Despite an exponential development of the understanding of the disease with availability of good therapy and feasibility of good control along with availability of globally accepted guidelines, there remains a significant gap between the guidelines and prevailing practice behavior for treating asthma all over the globe. This perhaps stands as the single most deterrent factor for good asthma care worldwide. The objective of the study is to analyze the asthma prescriptions to find out the available status of the practice behaviour and the deviations from the guideline in asthma practice.The asthma prescriptions of the referred patients presenting to the OPD services of the IPCR, Kolkata were photocopied and collected. They were further analyzed based on the available information upon a format being prepared on four major areas as qualifications, clinical recording habit, practice of evaluating patients, and treatment habit that stands apparent from the prescribed medications. The doctors were divided into three categories as a) MBBS, b) MD/DNB (medicine and respiratory medicine), and c) DM  and statistical analysis has been performed comparing the three groups as per the performance in the four pre-decided areas.All the groups fall short of any guideline or text of asthma care in all the areas involved.The practice behaviour of our doctors for asthma care appears deficient in several areas and seems far from guideline recommendations. This needs further evaluation and adoption of appropriate interventions. Despite tremendous improvement in knowledge and treatment of asthma and availability of guidelines, the asthma practice behaviour of the physicians concerned is perhaps the most important issue to determine the quality of care for asthma. There is always a gap between the guidelines and practice. UnderstaIt has been a cross sectional and observational study. Patients being referred to our OPD services and diagnosed as asthma on spirometry at the institute were requested to give consent and, thereafter, allowed to make photocopies of the prescriptions being carried by them for the study. These prescriptions were preserved and the available information was charted categorically as a) the qualification of the doctors b) the documentation habit that included the documentation of the diagnosis, vitals , co-morbidities (if any), and the clinical examination of the respiratory system in whatever form available, c) the investigation habit from the available record that includes advice for spirometry, chest X-ray, X-ray of the para-nasal sinuses, blood sugar, routine hemogram, IgE etc and d) the prescribing habit marked by advice for oral or inhaled medications, oral steroid, and inhaled corticosteroids.The doctors were divided into three categories as (i) MBBS, (ii) MD or equivalent including MD in respiratory medicine, and (iii) DM in any non respiratory sub-speciality of medicine. The different habits of the three different categories of the doctors were charted systematically and information derived was expressed in percentages. Furthermore, the performance of the three categories was compared statistically with unpaired‘t test’.n = 28), (B) post graduates (n = 46), and (C) post doctoral (n = 26). The comparison between the different categories and the overall situation is tabulated below in Table The distribution of doctors in different categories as described above was as follows: (A) MBBS  compared to the other categories (A and C). However, the latter group  has practiced advising chest X-ray (PA) and prescribed oral medication (p<0.03) in a significantly higher proportion. Although not significant, blood pressure measurement is apparently done more frequently by MBBS doctors compared to the other two categories. The evaluation habit of the doctors also falls short of the expected; overall the routine hemogram and chest X-ray were advised by about one fourth (24 %) and one fifth (21 %) of the prescribers. The post doctoral doctors were most smart to ask a chest X-ray and the overall consideration of allergic rhinitis appears low from the fact that only 5 % doctors asked a X-ray of the para nasal sinus. The prescription of the use of inhales  has scored out higher than advice for oral medication alone (58% versus 19%). When looked for, the use of inhaled medication alone, combination products (ICS+LABA) outscore the use of ICS+ SABA (44% versus 6 %); inhalers are prescribed more by the post graduate doctors.The overall impression from the available data is that there is still a huge dearth between the published guideline for asthma therapy and the expressed practice behaviour of doctors in this part of the developing world. The deficit is known as universal and seemingly unrelated to the level of qualification in our study. Thus, the behaviour noticed may not necessarily indicate the lack of knowledge regarding asthma but certainly points to the failure of achievement of guideline provided standard. It is not possible to implicate the reason which could be largely external and circumstantial for the doctors to observe a better documentation, evaluation, and prescription habits but, nevertheless, one cannot exclude a certain degree of lacunae in understanding the disease. The exceedingly low use of peak flow measurement or /and spirometry , failure to suspect asthma in about one fourth (24 %) of patients (were kept off any anti asthma medication) probably points to low level of understanding or motivation among the doctors. On the contrary, the level of the use of inhalational products either alone or in combination with oral medications was relatively impressive (58 %), along with the use of inhaled corticosteroid in combination with LABA; this suggests that the fundamental basis of use of anti-inflammatory medications in asthma has been already incorporated in the practice behaviour of the physicians concerned. If this is taken as a marker of guideline acquaintance, we may need to put more stress on the circumstantial and patient-related factors for such deficient practice behaviour.Several recommended asthma guidelines are available to help the physicians to treat the disease better on evidence-based information. However, the ability of guidelines to change a physician’s behavior or the patient outcomes has been limited. For asth9The prescribing habits of different categories of drugs are different at different places. A study to explore and compare treatment decisions and the influence of specific patient characteristics on the management of asthma in five different European countries revealed that there is a significant difference in the prescribing habit of oral or inhaled corticosteroid and antibiotics. PhysiciaThis small study has a lot of limitations; several factors as the number of the prescriptions studied (was not large), the disease control status and the lung function at the presentation, the reason for presenting to us (being referred or not), the educational and socioeconomic status of the patients, the practicing area of the doctors  etc. were not taken into consideration. The dose issue of the inhaled medication (ICS or non-ICS) is also not incorporated. It is not possible to ensure that the available record is the true one since some of the physicians may have been keeping their personal record separately and have written only the medications in the prescription. Moreover, the exact status of the patients presenting at the doctors is not known although the reason of attending our OPD was presumably a non satisfactory response to therapy for most of the patients. It is also possible that, in some occasions, the referring physician had just given a set of advice before referring the patient to us. Therefore, the prescriptions scanned may not be the exact representation of the actual status of the prescribing habit in our community and have some deviations from the exact prescription habit of our doctors.In our observation, the available information provides limited insight into the causes of non adherence but it amply elaborates the reality in asthma care in this part of the world and impresses upon the need of well planned and elaborate effort to look further into the dimension and factors for non adherence.Our experience from this small data suggests that there is huge gap between the guideline and the practice behaviour of our physicians. Further studies are needed to assess in-depth the factors responsible for the inappropriate and inadequate practice behaviour of our doctors to find out ways to eliminate the deficiencies to help millions of our patients.


Dermatofibrosarcoma protuberans (DFSP) is an uncommon, slow growing and locally aggressive tumor of the skin witha high rate of recurrence even after supposedly wide excision. The reports of regional lymph node metastasis and distantmetastasis are very rare. Because of the extreme rarity of these cases with metastasis, the experience with management ofsuch patients is very limited. A case of recurrent DFSP of scalp, with metastasis to the regional lymph nodes, in a 17-year-oldboy is reported here. This is the second case of DFSP involving scalp and 16th case of DFSP of all sites metastasizing to theregional lymph nodes reported in literature. The patient was treated with wide excision of the lesion and ipsilateral radicalneck dissection (including excision of overlying involved skin).


We report a case of traumatic inguinal hernia following blunt abdominal trauma after a road traffic accident and describe the circumstances and technique of repair. The patient suffered multiple upper limb fractures and developed acute swelling of the right groin and scrotum. CT scan confirmed the acute formation of a traumatic inguinal hernia. Surgical repair was deferred until resolution of the acute swelling and subcutaneous haematoma. The indication for surgery was the potential for visceral strangulation or ischaemia with the patient describing discomfort on coughing. At surgery there was complete obliteration of the inguinal canal with bowel and omentum lying immediately beneath the attenuated external oblique aponeurosis. A modified prolene mesh hernia repair was performed after reconstructing the inguinal ligament and canal in layers.To our knowledge, this is the first documented case of the formation of an acute direct inguinal hernia caused as a result of blunt abdominal trauma with complete disruption of the inguinal canal. Surgical repair outlines the principles of restoration of normal anatomy in a patient who is physiologically recovered from the acute trauma and whose anatomy is distorted as a result of his injuries. Blunt abdominal trauma may cause both crush and shearing effects on healthy abdominal wall and viscera . Acute oThe inguinal canal extends from the anterior superior iliac spine to the pubic tubercle. A defect in the posterior wall results in a direct hernia. In our case, all boundaries of the inguinal canal including the floor, posterior, inferior, medial walls and deep and superficial rings were obliterated causing traumatic herniation of the terminal ileum and caecum beneath an attenuated external oblique aponeurosis.We describe the timely reconstruction of the abdominal wall in the inguinal region and the importance of the restoration of normal anatomy with definitive repair after resolution of swelling and haematoma.A 24 year old man was admitted to hospital following a road traffic accident after his motorcycle collided with a lorry. The speed of collision was 35 mph and abdominal injuries were sustained as a result of impact against the motorcycle handle bars.On arrival to the Emergency Department the patient was haemodynamically stable and fully conscious. Primary survey revealed a soft abdomen with tenderness, swelling and bruising in right groin and scrotum. There was no previous history of groin hernia.Secondary survey, plain X ray and CT scan confirmed a fracture dislocation of the right shoulder, open fracture of right radius and ulna, multiple right lung contusions and a new right inguinal hernia. Internal fixation of the upper limb injuries was performed.Reconstruction of the abdominal wall was deferred, in the absence of obvious visceral damage, until resolution of groin swelling and bruising Fig. .12 days after admission, repair of the inguinal hernia was performed. At surgery, the external oblique aponeurosis overlying the inguinal canal was contused inferiorly, and the inguinal ligament was found to be sheared off the full length of its attachment from the anterior superior iliac spine to the pubic tubercle, with all boundaries of the canal obliterated Fig. . As a reThe edge of the peritoneum was sutured to the lacunar and pectineal ligaments and pectineal line. The overlying external oblique aponeurosis was re-attached as the inguinal ligament Fig. . A largeHere we discuss the first reported case of the formation and successful repair of an acute direct inguinal hernia resulting from blunt abdominal trauma where the inguinal canal was completely obliterated causing bowel to lie immediately beneath an attenuated external oblique aponeurosis. Technically there was no direct or indirect hernia as there was no inguinal canal. Traumatic injuries do not respect abdominal planes; normal anatomy is frequently distorted. Delayed repair afforded the resolution of haematoma and oedema that may have resulted in more challenging surgery.As the defect was unilateral and the procedure was exploratory in the first instance an open approach was undertaken. The size of the defect afforded easy inspection of the peritoneal cavity for visceral injury. As primary repair was feasible without tension this was undertaken by reconstructing the inguinal region in layers. An alternative technique of repair would have been a laparoscopic intraperitoneal approach rather than extraperitoneal due to the location of abdominal viscera beneath the skin and obliteration of the abdominal wall in the right inguinal region. After reduction of the abdominal viscera composite mesh would be fixed to edges of the defect rather than direct suture of the cranial and caudal borders of the defect  together.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.SB carried out the operation detailed in this report and drafted the case presentation section of the report. MV and GH drafted and compiled the document. AL gave approval of the manuscript before publishing. All of the above authors were involved in the care of the patient whilst in hospital.


