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cases of idiopathic recurrent benign aseptic meningitis were first described by mollaret . today , herpes simplex virus ( hsv ) a 40-year - old male was referred to our genitourinary medicine clinic with recurrent genital herpetic lesions . one year after the first infection , he developed severe recurrent attacks of headache associated with meningitis symptoms . the results of all radiological and biochemical tests were normal , but the patient reported a correlation between his attacks and genital herpes flare - ups . we diagnosed the patient with mollaret s meningitis and started him on continuous suppressive acyclovir therapy , which resulted in marked clinical improvement . mollaret s meningitis is a rare form of idiopathic recurrent aseptic meningitis that has a sudden onset , short duration , and spontaneous remission with unpredictable recurrence . we believe that the presence of concurrent or recurrent mucocutaneous herpetic lesions can aid its diagnosis , prior to which , affected patients usually have many unnecessary investigations and treatments . therefore , detailed sexual history should be sought in all patients with aseptic meningitis , and clinicians should also ask about history of recurrent headaches in all patients with recurrent herpetic anogenital lesions . continuous suppressive acyclovir therapy may reduce the frequency and severity of attacks and can dramatically improve lifestyle . mollaret was the first to describe a rare form of meningitis that presented as recurrent and brief self - limiting attacks of fever , headache , vomiting , and meningeal irritation with no obvious etiology.1 subsequently , all cases of idiopathic recurrent aseptic meningitis ( ram ) were collectively called mollaret s meningitis.2 today , herpes simplex virus ( hsv ) type 2 ( hsv-2 ) is thought to be the commonest cause of mollaret s meningitis , underlying up to 84% of cases,3 although other infectious and noninfectious causes have also been described.2 however , its diagnosis remains challenging despite the use of new sophisticated diagnostic tools , and some authors have advised restricting the term mollaret s meningitis to cases with no confirmed etiology.2 the frequency and severity of attacks are variable , and severe forms can be incapacitating if appropriate antiviral therapies are not promptly used . here , we describe a rare case of a patient with ram who presented with recurrent and severe self - limiting bouts of headache and responded well to suppressive antiviral therapy . a 40-year - old man was referred to our genitourinary medicine clinic with chronic recurrent herpetic genital ulcers . swabs taken from these initial lesions tested positive for hsv-2 and negative for hsv type 1 ( hsv-1 ) . the patient had a past medical history of migraines that started in adulthood as unilateral headaches and were controlled by triptans and simple analgesics . one year after his first genital infection , the patient started to develop severe holocranial headaches with distinct characteristics , which failed to respond to usual migraine therapy . the headaches were associated with neck stiffness , mild photophobia , and bilateral pedal paresthesia , but there was no fever , vomiting , or other cranial or radicular neuropathy symptoms . the patient went to the emergency department many times , but his biochemical markers and a computed tomography brain scan were normal . the patient repeatedly refused diagnostic lumbar puncture , but serologic assays ( hsv-1 , cmv [ cytomegalovirus ] , vzv [ varicella - zoster virus ] , and human immunodeficiency virus ) were negative apart from a positive hsv-2 immunoglobulin g titer . he was clinically diagnosed with meningitis and commenced on empirical parenteral ceftriaxone and acyclovir , to which he responded very well . his attacks often recurred two to three times per month and were usually self - limiting in 35 days , regardless of their severity , with no residual functional impairment . the attacks were often triggered by emotional stress or heat and were sometimes preceded by genital herpetic eruptions , for which he was referred to our clinic . the distinctive correlation between his meningitic recurrent headaches and recurrent genital lesions as well as his normal previous diagnostic tests raised our suspicion of a possible mollaret s meningitis diagnosis . we placed the patient on a continuous suppressive oral acyclovir therapy regimen ( 400 mg twice daily ) , which reduced the frequency of his headaches to one to two attacks every 23 months , each lasting 13 days . attempts to reduce the total daily dose to 400 mg or 600 mg have led to a remarkable increase in the severity and frequency of his acute relapses , so the total daily dose of 800 mg is being sustained indefinitely with regular follow - up in our clinic . in 1982 , hsv was linked to mollaret s meningitis when hsv-1 was detected in the cerebrospinal fluid of an affected patient.4 today , hsv-2 ( and less often hsv-1 ) is believed to be a leading cause of ram . its pathogenesis is not fully understood and may be due to retrograde seeding reactivation of the latent virus nested in the sensory ganglia.5 aseptic meningitis is known to complicate primary genital herpes infection in 36% of women and 11% of men , but meningitis following subclinical infections has also been reported.6,7 confirmed hsv-2 acute meningitis can recur in 19%27% of cases , especially in hsv-1 seronegative patients similar to our case.3,8 hsv-1 seroprevalence is declining in many countries , including the uk , and the incidence of recurrent hsv-2-associated meningitis may be increasing.3,9 practical diagnostic criteria for mollaret s meningitis historically included absence of any detectable etiological agents.10 however , occurrence of concurrent or separate episodes of recurring mucocutaneous herpetic lesions , or detection of hsv dna in the cerebrospinal fluid which can be positive in up to 82% of samples taken 25 days after the onset of symptoms3 can aid diagnosis recurrent attacks can be preceded by nonspecific self - limiting constitutional symptoms as paresthesias , neuropathic pain , and arthralgias.3,6 mollaret s meningitis usually resolves after a period of 35 years , but cases with longer periods , similar to our patient , have also been reported.2,11 the use of long - term suppressive rather than episodic anti - hsv therapy has shown satisfactory results in controlling hsv-2-associated mollaret s meningitis , but this practice is not yet supported by high quality evidence.2,7 in our patient and other reported cases , daily acyclovir or valacyclovir has been generally well tolerated with good bioavailability , and has reduced the severity and frequency of attacks.7,11 other medications such as colchicine and indomethacin have also been tried , but firm evidence of their efficacy is still lacking.12,13 incidence of hsv-2-associated recurrent meningitis is suspected to be increasing . however , most patients have unnecessary investigations and treatments prior to diagnosis , and some patients remain undiagnosed . history of herpetic anogenital infections should be sought in all patients with recurrent meningitic headaches and vice versa . continuous antiviral therapy appears to reduce the frequency of attacks and can dramatically improve lifestyle .

introductioncases of idiopathic recurrent benign aseptic meningitis were first described by mollaret . today , herpes simplex virus ( hsv ) is considered the cause of most cases of mollaret s meningitis.case reporta 40-year - old male was referred to our genitourinary medicine clinic with recurrent genital herpetic lesions . he had hsv-2-positive genital ulcers 8 years earlier . one year after the first infection , he developed severe recurrent attacks of headache associated with meningitis symptoms . the results of all radiological and biochemical tests were normal , but the patient reported a correlation between his attacks and genital herpes flare - ups . we diagnosed the patient with mollaret s meningitis and started him on continuous suppressive acyclovir therapy , which resulted in marked clinical improvement.discussionmollarets meningitis is a rare form of idiopathic recurrent aseptic meningitis that has a sudden onset , short duration , and spontaneous remission with unpredictable recurrence . we believe that the presence of concurrent or recurrent mucocutaneous herpetic lesions can aid its diagnosis , prior to which , affected patients usually have many unnecessary investigations and treatments . therefore , detailed sexual history should be sought in all patients with aseptic meningitis , and clinicians should also ask about history of recurrent headaches in all patients with recurrent herpetic anogenital lesions . continuous suppressive acyclovir therapy may reduce the frequency and severity of attacks and can dramatically improve lifestyle .

at the end of the 20th century , coronary heart disease ( chd ) remains the most common cause of death among both men and women in most of the westernized world . the increased relative risk for chd death in men ( 2.5- to 4.5-fold ) compared with women is seen in countries with high or low rates of heart disease . this male surplus of chd in diverse populations with very divergent lifestyles , eating patterns , and disease rates is only compatible with an intrinsic female advantage or a male disadvantage . the fact that chd is uncommon in women before 50 years of age ( average age of menopause 49 - 51 years ) , that postmenopausal women demonstrate increased rates of chd compared to premenopausal women of the same age range , and the increased risk of chd after premature menopause lend support to the estrogen - chd hypothesis . numerous in vivo and in vitro studies show at least a dozen estrogen effects that would be expected to prevent or delay chd . observational studies have almost universally reported a lower risk of chd in postmenopausal women who take estrogen alone or with a progestin as compared with those women who do not . on average , women develop heart disease approximately 10 years later than men , but the largest increase in coronary mortality coincides with the menopause . the degree to which estrogen deficiency contributes to chd risk in women has not been definitively established , and cross - sectional and prospective studies have generally failed to find an association between endogenous estrogen levels and chd risk factors in women or men . data from vital statistics also do not support a conclusion that menopause , apart from the effects of chronological aging , increases the risk for chd . obviously , these studies can not completely exclude a cardioprotective effect of endogenous estrogen since a single hormone assay may be inadequate to correctly classify individuals with regard to their usual endocrine status . data from women who undergo premature menopause -natural or surgical - indicate that chd develops prematurely in these women , supporting the concept that menopause and chd are linked . autopsy studies have shown a clear increase in coronary disease in women after oophorectomy or premature ovarian failure . there are many possible confounding variables in these studies , including changes in hypothalmic and pituitary hormone levels after surgery , and the antecedent disease processes that necessitated oophorectomy or caused the ovarian failure . more recent studies have yielded inconsistent results . in the nurses ' health study , bilateral oophorectomy , but not natural menopause , was associated with an increased risk for chd . no increased risk was observed in oophorectomized women who had been treated with estrogen . the fact remains , however , that after oophorectomy the incidence of chd in women is increased . perhaps the most dramatic evidence suggesting that loss of endogenous estrogen increases cardiac risk is the sharp increase in low - density lipoprotein ( ldl)-cholesterol that begins during the perimenopausal period and continues to at least age 60 years , with these higher levels sustained thereafter . interestingly , both cross - sectional and prospective studies show only a small decrease in high - density lipoprotein ( hdl)-cholesterol levels at the time of menopause ; on average , hdl - cholesterol levels in women remain higher than those in men for at least another 30 years after menopause . the postmenopausal estrogen / progestin intervention ( pepi ) trial examined the effect of hrt [ conjugated equine estrogen alone or in various combinations with medroxyprogesterone acetate ( mpa ) or micronized progesterone ] on cardiovascular risk factors . the pepi trial and numerous observational studies have shown that oral estrogen therapy is associated with a 10 - 15% increase in hdl - cholesterol and a similar decrease in ldl - cholesterol . the elevation in hdl - cholesterol is due to increased production of hdl2 and apolipoprotein a-1 , whereas the decrease in ldl - cholesterol is due to increased expression of hepatic ldl receptors . all progestins are not alike , however , and the pepi trial found differences in the effects of different hrt preparations on chd risk factors . while all women who received estrogen had an increase in hdl - cholesterol and a decrease in ldl - cholesterol , the hdl - cholesterol effect was more pronounced with micronized progesterone than with mpa . progestins , such as mpa , have been found to reduce the beneficial effects of estrogen on endothelial function and on atherosclerosis in several animal models . the benefits and risks of cyclic versus daily progestin regimens also have not been fully determined . oxidation of ldl - cholesterol is believed to be an initiating event in atherogenesis , and estradiol and/or other estrogens may inhibit this process . oral conjugated estrogens are also associated with increases in very low - density lipoprotein , triglycerides , and apolipoproteinb levels , as well as with decreases in lipoprotein(a ) levels . these are not large changes , however , and the effects of modest alterations in these molecules on the development of chd are uncertain . these include favorable changes in postprandial lipid metabolism , plasminogen activator inhibitor-1 , fibrinogen , antithrombin iii , homocysteine levels , carbohydrate metabolism , atheroma formation , cardiovascular hemodynamics , and endothelial dysfunction . on the other hand , the pepi investigators found that hrt rapidly increases the level of c - reactive protein ( a marker of inflammation that has been associated with increased risk of cardiovascular events ) while reducing the levels of soluble e - selectin ( a possible anti - inflammatory effect ) . as pointed out by those investigators , such data underscore the need to study the effect of hrt - mediated changes in inflammation on the risk of subsequent coronary events . since the 1970s , more than 30 case - control and prospective studies have reported a decrease in risk for chd in women on hrt . in the most recent meta - analysis , barrett - connor and grady estimated that estrogen therapy alone was associated with a 35 - 50% reduction , and estrogen - progesterone with a 33% reduction in the risk of coronary disease , as compared with women who were not on hrt . follow - up study , 2270 hyperlipidemic , caucasian women aged 40 - 69 years at study entry were followed for more than 8 years . over 60% fewer chd deaths occurred in women who received estrogen than in those who did not . this benefit remained after adjustment for age , hypertension , and smoking , and it was most pronounced in women with known chd . it has been suggested that observational studies may overestimate the amount of protection attributed to estrogen . numerous biases in the epidemiologic studies have been identified ( compliance , healthy user , prescription , prevention , survivor ) . only randomized trials can control for both known and unknown differences in women who do and do not elect to take medication . the only large , randomized clinical trial testing the benefit of hrt - the heart and estrogen / progestin replacement study ( hers ) - found no overall benefit of hrt on secondary prevention of chd in 2763 postmenopausal women with established coronary disease who were treated for an average of 4.1 years ( relative risk 0.99 , 95% confidence interval 0.80 - 1.22 ) . hrt was associated with more secondary cardiac events as compared to placebo during year 1 of treatment , and with a significant trend toward fewer events in years 4 and 5 . at face value the results of hers are not consistent with our knowledge of estrogen 's action on the cardiovascular system and the many observational studies showing estrogen 's benefit , and it is premature and counterintuitive to rely only on the results of this one study . this was an older cohort of women ( mean age 67 years ) with significant heart disease . more than 80% of the hers study group had revascularization within 6 months of study entry , which could have resulted in the low event rates in both the placebo and treatment arms ( the event rate in the placebo group was 50% lower than that in the treatment group during the first year ) . the hers selection criteria also excluded women with uncontrolled diabetes or hypertension , which also may have resulted in low event rates . most women in observational studies began using hrt during the perimenopausal or early postmenopausal period . in the hers study , women were an average of 18 years past the cessation of menses . only 46% of patients received cholesterol - lowering statins ( 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors ) and diet modification in addition to hrt , even though more than 90% had ldl - cholesterol in excess of 100 mg / dl at baseline . statins have been shown in clinical trials to reduce the risk of chd in women with or without known heart disease . another significant variable is if the choice of hrt used in the hers ( a fixed - combination estrogen and progestin ) played a role in increasing chd events . since a comparison group taking estrogen alone was not included , and some progestins are thought to attenuate the benefits of estrogen on the cardiovascular system , the possibility exists that a different regimen may have offered greater benefits . before hers , the real controversy over hormone therapy was whether all postmenopausal women were likely to derive cardioprotective benefit and should therefore be encouraged to use hrt . despite the nearly universal findings from observational studies that postmenopausal estrogen therapy reduces the risk of chd and the multiple mechanisms by which estrogen might be beneficial , hormone therapy had no benefit in the only large randomized clinical trial to date . at this time , what we have really learned from hers is that , in older women with severe chd , a fixed estrogen - progestin regimen should not be prescribed with the expectation that it will decrease the incidence of cardiovascular events in the short term . women who are already on hrt should probably continue with the regimen because there appears to be a protective effect of hrt on the cardiovascular system after the first few years of use . on the basis of the results of the hers trial , a consensus panel of the american heart association and the american college of cardiology has suggested that initiation or continuation of hrt should be considered in those women for whom the potential benefits of therapy may exceed the potential risks based on individualized patient history.thus , although there is significant evidence that hrt is protective in postmenopausal women in the primary prevention of chd , further large - scale studies of hrt in women with established chd are warranted , especially with other hrt regimens .

large numbers of observational studies have described a decrease in the incidence of cardiovascular disease in women taking hormone replacement therapy ( hrt ) . the potential mechanisms for this effect are numerous , including direct effects on lipid levels and lipid metabolism , cardiovascular dynamics , and endothelial reactivity . the beneficial effects of hrt are probably affected by various factors , including the age of onset of therapy , the presence of coronary artery disease , the type of estrogen and whether it is used in combination with progesterone , concurrent modification of other cardiac risk factors , and duration of therapy . until further prospective clinical trials are done , hrt should be considered in those women for whom the potential benefits exceed the potential risks , on the basis of an individualized patient evaluation .

individual response to drugs often differs significantly and these drug - response variations are frequently associated with polymorphisms of pharmacologically related proteins ( 15 ) . pharmacogenetic study of these proteins and their regulatory sites is important for the understanding of molecular mechanism of drug responses and for the development of personalized medicines ( 1,69 ) . resources that provide information about molecular mechanism of drug - response variations are useful for facilitating pharmacogenomics study and the development of personalized medicine ( 10 ) . there have been calls and efforts for developing such resources ( 11 ) and the related informatics tools ( 12,13 ) . a number of freely accessible web - based resources have been developed for providing information about genetic and clinical pharmacogenetic information ( 14 ) , polymorphisms in drug - related proteins ( 1520 ) and toxicogenomics data ( 21 ) . although pharmacogenetic knowledge , polymorphism and toxicogenomic information are provided in these databases , some of the reported pharmacogetic effects are given in web - pages separate from that of other important information such as protein and drug information , and are often given by relatively long descriptions quoted from literatures . to facilitate easy and quick assessment of the relevant information , it is helpful to develop databases that provide all the information related to a pharmacogenetic effect in the same web - page . we developed pharmacogenetic effect database ( pharmged ) with the aim to provide the information about the effects of a particular protein polymorphism , non - coding region mutation , splicing alteration or expression variation on the response of a particular drug . it currently contains 1825 entries covering 108 disease conditions , 266 distinct proteins , 693 polymorphisms , 414 drugs / ligands cited from 856 references . the entries of this database were derived from a comprehensive search of published literatures ( via medline ) by using a similar search and evaluation procedure as we have used for developing other databases of drug - related proteins ( 1518 ) . these methods include the search of protein name , drug / ligand name , disease name ( extracted from the related terms described in the relevant publications ) and drug class ( derived based on the related terms described in the relevant publications ) . full list of protein names , drug / ligand names , disease names and drug classes are separately provided in the pharmged main web - page for facilitating the search of particular entries . , a user can specify full name or any part of the name in a text field . wild character of * and ? is allowed in text field . here , ? represents any single character and * represents a string of characters of any length . for example , input of dehydrogenase in the field of protein / gene name enables the finding of all entries containing dehydrogenase in the protein name , such as 3-oxo-5-alpha - steroid 4-dehydrogenase 2 , alcohol dehydrogenase 1b , alcohol dehydrogenase 1c , fatty aldehyde dehydrogenase , glucose-6-phosphate 1-dehydrogenase , nad(p)h dehydrogenase ( quinone ) 1 , etc . on the other hand , all entries that satisfy the specified search criteria are listed along with protein name , polymorphism rules , drug / ligand name , drug classification , disease name and links to other related entries in this database . more detailed information of an entry can be obtained by clicking the corresponding protein name . the result is displayed in an interface shown in figure 2 . from this interface , one finds the accession number , name , sequence and function of protein , pharmacogenetic polymorphism , affected drugs and drug class , corresponding disease condition and pharmacogenetic effect . moreover , the information about the related references and links to the literature database pubmed ( 22 ) is also provided . all entries that satisfy the specified search criteria are listed along with protein name , polymorphism rules , drug / ligand name , drug classification , disease name and links to other related entries in this database . established links between polymorphisms of drug - related proteins and individual drug responses have been used in combination with genetic studies as indicators for predicting individual variations of drug response ( 2327 ) . based on the statistical analysis of the data of polymorphisms and variation of drug response of the participating patients , simple rules may be derived in some cases for predicting individual variations of drug response from polymorphism data ( 23,24,26,28,29 ) . these simple rules may be collected and used for developing a computer prediction system in a fashion similar to that of the hiv drug - resistant genotype interpretation systems ( 30 ) . table 1 gives examples of the drug - related proteins in pharmged with available information about pharmacogenetic polymorphism and drug - response variation from which a reasonably accurate rule have been derived in the literature for predicting responses to a specific drug or drug group . the reported percentage of patients who have a polymorphism and showed the expected effect is also given . based on the test of the patients described in these reports , most of these rules are capable of predicting drug responses at success rates of 50100% , which are not too much lower than and in many cases comparable to the accuracies of 8197% for predicting hiv drug resistance mutations from the hiv - resistant genotype interpretation systems ( 30 ) . this suggests that these simple rules have certain level of capacity for facilitating the prediction of pharmacogenetic effects and they may be used as the basis for developing more sophisticated interpretation systems similar to those of the hiv - resistant genotype interpretation systems ( 30 ) . prediction of specific drug responses from the polymorphisms of adme - associated proteins by using simple rules pharmged and other databases ( 1421 ) can be potentially used for facilitating the generation of these rules . for instance , one entry of pharmged describes that patients using classical neuropleptic such as fluphenazine , haloperidol have a higher incidence ( 81% ) of tardive dyskinesia if they are of the genotype cyp2d6 * 4 . these data combined with other information in pharmaged can be used to generate the rule for detecting this pharmacogenetic effect described in table 1 . in a second example , another entry of pharmged describes that the polymorphism c3435 t ( ile1145ile ) of protein mdr1 - 3435 variant is associated with different virologic response of nelfinavir in hiv-1 infected children . fifty - nine percent of the 31 c / c genotype and 91% of the 33 c / t genotype show virologic response at eighth week , respectively . these data can then be used to generate the rule for this pharmacogenetic effect as described in table 1 . knowledge about protein polymorphisms and drug responses appears to have reached a meaningful level for facilitating pharmacogenetic study and for predicting various types of individual variations of drug responses . specialized pharmacogenetics databases serve as convenient resources for obtaining the relevant information . with the rapid development of genomics ( 31 ) , pharmacokinetics ( 3235 ) and pharmacogenomics ( 6,8,9 ) , more information about drug - related proteins , polymorphisms and variations of drug responses are expected to become available . moreover , progress in the study of proteomics ( 36 ) and pathways ( 37 ) related to drug - related proteins will further facilitate our understanding of the mechanism of individual variations in drug response .

prediction and elucidation of pharmacogenetic effects is important for facilitating the development of personalized medicines . knowledge of polymorphism - induced and other types of drug - response variations is needed for facilitating such studies . although databases of pharmacogenetic knowledge , polymorphism and toxicogenomic information have appeared , some of the relevant data are provided in separate web - pages and in terms of relatively long descriptions quoted from literatures . to facilitate easy and quick assessment of the relevant information , it is helpful to develop databases that provide all of the information related to a pharmacogenetic effect in the same web - page and in brief descriptions . we developed a database , pharmacogenetic effect database ( pharmged ) , for providing sequence , function , polymorphism , affected drugs and pharmacogenetic effects . pharmged can be accessed at free of charge for academic use . it currently contains 1825 entries covering 108 disease conditions , 266 distinct proteins , 693 polymorphisms , 414 drugs / ligands cited from 856 references .

spontaneous nephrocutaneous fistula is a rare manifestation of renal disease that can occur due to various etiologies , such as renal calculus , chronic pyelonephritis , stricture of the ureteropelvic junction , and renal tuberculosis ( tb ) . an autonephrectomy with a nephrocutaneous fistula due to renal tuberculosis can be diagnosed quite late if it is not suspected . a 40-year - old white male with recurrent flank pain and intermittent purulent drainage from his right flank region for the previous 14 years was admitted to our outpatient clinic . fistulography and computerized tomography demonstrated a 51 60 mm area with a soft - tissue appearance that implied autonephrectomy of the right kidney , and a fistula tract with a 9 mm diameter between the skin and the retroperitoneal space . the patient was successfully treated with nephroureterectomy and excision of the fistulous tract , followed by antituberculous treatment . the pathological examination of the surgical specimen revealed chronic atrophic pyelonephritis , calcifications , and necrotizing granulomatous inflammation suggestive of tb . urogenital tb is difficult to diagnose due to the lack of specific symptoms and signs . in the case of a nonfunctioning kidney without an obvious cause and a chronic spontaneous nephrocutaneous fistula , the possibility of associated renal tb should be kept in mind , especially in immunocompromised patients or in places where tb is a common health problem . spontaneous nephrocutaneous fistula is a rare manifestation of renal disease that can occur due to various etiologies . genitourinary tuberculosis ( tb ) is seen in 15% - 20% of patients with pulmonary tb in developing countries . spontaneous nephrocutaneous fistulas can be secondary to strictures at the ureteropelvic junction , or to necrosis and scar formation due to renal tb . fibrosis , necrosis , and scar formation in the renal parenchyma creates a weak area , from which the leak begins ( 2 ) . renal tb can cause various complications , including autonephrectomy in 11.5% of affected patients ( 3 ) . in september 2014 , a 40-year - old white male who worked as a cook presented to the outpatient clinic with recurrent right flank pain and intermittent purulent drainage from his right flank region over the previous 14 years . there was no past history of any medical or surgical illness , including tb or trauma . the physical examination revealed a fistulous orifice in the skin of the right flank region . the patient had already used different kinds of antibiotics during this disease process , but the discharge from the fistula had never stopped . laboratory evaluations identified a normal urine analysis , a sterile urine culture , and normal serum hemoglobin , urea , and creatine levels . a fistulography was performed , revealing drainage of contrast agent to the kidney and the retroperitoneal space ( figure 1 ) . computerized tomography ( ct ) demonstrated a 51 60 mm area with a soft - tissue appearance that indicated autonephrectomy of the right kidney , and a fistula tract with a 9 mm diameter between the skin and the retroperitoneal space ( figure 2 ) . the right kidney was non - functioning on a tc99m - dimercaptosuccinic acid ( dmsa ) renal scan . the patient was assessed by the department of chest diseases , and his tuberculin test was negative for tb . dense adhesions of the kidney to the psoas muscle and posterior peritoneum were carefully dissected . the pathological examination of the surgical specimen revealed chronic atrophic pyelonephritis , calcifications , and necrotizing granulomatous inflammation , suggestive of tb . the postoperative recovery period was uneventful and the patient was discharged on the seventh day . a ziehl - neelsen stain of the nephroureterectomy specimen showed acid - fast bacilli , confirming the diagnosis of renal tb . the patient was successfully treated for six months after the nephroureterectomy with a four - drug antituberculous therapy ( isoniazid [ 300 mg / day ] , rifampicin [ 600 mg / day ] , pyrazinamide [ 2000 mg / day , 2 months only ] , and ethambutol [ 1500 mg / day , 2 months only ] ) . at his last follow - up visit in march 2015 , he had no complaints , and his abdominopelvic ct scan showed no pathological findings except for the solitary left kidney . genitourinary tb is the second most common form of extrapulmonary tb , after peripheral lymphadenopathy . tb may involve the kidney as part of a generalized disseminated infection , or as localized genitourinary disease . however , less than 50% of patients with renal tb have radiological evidence of pulmonary tb , and active pulmonary disease is present in approximately 5% of such patients ( 4 ) . the development of disease depends on the cellular immune response of the host , which determines the outcome of the infection . the healing process results in fibrous tissue , and the deposition of calcium salts can result in a non - functioning kidney , known as tuberculous autonephrectomy . renal calcifications may occur commonly in tb and require surgical intervention . in the treatment of this complication , the aim is to ensure the protection of the renal tissue as much as possible ( 5 ) . tuberculous bacilli reach the kidney via a hematogenous route and settle in periglomerular capillaries , leading to abscess formation . all of these inflammatory changes result in fibrosis , calcifications , ureteral and calyceal strictures that cause loss of renal function , and autonephrectomy ( 6 ) . in this situation , nephroureterectomy is unavoidable ; however , this is a debatable point if the kidney is non - functioning and symptomless . some authors have proposed nephrectomy in order to prevent reactivation , while others have recommended life - long follow up . with the development of antituberculous drugs , nephrectomy has become less important , but it can still be required in cases of uncontrolled hypertension or uncontrolled pain associated with the kidney . additionally , at the end - stage of the disease , fistulas can form to adjacent organs , requiring surgical excision of the fistulous tract and nephroureterectomy ( 7 ) . according to the european association of urology guidelines , the indications for nephrectomy include a non - functioning kidney with or without calcifications , extensive disease involving the whole kidney with hypertension and ureteropelvic junction obstruction , and coexisting renal carcinoma ( 5 ) . a spontaneous renal fistula to adjacent organs is not an uncommon condition , but a spontaneous nephrocutaneous fistula is still rare . the majority of such fistulas present as spontaneous drainage through the lumbar region , and their etiologies include chronic renal calculi , probably the most common cause . there are some cases of spontaneous nephrocutaneous fistula due to chronic renal tb ( 8 , 9 ) . urogenital tb is difficult to diagnose due to the lack of specific symptoms and signs . irritative lower urinary tract symptoms , hematuria , and pyuria are the most common complaints . abnormal radiological findings , including pyelocaliceal dilatation , ureteral stricture , hydroureter , parenchymal destruction , autonephrectomy , and calcifications , can be seen in 61.5% of patients . a definite diagnosis can not be made with these findings , but urogenital tb should be considered in the differential diagnosis ( 3 ) . great effort has been put into comprehensive vaccination policies throughout the world in order to eradicate tb , and although mankind has not managed eradication , the incidence has been markedly reduced . however , much scientific evidence is currently accumulating with regard to the increased incidence of multi - drug resistant , extensively drug - resistant , and totally drug - resistant tb , and the diagnosis and treatment of tb is becoming a major issue ( 10 ) . physicians should consider tb in the differential diagnosis for any chronic infection , and should do their best to treat accordingly . in the present case , although he had received various antibiotics and medical treatments over a long period , no benefit was seen . this interesting case report of a delayed diagnosis shows us that in cases of a nonfunctioning kidney with a spontaneous nephrocutaneous fistula , we must keep in mind the possibility of associated renal tb , especially in immunocompromised patients or in geographic areas where tb is a common health problem .

introduction : spontaneous nephrocutaneous fistula is a rare manifestation of renal disease that can occur due to various etiologies , such as renal calculus , chronic pyelonephritis , stricture of the ureteropelvic junction , and renal tuberculosis ( tb ) . an autonephrectomy with a nephrocutaneous fistula due to renal tuberculosis can be diagnosed quite late if it is not suspected.case presentation : we report a case of a spontaneous nephrocutaneous fistula with tuberculous autonephrectomy . a 40-year - old white male with recurrent flank pain and intermittent purulent drainage from his right flank region for the previous 14 years was admitted to our outpatient clinic . fistulography and computerized tomography demonstrated a 51 60 mm area with a soft - tissue appearance that implied autonephrectomy of the right kidney , and a fistula tract with a 9 mm diameter between the skin and the retroperitoneal space . the patient was successfully treated with nephroureterectomy and excision of the fistulous tract , followed by antituberculous treatment . the pathological examination of the surgical specimen revealed chronic atrophic pyelonephritis , calcifications , and necrotizing granulomatous inflammation suggestive of tb.conclusions:urogenital tb is difficult to diagnose due to the lack of specific symptoms and signs . in the case of a nonfunctioning kidney without an obvious cause and a chronic spontaneous nephrocutaneous fistula , the possibility of associated renal tb should be kept in mind , especially in immunocompromised patients or in places where tb is a common health problem .

nasopharyngeal carcinoma ( npc ) is scarcely reported in children,13 more often of undifferentiated type , while combined chemoradiotherapy constitutes the treatment of choice for this malignancy with promising results.35 overall survival between 50% and 77% is reported.24 however , the high radiation doses needed to be effective , resulted in long - term toxicity with hard and soft tissues growth complications , particularly in young children that still present growth potential.4,5 particularly , facial growth retardation , dental abnormalities , visual / orbital problems , neuroendocrine dysfunction , cognitive toxicity , and hypothyroidism have been reported in children with head and neck cancer post - irradiation.6,7 patient age at irradiation is significantly correlated with the severity of disorders.8,9 xerostomia , oral mucositis , late visual and auditory toxicity have also been reported as frequent and potentially severe complications of radiotherapy.10,11 the idea of pediatric oncologic pathology has been recently proposed by lacey and clarke,12 who reported on two children with leukemia , treated with combined radiotherapy and chemotherapy , survived from malignancy but suffered in long - term from bilateral slipped capital femoral epiphyses ( scpe ) or bilateral avascular femoral head necrosis , respectively , as a consequence of radiochemotherapy . we would like to further report on two male children ( 8 and 14 years old ) with head and neck cancer , who were successfully treated with combined chemoradiotherapy , survived malignancy , but presented with growth deficiency of middle face and mandible hypoplasia , eight years and one year later , respectively . a 16-year - old male presented to the outpatient radiotherapy oncology department , with severe growth deficiency of middle and lower face ( pierre robin - like syndrome ) , mandible hypoplasia , and poor oral hygiene for further evaluation and treatment . he had an eight - year known history of nasopharyngeal undifferentiated squamous cell carcinoma ( npc ) , histologically diagnosed ( according to world health organization , type ii ct3cn3t0 , grade iv ) . at that time , he was successfully treated with combined chemoradiotherapy according to the following protocol : radiotherapy followed by adjuvant endoxan fluouracil radiotherapy plan was conducted by two dimensional ( 2d ) computerized treatment planning system ( telemaque technos , technologies - informatiques sa , trappes , france ) . primary site and bilateral upper neck received 60 gy in 33 fractions over 6.5 weeks and lower neck a two - phase technique was used . following conventional simulation and using a cobalt-60 gamma rays unit , radiotherapy was initially delivered by large parallel - opposed lateral fields to a dose of 36 gy given in four weeks , 180 cgy per day . treatment field extended superiorly to the inferior orbital margin , inferiorly to c6 spinous process , anteriorly to the anterior border of masseter muscle and posteriorly to t2 spinous process , encompassing all macroscopic disease , including spinal cord . to cover undetectable microscopic disease , the clinical target volume included the base of the skull , posterior half of nasal cavity , nasopharynx , base of sphenoid , para - pharyngeal space , lateral pharyngeal , posterior and upper deep cervical nodes . brainstem , optic chiasm and anterior half of the orbit were shielded . during the second phase of treatment the parallel - opposed lateral fields were reduced posteriorly to exclude the spinal cord and a further dose of 24 gy was given over 2.5 weeks , 180 cgy per day , achieving a total dose of 60 gy in 33 fractions . the size of the malignancy before and after treatment was estimated with magnetic resonance imaging ( figures 1a , b ) . a complete response both of the primary tumor and the locoregional lumph nodes was achieved one month after the end of the treatment ( figures 1c , d ) . since then he is totally asymptomatic and free of malignancy . clinical examination during the eight - year follow - up post - irradiation showed partial mandible mobility and opening , mild xerostomia , mandible skeletal relation type ii with mandible hypoplasia while the mouth opening was slightly deteriorated ( higher opening diameter 35 mm ) . multiple caries lesions were found on almost all teeth , but the lesions of the canines , premolars , and molars were more significant . patient s oral hygiene was poor with plaque accumulation , severe localized inflammatory gingivitis , and gingival hyperplasia . radiological examination and cephalometric analysis showed sagital symmetric hypoplasia of the lower facial part , microgenia , maxillary protrusion in relation to the anterior skull base , mandibular retrusion , dolichofacial growth pattern , normal lower facial height , normal mandibular length and posterior rotation of the mandible ( clockwise rotation ) . lower incisors were positioned in a normal distance to a / pog plane , but with lingual inclination . the lower lip was found in posterior position in relation to the esthetic line and the nose seemed pronounced . maxilla was narrow anteriorly , maxillary anterior teeth presented crowding and mandibular dental arch presented spaces distal to canines . mandible hypoplasia was characterized as traumatic post - irradiation hypoplasia of condyloid apophysis , while the deteriorating mouth opening attributed to periarticular tissue fibrosis . the patient had one - year history of epipharyngeal carcinoma successfully treated with combined chemoradiotherapy . he was initially administered a total radiation dose of 6500 rads followed by chemotherapy with vincristine radiotherapy plan was conducted by 2d computerized treatment planning system ( telemaque technos ) . since the completion of chemoradiotherapy , he is totally free from malignancy . one - year post - irradiation clinical examination revealed decreased mouth opening , oral xerostomia , multiple caries lesions on almost all teeth , skeletal mandible relations type i and vertical dolicholic face with soft tissue hypoplasia of parotic area . radiological examination and cephalometric analysis showed lower normal development , with normal splachnic skull with small mandible corner . decreased mouth opening and vertical dolicholic face outline were attributed to post - irradiation soft tissue fibrosis and parotid atrophy , while the small mandible corner attributed to traumatic effect of radiotherapy to the cartilage of condyloid apophysis . oral hygiene guidelines in combination with tooth tissue replacement were also given to this patient . long - term radiotherapy - related complications in children with head and neck cancer have been frequently reported in literature , especially facial growth retardation , dental abnormalities , visual / orbital problems , neuroendocrine dysfunction , cognitive toxicity , and hypothyroidism.6,7 frequency and severity of radiotherapy related effects are generally depended on total radiation dose , dose per session , type of tumor irradiated and radiation technique ( treatment planning system ) . the lower harmful radiation dose reported is probably 18002000 rads.8,9 developing bones are radio - sensitive with a consequence of the normal development deteriorating post - irradiation . moreover , the severity of developmental disturbances is related to patient age and treatment onset . the younger the age , especially prior to six years , the more severe the abnormalities,8,9 as was the case in our patients . patient a , who was younger ( 8 years old ) at the time of irradiation , presented more severe abnormalities than patient b ( 14 years old ) . particularly , in patient a , who was irradiated when aged eight , when dentification was mixed and developmental activity of condyloid apophysis was also intense , more serious lesions were found , in relation to patient b , who was irradiated when aged 14 , when skeletal development was almost completed . xerostomia , oral mucositis , late visual and auditory toxicity have also been reported as frequent and potentially severe complications of radiotherapy.10,11 nasopharyngeal carcinoma ( npc ) is extremely rare in children13 with overall survival between 50% and 77%.24 combined chemoradiotherapy constitutes the treatment of choice for this malignancy , with promising results,35 which was also the case in patient a. however , the high radiation doses administered resulted in long - term toxicity with hard and soft tissues growth complications ( middle face deficiency and mandible hypoplasia ) , particularly in our 8-year - old child who still had growth potential.4,5 sagittal type mandible hypoplasia presents wide range of clinical manifestations , from slight hypoplasia to severe pierre robin - like syndrome , as in our patient a and is characterized as traumatic post - irradiation symmetric severe hypoplasia or agenesis of condyloid apophysis . furthermore , periarticular tissue fibrosis of temporomandibular articulation as a consequence of irradiation resulted in decreased mouth opening and articular motility limitation in patient a. moreover , soft tissue fibrosis and parotid atrophy resulted in vertical dolicholic face , while the small mandible corner in patient b was attributed to traumatic effect of radiotherapy to the cartilage of condyloid apophysis . many of these patients finally survive malignancy , but still suffer from severe morbidity due to the above complications , which need combined management and specific measures , such as surgical reconstruction and hormonal therapy.6,7 lacey and clarke12 recently introduced the term pediatric oncologic pathology to mark a new era for pediatric oncologists . they reported on two children with leukemia treated with combined radiotherapy and chemotherapy , who survived malignancy , but suffered in the long - term from bilateral scpe or bilateral avascular femoral head necrosis , respectively , as a consequence of radiochemotherapy . according to our study , we consider late sequelae in children with head and neck cancer due to chemoradiotherapy as another era for pediatric oncologic pathology in order for prevention , if possible , or to manage them efficiently .

long - term radiotherapy - related complications in children with head and neck cancer have been frequently reported , especially facial growth disorders and dental abnormalities . we report on two male children ( 8 and 14 years old ) with head and neck cancer , who were successfully treated with chemoradiotherapy and presented with growth deficiency of middle face and mandible hypoplasia , eight years and one year later , respectively . these severe growth complications attributed to chemoradiotherapy , while the patients survived primary malignancy . patient age at irradiation was significantly correlated with the severity of disorders . we consider late sequelae in children with head and neck cancer due to chemoradiotherapy another era for pediatric oncologic pathology for prevention , if possible , or to manage them efficiently .

from an anatomical point of view , the temporomandibular joint ( tmj ) is a small but very complex joint in the body . it is a synovial , ginglymoarthrodial joint in which the main bone structures are the mandibular condyle , the mandibular fossa and the articular eminence on the squamosal part of the temporal bone of the skull . between the two bone structures we find the articular disc . the condyle and the fossa are covered by a cartilage which is thinner than the disc and which also has a role in the absorption of compressive forces . because the tmj disk is softer than the cartilage of the other load - bearing joints in the body , it is logical to assume that the plowing effect on the disc is likely more pronounced than in the other joints . the tmj can be transformed by both physiological and pathological situations and have skeletal deformities , malocclusions , masticatory dysfunctions , or derangements of the articular disk appear . the structural investigations of the tmj today include radiographs , computed tomography ( ct ) , cone beam computed tomography ( cbct ) , magnetic resonance imaging ( mri ) . but there can be discrepancies between the degree of the structural alteration and the actual functional alteration of the tmj - the alterations are considered pathological only when accompanied by symptoms of pain or dysfunction . for the competent and reproducible investigation of the mandibular movements , computerized axiography ( ca ) was confirmed as a valuable complementary examination [ 1417 ] . the clinical daily use can be difficult because of time consumption and high acquisition costs , but its value is high in the functional analysis of temporomandibular disorder ( tmd ) cases , in planning and following orthodontic patients and for the programming of articulators based on the provided values . informed consent was obtained from the patient before performing the study . the procedures and protocol were approved by the institutional review board and by the ethic committee of the university . the purpose of this case report is to 1 ) explain the recordings of the mandibular movements on ca ; and 2 ) present the ca recordings of a case before and after orthognatic surgery in order to value the ca for the diagnostic and prognostic evaluation of patients . the cadiax compact ( gamma , vienna , austria ) records the movements of the mandible based on the registration of the movement of a stylus on an electromagnetically sensitive plate , elements which are placed in the area of the tmj . evaluation of the maximum amplitude of a recorded movement ; the evaluation will be described as limited , average or hypermobile ( table i ) . qualitative assessment normal recordings are reproducible , clear and frictionless of the synovial joint . normal graphs have a concave to the anterior aspect ( table iii ) . symmetry when comparing the right and left side graphs . within symmetrical movements , the right and left graphs should be identical ( table iv ) . the cadiax compact ( gamma , vienna , austria ) records the movements of the mandible based on the registration of the movement of a stylus on an electromagnetically sensitive plate , elements which are placed in the area of the tmj . evaluation of the maximum amplitude of a recorded movement ; the evaluation will be described as limited , average or hypermobile ( table i ) . qualitative assessment normal recordings are reproducible , clear and frictionless of the synovial joint . normal graphs have a concave to the anterior aspect ( table iii ) . symmetry when comparing the right and left side graphs . within symmetrical movements , the right and left graphs should be identical ( table iv ) . the case of a female patient , 20 years old , with a severe class iii skeletal anomaly was analyzed . first , the patient was treated orthodontically to eliminate dental compensations ; the second step was the surgical intervention ; and the third step was the orthodontic finishing of the case after the completion of the orthognatic surgery . the surgical intervention was performed in the department of cranio - maxillo - facial surgery , cluj - napoca , romania . the evaluation of the orofacial muscles did not reveal any tension or pain , before or after the surgery , as patients undergoing orthodontic treatment present a certain muscle relaxation due to the orthognatic treatment . the presurgical clinical investigation revealed bilateral cracking sounds during protrusion and opening of the mouth , hypermobility of the mandible in the opening movement , a deviation of the mandible to the left during protrusion , sagittal and transversal asymmetry of all movements , but with no accused pain . the mandible presented a deviation with reduction of the trajectory during opening of the mouth . the postsurgical clinical evaluation , one year after the surgery , revealed improved sagittal and transversal symmetry , normal range amplitude of the opening of the mouth and no cracking sounds . the movement of the mandible during protrusion had no deviation ; during opening of the mouth , a deviation of the mandible to the left remained . no occlusal evaluation was recorded , as it has been demonstrated that occlusal status has negligible influence on the tmj function . ca was performed before the orthognatic surgery and one year after the surgery in order to evaluate the modifications that appear in the function of the tmjs between the two moments . the ca recordings for the patient were collected from the cadiax compact database in order to illustrate the modifications that appear following an intervention in this case the orthognatic surgery at the level of the tmjs from a functional point of view ( figure 2 ) . the presurgical graphs indicated amplitude of movement for the protrusion and laterotrusion within normal limits and hypermobility of the tmj in the opening of the mouth . they also showed variable amplitude between the symmetrical movements and little symmetry of the right and left joints . in the movement of the opening of the mouth , there was no overlap of the excursion / incursion graphs , with both saggittal and transverse asymmetry . the postsurgical recordings that were taken at a distance of one year ( one year after the surgery ) show the reduction of amplitude for the protrusion and mediotrusion movements and the reduction of the amplitude for the open / close movements . for protrusion and mediotrusion the postsurgical amplitude was reduced compared to previous and normal values ; the amplitude for the open / close movement decreased and was within normal limits after surgery . also , the trajectories for the open / close movements had an improved overlap after the surgery . the transverse asymmetry which was present in both protrusion and opening of the mouth before the surgery disappeared almost completely in the postsurgical recordings . the aspect of the curves was convex and convex / concave presurgically and they changed to either straight or convex after surgery . assessment of favorable or unfavorable evolution of tmj symptoms may be difficult to perform along the same evaluation criteria at different times and it is highly dependent on the examiner s experience [ 2125 ] . that is why objective examination methods are more reliable and as often as possible preferred over clinical examination . the case we presented confirms the clinical contribution of the ca to the functional evaluation of the tmj over time . in this case , the ca recordings confirmed an improvement of the tmj situation after orthognatic surgery ; bone pieces were repositioned and , as a consequence of bone remodeling and muscle reattachment , occlusion improved . this is visible in the better symmetry , amplitude within normal limits , and better overlap of excursion / incursion movements described . all postsurgical modifications indicated an improvement of the tmj status by the reduction in amplitude of the mandibular movements as compared to the presurgical situation , by a better overlap of the excursion / incursion movements of the mandible and by an increased transverse and sagittal symmetry of the movements on the right and left sides , thus confirming the benefits of orthognatic surgery on tmj functionality . from a clinical point of view , the opening of the mouth was reduced in amplitude in order to reach normal values ; the right and left tmjs worked more symmetrical after the orthognatic surgery , especially during opening of the mouth ; and the symmetry during excursion / incursion of the movements improved significantly , again especially during open / close of the mouth . obviously , the modifications that appear in the tmj dynamics widely differ among patients and thorough analysis is required for each of them . the recordings of the mandibular movements documented with the cadiax compact ( gamma , vienna austria ) can be kept and reviewed as frequently as needed , can be compared with recordings performed at different times , and can provide details for the programming of articulators , as confirmed by recent studies . the recordings can also be used to diagnose tmd , because of the pathological elements that can be identified on the graphs . the evolution under treatment of the pathological elements ( hypermobility , limitations , disk displacement ) can be monitored on subsequent recordings . it was shown that the morphology of the tmj is correlated with the occlusal morphology and tooth position in balanced patients with no treatment needs . this way , the ca recordings help with the interpretation and evaluation of tmj function in patients that either need or have had done prosthodontic reconstructions [ 2831 ] . this case confirmed the results we found in literature . given that this was a case presentation , studies that involve more patients in conclusion , based on our case one can say : the ca is a valuable investigation that allows for a reproducible and objective assessment of the functionality of the tmj ; the ca facilitates monitoring over time the evolution of the functionality of the tmj structures ; the ca allows for comparative evaluation of the function of the two tmjs .

the aim of this case report is to give comprehensive information on the clinical use of computerized axiography ( ca ) in the evaluation of temporomandibular joint ( tmj ) mobility in a patient who undergoes orthognatic surgery . a 20-year - old female patient with class iii skeletal anomaly and who underwent orthognatic surgery is presented . pre- and postsurgical ca recordings for the patient are compared in order to evaluate the functional modifications that appear . the ca is a functional investigation of the tmj and records the border movements of the mandible : protrusion , lateral movements and open / close . the starting point for every movement is the centric relation position . this allows for very high reproducibility of the ca and the data can later become available for comparison of examinations performed at different times . the ca can offer data to programme an articulator or to evaluate the functional evolution of the tmjs after various occlusal interventions ( prosthodontic , orthodontic or orthognatic ) . after comparing the pre- and postsurgical ca recordings , a significant improvement of the tmj function after the repositioning of the maxilla and mandible through orthognatic surgery was confirmed . in conclusion , our case confirms the results in literature that ca is a reproducible and reliable investigation method in the evaluation of tmj function in orthognatic surgery patients , that it facilitates the monitoring of the evolution of the functionality of the tmj ever time and that it allows for comparative evaluation of the two tmjs .

however , the incidence of btc appears to be increasing worldwide over the last few decades , particularly in latin america and east asia ( 1 ) . btc is currently the sixth leading cause of cancer - related mortality in japan , and patients with btc have a poor prognosis ( 2 ) . however , the majority of patients are diagnosed at an advanced stage , when curative resection is no longer feasible ; in addition , even in cases where surgery may be performed , there is a significant likelihood of relapse ( 3 ) . patients with unresectable or recurrent disease appear to be clinical candidates for systemic chemotherapy ( 4,5 ) . after the abc-02 study reported that gemcitabine / cisplatin ( gc ) combination therapy significantly prolonged median survival time ( mst ) from 8.1 to 11.7 months over gemcitabine monotherapy in patients with advanced btc ( 6 ) , this combination therapy has become the standard treatment for btc worldwide . recently , kanai et al determined the optimal dose of gc / s-1 ( gcs ) combination therapy for patients with advanced btc in a phase i study ( 7 ) and reported a promising mst of > 15 months in a phase ii study ( 8) . based on these results , a phase iii randomized trial is underway to demonstrate the superiority of gcs therapy compared with gc in patients with unresectable btc ( umin000014371/nct02182778 ) . we herein report the case of a patient with unresectable intrahepatic cholangiocarcinoma ( icc ) who underwent conversion surgery and ultimately achieved a pathologically complete response using gcs combination therapy . a 68-year - old woman was referred to toyonaka municipal hospital with increased levels of biliary enzymes in march , 2015 . the patient suffered from hypertension and rheumatoid arthritis , which were controlled with oral medication . a physical examination revealed no abdominal abnormalities , but the laboratory tests revealed abnormal liver function , including an elevated serum alkaline phosphatase level of 839 u / l [ upper limit of normal ( uln ) , 328 u / l ) , a -glutamyltranspeptidase level of 324 u / l ( uln , 64 u / l ) and an alanine aminotransferase level of 82 u / l ( uln , 40 u / l ) . additionally , the serum carcinoembryonic antigen ( cea ) and carbohydrate antigen ( ca ) 19 - 9 levels were 9.8 ng / ml ( uln , 5.0 ng / ml ) and 32,806 u / ml ( uln , 37 u / ml ) , respectively . computed tomography ( ct ) revealed a 3-cm mass in the 1/8 segment of the liver , resulting in dilated bile ducts in both hepatic lobes , enlarged para - aortic and regional lymph nodes , and invasion of the portal vein ( pv ) ( fig . 1a ) . magnetic resonance imaging ( mri ) revealed an intrahepatic mass as a hypointense lesion compared with normal liver tissue in t1-weighted images . t2-weighted images revealed mild hyperintensity compared with the liver parenchyma . furthermore , diffusion - weighted mri revealed high signal intensity ( fig . 1b ) . positron emission tomography with f - fluoro - d - deoxyglucose ( f - fdg pet)/ct revealed abnormal uptake of the primary tumor and para - aortic lymph nodes , with an suvmax of 5.8 and 2.5 , respectively ( fig . the patient was diagnosed with unresectable intrahepatic btc with para - aortic and hilar lymph node metastasis [ ct3n1m1 , cstage ivb according to the union for international cancer control classification system ( http://www.uicc.org/sites/main/files/private/tnm_classification_of_malignant_tumours_website_15%20may2011.pdf ) ] . endoscopic retrograde cholangiopancreatography ( ercp ) revealed a 2-cm irregular stricture of the hilar bile duct with a lobulated tumor ( fig . the brush cytology specimens revealed atypical cells in a three - dimensional cluster and an isolated pattern strongly suggestive of adenocarcinoma ( fig . , the patient was diagnosed with unresectable icc with para - aortic lymph node metastasis and , therefore , systemic chemotherapy was considered . the patient underwent endoscopic biliary drainage using plastic stent placement for the biliary stricture prior to therapy . endobiliary stents ( 7f 12- and 7-cm at a light angle ) were successfully placed through the narrowed lumen at initial ercp , resulting in successful biliary decompression . the patient was subsequently enrolled in a phase iii randomized trial ( umin000014371/nct02182778 ) and randomly assigned to receive gcs combination therapy . / m on day 1 , and oral s-1 was administered daily at a dose of 80 mg / m on days 17 every 2 weeks . the patient received 12 cycles of the regimen for 6 months . on the first day of the 8th cycle , the patient presented with grade 3 malaise after receiving chemotherapy . this adverse effect was , however , manageable and improved within 2 days by fluid replacement therapy . after the scheduled 12 cycles of the regimen , ct revealed a marked reduction of the primary tumor and metastatic lymph nodes . f - fdg - pet / ct also revealed diminished abnormal uptake of the primary lesion and para - aortic lymph nodes ( fig . 3b ) . additionally , the serum cea and ca19 - 9 levels decreased to within the normal range ( 1.5 ng / ml and 11 u / ml , respectively ) . the patient achieved a good partial response to gcs therapy and was allowed to undergo conversion surgery . therefore , the patient underwent extended right hepatic lobectomy , lymph node dissection and left hepaticojejunostomy . the resected specimen exhibited almost complete occlusion of the right hepatic duct immediately before the junction ( fig . histological examination revealed scattered pigmented macrophages in the fibrotic tissue , suggesting that necrotic cells were scavenged from this location . although atypical epithelia in the bile duct were identified , invasive carcinoma and intraepithelial carcinoma components were not found , even following thorough examination . there were no viable carcinoma cells in the dissected nodes , but some contained fibrotic foci ( fig . a patient with unresectable icc at presentation achieved a pathologically complete response after undergoing preoperative gcs combination chemotherapy . at the last follow - up , 9 months after the operation ( september , 2016 ) , the patient remained alive and recurrence - free , without adjuvant therapy . btc , which originates in the intrahepatic and extrahepatic bile ducts , is a relatively uncommon type of cancer , comprising ~3% of all gastrointestinal malignancies ( 9,10 ) . the majority of btc patients are diagnosed at an advanced stage due to the lack of abdominal symptoms , and the prognosis is generally poor ( 1,2 ) . therefore , surgery is the optimal therapeutic approach , although systemic chemotherapy is considered for patients with unresectable btc . in the abc-02 study , valle et al reported that gc combination therapy was associated with a significant survival advantage compared with gemcitabine alone , with a overall mst of 11.7 months compared with 8.1 months , respectively ( hazard ratio = 0.64 ; p<0.001 ) ( 6 ) . based on that study , gc combination therapy has been the standard palliative chemotherapy for patients with advanced btc worldwide . the bt-22 study used the same regimen as the abc-02 study and evaluated the efficacy and safety for patients with advanced btc in a japanese population ; the study revealed that its outcome was similar to that of the abc-02 study , as the mst for gc combination therapy and g alone was 11.2 and 7.7 months , respectively , and the adverse events did not significantly differ between the two groups , although the incidence of hematotoxicity was higher with gc combination therapy compared with g alone ( gc vs. g : leukopenia , 29.3 vs. 19.0% ; neutropenia , 56.1 vs. 38.1% ; thrombocytopenia , 39.0 vs. 7.2% ; and decreased hemoglobin level , 36.6 vs. 16.6% , respectively ) ( 11 ) . therefore , this indicates that the new regimen exhibited a higher efficacy and fewer adverse events . s-1 is an oral fluoropyrimidine prodrug that is widely used for various solid tumors ( 1215 ) , and it is approved in japan as a chemotherapeutic agent for btc ( 16 ) . s-1 monotherapy has shown promising outcomes associated with mild toxicity in btc patients ( 13 ) . additionally , in combination with gemcitabine , s-1 has also achieved favorable response rates ( 3034% ) and mst ( 11.612.7 months ) ( 14,15 ) . on the basis of these reports , kanai et al expected that the addition of s-1 would exert an additive or synergistic effect with gc combination therapy to improve treatment results with respect to efficacy and safety . in a phase i study , the regimen described below had the fewest grade 34 adverse events ( maculopapular rash , vasovagal reaction and anemia ) . based on the incidental rates of adverse events in the phase i study , kanai et al established a recommended dose of the gcs combination therapy , which consisted of intravenous administration of gemcitabine ( 1,000 mg / m ) and cisplatin ( 25 mg / m ) on day 1 and oral administration of s-1 ( 80 mg / m ) on days 17 , every 2 weeks ( 7 ) a phase ii study demonstrated significantly prolonged mst ( 16.2 months , 95% confidence interval 10.222.2 months ) without uncontrollable adverse events compared with that of the abc-02 study ( 11.7 months , hazard ratio = 0.64 ; p<0.001 ) . interestingly , two patients ( 4% ) were able to achieve curative secondary resection after tumor downstaging following chemotherapy ( 8) . thus , gcs combination therapy should not only be considered to be a standard first - line chemotherapy , but also a conversion surgery or neoadjuvant chemotherapy. on the basis of these findings , a randomized phase iii study has now been launched ( umin000014371/nct02182778 ) . conversion surgery is radical resection performed for previously unresectable cases that become resectable as a result of regression following chemotherapy ; it should be distinguished from neoadjuvant chemotherapy , although a strict distinction between these two strategies is occasionally clinically difficult , as the definition of unresectable cancer varies among physicians . conversion surgery or neoadjuvant chemotherapy for unresectable cancers , including gastric , colorectal and pancreatic cancer , has been frequently reported ( 1719 ) . kim et al demonstrated that clinically curative conversion therapy resulted in the highest survival rate and best prognosis in gastric cancer patients with peritoneal seeding ( cstage iv ) . the mst of patients undergoing clinically curative conversion therapy and non - curative resection was 37 and 18 months , respectively , and the 3-year survival rates were 50 and 0% , respectively ( 17 ) . for colorectal and pancreatic cancer , several recent reports also demonstrated a clinical advantage with neoadjuvant chemotherapy ( 18,19 ) . however , the feasibility and efficacy of neoadjuvant chemotherapy for btc has not been determined ( 20 ) . kato et al reported that patients with initially unresectable locally advanced btc who underwent neoadjuvant chemotherapy ( gemcitabine ) had a significantly longer survival time compared with those unable to undergo surgery ( 2-year overall survival rate of 45 and 19% , respectively ) ( 21 ) . furthermore , a case of curative resection after gcs chemotherapy for initially unresectable biliary duct cancer and a case of a patient with extrahepatic cholangiocarcinoma after undergoing preoperative gemcitabine - based chemotherapy have been reported ( 22 ) . based on these reports , conversion therapy has recently attracted attention , although there is insufficient evidence regarding the safety and efficacy of performing conversion surgery . to the best of our knowledge , the present case is the first report of a patient diagnosed with unresectable btc who ultimately achieved a pathologically complete response with gcs combination therapy . further studies are required to verify the efficacy of conversion surgery in patients with btc using a prospective study design .

a 68-year - old woman was referred to our hospital with increased levels of biliary enzymes . on imaging , the patient was diagnosed with unresectable intrahepatic biliary tract cancer ( btc ) with invasion of the portal vein and para - aortic lymph node metastasis ( ct3n1m1 , cstage ivb ) and underwent endoscopic biliary drainage for the biliary stricture prior to therapy . the patient was subsequently enrolled in a phase iii randomized trial ( umin000014371/nct02182778 ) and randomly assigned to receive gemcitabine / cisplatin / s-1 ( gcs ) combination therapy intravenously at doses of 1,000 or 25 mg / m2 on day 1 and orally twice daily at a dose of 80 mg / m2 on days 17 every 2 weeks . after 12 cycles of scheduled therapy without uncontrollable adverse effects , the patient achieved a good partial response with chemotherapy . computed tomography ( ct ) revealed a marked reduction of the primary and metastatic lesions . in addition,18f - fluorodeoxyglucose - positron emission tomography / ct revealed diminishing abnormal uptake and no macroscopic evidence of factors adversely affecting tumor resectability . therefore , the patient underwent extended right hepatic lobectomy , lymph node dissection and left hepaticojejunostomy . finally , histological examination of the resected tissues revealed no residual cancer cells , suggesting a pathologically complete response . we herein present the case of a patient with intrahepatic btc who achieved a pathologically complete response following combination chemotherapy with gcs .

they drift from standard classifications , and their treatment is controversial . of such cases are hip dislocations with associated fractures of the ipsilateral femur . this case report describes the condition of a 30-year - old man involved in a motor vehicle collision . clinical examination , x - rays , and computed tomography scan revealed a posterior hip dislocation with an ipsilateral femoral head and mid - shaft fractures . the patient was treated by closed reduction of hip dislocation using a temporarily applied external fixator followed by intramedullary nailing of the femoral shaft . achieving a closed reduction is a challenge with ipsilateral fractures but it should be favored over open reduction due to a lower risk of complications . the type of femoral head fracture , in this case , may have aided in an easier reduction . hip dislocation is an orthopedic emergency and its treatment is challenging if associated with ipsilateral fractures . the decision of a closed versus an open approach should be made after considering the management plans of other injuries . there has been a significant increase in the complexity of fractures due to the increasing variety of traumatic mechanisms such as high - speed collisions , falls from heights , construction related high - energy injuries , and more . these fractures tend to drift from the standard classification systems , and their treatment is usually controversial because of varying outcomes . one such example is hip dislocations associated with head , neck , intertrochanteric , shaft , distal femur fractures , or knee dislocation . in this report , we study the case of a 30-year - old man who sustained a posterior hip dislocation with concomitant ipsilateral femur head and shaft fractures . only one similar case was previously published in the literature , and there were some differences noted between the two cases . a 30-year - old man presented to the emergency trauma room following a motor vehicle collision in which he was the front - seat unrestrained passenger . at the time of presentation , the patient was vitally stable , conscious , alert , oriented with a glasgow coma scale 15/15 . the trauma surgery team assessed the patient initially and implemented the advanced trauma life support protocol ; he was deemed to be hemodynamically stable with no other systemic injuries . the patient was , however , complaining of moderate left hip and thigh sharp pain as well as left shoulder pain . on examination , active and passive movements of the left thigh were not possible due to pain with no neurovascular deficits detected distally . x - rays of the pelvis and left femur revealed a posterior fracture dislocation of left femoral head with an ipsilateral femoral mid - shaft fracture and a computed tomography ( ct ) scan of the pelvis showed large and small fracture fragments within the acetabulum originating from the medial aspect of the femoral head ( fig . 1 ) . a shoulder x - ray also revealed a non - displaced left scapular body fracture . an attempt of left hip closed reduction was made while the patient was still in the emergency department and it was , however , unsuccessful . pre - operative ( showed fracture dislocation of left hip and an ipsilateral femoral shaft fracture ) . after being cleared by the trauma team , the patient was admitted to the orthopedic service with a working diagnosis of left posterior hip dislocation with a pipkin type 1 ipsilateral femoral head fracture and an ipsilateral femoral shaft fracture . the patient was taken to the operating theater for closed versus open reduction and intramedullary nailing of the left femur . within 5 h of his injury , the patient underwent closed reduction of the left hip with the aid of a temporary external fixator applied on the femoral shaft proximal to the fracture ( fig . the external fixator rod was used as a handle , and the reduction was successful after the first attempt , as confirmed by the c - arm and ct reconstruction ( fig . subsequently , the external fixator was removed , and intramedullary nailing of the left femur was carried out . after completion of the procedure , the left hip was examined and found to be stable with the femoral head fragment not affecting the movement . the patient was discharged after 3 days with a clean , dry wound and full weight bearing ambulation as tolerated . unfortunately , he was lost to follow - up and attempts to contact the patient were unsuccessful . intraoperative ( showed a temporary external fixator applied on the femoral shaft proximal to the fracture and intraoperative computed tomography scan reconstruction ) . the primary challenge , in this case , was achieving closed reduction of the hip dislocation ; this was particularly difficult due to the inability to transmit the force needed for reduction through to the hip and the difficulty controlling the thigh . this necessitated the use of other indirect methods of reduction like the temporary external fixator ( fig . 3 ) . postoperative ( showed congruent reduction of left hip fracture - dislocation with i m nailing of left femur shaft fracture ) these challenges were also faced by other treating surgeons in similar cases , and each team was able to achieve the reduction by closed manipulation or manual traction maneuvers , indirect reduction with the aid of external tools such as a loop and open reduction . early reduction of the dislocation is important to prevent significant complications associated with late reduction like osteonecrosis and subsequent hip arthritis . moreover , closed or indirect reduction is favored over open reduction especially if there is no plan for internal fixation of the acetabulum or proximal femur because of the significant risks involved with open surgery which include but is not limited to : sciatic nerve palsy , heterotopic ossification , avascular necrosis , blood loss and infection . it is worth noting that in the similar case described by galois et al . ; the femoral head fracture was suprafoveal pipkin type 2 while in our case it was infra foveal pipkin type 1 . the latter type may have contributed to an easier reduction which is possible through closed methods , while in the former case the fractured fragment may have necessitated open reduction , due to a mechanical block inhibiting reductions by closed methods , and internal fixation to restore and maintain the articular congruency and the weight bearing surface of the hip . traumatic hip dislocation is a significant orthopedic emergency and its treatment is more challenging if the dislocation is associated with other concomitant ipsilateral fractures . management should start with emergent reduction , and the treating orthopedic surgeon should make the decision of a closed versus an open approach after taking into consideration the other injuries and fractures and considering their definitive management plan . the use of indirect reduction instrument , such as an external fixator , may preclude an open procedure which will prevent surgical complications .

introduction : complex fractures are increasing because of various traumatic mechanisms . they drift from standard classifications , and their treatment is controversial . of such cases are hip dislocations with associated fractures of the ipsilateral femur.case report : this case report describes the condition of a 30-year - old man involved in a motor vehicle collision . clinical examination , x - rays , and computed tomography scan revealed a posterior hip dislocation with an ipsilateral femoral head and mid - shaft fractures . the patient was treated by closed reduction of hip dislocation using a temporarily applied external fixator followed by intramedullary nailing of the femoral shaft . achieving a closed reduction is a challenge with ipsilateral fractures but it should be favored over open reduction due to a lower risk of complications . the type of femoral head fracture , in this case , may have aided in an easier reduction.conclusion:hip dislocation is an orthopedic emergency and its treatment is challenging if associated with ipsilateral fractures . the decision of a closed versus an open approach should be made after considering the management plans of other injuries .

stage iv breast cancer ( metastatic breast cancer , mbc ) is still an uncurable disease with a median 5-year overall survival rate of 25% . however , this figure does not reflect the broad range of different courses of mbc with patients surviving only a few months , and others having a chronic disease for many years . the most important treatment issues in patients with mbc are to control the disease and its symptoms and to maintain the patients quality of life as long as possible . there are many treatment options for patients in the metastatic setting . to select the appropriate therapy , the individual patient and the special situation of her illness as well as her personal wishes must be respected . in elderly patients , comorbidities and performance status influence the available and feasible treatment possibilities . endocrine therapy alone is the first therapy of choice for patients with hormone receptor - positive , her2-negative mbc . after the failure of anti - hormonal agents ( anti - estrogens , aromatase inhibitors ) and/or rapid progression of existing metastases or new metastastic sites , either single - agent or combination chemotherapy the choice of treatment depends on the aggressiveness of the disease , metastatic sites and individual factors such as age , comorbidities and performance status of the patient . in this palliative setting , chemotherapy remains the mainstay of treatment . apart from disease control , one crucial treatment goal in this non - curative setting must be maintaining the patient 's quality of life . a new treatment option is nab - paclitaxel ( nanoparticle albumin - bound paclitaxel ) . although it is currently approved for second - line treatment after the failure of anthracycline - based chemotherapy , nab - paclitaxel can also be a possible therapeutic approach in first - line treatment , especially in a weekly schedule . albumin - bound paclitaxel with a mean particle size of 130 nm has significant practical advantages compared to solvent - based taxanes . it can be administered without antiallergic premedication and shows favorable linear pharmacokinetic characteristics . with albumin as the transport protein for the cytotoxic agent , albumin - specific pathways and mechanisms are used for nab - paclitaxel to gain access to the tumor interstitium [ 4 , 5 , 6 ] . an 82-year - old woman was diagnosed with an invasive ductal adenocarcinoma of the left breast in november 2012 . the tumor was well differentiated ( g2 ) , hormone receptor positive ( or 95% , pr 30% ) and her2 negative . the patient received antihormonal treatment with the antiestrogen tamoxifen 20 mg ( once / day ) from november 21 , 2012 , until february 5 , 2013 . while bilirubin levels remained low during that period ( 1.0 mg / dl at baseline , 0.8 mg / dl on february 5 , 2013 ) , tumor marker levels of ca 153 and cea increased from 1,068 u / ml ( ca 153 ) and 13.9 ng / ml ( cea ) to 2,779 u / ml and 43.5 ng / ml , respectively . due to this biochemical disease , progression therapy was switched to the nonsteroidal aromatase - inhibitor letrozole on february 5 , 2013 , upon which tumor marker levels continued to rise and bilirubin levels doubled , indicating a resistance to the antihormonal treatment and active growing process in the liver . the first course of chemotherapy consisting of gemcitabine 1,000 mg / m and paclitaxel 200 mg / m was administered on march 18 , 2013 . no response was observed , but progressive disease with a remarkable surge in tumor marker and bilirubin levels with a peak of 6,982 u / ml in ca 153 levels , 127.6 ng / ml in cea levels and 13.1 mg / dl in bilirubin levels on april 3 , 2013 . the oral symptoms made swallowing and , as a consequence , eating and drinking extremely painful , and her quality of life was dramatically reduced . due to the progression of the disease and the painful mucositis , we stopped the treatment with paclitaxel / gemcitabine . on april 22 , 2013 , after the severe mucositis had disappeared and symptoms had receded , we started a new therapy with nab - paclitaxel 200 mg / m and gemcitabine 1,000 mg / m every 3 weeks . on april 11 , tumor marker and bilirubin levels had gone to 4,232 u / ml ( ca 153 ) , 74 . 3 ng / ml ( cea ) and 3.8 mg / dl ( bilirubin ) and continued to decline during the 5 further cycles of nab - paclitaxel / gemcitabine . treatment with nab - paclitaxel / gemcitabine was tolerated well , with no severe toxicity , and especially no neurotoxicity was observed . on june 24 , 2013 , the ca 153 level was reduced to 947 u / ml , the cea level to 12.7 ng / ml , and the bilirubin level was at 0.7 mg / dl . all biochemical parameters were below baseline . due to the patients excellent tolerance of the applied dose of 200 mg / m nab - paclitaxel in combination with gemcitabine , the nab - paclitaxel dosage was escalated to 300 mg / m on june 24 , 2013 , for the 4th cycle of chemotherapy . by july 15 , 2013 , bilirubin levels had been reduced even further to 0.5 mg / dl , ca 153 level was at 770 u / ml , and cea level was 14.3 ng / ml ( see table 1 ) . on july 15 , the patient received the last cycle of nab - paclitaxel / gemcitabine , and treatment was still tolerated well , without any neurotoxicity . on a follow - up visit on july 19 , 2013 , the patient reported her well - being and presented with a karnofsky performance status ( kps ) of 100% . restaging examinations at the end of july showed a stable disease of the known primary tumor , and the liver metastases revealed multiple small ossary metastases in the spine as well as in the os sacrum and os ilium . a restaging ct performed on july 22 , 2013 , showed multiple liver metastases with partly irregular borders ( multiple metastatic sites in the liver ) in all segments and multiple small bone metastases in the spine without discernible fracture risk . a restaging mammography performed on july 22 , 2013 , showed the tumor in the left breast ( bi - rads assessment category 5 ) without infiltrations in the chest wall and axilla . a bone scan performed on july 29 , 2013 , revealed 3 vertebrae in need of further assessment upon which an mri scan was done on august 5 , 2013 . it showed the same metastatic sites in the thoracic and lower spine without any risk of fracture or further damaging the existing fractures . therapy with nab - paclitaxel had stabilized tumor and metastases , and disease symptoms were well controlled . on august 27 , 2013 , the patient was started on single - agent chemotherapy with capecitabine ( 14/7 regimen , 1,500 mg b.i.d . ) and denosumab 120 mg s.c . every 4 weeks as well as calcium and vitamin d for the metastatic bone disease . restaging with various imaging modalities on october 22 , 2013 , showed stable disease of the tumor in the breast as well as of all metastatic sites : an upper abdominal ultrasound scan showed no enlarged lymph nodes and no relevant changes compared to the abdominal scan performed in july . her breast ultrasound confirmed the known tumor in the left breast without enlarged or pathologic lymph nodes in the left axilla . chest and abdominal ct scans showed no pulmonary metastases and confirmed stable disease of the liver metastases . ossary metastases were reported to be stable without fractures or larger osteolysis . biochemical response to treatment was good with bilirubin levels remaining at 0.7 mg / dl . tumor marker levels of ca 153 were reduced to 280 u / ml . at a follow - up visit , the patient presented with a kps of 90% and reported a subjective well - being . as of july 2014 , the patient still receives capecitabine and denosumab and continues to show stable disease . in germany , nab - paclitaxel is currently approved for the treatment of mbc after failure of first - line chemotherapy and for whom anthracycline - containing chemotherapy is not indicated . relevant to everyday clinical practice is the more favorable safety profile of nab - palitaxel compared to the solvent - based , conventional paclitaxel . maintaining the patients quality of life is crucial in the metastatic , non - curative setting . since our patient developed severe mucositis and wanted to discontinue chemotherapy , good tolerability was one of the main aspects in the choice of the subsequent chemotherapy . roy et al . reported significant antitumor activity and a favorable toxicity profile of weekly nab - paclitaxel / gemcitabine in 50 previously untreated patients with mbc . although our patient was pretreated with conventional paclitaxel with considerable mucosal toxicity , we observed an excellent tolerability of nab - paclitaxel / gemcitabine as well as a considerable efficacy in our patient . excellent biochemical response was achieved with all parameters reverting to levels below base line . remarkably , the 82-year - old patient presented with a kps of 100% after the end of all 5 cycles of nab - paclitaxel / gemcitabine . despite metastatic disease in the liver and elevated bilirubin levels , treatment with nab - paclitaxel / gemcitabine was very well tolerated and no neuropathy or recurrent mucositis was observed . our findings suggest that patients with elevated bilirubin up to 10 mg / ml can be safely treated with nab - paclitaxel / gemcitabine with the initially reduced nab - paclitaxel dosage being escalated in the course of the treatment .

we report the case of an 82-year - old female diagnosed with her2-negative , hormone receptor ( hr)-positive metastatic breast cancer . upon biochemical disease progression of the initially hr - receptor positive disease under anti - hormonal treatment with tamoxifen and letrozole , she received combination chemotherapy with paclitaxel / gemcitabine . due to her suffering from severe toxicity , therapy was switched to nab - paclitaxel / gemcitabine . from april 22 , 2013 , to july 15 , 2013 , the patient received 5 cycles of nab - paclitaxel / gemcitabine as a 30-min infusion every 3 weeks , with excellent biochemical responses to treatment . tumor marker levels as well as bilirubin were reduced to baseline levels . chemotherapy with nab - paclitaxel / gemcitabine was well tolerated . at a follow - up visit immediately after the end of chemotherapy , the patient reported well - being and presented with a karnofsky performance status ( kps ) of 100% . at the last follow - up in october 2013 , she was alive with multiple metastatic sites in the liver and bone metastases in the spine without risk of fracture and a kps of 90% . she has received palliative single agent chemotherapy with capecitabine ( 14/7 regimen , 1,500 mg b.i.d . ) since august 2013 and continued to show a good biochemical treatment response at the last follow - up in october 2013 . since august 2013 , the patient has also received denosumab ( 120 mg sc , q4w ) for her metastatic bone disease . as of july 2014 , treatment has not been changed and the patient reports her well - being .

since roy - camille first introduced the pedicle screw system for achieving stability in the spine , various type instruments have been developed for transpedicular stabilization ( ts ) . of these instruments , the bone screw - plate is an effective , reliable instrument for ts . the transpedicular system was first described by boucher , and the pedicle system was first used by harrington for spinal stabilization . the pedicle systems provide stabilization between the vertebral segments and so it contributes to fusion . it has been reported that xenograft bones can be used in spinal surgery and xenograft bones contribute to osteoinduction and osteogenesis ; they help the fusion formation between the segments more than metal instruments do during a long time period after spinal surgery . however , the ideal integrity and stiffness values of these systems were not mentioned previously by an in vitro study . in addition , to the best of our knowledge , the xenograft bone plate - screw ( xbps ) system for lumbar transpedicular stabilization has not previously been reported on by any in vitro study in dogs . therefore , this study aimed to show the contribution of the xbps system for achieving transpedicular stabilization of l2 - 4 lumbar dog cadaveric specimens following laminectomy and bilateral facetectomy . twenty dog 's cadaveric l2 - 4 lumbar specimens ( all were large breeds of approximately the same size and all the dogs were non - pathologic ) were harvested and their muscles were removed , but the discs and ligaments were left intact in the specimens . these specimens were separated into four groups of equal size : the l2 - 4 intact group as control ( group i , n = 5 ) , the l3 laminectomy and bilateral facetectomy ( lbf ) group ( group ii , n = 5 ) , the lbf plus ts with the metal plate - screw ( mps ) system group ( group iii , n = 5 ) and the lbf plus ts with the xbps system group ( group iv , n = 5 ) . the xbpss were prepared from cadaveric cattle tibia . the screws were machined to a conical form with a width of 4 mm , a length of 3 cm and a pitch of 1 mm ( yunnan machine tool works , china ) . the plates were rectangular and their sizes were machined to 5.5 - 6 cm long with a width of 1 cm and a thickness of 3 mm ( yunnan machine tool works , china ) ( fig . preparation of the specimens included only dissection of the lumbar muscles , but the discs , ligaments and other tissues were kept intact from the dissection . iii and group iv , the l2 - 4 facet surfaces were flattened after lbf to place the plates and we drilled through the pedicle and vertebral corpus . a tensile - compression testing machine ( hounsfield test equipment , uk ) was used for the biomechanical tests ( fig . the specimens were tested under five different kinds of load : flexion , extension , left and right bending and rotation . a special apparatus shown in fig . the movements performed for the tests were non - destructive , and rotation was the last test because rotation was the most stressful test for loosening and instability . the load values were recorded in 1 mm intervals up to 16 mm ; using the moment - force relation , the forces were converted to the moment with using the radian angle definition , and the displacements were converted to angles ( fig . the stiffness values of each specimen were calculated in two steps : first , the stiffness in accordance with each 1 mm displacement was calculated by the relation where ( v ) = 1 , 2 , 3 ... 16 second , the average of these 16 stiffness values was obtained as the overall stiffness of the specimen : in the range of movements mentioned above , there was an almost linear relation between the angle and moment . the slope of the least square fit line of the displacement - force curve yielded the same stiffness value along with the average of the stiffness values . the stiffness values of each specimen for the different loadings were acquired and then this acquired data was statistically evaluated in two steps : first ; for classification of the data , the software ( statistica'99 ; statsoft , usa ) was used and the classification was performed with applying the euclidian distance . the euclidian distance provided four main clusters ( fig . 4 ) . second , by taking the average of 3 specimens , each group was represented by a unique stiffness value and these values are illustrated as a bar graphic in fig . after applying the euclidian distance , the similarities of the groups were 95% for group i , 90% for group ii , 72% for group iii and 83% for group vi ( fig . the average stiffness values and standard deviations of group i , ii , iii and iv are given in fig . 5 . the rotation test had higher stiffness values than the other tests ( fig . 5 ) because it was the most restrictive test in the lumbar zone . as can be clearly seen from fig . 5 , of all groups , group iii was the stiffest group and group ii was the weakest group for all the movements . the average stiffness value of group ii was 46% lower than that of group i , which indicated an instability problem . compare to group i , group iii had maximum stiffness values for right bending ( 279% ) and minimum stiffness values for rotation ( 47% ) . the stiffness values of group iv were not higher than those of group iii , except for rotation . compare to group i , group iv had maximum stiffness values at right bending ( 114% ) and minimum stiffness values in flexion ( 25% ) . but , for the average stiffness values of all the tests , group iii was 131% stiffer than group i , and group iv was 47% stiffer than group i. considering the all biomechanical data , except that at rotation , group iv showed the best stability . transpedicular bone plate - screw systems have been used for spinal stabilization , but there is no consensus about the reliability and clinical application of these systems . in addition , there have been no answers with the detailed information on which instrument is the best choice in spinal surgery . all the systems include screws , connecter rods , plates and crossing connecters , but the optimum rigidity of these systems is still unclear . therefore , the stiffness values of the xbps ( group iv ) in the ts of the l2-l4 cadaveric dog lumbar specimens were biomechanically compared in this study . clinic stability of the spine has been described as prevention of spinal displacement and damage to the nerves root and spinal cord from surgical trauma and other etiologic causes . hence , the group i stiffness values were used as a control group and this group data was evaluated as the normal stiffness values . taking these stiffness values into consideration , we carried out biomechanical and statistical comparisons of the groups in this study . instability is abnormal movements of the vertebral segments with the forces that it can be applied during a clinical examination . many lumbar spine pathologies ( cyphosis , scoliosis , disc pathologies , bone tumors , non - dislocated fractures degenerative vertebral disease etc . ) and invasive spinal surgery procedures ( multi - segment laminectomy , corpectomy , facetectomy etc . ) can cause instability of the vertebral segments . in this presented study , lbf was performed in group ii to create instability on the lumbar segments , and the biomechanical results showed that group ii was the weakest group with the lowest stiffness values for all the movements . the average stiffness values in group ii were 46% lower than those of group i , and the latter group was considered to have an instability problem . it has been emphasized in several reports that the mps systems provide maximum rigidity when the external load increases on the spine . in this study , of all the groups , group iii was the stiffest group . using the average stiffness values of all the tests , group iii was 131% stiffer than group i and group iv was 47% stiffer than group i. in ts , the usage of the mps system has some disadvantage such as loosening , bending , breaking or pulling out of the screws and plates , and the maximum inter - segmental rigidity and abnormal loading on the non - stabilized segments . therefore , as was reported by benzel , the usability of bone as a spinal implant or instrument in the spinal surgery is possible . compare to the group i average stiffness values , the use of the xbps system in group lv played an important role in ts . as a conclusion , considering the maximum stiffness values of group iii and the disadvantages of the mps system , the xbps system with its excellent stiffness values can be a good choice for achieving ts .

we performed biomechanical comparison of a xenograft bone plate - screw ( xbps ) system for achieving cadaveric lumbar transpedicular stabilization ( ts ) in dogs . twenty dogs ' cadaveric l2 - 4 lumbar specimens were harvested and their muscles were removed , but the discs and ligaments were left intact . these specimens were separated to four groups : the l2 - 4 intact group as control ( group i , n = 5 ) , the l3 laminectomy and bilateral facetectomy group ( lbf ) ( group ii , n = 5 ) , the lbf plus ts with metal plate - screw group ( group iii , n = 5 ) and the lbf plus ts with xbps group ( group iv , n = 5 ) . five kinds of biomechanical tests were applied to the specimens : flexion , extension , left - right bending and rotation . the averages of the 16 stiffness values were calculated and then these were statistically analyzed . the statistical results show that the xbps system contributes spinal stability and this system can be a good choice for achieving ts .

erg protein expression has been recently suggested to be reflective of erg gene rearrangements in prostate cancer ( pca ) documenting remarkable concordance between the two [ 16 ] . the rearrangements between the androgen receptor - regulated gene tmprss2 ( 21q22.3 ) and members of the ets family member of transcription factor gene , most commonly erg ( 21q22.2 ) , are among the most common genetic alterations detected in prostate cancer [ 711 ] . erg gene rearrangements have been detected in roughly half ( 4060% ) of pca of surgical cohorts compared to a rate of 12%15% in incidental or watchful waiting cohorts [ 7 , 1218 ] . previous studies investigating the prognostic significance of erg gene rearrangements have revealed mixed results [ 1922 ] . however , it is becoming more evident that erg gene rearrangements signify a molecular subtype of pca . some studies investigating the significance of erg protein expression in localized pca failed to show association with adverse clinical outcome [ 23 , 24 ] . however , a recent report by our group demonstrated an association of erg expression with lethal disease in patients with unsuspected and advanced / castrate resistant disease who were treated by transurethral resection of prostate . moreover , we documented significant association between erg expression and both gleason score and tumor volume . studies from our group and others have also linked erg status to responsiveness to hormonal therapy , and longer progression time to castration resistant disease , compared to men with no erg expression [ 24 , 25 ] . in the current study , we investigated the association of erg protein expression to clinical - pathological parameters in a cohort of men with localized prostate cancer . the study cohort consisted of 198 patients who were treated by retropubic radical prostatectomy for localized prostate cancer with a mean followup of 4.8 years ( range 015.8 ) . clinical progression was defined as a postoperative serum psa elevation of > 0.2 ng / ml . prostate samples were embedded onto three tissue microarray ( tma ) blocks using a manual tissue arrayer ( beecher instruments , silver spring , md , usa ) . one to nine cores ( average 3.3 ) , 0.6 mm in diameter , were sampled including benign , high grade intraepithelial neoplasia ( hgpin ) , and prostate cancer ( pca ) . after construction , 4 m sections were cut and stained with haematoxylin and eosin on the initial slides to verify the histological diagnosis . briefly , 4 m thick sections from formalin - fixed paraffin - embedded tissue blocks were stained with ventana autostainer . prior to the staining , heat - induced antigen retrieval was carried out by vegetable steamer in sodium citrate antigen retrieval buffer ( 10 mm ph 6.0 ) for 40 minutes and then cooled down to room temperature for about 20 minutes . the slides were incubated for 60 minutes at 37c with erg rabbit monoclonal antibody ( epitomics , clone epr 3864 ) at 1 : 50 dilution . a ventana iview dab detection kit ( ventana tucson , az , usa ) the diagnoses of all tma cores were confirmed by the three study pathologists ( lht , cw , and tab ) . for each patient , the two predominant patterns were sampled and included on the tmas for analysis . erg protein expression was assessed semiquantitatively using 3-tiered system ( 0 , negative ; 1 , low ; 2 , high ) . cases with either 1 or 2 intensity were considered positive based on previous correlation with erg gene rearrangement as detected by fluorescent in situ hybridization ( data not shown ) . the erg antibody was consistently strongly expressed in endothelial cells , which acted as internal control for expression and intensity level . patient characteristics were presented as frequencies and percentages for categorical variables and as means and ranges for continuous variables . chi - square tests were used to test for associations between erg protein expression and gleason score , surgical margin , and pathological stage . the kaplan - meier approach along with the log - rank test was used for the survival analyses to test the association between erg expression and serum psa relapse . in all statistical tests , mean patients ' age of this cohort was 64 years ( range 42.780.5 years ) with average follow - up time of 4.8 years ( range 0.015.8 months ) . table 1 demonstrates patients ' demographics of the study cohort with respect to erg expression . overall , there were no significant differences between the two subgroups ( erg pos & erg neg ) of patients except for pathological stage , with 37% of erg positive tumors detected in pt3 versus 24% in pt2 . to investigate erg expression in different diagnostic categories , we characterized erg expression based on individual cores sampled . when we accounted for foamy type pca morphology , the rate of erg expression was 15/84 ( 17.9% ) , compared to 302/704 ( 42.9% ) in acinar pca ( cases with no foamy type morphology ) ( p < 0.001 ) . there was no difference in high erg intensity between foamy type and acinar pca ( data not shown ) . however , mean intensity level of erg in acinar pca was significantly higher than foamy type pca , 1.01 1.27 versus 0.37 0.83 ( p < 0.001 ) . erg intensity levels in hgpin were comparable to those in foamy type pca but slightly lower ( 0.13 0.56 ) but significantly lower than those in acinar pca ( p < 0.001 ) ( figure 1 ) . erg expression was noted in 106/280 ( 37.8% ) , 175/463 ( 37.8% ) , and 37/108 ( 34.2% ) of gleason scores 6 , 7 , and 810 , respectively . figure 2 demonstrates examples of erg expression in tissue samples and the distribution of erg in relation to gleason score . when investigating relations between erg expression and pathological parameters , there was significant association between erg expression and higher disease stage . in this cohort , erg expression was present in 50/131 ( 38.1% ) patients with pt2 versus 30/55 ( 54.5% ) patients with pt3 ( p = 0.04 ) . a similar association was also noted between erg expression and extra - capsular extension . in this cohort , 52/134 ( 38.8% ) erg positive patients demonstrated organ confined disease versus 29/53 ( 54.7% ) erg positive patients showing extra - capsular extension ( p = 0.04 ) . similar trends were noted between erg expression and seminal vesicle invasion , but this was not statistically significant ( p = 0.10 ) ( data not shown ) . no significant association was noted between overall erg positivity and positive surgical margins ( table 1 ) . similarly , no association was observed with postsurgical psa levels when assessed by univariate or multivariate analysis ( figure 3 ) . although not informative due to limited patients ' numbers , the association between erg expression and higher stage disease was more pronounced in patients with higher gs . in this cohort , none of the patients with gs > 7 and erg positive ( 0/7 ) were of stage pt2 compared to 47% ( 7/15 ) of erg negative patients who were of pt2 stage ( p = 0.02 ) ( table 2 ) . this study reports on the potential significance of erg protein expression in localized prostate cancer . erg gene rearrangements and erg expression have been documented in roughly 50% of localized prostate and locally advanced castrate resistant prostate cancer compared to 12%15% in watchful waiting or incidental cohorts [ 16 , 17 , 22 , 25 , 29 ] . published reports on the significance of erg expression to patients ' outcome are conflicting with some showing association with adverse outcome , while others document no association . some suggest that it indicates a better prognosis [ 16 , 22 , 25 , 2933 ] . however , it is proposed that erg signifies a molecular class of prostate cancer and may play a role in disease progression within those tumors . this pathway is closely linked to increased rate of pten genomic deletions as well as increased erg expression or erg gene rearrangements [ 34 , 35 ] . erg gene rearrangements and erg expression are associated with adverse outcome and lethal disease in watchful waiting or expectant cohorts [ 16 , 25 ] . moreover , patients with erg overexpression demonstrated shorter progression times to castrate resistance , needing surgical intervention ( channel turp ) . in localized prostate cancer , the majority of the reported data suggest no prognostic implication for erg rearrangements or erg overexpression in relation to psa relapse or the recurrence of local disease [ 22 , 36 , 37 ] . however , two earlier reports suggested adverse association of erg rearrangements with psa relapse after radical prostatectomy [ 20 , 31 ] . in nam 's study , yashimoto 's group noted that the adverse prognostic association was linked to pten genomic deletions . of note , a study by reid et al . documented that erg gene rearrangements in addition to pten genomic deletions had actually favorable outcomes compared to pten deletion alone . these observations suggest that the method utilized in determining erg status , the inclusion or exclusion of other genomic aberration , and the cohort chosen may be the reason for the different results obtained in various studies investigating the role of erg in prostate cancer . our results support previous observations showing no prognostic relationship between erg overexpression and clinical outcome in localized prostate cancer . however , in contrast to earlier studies , we document significant association between erg expression and some pathological parameters . in this cohort , patients whose tumors were erg positive were at higher risk of exhibiting extra - prostatic extension and increased disease stage compared to patients whose tumors did not express erg . specifically , all patients with gs > 7 and erg expression showed pt3 stage disease compared to none of pt2 . however , this data is limited by the number of patients within each gs subgroup and need further confirmation . more importantly , in addition to not documenting any clinical prognostic significance for erg expression , we did not observe any association between erg expression and other pathological parameters such as gleason score or surgical margins , which further diminishes any potential prognostic significance for erg expression , at least in localized pca . another issue worth mentioning regarding erg is that , erg gene rearrangements have been previously associated with specific histopathological features and detected more frequently in some morphologic variants of prostate cancer than others . in this study , we confirm lower rates of erg expression in tumors with foamy / xanthomatous morphology which demonstrated lower mean expression intensities compared to acinar pca . the significance of this is not yet known , but suggests that those two types of tumors may be different at the molecular level . in conclusion , this study demonstrates significant association between erg expression and extra - prostatic extension and higher pathological stage in localized prostate cancer . moreover , the lack of association with any other pathological parameters also significantly diminishes any potential clinical application of erg expression , at least in men with localized prostate cancer .

background . the prognostic significance of erg expression in prostate cancer ( pca ) has generated mixed results . we sought to investigate the prognostic significance of erg expression in a localized cohort of men with pca . material and methods . we investigated erg protein expression in a cohort of 198 men with localized pca . erg expression was correlated with patients ' clinical outcome and several pathological parameters , including gleason score ( gs ) , pathological stage , surgical margin , and extra - capsular extension . results . erg expression was detected in 86/198 ( 43.4% ) patients exclusively in neoplastic epithelium . overall , erg mean expression intensity was 1.01 1.27 versus 0.37 0.83 in acinar pca compared to foamy type pca ( p < 0.001 ) . in hgpin , erg intensity levels were comparable to those in foamy type pca ( 0.13 0.56 ) but significantly lower than those in acinar pca ( p < 0.001 ) . erg expression was significantly associated with extra - prostatic extension and higher pathological stage and showed a trend toward seminal vesicle invasion . herein , erg expression was documented in 50/131 ( 38.1% ) patients with pt2 versus 30/55 ( 54.5% ) patients with pt3 ( p = 0.04 ) . erg association with higher pathological stage was more pronounced in patients with gs > 7 . grouping patients into those with gs 7 versus > 7 , there was no significant association between erg expression and gs . similarly , no association was present in relation to either surgical margins or postsurgical serum psa levels . conclusion . we report significant association between erg protein levels and extra - prostatic extension and higher pathological stage . erg expression is not associated with adverse clinical outcome and is of limited prognostic value in localized pca .

a 12-month - old girl underwent a complete repair of tetralogy of fallot that included a ventricular septal defect closure and right ventricular outflow tract ( rvot ) reconstruction . on the preoperative echocardiogram , rvot reconstruction was performed with an infundibulectomy , infundibular patch enlargement , pulmonary valvotomy , and pulmonary angioplasty . a thin walled gore - tex ( w.l . gore and associates , flagstaff , az , usa ) vascular graft was used as the material for an infundibular patch , which was attached to the rvot with a continuous 6 - 0 poly - propylene ( surgipro ; covidien , mansfield , ma , usa ) running suture . on intraoperative transesophageal echocardiography , the pulmonary valve residual pressure gradient was 49 mmhg and systolic pressure ratio between the right and left ventricles was 0.8 mmhg . however , we could not place a trans - annular patch because the patient had an anomalous coronary artery crossing the rvot . the left anterior descending artery originated from the right coronary artery crossing the rvot ( fig . , we did not continue the procedure and treated the patient with a beta - blocker . one month later , the patient was readmitted to kyungpook national university hospital complaining of cough , shortness of breath , and facial and upper extremity oedema over the previous three days . chest radiography revealed enlargement of the left upper cardiac border with a left pleural effusion ( fig . in addition , transthoracic echocardiography showed a large aneurysmal dilatation of the rvot with narrowing of the superior vena cava and main pulmonary artery , secondary to compression by the aneurysm . computed tomography ( ct ) showed a narrow communication between the rvot and an aneurysmal sac . through these findings because of the risk of a spontaneous rupture , we elected to perform emergency surgery . a careful median resternotomy was performed . a large serous pericardial and pleural effusion was present around the rvot . under cardiopulmonary bypass , the aneurysmal sac was opened , revealing patch dehiscence at the proximal suture line between the infundibular patch and the ventriculotomy site . communication between the rvot and the pseudoaneurysm was confirmed , and the previous infundibular patch and all aneurysmal tissue were excised . however , in this procedure , the infundibular patch was attached to the rvot with multiple interrupted pledgeted mattress sutures as well as full - thickness bites in the suturing of the right ventricular wall . intraoperative transesophageal echocardiography showed residual pulmonary stenosis ( pressure gradient , 36 mmhg ) and normal right ventricular systolic function . the patient s postoperative course was uneventful , and both her facial and upper extremity oedema improved . postoperative transthoracic echocardiography , performed eight months after the reoperation , showed residual pulmonary stenosis ( pressure gradient , 36 mmhg ) without any indication of the development of an aneurysm . pseudoaneurysm of the rvot is an infrequent complication of cardiovascular surgical procedures that involve both a right ventriculotomy and rvot reconstruction with patch repair or conduit replacement [ 13 ] . the pathogenesis and aetiology of pseudoaneurysms have been described as related either to obstructive rvot or to elevated right ventricular systolic pressure , leading to mechanical strain at the proximal suture line . however , other contributing factors such as pulmonary insufficiency , suture material and technique , trauma , complete heart block , and infection have also been implicated [ 13 ] . regardless of the aetiology , a pseudoaneurysm arises from the small dehiscence of a portion of the reconstructed rvot , permitting blood leakage into the surrounding space and resulting in a pericardial haematoma [ 14 ] . in this case , the pseudoaneurysm may have been caused by residual rvot obstruction , especially because of inappropriate suture techniques , such as continuous running sutures and partial - thickness sutures in the right ventricular wall . follow - up transthoracic echocardiography , performed eight months after reoperation , showed no aneurysmal changes in the rvot . however , pseudoaneurysms progressively increase in size and may present , albeit rarely , alongside symptoms secondary to the compression of adjoining mediastinal structures , rupture , thromboembolism , and infection [ 14 ] . in the present case , superior vena cava syndrome was caused by compression of the superior vena cava , which was a very unusual presentation . transthoracic echocardiography has been reported as a reliable method for diagnosing pseudoaneurysms [ 14 ] . however , it does not provide detailed information about the anatomical relationship between the pseudoaneurysm and surrounding structures . we found ct to be very helpful in evaluating the location and size of the pseudoaneurysm and determining its anatomical relationships . ct was also useful in evaluating the safety of performing another sternotomy in light of the possible need for femoral or neck vessel cannulation before another sternotomy . preoperative magnetic resonance imaging may also provide information helpful in choosing the best surgical approach . however , magnetic resonance imaging is more time - consuming than ct , and is difficult to perform in haemodynamically unstable patients . compared to true aneurysms , pseudoaneurysms pose an increased risk of rupture because of the absence of myocardial tissue in their walls . therefore , they are potentially life threatening if not treated . once diagnosed , pseudoaneurysms require either reoperation or another intervention . in conclusion , it should always be suspected in patients with the relevant symptoms , and such patients must be followed up closely . precise and careful preoperative assessment , using echocardiography and ct , is important for ensuring the safety of surgery performed on these patients .

pseudoaneurysm of the right ventricular outflow tract ( rvot ) has been reported as a rare complication of rvot reconstruction performed using conduit replacement or patch repair . rarely , it may present alongside symptoms secondary to the compression of adjoining mediastinal structures . we report the case of a patient who developed a symptomatic rvot pseudoaneurysm one month after a total correction of tetralogy of fallot . in the present case , superior vena cava syndrome was caused by compression of the superior vena cava , which was a very unusual presentation .

