Radiology-Pathology Conference: Bilateral renal oncocytomas

Oncocytoma is an uncommon benign, typically solitary renal tumor first reported in 1942. Renal oncocytomas are rarely multiple and/or bilateral. Accurate preoperative diagnosis and differentiation from renal carcinoma is difficult. We report the radiology and pathology of a patient with bilateral renal oncocytomas and review the literature of this rare presentation.     

Langerhans' cell histiocytosis: a clinicopathological study of 50 cases

To analyze the clinicopathologic features and outcome of patients with Langerhans cell histiocytosis (LCH). Fifty cases of LCH accrued over a 15-year period were analyzed and classified as having unifocal, multifocal, or multisystem disease. Events regarding progression, relapse, or death were noted. The 50 cases comprised of 34 men and 16 women. 92% of the patients were less than 15 years of age and 46% were less than 2 years. Involvement by LCH was unifocal in 22, multifocal in 8, and multisystem in 20. Bone was the commonest site (92%), followed by lymph node (30%). The histological features were relatively uniform regardless of the clinical severity, and consisted of Langerhans cells, eosinophils, histiocytes, plasma cells, giant cells and fibrosis. The treatment consisted of surgery, chemotherapy, and/or radiotherapy. Response to treatment was poor in patients with multisystem disease. The histology of LCH is very characteristic and patients with age less than 2 years are more likely to have increased risk or morbidity and mortality, due to widespread disease.     

Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism

BACKGROUND: alpha2-Adrenergic blockade responses suggest adrenergic dysfunction in hypertension. alpha2-Blockade is also used to treat autonomic dysfunction. However, pharmacokinetic determinants of yohimbine disposition are not understood. METHODS: We evaluated alpha2-blockade with intravenous yohimbine in 172 individuals. Specific cytochrome P450 (CYP) isoform-mediated metabolism was investigated. Results were evaluated by ANOVA and by maximum likelihood analysis for bimodality of response distributions. RESULTS: Yohimbine metabolism to 11-hydroxy-yohimbine displayed greater than 1000-fold variability, with 17 individuals showing no metabolism. Nonmetabolizers differed from others in ethnicity but not in age, sex, body habitus, blood pressure, heart rate, or family history of hypertension. Bimodality of metabolism was suggested by frequency histogram, as well as maximum likelihood and cluster analysis. Among ethnic groups, subjects of European ancestry had the highest frequency of nonmetabolism. In vitro oxidation suggested that the major route of metabolism (lowest Michaelis-Menten constant and greatest intrinsic clearance) was likely via CYP2D6 to 11-hydroxy-yohimbine. In vivo genotypes at both CYP2D6 and CYP3A4 were necessary to predict metabolism (overall F = 3.03, P =.005); an interaction of alleles at these 2 loci (interaction F = 3.05, P =.033) suggested an epistatic effect on drug metabolism in vivo. Nonmetabolizers had greater activation of sympathetic nervous system activity. Yohimbine increased blood pressure, an effect mediated hemodynamically by elevation of cardiac output rather than systemic vascular resistance. Blood pressure and cardiac output responses did not differ by metabolizer group. CONCLUSIONS: We conclude that heterogeneous, bimodally distributed yohimbine metabolism depends on common genetic variation in both CYP2D6 and CYP3A4 and contributes to differences in sympathetic neuronal response to alpha2-blockade. These results have implications for both diagnostic and therapeutic uses of this alpha2-antagonist.     

Community based trials and informed consent in rural north India

Disease control has increasingly shifted towards large scale, disease specific, public health interventions. The emerging problems of HIV, hepatitis, malaria, typhoid, tuberculosis, childhood pneumonia, and meningitis have made community based trials of interventions a cost effective long term investment for the health of a population. The authors conducted this study to explore the complexities involved in obtaining informed consent to participation in rural north India, and how people there make decisions related to participation in clinical research.     

Seeking help for sexual function complaints: what gynecologists need to know about the female patient's experience

OBJECTIVE: To further explore the patient experience of seeking help for a sexual function complaint. DESIGN: Survey administered on a Web-based instrument. SETTING: Healthy volunteers visiting an online Website. PATIENT(S): The majority of participants were married (73%), Caucasian (88%), and premenopausal (67%). Most commonly reported sexual complaints included low desire (77%), low arousal (62%), and difficulty achieving orgasm (56%). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Patient experience survey on a women's sexual health website. RESULT(S): Although 40% of the women reported that they did not seek help from a physician for sexual function complaints, 54% reported that they would like to. Although only a minority of the women internalized their experience with extremely negative emotions like shame, devaluation, or disgust, the experience was not a particularly emotionally positive one along the lines of relief, optimism, or confidence, and a great deal of frustration and anxiety about treatment was reported. CONCLUSION(S): The extent to which health professionals currently receive exposure to training in human sexuality as well as the way in which female sexual complaints are handled in the medical setting remain ambiguous. The inflow of patients with sexual function complaints only will increase, and it is time for physicians to start to acknowledge women's sexuality with the same importance their patients do.     

Vertebral cryptococcosis simulating tuberculosis

Infection with the fungus Cryptococcus neoformans is seen predominantly in two forms: (a) pulmonary and (b) cerebromeningeal. Skeletal cryptococcosis is uncommon. There have been only occasional case reports of thoracic vertebral cryptococcosis presenting as cord compression. A young female had cervical lymphadenopathy diagnosed as tuberculosis by fine needle aspiration cytology (FNAC) and was on antitubercular therapy (ATT) for 5 months. She developed rapidly progressive paraparesis and imaging demonstrated a destructive vertebral body lesion involving T2-3 with a paraspinal abscess producing cord compression. A costotransversectomy with excision of the diseased bone and bone grafting was done. Histopathological examination revealed cryptococcosis. The patient was put on antifungal medication, but expired 2 weeks after surgery. Radiological, magnetic resonance imaging and surgical finding of vertebral cryptococcosis can mimic tuberculosis. The definite diagnosis of cryptococcosis depends upon microscopic identification of the organism. A high index of suspicion leading to early surgical confirmation and institution of anti fungal therapy is necessary to reduce the mortality and morbidity.     

Recent progress in the design of selectin inhibitors

The selectins are a family of cell-adhesion proteins that mediate the early stages of leukocyte recruitment from the blood stream to sites of tissue damage through recognition of the carbohydrate epitope sialyl Lewis(x) (sLe(x)). Current development of small molecule based inhibitors of this process and their clinical potential to address numerous acute and chronic diseases are explored.