A rare malposition of central venous catheter in the left superior intercostal vein is described. The diagnostic features and the possible ways to prevent this complication are discussed. Central venous catheterization is an essential component of modern day critical care. But the insertion of central venous catheters is not free of complications. Numerous complications described both during placement of the catheter and later in the long-term maintenance, are both hazardous to the patients and expensive to treat. Malposition of the catheter tip is one of such complications, which usually involves placement of the catheter in various large tributaries of superior vena cava. This case report illustrates a rare malposition of a central venous catheter tip in a small tributary of left brachiocephalic vein.A 28-year-old male, was admitted to our ICU with surgical site infection and severe sepsis. Ten days prior to the present admission he underwent ileal resection and ileostomy for ileal perforation with underlying ileocaecal tuberculosis. On examination, he was in respiratory distress with tachypnoea, tachycardia and bilateral crepitations on chest auscultation. Arterial blood gas showed severe hypoxia. Possibilities of fluid overload as a result of aggressive fluid resuscitation and ARDS were considered and it was decided to place a central venous catheter for monitoring of central venous pressure. A catheter was placed through the left internal jugular vein with all aseptic precautions using the Seldinger technique. The catheter was gradually advanced up to the 13 cm mark without difficulty. After free return of venous blood was obtained, the catheter was felt to be placed correctly in the superior vena cava. Only unusual thing observed was patient complaining of left sided back pain on flushing the catheter with heparinized saline.An anteroposterior chest radiograph, obtained to confirm the position of the catheter, revealed the left paramedian location of the catheter following the aortic knob and pointing laterally . The inaet al, with their experience of 2104 central venous catheterization could find only one incidence of misdirected catheter in the smaller tributary.[Malposition of central venous catheters was reported to be between 1 to 33 percent by different investigators.[et al,[Thoracic pain syndromes on flushing of misplaced central venous catheters in the smaller tributaries have been described in the literature. Webb et al, reportedet al,–3 Thoughet al,5 A propeet al, In the pet al, In the let al, in whichBecause of the lack of experience, the importance of back pain on flushing of the misplaced catheter in our patient was appreciated only retrospectively. The malposition was evident only on review of the postprocedural chest X-ray. The characteristic location of the catheter in the frontal view and the associated classical back pain on flushing the catheter makes the left superior intercostal vein as the most likely position of the catheter. A lateral film and a venogram could have established the exact location of the catheter beyond any doubt.Because of the longer course and more transverse lie of the left brachiocephalic and more frequent smaller tributaries, malposition of the venous catheter is commoner when cannulation attempt is made via the left brachiocephalic vein rather than its right sided counterpart.4 The malAfter placement of all central venous catheters, a chest radiograph should be obtained. A posteroanterior or anteroposterior film is usually adequate; if not, a lateral view may be taken. If uncertainty still exists, a venogram through the catheter should be performed for precise localization.


Animals bearing metastatic fibrosarcomas were treated with cyclophosphamide (CY) alone or in combination with flurbiprofen (FP), an inhibitor of prostaglandin synthesis. FP did not affect local growth of fibrosarcomas, and the incidence of distant metastases after resection of the "primary" implants was comparable in treated and control groups. Treatment with CY retarded growth of the fibrosarcomas and reduced the proportion of animals which succumbed to metastases, but this was not altered significantly by additional treatment with FP. FP did not affect the survival of rats bearing a lymphoid leukaemia. The lifespan of animals treated with CY was increased significantly, but the concomitant administration of FP did not enhance this effect.


There is no case of simultaneous ipsilateral proximal interphalangeal and metacarpophalangeal dislocation of a finger in the literature.A 61 years old male patient sustained an ipsilateral dorsal dislocation of the PIP joint of his fifth finger and dorsal dislocation of the metacarpophalangeal joint. Closed reduction of proximal interphalangeal joint was achieved while open reduction of the metacarpophalangeal joint was carried out.The single most important element preventing reduction of the metacarpophalangeal joint was an interposition of the volar plate between proximal end of the phalanx and the head of the metacarpal. In this report we aimed to investigate and discuss an extremely rare injury that is bipolar dislocation of the fifth proximal phalanx due to a fall on hand. Although, simultaneous dislocation of metacarpophalangeal and carpometacarpal joints of the same digit had been previously reported, we did not find any case of simultaneous ipsilateral proximal interphalangeal and metacarpophalangeal dislocation of a finger in the English speaking literature.A 61 years old male patient fell from a height and sustained an ipsilateral dorsal dislocation of the PIP joint of his fifth finger and dorsal dislocation of the metacarpophalangeal joint. X ray examination of the finger revealed no fracture and closed reduction with wrist block was attempted  in the English speaking literature. Irreducible metacarpophalangeal dislocations are extremely rare injuries with buttonholing of the metacarpal head into the palm -3.The most important element preventing reduction is an interposition of the volar plate between the base of the proximal phalanx and the head of metacarpal. In this case report, taking the advantage of a direct access to the metacarpal head we had preferred volar approach for an open reduction of a complex metacarpophalangeal dislocation.To us, volar approach also has the advantage of an evaluating the integrity of the neurovascular bundle  which are tented tightly over the metacarpal head.Although, simultaneous dislocation of metacarpophalangeal and carpometacarpal joints of the same digit had been previously reported , simultaPIP: Proximal interphalangeal.The authors declare that they have no competing interests.KU, KO and EU contributed to conception and design, carried out the literature research, manuscript preparation and manuscript review. FUO was involved with the case and writing of themanuscript. AE revised the manuscript for important intellectual content. KB supervised the writing and the general management of the patient.Written consent was obtained from the patient for publication of the study.


The ingestion of carbon and benzpyrene particles in vitro by rat peritoneal macrophages, baby hamster kidney fibroblasts (BHK-21) and mouse L-cells has been shown to be significantly stimulated by the inclusion of histone or polylysine in the culture medium. Parallel studies using methylated bovine albumin did not significantly stimulate carbon or benzpyrene uptake relative to untreated control cultures. Incubation of carbon particles with histone before inclusion in the culture medium of macrophages resulted in the same degree of uptake as in the cultures where carbon and histone were added independently of each other. The implications of these findings to in vivo chemical carcinogenesis are examined.


Nitroimidazole markers of tumour hypoxia bind to normoxic liver and the question has been raised whether this is due to low oxygen concentration or microregional activity of specialised nitroreductases. To answer this question, the binding patterns of the 2-nitroimidazole, pimonidazole, were compared following perfusion of surgically isolated rat livers in anterograde and retrograde directions. Perfusion at low flow rates in anterograde or retrograde directions can be used intentionally to alter oxygen gradients without altering enzyme distributions. Perfusion by means of the portal vein (anterograde direction) produced pimonidazole binding in the pericentral region of liver similar to that observed for pimonidazole binding in vivo. A complete reversal of this binding pattern occurred when the isolated liver was perfused by way of the central vein (retrograde direction). In this case, pimonidazole binding occurred in the periportal region. The extent and intensity of binding in the periportal region during perfusion in the retrograde direction was similar to that in the pericentral region during perfusion in the anterograde direction. It is concluded that low oxygen concentration rather than the non-homogeneous distribution of nitroreductase activity is the primary determinant of 2-nitroimidazole binding in liver.