the methods of recruiting young men into the thai military have been described previously ( 3,4 ) . approximately 50,00060,000 men , mostly 21 years of age , are selected each year by lottery in their home province ( the province in which they are listed on the house registration ) . the system produces a representative national sampling of thai men . because of their young age , hiv prevalence in these annual recruit classes may serve as a proxy for hiv incidence . induction into the military occurs in may ( m ) and november ( n ) of each year . at the time when blood is collected , recruits provide information about the location of their main residence ( including province and district ) during the previous 2 years ( 3 ) . although the actual locations where infections occurred are unknown , residential data enables analysis of the association between hiv prevalence and this key geographic marker . to refine the hiv prevalence analyses , geographic localization uses districts as the first administrative subunit of provinces . when data were analyzed by using annual classes grouped at the district level , calculations of the percentage testing positive for hiv were statistically unreliable because the number of men tested in some rural districts was so small . therefore , we merged data in two ways to decrease variability attributable to the small sample size of the prevalence figures : classes were combined across time , and districts were combined across space . sixteen classes of men recruited from 1991 to 2000 were combined temporally into four larger classes , each representing discrete 2-year periods : 1 ) n91 , m92 , n92 , m93 ; 2 ) n94 , m95 , n95 , m96 ; 3 ) n96 , m97 , n97 , m98 ; and 4 ) n98 , m99 , n99 , m00 . data on classes recruited from the m91 , n93 , m94 , and n00 lotteries were not available for analysis ( m91 , before full implementation ; n93 and m94 , protocol under revision ; n00 , completed after dataset closed ) . however , even after combining classes into these 2-year periods , a number of districts still had numbers too low for statistical reliability . we also merged some districts with neighboring districts so that each had a minimum denominator of 20 in the hiv prevalence calculation . numbers of > 20 persons provide minimal , but acceptable , reliability in the percentage - positive calculations . districts with < 20 were combined with other districts according to the following protocol , following a sequence of priorities : we combined districts if they were in the same province , had historic connections ( formerly part of single larger district ) , had similarly small numbers tested , had similar demographics , and had similar topography or other geographic features . for the gis analysis , data tables provided in excel files ( microsoft corp . , redmond , wa ) by the armed forces research institute of medical sciences were joined to district - level gis maps obtained from the thai environmental institute and national statistical office . we used arcview 3.2a software ( esri , redlands , ca ) to create dot density and choropleth maps . ( a choropleth map uses shades or colors to demonstrate the geographic distribution of a range of values . ) each of the 10,043 dots represents a recruit who tested positive for hiv infection ( positive for hiv-1 by enzyme immunoassay and western blot ) among the 442,923 recruits tested . arcview software uses an algorithm that allows the random placement of dots within a geographic area ( in this case a district ) . by creating these dots at the district level but presenting them at the province level , we show the vivid geographic pattern of infection while illustrating the human impact of the epidemic . nevertheless , these absolute numbers provide important information regarding the potential hiv - related impact on the healthcare system and various other social structures . dot density map of young men who tested positive for hiv at time of entry into the royal thai army , thailand , november 1991may 2000 . the evolution of the hiv epidemic over the course of the decade is seen in the four maps shown in figure 2 . these maps use gradients of color shading to distinguish the percentage of men who tested positive for hiv during each 2-year period . the initial high prevalence of hiv in men from the upper north region is illustrated , as is the decline in prevalence over time ( which likely occurred as a result of public health interventions ) . the relative persistence of hiv prevalence in some districts in the far south of the country is also shown , suggesting that locale - specific features of the epidemic need to be well understood in that area , potentially leading to changes in public health interventions . choropleth maps of hiv prevalence in four classes of young men at time of entry into the royal thai army , thailand , 19912000 . prevalence is stratified by color and localized to district or group of districts so that calculations are based on > 20 men . previous analyses conducted at the province level identified regional variation quite clearly , but at a less detailed level ( 3,4 ) . the maps from our study indicate considerable variation even to the district level of analysis , which suggests important local factors may be at work in determining rates of transmission . the hiv epidemic in thailand seems to have largely missed some districts and devastated others , even within the same province . chiang mai and chiang rai provinces are examples of this phenomenon . these maps also show that , although the growth of the epidemic has slowed in most parts of the country , the epidemic has not decreased in some districts in south thailand . both types of imagery are required to describe and understand the epidemic and to suggest locales in which public health initiatives are needed . in areas where the intensity of the epidemic is highest , health and social services may require additional resources to serve persons with the disease . in areas where the prevalence rates are highest or are increasing , socially and culturally appropriate interventions these gis maps are the most accurate maps available to date and are built upon the unique hiv prevalence datasets collected over a decade by the royal thai army . more sophisticated methods of multivariate gis visualization could enhance this analysis even more but would require the royal thai army to assess recruits at induction on other variables , especially risk factors , or to use recruits home addresses rather than districts or provinces of residence . nonetheless , changes in time and place of chronic viral infection can be added to the recognized areas of gis application in epidemiology , transmission of vector - borne and water - borne diseases , and environmental health ( 7 ) . the maps also illustrate the point that political borders may have no relationship to epidemiologic boundaries . differences in hiv prevalence often occur , not only between regions and provinces but also within provinces and across provincial borders . when an epidemic can be visualized at this level of detail and accuracy , researchers can formulate and address questions regarding the bases of these differences . at the same time , policy makers can better direct intervention strategies and more finely assess the outcomes of these interventions . coordination of data collection and joint gis analysis by neighboring countries would enhance regional understanding of the emergence and spread of hiv epidemics and monitoring of control programs .

characterization of the hiv epidemic in thailand has benefited from the systematic testing of young men upon entry into the military . these data , which have shown that public health measures can reverse an hiv epidemic , have been reanalyzed with current geographic information systems methods . the resulting maps , thus far , are the best means of visualizing the geography of the dynamic hiv epidemic in thailand .

a 75 year - old male patient , who underwent endovascular repair of a 5.8 cm inflammatory abdominal aortic aneurysm two and a half years previously ( fig . 1 ) , was transferred from another centre complaining of acute abdominal pain and haematemesis of one day duration . he had several co - morbidities including chronic obstructive airways disease , hypertension and a cerebrovascular accident . upon arrival his blood pressure was 90/40 , heart rate 115 bpm and temperature 36 c . on examination , his abdomen was rigid with inaudible bowel sounds , and there was no melena by digital rectal examination . an oesophago - gastro - duodenoscopy ( ogd ) performed before transfer showed blood in the stomach down to the second part of the duodenum , the source of which could not be identified . a computerized tomography angiogram of the aorta showed multiple bubbles of gas within the aneurysm sac surrounding the stent graft ( fig . 2 ) with no discernible wall separating the aneurysm sac from the lumen of the distal third part of the duodenum , along with a psoas abscess measuring 6 4 cm . as soon as the patient arrived , he was resuscitated , received 3 units of packed rbc 's and was sent to the operating theatre for ogd . initially , the ogd found blood clots in the stomach which obscured the field , so a laparotomy was conducted in an attempt to localize the source . an enterotomy was done with retrograde passage of the enteroscope that detected a defect in the 3rd part of the duodenum as the source of the bleeding . 3 ) , after which dissection of the abdominal aorta and identification of the fistula ( fig . the infected aortic sac was debrided and samples taken for pathological and microbiological analysis , which later proved out to be streptococcus anginosus . finally , trimming of the edges of the duodenal defect with surgical repair via a doudenorraphy was done . owing to the presence of extensive infection , and the hemodynamic instability of the patient , a decision was made to ensure haemostasis , after which part of the greater omentum was mobilized through a window in the transverse mesocolon which was stapled to close the aneurysm sac preventing further adhesions with the duodenal wall . the abdomen was closed and we started preparing the patient for an axillo - bifemoral bypass ; however , owing to the critical condition of the patient , haemodynamic instability as well as upon anesthetics team requests , we decided to defer the axillo - bifemoral bypass to a second session after adequate resuscitation and stabilization . unfortunately , as soon as the abdomen was closed , the patient went into ventricular fibrillation and all trials of resuscitation failed . the incidence of aortoenteric and aortocaval fistulae is higher in inflammatory abdominal aortic aneurysm than in atherosclerotic abdominal aortic aneurysm , despite the higher incidence of rupture in atherosclerotic abdominal aortic aneurysm . moreover , the endovascular approach through evar for inflammatory abdominal aortic aneurysms is becoming the first - line therapy as it leads to improvement of periaortic inflammation . in addition ; the endovascular stent graft abolishes the contact between the suture line and the duodenum which was thought to play a major role in the development of aortoenteric fistulas following open repair of aaa . aortoenteric fistula after endovascular repair of abdominal aortic aneurysm occurs in approximately 0.36% of cases . such a complication has seldom been reported in literature following repair of an inflammatory abdominal aortic aneurysm , and this was attributed to the presence of thick aneurysm wall of inflamed tissues intervening between the aneurysm and surrounding structures . aortoenteric fistula represents one means of endograft infection , with other causes including skin contamination from interventional procedures , hematogenous graft seeding , and bacteremia . parry et al . reported the first case of inflammatory aaa treated by evar who developed aortoduodenal fistula 7 months later , presenting with a picture of sepsis . an argument could be made however to the accuracy of the decision to proceed with an evar in presence of increased inflammatory markers and suspicion of a pre - existing aortoenteric fistula as disclosed by the authors , and to this issue 's contribution to the development of the fistula later on . the definite aetiology of the development of aortoduodenal fistula in endovascularly managed inflammatory aaa is still not entirely understood . the most incriminated cause is infection , which may be spreading to the endograft either directly from a nearby source of infection , or haematologically from a distant source . hausegger et al as well as janne dothee et al both reported cases with other possible causes such as stent migration and kinking . another hypothesis attributes fistula formation to a reduction of the peri - aortic inflammatory mass after evar which brings the stent graft in proximity with the duodenum . there may be some merit in this postulation , especially since as many as 79% of cases with inflammatory aaa are adherent to the duodenum . moreover ratchford et al . discussed the involvement of endoleaks , especially type i endoleaks in the development of aortoduodenal fistula leading to failure of device attachment and aneurysm expansion with resultant bowel fistulation . likewise , type iv endoleaks were incriminated as one of the possible contributors to the development of the aortoduodenal fistula ; especially with the initial types of endografts , as reported by norgren et al . another question that is raised is the use of steroids in the peri - operative management of inflammatory aaa with raised inflammatory markers . this may be a difficult decision due to uncertainties regarding the origin of inflammatory reaction ( sepsis or non - specific peri - aortic inflammatory reaction ) and the effect of steroids on the outcome . parry et al . argued that in the presence of a nonspecific periaortic mass , the absolute aetiology of which is unclear , the use of prednisolone is misplaced . in our case , the source of endograft infection was most probably direct extension from the psoas abscess ; which is supported by the fact that microbiological examination of the infected aneurysm wall revealed s. anginosus , a subgroup of viridians streptococci . to our knowledge necrotizing fasciitis with s. anginosus endograft contamination these organisms are recognized as normal flora of the human oral cavity and gastrointestinal tract with the ability to cause abscesses and systemic infections . the unique characteristic of the s. anginosus group that sets these streptococci apart from other pathogenic streptococci , such as streptococcus pyogenes and streptococcus agalactiae , is their ability to cause abscesses . traditionally , management of aorto - enteric fistulas has consisted of extra - anatomic bypass combined with aortic ligation or in situ aortic reconstruction using femoral popliteal vein graft , or cryopreserved graft , in conjunction with removal of the infected graft and duodenal reconstruction or repair . most publications are single case reports , but a meta - analysis yielded a 35% mortality . some authors prefer a single session repair , while others recommend a staged procedure with an initial extra anatomical axillo - bifemoral bypass followed by ligation of the aorta and iliacs . aortoduodenal fistula is a rare but dangerous complication of evar , secondary to infection or endoleak . the inflammatory nature of the aneurysm does not protect the patient from such a complication , despite the documented decrease in inflammatory process surrounding the aneurysm following aneurysm exclusion via the endograft . the major cause of such a complication is either infection or endoleaks . there is no time limit for the fistula to occur , and adequate protection against endograft infection must always take place . management of aortoduodenal fistulas is usually through primary or staged ligation of the abdominal aorta and iliacs in addition to axillobifemoral extra - anatomical bypass or aortic tube grafting according to the etiology and extent of aneurysm wall infection . although early diagnosis and intervention increases chances of survival , this condition is usually fatal and carries a very grave prognosis ; as in the unfortunate case of our patient . written informed consent was obtained from the patient 's next of kin for publication of this case report and accompanying images . a copy of the written consent is available for review by the editor - in - chief of this journal on request . mr mahmoud alawy : data collection , data analysis and writing . dr mohammed elkassaby : data collection , data analysis and writing . mr sherif sultan : study design , revision of manuscript and final approval of manuscript .

introductionaortoenteric fistula is a rare but very serious complication of both surgical and endovascular abdominal aortic reconstruction . since the advent of endovascular abdominal aortic aneurysm repair ( evar ) , 20 cases of aortoduodenal fistula associated with aortic stent grafts have been reported.1 however , only a handful has been reported following inflammatory abdominal aortic aneurysm repair . it most commonly presents with bleeding , usually from the upper gastro - intestinal tract . with recent advances in the screening , diagnosis and management of abdominal aortic aneurysms either surgically or through an endovascular approach , the diagnosis of an aortoduodenal fistula in patients with gastro - intestinal bleeding must be suspected and excluded.presentation of casewe describe a case of secondary aortoduodenal fistula that occurred two and a half years following endovascular stent graft repair of an inflammatory abdominal aortic aneurysm . we also outline the emergency correction plan and the attempts at repair.discussionthis case defies the general concept that patients with inflammatory abdominal aortic aneurysms are relatively immune to rupture . although the presence of a peri - aneurysm thick inflammatory membrane decreases the possibility of rupture , these patients are more susceptible to other related complications such as aorto - enteric and aorto - caval fistulas.2 this case also demonstrates the peculiar presence of streptococcus anginosus as the pathological organism leading to graft infection and subsequent fistula , as opposed to enterococci which are often found in endograft infection.conclusionaorto-enteric fistulas are associated with a grave prognosis . early diagnosis is crucial and extra vigilance should be taken in cases of inflammatory aaa .

this phenomenon may be caused by a number of factors and may or may not be a pathological condition.1,2 this condition is also known as fetid halitus , mouth odor , bad breath and bad mouth odor.3,4 the odor may be a significant social and psychological disadvantage for affected individuals.5 halitosis is a common complaint of both genders . it occurs worldwide and has a multifactorial etiology , but its main cause is the decomposition of organic matter caused by proteolytic anaerobic bacteria in the oral cavity.6,7 generically , halitosis is classified as either primary or secondary . primary halitosis refers to respiration exhaled by the lungs , whereas secondary halitosis originates either in the mouth or upper airways . oral secondary halitosis results from the decomposition of organic matter that originates from flakes of epithelial cells retained on the posterior portion of the dorsum of the tongue . this decomposition is facilitated by mucin precipitation , a reduction in salivary flow and/or water imbalance , microbial attack and alkalization of the oral environment , all of which favor the growth of proteolytic bacteria and consequently result in the production of volatile sulfur compounds.8 - 10 the intensity of bad breath is significantly associated with the level of volatile sulfur compounds in the oral cavity5 . while halitosis may have physiological and/or pathological causes , the main cause is related to conditions in the oral cavity.11 from a biological standpoint , saliva performs essential roles . these roles include enzymatic digestion , antimicrobial action , regulation of ph , protection of oral tissues , lubrication , assistance in swallowing , potentiation of taste , elimination of the food bolus and facilitation of the removal of carbon.12 the normal salivary ph is generally 6.5 . this slightly acidic ph suppresses the growth and proliferation of gram - negative and anaerobic bacteria , hindering the activation of the enzymes necessary for the putrefaction of amino acids , the end products of which smell bad because the compounds contain reduced sulfur ( sh2).13 according to the literature , 50 to 60% of the population suffers from chronic halitosis , which can have consequences for both professional and personal life ; 85% of cases of halitosis are of stomatognathic origin.14,15 among the 50 to 65% of the population with halitosis , 8% of cases are associated with respiratory problems , and 90% are associated with oral problems.15 saliva plays a central role in the development of bad breath , as it provides the protein substrate that is readily used by bacteria . a reduction in salivary flow has a negative effect on the self - cleaning of the mouth and can generate odoriferous volatile compounds.7 - 15 there are a number of clinical conditions that can cause changes to salivary patterns . one such condition is a change from nasal breathing to mouth breathing , which causes adaptive changes in the dental arches and surrounding tissues , such as anatomic alterations of the palate and surface drying of the mucosa . surface drying of the mucosa in mouth - breathing children may be related to halitosis , which is one of the complaints of mouth - breathing individuals , along with restless sleep , facial rictus when swallowing , reduced hearing , audible breathing , snoring , hyponasality , drooping shoulders , enlarged nostrils , sleepiness , a tired appearance , hypotonic lower lips , hypertonic upper lips and protrusion of the anterior teeth.16 the consequence of mouth breathing is an adaptation of the entire facial musculature , which causes changes in the dental arches and positioning of the teeth , leading to structural alterations in the face , including the lips , tongue , palate and mandible , as these structures adapt to the new breathing pattern.17 the aim of the present study was to determine whether there is a correlation between halitosis and mouth breathing in children . this study was approved by the ethics committee of universidade metropolitana de santos ( process : cep - unimes 029/2009 ) . all children registered at the clinic that hosted a specialization course in pediatric dentistry in the abcd / sp region in so paulo in 2008 were included in the study . children were divided into two groups based on breathing pattern ( nasal or mouth ) for the evaluation of halitosis . breathing pattern was determined by clinical evaluation and specific tests ( the mirror test and the water - in - mouth test ) and was confirmed by the evaluation of an otolaryngologist . clinical evaluation determined the presence or absence of the following signs : long face , drooping eyes , thin upper lip , dry lips , hypotonic lips , inverted lower lip , narrow nostrils , high arched palate , inadequate lip seal and anterior open bite . the mirror test involved placing a two - sided mirror under the nostrils and observing the formation of vapor on the upper or lower part of the mirror ( denoting either nasal or mouth breathing , respectively ) or on both parts.18 the water - in - mouth test involved the child holding water in his / her mouth with the lips closed and without swallowing for three minutes . the lip commissure was observed for signs of effort ; children who were unable to keep their lips closed over the three - minute period were considered mouth breathers.18 oral halimetry was performed for the quantification of halitus and the differentiation of sources of odor using a portable breath alert device ( tanita corporation , japan ) ( fig . the portable sulfite monitor was used following the manufacturer 's instructions : the device was reset by shaking it 4 to 5 times to eliminate any odor left over from previous use . the button was held until a second beep sounded , at which point the volunteer blew into the air input . after a third beep , the breath was assigned a number between 1 and 4 based on a graphic depiction of the different levels ( fig . 2 ) : -1 no odor ( normal ) -2 mild odor ( normal ) -3 moderate odor ( bad breath perceptible ) when no number appeared , it was considered a reading error , and the procedure was repeated . a descriptive analysis was performed for halitosis in each group , expressed as percentage , mean and standard deviation ( sd ) . the chi - square test was used for comparisons between nasal- and mouth - breathing groups , with the level of significance set at 5% . 55 children between three and 14 years of age participated in the study ; the mean age was 7.33 ( sd = 2.82 ) . exams revealed that 40% ( n = 22 ) had a mouth - breathing pattern and 60% ( n = 33 ) breathed predominantly through the nose . there was a statistically significant association between mouth breathing and male gender ( table 1 ) . a total of 23.6% of the children ( n = 13 ) had a halitosis score of 1 ( no odor ) , 12.7% ( n = 7 ) had a score of 2 ( mild odor ) , 12.7% ( n = 7 ) had a score of 3 ( moderate odor ) and 50.9% ( n = 28 ) had a score of 4 ( strong odor ) . with regard to gender , 75.9% ( n = 22 ) of the boys and 50% of the girls ( n = 13 ) had scores of either 3 or 4 . there was no statistically significant difference between genders in relation to halitosis ( p = 0.056 ) . however , a statistically significant association was found between halitosis and mouth breathing ( tables 3 and 4 ) . the assessment of halitosis in children is essential because it has the potential to cause social restriction and reduced quality of life and may indicate the presence of more serious medical conditions . the literature describes methods for assessing bad breath , such as an enzyme analysis of the saliva and direct measurement of volatile sulfur compounds . these methods have considerable financial costs.11 the subjective halitosis detection test , also known as the organoleptic test , has limited use because it depends on the olfactory capacity of the examiner . climatic conditions and emotional states that affect the sensitivity of the examiner may mask the presence of halitosis.11 in this study , a portable breath alert device ( tanita corporation , japan ) was used to measure halitosis in children . this device is easy to use and facilitates the determination of halitosis , especially in children . the literature describes the prevalence of mouth breathing as ranging from 5 to 75% of children tested.19,20 in this study , 40% of children assessed exhibited a mouth - breathing pattern . there was a greater number of male than female mouth breathers , which has been noted in a previous study.20 however , most studies report a slight predominance of female mouth breathers.20 among the children studied , 63% exhibited a strong odor characteristic of halitosis . this figure is higher than that described in a previous study involving children , which found that only 30% of the participants had halitosis.2 foul odor occurs when anaerobic bacteria in the oral cavity break down the amino acids cystine , cysteine and methionine , converting them into volatile sulfur compounds.21 saliva contains important antibacterial characteristics , such as secreted immunoglobulin a ( iga ) and other specific types of glycoproteins that adhere to and eliminate bacteria ; additionally , salivary peroxidase , lysozyme and lactoferrin affect bacterial metabolism . any condition that alters these defense systems may make the host much more vulnerable to oral disease.22 the number of boys with halitosis was greater than the number of girls , but this difference was not statistically significant . a study on the association of halitosis with age and gender in an adult brazilian population found a greater number of cases of halitosis among men.23 there was a significant association between halitosis and mouth breathing in this study . . found that more than 70% of children analyzed had morning halitosis caused by dry mouth from breathing through the mouth during sleep.5 it is likely that the oral cavity becomes dry because the mouth remains open the majority of the time , thereby causing halitosis . according to weiler et al . , there is no difference in salivary flow or the buffering capacity of saliva in nasal- and mouth - breathing patterns.24 rather , the evaporation of the water in saliva among mouth breathers may explain the association between mouth breathing and halitosis found in this study . we observed that a greater number of nasal breathers in proportion to mouth breathers had grade 1 and 2 halitosis , but the difference was not statistically significant . the condition is embarrassing for patients and makes them feel insecure in social and family settings , which reduces their quality of life . the condition is also embarrassing for those who interact with the affected individual.11 these facts underscore the importance of studies of the incidence of halitosis among children and the factors linked to the etiology of this oral problem . the occurrence of halitosis among evaluated children was high , and there was a statistically significant association between halitosis and mouth breathing . there is a need for further studies on bad breath in children and the factors related to its etiology .

objective : to determine whether there is a correlation between halitosis and mouth breathing in children.study design : fifty - five children between 3 and 14 years of age were divided into two groups ( nasal and mouth breathing ) for the assessment of halitosis . a descriptive analysis was conducted on the degree of halitosis in each group . the chi - square test was used for comparison between groups , with a 5% level of significance.results:there was a significantly greater number of boys with the mouth - breathing pattern than girls . a total of 23.6% of the participants had no mouth odor , 12.7% had mild odor , 12.7% had moderate odor and 50.9% had strong odor . there was a statistically significant association between halitosis and mouth breathing.conclusions:the occurrence of halitosis was high among the children evaluated , and there was a statistically significant association between halitosis and mouth breathing .

pseudoexfoliation syndrome ( pes ) is characterized by the production and accumulation of fibrillar extracellular material within the ocular tissue . the presence of pes is of paramount clinical importance in patients undergoing cataract surgery , because it is associated with a high rate of complications such as zonular dialysis , rupture of the posterior lens capsule , vitreous loss and dislocation of the intraocular lens ( iol ) . pes has also been identified as a main factor predisposing to secondary open - angle glaucoma . spontaneous dislocation of a posterior chamber iol ( pc / iol ) represents an unusual , severe complication , which mostly occurs in the late postoperative period and requires exchange surgery of the pc / iol or pc / iol repositioning with scleral fixation [ 2 , 3 , 4 ] . in all cases reported in the literature , an in - the - bag pc / iol was subluxed posterior into the vitreous cavity . here , we report on a patient with pes who developed partial acute angle - closure glaucoma ( acg ) with a marked myopic shift due to anterior dislocation of the pc / iol almost 16 months after an uneventful phacoemulsification . to the best of our knowledge , this is the first case of late - onset anterior pc / iol dislocation with partial acg and a marked myopic shift , which resulted in a permanent alteration of the postoperative target refraction . a 70-year - old male underwent an uneventful clear - cornea phacoemulsification with pc / iol implantation in the right eye ( od ) in january 2006 . preoperative routine examination disclosed a bilateral corticonuclear cataract as well as features of pes od ( fig . there was no other medical history , and the patient did not receive any medication . , we implanted a capsular tension ring ( ctr ) in order to stabilize the posterior capsule and prevent zonular - capsular complications . a pmma ctr ( type 14 , 10-mm closed diameter ; morcher gmbh , stuttgart , germany ) was implanted , which , according to our personal experience , represents a simple and reliable solution for cases with moderate risk . finally , a foldable pc / iol ( hydrophilic acryl ) was inserted in the bag , without any complication occurring during the surgical procedure . after one week , the patient 's best corrected visual acuity ( bcva ) was 1.0 ( refraction 0.25/0.5/110 ) . slit - lamp examination demonstrated a marked shallowing of the anterior chamber , without any other visible pathological findings ( fig . intraocular pressure ( iop ) was 29 mm hg od and 11 mm hg os . evaluation of refraction unravelled a significant myopic shift od ; bcva was 1.0 with 3.75/0.5/110. the refractive status os was 0.25/0.75/115 and bcva was 1.0 . scheimpflug examination documented a prominent axial anterior dislocation of the pc / iol od , without fluid accumulation between the posterior capsule and the pc / iol ( fig . the pc / iol was sitting in the capsular bag os , and the anterior chamber depth was 5.21 mm ( fig . iop elevation resisted to topical therapy with -2 receptors agonists ( brimonidine eye drops ) and , therefore , one week later nd : yag iridotomy was performed . iop was successfully regulated od after nd : yag iridotomy ( direct postoperative iop : 14 mm hg ) . nevertheless , the shallowing of the anterior chamber did not significantly improve , and the anterior dislocation of the pc / iol remained unaltered ( refraction 2.75/0.75/110 , bcva 1.0 ) . although the myopic shift od was not eliminated , the patient was satisfied with the monovision , which was achieved unintentionally and , therefore , we did not proceed to an exchange surgery of the pc / iol . pes is associated with a high incidence of pc / iol dislocation in cataract surgery , whether it is an in - the - bag pc / iol or an out - of - the - bag pc / iol . this unusual complication may occur with any type of pc / iol on average 8.5 years after its implantation . it is important to note that all cases reported up to date in the literature manifested a posterior pc / iol dislocation in the vitreous cavity . our patient presented with a myopic shift and acg due to delayed anterior pc / iol dislocation od . slit - lamp examination did not reveal an anterior capsular opacification of elements of phimosis which could explain the anterior dislocation of the pc / iol - ctr complex . during a thorough preoperative explanatory discussion , the patient was informed about the complication risk due to the underlying pes , and he strongly insisted that we should implement any necessary precautionary measures during the operation to minimize this risk . therefore , we decided to implant a ctr during the operation in order to stabilize the posterior capsule and prevent zonular - capsular complications , although we did not observe phacodonesis or difficulties in pupil dilation preoperatively . von der lippe et al . first postulated that zonular weakness in some patients with pes may lead to anterior subluxation of the lens with consecutive ciliary block acg . use of a ctr during the cataract surgery did not prevent this complication , since ctr implantation in pes - associated zonular weakening does not guarantee long - term zonular stability . in our patient , nd : yag iridotomy resulted in a satisfactory iop regulation , but the emmetropic refractive status was not restored . our patient was satisfied with the monovision ( od refraction 2.75/0.50/110 , od bcva 1.0 ; os refraction 0.25/0.75/115 , os bcva 1.0 ) and , therefore , we did not proceed to pc / iol exchange or pc / iol repositioning . to the best of our knowledge , this is the first report of late - onset anterior pc / iol dislocation in pes , generating a permanent myopic shift . ophthalmologists should be aware of this potential complication , which may occur in patients with pes within a considerable period of time after cataract surgery , and these patients should be warned accordingly .

here , we report on a patient with pseudoexfoliation syndrome who developed acute angle - closure glaucoma with a marked myopic shift due to anterior dislocation of the posterior chamber intraocular lens almost 16 months after an uneventful phacoemulsification . examination with a scheimpflug camera was extremely useful in confirming the diagnosis . this is the fist case of late - onset angle - closure glaucoma with a significant myopic shift due to anterior dislocation of the posterior chamber intraocular lens , which resulted in a permanent alteration of the postoperative target refraction .

type 2 diabetes accounts for approximately 90 to 95% of all diagnosed cases of diabetes . multi - system effects of diabetes mellitus such as retinopathy , nephropathy , neuropathy and cardiovascular diseases are important public health concerns . diabetic retinopathy is one of the leading causes of blindness in the world . using new surgical and medical techniques , decrease in visual acuity in diabetic retinopathy is either associated with maculopathy or proliferative complications of it . hypomagnesemia has been reported to occur at an increased frequency among patients with type 2 diabetes compared with their counterparts without diabetes . despite numerous reports linking hypomagnesemia to chronic diabetic complications ; attention to this issue although , it is generally believed that stringent metabolic control delays the development of late complications in diabetes mellitus , it has not been demonstrated conclusively that such control holds back the development of diabetic retinopathy . many studies have been undergone to find out the precipitated factors of retinopathy such as duration and type of diabetes , hyperglycemia , hypomagnesemia and increased urinary total protein levels . hence this study was carried out to study the correlation between serum magnesium levels , glycosylated hemoglobin and urinary total protein levels in diabetic patients with retinopathy . the study was conducted after obtaining usual permission from ethical committee and consent from subjects and controls were taken before commencing the study . the study population comprised of 30 type 2 diabetic patients without retinopathy as group 2 , 30 type 2 diabetic patients with retinopathy as group 3 in the age group 45 - 75 years as cases and 60 age and sex matched healthy individuals as controls ( group 1 ) . all the diabetic patients enrolled in the study were screened for the presence of retinopathy by direct and indirect ophthalmoscopy and fundus photography who attended the outpatient and inpatient department of medical college . non - diabetics , diabetics with other complications such as chronic diarrhoea , alcoholism , use of diuretics , cardiac disease and thrombotic stroke were excluded from the study . determination of serum magnesium ( photometric xylidyl blue method ) , hba1c ( immuno - inhibition method ) , fasting blood glucose ( fbs ) , postprandial blood glucose ( ppbs ) ( glucose oxidase method ) and urine total protein ( pyrogallol red method ) was carried out . chi - square test has been used to find the homogeneity of sex distribution between apparently healthy controls and diabetic cases . student t - test ( independent two tailed ) has been used to find the significance of serum magnesium and other biochemical parameters between these two groups . the effect sizes due to hedges ( bias corrected ) have been computed to find the effect of diabetes on biochemical parameters over the control group . the statistical software spss 11.0 and systat 8.0 were used for the analysis of the data and microsoft word and excel have been used to generate tables and graphs . chi - square test has been used to find the homogeneity of sex distribution between apparently healthy controls and diabetic cases . student t - test ( independent two tailed ) has been used to find the significance of serum magnesium and other biochemical parameters between these two groups . the effect sizes due to hedges ( bias corrected ) have been computed to find the effect of diabetes on biochemical parameters over the control group . the statistical software spss 11.0 and systat 8.0 were used for the analysis of the data and microsoft word and excel have been used to generate tables and graphs . mean values of serum magnesium was found to be lower in cases , 1.38 0.39 mg / dl with diabetic retinopathy ( group 3 ) compared with both the diabetic cases without retinopathy ( group 2 ) , 2.02 0.29 mg / dl and healthy controls ( group 1 ) , 2.62 0.36 mg / dl and was statistically significant . the mean values of fbs , ppbs , hba 1c and urine total protein in diabetic cases with retinopathy ( group 3 ) were found to be higher from that of diabetic cases without retinopathy ( group 2 ) , and healthy controls ( group 1 ) , group 3 versus group 1 p < 0.01 and group 2 versus group 1 p < 0.001 . the values are depicted in table 1 . pearson 's correlation showed that serum magnesium correlated negatively to both fbs ( r = 0.527 , p < 0.01 ) and hba1c ( r = 0.48 , p < 0.01 ) and it was highly significant in cases with diabetic retinopathy , figures 1 and 2 . meansd values of fasting blood glucose , postprandial blood glucose , magnesium , hba1c and urine total protein in controls and cases correlation between serum magnesium and fbs in cases with diabetic retinopathy correlation between serum magnesium and hba1c ( % ) in cases with diabetic retinopathy magnesium is the fourth most abundant cation in the human body and the second most abundant intracellular cation . it serves as a cofactor for all enzymatic reactions that require atp and is a key component in various reactions that require kinases ( 300 enzymes ) . it is also an essential enzyme activator for neuromuscular excitability , cell permeability and is a critical element in cellular proliferation and apoptosis . in addition magnesium is a regulator of ion channels and mitochondrial function and is an important factor in both cellular and humoral immune reactions . cellular magnesium deficiency can alter the activity of membrane bound sodium - potassium atpase that is involved in the maintenance of gradients of sodium , potassium and in glucose transport . it has been suggested that hypomagnesemia may induce altered cellular glucose transport , reduced pancreatic insulin secretion , defective post receptor insulin signaling , and/or altered insulin - insulin receptor interactions . more - over patients who had retinopathy were found to have lowest levels of serum magnesium . these observations are similar to other workers suggesting that hypomagnesemia is a possible risk factor in the development and progression of diabetic retinopathy . the exact cause of hypomagnesemia is unknown but an increased urinary loss of magnesium may contribute to it . some studies revealed that hyperglycemia contribute to hypomagnesemia by causing depression in the net tubular reabsorption of magnesium . in the present study mean hba1c was significantly higher in type 2 diabetics with retinopathy ( p < 0.001 ) , indicating that higher level of hba1c was associated with increased risk for development of microangiopathy in diabetics . this may be due to the fact that hba1c has special affinity for oxygen thereby causing tissue anoxia and plays a role in causation of micro and macroangiopathy . we observed in our study that urinary total protein was significantly higher in type 2 diabetics with retinopathy as compared with both type 2 diabetics without retinopathy and controls . previous studies revealed that only small amount of protein is present in normal excreted urine ( 20 - 150 mg / day ) , and most of it is albumin . increased permeability of glomerular basement membrane is signaled first by increased amount of albumin in urine . numerous studies were carried out to determine the prevalence of retinopathy and albuminuria in type 2 diabetics . the variation in rate could be as a result of different methods used in those studies , the population and or the races involved , or variation in controlling blood sugar level . reported the incidence rate of 22% of microalbuminuria in type 2 diabetics whereas lunetta reported the incidence rate of 15% . the above mentioned studies show that there is significant relationship between the degree of retinopathy and albuminuria our study showed that in addition to hba1c , duration of illness , albuminuria is a contributing factor in the degree of retinopathy and this correlation can be explained by the common mechanism involved in tissue damage by diabetes mellitus . in addition to blood sugar level and blood pressure , there are also other factors which may damage vessels in retina and kidney . besides common mechanisms , renal damage may accelerate retinopathy , which is associated with increased blood pressure and serum levels of fibrinogen and lipoproteins . thus excretion of albumin in urine can be regarded as a sign of kidney involvement and can reflect generalized vessel damage throughout the body . further prospective studies should be carried out to evaluate the effect of lowering albumin excretion on the reduction of blood vessel damage . hypomagnesemia and albuminuria individually or in conjunction serve as indicators for dysglycemia and could be used as marker for the risk of development of diabetic retinopathy . if longitudinal studies confirm these findings , diabetic patients with hypomagnesemia and albuminuria may benefit from close ophthalmologic follow up .

background : diabetic retinopathy is one of the leading causes of blindness in the world . hypomagnesemia has been reported to occur at an increased frequency among patients with type 2 diabetes compared with their counterparts without diabetes . hypomagnesemia has been linked to poor glycemic control . many studies have been undergone to find out the precipitated factors of retinopathy such as duration and type of diabetes , hyperglycemia , hypomagnesemia and increased urinary total protein levels.aim:this study was carried out to study the correlation between serum magnesium levels , glycosylated hemoglobin and urinary total protein levels in diabetic patients with retinopathy.materials and methods : the study population comprised of 30 type 2 diabetic patients without retinopathy as group 2 , 30 type 2 diabetic patients with retinopathy as group 3 in the age group 45 - 75 years as cases and 60 age and sex matched healthy individuals as controls ( group 1 ) . determination of serum magnesium ( photometric xylidyl blue method ) , glycosylated hemoglobin , hb1c ( ifcc ) , fasting blood glucose , postprandial blood glucose ( glucose oxidase method ) and urine total protein ( pyrogallol red method ) was carried out . the statistical software spss 11.0 and systat 8.0 were used for the analysis of the data.results:hypomagnesemia was observed in cases compared with both group 2 and group 3 . fbs , ppbs , hba1c , urine total protein levels were increased in cases ( without retinopathy and with retinopathy ) compared with controls.conclusion:hypomagnesemia and albuminuria individually or in conjunction serve as indicators for dysglycemia and could be used as marker for the risk of development of diabetic retinopathy .

intracranial hypertension ( icht ) management in patients who have suffered a severe tbi remains a challenge . despite improvements in monitoring and medical treatment , morbidity and mortality remains high in patients with icht refractory to therapy . initially one should try to manage the patient 's icht after a severe tbi with medical treatment ( elevation of the bed side , sedation , relaxation , osmolar therapy , hyperventilation , cerebrospinal fluid drainage , and barbiturate coma ) . however , in 10 to 15% of the patients , icht is refractory to medical treatment , being in these cases a dc , an effective measure for reducing intracranial pressure , in up to 80% of the cases . there is a growing body of literature supporting the efficacy of dc , especially after tbi . it has been significantly demonstrated that in patients with icht , craniectomy alone lowered it , but opening the dura in addition to the bony skull resulted in an average decrease in intracranial pressure . although it is associated with a shorter stay in intensive care units , it is unclear whether dc improves the functional outcome in adult patients with severe tbi and icht refractory to treatment . moreover , it should be noted that this technique is not without complications , and those can appear following a sequence , in time . one of the first things that can occur is the expansion of a hemorrhagic contusion , followed by the appearance of a new subdural hematoma on the contralateral side , seizures , loss of cerebrospinal fluid through the scalp , and external brain herniation . the appearance of a subdural hematoma and postoperative infections are complications that can develop even four weeks after surgery . over time , some changes have been implemented in the manner in which the technique is carried out , by trying to find better surgical approaches , to avoid further complications . comparing the effect of standard trauma craniectomy ( stc ) versus limited craniectomy ( lc ) , the stc significantly improves the outcome in severe tbi , with refractory icht resulting from unilateral frontotemporoparietal contusion , with or without intracerebral or subdural hematoma . this suggests that stc , rather than lc , be recommended for such patients . at the moment it seems that the tendency has been to recommend unilateral frontotemporoparietal dc for the treatment of cerebral hemisphere injury or edema , where bifrontal dc is indicated if there is diffuse swelling . we present two cases of patients with tbi , who required dc and who suffered complications secondary to the technique . a 15-year - old female patient was admitted after a severe tbi . the axial computed tomography ( ct ) scan showed a frontoparietal subarachnoid hemorrhage , right frontal subdural hematoma , cerebral edema , and important bilateral uncal herniation . seventeen days after admission , when objectified 11 points in glasgow coma score ( gcs ) ( 4 - 1 - 6 ) , and obeying simple commands , the patient suffered a neurological deterioration to 3 points on the gcs and pupil anisocoria . the ct scan showed that frontal intraparenchymal hemorrhagic lesions opened to the ventricular system [ figure 1 ] . the patient died in a state of severe brain damage , within the context of nosocomial infection , 35 days after admission . ( a ) decompressive craniectomy performed after head injury and ( b ) the subsequent appearance of a frontal hemorrhage a 60-year - old man who suffered a severe tbi with a right subdural effusion , with a mass effect on the midline of 19 mm , ventricular compression on the same side , uncal and transfalcine herniation with effacement of cisterns and compression on the temporal horn , had a right frontotemporoparietal dc performed , and hematoma evacuation was done . the patient remained with 10 points ( 3 - 2 - 5 ) in the gcs , but with no connection to the environment . after 20 days of admission , a right subdural hygroma appeared , which required surgery and titanium cranioplasty [ figure 2 ] . the patient was discharged home with a 3-point gcs , with severe disability , conscious , but with basic family - support for daily activities , after 28 days of admission . ( a ) subdural hygroma next to the craniectomy area and ( b ) after evacuation of the hygroma and titanium cranioplasty a 15-year - old female patient was admitted after a severe tbi . the axial computed tomography ( ct ) scan showed a frontoparietal subarachnoid hemorrhage , right frontal subdural hematoma , cerebral edema , and important bilateral uncal herniation . seventeen days after admission , when objectified 11 points in glasgow coma score ( gcs ) ( 4 - 1 - 6 ) , and obeying simple commands , the patient suffered a neurological deterioration to 3 points on the gcs and pupil anisocoria . the ct scan showed that frontal intraparenchymal hemorrhagic lesions opened to the ventricular system [ figure 1 ] . the patient died in a state of severe brain damage , within the context of nosocomial infection , 35 days after admission . ( a ) decompressive craniectomy performed after head injury and ( b ) the subsequent appearance of a frontal hemorrhage a 60-year - old man who suffered a severe tbi with a right subdural effusion , with a mass effect on the midline of 19 mm , ventricular compression on the same side , uncal and transfalcine herniation with effacement of cisterns and compression on the temporal horn , had a right frontotemporoparietal dc performed , and hematoma evacuation was done . the patient remained with 10 points ( 3 - 2 - 5 ) in the gcs , but with no connection to the environment . after 20 days of admission , a right subdural hygroma appeared , which required surgery and titanium cranioplasty [ figure 2 ] . the patient was discharged home with a 3-point gcs , with severe disability , conscious , but with basic family - support for daily activities , after 28 days of admission . ( a ) subdural hygroma next to the craniectomy area and ( b ) after evacuation of the hygroma and titanium cranioplasty it is generally reported that the outcome of patients younger than 50 years or with an initial gcs score of 6 or more is significantly better than that for older patients or those with an initial gcs score lower than 6 . the factor having the greatest influence on the outcome is the time from injury to surgery . patients who undergo dc within the first four hours following trauma have a better outcome compared to those who undergo dc after four hours . although the dc is a simple technique , it can be risky , and risks must be considered , as they can alter the prognosis . complications are more frequent in patients with a low score on the glasgow scale and in those over 60 years . up to 50% of the patients the expansion of hemorrhagic contusions is the most common complication of neurological impairment and death in patients who have had a period of lucidity after a severe tbi , as in the cases that we have reported . the explanation for this phenomenon is that when performing the dc , the hemostatic effect is lost when removing the bone and this facilitates the expansion of the effusion on the same side , and is contralateral in a few cases . the dc seems to be useful in icht treatment and in reducing the mortality rate . it is relatively common and it can be developed in up to 50% of the cases . the main cause is a disruption between the dura and arachnoids , when performing the dc . among their most common locations are the subdural , subgaleal or the interhemispheric , being more common where the craniectomy it is site . it is rare that effusions present clinical expression and most of them are reabsorbed spontaneously , but when its expansion produces neurological impairment it is necessary to have an aggressive treatment such as surgical excision cranioplasty being a definitive solution , as in the case that we have reported . the presence of interhemispheric , subdural or subgaleal hygroma is a predictive radiographic sign of hydrocephalus in patients undergoing dc . hemorrhagic collections with mass effect are usually extra - axial collections , and are usually located at some distance from the craniectomy . its etiology can be explained by the sudden decrease in intracranial pressure , so they rapidly appear . its incidence is up to 25% and it is caused due to edema induced by cerebral high perfusion and due to the increase of the hydrostatic gradient from the capillaries , after decompression . when this complication occurs , it can generate brain parenchymal lacerations and can compromise the cortical venous flow against the edges of the bone defect , causing ischemia and necrosis . performing a wide craniectomy the dc is also a risk factor for the development of hydrocephalus in up to 30% of cases , and can complicate the prognosis . its appearance may be because this technique may induce alterations in the circulation of the cerebrospinal fluid ( csf ) . it is usually solved after placing the bone ; however , it can persist for a long time despite the replacement . the surgical emergency of the procedure can damage the superficial temporal artery , and reduce flow to the flap , or also can accidentally open the frontal sinus , contaminating the area . the wound infection decreases its incidence due to the administration of antibiotics during surgery , which remains at around 7% . moreover , the sealing of the dura prevents csf leaks , which can cause meningitis . replacing the bone is also associated with higher rates of infection , increasing when the bone flap is preserved for long periods of time under freezing conditions . the dc is a useful technique for the treatment of tbi with icht resistant to medical treatment . it increases the patient 's survival , but its role in the functional prognosis of patients is still not defined . early bi - frontotemporoparietal dc decreases the intracranial pressure and the length of stay in the icu , but is associated with more unfavorable outcomes . undertaking this decision requires that the clinicians involved take appropriate account of having used all the conventional weapons against icht and the absence of data indicating an already negative outcome . in addition , it is a technique that is not free of complications , which themselves can further increase the worst prognosis of these patients . just as more studies are needed to define the type of patient who can benefit from a dc , and to decide which technique is most appropriate , all the complications derived from this technique must be evaluated . we also recommend further studies to monitor brain oxygenation , because the normalization of intracranial pressure does not mean that the brain perfusion has been adequate . strategies to improve cerebral oxygenation suggest the benefit of multiple approaches to monitor these patients .

decompressive craniectomy ( dc ) is a useful technique for the treatment of traumatic brain injuries ( tbi ) with intracranial hypertension ( icht ) resistant to medical treatment , increasing survival , although its role in the functional prognosis of patients is not defined . it is also a technique that is not without complications , and may increase the patient 's morbidity and mortality . we report two cases of patients with tbi who required dc and suffered complications from the technique

a 41-year - old caucasian woman complaining of persistent diarrhea , diffuse neck myalgia , swollen fingers and fatigue was clinically evaluated . early morning fatigue and continuous neck pain started 6 months earlier and were initially attributed to stress by the patient s regular physician , who recommended psychotherapy . these symptoms did not improve and were worsened after a crisis of gastroenteritis due to seafood , associated with fever and severe abdominal pain , which resolved in 2 days . despite improvement of the acute gastroenteritis , an intermittent diarrhea , without mucous or blood , persisted for another 2 months while the patient developed swollen fingers and a sudden outbreak of acne . the patient s clinical history revealed that she had pre - eclampsia during her only pregnancy ( 9 years earlier ) , mumps and pancreatitis at 9 years old , and a myalgic crisis 4 years earlier , diagnosed at the time as fibromyalgia by her orthopedist . she had never smoked and was not under any medical treatment except for contraception with a levonorgestrel - releasing ( 20 mcg / day ) intrauterine system for the previous 5 years with complete amenorrhea . the myalgic episode was resolved with cyclobenzaprine hydrochloride ( 15 mg / day ) and a healthy sleep routine . family history revealed that her father died of glioblastoma multiforme ( gbm ) and her grandfather died of abdominal cancer of unknown origin . the only finding from the physical examination was a discrete tenderness upon palpation of the liver . she presented with borderline high levels of ldl , hdl and total cholesterol ( 138 mg / dl , 48 mg / dl and 207 mg / dl ) . triglyceride and vldl cholesterol levels were 104 mg / dl and 21 mg / dl , respectively . the values for serum apolipoprotein a1 and b were 125 and 106 mg / dl , respectively . urinalysis revealed normal findings . except for a slightly elevated gamma - gt ( 88 u / l ) , thyroid ultrasonography revealed a colloid cyst in the right lobe , but the tsh , free t3 and t4 levels were normal . although her fasting glucose was within normal limits , the patient presented with 2-hour post - challenge hyperglycemia ( 2 hpg > 140 mg / dl ) , which was suggestive of impaired glucose tolerance . u / l . the urea , creatinine , and electrolytes ( ca , inorganic p , na , k and mg ) values were normal . plasma acth was 9 pg / ml , serum hgh was 0.61 mg / l , cortisol levels were 8.5 and 7.7 mg / dl at 8 am and 4 pm , respectively , dhea was 400 ng / dl and dhea - s was 230 g / dl . immunological investigation was positive for the following autoantibodies : anas ( 1/320nuclear and metaphasic chromosome , 1/160cytoplasmic ) and anti - smooth muscle . the panel was negative for p - anca , c - anca , cea , ca 19 - 9 , ana ( nucleolar and nuclear mitotic apparatus ) , anti - nucleosome , anti - sm , anti - rnp , anti - thyroglobulin , anti - thyroid peroxidase and native dna . serum levels of folic acid ( 327 ng / ml ) , vitamin b12 ( 438 ng / l ) , 25 hydroxyvitamin d ( 23 ng / ml ) and 1 , 25 dihydroxyvitamin d ( 42 pg / ml ) were within normal ranges . the testosterone level was 34 ng / dl . abdominal and pelvic ultrasonographies were normal except for a discrete increase in liver lipid infiltration . the intrauterine device was adequately positioned . at this point , a dietary intervention ( a low carbohydrate diet with lactose restriction ) was prescribed , and the patient started a physical outdoor exercise program ( 50 minutes of walking , 5 times a week ) . further immunologic testing was performed , but the results were either negative or normal ( anti - mitochondrial antibody , ro / ss - a antigen , la / ss - b antigen , serum immunoelectrophoresis , seric proteins electrophoresis , and serum iga , igg and igm levels ) . during the following 5 months , the impaired glucose tolerance was controlled ( 2 hpg = 132 mg / dl ) , and she lost approximately 13 pounds ( lb ; starting weight : 156 lb , 58 ) ; the diarrheic episodes diminished , but the fatigue persisted . the acne outbreaks were resolved with antibiotic therapy ( tetracycline , 1 g / day , for 2 months ) . blood hematological parameters remained unremarkable , but at this time , serum ferritin was assessed . the elevated levels ( 216 mg / l ) indicated that the patient most likely had an iron overload syndrome . she was screened for c282y , h63d and s65c mutations and was homozygous positive for h63d . abdominal magnetic resonance image ( mri ) iron overload syndrome , amenorrhea and ius confirmed a hepatic iron overload of 50 mol / g with a standard deviation of 30 mol / g . the patient was referred to a hepatologist who prescribed 4 therapeutic bleedings ( phlebotomies ) of 500 ml , once a month for 4 months . initially , the patient experienced extensive extremities edema , decreased immunological resistance and some dizziness after the phlebotomies . regular monthly menses were established after 2 months , and there was an increase in libido , although this was not a previous complaint . after all the phlebotomies , the serum ferritin levels returned to normal ( 52 g / l ) and the abdominal mri findings showed a decrease in the hepatic iron concentration ( 40 mol / g , standard deviation of 30 mol / g ) . this patient most likely has had food - borne infectious diarrhea from eating raw shellfish , but its unusual persistence suggested that other problems were involved . the differential diagnosis of these infections is wide , ranging from viral infections to parasitic infections . parasites were ruled out by the stool exam ; however , no culture was performed , which might have been helpful . the symptoms persisted for over 4 weeks and were consistent with chronic diarrhea , which is mostly non - infectious in nature . she was afebrile , with normal blood pressure , with neither lymphadenopathy nor a tender abdomen , and had normal bowel sounds . chronic diarrhea and watery stools are suggestive of chronic and inflammatory conditions that may compromise the small bowel ( eg , lactose intolerance , malabsorption syndromes , infections such as shigella sp . , yersinia sp . , and escherichia coli , pancreatic diseases , bile salt - deficiencies ) and colon ( eg , inflammatory bowel disease , irritable bowel syndrome , infections , crohn s disease).1 in healthy persons , for example , yersinia enterocolitica seems relatively avirulent , but with increased iron availability , the infection can develop into septicemia or be persistent for months . the episodes in this case ceased while the patient was under the dietary intervention for the impaired glucose tolerance and taking high doses of tetracycline for the acne outbreaks . the glucose intolerance and the antigenic findings observed in the first set of exams pointed toward a different direction , so the original gastrointestinal infection was not further pursued . the patient s complaint of fatigue was further investigated by assessing a wide range of clinical conditions such as nutritional deficiencies ( serum levels of vitamin d , b12 , and folic acid ) , endocrine dysfunctions ( adrenal insufficiency , cushing s syndrome , diabetes , hyperparathyroidism , testosterone deficiency , thyroid dysfunction ) , anemia , and even neoplasias . stressful life events , such as loss of a family member , a job or a spouse , have all been associated with health deterioration and depression . however , clinicians should not readily rule out a systemic origin for fatigue when symptoms of depression are present.2 in fact , the first set of exams of this patient pointed to glucose intolerance and some immunological alterations . impaired glucose tolerance ( igt ) is a known risk factor for diabetes and for heart disease . it occurs in 15.6% of adults at 40 to 74 years of age4 and is diagnosed through a glucose tolerance test . this patient had a history of increased weight gain during pregnancy ( 88 lb ) due to pre - eclampsia ( no gestational diabetes ) , but otherwise had no weight problem ( 132.2 lb , 58 ) . igt increased the suspicions of impaired insulin release that could be associated with storage diseases , such as iron overload confirmed in this case with the elevated serum ferritin levels . pancreatic iron overload may cause insulin release impairment if not treated.5 a reduced carbohydrate diet and physical exercise were the first steps in dealing with this condition and proved to be adequate for this clinical scenario . it is likely that this patient s igt benefited not only from her eating habit changes and her improvement in physical conditions , but also from the phlebotomies , which decreased the hepatic iron deposits as observed in the mri images . non - invasive assessment of hepatic iron stores by mri avoids unnecessary hepatic biopsy and its complications . the joint discomfort was suggestive of inflammatory arthritis that could be have been related to a rheumatic disorder or a non - rheumatic systemic disease , such as inflammatory bowel disease . the patient had increased levels of antinuclear and anti - smooth antibodies , as well as symptoms easily attributed to fibromyalgia . joint pain complaints are referred to in storage syndromes such as iron overload , mimicking rheumatological disorders that should be considered in the differential diagnosis . this patient had unspecific symptoms except for eventual swollen proximal interphalangeal joints and neck myalgia . additional exams were conducted to rule out a series of autoimmune diseases and all were within normal parameters . women have numerous choices for contraceptive methods , including some that avoid menstruation ( necessary for therapeutic reasons or fitted for personal preferences ) , such as the levonorgestrel - releasing intrauterine system ( ius ) . it is an effective form of long - term reversible birth control that , by causing amenorrhea , may have a significant impact in populations where iron deficiencies are endemic . in a study conducted in india , women evaluated in terms of menstrual bleeding patterns and blood elements parameters after insertion of an ius and copper - releasing intrauterine device ( iud ) indicated that serum ferritin , hemoglobin concentration , menstrual bleeding and spotting days were significantly different depending upon the device type . both groups presented increased bleeding days during the months following insertion , but after a 12-month period , women using ius presented with a significant rise in hemoglobin and serum ferritin levels in addition to a reduced number of menstrual bleeding days . the authors concluded that the ius was a relevant contraceptive method that could improve health conditions in populations facing iron deficient situations , such as those of developing countries.6 similar results and conclusions were previously reported in brazil , reinforcing the importance of the levonorgestrel - releasing intrauterine system in terms of preventing anemia.7 alternatively , by stressing the relevance of the ius in preventing body iron loss , these data also suggest that it could be harmful in situations where the patient presents with health conditions related to iron overload , such as in the present case . the non - specific nature of early hemochromatosis symptoms usually delays the diagnosis , unless the family history triggers genetic or laboratory testing . in the initial stages , symptoms are non - specific and may evolve to manifestations , at an older age , of diabetes mellitus , hypogonadism , arthralgias , osteoporosis , cirrhosis , hepatocellular cancer , or cardiomyopathy . the clinical disease is less common in women due to physiological blood loss from menstruation and pregnancy . the benefits of blood loss in women with hereditary hemochromatosis are supported by the fact that iron overload symptoms commonly start after menopause.8 this should be considered whenever clinical or medical interventions that cause amenorrhea are implemented for women at risk of iron overload syndromes or must be considered whenever symptoms such as these are reported in situations associated with amenorrhea , even in circumstances with a decrease in blood loss due to excess physical exercise . the patient was a five - year user of the levonorgestrel - releasing intrauterine system when she first reported fatigue symptoms . clearly , hemochromatosis was not caused by the ius , but the amenorrhea it promoted may have triggered the symptoms that led to the diagnosis . after her findings , all brothers and sisters were tested and confirmed to be heterozygotes for the same mutation . hemochromatosis , the most important iron overload condition of the liver , is the most frequent genetic disease among the caucasian population , affecting 1 in 300 persons.9 an average of 20 mutations have been identified for the hfe gene , the gene responsible for hemochromatosis , but 2 mutations , c828y and h63d , are the most responsible for abnormal iron loading . the allelic frequencies of c282y and h63d mutation vary in different populations from under 5% for c282y to 15% for h63d.10 in conclusion , it is important to consider the diagnosis of iron overload syndromes in patients with the symptoms described above , but it is particularly important to consider this diagnosis in patients who wish to suspend menstruation for personal reasons . in these patients , monitoring ferritin levels may be necessary for the diagnosis of an underlying condition that may compromise different systems and have long - term implications .

severe fatigue is a common complaint among patients . this report presents a clinical case of a woman complaining of fatigue associated with diarrhea and myalgia that were first attributed to emotional stress and depression . initially , the patient was diagnosed with chronic fatigue and irritable bowel syndrome . the patient followed nutritional and physical exercise programs without any improvement . other clinical conditions , such as nutritional deficiencies , endocrine dysfunctions , autoimmune diseases and neoplasias , were then assessed . during clinical investigation , serum ferritin and iron levels were abnormally elevated despite normal hemoglobin levels , which pointed to an iron overload syndrome later diagnosed as hemochromatosis . it is possible that the symptoms were triggered by the amenorrhea caused by the levonorgestrel - releasing intrauterine system used for contraception .

so , it is essential for learners to understand this importance of environment in the epidemiological triad . based on our regular observation , the regular theory classes on environment usually had a negative response and students felt so due to the feeling of being dry and vague . so , it was planned to take one session on environmental health as group work using materials collected from various books and websites by their internet search . this method was very effective in learning and it has supported many of the earlier literature . this method was planned keeping in mind the guidelines given by the medical council of india in its revised regulations of graduate medical education-1997 , which has pointed out the inadequacies of lecture as a method of teaching and has suggested the use of active methods . to increase the interest and enhance student 's participation in acquiring knowledge in the environmental health using the air pollution as the model session . at the end of the session , students should know the importance of air as an environmental factor in disease causation in special reference to the public health hazards , the major sources of air pollution , major pollutants causing the health hazards , the way to measure pollutants and control them . at the end of the session , students should know the importance of air as an environmental factor in disease causation in special reference to the public health hazards , the major sources of air pollution , major pollutants causing the health hazards , the way to measure pollutants and control them . in our institute each class of students comprised of 75 students . the whole class was divided into two batches and one session was conducted for each batch . the specific learning objectives were spelt out as that at the end of the session students should know the importance of air as an environmental factor in disease causation ( including indoor air pollution ) , the major sources of air pollution , major pollutants , and the way to measure them and control them . then the whole class was divided into six small groups , each of 4 - 5 students . the groups were given task of reviewing the current situation of air pollution in india , sources and determinants of air pollution , effects of air pollution , measurements and indicators for air pollution , indoor air pollution , a case study of a city ( delhi ) for control of air pollution . the computer was used in teaching by making students access the internet to collect details from list of pre - selected websites and search . apart from this they were allowed to refer the text books of their choice for some specific information . all the students were asked to prepare collectively after their review and one student was made to present on that topic . at the end of each presentation moderator highlighted the key points and brought out its relevance to disease causation and public health . at the end of each session , the students gave feedback at the end of each session which is given in the table 1 . eighty seven percent of them found that internet assisted study or group work as interesting and 23% even liked involvement of students to present their findings . few of them felt inadequacy of time for preparation of the topics ( 28% ) . one of the main purpose of teaching undergraduate medical students the environmental health is to make them understand the role of environment in disease causation so that they can always consider it during their clinical / public health practice . teaching about environment to undergraduate students has been really a challenge due to the vastness and dryness of the subject . traditionally lecture has been the method of teaching , but it failed to create the desired interest or knowledge in students . group discussions have been used successfully in the past to teach undergraduate students in community medicine for various topics . this method was applied to the newer generation with adequate modifications considering the newer developments in information technology . this approach used the same group discussions but used the present day information technology of availability of internet . the objectives were clear and internet - assisted learning was interesting for majority of the students and hence shows that the teaching learning objectives were achieved . there were similar results from computer - assisted learning from other disciplines like dental education and otorhino laryngology . computer - assisted learning was shown to increase the knowledge of the students in these studies and it is very similar to our results . this apart from creating the facilitated learning environment also provided an opportunity for the students to improve their literature searching skills , reading and presentation skills . this also helped them as an orientation to search the medical literature in the internet . this study reflected that students were really interested as they gave a promising feedback . in our institute , the staff - student ratio is good ; hence this mode of study was possible and can be replicated to similar educational environment . however , selection of topic and teacher 's preparation plays a vital role in the success of such learning initiatives . internet - assisted collaborative study served as a valuable alternative , innovative , and interesting tool to teach and learn environmental health . this method ensured self - interested participation by the students as revealed by their feedback .

background : topics on environmental health are usually neglected by students and it is necessary for them to learn this area with a public health perspective as environment plays a vital role in multi - factorial causation of diseases . hence there is a need for alternative teaching / learning methods to facilitate students in acquiring the required knowledge.objectives:to increase the student interest and enhance their participation in acquiring knowledge in public health perspective of environmental health . teaching objectives / learning were : at the end of the session students should know the importance of air as an environmental factor in disease causation in special reference to public health hazards , the major sources of air pollution , major pollutants causing the health hazards , the way to measure pollutants and control them.materials and methods : the whole class of students was divided into two batches and one session was planned for each batch . each batch was divided into six small groups . the groups were given task of exploring the internet on the different topics mentioned in the learning objectives . all the students were asked to explore , compile information and collectively prepare a presentation and present their findings based on their reviews . students feedback was collected at the end of each session.results:eighty five percent of them were clear about the learning objectives and interested about internet learning . most of them gave a positive opinion about the newer teaching learning method.conclusions:internet assisted group study served as a valuable alternative , innovative , and interesting tool to teach and learn the environmental health as revealed by students feedback .

repeated assessment of the abundance and diversity of phytophagous and entomophagous arthropods in crops is needed for ecological studies of population dynamics and species interactions , including the study of biological control . rice is a major staple food , with a high potential for biocontrol by entomophagous arthropods , but which can be disrupted by insecticides . the diversity of arthropods in rice crops can be high , and arthropod species occupy various crop strata ( e.g. , ground , stem , canopy , flowers ) , differ in mode of movement ( e.g. , walking , jumping , flying ) and foraging strategy ( e.g. , sessile sucking insects , hunting predators and flower visiting pollinators ) . there is a wide range of arthropod sampling techniques , each with strengths and weaknesses . for instance , pitfall traps can be used to sample ground - dwelling arthropods , but provide activity - dependent relative population estimates . sweep nets can be used to sample fast - flying insects in the canopy , but give relative estimates of arthropod abundance . the beat sheet method can be used to sample the plant - dwelling arthropod community and provides absolute estimates of arthropod abundance , but it can not be used effectively in flooded crop fields such as rice paddies . suction sampling , when conducted in combination with an enclosure covering a standardized area of the field , provides absolute estimates of the densities of plant - dwelling arthropods . the dietrick vacuum ( d - vac ) is the first commercially developed suction sampler . although d - vacs are still widely used , they are relatively expensive , have a limited suction force and are relatively heavy , which makes them hard to handle in flooded rice fields . arida and heong developed a suction sampler using a petrol - driven leaf blower - vac , and advantages of the blower - vac suction sampler as compared to the d - vac are that it is much cheaper and easier to handle . although the blower - vac suction sampling method has been used in many ecological studies , the instructions for its modification and application have not been clearly described . here we present a video - based , detailed description of the modification and application of a petrol - powered leaf blower - vac for suction sampling of arthropod populations in flooded rice fields . the modification is inspired by arida and heong and domingo and schoenly , but the design has been further simplified compared to these original publications , facilitating construction and use . collect all parts listed in the materials list . connect all polyvinyl chloride ( pvc ) pipes with unplasticized polyvinyl chloride ( u - pvc ) glue ( pipes 1 - 2 - 3 - 4 - 5 and 6 - 7 ) . drill three holes that are evenly distributed around the suction mouth of the machine . connect the machine to the end 1 of pvc pipe 1 - 5 by inserting one screw into each of the three holes . do not use glue to connect pipe end 1 to the machine because the connection should be reversible to clean the fan . note : in case the diameter of the suction mouth of the machine differs from the model described here , the diameter of pipe end 1 should be adjusted to fit the machine seamlessly . put the piece of metal gauze between the hose and the mouth part ( pvc pipes 6 and 7 ) to prevent the sampling net from being sucked into the machine . connect the hose to pipe ends 5 and 6 with metal clamp hoops . remove the bottom from a plastic bucket ( 50 l , 40 cm bottom diameter ) . this size of the enclosure covers 2 - 4 rice hills in a transplanted rice field , depending on crop stage . attach a nylon mesh sleeve , with a length of 1 m , to the top of the bucket using a rubber band . for this sleeve , use a mesh size that is small enough to prevent the escape of the smallest target arthropods . use a diameter less than 0.5 mm . use two persons to operate the device in the field . one person operates the blower - vac and the other handles the bucket enclosure and the sampling nets . insert a sampling net into the mouth part of the blower - vac and fix it with a rubber band . for the net , use a mesh size that is small enough to catch the smallest target arthropods , but does not create obvious airflow resistance . use the light nylon material with a mesh diameter between 0.2 - 0.5 mm . place the enclosure quickly over the plants at a random location in the field and push the bottom of the bucket firmly into the soil . make sure that the sleeve is closed to prevent arthropods from escaping from the top of the enclosure . remove all arthropods from inside the enclosure in a top - down spiraling way , for a standardized sampling duration . for rice crops in the vegetative and reproductive stages , use sampling durations of 1 and 2 min , respectively . after finishing the sample , remove the rubber band from the sampling net , quickly close the net and take it out of the mouth part of the blower - vac and close it with a knot , while keeping the machine running . repeat steps 3.2 to 3.5 at random locations in the field for the next samples . the number of replications depends on the variation in the spatial distribution of arthropods in the field , the required accuracy of the estimate and the purpose of the study . typically , six replicates will give a good impression of the arthropod community and species abundances . collect all parts listed in the materials list . connect all polyvinyl chloride ( pvc ) pipes with unplasticized polyvinyl chloride ( u - pvc ) glue ( pipes 1 - 2 - 3 - 4 - 5 and 6 - 7 ) . drill three holes that are evenly distributed around the suction mouth of the machine . connect the machine to the end 1 of pvc pipe 1 - 5 by inserting one screw into each of the three holes . do not use glue to connect pipe end 1 to the machine because the connection should be reversible to clean the fan . note : in case the diameter of the suction mouth of the machine differs from the model described here , the diameter of pipe end 1 should be adjusted to fit the machine seamlessly . put the piece of metal gauze between the hose and the mouth part ( pvc pipes 6 and 7 ) to prevent the sampling net from being sucked into the machine . remove the bottom from a plastic bucket ( 50 l , 40 cm bottom diameter ) . this size of the enclosure covers 2 - 4 rice hills in a transplanted rice field , depending on crop stage . attach a nylon mesh sleeve , with a length of 1 m , to the top of the bucket using a rubber band . for this sleeve , use a mesh size that is small enough to prevent the escape of the smallest target arthropods . use a diameter less than 0.5 mm . one person operates the blower - vac and the other handles the bucket enclosure and the sampling nets . insert a sampling net into the mouth part of the blower - vac and fix it with a rubber band . for the net , use a mesh size that is small enough to catch the smallest target arthropods , but does not create obvious airflow resistance . use the light nylon material with a mesh diameter between 0.2 - 0.5 mm . place the enclosure quickly over the plants at a random location in the field and push the bottom of the bucket firmly into the soil . make sure that the sleeve is closed to prevent arthropods from escaping from the top of the enclosure . remove all arthropods from inside the enclosure in a top - down spiraling way , for a standardized sampling duration . for rice crops in the vegetative and reproductive stages , use sampling durations of 1 and 2 min , respectively . after finishing the sample , remove the rubber band from the sampling net , quickly close the net and take it out of the mouth part of the blower - vac and close it with a knot , while keeping the machine running . repeat steps 3.2 to 3.5 at random locations in the field for the next samples . the number of replications depends on the variation in the spatial distribution of arthropods in the field , the required accuracy of the estimate and the purpose of the study . typically , six replicates will give a good impression of the arthropod community and species abundances . a total of 295 arthropods were collected in 8 three - minute blower - vac samples from a rice crop in the ripening stage in jiangxi province , china , in september 2015 . to determine the relationship between relative yield ( proportion of the arthropods collected in the sample ) and sampling duration , the mean number of individuals per sample was 36.9 4.1 ( mean sem ) . a total of eight arthropod orders were found , with hemiptera ( 28.8% ) , araneae ( 27.5% ) and diptera ( 17.6% ) being dominant ( figure 1 ) . the relative yield , expressed as a percentage of the number of collected arthropods after three minutes , was 52.9% 5.1 , 92.4% 1.9 and 97.3% 0.9 after 30 seconds , 2 and 2.5 minutes , respectively ( figure 2 ) . figure 1.species composition ( at the order level ) of arthropod samples in the suburbs of nanchang city in jiangxi province , china . cumulative relative yield as a function of total sampling duration based on sub - samples of 30 seconds each . the total number of arthropods collected over a sampling duration of three minutes is set at 100% . suction sampling is one of many possible methods to sample arthropod communities in crops . for scientific research in rice systems , suction sampling is an appropriate option because the method provides absolute estimates of arthropod densities , it is non - destructive , and in contrast to visual counts allows collection and storage of samples for later processing . compared to the commercially available d - vac , the blower - vac is smaller , lighter and easier to handle in ( flooded ) rice fields and also easier to combine with an enclosure . for example , a blower - vac weighs about 6 kg , whereas the backpack d - vac model , presented as the international standard for insect sampling , has a weight 12 kg . more importantly , the sampling efficiency of the blower - vac is higher than the d - vac , while the cost of the blower - vac is less . the modification of a leaf blower - vac into a suction sampler does not require special skills or equipment and takes less than an hour after all additional parts have been collected . the blower - vac described here is easier to construct and operate than versions described previously in the literature , and the required parts ( table 1 ) are standard construction materials that are widely available . this makes the blower - vac also accessible to researchers with small budgets in developing countries . the power and displacement of the engine determines the suction force of the blower - vac . here we recommend a machine with a power between 0.7 - 1.2 kw and a displacement between 25 - 35 cc , which is adequate for sampling the plant - dwelling arthropod community in rice . the length of the flexible plastic hose and the diameter of the sucking mouth part ( pipe 7 ) are critical for a good sampling performance . a hose that is too long will reduce the suction power , whereas a hose that is too short will be inconvenient to use during sampling . similarly , a mouth part with too large a diameter will reduce the suction power , whereas a diameter that is too small will reduce the sampling efficiency due to the small surface . if sampling is conducted throughout the growing season , the sampling duration may have to be adjusted to the plant size , structure , and planting density to maintain a similar level of efficiency . sampling efficiency should be checked by careful visual inspection of the enclosed area after sampling . the recommended sampling durations for rice crops in the vegetative stage is 1 minute and in the reproductive and ripening stages it is 2 minutes . suction sampling with the blower - vac can be conducted in flooded fields , while alternative methods , such as pitfall and beat sheet sampling are not feasible in standing water . the blower - vac can also be used to sample the arthropod community on the water surface of flooded rice fields ( e.g. , predatory water bugs ) , as the machine is capable of sucking in some water . however , it is not recommended for sampling aquatic arthropods as the motor may stop running when the mouth part is inserted deeply into the water and the airflow is blocked . apart from rice , the blower - vac can also be used in other crops and non - crop habitat , as long as the height and structure of the vegetation allows proper placement of the enclosure . almost all arthropods collected in the sampling net survived , including those soft bodies such as mosquitos and damselflies . the blower - vac in the field will result in some disturbance , and therefore this method may underestimate disturbance - sensitive species such as grasshoppers . fast and abrupt placement of the enclosure in a relatively undisturbed area in the forward direction of movement may limit this potential bias . the loud noise of the blower - vac machine may also cause disturbance , and sampling at night in residential areas is not recommended . the method is not suitable for sampling highly mobile flying insects , such as predatory odonata or larger hymenopterous parasitoids . as with any sampling method , the combination of the blower - vac with other methods , such as sweep net sampling or destructive harvesting of plants , can provide a more complete and balanced assessment of the arthropod community .

rice fields host a large diversity of arthropods , but investigating their population dynamics and interactions is challenging . here we describe the modification and application of a leaf blower - vac for suction sampling of arthropod populations in rice . when used in combination with an enclosure , application of this sampling device provides absolute estimates of the populations of arthropods as numbers per standardized sampling area . the sampling efficiency depends critically on the sampling duration . in a mature rice crop , a two - minute sampling in an enclosure of 0.13 m2 yields more than 90% of the arthropod population . the device also allows sampling of arthropods dwelling on the water surface or the soil in rice paddies , but it is not suitable for sampling fast flying insects , such as predatory odonata or larger hymenopterous parasitoids . the modified blower - vac is simple to construct , and cheaper and easier to handle than traditional suction sampling devices , such as d - vac . the low cost makes the modified blower - vac also accessible to researchers in developing countries .

to stent or not to stent is a point debated since long time . this assumes importance in children and infants requiring intervention for ureteropelvic junction obstruction ( upjo ) . although literature supports stentless pyeloplasty , in laparoscopic pyeloplasty particularly , it is a common practice to stent the anastomosis . the advantages and disadvantages of both the approaches are well known . in infants , the urethra is narrow and runs the risk of injury and subsequent strictures with surgical manipulations . in addition , the stent - related morbidities which include dysuria and infections may make the postoperative course of the infant unpleasant . in the days of open surgery , it was our policy to employ the technique of open insertion of stent along with a nephrostomy , just prior completion of the anastomosis . this served the purpose of nephrostomy acting as a safety valve prior to removal of splint . in this article , we describe the technique of ante grade access of the ureter , thus potentially avoiding the urethral manipulations and the associated complications . a 7.5mhz ( b k medical , denmark ) ultrasound probe with puncture attachment is used . a pediatric probe is used for this purpose [ figure 1 ] . a 18 gauge echotip disposable two part trocar needle ( cook urological inc , indiana , usa ) which is available as a two part needle was used . a 0.035 guide wire or alternatively a terumo glide wire ( terumo corporation , tokyo , japan)with alken two part metallic needle helps simultaneously passing two guide / glide wires [ figure 1 ] . the dilatation is done with angiotech one step dilator ( pbn medicals , denmark ) , a14 fr nephrostomy tube ( devon innovations ( p ) ltd , parwanoo , hp , india ) with a 5 fr open end ureteric catheter ( devon innovations ( p ) ltd , bangalore , india ) is used . the armamentarium ( a ) telescopic metal two part needle ( b ) pediatric ultrasound probe the first step involves positioning the patient in a prone position , although the same can be done in supine position . line diagram ( a ) and picture ( b ) illustrating ultrasound - guided calyceal puncture the needle is housed in the needle attachment of the ultrasound probe and the posterior calyx identified [ figure 2 ] . the key for a successful ultrasound puncture is that the needle should be seen throughout the trajectory which includes the skin , subcutaneous tissue , cup of the calyx and the calyx in concern [ figure 3 ] . technique of ultrasound - guided access ( a ) an egress of clear fluid suggesting entry in the pelvicalyceal system ( b ) a successful ultrasound puncture - the needle should be seen throughout the trajectory which includes the skin , subcutaneous tissue , cup of the calyx and the calyx in concern an egress of clear fluid suggests entry in the pelvicalyceal system which can further be confirmed with a contrast study [ figure 3 ] . next a guide wire is parked in a distant calyx and the tract dilated up to 14 fr using a screw dilator . an alken needle , which is a two part needle , helps in passing a second guide wire after removing the inner stylet [ figure 4 ] . once both guide wires are in place , one wire is used for passing a ureteric catheter and the second one is used for placing a nephrostomy tube [ figure 5 ] . the salient feature of our technique is that all steps of percutaneous access which include access and dilation are done solely using ultrasound guidance . ( a ) the needle and guide wire are clearly seen in real time ultrasound , thus avoiding bowel injury ( b ) ( line diagram ) and c ( picture):-two glide wires passed into the renal pelvis through the telescopic metal two part needle after removing the inner stylet ( a ) line diagram showing completed anastomosis with nephrostomy and ureteric catheter ( splint ) in situ , ( b ) laparoscopic pyeloplasty performed after the ureteric catheter and percutaneous nephrostomy is in place c ) opened up renal pelvis showing presence of both malecot catheter and ureteric catheter in pelvis ( d ) ultrasound showing flower of malecot catheter opened in pelvis after the ureteric catheter and percutaneous nephrostomy is in place , the laparoscopic pyeloplasty is performed . once the pelvis is opened and the ureter spatulated , the ureteric catheter which is already coiled in the pelvis is passed under direct vision into the ureter after the posterior layer is completed following which the anastomosis is completed [ figure 6 ] . placement of ureteric splint under vision once the posterior wall is completed , the ureteric catheter is passed into the ureter under vision ureteric catheter is removed on the 3 post operative day and nephrostomy is clamped . the modified technique was successfully done in five patients aged less than one year old . a 7.5mhz ( b k medical , denmark ) ultrasound probe with puncture attachment is used . a pediatric probe is used for this purpose [ figure 1 ] . a 18 gauge echotip disposable two part trocar needle ( cook urological inc , indiana , usa ) which is available as a two part needle was used . a 0.035 guide wire or alternatively a terumo glide wire ( terumo corporation , tokyo , japan)with alken two part metallic needle helps simultaneously passing two guide / glide wires [ figure 1 ] . the dilatation is done with angiotech one step dilator ( pbn medicals , denmark ) , a14 fr nephrostomy tube ( devon innovations ( p ) ltd , parwanoo , hp , india ) with a 5 fr open end ureteric catheter ( devon innovations ( p ) ltd , bangalore , india ) is used . the armamentarium ( a ) telescopic metal two part needle ( b ) pediatric ultrasound probe the first step involves positioning the patient in a prone position , although the same can be done in supine position . line diagram ( a ) and picture ( b ) illustrating ultrasound - guided calyceal puncture the needle is housed in the needle attachment of the ultrasound probe and the posterior calyx identified [ figure 2 ] . the key for a successful ultrasound puncture is that the needle should be seen throughout the trajectory which includes the skin , subcutaneous tissue , cup of the calyx and the calyx in concern [ figure 3 ] . technique of ultrasound - guided access ( a ) an egress of clear fluid suggesting entry in the pelvicalyceal system ( b ) a successful ultrasound puncture - the needle should be seen throughout the trajectory which includes the skin , subcutaneous tissue , cup of the calyx and the calyx in concern an egress of clear fluid suggests entry in the pelvicalyceal system which can further be confirmed with a contrast study [ figure 3 ] . next a guide wire is parked in a distant calyx and the tract dilated up to 14 fr using a screw dilator . an alken needle , which is a two part needle , helps in passing a second guide wire after removing the inner stylet [ figure 4 ] . once both guide wires are in place , one wire is used for passing a ureteric catheter and the second one is used for placing a nephrostomy tube [ figure 5 ] . the salient feature of our technique is that all steps of percutaneous access which include access and dilation are done solely using ultrasound guidance . ( a ) the needle and guide wire are clearly seen in real time ultrasound , thus avoiding bowel injury ( b ) ( line diagram ) and c ( picture):-two glide wires passed into the renal pelvis through the telescopic metal two part needle after removing the inner stylet ( a ) line diagram showing completed anastomosis with nephrostomy and ureteric catheter ( splint ) in situ , ( b ) laparoscopic pyeloplasty performed after the ureteric catheter and percutaneous nephrostomy is in place c ) opened up renal pelvis showing presence of both malecot catheter and ureteric catheter in pelvis ( d ) ultrasound showing flower of malecot catheter opened in pelvis after the ureteric catheter and percutaneous nephrostomy is in place , the laparoscopic pyeloplasty is performed . once the pelvis is opened and the ureter spatulated , the ureteric catheter which is already coiled in the pelvis is passed under direct vision into the ureter after the posterior layer is completed following which the anastomosis is completed [ figure 6 ] . placement of ureteric splint under vision once the posterior wall is completed , the ureteric catheter is passed into the ureter under vision ureteric catheter is removed on the 3 post operative day and nephrostomy is clamped . the modified technique was successfully done in five patients aged less than one year old . the indications for stenting are well known , they include pyeloplasty in the presence of solitary functioning kidney , infection , or a previous failed procedure . placing a stent in a retrograde fashion involves urethral manipulation and the attendant complications ; in addition , this involves an additional procedure for removal of the stent . the advantages of stent placement following pyeloplasty include decreased risk of collection or edema , maintaining ureteric alignment woo et al . , in their study on the impact of internal stenting on the surgical outcome of dismembered pyeloplasty in infants under the age of 12 months with the open approach . they observed statistically significant increase in urinary leaks , length of hospital stay and need for repeat pyeloplasty in non stented versus the stented group . a variety of techniques have been described to place a stent or a splint antegrade thus avoiding the need for cystoscopy during insertion or removal . taveres et al describe a technique for inserting an internal - external nephroureteral antegrade stent during laparoscopic pyeloplasty which can be removed in clinic as outpatient . the advantages of the technique we have described are the following : 1)the ureteral access can be gained with ultrasound guidance . this minimizes the risk of bowel injury as well radiation in these patients.2)the nephrostomy tube acts as a safety valve and can be clamped to confirm the integrity of the anastomosis prior to its removal.3)if needed , the ureteric catheter can act as conduit to negotiate a ureteral stent across the anastomosis . the nephrostomy tube acts as a safety valve and can be clamped to confirm the integrity of the anastomosis prior to its removal . if needed , the ureteric catheter can act as conduit to negotiate a ureteral stent across the anastomosis . we acknowledge that there are a few disadvantages with this technique and the most significant is the need for additional equipment and expertise for gaining percutaneous renal access . in addition , at times , repeated attempts for gaining access lead to extravasation and oozing , which might hamper the vision and the anastomosis . in infants with pelviureteric junction obstruction when undergoing laparoscopic pyeloplasty ; ultrasound - guided antegrade nephroureteric , ureteric catheter placement is a safe technique . it avoids need for urethral manipulation for insertion and removal of stent , decreases radiation exposure to infant . furthermore , nephrostomy tube acts as a safety valve to confirm the integrity of anastomosis and ureteric catheter may act as conduit to put another ureteric stent if necessary at later date . this technique requires some additional equipments and expertise to get percutaneous renal access which can be mastered with practice .

background : access to urethras and ureters of infants may be hazardous and injurious through an endoscopic route . placement and removal of stents in infants requires anaesthesia and access through these small caliber urethras . we describe our technique of placing antegrade splint during a laparoscopic pyeloplasty in these infants.materials and methods : an ultrasound - guided percutaneous renal access is obtained . telescopic metal two part needle is passed into the kidney over a guide wire . a second guide wire is passed through the telescopic metal two part needle . the tract is dilated with 14 fr screw dilator . over one guide wire , a 5 fr ureteric catheter is passed and coiled in the renal pelvis . over the other wire , a 14 fr malecot catheter is placed as nephrostomy . laparoscopic pyeloplasty is then done . during pyelotomy , the ureteric catheter is pulled and advanced through the ureter before the pyeloplasty is completed . the ureteric catheter thus acts as a splint across the anastomosis . ureteric catheter is removed on the 3rd post operative day and nephrostomy is clamped . nephrostomy is removed on 4th post operative day if child is asymptomatic . the modified technique was successfully done in five patients aged less than one year old . all patients tolerated the procedure well . post operative period was uneventful in all.conclusion:ultrasound-guided ante grade nephroureteral ureteral splint for infant laparoscopic pyeloplasty is safe . it avoids the need for urethral instrumentation for insertion and removal of stents in these small patients .

glufosinate ammonium is one of the most widely used herbicides , which acts by inhibiting the synthesis of glutamine in plants ( 1 ) . given the differences in biochemical pathways and metabolism between plants and mammals , glufosinate ammonium formulations have been regarded as minimally toxic to humans and as safe products in agronomy , as long as they are handled according to the manufacturer 's instructions ( 2 ) . however , ingestion of undiluted glufosinate ammonium herbicide results in grave clinical outcomes ( 3 ) . in severe cases , patients either die or suffer severe toxic reactions ( 3 ) , such as shock , respiratory arrest ( apnea ) , unconsciousness , convulsions ( 4 ) , and amnesia ( 5 ) . to our knowledge , no study has shown sixth cranial nerve palsy as a neurologic manifestation in acute glufosinate ammonium intoxication . recently , we encountered a case of sixth cranial nerve palsy in a patient after acute glufosinate ammonium herbicide intoxication . here we describe the clinical features of glufosinate intoxication , while focusing on sixth cranial nerve palsy . a 34-yr - old man ingested 150 ml of glufosinate ammonium herbicide on november 06 , 2012 . formulation of the herbicide is as follows : glufosinate ammonium , 18% ; alcohol ( c12 - 14 ) , ethoxylated monoether with sulfuric acid , sodium salts ( cas no . 68909 - 66 - 0 ) as surfactants , 28.5% ; antifoaming agent and coloring agent , 0.5% ; and water , 53% . one hour after ingestion , gastric lavage was performed at the primary care clinic . at 5 hr after ingestion eleven hours after ingestion , the patient exhibited a stuporous mental state and was transferred to the toxicology center in our hospital . physical examination showed a blood pressure of 100/70 mmhg and pulse rate of 76 beats / min . initial laboratory findings , including complete blood cell count , liver function test , urea nitrogen , creatinine , and electrolytes , were within normal limits . about 1 hr after arrival at our emergency room , bronchial secretion increased and respiration become shallow with hypoxia ( arterial oxygen tension [ pao2 ] , < 70 mmhg ) and co2 retention ( arterial carbon dioxide tension [ paco2]>50 mmhg ) . tracheal intubation was performed and mechanical ventilation was initiated . according to the protocol for the management of large amounts of herbicide ingestion , a loading dose of an intravenous lipid emulsion ( ile ) was administered , and subsequently , the patient was maintained on lipid emulsion infusion . on the second day of the hospital stay , the patient exhibited drowsiness . in the intensive care unit , the patient was treated with hemoperfusion for extracorporeal elimination of toxic ingredients of the herbicide , and was put on mechanical ventilation for apnea . on the fifth day of the hospital stay , the patient underwent successful weaning trials and was extubated , after which he complained of double vision . ophthalmologic examination showed that he had esotropia ( 10 prism diopters ) , and the angle increased while gazing to the right and left . the lancaster red - green test ( 6 ) showed incomitant uncrossed diplopia at 9 different positions of gaze , and the deviation increased for both the right and left gaze ( fig . a second test performed 1 day later showed an improvement in the esodeviation with symptomatic relief . on the seventh hospital day , brain magnetic resonance imaging ( mri ) was performed to rule out organic disease . no structural abnormality was found , especially in the intracisternal , intracavernous , and intraorbital portions through which the sixth cranial nerve passes . in addition , diplopia and nystagmus intensity began to subside . on the ninth hospital day , the patient was discharged on the eleventh day without any ophthalmologic abnormality or abnormal blood chemistry results . the neurologic manifestations seen in the present case include mental change from stupor to drowsy , convulsions , respiratory arrest ( apnea ) , memory deficit , and sixth cranial nerve palsy associated with nystagmus . the patient recovered completely from all manifestations except memory deficit by the eleventh day of hospital stay . because of its long intracranial course , the sixth cranial nerve could be involved in microangiopathy , cerebral trauma , tumor , inflammation , and thrombosis in the sinus . systemic inflammations , such as herpes zoster ( 7 , 8) and infections caused by the epstein - barr virus ( 9 ) , cytomegalovirus ( 10 ) , and mycoplasma pneumoniae ( 11 ) , and immunization with attenuated live vaccines ( 12 , 13 ) , have been implicated in the development of sixth cranial nerve palsy . in the present case , moreover , no specific abnormality along the pathway of the sixth nerve was observed in the brain mri . taken together , these findings strongly suggest that sixth nerve palsy is one of the neurologic manifestations associated with acute glufosinate ammonium herbicide intoxication . to our knowledge , this is the first description of sixth cranial nerve palsy caused by glufosinate poisoning . although there is no direct evidence in the literature , many consider the toxic effects of surfactants used in herbicidal formulations as a possible cause ( 14 - 16 ) . we have also shown that surfactants in herbicides are more cytotoxic than the chief ingredient glyphosate ( 17 ) . furthermore , the toxic effects of surfactants and glyphosate are synergistic ( 18 , 19 ) . thus , we propose that the surfactants ( alcohol , ethoxylated mono ether with sulfuric acid , sodium salts ) used in the formulation of glufosinate ammonium herbicide are responsible for the neurologic manifestations , similar to those caused by the surfactants in glyphosate herbicides . despite this , the association between vulnerability of the nervous system and the suspected chemical remains unclear . in the present case , the skeletal muscles , liver , kidney , and heart were intact throughout the observation period . further studies are required to confirm this tissue - specific toxicity of the surfactant in glufosinate ammonium herbicide . in this case originally developed as a parenteral nutrition support agent , ile has received attention as a novel antidote for systemic toxicity caused by numerous drugs and toxic materials that are highly lipid - soluble , such as local anesthetics , calcium channel blockers , beta - adrenergic blockers , anti - arrhythmics , and herbicides ( 20 ) . the underlying mechanisms ascribed to ile include drug sequestration ( " lipid sink " ) and suppression of mitochondrial permeability transition , a key step in apoptosis ( 20 ) . since most commercial herbicide products are manufactured in combination with a surfactant that has a lipophilic nature , ile treatment could be an effective therapeutic modality in patients with acute herbicide intoxication ( 20 ) . the recommended protocol for its use is an initial bolus of 20% ile ( 1.5 ml / kg of lean body mass ) followed by a maintenance infusion of 0.25 - 0.5 ml / kg / min ( 20 ) . in conclusion , clinicians should give attention to apnea , mental deterioration , and neurologic manifestations in patients with acute intoxication of surfactant - containing glufosinate ammonium herbicide .

although glufosinate ammonium herbicides are considered safe when used properly , ingestion of the undiluted form can cause grave outcomes . recently , we treated a 34-yr - old man who ingested glufosinate ammonium herbicide . in the course of treatment , the patient developed apnea , mental deterioration , and sixth cranial nerve palsy ; he has since been discharged with full recovery after intensive care . this case report describes the clinical features of glufosinate intoxication with a focus on sixth cranial nerve palsy . our observation suggests that neurologic manifestations after ingestion of a " low - grade toxicity herbicide " are variable and more complex than that was previously considered .

ichthyosis is a defect of keratinization presenting as dry , rough skin with scaling over much of the body . ichthyosis hystrix is a type of congenital ichthyosis that clinically resembles epidermolytic hyperkeratosis with massive spiky or verrucous hyperkeratosis , erythema without blistering , mainly over the extensor aspect of the arms and legs . often the severity varies among the family members from only palmoplantar keratoderma to generalized involvement . palmoplantar keratoderma affects most of the patients and may be so severe that contracture , fissuring , nail dystrophy , or functional impairment may occur . with age , scaling may improve or stabilize . we are reporting this case of ichthyosis hystrix due to its atypical presentation with severe involvement of face and scalp , skip areas over trunk , onychogryphosis of most of the nails , and a negative family history . a 46-year - old male patient presented with generalized severely thick skin since early childhood . according to his mother he gradually developed thickening of skin with adherent scales starting from face and progressively involving other parts of the body . he had hyperkeratotic , thick , dry , adherent , mud - colored scales covering most of the body especially the face , scalp , and extremities including the flexures . facial skin was so thickened and rugose that it became expressionless giving him a masked appearance [ figure 1 ] . his trunk was least involved with islands of normal skin [ figure 2 ] . both , follicular prominence and atrophy were seen over the flexures of the forearm . hairs were sparse and less over occipital area as it was covered with thick scale . most of the teeth were absent and canine was peg - shaped [ figure 1 ] . subungual hyperkeratosis and prominent onychogryphosis were found in most of the nails [ figure 3 ] . on histopathology , we found orthokeratotic hyperkeratosis with sparse parakeratosis , irregular acanthosis , follicular plugging , and multiple binucleated keratinocytes in the epidermis along with upper dermal lymphocytic infiltrate , suggestive of ichthyosis [ figure 4 and 5 ] . on the basis of clinical features and histopathology thick confluent scales over face with teeth abnormalities areas of normal looking skin over trunk with flexural involvement onychogryphosis involving most of the finger nails hyperkeratosis , parakeratosis , acanthosis with upper dermal infiltrates ( h and e , 100 ) multiple binucleated keratinocytes in the epidermis ( h and e , 400 ) ichthyosis hystrix is a type of congenital ichthyosis associated with many rare conditions and presenting as generalized and nevoid forms . it was first documented in between 1731 and 1851 in the lambert family of suffolk . in addition to the extensors , flexures , and other sites of the body including scalp may be involved by mild scaling . palmoplantar keratoderma affects most patients and often extend to the dorsal hands and when it is severe ; fissures , contractures , nail dystrophy , and functional impairment may occur . patient may present at birth or there may be a delayed onset in infancy or childhood . our patient presented with a childhood onset of generalized severely thickened mud - colored verrucous hyperkeratosis including involvement of flexures with severe palmoplantar keratoderma without any contracture or functional impairment . his face was affected the most and over trunk we found a few spared areas with normal looking skin . his scalp was also involved with very thick scales and loss of hair at the occipital area . ichthyosis hystrix includes brocq , lambert , curth - macklin , rheydt and bfverstedt types . in lambert type , patients are alright at birth but develop dark warty scaling at the age of 7 weeks or later and face , palm , and soles were spared in those patients . bfverstedt type was reported by bfverstedt which was ichthyosis with striking hystrix scaling on the face . patients presenting with severe palmoplantar keratoderma are diagnosed as ichthyosis hystrix of curth - macklin type . porcupine spine or symmetrical hystrix with scaling of dull brown color over extensor aspect of limb , trunk is also seen in the above type . connexin 26 defect causing hystrix - like ichthyosis deafness ( hid ) syndrome is a variant of ichthyosis hystrix which is also known as rheydt type . histopathology of epidermis shows severe orthohyperkeratosis , patchy parakeratosis , acanthosis , and papillomatosis with scattered vacuolated and binucleate keratinocytes . in our case we also found hyperkeratosis , a small area of parakeratosis , acanthosis , and multiple binucleated keratinocytes . treatment of severe generalized cases is difficult . as was advised in our patient , keratolytics and emollients we decided to report this case because of a few atypical features in the form of childhood onset , severe involvement of scalp , face and flexures , dental abnormalities , and severe nail involvement without contractures ; and to the best of our knowledge , after extensive search in literature , this is the second case ( first case was reported in indian journal of dermatology in 1975 ) to be reported from india . to the best of our knowledge it is only the second case being reported from india.our case also has unusual presentation of facial involvement along withflexural and scalp involvement.the patient also had associated nail involvement in the form of onychogryphosis . to the best of our knowledge

ichthyosis hystrix is a term used to describe an ichthyosiform dermatosis which is characterized by hyperkeratotic spiny scales mainly over extensor aspects of limbs with palmoplantar keratoderma and occasionally associated with deafness and neurological deficit . it is a rare autosomal dominant form of ichthyosis and very few cases are reported in literature . we are presenting a 46 years - old - male patient of ichthyosis hystrix with unusual presentation . he had lesions mainly over the face and scalp with palmoplantar keratoderma and significant nail changes .

there are certain prognostic factors to determine the neurological outcome of the patients in spinal cord injury ( sci ) . etiology , severity of trauma , and preoperative neurological condition are the most important factors influencing the prognosis . patients with a complete sci have a < 5% chance of neurological recovery whereas the prognosis is much better for the patients with an incomplete sci . on the other hand , there is no consensus about the association between the severity of the sci and the radiological characteristics of the fracture . it is well known that posttraumatic neurological condition of the patient is the most important factor determining the extent of the neurological improvement which is the main goal of the treatment . to reach this aim , we need to evaluate radiology of the fractured vertebra and correlate this to the neurological condition of the patient . by assessing the morphology of the fracture , it might be possible to determine the severity of the injury and to identify the patients who would have a chance of neurological recovery . sagittal index ( si ) , canal compromise ( cc ) , and loss of vertebral body height ( lvbh ) are the most accepted measurement techniques to assess the radiological characteristics of thoracolumbar burst fractures . each measurement technique has certain limitations when evaluated individually . to make a more comprehensive evaluation , it might be useful to measure si , cc , and lvbh together and search for their correlation to the degree of neurological injury . for this reason , we calculated the si , cc , and lvbh in thoracolumbar burst fractures and aimed to determine whether- and to what extent these 3 parameters are associated with the severity of neurological injury . seventy - four patients with thoracolumbar burst fracture undergoing thoracolumbar instrumentation between 2010 and 2015 were analyzed retrospectively . all of the patients underwent a transpedicular screw fixation of 2-level above and 2-level below the fractured vertebra . patients with multisegmental fractures , pathological or osteoporotic fractures , and patients with ankylosing spondylitis were excluded from the study . magnetic resonance ( mr ) imaging scans of the patients were analyzed . to identify the morphology of the injury ; si , cc , and lvbh were calculated as proposed in the literature . mid - sagittal t2-weighted mr images were used to determine the si as proposed by farcy et al . , si was calculated as the kyphotic deformity at the fracture motion segment level minus the normal contour ( baseline value ) . an angle of 5 in the thoracic , 0 at the thoracolumbar junction , and 10 in lumbar region were considered baseline values [ figure 1 ] . si was classified as either < 20 and 20. mid - sagittal t2-weighted magnetic resonance image showing the calculation of the sagittal index . the sagittal index was calculated as the kyphotic deformity at the fractured motion segment level minus the normal contour ( baseline values ) . an angle of 5 in the thoracic , 0 at the thoracolumbar junction , and 10 in lumbar region were considered baseline values mid - sagittal t2-weighted mr images were used to measure the cc as originally described by fehlings et al . for cervical spine and applied to the thoracolumbar region by vaccaro et al . the percentage of the cc was calculated using the narrowest mid - sagittal diameter of the spinal canal at the level of fractured vertebra , and the average mid - sagittal diameters of the spinal canal at one level above and below the fractured vertebra [ figure 2 ] . the percentage of the canal compromise was calculated using the ratio of the narrowest mid - sagittal diameter of the spinal canal at the level of fractured vertebra to the average mid - sagittal diameter of the spinal canal at one level above and below the fractured vertebra mid - sagittal t2-weighted mr images were used to measure the lvbh as proposed by keene . the percentage of the lvbh was calculated using the anterior height of the injured vertebra and the mean of the anterior height of the adjacent two intact vertebrae [ figure 3 ] . lvbh was classified as either < 50% and 50% as suggested by mcafee et al . all measurements were done by two separate neurosurgeons , and the means were recorded to minimize the measurement errors . mid - sagittal t2-weighted magnetic resonance image showing the calculation of the loss of vertebral body . the percentage of the loss of vertebral body height was calculated using the ratio of the anterior height of the injured vertebra to the mean of the anterior height of the adjacent two intact vertebrae for the combined measurement , the patients were divided into two groups based on their si , cc , and lvbh values . group 1 included the patients with si 20 , cc 40% , and lvbh 50% . group 2 included the patients with si < 20 , cc < 40% , and lvbh < 50% . the international standards for neurological classification of sci , published by the american spinal injury association ( asia ) and revised in 2011 , was used to identify the neurological conditions of the patients . the degree of neurological injury was determined based on their asia scores on admission to the emergency department . the terms normal neurological function , neurologically intact , and no lesion were used for asia e whereas lesion was used for asia a , b , c , and d. the term complete sci was used for asia a whereas incomplete sci was used for the scores in between ( asia b , c , and d ) . the term high score was used for asia a , b , c , and d whereas low score was used for asia e. for scoring , neurological examination notes of both emergency department and the neurosurgeons were taken into consideration . statistical analysis was performed using number cruncher statistical system ( ncss ) 2007 statistical software ( ncss llc , kaysville , utah , usa ) . association between the radiological measurements and asia scores was measured using the fisher - freeman test and yates continuity correction . considering the inclusion criteria , 74 patients met the criteria ( 47 males and 27 females ) with a mean age of 45.8 years ranging from 16 to 81 years . si was > 20 in all of the patients with asia a , b , c , and d ( lesion ) . however , si was < 20 in 79% of the patients with asia e ( p = 0.001 ; p < 0.01 ) [ table 1 ] . the association between the si and the severity of neurological injury was significant with 100% sensitivity , 79% specificity , 77.5% positive predictive value , 100% negative predictive value , and 87.8% accuracy [ table 2 ] . the association between sagittal index , canal compromise , loss of vertebral body height and asia scores statistical characteristics of the measurements and their association with the severity of neurological injury cc was > 40% in all of the patients with asia a , b , c , and d ( lesion ) . however , cc was < 40% in 83.7% of the patients with asia e ( p = 0.001 ; p < 0.01 ) [ table 1 ] . the association between the si and the severity of neurological injury was significant with 100% sensitivity , 83.7% specificity , 81.5% positive predictive value , 100% negative predictive value , and 90.5% accuracy [ table 2 ] . lvbh was > 50% in all of the patients with asia a , b , c , and d ( lesion ) and < 50% in all of the patients with asia e ( p = 0.001 ; p < 0.01 ) [ table 1 ] . the association between the si and the severity of neurological injury was significant with 100% sensitivity , 100% specificity , 100% positive predictive value , 100% negative predictive value , and 100% accuracy [ table 2 ] . combining these three variables together , of the patients in group 1 ( si 20 , cc 40% and lvbh 50% ) , 70.4% had a high asia score ( asia a , b , c , d ) . similarly , of the patients in group 2 ( si < 20 , cc < 40% , and lvbh < 50% ) , all had a low asia score ( asia e ) ( p = 0.001 ; p < 0.01 ) [ table 1 ] . there is a strong association between fracture morphology ( high scores of ss , cc , and lvbh ) and the severity of neurological with 100% sensitivity , 69.7% specificity , 70.4% positive predictive value , 100% negative predictive value , and 82.4% accuracy [ table 2 ] . the thoracolumbar spine , which generally refers to the t11-l2 spinal segments , is located at the junction of two physiological spinal curvatures . since this region is the most mobile region , these spinal segments are particularly vulnerable to fractures . there is no consensus regarding the exact cause of neurologic deficits in thoracolumbar burst fractures . there is a general agreement that sci occurs at the time of trauma , but the debate still exists about the role of secondary factors such as persistence of a bone fragment compressing the spinal cord , segmental kyphosis , or compression of vertebral body . considering the anatomy and biomechanics of the vertebral column and spinal cord , segmental kyphosis , cc , and loss of height of vertebral body are among the leading factors playing role in sci . pointed out that thoracolumbar burst fractures with severe kyphosis have a better prognosis , in case the restoration of the sagittal alignment of the spinal column is achieved . si is the measurement of segmental kyphosis at a mobile segment of spinal column including 1 vertebra and 1 disc . they assessed si , instability grade , and neurologic status of the patients at injury and after treatment . surgical management was suggested for the patients with si > 15. in our series , the patients with si > 20 had a higher rate of neurological deficit ( p < 0.05 ) , 77.5% of them having lesion according to the asia classification system ( asia a , b , c , d ) . on the other hand , of the patients with asia e , 79% had a si < 20 ( p < 0.05 ) . the association between the si and the severity of neurological injury was significant with 87.8% accuracy . one of the most important factors leading to neurological deficit is believed to be the invasion of the spinal canal by the retropulsed bony fragments . hashimoto et al . reported a strong association between narrowing of the spinal canal and the level of the neurological injury . found a certain correlation between asia score and the amount of cc in thoracolumbar burst fractures . in our series , the patients with cc > 40% had a higher rate of neurological deficit ( p < 0.05 ) , 81% of them having lesion according to asia classification system ( asia a , b , c , and d ) . on the other hand , of the patients with asia e , the association between the cc and the severity of neurological injury was significant with 90.5% accuracy . emphasized a certain association between asia scale and loss of the height of vertebral body . studied experimental burst fractures of the l1 vertebrae of human cadaveric thoracolumbar spine and showed a significant correlation between the lvbh and the canal encroachment . in our series , the patients with lvbh > 50% had a higher rate of neurological deficit ( p < 0.05 ) , all of them having lesion according to asia classification system ( asia a , b , c , and d ) . on the other hand , of the patients with asia e , all had an lvbh < 50% ( p < 0.05 ) . the association between the lvbh and the severity of the neurological injury was significant with 100% accuracy . as seen from the relevant literature , association between fracture morphology ( si , cc , and lvbh ) , and the degree of neurological damage remains controversial . some authors suggest that the canal encroachment by bony fragments adds to the neurological damage while others report no correlation between the cc and neurological damage . although some authors reported an association between lvbh and neurological status of the patients , whereas some authors have found no such correlation . in our series , we combined these 3 parameters and detected that there is a strong association between this combination and the severity of neurological injury . the severity of neurological injury increases as long as the degree of si , the amount of cc , and the amount of lvbh increase . in other words , ss , cc , and lvbh were lower in patients with lower asia scores ( asia e ) whereas they were higher in patients with higher asia scores . there is a strong association between si , cc , and lvbh , and the severity of neurological injury in thoracolumbar burst fractures undergoing instrumentation . the patients with si > 20 , the patients with cc > 40% , and the patients with lvbh > 50% are likely to have a more severe neurological injury .

