were performed to diagnose any hernia . any actively incarcerated or strangulated hernias were intentionally excluded from this new operative approach ; however a history of incarceration or strangulation did not prevent using this approach . the one exception is an incarcerated ovary ; this did not prevent using this approach . after general anesthesia , in a supine position , a 1 - 1.5 cm midline transverse suprapubic skin incision is made along the skin crease [ figure 1 ] . incision is carried down through the dermis to expose the subcutaneous fat , camper 's fascia . using sharp and blunt dissection , scarpa 's fascia is identified , grasped and incised in the direction of the targeted hernia ( right or left ) . the sac is exposed and elevated off the inguinal floor [ figures 2 and 3 ] . from this point onwards , the steps of standard hernia repair with a high ligation are followed according to the surgeons technique . the external inguinal ring was not opened in any of the patients . after finishing the repair of one side , this new modification changes the skin incision , exposure and approach and does not alter the technical aspects of the high ligation . since electricity was intermittently available , no electrocautery was used , as a matter of preference . also , we neither dissected the round ligament from the sac , nor did we tack the round ligament to any structures . shows the midline transverse suprapubic incision shows the exposure of the round ligament and right hernia sac . the sac is subsequently separated from the round ligament and ligated using a high ligation approach shows the exposure of the round ligament and left hernia sac . the sac is subsequently separated from the round ligament and ligated using a high ligation approach shows the midline incision closure at the completion of the procedure after general anesthesia , in a supine position , a 1 - 1.5 cm midline transverse suprapubic skin incision is made along the skin crease [ figure 1 ] . incision is carried down through the dermis to expose the subcutaneous fat , camper 's fascia . using sharp and blunt dissection , scarpa 's fascia is identified , grasped and incised in the direction of the targeted hernia ( right or left ) . gentle retraction is needed laterally to maintain excellent exposure . the sac is exposed and elevated off the inguinal floor [ figures 2 and 3 ] . from this point onwards , the steps of standard hernia repair with a high ligation are followed according to the surgeons technique . the external inguinal ring was not opened in any of the patients . after finishing the repair of one side , this new modification changes the skin incision , exposure and approach and does not alter the technical aspects of the high ligation . subcutaneous tissue and skin are subsequently closed [ figure 4 ] . since electricity was intermittently available , no electrocautery was used , as a matter of preference . also , we neither dissected the round ligament from the sac , nor did we tack the round ligament to any structures . shows the midline transverse suprapubic incision shows the exposure of the round ligament and right hernia sac . the sac is subsequently separated from the round ligament and ligated using a high ligation approach shows the exposure of the round ligament and left hernia sac . the sac is subsequently separated from the round ligament and ligated using a high ligation approach shows the midline incision closure at the completion of the procedure ninety - nine girls with a pre - operative clinical diagnosis of bilateral inguinal hernia were included . all patients underwent general anesthesia ( 95% by hand - bag mask ventilation , 5% with laryngeal mask ) . one surgeon ( ma ) was scrubbed for every procedure as surgeon , first assistant , or teaching surgeon . post - operatively 2 patients developed non - expanding small hematomas , both treated non - operatively without sequelae or intervention . there were zero hernia recurrence and on follow - up was achieved in 99% of patients . the idea of exposing the bilateral inguinal hernia through a single small midline incision , to our knowledge , has not been described previously in pediatric surgical literature . we report 99 girls age 12 or younger that have undergone this approach with no recurrences , few complications and a reliable , excellent median follow - up of 5 years . we believe infant hernia repairs are particularly suited to this approach because the anatomy of the inguinal canal passes through a series of changes from infancy to adulthood that favors a single midline incision . in infants the internal and external inguinal rings almost overlap , therefore if the retractor exposes the external ring , it is easy to expose the internal ring by retracting a few millimeters more . as children grow , the internal inguinal ring becomes more lateral in position compared to the external ring . thus , the midline transverse incision can easily be used to expose both superficial and deep inguinal rings in younger patients . furthermore , exposing both inguinal canals through a transverse midline incision allows for simultaneous correction of the bilateral hernia through one incision . although not the only reason , this approach was initially considered as a mean of shortening the anesthetic time . when considering operating room scheduling , time