The thymus is considered to play an important role in the pathogenesis of Myasthenia gravis, an autoimmune disease characterized by antibody-mediated skeletal muscle weakness. However, its role is yet to be defined. The studies described herein summarize our efforts to determine how intrathymic expression of the neuromuscular type of acetylcholine (ACh) receptors is involved in the immunopathogenesis of this autoimmune disease. We review the work characterizing the expression of neuromuscular ACh receptors in the thymus and advance a new hypothesis that examines the intrathymic expression of this autoantigen in disease pathogenesis.


We describe a case of an 8-year-old boy who developed a combined motor and sensory neuropathy of the distal ulnar nerve, after sustaining a superficial injury to the right flexor carpi ulnaris tendon at the level of the distal wrist crease. Guyon's canal syndrome is a very rare entity during childhood. We have noted only one prior description of this syndrome in the pediatric age group in a review of the English literature. The distal ulnar tunnel, Guyon's canal, is 4–4.5 cm long. It begins at the proximal edge of the palmar carpal ligament and extends to the fibrous arch of the hypothenar muscles. The tunnel has frequently changing boundaries and does not have four distinct walls throughout its course. From proximal to distal, the roof consists of the palmar carpal ligament, the palmaris brevis, and the hypothenar fibrous and fatty tissue. The floor of the tunnel is made up of the flexor digitorium profundus, the transverse carpal ligament, the piso-hamate and piso-metacarpal ligament and the opponens digiti minimi. The flexor carpi ulnaris, the pisiform, and the abductor digiti minimi constitute the medial wall. The lateral wall is composed of the tendons of the extrinsic flexors, the transverse carpal ligament, and the hook of the hamate .There are four levels in which the ulnar nerve may be compressed at the wrist and hand: 1) The main trunk of the nerve at the entrance to, or within Guyon's canal. These lesions produce sensory loss in the distribution of the superficial termination branch and weakness of all the ulnar-innervated intrinsic muscles. 2) The deep terminal motor branch of the ulnar nerve distal to Guyon's canal but proximal to the branches that innervate the abductor digiti minimi (hypothenar muscles). This produces weakness of all ulnar-innervated muscles of the hand without sensory loss. 3) The deep motor branch distal to the branches that innervate the abductor digiti minimi and the hypothenar muscles. This produces no sensory loss but there is weakness of all the ulnar innervated intrinsic hand muscles except the hypothenar muscles. 4) The superficial terminal sensory branch which produces sensory loss without muscle weakness [Guyon's syndrome in the paediatric age group is extremely rare; a search of the literature in English yielded one case . To our An 8-year-old boy presented to our clinic complaining of numbness of the little finger and the ulnar aspect of the ring finger. Ten days prior to presentation, the patient sustained a 1 cm laceration at the level of the distal wrist crease after falling on a piece of broken glass. On examination, he had weakness of abduction and adduction of the fingers. Movement of the thumb was unaffected.The injury was managed at the emergency department by thorough wound irrigation. There was a partial irregular cut of about 30% of the radial aspect of the FCU with intact ulnar nerve and ulnar artery. The skin was sutured. After the primary management the patient was sent to our orthopaedic clinic for further follow up. The initial examination one week after the injury revealed a clean wound, no hematoma or swelling, normal sensation of the fifth and ulnar side of the fourth finger, and normal abduction and adduction of the digits. However a gradual numbness and weakness of intrinsic hand muscles was noted after 10 days that gradually worsened. On subsequent follow up a total ulnar nerve deficit was noted distal to the injury, at the wrist level involving motor and sensory branches.Three weeks after the initial injury he developed marked weakness of all ulnar supplied intrinsic muscles with total sensory loss at the fifth and the ulnar side of the fourth fingers. Due to the progressive nature of his symptoms, exploration and decompression of the Guyon's canal was done under general anaesthesia. Exploration revealed normal healing of skin and subcutaneous tissue with excessive scar tissue at the radial edge of the FCU which spanned the ulnar nerve, narrowing the entrance of Guyon's canal and causing severe compression and cicriatrical constriction of the nerve.The ulnar nerve was completely intact Fig. . No orgaIntrinsic lesions  as well as extrinsic pathologies (chronic repetitive trauma) can damage the terminal superficial and/or deep branches of the ulnar nerve at the wrist and at the hand leading to distinct clinical features -4.The most common lesion, to the proximal Guyon's canal (Type 1), is characterised by sensory loss at the ulnar portion of the hand and weakness of all ulnar intrinsic hand muscles (mixed sensory-motor dysfunction), whereas a more distal lesion within Guyon's canal Types 2 and 3) causes an isolated palsy of the deep terminal motor branch without sensory loss (pure motor dysfunction)  and 3 ca,5. NumerTo our knowledge this is the first case in the literature published in English language which reports Guyon's syndrome secondary to excessive healing tissue following partial tendon injury in the paediatric age group. This may be attributable to the high healing potential in paediatric patients. In addition, the experience of this case presents a challenge to the current dogma of withholding repair of tendon lacerations of less than 60% of the tendon's cross-sectional area .In the paediatric age group, glass penetrating injuries in proximity to neurovascular structures are best explored irrespective of distal neurologic deficits. Clearly the surgical exploration should not supplant a thorough preoperative clinical examination. The potential for otherwise missing incomplete tendon and vascular injuries is high. It also gives one the opportunity to more thoroughly irrigate the wound and evaluate hematomas.A neuroma-in-continuity found at delayed exploration is more difficult to treat than the original acute injury. Surgical exploration is indicated in all lacerations of the hand and upper extremity unless the level of injury is sufficiently superficial to enable exlusion of damage to vital structures in the emergency department. The experience of this case presents a challenge to the current dogma of indications for tendon repair, especially in the paediatric population.The authors declare that they have no competing interests.AK carried out the operation, YD participated in the sequence alignment and drafted the manuscript, TTS and ANY participated in the design and coordination of the manuscript. All authors read and approved the final manuscript.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.


Mucinous carcinomas are defined on the basis of the amount of the mucus component in the tumour mass. Apart from this quantitative criterion, a number of clinicopathological parameters  and genetic alterations  differentiate these tumours from the non-mucinous ones. Since a different set of genetic lesions implies different inducing agents, these observations suggest that there may be a 'mucinous pathway of carcinogenesis'. Further identification of genetic changes characteristic of the mucinous phenotype will help to understand the aetiology of these tumours and possibly establish markers for detection of the high-risk group.


Since the discovery of the epidermal growth factor more than 40 years ago by Stanley Cohen and colleagues, scientific research in this area has expanded to near exponential rates. The epidermal growth factor receptor family and its associated ligands have revealed much in terms of the molecular biology of receptor tyrosine kinases and definitely proved the first link of an activated oncogene to malignant disease. On the basis of this bedrock of science, the pharmacological development of targeted therapies against this signalling system has proved to be one of the most important areas of translational research over the last two decades. Now in the clinic, agents directed against the epidermal growth factor receptor are hugely important tools in the treatment of several different solid tumours. Ongoing clinical trials seek to refine the use of these therapies and further scientific research reveals additional applications such as the use of soluble receptor.An impressive set of experts active in the field have contributed towards the 14 chapters in this book, across a spectrum from epidermal growth factor receptor protein isolation to complex techniques such as sensitive assay for monoubiquitination of receptor tyrosine kinases. A comprehensive, yet succinct introductory chapter provides a highly readable historical perspective to those coming in this field of study. An entertaining final chapter underlines clinical and pharmacological issues in the use of monoclonal antibodies and small molecule tyrosine kinase inhibitors against this signalling system. Each chapter is well organised with a summary section followed by a brief introduction, outlining how the technique is useful while explaining its relevant application for epidermal growth factor. Materials and equipment are logically and meticulously listed and the methodology is provided with sample results using clear diagrams and simple figures. An impressive notes section at the end of each chapter, drawing upon the authors’ expertise, is sufficiently detailed lending highly useful practical advice at the cutting edge, as if the expert was present in the very same laboratory.The editors are to be applauded for the structure, presentation and choice of methods presented which are relevant to the ongoing research. The references are comprehensive and clearly laid out. The information is easily digestible and very hands-on and would provide a useful laboratory resource for planning and reference. For the clinicians, this book would provide an interesting tour into much of the biology of epidermal growth factor receptor and its increasing relevance to clinical application. Overall, this is a well-planned and well-written book covering a variety of techniques applicable to the study of epidermal growth factor receptor and would find a place in those laboratories both already established and those starting out in this ever expanding field of research.


The effect of cysteine on the immunosuppressive activity of three alkylating agents was tested. Cysteine strongly inhibited the ability of cyclophosphamide and nitrogen mustard to depress the direct plaque-forming cell response of mice to sheep red cells. In contrast, the activity of busulphan was usually potentiated by administration of cysteine. This throws doubt on the hypothesis that busulphan exerts its cytotoxic effects by alkylating thiol groups.


As assessed by decrease in tumour volume and inhibition of tumour cell respiration and glycolysis, hyperthermia (intra-tumour temperature 42°C for one hour) potentiated the destructive effect of radiotherapy (1000 rad) on the allogeneic VX2 carcinoma in the hind limb of rabbits, and chemotherapy (methotrexate) produced a similar potentiation of irradiation. The resulting regression of the primary tumour in each case after dual therapy was comparable to that occurring after 3 applications of local hyperthermia, which has been shown to cure 50% of animals with this carcinoma. Combination therapy did not increase the survival time of the rabbits, however, all of which had lung and lymph node metastases at autopsy. The results focus attention on the relationship between a primary tumour and its metastases. The histological picture and the animal survival data suggest that the mechanism of tumour cell death and resorption of necrotic material following treatment may be important in enabling the host to deal with metastatic cells. After combination therapy, many metabolically and mitotically active cancer cells remained in the tumour mass, and the incomplete destruction of the primary tumour may have left the host with a burden of tumour cells too large to be destroyed by the immune system.