aim : our aim was to determine whether a combination of sagittal index ( si ) , canal compromise ( cc ) , and loss of vertebral body height ( lvbh ) is associated with the severity of neurological injury in patients with thoracolumbar burst fractures.materials and methods : seventy - four patients with thoracolumbar burst fracture undergoing instrumentation between 2010 and 2015 were analyzed retrospectively . the degree of neurological injury was determined using the american spinal injury association ( asia ) scoring system . the association between the morphology of the fracture and the severity of neurological injury was analyzed.results:there was a strong association between fracture morphology and the severity of neurological injury . of the patients , 77.5% with si 20 , 81.6% with cc 40% , and 100% with lvbh 50% had lesion according to asia . all of 7 patients with asia a had si 20 , cc 40% , and lvbh 50% . on the other hand , 79% of the patients with asia e had si < 20 , 83.7% of the patients with asia e had cc < 40% , and all of the patients with asia e had lvbh < 50% . si , cc , and lvbh were lower in neurologically intact patients ( asia e ) , whereas they were higher in patients with neurological deficits ( asia a , b , c , d ) ( p = 0.001 ; p < 0.01 ) . these measurements had 100% negative predictive values and relatively high positive predictive values.conclusion:si , cc , and lvbh are significantly associated with the severity of neurological injury in patients with thoracolumbar burst fractures . the patients with si > 25 , the patients with cc > 40% , and the patients with lvbh > 50% are likely to have a more severe neurological injury .

less commonly , this condition presents in teenagers and young adults often with less aggressive features.4 coats disease is a major simulator of retinoblastoma , a life - threatening pediatric ocular malignancy.14 in a study of angiographic findings of patients with coats disease , we noticed that occlusion of the retinal microvasculature with peripheral nonperfusion and shunt or microshunt formation between arterioles and venules in the retina was a prominent finding.5 this led to a speculation regarding serum factors that could lead to the microocclusions , such as a hypercoagulability state . realizing that such a state would more likely lead to bilateral manifestations , we continued to explore serum features in coats disease . in 2012 , we found a significantly high level of anti - cytomegalovirus ( cmv ) immunoglobulin g ( igg ) in 92% of coats patients , higher serum proteins c and s , anti - herpes simplex virus ( hsv ) igg i / ii , alpha-2 globulin , and homocysteinemia in patients with coats disease.6 in the second step of the analysis , it was planned to compare these factors in patients with coats disease with a control group . herein , we evaluated serum hypercoagulable factors and viral and protozoan diseases in patients with coats disease versus normal controls . a prospective , single - center , comparative , consecutive cross - sectional study was conducted for evaluating blood hypercoagulability state and infectious diseases , including cmv , herpes simplex , epstein - barr virus ( ebv ) , toxoplasma and toxocara infections , in all patients with coats disease from february 2011 to december 2013 . the research adhered to the tenets of the declaration of helsinki and the study was approved by tehran university of medical sciences institutional review board . each patient or parents were carefully informed about the purpose of the research , and oral consent for laboratory examinations was obtained . each patient or coats disease was defined as unilateral or bilateral retinal vasculopathy characterized by retinal telangiectasia , capillary non - perfusion , multiple aneurysmal formation , exudation , and exudative retinal detachment.19 patients with coats disease were grouped into those aged 10 years or less versus those older than 10 years . clinical factors were compared to a control group , which consisted of patients with cataract undergoing lensectomy for congenital , traumatic , or senile cataract , with no evidence of retinal vascular disease . patients were evaluated with best - corrected visual acuity , indirect ophthalmoscopy for fundus features and color fundus photography , fluorescein angiography , and b - scan echography as needed . fluorescein angiography was performed using a scanning laser ophthalmoscope ( hra , heidelberg , germany ) or retcam 120 ( clarity medical systems , inc . , the blood sample for serum studies was obtained from patients immediately before the treatment of coats disease . treatment options included cryotherapy , photocoagulation , and intravitreal antivascular endothelial growth factor and/or subtenon triamcinolone depending on the patient s condition . serum studies included hemoglobinopathies by hemoglobin electrophoresis ; serum protein electrophoresis ; coagulable states by serum protein c , protein s level , antiphospholipid antibody , anticardiolipine antibody , antithrombin iii , homocysteine level , and lipid profile ; and infectious states by anti - hsv igg , anti - cmv igg , anti - epv , anti - toxoplasma and anti - toxocara serum antibodies were measured with a enzyme - linked immunosorbent assay ( elisa ) technique according to the manufacturer s protocol . statistical analyses were performed using statistical package for social sciences ( v 17.0 ; spss , chicago , il , usa ) . all data are presented as mean standard deviation ( sd ) or median ( range of data ) . a mann whitney test was used for quantitative or skewed distributed parameters . to assess the relationship between the qualitative variable and coats diagnosis , fisher s exact test was applied . logistic regression models were used to assess the relation of target exposure with coats diseases adjusting for possible confounding factors . statistical analyses were performed using statistical package for social sciences ( v 17.0 ; spss , chicago , il , usa ) . all data are presented as mean standard deviation ( sd ) or median ( range of data ) . a mann whitney test was used for quantitative or skewed distributed parameters . to assess the relationship between the qualitative variable and coats diagnosis , fisher s exact test was applied . logistic regression models were used to assess the relation of target exposure with coats diseases adjusting for possible confounding factors . a p - value of less than 0.05 was considered to be statistically significant . during the study period , there were 22 patients with coats disease ( figure 1 ) and 19 control patients . of those with coats disease , 13 were 10 years or younger and 9 were older . ( table 1 ) . the mean age for coats patients was 14.5 years ( median 8 years , range : 2 month to 59 years ) , and for the control group it was 30 years ( median 17 years , range : 282 years ) ( table 2 ) . for those 22 patients with coats disease , the mean time from the first notice of the disease by patients ( or parents ) to diagnosis was 7.15.4 months in the younger age group ( 10 years old ) and 7.89.9 months in the older age group ( > 10 years old ) . there were three ( 13.6% ) with bilateral involvement . using the coats disease classification,4 the conditions of the eyes were classified as stage 1 ( n=0 ) , stage 2 ( n=7 ) , stage 3 ( n=12 ) , stage 4 ( n=3 ) , and stage 5 ( n=0 ) . total retinal detachment was seen in six ( 28% ) cases , whereas macular detachment was seen only in three ( 14% ) cases . in two using fluorescein angiography , avascular non - perfused areas were found in 18 ( 82% ) cases , located in the periphery region in 10 ( 46% ) and in the macular region in 2 ( 9% ) ( table 1 ) . the first step of analysis was a comparison of the two age groups of coats disease ( 10 years vs > 10 years ) . this revealed no significant difference in the lipid profile , serum antithrombin iii , anticardiolipine and antiphospholipid antibody serum antibody titer as well as polymerase chain reaction test for toxoplasma , toxocara , or ebv in the two groups . there was statistical difference ( mann whitney test - skewed deviation ) in the two groups with regard to hemoglobin ( p=0.02 ) , serum anti - hsv igg ( p=0.05 ) , anti - cmv igg ( p=0.05 ) , protein c ( p=0.07 ) , homocysteine ( p<0.01 ) , serum alpha-2 globulin ( p<0.01 ) , and serum gamma globulin ( p=0.05 ) . due to the small sample size in each age group , the logistic regression analysis was inconclusive . the second step of analysis involved comparison of laboratory findings in coats disease versus the normal control group ( table 2 ) . there was no significant difference in the lipid profile , serum antithrombin iii , anticardiolipine , and antiphospholipid antibody serum antibody titer as well as polymerase chain reaction for toxoplasma , toxocara , or ebv . however , in the control group , the serum titer of anti - hsv igg was higher and that of anti - cmv igg was lower . in coats group , serum beta globulin was significantly higher in both young ( 10 years , p<0.001 ) and old ( > 10 years , p=0.05 ) subgroups compared to controls . applying bonferroni correction did not change the results of serum beta globulin in the group less than 10 years old . logistic regression analysis for the main serologic findings in coats patients ( irrespective of age ) and control group was performed . after adjustment for age and sex , a significant association persisted for the presence of higher titer of serum beta globulin in coats disease compared to controls ( odds ratio [ or ] : 1.8 , 95% confidence interval [ ci ] : 1.03.1 , p=0.02 ) ( table 3 ) . anti - hsv showed a mild negative impact ( p=0.01 , or = 0.94 ) on the diagnosis of coats disease . after adjusting for age and sex , in those less than 10 years , the serum beta globulin was found to be significantly associated with the diagnosis of coats disease ( or : 6.3 , 95% ci : 1.232.6 , p=0.02 ) . in patients greater than 10 years with coats disease , there was a non - significant association with the diagnosis of coats disease ( or : 1.3 , 95% ci : 0.82.0 , p=0.24 ) . for the older age , anti - hsv antibody was borderline significant ( or : 0.98 , 95% ci : 0.971.00 , p=0.05 ) . the small sample size precluded more conclusive results in the logistic regression analysis , adjusting for all other covariates . in this study , we could not find any association between hypercoagulability state and coats disease ( compared to controls ) . the only factor associated with coats disease was elevated serum beta globulin mainly in the younger age group . we also recognized the negative impact of anti - hsv antibody on coats disease in the older age group . serum protein electrophoresis is a technique to assess the two major fractions of protein in blood , including albumin and globulins.10 albumin is a transport protein that plays a significant role in fat solubility.11 the globulin fraction of blood includes hundreds of serum proteins , including carrier proteins , enzymes , complement , and immunoglobulins . globulins are divided into four groups by electrophoresis : alpha , alpha-2 , beta , and gamma , depending on their migratory pattern between the anode and the cathode of the electrophoresis test.11 the beta fraction of serum globulins is known to have two peaks , named as beta 1 and beta 2 . beta 1 is composed of mostly transferrin , and beta 2 contains beta - lipoprotein.12 iga , igm , and sometimes igg , along with complement proteins ( c3 ) , beta-2 microglobulin , plasminogen , angiostatins , properdin , sex hormone - binding globulin , transferrin , hemopexin , and factor h , can also be identified in the beta fraction.1012 these proteins carry out numerous biological functions in the human body , including iron transport and monitoring immune response.10,11 beta globulin protein can be elevated or depressed in various diseases . beta globulin is found to be elevated in iron deficiency anemia , hypercholesterolemia , pregnancy , estrogen therapy , and also substantially increased in liver disease.9,10,13,14 it is found to be decreased in malnutrition , cirrhosis , and immune deficiency due to decreased synthesis , and in nephrotic syndrome due to protein loss in the kidney.11 in this series of coats disease , the beta globulin fraction was elevated , which is particularly evident in patients lesser than 10 years . this age - related difference could correlate with milder manifestations of coats disease in older patients . the relationship of this fraction with coats disease is unclear , but could correlate to higher c3 ( complement protein 3 ) level or other factors . complement 3 is an important protein in the immune system , which plays a vital role in the acute phase response . it controls several biological processes , including cell lysis , chemotaxis , anaphylaxis , vascular permeability , and cellular membrane adhesion . this protein is categorized as a beta globulin and might represent the elevation of beta globulin in coats disease in this report.12,1518 chronic low - grade inflammation has been correlated with elevated c - reactive protein , as well as complement c3 plasma levels , and these can be predictive of arterial thrombotic events.1620 elevated c3 is also associated with prolonged fibrinolysis.18,2123 both of these roles could relate to the vascular pathology of coats disease . the discrepancy found in the younger and older age groups could suggest a difference in the main pathophysiological basis of coats disease in children and adults . there are limitations of this study , including the small sample size and unclear relevance of beta - globulin relationship to the condition studied . this relationship could be further explored with larger cohort and more precise fractionation of the beta - globulin subgroup to better understand the exact protein(s ) that contribute to this finding and its relationship to coats disease . this analysis demonstrated that children with coats disease showed elevated serum levels of beta globulin . we speculate that this finding could reflect the known fluorescein angiographic - evident ischemic component and possibly now a low - grade inflammatory component .

purposethe purpose of this study was to investigate the serum hypercoagulability state and common viral and protozoan infections in coats disease versus a normal control group.materials and methodsin this comparative case series , 22 consecutive patients with coats disease and 19 non - coats patients undergoing lensectomy for congenital , traumatic , or senile cataract between january 2011 and june 2014 were included . laboratory data for hypercoagulability states and common viral and protozoan infections were investigated.resultsthe mean age for the coats group was 14.5 years ( median 8 years , range : 2 months to 59 years ) , and for the control group it was 30.6 years ( median 17 years , range : 282 years ) . in patients aged 10 years or younger , anticytomegalovirus immunoglobulin g ( igg ) ( p0.01 ) , homocysteine ( p=0.03 ) , and serum beta globulin ( p<0.001 ) were associated with coats disease . in those older than 10 years , higher serum protein s ( p=0.04 ) , beta globulin ( p=0.05 ) , and gamma globulin ( p=0.04 ) were related to coats diagnosis . after adjusting for sex and age as confounding factors , only beta globulin was found to be associated with coats disease in logistic regression analysis ( odds ratio : 1.8 , 95% confidence interval : 1.03.1 , p=0.02).conclusionserum beta globulin levels appear to be elevated in patients with coats disease .

lipomas arise from adipocytes and are generally found in subcutaneous tissue of the proximal extremities and trunk . gastrointestinal ( gi ) lipomas are rare , benign , slowly growing , submucosal tumors , which can either be incidentally found as silent tumors of the gi tract or be the cause for gi bleeding , anemia , intussusception , and bowel obstruction . most of them are located in the colon , ileum , and jejunum , and are rarely found in the duodenum . gastrointestinal lipomas are typically found in patients who are in their fifth or sixth decade of life . although endoscopy was most helpful in establishing the diagnosis on the basis of their morphologic characteristics , surface inflammation and inadequate biopsy specimen often lead to confused diagnosis . endoscopic ultrasonography usually shows a homogenous , hyperechoic mass within the submucosal layer which is highly characteristic , while computed tomography ( ct ) examination is highly specific for the detection of fat , and identification for adipose density within the lesion convincingly narrows the differential diagnosis to lipoma , liposarcoma , hamartoma . duodenal lipomas manifest as homogenous adipose density in the literatures and there is no report about duodenal lipoma accompanying with ectopic duodenal glands so far . a 68-year - old woman experienced black stool three times over a period of 9 months and was admitted to our hospital for further investigation of recurrent gastrointestinal bleeding . the hematological and biochemical profiles were normal , including carcino - embryonic antigen , carbohydrated antigen 19 - 9 and alpha feto - protein . the patient underwent endoscopic examination and was found to have a large , lobulated , soft mass in the second portion of the duodenum . the polypoid mass measured 343 cm in size , and was covered with normal mucosa ( figure 1 ) . abdominal ct scan revealed a well - circumscribed adipose mass with heterogeneous density ( indicating a part density equivalent to fat ) at the second part of the duodenum ( figure 2 and 3 ) , leading to the diagnosis of intraluminal lipoma of the duodenum with suspected malignant transition . due to the large size and suspicion of partial malignant transition , histological examination demonstrated the tumor was predominantly composed of mature fat cell and combined with duodenal glands within the mass ( figure 4 ) . the patient had an uneventful recovery and was in good condition on the follow - up of 18 months . endoscopy showing a lobulated mass with smooth surface . figure 2coronary reconstruction image showing inhomogenous high density within adipose mass . coronary reconstruction image showing inhomogenous high density within adipose mass . sagittal reconstruction image showing inhomogenous high density within adipose mass . figure 4histologic examination showing a duodenal lipoma under a normal duodenal mucosal layer with ectopic duodenal glands ( hematoxylin - eosin stain , 4x and 10x ) . histologic examination showing a duodenal lipoma under a normal duodenal mucosal layer with ectopic duodenal glands ( hematoxylin - eosin stain , 4x and 10x ) . lipomas arise from adipocytes and are generally found in subcutaneous tissue of the proximal extremities and trunk . lipomas may occur in all parts of the gastrointestinal tract from the esophagus to the rectum . lipomas are rarely found in the esophagus , stomach , and duodenum . a study by mayo et al . showed that out of 4000 cases of benign gastrointestinal tumors , 164 ( 4% ) were lipomas . the site most common was the colon ( 64% ) , followed by small intestine ( 26% ) , duodenum ( 4% ) , stomach ( 3% ) and oesophagus ( 2% ) . in the duodenum , lipomas tend to be noted mostly in the second part and are most often situated in the submucosal plane , but can also be subserosal and can be sessile or pedunculated . most of these patients with duodenal lipoma are asymptomatic , less than one - third are symptomatic . lesions of less than 1 cm remain occult , where virtually all lipomas larger than 4 cm are symptomatic . the common symptoms of pain and bleeding are related to complications of obstruction , intussusception and hemorrhage . the present case had no other symptoms except for episodic bleeding and weight loss , the tumors were finally found due to searching for aetiology of gastrointestinal bleeding through endoscopy . duodenal lipomas are benign submucosal masses . on the endoscopic appearance , duodenal lipomas manifest as smooth masses with normal overlying mucosa or sometimes ulceration that might lead to a mistaken impression of carcinoma . ct examination is highly specific and sensitive for the detection of fat , and the presence of fat within a lesion strongly suggests a benign etiology , such as a lipoma , hamartoma or teratoma . the combination of fat and calcification within a lesion is essentially pathognomonic for a hamartoma or teratoma . however , in our case heterogeneous fat density lacking calcification confused us and exploratory laparotomy had to be performed . those hyperdense tissues arise from the ectopic duodenal glands basing on the pathological findings of the resected tumor . these new recognitions for this rare disease entity have not been reported in the literatures . the recommended treatment is endoscopic excision if the lesion is polypoid and of manageable size . however , for large , sessile lesions or suspected malignant transition endoscopic excision may prove technically difficult and increase the risk of bleeding and perforation , surgical excision would be the preferred approach in such cases . in our case , due to the broad - base and suspicion of partial malignant transition , they can be suspected on endoscopic examination but may require ct or endoscopic ultrasonography for further evaluation . endoscopic excision is the treatment of choice if the tumor is pedunculated or relatively small , but for those cases associated with large - sized or suspected malignant transition , open surgical excision is the preferred choice .

duodenal lipomas are relatively uncommon and are rarely responsible for clinical symptoms . occasionally , searching for aetiology of gastrointestinal bleeding leads to the final diagnosis of duodenal lipomas . here , we present the case of a 68-year - old woman who suffered with repeated melena and weight loss . endoscopy , abdominal computed tomography ( ct ) and histopathological outcomes are described in this case of duodenal lipoma with ectopic duodenal glands .

in recent years , mannanases ( 1,4--d - mannan mannohydrolase , ec 3.2.1.78 ) have gained increasing attention because of their various biotechnological applications in the food , feed , coffee extraction , oil drilling , detergent , as well as pulp and paper industries [ 14 ] . they can also be used in the production of mannooligosaccharides , which were reported to be excellent prebiotics stimulating growth of beneficial intestinal microorganisms [ 5 , 6 ] . mannanases from fungi such as aspergillus species [ 3 , 7 , 8 ] , trichoderma reesei , sclerotium rolfsii , and penicillium occitanis have been well described . these included locust bean gum ( lbg ) , guar gum , konjac flour , and copra meal [ 3 , 14 ] . the main purpose of employing this fermentation method was to remove the repressive effects of a rapidly utilized carbon source , to reduce the effect of toxic medium constituents and to extend the process product formation stage as long as possible . penicillium occitanis was previously described as an outstanding producer of cellulolytic and hemicellulolytic enzymes [ 11 , 16 ] . the production of cellulase by this strain under fed - batch culture was also studied . however , there are very few reports on fed - batch fermentation for efficient mannanase production . the aim of the present study was to develop a fed - batch process for enhanced production of mannanase by p. occitanis using acacia seeds as a novel inducer of substrate . the penicillium occitanis mutant pol6 was supplied by cayla co. ( toulouse , france ) . locust bean gum ( lbg ) was procured from sigma ( st . louis , mo , usa ) . samples of acacia were collected during april - may , in 2010 , from sfax ( tunisia ) . the dried seeds were transferred to a mortar , crushed with a pestle , and sieved with a standard 0.5 and 1 mm sieves to obtain two different particle sizes ( p1 ( < 0.5 mm ) and p2 ( 0.5 - 1 mm ) ) . mandels and weber 's medium modified by ellouz chaabouni et al . was used for the production of -mannan - degrading activity of p. occitanis pol6 . its composition was ( g / l ) kh2po4 , 2 ; nano3 , 5 ; mgso47h2o , 0.3 ; cacl2 , 0.3 ; yeast extract , 1 g ; tween 80 , 1 ml / l ; trace elements solution , 1 ml / l . the trace elements solution contained ( in g / l ) cocl2 , 2 ; mnso4h2o , 1.6 ; znso4 h2o , 1.4 ; feso4 7h2o , 5.0 . the initial ph value was adjusted to 5.5 with orthophosphoric acid ( 2 m ) before sterilisation at 121c for 20 min . the medium ( 100/500 ml erlenmeyer flasks ) , added with glucose at 2 g / l as a carbon substrate , was inoculated with a mycelial culture grown on potato dextrose agar plates for 1 week . the liquid culture was then incubated for 3 days at 30c on a rotary shaker at 180 rpm . cultures with carbon mannan sources ( coconut meal , acacia seeds at two different particle sizes ) were carried out in erlenmeyer flasks ( 50/250 ml ) . the fermenter was equipped with automatic control of agitation , temperatures , ph , dissolved oxygen concentration ( po2 ) , and foaming . batch cultures were carried out by adding a 7% inoculum to 7 l sterile medium in a presterilized fermenter ( 121c , 30 min ) . the ph was maintained at 5.5 by adding sodium hydroxide ( 2 m ) or orthophosphoric acid ( 2 m ) . aeration automatically varied from 0.1 to 1.0 volume of air per fluid volume per min ( v / m ) to maintain a po2 of 20% of air saturation . the fed - batch culture was started with a batch growth phase , followed by a feeding phase . the feeding procedure of the fermenter with coconut meal or acacia seeds powder ( 0.75 g / h ) began after 3 days . after centrifugation ( 7000 xg , 10 min ) , supernatants were used to determine mannanase activities . the release of reducing sugars in 5 min at 100c was measured as mannose equivalents using the dinitrosalicylic acid ( dns ) method . cell growth was followed indirectly by determination of the protein content of the cultivated material by the kjeldahl method . commercial mannans such as locust bean gum , guar gum , and konjac flour substrates were largely used for fungal mannanase production [ 7 , 12 , 13 ] . in the hope of improving the economics of the enzyme production for large scale , it is interestingly to use cheap substrates as coconut meal , date seeds , and carob pods . acacia seeds contained considerable amounts of carbohydrate ( 53.4% ) and organic nitrogen sources ( 23.37% ) ( table 1 ) essential for growth and protein biosynthesis . in this study , we tested acacia seeds as a novel substrate for mannanase production under submerged conditions , and we compared this production with coconut meal , extensively used as economical inducer of substrate [ 3 , 14 ] . the mannanase production data presented in figure 1 revealed that both substrates ( coconut meal and acacia seeds ) support p. occitanis growth and enzyme production . maximum mannanase yields were noticed at , 6th day of incubation ( about 8 u / ml ) , and further increase in fermentation time resulted in the reduction of mannanase activities . the enzyme production pattern , however , varied with acacia particle size . enhanced mannanase - production ( 7.9 0.15 u / ml ) was recorded with substrate particles size ranging from 0.5 to 1 mm . it was three times higher than the production yield obtained with substrate particles of an average size < 0.5 mm . this may be due to an increase in interparticle porosity which provided better aeration and efficient nutrient availability for mycelium growth . the mannanase yield obtained on acacia seeds in shake flask culture was higher than those obtained by other mannanase - producer fungi cultivated in various agricultural substrates / byproducts - based media ( table 2 ) . the mannanase activity and productivity reached the maximum of 41.1 u / ml ( at 72 h ) and 571.1 u / l / h , respectively , when using acacia seeds as substrate . these values were threefold higher than those obtained using coconut meal ( table 3 ) . the significant increase of mannanase production by batch fermentation compared to the shake flask culture could be explained by the improved oxygen transfer in the bioreactor . oxygen limitation could be a serious problem in the shaken flask cultivations due to the highly non - newtonian medium that is caused by the filamentous growth of the fungus . in order to improve the production of mannanase on acacia seeds , fed - batch fermentation was performed at a feed rate of 0.75 g / l / h . the profile of mannanase activity , cell growth , and ph was shown in figure 2(a ) . the mannanase production increased with feeding until approximately 120 h of growth and then stayed relatively constant for the remainder of the cultivation . in contrary to fed - batch culture using acacia seeds , the mannanase production on coconut meal decreased drastically in the latter phase of the cultivation ( figure 2(b ) ) . this result may be explained by the accumulation of the copra oil content which had an inhibitory effect on fungal growth and mannanase production as previously reported [ 3 , 14 ] . the highest mannanase activity and productivity obtained by fed - batch fermentation using acacia seeds as substrate were 76 3.1 u / ml and 649.5 53.6 these results were in agreement with others ; for example , growindhager et al . reported an increase in mannanase production by almost sixfold ( 462 u / ml ) by applying a fed - batch strategy in which a glucose solution was continuously fed to a culture of sclerotium rolfsii . the results obtained in the present study indicate high mannanase production and productivity by culturing p. occitanis in fed - batch using acacia seed as substrate . the highest mannanase activity reached 76 3.11 u / ml which was about 10-fold in the shake flask culture and about three - fold in coconut meal . so , acacia seeds could be used as a less expensive substrate for an efficient mannanase production at industrial scale .

by applying a fed - batch strategy , production of penicillium occitanis mannanases could be almost doubled as compared to a batch cultivation on acacia seeds ( 76 versus 41 u / ml ) . also , a 10-fold increase of enzyme activities was observed from shake flask fermentation to the fed - batch fermentation . these production levels were 3-fold higher than those obtained on coconut meal . the high mannanase production using acacia seeds powder as inducer substrate showed the suitability of this culture process for industrial - scale development .

drop foot deformity is one of the most common lower extremity paresis and usually caused by peroneal nerve palsy or damage of the tibialis anterior muscle ( 1 ) . although in nerve injury there is concomitant loss of sensation at the dorsum of the foot , the movement disability has been considered as a curative aim because lack of dorsal skin sensation usually does nt cause any problems but , the non - regulated gait of patients with deep peroneal nerve pulsy ( the steppage gait ) needs to be modified by orthopedic interventions . in 1933 in an attempt to compensate for this disability , transferring the posterior tibialis tendon to the dorsum of the foot was introduced by ober ( 2 ) . the indication for this operation was drop foot due to isolated loss of tibialis anterior function and the presence of a functioning tibialis posterior tendon ( 3 ) . most techniques use the posterior tibialis tendons as tendon donor and transfer this tendon to the dorsum of the foot and then anchor it to the cuneiform or metatarsal bones ( 4 ) . the tendon is able to provide enough strength for dorsiflexion and also the absence of this tendon at the plantar surface does nt cause any important disability . the transferred tendon is usually pulled out through the metatarsal bones and fixed at the plantar surface . the anchored point will present as a knop on the plantar skin that can cause chronic pressure ulcer ( fig . 1 ) ( 5 ) . given these explanations , we designed our method to provide less complicated surgery without any skin injury . we transferred the posterior tibialis tendon to the dorsum of the foot and then fixed it through the second cuneiform bone like other techniques but to anchor the tendon head we used an absorbable transoseous screw instead of pulling out process that could lead to skin lesions . in this article , we present 15 posttraumatic patients who suffered from deep peroneal nerve palsy and were rehabilitated with this new technique . ethical approval : this study was conducted in rasoul - e - akram clinical research development center ( rcrdc ) of tehran university of medical sciences ( tums ) and financial supports were provided by the related institutional review board . the surgical technique , advantages and probable disadvantages were explained to the patients . the written consent was signed by the patients once they were convinced to enter the study . subjects : since march 2009 till april 2012 all patients with posttraumatic common peroneal nerve pulsy were explained about the aim of the study . the pictures of previous methods of transferring the posterior tibialis tendon to the dorsal side were illustrated to the patients and benefits of the new method mainly lack of any chronic plantar ulcers at the insertion site were explained to them . the inclusion criteria included the peroneal nerve palsy that was not improved after 18 months even by using nerve releasing or nerve repairing . also the non - functional reaction of the injured nerve had to be confirmed by electromyography and neural conductive velocity . surgical method : all operations were performed by one orthopedic surgeon , the first author of the article . the procedure was started by an incision made along the medial plantar side starting form tendon insertion and 5 cm long . then the insertion of the posterior tibialis tendon was released and raised up through another 3 inch incision along the medial side of tibial bone . this incision also was used to make a window in the interosseous membrane of tibia and fibula . another 5 cm incision was made at the lateral part of the anterior tibialis on dorsum of foot for moving tendon anteriorly and exposing second cuneiform at the middle point of the dorsal site of the foot . after measuring the tendon diameter we made a hole in the middle point of the bone . the transferred tendon was sutured by a fiber wire number 2 and passed through the osseous tunnel . while the fibers were pulled out from the plantar side of the foot by another surgeon and the ankle hold dorsiflexed , an absorbable screw ( 256 mm ) was inserted in the hole beside the tendon ( fig . follow up : the plaster kept for 2 months during which the patients had to walk with toe - touch weight bearing . then the cast removed and a foot x - ray prepared and physiotherapy protocol initiated . third visit was scheduled after 3 month and final evaluation of functional improvement done after 6 month because the optimal time expected for recovery was 6 months . evaluation criteria : to assess the operation result , we used an objective score table known as the stanmore system . the system was used by yeap et al in 2001 to evaluate the result of their surgical method for dropped foot deformity ( 6 ) . the system included 7 factors : pain , need for orthosis , wearing normal shoes , activities of daily living ( functional outcome ) , muscle power , degree of active dorsiflexion and foot posture 1 ) . then results were categorized to excellent ( scores between 85 - 100 ) , good ( 70 - 84 ) , fair ( 55 - 69 ) and poor ( 0 - 55 ) . the force of the active dorsiflexion measured by modified british medical research council motor scale ( bmrc ) ( table . the patients age ranged between 20 and 55 years ( mean age 34.3 years ) , in which 9 were men ( 60% ) and 6 female ( 40% ) . of 15 patients in this study , one patient did not tolerate the plaster in the third week and failed to complete the period of therapy . in the remaining 14 , ten patients ( 66% ) received excellent score ( score 86 to score 96 ) with the average of 91.3 and 4 patients ( 26% ) gained good score ( score 72 to score 81 ) with the average of 76.5 . drop foot has diverse etiologies , traumatic peroneal nerve lesions are the most common cause ( 7 ) . in our study all drop foot deformities were due to peroneal nerve palsy . the peroneal division of the sciatic nerve is more prone to injury due to its location and has poor regeneration potential compared with the tibial division so a significant percentage of patients with peroneal nerve injury and subsequent drop foot deformity require tendon transfer for restoration of normal gait ( 8) . when compared with other surgical options such as arthrodesis or tenodesis , the golden standard in the treatment of drop foot is tendon transfer ( 9 ) . an important aspect of this tendon transfer is the type of fixation , pull out sutures may cause skin problems in patients especially those who have sensory problems . the frequency of this problem has been reported differently in different studies ( 10 ) . in this study we eliminated this possibility by changing fixation method while gaining good result according to stanmmore system although , there were some limitation in our study such as lack of a control group , the retrospective nature of the study and small number of cases . we used 2 cuniform in the middle of foot to control varus and valgus deformity better . some studies use 2 metatarsal bone due to longer lever arm but it need a longer length of tendon ( 11 ) . different methods have been proposed to evaluate the results of tibialis posterior transfer like carayon s criteria ( three variables ) , but we used stanmore system . in this series because it assesses more variable than other system ( 12 ) . given the satisfactory results with this method and the simplicity of the surgical technique and few complication we recommend this modification for tibialis tendon transfer .

background the transfer of the tibialis posterior tendon to the dorsum of foot can restore the function of theparalyzed dorsiflexor muscles of the foot and ankle . in order to reduce the wound complication in the insertionsite of tendon to bone by a plantar knop we used a new method of fixation by an absorbable screw inserted dorsally.methods we performed this operation on 15 patients in a 3 years period . all patients had drop foot deformitydue to irreversible lesions of the peroneal nerve . the inclusion criteria was the peroneal nerve palsy that wasnot improved after 18 months even by using nerve releasing or nerve repairing . all patients were evaluatedafter 6 months for ankle function and wound complications.result of 15 patients one was excluded from study . at 6 month ten patients got excellent score ( 66% ) and 4good score ( 26% ) further ankle function . there was no wound complication at insertion site conclusionthis simple modification for insertion site fixation had good result in restoring ankle functionwhiles eliminated the possibility of plantar pressure sores caused by fixation knop .

leptomeningeal carcinomatosis results from dissemination of malignant cells to leptomeninges and can be observed in about 5% of patients with malignancies , but it is likely to become more frequent with the increase of life expectancy in cancer patients . neoplastic cells may spread to the subarachnoid space through ( 1 ) arterial circulation or , less frequently , through ( 2 ) retrograde flow in venous systems or ( 3 ) as a direct consequence of preexisting brain metastases or ( 4 ) through migration of neoplastic cells from the original tumor along perineural or perivascular spaces [ 2 , 3 ] . clinical manifestations can be highly variable and may affect both central ( cns ) and peripheral nervous system ( pns ) . cns involvement may lead to generalised symptoms such as seizures , confusion , encephalopathy , or intracranial hypertension as well as , less frequently , to focal neurological symptoms , mainly consisting in hemiparesis or aphasia . ocular symptoms even in the absence of other clinical symptoms may represent the initial manifestation of meningeal carcinomatosis . thus , meningeal carcinomatosis should be considered in the differential diagnosis in selected patients even if making the diagnosis is often challenging . treatment options such as radiation and intrathecal chemotherapy are often palliative with an expected median patient survival of 2 to 6 months . a 52-year old lady was referred to our hospital for acute onset , ten days before hospitalization , of left orbital pain and visual loss associated with mild frontal throbbing headache . as symptoms progressed , she underwent ophthalmological evaluation as outpatient six days after symptoms onset , without evidence of significant visual loss and normal fundus oculi examination . ocular computed tomography performed at that time was unremarkable . on subsequent ophthalmological evaluation five days later a significant visual loss in the left eye was evident with substantially normal fundus oculi examination . she underwent right mastectomy and hormonal therapy ( tamoxifen ) for infiltrative breast carcinoma in 2007 followed by chemotherapy with ac ( cyclophosphamide and doxorubicin ) for six months , followed by letrozole . on admission in august 2011 neurological examination was normal except for mild anisocoria ( left > right ) with detectable markus gunn sign , left eye visual loss , and global reduction of deep tendon reflexes . she underwent contrast - enhanced cerebral mri showing nonspecific signal alteration involving frontal subcortical and periventricular white matter and focal contrast enhancement involving the left optic nerve sheath ( see figure 1 ) . vep revealed destructured response , reduced amplitude , and prolonged latency on the left ( see figure 2 ) . lumbar puncture revealed increased cell count ( 50 cells / mmc ) with normal glucose and proteins . cytology at that time was negative for neoplastic cells and repeated ophthalmological evaluations revealed further progression to complete visual loss in the left eye . serum antibodies ( lac , aca , anti - beta2-glycoprotein ana , anti - ds - dna , ena , c - anca , and p - anca ) were negative . a diagnosis of possible inflammatory optic neuropathy was done . she was started on ev steroids followed by oral tapering without improvement . in about two months brainstem auditory - evoked potentials were normal on the left ( see figure 2 ) and audiological evaluation evidenced mild neurosensorial failure more evident on the right . she underwent contrast - enhanced cerebral mri in october 2011 showing increased enhancement of the left optic nerve sheath . repeated ophthalmological evaluation revealed bilateral ( left > right ) papilledema and she was hospitalized . neurological examination on admission showed total blindness in the left eye with absent pupillary response to direct light stimulation . vep revealed absent response on the left and destructured response with normal amplitude and latency on the right ( see figure 2 ) . she underwent repeated lumbar puncture showing further increase of white cell count ( 105 cells / mmc ) and reduced glucose . references for this review were identified through a search of pubmed from 1966 to march 8 , 2012 with the terms meningeal carcinomatosis , meningeal carcinomatosis and review , meningeal carcinomatosis and optic neuritis , meningeal carcinomatosis and ocular manifestations , and neoplastic meningitis . reference lists of relevant articles were also reviewed . only articles with ocular manifestation as presenting or associated clinical features we found a total of 34 papers including 33 case reports ( 34 patients ) and 1 case series ( 7 patients ) . information about demographic details along with clinical , instrumental , and radiological findings were recorded and summarized in table 1 . in details we looked at latency between symptoms onset and diagnosis of meningeal carcinomatosis : the mean time was 4 months , while the mean time between primary tumor diagnosis and carcinomatosis diagnosis was 20 months . ocular symptoms were the presenting clinical feature in 34 out of 41 patients ( 83% ) and were the only manifestation of meningeal carcinomatosis in 3 patients ( 7% ) . visual loss was the presenting clinical manifestation in 17 patients ( 50% ) and was the most common ocular symptom ( 70% ) . additional ocular manifestations were diplopia ( 18 patients , presenting manifestation in 16 patients ) , ptosis ( 8 patients ) , papilledema ( 4 ) , anysocoria ( 3 ) , exophthalmos ( 2 ) , orbital pain ( 2 ) , scotomas ( 2 ) , hemianopsia ( 1 ) , and nystagmus ( 1 ) . other common symptoms were headache ( 24 patients ) , altered consciousness ( 10 patients ) , meningism ( 8 patients ) , hemiparesis ( 7 ) , ataxia ( 7 ) , dizziness ( 6 ) , and seizures ( 4 ) . v ( 4 ) , vii ( 6 ) , viii ( 4 ) , ix and x ( 2 ) , and xii ( 1 ) cranial nerves involvement has also been reported . twenty - three patients underwent enhanced mri which was diagnostic in 8 patients ( 35% ) . in 7 patients generalized meningeal enhancement was noted , and in 2 patients meningeal enhancement was associated with optic nerves enhancement , which was bilateral in 1 patient and unilateral in the other one . three patients had cranial nerves enhancement , while isolated optic nerve enhancement was seen in only 1 patient ( unilateral on the first mri and bilateral at the second mri ) . other mri findings included hydrocephalus ( 1 ) , infarction of basal nuclei ( 1 ) , and cerebellar enhancement ( 3 ) . all patients except five underwent csf examination which was normal in 1 patient , and increased cells count was found in 11 patients ( range : 9598/mm ) , increased protein levels were observed in 16 patients ( range : 62334 mg / dl ) , and decreased glucose levels were found in 8 patients ( range : 543 mg / dl ) . the histology of the original tumor was highly variable with solid tumors being more frequently associated with meningeal carcinomatosis . the most common was gastric cancer followed by lymphoma , breast , and lung cancer . 16 patients underwent chemotherapy ( see table 1 ) , and the mean life expectancy was 123 days ( range 5730 days ) . the highest leptomeningeal diffusion rate has been reported for small cell lung cancer ( 11% ) and melanoma ( 20% ) . neoplastic meningitis is more likely to occur in patients with disseminated cancer , but in , respectively , 20% and 10% of cases it may manifest after a disease - free period or as a first manifestation of systemic tumors . current diagnostic methods are limited and may fail to identify mc early enough to prevent the escalation of neurological damage . thus meningeal carcinomatosis should be included in the differential diagnosis in the presence of multifocal disease but also considered in the evaluation of isolated syndromes such as intracranial hypertension , cauda equine syndrome , or cranial neuropathy . the most common manifestation of cranial nerves involvement is diplopia due to vi cranial nerve palsy , followed by iii and iv involvement . v , viii , and optic nerve may also be affected . diagnostic workup includes csf examination and neuroradiological studies . the presence of malignant cells in the csf is diagnostic , other supportive features are increased opening pressure , pleocytosis , elevated proteins , and decreased glucose levels . csf cytology may be negative in 65% of patients on initial examination , but only in 20% of patients on second lumbar puncture . csf increased levels of vascular endothelial growth factors have been proposed as a promising biomarker with a reported sensitivity of 51100% and a specificity of 73100% for leptomeningeal metastases . gadolinium - enhanced mri is also useful for the diagnosis of meningeal carcinomatosis because enhancement on mri will reveal any irritation of leptomeninges resulting in cranial nerves or intradural extramedullary enhancement on spinal mri . the present report is an updated and systematic review of ocular manifestations of neoplastic meningitis . our data show that ocular symptoms often represent the first clinical manifestation of meningeal carcinomatosis ( 83% ) and the only clinical manifestation in a small proportion of subjects ( 7% ) . for this reason it should be considered in the differential diagnosis even in the absence of associated clinical symptoms more suggestive of meningeal carcinomatosis such as headache ( 58% ) , altered consciousness ( 24% ) , meningism ( 19% ) , focal signs ( 34% ) , dizziness ( 15% ) , seizures ( 10% ) , and cranial nerves other than ocular involvement ( 32% ) . the most common ocular manifestation was visual loss ( 70% ) followed by diplopia ( 41% ) , ptosis ( 19% ) , papilledema ( 10% ) , anysocoria ( 7% ) , exophthalmos ( 5% ) , orbital pain ( 5% ) , scotomas ( 5% ) , hemianopsia ( 2% ) and nystagmus ( 2% ) . meningeal enhancement was detected in about one third of patients ; in two of them ( 25% ) it was associated with focal optic nerve enhancement . in one patient ( 12% ) the most common finding was increased proteins level ( 44% ) , increased cells count ( 30% ) , and decreased glucose ( 22% ) . citology was positive in a high proportion of patients ( 76% ) with solid tumors being the more frequent . the first csf examination may be inconclusive , thus if clinical and radiological suspicion persist and cell count is increased , a repeated lumbar puncture is recommended . moreover clinicians should be aware that ocular involvement may mimic different diseases as shown in our case report , where neoplastic optic nerve involvement was indistinguishable from optic neuritis . thus meningeal carcinomatosis should be included in the differential diagnosis of diplopia and visual loss in selected patients because diagnosis is often challenging .

introduction . leptomeningeal carcinomatosis occurs in about 5% of cancer patients . ocular involvement is a common clinical manifestation and often the presenting clinical feature . materials and methods . we report the case of a 52-year old lady with optic neuritis as isolated manifestation of neoplastic meningitis and a review of ocular involvement in neoplastic meningitis . ocular symptoms were the presenting clinical feature in 34 patients ( 83% ) out of 41 included in our review , the unique manifestation of meningeal carcinomatosis in 3 patients ( 7% ) . visual loss was the presenting clinical manifestation in 17 patients ( 50% ) and was the most common ocular symptom ( 70% ) . other ocular signs were diplopia , ptosis , papilledema , anisocoria , exophthalmos , orbital pain , scotomas , hemianopsia , and nystagmus . associated clinical symptoms were headache , altered consciousness , meningism , limb weakness , ataxia , dizziness , seizures , and other cranial nerves involvement . all patients except five underwent csf examination which was normal in 1 patient , pleocytosis was found in 11 patients , increased protein levels were observed in 16 patients , and decreased glucose levels were found in 8 patients . cytology was positive in 29 patients ( 76% ) . conclusion . meningeal carcinomatosis should be considered in patients with ocular symptoms even in the absence of other suggestive clinical symptoms .

five gelding thoroughbred horses ( ages 57 year , weight 468535 kg ) were used in the forelimb experiment , and four gelding thoroughbred horses ( ages 57 year , weight 468544 kg ) were used in the hind limb experiment . two teflon - coated stainless steel electrodes ( a - m systems inc . , carlsborg , wa , u.s.a . ) with 1 cm of the tip bared were inserted into a 23 g needle of 6 cm in length , and 1 cm of the tip was bent back and twisted around the needle shaft . the electrodes were inserted into the splenius ( sp ) at the level of the second cervical vertebra at a depth of 20 mm , the middle point of muscle belly of the brachiocephalicus ( bc ) at a depth of 20 mm , the middle point of the biceps brachii ( bb ) at a depth 50 mm , and the middle point of the pectoralis descendens ( pd ) at a depth of 20 mm in the forelimb experiment ; in the hind limb experiment , they were inserted into the longissimus dorsi ( ld ) at the level of the first lumbar vertebra at a depth of 50 mm , the biceps femoris ( bf ) in the upper third portion of the muscle at a depth of 60 mm , the middle point of muscle belly of the vastus lateralis ( vl ) at a depth of 80 mm , and the middle point of the gluteus medius ( gm ) at a depth of 40 mm . electromyography ( emg ) data were collected from right and left side muscles ( type 271 nec san - ei sokki inc . , strain gauges ( n22-fa-10 - 120 - 11-vs3 ; nec san - ei instruments , ltd . , tokyo , japan ) were attached with glue to the dorsal midline of the fore or hind hooves in the applicable experiment , and they were connected to dynamic strain measuring instruments ( dp-612b , kyowa electronic instruments , tokyo , japan ) . emg and strain gauge data were recorded with pc using the windaq software ( dataq , akron , oh , u.s.a . ) . the horses performed a designated exercise protocol consisting of walking ( 1.6 m / sec ) and trotting ( 3.5 m / sec ) on a treadmill ( sto ab , knivsta , sweden ) at five gradients ( 6% , 3% , 0% , + 3% , + 6% ) . because the inclination of the slope for uphill training is 3 to 3.5% at the training center of the jra , the range of inclination was determined by doubling the value in ordinary use . the emg signal and strain gauge data were filtered with software ( bimutus , kissei comtec co. , ltd . , nagano , japan ) using a high - pass butterworth filter with a 10 hz cutoff point and a low - pass butterworth filter with a 40 hz cutoff point , respectively . stride time and duty factor ( the percentage of stance to stride time ) were determined by the strain gauge data from randomly selected right or left hooves . the integrated electromyogram ( iemg ) values for each muscle in each stride were calculated from the emg data . one recording on the right or left side of the emg signal was selected depending on the signal condition . comparisons between conditions were made using repeated measures analysis of variance ( r 3.0.2 , r core team ( 2013 ) . url http://www.r-project.org/ ) . where significant differences ( p<0.05 ) were identified , a pair - wise ryan test was applied . in the forelimb experiment , stride time and duty factor at a walk and a trot were not significantly different under any of the inclinations of the treadmill ( fig . 1.mean ( sd ) stride time and duty factor at inclinations from 6% to + 6% at a walk ( 1.6 m / sec ) in the forelimb experiment ( a ; n=5 ) and hind limb experiment ( b ; n=4 ) and at a trot ( 3.5 m / sec ) in the forelimb experiment ( c ; n=5 ) and hind limb experiment ( d ; n=4 ) . ) . on the other hand , in the hind limb experiments , stride time on the 6% incline was significantly shorter than that on the 0% and + 3% inclines during walking ( fig . stride time on the 6% incline was also significantly shorter than that on the 0% , + 3% , and + 6% inclines during trotting ( fig . duty factor at a walk and trot were not significantly different under any of the inclinations of the treadmill ( fig . 1 ) . mean ( sd ) stride time and duty factor at inclinations from 6% to + 6% at a walk ( 1.6 m / sec ) in the forelimb experiment ( a ; n=5 ) and hind limb experiment ( b ; n=4 ) and at a trot ( 3.5 m / sec ) in the forelimb experiment ( c ; n=5 ) and hind limb experiment ( d ; n=4 ) . at a walk , the iemg values for the muscles in the forelimb were not significantly different under any of the inclinations of the treadmill ( fig . iemg values for the forelimb ( left ; bc n=5 , bb n=3 , sp n=4 , pd n=5 ) and hind limb ( right ; ld n=3 , vl n=3 , gm n=4 , bf n=4 ) during downhill ( 3 , 6% ) , level ( 0% ) , and uphill ( + 6 , + 3% ) walking . significant differences ( p<0.05 ) are indicated by different letters . ) . in the hind limb at a walk , the iemg values for the ld and vl were not significantly different under any of the inclinations of the treadmill , while the iemg values for the gm at all inclinations other than + 6% were significantly less than that at + 6% inclination ( fig . the iemg of the bf significantly decreased as the inclination of the treadmill decreased . there was a significant difference between each different inclination with the exception of between 6% and 3% ( fig . 2 ) . mean ( sd ) iemg values for the forelimb ( left ; bc n=5 , bb n=3 , sp n=4 , pd n=5 ) and hind limb ( right ; ld n=3 , vl n=3 , gm n=4 , bf n=4 ) during downhill ( 3 , 6% ) , level ( 0% ) , and uphill ( + 6 , + 3% ) walking . significant differences ( p<0.05 ) are indicated by different letters . at a trot , the iemg values for the bc at the 6% , 3% , and 0% inclines were significantly less than that at the + 6% incline ( fig . 3fig . 3.mean ( sd ) iemg values for the forelimb ( left ; bc n=4 , bb n=2 , sp n=3 , pd n=5 ) and hind limb ( right ; ld n=3 , vl n=4 , gm n=4 , bf n=4 ) during downhill ( 3 , 6% ) , level ( 0% ) , and uphill ( + 6 , + 3% ) trotting . the iemg values for the other three muscles in the forelimb were not significantly different under any of the inclinations of the treadmill at a trot ( fig . the iemg values for the vl were not significantly different under any of the inclinations of the treadmill , while the iemg values for the ld at the 6% and 3% inclines were significantly decreased compared to that at + 3% and + 6% inclination . the iemg of the gm at 6% and 3% inclines were also significantly decreased compared with that at + 6% inclination . the iemg values for the bf at all inclinations other than + 6% incline were significantly decreased compared with that at + 6% inclination ( fig . 3 ) . mean ( sd ) iemg values for the forelimb ( left ; bc n=4 , bb n=2 , sp n=3 , pd n=5 ) and hind limb ( right ; ld n=3 , vl n=4 , gm n=4 , bf n=4 ) during downhill ( 3 , 6% ) , level ( 0% ) , and uphill ( + 6 , + 3% ) trotting . in the hind limb experiment , stride time at a walk and trot shortened as the inclination decreased , while stride time was not different under any of the inclinations in the forelimb experiment . in theory , stride time does not change whether it is measured in the forelimb or hind limb . in this study , the average stride time at a walk in the hind limb at a 6% incline was reduced by 0.035 sec ( 3.3% ) compared with that at a 0% incline . at a trot , the average stride time in the hind limb at a 6% incline was also reduced by 0.024 sec ( 3.5% ) compared with that at a + 3% incline . because the effect of inclination on stride time was very little , the results might be different between the forelimb and hind limb experiments . in previous reports , the effects of inclination on stride time at a walk and trot were also inconsistent [ 2 , 5,6,7 , 11 , 13 ] . the iemg values changes by horse and the position of the electrodes in each muscle . this method evaluated the effect of incline within each horse . in the bb at a trot , a statistical comparison could not be performed because emg data were only recorded for 2 horses . in some muscles at a walk and trot , emg data could not be recorded for 1 or 2 horses . the statistical powers of the test were low in these muscles . in the muscles of the forelimb , the effects of the inclines were observed through the iemg values for the bc at a trot , which decreased as the incline decreased . the iemg values for the bc , which protracts the forelimb , decreased on the downward slope possibly because gravity assisted the protraction of the forelimb . on the other hand , iemg values for this result was consistent with a previous report in which the iemg values for the bc increased on an upslope at a trot . there was no influence at a walk and trot on the iemg values for the bb , which acts as an antigravity muscle , although it was reported that the vertical ground reaction force in the forelimb decreased on an upslope . in the pd , which has a similar function as the bc the iemg values for the sp , which supports the head , were not influenced by the inclination because the movement of the head was not influenced by the inclination of the treadmill . in the hind limb muscles , the iemg values for the gm and bf decreased as the incline decreased at a walk and trot [ 2 , 7 ] . the iemg values for these muscles decreased because the propulsive force decreased as the incline decreased . the inclination had no effect on the bending of the back at a walk , while the iemg values for the ld increased significantly as the inclination increased . it was reported that the vertical ground reaction force in the hind limb increased on an upslope . it was assumed from these studies that the hind limb force decreases on a downslope . however , the iemg values for the vl were not influenced by the inclination , as reported by crook et al . , although this was different from the predicted result based on the previous report about the vertical ground reaction force . the inclination of + 6% might not be enough to influence the effect of the vertical ground reaction force on the iemg values for the vl . it was reported that heart rate and oxygen demand increased as the inclination increased [ 4 , 6 , 14 ] . the iemg values for the bc , gm , and bf on an upslope were higher than those on flat ground , while the iemg values for any muscles on a downslope were not different from those on flat ground . the rate of oxygen consumption was increased by about 250% on the 10% upslope compared with trotting on level ground and was only reduced by about 50% on a 10% downslope [ 4 , 6 , 14 ] . the present data suggested that the increased rate of oxygen consumption reflected the increased muscle activities . in conclusion , in the forelimb , the iemg values for the bc increased on an upslope at a trot , while the iemg values for the muscles that were measured did not change on a downslope at a walk and trot . in the hind limb , the iemg values for the gm and bf increased on an upslope , while the iemg values for these muscles did not change or decreased on a downslope . the effects of the inclination on the muscle activities were larger on an upslope and in the hind limb muscles compared with the forelimb muscles .

abstractit is important to know the effects of the inclination of a slope on the activity of each muscle , because training by running on a sloped track is commonly used for thoroughbred racehorses . the effects of incline ( from 6 to + 6% ) on the forelimbs and hind limbs during walking and trotting on a treadmill were evaluated by an integrated electromyogram ( iemg ) . the muscle activities in the forelimbs ( 5 horses ) and hind limbs ( 4 horses ) were measured separately . two stainless steel wires were inserted into each of the brachiocephalicus ( bc ) , biceps brachii ( bb ) , splenius ( sp ) , and pectoralis descendens ( pd ) in the forelimb experiment and into the longissimus dorsi ( ld ) , vastus lateralis ( vl ) , gluteus medius ( gm ) , and biceps femoris ( bf ) in the hind limb experiment . the emg recordings were taken at a sampling rate of 1,000 hz . at a walk , the iemg values for the forelimb were not significantly different under any of the inclinations . in the hind limb , the iemg values for the gm and bf significantly decreased as the inclination decreased . at a trot , the iemg values for the bc in the forelimb significantly decreased as the inclination of the treadmill decreased . in the hind limb , the iemg values for the ld , gm , and bf significantly decreased as the inclination decreased . uphill exercise increased the iemg values for the bc , ld , gm , and bf , while downhill exercise resulted in little increase in the iemg values . it was concluded that the effects of inclination on the muscle activities were larger for the uphill exercises , and for the hind limb muscles compared with the forelimb muscles .

a 70-year - old woman with diabetes diagnosed of breast cancer t1n1 several months ago treated with surgery and chemotherapy was admitted to our hospital because of severe asthenia and pain in her right lower extremity . glucose levels were not well controlled ( mean over 300 mg/ dl ) due to corticoids use as well as chemotherapy pre - medication . more than 1 106 colonies of e.coli grew from her urine and blood cultures . a computed tomography ( ct ) scan demonstrated a thickened , trabeculated bladder wall containing pockets of gas ( figure a ) . after one week of antibiotics , the patient improved clinically and another ct was taken , showing a considerable reduction of the gas inside bladder wall ( figure b ) . so far , there is no evidence of relapse and she is on follow - up in oncology department despite belonging to a low percentage of all the urinary tract infections , gas - producing infections are relevant as they may lead to death . three categories of this type of infections are recognized : emphymatous pyelonephritis , emphymatous pyelitis or emphymatous cystitis . the gas is produced in the renal and perirenal parenchyma and 90% of the cases are reported in diabetic patients . the delay on the appropriate therapy contributes to a high mortality rate , in some case series up to 80% ( 3 ) . emphymatous cystitis is a rare disease that is mainly diagnosed in diabetic and immunocompromised patients . it is also reported to be in association with neurogenic bladder , obstruction of the urinary tracts , catheter use and chronic infections of the urinary tract . the microorganisms most often involved in this infection are escherichia coli and klebsiella pneumonia and the less common are enterobacter , proteus , streptococci and candida ( 4 ) . though , bacteria are the most common agent , fungi may also be responsible for this clinical picture ( 5 ) . the exact mechanism by which the gas is produced in the emphysematous infection is not quite clear . in diabetic patients , one of the reasons seems to be the production of co2 by the microorganisms through the fermentation of glucose , which occurs when the glucose concentration is high . since the emphymatous infections may occur in nondiabetic patients , it has been suggested that the urinary lactulose and tissue proteins may be useful as substrate to the gas production ( 6 ) . another factor that may help in this process is the impaired transportation of gas due to the local inflammation or some kind of obstructive process increasing the local pressure and decreasing the circulation . this may involve tissue necrosis which becomes a good culture for pathogens to produce gas ( 7 ) . the most common clinical features are fever and abdominal pain along with dysuria , haematuria and pneumaturia ( 8) . in our patient , the presentation was unusual with pain in her right lower extremity , but without urinary symptoms . the diagnosis is provided by radiographic image ( x - ray or ct scan ) . the most obvious radiographic clues are small pockets of gas in the mucous membrane of the bladder , as we can see in this picture . other causes for the presence of air in the bladder such as fistula with the intestine or vagina , after trauma , cancer or instrumentation , have to be excluded ( 3 ) . the appropriate treatment involves endovenous antibiotic therapy with broad - spectrum such as fluoroquinolones , penicillin with inhibitor of the beta - lactamases ( imipenem , ticarcillin / clavulanate ) or third - generation cefalosporins . antifungal agents may be used ( systemic or intravesical ) , if a fungus infection is reported ( 6 ) . the full recovery from any infection with gas production depends on early diagnosis plus correction of the subjacent causes , glycemic control , long - term therapeutic with antibiotic therapy ( 3 to 6 weeks ) and surgery , if required ( 3 ) . the reported case shows the seriousness and the atypical presentation that this infection may assume . the diabetes mellitus and the poor glycemic control are the main risk factors for this type of infection . the agent isolated from this patient , the escherichia coli is reported as the most common . the empiric broad - spectrum antibiotic ( piperacillin / tazobactam ) used for the nosocomial urinary tract infection

we present the case of a 70-year - old woman with emphysematous cystitis . she was a diabetic patient and she was on chemotherapy treatment for a breast cancer . she complaint of severe asthenia and pain in her right lower extremity , but no fever or urinary symptoms . a computed tomography ( ct ) scan was suggestive of severe emphysematous cystitis . emphysematous cystitis is a rare clinically entity , more commonly seen in diabetic , immunocompromised patients . a conservative treatment approach using antibiotics and bladder catheterization is typically successful , with a complication rate less than 20% .

streptococcus pneumoniae ( the pneumococcus ) is responsible for the death of an estimated 800,000 children under the age of five annually , with the burden of disease falling predominantly in resource - poor countries . pneumococcal diseases range in severity from localized infections such as acute otitis media to severe life threatening infections such as sepsis , meningitis and pneumonia . current pneumococcal vaccines provide protection against the serotypes that are responsible for the majority of invasive disease . however , widespread use of vaccines has been associated with replacement of serotypes included in the vaccine by nonvaccine serotypes , both in nasopharyngeal carriage and invasive disease . this highlights the importance of serotyping for epidemiological surveillance and long - term vaccine impact studies . the gold standard method for pneumococcal typing is the capsular reaction test , known as the quellung reaction , first described by neufeld in 1902 ( see austrian ) . a high degree of concordance has been found between laboratories , and between the quellung reaction and other serotyping methods . the method described here does not require the use of a counter stain or the oil immersion lens ; rather , a drop of prepared specimen is mixed with the typing serum and examined immediately under 400x magnification . the method described here uses less antisera compared with some other methods , making it more cost effective . once an isolate is identified as a pneumococcus , it is sequentially tested with antisera pools until a positive reaction is observed . once the pool is established , the individual type and group antisera that are included in the reactive pool are tested individually in sequence . type antisera generally react with a single serotype ( e.g. type 1 antiserum reacts with serotype 1 ) , whereas group antisera react with all the serotypes in a particular group ( e.g. group 22 antiserum reacts with serotypes 22f and 22a ) . some serotypes within groups are further differentiated using factor antisera ( e.g. serotype 22f reacts with factor 22b , but not 22c ) . in this case testing the quellung reaction is simple and quick and can be performed in any laboratory that is equipped with a good quality microscope and appropriate set of antisera . using a sterile disposable 1 l loop , take a small sweep of fresh overnight pure culture of pneumococci grown on solid nonselective horse blood agar and inoculate 100 l heart infusion ( hi ) broth . gently agitate the tube to emulsify . note : other media such as brain heart infusion broth may also be suitable . addition of serum ( e.g. a final concentration of 10% ( v / v ) horse serum ) and incubation at 37 c for approximately 1 hr before use may be used to enhance the reaction . the cell suspension prepared in step 1.1 will also be used as the negative control , and should be checked for cell density before adding the typing sera . using a 1 l loop , transfer a drop of the inoculum prepared in step 1.1 onto a glass microscope slide . using a pair of forceps , observe the preparation microscopically under 400x magnification , to check the density of the suspension ( figure 1a ) . if the inoculum is too heavy ( figure 2a ) , add more broth to the cell suspension made in step 1.1 to dilute it . gently mix again.if the inoculum is too light , for example , there are < 50 cells visible in the microscopic field ( figure 2b ) , add more bacteria to the cell suspension preparation made in step 1.1 and gently mix . note : with experience , the density of the cell suspension can be judged by shaking and holding up to the light , where it should appear to be just visibly turbid . if the inoculum is too heavy ( figure 2a ) , add more broth to the cell suspension made in step 1.1 to dilute it . gently mix again . if the inoculum is too light , for example , there are < 50 cells visible in the microscopic field ( figure 2b ) , add more bacteria to the cell suspension preparation made in step 1.1 and gently mix . note : with experience , the density of the cell suspension can be judged by shaking and holding up to the light , where it should appear to be just visibly turbid . repeat steps 2.1 - 2.3 until a suitable number of cells are visible in the microscopic field . note : glass slides and coverslips present a sharps hazard . after use , slides and coverslips are contaminated with infectious material and must be disposed into a biohazard sharps container . transfer ~1 l of the prepared inoculum ( e.g. using a 1 l loop ) onto the glass microscope slide . add an equal volume ( 1 l loopful ) of room - temperature antiserum onto the slide and mix both drops well with the loop . using a pair of forceps , place a small circular coverslip on the suspension , taking care not to touch the drop . place the coverslip on the suspension immediately after the addition of antisera to prevent the fluid on the slide from drying out . using a microscope , a negative quellung reaction is observed when little or no swelling of the pneumococcal cells can be seen at 400x magnification , similar to what is observed in the pneumococcal cell suspension with no antisera added ( negative control ) . a positive quellung reaction is observed when the cells appear enlarged or ' swollen ' and more visible when compared to the cells in the negative control . note : equivocal reactions should be investigated further , for example by examining the reaction after 5 - 10 min incubation at room temperature , or by repeating the reaction with more antiserum . conduct pneumococcal serotyping with successive testing of individual antisera pools until a positive reaction is observed . rounds ensures that the pools containing antibodies to the most common serotypes are tested first , minimizing effort and cost . concurrent testing of several pools also provides additional negative controls , which can be useful in interpretation . if all the pools in a particular round are negative , test the isolate with subsequent rounds of pools . test the isolate using the appropriate type or group antiserum contained within the reactive pool . where appropriate , use factor antisera to further differentiate the serotype . note : keys to pneumococcal antisera supplied by the manufacturer are used in the selection of appropriate pool , type , group or factor antisera and interpretation of results ( including any cross - reactions ) . if negative results are obtained with all pools , test the isolate with omniserum reagent ( contains antibodies against 91 serotypes ) . if a positive quellung reaction is still not observed when testing a pneumococcal isolate with the omniserum reagent , this may be because the isolate is expressing little or no capsule , or that antibodies against the serotype are not represented in the omniserum . using a sterile disposable 1 l loop , take a small sweep of fresh overnight pure culture of pneumococci grown on solid nonselective horse blood agar and inoculate 100 l heart infusion ( hi ) broth . gently agitate the tube to emulsify . note : other media such as brain heart infusion broth may also be suitable . addition of serum ( e.g. a final concentration of 10% ( v / v ) horse serum ) and incubation at 37 c for approximately 1 hr before use may be used to enhance the reaction . the cell suspension prepared in step 1.1 will also be used as the negative control , and should be checked for cell density before adding the typing sera . using a 1 l loop , transfer a drop of the inoculum prepared in step 1.1 onto a glass microscope slide . using a pair of forceps , observe the preparation microscopically under 400x magnification , to check the density of the suspension ( figure 1a ) . if the inoculum is too heavy ( figure 2a ) , add more broth to the cell suspension made in step 1.1 to dilute it . gently mix again.if the inoculum is too light , for example , there are < 50 cells visible in the microscopic field ( figure 2b ) , add more bacteria to the cell suspension preparation made in step 1.1 and gently mix . note : with experience , the density of the cell suspension can be judged by shaking and holding up to the light , where it should appear to be just visibly turbid . if the inoculum is too heavy ( figure 2a ) , add more broth to the cell suspension made in step 1.1 to dilute it . gently mix again . if the inoculum is too light , for example , there are < 50 cells visible in the microscopic field ( figure 2b ) , add more bacteria to the cell suspension preparation made in step 1.1 and gently mix . note : with experience , the density of the cell suspension can be judged by shaking and holding up to the light , where it should appear to be just visibly turbid . repeat steps 2.1 - 2.3 until a suitable number of cells are visible in the microscopic field . note : glass slides and coverslips present a sharps hazard . after use , slides and coverslips are contaminated with infectious material and must be disposed into a biohazard sharps container . transfer ~1 l of the prepared inoculum ( e.g. using a 1 l loop ) onto the glass microscope slide . add an equal volume ( 1 l loopful ) of room - temperature antiserum onto the slide and mix both drops well with the loop . using a pair of forceps , place a small circular coverslip on the suspension , taking care not to touch the drop . place the coverslip on the suspension immediately after the addition of antisera to prevent the fluid on the slide from drying out . using a microscope , a negative quellung reaction is observed when little or no swelling of the pneumococcal cells can be seen at 400x magnification , similar to what is observed in the pneumococcal cell suspension with no antisera added ( negative control ) . a positive quellung reaction is observed when the cells appear enlarged or ' swollen ' and more visible when compared to the cells in the negative control . note : equivocal reactions should be investigated further , for example by examining the reaction after 5 - 10 min incubation at room temperature , or by repeating the reaction with more antiserum . conduct pneumococcal serotyping with successive testing of individual antisera pools until a positive reaction is observed . rounds ensures that the pools containing antibodies to the most common serotypes are tested first , minimizing effort and cost . concurrent testing of several pools also provides additional negative controls , which can be useful in interpretation . if all the pools in a particular round are negative , test the isolate with subsequent rounds of pools . test the isolate using the appropriate type or group antiserum contained within the reactive pool . note : keys to pneumococcal antisera supplied by the manufacturer are used in the selection of appropriate pool , type , group or factor antisera and interpretation of results ( including any cross - reactions ) . if negative results are obtained with all pools , test the isolate with omniserum reagent ( contains antibodies against 91 serotypes ) . if a positive quellung reaction is still not observed when testing a pneumococcal isolate with the omniserum reagent , this may be because the isolate is expressing little or no capsule , or that antibodies against the serotype are not represented in the omniserum . a positive quellung reaction occurs when type - specific antibody binds to the capsule of the pneumococcus , leading to a change in its refractive index . when viewed under a microscope figure 1a shows pneumococcal cells in hi broth . when type - specific anti - serum is added to the bacterial suspension , too many bacterial cells added to the broth may result in aggregation of cells or a false negative reaction . figure 2 shows inocula of pneumococcal cells in hi broth that are too heavy ( figure 2a ) or preparations of serotype 9v pneumococcal isolate with no antiserum ( 1a ) and with group 9 antiserum ( 1b ) , were viewed under 400x magnification . the latter shows the swelling and rounding of bacterial cells typically seen in a positive quellung reaction . preparations of pneumococcal cell suspensions that are too heavy ( 2a ) or too light ( 2b ) , when viewed under 400x magnification . a critical step in this technique is ensuring a pure culture is used to prepare the suspension along with adding a suitable number of bacterial cells to the broth . it should be noted that colony growth and morphology on agar plates varies between different pneumococcal isolates . some produce dry and rough colonies , which can be difficult to pick off with a loop and do not emulsify well in the broth . for this reason , a larger sweep of bacteria may be required when preparing the cell suspension . in any case , it is imperative that individual cells , and not aggregates , are obvious in the negative control so their relative size can be compared to the cells with antisera added . additionally , too many bacterial cells may result in a false negative reaction , where an excess of capsular antigen may inhibit the quellung reaction . for this reason , it is important to create a bacterial suspension with a suitable cell density ( figure 1 ) . the suspension may be preserved for several months by the addition of several drops of concentrated formalin . this enables easier batch testing and also sterilizes the broth reducing the risk of laboratory - acquired infections ; although this must be weighed against the safety risk of handling formalin , which is toxic , corrosive , carcinogenic , sensitizing , and flammable . in addition , we have observed that some isolates show weaker reactions in the presence of formalin ( data not shown ) . the use of phase contrast enhances the visibility of the capsule . in some laboratories , in addition , some laboratories use a counter stain ( methylene blue ) to further enhance the visibility of a positive reaction . the method presented here it is important to maintain good internal quality control procedures to ensure the antisera and testing procedures are in order . participation in an external quality assurance program is often beneficial . a major limitation of the quellung reaction for serotyping of pneumococci is the high cost of the antisera required . however , this is minimized in the above protocol due to the small amount of antiserum used for each reaction . however , quellung remains the gold standard and the development of new methods requires standardization against the quellung reaction . using appropriate antisera , the quellung reaction can also be utilized to identify and type other capsule producing bacteria . the quellung reaction is instrumental in the characterization of current and emerging pneumococcal serotypes , as well as providing information on vaccine efficacy and the long - term impact of vaccination on carriage and disease .

there are over 90 different capsular serotypes of streptococcus pneumoniae ( the pneumococcus ) . as well as being a tool for understanding pneumococcal epidemiology , capsular serotyping can provide useful information for vaccine efficacy and impact studies . the quellung reaction is the gold standard method for pneumococcal capsular serotyping . the method involves testing a pneumococcal cell suspension with pooled and specific antisera directed against the capsular polysaccharide . the antigen - antibody reactions are observed microscopically . the protocol has three main steps : 1 ) preparation of a bacterial cell suspension , 2 ) mixing of cells and antisera on a glass slide , and 3 ) reading the quellung reaction using a microscope . the quellung reaction is reasonably simple to perform and can be applied wherever a suitable microscope and antisera are available .

the population impact of arterial hypertension ( aht ) consists in its high prevalence and in the strength of its risk ratio with cardiovascular pathologic conditions . more than a quarter of the world adult population is already hypertensive and this number is projected to increase to 1,56 billion people by 2025 . this estimation relies especially on a steep increase of aht in the developing countries [ 1 , 2 ] . a large number of clinical trials have shown that the cardiovascular risk could be considerably diminished by a tight reduction of the blood pressure ( bp ) values . despite their encouraging data , the real rates of arterial hypertension awareness , and control are continuing to remain unsatisfactory in many areas of the world [ 3 , 4 ] . romania is an east european developing country , with a high mortality in cardiovascular disease , as was reconfirmed in the last european cardiovascular disease statistics report and it is supposed that uncontrolled aht is an important contributor to this result . in order to find out the prevalence , the awareness , and the control of blood pressure in romania , we have carried on a cross - sectional survey , named sephar : study for the evaluation of prevalence of hypertension and cardiovascular risk in adult population in romania . this study is the first assessment of blood pressure and major correlated cardiovascular risk factors accomplished on a representative sample for the entire adult population in romania . the design of the sephar study was similar with that of the natpol plus study , conducted earlier in poland [ 6 , 7 ] . the procedures applied in the sephar study were in accordance with the declaration of helsinki of 1975 , revised in 1983 . romania 's area was divided into ten regions , recommended by the national commission of statistics . the locations of interviewing were selected at random , on a basis of a computerized system elaborated and applied by a company specialized in research . the structure of the population aged 18 , according to sex , in each location , was obtained from the central bureau of statistics , having as a source document the census made in 2002 . the addresses of interviewing were selected from the database of the general direction of computerized evidence of the population . consequently , we were able to find out that in a specific location there is a person , male or female , aged of certain years . it is worth noticing that , using this procedure , we did not reach a person with a precise identity ; we found out a subject with certain demographic characteristics , with respect to the law no . 677/2001 on protection of persons regarding the processing of personal data and their free circulation in romania . on the whole , 2131 subjects agreed to participate in the study , to have the blood pressure measured , and to fill in the medical history questionnaires . among these , 2017 have accepted also the collection of blood samples . specially trained nurses obtained data for the respondents at the patients ' home . during the visit , the nurse had to obtain the informed consent for the participation in the study , to complete the questionnaire , and to measure the arterial blood pressure , weight , height , and waist circumference . the bp was measured at each arm with fully automatic devices ( oscillometric pressameters omron m5-i ) , adapted for the arm circumference . the highest value between the two arms was that of reference . if at the initial visit the bp was elevated and the subject was not known with arterial hypertension , two more visits for bp measurement were mandated to confirm the abnormal values , at one - to - three day interval . three measurements of bp had to be done at each visit with at least three minutes pause between the consecutive readings , ignoring the first one and calculating the average between the last two of them . the arterial ht was defined as values 140 mmhg for the sbp or 90 mmhg for the dbp , according to the european society of hypertension guidelines applicable in 2005 and reconfirmed by the guidelines issued in 2007 . new diagnosed cases of arterial hypertension were those who have denied a previous diagnosis of hypertension and were found at the initial and at the confirmation visits with high bp . the prevalence of arterial hypertension resulted from the addition of known to the new diagnosed cases . the general control of hypertension was calculated from the ratio of subjects with blood pressure below 140/90 mmhg to the number of hypertensive persons on a whole ( known and newly diagnosed ) . the control of treated hypertension was deduced from the ratio of subjects with blood pressure below 140/90 mmhg to the total number of treated hypertensive persons . data about the prevalence , awareness , rate of treatment , and control of hypertension were obtained for the whole sample and by comparing specific categories of population splitted by gender , age groups , and area of residence with the test . on the analysis of the results , the statistical significance was tested with an interval of confidence of 95% , for which the maximum error was of 2,18% for 2017 respondents . the age and gender structure , the repartition of subjects depending on the area of residence , and the mean values of blood pressure are represented in table 1 . we have to mention that bucharest , the capital , which was analyzed separately from the other nine regions of the country , was included in the urban area , conducting to a higher number of subjects in this category of residence . the mean systolic bp was 137.63 23.43 mmhg , with an important rise for every age group in each gender . the values have continuously increased from 119.99 13.70 mmhg in the youngest age group to 152.76 24.17 mmhg in the age group 65 years old . the mean diastolic bp was 83.13 13.12 mmhg , higher with every age group until the age of 5564 years , but starting to decline in the oldest age group ( 65 years ) . for both systolic and diastolic bp , the mean level was higher in men than in women for adult subjects , the gender difference diminishing by the sixth decade . the total prevalence of the arterial hypertension was 44,92% , significantly higher in men ( 50,17% ) than in women ( 41,11% ) ( p < .0001 ) , but with the gender difference beginning to diminish in the age group of 5564 years . the frequency of arterial hypertension was augmenting with age , reaching a rate above 70% after 65 years . a greater prevalence of arterial hypertension was observed in the rural area ( 49,47% ) as compared to the urban area ( 41,58% ) , which attended statistical significance ( p < .02 ) table 2 . the general rate of awareness was 44,26% , increasing with age , higher in women ( 52,8% ) than in men ( 34,58% ) ( p < .0006 ) , with the gender difference being noticed for every age group after 45 years old . the rate of treated hypertension was again in favor of women ( 46,56% ) in comparison with men ( 30,11% ) ( p < .003 ) table 4 . the number of the total hypertensive subjects who were on the target values of bp was 7,72% . the analysis of data regarding the treatment control has revealed a general rate of 19,88% , with no differences between gender or area of residence table 4 . sephar was the first study addressed to the prevalence , awareness , and control of hypertension on a representative sample for the entire population of romania . even if the selection of the subjects was based on the method of stratified proportional sampling , the results must be cautiously interpreted due to the limited number of subjects included , in comparison with the adult inhabitants as a whole . when referring the data to the literature , we have to notice the heterogeneity of different studies with regard to the sampling method ( stratified sampling or selection during clinical visits ) , age of subjects enrolled , number of visits for the measurements of blood pressure , adaptation of cuff size for the arm circumference , or the period of time when the survey has been done . therefore , a special attention will be focused on the comparison with the results of natpol plus , a study that has been realized with the same methodology in poland . our data are indicating a 44,92% prevalence of the aht in romania , higher than in poland , where was estimated at 29% [ 6 , 7 ] . in general , the rates of aht are greater in europe than in the united states ( 28% ) , canada ( 27% ) , or asian countries including china ( 20% ) or korea ( 22,9% ) [ 4 , 1012 ] . the prevalence of aht in romania can be integrated between lower values in europe like those in greece ( 31,1 ) , sweden ( 38% ) , italy ( 38% ) , united kingdom ( 42% ) , czech republic ( 42% ) , or portugal ( 42,1% ) and higher values such as those from spain ( 47% ) or germany ( 55% ) [ 4 , 1315 ] . for each gender the ratio of aht frequency between the two genders is varying from one study to another and in poland was greater in women . there are not many studies analyzing the results in regard to the area of residence . in contrast to other observations and the assertion that aht is more often encountered in the urban areas , we have found a bigger prevalence of high blood pressure in the rural areas . we are not able to comment , at this moment , if these results could be explained by some deleterious habits in lifestyle such as the excessive salt or alcohol consumption or by concomitant predominance of obesity in the rural zones . less than half of the hypertensive subjects were aware of their condition . in the polish study , . in europe , the hypertension awareness is varying from 46% in portugal to 60% in greece or even 70% in czech republic . in countries with national health programs effectuated for cardiovascular risk reduction , the level of aht awareness has much improved , rising to 66% in united kingdom or 76% in united states and attesting the success of a coordinated policy for high bp detection . the rate of treatment control in our sample ( 19,88% ) was similar with poland and comparable with the results of other studies [ 4 , 14 , 17 ] . the good survey has found that in the atlantic european mainland more patients had uncontrolled bp ( 80% ) compared with northwest , mediterranean , and central europe ( 70% ) . recent data from bp - care study , conducted in central and east european countries ( including romania ) with subjects selected from clinical visits to general practitioners or specialists , are showing that bp control was achieved in only 27,1% of treated hypertensive persons . as a whole , in comparison with the results of the natpol plus study in poland , the prevalence of aht was higher , the awareness was worse , and the bp control was similar . these data should be interpreted , in the future , taking into account the differences between the genetic background , the lifestyle habitudes , and the health policies in each country .

east european countries have reported high prevalence of arterial hypertension ( aht ) . in order to investigate the data for romania , we firstly performed a national survey the study for the evaluation of prevalence of hypertension and cardiovascular risk in adult population in romania ( sephar ) . a representative population was selected using stratified proportional sampling , including 2017 adult subjects , 18 years old . the general prevalence of aht was 44,92% , higher in men ( 50,17% ) than in women ( 41,11% ) ( p < .0001 ) and predominant in rural areas ( 49,47% ) in comparison to the urban ones ( 41,58% ) ( p < .02 ) . aht awareness attended 44,26% , rising with age , significantly lower in men ( 34,58% ) than in women ( 52,8% ) ( p < .0006 ) . we have found a 38,85% proportion of treated hypertensive persons , worse for men ( 30,11% ) then for women ( 46,56% ) ( p < .003 ) . the rate of aht control was 19,88% , with no significant differences between gender . in conclusion , we estimated for romania a high prevalence of aht , a level of awareness and treatment lower than in many european countries and a rate of treatment control at the inferior limit of the european average . males , characterized by a higher prevalence of aht , were also less aware and less treated than women .

september 2011 , mosquito larvae were collected in irrigated rice fields surrounding tiassal , southern cte divoire ( 55247n ; 44948w ) and reared to adults in insectaries on a diet of mikromin ( tetra , melle , germany ) fish food . mosquitoes , 35 days of age , were exposed to 1 of 5 insecticides ( 0.1% bendiocarb , 1.0% fenitrothion , 0.75% permethrin , 0.05% deltamethrin , 4% ddt ) or a control papers for 1 hour , according to standard who procedures ( 7 ) . dna was extracted from individual mosquitoes according to the livak method ( 8) , and a subsample of 500 mosquitoes were all found to be the m molecular form of an . the target site mutation g119s in the ace-1 gene ( ace-1 ) and l1014f and l1014s kdr mutations were screened by using restriction fragment length polymorphism ( 10 ) or taqman assays ( 11 ) , respectively . according to who criteria , an . gambiae mosquitoes from tiassal are resistant to all insecticide classes , and resistance is extremely prevalent ; more than two thirds of mosquitoes survived the diagnostic dose for 4 of the 5 insecticides tested ( table 1 ) . to assess the level of resistance , we exposed the tiassal population and a susceptible laboratory population of an . gambiae ( kisumu ) mosquitoes to the pyrethroid deltamethrin or the carbamate bendiocarb for a range of exposure times and assessed deaths 24 hours later ( technical appendix ) . we found an unexpectedly strong resistance phenotype to the 2 insecticides ( figure 1 , figure 2 ) . for deltamethrin , 4 hours of exposure were required to kill 50% ( median lethal time , [ lt50 ] ) ; in comparison , the lt50 for the susceptible kisumu strain was < 2 minutes ( resistance ratio = 138 ) ( technical appendix ) . similarly , the lt50 for bendiocarb was nearly 5 hours for the tiassal strain yet < 12 minutes for the susceptible strain ( resistance ratio = 24 ) ( technical appendix ) . all mosquitoes were resistant according to world health organization classification ( < 80% dead ) ( 7 ) . time - mortality curve for wild - caught anopheles gambiae mosquitoes from tiassal , southern cte divoire , exposed to deltamethrin ( median time to death = 248 minutes ) . logistic regression line was fitted to time - response data by using sigmaplot version 11.0 ( www.sigmaplot.com ) . time - mortality curve for wild - caught anopheles gambiae mosquitoes from tiassal , southern cte divoire , exposed to bendiocarb ( median time to death = 286 minutes ) . logistic regression line was fitted to time - response data by using sigmaplot version 11.0 ( www.sigmaplot.com ) . to investigate the causes of this resistance , we screened a subset of mosquitoes for the target site mutations , kdr 1014f and 1014s . only the 1014f kdr mutation was detected , and this resistance allele was found at high frequency ( 83% ) . there was a significant association between presence of the 1014f kdr allele and ability to survive exposure to ddt but not to either pyrethroid ( table 2 ) . in contrast , the ace-1 allele was strongly associated with survival after exposure to bendiocarb and fenitrothion ( table 2 ) . * f and l represent mutant resistant alleles ( phenylalanine ) and wild - type alleles ( leucine ) , respectively ; s and g represent mutant resistant alleles ( serine ) and wild - type alleles ( glycine ) , respectively . no resistant homozygotes gg were found among the 186 mosquitoes genotyped for ace-1 by restriction fragment length polymorphism ( a subset of 48 was further screened by using the taqman assay ; congruence between the 2 methods was 100% ) . the frequencies were calculated for each insecticide and mosquito status ( alive / dead ) after exposure . genotypic odds ratios ( ors ) are shown because these exceed allelic ors for ddt ( recessive model ) , bendiocarb , and fenitrothion ( both overdominant models ) , and are similar for permethrin and deltamethrin . for bendiocarb and fenitrothion absence of gg genotypes in the alive group means that ors are infinity , therefore ors are shown if one gg was present . f and l represent mutant resistant alleles ( phenylalanine ) and wild - type alleles ( leucine ) , respectively ; s and g represent mutant resistant alleles ( serine ) and wild - type alleles . gambiae mosquitoes was first reported from cte divoire in 1993 ( 12 ) ; carbamate resistance was detected in the 1990s ( 13 ) . nevertheless , 2 decades later , it is surprising and worrying to find complete resistance to all insecticides tested , particularly for deltamethrin and bendiocarb at such high levels . ace-1 is strongly associated with organophosphate and carbamate resistance , and the absence of 119s homozygotes might be attributable to the high fitness cost of the ace-1 allele in the absence of insecticide ( 14 ) . presence of the 1014f kdr allele alone does not confer the ability to survive diagnostic doses of pyrethroids ; thus , alternative mechanisms must be responsible for the high - level pyrethroid resistance in this population . the selective pressures responsible for this intense multiple - insecticide resistance in tiassal mosquitoes are unclear . there is a high coverage of insecticide - treated bed nets , but this coverage does not differ from that in other parts of the continent , and indoor residual spraying has not been conducted in this region . this use is perhaps the most likely explanation in this district of intense commercial production of rice , cocoa , and coffee . whatever the cause , the implications of this resistance scenario for malaria control are severe . with no new classes of insecticides for malaria control anticipated until 2020 at the earliest ( 15 ) , assessing the effect of pyrethroid resistance on the efficacy of insecticide - treated bed nets is complex because of the poorly understood associations between net integrity , insecticide content , net usage , and net efficacy . nevertheless , resistance levels , such as those reported here , combined with continual selection pressure will inevitably lead to suboptimal mosquito control by use of insecticide - treated bed nets and indoor residual spraying . if unchecked , this resistance could spread rapidly and threaten the fragile gains that have been made in reducing malaria across africa . time - mortality curve for anopheles gambiae mosquitoes , kisumu strain , exposed to deltamethrin and bendiocarb , and time - death data for adult female a. gambiae s.s . mosquitoes , tiassal strain , and standard susceptible colony kisumu 24 hours after exposure to bendiocarb or deltamethrin .

preventing malaria used to seem as simple as killing the vector , the mosquito ; however , a recent study shows that this concept is now anything but simple . the highly effective use of insecticide - treated bed nets and indoor insecticide spraying is being challenged by mosquito resistance to insecticides . in west africa , populations of this mosquito vector are now resistant to all 4 classes of insecticide approved for this use . and no new classes of insecticide are anticipated until 2020 , at the earliest . development of newer classes of insecticide is crucial because if resistance continues unchecked , the hard - earned progress in malaria control in africa could be quickly reversed .

neonatal suppurative parotitis commonly presents with facial swelling , irritability , tenderness of parotid region , and with or without fever . acute neonatal suppurative parotitis is one of the differential diagnoses of facial swelling with a prevalence of 3.8/10000 of neonatal admission . a 32-day - old girl with fever and restlessness was admitted in the hospital . left facial swelling birth weight was 3500 g. body weight , length , and head circumference were 4300 g ( 75 th percentile ) , 52 cm ( 50 th percentile ) , and 38 cm ( 75 th percentile ) , respectively . bilateral multiple reactive lymph node ( size = 6 10 mm ) at anterior cervical chain with a left facial swelling was observed in ultrasonography report . staphylococcus aureus was detected in the microscopic and microbiological evaluations.the patient received a seven - day treatment course with vancomycin and amikacin . acute suppurative parotitis should be suspected in infants with fever , and irritability in pre - auricular region ; and should be treated with appropriate antibiotics . neonatal suppurative parotitis is rare ( 1 ) and commonly presents with facial swelling , irritability , tenderness of parotid region , and with or without fever . acute neonatal suppurative parotitis is one of differential diagnoses of facial swelling with a prevalence of 3.8/10,000 of neonatal admission ( 2 ) . staphylococcus aureus was the most frequent offending organism , but other gram - positive , gram - negative and anaerobic organism may be involved ( 2 ) . intravenous antibiotic therapy is recommended for treatment . surgical treatment is needed in complicated cases such as intra - glandular abscess ( 3 ) . the current report is regarding a 32 day - old girl infant with suppurative parotitis . limited published case reports were found from our country after searching pubmed and google scholar with keywords of neonatal parotitis , suppurative parotitis , and infant . a 32- day - old girl with fever and restlessness was admitted in the hospital . birth weight was 3500 g. body weight , length , and head circumference were 4300 g ( 75 th percentile ) , 52 cm ( 50 th percentile ) , and 38 cm ( 75 th percentile ) , respectively . red blood cell ( rbc ) and white blood cell ( wbc ) counts were 3.1 10 cells / l and 12.6 10/l ( neutrophil : 60% ) , respectively . erythrocyte sedimentation rate and c - reactive protein were 20 mm / l and negative , respectively . results of urine analysis and culture were normal . bilateral multiple reactive lymph node ( size = 610 mm ) at anterior cervical chain with a left facial swelling was observed in ultrasonography report . due to suspected neonatal parotitis , with gentle pressure on stensen s duct , pus was evacuated and transferred to the laboratory . neonatal suppurative parotitis is a rare disease . since 2004 , 16 additional cases were reported ( 3 ) . neonatal suppurative parotitis is one of the differential diagnoses of facial swelling which include trauma , lipoma , and adenomas ( 1 ) . ascending bacteria from the oral cavity is the commonest source of infection ( 4 ) . the most common presentation of neonatal parotitis is fever , swelling , and erythema in the pre - auricular area . leuckocytosis above 1510/l with the neutrophil predominance was found in 71% of the cases , and erythrocyte sedimentation rate ( esr ) was elevated in 20% of the cases ( 5 ) . the patient under study had normal esr , wbc count was less than 1510/l , and serum amylase within the normal limit . insufficient breast feeding , hot weather ( 6 ) , excessive oral suctioning , naso - gastric tube feeding , and maternal breast abscess are the possible risk factors ( 7 ) . low birth weight , immunosuppression and oral trauma were reported as the risk factors for parotitis ( 1 ) . neonatal suppurative parotitis is more common among males , with a rate of 3:1 ( 2 ) . of the 16 cases reported since 2004 , escherichia coli , klebsiella pneumonia , and pseudomonas aeruginosa were also reported ( 4 ) . microscopic and microbiological evaluations showed s. aureus which was consistent with most of the reports . the present report found methicillin resistant s. aureus ( mrsa ) as a cause of neonatal suppurative parotitis ( 8) . the patient had unilateral swelling which was similar to that of similar literature ( 2 , 3 ) . penicillinase - resistant penicillins or first - generation cephalosporin are the good initial choices to effectively control s. aureus , along with clindamycin or a similar medication to control possible anaerobic infections . the present patient received a seven - day treatment . the shortest duration reported in treating s. aureus parotitis in neonatal suppurative parotitis is more prevalent among boys ( 2 , 10 ) . in the current report , antimicrobial treatment lead to clinical improvement in majority of the patients in the study by spiegel et al . complications such as facial palsy , mediastinitis , salivary fistula and extension to external ear are infrequent due prompt antibiotic therapy ( 12 ) . parotid swelling , purulent exudates from the stensen 's duct and growth of the pathogenic bacteria in the parotid plus culture were the diagnostic criteria ( 2 ) . in conclusion , acute suppurative parotitis should be suspected in infants presenting facial swelling , redness of pre - auricular region , and fever .

introduction : neonatal parotitis is a rare disease . neonatal suppurative parotitis commonly presents with facial swelling , irritability , tenderness of parotid region , and with or without fever . acute neonatal suppurative parotitis is one of the differential diagnoses of facial swelling with a prevalence of 3.8/10000 of neonatal admission.case presentation : a 32-day - old girl with fever and restlessness was admitted in the hospital . left facial swelling was found during physical examination . redness was observed in the face . prenatal history was normal . birth weight was 3500 g. body weight , length , and head circumference were 4300 g ( 75 th percentile ) , 52 cm ( 50 th percentile ) , and 38 cm ( 75 th percentile ) , respectively . she was breastfed . pulse and respiratory rates were 130/min and 50/min , respectively . axillary temperature was 37.8c . head examination revealed normal sized fontanel ( 1.5 1.5 cm ) without bulging . eye and ear were normal . abdominal examination revealed no abnormal findings . results of urine analysis and culture were normal . blood urea nitrogen , sodium , potassium , and blood sugar were normal . blood amylase was 10 u / l . bilateral multiple reactive lymph node ( size = 6 10 mm ) at anterior cervical chain with a left facial swelling was observed in ultrasonography report . pus was obtained following gentle pressure on stensen s duct . staphylococcus aureus was detected in the microscopic and microbiological evaluations.the patient received a seven - day treatment course with vancomycin and amikacin . neonate was discharged in a good condition.conclusions:acute suppurative parotitis should be suspected in infants with fever , and irritability in pre - auricular region ; and should be treated with appropriate antibiotics .

esophageal cancer ( ec ) is the 8th most common cancer and the 4th leading cause of cancer death worldwide . the most common pathological type is squamous cell carcinoma ( scc ) , in contrast to the predominance of adenocarcinoma ( ac ) in the west [ 3 , 4 ] . therefore , a study that takes into account the predominance of esophageal squamous cell carcinoma ( escc ) in china is more and more important . it is widely accepted that systemic inflammatory response ( sir ) plays an important role in cancer progression [ 5 , 6 ] . red cell distribution width ( rdw ) is a widely used laboratory parameter for inflammatory disease . recent studies revealed that rdw is associated with prognosis in several cancers , such as lung cancer and prostate cancer . however , to our knowledge , no studies regarding the prognostic value of rdw in ec are available . therefore , the aim of the current study was to investigate the prognostic role of rdw in patients with escc . in addition , we attempt to establish a predictive nomogram to predict the survival prediction in patients with escc . from july 2006 to december 2008 , a retrospective analysis was conducted for patients with escc who underwent radical esophagectomy . the inclusion criteria were as follows : ( 1 ) escc confirmed by histopathology and classified by the 7th edition of tnm classification ; ( 2 ) curative esophagectomy ( ivor lewis procedure or mckeown procedure ) with standard lymphadenectomy ( two - field or three - field lymphadenectomy ) [ 11 , 12 ] ; ( 3 ) limited disease without distant metastasis ; ( 4 ) without preoperative neoadjuvant therapy ; ( 5 ) without previous anti - inflammatory medicines ; and ( 6 ) preoperative laboratory results obtained before esophagectomy . at last , ethical approval was obtained from the ethical committees of zhejiang cancer hospital ( hangzhou , china ) . patients were followed up with a clinical examination in our outpatient department every 3 to 6 months for the first 2 years after surgery and then annually . a cancer - specific survival ( css ) analysis was ascertained in the current study . chicago , il , usa ) and r 3.1.2 software ( institute for statistics and mathematics , vienna , austria ) . independent t - tests and chi - squared tests were used to compare clinical characteristics and rdw . a receiver operating characteristic ( roc ) curve was plotted to verify the accuracy of rdw for css prediction . the area under curve ( auc ) was used as an estimation of diagnostic accuracy . a nomogram for possible prognostic factors ( including age and sex ) associated with css was established by r software , and the predictive accuracy was evaluated by harrell 's concordance index ( c - index ) [ 13 , 14 ] . a p value less than 0.05 was considered to be statistically significant . among the 277 patients , 37 ( 13.4% ) were women and 240 ( 86.6% ) were men . clinicopathologic characters between the high and low groups for rdw were shown in table 1 . patients with rdw < 14.5% had a significantly better 5-year css than patients with rdw 14.5% ( 43.9% versus 23.3% , p < 0.001 ) ( figure 2 ) . rdw 14.5% had a hazard ratio ( hr ) of 1.396 ( 95% confidence interval ( ci ) : 1.0221.908 , p = 0.036 ) for css ( table 2 ) . an roc curve was also plotted to verify the accuracy of rdw for css prediction in the current study . the area under the curve ( auc ) was 0.684 ( 95% ci : 0.6160.752 , p < 0.001 ) . it demonstrated that rdw ( cut - off point : 14.5% ) predicts survival ( css ) with a sensitivity of 44.3% and a specificity of 77.7% ( figure 3 ) . to predict the survival risk ( css ) for patients with escc , a novel model ( nomogram ) was established by prognostic factors combined with age and sex ( figure 4 ) . to the best of our knowledge , this is the first study to determine the prognostic value of rdw in predicting prognosis for patients with escc . we concluded two major findings : ( 1 ) rdw was associated with cancer stage ; ( 2 ) rdw was associated with cancer prognosis . in addition , our study was also the first attempt to establish a predictive nomogram to improve predictive accuracy based on rdw . the mechanism between inflammation and rdw has not been elucidated , but high levels of rdw are thought to be provoked by chronic inflammation and poor nutritional status [ 16 , 17 ] . recent studies demonstrated that rdw is associated with prognosis in several cancers , such as lung cancer and prostate cancer . therefore , in the current study , we investigated the prognostic role of rdw in patients with escc . we concluded that patients with rdw < 14.5% had a significantly better 5-year css than patients with rdw 14.5% ( 43.9% versus 23.3% , p < 0.001 ) . because the values of rdw were positively associated with cancer stage ( t stage and n stage ) in our study , it is not surprising that patients with higher rdw values had worse survival . in the present study , we attempt to establish a predictive nomogram to predict the survival prediction based on rdw and other prognostic factors . we believe that our model could be a simple and easy tool for both the doctors and patients for estimating the survival in the absence of treatment in patients with escc . thus , for example , a female ( 9 points ) patient aged 60 years ( 38 points ) with t2 ( 33 points ) , n1 ( 31 points ) , and rdw 14.5% ( 33 points ) would score 144 total points which converts to a risk probability for death of 57% . thus , we believe that nomogram based on css could be used as an accurately prognostic prediction for patients with escc . recent studies reported that sir plays an important role in cancer progression [ 5 , 6 ] . thus , more and more inflammatory indexes were confirmed . in our previous study , we showed that lymphopenia is an independent predictive factor in patients with escc . however , we also demonstrated in limitations that diabetes mellitus , renal and/or hepatic failure , and other inflammatory diseases may potentially affect the lymphocytes . in the current study , therefore , we attempted to investigate the new inflammatory index ( rdw ) in patients with escc . in addition , we created a nomogram based on the rdw and other associated risk factors . we believe that our model could be a simple and easy tool for both the doctors and patients for estimating the survival in the absence of treatment in patients with escc . based on the findings , we recommend that rdw , a very common , easy , and simple marker , should be considered as a potential prognostic biomarker in patients with escc . second , the c - index showed that the model has a good accuracy but it is not perfect . thus , there is still room for improvement of the predictive ability of the nomogram . the data in the current study was overlapped but from a different perspective . in our previous study , we mentioned the limitation that lymphopenia itself alone without other variables may not associate with the cancer prognosis . we concluded that rdw predicts survival similar to lymphocyte count and should be considered as an alternative to lymphocyte count . however , further studies are needed to illuminate the relationship between rdw and prognosis in patients with escc . in summary , based on the findings of the current study , we concluded that rdw is a potential prognostic biomarkers in patients with escc . the nomogram based on css could be used as an accurately prognostic prediction for patients with escc .