is of the essence in gaza as trauma often can disrupt an elective schedule . thereafter , the cosmetic result was considered superior to standard bilateral standard incisions , although we did not tabulate data to test this latter hypothesis . we intentionally performed this technique on girls and not boys because the technical repair in girls is much easier than male inguinal hernia repair where the vas deferens and testicular vessels need to be spared , whereas there is no need to save the round ligament in girls . another selection we made was to limit this approach to bilateral hernias ; there is probably no advantage to this approach in older children with unilateral hernias . having stated that , from our experience , it would not be difficult to repair a unilateral hernia using a midline suprapubic transverse incision approach with a laparoscopic contralateral exploration as described by bhatia et al . , and thereafter repair the contralateral side through the same incision if needed . however , this approach probably makes sense for younger children such as infants ( 2-years - old or younger ) where there is relatively high risk of a contralateral patent processus vaginalis . we did not perform any unilateral hernia ( with a contralateral laparoscopic groin exploration ) through our approach since there were no 3 - 5 mm laparoscopic scopes in gaza at the time of this manuscript . therefore we recommend this approach to be used in female patients with a confirmed clinical diagnosis of bilateral inguinal hernia . although an argument can be made that a laparoscopic approach could achieve superior cosmetic results through several 2 - 3 cm incisions , it can also be argued that remaining outside the peritoneum is the ideal method of hernia repair . furthermore , even in 2014 most pediatric surgeons across the world has neither developed the skill to perform a laparoscopic hernia repair nor do they have the mini - laparoscopic equipment to perform laparoscopic inguinal hernia repairs . as children grow , the internal ring becomes more lateral in position compared to the external ring . in this situation , more lateral retraction or making a bigger incision may be needed based on individual surgeon 's preference . in our series , a 1.5 cm provided an excellent exposure that allowed adequate hernia repair in children 12 years and younger . our follow - up of 5 years compares very favorably to other reports who have published new techniques for inguinal hernia repairs , in particular the laparoscopic approaches . we believe our follow up is excellent for two reasons . first , gaza has strict travel restrictions in place since 2005 ( beginning of this study ) and most patients therefore literally have little option to go elsewhere . second , there is a single payer system in gaza and patients are referred back to the initial surgeon if a complication occurs as a matter of practice patterns , therefore all but one patient had excellent follow - up . clearly there is a selection bias , as this was a retrospective study that selected excellent candidates . however , our paper adds to the literature a small , but significant technical modification that reduces two small incisions to one small incision in well - selected patients , which should reduce surgical time . although a pfannenstiel incision has been described as a single case , they entered the peritoneum and had an entirely different approach . ideally , the next step is to perform a randomized controlled study comparing our approach to the standard bilateral incision to determine any differences . we describe a new , safe , simple , and rapid approach for bilateral inguinal hernia in female pediatric population . a midline suprapubic transverse skin incision was adequate for exposing both inguinal regions with excellent postoperative results .

background : inguinal hernia repair remains one of the most common operations performed by pediatric surgeons . we described a new surgical approach for treating bilateral inguinal hernias in girls through a small single transverse supra - pubic incision.materials and methods : a new approach was performed on female children 12-years - old and younger with bilateral inguinal hernias between january 2005 and april 2012.technique:a single transverse suprapubic incision ( 1 - 1.5 cm ) was made . using sharp and blunt dissection bilateral hernias were exposed and repaired using a standard high ligation.results:ninety-nine girls with a preoperative clinical diagnosis of bilateral inguinal hernia were included . median age was 2 years ( range : 1 month to 12 years ) . all patients underwent general anesthesia . median operative time was 12 minutes ( range 5 - 22 ) . there were no intra - operative complications or misdiagnosis . two patients had bilateral sliding hernias and the remainder had indirect hernias . post - operatively two patients developed non - expanding small hematomas , both treated non - operatively without sequelae . there were zero hernia recurrence and median follow - up was 5 years ( range : 1 - 8 years ) on 99% of patients.conclusion:we described a new , safe , simple , and rapid approach for bilateral inguinal hernia repair in female pediatric population . a single transverse suprapubic skin incision was adequate for exposing both inguinal regions with excellent postoperative results .

