Rickets in adult cystic fibrosis with myopathy,pancreatic insufficiency and proximal renal tubular dysfunction

Rickets is reported in a 19 year old white man with cystic fibrosis in whom pancreatic and hepatic involvement was advanced. There was evidence of secondary hyperparathyroidism with proximal renal tubular acidosis, aminoaciduria, phosphaturia and hypophosphatemia. Treatment with oral pancreatic and parenteral vitamin D supplements led to full recovery of the rachitic syndrome and the proximal renal tubular dysfunction.     

Bilateral occurrence of pheochromocytoma in patients with the multiple endocrine neoplasia syndrome type 2A (Sipple's syndrome)

Two kindreds with the multiple endocrine neoplasia type 2A syndrome were studied. Of one of these we examined 150 members, 20 of whom were treated with thyroidectomy for medullary carcinoma and nine with bilateral adrenalectomy for pheochromocytoma. Of the second kindred 59 members were examined, seven of whom were thyroidectomized and seven treated with bilateral adrenalectomy. Pheochromocytomas were invariably found on both sides, even in four cases in which the adrenals on one side appeared to be completely normal, not only at preoperative roentgenologic examination but also on inspection during the operation. The microscopic finding of micronodules and a cluster of abnormal medullary cells identical with those found in pheochromocytomas in one of the apparently normal adrenals represents a first stage in the development of diffuse medullary hyperplasia as well as nodular hyperplasia. This is in accordance with the fact that in the MEN type 2A syndrome pheochromocytomas are always multicentric and multiple in origin. On the basis of these findings we conclude that all patients with the MEN 2A syndrome who show symptoms and signs of active pheochromocytoma should be subjected to bilateral adrenalectomy, even when one or both of the adrenals appear to be normal at roentgenologic investigation.     

Anal intraepithelial neoplasia and squamous cell carcinoma in HIV‐infected adults

Anal cancer is one of the most common non‐AIDS‐defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV‐infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV‐related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV‐infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV‐infected adults.     

GluN2B subunit deletion reveals key role in acute and chronic ethanol sensitivity of glutamate synapses in bed nucleus of the stria terminalis

The bed nucleus of the stria terminalis (BNST) is a critical region for alcohol/drug-induced negative affect and stress-induced reinstatement. NMDA receptor (NMDAR)-dependent plasticity, such as long-term potentiation (LTP), has been postulated to play key roles in alcohol and drug addiction; yet, to date, little is understood regarding the mechanisms underlying LTP of the BNST, or its regulation by ethanol. Acute and chronic exposure to ethanol modulates glutamate transmission via actions on NMDARs. Despite intense investigation, tests of subunit specificity of ethanol actions on NMDARs using pharmacological approaches have produced mixed results. Thus, we use a conditional GluN2B KO mouse line to assess both basal and ethanol-dependent function of this subunit at glutamate synapses in the BNST. Deletion of GluN2B eliminated LTP, as well as actions of ethanol on NMDAR function. Further, we show that chronic ethanol exposure enhances LTP formation in the BNST. Using KO-validated pharmacological approaches with Ro25-6981 and memantine, we provide evidence suggesting that chronic ethanol exposure enhances LTP in the BNST via paradoxical extrasynaptic NMDAR involvement. These findings demonstrate that GluN2B is a key point of regulation for ethanol's actions and suggest a unique role of extrasynaptic GluN2B-containing receptors in facilitating LTP.     

Skin cancer screening

BACKGROUND: Skin cancer is the most common malignancy occurring in humans, affecting 1 in 5 Americans at some time during their lives. Early detection of cancerous lesions is important for reducing morbidity and mortality. CASE DESCRIPTION: The patient was a 79-year-old woman who was receiving physical therapy for cervical stenosis. The physical therapist identified a mole with suspicious characteristics, using the ABCD checklist for skin cancer screening. The patient was referred to her primary care physician, and the lesion was removed and identified as basal cell carcinoma. OUTCOMES: Early detection of this lesion allowed for complete excision, with no further treatment of the area warranted. DISCUSSION: Physical therapists can aid in detection of suspect lesions with knowledge of the basic screening techniques for skin cancer, which may help reduce the morbidity and mortality caused by these lesions.     

Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase

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Abundant microsatellite polymorphism in Saccharomyces cerevisiae, and the different distributions of microsatellites in eight prokaryotes and S. cerevisiae, result from strong mutation pressures and a variety of selective forces

We examined the distributions of short tandemly repeated DNAs (microsatellites) in nine complete microbial genomes (Saccharomyces cerevisiae, Archaeoglobus fulgidus, Escherichia coli, Haemophilus influenzae, Helicobacter pylori, Methanococcus jannaschii, Mycoplasma pneumoniae, M. genitalium, and Synechocystis PCC6803.) These repeats contribute differently to the global features of these genomes, and we explore the evolutionary implications of these differences by empirical examination of length polymorphisms at 20 long triplet-repeats repeats in S. cerevisiae, and by comparison of observed and expected repeat distributions. All of a sample of 20 microsatellites found in S. cerevisiae are highly polymorphic in length, suggesting that mutation pressure overcomes overall selection for small genome size that will tend to shorten or eliminate unnecessary DNA. By comparison, prokaryotes have fewer long repeats than expected, except for a few statistically improbable repeats that appear to function in gene regulation. Finally, we find that in all these genomes there is an excess of repeats shorter than those traditionally considered to be microsatellites. This finding suggests that even in prokaryotes these repeats are being generated by mutational pressures. These results have important potential implications for understanding genome stability and evolution in these microbial species.