objectives . the prognostic value of inflammatory index in esophageal cancer ( ec ) was not established . in the present study , we initially used a nomogram to predict prognostic value of red cell distribution width ( rdw ) in patients with esophageal squamous cell carcinoma ( escc ) . methods . a total of 277 escc patients were included in this retrospective study . kaplan - meier method was used to calculate the cancer - specific survival ( css ) . a nomogram was established to predict the prognosis for css . results . the mean value of rdw was 14.5 2.3% . the patients were then divided into two groups : rdw 14.5% and rdw < 14.5% . patients with rdw < 14.5% had a significantly better 5-year css than patients with rdw 14.5% ( 43.9% versus 23.3% , p < 0.001 ) . rdw was an independent prognostic factor in patients with escc ( p = 0.036 ) . a nomogram could be more accurate for css . harrell 's c - index for css prediction was 0.68 . conclusion . rdw was a potential prognostic biomarker in patients with escc . the nomogram based on css could be used as an accurately prognostic prediction for patients with escc .

in 2010 , 209,060 patients are expected to be diagnosed with breast cancer in the united states.1 at least 20% of breast cancers are characterized by triple - negative receptor status ( negative for estrogen receptor [ er ] , progesterone receptor [ pr ] , and her2).2 triple - negative breast cancer ( tnbc ) is highly proliferative and sensitive to systemic chemotherapies . however , despite its relative sensitivity to chemotherapy , patient outcomes are poor compared with other subtypes of breast cancer ( her2 + or er+ ) . the cause of death of patients with tnbc is often recurrence ( 30 - 40% of tnbc cases ) , which presents as distant metastasis . therefore , the mechanism of metastasis needs to be studied separately from that of tumorigenicity . tnbc is the only major type of breast cancer for which no specific fda - approved targeted therapy is available to improve patient outcomes ; it is resistant to targeted therapies such as hormonal therapy and her2-targeting therapy . a parp inhibitor is under development , but it is not yet an established standard therapy . our preliminary data show that erlotinib inhibits tnbc in a xenograft model , a promising result . however , inhibition of metastasis by erlotinib is accompanied by nonspecific effects because erlotinib can inhibit other kinases ; thus , more direct targets that regulate tnbc metastasis need to be identified to improve its therapeutic efficacy . egfr is known to be overexpressed in tnbc.3 - 5 the question remains whether egfr is a valid target when many of the phase ii study of egfr tyrosine - kinase inhibitor in metastatic breast cancer has at most 5% response rate . however , at the european society for medical oncology meeting in october 2010 , a major breakthrough in egfr - targeted therapy was reported.6 in this randomized phase ii study , 173 patients with metastatic tnbc were randomized to receive either cetuximab , an anti - egfr antibody , plus up to six 3-week cycles of cisplatin ( n=115 ) or cisplatin alone ( n=58 ) . an overall response rate of 20% was seen in patients who received the cetuximab / cisplatin combination , compared with a response rate of 10.3% in the cisplatin - alone arm . adding cetuximab to cisplatin doubled the progression - free survival duration from 1.5 to 3.7 months ( hr 0.675 , p = 0.032 ) . human tnbc may have characteristics of epithelial - mesenchymal transition ( emt).4 , 5 emt is an essential developmental process by which cells of epithelial origin lose epithelial characteristics and acquire a mesenchymal phenotype with fibroblast - like morphology , cytoskeleton reorganization , increased motility , invasiveness , and metastatic capability.7 , 8 emt is characterized by loss of epithelial cell junction proteins ( e.g. , e - cadherin and cytokeratins ) and gain of mesenchymal markers ( e.g. , vimentin and fibronectin).7 , 8 it has been proposed that emt - like processes allow tumor cells to disassemble and migrate to tissue or organ sites distant from the primary tumor ( metastasis).7 , 8 it has become increasingly clear that emt may play a major role in invasion and metastasis of tnbc.3 - 5 we have previously shown that epidermal growth factor stimulates egfr - expressing tnbc cells such as sum149 , mda - mb-468 , and bt-20 and induces upregulation of phosphorylation of erk and/or akt . further , when these cells are treated with the egfr tyrosine kinase inhibitor ( tki ) erlotinib , erk and/or akt phosphorylation can be downregulated . these data suggest that the egfr pathway is intact in these cells.9 , 10 to further elucidate egfr pathway activity in tnbc , we examined whether tnbc cells ( sum149 ) exhibited epithelial or mesenchymal phenotypes . matrigel is a gelatinous protein mixture secreted by mouse tumor cells , which resembles the complex extracellular environment found in many tissues . this 3d culture system can be used to assess cell invasiveness and motility , which reflect part of the epithelial - to - mesenchymal morphological process due to the rapid formation of projections and filopodia . such projections or filopodia also may strongly correlate with metastatic potential.11 - 14 in a two - dimensional ( 2d ) culture system , using standard culture plates with f12 medium containing 5% fbs , sum149 cells showed an epithelial phenotype characterized by the localization of e - cadherin and -catenin at the sites of cell - cell contact ( data not shown ) . however , in a 3d - culture system , sum149 cells rapidly formed projections or filopodia and changed to a mesenchymal - like phenotype ( fig . sum149 cells with projections exhibited reduced e - cadherin expression and increased vimentin expression compared with sum149 cells in 2d culture . however , when these cells were treated with the egfr - tki erlotinib , the mesenchymal cell phenotype changed back to epithelial - like in the 3d system , e - cadherin was upregulated , vimentin was downregulated , and -catenin localized to the cell membrane ( fig . interestingly , the erlotinib concentration that inhibited the mesenchymal phenotype ( 0.1 m ) did not have a cytotoxic effect and was one log lower than the concentration that inhibited proliferation ( 1 m).15 after observing that erlotinib reversed the mesenchymal phenotype of sum149 tnbc cells in vitro , we hypothesized that erlotinib inhibits tumor growth and metastasis in a sum149 tnbc xenograft model.15 to address this hypothesis , we generated a sum149 xenograft model by implanting luciferase - expressing sum149 ( sum149-luc ) cells into the mammary fat pads ( mfp ) of athymic nude mice . sum149 tumors were readily apparent in the mfp after 14 d and grew rapidly . beginning 3 w after tumor cell implantation , the mice were treated with erlotinib or a vehicle control administered by oral gavage daily for 4 w. to identify the optimal doses that inhibit tumor growth and/or metastasis , we used three different doses of erlotinib ( 25 , 50 , or 100 mg per kilogram of body weight ) . the doses of 50 and 100 mg / kg / d were chosen based on previous studies of antitumor activity of erlotinib.16 , 17 the dose of 25 mg / kg / day was chosen because of its known subtherapeutic effect . the higher doses ( 50 and 100 mg / kg ) of erlotinib showed significant tumor - growth inhibition in the sum149 xenograft model ( fig . , the mean tumor - growth inhibition rates compared with the control group were 84% in the 50-mg / kg group ( p < 0.0001 ) and 103% in the 100-mg / kg group ( p < 0.0001 ) . some tumor growth inhibition ( 43% ) was observed in the 25-mg / kg group , but this inhibition was not significant compared with the control group ( p = 0.06 ) ( fig . to evaluate the anti - metastatic activity of erlotinib in tnbc , at the endpoint of the animal study , we collected lung tissues from the mice and then performed ex vivo luciferase imaging to detect spontaneous lung metastases ( fig . the metastatic tumors in bioluminescence - positive lung tissues were further confirmed by hematoxylin and eosin staining ( fig . bioluminescence - positive lungs , indicating the presence of metastatic tumors , were detected in 3 of 7 mice ( 43% ) in the control group . however , no bioluminescence - positive lungs were detected in mice in the three erlotinib - treated groups , indicating that erlotinib inhibited lung metastasis of tnbc ( p = 0.04 ) ( fig . 2d).15 in immunohistochemical analysis , erlotinib increased the expression of the epithelial marker e - cadherin and lowered the expression of the mesenchymal marker vimentin in all treated tumors compared with control tumors ( fig . inhibition of lung metastasis and reversal from a mesenchymal to an epithelial phenotype were observed even in the low - dose condition ( 25-mg / kg erlotinib ) , whereas at that dose primary tumor growth was similar between the treated and control groups.15 these findings suggest that emt modulation by targeting egfr may reduce metastasis of tnbc . the above results support a concept that metastasis and tumorigenicity should be considered separately and justify the need to study the role of egfr in tnbc metastasis .

our preliminary data show that erlotinib inhibits triple - negative breast cancer ( tnbc ) in a xenograft model . however , inhibition of metastasis by erlotinib is accompanied by nonspecific effects because erlotinib can inhibit other kinases ; thus , more direct targets that regulate tnbc metastasis need to be identified to improve its therapeutic efficacy .

in africa , the health impact of schistosomiasis , whether caused by schistosoma haematobium or by s. mansoni , is a well - known public health problem , one that is now receiving well - deserved attention . this attention is focused primarily on the most vulnerable part of the community , that part of the population that is heavily debilitated by the disease and will benefit from mass drug administration . for the purpose of control and local elimination of the parasites , a quick sensitive test that may be low in specificity is acceptable but there is need to improve the detection of infection in chronic stages of disease or when parasitaemia is low . the detection of infection among adults with long standing chronic infections is important particularly in the hospital environment when sequelae of the infection are suspected . bladder damage and even bladder cancer are common problems in endemic areas and a definitive diagnosis which has high sensitivity , specificity , and can be carried out in a diagnostic laboratory with adequate facilities is needed . definitive diagnosis of schistosomiasis is dependent on the demonstration of parasite eggs in urine or stool , and more recently the detection of circulating antigens ; however , these tests have not been assessed in adults . detection of parasite - specific dna is an option that is being used with several infections for example , malaria , and it presents an opportunity with schistosoma haematobium and perhaps with s. mansoni . the importance of this has been shown in a recent study involving s. haematobium , it was evaluated using latent class modeling and was shown to detect parasite - specific dna fragments in adults both when eggs were present in urine and in 10% of cases , where eggs were not present . gelfand in a very careful clinical analysis of mainly adults infected with bilharzia ( schistosomiasis ) concluded that in rhodesia ( now zimbabwe ) bilharziasis , both the urinary and intestinal is to be regarded as having serious consequences , he was speaking about the infection in adults as well as children . in a more recent review , king and dangerfield - cha reiterate this importance although they do not cover the material in clinical detail as does gelfand ( loc cit ) . more specifically and focusing on s. haematobium the role of this species in bladder cancer is well studied , not only in egypt but also in kenya , ghana , and zimbabwe . whereas in children this infection causes haematuria and frequently bladder polyposis , these problems ameliorate following treatment ; however , the more severe squamous cell carcinoma appears in the 3rd and 4th decades of life . the methods we have used to diagnose schistosomiasis decrease in sensitivity in adulthood and the question arises , are the current diagnostic tests sufficiently sensitive to detect infection in all age groups ? community - based surveys done using the presence of schistosome eggs in urine or faeces as positive infection always show a similar population trend . prevalence rises to a peak during the years 1015 , then declines through the 20s , 30s and 40s to well less than half of the childhood peak . this surely indicates that the parasite causes the greatest health impact among children , but does it ? as lesions form around the schistosome eggs , particularly in the bladder , granulomas develop and egg passage to the exterior becomes hindered . there is a strong inflammatory response from the host and over time metaplasia sets in and eventually the chronic inflammation initiates the development of cancer . ultrasound examinations done in the ghana study certainly show the extent of bladder damage in adult bladders ; yet there were numerous people in ages over 30 years who showed severe damage but no evidence of eggs in the urine . a detailed study of the sensitivity and specificity of various diagnostic tests used in this study included haematuria , antigen detection , egg detection , and antibody detection but the results were equivocal and indicated the need of a more sensitive , yet specific test for improved diagnosis of schistosome infection . detection of parasite dna in blood specimens is now an accepted procedure , whether the dna is intracellular or extracellular , the presence of trace but detectable quantities of specific fragments provides evidence of the organism . malaria parasites can be detected in haemolysed blood specimens , but an advance occurred when plasmodium falciparum - specific dna was also demonstrated in saliva and urine . this dna was free in saliva and in the urine clearly passed through the kidneys prior to excretion and was undamaged . collecting urine for subsequent pcr examination has logistic issues as the urine must be fixed or frozen rapidly to 20c for storage and transport . operating on the hypothesis that schistosome - specific dna is passed in urine , we proposed that it could be trapped in a convenient paper filter . as such , this would obviate considerable handling problems and it was shown to be the case . a 50 ml specimen of urine was passed through coarse filter paper ( whatman no . 3 ) ge healthcare , bucks , uk . the paper is sturdy and will hold a cone when folded , filtration could be processed in the neck of a disposable vessel , the paper subsequently dried away from aerial and insect contamination and if maintained dry , the dna would be preserved . workers in kenya and israel had identified a specific fragment of dna ( dra1 ) that was detectable from snails infected with s. haematobium miracidia . the fragment is specific for s. haematobium and was shown to be more sensitive than egg detection or haematuria with high specificity , particularly among adults where egg detection versus pcr showed a sensitivity of 59% . this infers that among adults , egg detection is unsatisfactory and supports the comment made above . analysis of results from a large - scale epidemiological study comparing three measurements , haematuria , presence of parasite eggs , and detectable parasite - specific dna using latent class modeling was undertaken . this is a statistical technique that models the probability of each combination of test results to give the true infection status ( this is the latent class variable true infection which is unobservable ) . this model provides response probabilities for sensitivity ( se ) and specificity ( sp ) for each of the test procedures and finally indicates statistically which test is the most sensitive ( i.e. , with fewest false positives ) and most specific ( with fewest false negatives ) . it was shown that presence of dra1 in males exceeded haematuria ( se 87.6% and sp 34.7% ) and detection of eggs ( se 70.1% and sp 100% ) . in females , presence of dra1 exceeded haematuria ( se 86.7% and sp 77% ) and presence of eggs ( se 70.1% and sp 100% ) . this suggests that detection of dra1 is a definitive test for the presence of s. haematobium infection . analysis of the dataset described above ( figure 1 ) shows that the proportion of positive cases detected for each age group in the study was higher when dra1 was detected by dna amplification than when parasite eggs were observed for all age groups ( p = 0.0005 ) , although when stratified across age groups , significant differences were only seen in the 2029- ( p = 0.004 ) and 4049- ( p = 0.02 ) year - old age groups . the message from these studies is that if adult populations are examined for schistosome infection , if the only test applied is examination of urine for eggs , a significant number of people will be declared uninfected , yet they may yet be infected . this example has shown that , for schistosomiasis , detection of parasite - specific dna in urine is feasible , highly sensitive , and specific . to make this applicable in endemic countries where it may be difficult to operate thermocyclers and electrophoretic equipment , there is an alternative method that is already being promoted , namely , the loop - mediated isothermal amplification ( lamp ) technique . this method is well established as a viable and economical approach to dna amplification and detection . work needs to be done on refining the process for both species and developing it in a way that it can be put to use in the field as well in the hospital and diagnostic centre . the introduction of tests of high sensitivity and specificity will be valuable in monitoring the elimination programmes that are being carried out in many parts of the endemic world . in particular , when interventions are introduced , monitoring of treated individuals with very low parasitaemia will be necessary because of the risk of maintaining transmission to snails , and reinfection of the community . detection of parasite - specific dna will become an important means of identifying and hopefully eliminating risk foci . there is no inference here that dna detection is promoted to supersede other standard means of diagnosing schistosome infection . they are well tried and serve a role in most circumstances ; however , as the need for more sensitive tests arise as outlined above , dna detection adds another diagnostic which will expand the ability of the epidemiologist to collect data pertinent to any programme designed to eliminate the disease or warn clinicians of the potential problem of bladder cancer or some other sequel of this debilitating parasitic infection .

schistosomes are long - lived parasites , hence schistosomiasis is a chronic disease with severe long - term implications . however , definitive diagnosis of active infection has been difficult because demonstration of infection has depended on detecting parasite eggs in urine and/or stool . in the case of schistosoma haematobium which parasitizes the urinogenital system , this method has low sensitivity in adults . detection of parasite - specific dna in urine has been demonstrated and this has similar specificity but improved sensitivity . the implications of this new procedure and the impact on diagnosis are discussed .

physiotherapy ( pt ) has been recognized as a mode of treatment over the years and is rapidly growing as a profession , especially in developing countries1 , 2 . according to the us department of labor , physical therapists are primary health care professionals who diagnose and treat patients of all ages3 . various subspecialties of pt have been recognized including cardiovascular and pulmonary , orthopedics , neurology , sports , etc.4 , which treat a variety of patients to decrease disability and dependency5 . with increases in the disabled population and life expectancy , disability has been reported to be one of the most imperative social and economic medical issues in saudi arabia ( sa)6 . this emphasizes the need for the development and recognition of pt in multidisciplinary healthcare structures . pt was introduced to sa a little later than the rest of the world7 and is still at the development stage . for professional growth , it needs support from fellow healthcare practitioners , who should be aware of role of pt professionals3 . if a physician were well informed about how pt could help the treatment of patients and prevent the development of complications , hospital stays could be decreased to a larger extent2 , 3 , decreasing the burden on the healthcare system . in order to deliver effective patient care , communication , cooperation and agreement between physicians and physical therapists patients need a physicians referral to see a physical therapist , and physicians are dominant and take decisions for other health care professionals9 , 10 . perceptions of physicians about pt affects the treatment received by the patient11 , 12 . to the best of our knowledge , no study has been performed in sa that has evaluated the awareness of physicians about the pt profession . hence , we decided to study awareness , perception and beliefs about pt among physicians working in sa . the results of this study should help to bridge the gap in the healthcare system and suggest ways for the development of the pt profession in sa for ideal patient care . three hundred and fifteen members of the saudi commission for health specialties ( scfhs ) with various specialties , nationalities , designation , and work experience , working in various hospitals in 5 regions of saudi arabia were invited to participate in this study . after exclusion of interns , academicians and incomplete questionnaires , 280 respondents were included in the study . the questionnaire used for data collection was based on similar studies done in other countries3 , 8 , 9 , 11 . it was first sent to two senior physical therapists who were experts in research design for their feedback . it was also sent to 10 physicians for a pilot study to ensure that the questions were clear and easily understood by the respondents . it included various sections about physicians demographics , educational levels and knowledge about pt . it also included questions about physician s attitudes and perceptions concerning pt as a profession and their beliefs about physical therapists ability to treat patients . first , in order to reach respondents working in different regions of the country , this study was extensively promoted on various social networking sites highlighting its purpose and objectives . the questionnaire was then placed online and an invitation to participate in the study along with an explanation of its importance , and a link to the questionnaire was sent to physicians via email . participants had to complete the questionnaire before the deadline and their response was considered as consent to participate in the study . all ethical permissions were obtained from the institutional review board of king saud university . the statistical package for social sciences ( spss ) 21 program was used for data analysis . the level of referral with regard to physicians experience and specialty , education , and work hospital was calculated by cross - tab analysis . to assess physicians perceptions and beliefs , of the 280 respondents , 29% were females while 71% were males : 46% were residents , 30% consultants , 21% registrars and 3% professors . the majority of the respondents ( 50% ) had work experience of 15 years . most of the respondents ( 60% ) reported working in the central region of sa . respondents who reported working in government and military hospitals were of 30% and 20% of the total , respectively . the distribution of respondents on the basis of their specialty is shown in table 1table 1.demographic characteristics of respondents : number and percentagework hospitalsn ( % ) government84 ( 30)military57 ( 20)educational 47 ( 17)national guard36 ( 13)primary care56 ( 20)experience < 5140 ( 50)520 years100 ( 36)>20 years40 ( 14)specialtyorthopedics30 ( 11)pediatrics15 ( 5)gynecology12 ( 4)surgery29 ( 10)emergency15 ( 5)neurology25 ( 9)medicine39 ( 14)radiology12 ( 4)general practitioners103 ( 37 ) respondents who reported attending awareness lectures about pt or had received special training on cases that can benefit from pt seem to have been more aware than other respondents . in all , 17% of the respondents reported attending awareness lectures about pt . among these , 15% reported referring patients to pt departments regularly . on the other hand , 10% of those who did nt attend any lecture about pt reported referring patients to pt departments . similarly , among 35% of respondents who reported receiving special training on cases that can benefit from pt , 20% reported referring patients to pt departments regularly ( table 2table 2.educational background of respondents in comparison to their referral rate : percentageattended a lecture about physiotherapyreferral ratenot at allrarelyoccasionallyregularlyyes51.1%19.1%14.9%14.9%no48.9%27%14.2%9.9%received special training on cases that benefit from physiotherapyyes41.3%30.6%35%20%no58.7%69.4%65%80%had physiotherapy facilities in medical schoolyes34.1%40.3%27.5%50%no42.8%37.5%52.5%36.7%not sure23.2%22.2%20%13.3% ) . among those who reported referring patients to pt departments regularly , at least 50% reported receiving pt education in their medical school . besides this , 41% of respondents also reported that they knew about the various specializations of pt . out of 280 respondents , 11% reported referring patients to pt departments regularly when necessary , while 49% reported that they never referred patients to a pt department . among the remainder , 26% reported referring patients rarely , and 14% occasionally ( table 3table 3.referral of patients to a physiotherapy department : number and percentagereferral to pt departmentn ( % ) do no refer at all138 ( 49)rarely refer72 ( 26)refer occasionally40 ( 14)refer regularly30 ( 11 ) ) . the majority of respondents working in government and military hospitals reported that they did not refer patients to pt departments at all . sixty - seven percent of respondents with 15 years of experience and 13% respondents with 1115 years of experience reported regularly referring patients to pt departments . in relation to respondents specialty , 29% from medicine , 21% from surgery , 13% from orthopedics , 11% from pediatrics and 9% from gynecology reported regularly referring patients to pt departments . perceptions and beliefs of participants about pt as a profession : among the 280 participants , 44% of the respondents reported that pt is a professional course , while the remainder either thought that it was not a professional course or that they were not aware of its status . overall , 58% reported a negative perception about pt ( table 4table 4.reasons for respondents negative perceptions about physiotherapycauses of negative perception about physiotherapypercentagebecause i do not know much about physiotherapy training17because physiotherapy is complimentary to medicine61because physiotherapy does nt have enough scientific basis22 ) . although 75% of the respondents reported believing that physical therapists are well trained to take decisions regarding patient treatment , 20% of respondents still reported include prescriptions in their referrals . among those who received some training or attended awareness lectures about pt , 20% and 9% of respondents respectively reported that they did not include prescriptions in their referrals ( tables 5table 5.respondents view on the ability of physical therapists to deduce treatment in relation to receiving special training : number and percentageability of physiotherapist to deduce patients treatmentreceived special trainingyesnoyes7326.1%13748.9%no269.3%4415.7% and 6table 6.respondents who attended awareness lectures or workshops about physiotherapy and their referrals with or without prescriptions : number and percentagereceived special training on cases that benefit from physiotherapyincluding prescriptionyesnoyes4616.4%5318.9%no5620%12544.6%attended lecture about physiotherapyyes238.2%248.6%no7928.2%15455% ) . at least 55% of respondents reported that they were not comfortable about referring patients to pt departments without prescriptions . this study was done to assess the awareness , perceptions and beliefs about pt among physicians working in sa . the majority of the respondents were from the central region of sa , where the highest number of hospitals and rehabilitation centers are located . the results show that although there was moderate awareness about pt among the respondents , there was variation in the referral of patients to pt departments , which was dependent on physicians specialty and work experience . compared to similar studies around the world3 , 8 , 11 , 13 this shows that awareness about the importance of pt treatment is unable to convince respondents to refer patients to pt departments when required . however , respondents who received some training or attended lectures about awareness of pt reported referring more patients than their counterparts . this highlights the need for organizing various workshops and lectures for physicians about the effectiveness of pt for various conditions , on a regular basis , to update physicians with evidence - based pt treatments14 . this would in turn increase physicians confidence in pt and encourage referrals to pt department5 , 8 . traditionally , physical therapists have more often been seen as technicians subordinate to physicians with no freedom to evaluate , diagnose or decide treatments for the patients2 , 12 . our results show that awareness about pt is higher among respondents with work experience of 15 years than among those with more experience . this indicates the growth of pt as a profession in recent times . with the advancement of information and technology , the results also show that respondents reported that they were more aware of pt if it had been offered as a course at their graduating institution . little difference was found in awareness and patient referrals among respondents working in different hospitals . patient referrals may be lower in government hospitals due to their higher patient load5 and lack of staff and facilities . despite rising awareness , most of the respondents reported that they refer patients with a prescription. this mode of referral , although practiced for long12 , has been widely criticized in the developed countries as a mistaken attitude of physicians towards physical therapists15 , 16 . moreover , prescriptions written by physicians contain differential diagnosis and treatment orders8 , most of which are often found to be wrong17 . physical therapists first contact with the patient is now widely practiced in countries like the uk and australia18,19,20 . the majority of insurance companies reimburse for pt services only if it is prescribed by physicians , which could be another reason for the upper hand of physicians over physical therapists21 . although some respondents reported that they considered pt is an independent branch of medicine , and that physical therapists were sufficiently qualified for clinical decision making , first contact of patient with physical therapists is still not common in saudi arabia . it has been shown in various studies around the world that physicians have limited knowledge about the role of pt in the healthcare system12 , 22 . this can be achieved by pursuing advanced studies and involving themselves more in research . more interaction with fellow physicians23 to discuss evidence - based treatment and prognosis of patients conditions also needs to be encouraged5 , 24 . the results of this study also highlight the need for research about pt services available in different hospitals , especially in rural areas . a similar study with a larger sample and equal representation of physicians experience should be done in order to find if awareness about the professional image of pt has changed over the past few decades . to the best of our knowledge , this is first study conducted in saudi arabia to evaluate the awareness of physicians about the physiotherapy profession . despite considerable awareness about the pt profession among physicians in sa , it is the responsibility of physical therapists to upgrade the perception of other members of healthcare teams about their profession .

[ purpose ] over the years physiotherapy has been recognized as a popular mode of treatment that decreases the disability and dependency rate of patients . however , there is still a need for its recognition in multidisciplinary health care structures . if a physician were well aware of how a physical therapist could help with treatment if patients and prevent complications , hospital patient load could be decreased to a greater extent . the aim of this study was to study the awareness , perception and beliefs of physicians working in saudi arabia about physiotherapy . [ subjects and methods ] three hundred fifteen members of the saudi commission for health specialties ( scfhs ) with different specialties , nationalities , designation , and work experience , working in various hospitals in 5 regions of saudi arabia were invited to participate in this study . a 22-item questionnaire was used for data collection including sections on physicians demographics , educational levels and knowledge about physiotherapy . [ results ] after applying the inclusion and exclusion criteria , data from 280 respondents was used for analysis . seventy - five percent of respondents reported to having some knowledge of physiotherapy , and 11% of them referred patients to physiotherapy departments regularly , while 14% referred patients occasionally . to the best of our knowledge , this is first study performed in saudi arabia to evaluate awareness of physicians about the physiotherapy profession . [ conclusion ] the results of this study highlight the need to organize various workshops and lectures about the effectiveness of physiotherapy in various diseases for physicians , on a regular basis , to update them with evidence - based treatment . it is the responsibility of physical therapists to raise the perceptions of other healthcare professionals about their profession .

the practice and scope of science , and of the scientist , are constantly evolving . with the emergence of new tools and techniques that can rapidly connect thousands , or tens of thousands , of citizen scientists however , these opportunities challenge the traditional scientific research model , whereby clearly defined research questions and hypotheses are implemented by a small , highly trained team of researchers at an academic , private , or government institution . indeed , a vast phalanx of citizen scientists can readily surpass several previous limitations of science , including the amount information that can be collected and the speed at which it can be processed . particularly in scientific fields that require large datasets for scientific progress , some researchers are looking beyond the traditional scientific team into the realm of citizen science . the concept of citizen science , or public participation in scientific research , is not new . for example , the national weather service launched the still - ongoing cooperative observer program in 1890 to help understand national meteorological changes in real time , and to aid long - term climate studies ( 24 ) . christmas bird count in 1900 to help raise awareness about the growing need for ecological conservation ( 13 ) . now in its 116 year , the christmas bird count has helped scientists to understand a variety of aspects of bird ecology and natural history ( 22 , 23 , 27 ) . however , these early projects revealed some of the challenges of large - scale citizen science , the importance of consistent training , data uniformity , and data reproducibility for efficacious use of the collected data . for example , in the context of the bird count , data had been collected on the number of deceased birds found along roadsides without providing a comparison with the total number of birds estimated to be in that geographical region , making it difficult to accurately calculate the health or death rates of specific bird populations . these issues have since been addressed , and new models have been implemented to provide more accurate measurements of bird ecology and population health ( 27 ) . regardless of their limitations , citizen - science projects have transformed the practice of science by democratizing access to scientific methods , encouraging scientific literacy , and engaging the next generation of scientists early in their life . for over a century , researchers have been finding new and more efficient ways to solve relevant scientific problems by tapping into the vast pool of science enthusiasts from the general public . historically , these citizen - science projects have been primarily associated with making skilled observations , particularly in archeology , ecology , and astronomy . for instance , citizen - science projects in astronomy might simply involve going out at night to observe stars an activity that does not require sophisticated equipment or a specialized environment ( such as a laboratory ) . however , since the early 2000s , the citizen - science movement has been greatly enhanced by the internet of things , wherein internet - connected devices and mobile software platforms have become ubiquitous , especially for smartphone applications . project information dissemination , detailed protocols for participation , and data collection methods are therefore available now to the majority of the world s population , giving rise to more sophisticated and democratized roles for citizen scientists , and a more effective strategy for completing large research projects ( 28 ) . this has opened up avenues for citizen - science projects in other disciplines , such as biology , bioinformatics , and microbiology , which have been historically inaccessible to the average citizen due to resource limitations . several striking examples have recently been published that show the power of utilizing modern - day citizen science to provide meaningful contributions to scientific progress . one of the earliest and largest success stories from such work by the general public was foldit an analysis of foldit showed that the game s 57,000 players outperformed advanced computer algorithms for predicting protein structure ( 7 ) and , in the following year , contributed to solving the crystal structure of the mason - pfizer monkey virus ( m - pmv ) retroviral protease ( 15 ) . similarly , over 100,000 citizen neuroscientists from over 130 countries are playing the citizen science game eyewire , significantly accelerating the work of traditional scientists in their quest to map the mouse retinal connectome ( 16 ) . recording observations and playing games over the internet are seemingly natural fits for engaging large populations of nonscientists for the purposes of scientific progress . however , as researchers realize the potential inherent in the citizen - science movement , this approach is being combined with emerging technologies and collection devices to create new opportunities . specifically , there has been a large increase in the number of citizens engaged in studies regarding the microbiome ( the ecosystem of microbes ) or metagenome ( the collection of genomes from a sample ) . driven in part by the steady drop in next - generation sequencing costs ( 21 ) , along with the increasing public interest in the quantified self and personalized medicine movements ( 19 ) , which aim to provide individuals with a deeper understanding of their own biology , the general public has shown a great curiosity to learn about the microorganisms living in , on , and around them to the delight of many scientists conducting research in this field . for most studies related to the microbiome , we are just starting to catalog the molecular basis of our environments ( 11 ) . widespread participation enables us to more quickly and efficiently survey various landscapes and systems in terms of microbial organisms , which is essential if we are to truly understand the implications of specific microbial profiles on or in a given sample . the desire to learn more about the elusive human microbiome has spurred the creation of many services that provide both individualized microbiome reports and population- and city - scale microbiome measurements . for instance , american gut , which is part of the human food project , is a service that primarily focuses on providing participants with information on their intestinal microflora . similarly , ubiome is a personalized microbiome service that can assess the gut , nose , mouth , skin , and genital microbiome . in addition to providing individualized reports to users , who typically send their samples to these services through the mail ( as per user kit instructions ) , both american gut and ubiome are using the collective datasets to more fully understand the impact of the human microbiome on health . academic groups have also used citizen scientists to create reports on the microbial communities pertaining to humans , such as the microbiome of the belly button ( 14 ) , and a survey of flu infections and outbreaks ( 12 ) for people when they begin to feel sick . other projects include a focus on the mouth or intestinal microbiome , such as the human oral microbiome database ( homd , 6 ) and metahit ( metagenomics of the human intestinal tract , 18 ) , whereas still others focus on areas of the land , sea , and air as part of the earth microbiome project ( emp , 11 ) , a collection of microbes from extreme environments called the extreme microbiome project ( xmp , 9 ) , and the metagenomics and metadesign of subways and urban biomes ( metasub , 9 ) . also , the work of the global ocean sampling day ( osd , 17 ) enables a global effort to catalog the diversity of life across the world s oceans . these and a wide variety of citizen - science projects can be found on the scistarter website ( http://scistarter.com/ ) . often , there are research projects or strategies that could provide a clear picture for the understanding of a specific scientific question , but scientists may not have the required manpower or funding ( or both ) to make it happen . however , by utilizing citizen science , scientists are gaining myriad research team members requiring little or no funding , who can collectively survey large geographical areas , analyze large datasets , or provide large sample numbers ( 8) . as alluded to above , having widespread participation in microbiome - themed citizen - science projects helps to greatly enhance the statistical power of data analysis and introduces nonscientists to more detailed information pertaining to microbiology . for instance , with regard to the microbiome , there is a widely held assumption that all bacteria are bad , or there are misunderstandings related to results from microbiome experiments . an example of the disconnect between research results and the media interpretation of said results was revealed through the new york city ( nyc ) pathomap project , which surveyed the microbiome of all 468 stations across nyc s subway system ( 1 ) . even though the vast majority of bacteria found were harmless , the general media ( newspapers , tv , online ) focused primarily on sequences that mapped to potential pathogens . however , this was also a learning opportunity for the pathomap team , highlighting the importance of transparent and thorough explanations for citizen - science projects . while pathomap participants were provided with necessary information about the precise experimental protocol and instructions for the real - time mobile app that recorded each part of the process of data and sample collection , it was important to also communicate the difference between identifying a match between a dna fragment in a sample and a known sequence versus finding actual living microbial organisms , including the publication of an update to the original paper ( 2 ) . by having an open channel for public engagement via citizen science , including twitter , blogs , and online forums ( 25 ) , researchers can improve communication on the current understanding of complicated project data and help dispel fear related to misinterpretation of data and/or the misunderstanding of the research process . in a 2015 study conducted by the pew research center , it was reported that the public s limited knowledge in science , technology , engineering , and math ( stem ) is a problem for scientific progress . furthermore , it was revealed that scientists and the general public see scientific issues through different lenses , creating a gap sometimes a chasm between the scientific consensus and public belief ( 10 ) . while the reasons for these results are many and complex , we suggest that citizen science is a valid mechanism to help rectify shortcomings in the public s understanding of science . for example , participation in citizen - science projects can introduce the framework for authentic science research practices . as there seems to be a disconnect between the actual pace and the public s perceived pace of scientific research , a well - designed citizen - science project can provide clarity to nonscientists when it comes to the general nature of science research , including concepts that contribute to a sound experimental design ( such as the inclusion of control groups , sample size and representation , and appropriate statistical analysis ) , and the nature of science as a process of sifting through types of evidence . this is particularly beneficial in providing the tools to discern between good and bad science , and possibly contribute to enhanced critical thinking , which is favorable regardless of the subject matter ( 29 ) . evaluations on a variety of citizen - science projects have suggested a positive impact on participants awareness of specific scientific issues and their content - knowledge gains , as well as improved skills related to scientific inquiry and critical thinking ( 3 ) . additionally , citizen - science projects have a large potential for making positive impacts when it comes to attitudes toward science . for instance , citizen - science opportunities can provide a mechanism for participants to become invested in science research in a way that is familiar to them ( either through providing personal samples or by sampling areas in their neighborhood ) , which can be empowering . furthermore , by encouraging inclusivity and openness , citizen science can break down the fear about or perceived distance from science , making science more accessible . this can be particularly important when it comes to efforts to improve diversity in science , since the message inherent to citizen science is that science is for everyone , regardless of personal , geographical , or socioeconomic background . while citizen - science projects have great potential for making positive impacts on both the science research enterprise and the general public , there are challenges related to crowdsourced research . the most obvious of these challenges is the varied skill level of citizen - science participants , which could lead to inconsistencies among data points . therefore , it is essential that citizen - science project leaders provide clear directions and expectations to participants and provide some type of feedback mechanism , akin to customer service , should there be questions or the need to troubleshoot . this is often easy to do on the websites of crowdsourced projects and usually includes faqs ( frequently asked questions ) , video - based guides with step - by - step training , and contact personnel for logistical or technical questions . as projects increase in their size and scope , these steps of coordination and uniformity become more essential for the data to be useful long - term . another challenge related to citizen science is the effective communication of big picture ideas , and having citizen - science participants fully understand the scope and limitations of the research project . as previously discussed , this type of challenge was evident with the nyc pathomap project ( 1 ) , particularly when it came to the limitations of the data analysis even when clearly delineated . depending on the nature of the research project area , addressing this can require a lot of work , and even still , efforts may not fully yield positive impacts among all participants . moreover , it is equally important that scientists communicate the ethical issues related to crowdsourcing research , especially when it pertains to human research ( 4 , 5 ) . the founders of ubiome reported examples of these issues , including the challenges associated with obtaining institutional review board ( irb ) approval , which helps to protect citizen - science participants when providing personal samples ( 26 ) . lastly , one can argue that the greatest strength of citizen science can also be its greatest weakness . because the science research is not entirely conducted by experts , some may discount the validity of the data or overall value of the project in promoting scientific progress . these issues can be addressed through proper training of citizen scientists ; incorporating things like geo - tagging , time - stamping , photo documentation , and sample tracking into the data collection mechanism can also help normalize the process . for example , sample double - checking was performed as part of the first project of metasub ( the nyc pathomap ) , wherein all data were manually validated by geo - coordinate , photo , and time - stamp as having been accurately collected as reported . since mobile phones today are almost all smartphones enabled with cameras , the pathomap project was the first to be able to use photo - based sample tagged data redundancy to confirm sample provenance and accuracy ( 1 ) , but this will likely be a continuing trend . as citizen science becomes better integrated into the science research enterprise , it is important that we continue to determine and refine best practices . furthermore , by engaging citizen scientists , researchers are helping to make real connections to both scientists and authentic scientific practice . too often , we see a stereotypical portrayal of scientists painting a picture that scientists are unapproachable or unrepresentative of the greater population . these stereotypes can also hinder the public s trust in the scientific process , subject matter , or results , and cloud judgment related to public health and policy , since the results are deemed too abstract or convoluted . this could , in turn , affect funding or other factors related to the progress of scientific research . thus , the incorporation of citizen science into the research model can benefit scientists in many ways . in addition to the direct contributions pertaining to a specific research project , the inclusion of citizen science can help scientists dispel misinformation associated with particular scientific topics and provide a channel for more effective public engagement , thus improving the science as well as the utilization of the scientific results to address medical and social problems .

citizen science has become a powerful force for scientific inquiry , providing researchers with access to a vast array of data points while connecting nonscientists to the authentic process of science . this citizen - researcher relationship creates an incredible synergy , allowing for the creation , execution , and analysis of research projects that would otherwise prove impossible in traditional research settings , namely due to the scope of needed human or financial resources ( or both ) . however , citizen - science projects are not without their challenges . for instance , as projects are scaled up , there is concern regarding the rigor and usability of data collected by citizens who are not formally trained in research science . while these concerns are legitimate , we have seen examples of highly successful citizen - science projects from multiple scientific disciplines that have enhanced our collective understanding of science , such as how rna molecules fold or determining the microbial metagenomic snapshot of an entire public transportation system . these and other emerging citizen - science projects show how improved protocols for reliable , large - scale science can realize both an improvement of scientific understanding for the general public and novel views of the world around us .

primary retroperitoneal cysts are rare with an estimated incidence of 1/5750 to 1/250,000.1 they can appear at any age but have a peak of incidence in the fourth decade of life with female preponderance.2 clinically , there are no pathognomonic signs or symptoms for retroperitoneal cysts , and in one - third of patients , the cyst is found incidentally.1 about two - thirds of patients present with an abdominal mass or chronic abdominal symptoms.1 other symptoms include back pain , pain and/or edema of the lower limbs , dyspnea , and anorexia accompanied by weight loss or fever . most of these cysts originate from vestiges of embryonic blastemas , and their inner lining is usually compatible with either a mesothelial or mesonephric origin , although in some instances the lining is of mllerian type with either a serous or mucinous appearance.3 g martino ( messina , italy ) in october 2009 because of right - sided abdominal pain which had been present for 5 h. abdominal examination revealed vague pain localized in the right upper quadrant and in epigastric and periumbilical regions with moderate resistance . abdominal ultrasonography revealed a fluid collection mass ( measuring 12 cm of maximum diameter ) localized in the upper right abdomen and in contact with right renal hilus . computerized tomography imaging of the abdomen showed a circumscribed , oval , dishomogeneous mass ( 8.5 5 5.5 cm ) in the right anterior pararenal space , anterior to the right kidney , lateral to the second portion of the duodenum , inferior to the right lobe of the liver , displacing and compressing the hepatic portal vein and the inferior vena cava ( figure 1 ) . at laparatomy , the cyst was found to be retroperitoneal , situated behind the mesentery of the hepatic flexure of the colon . the cyst compressed the liver , the gallbladder , and hepatic flexure of the colon anteriorly . macroscopically , the mass was a pouch - like structure with a hard - elastic consistency containing hematic fluid . gross examination of the specimen showed a collapsed , previously opened , dark gray to brown colored , unilocular , thin - walled cyst measuring 40 60 mm ( figure 2 ) . immunohistochemical staining was performed using antibodies against bcl2 ( 1:100 dako ) , cd10 ( 1:80 dako ) , ck ae1/ae3 ( 1:50 dako ) , ck7 ( 1:100 dako ) , ck8 ( 1:50 dako ) , ck18 ( 1:50 dako ) , ck20 ( 1:50 dako ) , ema ( 1:1000 dako ) , calretinin ( 1:100 dako ) , podoplanin ( d240 ) ( 1:200 dako ) , estrogen ( 1:35 dako ) and progesterone ( 1:50 dako ) receptors , cd34 ( 1:50 dako ) , cd31 ( 1:40 dako ) , and ca125 ( 1:20 dako ) . there was no cytological atypia or malignancy in the lining epithelium or stromal tissue components . the cyst wall consisted of a thin layer of fibrous tissue which showed areas of chronic inflammation and subepithelial vascular proliferation . the results of immunohistochemical analysis of the epithelium lining of the cyst are summarized in table 1 . in particular , immunohistochemistry showed diffused strong cytoplasmic staining for ckae1/ae3 antibodies . the epithelial cystic cells were immunoreactive to ck8 and ck18 , while the ck7 antibody did not show diffused cytoplasmic staining . the markers for the remaining antigens tested ( bcl2 , ck20 , calretinin , podoplanin ( d240 ) , cd10 , cd31 , cd34 , ca125 , er , pgr ) were negative . retroperitoneal cysts have been defined by handfield jones as those cysts lying in the retroperitoneal fatty tissues which have no connection with any adult anatomic structure except the areolar tissue.4 epithelium - lined retroperitoneal cysts can be categorized on an embryological and histogenetic basis as bronchogenic cysts , lymphatic cysts , mesothelial cysts , enteric cysts , and urogenital cysts.2,5,6 bronchogenic cysts result from abnormal budding of the developing tracheobronchial tree , with separation of the buds from the normal airways during the third to seventh weeks of development.36 they are usually found around the adrenal gland and may simulate a primary adrenal neoplasm.5 bronchogenic cysts are lined by respiratory epithelium with bronchial seromucous glands , smooth muscle , and nodules of hyaline cartilage.36 lymphatic cysts can be unilocular or multilocular containing clear or milky fluid and lined with a single layer of flattened endothelium.6 they occur due to failure of the developing lymphatic tissue to establish normal communication with the remainder of the lymphatic system.6 lymphatic cysts are more common in men and can occur at any age.6 they are subdivided into those formed in the lymphatic cysts returning from the intestine , known as chylous cysts , and those arising in the lymphatic field behind the peritoneum , not connected with the intestine , and analogous in their origin to the single cystic lymphangioma seen in the head and neck.1 solitary cysts have a translucent wall , watery fluid in the lumen , and a lining composed of one or more layers of mesothelial cells.5 they probably represent acquired inclusion cysts related to chronic inflammation.5 a probably related condition has been designated cystic or multicystic benign mesothelioma . grossly multiple thin - walled cysts containing watery secretion are present and measure up to 15 cm or more in diameter.6 microscopically , the cysts are lined by flattened or cuboidal mesothelial cells.5 when flat , the cells closely simulate the appearance of endothelial cells . the mesothelial cells react immunohistochemically for keratin and calretinin,5 are negative for fviii - related antigen and other endothelial markers,5 and sometimes show focal reactivity for hormone receptors.5 the wall , which is devoid of smooth muscle , usually shows foci of chronic inflammation , hemorrhage , and fibrin deposition.5 cystic mesothelioma is not related to prior asbestos exposure . it does not metastasize but may recur locally and occurs more frequently in women.6 enteric cysts are rare congenital multicystic lesions that arise from vestiges of the embryonic hindgut and occur between the rectum and sacrum , commonly in middle - aged women.6 lordon et al described the pathological criteria for diagnosis of these cysts . these criteria include the presence of alimentary mucous membrane lining a smooth muscle coat and intimate attachment to some part of the gastrointestinal tract.7 malignant degeneration of enteric cyst has also been reported and results in adenocarcinoma.6,7 urogenital cysts can be subclassified into pronephric , mesonephric , metanephric , and mllerian types.1,5,6 the majority of urogenital cysts occur near the kidney . they arise from the vestiges of the embryonic urogenital apparatus . when opened , they have a smooth , glistening lining membrane , are unilocular , and contain a clear serous fluid . histologically , the cyst wall is thin , consisting of a cellular fibrous tissue lined by a low columnar epithelium , or cubical and rarely flattened.1 occasionally , they display histologic features indicative of a mesonephric or metanephric origin . in particular , among the urogenital cysts , those with positive immunohistochemical expression for cd10 and bcl2 antibodies in epithelial cells are classified as mesonephric , evidencing an origin from mesonephric remmants810 and those containing nephric duct and metanephrogenic mesenchyme are classified as metanephric . cysts of mllerian origin are extremely rare in the retroperitoneum and occur in women aged from 19 to 47 years.6 they result from persistence of mllerian ducts derivatives,5 which might have the capacity to grow in later life under the influence of abnormal hormonal stimuli.26 histologically , those cysts are lined by fallopian tube - type epithelium ( cuboidal to columnar with cilia ) , and the cyst wall consists of thicker smooth muscle.5,6 clinical history may be useful for differentiating mllerian cyst from other retroperitoneal cysts because the former usually occurs in obese patients with menstrual irregularities.5 in our case , a mesothelial nature of the cyst was excluded by negative immunohistochemical expression of calretinin and podoplanin ( d240 ) , while the hypothesis of lymphatic origin was excluded by the absence of endothelium antigens cd31 and cd34 as well as by the negative staining for podoplanin ( d240 ) . moreover , the immunohistochemical absence of ca125 , estrogen , and progesterone receptors ruled out the possibility of mllerian origin of our observation . however , the histological features and immunohistochemical profile characterized by positive expression of ckae1/ae3 , ck7 , ck8 , ck18 , ema , and negative staining for ck20 strongly supported the epithelial nature of cuboidal cystic cells and also the diagnosis of a benign retroperitoneal cyst of urinary system origin.11 specifically , the retroperitoneal cyst observed in the present case may be classified as pronephric , since one diagnosis should be confirmed by : negative immunohistochemical staining for cd10 and bcl2 in epithelial cystic cells,810 positive immunoreactivity for ck18,12 and the histological absence of renal tissue within cystic wall . in particular , either immunohistochemistry or histomorphological aspects could exclude both the mesonephric and metanephric nature of the present case .

primary retroperitoneal cysts are rare benign lesions which often present as an incidental radiological finding and also cause abdominal symptoms . a 47-year - old woman was admitted to the surgery unit because of right - sided abdominal pain . computed tomographic scan investigation confirmed a circumscribed , oval , dishomogeneous mass in the right anterior pararenal space . the final diagnosis was obtained after laparotomy excision and pathological evaluation . immunohistochemical profile was characterized by positive expression of epithelial cystic cells for ckae1/ae3 , ck7 , ck8 , and ck18 , with ema sustaining the diagnosis of a benign retroperitoneal cyst of urinary system origin .

nitric oxide ( no ) is a key mediator for penile erection . in the penis , no is normally produced by neuronal and endothelial no synthase ( nnos and enos ) . the nnos - derived no is involved in initiation of penile erection , while enos - derived no is involved in maintaining the penile erection . the endogenous no moves into corpus cavernosum smooth muscle cells , activates guanylate cyclase ( gc ) , and then converts guanosine 5'-triphosphate to cyclic guanosine monophosphate ( cgmp ) . next , cgmp activates cgmp - specific protein kinase and causes relaxation of the corpus cavernosum smooth muscle , which allows penile erection . phosphodiesterase-5 ( pde-5 ) degrades cgmp following erection initiation . as a first therapy for erectile dysfunction ( ed ) , pde-5 inhibitors are used to increase cgmp concentration ; however , in some patients with diabetes - induced ed , those who are postprostatectomy , or have other types of severe vascular dysfunction , a pde-5 inhibitor may not necessarily improve erectile function . reported that patients with ed and diabetes had an impaired endothelialderived no - stimulated relaxation response in the penile corpus cavernosum . in these cases , increasing no production may be key to improving erectile function , while pde-5 inhibitor effects may be low . making this no - based therapy potentially even more attractive to clinicians and patients , thus , controlling no production may be a novel , condition - specific , noninvasive therapy for ed and/or penile rehabilitation . accordingly , we created a tool to facilitate this task , the no releaser , nobl-1 . designed by ieda et al . , nobl-1 is a light - controllable releaser of no ( fig . though some light - sensitive no donors already exist , they are limited by factors such as cytotoxicity , due to transition metal components , or expense , requiring two photon devices . nobl-1 does not contain transition metals that can cause cytotoxicity and is composed of n - nitrosoaniline and a bodipy dye . in spite of the carcinogenic property of the n - nitroso structure , namiki et al . reported that the n - nitrosoaniline structure did not show strong toxicity , and bodipy dyes have been utilized for molecular imaging owing to their less cytotoxic fluorescent molecules . considering these advantages , we aimed to determine whether nobl-1 could be an effective and simple ed therapy by allowing light - controlled relaxation of the penile corpus cavernosal smooth muscle . fifteen - week - old male wistar - st rats ( slc , shizuoka , japan ) were used in this study . animals were housed in a temperature and humidity - controlled room with a 12-hour light / dark cycle and free access to laboratory chow and water . all experiment protocols were performed with approval by the animal care and use committee of nagoya city university . the remaining corpus cavernosum was prepared in a chilled krebs solution composed of 119 mm nacl , 4.6 mm kcl , 1.5 mm cacl2 , 1.2 mm mgcl2 , 15 mm nahco3 , 1.2 mm nah2po4 , and 11 mm glucose . one side of the prepared corpus cavernosum was clipped , and the other side was ligated and connected to a force transducer ( adinstruments , bella vista , australia ) . the force transducer was connected to a bridge amp and powerlab 4/26 ( adinstruments ) , and tension was measured using labchart 7 software ( adinstruments ) . the experimental tools were placed in a dark room to avoid ambient room light ( fig . measurements were taken at least 1 hour af ter collecting and preparing the corpus cavernosum . the corpus cavernosum was treated with l - name ( 10 m ) to inhibit endogenous no production . first , to measure the effects of light irradiation in the absence of nobl-1 , noradrenaline ( 10 m ) was allowed to promote precontraction , and the sample was irradiated with light for 15 and 30 seconds ( wavelength 470500 nm , intensity 31 mw / cm ) . light was irradiated from outside of the organ bath by max-302 ( asahi spectra , tokyo , japan ) in the dark room ( fig . next , nobl-1 ( 10 m ) was added , and the sample received light for a further 15 and 30 seconds . next , to investigate the synergistic effects of pde-5 inhibitors , the sample was washed in kreb 's solution , vardenafil ( 10 m ) was added , and the corpus cavernosum was precontracted by noradrenaline ( 10 m ) . then , nobl-1 ( 10 m ) was added to the organ bath , and the sample received light for 15 and 30 s. to confirm that these effects were indeed induced via the no - gc - cgmp pathway , we then added a gc inhibitor , ( 1h - oxadiazolo[4,3-a]quinoxalin-1-one , odq ) ( 10 m ) , and measured light - induced relaxation in the presence of nobl-1 . fifteen - week - old male wistar - st rats ( slc , shizuoka , japan ) were used in this study . animals were housed in a temperature and humidity - controlled room with a 12-hour light / dark cycle and free access to laboratory chow and water . all experiment protocols were performed with approval by the animal care and use committee of nagoya city university . penises were obtained from rats after euthanasia . the tunica albuginea , urethra , and veins were removed . the remaining corpus cavernosum was prepared in a chilled krebs solution composed of 119 mm nacl , 4.6 mm kcl , 1.5 mm cacl2 , 1.2 mm mgcl2 , 15 mm nahco3 , 1.2 mm nah2po4 , and 11 mm glucose . one side of the prepared corpus cavernosum was clipped , and the other side was ligated and connected to a force transducer ( adinstruments , bella vista , australia ) . the force transducer was connected to a bridge amp and powerlab 4/26 ( adinstruments ) , and tension was measured using labchart 7 software ( adinstruments ) . the experimental tools were placed in a dark room to avoid ambient room light ( fig . measurements were taken at least 1 hour af ter collecting and preparing the corpus cavernosum . the corpus cavernosum was treated with l - name ( 10 m ) to inhibit endogenous no production . first , to measure the effects of light irradiation in the absence of nobl-1 , noradrenaline ( 10 m ) was allowed to promote precontraction , and the sample was irradiated with light for 15 and 30 seconds ( wavelength 470500 nm , intensity 31 mw / cm ) . light was irradiated from outside of the organ bath by max-302 ( asahi spectra , tokyo , japan ) in the dark room ( fig . next , nobl-1 ( 10 m ) was added , and the sample received light for a further 15 and 30 seconds . next , to investigate the synergistic effects of pde-5 inhibitors , the sample was washed in kreb 's solution , vardenafil ( 10 m ) was added , and the corpus cavernosum was precontracted by noradrenaline ( 10 m ) . then , nobl-1 ( 10 m ) was added to the organ bath , and the sample received light for 15 and 30 s. to confirm that these effects were indeed induced via the no - gc - cgmp pathway , we then added a gc inhibitor , ( 1h - oxadiazolo[4,3-a]quinoxalin-1-one , odq ) ( 10 m ) , and measured light - induced relaxation in the presence of nobl-1 . in the absence of nobl-1 , light irradiation did not cause any change in the corpus cavernosum ( fig . 3 , left ) ; however , when the corpus cavernosum smooth muscle was precontracted by noradrenaline and nobl-1 was added , the sample relaxed when irradiated with light . 3 , right ) , although the tension returned when the light was removed ( fig . 3 , right ) . upon examining the synergistic effects between nobl-1 and vardenafil , a pde-5 inhibitor , we saw that the corpus cavernosum 's light - induced relaxation response was obviously enhanced as a result of vardenafil pretreatment ( fig . the penile corpus cavernosum were significantly relaxed with the response to light both with only nobl-1 and nobl-1 under vardenafil compared with the response to light without nobl-1 . to confirm whether those responses were induced by no , we examined the sample 's response to light in the presence of a gc inhibitor , odq . the response to light irradiation completely disappeared in the presence of odq treatment , suggesting that the relaxation response occurred via the gc pathway ( fig . this study showed that the corpus cavernosum 's relaxation response was controllable by nobl-1 and light irradiation . in addition , the response was enhanced in the presence of vardenafil . when treated with odq , the relaxation response ceased , suggesting that no , known to be both the cause of this relaxation response and ultimately initiate and maintain penile erection , was produced by the effects of nobl-1 and light irradiation . in turn , this suggests that nobl-1 might be useful for treating ed caused by low levels of no penile rehabilitation commonly focuses on three interrelated concepts as follows : ( 1 ) improving cavernosal oxygenation , ( 2 ) preserving endothelial structure and function , and ( 3 ) preventing smooth muscle structural changes . currently , injecting prostaglandin e1 into the corpus cavernosum or long - term treatment with pde-5 inhibitors are the standard therapies for these patients . unfortunately , prostaglandin e1 injections are invasive and may cause pain , and pde-5 inhibitor regimens may not be useful if low levels of no are the cause of the ed . nnos plays an essential role in initiating erection by no production from the nitrergic nerve . bilateral transection of cavernous nerves was reported to cause a reduction in the nnos - positive nerve fibers from 3 weeks after surgery , and regeneration was not observed in an animal study . thus , the reduction in nnos is suggested to be a cause of ed after radical prostatectomy . in these cases , patients with ed have generally been treated with oral pde-5 inhibitors as a first - line therapy , although approximately 30% of patients fail to respond to this treatment . common causes of this response failure are diabetes mellitus and severe neurological or vascular disease . only if no is being produced after sexual arousal can pde-5 inhibitors affect penile tissue ; in the aforementioned conditions , no production may be too low to initiate pde-5 effects or entirely nonexistent . on the other hand , in this study , nobl-1 could freely initiate and maintain an erection in the presence of light without any need for sexual stimulation . we also investigated whether nobl-1 and light irradiation could still produce a relaxation response in the presence of a pde-5 inhibitor , since patients may still take pde-5 inhibitors . thus , a combination of nobl-1 and a pde-5 inhibitor treatment might be effective for ed . in that case , attention to hypotension is considered necessary , although the method that uses nobl-1 and light irradiation can produce no focally . in addition to its occasional lack of effectiveness , some patients treated with pde-5 inhibitor therapy also experience systemic side effects such as headaches , flushing , dyspepsia , and back pain . because nobl-1 was able to produce site - specific no upon light irradiation , such adverse events may be less likely to occur using this novel therapy . primarily , the use of rat models makes generalizability to humans difficult , and the small sample size and short follow - up should be addressed in future efforts to improve novel methods of penile rehabilitation . in conclusion , the corpus cavernosum 's relaxation response was controlled by light irradiation in the presence of nobl-1 . in addition , pretreatment with vardenafil enhanced the relaxation response . both with and without pretreatment , the corpus cavernosum 's relaxation response was controlled by light irradiation in the presence of nobl-1 . in addition , pretreatment with vardenafil enhanced the relaxation response . both with and without pretreatment ,

purposeto investigate whether relaxation of the rat penile corpus cavernosum could be controlled with nobl-1 , a novel , light - controllable nitric oxide ( no ) releaser.materials and methodsfifteen - week - old male wistar - st rats were used . the penile corpus cavernosum was prepared and used in an isometric tension study . after noradrenaline ( 10 - 5 m ) achieved precontraction , the penile corpus cavernosum was irradiated by light ( 470500 nm ) with and without nobl-1 ( 10 - 6 m ) . in addition , we noted rats ' responses to light with vardenafil ( 10 - 6 m ) , a phosphodiesterase-5 ( pde-5 ) inhibitor . next , responses to light in the presence of a guanylate cyclase inhibitor , odq ( 1h-[1,2,4 ] oxadiazolo[4,3-a]quinoxalin-1-one ) ( 10 - 5 m ) , were measured . all measurements were performed in pretreated l - name ( 10 - 4 m ) conditions to inhibit endogenous no production.resultscorpus cavernosal smooth muscle , precontracted with noradrenaline , was unchanged by light irradiation in the absence of nobl-1 . however , in the presence of nobl-1 , corpus cavernosal smooth muscle , precontracted with noradrenaline , relaxed in response to light irradiation . after blue light irradiation ceased , tension returned . in addition , the light response was obviously enhanced in the presence of a pde-5 inhibitor.conclusionsthis study showed that rat corpus cavernosal smooth muscle relaxation can be light - controlled using nobl-1 , a novel , light sensitive no releaser . though further in vivo studies are needed to investigate possible usefulness , nobl-1 may be prove to be a useful tool for erectile dysfunction therapy , specifically in the field of penile rehabilitation .

persistent injurious stimuli derived from hepatitis c virus ( hcv ) infection can lead to cirrhosis and hepatocellular carcinoma . therapeutic strategies for hcv infections include a combination of pegylated interferon ( ifn ) and ribavirin . however , several adverse effects associated with the use of pegylated ifn alpha-2a and -2b are known . most reports describe flu - like symptoms , myalgia , fatigue , gastrointestinal , psychiatric and hematologic abnormalities . pulmonary manifestations are rare , though findings included interstitial pneumonia , pleuritis , organized cryptogenic pneumonia and exacerbations of asthma . the majority of the descriptions have been reported as a consequence of pegylated ifn -2b ; while few events with pegylated ifn -2a . lung function evaluation is important for diagnosis , follow - up and prognosis in several respiratory diseases . reports of pulmonary complications due to the aforementioned treatment that have included lung function measurement are limited to baseline descriptions ; however , current standards recommend functional assessments as part of the follow - up procedure for all respiratory conditions that have received a therapeutic intervention . instead , cases that have had respiratory complications due to the treatment of hcv infection are considered to be discharged based in resolution of imaging abnormalities ; notwithstanding , we must keep in mind that any change in x - ray scan following lung injury can occur much later and may not correspond to the evolution of symptoms . therefore , the main purpose of this paper is to analyze the case of a woman in her mid-60s who developed interstitial pneumonia associated with pegylated ifn -2a with special focus in lung function . although is an infrequent adverse effect , the number of reports that developed any respiratory symptom is increasing ; thus , it is important to remain alert in order to identify complications opportunely since in some scenarios has resulted in life - threatening conditions and death . a 64-year - old woman whose relevant clinical history included : ( 1 ) a well - controlled asthma based on symptoms ( 22-point asthma control test or act ) and lung function measured by post - bronchodilator spirometry [ fev1/fvc 80% , fvc 2.26 l ( 76%p ) , and fev1 1.81 l ( 80%p ) ] ; and , ( 2 ) a history of mild , intermittent allergic rhinitis . however , the medication was stopped in the next 3 weeks due to diarrhea and vomiting ; thereafter , the treatment was modified to lamivudine + ribavirin for the subsequent 2 years and 6 months . once again , the drug therapy was suspended because the patient complaint with gastrointestinal symptoms . recently , in march 2014 , she started a treatment with only ifn -2a ( 180 g per week ) . after 8 weeks of treatment , the patient developed dyspnea when climbing stairs and progressed in the next 4 weeks being evident when she performed routine activities such as personal grooming and housework . in addition , the patient started to use short - acting bronchodilators due to excessive nighttime coughing , together with a perception of uncontrolled asthma ( act 14 points ) . moreover , the patient suffered isolated episodes of epistaxis that required cryotherapy , and recurrent episodes of flu - like symptoms . during the physical examination both nostrils with hematic clots and scabs ; in the chest , fine bilateral inspiratory crackles were identified . based on these clinical findings , high resolution computed tomography ( hrct ) of the chest was performed [ figure 1 ] . the most significant findings were the presence of diffuse ground glass opacities in the lung lower lobes . initial high - rresolution computed tomography ( hrct ) of the chest demonstrates bilateral interstitial infiltrates . the main abnormalities were ground - glass opacities more prominent in the lower lung lobes the lung function evaluation showed a moderate restrictive pattern [ table 1 ] with mild hypoxemia while breathing on room air ( spo2 of 93% ) based on these findings it was decided to stop the medication ( ifn -2a ) and maintain only with asthma treatments ( salmeterol / fluticasone 50/250 mcg bid ) . description of lung function evaluation ( baseline , symptoms and follow - up ) in the follow - up evaluation ( 8 weeks after symptom onset ) , there was no evidence of epistaxis , flu - like symptoms , and a marked improvement in the perception of dyspnea during physical activity . the images from the scan are showed in figure 2 ; while the functional results are reported in table 1 ; in addition , spo2 of 97% while breathing on room air . follow - up ( 10 weeks ) high - resolution computed tomography ( hrct ) of the chest . there is still evidence of ground - glass opacities ; however , less attenuation regarding the initial hrct scan at present , the patient remains in stable condition with both her asthma ( act questionnaire = 20 points ) and pulmonary function under control [ figure 3 ] . possible options for a new treatment scheme to control chronic hcv infection are being analyzed . a 64-year - old woman whose relevant clinical history included : ( 1 ) a well - controlled asthma based on symptoms ( 22-point asthma control test or act ) and lung function measured by post - bronchodilator spirometry [ fev1/fvc 80% , fvc 2.26 l ( 76%p ) , and fev1 1.81 l ( 80%p ) ] ; and , ( 2 ) a history of mild , intermittent allergic rhinitis . however , the medication was stopped in the next 3 weeks due to diarrhea and vomiting ; thereafter , the treatment was modified to lamivudine + ribavirin for the subsequent 2 years and 6 months . once again , the drug therapy was suspended because the patient complaint with gastrointestinal symptoms . recently , in march 2014 , she started a treatment with only ifn -2a ( 180 g per week ) . after 8 weeks of treatment , the patient developed dyspnea when climbing stairs and progressed in the next 4 weeks being evident when she performed routine activities such as personal grooming and housework . in addition , the patient started to use short - acting bronchodilators due to excessive nighttime coughing , together with a perception of uncontrolled asthma ( act 14 points ) . moreover , the patient suffered isolated episodes of epistaxis that required cryotherapy , and recurrent episodes of flu - like symptoms . during the physical examination both nostrils with hematic clots and scabs ; in the chest , fine bilateral inspiratory crackles were identified . based on these clinical findings , high resolution computed tomography ( hrct ) of the chest was performed [ figure 1 ] . the most significant findings were the presence of diffuse ground glass opacities in the lung lower lobes . initial high - rresolution computed tomography ( hrct ) of the chest demonstrates bilateral interstitial infiltrates . the main abnormalities were ground - glass opacities more prominent in the lower lung lobes the lung function evaluation showed a moderate restrictive pattern [ table 1 ] with mild hypoxemia while breathing on room air ( spo2 of 93% ) based on these findings it was decided to stop the medication ( ifn -2a ) and maintain only with asthma treatments ( salmeterol / fluticasone 50/250 mcg bid ) . description of lung function evaluation ( baseline , symptoms and follow - up ) in the follow - up evaluation ( 8 weeks after symptom onset ) , there was no evidence of epistaxis , flu - like symptoms , and a marked improvement in the perception of dyspnea during physical activity . the images from the scan are showed in figure 2 ; while the functional results are reported in table 1 ; in addition , spo2 of 97% while breathing on room air . follow - up ( 10 weeks ) high - resolution computed tomography ( hrct ) of the chest . there is still evidence of ground - glass opacities ; however , less attenuation regarding the initial hrct scan at present , the patient remains in stable condition with both her asthma ( act questionnaire = 20 points ) and pulmonary function under control [ figure 3 ] . possible options for a new treatment scheme to control chronic hcv infection are being analyzed . the current case was considered relevant because it illustrates the evolution of the pulmonary function in a patient with chronic hcv infection who developed an interstitial pneumonia related to the use of ifn -2a . also , this case adds evidence about pulmonary toxicity related to this specific drug ; the awareness of the side effects will lead us to recognize such eventualities since some of them may result in permanent lung damage or even fatal outcomes . it is important to emphasize that current treatments for chronic hcv infections are not exempted from adverse events ; the frequency of pulmonary toxicity is less than 1% . moreover , the prevalence of interstitial pneumonia is uncertain , some estimates place it between 0.01 and 0.3% ; the precise mechanism that causes such damage has not been clarified . to the best of our knowledge , previous reports of any respiratory side effect due to the treatment with ifn -2a or -2b describes improvements in clinical symptoms , pharmacological strategies implemented to treat this adverse effects , time to chest x - ray resolution and outcome ; however , very few are focused on lung function evolution . patients who manifest interstitial pneumonia while using ifn tend to develop any complaint within an average time of 12 weeks , though the range varies from 2 to 48 weeks . the main intervention for the side effects includes suspending the drug immediately and , some reports recommend beginning treatment with a systemic corticosteroid ( cs ) . however , the precise indication to use systemic cs is uncertain since there is no guideline that clarifies which patients are candidates for it , or the exact dosage and time required to treat the adverse effects . it is important to note that among cases previously reported who were taking ifn -2a , 66.7% were resolved simply by suspending the drug . the case analyzed here allows us to add that evolution toward improved pulmonary function coincided with improvements in the symptomatology . our findings emphasize the importance of lung function evaluation during the follow - up , since it can identify early functional changes and the severity of such abnormalities . the only study that has evaluated pulmonary function in patients with chronic hcv infection undergoing treatment with ifn plus ribavirin was published in 2013 . described a group of patients who were subjected to treatment for 24 weeks , and then were re - evaluated in the subsequent 24 weeks . according to their functional findings , the average allowable decrease in the forced vital capacity ( fvc ) is 6% at the end of treatment . the maximum effect occurs in the first 12 weeks and , in general , after suspending the drug the abnormalities subside in the ensuing 24 weeks . nonetheless , 13% of cases persisted with a decrease equal to or greater than 10% . therefore , despite the fact that the patient in our case experienced a substantial decrease in her lung function ( -12.4%p in fvc ) after 12 weeks of treatment with ifn -2a , she recovered it over the ensuing 3 months , once the drug was suspended . based on these findings , clinicians that evaluates and treats this group of patients should be encouraged to monitor their lung function in order to opportunely detect any alterations that prevent disease progression , since in isolated cases may lead to death due to events of acute respiratory failure . frequent monitoring of the pulmonary function of patients with chronic hcv infections who are prescribed a combined treatment with ifn and ribavirin may alert clinicians to the onset of respiratory complications . also , functional follow - up during at least 8 weeks will help define the need - or lack there of - for other pharmacological strategies .

pulmonary toxicity related to the use of pegylated interferon alpha-2a during treatment of hepatitis c infections is rare ; nonetheless , some cases with fatal outcomes have been reported . evaluating patients pulmonary function is a key to diagnosis , follow - up and prognosis of several respiratory diseases , but case reports of respiratory manifestations related to the use of pegylated interferon alpha-2a have limited their findings to only baseline measurements . this paper examines the case of a 65-year - old woman with chronic hepatitis c virus infection who developed interstitial pneumonitis associated with pegylated interferon alpha-2a . initial lung function evaluation revealed a marked reduction compared to an earlier assessment ; the results were consistent with a moderate restricted pattern . fortunately , over the ensuing 8 weeks of follow - up after discontinuing the drug , the patient recovered her lung function and experienced an overall improvement in her respiratory symptoms .

neuroleptic malignant syndrome ( nms ) is a fatal reaction to neuroleptics which occurs in 0.02 - 3% of patients on neuroleptics and has mortality risk of 10 - 20% respectively . bromocriptine , dantrolene and benzodiazepines are drugs that may be tried in the treatment of nms . risk factors for nms include dehydration , psychomotor agitation , parenteral antipsychotics and low serum iron . the effects of anti - psychotics in a patient with low serum iron can be avoided by early detection , adequate monitoring and specific treatment . mrs . a , 30-year - old woman was admitted for the first episode of suspiciousness , irrelevant speech and very violent behavior for 1 month . there was no history of any medical or neurological illness in the patient . her physical examination was normal and her mental status examination revealed a fearful mood , formal thought disorder loosening of association and tangentialityand auditory hallucinations ( second person ) . she was diagnosed as brief psychotic disorder and put on injection haloperidol 5 mg i.m . her vital signs showed significant fluctuations - temperature : 100 - 102 f , pulse rate : 80 - 120 beats / min , blood pressure : 130/80 - 150/110 mm of hg . her blood investigations revealed white blood cell ( wbc ) count of 12,000/mm(normal range : 4000 - 11,000/mm ) and her hemoglobin ( hb ) was 8 g / dl ( normal range : 12 - 16 g / dl ) . iu / l ( normal range : 40 - 150 iu / l ) . her x - ray chest , electrocardiography , liver and renal function tests , serum electrolytes were within the normal limits . on detailed hematological investigations we found her serum iron low i.e. , her serum ferritin was 20 ug / dl ( normal : 30 ug / dl ) , her total iron - binding capacity was 380 ug / dl ( normal : 300 - 360 ug / dl ) and transferrin saturation was 18% ( normal : 25 - 50% ) . she was diagnosed as a case of nms and started orally on bromocriptine 2.5 mg t.d.s . and lorazepam 2 mg t.d.s . along with nutritional support and serial monitoring of serum cpk . over the next 2 days , iu / l ) and wbc count ( 8000/mm ) fell concomitant with clinical recovery . bromocriptine was tapered off and the patient was maintained on lorazepam 2 mg b.d . patient was started on ects for behavioral control . patient was discharged after a month 's stay in the hospital and at the time of discharge patient started on olanzapine 5 mg a day . in addition , hematinics started to correct underlying iron deficiency . during a 3 months follow - up period the major criteria include fever , rigidity and raised levels of cpk while the minor criteria include tachycardia , abnormal blood pressure , tachypnea , altered consciousness , diaphoresis and leukocytosis . the presence of all the three major or two major and four minor criteria is essential for the diagnosis of nms . our patient satisfied all the major and minor criteria thereby substantiating the diagnosis of nms . a rapid loading with potent neuroleptics like haloperidol is considered to be the major contributing factor in the development of nms , by causing a sudden hypodopaminergic state . what is interesting in this case was the rapidity of development of nms with just 10 mg of parenteral haloperidol . this led us to investigate other associated etiology and what we found was that serum iron may reduce the number of functional dopamine receptors , thereby making the patient more vulnerable to an even seemingly low dose of anti - psychotics . in a population where we often deal with individuals ( particularly women ) having anemia , diagnosed by low hb and low serum iron levels , this becomes a vital clinical experience . in patients with suspected anemia with the requirement of parenteral anti - psychotics , it would be wise to not only do a complete hemogram , but also to initiate correction of the anemia early on and give a lower dose of parenterals ( if really required ) ; whilst being vigilant of the potential chance of early development of nms . iron deficiency anemia is an easily reversible condition , treatment for which is cheap and can be initiated in our psychiatric clinics itself ; and does not require a specialist referral unless very severe ( hb < 7 g / dl ) . nevertheless , nms can be a fatal condition if not detected early and if intervention is not done rapidly . complications may arise mainly secondary to hyperthermia and metabolic abnormalities and patients require an intensive care setting due to the rapidity of complications . it is thus imperative to assess any correctible factor which may help in decreasing the morbidity .

neuroleptic malignant syndrome ( nms ) is a rare , but fatal condition characterized by rigidity , fever , dysautonomia and altered consciousness along with elevated serum creatinine phosphokinase levels and leukocytosis . treatment of nms includes symptomatic and specific treatment with drugs like bromocriptine may be given . risk factors for nms include dehydration , parenteral antipsychotics and high potency antipsychotics . one of the important , but lesser known risk factors for nms is low serum iron . pronounced reduction in serum iron suggests that acute phase reactants do have a role in nms . the present case report focuses on the importance of low serum iron as a risk factor for nms .

eagle 's syndrome encompasses multiple symptoms , which include pharyngodynia , dysphagia , foreign body sensation in pharynx , otalgia , headache , pain on neck rotation , and facial pain . these symptoms are produced due to elongated styloid process ( sp ) or calcified stylohyoid ligament exerting pressure symptoms on neurovascular structures in its vicinity . normal length of sp varies from 2.5 cm to 3.0 cm and it is said to be elongated if its length exceeds 3.0 cm . estimated incidence shows that an average of 4% of population has elongated process , but only 4 - 10.3% of these individuals presents with symptoms . however , the number of reported cases is underestimated because it is an incidental finding in radiographs and is usually asymptomatic . diagnosis is supported by description of symptoms by patient , previous history of any cervical trauma and tonsillectomy , physical examination , and radiographs . a 24-year - old male patient referred to the department for opinion regarding radiating head and neck pain . patient 's complaints were on and off pain over neck region radiating to shoulders and arms for the past 5 years , headache and giddiness on the side to side neck movements , difficulty and pain while swallowing , and foreign body feeling in the throat . previous history of any surgery and trauma was unremarkable . on examination , all third molars were completely erupted in proper occlusion and no abnormal finding was present on temporomandibular joint ( tmj ) examination , but tenderness was present bilaterally in tonsillar fossae region on palpation . there was no evidence of any palpable mass in neck . based on clinical findings , presumptive diagnosis of neuralgic pain and elongated sp ( eagle 's syndrome ) patient was preceded with a panoramic radiograph , which revealed bilateral elongated sp [ figure 1 ] and tmj morphology was also normal . after evaluation of panoramic radiograph , patient was subjected to computed tomography ( ct ) scan to obtain accurate information about sp including its length and direction as superimposition of several anatomical structures , distortion , and magnification are the drawbacks of conventional radiographs . coronal section of ct scans showed bilateral elongated sp reaching upto the hyoid bone [ figure 2 ] . right lateral view showed segmentations present along the elongated sp and left lateral view showed uninterrupted elongated sp [ figures 3 and 4 ] . 3d - ct reformatted image better defined anatomy and measurements were done using a software tool which gave length of 6.8 cm on left side and 6.7 cm on the right side [ figure 5 ] . since the patient had persistent pain and giddiness , however , possible causative factor for giddiness could be impingement on carotid arteries , surgical removal of bilateral elongated sp was planned and was done through extra - oral approach on left side and intraoral approach on the right side after performing tonsillectomy . approximately , 4.5 - 5.0 cm of the segment was removed on both the sides [ figures 6 ] . patient was completely symptom free after 2 months and is under regular follow - up . panoramic radiograph showing bilaterally elongated styloid process coronal computed tomography image showing bilateral elongated styloid process reaching upto hyoid bone right lateral view showing segmentations along elongated styloid process left lateral view showing uninterrupted elongated styloid process 3d - computed tomography image showing bilateral elongated styloid process photograph of surgically excised specimen post - operative 3d - computed tomography image after 40 days sp is a small tapering projection from the base of temporal bone lying anteriorly to mastoid process . vital structures lying in close proximity to it are internal and external carotid artery , internal jugular vein , glossopharyngeal , hypoglossal , and vagus nerve . elongated sp giving rise to clinical symptoms of cervico - facial pain is known as eagle 's syndrome . pain from elongated sp is due to constant mechanoreceptor discharge in area of v , vii , ix , x cranial nerve endings initiated by mechanical irritation from sp . the compression depends on the size , shape , and orientation of ossified the sp . eagle 's syndrome presents with plethora of symptoms , which includes pain in throat , sensation of the foreign body in pharynx , dysphagia , otalgia , headache , pain on cervical rotation , pain along the distribution of external and internal carotid artery , and syncope . if the external carotid artery is affected , pain in the neck on turning head , or pain radiating to the eye , ear , angle of the mandible , soft palate and nose may be present , when the internal carotid artery is involved , pain over the entire head and larynx may be there . since the presentation of symptoms is highly variable , patients report to different specialties like otolaryngology , neurology , and dentistry for seeking treatment . in 1937 , eagle described two possible clinical presentations of elongated sp , which are classical eagle syndrome and stylocarotid syndrome . classical eagle syndrome is typically seen after tonsillectomy or pharyngeal trauma , characterized by pharyngeal pain with swallowing , dysphagia , facial , and cervical pain . stylocarotid syndrome is due to the pressure of the elongated sp on the internal or external carotid artery and sympathetic fibres in the wall of these vessels , characterized by pain and recurrent syncope provoked by cervical movements , particularly rotation . the exact cause of the elongated sp is not clear but various etiologies suggested are local chronic irritations , surgical trauma , endocrine disorders in female at menopause , persistence of mesenchymal elements , growth of the osseous tissue and mechanical stress or trauma during development of sp . gokce et al . , reported that ectopic calcification might have a role for elongation of sp , especially in patients with abnormal calcium , phosphorus , vitamin d metabolism as in end stage renal disease . the syndrome is reported more frequently in women than in men , with an age distribution greater than 40 years . in this case , it was reported in young age . differential diagnosis includes neuralgia ( trigeminal , glossopharyngeal , and sphenopalatine ) , tmj disorder , tonsillo - pharyngitis , cervical vertebra arthritis , otitis , impacted molar teeth , cluster headache , migraine , benign or malignant neoplasm , and salivary gland disease . while examination , palpable sp through tonsillar fossae is suggestive of elongated sp , which is not palpable in normal condition , also pain is exacerbated . temporary relief from pain after infiltration of anesthetic solution in tonsillar fossae is highly suspicious for diagnosis of eagle 's syndrome . conventional radiographs , which can be used are panoramic radiograph , posteroanterior skull view , lateral cephalogram , lateral oblique mandible view , towne 's view . however , moreover conventional radiographs have inherent drawback of superimposition of anatomical structures , and hence reducing the diagnostic information . however , no 2d - ct image provides exact value of length of sp because no plane of image is exactly parallel to the sp leading to underestimation of the length . moreover 3d - ct is a valuable and preferred diagnostic tool , which facilitates in providing accurate information regarding length , angulation , and anatomical relationship . langlais et al . , classified elongated sp into ; type i pattern , which is uninterrupted , elongated process , type ii characterized by the sp apparently being joined to the stylohyoid ligament by a single pseudo - articulation giving the appearance of an articulated elongated sp , and type iii consisting of interrupting segments of the mineralized ligament , sometimes creating the appearance of multiple pseudo - articulations . in this case , elongated sp on the right side was langlais type iii and left side was langlais type i. conservative modality of treatment includes local infiltration of anesthetics , ( nsaids ) non steroidal anti - inflammatory drugs , and steroids in tonsillar fossae region . surgical treatment includes styloidectomy , for which both extra - oral and intraoral approach can be used . advantages of intraoral approach are less time consuming , simple , no scarring and disadvantages are poor visualization of surgical field , possible injury of nearby neurovascular structures , and risk of deep neck space infection . advantages of extra - oral approach are better visualization of surgical field and disadvantages are time consuming , neck scar , and risk of damage to facial nerve . in this case , the surgical intervention was adopted using an extra - oral approach on the left side and intraoral approach on right side without any post - operative complications . in conclusion , patients presenting with radiating cervico - facial pain detailed physical examination should be carried out and possibility of eagle 's syndrome should also be considered though it is rare .

patients presenting with vague head and neck pain can lead to wide - ranging differential diagnosis . elongation of styloid process ( sp ) should also be considered as one of the etiological factors for cervical pain radiating to jaws , pharyngodynia , and difficulty in swallowing . symptomatic elongation of sp or mineralization of stylohyoid ligament is referred as eagle 's syndrome . it is a rare entity presenting with an array of symptoms like recurrent throat pain , dysphagia , otalgia , and neck pain . history and physical examination play a vital role in diagnosing this condition and further radiological investigation confirms the diagnosis . the preferred radiologic modality is 3d - computed tomography , which gives accurate information about length , angulation , type of elongation , and relation to vital structures and hence helps in execution of treatment planning . this paper describes clinical approach , imaging investigations , and management of a case of eagle 's syndrome .

a 42-year - old male patient with a two - month history of headache underwent conservative therapy at a local clinic , but the symptoms showed no improvement . abrupt - onset diplopia developed four days before admission into the neurology ward of our hospital , but the patient 's medical history was otherwise unremarkable . neurologic examination revealed limitation of the extraoccular muscles during right lateral gaze , with aggravated diplopia , suggesting right 6th cranial nerve palsy . t2-weighted mr imaging of the brain demonstrated replacement of the entire clival bone marrow and cavernous sinus by heterogeneous low signal intensity and small areas of high signal intensity , and there was evidence of sphenoid sinusitis ( figs . the prevertebral muscles showed mixed high and intermediate signal intensity at t2-weighted axial imaging ( fig . 1b ) , and the pituitary gland was normal in size and shape , with an intact cortical signal void of sellar floor . 1d ) , and at gadolinium - enhanced t1-weighted imaging , intense enhancement was observed ( fig . the bilateral cavernous sinuses were also involved by the lesion , with diffuse narrowing of the cavernous portion of the right internal carotid artery ( figs . differential diagnoses included metastatic carcinoma , lymphoma , and an indolent aggressive infectious disease such as fungal infection . transsphenoidal clival biopsy was performed , but there was no evidence of fungal infection in the nasal cavity or sphenoid sinus . immunohistochemistry was positive for vimentin but negative for cytokeratin , cea , and cd 34 . after clival biopsy , a ct examination was performed : the images obtained depicted multifocal permeative bone destruction in the clivus ( fig . a biopsy of the retropharyngeal mass was subsequently perfomed , but the mucosal lining of the nasopharynx revealed no abnormality . biopsy specimens from the retropharyngeal soft tissue mass - like lesion showed bundles of fibroblasts admixed with inflammatory cells composed of lymphocytes and plasma cells ( fig . the patient was treated with high - dose corticosteroid and discharged after showing clinical improvement . because the term ' inflammatory pseudotumor ' is nonspecific and lesions have a variety of histologic presentations , several alternative names have been used to refer to them : inflammatory myofibroblastic tumor , plasma cell granuloma or pseudotumor , xanthomatous pseudotumor , pseudosarcomatous myofibroblastic proliferation , inflammatory myofibrohistiocytic proliferation , and myofibroblastoma ( 1 ) . although early descriptions of lesions classified as inflammatory pseudotumors focused on their occurrence in the lung , the lesions occur in diverse extrapulmonary locations . in the head and neck , inflammatory pseudotumor most commonly involves the orbit . according to the pathology literature , a diagnosis of inflammatory pseudotumor of the head and firstly , the tumor was found to consist of a mixed proliferation of vimentin - positive fibroblasts and smooth muscle actin - positive myofibroblasts , with the former predominating . the cells were arranged in fascicles or sheets , or occasionally in whorls , and mitoses were absent . secondly , inflammatory cells were present . these lesions probably have a neoplastic origin , and authors have preferred to use the term ' inflammatory myofibroblastic tumor ' or ' inflammatory fibrosarcoma ' ( 1 ) . reports have stated that extraorbital inflammatory pseudotumors of the head and neck involve the maxillary sinuses ( 2 , 3 ) , infratemporal fossa ( 4 , 5 ) , nasopharynx ( including the parapharyngeal space ) ( 4 - 6 ) , pterygopalatine fossa ( 6 , 7 ) , and the major salivary gland ( 6 ) . involvement of the clivus or cavernous sinus by fibrosing inflammatory pseudotumors centered in the nasopharynx , orbit , or masticator space has been described in a previous article ( 4 ) . to our knowledge , however , a case in which an expansile and infiltrating lesion mainly involved the clivus has not previously been reported . according to previous reports ( 2 - 7 ) , it is very difficult , both clinically and radiologically , to decide whether a lesion involving an infiltrating soft tissue mass , with bony destruction , is a pseudotumor or a malignant neoplasm . in our case , for example , the tumor was at first thought to be a malignant neoplasm such as a lymphoma or metastatic carcinoma , or an aggressive infectious process . there were no signs or symptoms of infection such as fever , and it was unlikely that the heterogeneous signal observed at t2-weighted imaging indicated malignant lymphoma . the coincidence of lesions of differing signal intensity involving the clivus and prevertebral muscle was thought to be unusual for metastatic carcinoma . without a biopsy , however , differentiation between metastatic carcinoma , lymphoma , and chronic fungal disease was impossible . multiple biopsies of the clivus and retropharyngeal soft tissue showed only chronic inflammatory cells with thick fibrosis but no mitoses , and the mucosal lining of the nasopharynx was free of both malignancy and infection . although pathologists eschew the term ' inflammatory pseudotumor ' this was our diagnosis on the basis of these findings , and high - dose corticosteroid therapy was indicated . the administration of high - dose corticosteroid is the primary treatment of choice for inflammatory pseudotumor , and response to medical therapy is thought to roughly parallel the acuity of the inflammatory process . acute lesions typically respond to high doses of corticosteroid , but chronic lesions , which tend to have more fibrosis , generally do not respond to medical therapy ( 8) . in their series , however , han et al . ( 4 ) found no relationship between the duration of signs and symptoms , and degree of fibrosis . we consider that the findings of mr imaging are a good predictor of therapeutic response . it is postulated that in lesions which show high signal intensity at t2-weighted imaging and strong enhancement , there is a relative abundance of free water and mobile protons . if the response to steroid is poor , complete surgical resection is advocated ; when such resection is not possible , local radiation therapy has been shown to be effective in some cases ( 3 , 8) . where a soft tissue mass involving the clivus shows heterogeneous low signal intensity at t2-weighted imaging , has an infiltrative appearance in the presence of an apparently normal pituitary gland , and there is no known underlying malignancy , inflammatory myofibroblastic tumor , in other words ' inflammatory pseudotumor ' ,

the authors describe a rare case of inflammatory pseudotumor involving the clivus , where a soft tissue mass lesion , with extension into the prevertebral retropharyngeal space and the cavernous sinuses , was detected by ct and mri . the mass resembled a malignant tumor or aggressive infectious lesion , and the final diagnosis of inflammatory pseudotumor was a diagnosis of exclusion , decided after histopathological examination .

we herein report the imaging features of a rare case of extramedullary plasmacytoma ( emp ) in the carotid space . a 66-year - old male presented with a solitary painless swelling in the right parotid region since 2 months and dysphagia since 1 month . , a non - tender fixed mass was noted in the right posterior triangle of the neck , extending posteriorly upto the cervical vertebrae . multi - planar magnetic resonance imaging ( mri ) using a 1.5 tesla ge signa hdxt scanner ( ge healthcare , milwaukee , united states ) revealed an 8.2 9.3 10 cm sized mass , with the epicenter in the right carotid space . it was seen to displace the carotid sheath anteriorly . the mass was isointense to muscle on t1-weighted ( t1w ) images [ figure 1a ] and heterogeneously hyperintense on t2-weighted ( t2w ) images [ figure 1b ] . medially , the right prevertebral muscles were infiltrated and the anterior cortices of the adjacent c2-c5 vertebral bodies were eroded . further extension and invasion of the posterior paraspinal muscles was also observed [ figures 1 and 2 ] . the right parotid gland and masticator muscles were not involved . ( a ) axial t1w mri reveals an ill - defined mass isointense to muscle with epicenter in the right carotid space ( arrow ) ( b ) axial t2w mri shows an ill - defined heterogeneously hyperintense mass ( long arrow ) displacing the right carotid sheath anteriorly ( short arrow ) post gadolinium fat - saturated t1w axial mri showing infiltrating margins and heterogeneous moderate enhancement in the mass without necrosis ( arrow ) computed tomography ( ct ) using ge lightspeed vfx 16 ( ge healthcare , milwaukee , united states ) was performed , which corroborated these findings , delineating the cervical vertebral erosion well . it also demonstrated focal erosion of the posterior border of the mandible at the anterior limit of the mass [ figure 3 ] . axial bone window ct image showing cervical vertebral erosion due to the carotid space mass ( long arrow ) . also seen is focal mandibular erosion ( short arrow ) tru - cut biopsy of the mass showed diffuse infiltrate of neoplastic plasma cells in soft tissue with vascular stroma [ figure 4a ] . on immunohistochemistry , tumor cells showed membrane positivity with cd138 [ figure 4b ] . tumor was lambda light chain immunonegative [ figure 4c ] , but expressed kappa light chain on immunochemistry [ figure 4d ] . ( a ) tru - cut biopsy shows diffuse infiltrate of neoplastic plasma cells ( b ) on immunohistochemistry , the tumor cells show membrane positivity with cd138 ( c ) the tumor is lambda light chain immunonegative and ( d ) expresses kappa light chain on immunochemistry the patient underwent complete workup for myeloma , and underlying multiple myeloma with extramedullary dissemination was ruled out . . however , follow - up of our case revealed conversion into multiple myeloma after 13 months of initial diagnosis . dalrymple and bence jones were the first to describe the plasma cell neoplasms in 1846 , classifying them as follows : ( 1 ) multiple myeloma , ( 2 ) emp , and ( 3 ) the solitary plasma cell tumors of the bone . in 2002 , the international myeloma working group defined the criteria for primary emps as : ( 1 ) absence of m - protein in serum and/or urine , ( 2 ) extramedullary tumor of clonal plasma cell , ( 3 ) normal bone marrow , ( 4 ) normal skeletal survey , and ( 5 ) no related organ or tissue impairment . nearly 80% of these are found in the upper aerodigestive tract , predominantly in the head and neck , presenting as submucosal masses in the nasal cavity , paranasal sinuses , and the nasopharynx . emps arising in non - submucosa related areas including the carotid space are rare . the carotid space or retrostyloid parapharyngeal space is located posteriorly , separated from the prestyloid parapharyngeal space by the tensor vascular styloid fascia . figure 5 shows the relation of carotid space to other spaces of the suprahyoid neck . radiologically , the usual differential diagnoses of carotid space masses are schwannomas , paragangliomas , neurofibromas , metastatic or tuberculous lymphadenopathy , rarely extracranial meningiomas and lymphomas [ figures 610 ] . however , schwannomas , paragangliomas , neurofibromas , and extracranial meningiomas are well - defined masses which usually do not cause bone erosion or muscle invasion . metastatic lymphadenopathy , even from an unknown primary , is usually seen at multiple levels and vertebral erosion is infrequent . tuberculous adenopathy is seen as matted nodal masses with multiple necrotic areas with or without abscess formation . lymphomas present as well - defined homogenously enhancing nodal masses , with no appreciable pre - treatment necrosis . they rarely cause bone erosion except when aggressive varieties of lymphoma like nk - t cell lymphoma present in extranodal sites like the paranasal sinuses or orbits . the involvement of multiple contiguous vertebrae , focal erosion of the mandible , and a large soft tissue mass with epicenter in the carotid space ruled out solitary plasmacytoma of bone . carotid space and relations . axial ct section showing dotted lines enclosing parotid space containing parotid gland ( p ) , masticator space m ( solid outline ) , carotid space ( circle ) containing the internal carotid artery ( medial ) and internal jugular vein ( lateral ) , prestyloid parapharyngeal space ( ellipse ) containing parapharyngeal fat ( dashed arrow ) and deep lobe of parotid ( solid arrow ) carotid space : contents and differential diagnoses schwannoma . ( a ) axial section contrast - enhanced ct shows a very well - defined non - infiltrating mass in the carotid space displacing the carotid sheath anteriorly ( arrow ) . note , the hypovascular nature of the mass in early phase ct ( b ) post - contrast mri shows delayed central enhancement due to retention of contrast . axial contrast - enhanced ct shows striking enhancement in bilateral carotid body tumors ( paragangliomas ) with splaying of left - sided internal carotid artery ( short arrow ) and external carotid artery ( dashed arrow ) . axial non - contrast ct shows dense amorphous calcification in an extracranial meningioma in the right carotid space ( solid arrow ) displacing , but not eroding the right styloid process ( dashed arrow ) metastatic node . axial contrast - enhanced ct shows a primary squamous carcinoma in the left vallecula ( short arrow ) and a left level ii metastatic node ( long arrow ) that has invaded the sternomastoid muscle ( m ) and closely abuts the internal carotid artery tuberculous adenopathy . coronal multi - detector computed tomography ( mdct ) reformation showing multiple necrotic nodes inthe right neck at levels ii - iv ( arrows ) . tuberculous nodes tend to be multiple , necrotic , and can exhibit matting reports in literature describe emps as mildly heterogeneous soft tissue density masses with moderate - to - marked post - contrast enhancement on ct imaging . on mri , the signal intensity is moderately higher than that of muscle , but lower than that of the mucosa . moderate - to - marked heterogeneous post - contrast enhancement occurs in all the masses . ooi et al . also found that aggressive emps may be associated with contiguous bone erosions , muscle and fat infiltration , vascular encasement , and regional lymphadenopathy . vogl et al . also studied the mri characteristics of emps and found similar results . our case too displayed a mass in the carotid space with moderate heterogeneous enhancement and associated contiguous bone erosion , muscle infiltration , and vessel encasement . we hereby infer that in the carotid space , imaging features such as contiguous bone erosion , muscle or vessel infiltration , and adjacent nodal involvement may help rule out the more common aforementioned differential diagnoses and point toward a diagnosis of emp . final diagnosis is with histopathology . once diagnosed , it is necessary to rule out multiple myeloma by a series of investigations . primary solitary emp is managed with radiotherapy , surgery , or both . in our case , the lesion regressed following 4 months of treatment with external beam radiotherapy ( 55.8 gy in 31 cycles ) . however , new soft tissue lesions developed in the right neck at level iv , in the groin and thigh on the next follow - up visit . investigations at this stage revealed transformation to multiple myeloma , which was treated with chemotherapy . long - term monitoring is , therefore , mandatory to detect early local recurrence or conversion to multiple myeloma for obvious therapeutic implications .

plasma cell neoplasms have been classified into various types , with a range of clinical and radiological presentations . extramedullary plasmacytoma ( emp ) is a subset of plasma cell neoplasms which presents as an isolated non - osseous soft tissue mass . though carotid space neoplasms are commonly encountered , emp in the carotid space is rare and seldom considered in the initial differential diagnosis of a carotid space mass . these tumors can be treated by surgery or radiotherapy . on the other hand , the commonly encountered tumors in the carotid space are treated surgically . also , it is mandatory to exclude multiple myeloma in the patients presenting with emp . hence , accurate and early diagnosis has therapeutic and prognostic implications . we report a rare case of emp of the carotid space , describing the imaging features and the differential diagnoses with clues pointing to this rare entity .

polymyositis ( pm ) is an idiopathic inflammatory myopathy with a prevalence of 1013 cases per 100,000 people in japan1 . in pm , respiratory symptoms , such as interstitial pneumonia , are frequently observed in patients with dermatomyositis3 . therefore , physiotherapy may improve the limb muscle strength and activities of daily living ( adl ) of pm patients , and according to previous studies , physiotherapy improves the lower limb muscle strength and physical function of pm patients4,5,6 . dysphagia is an important issue for pm patients , and the frequency of dysphagia is approximately 1262% among pm patients8,9,10 . thus , respiratory disorders may be associated with an increased risk of dysphagia in pm patients . therefore , the aims of this study were to quantify the serial changes in lower limb and respiratory muscle strengths , and to evaluate the effectiveness of physiotherapy accompanied by prednisolone treatment in pm patients . five pm patients ( 57.6 9.0 years of age , range 50 to 72 years , four females ) who had initiated physiotherapy within two weeks of pm diagnosis were admitted to hiroshima university hospital for treatment between april 2010 and march 2014 . table 1table 1.patient characteristics and medicationscasegenderage ( years)bmi ( kg / m)medication1female5519.4prednisolone 0.9 mg / kg / day2female6123.5prednisolone 0.49 mg / kg / day3female6016.4prednisolone 0.26 mg / kg / day4male7224.6prednisolone 0.4 mg / kg / day5female5128.1prednisolone 0.6 mg / kg / day shows the main features of the patients . this study was approved by hiroshima university s committee of ethics in research ( no 1153 ) , and all of the subjects signed an informed consent form prior to enrollment . the knee extensor muscle strength was evaluated using a hand - held dynamometer ( hhd ; anima corp . , the subjects were seated , and their hip and knee joints were flexed at 90 degrees . the subjects ramped up to maximum force for each of the five actions over a 3-second period , then maintained a static position for approximately 5 seconds , during which the maximum force was measured11 . the respiratory function was evaluated as the maximal inspiratory mouth pressure ( pimax ) , maximal expiratory mouth pressure ( pemax ) , and % vc using a spirometer ( autospiro , minato corp . these parameters were measured according to the american thoracic society / european respiratory society statement on respiratory muscle testing12 . the pimax and pemax values were calculated as percentages of the predicted values according to gender , age , weight , and height . first , each patient was requested to continuously repeat simple isotonic movements ( i.e. , shoulder flexion , hip flexion , and knee extension ) until they felt fatigued . the number of repetitions completed by each patient was counted weekly . during daily training the patients placed a 500-g weight on their abdomen and performed abdominal breathing against the weight until they felt fatigued . the data are presented as the means standard deviation ( sd ) or medians ( minimum maximum ) . the paired t - test or the mann - whitney u test was performed to test the significance of differences between the values observed at baseline and those obtained after four weeks of treatment . all five patients completed the exercise program and underwent prednisolone treatment . the patients laboratory results ( i.e. , creatine kinase values ) did not change during the intervention ( fig creatine kinase levels and respiratory muscle strengths of the five patients during the observation period . ) . after four weeks of intervention , all patients exhibited significantly increased knee extensor muscle strength and pimax , pemax , % vc , and barthel index values compared with the baseline ( p<0.001 , table 2table 2.mean value of respiratory function , muscle strength , barthel index , and ck value in patients with pm baseline and after interventionbaseline ( n=5)after intervention ( n=5)change ( % ) respiratory function pemax ( % ) 42.5 6.068.6 9.0 * 61.9 14.0pimax ( % ) 33.1 10.540.3 10.4 * 23.9 9.5% vc ( % ) 58.7 7.062.6 5.4 * 6.9 4.0lower limb muscle strength right knee extension ( n)75.9 12.8149.6 37.5 * 97.3 37.5left knee extension ( n)82.8 14.9159.8 24.0 * 94.2 13.4barthel index score75 ( 5080)95 ( 85100)*33.3 ( 2570)ck value ( iu / l)3,735.2 3,106.11,254 1,104.060.8 18.4the data are presented as the means standard deviations or medians ( minimum maximum ) for each outcome.change ( % ) = change in mean values . pemax : maximal expiratory mouth pressures ; pimax : maximal inspiratory mouth pressures ; % vc : % vital capacity ; ck : creatine kinase ) . differences in recovery with respect to improvements in expiratory and inspiratory muscle strength were also found ( p<0.001 , table 2 ) . the inspiratory muscle strength of the patients showed little improvement compared with their expiratory muscle strengths . creatine kinase levels and respiratory muscle strengths of the five patients during the observation period . the data are presented as the means standard deviations or medians ( minimum maximum ) for each outcome . pemax : maximal expiratory mouth pressures ; pimax : maximal inspiratory mouth pressures ; % vc : % vital capacity ; ck : creatine kinase in the present study , the serial changes in the knee extensor muscle strength , respiratory function , and adl of pm patients were evaluated . physiotherapy accompanied by prednisolone treatment for four weeks did not exacerbate the patients symptoms . the treatment also showed different recovery ratios between the expiratory and inspiratory muscles . performing intensive physiotherapy during the acute disease phase however , none of the patients included in the present study experienced exacerbated symptoms , and their creatine kinase values remained the same during the intervention period . this result supports previous findings regarding the safety of acute - phase rehabilitation5 , 15 . the present study showed that pm symptoms are not exacerbated by physiotherapy when it is performed cautiously , based on the patient s degree of subjective fatigue , muscle pain , and creatine kinase values . the knee extensor muscle strength , pemax , pimax , % vc , and barthel index significantly increased ( table 1 ) . however , the % vc and pimax values did not improve satisfactorily compared to the knee extensor muscle strength and pemax . previous studies have reported improvements in knee extensor muscle strength and physical function in pm patients after physiotherapy , as evaluated via a functional index for myositis4,5,6 , 16 . notably , previous studies showed that the respiratory muscle strength of patients with chronic obstructive pulmonary disease was improved by physiotherapy , and that these improvements in inspiratory and expiratory muscle strength did not differ significantly17 , 18 . our results indicate there is a difference between inspiratory and expiratory muscle strength improvements among pm patients . the recovery of inspiratory muscle strength was lower than that of expiratory muscle strength . the present results may explain some of the characteristics of muscle dysfunction experienced by pm patients . teixeira et al . reported a more than 75% prevalence of diaphragm dysfunction in patients with pm , dermatomyositis , and inclusion body myositis20 . therefore , myositis of the diaphragm may reduce the recovery potential of inspiratory muscle strength . first , this study was performed at a single center with a small sample . second , our physiotherapy intervention was performed for only four weeks ( five days per week ) . it is thus necessary to evaluate the chronic effects of physiotherapy in pm patients . third , this study did not include a control group without prednisolone treatment or physiotherapy to determine the treatment - dependent effects . different levels of improvement were observed between inspiratory and expiratory muscle strengths following physiotherapy . larger studies and mechanistic studies are imperative to determine the related pathology and therapeutic effects .