on page 24 of this issue of critical care , meduri introduces a new layer of complexity to our understanding of the inflammatory response in acute respiratory distress syndrome ( ards ) . he postulates that cytokines secreted by the host during ards may favor the growth of some strains of bacteria and consequently explain the association between exaggerated and protracted systemic inflammation and the development of nosocomial infections . evidence for this novel theory comes from in vitro studies evaluating the extracellular and intracellular responses of clinically relevant bacterial species to graded concentrations of pro - inflammatory cytokines . bacterial growth was enhanced at both extremes of this curve , suggesting that insufficient or dysregulated inflammation may play an active role in stimulating bacterial growth and/or impairment of bacterial clearance , with the subsequent development of nosocomial infections . this new finding has important implications for our understanding and management of patients with ards . over the past two decades , the recognition that neutrophils , macrophages , and other components of the inflammatory cascade participate in the generation and progression of acute lung injury ( ali ) and ards has resulted in the use of anti - inflammatory agents as pharmacological probes to define this syndrome . furthermore , preclinical models of endotoxin - induced sepsis demonstrated a survival benefit if pro - inflammatory cytokines were neutralized , leading to a number of studies in which this therapy was used in patients with ards . the u - shaped bacterial growth curve may be a partial explanation for the lack of efficacy of these trials as decreasing cytokine activity may be beneficial , or may be harmful , depending on the specific location on the dose response curve . for an effective host response to be mounted against infection , the cellular components of the innate and acquired immune system need bidirectional communication . the interaction between cytokines and bacteria may be an important factor in the development of organ injury and death from severe infections , although numerous host and local factors , including inflammatory cells , profoundly influence the role of a specific cytokine . it has recently been proposed that patients with sepsis or a systemic inflammatory response have an ' immunoparalysis ' and are , in fact , immunosuppressed . the use of growth factors or cytokines to augment the host response to infection has been proposed in the critically ill . a small preclinical trial with granulocyte colony stimulating factor showed favorable mortality results in patients with community acquired pneumonia and sepsis . although a recent phase iii trial did not detect a mortality difference between the treatment and the placebo group in a post hoc analysis , nelson and colleagues documented faster radiological resolution of pneumonias , which was associated with a decreased incidence of ards . further evidence for the role of augmentative cytokine therapy comes from clinical data using interferon to upregulate hla - dr expression and consequently increase the lipopolysaccharide - induced tumor necrosis factor- responses ex vivo , and from improved clinical outcome in eight out of nine septic patients . in contrast , agents that block tumor necrosis factor- , interleukin-1 , and endotoxin have been shown to attenuate nuclear factor-b ( nf-b ) activation , inflammation , and organ dysfunction . these studies , however , did not look at the incidence of nosocomial pneumonia as an outcome in patients with ards . from a biological standpoint , it may be that blocking a single mediator , especially after the initiating insult , is insufficient to inhibit nf-b activation in complex clinical conditions . this is primarily because of the redundancy of proximal mediators with the potential to activate nf-b . furthermore , none of these molecules appears to be both a critical and essential pathway for activation of nf-b . if we have learned anything from clinical trials in sepsis / inflammation it is that the transfer of information from the bench to the bedside can be fraught with difficulty . the intricate relationship between innate and adaptive response shapes patient outcome , and this is rarely determined by a single factor . there are , in fact , many more levels of complexity ; with multiple cytokines and multiple u - shaped curves that interact , it may be impossible to predict whether a specific anti - cytokine therapy will benefit or harm a given patient , especially as the cytokine profiles change during the course of the disease . secondly , even if these concepts are correct in vivo , the impact of nosocomial pneumonias on the mortality of patients with ali / ards in not entirely clear . despite the fact that at postmortem almost two - thirds of non - survivors have histological evidence of pneumonia , sutherland et al . found that the incidence of nosocomial pneumonia in patients with ards was only 15% ( antibiotic use may have inhibited bacterial growth in this study ) . in all three studies , however , the presence or absence of ventilator - associated pneumonia had little or no effect on mortality . in contrast , headley et al . reported that the rate of nosocomial infection per day of mechanical ventilation was 1% in survivors and 8% in non - survivors . even if nosocomial infections do not directly determine outcome in this population of patients , they may play a key role in the loss of pulmonary compartmentalization of the inflammatory response , and consequently the development and progression of multi - organ dysfunction