Creutzfeldt-Jakob disease (CJD) has been considered infectious since the mid-1960s, but its transmissibility through the transfusion of blood or blood products is controversial. The causative agent's novel undefined nature and resistance to standard decontamination, the absence of a screening test, and the recognition that even rare cases of transmission may be unacceptable have led to the revision of policies and procedures worldwide affecting all facets of blood product manufacturing from blood collection to transfusion. We reviewed current evidence that CJD is transmitted through blood.


Zoo authorities of Central Indian State of Chattisgarh reported a hyena suffering from the fatal anthrax disease in Nandanvan zoo in capital city Raipur. After laboratory confirmation of anthrax, the zoo was closed for 15 days as precautionary measure. According to the veterinarians of the zoo, all symptoms of anthrax were found in one of the hyenas. The Forest department officials decided to vaccinate animals within the 5 km radius of zoo to contain the disease. All employees of Nandanvan zoo had been put on prophylactic antibiotic medicine.;Like Orissa, Chattisgarh has very high concentration of tribal population (>35%);Both the states have extensive forest cover;The indigenous population of both these states depend less on agriculture and more on forest and animal produce for food;Overwhelming majority of people in both these states live below the poverty line.Both the states have poor public health infrastructure. This is the perfect amalgamation and interface of risk factors that are conducive for zoonotic transmission of anthrax to the human population. Hence the probability of occurrence of anthrax outbreak in the human population would increase on logarithmic scale, each time an episode of anthrax detected in animal population in a state like Chattisgarh.So, epizootology and epidemiology should be both applied not only for anthrax, but for every zoonotic disease, hence the importance of veterinary and doctors putting heads together.Anthrax disease needs to be prevented with proper legislation for meat handling as well as effective immunization of animals. RegulatiCoordination with veterinary department and animal husbandry department and for surveillance and livestock vaccination drive for of all the cattle.Behavioral change communication for anthrax prevention--all the hamlets educating the inhabitants with very important one line health education input. Not to consume raw meat, cook it well before eating else you may be at risk of contracting anthrax.Inter-state cooperation between Chattisgarh and Orissa on ways on the management of anthrax prevention and control.Orissa is carrying out annual vaccination drive of livestock in the affected districts like Koraput, Kalahandi, Malkangiri, etc. Chattisgarh state could find the sources for funding for this program in Orissa.It is important to take up live stock vaccination against anthrax. It is one of the most credible way of providing health security to the vast majority of underprivileged sections of the society, to prevent them from further impoverishment by breaking the cycle of poverty and infection.The actual incidence of anthrax in India is not known accurately mostly due to underreporting. Hence ev


Malarial anaemia is an enormous public health problem in endemic areas and occurs predominantly in children in the first 3 years of life. Anaemia is due to both a great increase in clearance of uninfected cells and a failure of an adequate bone marrow response. Odhiambo, Stoute and colleagues show how the age distribution of malarial anaemia and the haemolysis of red blood cells may be linked by an age-dependent increase in the capacity of red blood cells to inactivate complement components absorbed or deposited directly on to the surface of the red blood cell. In this commentary, we discuss what has been established about the role of complement deposition on the surface of red blood cells in the pathology of malarial anaemia, how genetic polymorphisms of the complement control proteins influence the outcome of malaria infection and how the findings of Odhiambo, Stoute and colleagues and others shed light on the puzzling age distribution of different syndromes of severe malaria. In the accompanying article, Odhiambo, Stoute and colleagues show how the age distribution of malarial anaemia and the haemolysis of red blood cells (RBCs) may be linked by an age-dependent increase in the capacity of RBCs to inactivate complement components absorbed or deposited directly on to the surface of the RBC . The worMalaria remains an enormous problem in public health around the world . Over 2 Furthermore, there remain major unsolved problems about the fundamental pathophysiology of all syndromes of severe malaria. The rapid drop in haemoglobin during acute infection and the slower decline in chronic infection appear to be due to increased extravascular haemolysis of RBCs with a concomitant failure of the bone marrow to increase red cell production to compensate for these losses .The increased clearance of infected cells is readily explained by the rupture of cells after completion of the parasite's intra-erythrocytic life cycle and opsonisation and clearance of intact infected RBCs. Rather less obvious is why and how uninfected cells are also cleared. It has been estimated that approximately 10 uninfected cells are cleared from the circulation for every infected cell and so the clearance of uninfected cells is of crucial importance for the development of malarial anaemia .Why are uninfected RBCs cleared in such large numbers? Certainly the number and activation of splenic and other macrophages for phagocytosis of red cells is greatly increased during malarial infection -9. The iUninfected RBCs have a reduced deformability leading to enhanced clearance in the spleen and a severe reduction in red cell deformability is also a strong predictor for mortality measured on admission, both in adults and children with severe malaria ,11. SecoThe role of immunoglobulin and complement in marking uninfected RBCs for clearance by phagocytes was first studied by Facer and colleagues ,13 in ThThe story of how absorbed immune complexes may contribute to increased clearance of uninfected RBCs lay dormant for 20 years when Waitumbi, Stoute and colleagues based in Western Kenya began to study how immune complexes caused haemolysis . AppreciHere, a number of proteins are involved in the control of complement activation. Complement receptor 1 (CR1 or CD35), decay accelerating factor (DAF or CD55) and the membrane inhibitor of reactive lysis (MIRL or CD59) may enhance binding of C3b in immune complexes (CR1), enhance inactivation of C3 convertases (CR1 and CD55) and interfere with the assembly of the terminal components of complement that form the membrane attack complex (CD59) . Immune in vitro than RBCs from controls. Decline in CD35 or CR1 expression and increases in immune complexes bound on uninfected RBCs were associated with anaemia but these declines in CD35 (CR1) and CD55 expression were only transiently associated with malaria infection and levels returned to normal after infection had been cleared [In previous papers, Waitumbi, Stoute and colleagues have shown that the amount of red cell surface IgG is increased but red cell surface CR1 and CD55 reduced in children with severe malaria compared with asymptomatic and symptomatic controls . The dif cleared . These dHow does this relate to the age-dependent incidence of malarial anaemia? Population studies in Europe and Africa showed the CR1 expression was strongly age-dependent and increases of both CR1 and CD55 were seen after 4 years of age and low levels of CR1 and CD55 expression were seen in a cases of severe malarial anaemia compared with slightly older children with cerebral malaria . OdhimboHow do these findings help explain the age distribution of syndromes of severe malaria? If clearance of the immune complexes absorbed on to the surface of uninfected cells is reduced in younger children expressing lower levels of CD35 and CR1, then clearance of these cells would be increased, leading to more anaemia in these younger age groups.Genetic polymorphisms also affect the expression levels, sequence and domain  structure of CR1 in Africans and other populations ,20. MoreIt is possible therefore, that age-related and genetically determined reduction of levels of CR1 expressed on RBCs are associated with an increased susceptibility to anaemia but protection from other forms of severe malaria and may provide an example of how innate resistance to one syndrome of malaria may be at the expense of susceptibility to other pathophysiological pathways involved in malaria infection.These hypotheses should ideally be tested in longitudinal studies using genetically and phenotypically well-characterised children to ascertain the levels of these age-dependent, complement regulatory proteins prior to infection and determine their association with haemoglobin levels during acute infection and with the incidence of severe disease through childhood. Such studies can only be done in a few sites in Africa where large populations can be followed before and after infection and presentation to a health facility using a demographic surveillance system.In assessing the role of these age-related changes to the complement regulatory proteins in the differential presentation of anaemia and coma, one would also have to consider the recently described findings of increased levels of erythropoietin (EPO) seen in younger children with anaemia  and malaBMC Medicine provide us with a clearer understanding of the causes of anaemia in children with malaria. Translating this new understanding of pathology into fruitful avenues to investigate prevention and treatment of malaria is perhaps the greatest challenge of clinico-pathological studies in this and other disciplines.Finally, we would ask where these studies will lead in the quest for new methods to prevent or treat malarial infection. The findings of Odhiambo, Stoute and colleagues presented in the accompanying article in CR1: complement receptor 1; DAF: decay accelerating factor; DCT: Direct Coombs' Test; EPO: erythropoietin; MIRL: membrane inhibitor of reactive lysis; RBC: red blood cell.The pre-publication history for this paper can be accessed here:


Slices of human prostatic adenocarcinoma obtained by transurethral resection were maintained in organ culture for 4 days. Preservation of histological appearance was good with little evidence of necrosis within the viable tissue. Slices of tumour cultured in the presence of testosterone showed a morphological change to a more differentiated type of neoplasm whereas explants cultured in the absence of steroid hormone, or with stilboestrol diphosphate, showed no change. In the case of a relatively anaplastic tumour, testosterone produced a significant increase in the number of mitotic figures seen.