[ purpose ] the purposes of this study were to quantify the serial changes in lower limb and respiratory muscle strengths and to evaluate the acute effects of physiotherapy in polymyositis patients . [ subjects and methods ] five patients ( 57.6 9.0 years , 50 to 72 ; four females ) received physiotherapy five days a week for four weeks . the lower limb and respiratory muscle strength , the % vital capacity , and the barthel index were evaluated at baseline and after the intervention . [ results ] the patient s symptoms and creatine kinase values did not change , and after four weeks , all of the patients exhibited significantly increased outcomes compared with the baseline . however , the inspiratory muscle strength of the patients presented smaller improvements than the expiratory muscle strength . [ conclusion ] differential changes in inspiratory and expiratory muscle strength were observed following physiotherapy , and an unbalanced muscle distribution may explain the pathological and therapeutic effects .

concerns about the side effects associated with antihyperglycaemic medications , such as weight gain and hypoglycaemia , have led to the development of diabetes treatments with novel mechanisms of action 1 . the kidney has been the focus of most recent efforts because of the significant role it plays in maintaining glucose homeostasis 2 . sodiumglucose cotransporter 2 ( sglt2 ) is a highcapacity , lowaffinity glucose transporter found in the proximal convoluted tubule of the kidney , and accounts for the majority of glucose reabsorption 2 . the use of sglt2 inhibitors , such as canagliflozin , provides an insulinindependent method of increasing urinary glucose excretion and improving glycaemic control in patients with type 2 diabetes mellitus ( t2 dm ) 1 . probably linked to this mechanism of action , canagliflozin was associated with a higher incidence of certain adverse events ( aes ) in clinical trials ( e.g. genital mycotic infections , urinary tract infections , osmotic diuresisrelated aes , volume depletionrelated aes ) . most of these aes were mild or moderate in intensity and few led to discontinuations 3 . in addition to reducing blood glucose levels , sglt2 inhibitors have been reported to lower serum uric acid levels 2 . uric acid is a byproduct of metabolism that can be influenced by diet , breakdown of cellular material and impaired renal elimination . the buildup of serum uric acid in the body can lead to an increase in uric acid crystals in various organs , which can result in gout or the formation of kidney stones 4 . there is evidence of an association between elevated serum uric acid levels , also known as hyperuricaemia , and risk of renal and cardiovascular disease 5 . several studies have identified hyperuricaemia as a predictor of the development of metabolic syndrome , diabetes and hypertension 6 . patients with both t2 dm and hyperuricaemia are at an increased risk of developing gout , kidney stones and vascular complications 5 , 7 . in addition , studies have identified an association between serum uric acid levels and mortality risk in patients with t2 dm 7 . given the various disorders associated with hyperuricaemia , lowering serum uric acid may be beneficial for patients with t2 dm , who may have a higher risk of microvascular and cardiovascular disease . the aim of the present post hoc analysis was to further characterize the effects of canagliflozin on serum uric acid levels in both a pooled t2 dm cohort and a subset of this cohort who had hyperuricaemia at baseline compared with placebo . in addition , the incidence rates of gout and kidney stones were evaluated across treatment groups in both cohorts . in a post hoc analysis , serum uric acid level changes were evaluated in pooled data from four randomized , phase iii , multinational , 26week trials , where canagliflozin ( 100 or 300 mg ) was compared with placebo as monotherapy , or dual or triple combination therapy ( addon to metformin , metformin and sulphonylurea , or metformin and pioglitazone ) 1 , 8 , 9 , 10 . changes in serum uric acid levels were evaluated in the overall pooled cohort and in the subset of patients ( n = 115 ) in the pooled cohort whose baseline serum uric acid levels indicated hyperuricaemia [ defined as serum uric acid level 475 mol / l ( 8 mg / dl ) ] . furthermore , attainment of serum uric acid levels of < 360 mol / l ( 6 mg / dl ) , a common target for uricosuric agents , was assessed in the patients with hyperuricaemia 11 . inclusion in the post hoc analysis required a baseline serum uric acid measurement and 1 postrandomization serum uric acid measurement . serum uric acid can be converted from mg / dl to mol / l by multiplying by 59.48 . the least squares mean percent change and least squares mean change from baseline in serum uric acid were calculated using an analysis of covariance model with treatment and study as factors and baseline serum uric acid as a covariate . statistical comparisons between groups were not performed as they were not prespecified ; therefore , no p values are reported . in a post hoc analysis , serum uric acid level changes were evaluated in pooled data from four randomized , phase iii , multinational , 26week trials , where canagliflozin ( 100 or 300 mg ) was compared with placebo as monotherapy , or dual or triple combination therapy ( addon to metformin , metformin and sulphonylurea , or metformin and pioglitazone ) 1 , 8 , 9 , 10 . changes in serum uric acid levels were evaluated in the overall pooled cohort and in the subset of patients ( n = 115 ) in the pooled cohort whose baseline serum uric acid levels indicated hyperuricaemia [ defined as serum uric acid level 475 mol / l ( 8 mg / dl ) ] . furthermore , attainment of serum uric acid levels of < 360 mol / l ( 6 mg / dl ) , a common target for uricosuric agents , was assessed in the patients with hyperuricaemia 11 . inclusion in the post hoc analysis required a baseline serum uric acid measurement and 1 postrandomization serum uric acid measurement . serum uric acid can be converted from mg / dl to mol / l by multiplying by 59.48 . the least squares mean percent change and least squares mean change from baseline in serum uric acid were calculated using an analysis of covariance model with treatment and study as factors and baseline serum uric acid as a covariate . statistical comparisons between groups were not performed as they were not prespecified ; therefore , no p values are reported . in the overall cohort , the mean patient age was 56.0 years , glycated haemoglobin ( hba1c ) 8.0% , body mass index ( bmi ) 32.1 kg / m and estimated glomerular filtration rate ( egfr ) 88.1 ml / min/1.73 m. in the cohort of patients with hyperuricaemia , the mean age was 54.5 years , hba1c 7.9% , bmi 35.9 kg / m and egfr 75.9 ml / min/1.73 m. baseline demographics and clinical characteristics were generally similar across treatment groups within each cohort ( table 1 ) , but the cohort with hyperuricaemia had a greater proportion of men and tended to have a higher bmi and lower egfr compared with the overall cohort ( table 1 ) . baseline demographic and disease characteristics of the overall pooled cohort and subset of patients with hyperuricaemia ( baseline serum uric acid 8 mg / dl ) bmi , body mass index ; egfr , estimated glomerular filtration rate ; hba1c , glycated haemoglobin ; s.d . , standard deviation . from mean baseline serum uric acid levels of 5.35.4 mg / dl in the canagliflozin groups , both canagliflozin 100 and 300 mg reduced serum uric acid levels by 13% ( or 0.7 mg / dl ) relative to placebo at week 26 in the overall cohort ( figure 1a ) . in patients with hyperuricaemia ( mean baseline serum uric acid 8.58.6 mg / dl ) , the placeboadjusted percent reductions in serum uric acid with both doses of canagliflozin were generally similar to those observed in the overall cohort ( figure 1b ) . furthermore , in the cohort with hyperuricaemia , the proportion of patients achieving serum uric acid levels < 6 mg / dl at week 26 was 23.5% for canagliflozin 100 mg and 32.4% for canagliflozin 300 mg compared with 3.1% for placebo [ placebosubtracted differences ( 95% ci ) = 20.4% ( 1.9 , 38.9 ) and 29.3% ( 9.4 , 49.1 ) with canagliflozin 100 and 300 mg , respectively ] . percent change in serum uric acid levels in ( a ) the overall pooled cohort and ( b ) the subset of patients with hyperuricaemia ( baseline serum uric acid 8 mg / dl ) . the overall pooled cohort and the subset of patients with hyperuricaemia comprised the safety analysis set , regardless of rescue medication . patients needed baseline and 1 uric acid measurement at week 26 for inclusion in this analysis . the incidence rates of gout and kidney stones were similar between treatment groups in the overall pooled cohort . gout was reported in 0.1 , 0.2 and 0.5% of the patients in the canagliflozin 100 mg , canagliflozin 300 mg and placebo groups , respectively . kidney stones were not reported in either of the canagliflozintreated groups , and occurred in 1 ( 0.2% ) patient in the placebo group . in the cohort with hyperuricaemia , gout was reported in 1 patient in each of the canagliflozin 100 mg , canagliflozin 300 mg and the placebo groups ( 2.5 , 2.6 and 2.7% , respectively ) . the incidence rates of gout and kidney stones were similar between treatment groups in the overall pooled cohort . gout was reported in 0.1 , 0.2 and 0.5% of the patients in the canagliflozin 100 mg , canagliflozin 300 mg and placebo groups , respectively . kidney stones were not reported in either of the canagliflozintreated groups , and occurred in 1 ( 0.2% ) patient in the placebo group . in the cohort with hyperuricaemia , gout was reported in 1 patient in each of the canagliflozin 100 mg , canagliflozin 300 mg and the placebo groups ( 2.5 , 2.6 and 2.7% , respectively ) . canagliflozin decreased serum uric acid levels in patients with t2 dm , including a subset of patients with hyperuricaemia . furthermore , 2030% of patients with hyperuricaemia were able to achieve normal serum uric acid levels ( < 6 mg / dl ) with canagliflozin . previous pharmacokinetic and pharmacodynamic studies have shown that this reduction in serum uric acid levels relates to an increased fractional excretion of uric acid during the first weeks of canagliflozin treatment 12 . by week 12 , the total urinary uric acid excretion returned to near baseline levels , probably reflecting the persistent reduction in serum uric acid concentrations . the mechanism by which sglt2 inhibitors reduce serum uric acid has not been established ; however , it may possibly involve the renal slc2a9 ( glut9 ) transporter , which is known to exchange glucose for uric acid 13 . higher glucose concentrations in the urine attributable to canagliflozin treatment could lead to an increased exchange of uric acid in the apical membrane of tubular cells . consequently , this would result in increased release of uric acid from blood into the urine , reducing serum uric acid levels 13 . this potential mechanism is supported by evidence of transstimulation of uric acid efflux with high glucose concentrations in xenopus oocytes expressing slc2a9b 14 . in conclusion , both doses of canagliflozin reduced serum uric acid levels in patients with t2 dm . furthermore , up to 30% of patients with baseline hyperuricaemia and t2 dm achieved normal serum acid levels with canagliflozin after 26 weeks . whether such changes have other beneficial effects on renal and/or cardiovascular complications will require evaluation in longerterm studies . m. j. d. and a. t. are employees of janssen scientific affairs llc ; u. v. , c. v. d. and g. m. are employees of janssen research and development llc . all authors participated in the analysis and interpretation of the data and the writing of the manuscript .

hyperuricaemia is associated with an increased risk of gout , kidney stones and cardiovascular disease . the present post hoc analysis of pooled data from four placebocontrolled phase iii studies assessed the effect of canagliflozin , a sodiumglucose cotransporter 2 inhibitor , on serum uric acid levels in patients with type 2 diabetes mellitus ( t2 dm ) and in a subset of patients with hyperuricaemia [ defined as baseline serum uric acid 475 mol / l ( 8 mg / dl ) ] . at week 26 , canagliflozin 100 and 300 mg were associated with a 13% reduction in serum uric acid compared with placebo . in the subset of patients with hyperuricaemia , placebosubtracted percent reductions in serum uric acid were similar to those in the overall cohort . more patients in the hyperuricaemic group achieved a serum uric acid level of < 360 mol / l ( 6 mg / dl ) with both canagliflozin 100 mg ( 23.5% ) and 300 mg ( 32.4% ) compared with placebo ( 3.1% ) . incidences of gout and kidney stones were low and similar across groups . in conclusion , canagliflozin treatment decreased serum uric acid in patients with t2 dm , including those with baseline hyperuricaemia .

this research is a case study on the medical mycology and parasitology course at the school of medicine of shiraz university of medical sciences ( sums ) . the medical mycology and parasitology course is a sophomore - level course on the pathogenesis and treatment of mycotic and parasitic infections for medical students . the class included 106 medical students who attended two 90-min lectures and one 2-hours laboratory session each week for 25 weeks . the lectures were presented using powerpoint and included some case studies . to encourage active learning , the students were informed that they may be randomly called on to answer questions . moreover , the students were free to ask questions during the lectures . the course was presented in a large - sized lecture hall . as shown in the architectural plan of the hall ( fig . 1 ) , a 5 m wide screen was placed on the stage in the front of the class 10 m from the first row . there were 14 columns and 15 rows of seats arranged on a gentle slope and subdivided by aisles into six areas , as shown in fig . the position of each seat was coded in two dimensions : x ( horizontal axis ) and y ( vertical axis ) . x in each seat corresponded to the position of that seat in a row ( or number of the column ) and y in each seat corresponded to the position of that seat in a column ( or the number of the row ) y in each seat corresponded to the position of that seat in a column ( or the number of the row ) . as the distance of the seats in a column from each other is about 63.5 cm , the distance of each seat from the lecturer and the board can be estimated by its corresponding y. the architectural plan of the classroom . random sampling was performed and each student 's position was recorded using digital photos taken during 15 of the 26 sessions of the course . following identification of each student in the photos , the positions were coded by superposing ( placing ) the positions within the architectural plan . the students were told that the photographs were used to check their attendance throughout the course . to determine students preferred seating position in medical school courses , students were asked to record their preferred seating position by marking it on an architectural plan of the classroom distributed during the last session . first , as described by mccroske and mcvetta ( 7 ) , we divided the classroom into three student - teacher interactional zones : high , medium , and low . 1 , the students sitting within the triangle in the front of the class next to the teacher had a high interactional level ( h ) . the remaining students sitting in the front half of the classroom had a medium interactional level ( m ) . the students sitting at the back of the classroom had the lowest interaction level ( l ) . second , since previous studies ( 1 , 2 , 5 ) showed that the distance from the lecturer influenced students educational achievement , the classroom was divided in the y orientation into three areas named i , ii , and iii . third , the seats were divided into two groups based on the students access to the aisles : direct access ( were shown in bold ) and indirect access . the exams were composed of multiple choice questions , short essays , and true / false questions . only the multiple choice questions were used for the both mid - term and final exams and the scores of each of them were calculated out of 20 . reliability of the tests was measured by the split - half and kuder richardson methods and indicated respectively a reliability of 0.81 and 0.84 for the final exam . the final exam has been validated by measuring the correlation coefficient between midterm and final exams ( r = 0.77 , p = 0.01 ) . the students presence in the classroom was recorded by digital camera and students were divided into two groups based on the number of absences ( having more than 10 absence sessions or not ) . the study was approved by the institutional review board and ethical committee of shiraz university of medical sciences . all the students willingly signed an informed consent that was attached to the distributed architectural plan of the classroom . in addition , in the last session , the students were informed about the details of the study and gave permission to issue the results . the mantel - haenszel chi - square test was used to test for associations between categorical variables in the presence of confounding factors . one - way analysis of variance ( anova ) , the independent sample t - test , and the nonparametric mann - whitney u test were applied to test for differences between group . additionally , the chi - square test was used to test for differences between categorical variables . for the statistical analysis , the mantel - haenszel chi - square test was used to test for associations between categorical variables in the presence of confounding factors . one - way analysis of variance ( anova ) , the independent sample t - test , and the nonparametric mann - whitney u test were applied to test for differences between group . additionally , the chi - square test was used to test for differences between categorical variables . for the statistical analysis , the students mean seating positions were classified in three manners as described in the materials and methods section . under the interactional zones classification , 27 ( 25.5% ) students had high interactions with the teacher , 60 ( 56.6% ) had medium interactions , and 19 ( 17.9 ) had low interactions . based on the area classification , 39 ( 36.8% ) students sat in area i , 49 ( 46.2% ) sat in area ii , and 18 ( 17% ) sat in area iii . under the classification based on student access to the aisles , 48 ( 45.3% ) of the 106 students had direct access and 58 ( 54.7% ) had indirect access to the aisles . in addition , the students seat position changes were measured by calculating the standard deviations from their mean positions in the x ( sd - x ) and y ( sd - y ) orientations . of the studied students , 56 ( 54.9% ) had an sd - x2 , 24 ( 23.5% ) had 2<sd - x3 , and 22 ( 21.6% ) had an sd - x>3 . in addition , the majority of the students ( 71 students , 69.6% ) had an sd - y2 , 18 ( 17.7% ) had 2<sd - y3 , and 13 ( 12.7% ) had an sd - y>3 . there was a significant correlation between sd - x and sd - y ( r=0.31 , p=0.001 ) . the students preferred positions were determined from the questionnaire , and there was a significant correlation between the students seating positions and their preferred positions in both the x ( r=0.62 , p<0.001 ) and y ( r=0.72 , p<0.001 ) orientations as shown in fig . the students preferred seating positions and mean seating positions in the x ( a ) and y ( b ) orientations . the seating distribution of the female and male students in the three classifications is shown in table 1 . statistically , the proportion of females in areas i and ii was significantly higher than the number of males . however , in area iii , the proportion of males was significantly higher than the proportion of females ( odds ratio=8.3 , p<0.01 ) . moreover , independent sample t - tests showed that there were no significant differences in sd - y and sd - x between males and females . by focusing on the 10% of the students with the highest level of changes in seat position ( sd - y5 ) , there were significant differences between the sexes ( eight males vs. two females , p=0.041 ) . distribution of female and male students in the three seating classifications the students educational performance was assayed by their final exams scores . our results showed that there were statistically significant correlations between the final ( r=0.2 , p=0.031 ) exam scores and the students seating positions in the y orientation ( fig . 3a ) . of the nine students with final exam grades of a ( grades 17 ) , six students ( 66.6% ) were seated in the h zone and three were seated in the m zone . none of the a - level students were seated in the l zone . as shown in fig . 3b , a statistically significant correlation was found between the students final exam scores and sd - y ( r=0.29 , p=0.003 ) . of the students , 97 ( 90.7% ) had a sd - y4 , and interestingly all nine students with final exam grades of a ( scores17 ) had a sd - y2 . moreover , the students with a sd - y5 had average final exam scores of 12.20.9 , while the other students had average final exam scores of 13.92.2 . distribution of the students based on their final exam scores and either their mean seating positions ( a ) or the standard deviations of their seating positions ( b ) in the y orientation . 4a , there was a significant positive correlation between the number of absences and the distance from the board ( r=0.41 , p<0.001 ) . in other words , the number of absences increased with increasing distance from the board . there were significant negative associations between the number of absences and the students final exam scores ( r=0.36 , p<0.001 ) as shown in fig . although there was no significant correlation between the number of absences and sex , when we divided the students into two groups based on the number of absences , there were significant differences between the sexes ( p<0.01 ) . of the 21 ( 20.4% ) students who were absent from more than 10 class sessions , 16 ( 76.2% ) were male and 5 ( 23.8% ) were female . distribution of the students based on their number of absences and either their mean seating positions in the y orientation ( a ) or their final exam scores ( b ) . traditional classrooms are the most common type of educational setting in universities , especially for medical students ( 13 ) . in this study , we examined the mutual interactions among the chosen seating of medical students , exam scores , and the students attendance . we observed that only five ( 4.6% ) of the students sat in the same seat , all of whom , interestingly , had no movement in the y orientation during the semester . we compared the students educational achievements and attendance based on three types of spatial classification : distance from the lecturer in the y orientation , interactional zones , and access to the aisles . the majority of the students ( n=88 , 82.2% ) chose seats in specific areas . the remaining students changed their positions frequently in both the x and y orientations ( sd - x>3 , sd - y>3 ) . previous studies distributed the students in the classroom by assigning their positions randomly or by assigning the students their favorite seating positions . in our study , students had the opportunity to choose their seat since the number of seats was nearly double the number of students . moreover , the students actual seating positions and their preferred seats were correlated , indicating that the association between seating position and educational performance was not a random event as the students intentionally chose the places where they sat . a previous report by cinar ( 13 ) showed that the distance to the stage is negatively associated with feeling secure in large spaces . in the present study , the number of males in area iii was five times greater than the number of females . several authors ( 1 , 2 , 4 , 5 ) have shown that there is an association between better academic performance and the option of sitting close to the board , while other researchers did not observe this correlation even when the students sat a considerable distance away from the board in very large classrooms ( 11 , 12 ) . although the data presented in this report demonstrated no significant correlation between the students exam performance and their seating in different areas ( i , ii and iii ) of the classroom , a significant association was found between the students performance and seating positions in the high and medium interactional zones . the differences between the results of this study on student performance in different interactional zones or area classifications and previous reports ( 1 , 2 , 4 , 5 ) may be due to differences in the types and sizes of the classrooms . in the present study , the comparison of area i with zone i showed that those students seated in the corners of the area i did not have a high level of interaction with the lecturer despite their close proximity to the stage . moreover , of all the a - level students , almost two thirds were seated in the h zone , and the rest were in the m zone , which suggests that eye - contact and interaction with the lecturer contributed to better performance . these data supported the previous hypotheses ( 10 , 13 , 14 ) that proximity to the lecturer enhances student motivation and improves their scholastic performance . another possible explanation for these results was provided by a recent study , which noted the possible relationship between seat location and test scores was mainly due to the motivation of the students who sat in the front of the class rather than their seat position ( 11 ) . in large classrooms with assigned seating , the researchers observed no effect or a negative correlation between the seat location and exam scores . meanwhile , when the students were free to choose their seats , those in the front received higher grades than those in the back , suggesting that more motivated and engaged students chose seat nearer to the lecturer ( 11 ) . on the other hand , we observed a negative significant association between student performance and changes in seat location , with a - level students rarely changing their seating locations ( sd - y2 ) . likewise , the students who changed their seating locations frequently received significantly lower grades than the rest of the class . however , another variable like motivation may exist that affects both seat location and educational performance . these students might have lower motivation than the fixed seat students , which may in turn affect their educational performance . typically in classes , those who are frequently late also perform less well than those who arrive on time . tardy students also have to take whatever empty seats are left and easy to get to , rather than the seats they would prefer if they had more choice . our results demonstrate that the students number of absences increased with increasing distance from the board . as in previous studies ( 4 , 10 , 15 ) although no significant correlation was found between the number of absences and sex , when we divided the students into two groups based on the number of absences , we observed there were significantly more males in the group of students that was absent from more than 10 sessions . on the other hand , the low number of students attending the educational classes might be natural consequence of modern educational techniques used . in some medical schools such as ours , all the lectures are presently recorded , typed and accessible for all students and these together with the online atlases and slides , has resulted in the students feeling no necessity to attend the class physically . by monitoring the students participation through taking unannounced quizzes , we are making an attempt to obligate the students to participate in the class . ( 16 ) reported that there was a relationship between educational achievement in sophomore students and sex . we conclude that two factors may impact educational achievement : student seating in the high interactional zone and minimal changes in seating location . our results showed that the students in the high interactional zone had higher educational performance and attendance than the rest of the class . this observation is consistent with the view that students in the front of the classroom are likely more motivated and interact with the lecturer more than their classmates . these results suggest that engaging students at the back of the class ( area iii ) or persuading them to sit closer might positively influence their academic performance and participation . however , further studies in large size lecture halls is still needed to verify if assigning poorer performing students and those who change their seat frequently to the seats , would improve their performances and participation . the authors have not received any funding or benefits from industry or elsewhere to conduct this study .

backgroundthe seat selection and classroom dynamics may have mutual influence on the student performance and participation in both assigned and random seating arrangement.purposethe aim of the study was to understand the influence of seat selection on educational achievement.methodsthe seating positions of the medical students were recorded on an architectural plan during each class session and the means and standard deviations of the students locations were calculated in x and y orientations . the locations of the students in the class were analyzed based on three architectural classifications : interactional zone , distance from the board , and access to the aisles . final exam scores were used to measure the students educational achievement.resultsour results demonstrate that there is a statistically significant relationship between the student 's locations in the class and their attendance and educational achievements.conclusiontwo factors may effect on educational achievement : student seating in the high interactional zone and minimal changes in seating location . seating in the high interaction zone was directly associated with higher performance and inversely correlated with the percentage of absences . this observation is consistent with the view that students in the front of the classroom are likely more motivated and interact with the lecturer more than their classmates .

urinary tract infection ( uti ) is the most common serious bacterial infection in infants and children . uti is an infection of the lower urinary tract , the upper urinary tract , or both . it is acquired by an estimated 3% to 5% of girls and 1% of boys in childhood . boys are more susceptible during the first year of life ; thereafter the incidence is substantially higher in girls . rapid diagnosis and prompt antimicrobial treatment are required to minimize renal scarring and progressive kidney damage . reporting of antimicrobial susceptibility testing of the urinary tract is usually achieved 48 hr following sampling , and therefore , in the majority of uti cases , the treatment decision is empirical , being influenced by available data reflecting antibiotic resistance . since the initiation of antimicrobial therapy in uti is empirical , knowledge of the antimicrobial resistance patterns of common uropathogens in each region is essential to provide clinically appropriate therapy . hence , there exists a great need for antimicrobial resistance surveillance at the local , national , and international levels . unfortunately , data regarding the isolation frequency and antimicrobial susceptibility patterns of endemic uropathogens are scarce in iran . the aim of the present study was to determine the frequency of isolation and antimicrobial resistance patterns of uropathogens among children subjected to urine culture at the tabriz children hospital , a teaching and referral hospital in the northwest of iran . the prospective study was carried out with uropathogenic bacteria isolated from outpatients and inpatients children with uti submitted to tabriz children educational - health care center the only children 's referral hospital in northwest of iran from april 2010 to march 2014 . during the study period , uti was considered by the presence of a pure bacterial growth of > 10 colony forming units / ml by properly collected urine specimen ( suprapubic aspiration , transurethral catheterization or clean - catch midstream voiding ) in children with urinary symptoms such as fever 38c , chills , frequency , urgency , dysuria , suprapubic , and/or flank tenderness , pyuria ( defined as 5 leukocytes / hpf ) , and in neonates clinical evidences of sepsis . data about age and sex of patients were also collected . to use the data from this study , one calibrated loopful ( 0.01 ml ) of well - mixed urine samples were cultured on 5% blood agar plates ( merck kgaa , tabriz , germany ) and incubated aerobically at 37c for 24 hr . the isolates obtained were further processed as per the standard procedures to identify the pathogens . the antibiotic susceptibility of urine isolates bacteria was determined by the disc diffusion method ( kirby bauer ) according to the clinical and laboratory standards institute ( clsi ) recommendations . the sensitivity of isolates to 9 antibiotics , commonly used in the utis , was determined . the antibiotics used were amikacin ( an ) , nalidixic acid ( na ) , ciprofloxacin ( cp ) , gentamicin ( gm ) , co - trimoxazole ( sxt ) , cefotaxime ( ctx ) , ceftriaxone ( cro ) , ceftizoxime ( ct ) , and nitrofurantoin ( fd ) . for statistical analysis , was defined as resistance in an isolate to 3 or more unrelated drugs tested.escherichia coli atcc 25922 was used as a control strain . hinton agar medium for antimicrobial testing and antibiotic discs were obtained from hi - media laboratories , mumbai , india . the prospective study was carried out with uropathogenic bacteria isolated from outpatients and inpatients children with uti submitted to tabriz children educational - health care center the only children 's referral hospital in northwest of iran from april 2010 to march 2014 . during the study period , uti was considered by the presence of a pure bacterial growth of > 10 colony forming units / ml by properly collected urine specimen ( suprapubic aspiration , transurethral catheterization or clean - catch midstream voiding ) in children with urinary symptoms such as fever 38c , chills , frequency , urgency , dysuria , suprapubic , and/or flank tenderness , pyuria ( defined as 5 leukocytes / hpf ) , and in neonates clinical evidences of sepsis . data about age and sex of patients were also collected . to use the data from this study , one calibrated loopful ( 0.01 ml ) of well - mixed urine samples were cultured on 5% blood agar plates ( merck kgaa , tabriz , germany ) and incubated aerobically at 37c for 24 hr . the isolates obtained were further processed as per the standard procedures to identify the pathogens . the antibiotic susceptibility of urine isolates bacteria was determined by the disc diffusion method ( kirby bauer ) according to the clinical and laboratory standards institute ( clsi ) recommendations . the sensitivity of isolates to 9 antibiotics , commonly used in the utis , was determined . the antibiotics used were amikacin ( an ) , nalidixic acid ( na ) , ciprofloxacin ( cp ) , gentamicin ( gm ) , co - trimoxazole ( sxt ) , cefotaxime ( ctx ) , ceftriaxone ( cro ) , ceftizoxime ( ct ) , and nitrofurantoin ( fd ) . for statistical analysis , bacteria with intermediate susceptibility was defined as resistance in an isolate to 3 or more unrelated drugs tested.escherichia coli atcc 25922 was used as a control strain . hinton agar medium for antimicrobial testing and antibiotic discs were obtained from hi - media laboratories , mumbai , india . sixty - five ( 69% ) of them were girls and 29 ( 31% ) were boys , with mean age of 4.5 years and 4.2 months for them , respectively . frequency of uti among the children examined by urine culture was 3.6% ( n = 940 ) . only 79% of our cases showed a high white blood cell count ( pyuria ) in urinalysis . furthermore , nitrites and leukocyte esterase and were positive in only 85% and 67% of our patients , respectively . approximately two - thirds of patients ( 69% ) had all 3 positive findings present on urinalysis . ( 6.4% ) other than serratia spp . , enterobacter spp . , and pseudomonas aeruginosa ( 4.2% each 1 ) of the total of 940 confirmed utis , 550 ( 58.5% ) was in outpatients and 390 ( 41.5% ) from inpatients . e coli isolates were resistant to co - trimoxazole in 75.3% of cases , followed by cefotaxime ( 48.1% ) , ceftizoxime ( 43.2% ) , ceftriaxone ( 42% ) , gentamicin ( 32% ) , amikacin ( 30% ) , nalidixic acid ( 24.6% ) , ciprofloxacin ( 14.8% ) , and nitrofurantoin ( 11.1% ) . among the antibiotics used for susceptibility testing of the isolates , ciprofloxacin , nitrofurantoin , and nalidixic acid showed the highest activity ( 100% ) against klebsiella spp . isolates and gentamicin , amikacin as well as ciprofloxacin ( 100% ) against p aeruginosa . the antibiotic susceptibility pattern of other isolates is shown in table 1 and figure 1 . antimicrobial susceptibility ( % ) of isolated uropathogenic bacteria overall resistance of urinary pathogens to tested antibiotics . as indicated in table 1 , alarming antimicrobial resistance was seen in serratia and enterobacter isolates against the most antibiotics tested . mdr of the uropathogenic isolates was analyzed and 48.2% of e coli isolates , 50% of klebsiella spp . 89% , 87% , and 81% of mdr isolates were resistant to cefotaxime ( ctx ) , ceftizoxime ( ct ) , and ceftriaxone ( cro ) as well as co - trimoxazole ( sxt ) , respectively . resistance of mdr isolates to antimicrobials the antibiotic resistance pattern of the isolated uropathogens was also evaluated by patient sex . isolated bacteria in male patients tended to be more resistant to tested antibiotics ( data not showed ) ; however , this difference did not reach statistical significance . to the best of our knowledge , there was no comprehensive study before this study in northwest of iran to estimate the most common uropathogens and their resistance pattern in pediatrics . this study showed the prevalence of isolation and antibiotic resistance pattern of uropathogenic bacteria in a referral pediatric hospital in tabriz in the northwest of iran , during 5 years period . according to our findings , frequency of uti among children was 3.6% and the girls were affected by uti more often than boys , but boys were significantly younger than girls ; these results are similar to the most of previous reports . however , in a study from southern iran , about 7.9% of children were positive for uti and uti was reported more frequent in male patients possibly because the most of their participants were neonates and male infants are usually infected more than girls during the first 3 months of their life . as indicated in the previous studies , e coli and klebsiella spp . uropathogenic e coli isolates , showed the most resistance to co - trimoxazole ( 75.3% ) and then to third - generation cephalosporins ( 42% to 48% ) , used to testing . as indicated , the most strains of isolated e coli were resistant to co - trimoxazole . unfortunately , this is a significant problem in the northwest of iran and has also been reported by other laboratories in iran . on the other hand , greater concern is that increasing resistance is eroding the usefulness of third - generation cephalosporins , aminoglycosides and nalidixic acid for the management of uti in our region . however , it has also been shown in previous studies of iran , for example , mirsoleymani et al have reported a high rate resistance to third - generation cephalosporins including ceftriaxone and cefixime from southern iran . our observation supports previous studies indicating that nitrofurantoin still exhibited low resistance rates in the most countries investigated . in this study , a considerable portion of the uropathogens , especially e coli isolates , were found to be sensitive to nitrofurantoin ( tables 1 and 2 ) . this may have been due to the fact that this antibiotic has not been widely used in treating uti cases . therefore , nitrofurantoin may be a good option for the empirical treatment of uti in the northwest of iran . however , it should not be used to treat uti in febrile infants because it is excreted in the urine and do not achieve therapeutic concentrations in the bloodstream . overall , our findings showed that the highly active antibiotic against gram - negative and gram - positive uropathogens was amikacin and then ciprofloxacin with susceptibility rates of 90.9% and 80.9% , respectively ( figure 1 ) . ciprofloxacin was also the most effective antimicrobial against gram - negative uropathogens with susceptibility rate of 97.0% ( results not showed ) . among the total isolates that were tested against all 9 antibiotics , the half ( 50% ) of them were resistant to 3 or more antibiotics and considered mdr . as indicated in table 2 , 89% , 87% , and 81% of mdr isolates were resistant to cefotaxime , ceftizoxime , and ceftriaxone as well as co - trimoxazole , respectively . overall , the evaluation of antimicrobial resistance among mdr isolates , indicated a high resistance against all antibiotics tested , except nitrofurantoin and ciprofloxacin . however , the multidrug - resistant isolates ratio in that study was lower than in our observation ( 24.5% vs 50% ) . in this study , higher resistance rates to all antibiotics tested with the exception of amikacin , ciprofloxacin , and nitrofurantoin may be explained by high and uncontrolled usage of these antimicrobial agents , especially third - generation cephalosporins , during the past few years in our country . unfortunately , these antibiotics were widely prescribed not only for uti but also for other infections in iran . in conclusion , in the northwest of iran including tabriz , children , who are receiving prophylactic antibiotics and are admitted to the hospital for a uti , are often infected with an organism that is resistant to third - generation cephalosporins and co - trimoxazole . therefore , a larger number of these children may be empirically treated with ciprofloxacin , nitrofurantoin , or amikacin . however , it is necessary to regular monitoring of the usage of antibiotics in order to make reliable information available for optimal empirical therapy for children with utis . moreover , regular reporting of the antimicrobial susceptibility patterns of uropathogens can be a useful guide for appropriate initiating empiric therapy of utis in children . although our study was the first investigation about epidemiology of children uti in northwestern part of iran , nonetheless , we could investigate the uropathogens from other parts of iran to find more accurate and more comprehensive results about etiology and their antimicrobial resistance pattern and it can be our limitation of this research .

abstracturinary tract infection ( uti ) is 1 of the most common bacterial diseases in children with a considerable resistance to antimicrobials.this 5 years prospective study was carried out to determine the frequency of isolation and antimicrobial resistance patterns of uropathogens among children subjected to urine culture at tabriz children educational - health care center , in the northwest of iran . organisms were isolated using standard culture techniques.frequency of uti among children examined by urine culture was 3.6% . the isolated bacteria were escherichia coli ( 71.4% ) , followed by klebsiella spp . ( 9.6% ) , enterococcus spp . ( 6.4% ) , pseudomonas aeruginosa ( 4.2% ) , serratia spp . ( 4.2% ) , and enterobacter spp . ( 4.2% ) . e coli resistance levels were 11% for nitrofurantoin , 15% for ciprofloxacin , 25% for nalidixic acid , and 30% to 75% for amikacin , gentamicin , ceftriaxone , ceftizoxime , cefotaxime , and co - trimoxazole . among the tested antibiotics , ciprofloxacin , showed the highest activity ( 100% ) against klebsiella and p aeruginosa isolates followed by amikacin , nalidixic acid , and gentamicin.overall , the highly active antibiotic against gram - negative and gram - positive organisms was amikacin and then ciprofloxacin . on the other hand , the empirical initial therapy with co - trimoxazole and third - generation cephalosporins would be inadequate for more cases of uti in the study area . moreover , susceptibility testing should be carried out on all clinical isolates , and the empirical antibiotic treatment changed accordingly .

an 87-year - old caucasian female with a history of hypertension , atrial fibrillation ( non - valvular ) on coumadin anticoagulation , diabetes mellitus type 2 , and copd was admitted to the hospital with severe back pain , right hip pain , and weight gain over 20 pounds over the past week . , she was afebrile and the physical examination revealed jugular venous distention , few rales in left lower lung field , no wheezing , grade 2 systolic murmur at the aortic area radiating upward , and severe pitting edema over bilateral lower extremities . laboratory studies disclosed the following data : wbc 8,690/mm ( 10% bands , repeated wbc 11,730 ) , hb 10.5 g / dl , hematocrit 32.5% , platelet 162,000/mm , mcv 98 , rdw 17.0 , sodium 128 meq / l , cr 1.5 mg / dl , bun 39 mg / dl , bicarbonate 21.7 mmol / l , pro bnp 4,841 , total protein 10.6 g / dl , and albumin 3.2 g / dl . we treated her with furosemide , short period of prednisone , and tiotropium bromide inhalation . subsequently , transthoracic echocardiogram revealed lvef 6065% , mild aortic stenosis , and one small vegetation on the non - coronary aortic leaflet ( fig . we diagnosed infective endocarditis ( ie ) , and we started ampicillin ( 2 g every 6 h ) and gentamicin ( 100 mg daily , renal dosing ) according to the sensitivities . we continued both ampicillin and gentamicin for 4 weeks from the date of first negative blood culture . tte : a small , mobile 45 mm echodensity at the tip of the non - coronary leaflet . mri of lumbar spine with contrast does not show any evidence of discitis , vertebral osteomyelitis , and epidural abscess , but mild t12 compression fracture . given the patient 's age , anemia , back pain , and elevated gamma gap , we have the suspicion of plasma cell disorder . patient 's immunofixation electrophoresis showed an igg lambda monoclonal protein comprising 39.9% of the total protein , equivalent to 3.8 mg / dl ; therefore , we performed bone marrow aspiration and biopsy , which revealed plasma cell myeloma , monoclonal lambda type ( 35% of the cellular elements ) . the members of gemella species have been classified as g. morbillorum , g. haemolysans , g. bergeri , g. sanguinis , g. palaticanis , and g. cuniculi on the basis of dna hybridization and comparative 16s rrna gene sequencing ( 2 ) . for the first time , thjotta and boe described g. haemolysans as neisseria haemolysans in 1938 ( 4 ) . ( 5 ) showed that the structure of the cell wall of g. haemolysans was typical of gram - positive cocci by electron microscopy . the comparative thinness ( 1020 nm ) of its cell wall accounts for easy decolorization during gram staining . g. haemolysans often colonizes in the upper respiratory , gastrointestinal , and genitourinary tract as a commensal organism and occasionally causes localized and/or disseminated infections . it is a rare cause of endocarditis , with 19 cases reported in the literature and only four cases associated with prosthetic valve endocarditis ( 1 , 2 , 3 , 6 ) . most documented cases of g. haemolysans endocarditis occur in patients with underlying mitral or aortic valve disease ( including prosthetic valves ) and/or poor dentition or dental manipulation , which was not the situation with this patient . infected valves were aortic and mitral , both of them with the same percentage ( 50% ) ( 13 ) . there are also case reports about meningitis ( 8) and brain abscess ( 9 ) . for diagnosing ie , there is generally good agreement between transthoracic echocardiography ( tte ) and pathologic findings from autopsy or surgery . however , there are limitations in ultrasound measurements of small vegetations ( <3 mm ) , which might be undetectable by tte ( 10 ) . since our patient 's vegetation size was 45 mm , and she was fragile , we defer the transesophageal echocardiography . antimicrobial therapy for g. haemolysans ie would typically include penicillin or ampicillin in combination with gentamicin . in all published cases , patients were successfully treated with antibiotics alone or in combination with cardiac valvular replacement , one patient with prosthetic valve endocarditis requiring implantation of a total artificial heart as a bridge to heart transplantation ( 6 ) . the results of antimicrobial susceptibility studies by buu - ho a ( 11 ) demonstrate that all strains of g. haemolysans were highly sensitive to penicillin g and ampicillin . their results suggest that penicillin g combined with an aminoglycoside can be recommended for the treatment of endocarditis caused by g. haemolysans . patients with multiple myeloma are more susceptible to infections , which are the major causes of morbidity and mortality . despite the common occurrence of bacteremia , ie is seldom reported . by searching pubmed , we can only find scattered case reports without statistic data about ie in multiple myeloma patients . patients with multiple myeloma are susceptible to infection due to compromised immunoglobulin synthesis and function . in summary , because of the lack of other risk factors , we felt that multiple myeloma maybe a under recognized risk factor for endocarditis due to g. haemolysans . none of the authors have any financial or personal bias that would inappropriately compromise the publication of this work . the authors have not received any funding or benefits from industry or elsewhere to conduct this study .

an 87-year - old caucasian woman with hypertension , diabetes mellitus type 2 , and copd was admitted with 1-week duration of back pain and weight gain . the physical examination revealed jugular venous distention , rales in the left lower lung field , and severe pitting edema over lower extremities . as workup for leukocytosis , blood cultures grew gemella haemolysans . subsequently , a transthoracic echocardiogram revealed vegetation on the non - coronary aortic leaflet and mild aortic stenosis . she was treated with ampicillin and gentamicin . after further investigation , the patient was diagnosed with plasma cell myeloma , the monoclonal lambda type . this is the first reported case of g. haemolysans endocarditis in a multiple myeloma patient .

acute kidney injury ( aki ) secondary to immersion and near - drowning is rarely described and poorly understood . much of the literature of near - drowning has concentrated on the respiratory effects of aspiration of salt and freshwater , and on the management of both early and late respiratory complications such as aspiration pneumonia and adult respiratory distress syndrome ( 1 ) . however , near - drowning and immersion can have profound effects on other end organs such as cerebral ( hypoxic brain injury , cerebral edema ) ( 2 ) , cardiac ( atrial fibrillation ) ( 3 ) and hematologic complications ( coagulopathy and hemolysis ) ( 4 ) . moreover , multisystem failure resulting from near - drowning is also well described ( 5 ) . near - drowning induced acute kidney injury ( aki ) is not uncommon and is heterogenous clinical entity ( 6 ) . although the resultant aki is usually mild and self - limited , severe cases such as aki associated with shock , multisystem failure , rhabdomyolysis ( 7 , 8) and isolated aki can occur ( 6 ) . only few cases of severe isolated aki due to acute tubular necrosis ( atn ) resulting from near - drowning exist in the literature . we report a case of near - drowning who developed severe isolated aki requiring dialysis due to biopsy - confirmed atn . a 21-yr - old man was admitted to this hospital because of anuria and nausea on june 11 , 2011 . he had been well until 3 days before admission , when he went to swim in the lake with his friends . he was unconscious briefly ( about 2 - 3 min ) until rescued by his friend . , he was conscious but sleepy ; blood pressure was 132/68 mmhg , body temperature was 36.9 , and pulse was 114 beats per minute ; respiration was 20 per minute , and the oxygen saturation was 96% while the patient was breathing ambient air . laboratory tests revealed serum creatinine level of 1.4 ( 0.4 - 1.3 ) mg / dl , total carbon dioxide ( tco2 ) of 9.8 ( 24 - 30 ) mm / l , anion gap of 27.2 mm / l , hemoglobin concentration of 16.7 g / dl , and leukocyte count of 12,300/l ( lymphocyte 41.1% ) . he was admitted to our hospital 3 days later , complaining of being tired , anorexic and anuric . the vital signs were as follows : blood pressure , 140/90 mmhg ; pulse , 75 beats per minute ; respiration , 20 per minute ; and body temperature , 37.6. laboratory findings showed blood urea nitrogen ( bun ) of 42.7 ( 6 - 26 ) mg / dl , serum creatinine of 11.5 mg / dl , seum cystatin c level of 3.39 ( 0.5 - 1.10 ) mg / l , aspartate aminotransferase ( ast ) of 6 ( 10 - 40 ) iu / l , alanine aminotransferase ( alt ) of 9 ( 6 - 40 ) iu / l , lactate dehydrogenase ( ldh ) of 435 ( 218 - 472 ) iu / l , creatine kinase ( ck ) of 225 ( 5 - 217 ) u / l , myoglobin of 87.9 ( 15.2 - 91.2 ) ng / ml , tco2 of 15.4 ( 20 - 28 ) mm / l , anion gap of 19.3 mm / l , hemoglobin concentration of 13.1 g / dl , and leukocyte count of 11,180/l ( segmented neutrophil 86.5% , lymphocyte 8.1% ) . the hourly urine output was less than 10 ml despite of bolus infusion of normal saline and continuous infusion of furosemide . non - contrast enhanced abdominal computed tomography showed normal sized kidneys without urinary tract obstruction . a bone imaging study using the patient needed five sessions of dialysis over the succeeding 5 days and serum creatinine level was 5.12 mg / dl on the next day after the last hemodialysis session , then we stopped hemodialysis treatment . on the 9th hospital day , serum creatinine level was 3.05 mg / dl , we planned renal biopsy that had been postponed because of bleeding risk . the next day , serum creatinine level was 1.98 mg / dl and renal biopsy was performed . the renal tubular epithelial cells were denuded and had exfoliating brush borders and intermittent mitosis due to regeneration . the interstitium was edematous and had mild infiltration of lymphocytes , but the glomeruli showed unremarkable finding ( fig . the patient 's renal function recovered spontaneously , 1.24 mg / dl 3 weeks later and 1.07 mg / dl 5 weeks later . aki secondary to near - drowning is not uncommon , but the resultant severe aki requiring dialysis is exceedingly rare : we found only 7 reported cases , including the present report ( 6 - 10 ) . the two other cases were related with rhabdomyolysis ( 7 , 8) , 1 case resulted from hypothermia ( 9 ) , 1 case were related with both ( 10 ) , and 2 cases had isolated aki ( 6 ) . ( 6 ) ; usually the term means that disproportionately severe aki even several days after the immersion episode who did not require cardiopulmonary resuscitation ( cpr ) or did not experience shock , hypothermia or myoglobinuria after their near - drowning . this case is the third report of severe isolated aki in the literature and first report in korea . immersion and drowning injury has been widely reviewed ( 1 - 3 ) , and widespread tissue hypoxia and subsequent reperfusion injury are thought to be the predominant underlying pathophysiology , although hypovolemia and hypothermia may also contribute to tissue damage . the initial event leading to tissue injury in kidney ischemia - reperfusion injury ( iri ) is the acute reduction of blood flow that produces hypoxia - induced vascular and tubular dysfunction . following reperfusion , various intracellular events occur that lead to cellular dysfunction , apoptosis and cell death ( 11 ) . the morphological changes occur mainly in proximal tubules , susceptible to ischemic injury , including loss of polarity , loss of the brush border ( 12 ) , and redistribution of integrins and na / k - atpase to the apical surface ( 13 ) . calcium ( 14 ) and reactive oxygen species ( 15 ) may also have a role in these morphological changes , in addition to subsequent cell death resulting from necrosis and apoptosis . both viable and nonviable cells are shed into the tubular lumen , resulting in the formation of casts and luminal obstruction and contributing to the reduction in the gfr ( 16 ) . inflammation is also an important early event leading to intracellular responses that ultimately result in apoptosis and necrosis . the involvement of the immune system in kidney iri is very complex ; dendritic cells and macrophages may contribute early in the innate immune response to kidney iri and promote neutrophil infiltration ( 17 ) , while t regulatory cells have been shown to suppress the extent of kidney iri through an il-10 dependent mechanism ( 18 ) . dendritic cells , neutrophils , phagocytic macrophages and lymphocytes participate in the early phase of kidney iri as well as the late reparative phase ( 19 ) . a retrospective study to assess clinical predictors of near - drowning associated aki concluded that lymphocytosis may also predict renal impairment ( 6 ) . in our case , the patient had not lymphocytosis but mild lymphocyte infiltration in interstitium was seen . metabolic acidosis is common after near - drowning , and is due to lactic acidosis induced by tissue hypoxia ( 5 , 20 ) . that lactate was the probable cause of acidosis supported by the increased anion gap and reversible nature of the acidosis . in this case , unfortunately , serum level of lactic acid and arterial blood gas analysis just after immersion episode were not checked , but severe high anion gap metabolic acidosis was seen on presentation . the acidosis was quickly corrected , but the initial mild renal dysfunction progressed to establish severe aki and required supportive dialysis . why renal injury predominates in the absence of other post - immersion injury sequelae is not known . the possible explanation is renin - angiotensin surge when returning to dry land after whole - body immersion may play a role ( 3 ) . although the pathology of isolated aki is controversial , renal hypoxia and subsequent reperfusion injury play major role in developing severe aki due to atn in our case . it is plausible that the patient had not hemodynamic instability , hypothermia or rhabdomyolysis that related with aki after near - drowning . in summary , we describe a case of severe isolated aki caused by near - drowning . to the best of our knowledge , this is the first such case report in korea . our case differs from the 2 other cases we reviewed in the literature in that our patient 's aki was confirmed by kidney biopsy as atn . although near - drowning associated aki is usually mild and self - limited , severe aki required dialysis can occur even several days after immersion event , it is recommended that any patient who presents after near - drowning or immersion should be assessed for potential aki .

acute kidney injury ( aki ) secondary to near - drowning is rarely described and poorly understood . only few cases of severe isolated aki resulting from near - drowning exist in the literature . we report a case of near - drowning who developed to isolated aki due to acute tubular necrosis ( atn ) requiring dialysis . a 21-yr - old man who recovered from near - drowning in freshwater 3 days earlier was admitted to our hospital with anuria and elevated level of serum creatinine . he needed five sessions of hemodialysis and then renal function recovered spontaneously . renal biopsy confirmed atn . we review the existing literature on near - drowning - induced aki and discuss the possible pathogenesis .

in spite of defects , such as poor sealing ability and lack of providing additional strength , it is more than 100 years that gutta - percha in combination with a root canal sealer has been the most commonly used root canal filling material . resilon ( pentron clinical technologies , wallingford , ct ) is a synthetic thermoplastic polymer - based root canal filling material which has been introduced to endodontic since 2004 . a resin - based sealant or bonding in conjunction with resilon may be a possible replacement for gutta - percha . by production of an adhesive bond between the solid core material and the sealer , resilon forms a monoblock within the canals bonding to the dentinal walls as well . furthermore , as the handling properties of resilon are similar to gutta - percha , it could be used with any current obturation . for retreatment purposed resilon might be heat - softened or dissolved with solvents such as chloroform . fillers which compose approximately 70% of resilon weight are added to facilitate the removing of materials from root canal during retreatment . . since resin - based obturation systems ( resilon ) are developed as viable alternatives to gutta - percha , their acclaimed superiority have been investigated in different aspects of root canal treatment . based on preliminary investigations , advantages of these new systems include a better biocompatibility than gp , increase in the resistance of instrumented roots to vertical fracture [ 79 ] and increased resistance to micro leakage . judging the advantages claimed by companies , it appears that in the close future a considerable number of treated root canals will be filled with resilon ; consequently , for comparable reasons such as inadequate debridement and filling of the root canal system , procedural errors or reinfection of the primary sealed root canal caused by coronal or apical leakage , resilon filled root canals may also need nonsurgical endodontic retreatment as well . the methods for removal of root filling materials are thermal , mechanical , chemical or the combination of the above three . in other words , apart from the different techniques and equipments which could be used , application of heat and chemical solvents , especially in problematic canals is usually a part of the retreatment process . different solvents for gutta - percha as well as various root canal sealers have been very well researched in the past . based on those researches , chloroform is known as the most efficient organic solvent of gutta - percha as well as various root canal sealers . the manufacturer suggests that resilon filled root canals are retreatable by current retreatment techniques and they might be heat softened or dissolved with solvents such as chloroform . according to ezzie and coworkers , who studied the efficacy of retreatment techniques , in addition to having lower melting temperature this could be considered as a contributing factor which results in cleaner canal walls in teeth obturated with resilon when compared to gutta - percha . so , this study was designed to compare the solubility of gutta - percha and resilon in chloroform and to find the impact of sample thickness as well as the time of shaking on their solubility . samples were prepared from specific weights ( range , 0.080.085 gm ) of resilon and gutta - percha in form of disks with various thicknesses ( 1.6 , 0.8 and 0.4 mm ) . shimadzu ssp 10a solid sample press and micrometer ( shimadzu corp . , kyoto , japan ) were used for preparing various thicknesses . each sample was placed in a sample tube and after adding 1.0 ml chloroform at 37c , the tubes were capped and shaken for 1 , 3 and 5 minutes with the speed of 600 vibration / min . shaking of the samples were performed using ika - vibrax - vxr , janke & kunkel vx8 vibrator ( germany ) . then , the mixture was filtered on a weighted filter paper and was dried on harvard / lte qualivac vacuum dryer ( united kingdom , england ) . the amount of non - dissolved material was determined by reweighting of each sample and the percent of solubility was assessed according to the exact weight loss of the samples . gutta - percha and resilon were purchased from suredent corporation ( korea ) and pentron clinical technologies ( usa ) companies , respectively . the difference between the solubility of gutta - percha and resilon as well as the effect of sample thickness and time of shaking on solubility were assessed statistically by repeated measurement anova ( p<0.05 ) . table 1 shows that irrespective of time , there is a significant difference between the amount of weight loss ( solubility ) of gutta - percha and resilon in chloroform and resilon has a significantly higher solubility than gutta - percha ( p<0.05 ) . in addition , as it is shown in fig 1 , the weight loss of the samples , which is actually indicated the amount of solubility , increases significantly over time and there is an interaction between the amount of weight loss and time . table 2 . shows the mean percentage of weight loss ( solubility ) of various sample thicknesses in chloroform for each immersion period .solubility is not affected significantly by the sample thicknesses ( p > 0.05 ) fig 2 has shown that regardless of time , sample thickness has no significant effect on solubility and the percentage of the weight loss of the samples ( dissolution changes ) were comparable among different thicknesses . ideal root canal filling material should be easily removed whenever necessary for retreatment purposes ; regardless of significant statistical evidence for better prognosis , non surgical endodontic retreatment of previously filled root canals has priority to surgical intervention for the management of endodontic failures . in well condensed obturated canals , removal of the obturating material could be tedious and time - consuming ; whereas , purely mechanical means are dangerous and may lead to root perforation , canal straightening or alteration of the original canal shape . generally , hand or rotary instruments are used in combination with heat or solvents for complete elimination of filling materials from the root canals . the use of solvent both reduces the time of retreatment and the amount of residue . since resilon was introduced to dentistry , apart from the different techniques used , several studies have reported its superior retreatment ability compared to gutta - percha . its lower melting point and higher molecular weight as well as better solubility in chloroform compared to gp have contributed to this issue [ 1,2,2224 ] . chloroform was selected as a solvent in this study as it is known to be more efficient than other organic solvents in dissolving root canal filling materials .in addition , it has been recommended by the resilon manufacturer for the retreatment procedure . regardless of its undesirable properties such as being a possible carcinogen , hepatotoxic , nephrotoxic and locally toxic in contact with periradicular tissues , chloroform is the most used solvent in clinic . in addition according to vajrabhaya et al other gp - solvent was not less cytotoxic than chloroform . methods which were used in the present study are compatible with numerous basic researches conducted on gutta - percha and root canal sealer solvents in which the dissolving efficacy of solvents were assessed by the difference between the original pre - immersion weight and the post - immersion weight . in conclusion , considering the observed higher solubility of resilon in chloroform and the fact that there is no need for complete solution of obturating material during the retreatment procedure , there is a possibility for using safer and weaker solvents . this claim is somewhat supported by the fact that over the years , retreatment of gutta - percha filled root canal has been preformed successfully and even if an appropriate substitute for chloroform is not found , there is still a chance to use a weaker dose of it in the form of pastes and gels .

objective : application of chemical solvents especially in problematic canals is usually a part of the retreatment process . this study was performed to compare the solubility of gutta - percha and resilon in chloroform and to find the effect of sample thickness as well as the time of shaking on their solubility.materials and methods : specific weight of resilon and gutta - percha was placed in a sample tube and after adding 1.0 ml of chloroform at 37c , the tubes were capped and shaked for 1 , 3 and 5 minutes . the amount of non dissolved material was determined by reweighting of each sample and the percent of solubility was assessed according to the exact weight loss of the samples . the procedure was repeated three times for a given thickness and time of shaking . the difference in the solubility of gutta - percha and resilon as well as the effect of sample thickness and time of shaking on solubility were assessed by repeated measurement anova ( p<0.05).results : resilon has significantly higher solubility than gutta - percha in chloroform ( p<0.05 ) . resilon as well as gutta - percha solubility are increased significantly over the time .the amount of solubility is not affected by sample thickness.conclusion:comparison of resilon and gutta - percha solubility in chloroform shows that one of the advantages for resilon could be the chance for using possible safer organic solvents during retreatment .

prostate cancer is the fourth most common cancer in men , comprising approximately one - eighth of all male - specific cancers in the world . identifying risk factors for prostate cancer is critically important to develop potential interventions and to expand our understanding of the biology of this disease [ 2 , 3 ] . the etiology of prostate cancer remains unknown , but race , age , family history of prostate cancer , and steroid hormone levels have been suggested as contributing factors . the literature has revealed that eunuchs ( men lacking testosterone ) do not develop prostate cancer , generating the theory that testosterone plays a vital role in the development and progression of the disease . as a corollary , testis ablation is a well - established and effective way to stop progression of the disease . androgens , responsible for the healthy growth and maintenance of the prostate , are steroid hormones expressed in the prostate . the two main types of androgens found in males , testosterone and dihydrotestosterone ( dht ) , have been postulated to modify the risk of prostate cancer [ 8 , 9 ] . most epidemiologic studies of prostate cancer have focused on the genes involved in the steroidogenic pathway , such as p450 cytochrome 3a4 ( cyp3a4 ) , cyp17 , and srd5a2 . although differences in androgen levels may also reflect variations in catabolism / inactivation , few studies have evaluated this hypothesis [ 1013 ] . different ethnic groups differ in the risk to develop prostate cancer , afro - americans having the highest incidence followed by caucasians and asians having the lowest incidence . lower levels of testosterone metabolites such as androsterone glucuronide and androstanediol glucuronide were observed in the plasma of asian subjects [ 15 , 16 ] . this finding was interpreted as a sign of lower androgen load , which may contribute to the lower incidence of prostate cancer in asians . studies indicate that environmental and lifestyle factors account for 1015% of the racial differences in risk . uridine diphosphosglucuronosyltransferases ( ugts ) constitute a family of enzymes that glucuronidate a wide variety of substrates including exogenous and endogenous compounds such as bilirubin , bile acids , and steroids . the glucuronidated product is more polar , water soluble , and more easily excreted in the bile and urine . on the basis of homology of protein primary structure , the ugt enzymes have been grouped into two families , ugt1 and ugt2 . enzymes of the ugt2 family are encoded by separate genes and are subdivided into two subfamilies , ugt2a and ugt2b . seven functional ugt2b enzymes have been identified in humans to date , all of which are important in the homoeostasis and metabolism of steroids . it has been found to have the highest activity for androsterone , testosterone , and dihydrotestosterone as compared with the other ugt2b members . previous studies have demonstrated deletion of the ugt2b17 gene [ 21 , 22 ] . to date , a number of molecular epidemiological studies have been conducted to evaluate the effect of the ugt2b17 deletion on risk of prostate cancer [ 2328 ] . however , until now , those studies that investigated associations between the ugt2b17 polymorphism and prostate cancer risk have yielded inconsistent results . considering the potential important role of ugt2b17 in prostate cancer , a meta - analyses of published studies was conducted to assess the association between ugt2b17 polymorphism and cancer risk . relevant studies to be included in the study were searched from the following databases pubmed , embase , google scholar , and china national knowledge infrastructure ( cnki ) . relevant publications were identified using the following search strategies : uridine diphosphoglucuronosyl tranferases 2b17 or ugt2b17 or ugt2b17 deletion or polymorphism and prostate cancer or prostate carcinoma . all human associated studies were included , if they met the following criteria : ( 1 ) evaluation of the ugt2b17 present / null polymorphism and prostate cancer risk , ( 2 ) case control studies , ( 3 ) report on an or with 95% ci , and ( 4 ) being original and published in english with an availability of a full - text . exclusion criteria were ( 1 ) insufficient original data for the calculation of odds ratios ( ors ) with corresponding 95% confidence intervals ( 95% cis ) , ( 2 ) not case control study , and ( 3 ) review studies . information was carefully extracted from all the eligible publications independently by two authors according to the criteria listed previously . the following information was recorded for each study : first author , year of publication , country or region of origin , ethnicity , or ( 95% ci ) , number of cases and controls , source of control group ( population or hospital based ) , and genotype frequency of ugt2b17 . for studies that included subjects of different ethnic descents , data were extracted separately for each ethnicity , which was categorized as caucasian , whites , and african americans . the strength of the association between ugt2b17 polymorphism and prostate cancer risk was assessed by calculating the pooled or with its 95% ci . the pooled ors were obtained using either the fixed - effect ( mantel - haenszel 's method ) or random - effect ( dersimonian and laird method ) models , and the significance of the pooled or was determined by the z - test . heterogeneity assumption was checked by the chi - square test based q statistic and the i statistic . a significant q statistic ( p < 0.10 ) or i statistic ( i > 50% ) indicated obvious heterogeneity across studies , and the random - effect model was selected to pool the ors . subgroup analyses were firstly performed by ethnicity , and ethnicities were categorized as caucasians , whites , and african americans . the funnel plot should be asymmetric when there is a publication bias , and the funnel plot asymmetry was further assessed by the method of egger 's linear regression test . all statistical analyses were performed using stata statistical software ( version 10.1 ; stata corporation , college station , usa ) . the flow chart of study selection for this meta - analysis is presented in figure 1 . a total of 69 published records up to december 15 , 2012 , were identified , of which 9 were considered potentially eligible for inclusion in this meta - analysis and were retrieved in full texts . among these , 3 studies were excluded because they had insufficient data on or calculation [ 3436 ] . in addition , the study investigating multiple ethnicities was separated into two studies in the subgroup analysis . overall , 6 publications , including 3,839 cases and 3,190 controls , were included in this meta - analysis . among the 6 studies included in this meta - analysis , 4 studies were conducted on caucasians , 1 on whites , and 1 on african americans and caucasians . the summary of meta - analysis for ugt2b17 polymorphism with prostate cancer risk is shown in table 1 . overall , there was a significant association between ugt2b17 polymorphism and increased risk of prostate cancer ( or = 1.74 , 95% ci 1.142.64 , p < 0.001 ) ( figure 2 ) . subgroup analyses were firstly performed by ethnicity ( caucasians , whites , african americans ) . there was an obvious association between ugt2b17 polymorphism and increased risk of prostate cancer in caucasians ( or = 1.83 , 95% ci 1.083.12 , p = 0.026 ) ( figure 3 ) . in the subgroup analysis which were performed by types of controls ( population and hospital based ) , there was an obvious association between ugt2b17 polymorphism in hospital based and increased risk of prostate cancer ( or = 1.96 , 95% ci 1.163.31 , p = 0.011 ) ( figure 4 ) . to examine the effect of heterogeneity between studies included in the meta - analysis results , subgroup analyses stratified by the following factors were conducted : ethnicity and sources of controls . the results were as follows : ethnicity ( p = 0.026 and i = 91.4% for caucasians ) and sources of controls ( p = 0.011 and i = 86.7% for hospital based ) . ugt2b17 polymorphism was significantly associated with prostate cancer risk in overall analysis ( i = 87.4% ) . in the sensitivity analysis , the influence of each study on the pooled or was examined by repeating the meta - analysis while omitting each study , one at a time . begg 's funnel plot and egger 's test were conducted to assess a possible publication bias in the literature . the results egger 's test showed no indication of publication bias ( p = 0.19 ; figure 6 ) . genetic susceptibility to cancer has been a research focus and many genetic association meta - analyses have been published to find some possible susceptibility polymorphisms . previous study assessing the association between ugt2b17 deletion and the risk of prostate cancer reported inconclusive and inconsistent findings . therefore , to get a reliable conclusion of the association between ugt2b17 polymorphism and prostate risk , we conducted the present meta - analysis of 6 independent studies including a total of 7,029 subjects ( 3,839 cases and 3,190 controls ) [ 2328 ] . overall , there was a significant association between ugt2b17 status and increased risk of prostate cancer ( figure 2 ) . moreover , the association remained significant among caucasians and hospital - based subgroup analysis . the ugt2b17 enzyme is particularly active in androgen glucuronidation and is highly expressed in prostate tissue [ 19 , 20 , 37 ] . the data are consistent with the hypothesis that the ugt2b17 enzyme may play a role in degradation of dihydrotestosterone and that an excessive amount of dihydrotestosterone may be associated with carcinogenesis in the prostate tissue . unfortunately , most of studies have only a few hundred participants , even less , which is too small to precisely evaluate the overall effects . meta - analysis has been considered to be a powerful tool to overcome this problem by combining the results from independent studies together . this study has shown that the ugt2b17 polymorphism may be involved in the development of prostate cancer . a previous meta - analysis indicated that there was a marginally significant association with the ugt2b17 del polymorphism under del / del versus ins / ins + ins / del ( p = 0.05 ) . it is known that the allele frequencies of metabolic genes are not equally distributed throughout the human population but follow diverse ethnic patterns ; therefore , the subgroups according to ethnicity were performed . our results indicated that significant prostate cancer risks of people with ugt2b17 polymorphism are in caucasians with or = 1.83 ( 1.083.12 ) and p = 0.026 . it was previously reported that the ugt2b17 deletion polymorphism was not associated with an increased risk of prostate cancer in african - americans from arkansas but was associated with an increased risk ( or = 1.9 ) in caucasian subjects from florida that included 293 cases and a similar number of controls . obviously , the genetic variation in ugt2b17 ( and ugt2b15 ) does not explain the ethnic differences observed in prostate cancer that was discussed previously . the interethnic differences observed for the ugt2b17 polymorphism frequency are consistent with the ethnic distribution of the ugt2b15 y85d polymorphism . on one hand , it is conceivable that an increased local enzymatic degradation in the prostate may decrease the androgen exposure of the androgen receptors thereby counteracting the postulated proliferative role of these receptors . on the other hand , ugt2b17 and ugt2b15 alleles that are associated with an increased risk of prostate cancer are more common in asian populations than in caucasian populations . obviously , the genetic variation in ugt2b17 ( and ugt2b15 ) does not explain the ethnic differences observed in prostate cancer that was discussed previously . additionally , as limited sample size may not have enough statistical power to detect a real effect or generate a fluctuated estimation , the small sample size of whites and african americans in this meta - analysis furthermore , the results of this meta - analysis showed that ugt2b17 polymorphism has strikingly increased the risk of prostate cancer risk susceptibility when stratified by control source . however , we obtained the highest risk of prostate cancer in hospital - based controls with or = 1.96 ( 1.163.31 ) and p < 0.001 . the possible reason may be that ugt2b17 polymorphism could influence the susceptibility to noncancer diseases , so its genotype frequency possibly differed between the hospital - based and population - based controls . also the small sample size of population based in this meta - analysis should be taken into consideration . if significant heterogeneity is present , pooled summary estimates from such meta - analyses are hard to interpret . in our meta - analysis , the current meta - analysis has vital advantages compared to other studies ; however , there are some limitations in this meta - analysis . firstly , only published studies in english with full text were included in this meta - analysis ; therefore , the publication bias may have occurred . secondly , the small sample size in subgroup analyses may have limited statistical power . furthermore , due to limited studies included in this meta - analysis , we were unable to perform further subgroup analyses such as by genotyping method . thirdly , the results of subgroup analysis should be interpreted with caution because of the limited statistical power . we anticipate that issues will be addressed in future studies . finally , most studies in the meta - analysis were retrospective design which could suffer more risk of bias owing to the methodological deficiency of retrospective studies . though there was no obvious risk of publication bias in the present meta - analysis , the risks of other potential bias were unable to be excluded therefore , more studies with prospective design and low risk of other bias are needed to provide a more precise estimate of the association between ugt2b17 polymorphism and prostate cancer . in summary , this meta - analysis with a total of 3,839 cases and 3,190 controls suggests that the ugt2b17 polymorphism is associated with increased risk of prostate cancer in caucasians ; well - designed studies with large sample sizes involving various ethnic populations are warranted .

objective . recent studies on the association between uridine diphosphosglucuronosyltransferases ( ugts ) 2b17 polymorphism and risk of prostate cancer ( pca ) showed inconclusive results . to clarify this possible association , we conducted a meta - analysis of published studies . methods . we searched the published literature from pubmed , embase , google scholar , and china national knowledge infrastructure ( cnki ) . according to our inclusion criteria , studies that observed the association between ugt2b17 polymorphism and pca risk were included . the principal outcome measure was the adjusted odds ratio ( or ) with 95% confidence interval ( ci ) for the risk of pca associated with ugt2b17 polymorphism . results . a total of 6 studies with 7,029 subjects ( 3,839 cases and 3,190 controls ) were eligible for inclusion in the meta - analysis . overall , there was a significant association between ugt2b17 polymorphism and increased risk of prostate cancer ( or = 1.74 , 95% ci 1.142.64 , p < 0.001 ) . similar results were found in the subgroup analyses by ethnicity and types of controls . conclusion . this meta - analysis demonstrates that ugt2b17 polymorphism is associated with prostate cancer susceptibility , and it contributes to the increased risk of prostate cancer .

cancer is a hyperproliferative disorder that involves transformation , dysregulation of apoptosis , proliferation , invasion , angiogenesis and metastasis . cancers with alarming statistics , cause more than 7 million deaths per year worldwide , more than hiv / aids , malaria and tuberculosis combined . it is estimated that the number of new cancer cases will reach 15 million every year by 2020 ; 70% of which will be in developing countries . patients confronting a diagnosis of advanced cancer face the statistical reality that conventional chemotherapy can affect a cure for only a tiny minority of all such cases . more often than not , the reasonable impulse of these patients to investigate alternative treatment options such as herbal medicine is met with physician 's doubt . for a long time , natural and herbal products have been considered as precise sources of treatment used in traditional medicine to treat a variety of diseases including infections and malignant diseases . several researches demonstrated the fact that extracts from a number of herbal plants exhibit anticancer activities both in vitro and in vivo [ 4 - 10 ] . a growing number of studies indicate that herbal medicine ( looking at frequency , type and reasons for use ) might have the anti - cancer effect by enhancing the immune system , inducing cell differentiation , inhibiting telomerase activities and inducing apoptosis of cancer cells . it is strongly believed that herbal medicines are natural and hence without significant side effects and less likely to cause dependency . nevertheless , many herbs can be toxic especially in higher quantities and with frequent use . the prevalence of herbs use ranges from 60 to 80% among cancer patients depending on the definition of herbal medicine used in each study , sample size , and the place where the study was conducted . in uk , a population - based survey indicates that about 25% of cancer patients had consulted an herbal medicine practitioner in the past , although authors suggest that this number maybe underestimated . a canadian study shows that 20% of breast cancer patients used at least one herbal medicine treatment in the past , whereas american studies more consistently report rates well above 65% , such rates are considerably higher than those reported in general population or among other cancer diagnostic groups . despite extensive use of herbal medicines in cancer care , most of the evidence is anecdotal and has not been properly studied with significant clinical trials , especially in human subjects . further , interaction of chemical drug - herbs should be considered as another important factor , because herbs can not replace surgery or radiotherapy for early stages of cancer , even though it is believed that they do have merits of their own . the objective of this review is to identify the available evidence on the use of herbs and their clinical effects in cancer care . the present work intends to make a review about this subject using isi web of knowledge ( thomson reuters ) database from 2000 up to 2011 . in some few cases , references other than 2000 to 2011(publishing date ) can be cited as introductory to more recent works . therefore , some references are mentioned whose dates do not match the period of the study . search keys used for the study were a combination of : cancer ; medicinal herbs ; immunomodulator ; preventive therapy ; safety ; 2000 to 2011 ( year published ) . about 100 works were found including proceedings and articles . patents , abstracts , and other scientific documents whose availability was restricted were not used . from 200 to 1800 ad , following the teachings of aristotle and galen , which was believed that cancer , was a consequence of the coagulation of black bile till now when prevalence of biology has contributed to a 25% reduction in mortality , herbs play an important role in cancer symptom management , patients ' quality of life and survival . the main objectives of herbal therapies are : primary prevention of cancer ; this is important for those who have a strong family history of cancer secondary presentation ; prevention of a recurrence of cancer is therefore the objective for this group to enhance body 's immune system to reduce the side effects resulting from conventional therapies such as chemotherapy or radiation therapy in advanced stages of cancer , when conventional therapies have failed , many patients have no choice but resort to alternative treatments the way herbal medicine fight cancer is significantly different from conventional chemical drugs , where no dna mutation in surviving cell occurs . specifically , natural compounds fight cancer by strengthening the immune system preventing the spread of cancer cells through inhibition of angiogenesis or growth of new blood vessels feeding the cancer cells , detoxifying the body and preventing further toxic build - up in the body , quenching free radicals that cause mutational changes that lead to cancer formation and supporting all targeted organs , especially those affected directly by the cancer . besides creating an unfavourable environment for cancer growth is another benefit of herbal medicines , where , the ideal environment creates a high level of oxygen and temperature including increased metabolism rate , low sugar level and a high alkalinity space in the body . some of the herbs commonly used in traditional knowledge are listed in figure 1 , 2 and 3 based on active component , chemical structure and source . the approach to treat advanced cancer using natural medicines has consisted of two main different visions . indeed many herbal medicines are widely used as immunomodulators , although another group was known as chemopreventive ( adaptogenic ) plant compounds . such natural medicines have been reported to serve as biological response modifiers by activating , increasing and restoring the reactivity of immunological effector mechanisms that are involved in resistance to tumor growth and metastasis [ 30 , 31 ] . in fact , cancer evades immune system surveillance because of low immunogenicity of most tumors . nonetheless , many cancer patients with advanced malignancy do have lowered levels of innate ( th1 ) immunity , the branch of immune system whose cells , such as natural killer ( nk ) cells , directly kill the tumor . these same agents can be used to help protect bone marrow against the myelosuppressive effects of conventional chemotherapy . as it is described in figure 4 , the two most important classes of herbs here are immunomodulating and adaptogens . as it is described in figure 1 , in neither of the cases the herbal medicines have equivalents among pharmaceutical drugs . the mushrooms contain polysaccharides , which are not only immunostimulating of anticancer effects ; they also have non - specific effects of increasing longevity and reducing stress . for instance , ginseng is an angiogenic in wound healing , versus cancer , and it is also antiangiogenic . this apparent paradox is typical of normalizing properties of adaptogens , which also have multiple anticancer effects as well as beneficial interactions with conventional chemotherapy and radiation . most of these herbs operate on several of the mentioned targets simultaneously and often synergistically . ganoderma lucidum , a highly ranked medicinal mushroom has potent enhancing effect on immune system and anticancer activity . preclinical studies demonstrated its anti - tumor activity , and further studies indicated that the polysaccharide ( ps ) fractions were the major active components for the anti - tumor action [ 33 , 34 ] . ganoderma lucidum was found to activate macrophages , t lymphocytes and nk cells and to induce the production of cytokines such as tumor necrosis factor , interleukins and interferons in in - vitro with human immune cells and in vivo in mice [ 35 - 37 ] . studies indicate that its chemical constituents such as taraxasterol , taraxacin , choline , inulin and pectin remove toxic heat , swelling and nodulation . scutellaria baicalensis is another potent heat and toxin- clearing with anti- tumor and immune - stimulating properties in vivo and in vitro that inhibits platelet aggregation and induces apoptosis . isatis tinctoria contains the compound indirubin , inhibits dna synthesis in neoplastic cells , while simultaneously stimulating immune response . also , herbs such as panax ginseng , poria cocos , atractylodes macrocephala , angelica sinensis , ligustici wallichii , paeonia lactiflora , rehmannia glutinosa and astragalus membranaceus show an increase of white blood cell counts to normal levels in cancer patients . decades of pharmacological research have revealed that the polysaccharides and other compounds in astragalus membranaceus promote cellular and humoral immune function and have vitro anti - tumor effects on cancer cell lines [ 42 - 44 ] . multiple studies on patients with stomach cancer were conducted using formula pishen fang , which has immunostimulating properties . the formula contains : codonopsis pilolusa , atractylodes macrocephala , lycium barbarum , ligustrum lucidum , cuscuta chinensis and psoralea corylifolia . the inhibitory effect of a herbal formula comprising ginseng and carthamus tinctorius on breast cancer was studied by wings et al . . this formula could be a useful anticancer compound against breast cancer by inhibiting proliferation in solid tumor . the compounds isolated from the pacific yew " taxus brevifolia " has developed as the anticancer drug " taxol " . the extract from plant scutellaria barbata has been shown to be cytotoxic to a549 human lung cancer cell lines [ 47 , 48 ] . the synergetic effect on antiproliferative activity of chemotherapeutic agents ( doxorubicin ) in combination with thai herbal remedies ( stem of albizia procera , diospyros mollis , ficus hispida , smilax glabra , gelonium multiflorum and millingtonia hortensis ) against lung cancer cells may induce dna damage in lung cancer . amooranin extract ( stem ) which is a triterpene acid showed a strong inhibitory effect on survival of human breast carcinoma mda-468 and breast adenocarcinoma mcf-7 cells compared to breast epithelial mcf-10a control cells . impact of herbal medicines on human breast cancer was studied by many research groups through reducing tumor burden by resveratrol chemically modified extract , inhibition of estrogen - dependent gene transcription by shikonin ( gromwell ) , cell cycle delay / arrest by carcinosin , phytolacca , conium and thuja and modulating signal pathway by cacalol which is a free radical scavenging compound from cacalia delphinifolia plant . ganoderma lucidum , astragalus mongholicus , polygonatum sibiricum , and chinese sage herb , were observed to be effective on non - small - cell lung cancer for stage iii or iv . rasagenthi lehyam ( rl ) is a siddha medicine , which is a poly herbal formulation for the treatment of cancer in india . it is reported that the chloroform extract of rl inhibited the growth of prostate and lung cancers ; its governing mechanism is inhibition of pro - survival genes and up - regulating the pro - apoptotic genes . anti - proliferative effect of melissa officinalis on human colon cancer cell line was well studied by encalada et al . . thymoquinone ( tq ) is the bioactive- constituent of the volatile oil of black seed whose anti - neoplastic and anti - inflammatory effects were studied by gali - muhtasib et al . . the combination of tq with clinically used anti - cancer drugs led to improvements in their therapeutic index and prevented non - tumor tissues from sustaining chemotherapy - induced damage . vinca alkaloids which are isolated from the periwinkle plant catharanthus roseus , also known as vinca rosea , possess many therapeutic effects including anti - tumor activity . vinca alkaloids are most commonly administrated weekly by short iv injection ( 1 - 15 min ) more rarely by continuous infusion . other examples of plant - derived compounds fight cancer by inhibition of protein synthesis , and cell - cycle progression blocking are currently under investigation . extracts isolated from the leaves and stem of amoora rohituka , alkaloid isolated from cephalotaxus harringtonia , -lapachone which is a quinine obtained from the bark of the lapacho tree ( tabebuia avellanedae)and combretastatin a4 which is isolated from the stem wood of south africa tree combretum caffrum are the most important objectives of related researches . it is a natural compound extracted from the rhizome of curcuma longa that allows suppression , retardation or inversion of carcinogenesis [ 62 - 85].evidence from numerous in vitro and in vivo studies have confirmed resveratrol's(a polyphenol found in numerous plant species including peanuts and grapes ) ability to modulate various targets and signalling pathways . in addition , some vivo ( human ) studies are summarized in table2 ; this table demonstrates herbal medicine effectiveness in cancer treatment . herb safety and herb - drug interactions are complex and controversial issues . with the increasing use of herbs , their potential abuse and toxicity effects should be considered legitimately . the safety of a drug , herb or a complex compound is always relative and contextual . safety is determined by defining the conditions under which a substance is considered to be safe or dangerous and weighing potential benefits against possible short and long - term adverse effect . as a matter of fact , compared to the record of approved pharmaceutical drugs with a few well - known exceptions , medicinal herbs are safer . common use of herbs is rarely associated with adverse effects that are not easily reversible . these effects are seldom serious and include such transient reactions as : hot flashes , dizziness , headache , indigestion and rashes that are rapidly abated by discontinued use or dose reduction . the preponderance of evidence shows that when used as an adjunct to conventional medicine , herbs both enhance the desired effects and mitigate the harmful ones . it is estimated that more than 70% of the world 's population can not afford modern cancer medicines . in addition to cost , current cancer therapies are minimally effective and exhibit toxicities that are intolerable in most cases . by this review , evidence presents that agents derived from plants used in herbal medicine can be used not only to prevent cancer but also to treat it . because of their pharmacological safety , these agents can be used alone or as adjacent to current chemotherapeutic agents to enhance therapeutic effects and minimize chemo therapy - induced toxicity . this research indicates that the molecular targets of chemopreventive agents are similar to those currently used to treat cancer . it is also evident that more research is required on herbal medicine to ensure and reach their full therapeutic potential .

based on a common belief , herbal medicine with the least possible side effects should be the center of attention in cancer care ; however , in many cases they have not been properly studied with reliable clinical trials in human subjects . in this review , it was attempted to identify the available evidence on the use and clinical effects of herbs in cancer care . the research consists of two major parts including immunomodulator and chemopreventive herbal compounds whose mechanism , biological response , anticancer element of extract and related benefits were completely studied . also , the safety of herbal anticancer compounds was discussed . although the use of herbal medicines in treating cancer shows less chemotherapy - induced , toxicity , more researches are required to reach their full therapeutic potentials .

fibroadenomas are among the most common tumours of the female breast , occurring most frequently in women of child - bearing age , especially those under 30 years . most present as single mass , however the presence of multiple fibroadenomas can be seen in 1520% of patients . it has been reported that the average number of masses in cases of multiple fibroadenomas is typically 34 in a single breast but occurrence of more than five fibroadenomas in an individual patient is much less common . a 46-year old woman presented with multiple lumps in both breasts which she first noticed a year earlier . she had not been exposed to any chemicals or harmful materials and had never taken any oral contraceptives or other medications . the overlying skin was normal , not associated with any lymphadenopathy . within the breasts , there were many palpable , non - tender masses throughout all quadrants , ranging from less than 15 cm in size . the masses were well circumscribed with regular margins , smooth surfaces , firm in consistency , and mobile . ultrasonography showed solid masses that had a distinct , clear envelope like appearance and relatively uniform echoes . fine needle aspiration cytology showed monolayered sheets of benign duct epithelial cells with base nuclei . mammography of both breasts showed multiple well defined round to oval lobulated masses in both breasts ( birads - iii ) . there were 27 masses identified from both breasts ( 17 from right breast and 10 from left breast ) , sizes ranging from 0.5 cm 0.5 cm 1 cm to 3 cm 4 cm 4 cm . the cut sections of the masses showed greyish - white colour with rubbery texture . on microscopic examination , most fibroadenomas present as a single mass , although the presence of multiple fibroadenomas can be seen in 1520% of the patients . unlike women with a single fibroadenoma , most of the patients with multiple fibroadenomas have a strong family history of these tumours . a possible connection between multiple fibroadenomas and oral contraceptives was proposed but has not been well investigated yet . other possibilities include imbalance of in vivo oestrogen levels , hypersensitivity of local breast tissue to oestrogen , dietary factors , or inherited predisposition . the increased sensitivity to oestrogen may subsequently lead to mammary gland hyperplasia and even the development of carcinoma . a study of a large cohort of women with fibroadenoma revealed that the overall prevalence of atypical epithelial hyperplasia within fibroadenomas was 0.81% and only around 7% of women with atypia developed invasive carcinoma on follow - up . therefore , patients with fibroadenomas may have a slightly increased risk of developing breast cancer . the pathogenesis of formation of the numerous breast fibroadenomas in this patient is unknown . with increasing age the surgical treatment of choice of fibroadenoma is breast conserving , however multiple fibroadenomas pose a particular challenge . in 1971 , liacyr ribeiro described his new technique for reduction mammoplasty . this technique was introduced by rezai in oncoplastic surgery . with free hand design , preoperative marking multiple fibroadenomas of the breast are safely removable with the ribeiro technique modified by rezai . we report this case hoping to expand the literature and to provide insight to aetiology of multiple fibroadenoma formation and advice on management . dr sangram keshari : study design , writing ; dr jaradanda mishra : data analysis , writing ; dr b. swagat k. subdhi and dr byomkesh patro : data collection , writing .

introductionfibroadenomas are among the most common tumours of the female breast , occurring most frequently in women of child - bearing age , especially those under 30 years.presentation of casewe report a case with a total of 27 fibroadenomas presenting bilaterally of a 46-year - old woman . the histopathologic and immunophenotypic features of the fibroadenomata are described.discussionmost fibroadenomas are present as single mass , however the presence of multiple fibroadenomata can be seen in 1520% of the patients . it has been reported that the average number of masses in cases of multiple fibroadenomas is 34 in a single breast but occurrence of more than five fibroadenomas in an individual patient is much less common.conclusionthere are few reports of multiple fibroadenomas . we report this case hoping to expand the literature and to provide insight to aetiology of multiple fibroadenoma formation and advice on management .

reactive perforating collagenosis is a rare perforating disorder.it is characterised by collagen bundles perforating the epidermis . reactive perforating collagenosis ( rpc ) is a rare form of transepidermal elimination ( tee ) disorder in which there is extrusion of altered collagen from the epidermis . rpc can exist in two forms ; the commoner acquired form and the rare familial form . in the familial form , the lesions manifest in early childhood is not associated with pruritus and usually spontaneously resolves . we herein report a rare case of rpc in a young child with similar complaints in sibling . a 4 year old boy presented with complaints of multiple , recurrent , dark coloured raised lesions on face , elbows and outer aspect of both legs of 2 years duration . the lesions would start as skin coloured papules which later developed dark central material . some of the lesions would heal on its own in about a month leaving behind residual hyperpigmentation . patient 's mother complained that she had noticed new lesions occurring at sites of trauma . there was history of similar complaints in his elder brother who was staying with his grandparents . dermatological examination revealed multiple , discrete , symmetrical , hyperpigmented , hyperkeratotic papules distributed over face , both elbows and lateral aspect of both legs [ figure 1 ] . hyperkeratotic papules with central plugging over elbows and evidence of koebnerisation similar lesions on lower limbs routine lab investigations were normal . epidermis showed a hyperkeratotic crater filled with keratin , few polymorphonuclear leucocytes and occasional acellular basophilic fibrous strands . the adjacent papillary dermis showed vertically oriented collagen bundles perforating the epidermis [ figure 3 ] . the perforating collagen bundles were better delineated on van gieson stain [ figure 4 ] . based on clinical and histopathological features , the lesions showed some flattening with therapy but the patient continued to get new lesions at sites of minor trauma . histopathology of skin lesions revealing epidermal parakeratosis and perforating bundles of collagen ( h and e , 40 ) perforating collagen bundles evident in van gieson stain ( van gieson stain , 40 ) . there are four different types of perforating disorders and all are characterized by transepidermal elimination of altered dermal substances . they are kyrle 's disease , perforating folliculitis , elastosis perforans serpiginosa and reactive perforating collagenosis . the inherited form of rpc is associated with a positive family history in about two thirds of patients . consanguinity in parents is present in some cases with an autosomal recessive mode of inheritance , though dominant types have also been mentioned . there is a slight male preponderance with siblings being affected as in our case . in the acquired variant , the lesions manifest after the age of eighteen years and are usually associated with itching . it is also associated with hypothyroidism , hyperparathyroidism , liver disorders , hodgkin 's disease , neurodermatitis , hiv and iga nephropathy . the morphology of lesions is similar in both the entities and consists of umbilicated papules and nodules that can be skin coloured , erythematous or hyperpigmented and characteristically have a central keratotic plug . koebnerisation is commonly seen as in our patient . in genetically predisposed individuals , trauma results in altered collagen and scratching induces lesions and common sites of involvement are the accessible and trauma prone sites , as seen in our patient also . research has shown that in most cases no abnormality exists in the ultrastructure of the extruded collagen , but histochemical changes may be present . histologically , early lesions show variable acanthosis and accumulation of collagen , which is basophilic in dermal papillae . mature lesions show characteristic features of rpc where there is plug of parakeratotic material , basophilic debris and degenerated collagen lying within cup - shaped depressions in epidermis . as the condition resolves the important treatment options are topical retinoids , topical corticosteroids , intralesional steroids , psoralen ultra violet - a , narrow band uv - b ( puva , nbuvb ) and allopurinol . the familial form can also be associated with pruritus and may not spontaneously resolve as in our patient , which is not reported before . reactive perforating collagenosis can be rarely familial.the familial form can also be associated with pruritus and may not spontaneously resolve as in our patient . the familial form can also be associated with pruritus and may not spontaneously resolve as in our patient .

a 4 year old boy presented with history of itchy raised lesions on body of 2 years duration . though parental consanguinity was not present , his elder brother had similar complaints . dermatological examination revealed multiple hyperpigmented papules with a central keratotic plug distributed mainly over face and extensors of upper and lower extremities . koebnerisation was present . skin biopsy revealed perforating collagen bundles in the upper dermis and epidermis which was confirmed by van gieson staining . patient was being treated with topical retinoids and intralesional corticosteroids with minimal relief .

various types of cages are currently widely used for the treatment of degenerative cervical disc disease . however , controversy remains regarding a high incidence of complications , such as cage subsidence , kyphotic deformity , and pseudarthrosis [ 13 ] . anterior cervical discectomy and fusion ( acdf ) with plate fixation have been reported to reduce the above - mentioned complications [ 46 ] . unfortunately , plate - related complications such as screw breakage , screw pullout , and esophagus perforation still exist though not very high [ 710 ] . recently , good results have been reported regarding peek cages alone for treatment of one- or two - level acdf [ 1115 ] . in our institution , peek - cage - assisted acdf was performed without additional plate fixation as a routine procedure since 2003 , and we have achieved good clinical outcomes . up to now , there are few reports demonstrating the fusion results after three - level peek cage implantation without additional plate fixation . here , we reported 25 consecutive three - level acdfs with peek cages alone . from 2003 to 2008 , 25 consecutive patients underwent three - level acdf with peek cages in our institution . patients with trauma , posterior longitudinal ligament ( opll ) or disc ossification , infections , or tumors were excluded . all patients were available for follow - up evaluation for more than 2 years after surgery . the ages ranged from 35 to 81 years , with a mean of 52.6 years ( table 1 ) . a standard smith - robinson procedure was used to approach the cervical spine anteriorly on the right side . after adequate decompression of the spinal cord and nerve roots , endplate cartilage was removed , but bony endplates were always preserved . the endplates were prepared for fusion by abrasion with a high - speed burr until they were matching the shape of the cage . care was taken not to remove the bony endplate to prevent the subsidence of the cage . intraoperative sizing of the cage using templates was carried out after distracting the disc space with the caspar system . the key was not to overdistract the disc space in order to choose the appropriate size of cage . the cages ( solis , stryker , cestas , france ) were packed with allograft ( demineralized bone matrix , dbm , baiao , shanxi , china ) inside and then inserted into the disc space . finally , the caspar distractor was always compressed to remove any possible gap between the endplate and the cage and , thus , to provide ideal contact surface for fusion . the involved surgical levels were c3 - 4 , c4 - 5 , c5 - 6 , and c6 - 7 . neck pain and arm pain were graded using a 10-point visual analog scale ( vas ) . plain radiographs and flexion - extension films were taken preoperatively and at 2 , 6 , and 12 months after surgery . the following criteria were used for assessing radiographic success of fusion : ( 1 ) no lucent lines seen adjacent to endplates , ( 2 ) obliteration of disc space by bony trabeculae , ( 3 ) less than 2 of intervertebral motion or 2 mm of motion between the spinous processes at the operated segment on flexion - extension lateral radiographs [ 17 , 18 ] . ct scans were used as a secondary measure when bridging trabecular bone was not observed or fusion was uncertain on plain radiographs [ 1719 ] . the fused segment cervical lordosis ( fused segment angle ( fsa ) ) was measured using the cobb angle formed by the perpendicular line of the upper margin of the upper vertebral body and the one of the lower margin of the lower vertebral body of the fused segment . the fused segment height ( fsh ) was set as the distance between the midpoint of the upper margin of the upper vertebral body and the lower margin of the lower vertebral body of the fused segment . cage subsidence was defined as greater than 3 mm reduction of fsh in the follow - up period . statistical analysis was performed with spss 13.0 software ( spss inc , chicago , il , usa ) , and statistical significance was defined as p < 0.05 . the mean follow - up time was 25.6 months ( range of 2433 months ) . the mean sd joa score before surgery , at 2 months after surgery , and at the final followup was 10.7 2.17 , 13.6 1.47 , and 14.1 1.83 , respectively . similarly , mean sd vas score before surgery , at 2 months after surgery , and at the final followup was 8.2 1.23 , 2.7 0.96 , and 1.9 1.03 , respectively . there was a significant difference in terms of both joa and vas scores before and after surgery or at the last followup ( p < 0.001 ) ( table 2 ) . radiographs of the cervical spine at the last followup revealed a solid fusion without signs of pseudoarthrosis in 18 cases with a fusion rate of 72% ( figure 1 ) . the mean sd fused segment lordotic angle ( fsa ) was 1.3 5.86 before surgery , 7.9 3.62 at 2 months after surgery , and 7.0 3.40 at the last follow - up examination . there was a significant increase in terms of fsa between preoperative and postoperative ( at 2 months and at the last followup ) measurements ( p < 0.001 ) ( table 2 ) . the mean sd fused segment height ( fsh ) was 71.3 3.56 mm before surgery , 75.9 4.12 mm at 2 months after surgery , and 75.3 3.90 mm at the final follow - up examination . there was a significant increase in terms of the fsh between preoperative and postoperative ( at 2 months and at the last followup ) measurements ( p < 0.001 ) ( table 2 ) . there was one patient who had cerebral spinal fluid leakage , but he recovered in the first week following surgery . two patients felt mild swallowing discomfort , but it disappeared within one month after surgery . subcutaneous hematoma occurred in one patient due to obstructed drainage that was cleared two days postoperatively . nonunion was seen in 6 asymptomatic patients at c34 and c56 , respectively , but no motion instability was found on flexion - extension radiographs . cage subsidence occurred at only one level ( c67 ) in a patient with a c4c7 fusion . fortunately , no progressive cage migration was observed during the follow - up period , and reoperation was not necessary . no other surgical complications occurred , such as infection , cage migration or extrusion , and aggravating neurologic symptoms . anterior cervical discectomy and fusion ( acdf ) is currently the gold standard for surgical treatment of degenerative disc disease of the cervical spine [ 2 , 3 ] . however , high - rate complications relating to tricortical iliac crest bone graft include pseudarthrosis , collapse , extrusion , subsidence , and resorption as well as donor site problems . as a solution to these problems so far , cage - assisted acdf has proven to be a safe and effective procedure for the treatment of degenerative disc disease [ 13 , 5 , 12 , 14 ] . however , augmentation with plate fixation is usually needed , especially for multilevel acdf [ 6 , 19 ] . although plate fixation has been found to increase the fusion rate , decrease cage subsidence rate , and thus maintain cervical lordosis , its inherent hardware complications consisting of screw pullout , screw breakage , and injury of esophagus still exist though not high [ 610 ] . in an attempt to solve the above - mentioned problems , peek cages alone for three - level acdf were used at our institution . in our study , although the fusion rate was not as high as reported in the literature for cages with additional plating , good clinical results are still achieved [ 6 , 11 , 12 , 19 ] . cage subsidence rate was very low , and the cervical lordosis was well preserved at the final followup . the main reason for additional plate fixation in cage - assisted acdf was the high cage subsidence rate in studies using cages without plating [ 13 ] . however , most of the studies included metal cages which had very different elasticity with bone and , consequently , led to high rate of cage subsidence [ 2 , 4 , 5 ] . furthermore , another cause of cage subsidence might be the intraoperative overdistraction of the disc space and cage oversizing [ 12 , 20 ] . a key point to prevent cage subsidence in our study was the avoidance of bony endplates removal ( as it occurred in only one patient within the early practice of our study ) , but only abrasion of the cartilaginous portion was performed . the close match in the elastic modulus aids in minimizing cage subsidence and optimizing fusion rate that our study has revealed . good clinical and radiographic results had been reported regarding peek cages alone for the treatment of one- or two - level acdf [ 1115 ] . also , in a comparative study of efficacy of plate construct augmentation versus peek cage alone for one- or two - level acdf , no significant clinical difference was found between groups . to our experience , the presence of titanium spikes and retention teeth on the superior and inferior surfaces of the cage used in our study provides a secure fixation and prevents migration or extrusion of the cage . for this reason , peek cages alone without plate fixation can be used even for three - level cervical fusion without additional posterior fixation . however , though our preliminary results are encouraging , good filling material is warranted to further improve the fusion rate , and long - term followup of the surgically treated cases is still needed . moreover , prospective randomized and controlled clinical studies are warranted to compare the usefulness of peek cages alone and that of plate fixation and autograft for acdf . in summary , peek cages alone with allograft proved to be a safe and effective alternative in the treatment of three - level degenerative cervical disc disease . they may obtain clinical improvement , can maintain cervical spines sagittal profile , and obviate the complications related to iliac crest graft harvest and plate fixation .