syndrome . data presented by meduri suggest that bacterial growth and impaired clearance is secondary to a dysregulated inflammatory response and is not the inciting event leading to loss of pulmonary compartmentalization . ranieri and slutsky , however , showed that an injurious ventilatory strategy increases the level of serum inflammatory mediators and that this increase is related to an increased incidence of organ dysfunction . whether this may be , in part , amplified by concurrent nosocomial pulmonary infections and the u - shaped dose response to cytokines is yet to be determined . moreover , treating cytokines in isolation of the underlying pathophysiology may not alter important clinical outcomes . compelling evidence looking at different ventilatory strategies in the management of patients with ards has demonstrated that protective ventilatory strategies that attenuate the pulmonary and systemic inflammatory responses , by addressing the underlying pathophysiology of ventilator - induced lung injury in patients with ards , improve outcome . evidence from both animal and clinical studies suggest that cyclic stretch induces changes in pro - inflammatory and anti - inflammatory gene expression . if this is the case , mechanical ventilation primarily used in the treatment of respiratory failure and responsible for ventilator - induced lung injury may now become a therapeutic tool in the immunomodulatory management of ventilated patients with ards . this is an exciting time for intensivists involved in the care of patients with ards / ali . the rate - limiting step in developing novel therapies for acute inflammatory diseases of the lung is not delineating the molecular mechanisms of lung injury , but understanding how the pieces of the puzzle fit together . to this end , meduri has made a significant contribution to our understanding of the mechanisms underlying nosocomial infections in patients with ards . the challenge now is in the generation of meaningful questions that will pave the way towards novel strategies in the management of this patient population . ali = acute lung injury ; ards = acute respiratory distress syndrome ; nf-b = nuclear factor-b .

the recognition that neutrophils , macrophages , and other components of the inflammatory cascade participate in the generation and progression of acute lung injury / acute respiratory distress syndrome has resulted in the use of anti - inflammatory agents in an attempt to attenuate this inflammatory response and to prevent further progression of the acute lung injury . the recent finding that cytokines , in part mediators of this ' overwhelming ' inflammatory reaction , may also stimulate bacterial growth , impair bacterial clearance , and promote the subsequent development of nosocomial infections may have important implications to the management of the acute lung injury / acute respiratory distress syndrome patient .

an impression is a record , a facsimile of the oral tissues recorded at an unstrained or in the various positions of displacement . the excellent tooth preparation is of little value unless its details are accurately transferred to the dental laboratory . the previous studies observed the inaccurate and poorly adapted restoration that led to compromised esthetics along with the biological failure of fixed partial denture . over the years , the dental materials are developed to improve their dimensional stability , reproducibility , and handling . the impression methods are also evolved to complement the recent material advancement to improve the impression accuracy . the elastomeric impression materials are most widely used in the restorative dentistry due to multiple advantages like good reproducibility , elastic recovery , and dimensional stability . the high viscosity material is used as a preliminary impression and low viscosity material is utilized to record the finer details of preparation . both single - stage and two - stage impressions the accuracy of an impression with repeated pour is of great advantage for the clinician and laboratory technicians . the change of interabutment distance during cast sectioning and loss of gingival reference during die ditching necessitate the additional intact duplicate cast for verification of finished restoration . the dimensional accuracy of the cast from repeated pour is influenced by the extent of elastic recoil from distortion during cast retrieval and continued polymerization shrinkage . these factors are greatly affected by the thickness / nature of impression material and stress induced during impression procedures . hence , it is important to understand the role of different impression methods on the dimensional accuracy of the resultant dies , especially on the multiple pours . the objective of the study was to compare the dimensional accuracy of the cast obtained from different impression methods on the multiple pours of a single impression at various time intervals . the impression methods evaluated in the study were two - stage putty relined with light body additional polyvinyl siloxane , single - stage heavy - light body additional silicone , single - stage monophase , and single - step polyether . the institutional ethical committee approval was obtained for the study research proposal ( src / reg/2014 - 2015/17 ) . the stainless steel working cast model assembly consisting of two abutments and one pontic area was fabricated ( figure 1 ) . the stainless steel abutments were made to simulate the full veneer crown preparation with uniform 2 mm shoulder finish line and 6-degree taper . the first abutment was 8.2 mm in height and 9.9 mm in diameter