Human lactate dehydrogenase is a tetramer made up of two typesof subunits, either H (heart) or M (muscle). Combination of thesesubunits gives rise to the five isoenzymes of lactate dehydrogenasewhich are found in mammalian tissues. The relative proportionsof the individual isoenzymes found in serum of patients is relatedto the severity of the lesion in the organ or tissue from which theyoriginate and the half-life of the individual tissue-specific enzymes.Thus, one cannot predict the relative proportions of the differentisoenzymes in any one patient sample.Lactate dehydrogenase catalyses the reversible oxidation of lactateto pyruvate and either reaction can be measured readily. However,in this method, the lactate to pyruvate reaction has been selectedbecause of the following reasons; the time-course of the reaction ismore linear, the reaction results in an increase in absorbance andoptimization of substrates is possible (see appendix A).The principles applied in the selection of the conditions ofmeasurement are those stated in previous publications by the IFCC’sCommittee on Enzymes [1]. Human serum and tissue extracts havebeen used as the sources of enzymes. The final concentration ofsubstrates and the pH have been selected on the basis of experimentsand empirical optimization techniques and have been confirmed bycalculation from rate equations. The catalytic and physicalproperties of the isoenzymes differ, but because of the importance ofthe heart specific isoenzyme (LD1) in the assessment of coronaryheart disease and as a tumour marker, this method has beenoptimized for this isoenzyme. However, the method is also suitable,although less optimally, for the determination of the otherisoenzymes of lactate dehydrogenase which may be present in serum.


Dear Sir,Use of laparoscopy in trauma is still a controversial issue. The high rate of missed injury and possibility of induction of severe complications should be carefully considered. In the recent publication by Umman, the unfavourable outcome can also be seen. The sugg111


The relative proportions of the various classes of cells are maintained when Hodgkin's tissue increases in bulk. Histological progression from LP/MC to MC Hodgkin's disease was associated with an increase in aneuploidy of the Hodgkin cell line and an increase in the proportion of large basophilic blast cells. Splenic Hodgkin's disease in the same patient contained fewer aneuploid cells. The significance of these findings in terms of the histogenesis of Hodgkin and Sternberg-Reed cells is discussed.The cellular composition of Hodgkin's tissue from two patients has been examined. The labelling pattern with


A series of 237 cases of oesophageal carcinoma admitted to two thoracic units in Ceylon is analysed.Evidence suggestive of an aetiological link between betel chewing and high incidence of the tumour in Ceylon is presented. The sex incidence is unusual in that there is a preponderance of females in the series. A significant proportion of patients were women under 40 years of age. The middle third of the oesophagus was the commonest site affected.


Daylight saving time affects millions of people annually but its impacts are still widely unknown. Sleep deprivation and the change of circadian rhythm can trigger mental illness and cause higher accident rates. Transitions into and out of daylight saving time changes the circadian rhythm and may cause sleep deprivation. Thus it seems plausible that the prevalence of accidents and/or manic episodes may be higher after transition into and out of daylight saving time. The aim of this study was to explore the effects of transitions into and out of daylight saving time on the incidence of accidents and manic episodes in the Finnish population during the years of 1987 to 2003.The nationwide data were derived from the Finnish Hospital Discharge Register. From the register we obtained the information about the hospital-treated accidents and manic episodes during two weeks before and two weeks after the transitions in 1987–2003.The results were negative, as the transitions into or out of daylight saving time had no significant effect on the incidence of accidents or manic episodes.One-hour transitions do not increase the incidence of manic episodes or accidents which require hospital treatment. Daylight saving time (DST) is used to balance the seasonal caused daylight exposure changes to the activity peaks of a population. It is important to explore the effects of transitions into DST to the public health as DST affects millions of people annually and its impacts are still widely unknown. Turning clock forwards (on spring) or backwards  by one hour presumably impacts our circadian rhythms. DST study can provide interesting knowledge about the importance of individual differences in the adjustment of changes in circadian rhythms. DST studies can also provide a useful indication of which type of people will generally find it easy to adjust  and whicCircadian clocks regulate the endogenous rhythms of vital functions. Circadian rhythms are not able to adjust instantaneously to sudden changes in sleep-wake cycle and thus sudden changes as transitions into DST can cause circadian rhythm disruptions . DisturbBoth the Parliament and Council of the European Union (EU) have stated that personal injuries are one of the central health problems in societies . According to the Ministry of Social Affairs and Health of Finland, accidents cause annually costs of approximately 3.3 – 5 billion euros (counted for accidents happened for fifteen year olds and elder). It is presumable that if functioning systems to prevent the accidents can be developed it decreases the amount of accidents. Even small reduction in amount of accidents can cause major profits; if the number of hospital treated accidents can be reduced even 5%, 10 billion euros will be saved from treatment and social expenditures inside EU area [On our earlier studies we have shown that fall and spring transitions into DST may have disruptive effects on the rest-activity cycle of healthy adults . TransitWe hypothesized that transitions into and out of daylight saving time may influence the incidence of hospital-treated accidents and manic episodes. This hypothesis was based on the earlier findings of sleep disruption being able to cause accidents and manic episodes. We assumed a peak in the number of hospital-treated manic episodes and accidents after DST transitions.The material was derived from the Finnish Hospital Discharge Register which is supported by the National Research and Development Centre for Welfare and Health. Permission for the study was authorized by the National Research and Development Centre for Welfare and Health (STAKES), Helsinki, Finland, which is the holder of the nationwide data for the National Hospital Discharge Register. For the analysis, all the data were anonymous. The Finnish Hospital Discharge Register covers all mental and general hospitals, as well as in-patient wards of local health centers, military wards, prison hospitals and private hospitals in Finland. From the register we obtained the information about the hospital-treated accidents and manic episodes during two weeks before and two weeks after the transitions in 1987–2003. The into-transitions took place on the last Sunday of March during the study period. Prior to 1996, the out-of-transitions took place on the last Sunday of September. Since 1996, Finland as a member of the European Union adopted the last Sunday of October as the out-of-transition date.Accidents and manic episodes were classified according International Classification of Diseases (ICD). Before 1995 the diagnoses were coded according to ICD-9, and for 1996–2003 they were coded according to ICD-10 . All periods of hospital treatment due to accidents and manic episodes appearing under the two preceding or two following weeks of spring and fall transitions were mapped out and from this data we gathered information as follows: the start and end days of treatment, diagnosis, the year of birth, sex and personal identity number.We constructed a contingency table of frequencies of accidents and manic episodes in respect to year (1987–2003), season , age , sex , geographical location , and period (before or after transitions). This table was modeled using Poisson regression with the cell frequency as response variable and the table marginal as the explanatory variable . The sigTransitions into or out of DST had no significant effect on the incidence of accidents or manic episodes in the Finnish population during the years of 1987 to 2003 .The reason why not seen any impact of fall and spring transitions to manic episodes and accidents can derive from following factors; Genetic contributions are important explainers of the appearance of manic episodes and it seems that in a Finnish population the prevalence of manic episodes is quite low  thus theConcerning accidents the spring transition into DST might increase the number of minor accidents, such as small pedestrian casualties and tin crashes. However, since such accidents are unlikely to lead to admission, they will not be recorded in statistics. Accidents took place slightly more often in spring than in fall table . This fiThis study indicated no effect of DST transitions on admissions due to manic episodes or accidents.The author(s) declare that they have no competing interests.TAL made contributions to the analysis and interpretation to the drafting and writing of the manuscript.JH made contributions to statistical modeling and analysis and to the drafting of the manuscript.JL participated in the planning of drafting of the manuscript.TP participated in the planning of the study, in the analysis of data, and in the drafting of the manuscript.All authors red and approved the manuscript.The pre-publication history for this paper can be accessed here:


Insects are not only of immense economic and medical importance, they provide important models for the advancement of knowledge and many are of ascetic value. They are also beset by an array of pathogens, despite their well developed defence systems. Interest in these pathogens revolves around their potential use as biological control agents for insect pests or the desire to protect beneficial insects against infection. The adoption of molecular approaches to the investigation of insect pathogens and pathogen-insect interactions has had a large impact on research and this volume provides a timely review of how these techniques are being applied.The multi authored book, consisting of sixteen chapters, is broken down into four themes; identification and diagnostics, evolutionary relationships and population genetics, host-pathogen interactions and genomics and genetic engineering. The chapters follow a standard format and consist of several short sections covering a wide range of topics related to the chapter heading. In some cases this results in a superficial overview, but all chapters contain a comprehensive list of references so that readers can follow up areas of specific interest. Most chapters deal with particular taxa of entomopathogenic organisms thus the reader may wish to focus upon chapters pertaining to their particular study group or take a comparative approach. Emphasis throughout is on molecular techniques, often discussed and evaluated from the point of view of the authors' personal experience. Although a useful glossary is provided the extensive use of acronyms warrants, in addition, a list of abbreviations.In the first section of the book authors of all the chapters emphasise the importance of molecular techniques to the revision of taxonomy and classification on a phylogenetic basis. Likewise in the second section authors emphasise the significant changes made to hypothesis concerning the evolutionary biology of insect pathogens following the application of DNA sequencing and analytical methods. Chapters on host-pathogen interactions cover an eclectic range of topics including the development of a baculovirus expression vector, tsetse fly immune responses and gene expression in tripartite nematode-bacterium-insect symbiosis. In the last chapter in this section and those in the final section on genomics and genetic engineering, detailed overviews of molecular strategies are given, a case study approach is frequently taken and future prospects and pitfalls discussed.As someone not directly involved with the fields of work presented in this book I found aspects of all chapters interesting. The overviews of techniques may prove valuable to PhD students or researchers considering taking a molecular approach to their work on insect pathogens however, consultation of detailed technical manuals is likely to be required before investigations can begin.The author declares that they have no competing interests.