a total of 25 consecutive patients suffering from degenerative cervical disc disease who underwent three - level anterior cervical discectomy and fusion ( acdf ) including polyetheretherketone ( peek ) cages packed with allograft were followed up for at least two years . the fusion rate reached 72% ( 18/25 ) , and asymptomatic pseudarthrosis was seen in 6 patients but without mobility on flexion - extension radiographs , and revision surgery was not needed . cage subsidence occurred at one level ( c67 ) , but it was not progressive , and reoperation was not necessary . a significant increase ( p < 0.001 ) in fused segment angle ( fsa ) and fused segment height ( fsh ) was observed postoperatively . similarly , a significant clinical improvement ( p < 0.001 ) was demonstrated postoperatively in terms of japanese orthopedic association ( joa ) score and visual analog scales ( vass ) score . peek cages alone with allograft proved to be a safe and effective surgical option in the treatment of three - level degenerative cervical disc disease . although the fusion rate was not high , this technique may offer improvement of symptomatology and maintenance of cervical spine 's sagittal profile .

we report on a young ethiopian woman who experienced acute bilateral blindness . in the presence of normal ophthalmological findings a 21 years old woman was admitted to the psychiatry clinic at jimma university specialized hospital , jimma , south west ethiopia . an attitude of accepting the perspective of the patient of a seemingly organic disease is a precondition for a successful intervention . the most frequent cause of visual impairment in about 50% of all forms of blindness in all areas of the world , except for developed countries is cataract . in the least - developed countries , particularly in sub - saharan africa , the causes of avoidable blindness are primarily cataract ( 50% ) , glaucoma ( 15% ) , corneal opacities ( 10% ) , trachoma ( 6.8% ) , childhood blindness ( 5.3% ) and onchocerciasis ( 4% ) ( 1 ) . visual function is defined in four levels : normal , moderate visual impairment , severe visual impairment and blindness . the most frequent causes of visual impairment are uncorrected refractive disorders , unoperated cataract and glaucoma ( 2 ) . persons with visual impairment as well as persons with blindness need to adapt to everyday demands . loss of vision despite normal ophthalmological findings , accompanied by neurological abnormalities , indicates that the visual cortex of the brain is affected . acute loss of vision as well as loss of voice may have an organic and a psychogenic etiology . the majority of people affected by the conditions seek help in health care facilities with an organic orientation . when examinations result in normal findings , patients are sent towards a mental health care facility . the symptoms are summarized under the heading of emotional and medically unexplained medical complaints and are a priority condition in mental health ( 4 ) . the national mental health strategy of ethiopia identified limited resources for non - medication alternatives for rehabilitation , for psychological treatments and for children as weaknesses of the mental health system ( 5 ) . we report on a young woman who experienced acute bilateral blindness preceded by an episode of loss of voice ( aphonia ) . the purpose of this case report is to describe the implementation of a psychosocial intervention in a health system with limited resources for mental health care ( 6 ) . the 21 years old female patient came to jimma university specialized hospital accompanied by her mother . she was single and never married , protestant by religion and amhara by ethnicity , and she was living in jimma . at the ophthalmic clinic , an ophthalmologic evaluation was done . visual acuity was diminished to + 3 dioptres on both eyes , and had already been corrected by glasses . malingering was suspected and , a psychiatric consultation was made . at the initial contact at the department of psychiatry , an approach to the patient was developed through cooperation among the local ethiopian clinicians and guest lecturers , a child psychiatrist and a children 's nurse , who took part in an international exchange program ( 7 ) . however , she remained very cautious and was performing slowly . when encouraged after some exercises , she performed faster . a month before her visit to the clinic , she had had difficulties in studying for her bsc degree . at the same time , her mother informed her about a life threatening illness of her father . one week later , the patient was preparing for an exam to be held the next day . in the early evening , she became completely unable to see . due to the impairment of her vision , the patient was not able to sit for her exam . she reported feeling of occasional sadness , crying , hopelessness and suicidal idea but without plan or attempt . eight months prior to her presentation , she became voiceless for about one and half months , and was admitted to the psychiatric clinic . she was treated with 5 mg diazepam at bed time , and some psychotherapy made her free of stress and anxiety like imaginary relaxation technique , slow breathing and progressive muscle relaxation therapy . after 3 days of therapy , she was able to produce sounds like coughing . on the fourth day , she was able to say a few words and the next day she became fully communicative . her development was normal . at the age of 10 , about 10 years ago , she had suffered a car accident - she had been unconscious for 10 days . after awakening from unconsciousness , her left side was paralyzed and she was not able to hear with her left ear . actually , her left side was still slightly weaker when compared to her right side . she had occasional falling attacks characterized by loss of consciousness but no jerky movements and no muscle rigidity . the diagnostic formulation according to the psychiatric classification system dsm iv - tr relies on the history and the clinical findings : conversion disorder with mixed presentation ( sensory = vision and motor = voice ) . the basic element is an attitude to accept the patient 's views and to build bridges . a treatment program was tailored to the situation of the clinic and to the needs of the patients mainly relying on the who mental health gap intervention guide , section the approach was symptom oriented on how to give orientation to a blind person irrespective of etiology . the patient was asked to reproduce the pattern of different shapes by means of little knobs which had to be placed into a plate with holes . she was able to draw nice scenery using different colors and to paint precisely a face ( figure 3 ) . later on , she was able to make pearls from paper by wrapping colored paper around a stick of wood . she could make a necklace for herself and she provided a lot of paper pearls to other patients . there was a discrepancy between her attitude of an insecure , dependent blind person while reproducing shapes of blocks and the elaborate drawing she was able to do . in addition , she received imaginary relaxation technique , slow breathing and progressive muscle relaxation therapy by sm . diazepam 10 mg orally was given daily for 1 week and 5 mg for another1 week , then stopped . she became opener in contact , and she began to recognize some people , beginning with her mother , who accompanied her . she participated in group work : put leaves on a paper to form a tree . she was discharged from the hospital after 3 weeks , when she was able to see normally . at first follow up as an outpatient after two days , she showed good and adequately modulated mood , bright and could see normally . psychogenic blindness may be suspected when patients complain of recent onset of blindness without injury . at a closer look , frequently , there may be a diminution of vision , blurred vision or a tunnel vision ( 9 ) . the common feature of the whole group of disorders is the prominence of somatic symptoms associated with significant distress and impairment ( 8) . due to the many different languages spoken in ethiopia a lot of descriptions and expressions indicating somatic symptoms resulting from distress appear difficult to translate into english . students before or during examinations complained of heat in the head ( 10 ) . burning or complain of yazorehnyal , spinning , . in medical terms , it means vertigo , but it seems to have a broader meaning . from the view of clinicians , the symptoms may seem diffuse , exaggerated and difficult to pinpoint ( 11 ) . conversion disorders are characterized by signs and symptoms clearly inconsistent with what is known about anatomy and pathophysiology ( 8 , 9 ) . patients who suffer from conversion symptoms do not intentionally fabricate such symptoms , as malingerers do . the diagnosis of conversion disorder should be made after appropriate investigations that can exclude neurologic conditions , medical conditions , and other psychological disorders . however , organic and psychogenic conditions such as epileptic seizures and psychogenic seizures can co - occur in one person . individuals with prominent somatic symptoms are commonly encountered in primary care and other medical settings , but are less commonly encountered in psychiatric and other mental health settings ( 8) . north west ethiopia , 1240 patients were seen as first attendees in the outpatient department within half a year in 1986 . one hundred and fifty - five or 12.5% were classified as disorders from hysteric type or conversion disorders in the actual classification . these behavior patterns were interpreted as mechanisms of problem - solutions with secondary gain of illness under rapidly changing social conditions ( 12 ) . there was a large group of military men with motor disturbances unable to continue the service and a small group of students who needed permission to repeat a year of study or to change fieldof study . complications perpetuating the duration of illness arise when patients restrict their activities such as staying in bed . physician - initiated perpetuating factors are potentially dangerous or costly diagnostic procedures and interventions ( 8) . looking at the history of our patient and reflecting on precipitating and perpetuating factors in previous experiences helps to predict possible relapses when emotionally difficult situations reoccur ( 13 ) . being unconscious for ten days and having motor problems and hearing problems for a long time indicates a severe affection of the brain with slow recovery . the neurological examination was normal as well as the performance of some tasks testing cognitive functioning . however , it was not possible to do an in depth examination of cognitive abilities . functioning in everyday situations can be normal . problems may arise due to minor cognitive impairment in situations with high demands - either emotional or cognitive -and result in a breakdown of abilities . the patient had experienced emotionally stressful situations : a life threatening illness of a close family member accompanying the demands of a final examination can be interpreted as precipitating event . previously , the patient had experienced training as helpful . the intention of the training was to build a bridge for the patient by accepting her inability to see . from detailed observation of the patient in different situations , a plan of management could be developed . the who mhgap intervention guide ( 4 ) excludes psychotropic medications for the management of medically unexplained and emotional symptoms . a meta - analysis done on the evidence drug effectiveness showed that effectiveness of drugs is of poor quality , but may be of use in the treatment of acute and treatment - resistant conversion disorder ( 14 ) . psychotherapeutic treatments have to be targeted in a range of potentially modifiable factors such as illness perceptions and emotionally processing of previous traumatic events ( 15 ) . in the united kingdom , follow up after about 4 years , 25% became seizure free and 40% had seizure reduction . health care utilization had declined significantly from baseline to follow - up ( 16 ) . on the long term , the patient should be supported to recognize difficult situations in time such as how to prepare an examination and to learn how to handle them . in conclusion , a complicated situation could be managed successfully in a specialized mental health facility by local means and external support . the reflection on the process and the outcome is encouraging . as suggested by the national mental health strategy ( 5 ) , supervision and ongoing training of clinicians and the nursing staff

backgroundacute loss of vision needs urgent attention and treatment . we report on a young ethiopian woman who experienced acute bilateral blindness . in the presence of normal ophthalmological findings psychogenic blindness has to be considered.case detailsa 21 years old woman was admitted to the psychiatry clinic at jimma university specialized hospital , jimma , south west ethiopia . she had not been able to see for a few days . ophthalmological and neurological examinations showed normal findings . no severe psychopathology was found . stressful life events had preceded the appearance of the symptoms . an attitude of accepting the perspective of the patient of a seemingly organic disease is a precondition for a successful intervention . treatment aimed at a gradual return to normal functioning . the patient regained her sight and fully recovered . the final psychiatric diagnosis was psychogenic blindness.conclusionthe psychosocial intervention was successful and encouraging for the patient and clinicians .

imaging findings , even with computed tomography ( ct ) , of such tumors are rarely described in literature . f-18 fluorodeoxy glucose positron emission tomography / computed tomography ( f-18 fdg pet / ct ) is emerging as a useful modality in assessment of genito - urinary malignancies . f-18 fdg pet / ct findings in penile leimyosarcoma have not been reported in literature . we present here a case of penile leiomyosarcoma with emphasis on findings on f-18 fdg pet / ct with histopathology correlation . a 47-year - old male presented with a palpable penile mass , with rapid growth over a period of 1 month . he was examined at an outside center and an incision biopsy of the tumor was done that revealed penile leiomyosarcoma . he was later referred to our institute , a tertiary care center , for further management . on examination of the patient at our institute , the patient was found to have 2 2 cm a typical nodular lesion in the proximal penile shaft . review of the histopathology examination after biopsy revealed tumor composed of spindle cells with hyperchromatic nuclei , inconspicuous nucleoli , and frequent mitoses . tumor cells also stained positive for smooth muscle antigen ( sma ) consistent with diagnosis of leiomyosarcoma of penis [ figures 1c and 1d ] . as a part of staging , the patient was subjected to f-18 fdg pet / ct examination 2 months after the biopsy ( this delay was due to late reporting of the patient to our institute from the peripheral center ) . the ct scan revealed moderate fdg uptake in the periphery of an ill - defined heterogeneously enhancing soft tissue lesion 2.9 2.2 cm in size involving corpora cavernosa on the left side of the distal penile shaft . this mass showed slightly thick , peripheral rim enhancement on the contrast - enhanced ct images corresponding to an area of increased f-18 fdg uptake , with an internal homogeneous region of low density , compared to the adjacent normal shaft of the penis , representing residual disease [ figures 1a and 1b ] . taking into consideration possible microscopic lymph node metastases total penectomy and bilateral inguinal lymphadenectomy was planned and the patient was counseled . however , the patient refused to undergo lymphadenectomy and only total penectomy was done . on follow - up after 8 months , the patient was found to be disease free . ( a ) contrast - enhanced axial ct through the penis demonstrates a low attenuating lesion in the corpora of the penis with peripheral enhancement . ( b ) f18-fdg pet image fused with corresponding ct demonstrates increased fdg uptake in the periphery of an ill - defined lesion within the corpora of the penis . ( c ) histopathological examination shows tumor composed of spindle cells with hyperchromatic nuclei , inconspicuous nucleoli with frequent mitoses ( d ) histopathological examination shows positivity for smooth muscle antigen penile cancer is a rare neoplasm and accounts for approximately 0.4% of all male malignancies . the most common primary malignant neoplasm of the penis is squamous cell carcinoma , constituting more than 95% of cases , followed by metastatic neoplasms of the prostate , bladder , rectum , kidney , and testis , as well as those spreading by direct extension from the adjacent structures . it accounts for 1020 % of all malignancies in males in asia , africa , south america , and it has a prevalence of only 1% in western countries . predisposing factors are phimosis , cigarette smoking , and human papilloma virus ( hpv ) infection . other tumors of the genitourinary tract include sarcoma , melanoma , basal cell carcinoma , and lymphoma . sarcomas are uncommon penile neoplasms , which include epithelioid sarcoma , kaposi sarcoma , leiomyosarcoma , and rhabdomyosarcoma . in general , very little literature exists that discusses the management of penile leimyosarcoma , due to the rarity of disease . role of routine lymphadenectomy is controversial as few authors have suggested that regional lymph node dissection is usually not indicated , since nodal metastases are uncommon . in our case lymphadenectomy was planned ; however , patient refused to undergo lymphadenectomy and was managed only with total penectomy . the ct findings of penile leiomyosarcoma are also rarely reported in literature in which the tumor may appear as a mass showing a relatively thick peripheral rim enhancement with internal regions of homogeneous low density , compared to the adjacent normal shaft of the penis , ( similar to findings in our case ) or as a soft tissue mass . fdg uptake has been described in penile squamous cell carcinomas and f-18 fdg pet / ct has been shown to be useful in detection of lymph nodal and distant metastases in penile carcinoma . f-18 fdg uptake has also been described in leiomyosarcomas and tumoral f-18 fdg uptake correlates well with the grade of the tumor in case of leiomyosarcomas . f-18 fdg pet / ct plays an important role in diagnosis , staging , treatment response monitoring , and follow - up in patients with sarcomas . this is the first case demonstrating f-18 fdg pet / ct findings in a case of penile leimyosarcoma .

penile cancer is a rare entity accounting for only 0.4% all male malignancies . penile leiomyosarcomas are even rarer with only around 35 cases reported in literature . we report a rare case of penile leiomyosarcoma illustrating f-18 fluorodeoxy glucose ( fdg ) positron emission tomography / computed tomography ( pet / ct ) features and histopathology correlation .

nowadays , osteoporosis - related vertebral compression fractures have important health consequence particularly for older patients , including morbidity and increased mortality5 ) . while the diagnosis can be suspected from history and physical examination , plain radiography , computed tomography and bone scanning , however , since the mid-1980s , magnetic resonance imaging ( mri ) has become an instrument of choice for imaging the spinal disease1,17 ) . in general , mri features suggestive of acute osteoporotic compression fractures were low signal intensity band on t1-weighted image ( t1wi ) and spared normal marrow signal intensity on t2-weighted image ( t2wi)10 ) . although these images have high sensitivity and specificity , the fat suppression technique gives more clear delineation of this abnormalities . accordingly , we re - evaluated the sensitivity and specificity of the t2-spectral adiabatic inversion recovery ( spair ) image for the imaging diagnosis of osteoporotic compression fractures in our cases . for additional information about the osteoporotic compression fractures , we evaluate the fracture lines , fluid sign and adjacent discs change on the mri retrospectively , this study included 85 patients who had been diagnosed with acute osteoporotic compression fractures and admitted to our neurosurgical department with recent back pain from january 2010 to april 2012 . almost all patients complained of back pain and/or radicular pain within 2 months after trivial events , such as lifting something , slipping down and falling from standing height , or even spontaneously . according to dennis et al.4 ) , the acute compression fracture was defined within 10 weeks after event . they all had underwent magnetic resonance image ( mri , philips 1.5-tesla x - series ) and bone mass density ( bmd , lunar prodigy advance 3 generation ) for the diagnosis of acute osteoporotic compression fractures . we evaluated the signal changes , fluid sign , fracture lines and adjacent discs change of the fracture segments by two neurosurgeons under the direction of one musculoskeletal radiologist . fluid sign was defined as a focal , linear , or triangular area of strong hyperintensity on spair images on a background of diffuse hyperintensity in the vertebral body because of acute collapse2 ) . exclusion criteria were mentioned as below ; any metastatic tumors , plasmacytomas , multiple myelomas , primary bone tumors , infectious diseases , old compression fractures or kummel 's diseases . statistical analysis was evaluated by using the spss v12.0 and statistical significance was assumed at a p value below 0.05 . in selected cases , we performed the vertebro- or kyphoplasty for pain relief ( fig . of the total 85 patients , there were 16 males ( 18.9% ) and 69 females ( 81.1% ) . the most common fracture level was the thoracolumbar junction ( 81 segments , 67.5% ) . there were 63 single fracture segments ( 74.1% ) and 57 multiple fracture segments ( 25.9% ) , even five segments in a patient ( table 1 ) . 2 ) and signal intensity patterns on mri of osteoporotic compression fracture summarized in table 2 . notably , the incidence of " high signal intensity on t2-spair image " was very high in this study ( 0.9917 ) . the incidence of " low intensity " on t1wi and " essentially iso - signal intensity " on t2wi were also high ( table 2 ) . however , they did not reached within 95% confidence interval from 0.9476 to 0.9996 of " the high signal intensity " on t2-spair images , which means " high signal intensity on t2-spair image " is more valuable than " low intensity " on t1wi and " essentially iso - signal intensity " on t2wi . the fluid sign2 ) on t2-spair image was observed in 56% of the acute osteoporotic compression fractures in this study ( fig 3 ) . we evaluated the fracture lines according to the sequences ( t1w , t2w , t2-spair images ) of mri ( table 2 , 3 , fig . 4 ) . using chi - square test , observed incidence of fracture lines between t1wi and t2wi was calculated and revealed difference with statistical significance ( p=0.0048 ) ( table 3 ) . the fracture lines were more observed on t2wi than t1wi by z - test ( one - tailed test , p=0.0062 ) . another interesting finding was the abnormal signal intensities of the adjacent discs on mri in the acute osteoporotic compression fractures ( table 4 ) . the observed incidence through z - test ( pairwise ) revealed that " high signal change " on t2wi occurred more frequently than " low signal change " on t1wi ( p<0.0001 ) . " high signal intensity " on t2-spair image is more frequent than " low signal change " on t1wi ( p<0.0001 ) . as the population ages , senile disorders are markedly increasing in this community . according to the national health statistics in 20088 ) , the prevalence rate of osteoporosis over 65 years old people was 51.43.2% in female and 9.12.0% in male , and overall 34.02.3%14 ) . recently , domestic researchers reported that osteoporotic compression fracture occurred about 75,000 cases per year and one year mortality was 3.6%16 ) and primary osteoporosis is responsible for about 85% of vertebral compression fractures18 ) . therefore , osteoporotic compression fractures now come into the picture as days go by . obviously , this osteoporotic compression fracture is predominant in the female because of estrogen defect after menopause bringing osteolysis , and finally decreasing bone mass6 ) . the number of female patients was more than four times of male patients in this study ( table 1 ) . in general , the most common fracture level is thoracolumbar junction ( from t11 to l2 ) because the region forms a transition zone between the relatively fixed , kyphotic thoracic spine above , and the relatively mobile , lordotic lumbar spine below , which causes stress forces to concentrate upon the thoracolumbar junction20 ) . the number of thoracolumbar junction fractures was more than four times of the other levels in this study ( table 1 ) . in general , acute vertebral compression fractures ( shorter than 10 weeks old ) produce " a low signal intensity " on t1wi and " high signal intensity " on t2wi because of edema , inflammatory infiltrates , bone necrosis , and disruption of fatty marrow8 ) ( fig . 2 ) . in detail , on t1wi , acute osteoporotic compression fractures characteristically show " a focal band - like area of low signal intensity adjacent to the fractured endplate"7,8,12,13 ) and " at least one area of normal signal intensity " is seen within the collapsed vertebra , and it means preservation of marrow that contrasts to the diffuse malignant fracture . increased signal intensity on t1wi may occur in a small number of benign fractures , but is not always associated with malignant fractures21 ) . this is believed to be caused by fatty replacement of marrow cells in the degenerative disease or compaction of the marrow in benign processes19 ) . on t2wi , edema or disruption makes it to " high signal intensity " and a collapsed segment is " essentially iso - intense " with adjacent non - collapsed segment3,7 ) . in this study , these findings on t1wi and t2wi were all high , which was similar to that of the acknowledged fact in broad outline ( table 2 ) . in this study high signal intensity shown on t2-spair image presented in 99.17% . however , " abnormal signal intensities " on t1wi and t2wi and " essentially iso - signal intensity " on t2wi did not reached within 95% confidence interval from 0.9476 to 0.9996 of " the high signal intensity " on t2-spair images . therefore , this result came to a conclusion that t2-spair image is the most specific mode compared with t1wi and t2wi to detect the signal changes of the acute osteoporotic compression fracture ( table 2 ) . the presence of focal , linear or triangular areas of high signal intensity ( " fluid sign " ) ( fig . 3)2 ) adjacent to vertebral end - plate on spair images is said to be a feature of acute osteoporotic compression fractures2,13 ) and is rarely seen in metastatic fractures2,15 ) . this fluid sign means bone marrow edema exhibiting iso - intense signal to that of cerebrospinal fluid2 ) . baur a. et al.2 ) reported that " fluid sign " was seen in 40% of osteoporotic benign compression fractures and 6% with malignant fractures . me abdel - wanis et al.10 ) reported that " fluid sign " was demonstrated in 35% in the osteoporotic compression fractures , 2% in the malignant fractures and no in the infective fractures . in our study , the incidence of " fluid sign " was observed in 56.7% in the acute osteoporotic compression fractures ( 68 of the total 120 segments ) on t2-spair image . there are some differences of the incidence of this " fluid sign " according to the authors . this " fluid sign " is one of the suggestive findings of the acute osteoporotic compression fractures when considered the above studies2,10,13,15 ) . at the moment , we are studying this finding compared with malignant fractures . on the other hand , a linear area of low signal intensity corresponding to the fracture line or trabecular impaction can be seen on t2wi and/or t1wi ( fig . the observed incidence of fracture line or trabecular impaction on t2wi was higher than t1wi ( table 3 ) ( p=0.0062 ) . we thought t2wi is more helpful than t1wi to detect the location of fracture and vector of traumatic force . this signal change of adjacent disc is thought that it is caused by change of biochemical and histological composition of the annulus and nucleus pulposus followed by alteration of pressure profile due to fracture of vertebra9,11 ) . furthermore , depression of the fractured endplate alters the pressure profile of the damaged disc resulting in increased compressive loading of the anterior wall of adjacent vertebra that predisposes it to wedge fracture11 ) . however , its incidence is rarely reported until now . we investigated abnormal signal intensity patterns of the adjacent discs manifested as " hypointense " on t1wi and " hyperintense " on t2wi and t2-spair image in the acute osteoporotic compression fractures . adjacent discs mean the above and below discs of the osteoporotic compression fracture segment compared with other discs of the non - fractured segments ( fig . incidence of signal changes were 7.5% on t1wi , 63.3% on t2wi and 73.3% on t2-spair images ( from 3.7 to 14.2 on t1wi , from 54.0 to 71.8 on t2wi , and from 64.4 to 80.8% on t2-spair image in 95% confidence interval ) ( table 4 ) . statistically , the observed abnormal signal change on t2wi and t2-spair image occurred more frequently than t1wi ( p < 0.0001 , p<0.0001 , each other ) . however , there was no difference between t2wi and t2-spair image ( p=0.0635 ) . on the contrary , some authors reported that disc involvement was found in the infective fractures ( 97% ) and malignant fractures ( 2% ) . there was no disc involvement in the osteoporotic fracture cases on the t1wi and t2wi10 ) . we are planning to compare the osteoporotic fractures with infective and malignant fractures according to the all modes of mri . t2-spair image is the most specific compared with t1wi and t2wi to diagnosis the acute osteoporotic compression fracture of the all sequences ( 99.17% , from 0.9476 to 0.9996 with 95% confidence interval ) . the fluid sign on t2-spair image was observed in 56.7% of the acute osteoporotic compression fractures in this study and it is supplementary suggestive findings of the acute osteoporotic compression fractures . accordingly , t2-spair image is very useful and gives more information to detect the acute osteoporotic compression fractures . t2wi is the more useful mode to detect the fracture line or trabeculation in the acute osteoporotic compression fracture than t1wi ( p=0.0062 ) . we suppose t2wi is helpful to detect the location of fracture and vector of the traumatic force . the incidence of abnormal signal intensity on the adjacent discs was high on the t2wi ( 63.33% ) and t2-spair image ( 73.33% ) in this study . accordingly , this abnormal signal intensity on the adjacent discs may provide additional information on the acute osteoporotic compression fractures .

objectiveosteoporotic compression fracture is an increasing issue in this community and its diagnosis depends on the magnetic resonance images ( mri ) . although t1- and t2-weighted images ( t1wi and t2wi ) have high sensitivity and specificity , the fat suppression technique gives more clear delineation of this abnormalities . accordingly , we re - evaluated its exact sensitivity and specificity for the imaging diagnosis of osteoporotic compression fractures in our cases . for additional information about the osteoporotic compression fractures , we evaluate the fracture lines , fluid sign and adjacent discs change on the mri.methodsretrospectively , total 85 patients who had been diagnosed with acute osteoporotic compression fracture were enrolled . they all had been underwent mri including t1wi , t2wi and t2-spectral adiabatic inversion recovery ( spair ) sequence.resultsin this study , the incidence of high signal intensity on t2-spair image was very high ( 0.9917 ) . the fluid sign was seen in 56.7% on the spair image . the fracture lines were more observed on the t2wi than t1wi ( p=0.0062 ) . the adjacent discs change on t2wi and t2-spair image were higher than t1wi ( p<0.001).conclusionfor the acute osteoporotic compression fracture , t2-spair image is the most specific sequence of the all sequences . the fluid sign is another suggestive finding when considered other studies . t2wi is more useful to find the fracture line than t1wi . abnormal signal intensity on the adjacent discs may provide additional information for the acute osteoporotic compression fractures .

based on a study which has conducted in iran , the subjects experienced the drug use before they were 14 years of age in the 1 time . it seems that drug abuse among youth is spending a progressive trend in the country . hence , finding new ways to deal with this problem is one of the main priorities of iranian government . in many countries , young adults aged 18 - 24 years have become a critical population who need to be addressed . anderson ( 2007 ) noted that the majority ( 85% ) of relapse occurs among young people when they join together with their peers . research evidences indicate that many psychological factors are involved in drug addiction and subsequent relapse . coping skills is one of these factors has been confirmed their effectiveness in many studies . research has shown that relapse prevention can be some extent predicted by increased the types of cognitive coping responses and coping behaviors . addiction treatment is a complex process that can be handled through addicts desire to quit , family involvement and physical and psychological treatments . coping cognitive behavioral therapy helps individuals to recognize the difficult situation , teaching coping skills , changing reinforcement contingencies , and fostering motivation are the some of the basic tasks in this approach . numerous studies indicate that learning coping skills is associated with a high degree of ability to prevent relapse among addicts . unfortunately , the relapse rates are high among who are not capable to use effectively coping skills in stressful events ( family conflict , peer pressure , financial difficulties or temptations ) . this study aimed to study relapse coping strategies in young adults self - referred to substance abuse treatment centers in the south iran . this study aimed to study relapse coping strategies in young adults self - referred to substance abuse treatment centers in the south iran . a cross - sectional descriptive study was conducted to examine relapse coping strategies in young adult addicts to bushehr public and private substance abuse treatment centers in summer 2013 . all of young adult addicts aged 18 to 24 who were treated at these centers were voluntarily recruited . finally , 70 people ( total response rate 75% ) of them accepted to participate in the study . the questionnaire was developed by myers a 34-item self - report measure to evaluate substance abuser coping skills . the questionnaire introduces a hypothetical situation you arrive at a friend 's house in the evening . there are a few other people ; everyone is sitting around talking , drinking , and using drugs . when you sit down , you are offered drugs and something to drink . the questionnaire consisted of two parts : the first , assess appraisal and how he / she response to this hypothetical situation by 10 points scale in six items and the second , evaluates the relapse coping strategies in seven points with 28 items . this part assesses scales of relapse coping strategies including cognitive and behavioral problem solving ( 12 items ) , self - critical thinking ( 7 items ) , and abstinence focused coping ( 9 items ) . the validity of this survey has been confirmed by expert 's views , and the reliability was calculated using cronbach 's alpha coefficient as 0.84 . results were reported as a mean standard deviation for the quantitative variables and percentages for the categorical variables . seventy young adult addicts aged 18 - 24 ( mean 21.7 ) who were treated at public and private substance abuse centers participated . the highest level of education was diploma , and the lowest was bachelor 's degree . the most substance people taking were opium ( 37.7% ) and heroin ( 29% ) , respectively . participants mentioned their age at the onset of addiction about 17-year - old . regarding individuals experience in the hypothetical situation mentioned above , 14.7% of them mentioned they have never been in the situation , 42.6% of them 1 - 2 times , 22.1% 3 - 4 times , and 20.6% of them are more than 5 times were facing to this situation . response to the hypothetical situation as shown in table , this situation has been difficult for participants to cope with ( 7.39 out of 10 ) and , furthermore , it was important for them not to use drug ( mean 8.03 ) . however , they thought it was something that they could be able to keep themselves from using ( 7.51 ) . table 2 shows findings from the arcq questionnaire and priority items to action by identified response pattern . findings from the arcq questionnaire according to the findings from table 2 , the total mean score of coping skills was 5.19 . in this regards the highest mean score is related to self - critical thinking subscale ( 5.45 ) . in self - critical thinking subscale the item wish that you could change what had happened was the highest and finally , think that using is bad , you do not want to be part of it was the highest in the abstinence focused coping subscale . by prioritizing items based on response pattern to identify interventional areas for action and improvement , we found that the top items are in the subscales are : let your feelings out somehow , try to forget the whole thing , and use the support of a higher power , respectively . in this study , 85.3 % of addicts have experienced the hypothetical high - risk situation at least once . it can be said that this situation which individuals is tempted and return to drug use are easily provided in the community . in this regard , it is recommended actions by the families and related institutions to control and prevent the establishment of such circles occur . based on the findings , it is important for addicts to avoid substances use but it was hard for them and they tend to reuse . these people were listed relapse risk rate and assistance from them in average level . by evaluating individuals responses along with appropriate measures encountering these conditions and cognitive - behavioral coping skills training and upgrading can be helped to prevent recurrence . in this study , participants have used coping skills in average level ( 5.19 out of 10 ) while they could take advantage of these skills at a higher level . it is recommended that authorities especially psychologists working in substance abuse treatment centers should strive to improve addict 's skills to be able to avoid substance use if they faced to the similar situations . given the importance of the third factor - abstinence focused coping - as the best predictor of current and future substance use in individuals , more attention needs to be paid to the training , and improving the skills . , it suggested that decision - makers develop an action plan to strengthen these skills . in addition , establishing continuous training programs and develop coping skills by an expert especially , a psychologist can empower addicts to maintain themselves against any temptation and craving . this study examines relapse coping strategies in young addicts in substance abuse treatment centers in iran . based on the findings , addicts desire to reuse substance in a hypothetical high risk situation and it was hard to handle this situation . they used coping skills to avoid this situation at an average level . improving self - efficacy skills through teaching

background : cognitive - behavioral coping approach is known as an effective strategy to preventing relapse . its goal is to forget incompatible behaviors and replaces them with the compatible answers.objectives:this study examines relapse coping strategies in young adults in selected substance abuse treatment centers in iran.patients and methods : the present is a descriptive cross - sectional study . the sample consisted of 70 self - referred young addicts ( 18 - 24 years ) . adolescence relapse coping questionnaire was used to assess relapse coping strategies . descriptive statistics was used to analyze the data.results:the findings revealed that 71.2% have experienced a relapse totally . it was hard to control the hypothetical high risk situation and they greatly wanted to use the substance ( mean 7.39 of 10 ) . addicts have used of all three coping skills in definitely would do level.conclusion:enhancing self - efficacy through training coping skills , especially abstinence - focused coping skills to react properly in high risk situation can be useful .

vital organ structures , including the major blood vessels , spinal cord , trachea , and esophagus , pass through the neck region , and are tightly packed in a relatively small area . mahmoodie et al.10 ) reported that vascular exploration was the most common reason for surgery ( in 67.2% of their patients ) and the most common surgical intervention was vein ligation . complications were reported in 9.3% of their patients and the mortality rate was 1.5% . penetrating brain injury ( pbi ) is less prevalent than blunt injury , but has a worse prognosis and a higher mortality rate.9 ) foreign bodies can cause immediate complications such as intracranial hemorrhage , pneumocephalus , contusion , and brain or brain stem injury , and can lead to infarction due to damaged vascular territories , abscess , meningitis , and encephalitis . several imaging techniques have been recommended and a flow chart has been developed for precise evaluation of pbi . however , there is no definite guideline in these patients.1814 ) here we describe a patient who presented with an injury penetrating through the neck to the posterior fossa as the result of an accidental stabbing , focusing on imaging studies for rational and precise decision - making . a 54-year - old man was brought to the emergency room with a stab wound on the left side of the upper posterior neck ( figure 1 ) . he was intoxicated , with an initial blood ethanol level of 255 mg / ml . he was not able to communicate and was not cooperative on neurologic examination . the initial blood pressure was 143/90 mmhg , pulse rate was 109 beats / minute , and respiratory rate was 15 times / minute . there was no massive hemorrhage in the head or neck on three - dimensional high - resolution computed tomography ( hrct ) and the cervical spine , trachea , and esophagus were intact . the knife had pierced the paraspinal muscles and the base of the occipital bone behind the stylomastoid foramen ( figure 2 ) . the patency of the left cervical carotid artery was suspected to be intact because there was no perivascular hematoma or leakage of blood around the vessel ( figure 3 ) . no signs of tearing were seen in the basilar artery or its major vessels , including the posterior inferior cerebellar artery . however , because of the metal artifact , we could not guarantee that there were no combined vascular injuries . computed tomography ( ct ) we then performed digital subtraction angiography ( dsa ) to further investigate possible damage to the vascular structures . on injection of the left carotid artery , the blood flow was intact and showed no signs of arterial damage ( figure 4 ) . on injection of the left vertebral artery , the arterial and venous phases indicated normal patency ( figure 5 ) . based on these imaging findings , we proceeded to surgery to remove the knife and explore the penetrating wound using a microscope with simultaneous preparation for open craniotomy . there was minimal bleeding from the stabbing canal and there appeared to be no active bleeding from the major vessels . after about 20 minutes of observation , the wound was carefully irrigated and subsequently closed . on the postoperative ct scan , a small hemorrhage was noted on the left cerebellar tonsil , but this was seen to resolve gradually on follow - up ct . the patient made a full recovery without any neurologic deficit , and was discharged on postoperative day 18 . it is widely known that when assessing a pni , the neck region can be divided into three areas according to the point of entry of the foreign body . the common carotid arteries , proximal vertebral arteries , subclavian arteries , trachea , and esophagus are located in this area . zone ii is the area between the cricoid cartilage and the angle of the mandible . zone iii is the area between the angle of the mandible and the base of the skull , through which pass the distal external carotid arteries , vertebral arteries and jugular veins . a foreign body in the neck can damage vital structures , including the major blood vessels , trachea , and esophagus , resulting in increased risk of mortality and morbidity . singh et al.13 ) reported that the current mortality rate for pni is 3% to 6% and one of the most common complications of pni are vascular trauma , occurring in 25% of cases , with mortality rates approaching 50% . evaluation for injury to major structures is the first important task to perform in the emergency room . gracias et al.6 ) have recommended ct scanning as an accurate and rapid method for evaluating the trajectory of penetration and saito et al.12 ) have reported that ct angiography has high sensitivity and a negative predictive value for vascular injury . however , the artifact generated by the foreign body on ct scan is a major obstacle when trying to determine if the surrounding structures are free from injury , as it was in this case . some authors have also reported dsa to be a useful tool for evaluation of pbi and pni.37 ) dsa can provide clinicians with much information , including on vessel patency , leakage of blood , delayed capillary refill time , and any other vascular abnormalities . first , it is time - consuming to perform and requires the patient to be taken to the angiography suite , so may not be suitable for unstable patients . in addition , as ferguson et al.5 ) have pointed out , dsa still misses about 1% of vascular injuries . nevertheless , the use of three - dimensional rotational angiography can provide detailed structural information enabling precise pre - surgical planning . in our case , the blade was crossing over the major arterial passage . the vessel injuries were not fully appreciated on conventional two - dimensional images because the vessels and the foreign body were seen as overlapped . because of high - resolution image study modality , the selective operation and conservative management is one of options in treatment of pni . also , adequate exploration can reduce tissue damages and decrease morbidity rate . cosan et al.4 ) reported that simple withdrawal of material can be one of the treatment methods in penetrating injuries . for using this simple withdrawal method , the shape of penetrating material and vector are also considerable factors in penetrating injuries . in the stab wound cases , the tract is cone shape . cerebrospinal fluid ( csf ) leakage is one of the most common complications after traumatic brain injury . bell et al.2 ) reported that 4.6% cases of traumatic brain injury developed post - traumatic csf leakage . in this case , there was no definite clue for suggesting csf leakage on post - operative ct scan and clinical presentation . because it is one of the most common complications and it can increase the mortality , close observation and image study should be done for follow up period the most common treatment of csf leakage is an exploration and closure of leakage point tightly . interestingly , meirowsky et al.11 ) reported there was a spontaneous closure of csf leakage in 44% patients who had fistulas complicating missile wounds of the brain . the characteristics of the entry and exit zone , transventricular trajectories , existence of air sinus penetration are risk factors of csf leakage . in this case the distance between entry zone and penetrated dura is longer than a skull vault penetrating injury . in that reasons , we do not explore penetrated dura site , just tightly close neck muscle and fascia . but , the risk of simple withdrawal of material and comparison to mandatory exploration should be evaluated near future . as in this case , when a vessel injury is suspected , the initial hrct evaluation should be coupled with dsa to avoid inappropriate management of pni and pbi . the most common cause of these complications is vascular injury . the initial evaluation of a combined injury in zone iii and the posterior fossa should include not only the soft and musculoskeletal tissue but also assessment for vascular injury . hrct is a suitable tool for the initial overall evaluation and dsa is a specific and accurate tool for detection of vascular injury . after careful evaluation and interpretation , simple withdrawal of stabbed material can be a choice of treatment .

here we report a case of penetrating neck injury to the posterior fossa that was shown , using high - resolution computed tomography ( hrct ) and digital subtraction angiography ( dsa ) , to involve no vascular injury . a 54-year - old man was brought to the emergency department after a penetrating injury to the left side of the posterior neck and occipital area with a knife . he was in an intoxicated state and could not communicate readily . on initial examination , his vital signs were stable and there was no active bleeding from the penetrating site . because of concern about possible injury to adjacent vessels , we performed hrct and dsa sequentially , and identified that the blade of the knife had just missed the arteriovenous structures in the neck and posterior fossa . the patient was then transferred to the operating room where the knife was gently removed . further careful exploration was performed through the penetrating wound , and we confirmed that there were no major injuries to the vessels and neural structures . postoperative computed tomography revealed that there was minimal hemorrhage in the left cerebellar hemisphere . the patient made a full recovery without any neurologic deficit . in this case , hrct is a suitable tool for the initial overall evaluation . for the evaluation of vascular injury , dsa can be a specific and accurate tool . mandatory exploration widely used for penetrating injuries . after careful preoperative evaluation and interpretation , simple withdrawal of material can be a choice of treatment .

we performed a retrospective cohort analysis of all legal immigrants notified as having pulmonary tuberculosis in the netherlands between 1996 and 2000 ; pulmonary tuberculosis referred to any form of active tuberculosis that involved the lungs . patient data were obtained from the netherlands tuberculosis register and included date of birth , date of arrival in the netherlands , time of diagnosis , localization of tuberculosis , country of origin , and sex . to account for fact that the reported time of immigration was often exactly 1 , 2 , 3 , . . . years before diagnosis ( digit preference ) , time since immigration was categorized with boundaries well apart from the preferred digits ( table ) . data on the number of immigrants residing in the netherlands were obtained from the organization for reception of asylum seekers ( coa ) and from municipal population registers ( gba ) as provided by statistics netherlands . person - years at risk for pulmonary tuberculosis were first calculated separately for both the coa and gba registers . privacy regulations prohibit matching of the two datasets . since asylum seekers are allowed to register themselves in the gba after 1 year of stay in the netherlands , overlap between the two registers had to be accounted for . we assumed that the percentage of asylum seekers registered twice increased linearly from an initial 0% of asylum seekers in the coa register during the first 6 months after immigration , to 80% at 3.5 years after immigration . asylum seekers were never versus always registered twice to assess the consequences of the uncertainty regarding double registrations . this did not alter the conclusions ( results not shown ) . by the end of 2000 , close to two million immigrants were residing in the netherlands , of a total population of nearly 16 million . among the immigrant population , 2,661 patients with pulmonary tuberculosis patients information about country of origin and time since immigration was missing in 3% and 13% of the study patients , respectively , and was accounted for by multiple imputation ( five times ) to avoid bias in the calculation of incidence rates , relative risks , and confidence intervals ( 1 ) . for country of origin and time since immigration , all information presented is based on the average number of cases in the imputed datasets . incidence rates were only calculated for the 2,005 patients in whom tuberculosis was diagnosed more than half a year after immigration because many patients with a case diagnosed within 6 months may already have had active tuberculosis at the time of immigration . the figure shows that incidence rates decreased after 0.51.4 years since immigration for immigrants from most of the countries . subsequently , the incidence rates were mostly stable from 1.5 to 9.4 years since immigration for the countries with initial incidence rates above or around 50/100,000 ( as a general rule , immigrants from countries with incidence rates above this level are eligible for screening ) . since few somalis immigrated before 1991 , the observed increase in incidence rates > 9.4 years after immigration has wide confidence intervals . in contrast to the incidence rates for most of the countries , incidence rates for immigrants from surinam and the netherlands antilles were initially low and significantly increased after an initial decrease . average incidence rates after immigration varied from 379/100,000 in somalis to 5/100,000 in immigrants from the category other countries ( table ) . for comparison , the current incidence rate of pulmonary tuberculosis in the indigenous dutch population is approximately 3/100,000 . univariate and multivariate poisson regression were performed by using stata ( stata corp , college station , tx ) . for each imputed dataset , a clear pattern in incidence rates was not observed in the first 3.4 years after immigration , but overall the incidence rates gradually decreased as time since immigration increased . nonetheless , compared to 1.52.4 years , the incidence rate for 9.519.4 years since immigration had decreased by only 42% . fifty - eight percent of patients , including those in whom tuberculosis was detected in the first 6 months , were found more than 2.5 years after immigration to the netherlands , and 29% were found after more than 9.5 years . as often observed , we found considerably lower incidence rates for children than for young adults and a significantly higher rate for males than females . except for age , the univariate incidence rate ratios were largely similar to the multivariate ratios . in univariate analysis , incidence rate ratios in adults decreased with age , whereas in multivariate analysis the oldest age group had an increased risk . this result is due to confounding with country of origin and time since immigration : african immigrants had the highest incidence rates , but relatively few of them were older than 65 years , and they had immigrated relatively recently . statistically significant , but small , differences in incidence rates according to year of diagnosis our study shows that , in spite of a gradual decrease , the incidence rates of pulmonary tuberculosis in immigrants remain high even a decade after immigration . the persistent high incidence rates are consistent with results of previous studies ( 25 ) . our study combines data on all immigrant patients in whom tuberculosis was detected and all legal immigrants present in a 5-year period in a low incidence country , enabling detailed analysis with a long follow - up period . one might anticipate such a decline , since the proportion of recently infected or reinfected persons will be higher sooner after immigration than later due to relatively low levels of transmission in the netherlands . several explanations may account for the absence of an initial steep decline in incidence rates . first , the proportion of immigrants who were recently infected or reinfected may already have been low at the time of immigration . next , the risk of reactivation of latent tuberculosis infection in these immigrants may have been higher than previously modeled in white nonimmigrant populations ( 8,9 ) . finally , immigrants residing in the netherlands may have acquired new infections or reinfections , either through transmission within the netherlands or through frequent visits to their country of origin . dna fingerprinting data suggest that transmission within the netherlands may indeed have occurred , although it is not the key factor ; in a recent study , infections in 30% to 40% of turkish , moroccan , and somali patients could be attributed to recent transmission , but 58% of all immigrant patients were not part of a cluster ( 10 ) . the dutch screening policy consists of mandatory screening of immigrants at entry and voluntary screening in the next 2 years . less than 50% of immigrants undergo voluntary screening in the second year ( 11 ) . screening identified 41% of the patients with a case diagnosed from 0.5 to 2.4 years after immigration . screening may have influenced the observed incidence pattern slightly by diagnosing cases earlier than in the absence of screening . however , the average delay in detecting tuberculosis in immigrant patients who seek medical care themselves ( passive detection ) in the netherlands is <3 months ( 12 ) , and several studies reported upon by toman ( 13 ) suggest that the period in which tuberculosis is detectable by x - ray , but has not yet led to clinical symptoms ( preclinical detectable phase ) , is < 6 months . thus the incidence pattern in the first view years after immigration would not be very different in the absence of screening . the possible influence of screening on transmission has apparently not resulted in a pronounced downward trend in incidence rates over time : they would only have remained somewhat higher without screening . in many industrialized countries , an increasing proportion of tuberculosis patients control policies with regard to immigrant tuberculosis usually rely on chest x - ray screening and treatment of active tuberculosis . a supplemental approach , recommended by the institute of medicine ( 14 ) , is to conduct tuberculin skin testing and to apply preventive treatment of latent infections . whether all tuberculin skin test positive immigrants should be treated , or only selected high - risk groups such as immigrants with radiographic evidence of inactive disease , is under debate ( 15 ) . adhering to preventive treatment is also a point to consider ( 15 ) . to answer the question of why the incidence rates remain high , the relative importance of three factors needs to be established : reactivation of old infections , transmission in the host country , and infections acquired during visits to the countries of origin . these answers are essential to evaluate the cost - effectiveness of the dutch screening policy and of alternative options , including other screening policies and use of preventive treatment .

incidence rates of pulmonary tuberculosis among immigrants from high incidence countries remain high for at least a decade after immigration into the netherlands . possible explanations are reactivation of old infections and infection transmitted after immigration . control policies should be determined on the basis of the as - yet unknown main causes of the persistent high incidence .

the sun is a rotating magnetic star consisting of a hot plasma entangled with fluctuating magnetic fields . a vast amount of energy is continuously released from the sun in the form of electromagnetic radiation as well as in the form of charged particles , called the solar wind . the latter is accelerated and ejected omni - directionally into interplanetary space . the region around the sun filled with the solar wind and its imbedded magnetic field b is known as the heliosphere . this magnetic field , called the heliospheric magnetic field ( hmf ) , remains rooted on the sun as it rotates , resulting in the formation of an archimedean spiral , referred to as the parker spiral. turbulent processes that occur on the surface of the sun cause cyclic variations e.g. in the number of sunspots . the direction of b also changes every 11 years resulting in polarity cycles of 22 years . positive polarity epochs , indicated by a > 0 , are defined as periods when b points outwards in the northern and inwards in the southern heliospheric regions while for a < 0 epochs , the polarity switches ; see the top panel in fig . the thin region where the magnetic polarity abruptly changes creates the heliospheric current sheet ( hcs ) that becomes increasingly wavy with growing solar activity . this waviness is caused by the fact that the magnetic axis of the sun is tilted with respect to its rotational axis , forming an angle which is equal to the angle with which the hcs is tilted . values of have been computed by applying models to solar magnetic field maps as shown in the middle panel of fig . the time series for correlate with that for b so is frequently used in cosmic ray ( cr ) modulation studies as a proxy for solar activity . in terms of , solar activity is classified as solar minimum when 530 , moderate when 30>60 and maximum when 60<90. variations in b , observed at earth as shown in fig . 1 , and changes in are propagated throughout the heliosphere by the solar wind . for additional background and details , see the reviews by heber and potgieter and strauss et al . . information about the global properties of b , at earth and in the heliosphere at large , forms important input for various fields of space research including past terrestrial climate effects and very long - term ( > 100 years ) modulation of crs . unfortunately records of in situ space measurements of b , and most other indicators of solar activity cover only a few decades so that various models have to be used to reconstruct solar activity parameters via indirect proxies . however , this paper focuses on and b , as they change with time at earth , as input for a numerical model describing the global modulation and variability of crs in the heliosphere . if successful , this approach can be applied for solar activity cycles longer than 22 years . galactic crs are charged particles that come from outside the heliosphere with energies ranging from 10 ev to as high as 10 ev [ e.g. 4,5 ] . 30 gev traverse the heliosphere with little effect on their intensity while crs with lower e are modulated , progressively with decreasing e. the reason is that they get scattered ( diffused ) by irregularities in b , so that its geometry and magnitude together with the level of variance in b , as a proxy for turbulence , largely determines the passage of crs inside the heliosphere . this process of changing the intensity with time as a function of energy and position is known as the heliospheric modulation of crs . increased solar activity ( turbulence ) leads to lowering the energy spectrum of crs , with the largest effects at low energy [ see also 1,2 ] . ground based observations made since the 1950s when cr detectors , called neutron monitors ( nms ) , were deployed worldwide , convincingly reflect anti - correlated cycles in the time series of crs , also in sunspot numbers , in b and in , as illustrated in fig . however , there is also a subtle difference in the time histories of crs and b. the time evolution of crs at earth is different in successive activity cycles . in a < 0 epochs , the cr intensity as a function of time is peaked and narrow while in the a > 0 cycles the profiles are much less peaked , as shown in the bottom panel of fig . this 22-year cycle is caused by reversals in the polarity of b responding to changes in the drift patterns of crs that reverse every 11 years when the polarity of the hmf changes . galactic crs thus respond to the curvature and gradients in the hmf and to variations in the hcs . they also diffuse towards the sun while getting convected back towards the heliospheric boundary by the solar wind , experiencing significant adiabatic energy losses . they thus respond to what had happened on the sun after these solar activity variations reached the earth . however , the total modulation effect is observed only after these variations have reached the outer heliospheric boundary several months later . the method of describing the transport mechanisms for the modulation of crs is through a simplified fokker planck type equation , called parker s transport equation ( tpe ) : ( 1)ft=(sf)-(vsw+vd)f+13(vsw)flnpwhere f(r , p , t ) is the cosmic ray distribution function at position r , time t , and rigidity p = pc / ze of a cr particle with charge ze , atomic number z , momentum p , and with c the speed of light . the differential intensity j is commonly used and is given by j = pf , in units of particles mev m s sr . the diffusion tensor , in terms of the hmf orientation is given as(2)s=||000d0-drwith || being the diffusion coefficient parallel to the average background b , with r and being the diffusion coefficients perpendicular to b in the radial and polar directions , respectively . the effective diffusion coefficient in the radial direction in a heliocentric , spherical coordinate system is then given by(3)rr=||cos2+rsin2where is the spiral angle of b , the angle between the radial direction and the averaged direction of b. see also . under the assumption of weak scattering , the drift velocity is given by vd=(deb ) with the drift coefficient(4)d=p3b10p21 + 10p2describing the effects of gradient and curvature drifts . here , p=p / po with po = 1.0 gv , = v / c with v the speed of the cr particle ; eb = b / b is a unit vector in the direction of b. using as the only time - dependent parameter , it was shown that time - dependent modulation including gradient , curvature , and hcs drifts could reproduce the basic features of observed cr modulation . however , it was later shown that the model could not reproduce cr variations during a phase of increased solar activity . this was especially true when large step decreases in the observed cr intensities occurred prominently during periods of enhanced solar activity . in order to simulate cr intensities during moderate to high solar activity , propagation diffusion barriers ( pdbs ) had to be introduced . these pdbs are in the form of merged interacting regions in the hmf caused by interacting outflows of the solar wind . regions of fast and slow solar wind speeds are separated by sharp boundaries , resulting in strong longitudinal speed gradients . fast solar wind speeds are typically 800 km s , while the slow solar wind speed is 400 km s. when fast streams of the solar wind run into slower streams ahead of them , interacting regions ( irs ) are formed where the magnitude of b and the turbulence are higher . if the structure is stable for several rotations these irs become corotating interacting regions ( cirs ) . when two or more cirs merge , corotating merged interacting regions ( cmirs ) form and when they merge , global merged interaction regions ( gmirs ) forms which produce very effective cr modulation barriers . large step decreases of crs are caused by these pdbs ; see the lower panel of fig . the degree with which gmirs affect long term modulation depends on the size of the heliosphere ( modulation volume ) , their rate of occurrence , their spatial extent ( they may encircle the sun , stretching up to high heliolatitudes ) , and how the background b is disturbed consequently . large gmirs are not common inside 20 astronomical units ( au ) , with the earth at 1 au . by including a combination of drifts and gmirs in a comprehensive time - dependent cr model it was shown that it is possible to simulate , to first order , a complete 11 year cr modulation cycle . the numerical solution of the full tpe ( five numerical dimensions ) is seldom used because of its complexity so that in order to make progress various approximations have to be introduced . the two - dimensional ( 2d ) compound numerical model used here was developed by ferreira and potgieter , applied to ulysses observations by ndiitwani et al . and recently improved and applied to voyager 1 and voyager 2 ( v1 and v2 ) observations by manuel et al . . in this model , azimuthal symmetry is assumed which in turn eliminates cross - terms in the numerical solution of tpe but also reduces its applicability and validity to time scales of one solar rotation or more . the diffusion and drift coefficients used were described in detail by manuel et al . and is not repeated here because of page limitations . it suffices to say that these authors introduced theoretical advances in diffusion and turbulence theory to derive cr transport parameters applicable to the heliosphere in order to establish a time - dependence for the relevant transport parameters used in this compound model . according to this approach , the coefficients in eq . ( 2 ) scale time - dependently as the ratio of the variance in b with respect to the background b. 2 as a function of time , compared to 2.5 gv proton observations at earth ( blue line ) and along the ulysses trajectory ( red line ) . vertical lines indicate the three fast latitude scans ( indicated by fls1,2,3 ) that ulysses made in 1995 , 2001 and 2007 , respectively . the hmf switches polarity from a > 0 to a < 0 at the time of year 2000.2 as indicated by the darker vertical line . in fig . 3 proton observations with e > 70 mev are shown as a function of time for v1 , at earth by the imp spacecraft and for 2.5 gv from ulysses . this was done for two approaches in simulating the time dependence of the transport parameters ; the previous compound approach ( solid line ) and for the advanced compound approach using improved diffusion theory ( dashed line ) . although the model can not reproduce variations shorter than one solar rotation , it is quite realistic in producing the 11-year and 22-year cycles , including the two voyager spacecraft and the latitude dependent modulation observed by ulysses . the model is clearly suited to produce cr intensities on a global scale but still needs improvement for increased solar activity conditions when gmirs seem required to simulate all the larger step decreases . the modeling approach can successfully reproduce cr intensity variations at earth , along v1 and v2 trajectories , as well as along the ulysses trajectory , as shown in comparison with proton observations from imp , ulysses , v1 and v2 . input parameters , such as the tilt angle , hmf magnitude and total variance can be extrapolated to predict future cr intensities at earth and along spacecraft trajectories as well as for past and future solar activity cycles . the model is suitable to study very long - term cr variations , even over centuries , including exceptional periods such as the maunder minimum and other grand minima .

galactic cosmic rays are charged particles created in our galaxy and beyond . they propagate through interstellar space to eventually reach the heliosphere and earth . their transport in the heliosphere is subjected to four modulation processes : diffusion , convection , adiabatic energy changes and particle drifts . time - dependent changes , caused by solar activity which varies from minimum to maximum every 11 years , are reflected in cosmic ray observations at and near earth and along spacecraft trajectories . using a time - dependent compound numerical model , the time variation of cosmic ray protons in the heliosphere is studied . it is shown that the modeling approach is successful and can be used to study long - term modulation cycles .

clinical lore suggests that methadone treatment for opiate dependency leads to increase in body mass , however , very few studies measured this statistically . in the slovak republic , okruhlica and slezakova ( 1 ) followed 274 methadone patients for a year , starting with their admission to treatment . a significant increase ( p < 0.001 ) was noted on all bmi categories from admission to one year follow up . the proportion of those underweight decreased from 10 to 5% , the proportion of normal weight changed from 72% to 58% , the proportion in the overweight category increased from 15 to 29% , and the proportion of obese patients increased from 3 to 8% . however , even at the one year follow up , these patients still remained significantly below proportions of these bmi categories in the general population ( 4% , 49% , 34% and 13% , p < 0.001 ) . similarly , the polish study by szpanowska - wohn et al . ( 2 ) noted an increase in average body mass from 71.7 kg to 75.7 kg within 9 months following entry to methadone treatment . a study by montazerifar et al . ( 3 ) noted a significant increase in bmi already within the first 8 weeks on admission to methadone treatment . within the 8 weeks , the average weight of patients treated by montazerifar s team showed a statistically significant increase from 61.4 kg on admission to treatment to 65.3 kg which corresponded to a bmi increase from 21.4 to 23.0 . the rapid weight increase within the first 8 weeks is remarkable , but was perceived as medically valuable with respect to those underweight and malnourished . the proportion of the underweight patient decreased by half . ( 3 ) , the percentages of underweight , overweight and obese patients were 27.3% , 18.2% and 3.6% , respectively before methadone treatment , and 12.7% , 18.2% and 7.2% at the end of the 8 weeks . ( 4 ) also found a significant increase in bmi from admission to follow up . the data published by fenn s team indicated a mean increase by 8.1 kg which corresponded , on average , to an increase of 10% in body weight . ( 4)increased from 27.2 ( overweight category ) to 30.1 ( lowest section of the obese category ) . okruhlica and slezakova ( 5 ) examined the bmi of 42 methadone patients over 4 years . the bmi significantly increased in the first year of treatment and also from the first to the second year ; however , no significant change was noted in the subsequent 2 years . the correlation of methadone dose to bmi was not significant at the end of this follow up . according to data in okruhlica and slezakova ( 5 ) , the weight of their 42 patients at the end of the 4 year follow up did not differ from the measures in the general local population . at that point in the follow up , there was no significant correlation between the daily dose of methadone and the patients bmi . okruhlica and slezakova ( 5 ) hypothesized that the weight gain of their patients in opiate substitution treatment is most probably a consequence of the changes in their lifestyle and not the result of direct adverse pharmacological effect of methadone medication . the findings by okruhlica and slezakova ( 5 ) , if replicated , are of crucial medical importance because they suggest that the rapid weight increase such as the twofold increase of patients within the obese category observed by montazerifar et al . ( 3 ) within the time span as short as only 8 weeks does not continue beyond the first or the second year of methadone treatment and is perhaps more related to changes in lifestyle than to pharmacological properties of methadone . in our effort to reduce the risk of metabolic syndrome , it is important to know which parameters of body composition ( e.g. , % body fat versus % muscle mass ) are primarily affected by the weight increase observed in the first year of methadone treatment . we measured , via bioelectrical impedance , the changes in body composition and in the body mass index ( bmi ) within one year following admission to methadone treatment . on their admission and also at one year follow - up , 29 methadone maintenance patients ( age 18 to 44 , mean = 29.3 , sd = 7.0 , 13 men , 16 women ) completed the symptom check list 90 revised ( scl-90-r ) and we measured their weight , bmi , and body composition ( muscle mass , bone mass , % of fat , % of water , and basal metabolic rate , ) via bioelectrical impedance , using tanita ironman body composition monitor bc554 . within one year following their admission to methadone treatment , our patients showed a significant decrease ( t - tests , p < 0.05 , 2-tailed ) on scl-90-r scales of depression , anxiety , and overall psychopathology . a significant increase was noted in their mean bmi ( increase from 24.1 , sd = 4.1 to 26.3 , sd = 4.8 ) , mean body mass ( from 71.8 kg , sd = 14.4 to 78.3 kg , sd = 15.9 ) , % fat ( from 25.3% of total body mass , sd = 10.0 to 30.6% , sd = 9.3 ) , and basal metabolic rate ( from 1593.4 , sd = 267.0 to 1633.5 , sd = 288.6 ) and a significant decrease in % of muscle mass ( from 71.0% of body mass , sd = 9.6 to 65.8% , sd = 8.9 ) , in % of water ( from 52.0% , sd = 6.1 to 48.8% , sd = 5.5 ) and in % bone mass ( from 3.7% , sd = 0.5 to 3.5% , sd = 0.5 ) . neither absolute muscle mass nor absolute bone mass changed significantly within one year of admission to methadone treatment . the overall body mass has increased chiefly due to an increase in the proportion of body fat . hopefully , future studies might clarify the relative contribution of biochemical , environmental , and lifestyle mechanisms responsible for the increase in percent of body fat . the patients average bmi increased from the normal to overweight category . on the one hand , this points to an increased risk of metabolic syndrome and associated conditions . for example , with respect to insuline resistance , a recent us study found that diabetes mellitus was significantly more common in patients receiving opiate dependence treatment via methadone than via buprenorphine ( 6 ) . in methadone patients with sleep difficulties , obstructive sleep apnea was more common in those with higher bmi and longer duration of methadone maintenance treatment ( 7 ) . on the other hand , methadone treatment helps the patients to avoid conflicts with the law and dramatically increases their chances of long term survival . an australian retrospective study of a cohort of 307 heroin addicts indicated that these patients were nearly three times as likely to die if outside of methadone maintenance treatment than in it . a retrospective analysis of uk data showed that the total number of convictions , theft and fraud convictions , and weeks spent in prison per year were reduced by 39.3% , 52.17% , and 82.8% , respectively ( 8) . a recent chinese neta - analytic study of the total of 30,239 patients found a decrease in arrest rates from 13.1% to 4.3% and increase in employment rates from 26.4% to 59.8% within 12 months following admission to methadone treatment ( 9 ) . furthermore , some comparative studies of methadone and buprenorphine indicate that the former is associated with higher treatment retention rates ( 10 ) . such data show that medical , societal , and economic benefits of methadone treatment outweigh the potential adverse side effects . however , physicians involved in care of methadone patients should preventively recommend dietary and lifestyle changes to improve their overall health .

background : methadone is associated with a statistically significant increase in bmi in the first 2 years of treatment.objectives:to evaluate the changes of body composition ( bone mass , % fat , % muscle mass , % water , and basal metabolic rate ) related to this increase.patients and methods : changes in body composition were monitored , via bioelectrical impedance , in 29 patients in methadone treatment for opiate dependency ( age 18 to 44 , mean = 29.3 , sd = 7.0 , 13 men , 16 women).results : within one year from admission to treatment , a statistically significant ( t - tests , p < 0.05 ) increase was noted in their body mass index ( bmi ) , % of body fat , average body mass , and average basal metabolic rate , and relative decrease in their % of muscle mass and % of bone mass . neither absolute bone mass nor muscle mass changed significantly.conclusions:physicians involved in care of methadone patients should recommend dietary and lifestyle changes to improve their overall health .

simkania negevensis is an obligate intracellular gram - negative bacterium belonging to the family of simkaniaceae in the order chlamydiales , discovered as a contaminant in a variety of cell cultures , and is able to grow also in various environmental free - living amoebae such as acanthamoeba poliphaga . epidemiologic studies have reported a human widespread exposure to this bacterium [ 4 , 5 ] , both in healthy subjects and in association with respiratory diseases in infants and adults [ 610 ] . coinfections with other pathogens have been described , such as respiratory syncytial virus in children and influenza virus and other bacterial species in adults [ 7 , 8 , 11 ] . a possible association between s. negevensis and acute rejection in lung transplant recipients has been suggested . s. negevensis dna has also been amplified from an aortic aneurysm [ 13 , 14 ] . previous investigations reported s. negevensis in vitro susceptibility to azithromycin , minocycline , erithromycin , doxycycline , and ofloxacin like chlamydiae and the lack of susceptibility to ampicillin , penicillin g , bacitracin , cyclosporine , and fluoroquinolones [ 2 , 15 , 16 ] . several studies [ 1720 ] demonstrated the in vitro antichlamydial activity of peptides , such as cathelicidins , stored by mammalian leucocytes and show an antimicrobial activity against bacteria , fungi , protozoa , and enveloped viruses . with regard to the mode of action of these peptides against chlamydiae , previous investigations on the activity of protegrins suggested an initial binding to lipopolysaccharide followed by insertion into the membrane that results in permeabilization . . demonstrated that the antichlamydial activity of protegrins resided especially in residues 5 to 15 of native protegrin-1 and required both intramolecular disulfide bonds . in the present study , we investigate the in vitro activity of six antimicrobial peptides against the reference strain z of s. negevensis . the cathelicidin peptides pg-1 from pig , bac7 ( 135 ) from cattle , smap-29 from sheep , ll-37 from human , bmap-27 , and bmap-28 from cattle were chemically synthesized , purified , characterized , and provided as lyophilized peptide , as previously reported . the reference strain z of s. negevensis ( american type culture collection vr-1471 ) was grown in llc - mk2 cells in 6-large well plates and elementary bodies ( ebs ) were purified by use of sucrose gradients , resuspended in sucrose - phosphate - glutamic acid buffer ( spg ) ph 7.4 ( 75 g sucrose , 87 ml 0.2 m na2hpo4 , 13 ml 0.2 m nah2po4 , 0.72 g l - glutamic acid ) , and frozen in aliquots at 80c . stock solutions of each peptide at 1 g / liter were prepared in phosphate - buffered saline ( pbs ) , ph 7.4 , and stored frozen in 20-l aliquots at 80c until used . to determine the lowest peptide concentration required to achieve 50% reduction of inclusions with respect to untreated control , the various peptides were diluted tenfold from 200 to 0.02 g / ml , in a volume of 100 l with pbs in polypropylene tubes . an equal volume of 5 10 inclusion - forming units ( ifu)/ml of purified s. negevensis ebs in spg medium was then added , so obtaining a final cathelicidin concentration ranging from 100 to 0.01 g / ml in a mixture of pbs and spg at a final ph 7.4 . after incubation at room temperature for 2 h , a 200 l aliquot was added to 800 l chlamydial growth medium and inoculated onto llc - mk2 cells grown in 24-well plates in a 5% co2 atmosphere . after centrifugation at 800 g for 1 h at 33c and incubation at 35c for 72 h , the cultures were fixed and stained for the presence of inclusions by immunofluorescence using an in - house rabbit polyclonal hyperimmune serum raised against s. negevensis . the number of ifu per coverslip was counted in 40 microscopic fields using a zeiss uv microscope at a magnification of 200 . the activities of the six cathelicidin peptides against s. negevensis are reported in figure 1 and are the means of results from the three experiments . in comparison with the infectivity of the untreated control ( mean value 74 ifu / ml ) , bac7 and smap-29 reduced by > 50% ( < 37 ifu / ml ) the inclusion numbers of s. negevensis at a concentration of 0.1 g / ml , whereas pg-1 , bmap-27 and bmap-28 showed the same activity at a concentration of 1 g / ml . all these five cathelicidins demonstrated a very slow decrease in their inhibitory effect while their concentration has been reducing from 100 to 1 or 0.1 g / ml . ll-37 peptide did not exert any inhibitory effect , even at a concentration of 100 g / ml . in our previous study , the activity of six cathelicidins pg-1 , bac7 , smap-29 , bmap-27 , ll-37 and bmap-28tested on chlamydiae of human and animal origin showed that five of them had inhibitory effect on chlamydia trachomatis strains , smap-29 being the most active peptide at a concentration of 10 g / ml ; on the contrary , ll-37 peptide was ineffective even at a concentration of 80 g / ml . with regard to the other chlamydial species tested , only chlamydophila pneumoniae and chlamydophila felis were sensitive to 10 g / ml of smap-29 and 80 g / ml of smap-29/bac7 , respectively . in the present investigation , the same six cathelicidins were tested against the reference strain z of s. negevensis . in comparison with chlamydiae , s. negevensis was not sensitive to ll-37 even at the concentration of 80 g / ml , but very sensitive to all the other five cathelicidins that showed an inhibitory effect at very low concentrations from 1 to 0.1 g / ml . to our knowledge no study on s. negevensis susceptibility to cathelicidins has been performed , until now . these preliminary results suggest a higher sensitivity of s. negevensis to cathelicidins respect to chlamydiae . a previous study showed differences in the susceptibility of different c. trachomatis serovars to antimicrobial peptides , suggesting that limited variations in the disulfide bonding in the membrane structure of these organisms may influence their susceptibility to peptides . the membrane structure of s. negevensis probably differs significantly from that of other members of chlamydiales , as monoclonal antibodies recognizing family - specific epitopes of chlamydial omp-2 , momp , and lps did not bind s. negevensis antigens [ 2 , 25 ] ; in addition , only a relatively small number of common epitopes were shown to be shared when s. negevensis and other chlamydiales members were tested for cross - reactivity by western blot using polyclonal antisera . the higher susceptibility of s. negevensis to cathelicidins in comparison to chlamydiae could be referred , to a great extent , to its different polypeptides pattern .

the in vitro activity of six cathelicidin peptides against the reference strain z of simkania negevensis was investigated . five peptides pg-1 , bac7 , smap-29 , bmap-27 , and bmap-28proved to be active at very low concentrations ( 1 to 0.1 g / ml ) , while ll-37 cathelicidin was ineffective even at a concentration of 100 g / ml . in comparison to chlamydiae , s. negevensis proved to be more susceptible to the antimicrobial peptides tested .

lipoma is the most common soft tissue mesenchymal neoplasm in adults , which is located in any part of the body . the majority occurs in the upper - half of the body , particularly the trunk , head , and neck region , and it is rarely described in the oral cavity . conventional lipoma has been divided into three forms according to the origin of the localization : superficial lipoma ( arise within subcutaneous tissue ) , deep lipoma ( arise within deep soft tissue ) and parosteal lipoma ( arise within the surfaces of bone ) . the histological characteristics and types vary , which include angiolipoma , angiomyolipoma , myolipoma , osteolipoma and chondrolipoma . both osteolipomas and chondrolipomas are rare entities.[24 ] however , occurrence of osteolipomas or in other term lipomas with oseous and cartilagenous metaplasia are less common than other subtypes of lipomas . the term of osteochondrolipoma has been used for the lipomas containing both cartilage and bone which , are very rarely seen and generally associated with a paraosteal localization . to our knowledge , a 64 year old male patient with painless mass on his mandibulary symphysis region , was referred to the department of oral and maxillofacial surgery , faculty of dentistry on september , 2007 . the lesion had been first noticed 2 months prior of the presentation to the clinic with no significant enlargement . clinical examination of the oral cavity revealed a well demarcated , firm , round and exophitic lesion of approximately 2 cm in diameter at the symphysis region of the left mandible . the lesion was firmly attached to the bone in the clinical examination and the overlying mucosa was intact and of normal color . radiographically , at the site of the lesion some degree of radioopacity was observed [ figure 1 ] . under local anesthesia , the patient was taken to the operating room and the lesion was completely excised with an intraoral approach . during the surgical intervention , the encapsulated lesion was not adherent to the underlying periosteum and overlying mucosa , thus the lesion was dissected and removed easily [ figure 2 ] . the surgical specimen was histopathologically evaluated for final diagnosis at department of oral pathology , faculty of dentistry , gazi universitys . the 6-month postoperative follow - up showed healing of the oral mucosa without any recurrency . preoperative panoromic radigoraph exhibiting the dense radioopacity ( arrow ) in the symphysis region of the mandible intraoperative view of the lesion with encapsulation macroscopically , the gross specimen was a 2.7 1.8 1.4 cm encapsulated mass mostly comprising of adipose tissue with a few number of encapsulated nodular structures . on section , focal areas of hyaline chondroid structures and lamellar bone with fatty marrow were seen throughout the lesion . both islands of bone and cartilage were surrounded with well defined fibrous tissue [ figure 3 ] . there was no histological evidence of malignancy , such as mitosis , cellular atypia , necrosis , and hemorrhage . histochemistry with alcian blue periodic acid - schiff stain showed acid mucopolysaccaride presence in chondroid tissue ; hence , this was hyaline chondroid . on immunohistochemistry , adipocytes were positively stained with vimentin antibody , while both adipocytes and chondrocytes were positive for s-100 protein [ figure 4 ] . histopathological features of osteochondrolipoma showing mature adipose tissue containing cartilage islands and lamellar bone trabecules ( h and e , 40 ) chondrocytes and adipocytes demonstrating positivity for s 100 protein ( immunoperoxidase , 40 ) however , they are relatively uncommon in the oral cavity with incidence of 14% . variants of lipoma especially osteolipoma and chondrolipoma are very rare lesions which are located in the oral cavity . furthermore , intaoral lipoma with both osteoid and cartilaginous metaplasia has been reported just in two cases . we presented an osteochondrolipoma case that differed from the typical arrangement by two rare alterations . first , the lesion showed well - defined cartilaginous and osseous areas within lipoma that is also considered as osseous and cartilaginous metaplasia . in the a study of fregnani et al . , fibrolipoma was reported as the dominant subtype in 46 lipoma cases , in which neither osteolipoma nor chondrolipoma was found . two lipomas with cartilaginous or osseous metaplasia was reported out of 125 lipoma cases in another study , whereas none of the cases represented osteochondrolipoma . although , any case in the name of oral osteochondrolipoma has not been reported , lipoma with osteoid and cartilaginous metaplasia has been represented by two cases in the oral region . the osteochondrolipoma is the specific term of the lipoma with mature cartilaginous and osseous differentiation ; thus , both terms represents the same entity . some authors consider such type of lipoma as a benign mesenchymoma due to consisting of two or more mesenchymal elements such as lipocytes , chondrocytes , osteocytes , and fibroblasts . jones et al . stated that the term of benign mesenchymoma should be used strictly to describe an unencapsulated neoplasm composed of two or more mature mesenchymal tissues not ordinarily associated with each other , excluding fibrous connective tissue . in the present case , as the tumor is well demarcated and partially encapsulated and moreover the prominent component is mature adipose tissue , the tumor is considered as osteochondrolipoma . second alteration that took part in this case , was the parosteal localization of the lesion . the parosteal lipoma which is defined as lipoma exhibits a conguous relationship with the periosteum , usually demonstrating some form of attachment to periosteum with an underlying osseous reaction , is rarely seen in the oral cavity . various types of osseous cortical responses from a reactive overproduction of bone to cortical erosion can be seen underlying bone . the radiopacity in our case may reflect either the reactive bone production of underlying bone or the density of cartilagenous and ossous component of the tumor . multipotent cells of mesenchyme , different cell lines and metaplastic differentiation of the adipose tissue are three hypothesis regarding the origin of the tumor . however , considering its parosteal location , histological findings of well - formed cartilage and bone tissue within the adipose tissue neoplasm , it is decided to be a true neoplasm of mesenchymal tissue stem cells showing characteristics of three different tissues originating from the mesenchyme .

osteochondrolipoma is a rare benign soft tissue neoplasm . it is occasionally considered to be a variant of adipose tissue neoplasm lipoma showing multiple differentiation pathways of pluripotent stem cells . as with the lipomas they can be seen at any location and show cartilagenous and osteoid differentiation when located parosteally . we present a case of osteochondrolipoma located at the symphysis of the mandible . to our knowledge , this is the first reported case of an oral osteochondrolipoma associated with parosteal localization .

although levetiracetam ( lev ) is a relatively well - tolerated anti - epileptic drug ( aed ) that is used to control partial and generalized seizures , an encephalopathy resulting from lev administration has been previously reported.1,2 encephalopathy induced by aed has been observed in patients with vpa , however , it is debatable whether the concomitant use of lev with valproic acid ( vpa ) causes the encephalopathy or not . we report here on the manifestation of a vpa induced hyperammonemic encephalopathy promoted by lev . a 60-year - old female suffering from frontal lobe epilepsy was presented to our hospital with a mental obtundation . we have treated the patient for a period of 5 years and have registered an electroencephalogram ( eeg ) with ictal fast activity in the right frontocentral area . a brain mri showed a t2 high , t1 low signal intensity of a single lesion without enhancement in the right anterior basal frontal lobe white matter ( fig . 1 ) . she used to have partial seizures with a secondary generalization , and she has been on 1,200 mg / day vpa for the last 4 years . generalized tonic - clonic seizures ( gtcsz ) were well controlled , but partial seizures of left head version following left arm clonus occurred one to two times per several months . we added lev to vpa and increased the daily dosage of lev to 1,000 mg / day . the neurologic findings showed no ataxia or nystagmus , and routine hematological and biochemical laboratories presented a normal complete blood count ( wbc 6,600/mm , hb 13.4 g / dl , platelet 168,000/mm ) , electrolyte ( na 138 mmol / l , k 4.1 mmol / l ) , renal ( bun 11.1 mg / dl , creatinine 0.72 mg / dl ) , and thyroid function test ( free t4 1.230 ng / dl , tsh 0.779 uiu / ml ) . however , her liver function test showed a mild impairment ( aspartate aminotransferase 46 iu / l , alanine aminotransferase 44 iu / l ) , and the serum ammonia level was high ( 154 umol / l , normal : 12 to 47 an abdomen computed tomography ( ct ) with a contrast enhancement showed no remarkable finding , except for a 0.6 cm - sized liver cyst . the blood concentrations of vpa was of 82.4 ug / ml ( therapeutic range : 50100 ug / ml ) . we suspected the possibility of side effects associated with lev because she tolerated medication with vpa for 4 years and stopped lev . her mental function was gradually restored , with a decrease in the blood ammonia level ( 56 umol / l ) , and the generalized slowing disappeared in a follow - up eeg ( fig . 2c ) . we added carbamazepine to treat for partial seizures , and the patient was asymptomatic until the last visit in july 2014 . our patient showed mental obtundation and hyperammonemia following administration of lev receiving vpa , and the condition was resolved completely after discontinuation of the drug . we consider the patient to have had vpa - induced hyperammonemic encephalopathy promoted by lev . an encephalopathy induced by aed has been described in patients with vpa medication.3 however , the condition has been rarely seen with lev and only in specific conditions , such as when there is renal failure or when there is concomitant use of vpa.1,2 lev undergoes minimal hepatic metabolism via enzymatic hydrolysis , and it is eliminated entirely by renal excretion.4 the clearance of the lev decreased in subjects with renal impairment , wheareas no significant pharmaco - kinetic changes for lev were observed in patients with hepatic dysfunction.4 vulliemoz et al . observed that the administration of lev in a patient with chronic renal failure caused a myoclonic encephalopathy due to the toxic accumulation of lev.1 previous studies indicated that lev has no clinically relevant interactions with other aeds due to its minimal protein binding and lack of hepatic metabolism.4,5 however , a recent meta - analysis observed that the enzyme inducing aeds have a modest influence on the kinetics of lev.6,7 serum concentrations of lev might be increased or decreased about 20 to 30% as the enzyme inducing or inhibiting aeds are added.6 these results suggest that lev is metabolized by cytochrome p450 enzymes to a greater extent than what previously observed data had suggested . a few reports on the pharmacokinetic influences and of the comedication effects of new aeds on vpa toxicity have been noted.4 hamer et al.8 described that patients receiving topiramate in addition to vpa suffered from an encephalopathy , and topiramate was concluded to have facilitated the toxic effect of vpa and to have contributed to the increase in the ammonia levels through its inhibition of carbonic anhydrase and cerebral glutamine synthetase.8 although the mechanism for vpa - induced hyperammonemia is not fully understood , it is known that a propionate , metabolite of vpa , leads to a carbamyl phosphate synthetase-1 activity deficit , the decrease in hepatic carnitine concentration via vpa induces oxidation suppression of fatty acid , and an increase in the mitochondrial glutamine receptors causes the absorption of glutamine in the kidney.9 the hyperammonemia resulting from vpa causes encephalopathy mainly by influencing the astrocyte , which has the function of ammonia detoxication and leads to mitochondrial proliferation and cerebral edema through glycogen precipitation in the astrocyte cytoplasm.10 previous reports on vpa - induced hyperammonemic encephalopathy have usually observed that patients with a concomitant use of other aeds , such as phenytoin or phenobarbital , rather than those with single use , experienced oxidation suppression in the urea cycle which led to hyperammonemic encephalopathy without hepatic dysfunction.3,10 the mechanisms that cause encephalopathy with only lev itself or with the comedication with vpa are debatable since vpa is usually well tolerated with a concomitant use with other new aeds , and both increased serum lev concentration with enzyme inhibiting vpa use and the vpa toxicity may induce an encephalopathy , even when within a therapeutic range . however , the lack of toxicity of vpa when used without lev for an extended period of time , the insidious onset of mental obtundation after lev add on , the generalized eeg slowing , the elevated ammonia level , and the complete recovery of mental symptoms after stopping the drug support the conclusion that a vpa - induced hyperammonemic encephalopathy was promoted by lev . our case demonstrates that a lev provoke a condition of hyperammonemic encephalopathy in a patient receiving vpa , and such cases can be suspect when diagnosing this condition .

encephalopathy resulting from the administration of levetiracetam ( lev ) is a rare occurrence . we experienced a patient receiving lev treated with valproic acid ( vpa ) for partial seizures with secondary generalization , following which she developed hyperammonemic encephalopathy and showed complete recovery after the drug was withdrawan . lev is able to promote hyperammonemic encephalopathy when added to vpa .

the meniscus is frequently damaged in anterior cruciate ligament ( acl ) injuries or in the degenerative process over a period of several years1 ) . the predominance of lateral meniscal tears has been demonstrated with acute acl rupture , whereas the incidence of medial meniscal tears significantly increases with chronic acl insufficiency2 ) . the lateral meniscus is relatively loosely attached to the tibial plateau , which allows it to be quite mobile , and performs little or no stabilizing function on the knee . the medial meniscus , however , is firmly attached to the tibia , especially at the posterior horn3,4 ) . this firm attachment allows the medial meniscus to serve as a knee stabilizer , and various studies have shown that it is a significant restraint to anterior tibial translation in acl - deficient knees5 - 7 ) . biomechanical studies have indicated that the meniscus performs this function by acting as a mechanical block or wedge8,9 ) . their results suggest that the loss of acl function increases anterior tibial translation , allowing the meniscus to engage the femoral condyle and act as a wedge against the tibia . radiographic studies have shown that there is a linear relationship between posterior tibial slope ( pts ) and anterior tibial translation during weight bearing : the greater the pts , the greater the anterior tibial translation , in both acl - intact and acl - deficient knees10,11 ) . our hypothesis is that secondary medial meniscal tears occur more frequently in acl deficient knees with greater pts . the objectives of this study were to evaluate the incidence of meniscal tears in patients with chronic acl - deficient knees and to determine the influence of pts on secondary medial meniscal tears in acl - deficient knees . a retrospective review was performed on 202 patients who underwent acl reconstruction by the senior author between january 2005 and may 2009 . we excluded 28 patients who had multiple ligament injuries and/or reconstruction in the acute phase ( within 3 months of injury ) . the remaining 174 patients ( 148 males and 26 females ) were included in this cohort study . the average time to surgery was 14.8 months ( range , 3 to 140 months ) . although meniscus tears could be classified according to the location and type , we classified meniscus tears only according to the location . to classify the location of a tear on arthroscopy , each meniscus was considered to have three segments : the anterior horn , body , and posterior horn . in addition , the tears were divided into peripheral tears ( those involving the red zone ) and central tears ( those involving the red - white zone and the white zone ) . in order to measure the pts , we used the tibial proximal anatomic axis ( tpaa ) , which gives high reliability among the tibial axis12 ) . on lateral radiographs , the tpaa was defined as a line connecting the two central points of the tibial cortex at 5 cm and 15 cm below the tibial tuberosity . on the lateral radiographs , the line connecting the highest anterior and posterior points of the medial plateau was regarded as a line for the tibial slope . the angle between the tangent line to the medial plateau and the perpendicular line to the tpaa was defined as pts ( fig . the mean values of the measurements taken by the two surgeons were used in the assessment . the average pts measured on lateral radiographs is 103 in the literature , which was used as a reference for our study10 ) . in order to analyze the influence of pts on secondary meniscal tears , we divided the patients into two groups : low group ( pts<13 ) and high group ( pts13 ) . the statistical analyses were performed using sas ( sas institute , cary , nc , usa ) soft ware . descriptive statistics including means , standard deviations , and minimum and maximum values were calculated for every group . mann - whitney u test was performed to detect significant effects of age , sex , body mass index ( bmi ) and the interval from injury to acl reconstruction between the two groups . the chi square test was used to determine whether there were significant differences in tear pattern between two groups . if there were significant differences , a post - hoc test with the bonferroni adjustment was used to determine which groups were significantly different from the others . the overall incidence of meniscal injuries was 65% ( 113/174 ) in the total chronic acl - deficient knees . the incidence of medial meniscal tears was 44% ( 77/174 ) , and that of lateral meniscal tears was 35% ( 61/174 ) . the average pts measured on the lateral radiographs was 10.52.8. the mean pts in patients with medial meniscal tears was 11.43.0 , whereas that in patients without medial meniscal tears was 9.82.4. in contrast , the mean pts in patients with and without lateral meniscal tears was 10.62.9 and 10.52.8 , respectively . between the low group and high group , no significant differences were found with regard to age , sex , bmi , the interval from injury to acl reconstruction , with the exception of pts ( table 4 ) . the incidence of medial meniscal tears was 22.2% ( 30/135 ) in the low group and 56.4% ( 22/39 ) in the high group ( table 5 ) . the difference in the incidence of medial meniscal tears was significant between the two groups ( p<0.001 ) . prior studies have suggested several factors related to anterior tibial translation including axial loading , degree of knee flexion , and pts13 - 15 ) . allen et al.5 ) suggested that the meniscal wedge is the cause of medial meniscal tears in chronic acl - deficient knees . on the other hand , a more mobile lateral meniscus is less likely to undergo shear stress in the acl - deficient knees . the present study showed that the pts was larger in the knees with medial meniscal tears than those without , but the slope was similar between the knees with lateral meniscal tears and those with intact meniscus . although the pts was larger in patients with medial meniscal tears , this may not be clinically significant because of the relatively small difference in the mean pts . however , when we analyzed using a different method , the difference between the low and high group was significant . therefore , we concluded that a pts 13 is one of the risk factors for secondary medial meniscal tears in patients with acl deficiency . weiss et al.15 ) reported that acute stable peripheral meniscal tears with acute acl injury have potential for healing . an accentuated anterior tibial shift in knees with increased tibial slope would focus a great deal of stress at the medial meniscal tear site and possibly prevent spontaneous healing of a meniscal tear . thus , we suggest that pts is one of the considerations for determining early acl reconstruction to prevent secondary meniscal tears in patients with acl injury and intact meniscus . however , the present study has some limitations that require consideration . in order to know the exact time of meniscal injury , we need serial magnetic resonance ( mr ) images , including those taken immediately after trauma . unfortunately , most patients do not have mr images taken immediately after a traumatic event . also , other risk factors for secondary medial meniscal tears in acl - deficient knees such as repetitive injury and patient activity level were not considered in this study . a pts13 is one of the risk factors for secondary meniscal tears in chronic acl - deficient knees . therefore , we suggest that pts is one of the considerations for determining early acl reconstruction to prevent secondary meniscal tears in patients with acl injury and intact meniscus .

purposeto evaluate the incidence of meniscal tears in patients with chronic anterior cruciate ligament ( acl)-deficient knees , and to determine the influence of posterior tibial slope ( pts ) on medial meniscal tears in acl - deficient knees.materials and methodswe reviewed 174 patients ( 174 knees ) with a mean age of 30.7 years who underwent acl reconstruction for chronic acl tears . we divided the patients into two groups : low group ( 135 knees with a pts<13 ) and high group ( 39 knees with a pts13).resultsthe incidence of medial meniscus tears was 44% ( 77/174 ) , and that of lateral meniscus tears was 35% ( 61/174 ) . the mean pts in patients with medial meniscal tears was 11.43.0 , whereas that in patients without medial meniscal tears was 9.82.4. the incidence of meniscal tears was 57.8% ( 78/135 ) in the low group and 89.7% ( 35/39 ) in the high group ( p<0.001).conclusionsour data demonstrate that pts13 is a risk factor for secondary medial meniscal tears in acl - deficient knees . so , we suggest that pts is one of the considerations for determining early acl reconstruction to prevent secondary meniscal tears .

ectopia lentis can be congenital , acquired , isolated , or associated with systemic abnormalities such as marfan syndrome , homocystinuria , weill - marchesani syndrome , hyperlysinemia , sulfite oxidase deficiency , and ehlers danlos syndrome.13 several surgical techniques have been described for ectopia lentis in children . intracapsular and extracapsular extraction of the lens with anterior or posterior iol implantation and pars plana lensectomy with primary and secondary iol implantation are the current treatment options.14 however , difficulties in these cases may result in perioperative and postoperative complications such as crystalline lens dislocation , intraocular lens ( iol ) decentration , cystoid macular edema , uveitis , and retinal detachment.4 we present a case report of transient bilateral pupil closure following crystalline lens extraction and iris - fixated intraocular lens implantation in a patient with marfan syndrome . the best - corrected visual acuity ( bcva ) was 0.3 ( decimal notation ) in the right eye and 0.3 in the left eye . slit - lamp examination revealed an bilateral inferior dislocation of the crystalline lens [ figure 1 ] . intraocular pressure was 15 mmhg in the right eye and 13 mmhg in the left eye . the patient was fully informed about the nature of the procedure , its complications , and a written consent was obtained . preoperative photograph of the left eye showing the subluxated crystalline lens preoperatively , mydriasis was achieved with topical tropicamide ( tropamid , bilim , istanbul , turkey ) and phenylephrine 2.5% ( mydfrine , alcon , usa ) . the anterior chamber was filled with sodium chondroitin sulfate 4% , sodium hyaluronate 3% , and sodium hyaluronate 1% ( duovisc , alcon inc . , fort worth , tx , usa ) . , fort worth , tx , usa ) was injected into the anterior chamber to constrict the pupil . abbott park , il , usa ) was implanted in the anterior chamber with forceps and fixated to the iris with enclavation needles . the corneal wound was closed with 10 - 0 nylon sutures , and the viscoelastic material was aspirated . at the end of the surgery the pupils were round and 2 - 3 mm in diameter [ figure 2 ] . subconjunctival injection of gentamycin ( 1% ) and dexamethasone ( 0.4% ) were delivered at the end of surgery . photograph of the left eye at the end of the surgery at 1 day postoperatively the bcva was light perception in both eyes . slit - lamp examination showed total pupil closure in both eyes [ figure 3a ] . the intraocular pressure ( iop ) was 14 mmhg in the right eye and 16 mmhg in the left eye . b - scan ultrasonography was normal in both eyes . at this visit , topical tropicamid was instilled at 5-minute intervals three times . six hours later , the bcva improved to 0.5 in the right eye and 0.4 in the left eye and the pupil shape was normal bilaterally [ figure 3b ] . at 1 week the appearance of the left eye 1 day postoperatively photograph of the left eye after tropicamide therapy showing the normal pupil shape marfan syndrome is a connective tissue disorder that is caused by mutations in the fibrillin gene . fibrillin is widely distributed in ocular connective tissues such as iris , ciliary body , and ciliary processes.5 ocular abnormalities of marfan syndrome include subluxation of the crystalline lens , extreme myopia , and astigmatism.13 subluxated clear crystalline lenses are one of the most surgically challenging cases . in recent years , crystalline lens extraction with an aphakic iris - supported iol implantation in cases with subluxated lenses has become the favoured procedure.36 in our case , the lens and capsular bag was removed with a vitrector and an iris enclavated aphakic iol was implanted . however , the most frequent complications following iris - fixated iol implantation are an irregular pupil , damage to the endothelial cells , transient corneal edema , transient iop elevation , cataract formation , and iol decentration.78 lifshitz et al.3 reported four eyes with subluxated crystalline lenses and successfully implanted artisan ( ophtec bv , the netherlands ) aphakic iol . three of the eyes required intraoperative anterior vitrectomy and no complications such as irregular pupil were observed postoperatively.3 irregular pupil occurs in 0.4% to 1.2% of similar case postoperatively . this complication also can occur secondarily to chronic inflammation , atrophic iris changes , asymmetric enclavation , or dislocation of iris - fixated iols.3910 in the current case , we did not observe inflammation , asymmetric enclavation or iol dislocation . we believe that this pupil closure was caused by excessive mechanical effects of the iris - supported iol in the more flaccid iris tissue , related to marfan syndrome . although there is no support in literature , patients with marfan syndrome may have floppy iris especially after anterior vitrectomy . presumably , after implantation of an iris enclavated aphakic iol , an excessive and chronic traction of the haptic at the midperipheral iris might induce iris retraction and pupil closure . alternately , the effect of the carbachol on the iris could have caused pupil closure . these changes can be excessive in special conditions such as marfan syndrome due to characteristics of the iris tissue . therefore cases with marfan syndrome should be carefully monitored in terms of pupil changes after crystalline lens extraction and iris enclavated aphakic iol implantation .

a 16-year - old woman presented with marfan syndrome and bilateral ectopia lentis . the surgical treatment including removal of the crystalline lens and implantation of an iris - supported intraocular lens in both eyes at a week interval . postoperatively , the biomicroscopic examination showed total pupil closure bilaterally . after the topical tropicamide treatment , the pupil returned to normal shape .