at the occlusal surface . the measurement at the same location for the second abutment was 7.6 mm and 7.04 mm , respectively . the occlusal surface of the abutment was flat with reference cross groove for precise measurement . two sets of perforated , rectangular custom aluminum trays were fabricated for making an impression ( figure 2 ) . the first set of six impression trays were used for putty wash impression technique ; they possessed uniform spacer width of five mm . another set of impression trays were having two mm uniform spacer area for a heavy body - light body one - step impression method . the impression tray stopper on working cast model base maintained the uniform space for the impression . the corresponding pin on the cast and groove in the impression trays was helpful in accurate position and immobilization of trays during impression procedure . the impression methods compared in the study were the two - step putty reline technique , one - step heavy - light body , and one - step monophase polyvinyl siloxane material . the impression procedures were conducted at controlled room temperature ( 25 10c ) and handled according to the manufacturer 's instruction . the silicone / polyether tray adhesive applied over the tray allowed it to dry for 10 minutes prior to the impression procedure . weighing the materials in precision scale established the accurate base and catalyst proportion ; twenty gm of each constituent was used during the study . two mm uniform spacer thickness was obtained by adapting vacuum resin sheet over model for two - stage putty wash technique . at the first stage , the mixed putty was loaded into the tray and allowed it to set over the cast for four minutes . the second stage involved the removal of the spacer and relining the preliminary putty impression base with light body elastomers . the single - stage heavy - light body impression was accomplished by simultaneous loading of the heavy consistency material to the tray , and light viscosity material was spread over the stainless steel die . the impression tray was placed over the cast ; the layer of the impression materials was allowed to set for 5 minutes . the single - stage impression from polyvinyl siloxane monophase and polyether single consistency impression were done in a similar procedure except for the overlying light body impression material ( figure 3 ) . after impression procedure , all polyvinyl siloxane impressions were rinsed in water and disinfected with sodium hypochlorite ( 1 : 10 ) immersion for 3 minutes . after the disinfection , the impressions were stored at 25 10c for one hour for elastic recovery and hydrogen release of vinyl polysiloxane . according to the manufacturer 's instruction , 30 gm of preweighed type iv gypsum was mixed with six ml of distilled water to obtain 0.20 water - powder ratio . the vacuum mixer was utilized for gypsum mixing , and it was poured into the impression under mechanical vibration ( figure 4 ) . the stainless steel retentive struts were attached to the cast base for easy removal of the set cast . the set gypsum cast was removed from the cast after one hour with due care , to avoid the impression damage . the second , third , and fourth dental casts were obtained following the same procedure after 8- hour , 24-hour , and 3-day interval from the same impression . all the measurements were performed after complete drying of gypsum cast . the measurement of set gypsum cast for linear dimensional change to the reference points was accomplished by traveling microscope with 0.01 m accuracy . the obtained data obtained was subjected to analysis of variance test at significance level < 0.05 . the percentage of variation of stone dies from the master cast was calculated by the following formula:(1)percentage of deviation = mean stone dimensionmean master dimensionmean master dimension100 . the present study evaluated the accurate reproducibility of dental die from repeated pour of an impression at the different time intervals . table 1 lists the mean values , standard deviation , and percent of deviation of the stone die obtained from two - step putty reline impression technique . there was a progressive reduction of the percentage of variation in the height on repeated pour from 0.36 to 0.97% . the upper diameter of the die was increased by 0.40.90% ; the lower diameter showed an increased diameter by 0.040.12% . the one - way anova showed the significant variation among all the measurements except the upper diameter of abutment with p value of 0.424 . table 2 shows the mean measurement values with the percentage of deviation for die in a heavy - light body one - step impression method . the abutment height was reduced to the range of 0.73 to 1.21% , while the upper diameter of the abutment was increased by 0.500.80% . the interabutment distance between the abutments was having 0.53% variation after pour at 24 hours . the percentage of variation for dies was progressively increased over the repeated pouring of the same impression . p value was statistically significant for all measurements except upper diameter of abutment with a value of 0.647 . table 3 displays the stone die measurement obtained from monophase impression along with the percentage of variation from the master die . the mean percentage of variation for interabutment width was at 1.47% , and the abutment height variation was up to 1.34% . the dimensional accuracy of dies was significantly varied over the repeated pour at abutment upper and lower diameter with p value of 0.00 and 0.002 , respectively . table 4 shows the mean measurement values and percentage of variation for the polyether