Minimally displaced fractures of the surgical neck of the humerus are rarely associated with axillary artery injury. The innocuous appearance of the x-rays can be misleading and a missed arterial injury in these fractures could potentially lead to disastrous consequences. We report the case of a patient who sustained a minimally displaced fracture of the proximal humerus with vascular compromise requiring immediate investigation and referral to vascular surgeons. Despite spontaneous resolution of the vascular insult, it is important to remember the association of such fractures with vascular injuries in order to diagnose them early and prevent serious complications including amputation. Minimally displaced fractures of the neck of the humerus are rarely associated with injury to the axillary artery . In thisA relevant case is discussed and mechanisms related to vascular injuries in association with proximal humerus fractures are described with the emphasis on having a low threshold of suspecting and immediately treating such injuries in order to prevent catastrophic results.A 74-year-old white British lady attended the Accident and Emergency department after having fallen from a low height at home. She complained of pain around the right shoulder and had bruising extending from the shoulder to the elbow. There was no gross deformity of the shoulder. The fingers were cold to the touch with a delayed capillary refill. The nail beds were cyanosed. Further examination of the right upper limb revealed loss of pulsations in the brachial and radial arteries with preservation of sensations in the hand. A Doppler ultrasound also failed to detect distal pulsations. X-rays of the shoulder showed a minimally displaced fracture of the surgical neck of the humerus Figure . VasculaThe patient was admitted for monitoring of the distal pulses, but no further loss of pulsations was documented. At 12 months of follow-up, she had good functional outcome with a normally perfused limb.Fractures of the proximal humerus account for 4-5% of all fractures . AxillarThere are several mechanisms by which the axillary artery can be injured in proximal humeral fractures. A direct injury to the artery by a sharp bony fragment can cause laceration and rupture , violentDiagnosis of axillary artery injury may be difficult as peripheral pulses may remain intact initially and later disappear. As a result, vascular injury can occasionally manifest several days after a fracture of the proximal humerus .Paraesthesia is probably the most reliable symptom of inadequate distal circulation and should always be taken seriously. Collateral circulation around the shoulder is effective, and depending on the level of injury to the axillary artery, distal circulation might remain adequate and the patient asymptomatic . In DrapArterial injuries associated with proximal humeral fractures can be easily missed. Our case illustrates that minimally displaced fractures of the surgical neck of the humerus can be associated with vascular compromise and this can occur in the elderly with lesser degrees of force because of atherosclerotic rigidity of the artery. Potential complications can be avoided by careful examination of the patient and avoiding treatment of the x-ray alone.Once a vascular injury is suspected, Doppler examination is necessary to establish the magnitude and quality of the arterial signal. Angiography should be performed immediately if arterial compromise is suspected after Doppler examination, and vascular surgeons should be consulted early in the management of such patients.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.The authors declare that they have no competing interests.MS co-ordinated the entire effort and wrote the manuscript. GV helped with the draft of the case report, and obtained consent from the patient. NS was the treating and supervising consultant in charge. All authors read and approved the final manuscript.


Despite semen being the main vector of human immunodeficiency virus (HIV) dissemination worldwide, the origin of the virus in this bodily fluid remains unclear. It was recently shown that several organs of the male genital tract (MGT) are infected by HIV/simian immunodeficiency virus (SIV) and likely to contribute to semen viral load during the primary and chronic stages of the infection. These findings are important in helping answer the following questions: (i) does the MGT constitute a viral reservoir responsible for the persistence of virus release into the semen of a subset of HIV-infected men under antiretroviral therapy, who otherwise show an undetectable blood viral load? (ii) What is the aetiology of the semen abnormalities observed in asymptomatic HIV-infected men? (iii) What is the exact nature of the interactions between the spermatozoa, their testicular progenitors and HIV, an important issue in the context of assisted reproductive techniques proposed for HIV-seropositive (HIV+) men? Answers to these questions are crucial for the design of new therapeutic strategies aimed at eradicating the virus from the genital tract of HIV+ men – thus reducing its sexual transmission – and for improving the care of serodiscordant couples wishing to have children. This review summarizes the most recent literature on HIV infection of the male genital tract, discusses the above issues in light of the latest findings and highlights future directions of research. Shortly after the first cases of acquired immuno-deficiency syndrome (AIDS) were described in 1981 in the United-States, two main populations at risk were identified, homosexual men and haemophiliacs. Based on these observations, the cause of AIDS was hypothesized to be due to a sexually and blood transmitted pathogenic agent, even before the discovery of its aetiological agent, the human immunodeficiency virus (HIV). Twenty six years later, the spread of HIV has become a global phenomenon and infected more than 65 million people of whom 25 million are deceased, according to the latest estimates. In 2007, 2.7 million people were newly infected, 80% of whom were through sexual transmission.Semen represents the main vector of HIV dissemination, evidenced by transmission occurring more efficiently from men to women and men than from women to men ? It is established that the viral strains present in semen do not solely arise from the blood compartment but is/are the MGT organ(s) responsible for the seminal viral load?What is the nature of the interactions among HIV, the spermatozoa and their progenitor cells the testicular germ cells?Does the MGT constitute a viral reservoir resistant to current anti-HIV therapy? Highly Active Antiretroviral Therapy (HAART) does not always eradicate the virus from semen, even when achieving an undetectable viral load in blood and can favour the sexual transmission of drug-resistant strains;What is the cause of the semen abnormalities recently described in HIV+ men?Answering these questions is crucial for the design of new therapeutic strategies aimed at eradicating the virus from the genital tract of HIV+ men  and for improving the care of serodiscordant couples wishing to have children. The aim of this review was to summarize the current knowledge on HIV infection of the male genital tract, discuss the above questions in view of the latest findings and highlight future directions of research.HIV is present in semen as free viral particles and infected cells. It was originally believed that the only source of HIV in semen was infected lymphocytes and macrophages coming from the blood. It has now been shown that the HIV strains present in semen evolve separately from the strains in the blood or in other anatomical compartments ]. Thus iAs infected leucocytes in semen produce viral strains that are different from those in blood leucocytes  in spermatozoa purified using a gradient of Percoll without swim-up (which further separates motile spermatozoa from non-motile), these positive finding were assumed to result from contaminations of this fraction by a few remaining infected leucocytes or from false positives . In the In conclusion, spermatozoa display several receptors that could allow HIV specific binding during their progression through the male genital tract. Thus it is likely that spermatozoa can act as a carrier for viral particles encountered within the testis or epididymis, i.e. in the absence of seminal plasma, an inhibitor for some of the HIV receptors present on spermatozoa. It is established that spermatozoa do not produce HIV particles. Whether they can support the early steps of HIV replication  as proposed by some authors remains speculative, as the vast majority of studies did not evidence any HIV genetic material and spermatozoa are considered as metabolically inert cells. However, non-specific mechanisms such as foreign RNA uptake could be at play and explain the detection of HIV DNA in a subset of abnormal spermatozoa. The exact nature of the interactions between HIV and spermatozoa, and their impact on spermatozoa morphology, are far from fully understood and require further studies.The infection of the testis by HIV can have important consequences for the eradication of the virus from the MGT by antiretroviral therapies. Thus, the existence of the blood testis barrier and of the drug efflux pumps of the ABC transporter family expressed by a wide range of testicular cell types, restrict the drug access to this organ, as shown for some HIV replication inhibitors . The in During the later stages of the disease, the testis morphology is severely damaged , with diTo conclude, recent data show that the testis is infected early during the course of HIV infection. This infection is not associated with either any apparent change in testicular morphology or inflammation of the organ  or a cellular (e.g. the latently infected resting memory lymphocytes) site, impermeable to the action of one or several antiviral drugs and within which the virus replicates or persists despite treatment. Such sanctuaries are called reservoirs when they replenish the body in free virus or infected cells. Thus when HAART is discontinued, the blood plasma viral load that was undetectable under the pressure of the antiretroviral drugs systematically rises again from these reservoirs  to have children without contaminating the partner and embryo. ART uses spermatozoa isolated from the infected components in semen  and tested negative for viral DNA/RNA  determining whether one or several of the infected MGT organs constitute a viral reservoir, which could explain the persistence of HIV in the semen of men under effective treatment with undetectable blood viral load; (ii) determining the aetiology of the semen parameter modifications in HIV+ men under HAART; (iii) deciphering the exact nature of the interactions between HIV, the testicular germ cells and the spermatozoa, both important issues in the context of ART; (iv) analysing the effect of HIV infection on the seminal plasma composition and its impact on HIV infectivity, which may reveal new mechanisms that could be useful in the fight against the AIDS pandemic as a few studies suggest that seminal plasma factors may influence HIV sexual transmission.


