How to use Chlamydia antibody testing in subfertility patients

Screening for tubal factor subfertility by means of Chlamydia antibody testing (CAT) was introduced into the initial work-up of subfertile couples several years ago. The results reported, however, are heterogeneous, and no uniformity exists in cut-off levels of titres, or in definitions of tubal factor subfertility. We performed a prospective cohort study to evaluate the implications of varying the definitions of tubal pathology and of modifying the cut-off levels on the clinical impact of CAT in predicting tubal factor subfertility. In 227 consecutive patients who attended our fertility clinic, the Chlamydia IgG antibody titre was determined and related to tuboperitoneal abnormalities at laparoscopy as a reference standard. According to received operating characteristic (ROC) curve analysis, a titre of 16 is the optimum cut-off level. Increasing the cut-off level improves specificity and positive likelihood ratio (LR+), at the expense of sensitivity and negative LR (LR-). Changing the definition of tubal factor subfertility from unspecified tuboperitoneal abnormalities into extensive adhesions and/or bilateral distal tubal occlusion improves LR+, LR- and kappa significantly. We conclude that CAT is more accurate in predicting severe distal tubal pathology than unspecified tuboperitoneal abnormalities. Although from a statistical point of view a titre of 16 is the optimum cut-off level, from a clinical point of view 32 or 64 may be preferable, depending on the aim of screening and the inception cohort.      

von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.     

Indian Systems of Medicine: A Brief Profile

Medicinal plants based traditional systems of medicines are playing important role in providing health care to large section of population, especially in developing countries. Interest in them and utilization of herbal products produced based on them is increasing in developed countries also. To obtain optimum benefit and to understand the way these systems function, it is necessary to have minimum basic level information on their different aspects. Indian Systems of Medicine are among the well known global traditional systems of medicine. In this review, an attempt has been made to provide general information pertaining to different aspects of these systems. This is being done to enable the readers to appreciate the importance of the conceptual basis of these system in evolving the material medica. The aspects covered include information about historical background, conceptual basis, different disciplines studied in the systems, Research and Development aspects, Drug manufacturing aspects and impact of globalization on Ayurveda. In addition, basic information on Siddha and Unani systems has also been provided.     

Molecular pharmacology of the Na+-dependent transport of acidic amino acids in the mammalian central nervous system

The Na+-dependent transport of L-glutamate (GluT) has been identified in brain tissue more than thirty years ago. Neurochemical studies, performed in various experimental models during 1970's, defined the basic rules for the selection or synthesis of GluT-specific substrates and inhibitors. The protein molecules (transporters) that mediate the translocation of the substrates across the plasma membrane have been cloned and studied during the last ten years. The sites on the transporters that bind the substrates favour glutamate-like or aspartate-like molecules with one positively charged and two negatively charged ionised groups. Substituents at C3 and C4 are often tolerated but substitutions at C2 or alterations of the ionisable groups usually impede the binding. The substrate binding sites display an "anomalous" selectivity towards stereoisomers. These structural requirements are shared by all Na+-dependent glutamate transporters thus making the design of transporter-selective ligands a challenging task. Moreover, the molecular mechanisms of the transport have not yet been adequately elucidated. Data from a wide variety of experimental studies strongly indicate that Na+-dependent GluT regulates the functioning of the glutamatergic excitatory synapses-the most important rapid inter-neuronal signalling system in the mammalian brain. Altered structural and/or functional properties of the Na+-dependent glutamate transporters have been implicated in the damage to the brain tissue following cerebral ischaemia and in the progressive loss of neurons in conditions such as Alzheimer dementia and amyotrophic lateral sclerosis. Furthermore, it seems that fine-tuning of glutamatergic neurotransmission by regulating the Na+-dependent GluT could be useful in the therapy of schizophrenia.     

The bottom line: Outcomes after conservation treatment in anal cancer

At the Department of Radiation Oncology, Westmead Hospital, between 1980 and 2000, 60 patients with squamous cell carcinoma of anal canal or margin (including 15 with Stage IIIA or IIIB) were treated radically; 55 received chemoradiation (89% were prescribed mitomycin C and 5‐fluorouracil). Five‐year overall survival was 64% (95% confidence interval (CI): 48–79%), with a median survival of 9.75 years (median follow up 5.6 years, range 5 months to 22.5 years). Ten patients have died of disease. At 2 years the local control rate was 86%, and colostomy‐free survival was 83%. Relapse after 2 years was uncommon. Tumour size was the main factor driving outcomes, especially survival. Patients with larger tumours (T > 4 cm) had a hazard ratio for survival of 5.7 (95% CI: 1.8–17). Fourteen (24%) patients experienced treatment interruptions as a result of acute toxicity, including one death from neutropoenic sepsis. Seven (12%) patients, in total, experienced one or more late toxicities, grade 3 or above, including four women (all postmenopausal) who developed a radiation‐induced bone injury. Most patients with anal cancer can expect to retain a functional sphincter after chemoradiation/radiation. Further studies are in progress to determine the optimal chemoradiation protocol.     

Muscle necrosis in the extremities: evaluation with Tc-99m pyrophosphate scanning--a retrospective review

A retrospective review was done of 34 extremities studied between 1981 and 1985 with technetium-99m pyrophosphate scanning; 22 were subsequently amputated. Results of detailed pathologic examination or immediate postoperative examination of the resected extremity were available in 16 cases. In these cases, scanning had allowed correct prediction of the level of amputation and of the specific areas of muscle infarction in 13 cases. In the one case in which amputation was performed for infection rather than muscle necrosis, the lack of necrosis was correctly predicted with the scan. The limited results of this study indicate that the Tc-99m pyrophosphate scan allows the location of necrotic muscle to be predicted accurately and may therefore be a useful adjunct in determining the best level for ultimate amputation. Special caution is required in those cases in which muscle necrosis is due to acute causes (e.g., traumatic thrombosis) rather than chronic vascular disease.     

Intrauterine spermatic cord torsion in the newborn: sonographic and pathologic correlation

In five newborn patients with spermatic cord torsion, sonography demonstrated an enlarged and globular testis, hydrocele, and skin thickening. In four of these patients the testicular parenchyma was heterogeneous. Peripheral hypoechoic areas were seen in two of the four patients; the other two had a central hypoechoic region and a peripheral echogenic rim. The testis in the fifth patient was diffusely hyperechoic. Duplex Doppler sonography performed in two patients failed to demonstrate any signal in the spermatic cord in either the abnormal or contralateral hemiscrotum. Scintigraphic findings were positive for testicular torsion in two patients and equivocal in three patients. Surgery was performed 2-12 days after sonography and established the diagnosis of spermatic cord torsion. Pathologic examination demonstrated hemorrhagic infarction of the entire testis as well as scattered calcifications. The authors conclude that a solid globular testicular mass seen during the neonatal period is suggestive of intrauterine spermatic cord torsion.