impression group . the resultant dies after repeated pour were shrunk both in diameter and in height . the change for dies varied from 0.36 to 1.46 in height and 0.50 to 1.30 for upper diameter . the favorable prognosis of cast restorations is mainly dependent on the well - adapted margins . the multiple pours of the dental impression are required in various situations ranging from inadvertent damage to verification of contact and emergence profile on intact cast . the impression materials and methods that are capable of providing dimensionally accurate die on repeated pour are great advantage to clinicians and laboratory technician . the study explored the commonly used impression methods in their ability to produce the accurate die after the multiple pours . the accuracy of impression material is attributed to multiple factors , including elastic recovery , the direction of setting contraction , continuous polymerization , and evaporation of volatile contents . the additional silicone impression materials are most commonly used in dentistry due to their better accuracy , easy manipulation , and patient acceptance . according to the researchers of the opinion , the impression methods significantly influence the accuracy compared to the material used during the impression . the results from the study reinforced the opinion of the previous researchers ; the accuracy of dies varied significantly between different impression methods . chee and donovan , on a comparison between double mix and single mix putty reline technique , concluded that the double mix two - stage impression provided the more accurate cast . the main disadvantage of single mix technique reported by the researchers was the failure to record the finer details . the study evaluated the two - step putty reline with light body additional silicone impression method . according to the recommendation of earlier researchers , the wash bulk of two mm was utilized during the study for improved dimensional accuracy of dies . the study results showed that the dies obtained of one - step heavy - light body impression and monophase impression were relatively wider in diameter than the master dies in comparison with two - stage putty reline technique . the wider dies on multiple pours were due to the polymerization shrinkage towards the wall of the impression tray . the polymerization shrinkage was least in putty relined technique due to the low matrix and filler ratio . few researchers recommend the double mix single - step impression to eliminate the inaccuracies in the cast due to deformation and elastic recoil of first - phase material . the reseating and removal for the light body relining process lead to the deformation of already set high viscosity putty material . hence , the resultant dies from putty reline technique showed a slight variation in dimension . the results from the study also indicate the extended time allowed the recovery of an impression from the strain and improved the accuracy of the dies . the results of the study indicated that the single - step heavy - light body impression technique showed the percentage of variation in the width ranging from 0.04 to 0.90 . the second and the third pour exhibited the percentage of variation of 0.05% and 0.06% , respectively . the compromised elastic recovery of heavy body impression material is due to the less proportion of filler particle in comparison with the putty material . the inability in maintaining the uniform thickness of light body material also leads to larger dimensional changes . the results of the study are in agreement with stackhouse . the shorter dies due to contraction of vertical dimension towards the occlusal preparation with the impression attached to the tray . the larger section of clinicians prefers the monophase impression material due to its quick and easy impression procedure . the results from the study indicate that the upper diameter of the dies had increased the percentage of variation within the range of 0.701.20 . the die produced after repeated impression pour was shorter than the master cast by 1.34% . the percentage of variations were significantly higher in comparison to putty reline and single - step heavy - light body impression technique . the results are in compliance with the observation of millar et al . ; they reported the poor dimensional accuracy and high surface defects in monophase impression material because of its relatively high viscosity and reduced flow . johnson and craig reported the larger die diameter due to the contraction of impression material towards the walls of the impression tray . the polyether impression materials continue to be preferred by the clinicians due to its hydrophilic nature , improved flow , and easy manipulation . the rigidity of the polyether is its main disadvantage , leading to difficulty in removing the impression . the dies prepared with polyether impression material were small both in diameter and in height . the results could be due to the inability of polyether impression material in its elastic recovery . the water imbibition from gypsum during setting reaction also leads to the dimensional inaccuracy of dies . within the limitation of the study , following conclusions were drawn . the putty reline technique ( two steps ) and heavy - light body additional silicone ( 1 step ) resulted in the lowest percentage of variation from a master model . the polyether impression showed the highest distortion over the repeated pour , due to lesser ability to recover . all the impression techniques showed the statistically significant changes in dimension over the repeated impression pour .