Recent studies support the hypothesis of a close aetiological and pathogenic association between the presence of patent foramen ovale (PFO) and cryptogenic stroke. The therapeutic options currently used in the treatment of these patients range from standard antiaggregation and standard-dose anticoagulation to the percutaneous occlusion of the PFO. The use or recommendation of treatment is based both on clinical risk factors associated with PFO, such as age, detection of states of hypercoagulability and previous history of stroke, and on the risks associated to right-to-left shunt (RLSh) and PFO, such as the size of PFO, magnitude of RLSh and the presence of atrial septal aneurysm (ASA). However, there is currently no consensus regarding the most suitable treatment and it is surprising to observe the widespread use of certain therapeutic approaches which are not supported by clinical evidence. In this revision, we analyse the relevance of PFO in cryptogenic stroke, consider the main evidence available for determining the best management of these patients and make diagnostic and therapeutic management recommendations. I). Some of these studies have shown an association between the size of PFO, the magnitude of right-to-left shunt (RLSh), and the presence of atrial septal aneurysm (ASA) with increased stroke risk  vs. 6.5 ml [1.3-16.6]) and suggests that the mechanism of stroke in patients with and without RLSh/PFO is different. This hypothesis is supported by the greater prevalence of risk factors in patients with cryptogenic stroke without RLSh. The mechanisms of the stroke involved in RLSh appear less severe than those involved in patients without RLSh. We must be careful not to fall into the logical error of confusing the identification of a specific aetiology for a condition with the need to aggressively combat it. One aspect which has been little evaluated but which is very interesting when deciding which type of therapeutic intervention to undertake is the analysis of the consequences of suffering a stroke associated with RLSh/PFO. The fact that cryptogenic stroke associated with a RLSh presents a low annual risk of recurrence together with the lesser severity of stroke associated with RLSh shown by the CODICIA study ,60 advisBefore indicating PFO closure, anticoagulation or antiplatelet therapy, we need to identify the subgroup of patients at high risk of stroke recurrence which may benefit from the application of these therapies. Several stroke associations, including the American Heart Association, American Stroke Association, American Academy of Neurology ,61 and tAnticoagulant therapy may be used in selected cases with high risk of thromboembolic events such as hypercoagulable states or evidence of deep venous thrombosis . In clinical practice, PFO closure should be individualized and considered in young patients with recurrent stroke receiving medical treatment or in previously mentioned situations where anticoagulant treatment is considered . Ongoing trials have a low recruitment rate with a risk of bias if younger patients or those with severe PFO or associated anomalies are treated out of the trials. It is therefore important that effort should be made to randomize patients systematically in these trials  and to improve the collaboration between neurologists, basic scientists and cardiologists so that reliable results regarding the best treatment options can be established for our patients as soon as possible.


We report from the second ESF Programme on Functional Genomics workshop onData Integration, which covered topics including the status of biological pathwaysdatabases in existing consortia; pathways as part of bioinformatics infrastructures;design, creation and formalization of biological pathways databases; generatingand supporting pathway data and interoperability of databases with other externaldatabases and standards. Key issues emerging from the discussions were the need forcontinued funding to cover maintenance and curation of databases, the importanceof quality control of the data in these resources, and efforts to facilitate the exchangeof data and to ensure the interoperability of databases.


The use of restrictive measures such as quarantine draws into sharp relief the dynamic interplay between the individual rights of the citizen on the one hand and the collective rights of the community on the other. Concerns regarding infectious disease outbreaks  have intensified the need to understand public perceptions of quarantine and other social distancing measures.We conducted a telephone survey of the general population in the Greater Toronto Area in Ontario, Canada. Computer-assisted telephone interviewing (CATI) technology was used. A final sample of 500 individuals was achieved through standard random-digit dialing.Our data indicate strong public support for the use of quarantine when required and for serious legal sanctions against those who fail to comply. This support is contingent both on the implementation of legal safeguards to protect against inappropriate use and on the provision of psychosocial supports for those affected.To engender strong public support for quarantine and other restrictive measures, government officials and public health policy-makers would do well to implement a comprehensive system of supports and safeguards, to educate and inform frontline public health workers, and to engage the public at large in an open dialogue on the ethical use of restrictive measures during infectious disease outbreaks. Prior to the 2003 outbreak of severe acute respiratory syndrome (SARS), it had been more than 50 years since mass quarantine measures had been invoked in North America  and 'infectious disease' . At the conclusion of the survey, respondents were asked to supply general demographic information.After the response format was explained and before the first survey item was asked, all participants were provided standardized definitions of 'quarantine' : (a) parking in a no-parking zone; (b) driving way above the speed limit on a busy street; or (c) physical assault." Fully 59% responded that breaking quarantine is most like 'physical assault,' whereas 27% selected 'driving above the speed limit' and 8% chose 'parking in a no-parking zone' (6% did not answer).Principal components factor analysis of the survey data yielded an underlying factor structure of four independent factors. Based on a subjective analysis of the content of items loading on each individual factor, the four factors were labelled as follows: 'Justification,' 'Sanctions,' 'Burdens,' and 'Safeguards' , p < .001], thereby indicating greater agreement that the use of quarantine is justified in the context of an infectious disease outbreak. With respect to age, older respondents (>65 yrs) indicated greater agreement that use of quarantine is justified than did the young (18-35 yrs) . Also, older respondents agreed more strongly that the use of sanctions for quarantine absconders is appropriate when compared both with the young and with the middle-aged (36-65 yrs) . There were no significant differences by region.The quarantine of exposed persons  has been properly described as the most complex and most ethically and legally controversial intervention within the jurisdiction of public health . ComplexData on public attitudes toward quarantine in the wake of SARS are scarce. Public opinion polls have indicated high levels of acceptance of quarantine among samples of Toronto-area residents (97%) and US citizens (93%) . These fComparative data from international studies do lend support to the theory that cultural values and societal norms impact upon quarantine compliance rates. Researchers at the Harvard School of Public Health and the U.S. Centers for Disease Control and Prevention surveyed residents of Hong Kong, Taiwan, Singapore, and the U.S. and found significant regional variability . The proIn view of this inter-region variability, it is not surprising that the global community of public health experts is itself conflicted about the use of quarantine and other restrictive measures that impinge upon the intrinsic rights of individuals. Those who favour the consideration of quarantine during infectious disease outbreaks maintain that it is prudent public health policy , whereasWith a view to fostering further deliberation and constructive debate, we are proposing a conceptual framework for the ethical use of restrictive measures in public health emergencies (see Figure Much has been learned from the unexpected arrival of SARS in the spring of 2003 ,27. LikeOwing to the global threat of pandemic influenza, considerable planning and preparation for infectious disease outbreaks has been undertaken . There rWhile we believe the data reported here contribute to the goal of better planning and better preparedness, the present study is limited by its sample of respondents who were drawn only from the Greater Toronto Area. Our goal was to assess the attitudes and perceptions of those living in an area significantly impacted by the SARS outbreak, but further research is now required to determine the generalizability of the present findings to other geographic regions and other populations. Also, our survey was conducted after the conclusion of the outbreak; it is conceivable that public perceptions and attitudes toward the use of restrictive measures could be different during the course of an outbreak. Finally, a relatively small proportion of our survey respondents were directly affected by quarantine during SARS, which precluded any analysis of differences between those who were directly affected and those who were not.The use of restrictive measures such as quarantine draws into sharp relief the push and pull of opposing forces that characterize the dynamic interplay between the personal autonomy of the citizen on the one hand and the collective rights of the community on the other. As Bensimon and Upshur  have argThe authors declare that they have no competing interests.CST performed the statistical analysis of the survey data, drafted the first version of the manuscript, and contributed to subsequent revisions. ER initiated the study, participated in the design of the survey instrument, and contributed to the revising of the manuscript. REGU participated in the statistical analysis, contributed to the revising of the manuscript, and will act as guarantor. All authors have read and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/9/470/prepub