streptococcus canis ( sc ) is a zoonotic pathogen that is transferred primarily from companion animals such as dogs and cats to humans through both animal bites and other mechanisms , and usually infects immunocompromised rather than immunocompetent hosts . this species has also been isolated from a variety of other animals , including cows , rats , mink , mice , rabbits , and foxes . sc strains are -hemolytic , and they appear as large white colonies surrounded by zones of complete hemolysis when cultured on sheep blood agar plates . furthermore , lancefield grouping , based on the composition of carbohydrate antigens in the cell wall , was used to classify sc as a group g streptococcus . the filamentous m protein is a major somatic virulence factor in group a streptococci , and the m - like protein produced by sc strains is thought to play a similar role in sc . we present the first reported human case of uncomplicated bacteremia following a dog bite , caused by sc harboring the scm gene , which encodes m - like protein . furthermore , we review published reports of the clinical and microbiological characteristics of sc infection in humans . a 71-year - old man was admitted to our hospital with swelling and redness in his right leg , complicated by fever and rigor . his underlying medical conditions included atrial fibrillation , hypertension , superior mesenteric vein thrombosis , liver cirrhosis ( lc ) following infection with hepatitis c virus . one year prior to admission , he had received the non - conjugated , pneumococcal polysaccharide vaccine because of the splenectomy . the patient was the owner of a dog that had become sick and had bitten his right leg several days previously . on admission to the emergency room , the patient exhibited a temperature of 40.2 c , blood pressure of 150/110 , a respiratory rate of 25 breaths / min , and an oxygen saturation of 94% ( equivalent to the ambient concentration ) , and he was tachycardic with a heart rate of 106 bpm . the clinical examination was unremarkable with the exception of a systolic murmur ( levine ii / vi ) at the apex and the remarkable swelling and redness of his right leg . the leukocyte cell count and c - reactive protein concentration were 8500/l and 0.30 mg / dl , respectively . transthoracic echocardiography showed no evidence of vegetation that might indicate endocarditis , and a computed tomography scan of the chest , abdomen , and pelvis revealed no evidence of infective foci . cellulitis was diagnosed and the intravenous administration of the antibiotic cefmetazole was initiated ( 4 g per day , administered as two 2-g doses ) ; however , concerns about severe infection were raised , because he had undergone a splenectomy . after admission , duplicate blood cultures revealed the presence of gram - positive cocci , and the cefmetazole treatment was replaced by the combined intravenous administration of ampicillin ( 12 g per day , administered as six 2-g doses ) and clindamycin ( 1800 mg per day , administered as three 600-mg doses ) . the patient - origin samples were cultured on a sheep blood agar plate for 24 h at 35 c in 5% co2 , resulting in the growth of large , smooth , white , non - mucoid -hemolytic colonies with group g carbohydrate antigens ( fig . the infecting species was matched to sc with 99.9% probability , using a rapid i d 32 strep api system ( sysmex biomrieux co. ltd . , unfortunately , the dog died from the disease and the sc strain could not be isolated from the dog . the isolate from the patient was stored at 80 c for further characterization . in summary , the patient was diagnosed with uncomplicated bacteremia caused by sc , and was treated with a 2-week course of combined ampicillin and clindamycin therapy at set doses . the treatment was successful , and the patient remained well with no recurrence of bacteremia during the 4-month follow - up period . the phenotypic and genotypic characteristics of the isolate were determined , and are summarized in table 1 . the identification of the isolated species as sc was confirmed by sequencing the 16s rrna ( read length 1426 bp ) ; the isolate displayed 99.02% identity to sc strain atcc 43496(t ) . furthermore , it was possible to amplify the cfg gene , encoding a camp factor co - hemolysin found in sc , from the extracted dna . additionally , it was possible to detect the presence of a scm gene , encoding the major virulence factor m - like protein ; the amplified sequence ( read length 912 bp ) was closely related to scm from other two sc strains : 321 324a ( accession no . 2 ) . multilocus sequence typing ( mlst ) was performed by cross - referencing the sequences of 7 housekeeping genes ( gki , gtr , muri , muts , recp , xpt , and yqiz ) from our isolate with those registered into the sc mlst database ( http://pubmlst.org/scanis/ ) . the isolate was found to be a sequence type ( st ) 9 strain , possessing the allelic profiles 3 , 5 , 3 , 3 , 1 , 2 , and 3 for each of the seven genes , respectively . antimicrobial susceptibility assays revealed that the sc isolate was susceptible to penicillin , cephalosporin , tetracyclines ( tcs ) , glycopeptides , lincomycins , sulfamethoxazole / trimetoprim , chloramphenicol , and fluoroquinolones . susceptibility to macrolides was mixed , as the isolate was susceptible to erythromycin but not to azithromycin : its susceptibility was intermediate . it should be noted , however , that the breakpoints of antibiotic concentrations used to determine susceptibility were those for viridans group streptococci , since no breakpoints for sc are described in the clinical and laboratory standards institute guidelines . while this susceptibility testing suggested that the isolate might be resistant to azithromycin , our pcr - based results indicated that this isolate did not possess the macrolide / lincosamide ( ml ) resistance genes , erm(a ) , erm(b ) or mef(a ) . to the best of our knowledge , this is the first reported human case of uncomplicated bacteremia caused by an st9 sc harboring the scm gene . the m - like protein expressed by the scm gene is a novel virulence factor with possibility of anti - phagocytic activity . additionally , this protein acts cooperatively with enolase to bind to the c - terminal mini - plasminogen region of plasminogen , recruiting the latter to the bacterial surface and enhancing the transmigration and survival of the bacterium , . however , not all sc strains isolated from animals possess the scm gene ; one study detected the scm gene in only thirteen of nineteen strains examined ( 68.4% ) . consistent with this result , a separate study found that 90.0% of canine and 83.3% of feline sc strains harbored the m - like protein . in this study , it was not possible to isolate and identify the sc strain directly from the pet dog of the patient , since the dog died from the illness while the patient was hospitalized , and we need to confirm the presence of the scm gene among sc strains prospectively recovered from companion animals in japan . the mlst method for typing sc strains has been established , and st9 was found to be the most prevalent type among the 85 sc isolates ( 23/85 ; 27.1% ) , including among strains originating in humans ( n = 5 ) . according to information in the mlst database , st9 strains are isolated from cats , dogs , and cows from germany , portugal , and the us . reported sources of st9 sc isolates were skin and soft tissue exudate , vaginal exudate , ear exudate , urine , and others . several human infections with the st9 , the prevalent st , originating from portugal , are registered into the database ; the tissue sources of infection were skin and soft tissue exudate , respiratory tract secretions , and blood specimens . the human cases caused by other sts 2 , 3 , 4 , 12 , and 14 also originated in portugal and the us . in this case study , we describe a human infection with a pathogenic st9 sc strain harboring the scm gene , and in future it will be interesting to analyze the relationship between the presence of the scm gene and the st of the sc strains isolated from companion animals and humans in japan . the isolate in this case did not possess the ml - resistance genes , erm(a ) , erm(b ) , or mef(a ) , although azithromycin was not effective against this bacterium . previously , resistance rates of 27% against tc and 10.8% against ml were reported among 37 sc strains isolated from dogs between 2000 and 2005 . additionally , the presence of the resistance genes tet(m ) or tet(o ) alone , or combinations of resistance genes [ tet(m)/tet(l ) , tet(l)/tet(s ) , and tet(o)/erm(b ) ] have been detected in tc - resistant sc isolates ( n = 23 ; resistance rate , 27% ) . therefore , ml- and/or tc - resistance should be considered when antimicrobials are found to be ineffective in veterinary clinical practice . sc infection is rare , but host characteristics linked to susceptibility to infection , including the immunity , have been described previously . in humans , underlying medical conditions , particularly diabetes mellitus , can increase the susceptibility , as can a compromised immune system , . on the other hand , the presence of virulence factors could enhance the potential infectivity with sc ; we have described the presence of the m - like protein virulent factor in this case , but it is possible that other virulent factors might enhance sc pathogenesis in immunocompetent individuals , and their investigation using comprehensive approaches including genome sequencing and proteomics will be important in the future . the entry site of sc into human host should also be considered . most cases of sc infection , except for dog bites , originate in pre - existing wounds and skin ulcers , . notably , however , ohtaki and colleagues recently reported the first documented human case of sepsis caused by sc without a dog bite in japan . while the entry mechanism remains unclear , we speculate that the pathogenic sc , which may be resident at / around the oropharynx , skin , genitourinary tract , and anal tract , seem to invade the host through invisible wounds on human skin , . companion animals kept in households are hugely important to individuals of all ages in japan , so much so that some human hospitals have introduced animal - assisted therapy to improve the mental health of human patients . therefore , when presented with feverish patients who maintain close contact with these animals , clinicians should consider infection with sc as well as with pasteurella sp . , prevotella sp . furthermore , since an animal s life is completely controlled by its human owner , the one health concept , which recognizes that human health and animal health are connected , should be employed to study the crosstalk concerning bacteria , including sc , that infect both humans and animals , to maintain their future health .

highlightsthis is the first reported human case of bacteremia caused by streptococcus canis having scm gene encoding m - like protein.the identity was based on similarity of its 16s rrna and detection of the specific cfg gene encoding a co-hemolysin.this isolate was confirmed to be sequence type 9.this strain did nt have the erm(a ) , erm(b ) , or mef(a ) , macrolide resistance genes , but was not susceptible to azithromycin .

many pregnant women around the world eat diets that are nutritionally inadequate , and result in undernourished infants who are at greater risk for health problems later in life . infants should be exclusively breastfed for the first six months of life to achieve optimal growth , development and health . thereafter , to meet their evolving nutritional requirements , infants should receive nutritionally adequate and safe complementary foods , while continue to be breastfed for up to two years or more . the 2006 - 2007 pakistan demographic and health survey ( pdhs ) was designed to provide data for monitoring the health situation in . the survey , showed that the infant mortality rate in pakistan was 78 deaths per 1,000 live births , which was higher than those in nepal ( 48 in 1,000 live births ) , india ( 57 in 1,000 live births ) and bangladesh ( 65 in 1,000 live births ) . the leading causes of infant death were sepsis and infections ( 38% ) followed by asphyxia ( 22% ) . breast feeding plays an important role in the life of an infant as it is not only a source of nutrition , but also derives and strengthens the baby s immunity and response . the survey , also highlighted that in pakistan exclusive breast feeding for 6 months was only 37% of which only 55% continue to breast feed for 2 years . world health organization stresses the need of breast feeding by reiterating that about 33% of infant deaths are preventable with the introduction of exclusive breast feeding initiated within an hour of delivery and continued for at least 6 months . with improvement in neonatal survival , due to obstetricians ' choice and failure of induction at early gestations the common mode of delivery at these gestations is cesarean . these factors along with newer surgical and anesthetic skills have made cesarean to be a safer method of delivery than previously thought . the safety of cesarean has resulted in a rise in the rates of cesarean delivery , and more and more patients and doctors feel more comfortable with it . operative delivery has great psychological impact , and not only the patient and her family , but sometimes even the doctor becomes less motivated to initiate breast feeding . prolonged periods of separation between babies and mothers , which are due to anesthesia , baby being kept in nursery , or mother being sedated for pain and unable to feed can lead to poor maternal milk surge . poor maternal milk surge results in a vicious cycle of less milk , baby being hungry and irritable , and mother too exhausted to put in an extra effort . these factors lead to the failure of breast feeding rates , and in a larger perspective , result in infant morbidity , mortality and malnutrition . the objective of the present study was to evaluate the effects of mode of delivery on maternal initiative to breast feed . this study was conducted in a period of two years ( 2008 - 2009 ) in the department of obstetrics and gynecology at shifa international hospital and shifa foundation community health centre , islamabad , pakistan . all mothers delivering live babies irrespective of gestation , mode of delivery , and babies ' weight were included in the study . women who were extremely sick including those with acute heart failure or eclampsia , those who delivered a dead baby or the babies who required ventilatory support , because they were very sick or severely malformed , were excluded . two lady health visitors ( lhvs ) trained as lactation counselors , routinely saw all mothers delivering in the hospital within two hours of their delivery . after obtaining participants ' consent and through interview the counselors filled in a questionnaire containing questions regarding the mothers , their modes of delivery , problems with feeding their baby along with time taken to resolve the problem . applying the inclusion and exclusion criteria , the data of 2500 women were entered in statistical package for social sciences ( spss , version14 ) for analysis . a comparative analysis between feeding problems of women delivering vaginally was done with those undergoing cesarean delivery . chi square test was used to calculate odds ratio and compare various demographic factors between the groups . vaginal delivery took place in 54% of the cases and was inclusive of vaginal vertex , breech delivery and instrumental ( vacuum and forceps ) delivery . when they were matched for the mode of delivery , 58% of women with feeding problems belonged to the cesarean delivery group and 42% of complaining mothers had vaginal delivery . the relative risk of cesarean to have problems with breastfeeding was 1.38 and the odds ratio was 0.61 . the number and ( rate ) of women with and without feeding problems of their babies based on the mode of delivery of their babies . women coming from rural background comprised of about 40% of the total cases and the overall educational status of the study group showed that 58% mothers had attained education above secondary school ( table 2 ) . when the various lactation problems were analyzed , it was seen that the two most common maternal complaints regarding feeding were problem with position of the baby inside the womb ( 52.6% ) and a feeling that not enough milk for baby was being produced ( 25.3% ) ( table 3 ) . the odds ratio and 95% confidence interval for mode of delivery ( vaginal versus cesarean ) , cohort of no lactational problem and cohort of any lactational problem in our study we saw that despite adequate analgesia and the patient subjectively feeling pain free and comfortable , there was a statistically significant difference between the breast feeding rates of women delivering vaginally as compared to those delivered through cesarean section . the number and ( rate ) of lactation problems stratified based on the modes of delivery . nem ; not enough milk , bdtf : baby does n't take feed , cn : cracked nipples , in : inverted nipples , eb : engorged breast , pwp : problem with positioning , mnitf : mothers not inclined to feed risk estimate ( odds ratio with 95% confidence interval ) for the mode of delivery ( cesarean vs. vaginal ) , the cohort of no lactation problem and cohort of any lactation problem . fifty eight percent of women with feeding problems belonged to the cesarean delivery group and 42% of complaining mothers had vaginal delivery . the relative risk of cesarean to have problems with breastfeeding was 1.38 and the odds ratio was 0.61 . ( in our hospital as per policy all women are encouraged to breast feed as soon after delivery as possible . ) after excluding cases that had complications causing mother baby separation , the group we studied was divided on the basis of their mode of delivery as rest of the characteristics were the same . after obtaining participants ' consent and through interview the counselors filled in a questionnaire containing questions regarding the mother , her mode of delivery , problem with feeding her baby along with time taken to resolve the problem . this showed that the women who had cesarean had more complaints , needed greater counseling , and even than the prevalence of breast feeding in that group was lower as compared to the vaginal delivery group . women delivering their babies by cesarean section run a 1.38 fold greater risk of having problems with breastfeeding in comparison to women delivering theirs vaginally . one of the factors affecting this rate is the improvement of neonatal survival at earlier gestations ( 26 weeks pregnancy and more ) , which has resulted in increased number of pre - mature births . these premature births may be triggered by fetal factors including severe oligohydramnios , reversed doppler flows or hydrops fetalis , or maternal factors such as eclampsia , antepartum hemorrhage or cardiac diseases . it is well - understood that vaginal delivery at gestations with a compromised baby or mother , similar to such situations , may become difficult , and lead to increased proportion of cesarean sections . cesarean section in turn effect the maternal initiative to breast feed , as 97.5% of women who did not feel inclined to breast feed in our study was from the cesarean group . a norwegian study , reported that the increased rate of caesarean sections depended on both medical and non - medical factors . among the medical factors were increases in maternal age and body mass index , as well as changes in obstetric practice and technology . non - medical factors included caesarean section requested by the mother , fear of litigation among caregivers , and inappropriate organization of maternity care . caesarean sections were associated with maternal postpartum morbidity , child postpartum respiratory morbidity , less breastfeeding and possibly more atopic diseases . the findings of the present study showed that women with cesarean deliveries had a definitely greater chance of having problems with breastfeeding . the odds ratio for women with cesarean deliveries was 0.61 for having any problem with feeding the baby . similarly , qiu et al . concluded that the adjusted odds ratio for exclusive breastfeeding in caesarean section deliveries in urban and suburban mothers was 0.64 ( 95% ci : 0.46 - 0.88 ) . caesarean section was increasingly being used for routine deliveries in china , and mothers who had an operative delivery had lower rates of exclusive breastfeeding on hospital discharge . this study did not find a statistically significant difference between women delivering their babies by vaginal delivery or cesarean in terms of the problem of not enough milk(n=232 vs n=213 ) . wang and colleagues found that there was a significantly lower postpartum serum prolactin ( prl ) levels in the caesarean group ( 8.48 nmol / l , 95% ci : 7.80 - 9.21 nmol / l ) compared with the vaginal delivery group ( 9.61 nmol / l , 95% ci : 8.99 - 10.26 caesarean section was an important hazard for a shorter duration of breastfeeding ( rr=1.21 ; 95% ci : 1.10 - 1.33 ) within one year after childbirth . the present study also showed that there was a greater degree of apprehension among patients and her relatives in the cesarean group as it is regarded as an abnormal form of delivery , which leads to lower rates of breastfeeding . the problems recorded by the lactation assistants in the cesarean group were most commonly being unable to position herself and the baby correctly(54.6% ) followed by the problem of not enough milk for the baby ( 21% ) and mother not inclined to feed ( 15.2% ) . the problems with positioning were basically as the patient felt that sitting for too long will hamper healing in her stitches and the fear that the baby might kick and spoil her stitches . we felt that even in the educated women , in whom 44.4% of the cesarean deliveries had more than secondary education , there was a need for repeated and longer counseling to overcome their issues related to breastfeeding in the cesarean group . the mean counseling time for cesarean deliveries was 35 minutes as compared to 18 minutes for vaginal deliveries . the women delivering vaginally had the confidence that every thing had gone normally , and were more keen to initiate immediate feeding and handling of their babies . there is a proportionately increasing trend of bottle feeding with the increases in the rates of cesarean section . in developing countries infant feeding practices play a crucial part in the health and immunity of the baby . there is a need to re - emphasize the role of breastfeeding in woman undergoing cesarean delivery to improve infant health and nutrition .

breast feeding has a great impact on the infant morbidity and mortality . according to pakistan demographic and health survey ( pdhs ) infant mortality rate is 78 deaths per 1,000 live births . world health organization recommends that exclusive breast feeding for six months can decrease infant mortality rate by one - third . the objective of the study was to find out how the mode of delivery had impact on the practice of breast feeding . data were collected for 2500 consecutive patients during a period of two years , and it was seen that maternal initiative to breast feed was low and problems with lactation were much more in cases delivering their babies via cesarean sections than those delivering theirs by normal delivery . vaginal and cesarean section deliveries took place in 54% and 46% of the case , respectively . thirty percent of the women studied felt that they had no problems regarding breastfeeding , but 70% of them had some sort of problems with breastfeeding their babies . when the women were matched for the mode of delivery , 58% of women who had breastfeeding problems belonged to the cesarean delivery group and 42% of complaining mothers were from women with normal delivery . the relative risk of having problems with breastfeeding for women subjected to cesarean was 1.38 and the odds ratio was 0.61 . the findings of the present study indicate that more in depth counseling sessions are required for women undergoing operative delivery to improve breast feeding among them .

host - seeking mosquitoes were collected in and around grand forks , north dakota , by using mosquito magnet traps ( american biophysics corp . , north kingston , ri , usa ) for 4 transmission seasons , from early summer 2002 through fall 2005 . mosquitoes were sorted by species and tested for wnv by using reverse transcriptase pcr assays . passerine birds in and around grand forks were surveyed for antibodies to wnv for 3 transmission seasons : june 24october 27 , 2003 , april 4july 7 , 2004 , and may 17august 11 , 2005 . in 2003 and early 2004 , birds were captured by using mist nets , blood ( < 0.1 ml ) was obtained by brachial venipuncture , and birds were released . later in 2004 and in 2005 , necropsies were performed on dead birds . samples were tested for anti - wnv antibodies by using a qualitative epitope - blocking elisa ( 3 ) . this is the first report of seroprevalence of wnv in passerines in the northern prairies . a total of 277 birds ( 11 species ) were tested ( table 1 ) . in 2003 , seroprevalence was relatively low ( 17% ) . the first seropositive bird was captured july 24 , 2003 , 4 days after the first wnv - positive pool of cx . most seropositive birds ( 11 of 14 ) were collected in september , when migratory species were leaving and vector populations were waning . thus , a lag occurred between peak abundance of infected vectors in mid- to late august 2003 ( 2 ) and seroconversion of passerines . seroprevalence rates were significantly higher in 2004 and 2005 than in 2003 ( table 1 , fisher exact tests , p<0.0001 ) and were higher than most seroprevalences reported for passerines in the eastern and southeastern regions of the united states ( 46 ) . all passerine species sampled in 2004 and 2005 contained seropositive birds , which indicated that all these species were preyed on by vectors regardless of differences in their nesting habitats ( e.g. , cattail marshes , peridomestic ) . american robins , common grackles , and red - winged blackbirds showed increased seroprevalence from 2003 to 2004 . high seroprevalence was maintained in passerines in 2005 despite low wnv activity ( i.e. , low natural boosting ) during 2004 ( 2 ) , which suggests that passerine immunity to wnv may last longer than a single season ( 7,8 ) . previous laboratory and field studies have indicated that most american crows die so quickly from wnv infection that they never have time to seroconvert ( 911 ) . why crows in the red river valley survive wnv infection is not known . one possibility is that wnv has undergone genetic changes with a concurrent loss in virulence as it spread westward from forest ecosystems with cx . annual data on seroprevalence in passerines , environmental temperatures , reporting of human cases , and minimum infection rates ( mir ) in vector populations are summarized in table 2 . time between first and last appearances of host - seeking culex tarsalis mosquitoes in mosquito magnet traps . data from north dakota department of public health ( 15 ) . # no . of wnv - infected cx . environmental conditions from 2002 to 2005 produced a natural field experiment , which demonstrated the differing magnitudes by which environmental temperature and host immunity affected local wnv activity . despite warm temperatures and high vector abundance , wnv activity was low during its introductory year ( 2002 ) , as indicated by low numbers of human cases , undetectably low seasonal mir , and by low seroprevalence in passerines in 2003 . because wnv had only recently arrived , presumably there was neither sufficient time nor number of infection nidi to promote extensive amplification cycles . however , 2003 was an epidemic year for wnv , as indicated by the increased number of human cases statewide and the high mir in the local vector population . the relatively low level of immunity in passerines at the time also likely contributed to the epidemic . in 2004 , unusually cool environmental temperatures prolonged vector larval development , adult emergence , and the arboviral extrinsic incubation period . as a result , duration of the 2004 transmission season was nearly half that of the preceding seasons ( table 2 ) . thus , wnv activity during 2004 was low ( i.e. , reduced vector abundance , number of human cases , and seasonal mir ) , and the virus had insufficient time to undergo extensive amplification cycles , similar to the situation that occurred during the introductory year of 2002 . however , the epidemic conditions of 2003 had produced a high level of herd immunity in the local bird population in 2004 . ( note : most migratory passerine species live for several years and return each year to the same general locale to breed . ) in 2005 , environmental temperature , length of transmission season , and vector abundance were all nearly identical to those of the epidemic year of 2003 . yet the high prevalence of immunity during 2005 may have contributed to preventing another epidemic , but it did not totally eliminate wnv activity . levels of wnv activity during 2005 ( as measured by human cases and mosquito mir ) were intermediate between those of the epidemic year ( 2003 ) and both the introductory year ( 2002 ) and the coldest year ( 2004 ) . thus , environmental temperature dictated the ultimate success ( or more precisely , the failure ) of wnv amplification within the central red river valley during 2004 , whereas even high levels of herd immunity among the reservoir population exerted only a moderating effect on wnv activity during 2005 . whether the level of wnv activity observed during 2005 will be representative of the arbovirus 's natural equilibrium within the central red river valley remains to be seen . is wnv reintroduced every spring through infected migratory birds or wind - blown mosquitoes from the south ? or does wnv survive the harsh winters inside mosquitoes undergoing diapause , only to reemerge in the spring ? either or both of these scenarios could be correct , but one conclusion is certain : the incidence of wnv disease in horses from north dakota during june of 2002 and again in may of 2005 ( 15 ) indicates that wnv becomes active in the northern great plains well in advance of the first summer brood of its primary vector , cx .

west nile virus ( wnv ) epizootiology was monitored from 2002 through 2005 in the area surrounding grand forks , north dakota . mosquitoes were tested for infection , and birds were surveyed for antibodies . in 2003 , wnv was epidemic ; in 2004 , cool temperatures precluded wnv amplification ; and in 2005 , immunity in passerines decreased , but did not preclude , wnv amplification .

vertebral hemangiomas are common benign lesions of the spinal column usually asymptomatic and are discovered incidentally or found during evaluation of neck or back pain.13 they comprise 12% of the benign tumors affecting the general population.47 they are congenital vascular malformations and not true neoplasms . they consist of remnants of embryonic capillaries and veins , but unlike congenital vascular malformations , arteriovenous shunting does not occur in these hemangiomas . rarely they may enlarge and cause pain and neurological deficit because of spinal cord compression , vertebral body or arch expansion , or pathological fracture . plain spine films often suggest the diagnosis of vertebral hemangiomas by the presence of coarse vertical striations ; however , one - third of the vertebral body must be involved for these findings to be evident . computed tomography ( ct ) scan helps in determining the extent of vertebral involvement and magnetic resonance imaging ( mri ) provides information regarding the aggressiveness of the disease . treatment options for symptomatic vertebral hemangiomas include transarterial embolization , surgical excision , radiotherapy , and percutaneous injection of alcohol or methyl methacrylate . embolization alone is not quite effective in the treatment of symptomatic hemangiomas causing compression of the neuraxis . nowadays , preoperative embolization followed by surgical excision is the preferred treatment modality in many centers . radiotherapy may be successful in obliterating the hemangiomas , but the effect may be too delayed for patients with cord compression.89 we have analyzed seven cases of vertebral hemangiomas causing significant cord compression and features of myelopathy . the problems of differential diagnosis in such cases , their surgery and postoperative management are discussed in this article . we retrospectively collected the data of patients of symptomatic vertebral hemangiomas with neuraxial compression that were managed from 2006 to 2009 and have a followup at our institute . patients were evaluated for clinical features such as backache , radiculopathy , myelopathy , sensory deficits , and bowel/ bladder involvement . the patient who opted for other treatment modalities such as embolization or percutaneous ablation a total of seven patients were analyzed preoperatively according to frankel grading system [ table 1 ] and compared with the postoperative status . frankel grading system postoperatively , x - ray was done in all cases to assess the adequacy of decompression and instrumentation . all patients were assessed in the wards postoperatively and long term followup was obtained in the outpatient departments or on regular correspondence . followup was done regularly at 3 months , 6 months , 12 months , and then yearly . the clinical signs developed insidiously in two patients and rapidly in five patients ( 35 months ) . grossly the motor power was mrc grade 0 in three patients and grade 34/5 in the remaining four patients . bowel and bladder involvement in the form of urinary retention and constipation was present in three cases . the paralysis was graded by frankle grade c. all patients were evaluated radiologically with x - rays and mri . the thoracic vertebrae were involved in five and lumbar vertebrae in two of the patients . radiology revealed complete destruction of the vertebral body in all seven cases with destruction of posterior elements in one of them . t1-weighted images revealed isointense changes in the destroyed vertebral bodies in three patients and hyperintense changes in four patients . all were associated with epidural soft tissue changes with extension and compression onto the thecal sac . clinical profile of patients all these cases were treated surgically and we used a retroperitoneal approach in two lumbar lesion and transthoracic approach in five of the cases . excision of the vertebral bodies was done in the seven cases and all had brisk bleeding during surgery . the blood loss ranged from 1.5 to 3 l. the loss was adequately and immediately replaced with blood and fresh frozen plasma . after excision of the vertebral bodies , the dura was seen thoroughly superiorly , inferiorly , and laterally , indicating adequate decompression . these patients underwent instrumentation in the form of caging and stabilization with screws in the vertebral bodies and rod construct . two patients had abnormal bleeding parameters postoperatively , but were corrected with fresh frozen plasma and vitamin k. at average followup of 24 months , their comparison showed significant improvement in their neurological status [ table 3 ] . pre and postoperative frankel grading it was found that of the three patients who had a grade a preoperatively , two improved to grade c and one to grade b postoperatively . one patient who had grade b preoperatively improved to grade d. three patients who had grade c preoperatively improved to grade e in two patients and grade d in one patient . four patients had features of intercostal neuralgia , but it gradually resolved over a week following surgery . postoperative radiology taken on the third and twelfth month after surgery showed the stability of implants and grafts and no spinal deformation was noticed . there was no mortality , and in all cases , the biopsy showed features suggestive of hemangioma . vertebral ( intraosseous ) hemangiomas account for 2.3% of spinal tumours and are benign vascular tumors composed of proliferation of blood vessels . they are classified histologically by the predominant type of vascular channel as capillary , cavernous , arteriovenous , or venous type . they usually have an indolent course , but may cause pathological fractures , hemorrhage , extraosseous extension into the paravertebral space , and rarely , epidural extension . spinal cord or cauda the thoracic region is the most common site for vertebral hemangiomas presenting with features of spinal cord compression.1012 causes of neural compression include : ( 1 ) expansion of the involved vertebrae , ( 2 ) extension of the tumor into the extradural space , ( 3 ) compression fracture , and ( 4 ) hemorrhage resulting in extradural hematoma.13 of these , the first two are the most common mechanisms . however , in our series , the mechanism was compression fracture of the vertebrae and extension of the tumor into the epidural space leading to spinal cord compression . since all patients presented with features of vertebral collapse , they underwent investigations to rule out metastatic , tubercular , or osteoporotic etiology , but all were inconclusive . though vertebral hemangiomas have typical x - ray and mri findings , these were lacking in our cases probably because of the soft tissue component predominating in advanced stages of the disease . it is important to realize that by the time compressive collapse occurs , the classical radiology of vertebral hemangioma is quiet difficult to be demonstrated . hence , the differential diagnosis of other epidural compressive lesions such as pott 's spine , metastases , and bony neoplasms must also be borne in mind . they tend to erode the horizontal trabeculae of the vertebral bodies , thus leading to the appearance of accentuated , thickened vertical trabeculae , giving rise to corduroy or jailhouse striation appearance in lateral x - ray or sagittal ct scan.14 in axial ct scans , they give the appearance of a polka - dot or spike of bone pattern because the vertical trabeculae are imaged in cross section.15 mri may provide additional information regarding the aggressiveness of the hemangioma . increased fatty signals with mottled appearance on both t1- and t2-weighted images are suggestive of non - evolving intraosseous lesions [ figure 1a , b ] . conversely , osseous or extraosseous hemangiomas that are isointense on t1-weighted images are commonly found with symptomatic lesions . laredo concluded that fat - intensity lesions are generally inactive , while hemangiomas demonstrating low or isointense signal on t1-weighted images indicate a hypervascular lesion with the potential to compress the spinal cord.16 this was true in five of our cases where t1-weighted images were isointense [ figure 2a , b ] . another interesting feature noted was that all patients who had t1 isointense changes had a short duration of symptoms . this indicates that t1 isointensity to a certain extent helps in predicting the aggressive potential of the lesion . ( a ) sagittal t2wi showing l1 collapse with hyperintensity changes within the vertebral body and compression on the thecal sac . ( b ) sagittal t2wi showing hyperintensity changes with extradural soft tissue component causing thecal sac compression at l1 level ( a and b ) sagittal images with t1 isointensity and t2 hyperintensity changes within the l1 vertebral body with significant extradural soft tissue component . this patient had a short duration of symptoms treatment options for symptomatic vertebral hemangiomas include surgery , transarterial embolization , direct ethanol injection , and vertebroplasty ; each with varying degrees of success.1719 surgery is indicated when there is significant or progressive neurological deficit . surgical options include corpectomy or vertebrectomy if there is significant vertebral body involvement with epidural extension causing spinal cord compression . patients undergoing corpectomy are subjected to instrumentation to provide spinal stability.6720 in our series , patients underwent caging and pedicle screw instrumentation in six patients and only pedicle screw fixation in one of them [ figure 3a , b ] . surgery was encountered with significant bleeding ranging from 1.5 to 2.5 l in all these patients . but with timely replacement of the lost blood volume , surgery could be continued and adequate excision achieved . all patients were replaced adequately and timely with fresh frozen plasma , blood , and colloids . patients were regularly followed up for a period of 2 years with periodic radiological investigations . postoperative radiology revealed the screws well in place with adequate canal decompression [ figure 4a , b ] . anteroposterior and lateral postoperative x - rays ( a and b ) showing adequate excision of the vertebral bodies and instrumentation intraoperative images showing ( a ) the gutter created after adequate excision of the vertebral bodies . ( b ) cage filled with autograft placed in the gutter created after excision of the vertebral hemangioma endovascular embolization has also been used by some as a sole therapy for vertebral hemangiomas.21 hekser et al . were the first to report reversal of spinal cord compression following percutaneous embolization of feeding vessels.22 however , this may not be helpful in the setting of acute spinal cord compression and neurological deterioration . embolization followed by surgery is another option that is highly propagated in the present era . however , there are reports where preoperative embolization failed to reduce the intraoperative blood loss . this is due to the fact that though transarterial embolization may occlude the feeding vessels , it may fail to destroy the hemangioma due to an intervening capillary bed that separates the hemangioma from the arterial feeders . reflux of the embolization material into the lumbar and intercostal arteries may occur and this may lead to spinal cord infarction with severe pain and paresis.23 in case of recurrent or residual disease , a second attempt is not possible because feeding arteries have already been occluded . at our institute , we attempted preoperative embolization in two patients , but could not succeed because the vertebral bodies were collapsed and converted into a solid mass . considering the impact of neuraxial compression , we felt it unwise to subject the patient to multiple treatment modalities , and hence direct surgery was adopted in all our patients . radiation therapy is also an effective mode of treatment , especially in lesions associated with pain . vertebral hemangiomas are radiosensitive tumors and reports have shown symptomatic improvement following radiotherapy.24 however , the effects of radiotherapy are delayed and radionecrosis of the spinal cord and vertebral bodies still remains a risk . percutaneous ablation with ethanol or methyl methacrylate constitutes some of the newer options in the treatment of vertebral hemangiomas . this leads to devascularization of the hemangioma , and thereby reduces its size alleviating the cord compression . however , for its success , it is necessary that the ethanol is injected into the vascular spaces of the hemangioma . this is critical in elderly patients as bone is quiet fibrotic and the vascular component of the hemangioma may be small . moreover , the technique seems to be cumbersome as the needle has to be localized with the help of prior and intraoperative angiography . goyal et al . in their study of 14 patients suffering from symptomatic vertebral hemangiomas reported neurological deterioration in three patients.25 one developed infection due to extravasation of contrast material into paraspinal tissues , another a recurrence at 1 month followup , and the third patient developed vertebral fracture 5 months following the procedure . niemeyer et al . have reported a case of brown sequard syndrome following alcohol ablation.26 alcohol ablation deals with the vertebral hemangioma per se , but does not restore the strength of the vertebral body that has been fractured . injection of methyl methacrylate is usually performed under fluoroscopic guidance and is indicated for stabilizing vertebral bodies at risk for collapse or to reduce pain . however , when a patient is paraparetic , methyl methacrylate may extend into the spinal canal and exacerbate spinal cord compression that is already present . in such cases , however , surgery with adequate blood replacement can be done in some cases . in others , though the treatment modalities are many and have their own pros and cons , to use them singly or in combination is a difficult decision to be taken by the treating surgeons .

background : hemangiomas are benign vascular tumors associated with proliferation of blood vessels in bone or soft tissue and they are usually incidental findings in vertebrae . when symptomatic , they present with features of radiculopathy , myelopathy , or vertebral fractures . treatment options are varied , include sole embolization , embolization combined with surgical excision , surgical excision alone , percutaneous ablation , and radiotherapy . we hereby describe a series of seven cases of symptomatic vertebral hemangiomas operated from 2006 to 2009.materials and methods : their clinical and radiological profile and outcome have been described . all patients were subjected to surgical excision followed by instrumentation . outcome was assessed at a followup of 2 years following surgery with frankel grading system.results:seven patients ( five females and two males ) were included in the study . the mean age was 33.85 years with the mean duration of symptoms of 12 months . all seven cases were symptomatic vertebral hemangiomas with cord compression and underwent surgical excision . preoperatively , patients with poor frankel grade such as a and b improved postoperatively to c , d , or e.conclusion:surgical excision of these lesions is difficult due to the tremendous amount of intraoperative bleeding . during surgery , brisk bleeding is usually encountered , but can be brought under control with adequate preoperative preparation and expertize . preoperative embolization may help to reduce the bleeding , but at times it may be difficult to do if vertebrae are replaced by a solid hard mass . in spite of the risks associated with surgery , it still is the treatment of choice as a single intervention , especially in aggressive vertebral hemangiomas .

iron deficiency anemia ( ida ) is prevalent and a major public health care issue [ 1 , 2 ] . ida has been associated with motor and cognitive developmental deficits in children and may be irreversible [ 37 ] . ida may have an even greater impact on select populations who are already at risk for intellectual and developmental compromise . down syndrome ( ds ) is the most common human aneuploidy with an approximate incidence of one in 800 live births . clinical manifestations of ds include cognitive impairment , craniofacial dysmorphism , gastrointestinal tract abnormalities , congenital heart defects , endocrine abnormalities , immunologic defects , and neurologic deficits associated with early onset dementia . regarding the hematopoietic system , children with ds frequently show macrocytosis , abnormalities in platelet counts , and an increased prevalence of leukemia [ 913 ] . similar to the general population , individuals with ds may be at risk for ida and its consequent complications . those studies which have been published often focused on a select population of children with ds and may not be representative of the general ds population . for example , awasthi et al . investigated the hematological profile of patients with ds who presented with initial manifestations of a hematological disorder to a genetics clinic . of the 239 children with ds who were examined over a 10-year period , 6.2% were found to have a hematological disorder . of those 6.2% only 4 of the 239 children in the study ( 1.7% ) were found to have anemia . these tests revealed the prevalence of anemia to be no different from the general neonatal population . the authors suggested that anemia in this age group may be more of a reflection of either maternal iron stores or delivery - related newborn blood losses . performed blood counts and iron studies on 114 children with ds and found ida in 3% and i d in 10% , comparable with their prevalence in the general pediatric population . the paucity of data on the prevalence of anemia in ds patients of different age groups and the deleterious consequences associated with ida lead us to investigate the prevalence of anemia in this population and the specific risk factors associated with ida in children with ds . during 20042007 , 149 children and young adults with ds were seen at the center for down syndrome at the hadassah mount scopus university medical center , and these individuals were included in the study . the center for down syndrome serves the entire population of israel , and patients from the predominantly arab neighborhoods of east jerusalem are actively recruited as part of a cooperative ( israeli / palestinian physicians ) community - based program to enhance the care of children with ds from all ethnic backgrounds . as such , the center 's patient population is representative of the general population of the region . the study protocol was approved by the hadassah - hebrew university institutional review board ( helsinki committee ) . the study was prolective , with the patient population and data parameters defined before data acquisition . the patient population included children and young adults with ds aged 020 years at their first visit to the center ( before any intervention ) . patients were eligible for the study if they had a complete blood count ( cbc ) performed as part of their evaluation or had undergone blood testing within 3 months of their visit ( as part of the center 's protocol , we request that parents or patients bring recent laboratory results ) . it should be noted that all laboratory studies for outpatients in israel ( there is universal health coverage for israeli citizens ) must be approved by the patient 's health maintenance organization ( hmo ) , and hmos have different policies regarding approval of laboratory testing . a subgroup of 38 children also had iron studies ( iron , ferritin , and transferrin levels ) either performed at our center or at the child 's hmo . information collected for the study included birth history , initial nutrition , motor development , congenital malformations , and ds - related complications ( e.g. , feeding disorders , oropharyngeal hypotonia , etc . ) . height and weight measurements were analyzed in the context of growth charts developed for individuals with ds . the nutritional status of the patients was assessed , and every patient was evaluated for the presence of a feeding or nutritional disorder by the center 's dietitian and speech therapist . all hematinic study data was analyzed in terms of established age appropriate norms based on the nhanes iii . data was entered into a spreadsheet and imported to the spss statistical program ( spss 15 , chicago ) . both nonparametric and parametric associations between categorical variables were explored using the test or fisher 's exact test . categorical variables found to be associated with anemia in univariate analysis were further analyzed in a logistic regression model . during the years 20042007 , 303 children and young adults were evaluated as first - time patients at the center for down syndrome . of these , 149 ( 49.0% ) there was a greater proportion of males which is to be expected , as there is male predominance among patients with ds . the division between jewish and arab patients was close to the population distribution in the region . more than half the patients had heart defects , feeding disorders , and motor delay . with regard to feeding disorders and delayed walking , not all parents could recall this information or children had not reached an age at which this could be determined . the overall prevalence of anemia in our study group was 8.1% ( table 2 ) . the proportion of children with anemia increased with age , with 13.7% of children over the age of 10 years having anemia . likewise , the number of children having blood hemoglobin that was lower than the published nhanes iii averages for different age groups increased with age . iron stores as measured by serum ferritin indicated that nearly all children ( 26/27 ) tested had below normal levels for age . in contrast , 26 children had their serum transferrin measured , and their levels were normal for their age . in univariate analysis , it was found that age , ethnicity , weight , and motor development were related to an increased risk for anemia . height , history of feeding disorder , or congenital heart defects did not increase the risk for anemia . to determine the adjusted odds ratio for anemia , weight also had an impact on anemia , with the rate of anemia decreasing by 0.03 with every increase by one percentile in weight . interestingly , an association between motor development and below average hemoglobin concentration for age was found . when looking at the age of independent walking in 53 children , a lower than average hemoglobin for age was more prevalent among those who started walking after the age of 2 years ( 53.1% versus 24.0% , p < 0.05 ) . ida is relatively common in the general population , and in many countries and states , there are screening programs to identify children with anemia . the reason for the heightened concern regarding anemia is that ida has been associated with motor and cognitive developmental deficits in children [ 37 ] . in children with ds , whose intellectual capacity is compromised to begin with , utmost attention should be given to preventing anemia and its potentially deleterious developmental consequences . in the present study , we show that the prevalence of anemia in a general population of children with ds is 8.1% , with the rate increasing with age . there is a question of whether the relatively high rate of anemia in our population is unique to ds or more a reflection of the general population . review of studies done in the general israeli population shows that ida is an endemic problem ( similar to other countries in the middle east ) [ 1724 ] , and it appears that the rates of anemia for patients with ds in our clinic population were lower than those of the general population . for example , meyerovitch et al . found anemia to be as high as 15.5% in 918-months old infants . fraser et al . found a similar prevalence of 15% among jewish children and approximately 25% among bedouin children . it should be noted that the great variability between studies may represent regional differences and different criteria for defining anemia . the higher prevalence of anemia among arab children with ds reflects a more wide - ranging trend among the general population . found a higher prevalence in arab children : among jewish children , the rate of anemia was 44.3% from birth to 6 months and increased to 60% from the age of 6 months to one year . for similar age groups in the arab population , similar differences between groups have been noted in other studies [ 18 , 23 ] . it is possible that ethnic and religious differences related to anemia are secondary to socioeconomic factors which have an impact on adherence to health ministry recommendations regarding iron supplementation . the association that we found between low weight and anemia supports the hypothesis that inadequate nutrition may contribute to ida and even explain some of the differences found between different ethnic populations . cause and effect are difficult to determine , as severe iron deficiency alone may cause anorexia and poor weight gain . other factors , such as various chronic diseases which are more prevalent in ds may also contribute to anemia . as part of our initial evaluation of the participants , we ruled out celiac disease , thus excluding this condition as a contributing factor to ida . however , it is possible that feeding disorders , which are common among children with ds , may have caused nutritional deficits leading to anemia . the prevalence of anemia is declining among the general pediatric population in israel [ 21 , 22 ] . public health initiatives have played a role in lowering the rate of anemia , and children with ds have most likely benefited from these interventions which include iron supplementation for all children aged 4 months to one year , with continuation of supplementation if the cbc at one year of age indicates anemia . the results of iron studies were available for only 38 of the 149 children we evaluated for anemia in this study . thus , we can not truly characterize the anemia we found as ida , or identify risk factors associated with iron deficiency . we are further limited in this by the presence of relatively high mcv in this population , as discussed further below . however , as iron deficiency is the most common cause of anemia in all age groups worldwide , and in the absence of other proven causes of anemia in our study population , iron deficiency remains the most likely cause of the anemia found in this study . the study population consisted of children who are in the care of the center for children with down syndrome . it is possible that they do not adequately represent the general population of children with ds in israel . our population may overrepresent families with high compliance for medical followup and treatment , and for this reason , they may have a lower prevalence of anemia than other children with down syndrome . on the other hand , children with relatively mild manifestations of ds may be underrepresented in our clinic so that our study population is biased towards children with more severe manifestations of ds which may impact the rates of anemia . an interesting finding in our study was the tendency to macrocytosis in all age groups . macrocytosis is a common finding in children with ds and has been widely reported [ 16 , 2729 ] . macrocytosis is not related to vitamin b12 or folic acid deficiencies , and most likely , there is a metabolic or genetic reason for the macrocytosis . as a result , there may be difficulty in completely characterizing ida due to macrocytosis . the clinical significance of this point is that the iron status of children with ds should be monitored by both serial cbcs and iron studies . the prevalence of ida in children with ds does not greatly differ from the general population . nevertheless , children with ds and ida might be more susceptible to the effects of anemia based on the fact that they already have ds - related deficits in motor and neurocognitive development . since ida is an easily preventable and treatable problem when diagnosed in a timely manner , it is important to monitor children with ds by periodically performing a cbc and measuring iron stores .

background . iron deficiency anemia impacts on cognitive development . the objective of this study was to determine the prevalence of anemia and iron deficiency in children with down syndrome and identify risk factors for anemia . methods . we conducted a prolective cross - sectional study of children attending a multidisciplinary down syndrome medical center . one hundred and forty nine children with down syndrome aged 020 years were enrolled in the study . information obtained included a medical history , physical and developmental examination , nutritional assessment , and the results of blood tests . results . of the patients studied , 8.1% were found to have anemia . among the 38 children who had iron studies , 50.0% had iron deficiency . in a multivariate analysis , arab ethnicity and low weight for age were significantly associated with anemia . gender , height , the presence of an eating disorder , and congenital heart disease were not risk factors for anemia . conclusions . children with down syndrome are at risk for anemia and iron deficiency similar to the general population . children with down syndrome should be monitored for anemia and iron deficiency so that prompt intervention can be initiated .

following the first report of 2009 pandemic influenza a ( h1n1 ; hereafter referred to h1n1 2009 ) in april 2009 , the infection became a pandemic . the drugs of choice for the treatment and prophylaxis of h1n1 2009 are neuraminidase inhibitors including oseltamivir ( tamiflu [ roche ] ) and zanamivir ( relenza [ glaxosmithkline ] ) . however , increasing use of oseltamivir has led to the emergence of the oseltamivir - resistant h1n1 2009 virus , which harbors an h274/275y or i223v neuraminidase mutation . as of 9 february 2011 , 370 cases of oseltamivir - resistant h1n1 2009 infection had been reported to the world health organization.1 it has been suggested that oseltamivir - resistant seasonal influenza or h1n1 2009 harboring the h274/275y mutation is less virulent than are strains that are oseltamivir - sensitive.2 - 4 for this reason , fatal infections by these resistant viruses are rarely reported,5 - 7 although fatalities have occurred in severely immunocompromised patients with hematologic disorders or cancer with prolonged viral shedding despite oseltamivir therapy . some adult cases of oseltamivir - resistant h1n1 2009 have also been reported in korea ; however , these were not fatal despite the presence of prolonged viral shedding.8,9 here , we report a rapidly fatal case of oseltamivir - resistant h1n1 2009 in an adult patient in korea . a 60-year - old male korean visited chonnam national university hospital because of chest pain and shortness of breath for 7 days . the patient had hypertension and the patient had end - stage renal disease and had been receiving hemodialysis for 2 years . the patient also had dilated cardiomyopathy ; his cardiac ejection fraction was 36% with global hypokinesia , and the end - diastolic and end - systolic diameters of the left ventricle were 65 mm and 54 mm , respectively , on echocardiography . the patient began empiric therapy with oseltamivir ( 75 mg twice per day ) within 24 h of the development of symptoms , which was prescribed at a local clinic . other examination findings were a blood pressure of 120/80 mmhg , pulse rate of 63 beats / min , respiratory rate of 20/min , and body temperature of 36. crackle was present in both lower lung fields on chest auscultation . the initial laboratory examination revealed a white blood cell count of 15,400/mm , a hemoglobin level of 10.1 g / dl , and a platelet count of 141,000/mm . his c - reactive protein level was 8.6 mg / dl . on initial arterial blood analysis , the values of ph , pao2 , paco2 , and bicarbonate ions were 7.365 , 49.0 mmhg , 33.3 mmhg , and 18.6 mmol / l , respectively . cardiomegaly and pulmonary infiltration in the right lower , right middle , and left lower lobes were observed on chest radiography and computed tomography ( fig . the acute physiology and chronic health evaluation ( apache ) ii score and pneumonia severity index of the patient upon presentation were 26 and 151 , respectively . after blood and sputum sampling for respiratory virus analysis , reverse - transcriptase polymerase chain reaction ( rt - pcr ) and bacterial culture , empirical intravenous antibiotic therapy with ceftriaxone and clindamycin was initiated . on the second day of hospitalization , sputum rt - pcr for h1n1 2009 was performed on hospital days one and three . on the fourth day of hospitalization , sputum rt - pcr for h1n1 2009 from a specimen acquired on hospital day the apache ii score and pneumonia severity index of the patient were aggravated to 37 and 191 , respectively . the patient was isolated and began to receive a double dose of oseltamivir therapy ( 150 mg twice per day ) . the initial antibiotics were changed to ceftriaxone and levofloxacin . despite administration of oseltamivir and antibiotics , mechanical ventilation , inotropics , and continuous renal replacement therapy , the patient 's pneumonia worsened and led to multi - organ failure . the patient died on the sixth day of hospitalization , despite 3 days of antiviral therapy and 6 days of antibacterial therapy . sequence analysis performed at the korea centers for disease control and prevention revealed an h275y neuraminidase gene mutation , as described elsewhere.10 we have presented the case of a 60-year - old korean male patient who was infected with oseltamivir - resistant h1n1 2009 , which proved lethal . oseltamivir - resistant h1n1 2009 was first reported in september 2009 , and the number of cases has been steadily increasing , including in south korea.1,10 although the incidence of oseltamivir - resistant h1n1 2009 infections is increasing , fatal cases have been reported only rarely . in south korea , the present case shows some differences in clinical characteristics compared to previously reported fatal cases . first , unlike our case , most fatal cases of oseltamivir - resistant virus infection have occurred in patients with severe immunosuppression associated with hematologic disorders or cancer.5 - 7 second , the clinical course of oseltamivir - resistant virus infection is usually insidious despite inappropriate antiviral therapy , because the virulence of oseltamivir - resistant influenza virus is thought to be lower than that of oseltamivir - sensitive viruses.8,9 animal studies have suggested that oseltamivir - resistant h1n1 2009 , as well as seasonal influenza , is less virulent and less transmissible than oseltamivir - sensitive viruses . in the present case , however , although the infection was caused by oseltamivir - resistant virus , pneumonia progressed rapidly and led to death . this suggests that some clone of oseltamivir - resistant h1n1 2009 is sufficiently virulent to cause rapidly fatal pneumonia . third , most cases of oseltamivir - resistant virus infections have occurred in patients who had undergone prolonged oseltamivir therapy.5 - 9 the present patient was treated short - term with oseltamivir before acquisition of oseltamivir resistance . this highlights that oseltamivir resistance after short - term drug exposure is also possible , and that the use of zanamivir should be considered in patients with clinical deterioration , despite oseltamivir therapy .

it has been suggested that oseltamivir - resistant influenza viruses harboring the h274/275y mutation are less virulent than are those that are oseltamivir - sensitive , and fatality attributed to infection with an oseltamivir - resistant virus is very rare . here we report the first fatal adult case of oseltamivir - resistant 2009 pandemic influenza a ( h1n1 ) in korea . a 60-year - old korean male who had hypertension , diabetes mellitus , chronic kidney disease , and dilated cardiomyopathy visited chonnam national university hospital because of a 7-day history of chest pain and dyspnea . the patient was at another clinic and had been medicated with oseltamivir ( 75 mg twice daily ) beginning 7 days before admission . empirical antibiotics were started on the first day of hospitalization . reverse - transcriptase polymerase chain reaction for 2009 pandemic influenza a ( h1n1 ) was reported to be positive , and a double dose of oseltamivir ( 150 mg twice per day ) was started on day four of hospitalization . however , the pneumonia worsened and the patient died , despite 3 days of high - dose antiviral therapy and 6 days of antibacterial therapy . an h275y mutation was detected in the neuraminidase gene sequence . this case shows that oseltamivir resistance after short - term drug exposure is possible and can be fatal , emphasizing that early use of zanamivir should be considered in suspicious cases .

hospitalization constitutes an unpleasant experience both for adults and mostly for children , who suddenly have to leave the familiar place of their home and the persons who are important for them , and stop their favorite activities , including play ( 1 ) . removal from one s home and entry to the intimidating environment of a hospital cause acute anxiety and stress both to the child and to the child s family ( 2 , 3 ) . these negative feelings are intensified whenever there is a chronic or severe and life - threatening disease . the main causes of such feelings seem to include fear of medical examinations , pain , death , fear of separation from the parents , and fear of diagnosis , uncertainty , loss of control and safety ( 4 , 5 ) . upon hospital admission , particular attention is paid to the improvement of the clinical symptoms of the disease and to a reduction in the psychological burden . as a result however , the role and value of play increases when the child is repeatedly hospitalized , mostly due to a chronic disease or disability , since it decisively contributes to emotional , mental well - being , self - confidence and self - esteem ( 6 , 7 ) . therapeutic play is defined as a framework of activities taking the psychosocial and cognitive development of children into account , in order to facilitate the emotional and physical well - being of hospitalized children ( 8) . another definition refers to play as a structured form of play activities designed based on the age , development of cognitive functions , and health condition of a child ( 9 ) . a child s ability to play while being in the hospital constitutes a sign of health in a particularly difficult environment , which shows that the child may continue his / her usual activities , or that there is some progress in the course of the disease ( 10 ) . certainly , there are also other activities which may be helpful to achieve this goal , e.g. dancing , provided that the appropriate conditions are ensured and the child may cope with them ( 11 ) . play is a form of communication and self - expression , which gives them the possibility of communicating with both the family and the medical and nursing staff , while helping them process a series of emotions ( 7 , 12 ) . in addition , play helps children become familiar with the unknown until then environment of the hospital , express their feelings and their concerns , feel more comfortable , or familiarize themselves with the medical procedures required ( e.g. , venipuncture ) , and make choices so as to feel that they maintain control . many children use a toy ( e.g. a stuffed animal ) in order to cope with different medical procedures . teddy bears often accompany children to the hospital and stuffed animals are in the arms of young children whenever there is a blood test or , for example , when they are vaccinated ( 7 ) . nurses may use play as healthcare strategy for hospitalized children in three main fields : in everyday practice , during the preparation of children for surgery and invasive procedures , and also during painful and unpleasant procedures ( 13 , 14 ) . the therapeutic use of play presupposes theoretical training , patience , and willingness to occupy oneself with children . therefore , it constitutes a main component of healthcare of ill children and helps them better understand the needs of the children and help them prepare themselves as much as possible for therapeutic procedures ( 15 ) . play in the hospital has multiple objectives , while it is of such considerable importance that it is thought that it may be of assistance in the recovery of ill children ( 16 , 17 , 18 , 19 ) : play in the hospital ensures a type of connection with the familiar , friendly environment of home.helps to create a continuity of everyday life.provides a way out of all negative feelings and disappointment that may possibly accompany a child upon hospital admission and hospitalization , while they may be transformed through play.reduces distress and anxiety , while developing respect for other people s views and feelings.helps children maintain their self - esteem and confidence , and , thus , feel that they may have control of the entire situation.contributes in the development of new creative solutions in the problems observed.teaches in an amusing way . almost in all cases of hospitalization , play may help young patients become familiar with such procedures and learn exactly how they are carried out , so as to reduce their fear and help their adaptation.encourages the participation of parents and brothers and sisters . thus , children achieve a stronger feeling of normality and continuation of their past life , while alleviating parents anxiety.facilitates communication among children . play is an excellent means of communication and development of social relationships and mutual assistance.reduces regression , i.e. , return to previous stages of development . such regression among children may be shown by various disorders , e.g. , enuresis , or behaviors including continuous crying , continuous search for parental care , outbursts of anger , and aggression . play gives a way out of repressed desires , anxiety , and fear , and allows children express themselves in a more creative and pleasant way.offers joy and amusement . play in the hospital ensures a type of connection with the familiar , friendly environment of home . helps to create a continuity of everyday life . provides a way out of all negative feelings and disappointment that may possibly accompany a child upon hospital admission and hospitalization , while they may be reduces distress and anxiety , while developing respect for other people s views and feelings . helps children maintain their self - esteem and confidence , and , thus , feel that they may have control of the entire situation . almost in all cases of hospitalization , children undergo invasive medical procedures , including catheterization , venipuncture , and blood tests . play may help young patients become familiar with such procedures and learn exactly how they are carried out , so as to reduce their fear and help their adaptation thus , children achieve a stronger feeling of normality and continuation of their past life , while alleviating parents anxiety . play is an excellent means of communication and development of social relationships and mutual assistance . such regression among children may be shown by various disorders , e.g. , enuresis , or behaviors including continuous crying , continuous search for parental care , outbursts of anger , and aggression . play gives a way out of repressed desires , anxiety , and fear , and allows children express themselves in a more creative and pleasant way . focused play techniques used among hospitalized children are used to prepare them for surgery or other unpleasant medical procedures . sometimes , even before hospital admission , the children may be encouraged to play with masks , nursing uniforms , syringes , stethoscopes . teddy bears or dolls may also be used for demonstrations , for example , a demonstration of how placing of a peripheral venous catheter is done ( 20 ) . painting and sketching may be used when other means are unavailable , for example , among children confined to bed , e.g. , after a car accident ( 21 ) . therapeutic play is effective in reducing children s anxiety and fears from the time of hospital admission to the post - operative period or hospital discharge ( 22 , 23 , 24 ) , achieving self - expression ( 25 ) , cooperation during painful procedures , and willingness to return to the hospital to continue their treatment ( 24 ) . apart from the alleviation of psychological distress , therapeutic play also seems to be effective in reducing the physical symptoms of anxiety ( 24 ) . the hospital area makes spontaneous play very difficult , since family and known objects are absent , daily routines have been interrupted , and , at the same time , there are real or suspected risks of infections , medication , and invasive medical procedures ( 26 , 27 ) . assistance provided by therapists is of great importance , since young children usually find it hard to play spontaneously , especially in an environment like hospital environment . however , even when they manage to play spontaneously , their play is usually not so productive as if it had been organized by a specialist ( 28 ) . to maximize the benefit resulting from playing , its use as a part of a well - designed healthcare plan must be systematically promoted ( 26 ) . a therapist may make a list of the things that the child does not like , which are related to hospitalization . the therapist may write a letter , together with the child , addressed to the parents , to friends , to the doctors or nurses , even to a stuffed animal . they may even write and paint a book about disease and hospitalization ( 28 ) . it must always be taken into account that there are certain factors determining how effective play therapy may be in the hospital . certain limits are necessary too , but there must be a balance ( many limits prevent children s play , very few allow bad behavior ) and one must always consider a child s level of development . limits in play therapy are helpful in ( 29 ) : providing physical and emotional safety for therapists and children;adopting a positive attitude towards children;strengthening reality;safely expressing any negative feelings;promoting a child s sense of responsibility and control , so as to enhance the development of consistency and stability in relationships;providing a cleansing experience for children;protecting the play area . providing physical and emotional safety for therapists and children ; adopting a positive attitude towards children ; strengthening reality ; safely expressing any negative feelings ; promoting a child s sense of responsibility and control , so as to enhance the development of consistency and stability in relationships ; providing a cleansing experience for children ; protecting the play area . in research , there are papers documenting the efficacy of play therapy . in one of them , 30 minutes of play therapy every day seemed to help children hospitalized in a pediatric department to avoid an increase in anxiety levels during their hospitalization , unlike the children of the control group ( 30 ) , while another paper has found a considerable decrease in the children s fear , according to their reports , with just two half - hourly sessions of play therapy ( 23 ) . apart from the aforementioned points , play therapy also seems to be an appropriate treatment for abused children who are admitted to a pediatric department . thus , play therapy in a safe environment may teach them to express themselves and be able to cope with their difficulties ( 31 ) . when a child is admitted to hospital for surgery , anxiety , both for the disease and for the imminent surgical procedure , may be the first component of the crisis the child is faced with . thus , surgical anxiety is an answer to the fear of hospitalization , disease , anesthesia , and surgery ( 32 ) . anxiety among children is a frequent phenomenon and has been associated with several negative behaviors , both pre - operatively ( stimulation , enuresis , intense crying ) and post - operatively ( pain , sleep disorders , stress of separation ) ( 33 ) , while children are more vulnerable than adults ( 34 ) . post - operative anxiety is related to anxiety in the pre - operative period and in the beginning of anesthesia ( 35 ) , while post - operative recovery presents more complications among children with high levels of pre - operative anxiety ( 36 ) . children often experience anxiety when they are separated from their parents for the operation ( 37 , 38 ) , while pediatric anxiety is associated with a high frequency of post - operative stress of separation , fear , eating and sleep disorders ( 39 ) . personalization of play prior to surgery is an intervention effectively reducing anxiety , since it is based on the patient s history , any previous negative experiences from hospitalization , and , mostly , age ( 40 ) . ghabeli f. , moheb n. , and nasab sdh , ( 2014 ) , have conducted a study among 60 children , aged 3 - 8 years , who were about to undergo ent surgery , and have found , among other things , that play and participation in team games prior to surgery contributed to a considerable decrease in their anxiety ( 41 ) . in other research has shown that , when the children were left to play with dolls or other toys before surgery , they were calmer and showed less negative behavior ( 42 ) . apart from normal stress caused by hospitalization , children suffering from cancer have to face a disease which is accompanied by a long - term treatment with several difficult side effects , including frequent , probably long - term periods of hospitalization , a disease which may result in death ( 43 ) . play therapy among children suffering from a terminal disease may create an atmosphere where young patients , even for a short period of time , will be able to develop a sense of control of the situation , they will have the chance to handle their lives in their own way , and will be able to externalize their frustrations , fears , and feelings ( 43 ) . in order to provide complete care to dying children , nurses working in the context of pediatric palliative care must realize that children need opportunities to talk about their lives and incorporate it into the way for death . play is the most convenient way to help children have the chance to say whatever they want . for children suffering from a serious disease restricting their life expectancy , play is the most natural means to release their aggression and assume control of their world ( 6 , 44 ) . all children receiving palliative care need play and , despite the fact that not all of them need play therapy , the need for this kind of therapeutic intervention is higher in this vulnerable group of children ( 6 ) . it is also an important means of communication in childhood , while the effects of the child s physical or mental disease may affect the child s ability to play . in hospital , play can have a special therapeutic value for ill children , thus contributing to their physical and emotional well - being . it helps to investigate issues related to the experiences of children in the hospital and lead to a reduction in the intensity of negative feelings , which often accompany hospital admission and hospitalization . play has multiple characteristics which , when used in the context of treatment , are of great assistance in the development and improvement of a child s function . healthcare professionals can use play as treatment and care strategy for hospitalized children , and its role and value increase when children become more vulnerable due to a life - threatening disease or disability . a child s ability to play in the hospital restores the discontinuity resulting in his / her life due to hospital admission and shows somehow that the child may continue his / her normal life even inside the hospital . through this understanding of play , healthcare professionals can accurately understand the effects of hospitalization and disease on children , on the one hand , and , on the other hand , enhance the emotional development of children . though the use of play , they have the chance to gain control in many situations , thus changing hospitalization into a positive rather than a negative experience . they must choose the appropriate activities , which help the children grow , while encouraging the parent to bring the child s favorite toys to the hospital and actively take part in the entire procedure .

introduction : play constitutes an essential parameter of the normal psychosomatic development of children , as well as their statutory right . it is also an important means of communication in childhood.objective:to review , detect and highlight all data cited regarding the role of play during the hospitalization of children.methodology:literature review was achieved by searching the databases scopus , pubmed , cinhal in english , using the following key words : therapeutic play , play therapy , hospitalized child , therapist.results:during hospitalization , play either in the form of therapeutic play , or as in the form of play therapy , is proven to be of high therapeutic value for ill children , thus contributing to both their physical and emotional well - being and to their recovery . it helps to investigate issues related to the child s experiences in the hospital and reduce the intensity of negative feelings accompanying a child s admission to hospital and hospitalization . play is widely used in pre - operative preparation and invasive procedures , while its use among children hospitalized for cancer is beneficial.conclusion:the use of play in hospital may become a tool in the hands of healthcare professionals , in order to provide substantial assistance to hospitalized children , as long as they have appropriate training , patience , and will to apply it during hospitalization .

the neurovascular compression of the fifth and seventh cranial nerves is known as the cause of trigeminal neuralgia ( tn ) and hemifacial spasm . the rate of success of surgical decompression for these two syndromes is satisfactory.1 2 however , it is still difficult to consider neurovascular compression of the eighth cranial nerve as a major cause of disabling vertigo and tinnitus.3 in the last decade , microvascular decompression ( mvd ) of the vestibulocochlear nerve was reported as an efficient treatment option with a high rate of success ( up to 80% ) for several vestibulocochlear compression syndromes.4 5 6 as an anatomical consideration , vascular anomalies may cause compression at the root entry or exit zone of the cranial nerves.7 in contrast to tn , which almost always results from a compression at the nerve root entry zone , vestibulocochlear compression syndrome results from the nerve 's conflict over its entire segment in the cerebellopontine angle.8 although a loop of the anterior interior cerebellar artery ( aica ) can frequently lead to the dislocation and compression of the eighth cranial nerve at the cerebellopontine angle,9 the intracanalicular neurovascular compression of the vestibulocochlear nerve has been reported in only two cases8 10 ( table 1 ) . we present an unusual case of an intrameatal aica loop compressing the vestibulocochlear nerve in a patient who developed the symptoms of disabling vertigo and tinnitus without a unilateral hearing loss , and we also consider the surgical issues . a 40-year - old woman was admitted to our clinic with a 4-year history of recurrent vertigo and nonpulsatile tinnitus in the left ear , along with left - sided aural fullness without any hearing loss . the episodes of vertigo lasted up to 2 hours ( which was workload dependent and not positional ) and had significantly impaired the patient 's ability to work for the past 2 years . the tinnitus episodes did not have any relationship to the vertigo . during the physical examination , her neurologic examination was normal . a preoperative auditory brainstem response ( abr ) examination showed latency of wave i and iii brainstem potentials . a balance examination of the patient did not show any imbalance tendencies to the right or the left , even though she had complained about subjective disequilibrium that was noted in her medical record . further medical treatment of the condition including intravenous infusions according to the protocol proposed by stennert10 11 did not show any improvement . due to the unfavorable results of the primary neurotologic examinations , the patient additionally underwent magnetic resonance imaging ( mri ) ( fig . 1 ) . the preoperative magnetic resonance imaging examination did not show any pathologic findings . the mri did not show any pathologic findings , but an additional magnetic resonance angiography ( mra ) examination revealed a loop of the aica extending into the left internal auditory meatus ( fig . 2 ) . an additional preoperative magnetic resonance angiography examination revealed a loop of the anterior interior cerebellar artery extending into the left internal auditory meatus . after a long discussion with the patient about the relative indication of vestibulocochlear decompression and explaining the details of our experiences as well as the surgical risks , the patient decided to go ahead with the operation due to the negative influence of the vertigo and tinnitus on her quality of life . as preparation for a lateral suboccipital retrosigmoidal craniotomy in a semisitting position , the left retrosigmoid craniotomy ( with cranioplasty ) was performed in the semisitting position with intraoperative monitoring of the facial and vestibulocochlear nerve ( abr ) ( fig . a left retrosigmoid craniotomy ( with cranioplasty ) was performed in the semisitting position with intraoperative monitoring of the facial and vestibulocochlear nerve . microsurgical exploration of the vestibulocochlear nerve after drilling the posterior wall of the internal auditory canal ( iac ) revealed the aica entering the internal auditory meatus and looping into the canal for 8 mm , as expected from the mra , thereby compressing the vestibulocochlear nerve . the aica contact to the vestibular nerve extended from the porus into the middle part of the iac . after dissection of the arachnoid membrane , the aica was gently mobilized from the vestibulocochlear nerve and removed from the iac into the cerebellopontine angle ( fig . , two pieces of muscle were interposed between the eighth cranial nerve and the aica . the intraoperative mobilization of the intrameatal anterior interior cerebellar artery from the internal auditory canal ( iac ) after drilling the posterior wall of the iac . finally , the posterior wall of the iac was closed with muscle and fibrin glue . facial and abr monitoring was performed continuously during the surgery and did not show any significant changes compared with the preoperative findings . notably , there was no change in hearing ability at the postoperative audiogram examination ( fig . follow - up tests were performed six times during the last 2 years without any recurrence of the symptoms or changes in the audiogram examinations . the vestibulocochlear parameters ( including the caloric test , posturography , and general balance ) were normal during direct postoperative as well as follow - up examinations . the preoperative ( left ) and postoperative ( right ) audiogram of the patient did not show any hearing loss before or after the operation , respectively . the labyrinthine artery ( auditory artery , internal auditory artery ) is a long slender branch of the aica ( 85100% of cases ) , basilar artery ( < 15% of cases ) , or vertebral artery ( 4.1% ) . it arises from the middle of the artery , accompanies the vestibulocochlear nerve through the internal acoustic meatus , and is distributed to the internal ear.12 as shown in fig . 6 , the labyrinthine artery of our patient arose from the intrameatal aica loop and entered the internal acoustic meatus . during surgery , the aica should be mobilized and removed from the iac into the cerebellopontine angle . any direct or indirect injury to the labyrinthine artery during the mobilization of aica would result in postoperative hearing loss.13 fig . ( a ) the preoperative magnetic resonance angiography of the patient shows the labyrinthine artery ( red arrow ) arising from the anterior interior cerebellar artery ( aica ) and entering into the internal auditory canal ( iac ) . ( b ) the intraoperative image shows the labyrinthine artery ( yellow arrow ) arising from the aica and entering the iac ( see surgical considerations in the text ) . the anatomical variations of the neurovasculature in the cerebellopontine angle result from the late development of the aica and the posterior inferior cerebellar artery ( pica ) from the primitive lateral basivertebral anastomosis.8 14 15 16 17 these vascular variations may cause dislocation and compression of the cranial nerves in the posterior cranial fossa . over the past decade , neurosurgical clinical and anatomical experience has attributed several symptoms to the microvascular compression of the vestibulocochlear nerve . several cases of disabling vertigo , tinnitus , hearing loss , and imbalance were noted to be caused by vascular compression of the eighth cranial nerve.3 4 5 however , significant controversy persists among clinicians in the neurotologic diagnosis of neurovascular compression of the eighth cranial nerve . abnormal abr , brief spells of vertigo , unilateral sensorineural hearing loss , abnormal vestibular findings , continuous tinnitus , hearing loss , abnormal electronystagmograms , and other findings have been reported to be diagnostic for neurovascular compression of the eighth cranial nerve.18 19 20 21 22 many reports in the literature explain the role of aica or pica or their branches , resulting in the microvascular compression of the vestibulocochlear nerve in the cerebellopontine angle that causes symptoms of disabling vertigo , tinnitus , and hearing loss.14 23 as a theory , curves and loops of vessels running near the cranial nerves may be created mostly by degenerative alterations of aging , and such vessels can compress surrounding neural elements.24 furthermore , the different results of mvd of the eighth cranial nerve , including the surgical treatment of tinnitus and disabling positional vertigo , have been reported in the literature.4 19 25 in 1984 , janetta et al introduced a new term , disabling positional vertigo ( dpv ) , and they identified a group of patients with vestibular disorders whose symptoms were totally relieved by mvd of the eighth nerve.19 in 1993 , mller et al reported the results of mvd of the eighth cranial nerve in 207 patients with dpv and reported a cure rate of 80%.4 these reports were subsequently supported by numerous studies on vertigo and tinnitus . in 1998 , ryu et al reported the results of neurovascular decompression of the eighth cranial nerve in 43 cases of vertigo and tinnitus , and they established diagnostic criteria and operative indications . they reported a complete recovery or marked improvement of subjective symptoms in 100% of the patients with vertigo and 65.5% of the patients with tinnitus . they demonstrated that the symptoms of neurovascular compression of the eighth cranial nerve depend on the part of the nerve compressed by blood vessels . for example , in patients with vertigo and tinnitus , there was vascular compression of the rostroventral and caudal surface of the nerve , respectively.26 this review of the literature shows that the neurovascular compression of the vestibulocochlear nerve is usually located in the cerebellopontine angle but not the intrameatal angle . to the best of our knowledge , only two case reports have presented intrameatal vascular compression as a cause of vestibulocochlear compression syndrome ( table 1 ) . our case along with the two cases just cited adds another avenue to explore in the diagnosis and treatment of vestibulocochlear compression syndrome . it is still debatable if the exploration of the vestibulocochlear nerve should continue into the iac if no clear neurovascular conflict in the cerebellopontine angle is found.8 such case reports may introduce a new concept to the intrameatal exploration of the vestibulocochlear nerve in such situations . however , there are articles reporting that the radiologic demonstration of contact between a vascular loop formed by the aica and the eighth cranial nerve on mri scans should be considered a normal anatomical finding and should not be used to support the diagnosis of a vascular compression syndrome.27 28 also , mvd of the vestibulocochlear nerve ( especially with regard to the improvement of tinnitus ) is not always successful . in a study regarding mvd treatment for a selected group of 72 patients with severe tinnitus , mller and mller showed that 11% of patients had only slight improvement , 45.8% had no improvement , and 2.8% became worse . they showed that the success of such surgery depends on the duration of symptoms before the operation.29 the diagnosis of vestibulocochlear compression based on symptoms , signs , and radiologic findings is thus not easy to make . in addition , the surgery should be done in the hands of an expert surgeon because the indication of such decompression surgery is not really absolute . in addition to other common causes , disabling vertigo and tinnitus can rarely be caused by intrameatal vascular compression of the vestibulocochlear nerve and may be treated successfully by mvd . because the results of mvd of the vestibulocochlear nerve in the literature are not always acceptable , the other common causes of vestibulocochlear compression syndrome must be excluded before the decision to operate is made .

microvascular compression of the vestibulocochlear nerve is known as a cause of tinnitus and vertigo in the literature , but our review of the literature shows that the compression is usually located in the cerebellopontine angle and not intrameatal.we present a case of intrameatal compression of the anterior inferior cerebellar artery ( aica ) on the vestibulocochlear nerve of a 40-year - old woman with symptoms of disabling vertigo and intermittent high - frequency tinnitus on the left side without any hearing loss for 4 years . magnetic resonance imaging of the brain did not show any abnormality , but magnetic resonance angiography showed a left intrameatal aica loop as a possible cause of the disabling symptoms . after the exclusion of other possible reasons for disabling vertigo , surgery was indicated . the intraoperative findings proved the radiologic findings . the large aica loop was found extending into the internal auditory canal and compressing the vestibulocochlear nerve . the aica loop was mobilized and separated from the vestibulocochlear nerve.the patient 's symptoms resolved immediately after surgery , and no symptoms were noted during 2 years of follow - up in our clinic . her hearing was not affected by the surgery.in addition to other common reasons , such as acoustic neuroma , disabling vertigo and tinnitus can occur from an intrameatal arterial loop compression of the vestibulocochlear nerve and may be treated successfully by drilling the internal acoustic meatus and separating the arterial conflict from the vestibulocochlear nerve .

the first screening method of screening for trisomy 21 was based on the maternal age . since the late 1980s , a test was universalized for three fetoplacental products ( alpha - fetoprotein , unconjugate estriol , and total hcg ) in the maternal serum at the second trimester of gestation . in addition , various sonographic markers such as nuchal fold thickness and femur length in second trimester were introduced , and the nuchal translucency ( nt ) became important as the early screening method for chromosomal abnormality ( 1 - 3 ) . the test , using maternal serum biochemical markers , has a relatively fixed cut - off of 1:270 , and the sensitivity is known to be about 60% . many studies have reported that the thickened nt could identify about 75% of affected fetuses for a false positive rate of 5% , but various cut - offs were used in those studies ( 4 - 7 ) . although many studies have asserted that different cut - offs of nt according to the crown rump length ( crl ) should be used for screening chromosomal aberration , there are few studies actually comparing the sensitivities and false positive rates of nt with different cut - offs within the same group . in this study , we report herein on those values of nt for chromosomal aberration with three different cut - offs , 2.5 mm , 3.0 mm and the 95th percentile for the crl in a korean population . this study was conducted with 2,570 pregnancies by searching our clinical database from january 2001 through december 2001 . the inclusion criteria were singleton pregnancies who examined ultrasonographic fetal nt measurement between 11 weeks and 14 weeks of gestation at our institution and performed regular antenatal care during the pregnancy with known pregnancy outcome . the ultrasonographic scans of fetal nt measurement were carried out by 5 sonographers and 2 obstetricians experienced first - trimester scans more than 5 yr . fetal nt thickness was measured using the transabdominal ultrasonography ( hdi 3000 , atl , bothell , wa , u.s.a . ) in a good mid - sagittal section of the fetus with magnification so that the fetus occupied at least 75% of the image ( 8) . in cases of visualization proved difficult or suspicious findings , a transvaginal ultrasonography was also used . the nt was defined as the black area between the inner skin on the outline echo and the outer border of the soft tissue overlying the cervical spine . the maximal thickness of the black area was measured with a caliper placed on the lines to 0.1 mm when the sagittal section of the fetuses was obtained . at same time , the fetal crl was also measured . great care was also taken to clearly distinguish between the fetal skin and the amniotic membrane . in some cases this could only be achieved by asking the mother to cough or by tapping the maternal abdomen . in some cases , it was helpful to use the cineloop function ( a function that permits the replay of ultrasound images taken in the past few seconds ) to visualize the fetus in a satisfactory position . at least three measurements were taken during the scan and the largest of the three measurements was recorded . we underwent fetal karyotyping in one hundred twenty five women with increased fetal nt ( 2.5 mm ) by chorionic villus sampling or amniocentesis . fetal karyotyping was also offered to women who were maternal age of 35 yr old or more at the time of delivery ( n=158 ) , had a positive result on the triple test ( n=92 ) , had the history of chromosomal abnormality in any previous pregnancy ( n=8 ) , had major fetal structural anomalies on ultrasound examination ( n=12 ) , and others ( n=24 ) . the karyotyping was also performed in intrauterine fetal death ( iufd ) ( n=4 ) cases . among the cases who had not been offered fetal karyotyping , we examined the neonates or stillborn for phenotypic abnormality indicating chromosomal aberrations . we excluded the cases ( n=8 ) who had terminated their pregnancies because of major structural anomaly on antenatal ultrasound without fetal karyotyping . the frequencies of chromosomal aberrations were analyzed and the sensitivities and false positive rates were calculated according to three different cut - offs , namely 2.5 mm , 3.0 mm and the 95th percentile for each fetal crl . we used the data about the 95th percentile of nt for each crl of our institution ( 9 ) . the frequencies of fetuses with increased nt according to cut - offs of 2.5 mm , 3.0 mm , and the 95th percentile of each crl were 7.1% , 4.1% and 6.5% respectively . table 1 shows the types and frequencies of chromosomal aberrations according to the various cut - offs of nt . there were a total of 31 cases ( 1.2% ) of chromosomal aberrations in this study . among these cases , the frequencies of chromosomal aberrations that ultrasonographic nt measurement was thickened than that of 2.5 mm , 3.0 mm , and the 95th percentile of nt measurement at each crl were 11.5% ( 21/161 ) , 15.9% ( 17/89 ) , and 13.2% ( 22/146 ) , respectively . we could detect one more case of trisomy 18 when we used the 95th percentile as the cut - off than the fixed cut - off of 2.5 mm . table 2 shows the sensitivities and false positive rates of nt with each cut - off for screening all the chromosomal aberrations and trisomy 21 . the sensitivity for detection of chromosomal aberrations was high ( 70.9% ) in the 95th percentile as the cut - off compared with the fixed cut - offs . the false positive rate was 3.5% when using 3.0 mm , but the sensitivity was 54.8% . when using the 95th percentile of nt , the sensitivity was higher and the false positive rate was lower than those of using 2.5 mm for detecting chromosomal aberrations . the sensitivities of the nt measurement to detect trisomy 21 with two cut - offs , 2.5 mm and the 95th percentile were same ( 75% ) , and the false positive rate of the 95th percentile ( 6.2% ) was lower than that of 2.5 mm ( 6.8% ) . the various screening methods for detecting chromosomal aberration have been investigated and many studies are ongoing to search for a more efficient screening method . among the various methods , we evaluated the sensitivities and false positive rates of the screening test of nt measurement alone ( not including maternal age ) in the first trimester for chromosomal aberrations by using three different cut - offs in a korean population . the sensitivity of the nt measurement with 3.0 mm as a cut - off was 54.8% in this study . the early studies about nt measurement mainly used 3.0 mm as the cut - off and the reported various sensitivities were from 39% through 93% ( 10 - 12 ) . this wide range of results may be due to the different study populations and/or to an inadequate gestational age at the time of nt measurement . most of these studies were mainly targeted to a high risk population that was scheduled for fetal karyotyping ( 11 , 12 ) , so the sensitivity of detecting an affected fetus with an increased nt would be higher than that used in the general population . on the other hand , some early studies reported low sensitivity in their results ( 13 , 14 ) . in those studies , the adequate gestational age ( in weeks ) of the nt measurement was not established , so cases that measured earlier than 11 weeks of gestation were also included as a large proportion of the subjects . all the cases in which the translucency was not visible or measurable were included in the classification of less than 1.0 mm . the cases under 10 weeks of gestational age had the probability of having an immeasurable nt , and the studies that included these subjects would have results with low sensitivity . currently , the adequate period of the nt measurement is known to be the time between 11 and 14 weeks of gestation ( 8) . in this study , we included pregnant woman in this period . as extensive data is accumulated regarding the first - trimester nt screening of populations at high risk , attention has been drawn to those populations at low risk and general population ( 15 - 17 ) . this data is of major importance because these populations represent the women for whom the vast majority of pregnancies with fetuses having abnormal chromosomes will occur . the results of the present study are similar to those results of hafner et al . they assessed what percentage of chromosomal anomalies could be detected by a nt measured in 4,233 unselected women . they diagnosed one additional down syndrome case by using a sliding scale for the cut - off value with two standard deviations instead of the fixed value of 2.5 mm . so , they suggested that detection rate could probably be improved by raising the values with increasing gestational age . we used the 95th percentile of each crl as the cut - off value in this study , and we could detect one additional case of trisomy 18 . recent studies have reported the sensitivities of nt according to various gestational age - dependent cut - offs for detecting chromosomal abnormality ( 15 , 17 , 18 ) . one of the largest multicenter study ( 18 ) showed that the sensitivity of nt with gestational age - dependent cut - offs for trisomy 21 was 77% for a false positive rate of 5% . we presume the reason for high occurrence of trisomy in this study is that we included two cases of trisomy referred from private clinics with abnormal ultrasound findings in first trimester and another two cases of trisomy with iufd before amniocentesis ( the nt thickness of those cases were all increased over 3 mm ) . although the sensitivities and false positive rates of nt for detecting of chromosomal aberration were changed after excluding those four cases ( 62.9% , 48.1% , 66.6% and 6.4% , 3.6% , 5.8% according to cut - offs 2.5 mm , 3.0 mm , 95th percentile ) , the superiority of 95th percentile nt value as the cut - off for screening test was not changed . this study is the first study to compare the sensitivities of nuchal translucency alone as a screening test for chromosomal aberration with different cut - offs in a korean population . when using the 95th percentile of nt , we identified that the sensitivity was higher than that of fixed cut - off for detecting chromosomal aberrations . so , we can suggest that this cut - off should be used for the nuchal translucency measurement screening method in korean population .

this study evaluated the sensitivities and false positive rates of the screening test using ultrasonographic measurement of thickness of nuchal translucency ( nt ) with different cut - offs for chromosomal aberration in a korean population . we included 2,570 singleton pregnancies undergoing ultrasound between 11 weeks and 14 weeks of gestation in this study . we analyzed the sensitivities of nt alone for screening chromosomal aberration using three cut - offs -2.5 mm , 3.0 mm , and 95th percentile for each crown rump length ( crl ) . there were 31 chromosomal aberrations ( 1.2% ) including 12 cases of trisomy 21 . the numbers of chromosomal aberrations that were detected by nt with different cut - offs of 2.5 mm , 3.0 mm and the 95th percentile crl were 22 , 18 and 23 , respectively . at a threshold of 2.5 mm , the sensitivity and the false positive rate for total chromosomal aberrations were 67.7% and 6.3% , respectively . at 3.0 mm , those were 54.8% and 3.5% , respectively . at the 95th percentile crl , those were 70.9% and 5.8% , respectively . the use of crl - dependent cut - offs for nuchal translucency improves the detection of chromosomal aberrations when compared to fixed cut - offs in a korean population .

beside the published recommendations scientist keep still looking for a more effective way of training in healthy and weak elderly . this was also the main frequency of the force peaks of 16 hz and 14 hz in the concentric and eccentric phase respectively ( figure 2 ) . the training session of the st consisted of 5 sets with 12 14 second contraction time ( first two weeks 4 sets of 8 10 sec ) , performed with a maximal effort . fes ( n= 14 , 70.2 3.26 years ) underwent transdermal surface electrical stimulation of both knee extensors muscles , using a custom build programmable voltage - controlled stimulator , three times per week ( figure 3 ) with an additional load placed on ankles ( 1 to 2.5 kg ) . one training session of the fes consisted of 3 sets of 10 minutes ( first two weeks 3 sets of 6 minutes ) of stimulation . subjects were tested for lower extremity isometric muscle strength habitual and maximal walking speed over 10 m and chair - rising test both before and after the intervention . we observed that post - training maximum voluntary isometric contraction measured on training - non specific force chair increased after both training methods ( figure 4 ) . similar results were found in functional tests . both groups improved in sit to stance performance ( chair rising test ) ( figure 5 ) , maximal gait speed ( figure 6 ) and time up - and - go test ( figure 7 ) . the only difference was in the postural stability test , in which only the leg press group increased significantly . in conclusion , we found that both strength training with proprioceptive stimulation and functional electrical stimulation similarly improve the maximal strength and motor function in elderly . both methods represent an effective and safe way to improve strength and functional capabilities in sedentary elderly people .

aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions . one of the most efficient methods to counteract age - related changes in muscle mass and function is physical exercise . an alternative effective intervention to improve muscle structure and performance is electrical stimulation . in the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared .

a 66-year - old male visited our hospital with painless gross hematuria with blood clots for the previous 1 month . a cystoscopic examination revealed a huge bladder neck mass and a transurethral resection of the bladder tumor ( turbt ) was performed . the histology showed an adenocarcinoma of the prostate , with a gleason score of 9 ( 5 + 4 ) . the patient 's initial prostate - specific antigen ( psa ) was 2.0 ng / ml . magnetic resonance imaging ( mri ) , computed tomography ( ct ) , and bone scans did not show metastatic lesions . the clinical stage of prostate cancer was pt4a cn0 cm0 at the time of diagnosis . the patient underwent a course of prostatic intensity - modulated radiation therapy ( imrt ) to 7,800 cgy in 39 fractions 1 month after the diagnosis . an adjuvant treatment of total androgen blockade ( tab ) with a luteinizing hormone - releasing hormone ( lhrh ) agonist and an anti - androgen was administered 3 months after the diagnosis . the patient 's psa level rose to 2.5 ng / ml 7 months after radiation treatment and then rose to 17.9 ng / ml after 9 months . a follow - up bone scan showed multiple bone metastases in the thoracic spine , both iliac bones , and the left femur 9 months after radiation treatment . . the patient complained of abdominal discomfort , nausea , and vomiting 18 months after the diagnosis . multiple small , elevated mucosal ulcerations on the anterior wall of the gastric antrum were observed by use of esophagogastroduodenoscopy ( fig . the histopathology of the gastric biopsy showed infiltration of neoplastic cells with marked atypical nucleoli and abundant eosinophilic cytoplasm ( fig . he was given an intravenous dose of 120 mg ( 75 mg / m ) docetaxel with prednisolone every 3 weeks for three cycles . the bone and lymph node disease remained stable for several months with an acceptable performance status and no significant treatment - induced toxicity . the patient complained of facial numbness on the right side 21 months after the diagnosis . a mri brain scan confirmed an intracerebral mass measuring 21.6 cm in the right cerebellum ( fig . pulmonary edema was noted and unfortunately the patient died of cardiac arrest 5 months after the diagnosis of stomach metastasis . prostate cancer commonly metastasizes to the bones and lymph nodes ; its spread to the gastrointestinal ( gi ) tract is rare . a search of published reports revealed only three cases of prostate cancer metastatic to the stomach [ 1 - 3 ] . however , there have been reports of prostate cancer metastatic to other sites of the gi tract [ 4 - 6 ] . two postmortem studies of between 67 and 347 patients with metastatic prostate cancer revealed an incidence of gastric metastasis in 1% to 4% of cases . the initial psa of the patient in the first case reported by onitilo et al was 1,565 ng / ml . our patient had hormone - refractory prostate cancer with systemic tumor disease involving the lymph nodes and bone metastasis . the patient in the first case reported by onitilo et al had indolent disease before presenting with gastric metastasis . the patient responded rapidly and dramatically to treatment and his gi bleeding and other symptoms were resolved . our patient died of cardiac arrest 23 months after the initial diagnosis of prostate cancer . the patient in the first case reported by onitilo et al died 19 months after the initial diagnosis of prostate cancer . hematogenous , lymphatic , and direct infiltrations are the typical routes of spread . because the prostate is richly supplied with lymphatic channels , most gi spread to the abdomen the most common symptoms associated with stomach metastases from prostate cancer were nausea and vomiting [ 1 - 3 ] . we emphasize that in patients with a history of prostate cancer and new - onset gi manifestations with nausea and vomiting , the elevation of intracranial pressure with brain metastasis and stomach metastasis should be considered in the differential diagnosis .

prostate cancer commonly manifests with bony metastases . visceral metastasis can also occur in the lungs and liver . however , stomach metastasis related to prostate cancer is rare . here , we report a case of prostate cancer metastatic to the stomach . a 66-year - old male was diagnosed with prostate adenocarcinoma . he was noted as having abdominal discomfort , nausea , and vomiting 18 months after the diagnosis . a histopathologic examination and an esophagogastroduodenoscopic gastric biopsy revealed stomach - metastatic adenocarcinoma . he was also noted as having cerebellar metastatic lesions , which were identified by using a brain magnetic resonance imaging ( mri ) scan . the patient died of cardiovascular complications 5 months after the diagnosis of stomach metastasis .

it is well - known that blood pressure is often elevated in the early stage of acute ischemic stroke . this early elevation in blood pressure is considered to play an important role in maintaining the cerebral circulation and collateral blood circulation in the penumbra region ; however , the mechanism is not fully understood . some reports suggest that an initially high blood pressure is associated with a poor prognosis , while other reports suggest that it contributes to a more favorable prognosis or does not affect the prognosis , and evaluations have not been adequately conducted . in this study , we evaluated the clinical characteristics of acute ischemic stroke cases with very high blood pressure in acute phase . we studied 515 consecutive patients ( 309 male and 206 female patients , mean age : 73 years old ) admitted within the first 48 hours after the onset of ischemic stroke between april 2003 and december 2007 from our hospital . those who showed a mean of at least 2 blood pressure recordings of 200 mmhg systolic and/or 110 mmhg diastolic at 6 to 24 hours after admission or 180 mmhg systolic and/or 105 mmhg diastolic at 24 to 36 hours after admission were assigned to group 1 , and the remaining patients were assigned to group 2 ( 90 mmhg systolic or 48 mmhg diastolic ) . we compared the clinical entity of the stroke , the site of the infarct , risk factors , carotid artery stenosis , cerebral white matter lesions , severity , and mortality between the two groups . the study protocol was acknowledged and authorized by the institutional review board of okayama medical center in japan . clinical entities were classified into lacunar , atherothrombotic and cardioembolic infarctions according to the 3rd edition of cerebrovascular disease classification by the national institute of neurological disorders and stroke ( ninds - iii ) . the site of the infarct was classified into supratentorial small vessels , supratentorial cortical branches , as well as supratentorial and supra- and sub - tentorial lesions . risk factors were defined as follows : high blood pressure those who had been diagnosed with hypertension , and had already taken anti - hypotensive drugs ; diabetes mellitus those who had a fasting glucose level above 126 mg / dl and hba1c higher than 6.5% , or those who had been taking antihyperglycemic drugs ; hypercholesterolemia those who exhibited a total cholesterol level higher than 220 mg / dl during hospitalization , or those who had been taking antihyperlipidemic drugs ; degree of severity according to the nih stroke scale ( nihss ) and the modified rankin scale ( mrs ) ; carotid artery stenosis of more than 70% as assessed by the nascet index was considered significant ; cerebral white matter lesions were divided into grade 03 based on the study by fazekas et al . grade 0 , no cerebral matter lesions ; grade 1 , periventricular hyperintensities ( pvh ) on the bilateral anterior or posterior horn or patchy lesions ; grade 2 , enlarged , patchy lesion and early confluent stage ; grade 3 , enlarged pvh surrounding the lateral cerebral ventricle although the general recommendation in japan is not to treat elevated blood pressure during the first day of ischemic stroke , antihypertensive ( a calcium antagonist ) was administered only when extreme hypertension of 220 mmhg systolic and/or 130 mmhg diastolic continued or patients had aortic dissection , acute myocardial infarction , heart failure or kidney failure . we employed the test to compare the backgrounds of the patients , and non - parametric mann - whitney test to compare the clinical evaluation scales between the two groups . logistic regression analysis was conducted to evaluate the association of the risk factors and presence of a high blood pressure , and the odds ratio and 95% confidence interval ( ci ) were evaluated . no significant differences in mean age , sex and clinical entities were noted between the groups . in both groups , concerning the risk factors , the percentage of patients with a history of hypertension was 75.9% and 57.6% , and that of kidney disease was 12.0% and 3.5% in groups 1 and 2 , respectively , with significant differences . there was no significant difference regarding other risk factors ; however , the incidence of risk factors was higher in group 1 . concerning the degree of severity , mrs on discharge and the length of stay were significantly higher in group 1 . there was no significant difference in nihss on admission and the mortality rate , but it was higher in group 1 ( table 1).to clarify the association of the risk factors and the presence of a high blood pressure , logistic regression analysis was conducted . regarding the factors excluding a history of hypertension , a history of diabetes mellitus , arterial fibrillation , and kidney disease were significantly associated with an odds ratio ( or ) of 1.85 ( 95% confidence interval ( ci ) : 1.063.22 , p=0.02 ) , 1.89 ( 95% ci : 1.113.22 , p=0.02 ) , and 3.31 ( 95% ci : 1.368.04 , p=0.01 ) , respectively , and they were independent risk factors for having elevated blood pressure during the acute phase of stroke . table 1baseline characteristics of subjects.characteristicgroup 1group 2p valuen=83n=432mean age ( years ) [ meansd]75.011.173.111.9n.s.male [ % ] 54.261.1n.s.clinical entities [ % ] lacunar infarction33.735.5n.s . atherothrombotic infarction26.526.3 cardioembolic infarction25.626.6 unknown cause14.211.6the site of the infarct [ % ] supratentrial small vessels36.141.2n.s . supratentrial cortical branches51.840.5 subtentrial lesions12.017.1 supra- and sub - tentrial lesions01.2hypertension [ % ] 75.957.60.001diabetes mellitus [ % ] 36.125.0n.s.hypercholesterolemia [ % ] 26.525.0n.s.atrial fibrillation [ % ] 39.825.7n.s.ischemic heart disease [ % ] 18.314.2n.s.stroke history [ % ] 33.729.4n.s.kidney disease [ % ] 12.03.50.003carotid artery stenosis [ % ] 10.86.9n.s.leukoaraiosis [ % ] 18.118.3n.s.nihss on admission [ meansd]8.77.07.57.8n.s.mrs on discharge [ meansd]3.11.82.41.80.005the length of stay ( days ) [ meansd]28.221.422.717.50.007mortality [ % ] 6.03.5n.s.group 1 represents subjects with high blood pressure . group 2 represents the remaining patients;mrs : modified rankin scale ; nihss : nih stroke scale ; n.s . : group 2 represents the remaining patients ; mrs : modified rankin scale ; nihss : nih stroke scale ; n.s . : not significant . table 2odds ratio for an association of risk factors with the presence of a high blood pressure.or95%clp valueage ( > 75)1.120.651.920.69male0.730.441.220.23diabetes mellitus1.851.063.220.03*hypercholesterolemia1.050.591.880.86atrial fibrillation1.891.113.220.02*stroke history1.110.661.890.69ischemic heart disease1.230.642.360.53kidney disease3.311.368.040.01*carotid artery stenosis1.480.623.500.38leukoaraiosis0.950.491.840.88mortality1.400.464.200.55*p<0.0.5 in this study , group 1 indicated the very high blood pressure group ; the size of this group ( n=83 ) was relatively small although the entire study group as a whole was large at n=515 . the rates of patients with a history of high blood pressure , and kidney disease were significantly higher in group 1 , and they were more likely to have a history of being prescribed several kinds of antihypertensive drugs . they were also more likely to show atrial fibrillation and diabetes mellitus , although the difference was not significant . their mrs scores on discharge and the length of stay were significantly higher , though nihss on admission was not significant between the two groups , which suggested that they were more likely to have a poorer prognosis . on logistic regression analysis with no previous history of hypertension , diabetes mellitus , arterial fibrillation , and kidney disease were independent risk factors associated with the presence of a high blood pressure . in patients without a history of hypertension , patients with diabetes , atrial fibrillation , and kidney disease were more likely to have elevated blood pressure early during stroke . atrial fibrillation and kidney disease are common complications of late hypertensive disease and hypertension is more prevalent among patients with diabetes . these results suggest that multi - organ injury may be present in patients with high blood pressure , and thus acute phase high blood pressure is related to a poor prognosis . generally , the blood pressure is elevated in the early stage of stroke , and it reaches a plateau within 24 hours , and then gradually starts to decrease in a week . in this study , only 28 ( 5.4% ) and 10 ( 1.9% ) acute inpatients spontaneously had a blood pressure of higher than 180/105 mmhg one week and two weeks after admission , respectively . the acute phase elevation in blood pressure is considered to play an important role in maintaining cerebral and collateral blood circulation in the penumbra region however , the continuation of an elevated blood pressure has been suggested to lead to brain edema and reinfarction of ischemic lesions . large epidemiological studies of acute ischemic stroke patients have demonstrated a u - shaped curve with respect to presenting blood pressure and outcomes . our study demonstrates that high blood pressure values were highly associated with early recurrent stroke and fatal brain edema . regarding the management of hypertension , the 2004 japanese guidelines for the management of the stroke states that the careful administration of antihypertensive drugs is recommended only when extreme hypertension of 220 mmhg systolic and/or 130 mmhg diastolic continues or patients have aortic dissection , acute myocardial infarction , heart failure or kidney failure . however , the grade of recommendation is c1 , which means that it is not based on adequate scientific evidence . some studies have reported that , in patients who were administered a high - dose bolus of nimodipine , a calcium antagonist , in the acute stage of stroke , a decrease in the diastolic pressure and deterioration of neurological scores were observed , which suggests the risk of rapid blood pressure reduction . however , the target blood pressure specifically related to the clinical entity , history and coexisting illnesses has not yet been proposed . the access study which was published recently reported that a 7-day course of candesartan , an angiotensin receptor ii blocker ( arb ) , started within 36 hours rather than seven days after an acute ischemic stroke reduced the occurrence of cardiovascular events within a year after the stroke by 47.5% . these findings indicate the need to re - examine the conventional management of hypertension in the early stage of acute brain stroke . in the present study , it was suggested that patients with high blood pressure were more likely to have a history of hypertension , kidney disease and carotid stenosis . in these patients , a gradual decrease in the blood pressure on careful follow - up of the clinical symptoms may be favorable . first , the number of patients was relatively small . therefore , further evaluation with a larger number of patients is required . second , the prognosis was measured by mrs scores on discharge ; thus a follow - up period of three or six months is necessary . a large randomized comparison trial to investigate indications of antihypertensive drugs in the early stage of acute stroke in this study , the rates of patients with a history of high blood pressure , kidney disease , the mrs scores on discharge and the length of stay were significantly higher in group 1 . multi - organ injury may be present in these patients , and acute phase high blood pressure can be one of the factors indicating a poor prognosis . it was suggested that antihypertensive treatments specifically related to the history and coexisting illnesses are required .

this study aimed to evaluate the prognostic value of acute phase blood pressure in patients with acute ischemic stroke by determining whether or not it contributes to clinical outcome . we studied 515 consecutive patients admitted within the first 48 hours after the onset of ischemic strokes , employing systolic and diastolic blood pressure measurements recorded within 36 hours after admission . high blood pressure was defined when the mean of at least 2 blood pressure measurements was 200 mmhg systolic and/or 110 mmhg diastolic at 6 to 24 hours after admission or 180 mmhg systolic and/or 105 mmhg diastolic at 24 to 36 hours after admission . the high blood pressure group was found to include 16% of the patients . age , sex , diabetes mellitus , hypercholesterolemia , atrial fibrillation , ischemic heart disease , stroke history , carotid artery stenosis , leukoaraiosis , nih stroke scale ( nihss ) on admission and mortality were not significantly correlated with either the high blood pressure or non - high blood pressure group . high blood pressure on admission was significantly associated with a past history of hypertension , kidney disease , the modified rankin scale ( mrs ) on discharge and the length of stay . on logistic regression analysis , with no previous history of hypertension , diabetes mellitus , atrial fibrillation , and kidney disease were independent risk factors associated with the presence of high blood pressure [ odds ratio ( or ) , 1.85 ( 95% confidence interval ( ci ) : 1.063.22 ) , 1.89 ( 95% ci : 1.113.22 ) , and 3.31 ( 95% ci : 1.368.04 ) , respectively ] . multi - organ injury may be presented in acute stroke patients with high blood pressure . patients with high blood pressure had a poor functional outcome after acute ischemic stroke .