the accurate duplicate cast obtained from a single impression reduces the profession clinical time , patient inconvenience , and extra material cost . the stainless steel working cast model assembly consisting of two abutments and one pontic area was fabricated . two sets of six each custom aluminum trays were fabricated , with five mm spacer and two mm spacer . the impression methods evaluated during the study were additional silicone putty reline ( two steps ) , heavy - light body ( one step ) , monophase ( one step ) , and polyether ( one step ) . type iv gypsum casts were poured at the interval of one hour , 12 hours , 24 hours , and 48 hours . the resultant cast was measured with traveling microscope for the comparative dimensional accuracy . the data obtained were subjected to analysis of variance test at significance level < 0.05 . the die obtained from two - step putty reline impression techniques had the percentage of variation for the height 0.36 to 0.97% , while diameter was increased by 0.400.90% . the values for one - step heavy - light body impression dies , additional silicone monophase impressions , and polyether were 0.73 to 1.21% , 1.34% , and 1.46% for the height and 0.500.80% , 1.20% , and 1.30% for the width , respectively .

the injury pattern of open fracture dislocation of elbow with fracture both bones forearm with radial nerve injury is very rare . this rare injury needs special attention by early intervention and biological fixation to achieve good results . a 22 year old female presented to us with history of road traffic accident . on evaluation patient had combination of open fracture dislocation of elbow with open diaphyseal fracture of both forearm bones with radial nerve palsy . early intervention and biological fixation with minimal invasion gives good results in terms of range of movements and patient satisfaction . a complex injury of the elbow joint is a fracture and with or without dislocation of the elbow in association with multiple other fractures of the upper extremity , or severe soft tissue trauma , or a concomitant injury to vessels or nerves . the surgeon should apply any available method that can provide stability to the bone fragments and safe handling of the soft tissues giving priority to internal fixation of the fractures . severe osseous , soft tissue and neural trauma affect the functional results of the elbow region . this rare injury needs special attention by early intervention and biological fixation to achieve good results . a 22 year old female patient , tailor by occupation came to emergency department with history of road traffic accident and injury sustained to her right elbow and forearm . on examination there was type 3b open fracture having wound over the lateral side of elbow with fractured lateral epicondyle , extensive lacerated wound over the dorsum of proximal 1/3rd forearm with open diaphyseal fracture of both ulna and radius in middle 3rd . on assessment of distal neurovascular deficits , patient found to have low radial nerve palsy with intact vascularity . standard anteroposterior(ap ) and lateral radiographs were taken which showed lateral epicondylar fracture of humerus with posteromedial dislocation of elbow [ fig . 1 ] and diaphyseal fracture of both ulna and radius at middle 3rd level [ fig.2 ] . after primary wound toilet at emergency , case was posted to emergency operation ( 2hours since injury ) with plan of wound debridement and open reduction and internal fiation / external fixation with minimal possible implants aiming biological fixation and radial nerve exploration . in the operation theatre the elbow was examined under general anaesthesia where no other findings were found except for lateral laxity tested by varus stress test after elbow was reduced . the radius was fixed with rush pin and ulna was checked , where it was well reduced and in alignment . in view of post traumatic raw area , external fixator pins over the ulna spanning the elbow was planned on table and same was done [ fig . 3 ] . then radial nerve was explored utilising the wound and posterior approach where no obvious findings were found . wound debridement was done every 2nd day and posted to operation theater after a week for wound coverage with split skin graft . post op 5th day wound inspection showed well taken graft and no infection was found [ fig . 4 ] . after 2 weeks , pins of humerus were taken out and elbow physiotherapy started and patient was discharged . after 2 months , pins of ulna taken out when she had 400 to 1200 of flexion and 600 - 600 of supination - pronation movements . 