Ectopic internal carotid artery (ICA) is a very rare variation. The major congenital abnormalities of the ICA can be classified as agenesis, aplasia and hypoplasia, and they can be unilateral or bilateral. Anomalies of the neck artery may be vascular neoplasms or ectopic position. Carotid angiograms provide absolute confirmation of an aberrant carotid artery, while EcoColorDoppler (ECD) gives also important information about the evaluation of carotid vassels. Nevertheless Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) of the neck provide spatial information about the adjacent pharyngeal anatomy and are less invasive than angiogram. Injuries to the ICA during simple pharyngeal surgical procedures can be catastrophic due to the risk of massive bleeding. We report a case of a 56 year-old male patient suffering from dysphagia associated with aberrant ICA manifesting itself as a pulsative protruding of the left lateral wall of the oropharynx. The congenitally tortuous internal carotid artery (ICA) is an uncommon but important anomaly for the otolaryngologist, to recognize. Numerous descriptions of the anomalies of the greatest vessels of the head and neck, as well as of the ICA have been presented in the literature. The deformities of the ICA have been reported with a large variability of pattern and degree. Some of them determine a dislocation of the ICA that can be found at the level of the pharyngeal wall in some cases. Because of this dislocation, the ICA may cause a widening of the retropharyngeal and lateropharyngeal soft tissues. The ectopic ICA poses a risk during both major oropharyngeal tumor resection and less extensive procedures, such as tonsillectomy, adenoidectomy, and uvulopalatopharyngoplasty. We report a case of a 56 year-old male patient suffering from dysphagia associated with aberrant ICA manifesting itself as a pulsative protruding of the left lateral wall of the oropharynx.A 56 year-old male patient was admitted to our service with dysphagia, and malaise that had progressed over the last week. Oral examination revealed an edema at the gingival and the soft palate area, as well as a redness and pulsative protruding of the left lateral wall of the oropharynx. The rest clinical evaluations, as well as the blood tests were normal. Because of the palatal edema, he was administered methylprednisolone per os. No other medication was given.A Computed Tomography (CT) of the neck was then performed, which revealed the helicoids, ectopic course of the right internal carotid artery (ICA) at the level of the oropharynx figure . MultiplThe abnormal extension of the ICA subsequently was confirmed by Magnetic Resolution Angiography (MRA) of the neck figure . This abEctopic internal artery is a very rare variation. The venous anomalies are relatively more frequent than arterials . The ICAThe ICA ascends within the carotid sheath towards the scull base. It is first crossed laterally by the hypoglossal nerve as this nerve passes forward from its position behind the internal carotid. ICA then crosses the occipital artery, as this artery passes posteriorly from its origination of the external carotid artery. Near the skull base the ICA crosses laterally towards the posterior belly of the digastric muscle and the muscle attached to the styloid process. Laterally to the carotid canal is the deep lobe of the parotid gland. Medially to the carotid are the retropharyngeal space and the superior constrictor muscle.Other vital structures located close to the ICA, are the internal jugular vein, the cranial nerves IX to XII, and the external carotid artery. Inferiorly the internal jugular vein lies laterally to the ICA. The glossopharyngeal nerve passes forward between the internal and external carotid artery at the bifurcation. The hypoglossal nerve passes forward laterally to the internal carotid artery just above the bifurcation. The external carotid artery travels anterior to the ICA throughout its entire course.The major congenital abnormalities of the ICA can be classified as agenesis, aplasia and hypoplasia, and they can be unilateral or bilateral. Absence of the ICA is referred to as agenesis or aplasia .Anomalies of ICA in the neck may be vascular neoplasms or ectopic position. Vascular neoplasms are more common in children, but two relatively rare neoplasms that occur in the adults are the angiosarcoma and hemangiopericytoma.The ectopic carotid artery usually occurs in the temporal bone . AngulatWhile the reports of fatal posttonsillectomy hemorrhage and the dissections of Kelly clearly describe the unusual laterally placed of the ICA, midline carotid arteries are even less commonly reported . Kelly nEctopic ICAs should be differentiated from other vascular lesions, such as angiosarcoma and hemangiopericytoma. Peritonsillar abscess, masses as lymphomas, and other tumors must be take under consideration, when a panicula in the oropharynx is detected.We prefer the use of CT or MRI since they are less invasive than angiogram and provide spatial information about the adjacent pharyngeal anatomy. In MRA the resolution of details is not as precise as in angiograms and imaging artifacts due to turbulent flow or patient movement may be a major limitation. Another one examination for the evaluation of carotid vessels is the EcoColorDoppler (ECD), which is easy to perform, and gives quick and important information that MRI and CT do not provide  .Transposition of the ICA bulging the posterior pharyngeal wall constitutes a risk factor for impressive intraoperative and postoperative hemorrhage in surgical procedure such as adenoidectomy, tonsillectomy, uvulopalatopharyngoplasty and incision of peritonsillar abscess, which are often performed by young and inexperienced ENT doctors. The surgeon should be careful in performing routine surgical procedures in the area of the upper pharynx, which generally represent the most frequent interventions carried out by inexperienced surgeons as the first steps of their surgical training. The hidden presence of an asymptomatic anomaly of the internal carotid artery may cause impressive and life-threatening hemorrhage. In the literature is reported a massive blood loss during tonsillectomy in a child with congenital vascular malformation of the lips and the oropharynx .In our case the referring physician thought that panicula in the lateral wall of oropharynx was edema. The otolaryngologists surgeons must use caution in evaluating patients with masses in the pharynx and augment a careful and complete head and neck examination with appropriate imaging studies before operating. A thorough ocular and digital exploration of the pharynx for arterial pulsations should never be omitted.


Most modern commercial graphite furnace atomic absorption spectrometers have built in microprocessors for this purpose but they often have limited capability for extensible user programs and limited data storage facilities. In this communication we describe the use of an Apple IIe microcomputer for the acquisition of data from a Pye Unicam SP9 graphite furnace atomic absorption spectrometer. Details of the interface which utilizes an in-house designed AD converter, and an overview of the Pascal and assembler programs employed are given. The system allows the user to record, store and dump the graphical display of the furnace signalsfor all analyses performed. Files containing details of peak height, and area are formatted on an eight-column spreadsheet. Details of sample type, concentrations of standards, dilutions and replication are entered from the keyboard. The calibration graph is constructed using a moving quadratic fit routine and the concentrations of the analyte in unknown solutions calculated. In addition to this, greater processing power and integration of the data into other analytical schemes can be achieved by exporting the data to other software packages and computers. Details of data transfer between the Apple IIe and an Amstrad PC 1512 are given. Some examples of the use of the system in the development of an analytical methodfor silver in plant material are given.Since its inception as an analytical technique some 30 years ago atomic absorption spectrometry has become a firmly established method for the analysis of trace metals. Graphite furnace atomic absorption spectrometry provides the analyst with the capability of analysis of solutions containing μg l


The high prevalence and incidence of prostate cancer is a global phenomenon ,2. In thOver the past 15 years, there has been has been a notable change in the clinical presentation of prostate cancer, with more organ confined disease ,12. StudIn the Bahamas, a country where 85% of the population are of African ancestry, prostate cancer represents both the highest incidences of male malignancy occurrences and cancer specific deaths. Unfortunately, despite the increased campaigns for early detection since the introduction of PSA testing, there has been no down stage migration of clinical presentations of this malignancy in the Bahamas, as has occurred in the developed countries . The culWith this high incidence of advance disease and noting that hormonal therapy remains the first treatment of choice, we sought to determine the most common treatment modality employed in our institution with regards to surgical versus medical castration. Emphasizing the need for cost effective and affordable care in our developing country, would men of African ancestry in a macho dominated society opt to have surgical castration as the preferred treatment?All men presenting with advanced prostate cancer at the government-owned public health facility, the Princess Margaret Hospital, are informed by the Consultant Urological Surgeon of the various medical and surgical hormonal options and their advantages and disadvantages. They are informed also that the institution would provide the surgical option of bilateral orchiectomies at no charge, but the cost of the medical treatment option must be borne by the patient.At the only two hospitals on New Providence Island in the Bahamas, the Princess Margaret Hospital, (450 beds) and the privately-owned Doctors Hospital (70 beds), all pathology reports for biopsy proven cancers and the operative log for the number of surgical castration procedures were reviewed during a thirteen years period from 1987 to 2000. The data base is compiled from that of a solo urology service providing care in both the private and public sectors in the Bahamas; this service represents 70% of the urological health care delivered in the country. It is important to note that almost 70% of the population of the Bahamas resides on New Providence Island on which the capital city of the Bahamas is located.There were 535 pathology-diagnosed cases of prostate cancer identified. 275 bilateral orchiectomies were performed in patients presenting with advance prostate cancer during this period, an average of 21.5 bilateral orchiectomies performed annually.For the five years period 2003 to 2007 at the government's public hospital, all cases of pathology proven prostate cancer were reviewed. There were 363 documented cases of prostate cancer. During this period, there were 103 cases of bilateral orchiectomies recorded in the operative log of the hospital, averaging 20.6 cases per year. The frequency of bilateral orchiectomies performed annually was similar to that of the thirteen year period.This high rate of hormonal treatment is an indication of the continuing trends of advance disease as the initial presentation of males diagnosed with prostate cancer in the Bahamas. The trend of increasing annual mortality rates for prostate cancer has continued unabated for the past 15 years, contrary to that of the developed countries; this is well documented in the annual cancer mortality reports by the Health Information and Research Unit of the Ministry of Health and Social Services of the Bahamas.This study concludes that men in the Bahamas with advanced prostate cancer would opt for surgical castration when presented 'positively' as the preferred treatment. These findings are contrary to the perception of the macho-male image of the Caribbean male and invite further studies into the complex psyche of our Bahamian males.The author declares that they have no competing interests.


Similar manifestations of density dependent inhibition were found in the isolated cultures of normal and neoplastic cells: at saturation densities these cultures had low labelling indices; these indices considerably increased when the cells migrated into the wound from the dense sheet, prelabelled cells seeded on the dense sheets of unlabelled homologous cells did not proliferate. However, proliferation of neoplastic cells was not inhibited when they were seeded on the dense sheet of normal fibroblasts. Thus, neoplastic hamster fibroblasts of both lines retained sensitivity to the inhibiting effect of homologous neoplastic cells but completely lost sensitivity to the inhibiting effect of normal fibroblasts. The possible significance of this selective loss of the sensitivity to normal cells is discussed briefly.


The relationship between ageing and transformation has been investigated by a serial study of the changes in cell-surface morphology as normal and carcinogen-treated cells progressed in culture. A progressive increase in the density of cell surface microvilli occurred in association with the adoption of a more rounded profile and concomitant increase in the rate of cell detachment. These changes occurred earlier after carcinogen treatment, which appeared to indicate a carcinogen-induced acceleration of ageing. The alterations have also been described as characteristic of the transformed state. The observations suggest that the expression of in vitro transformation may be the result of continuous selection from a population with genetic instability and variable morphology.