under the leadership of the ministries of health ( mohs ) of liberia ( july december 2014 ) ( 2 ) and guinea ( december 2014june 2015 ) , epidemiologists from multiple agencies investigated rural outbreaks of evd . within a community outbreak , field epidemiologists identified case - patients , monitored their contacts , and developed diagrams of infection sequences on the basis of interviews with patients , families , and community members . transmission diagrams began with the first case identified in the community ( index case ) and ended when all known contacts had completed 21 days of monitoring with no new cases identified . in both countries , information from evd case report forms included age , sex , date of symptom onset , date of isolation in an ebola treatment unit ( etu ) , and date of recovery or death . data from guinea also included whether the person who died at home received a safe and dignified burial performed by trained teams ( 3 ) . these investigations were conducted as part of the ebola public health response in west africa and were not considered to be human subjects research . we used generalized estimating equations with a negative binomial distribution to compare the number of secondary infections between groups , including between persons with evd who died at home in the community and those admitted to an etu , between persons who were severely ill ( death <3 days after admission ) and those less ill ( death > 3 days of admission or recovery ) at the time of admission to an etu , and between persons who were buried safely by trained burial teams and those buried by untrained persons ( in guinea only ) . data were available for 347 persons with evd from 17 transmission chains ; 240 ( 69% ) persons were confirmed by using laboratory analysis ( real - time pcr ) as having evd ( table ) . most ( 185 , 53% ) persons with evd were admitted to an etu , of whom 102 ( 55% ) died , 78 ( 42% ) recovered , and 5 ( 3% ) had a missing outcome . a total of 162 ( 47% ) persons were not admitted to an etu , of whom 157 ( 97% ) died at home in the community and 4 ( 2% ) recovered without hospitalization ( 3 had confirmed cases and 1 had a probable case ) . etu , ebola treatment unit ; evd , ebola virus disease ; na , not available . we determined the number of secondary infections for 317 ( 91% ) persons with evd who had outcome data ; 99 ( 31% ) resulted in > 1 secondary infections , and there were differences by outcome status ( table ) . when we excluded the 4 case - patients who recovered in the community without hospitalization , the mean number of secondary infections was significantly higher for persons with evd who died at home in the community ( 1.8 , 95% ci 1.32.3 ) than for persons admitted to an etu ( 0.2 , 95% ci 0.10.3 ; p = 0.003 ) ( figure 1 , panel a ) . percentile distribution , by number of secondary infections , of persons with ebola virus disease ( evd ) in rural outbreaks in liberia and guinea , 20142015 . a ) comparison of persons with evd who died at home in the community and those who were isolated and treated in ebola treatment units ( etus ) . b ) comparison of persons admitted to etus who died <3 days or 3 days after admission . we found no significant difference in the mean number of secondary infections between those who died <3 days after admission to the etu ( 0.4 , 95% ci 0.050.90 ) and those who died later in their hospitalization or recovered ( 0.1 , 95% ci 0.060.30 ; p = 0.24 ) ( figure 1 , panel b ) . we also found no significant difference in the mean number of secondary infections associated with cases of evd in persons who received a safe burial ( 1.2 , 95% ci 0.81.7 ) versus those who did not receive a safe burial ( 1.8 , 95% ci 1.12.5 ; p = 0.40 ) ( figure 2 ) . percentile distribution , by number of secondary infections , of persons with ebola virus disease in rural outbreaks who died at home in the community , by safe burial status , guinea , 2015 . in rural outbreaks in liberia and guinea , ebola virus transmission was driven by contact with persons who died of evd at home , and isolation before death was associated with 88% fewer secondary infections . possible reasons for a larger number of secondary cases associated with deaths at home in the community include 1 ) a higher per - contact probability of transmission caused by higher levels of viremia or more exposure to body fluids during terminal illness and death ( 4 ) ; 2 ) a greater number of contacts between uninfected persons and persons with evd during their terminal illness or after death ; and 3 ) a greater number of uninfected persons having contact with persons with evd during their terminal illness or after death . because we did not find an increase in secondary infections according to severity of illness at the time of etu admission ( a proxy for level of viremia ) , we believe that factors associated with the death are critical in transmission . traditional burial practices in west africa include touching and washing the body after death ( 5 ) . extensive postmortem exposures to body fluids and skin could occur during that time , and postmortem studies of nonhuman primates have shown that ebola virus is stable in body fluids for as long as 3 weeks ( 6 ) . however , it is also likely that there is an increased number of secondary infections because more persons touch the corpse while paying respect to the deceased than would touch a living patient during their illness ( 7 ) . used a stochastic modeling approach to integrate epidemiologic data on ebola from liberia to identify potential intervention targets ( 8) . similar to our data , they found that secondary cases were most associated with nonsurvivors , and that isolation within 4 days of symptom onset could eliminate disease transmission . our findings differ slightly from those of yamin et al . because they suggest that isolation of cases of evd at any time before death would reduce transmission . in guinea , we did not find burials reported as safe to have had an effect on reducing the number of secondary infections . although some of the safe burials might have been misclassified , it is more likely that traditional mourning practices occurred before safe burial teams arrived ( 7 ) . response to future outbreaks should emphasize prevention of exposure to ebola virus during mourning and burial , and cadavers should be classified as safely buried only if they have not been touched after death . classifying contacts of persons who died of evd at home in the community as high - risk , regardless of whether they were reported to have received a safe burial , is an evidence - based approach to prioritizing those persons who should receive more rigorous monitoring . intensive follow - up could include assignment of highly trained staff to evaluate high - risk contacts more frequently , provision of incentives to complete the 21-day monitoring period , and housing high - risk persons in managed voluntary quarantine facilities . additional information on statistical analysis for secondary infections with ebola virus in rural communities , liberia and guinea , 20142015 .

persons who died of ebola virus disease at home in rural communities in liberia and guinea resulted in more secondary infections than persons admitted to ebola treatment units . intensified monitoring of contacts of persons who died of this disease in the community is an evidence - based approach to reduce virus transmission in rural communities .

certain colorectal conditions , such as ulcerative colitis and diffuse polyposis of the colon and rectum , and congenital intestinal abnormalities , such as total colonic aganglionosis , require a proctocolectomy and some type of intestinal restoration 1 . although these procedures are technically demanding for surgeons , they are more challenging for the patients following the restoration of intestinal continuity . frequency of bowel evacuations typically increases dramatically postsurgery , contributing to induced metabolic derangements 2,3 . we present a case of juvenile polyposis coli , initially treated with a subtotal colectomy and ileostomy , followed by a proctectomy , ileal - j - pouch and serial transverse enteroplasty ( step ) of the distal ileum 4 . an eight - year - old female patient was referred to our department with a chronic history of unremitting bloody diarrhea , weight loss , anemia and intractable rectal prolapse . there was no other significant past medical history or family history and her vaccinations were up to date . the initial clinical examination revealed a pale child who was underweight for age with mild clubbing of the fingernails . the abdominal examination was unremarkable , and the rectal examination was unnecessary because the cause of the prolapsed rectum was obvious , with a presentation of multiple polyps ( fig1 ) . blood tests confirmed clinical evident anemia with a hemoglobin of 7 g / dl , and her albumin level was 19 rectal polyposis was ratified by sight ( fig1 ) , and total colonic involvement was suspected on the contrast enema ( fig2 ) and was substantiated by colonoscopy ( fig3 ) and by the subtotal colectomy specimen ( fig4 ) . the histological diagnosis of hamartomatous juvenile polyposis was confirmed from the colonoscopic biopsies and the operative specimen . despite the initial temporizing approach of subtotal colectomy and ileostomy , anemia and protein - losing enteropathy persisted . the patient was discharged with dietary supplementation , and she had regular outpatient follow - up . the child s nutritional status improved over time , and she had albumin levels consistently over 36 a proctectomy was performed to remove the residual rectal polyps , and the ileostomy was taken down and fashioned as a j - pouch ( fig5 ) . multiple serial enteroplasties ( fig6 ) starting just above the pouch over a length of approximately 80 cm was performed , followed by a hand sewn ileo - anal anastomosis . the postoperative course was uneventful , and the patient was discharged 2 weeks later . at that stage , she was passing two soft stools per day without any medication or dietary restrictions . the follow - up at 3 months postsurgery confirmed a well - child who had gained 1.5 kg . she had returned to school and continued to pass one to two soft stools per day . restorative proctocolectomy has replaced disparate surgical options such as a hartmann s procedure and permanent ileostomy or ileo - rectal anastomoses because of their technical inadequacy , inability to improve quality of life and persistent cancer risk 5,6 . it removes the diseased intestine , thereby improving quality of life and reducing cancer risk 3 . intestinal leaks and pouchitis are major morbidities that might result in a long term or permanent ileostomy . an increased frequency and volume of enzyme - rich liquid stools although dietary restrictions and opioids might temporarily reduce the symptoms , they fail to cure these patients 7,8 . in these cases , the postoperative quality of life is indisputably not better than the pre - operative status . it is well reported that patients affected by severe short bowel syndrome benefit from the step procedure , because such an intervention can significantly reduce the frequency of stooling 913 . such large volumes must therefore have time and an appropriate intestinal length for water , electrolytes and other nutrients to be absorbed . this process is expected to occur within the j or other pouch configurations following restoration 14,15 . these pouches are quickly filled , and they easily surge ; the anal sphincter does not effectively counteract and contain the volume , which is usually controlled by the ileocaecal valve . large amounts of nutrients , electrolytes and water are wasted because evacuation is inevitable and continence training is not possible . step is a technique for lengthening the intestine in short bowel syndrome by interrupting the intestinal lumen thereby also slowing peristalsis . this procedure allows time for the nutrients , water and electrolytes contained within the intestinal lumen ( and distant from the distal anal anastomosis ) to be absorbed 4,11 . the outcome of our technical option was rewarding because the stool frequency and consistency were immediately in an acceptable range of two to three times per day and a soft consistency , respectively . this outcome was achieved without the use of opioids or the need for dietary restrictions . the child tolerated an unrestricted hospital diet and was discharged after 2 weeks when we were certain of her bowel habits and that she had maintained her physiological parameters . at 3 months follow - up , she was growing well and maintained a stool frequency of one to two soft stools per day . stool frequency can be crippling following proctocolectomy , and although opioids might provide temporary relief of the symptoms , they can not prevent relapses . we believe that step alone , performed in an adequate length of bowel , can control the stooling of such patients .

key clinical messagewe present a pediatric case of medically unmanageable juvenile colonic polyposis , initially treated with subtotal colectomy and an ileostomy followed by a proctectomy , ileal - j - pouch and serial transverse enteroplasties ( step ) of the distal ileum . the step procedure in an adequate length was able to control stooling of our patient .

amyloidosis is a group of diverse disorders characterized by extracellular deposits of abnormally folded protein that interferes with tissue function . these proteins form fibrillar , insoluble deposits with specific staining characteristics [ 1 , 2 ] . amyloidosis falls into several major categories : primary , secondary , dialysis - associated , and a variety of hereditary forms . primary amyloidosis is the most common form and is associated with the deposition of excess immunoglobulin light chains . secondary amyloidosis is associated with deposition of serum amyloid protein a in inflammatory and infectious conditions . patients on long - term hemodialysis form 2 microglobulin deposits [ 1 , 2 , 3 , 4 ] . amyloid deposits share distinct immunohistochemical characteristics and , at present , congo red staining of involved tissues remains the gold standard for detection . these deposits appear pink under bright - field microscopy and have apple - green birefringence under polarized light . some forms are exclusively localized , including some cerebral amyloidoses , but most exist in both localized and systemic forms . in either case , the goals of treatment are to prevent organ dysfunction and to eliminate the source of the abnormal protein [ 1 , 2 ] . the gastrointestinal tract is among the most common places for deposition of amyloid . the mouth is involved in 1020% of primary amyloidosis patients , most commonly as macroglossia . the esophagus , with symptoms including dysphagia , heartburn , and hematemesis , is involved in 1322% of patients . the stomach is involved in 812% of patients , but is usually asymptomatic [ 2 , 5 ] . small bowel manifestations include diarrhea , constipation , obstruction , ischemia , and infarction [ 2 , 3 ] . large bowel involvement presents with symptoms mimicking ischemia , malignancy , or irritable bowel disease and can eventually result in obstruction , stricture , and perforation [ 2 , 4 ] . large , localized deposition of amyloid is an uncommon occurrence and gives rise to amyloid pseudo - tumor , or amyloidoma . amyloidomas have been described in a variety of organs , including the heart , lungs , larynx , tongue , orbits , mediastinum , breast , bones , stomach , small bowel , and colon [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ] . we report a patient who presented with signs of bowel obstruction and was found to have a multitude of small amyloid implants throughout the abdomen and a solitary large amyloidoma encasing the ureters and rectosigmoid colon , resulting in obstruction . the patient was an 82-year - old male with a history of hypertension , osteoarthritis , and coronary artery disease who was in his usual state of fair health until approximately 3 years prior to the current hospital admission . at that time he noticed a slowly enlarging mass beneath his right mandible . he then underwent resection of his submandibular gland for what was ultimately found to be an extranodal marginal zone b - cell malt ( mucosa - associated lymphoid tissue ) lymphoma . he was treated at that time with cyclophosphamide , vincristine , and prednisone , and later with rituximab . laboratory studies showed that total serum protein , gamma chains , 1 protein , 12 protein , igg , igm , and 2 microglobulin were all elevated ( table 1 ) . the patient again presented to medical attention approximately 12 months ago due to symptoms of constipation and partial bowel obstruction . physical examination at that time showed a chronically ill - appearing elderly man with a distended abdomen and mild tenderness to deep palpation in the region of the umbilicus ; there was no rebound tenderness and no guarding . computed tomography of the abdomen showed a pelvic mass that measured 7.0 cm in greatest dimension and was localized to the left pelvic wall in the region of the rectosigmoid junction . over the intervening 12 months he underwent additional rounds of chemotherapy and radiation for what was presumed to be a part of his lymphoproliferative disease , but was never proven on biopsy . at the time of his final hospitalization , again for symptoms of bowel obstruction , he underwent a barium enema that showed a significant stricture at the rectosigmoid junction . the pelvic mass had progressively grown in size and now caused near - complete colonic obstruction . a contrast enema just prior to surgery revealed a string sign consistent with a long - segment , non - transient stricture of the colon at the rectosigmoid junction . the patient was taken to the operating room for exploratory laparotomy with the intention of resecting the pelvic mass to relieve his obstruction . at laparotomy , he was found to have multiple small nodules in the abdomen and pelvis not visualized on ct scan . the dominant mass was found in the pelvis and completely encased his ureters , the iliac vessels , and the rectosigmoid colon . given the extent of disease , it was felt that the mass could not be safely resected and to relieve his obstruction an end - colostomy was created . 2 ) . special stains to determine the specific protein responsible for forming the amyloidoma were not performed . abnormal glycoprotein , usually light chain immunoglobulin , or less commonly serum amyloid a protein , is deposited locally , forming a solitary mass . amyloidomas have been reported in a variety of anatomical sites including the gastrointestinal tract , central and peripheral nervous systems , soft tissue , bone , and the lung . malt lymphomas of the stomach are frequently associated with gastric helicobacter pylori colonization , which this patient did not have . when malt tumors are found at other sites malt lymphomas have been associated with amyloidomas on a number of occasions and there are reported cases in whom intraluminal amyloidoma was the cause of intestinal obstruction [ 3 , 4 ] . this is the first report we are aware of in which an extraluminal amyloidoma caused bowel obstruction by external compression . it is often mistaken for a malignant neoplasm such as metastatic carcinoma or lymphoma , and while it is not a true neoplastic process , amyloidosis can have devastating consequences for the patient . accurate diagnosis is only possible with histological examination of the involved tissues . staining with congo red and observation of apple - green birefringence under polarized light is essential to detect amyloid deposits . management of this patient 's disease was complicated due to extensive spread throughout the peritoneal cavity and its proximity to vital structures . surgical debulking has been described in treatment of limited disease by relieving the space - occupying effects of the amyloidoma . aggressive chemotherapy has been used in cases where underlying lymphoproliferative disorders were known , sometimes in combination with marrow ablation and stem cell rescue [ 1 , 3 ] . this patient 's underlying extranodal marginal zone b - cell malt lymphoma complicated the picture as amyloidosis is very rare in this subtype of malignancy . this erroneous assumption led to treatment of peritoneal disease for over a year with chemotherapy and radiation targeted at the lymphoproliferative malignancy without knowledge of the amyloidosis component . this case highlights the difficulty in diagnosis and management of this uncommon condition in combination with an underlying lymphoma , and the overall poor prognosis of disseminated amyloidosis .

amyloidosis is a group of diverse disorders that fall into several major categories : primary , secondary , dialysis - associated , and hereditary forms . clinically , amyloidosis may be categorized as localized or systemic . the gastrointestinal tract is among the most common places for deposition of amyloid , but large , localized amyloid deposits are an uncommon occurrence and rarely cause extraluminal bowel compression resulting in obstruction as was seen in the case presented in this clinical scenario .

genitalia are a key element for male self - esteem , especially among young men , contributing towards mental and physical balance , and influencing their social lives . the most popular surgical procedures requested are circumcision , penis elongation or enlargement . although circumcision is considered to be a simple surgical procedure , it requires particular attention and accurate surgical planning to avoid major complications such as extensive penile skin loss , , . various techniques are available for penile skin covering such as skin graft or cutaneous flaps . this specific surgery poses a particular challenge for plastic surgeons , regarding both aesthetical and functional aspects . in this article , the authors describe the use of the scrotal dartos - fascio - myo - cutaneous flap to recuperate penile shaft length after a catastrophic iatrogenic skin penis sub - amputation that provoked a drastic reduction in the length of the penis of a young hiv positive individual who underwent surgery for aesthetical purposes . a 27-year - old hiv positive man underwent circumcision for personal aesthetical reasons . a day after the procedure , a full dehiscence of surgical sutures was reported , probably due to excessive tension at the skin flap . 24 h later , it became obvious that recurrence of wound dehiscence had occurred for the second time . in this case , no surgical repair was performed and the patient was admitted to hospital . because of his hiv condition he was treated with antibiotic therapy : clavulanic acid + amoxicillin and levofloxacin and he was treated daily with local medical dressing to obtain a second intention repair . three months after his discharge he came to our attention because of a serious penile skin retraction . he also reported pain and constant sensation of tension in flaccidity ; he found it impossible to achieve a full erection due to a mechanical retraction . this condition did not permit him to have normal sexual activities and caused him extreme frustration . in addition , the patient was significantly dissatisfied with the aesthetical appearance of his penis because of a significant decrease in length even during flaccidity . a local physical examination revealed that the length of penis in flaccidity was 2.7 cm . a cutaneous brownish ring 1.8 cm in width was present at the base of the shaft in which some pillar elements could be observed . a pearly white scar 1.7 cm in width connected this cutaneous ring with a normo - trophic semi - mucosa portion immediately beneath the gland . during physical examination the consistency of the penis lacked elasticity , similar to a scar and it suggested secondary intention repair . the constricted scar was removed and all the adhesion scar tissue that entrapped the penis inside the pubis was released . when the shaft was completely free to come out of the pubis , two scrotal dartos fascia myo - cutaneous flaps were harvested on the lateral part of the scrotum ( fig . the flap pedicle base was 4 cm in width and 7 cm in length . the flap was planned in a racquet shape with the terminal part enlarged in order to completely wrap the entire circumference of the shaft.the flaps did not include the tunica vaginalis . they were rotated to cover the dorsal part of the shaft following the removal of two burrow 's triangles . the ventral part of the neo - shaft was covered advancing the remaining part of the scrotum containing the median rafe . in order to stabilize the flap , an urethral catheter was left in and the penis was kept strictly in a vertical position for 5 post op days . the preoperative length in flaccidity was approximately 2.7 cm and the result at the end of surgery was about 7 cm . in order to reduce nocturnal erection , the patient received 100 mg of cyproterone acetate , starting from the first dayafter the operation , and 5 mg diazepam before sleep ( fig . the constricted scar was removed and all the adhesion scar tissue that entrapped the penis inside the pubis was released . when the shaft was completely free to come out of the pubis , two scrotal dartos fascia myo - cutaneous flaps were harvested on the lateral part of the scrotum ( fig . the flap pedicle base was 4 cm in width and 7 cm in length . the flap was planned in a racquet shape with the terminal part enlarged in order to completely wrap the entire circumference of the shaft.the flaps did not include the tunica vaginalis . they were rotated to cover the dorsal part of the shaft following the removal of two burrow 's triangles . the ventral part of the neo - shaft was covered advancing the remaining part of the scrotum containing the median rafe . in order to stabilize the flap , an urethral catheter was left in and the penis was kept strictly in a vertical position for 5 post op days . the preoperative length in flaccidity was approximately 2.7 cm and the result at the end of surgery was about 7 cm . in order to reduce nocturnal erection , the patient received 100 mg of cyproterone acetate , starting from the first dayafter the operation , and 5 mg diazepam before sleep ( fig . suitable aesthetical appearance was obtained in terms of color match , consistency and acceptable penis length and girth . the patient stated that he was more confident with his penis after the surgical procedure . functional results were also reported as satisfactory in terms of skin laxity , pliability , elasticity during erection , sensibility and penetration during sexual intercourse ( fig . penile skin loss may occur as a consequence of trauma , carcinoma , infection , burns or iatrogenic causes such as excessive surgical excision during circumcision . it can cause severe retraction of the penis provoking a dramatic decrease in length with intra pubis entrapment . this condition severely limits sexual function and seriously impairs the aesthetical appearance , affecting both the psycho - physical balance and social life of the patient . a patient , with no local pathology , who underwent circumcision for aesthetical purposes that resulted in a mutilation due to an iatrogenic error , has very high expectations both for aesthetical and functional results . for these reasons , several techniques are available for recovery of the length of the shaft , such as skin grafts , local or free flaps . the stabilization of the skin graft during the healing is a crucial moment of this process and the medical dressing has a vital function . thin grafts heal more easily than full thickness grafts ; they provide better cosmetic results but , on the other hand they have less elasticity , offering less resistance to sexual intercourse . they also have a higher risk of retraction , restricting the filling of corpus spongiosa . full thickness skin grafts provide a better coverage quality but engraft with more difficulty , , . the most common flaps used for skin cover of the penile shaft are local perforators flap from the lower abdomen . among the free flaps , furthermore , when they are wrapped around the penis they offer a poor aesthetical result because of their unnatural appearance , , . satisfactory reconstruction requires regaining a good aesthetical appearance , a valid recovery of functionality with redundant and durable skin envelope for complete erection providing acceptable sexual intercourse and satisfactory sensation . the scrotum seems to be the most suitable tissue to reconstruct the skin coverage of the shaft as it is the most similar . its multi - origin vascular system provides its support basing each side on 4 different vessels : the anterior and lateral scrotal artery , the lateral branch of posterior scrotal artery and the septal scrotal artery . these vessels run through the dartos fascia of the scrotum ; it renders the scrotal dartos - fascio - myo - cutaneous flaps an axial flap . this subcutaneous network supports the vascular system of the scrotum very well , so that these flaps can be considered to be very resistant to ischemia , permitting wide variability in their planning both regarding dimension and shape , . the skin of the scrotum is the most similar to the skin of the shaft both for its color , thickness , elasticity and consistency its thinness , pliability and extensibility provide a better skin laxity during erection offering optimal functionality . use of the skin of the scrotum provides the best reconstruction in length and girth , and has the best aesthetical and functional results . the scars in the scrotum are hardly visible when compared to other parts of the body , and donor site morbidity is very low . on the other hand , to summarize , the authors believe that the dartos - fascio - myo - cutaneous flap works successfully for penile skin reconstruction . these flaps are axial flaps , based on a properly vascularized subcutaneous network that enablesa wide range of surgical planning regarding both dimension and shape . the quality of the skin tissue allows both satisfactory functional and aesthetical results with low morbidity of the donor site . in conclusion , the authors believe that it is a versatile strip , first choice for like - for - like reconstruction of the shaft , particularly suitable as it offers excellent functional advantages that are also useful for restoring self - confidence to the patient . all the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 helsinki declaration and its later amendments or comparable ethical standards . written informed consent was obtained from the patient for publication of this case report and accompanying images . a copy of the written consent is available for review by the editor - in - chief of this journal on request . yes , the guarantor accepts full responsibility for the work and conduct of the study , had access to the data , and controlled the decision to publish .

introductiongenitalia are linked to self - esteem and male sexual identity , especially among young men , who sometimes require a surgical procedure to acquire more confidence . among the surgical procedures requested for aesthetical purposes , circumcision is one of the most popular . although it can be considered to be a simple surgical practice , it may cause severe complications such as penile skin necrosis.presentation of casewe report a case of a catastrophic situation after a circumcision performed on a 27-year - old hiv positive man resulted in a drastic reduction in the length of the penile shaft due to extensive skin loss ; this was subsequently restored using dartos - fascio - myo - cutaneous flaps . primary healing occurred in 10 days . no infection , dehiscence or flap ischemia were reported . donor site morbidity was minimal . an adequate aesthetical appearance and satisfactory functional results were obtained.discussion and conclusionvarious techniques are available for penile skin covering , such as skin grafts or cutaneous flaps . the skin of the scrotum seems to be the most suitable tissue to be used to reconstruct the skin covering of the shaft as it is the most similar . dartos - fascio - myo - cutaneous flap is a single stage procedure that is easy and safe to perform . it can provide satisfactory cosmetic and functional results , offering a large amount of tissue , with minimal donor site morbidity .

left ventricular pseudoaneurysm ( lvp ) is a noncommon complication of myocardial infarction ( mi ) . other less frequent causes include mitral valve surgery , bacterial endocarditis , and previous chest trauma . its formation is consequent to the incomplete rupture of the myocardial free wall contained by adherent pericardium or scar tissue . its noninvasive diagnosis can be easily obtained by transthoracic echocardiography or magnetic resonance imaging ( mri ) , left ventriculography is the most accurate diagnostic method but requires an invasive procedure . we refer on a patient who presented an lvp occurred as a consequence of an inferior mi and evaluated with both traditional , noninvasive methods and three - dimensional echocardiography ( 3d - e ) . three - dimensional echocardiography findings add adjunctive and more accurate informations about lv pseudo - aneurysm respect to those of two - dimensional echocardiography a 79-year - old nondiabetic man joined to the emergency department complaining chest discomfort and pulmonary congestion , restlessness , perspiration , and anxiety . physical examination evidenced the arterial pressure of 115/75 mmhg and the heart rate of 72 beats min . electrocardiogram ( ecg ) showed s - t segment elevation in leads iii and avf and q waves in leads ii , iii , and avf [ figure 1 ] . at two - dimensional echocardiography ( 2d - e ) , decreased lv systolic function ( ejection fraction of 40% ) with akinesia of the inferior septum and posterolateral wall , was evident . immediately , the patient was submitted to two - stent implantation in the same arteries . four weeks after the percutaneous angioplasty , he presented dyspnea , weakness , and stertors in both pulmonary bases . the continuity of the myocardium at the posterior wall was disrupted and a narrow neck communicating with a small sac was seen at repeated 2d - e [ figure 2 ] . cardiac mri also pointed out a small dilation with a narrow neck in the posterior wall of the lv [ figure 3 ] . a full volume acquisition was obtained during held respiration and volume of lvp acquired at end - diastole was of 59.3 ml [ figure 4 ] . the 12-lead electrocardiogram shows st elevation and q waves in inferior derivations ( diii and avf ) and negative t in lateral derivations . two - dimensional echocardiography shows the pseudoaneurysm ( ps . ) and its neck interesting the left ventricular inferior wall . it was been primarily found in the posteroinferior wall and in basal segments of lv myocardium while less frequently occurs in the anterior lv wall . the most common clinical presentation is dyspnea or congestive heart failure . in other cases , mri is an effective diagnostic method to confirm the presence of an aneurysmal dilation and disruption of the epicardial layer . 3d - e is able to define the size and shape of lvp , making easier to evaluate its dimensions , the visualization of diastolic volume , and the neck identification . in addition , this noninvasive method is more useful in its presurgical assessment and for diastolic volume evaluation of lvp . conclusively , 3d - e is able to add further and more useful informations on lvp respect to those supplied by conventional , noninvasive methods . , 3d - e appears as a more useful and less time - consuming in comparison with 2d - e , in order to evaluate lv size and shape , its global function and the extension of myocardial scar .

we present a case of posterior left ventricular pseudoaneurysm , a rare but potentially lethal complication of inferior acute myocardial infarction . the clinical findings and the customary , noninvasive diagnostic methods used are illustrated . particularly , the most evident display obtained by the employment of three - dimensional echocardiography in comparison to those supplied by two - dimensional ultrasonic method was illustrated .

medication errors refer to a failure at some point during a treatment process , which may lead to patient harm.1 several studies in current literature identify key issues regarding medication errors , specifically , that they are more likely to occur at interfaces of care where there is an element of data transcription.2 the world health organization has explicitly identified confusing drug names as one of the most common causes of medication error.3 factors that contribute to potential confusion between drug names include spelling - related , phonetic , or packaging similarities.48 it has been established that confusion , and therefore error , is more likely if medicines appear in the same context or if drugs are being selected from a drop - down list.4 multiple studies have concluded that look - alike , sound - alike ( lasa ) errors stem from both human error and the failure of prescribing systems across the health care spectrum to be able to recognize the potential for these errors.4,5,8 one method consistently recommended to decrease lasa errors is tall man lettering a textual format recognized and recommended by the us federal drug administration ( fda ) , which involves writing the confusable parts of lasa drug names in uppercase.9 it has been established that tall man lettering does improve accuracy in the perception of drug names.9 the home medicine review ( hmr ) program was established in australia in 2001 in order to facilitate quality use of medicines through pharmacist intervention . hmrs are initiated by a patient s general practitioner and have been established to be an effective tool in medicine safety in a number of patient groups , including those with multiple medications , medication barriers ( eg , language barriers or visual impairment ) , or patients undergoing medication changes such as a recent discharge from hospital.1012 a hmr conducted by an accredited community pharmacist in australia in 2011 revealed that a patient was mistakenly prescribed slow - na instead of slow - k . the patient had a medical history of deep vein thrombosis , right hip fracture , pulmonary embolism , chronic obstructive airway disease , and ischemic heart disease . at the time of the hmr , the patient had current prescriptions for warfarin sodium ( 5 mg ) , frusemide ( 20 mg ) , fluticasone propionate / salmeterol , tiotropium , and salbutamol sulfate , in addition to the prescription for slow - na ( 600 mg ) . it was established that the patient was prescribed slow - k after being diagnosed with hypokalemia following an 8-week hospitalization for pneumonia . during the prescribing process , slow - na was mistakenly selected from a drop - down software list ( figure 1 ) . due to financial reasons , the patient had not filled the incorrect prescription , and the error was identified before the patient obtained slow - na . adverse events that may have eventuated due to untreated hypokalemia include increased risk of arrhythmias , skeletal myopathy , metabolic acidosis , and acute kidney injury.13 increased sodium intake may have also resulted in altered mental status.13 given that this particular lasa error has not been reported in the literature to date , it presents a novel drug pair listing in lasa errors . although this particular lasa error is unlikely to recur in australia due to the discontinuation of slow - na in 2011 , it highlights the ongoing need for vigilance with respect to lasa errors , as new drug pairs continue to be identified as potential and actual sources of error . a recent australian study commissioned by the australian national medicines policy committee reviewed 32 publications on lasa medication errors and strategies that may be implemented to decrease their incidence.6 the review determined that in order to decrease errors from lasa medications , all stages of the medication process , from manufacture through to administration , must be perused and strategies must be designed to address potential problems.6 this finding is consistent in current literature.1,6 a national tall man lettering standard in prescribing software was the recommendation provided by the australian commission on safety and quality in healthcare following a review.14 the recommended standard would only incorporate a set list of medications associated with orthographic error.14 in the case reported herein , tall man lettering may have drawn attention to the lasa error before it perpetuated through the medication process to the patient . given that lasa errors are well described in the literature , australia should aspire to develop and apply innovative solutions to decrease the incidence of lasa errors to facilitate quality use of medicines . although the error described in the case herein was identified before the patient commenced treatment with the incorrect drug , it highlights the ongoing need for vigilance with respect to lasa errors , as new drug pairs continue to be identified as potential and actual sources of error . the slow - na , slow - k lasa error reported here was identified during a hmr . the recognition of the error is a significant example of the importance of medication review throughout the entire medication process . pharmacists in particular have an important role in the community in implementing and undertaking strategies , such as hmrs , to minimize adverse drug events to ensure quality use of medicines . this case highlights the fundamental role of hmrs in the community and these should continue to be utilized as an effective tool in identifying lasa errors .

a 59-year - old man was mistakenly prescribed slow - na instead of slow - k due to incorrect selection from a drop - down list in the prescribing software . this error was identified by a pharmacist during a home medicine review ( hmr ) before the patient began taking the supplement . the reported error emphasizes the need for vigilance due to the emergence of novel look - alike , sound - alike ( lasa ) drug pairings . this case highlights the important role of pharmacists in medication safety .

mother s breast milk is known to contain a variety of biologically active compounds , these include immunological growth factors , cytokines , hormones , oligosaccharides , antimicrobial peptides , enzymes , and immunoglobulins ( 1 ) . growth factors are such as epidermal growth factor ( egf ) , insulin - like growth factor - i ( igf - i ) , transforming growth factor ( tgf ) , and hepatocyte growth factor ( hgf ) ( 2 ) . the hormone igf-1 is a mediator of human growth hormone ( hgh ) and serves to stimulate bodily growth , regulates growth hormone independent anabolic reactions in many types of cells and tissues . igf-1 is an atypical peptide in that it is composed nearly 99% of bound proteins ( 3 ) . igf-1 uses specified cell receptors located on the cell membrane surface to accomplish many mitogenic cell functions that include the induction of cell growth , cell division , and differentiation ( 4 ) . igf-1 tends to initiate an anabolic effect , which increased the utilization of glucose and amino acids while inhibiting protein catabolysis ( 5 ) . since mothers with diabetes tend to suffer from perioidic hyperglycemia , this exposes their fetuses to high glucose levels causing fetal hyperglycemia that stimulates fetal growth and glycogen disposition encouraging macrosomia ( 6 ) . the goal of this research study seeks to determine the igf-1 levels in breast milk of mothers with diabetes and the blood serum of their newborn babies and to establish if their exists any relationship between these measures and the anthropometric measurements of diabetic mother s babies . mother s breast milk is known to contain a variety of biologically active compounds , these include immunological growth factors , cytokines , hormones , oligosaccharides , antimicrobial peptides , enzymes , and immunoglobulins ( 1 ) . growth factors are such as epidermal growth factor ( egf ) , insulin - like growth factor - i ( igf - i ) , transforming growth factor ( tgf ) , and hepatocyte growth factor ( hgf ) ( 2 ) . the hormone igf-1 is a mediator of human growth hormone ( hgh ) and serves to stimulate bodily growth , regulates growth hormone independent anabolic reactions in many types of cells and tissues . igf-1 is an atypical peptide in that it is composed nearly 99% of bound proteins ( 3 ) . igf-1 uses specified cell receptors located on the cell membrane surface to accomplish many mitogenic cell functions that include the induction of cell growth , cell division , and differentiation ( 4 ) . igf-1 tends to initiate an anabolic effect , which increased the utilization of glucose and amino acids while inhibiting protein catabolysis ( 5 ) . since mothers with diabetes tend to suffer from perioidic hyperglycemia , this exposes their fetuses to high glucose levels causing fetal hyperglycemia that stimulates fetal growth and glycogen disposition encouraging macrosomia ( 6 ) . the goal of this research study seeks to determine the igf-1 levels in breast milk of mothers with diabetes and the blood serum of their newborn babies and to establish if their exists any relationship between these measures and the anthropometric measurements of diabetic mother s babies . this prospective case - control study was conducted on 45 neonates and their mothers who were selected from among the neonates present at the nicu and outpatient clinic of neonatology at al minia university pediatric hospital during the period from may 2012 to may 2013 . the neonates and their mothers were divided into two groups : group i ( cases ) included 30 diabetic mothers and their infants , with a gestational age from 3740 weeks , group ii ( control ) included 15 non - diabetic healthy mothers and their infants with a gestational age from 3740 weeks . newborns having congenital anomalies , chromosomal disorders , perinatal asphyxia , sepsis , and whose mothers had disease complications during pregnancy all the newborns included in the study were subjected to a comprehensive medical history as well as taking complete medical examination including anthropometric measurement ( body weight , length , rohrer s neonatal ponderal index ( npi ) , skin fold thickness at triceps and subscapular areas , abdominal circumference , and head circumference ) were performed on the same day , using standardized equipment . three consecutive measurements were taken and when the differences between the readings were acceptable , then the mean was recorded . neonatal blood sample : under complete aseptic technique , 3 cc of venous blood withdrawn into plain tubes for clotting , centrifugation , and serum fractionation . these sera are collected in sterile tubes , then stored at 20 c until used , breast milk samples ( 10 ml ) were collected by a trained nurse from both breasts by manual expression before feeding and then frozen at 20 c within 24 hours or until used . the assay of the igf-1 : this was accomplished by using the enzyme - linked immuno - sorbent assay ( igf-1 600 elisa ) technique ( raybiotech inc . ) by awareness technology inc . chicago , illinois , usa ) using descriptive statistics , t - test , chi - square test , and the pearson product - moment correlation coefficient . the study group consisted of 30 infants and their diabetic mothers and the control group consisted of 15 healthy infants and their mothers . in this study , the infants of diabetic mothers ( idm s ) showed a highly significant increase in the mean of weight , neonatal ponderal index , abdominal circumference , head circumference , triceps skin fold thickness , and sub - scapular skin fold thickness ( p < alao , regarding the mode of delivery of the idms born by cesarean section ( cs ) significantly increased over the control group ( p < 0.001 ) ( table 1 ) . in addition , idms showed highly significant increases in the level of igf-1 in the blood serum as well as their mother s breast milk when compared to the control group ( p < 0.001 ) ( table 2 ) . there was a highly significant positive correlation between serum igf-1 and all anthropometric measures ( weight , head circumference , abdominal circumference , triceps skin fold thickness , sub - scapular skin fold thickness , npi ( p < 0.001 ) , and length ( p < 0.01 ) ( table 3 ) . also , there was a highly significant positive correlation between the milk igf-1 and all of the anthropometric measures ( weight , head circumference , abdominal circumference , triceps skin fold thickness , sub - scapular skin fold thickness , and npi ( p < 0.001 ) with the exception of length ( table 3 ) . insulin - like growth factor-1 ( igf-1 ) is a pleiotropic factor with a wide spectrum of actions in the central and peripheral nervous system ( 7 , 8) . it belongs to a superfamily of structurally related proteins that include insulin , igf-1 , and igf-2 . the biological functions of igf-1 are mediated by specific membrane receptors designated as igf-1 receptors . there are six igf - binding proteins ( igfbps ) , which modulate the bioavailability and receptor targeting of the igfs ( 9 ) . ( 10 ) demonstrated that igf-1 was present in mature and premature human milk samples , its levels were several - fold higher in colostrum than in mature milk and it tends to decrease over the first few days of lactation , they believed that igf-1 could be either synthesized by the mammary gland or transferred from the maternal circulation . additionally , sevigny et al . , ( 11 ) identified igf - binding proteins ( igfbps ) in the human milk of term and preterm infants and found that infants fed with artificial formula during the first months of life showed higher igf-1 levels than breast feeding ones . in the present study , diabetic mothers showed higher rates of performing cs when compared to the control group ( p < 0.0001 ) and this is in agreement with oussama et al . , ( 12 ) their findings suggested that high birth body mass or fetal macrosomia could be considered to be a typical complication of gdm and may be linked to negative maternal and newborn health factors that could include a tendency for maternal postpartum hemorrhaging , perineal tearing , and a greater chance for the need for cs . in the current study , idms showed a significantly higher mean weight , higher npi , greater abdominal circumference ( ac ) , greater triceps skin fold thickness ( tsft ) , greater sub - scapular skin fold thickness ( ssft ) , and head circumference ( hc ) when compared to the control group ( p < 0.001 ) , but there was no significant difference between the case and control groups with regards to neonatal length ( p > 0.05 ) ; this is in agreement with lauszus et al . they studied diabetic pregnancy and noted increases in all of the anthropometric measures in idm as compared to infants of non - diabetic mothers . in our study , idms showed a significantly higher mean serum igf-1 when compared to the control group ( p < 0.001 ) . this may be related to the pronounced metabolic disturbances characterized by hyperinsulinemia in these neonates , which was resulting from maternal hyperglycaemia , with this remaining in a negative correlation with igfbp-1 , intensifies igf-1 secretion , which results in higher concentrations of igf - i in infant serum . additionally , this high level of serum igf-1 may be due to the increased level of placental growth hormone ( gh ) found in serum of idms . ( 14 ) who found that mean levels of igf-1 were significantly higher in the cord blood of the offspring of mothers with gestational diabetes . studies done to investigate igf-1 in the breast milk of diabetic mothers were very scarce . in this study , we found that there was a highly significant increase in the mean maternal milk igf-1 when compared to the control group ( p < 0.001 ) . the breast milk of diabetic mothers has been shown to have a different composition from that of non - diabetic mothers , it may contain elevated levels of glucose and insulin as well as decreased polyunsaturated fatty acids and it is possible that this high level of insulin may elevate the level of igf-1 . also , maternal serum seems to be the primary source of milk igf-1 , so this leads to a high level of igf-1 in the breast milk of diabetic mothers . ( 15 ) who found that the igf-1 concentration in serum of the pregnant diabetic women was significantly higher in comparison with healthy pregnant women . it can be suspected that the observed increased concentrations of igf-1 in dm is a type of compensatory reaction to the increased insulin resistance and hyperinsulinemia , which increases the igf-1 secretion , resulting in a higher concentration of igf-1 in blood serum or manifesting a high level of igf-1 in maternal serum that may be due to a higher level of placental gh found in the serum of pregnant diabetic women , which is the main driver of igf-1 production . the present study found that serum igf-1 levels in idms was positively related to neonatal weight , length , npi , hc , ac , tsft and ssft ( p < 0.05 ) . it has been reported that igf-1 is an important modulator of growth hormone activity in linear growth . also , igf-1 plays a central role in the regulation of prenatal and postnatal growth and also exerts a growth modulating effect by decreasing apoptosis and increasing cell proliferation and angiogenesis so it may be said that igf-1 is positively related to macrosomia and increasing anthropometric measures in idm . this is in agreement with previous research studies ( 5 , 1619 ) that found that igf-1 in cord blood of idm was positively correlated to weight , length , hc , tsft , and ssft . all these findings were corroborated by the data , pointing to the fact that igf-1 plays an active role in the regulation of fetal growth . also , lindsay et al . ( 14 ) emphasized that igf-1 and igfbp-1 showed significant positive and negative correlations , respectively , with birth weight in all of the offspring of diabetic mothers . this study found that maternal milk igf-1 level in diabetic mothers was positively related to neonatal weight , npi , hc , ac , tsft , and ssft ( p < 0.001 ) , but had no significant relationship to neonatal length . igf-1 increased in the milk of diabetic mothers and the serum of their infants there is an association between intrauterine fetal growth and igf-1 in idms , as reflected by anthropometric measurements . there is evidence that the increased action of igf-1 is likely in the offspring of diabetic mothers and represents part of the mechanism of fetal overgrowth . further studies on larger scale are recommended to specify the exact effects of igf-1 on idms and further studies are recommended to clarify the exact level and role of igf-1 in the milk of diabetic mothers .

introductionsince research investigating igf-1 levels in breast milk are few , the goal of this study was to analyze the igf-1 levels in the breast milk of diabetic mothers as well as in the serum of their newborn babies and to identify what relationship exists between blood serum and igf-1 milk levels through patient measurement of mothers and their babies.methodsthis case control study was undertaken under the auspices of the clinic of neonatology at al minia university pediatric hospital over may 2012 through may 2013 . with a total of 30 diabetic mothers and their babies forming the experimental group and the control group consisting of 15 non - diabetic mothers and their babies . a detailed medical history , anthropometric assessments , as well as the measurement of the baby s serum igf-1 and their mother s breast milk igf-1 levels were taken from all participants using elsia . the resulting data were analyzed via statistical package for the social sciences ( spss ) version 16 and measurements of descriptive statistics , t - test , chi - square test , as well as the pearson correlation coefficient.resultsthe infants born to diabetic mothers ( idms ) demonstrated significantly greater anthropometric measurement . both the serum levels and the milk igf-1 levels as well as all of the physical measurements taken were found to have a positive correlation between the level of igf-1 in mother s milk and all of the anthropometric measurements studied with the exception of delivered baby s length.conclusionhigher levels of igf-1 are present in the milk of diabetic mothers and the blood serum of their babies and this characteristic could be used as a prenatal biomarker for macrosomia .

we assessed hev seroprevalence in a large subsample ( n = 4,422 ) of the 20082011 german health examination survey for adults ( deutscher erwachsenen gesundheitssurvey ; www.degs-studie.de ) , a 2-stage national probability sample that assessed the health status in the general population . the sampling frame comprised persons 1879 years of age whose principal residence was in germany and who were fluent in german . our subsample reflects the total adult population with respect to age , sex , and geographic region , but persons with migration background are underrepresented ( non - german citizenship 4.6% in the sample vs. 8.7% in the total adult population ) . serum samples were screened for hev igg by using the recomline hev - igg / igm immunoassay ( mikrogen , neuried , germany ) . the assay is based on 7 recombinantly expressed antigens of genotypes 1 and 3 of open reading frames 2 and 3 . according to the manufacturer s and our data ( j.j . data ) , the test is 97%100% sensitive for detecting acute or previous hev infections . the intensity of 3 quality assurance and other bands was determined by densitometrical detection algorithms . each antigen band with an intensity greater or equal to the cutoff was assigned a point value . the final results were classified into 3 categories : no antibodies detectable ( negative ) , test inconclusive ( borderline ) , and antibodies detectable ( positive ) . persons whose test results were borderline ( n = 70 ) were excluded from further analysis . we poststratified the remaining survey population ( n = 4,352 ) by age group and location of residence ( 16 states ) to account for per protocol oversampling in eastern germany and to restore the distribution of age groups to match the distribution in the total population . associations between demographic characteristics and seropositivity were analyzed by using adjusted wald test p values . we also estimated mean annual incidence of hev seroconversion from the seroprevalence data by using a catalytic model with age - constant force of infection , similar to that of faramawi et al . the 4,352 persons who were included in the analysis were from 108 communities of all federal states in germany ( table 1 ) . weighted prevalence of hev igg was 16.8% ( 95% ci 15.6%17.9% ) ; prevalence ranged from 6.1% ( 95% ci 4.5%7.8% ) in the 1834-year age group to > 20% in the > 50-year groups , with a maximum of 26.4% ( 95% ci 21.6%31.1% ) in the 6064-year group ( figure ) . in the univariable analysis ( table 2 ) , only age group was significantly associated with seropositivity ( p<0.01 ) ; results were not significant for sex ( p = 0.97 ) , residence ( northern / middle / southern germany , p = 0.29 ; west / east , p = 0.43 ) , or population of municipality ( 4 categories ; p = 0.10 ) . in separate multivariable models , each including age group and 1 other variable , age remained the only significant variable . mean annual incidence of hev seroconversion estimated from the catalytic model was 3.9 ( 95% ci 3.6%4.2% ) per 1,000 population . adults 1879 years of age as of december 31 , 2009 ( www.destatis.de ) . estimated prevalence of hepatitis e virus ( hev ) igg , by age group , germany , 20082011 . we found an overall hev seroprevalence of 16.8% among adults in germany ; seroprevalence increased with age but was not dependent on sex or location of residence . similarly high seroprevalence was found in blood donors in denmark ( 20.6% ) , southwestern england ( 16% ) , and the united states ( 18% ) ( 6,7,9 ) . estimates from switzerland and the netherlands , on the other hand , are considerably lower ( 10,11 ) . reasons for these differences could be effects of sample selection , different lifetime exposures ( e.g. , to foods that may serve as transmission vehicles ) , or use of different test systems with varying sensitivity . recently reported 53% prevalence of hev antibodies in blood donors in southwestern france ( 13 ) , a figure considerably higher than the 17% prevalence reported earlier for the same geographic region , when a different test system was used ( 8) . the assay applied in our study was designed to also detect previous infections with hev genotype 3 ; therefore , it is likely to be more sensitive than assays used in previous studies . our data show that hev exposure is common among the general adult population in germany , which is consistent with increasing evidence for pigs as a reservoir for foodborne transmission of hev in industrialized countries . hev seroprevalence is high in domestic pig herds in germany and other countries ; closely related hev strains were found in pig livers on retail sale and in autochthonous cases of hepatitis e , and hev seroprevalence was higher in persons with occupational exposure to pigs than in control groups ( 4,10,14,15 ) . our data and other studies ( 1114 ) have shown no significant difference in seroprevalence between sexes , despite an assumed higher frequency of alimentary or occupational exposure and the higher incidence of clinical cases among men . this finding may indicate sex - specific differences in disease development or application of laboratory testing or that foods frequently consumed by both sexes play a substantial role as vehicles for transmission . these results also may highlight the lack of evidence for 1 main risk factor or food vehicle ( 14 ) . the strong association between age and hev seroprevalence in our study most likely reflects cumulative lifetime exposure to the virus . however , hev seroprevalence remains relatively stable from 18 to 34 years of age , which could indicate a birth cohort effect resulting from a decrease in the overall risk over the past few decades , as was reported for denmark ( 6 ) . the leveling off of the seroprevalence above age 60 years could be caused by a loss of antibodies in the elderly . we found a striking difference between the estimated annual incidence of seroconversion and the relatively low incidence of notified disease in germany . besides underdiagnosis , a possible explanation is a high proportion of asymptomatic infections . the survey response rate is similar to those achieved in other comprehensive national health examination surveys in europe . in the statistical analysis , we corrected for differences in the distribution of age and place of residence between the sample and the general population . however , foreign - born persons are underrepresented in the survey because participation required fluency in german . a high proportion of foreign - born persons in germany are muslim , and their avoidance of raw pork products likely decreases their risk for hev infection , which means we may have slightly overestimated the seroprevalence in the adult general population . autochthonous hev infections are common in the industrialized world , and testing for hev is indicated in patients with acute hepatitis , irrespective of history of travel to developing countries . recommendations against eating undercooked pork products exist , but further studies are needed to specify implicated food products and to better target recommendations for safer food production , preparation , and consumption . details of mathematical methods used to compute the yearly incidence from the seroprevalence data in the manuscript .

we assessed hepatitis e virus ( hev ) antibody seroprevalence in a sample of the adult population in germany . overall hev igg prevalence was 16.8% ( 95% ci 15.6%17.9% ) and increased with age , leveling off at > 60 years of age . hev is endemic in germany , and the lifetime risk for exposure is high .

it has been found at autopsy in 8 to 9% of cases of extraneural malignancy.1 laigle - donadey et al2 found in a series of 198 cases of dural metastasis that the tumor types metastasizing to the dura mater are cancers of the prostate ( 19.5% ) , breast ( 16.5% ) , lung ( 11% ) , and stomach ( 7.5% ) ; thus prostate cancer is evidently more susceptible to spread to the dura . tremont - luktas et al3 reported that in 118 cases of brain metastasis of prostate cancer , 19 spread to the dura . in a few cases , the diagnosis of dural metastasis was made following subdural bleeding . however , in other cases no blood was found during surgery , thus revealing the mimicking appearance of the subdural metastasis . recognition of this latter occurrence may help determine the best management for each individual case . we report a case of dural metastasis of prostate cancer mimicking subdural hematoma ( sdh ) . we reviewed the english and french literature for cases presenting with suspected sdh to ascertain common clinical and imagery characteristics of metastasis mimicking sdh . a 65-year - old man was admitted to the emergency department presenting with headache , confusion , and progressive right upper limb weakness . past history included a metastatic prostate adenocarcinoma 3 years earlier , for which he underwent hormonal therapy . his prostate - specific antigen ( psa ) fell from 377 to 190 g / l . computed tomography ( ct ) scan of the head without contrast revealed a multinodular bilateral hyperdense extra - axial lesion ( fig . 1a ) with a midline shift of 4 mm to the right ( fig . this image was interpreted as acute sdh . the patient was initially observed . the next day he became more confused and progressively nonresponsive . a left parietal burr hole was performed for sdh drainage . upon opening the dura , a craniotomy was performed , revealing an en plaque frontoparietal temporal subdural yellowish tumor , with no cortical involvement . postoperative magnetic resonance imaging ( mri ) showed prominent irregular enhancing tissue along the dura consistent with bilateral dural metastasis ( fig . the patient progressively recovered and left the hospital at day 15 with little weakness of the arm . retrospectively , we suspect that the clinical deterioration and the rapid increase of the midline shift might be due to an impaired brain venous drainage secondary to the extensive dural metastasis . histopathologic examination of the obtained tissue was consistent with metastatic adenocarcinoma of the prostate . due to the extensive generalized bone metastasis that was nonresponsive to previous chemotherapy ( a ) axial nonenhanced computed tomography scan of the head without contrast showing a multinodular bilateral hyperdense extra - axial lesion with ( c ) postoperative magnetic resonance imaging showed prominent irregular enhancing tissue along the dura consistent with bilateral dural metastasis . ( c ) large en plaque subdural tumor . in the literature we found 11 cases4 5 6 7 8 9 10 11 ( table 1 ) reported as dural metastasis of prostate cancer presenting as or mimicking an sdh . between the first diagnosis of prostate cancer and the discovery of the dural metastasis , the time ranged from 3 months to 7 years ( mean : 33 months ) ; the mean age of these patients was 64.5 years . all patients ( when data were known ) presented in the advanced stage with metastasis . no correlation was found between an anterior history of head trauma and the finding of blood on surgery . two cases were not operated on because of the obvious evidence of dural metastasis , seen on ct scan and mri . in all the other cases surgery was performed with no suspicion of dural metastasis . in five cases in these cases the burr hole or craniotomy that had been preoperatively planned had to be converted into a larger craniotomy . when reviewing the preoperative nonenhanced ct scan images of all of the 11 patients , we can describe three types of image patterns ( fig . c ) : a nodule in sdh ( two cases),4 9 multinodular metastasis surrounded by sdh ( three cases),4 7 8 and large en plaque subdural tumor ( six cases).5 6 10 11 12 13 this latter group consists of those cases where no blood was found at surgery . abbreviations : ct , computed tomography ; na , not available ; nmr , nuclear magnetic resonance ; sdh , subdural hematoma . a , single nodular ; b , multinodular ; c , en plaque . a 65-year - old man was admitted to the emergency department presenting with headache , confusion , and progressive right upper limb weakness . past history included a metastatic prostate adenocarcinoma 3 years earlier , for which he underwent hormonal therapy . his prostate - specific antigen ( psa ) fell from 377 to 190 g / l . computed tomography ( ct ) scan of the head without contrast revealed a multinodular bilateral hyperdense extra - axial lesion ( fig . 1a ) with a midline shift of 4 mm to the right ( fig . this image was interpreted as acute sdh . the patient was initially observed . the next day he became more confused and progressively nonresponsive . a left parietal burr hole was performed for sdh drainage . upon opening the dura , a craniotomy was performed , revealing an en plaque frontoparietal temporal subdural yellowish tumor , with no cortical involvement . postoperative magnetic resonance imaging ( mri ) showed prominent irregular enhancing tissue along the dura consistent with bilateral dural metastasis ( fig . the patient progressively recovered and left the hospital at day 15 with little weakness of the arm . retrospectively , we suspect that the clinical deterioration and the rapid increase of the midline shift might be due to an impaired brain venous drainage secondary to the extensive dural metastasis . histopathologic examination of the obtained tissue was consistent with metastatic adenocarcinoma of the prostate . due to the extensive generalized bone metastasis that was nonresponsive to previous chemotherapy ( a ) axial nonenhanced computed tomography scan of the head without contrast showing a multinodular bilateral hyperdense extra - axial lesion with ( c ) postoperative magnetic resonance imaging showed prominent irregular enhancing tissue along the dura consistent with bilateral dural metastasis . in the literature we found 11 cases4 5 6 7 8 9 10 11 ( table 1 ) reported as dural metastasis of prostate cancer presenting as or mimicking an sdh . between the first diagnosis of prostate cancer and the discovery of the dural metastasis , the time ranged from 3 months to 7 years ( mean : 33 months ) ; the mean age of these patients was 64.5 years . all patients ( when data were known ) presented in the advanced stage with metastasis . no correlation was found between an anterior history of head trauma and the finding of blood on surgery . two cases were not operated on because of the obvious evidence of dural metastasis , seen on ct scan and mri . in all the other cases surgery was performed with no suspicion of dural metastasis . in five cases no blood was found ; there was an en plaque subdural tumor . in these cases the burr hole or craniotomy that had been preoperatively planned had to be converted into a larger craniotomy . when reviewing the preoperative nonenhanced ct scan images of all of the 11 patients , we can describe three types of image patterns ( fig . c ) : a nodule in sdh ( two cases),4 9 multinodular metastasis surrounded by sdh ( three cases),4 7 8 and large en plaque subdural tumor ( six cases).5 6 10 11 12 13 this latter group consists of those cases where no blood was found at surgery . abbreviations : ct , computed tomography ; na , not available ; nmr , nuclear magnetic resonance ; sdh , subdural hematoma . a , single nodular ; b , multinodular ; c , en plaque . however , prostate cancer appears to be the most common origin of dural metastases.2 14 in their large series on dural metastases , laigle - donadey et al2 observed that dural metastasis originated from the direct extension of skull metastasis in 57% of cases and from a hematogenous route in 43% of cases . another potential mechanism for skull and subdural metastases of prostate cancer could be retrograde spread through the vertebral venous plexus . it is also known that dural metastasis can present as , or mimic , sdh.4 5 7 8 9 10 12 13 including the present case , 12 cases have been reported.4 5 6 7 8 9 10 12 13 of the 104 5 7 8 9 10 12 13 operated cases , the preoperative diagnosis of subdural metastasis was missed . in five cases5 10 11 12 13 no blood was found during surgery ; instead there was an en plaque subdural tumor . all 12 cases were known for prostate cancer with most of them in an advanced stage with bone or lymph node metastasis . in fact , as shown in table 1 , prognosis was grim in all cases regardless of whether there was trauma or not , with survival ranging from a few days to 5 months , except for one patient who survived for 25 months . the time between the first diagnosis of prostate cancer and the discovery of the dural metastasis was highly variable ranging from 3 months to 7 years . the preoperative appearance on the ct scan of the subdural collection was nodular or multinodular , associated at times with brain edema . the bone views often revealed diffuse sclerotic changes of the skull suggestive of bone metastasis . including our case , only one other case11 was bilateral . also , on postoperative mri , there were diffuse pachymeningeal thickening with enhancement and areas of nodular enhancing soft tissues . reexamining the ct scans provided in the literature of these 12 cases , we identified three patterns ( fig . 2 ) that could lead us to a more accurate diagnosis upon admission : ( 1 ) a nodule in an sdh4 9 ( fig . 2a ) , ( 2 ) multinodular metastasis surrounded by an sdh4 7 8 ( fig . 2b ) , and ( 3 ) an extensive en plaque subdural tumor5 6 10 11 12 13 ( fig . types 1 and 2 may be particularly misleading because a burr hole to drain the blood may miss the tumor . in type 3 cases , where unexpectedly no blood is found , a larger craniotomy reveals an extensive tumor not amenable to surgical treatment . knowing these imagery features in advance helps us to be more vigilant and thus make a more accurate diagnosis to choose the right course of treatment and possibly avoid unnecessary surgery . indeed , of the 10 patients who underwent surgery , 6 died within 4 days to 3 months.4 5 8 9 10 this suggests that dural metastasis secondary to prostate cancer occurs at an end stage of advanced disease . although rare , dural metastasis should be considered among the differential diagnoses in a patient known for prostate cancer , particularly with bone metastasis . the nodular features of the subdural collection on a nonenhanced ct scan should alert us to the possibility of subdural metastasis and prompt us to investigate further . this can lead to better management and possibly avoid unnecessary surgery . simply being aware of the possibility that dural metastasis may mimic hematoma in cases of metastatic prostate cancer may help evaluate the indication for surgery , especially in this group of patients often harboring a poor prognosis .

dural metastasis from prostate cancer is rare and may mimic a subdural hematoma ( sdh ) . preoperatively diagnosis may be difficult and only reveal its presence during surgery . we present such a case and review the literature to identify common characteristics . a 65-year - old man presented with headache , confusion , and progressive right upper limb weakness . past history included a prostate adenocarcinoma with bone metastasis 3 years earlier . head computed tomography ( ct ) scan without contrast revealed a multinodular bilateral hyperdense extra - axial lesion interpreted as acute sdh . at surgery planned for sdh drainage no blood was found ; instead there was an en plaque subdural yellowish tumor . histopathologic examination was consistent with metastatic adenocarcinoma of the prostate . we found 11 cases reported as dural metastasis of prostate cancer mimicking sdh . surgery was performed on nine cases with no suspicion of dural metastasis . on preoperative nonenhanced ct scan images , three types of image patterns can be described : a nodule in sdh , multinodular metastasis surrounded by sdh , and large en plaque subdural tumor . the latter group consists of those cases where no blood but rather an en plaque subdural tumor was found at surgery . even though rare , dural metastasis should be considered among the differential diagnoses in a patient known for prostate cancer .

trichorhinophalangeal syndrome ( trps ) type i ( trpsi , online mendelian inheritance in man [ omim # 190350 ] ) is a rare autosomal dominant disorder , which was first described in 1956 by klingmuller . the culprit gene is trps1 , localized on chromosome 8q24 , which encodes a zinc finger transcriptional repressor involved in hair development and chondrocyte modulation . based on the severity of the clinical manifestations , two additional subtypes have been described : trps type ii ( omim # 150230 ) and trps type iii ( omim 190351 ) . trps type iii is also caused by mutations in trps1 , but the allelic correlation between trps type iii and trps type i is still unknown . we present a trps type i patient of ukrainian origin with a novel trps1 mutation . the present case report is about a 17-year - old female patient , born to a non - consanguineous family of a ukrainian origin , who presented with short and sparse scalp hair , most pronounced in the temporal area [ figure 1a ] and in a unique triangular shape in the mid occipital scalp [ figure 1b ] . additional findings included beaked nose with a long philtrum and an allergic crease [ figure 1c ] , widened proximal interphalangeal joints [ figure 1d ] , short toes [ figure 1e ] and onycholysis of finger- and toenails . sequence analysis of the trps1 gene revealed a novel c. 2396_2397 insg frameshift mutation in exon 5 , leading to a premature stop at codon 800 [ figure 1f ] . ( a - e ) clinical manifestations of the patient , demonstrating hair loss , finger and toe malformation and facial deformities ( f ) sequence analysis of trps1 showing the heterozygous mutation 2396_2397 insg here we describe a case of trps type i , who presented to our hair clinic with the complaint of hair loss . nevertheless , detailed examination of facial features and joints uncovered the diagnosis of trps type i , emphasizing the importance of the hair specialist in diagnosing this syndrome . this case underlines the fact that whenever the dermatologist is encountered with a severe alopecia in young age , the possibility of a congenital hair disease should always be borne in mind . this is especially true in trps , where androgenetic alopecia type of hair loss has been described . interestingly , the patient showed a unique pattern of scalp hair loss , manifesting as triangular loss of hair in the mid occipital scalp , which was previously described in this syndrome and might have been overlooked in additional patients . our patient was diagnosed in a relatively advanced age , suggesting that the prevalence of trps type i is probably still underestimated and should be considered by dermatologists when examining new patients . to the best of our knowledge , therefore , this report adds one more mutation to the growing list of mutations reported in this syndrome . considering the fact that the correlation between genotype and phenotype of trpsi is still obscure , the report of additional mutations can enhance our knowledge on this complicated and severe genetic disease .

trichorhinophalangeal syndrome ( trps ) type i is a rare autosomal dominant disorder , caused by mutations in the trps1 gene . it is characterized by slowly growing hair , craniofacial manifestations and orthopedic abnormalities . we present a 17-year - old female of ukrainian origin who presented to the hair clinic with the complaint of hair loss . further examination revealed the presence of craniofacial features characteristic for trps type i. sequence analysis of the trps1 gene revealed a novel c. 2396_2397 insg frameshift mutation in exon 5 , leading to a premature stop at codon 800 . this case underlines the importance of the hair phenotype to the diagnosis of this syndrome and emphasizes the fact that when encountered with a severe alopecia in young age , the possibility of a congenital hair disease should always be borne in mind .

guinea worm disease ( gwd ) also known as dracunculiasis , is a preventable waterborne parasitic disease affecting rural parts of developing nations of south asia and africa which do not have access to safe drinking water . banwari lal , a 25-year - old man from the jodhpur district in rajasthan , was india 's last reported case of guinea worm disease in july 1996 . annual number of reported cases worldwide has been declined from approximately 900,000 in 1989 to only about 3000 in the year 2009 and about 1000 in the year 2011.[24 ] asia is considered as free of disease . an 8-year - old girl from rural area came with chief complaints of pain in left leg and ulcer on left shin of 15 days duration . she was given anti - tubercular therapy and then multidrug therapy ( mdt ) for leprosy but the ulcer recurred . on examination , there was an ulcer of size 3 3 cm on shin anterior aspect and a healed ulcer just above the present ulcer . a x - ray of left leg showed no evidence of osteomyelitis however , it revealed a linear calcification ending in the ulcer . a provisional diagnosis of gwd was made , on the basis or radiological features long linear chain mail type of calcification typical of calcified gunieworm . as the lesion was chronic and recurrent , we decided to surgically remove the worm . when it was opened , a long linear calcified worm was found which was removed from the subcutaneous plain [ figures 24 ] . x - ray showing linear calcification intra operative demonstration of worm intra operative demonstration of worm case 2 clinical presentation a 25 year old woman came with complaints of nodular lesion left side abdomen for 5 to 7 years [ figure 6 ] . dermatological examination showed large nodular lesion of size 5 cm in diameter left side abdomen , not adherent to the deeper structures . we decided to rule out squamous cell carcinoma ( scc ) and a biopsy was done . lesion was excised and the whole specimen was again sent for histopathology which showed calcified worm . an 8-year - old girl from rural area came with chief complaints of pain in left leg and ulcer on left shin of 15 days duration . she was given anti - tubercular therapy and then multidrug therapy ( mdt ) for leprosy but the ulcer recurred . on examination , there was an ulcer of size 3 3 cm on shin anterior aspect and a healed ulcer just above the present ulcer . a x - ray of left leg showed no evidence of osteomyelitis however , it revealed a linear calcification ending in the ulcer . a provisional diagnosis of gwd was made , on the basis or radiological features long linear chain mail type of calcification typical of calcified gunieworm . as the lesion was chronic and recurrent , we decided to surgically remove the worm . when it was opened , a long linear calcified worm was found which was removed from the subcutaneous plain [ figures 24 ] . x - ray showing linear calcification intra operative demonstration of worm intra operative demonstration of worm case 2 clinical presentation a 25 year old woman came with complaints of nodular lesion left side abdomen for 5 to 7 years [ figure 6 ] . dermatological examination showed large nodular lesion of size 5 cm in diameter left side abdomen , not adherent to the deeper structures . we decided to rule out squamous cell carcinoma ( scc ) and a biopsy was done . lesion was excised and the whole specimen was again sent for histopathology which showed calcified worm . the cases presented here are rare and were difficult to diagnose and physcians may not have seen such case for many years . dracunculiasis ( gwd ) is a parasitic disease caused by the parasite worm dracunculus medinensis commonly known as guinea worm . the mode of transmission is by drinking stagnant water containing copepods that carry gunieworm larvae . guinea worm larvae are eaten by the copepods that live in these stagnant water sources . after ingestion , the copepods die and release the larvae , which penetrate the host stomach and intestinal wall and enter the abdominal cavity and retroperitoneal space . after maturation into adults and copulation , the male worms die and the females migrate in the subcutaneous tissues towards the skin surface . about a year after infection , the female worm induces a blister on the skin , generally on the distal lower extremity , which ruptures when it comes into contact with water , a contact that the patient seeks to relieve the local discomfort . the clinical features include slight fever , itchy rash , nausea , vomiting , diarrhoea , and dizziness . it enlarges and cause severe pain and burning sensation , which relieves on submerging the part in water . acute stage complications include cellulitis , abscesses , septic shock , septic arthritis , while in late stage calcification of worm and joint deformities can occur . acute stage is treated with local care of ulcer , combined with slowly removal of the worm . in chronic stage , rarely the calcified worm may cause recurrent problems as in our case and need surgical removal . the radiological diagnosis can be made easily when the characteristic long linear , serpiginous or coiled , whorled chain mail types of calcification are present in the soft tissues.[46 ] several filarial worms , particularly loa loa and onchocerca volvulus , may calcify but these are much smaller and almost always seen in the hands and feet . either may cause small , coiled masses of calcification and occasionally may be linear , but neither is as large or extensive as the guinea worm . in summary , although considered eradicated long ago physicians should be aware of this rare diagnosis and should have high index of suspicion for early diagnosis and treatment .

dracunculiasis ( guinea worm disease ) is a debilitating disease caused by parasite dracunculus medinensis . the condition is not life threatening , but causes significant morbidity . patients may be sick for several months . dracunculiasis has been claimed to be eradicated in india since 1999 . we report two patients with calcified guinea worm . both patient required surgical removal of calcified worm . the cases document that the parasite can cause chronic recurrent nodules and ulcers .

echocardiography revealed the diagnosis of atrioventricular septal defect ( avsd ) with two adequate ventricles , closed atrial component and almost closed ventricular component , with what seemed to be aneurysmal tissue that had a tiny leak ( figures 1 , 2 ) . the patient also had a subaortic membrane with a peak gradient of 70 mmhg across the left ventricular outflow tract , mild aortic regurgitation and left ventricular hypertrophy . the patient was referred to surgery for resection of the subaortic membrane and repair of the left av valve . in surgery , the right atrium was opened for trans - septal access of the left av valve . on opening the right atrium , two av valves were found : a bigger av valve opening to the right ventricle , directly attached to the muscular interventricular septum with no ventricular septal defect or aneurysmal tissue ; and another small orifice opening to the left ventricle ( figure 4 ) . so the atrial septum was incised at the fossa ovalis , through which the left av valve was seen opening to the left ventricle with a cleft the fossa ovalis was excised , creating good communication and the cleft in the left av valve was closed . then a fresh autologous pericardial patch was used to separate the two right av valve orifices ( figure 5 ) . the patch was then used to separate the right and left atria , leaving the small orifice connected to the left atrium ( figures 6 , 7 ) . the coronary sinus was kept in the left atrium to avoid making a waist between the left av valve and the small orifice . the patient had a smooth post - operative course and was discharged from hospital after 5 days . the patient remained symptom - free and with the same echo findings in the routine follow - up after 2 months . this report illustrates several features of a rare variant of av septal defect , with three av valve orifices . the patient had avsd with totally closed atrial component dividing the common av valve into a right and left components . misalignment between the atrial septum and muscular ventricular septum caused overriding and straddling of the right component of the common av valve . the ventricular component of the avsd has also totally closed causing the crest of the ventricular septum to divide the right av valve into a valve connecting the right atrium to the right ventricle and another smaller valve connecting the right atrium to the left ventricle . thus although the atrioventricular connections were seemingly concordant , at the same time there was double outlet right atrium and double inlet left ventricle with two balanced ventricles ( figure 8) . the tiny systolic flow , detected pre - operatively , that was thought to be a leak in the aneurysmal tissue closing the ventricular septal defect , was actually trivial regurgitation in the small orifice of the right av valve connecting the right atrium to the left ventricle ( figure 2 ) . although there was a communication between the right atrium and the left ventricle , the patient did not give history of cyanosis and her resting oxygen saturation was 98% . this can be explained by the fact that the blood preferentially flowed from the right atrium to the right ventricle because the av valve connecting them was significantly bigger than the other small orifice opening to the left ventricle , in addition the left ventricular compliance was much less than that of the right ventricle , which is secondary to the coexisting left ventricular hypertrophy due to the subaortic membrane . due to the difference in compliance between the right and left ventricles , which is increased further in our patient by the presence of left ventricular hypertrophy , due to the co existing subaortic stenosis this is clearly evident by color doppler in the pre - operative echo that shows almost no forward flow ( from the right atrium to the left ventricle ) across the small orifice ( figure 1 ) , in comparison to the post - operative echo , that shows good flow across both orifices ( figure 7 ) . we chose to connect the small orifice to the left atrium rather than just closing it , because the left av valve alone would have been small for the patient 's body size , especially after closing the cleft . . the hallmark of diagnosis would then be the presence of common av junction with trileaflet left av valve . double orifice left av valve occurs in avsd when a tongue of tissue extends between the mural leaflet and one of the lv components of the bridging leaflets . . surgical repair of the left av valve involves closure of the cleft in the main orifice leaving the accessory orifice intact , and the bridging tissue should not be divided as it is crucial for valve function . double orifice left av valve occurs when the two left valve orifices drain to the same ventricle . but if each orifice drains to a different ventricle , this is called double outlet atrium . it can be double outlet right atrium or double outlet left atrium , and is generally caused by misaligned atrial or ventricular septae . in some situations , as in our case , this can result in the presence of three av valves . if one av connection is absent with straddling of the solitary av valve , the condition will represent uni - atrial but bi - ventricular connection . in conclusion , this was a rare case of avsd with intact and misaligned atrial and ventricular septae and overriding and straddling of the right av valve resulting in double outlet right atrium and double inlet left ventricle ; in addition to subaortic membrane .

the atrioventricular ( av ) valves are complex anatomical structures which perform sophisticated functions . 1 a wide spectrum of malformations of these valves can occur in patients with av septal defects . we here describe the anatomic and functional abnormalities of a rare form of the disease , where two valves connected the right atrium to both the right and left ventricles , in addition to a third valve that connected the left atrium to the left ventricle , with no evidence of regurgitation or cyanosis in spite of the relatively large communication between the right atrium and the left ventricle . in addition , the patient had severe subaortic stenosis . the pathophysiology , hemodynamics and method of repair of the condition are discussed .

the american college of sports medicine ( acsm ) recommends that healthy adults should participate in moderately intense aerobic exercise , defined as 64 76% of one s maximal heart rate , for at least thirty minutes , five days per week . this is considered the minimum threshold of aerobic exercise for one to maintain health and reduce risk for chronic disease . this exercise may be attained through any number of different means , such as walking , jogging , swimming , or cycling . these activities are likely the most popular and preferred methods of exercise as one can perform them for various durations , depending upon one s chosen exercise intensity . another form of aerobic exercise in which people may participate to improve their health is repetitive jumping . most people are likely familiar with repetitive jumping , as rope skipping or jumping rope is an activity often observed in elementary school children . repetitive jumping is an intense activity where the heart rate will often rise quickly after as little as two minutes of jumping . previous research has demonstrated that this type of activity can contribute to a substantial caloric expenditure as it elicits a high metabolic demand from both aerobic and anaerobic sources , and that regardless of jumping cadence there appears to be no difference in physiological stress . however , as these early studies were conducted with subjects turning and skipping a rope , the present study employed the use of a new exercise device specifically designed for repetitive jumping . an innovative device ( the digi - jump ) has been developed which allows one to use jumping as a training technique without some of the limitations of jumping rope . this device allows one to jump at a predetermined rate ( jumps per minute ) and at a pre - determined height per jump , while not having to utilize one s hands and arms , thus possibly reducing localized fatigue and enabling one to continue exercising longer and more consistently . also , as the jumping rate is governed by a series of lights and audible beeps , one may continue to exercise even if the person has an error . in traditional rope jumping , when the rope catches the foot , one must stop exercising and then start again . this device has only recently been developed and is patent pending ( patent application # 10/464,373 ) . the only previously published research employing this device was a 2008 study by sivley , et al . , which examined the test - retest reliability of this device . ( 2008 ) demonstrated that the digi - jump has test - retest reliability coefficients that are comparable to other commonly used exercise modalities ( absolute vo2 : 0.95 ; relative vo2 : 0.71 ; hr : 0.89 ; rpe : 0.75 ) . early research on rope skipping revealed no differences in metabolic demand between jumping at different cadences , nor did these studies employ a jumping cadence lower than 120 jumps per minute ( jpms ) . however , those studies used a rope while the present study allowed the subjects arms to swing freely , and the present study also required subjects to jump at a lower cadence of 100 jpms . therefore , the purpose of this study was to investigate the difference in metabolic stress between repetitive jumping at 100 vs. 120 jpms on the digi - jump machine . twenty - eight subjects ( 18 males and 10 females ) between the ages of 18 and 25 years voluntarily completed this study . subjects were recruited from the local university and city community , and consisted of individuals who were already participating in at least 30 minutes of moderate recreational physical activity on most days of the week . each subject completed a physical activity readiness questionnaire ( par - q ) and a health status questionnaire to screen for any health risk , and acsm guidelines were employed to eliminate any potential subjects with known risk factors . subjects also understood and signed a written informed consent consistent with the requirements of the western kentucky university human subjects review board . all jumping trials were conducted on a digi - jump machine . during both exercise trials , metabolic measurements were obtained using a two - way low - resistance breathing valve and a respiratory mask , which covered the mouth and nose . expired gases were analyzed using a vacumed vista mini - cpx ( vacumed , ventura , ca ) . a heart rate monitor was also worn during testing ( polar vantage xl , port washington , ny ) , and hr was monitored using telemetry . carbon dioxide and oxygen analyzers were calibrated before each test , using calibration gases of known concentration . the flowmeter was calibrated using a hans rudolph ( series 4900 ) 3.0 l calibration syringe ( kansas city , mo ) . rating of perceived exertion ( rpe ) was determined at the end of each minute during each test , using borg s 15-point scale . they were instructed to report for testing after refraining from strenuous activity for a minimum of 48 hours , and from caffeine , nicotine , and alcohol for a minimum of 24 hours . during the initial visit a thorough explanation of the study was given , along with completion of initial screening procedures and instructions regarding subsequent lab sessions . percent body fat was measured based on age , gender and the sum of three skinfold sites ( males : chest , abdomen , and thigh ; females : triceps , suprailiac , and thigh ) using lange skinfold calipers . subjects were instructed to jump at the defined cadence until volitional exhaustion , or for a maximum of fifteen minutes . the second visit consisted only of the remaining exercise trial ( 120 or 100 jpms ) . jumping trials were performed on separate days in a counterbalanced order with a minimum of 48 hours rest between each . statistical package for the social sciences ( spss ) software was used to perform all analyses . all data is reported as mean ( m ) + standard deviation ( sd ) . analysis of variance ( anova ) was used to test for differences among subjects responses from the two exercise protocols . twenty - eight subjects ( 18 males and 10 females ) between the ages of 18 and 25 years voluntarily completed this study . subjects were recruited from the local university and city community , and consisted of individuals who were already participating in at least 30 minutes of moderate recreational physical activity on most days of the week . each subject completed a physical activity readiness questionnaire ( par - q ) and a health status questionnaire to screen for any health risk , and acsm guidelines were employed to eliminate any potential subjects with known risk factors . subjects also understood and signed a written informed consent consistent with the requirements of the western kentucky university human subjects review board . all jumping trials were conducted on a digi - jump machine . during both exercise trials , metabolic measurements were obtained using a two - way low - resistance breathing valve and a respiratory mask , which covered the mouth and nose . expired gases were analyzed using a vacumed vista mini - cpx ( vacumed , ventura , ca ) . a heart rate monitor was also worn during testing ( polar vantage xl , port washington , ny ) , and hr was monitored using telemetry . carbon dioxide and oxygen analyzers were calibrated before each test , using calibration gases of known concentration . the flowmeter was calibrated using a hans rudolph ( series 4900 ) 3.0 l calibration syringe ( kansas city , mo ) . rating of perceived exertion ( rpe ) was determined at the end of each minute during each test , using borg s 15-point scale . they were instructed to report for testing after refraining from strenuous activity for a minimum of 48 hours , and from caffeine , nicotine , and alcohol for a minimum of 24 hours . during the initial visit a thorough explanation of the study was given , along with completion of initial screening procedures and instructions regarding subsequent lab sessions . percent body fat was measured based on age , gender and the sum of three skinfold sites ( males : chest , abdomen , and thigh ; females : triceps , suprailiac , and thigh ) using lange skinfold calipers . subjects were instructed to jump at the defined cadence until volitional exhaustion , or for a maximum of fifteen minutes . the second visit consisted only of the remaining exercise trial ( 120 or 100 jpms ) . jumping trials were performed on separate days in a counterbalanced order with a minimum of 48 hours rest between each . statistical package for the social sciences ( spss ) software was used to perform all analyses . all data is reported as mean ( m ) + standard deviation ( sd ) . analysis of variance ( anova ) was used to test for differences among subjects responses from the two exercise protocols . subjects were lean ( body fat 13.6 + 5.6% ) and reported being recreationally active , but none were competitive athletes nor had any participated in a structured aerobic exercise or training program for a minimum of six months prior to the study . tables 2 and 3 depict subjects metabolic responses to each jump cadence ( 120 jpm vs. 100 jpm ) used for this study . table 2 reflects peak metabolic values for each trial , while table 3 displays average values for each trial . differences in both peak and average rer ( 1.08 .087 vs. 1.17 .1 p0.001 ; 0.99 .076 vs. 1.04 .098 p=0.002 , respectively ) were observed across the trials . though rer values indicated that these protocols were both primarily anaerobic , the slower cadence ( 100 jpm ) appeared to be a significantly more strenuous activity . differentiated rpe was collected each minute , and though total body rpe was not different for either peak or average analysis , differences were observed in peak rpe for the upper - leg ( 15.29 3.89 vs. 16.75 2.52 p=0.022 ) and in average rpe for the lower leg ( 15.04 2.55 vs. 13.94 2.02 p=0.019 ) . subjects were able to exercise for a longer duration at 120 jpms compared to 100 jpms ( 12.4 3.42 mins vs. 9.68 4.31 mins p=.000 ) . seventeen of the twenty - eight subjects completed the full fifteen minutes on the 120 jpm trial , while on seven of the twenty - eight completed fifteen minutes on the 100 jpm trial . there were no differences observed in vo2 , hr , or total body rpe across trials . the present study examined the differences in metabolic stress between jumping at 120 jpms compared to 100 jpms on the digi - jump machine . statistics revealed that for both peak and mean values , subjects had similar vo2 , hr , and total body rpe values during the two trials . however , for both peak and mean values , subjects showed a significantly different rer , with the 100 jpm trial being the more anaerobic of the two trials . the 100 jpm trial also resulted in a significantly greater upper - leg rpe when considering only peak values . lower - leg rpe was significantly higher for the 120 jpm trial when considering average values . there was also a significant difference in trial duration , as subjects were able to sustain the 120 jpm trial longer than the 100 jpm trial . considering the differences in rer and the fact that subjects were able to sustain longer the 120 jpm cadence , the similarities in vo2 and hr are intriguing . while the subjects were not tested prior to the jumping trials for maximal oxygen uptake , it can be assumed that , based on age - predicted max heart rate and the average hr observed during the trials , that subjects exercised at approximately 80% of their max . however , that might be an overestimation considering the peak and average vo2 values observed during the trials . the subjects were college - aged , recreationally active college students , and if they reached 80% of max , then that would infer that their max vo2 would only average around 50 ml*kg*min , based on peak vo2 observed . previous research on rope skipping reported exercise intensities of between 8 12 metabolic equivalents ( mets ) [ 3 , 5 , 6 , 11 ] , and these digi - jump trials , where jumping was done without a rope , elicited similar levels of exertion . the significantly greater rer found with the 100 jpm trial is consistent with subjective comments provided by subjects following the trials . all subjects commented that the 100 jpm trial was more difficult and resulted in more upper - leg fatigue , due probably to the difficulty in maintaining the slower cadence . though contact time with the jumping platform was not measured , the subjects appeared to experience a protracted eccentric contraction , particularly in the quadriceps and hamstrings , due to the added deceleration required between jumps to follow the slower cadence . a rope skipping study by quirk and sinning ( 1979 ) did not measure rer , but did measure lactate , and their results revealed higher lactate values elicited from slower cadences . our results are consistent with this finding in that the lower cadence ( 100 jpm ) had a greater anaerobic contribution as reflected through the rer measurement . subjects were able to exercise approximately 25% longer during the 120 jpm trial compared to the 100 jpm trial . however , subjects did report a significantly greater average lower - leg rpe from the faster 120 jpm cadence . subjects comments seemed to suggest that this was due to fatigue in the anterior tibialis region and primarily the result of being able to exercise for a longer duration , thus greater localized fatigue . post - trial comments were consistent in that while the faster , 120 jpm trial was preferred , it did result in more localized lower - leg fatigue and foot fatigue . a possible explanation for this observed phenomenon is both an increased duration compared with the 100 jpm trial in combination with a greater volume of jumps at the faster rate . this study examined repetitive jumping at two different cadences on the digi - jump machine . consistent with previous research on rope skipping , repetitive jumping without a rope is also a strenuous activity , regardless of jumping cadence . however , it does appear that jumping at more rapid cadences is preferred and will allow for a more protracted exercise session . future research in this area should focus on the effects of jumping on different surfaces and the role of repetitive jumping in bone and joint health .

the american college of sports medicine ( acsm ) recommends that healthy adults achieve a minimum of thirty minutes of moderate intensity aerobic exercise five days per week . while cycling , walking , and jogging are commonly observed methods of achieving these recommendations , another option may be repetitive jumping . the purpose of this study was to examine the metabolic responses between repetitive jumping at a cadence of 120 jumps per minute ( jpms ) vs. 100 jpms when utilizing the digi - jump machine . twenty - eight subjects completed two jumping trials , one at 120 jpms and one at 100 jpms . subjects jumped until volitional exhaustion , or for a maximum of fifteen minutes . oxygen uptake ( vo2 ) , heart rate ( hr ) , respiratory exchange ratio ( rer ) , and rating of perceived exertion ( rpe ) were assessed each minute of each exercise trial . rpe was differentiated , in that subjects reported perceived exertion of their total body , their upper - leg , and their lower leg . results of this study indicated that there was no significant difference between the two trials for vo2 , hr , or total body rpe . differences were reported between trials for peak and average rer , with the 120 jpm trial eliciting a lower rer for both ( peak : 1.08 .087 vs. 1.17 .1 p=.000 ; average : .99 .076 vs. 1.04 .098 p=.002 ) , peak upper leg rpe ( 120 : 15.29 3.89 vs. 100 : 16.75 2.52 p=.022 ) , and average lower leg rpe ( 120 : 15.04 2.55 vs. 100 : 13.94 2.02 p=.019 ) . also , there was a significant difference in exercise duration between the trials , with subjects able to exercise longer during the 120 jpm trial ( 12.4 3.42 mins vs. 9.68 4.31 mins p=.000 ) . these data indicate that while the physiological stress may not be different between the two trials as indicated by vo2 and hr , the 120 jpm trial appears less strenuous as evidenced by rer values and by subjects ability to exercise longer at that cadence .

since first described by quain in 1847 ( 1 ) , hundreds of abdominal aortic stenosis have been reported with many variations in anatomy . though , the complete absence of infrarenal aorta , seen in presenting case , is extremely rare . this represents the first case of complete segmental occlusion of infrarenal aorta in the old patient . a 52-yr - old woman presented to the clinic with one - year history of bilateral claudication . blood pressures were measured at 130/80 mmhg in the forearms and at 100/70 mmhg in the thighs , with ankle - brachial indexes of 0.77 . serologic tests including c3 , c4 , venereal disease research laboratory test ( vdrl ) , and immunoglobulin g were unremarkable except mild elevated erythrocyte sedimentation rate ( esr ) of 22 mm / hr and low tittered anti - nuclear antibody of 1:80 with speckled pattern . the abdominal aorta was reconstituted by multiple collaterals , such as marginal artery of drummond , the anastomosis between superior mesenteric and inferior mesenteric artery , bilateral epigastric , lumbar , and abdominal superficial arteries . for her knee joint arthritis , she was started with methylprednisolon of 8 mg and non - steroid anti - inflammatory drug . after negative results of pathergy test and human lymphocyte antigen b 51 , we ruled out the behcet 's disease and she tapered the medications to stop successfully . she wanted the antihypertensive drug for mild hypertension and was taken amlodipine at 5 mg daily . one year later , computer tomographic angiography showed patent bypass graft and decreased collateral vessels ( fig . the etiology of abdominal aortic stenosis is poorly understood . the young age of most of the patients suggests that the malformation may be congenital . maycock first proposed an unequal fusion of embryonic aorta as a congenital mechanism ( 3 ) . in first month of fetus , the paired primitive dorsal aortas fuse to form the abdominal aorta . incomplete fusion due to infection or inflammation may lead of kinking of the aorta resulting to permanent constriction . congenital rubella has been suggested for such vascular anomaly ( 4 , 5 ) . in alagille syndrome which is congenital pulmonary artery stenosis transmitted in an autosomal dominant inheritance , deletion of the jagged 1 gene has been suggested to relate with abdominal aortic coarctation ( 6 ) . acquired etiologies were also suggested in fibromuscular dysplasia or takayasu 's arthritis ( 7 , 8) . in our patients , several inflammatory presentations including the knee joint arthritis , recurrent oral ulcers , and elevation of esr have suggested the possibility of behcet 's disease . we ruled out the behcet 's disease after the negative study of pathergy test . considering the complete absence of infrarenal aorta without any inflammatory reaction , in review of cases for abdominal aortic stenosis , coarctation , hypoplasia , and middle aortic syndrome were used diversely . the term " coarctation " implies a congenital anomaly , and " hypoplasia " is to longer segment of coarctation . middle aortic syndrome is the clinico - anotomical entity involving long segmental narrowing of the abdominal aorta and various visceral arteries irrespective of its etiology . we described this case by " hypoplasia " , because 4 cm of infrarenal aorta was absent . presenting symptoms of abdominal aortic hypoplasia are related to the extent of the stenosis , and the collateral system . in case involving renal artery , patients typically present with uncontrolled hypertension . infrarenal aortic hypoplasia can give rise to claudication when the collateral circulation is not sufficient . an abdominal aortogram via angiography , ultrasound , computed tomography , or magnetic resolution imaging can be used to diagnose and to determine the location and extent of disease . in case of renal artery stenosis claudication and aneurysmal dilatation also need surgical correction . in this case , as the subrenal aortic stump was too short , graft was interposed between the subdiaphragmatic thoracic aorta to the iliac bifurcation . careful physical examination for inspection of dilated superficial arteries and auscultation of bruits can provide a clue for rare causes of ileofemoral insufficiency such as abdominal aortic stenosis . when suspected , an angiography is mandatory to diagnose , and surgical intervention is necessary to improve severe claudication .

we describe a case of infrarenal aortic hypoplasia in a 52-yr - old woman who presented with claudication . computed tomographic angiography revealed an abrupt absence of the infrarenal aorta , with collateral flow reconstituting the iliofemoral systems . after a polytetrafluoroethylene graft was interposed between the aortic stump and the iliac bifurcation , the patient 's claudication resolved .

dr victor a. mckusick wrote an article in 1962 for the quarterly review of biology titled on the x chromosome of man ( 1 ) . at that time , x - linkage had been established for about 60 traits in man and a genetic map of the x chromosome was presented . four years later , with the addition of dominant and recessive traits , dr mckusick published a book , mendelian inheritance in man : catalogs of autosomal dominant , autosomal recessive and x - linked phenotypes ( mim ) ( 2 ) . each catalogue contained summaries of genetic phenotypes reported in the biomedical literature , which were organized into numbered entries with descriptive synopses and references . with the addition of descriptions of genes , over the years , catalogues for y - linked and mitochondrial phenotypes and genes were added and by the 12th edition , the subtitle had been changed to a catalog of human genes and genetic disorders(3 ) . today the online version of mim , omim , contains 18 961 entries ( figure 1 ) . it continues with the same basic organization but has grown to include complex traits and descriptions of the consequences of gene copy number variation and recurrent deletions / microdeletions and duplications / microduplications . this paper describes the content and organization of omim and the modifications that have been made to accommodate advances in our understanding of genomic architecture and complex traits . the content of omim continues to be based on the peer - reviewed biomedical literature . journals are scanned every day for new information on mendelian disorders and genes already in the database as well as newly described genes and disorders . articles are then selected for review and possible inclusion with priority given to papers describing genes associated with disease phenotypes , genes with substantial new biology and disorders and genes not in omim. in addition , other online genetics resources are scanned for information and articles that may be relevant to omim. as can be seen from the update log on the blue bar of the omim home page , approximately 70 new entries are created and 700 existing entries are updated per month . each omim entry is given a unique six digit number . the symbol ( * , # , % or ) that precedes the number distinguishes between phenotype entries and gene entries . as of 16 september 2008 , omim contains 18 961 entries ( figure 2 ) . of these , as always , the primary focus of omim is mendelian phenotypes and their genes . with the completion of the sequencing of the human genome , and the proliferation of cloned genes , omim has directed its attention to genes with direct disease relationship and those of known function . the relationship between phenotype and genotype can be complex . at the most simple level , when the molecular basis is known for a phenotype , a number sign ( # ) is added to the mim number of the phenotype entry and allelic variants ( mutations ) are added to the gene entry . the first paragraph of the phenotype entry will always state why a number sign is used . some entries with a plus sign ( + ) include both phenotype and gene information and are awaiting review and separation . an allelic variant is designated by the mim number of its parent entry , followed by a decimal point and a unique 4-digit variant number . for example , allelic variants in the cystic fibrosis transmembrane conductance regulator gene ( cftr , mim 602521 ) are numbered 602 421.0001 to 602 421.0136 . the -globin locus ( hbb ) is numbered 141900 ; sickle haemoglobin ( hbs ) is numbered 141900.0243 . descriptions of sickle cell anaemia and cystic fibrosis are contained in entries 603903 and 219700 , respectively . criteria for inclusion are the first mutation to be discovered , distinctive phenotype , high population frequency , historic significance , unusual mechanism of mutation , unusual pathogenetic mechanism and distinctive inheritance ( e.g. dominant with some mutations , recessive with other mutations in the same gene , as in the case of mutations in connexin 26 ( mim 121011 ) , which can cause recessive and dominant forms of deafness , among other phenotypes ) . a few polymorphisms are included , many of which show a positive statistical correlation with particular common disorders these links , when available , appear after the mutation listed in each allelic variant . a list of the 2239 gene entries in omim with disease - causing mutations can be obtained by searching on 0001 with the limits restricted to allelic variants. because omim does not catalogue all allelic variants in any gene , it includes links to several complementary resources . these include the human gene mutation database ( hgmd , www.hgmd.cf.ac.uk/ ) , a repository for published mutations , and over 500 locus - specific mutation databases through the human genome variation society ( hgvs , www.hgvs.org/dblist/dblist/html ) . these links are available from the blue bar to the left of the screen when viewing an omim entry . in the early days of omim , information added to an existing entry was placed at the end of the text to reflect the historical development of knowledge of the phenotype or gene . as the knowledge of genes and phenotypes expanded and became more detailed , greater structure headings and subheadings have been added to organize related information while retaining historical development ( table 1 ) . free - text within these headings and subheadings allows discussion of the nuances of genotype / phenotype correlation that is not possible when bound by more rigid data structures . for example , the complex subject of imprinting that occurs in genes and results in variable phenotypes can be discussed in separate imprinting headings in the gene and the related phenotype entry , thus providing complementary perspectives on the subject . table 1.major omim text headingsphenotype entry description clinical features biochemical features inheritance mapping pathogenesis diagnosis genotype / phenotype correlations clinical management population genetics molecular genetics animal model historygene entry description cloning gene structure gene function evolution mapping molecular genetics genotype / phenotype correlations animal model history allelic variantsan omim entry contains headings based on current knowledge of the topic . text headings can contain subheadings to provide additional organization to each entry.allelic variants , a section found only in gene entries , is a field heading in the same hierarchy as number , title , text and references . major omim text headings an omim entry contains headings based on current knowledge of the topic . allelic variants , a section found only in gene entries , is a field heading in the same hierarchy as number , title , text and references . in general , this has proven to be a good strategy , as the different long qt syndromes ( lqt1 - 10 ) , initially clinically indistinguishable , have now been shown to be caused by mutations in different ion channel genes . the first member of a phenotypic series ( e.g. lqt1 , mim 192500 ) will usually include the overview information on the group of disorders . the morbid map and the synopsis map provide a shorthand view of the relationship between disease and gene . the disorders with a ( 3) after them represent phenotypes for which the molecular basis is known . currently , there are 3770 diseases or disease susceptibilities that have an underlying molecular basis . clicking on the cytogenetic location in either the morbid or synopsis map reveals a more detailed , sequence - based view of the latest genome build and transcripts within that cytogenetic region . the morbid map data are included in ncbi 's entrez gene , and users are encouraged to use mapviewer directly . over 4500 phenotype entries have associated clinical synopses . over 1500 of these have been revised or are newly written . each feature in a new or revised synopsis is derived from the published literature and standard clinical references . the structure of the clinical synopses is based on an anatomic template , beginning with inheritance and ending with molecular basis , when known . omim uses regular , but not controlled vocabulary and often defers to the author 's original description . omim clinical feature terms are incorporated into the national library of medicine , umls project ( unified medical language system ) and snomed ( systematized nomenclature of medicine ) . because omim is a free - text database , it can easily accommodate descriptions of paradigm shifts in biology . omim now includes descriptions of micrornas , non - coding regulatory elements and modifier genes . contiguous gene syndromes such as williams syndrome and miller - dieker syndrome have long been included in omim. the advent of microarray technology has enhanced the ability to detect and characterize these chromosomal duplication and deletion syndromes . omim includes such chromosomal aberrations when the genes identified in the region can be related to the phenotype at the gene function level . the cytogenetic location of the duplication / deletion is included in the title [ e.g. chromosome 11p13 deletion syndrome ( mim 194072 ) , chromosome 10q26 deletion syndrome ( mim 609625 ) ] . it is now known that some genes occur in multiple copy number that varies among individuals ( e.g. ccl3l1 , -defensin , amylase 1 ) . for example , variation in ccl3l1 ( mim 601395 ) copy number is known to influence immune reconstitution after antiretroviral therapy for hiv infection . when the copy number variation has recognized relevance to human disease , genome - wide association ( gwa ) studies of complex traits represent the next step in genetic mapping of phenotypes . gwa studies implicate numerous chromosomal regions , but the findings are often not replicated . to limit as much as possible the creation of invalid phenotypic loci , omim has established criteria for the inclusion of complex trait loci based on such studies . these criteria include observation of similar results in at least three independent samples , p - values of < 10 after bonferroni correction , effect size of at least 1.2-fold relative risk or odds ratio , and characterization of the functional effect . when the criteria have been met , a phenotypic series is created [ e.g. inflammatory bowel disease ( ibd ) 120 ] . the series can be retrieved by typing the root symbol followed by an asterisk ; in this case ibd*. information from gwa studies will often be put into the mapping heading of an entry , unless a functional relationship has been shown . in that case , the information will be put in as an allelic variant of the gene . normal ranges in human anatomy and physiology . to address the spectrum in these phenotypes , omim is creating phenotypic quantitative trait loci ( qtl ) series ( e.g. , body mass index , cholesterol , bone mineral density and blood pressure ) . discussions of the disease states of these qtls were already in omim ( obesity / leanness , hypercholesterolemia , osteoporosis / osteopetrosis and hypertension , respectively ) . bringing together these phenotypic spectra under the qtl heading is an ongoing challenge . omim numbers are stable , cross - referenced and frequently included in many publications . other databases are encouraged to include omim numbers in their datasets . this will facilitate linking to and from omim ( see how to link in the blue bar on the left of the omim home page ) . additionally , the text of omim and the morbid map are available for download subject to some restrictions ( see restrictions on use in the blue bar ) . finally , ncbi has created some useful web and programming tools for data retrieval from omim and other entrez databases ( http://eutils.ncbi.nlm.nih.gov/entrez/query/static/advancedentrez.html ) , and a file cross - referencing omim numbers to gene i d numbers is maintained for ftp download ( ftp.ncbi.nlm.nih.gov/gene/data/mim2gene ) . the national human genome research institute ( to omim ) ; the national library of medicine ( to omim ) . funding for open access charge : n01lm43504

mckusick 's online mendelian inheritance in man ( omim ; http://www.ncbi.nlm.nih.gov/omim ) , a knowledgebase of human genes and phenotypes , was originally published as a book , mendelian inheritance in man , in 1966 . the content of omim is derived exclusively from the published biomedical literature and is updated daily . it currently contains 18 961 full - text entries describing phenotypes and genes . to date , 2239 genes have mutations causing disease , and 3770 diseases have a molecular basis . approximately 70 new entries are added and 700 entries are updated per month . omim is expanding content and organization in response to shifting biological paradigms and advancing biotechnology .