5 and 6 ] was taken which showed union of forearm bones when pin was removed and all activities were encouraged except for lifting heavy weight . range of motion by 6 months were 300 - 1400 flexion [ fig 7 and 8 ] , 700 - 800 supination - pronation . regel et al defined a complex injury of the elbow joint as a fracture and with or without dislocation of the elbow in association with multiple other fractures of the upper extremity , or a severe soft tissue trauma , or a concomitant injury to vessels or nerves . our case had open elbow dislocation with lateral epicondylar fracture with lateral laxity associated radial nerve palsy and associated open fracture both bones of forearm in middle3rd . the surgeon should apply any available method that can provide stability to the bone fragments and safe handling of the soft tissues giving priority to internal fixation of the fractures . severe osseous , soft tissue and neural trauma affect the functional results of the elbow region . early coverage of the open wounds about the elbow by flaps or skin grafts is recommended in order to provide wound closure , decrease infection and tissue oedema and allow early mobilization of the elbow joint . we initiated elbow range of motion by the end of 2nd week , which resulted in fairly good range of motion at the subsequent follow ups . this rare injury of radius and ulnar shaft fractures with elbow posterior dislocation has been described as a unique monteggia - equivalent injury . the postulated mechanism of injury in these injuries is the initial elbow dislocation as a result of the fall on the outstretched arm . then , both the bones of the forearm fractured while the elbow was in extension , the forearm in hyper - pronation and the wrist in radial deviation . it is unlikely for the elbow dislocation to follow fractures of both the forearm bones . in managing such a complex elbow fracture - dislocation , there must be due consideration for restoration of joint congruity , skeletal stabilization as well as ligamentous reconstruction with careful handling of soft tissues around the elbow joint . as such , a combined single stage approach for radius and ulnar shaft stabilization with joint reduction and collateral ligament reconstruction may be useful . there is little evidence in the literature that operative repair of the collateral ligaments has significant advantage over nonsurgical treatment in a plaster cast . for surgical treatment of the collateral ligaments , medial collateral ligament reconstruction is particularly indicated when there is residual instability following lateral ligament reconstruction or in throwing athletes . the rotational stability of fractures of the radius and ulna treated with rush pins and/or fracture bracing was studied in six fresh cadaver forearms rotation and fracture site motion ( rotation ) were measured as functions of applied forearm torque and rotation ( pronation - supination ) . when loading to specific torque levels , the brace reduced fracture site motion to one - half the motion with no fixation treatment . under both loading conditions , rush pin fixation significantly and markedly reduced the fracture site motion ( to approximately one eighth of the motion with no fixation treatment ) , whereas a brace in conjunction with rush pins did not significantly further reduce the fracture site motion . in our case rush pin for radius with external fixator for ulna significantly reduced fracture site motion and , showed that most of the activities of daily living could be accomplished with a 100 aarc of motion ( from 30 to 130)and 100 of forearm rotation ( 50 of pronation and 50 of supination ) . our patient achieved 1100 arc of motion ( 300 to 1400 ) and forearm rotation of 150 ( 70 pronation to 80 supination ) . the implants used for reconstruction are not ones that are up to recommended standards . however the principle of early intervention and biological fixation can be generalized for these rare injuries which may give good reproducible results . the open fracture dislocation of elbow with open fracture both bones forearm with radial nerve injury is a rare combination . early intervention and biological fixation with minimal invasion gives good results in terms of range of movements and patient satisfaction . early identification of injury and timely intervention with biological fixation gives better results in complex fracture dislocation of elbow .

introduction : the injury pattern of open fracture dislocation of elbow with fracture both bones forearm with radial nerve injury is very rare . very few reports are there in literature related to this kind of injury . however this combination is first of its kind . this rare injury needs special attention by early intervention and biological fixation to achieve good results.case report : a 22 year old female presented to us with history of road traffic accident . on evaluation patient had combination of open fracture dislocation of elbow with open diaphyseal fracture of both forearm bones with radial nerve palsy . the patient was treated in emergency and followed for 2 years.conclusion:open fracture dislocation of elbow is a rare entity . our case additionally had open fracture both the bones forearm with radial nerve palsy . early intervention and biological fixation with minimal invasion gives good results in terms of range of movements and patient satisfaction .