Shashi XLMR syndrome: report of a second family

This report describes a family with mental retardation in two brothers. The pedigree is consistent with either X-linked mental retardation or autosomal recessive inheritance. The clinical features consist of coarse face, prominent lower lip, large testes, and obesity. This same constellation of findings was observed in a family with X-linked mental retardation (XLMR) reported by Shashi et al. [2000: Am J Hum Genet 66:469-479]. Furthermore, haplotype analysis was consistent with localization of the Shashi XLMR syndrome in Xq26-q27. Thus, the family likely represents a second occurrence of the Shashi XLMR syndrome.     

Chromosomal aberrations in follicular thyroid carcinoma. Case report of a primary tumor and its metastasis

We present the result of a cytogenetic study of a case of follicular carcinoma of the thyroid and its metastasis. Both tumors have a low number of chromosomes. The primary tumor is characterized by a idic(22;22)(p11;p11). The skeletal metastasis has also structural abnormalities of chromosome 22.     

Lectin histochemistry of the lymphoid organs of the chicken

Cellular interactions within the immune system are in part mediated via the carbohydrate-rich coat of the cell membrane, the glycocalyx, of which the terminal carbohydrate residues are of particular functional importance. Thus, these carbohydrate residues from thymus, bursa of Fabricius, spleen and bone marrow of 2- and 30-day-old chickens were investigated by lectin histochemistry. In the thymus, mannose as well as N-acetyl-glucosamine (glcNAc)-specific lectins labelled macrophages, epithelial reticulum cells and lymphocytes within the cortex. In the bursa of Fabricius, the brush border of the lining epithelium, the macrophages and the endothelium were labelled by mannose-specific lectins. The follicle-associated epithelium was labelled by a broad spectrum of lectins. Epithelial cells that separated the cortex from the medulla and large mononuclear cells in the cortex were only being labelled by N-acetyl-galactosamine (galNAc)-specific and glcNAc-specific lectins, respectively. In the spleen, lymphocytes of the peri-ellipsoid lymphocyte sheaths and macrophages of the red pulp were labelled by lectins of nearly all sugar specificities. In general, glycotopes of these organs were more intensively labelled in the 2-day-old chicken than in the 30-day-old chicken, indicating changes in glycotope expression during post-hatching development. Thus, cells of the avian immune system are as rich and diverse in their lectin binding sites as their mammalian counterparts, indicating that similar carbohydrate lectin interactions between cells and matrices take place in birds as well.     

Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV

BACKGROUND: Atazanavir, an azapeptide protease inhibitor (PI), has pharmacokinetics that allow once-daily dosing, and it is not associated with significant PI-associated dyslipidemia. METHODS: A randomized, double-blind, double-dummy, active-controlled, 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily. The 810 treatment-naive patients were stratified by HIV RNA level. The primary efficacy end point was the proportion of treated patients with HIV RNA levels <400 copies/mL through week 48. RESULTS: At week 48, HIV RNA levels were <400 copies/mL in 70% of patients receiving atazanavir and 64% of patients receiving efavirenz (intent-to-treat, difference; 95% confidence interval: 5.2%; -1.2%, 11.7%). Median CD4 cell counts increased at comparable magnitudes and rates in the 2 treatment arms (mean change at week 48: 176 cells/mm with atazanavir, 160 cells/mm with efavirenz). Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol, fasting low-density lipoprotein cholesterol, or fasting triglycerides over 48 weeks of therapy. Atazanavir-linked bilirubin elevations infrequently resulted in treatment discontinuation (<1%). Atazanavir treatment did not increase fasting glucose or insulin levels. CONCLUSIONS: For initial HIV treatment, a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine.     

The M2 selective antagonist AF-DX 116 shows high affinity for mnscarine receptors in bovine tracheal membranes

Summary We have characterized the muscarine receptors in bovine tracheal and left ventricular membranes using ³H-dexetimide/pirenzepine and ³H-dexetimide/AF-DX 116 competition studies. Pirenzepinc exhibited low (M₂) affinity binding to both preparations; K _d was 590 nM in left ventricle and 463 nM in trachea. AF-DX 116 exhibited high (M₂) affinity binding to left ventricle (K _d = 95.6 nM); in tracheal membranes it bound with high (M₂) affinity (K _d = 40.7 nM) to 74% of the receptors and with low (M₃) affinity (K _d = 2.26 M) to 26% of the receptors. It is concluded that bovine tracheal muscle membranes contain a heterogeneous population of muscarine binding sites, the majority having M₂ (heart) subtype characteristics and being located on the smooth muscle membranes; a minority having M₃ (exocrine gland) subtype characteristics and presumed to be located in submucosal glands. This is the first report of high affinity binding of AF-DX 116 to non-cardiac peripheral muscarine receptors. Send offprint requests to A. F. Roffel at the above address     

Enzyme activities in the rabbit cornea during immunogenic keratitis

In rabbits inflammation of the cornea was induced by intrastromal injection of horse serum. Between 2 and 4 weeks after injection, infiltration of the cornea with leukocytes and neovascularization could be observed. During this period, the rabbits were killed and their corneas analyzed for protein, alkaline phosphatase, acid phosphatase,N-acetyl--D-glucosaminidase, and lactate dehydrogenase. The enzyme activities in the inflamed corneal stroma reflect the high lysosomal activity, which probably originates from the leukocytes. The enzyme activities in the epithelium indicate that the tissue is abnormal and undergoing repair processes.     

Gaps in coverage and access in the European Union

This study identifies gaps in universal health coverage in the European Union, using a questionnaire sent to the Health Systems and Policy Monitor network of the European Observatory on Health Systems and Policies. The questionnaire was based on a conceptual framework with four access dimensions: population coverage, service coverage, cost coverage, and service access. With respect to population coverage, groups often excluded from statutory coverage include asylum seekers and irregular residents. Some countries exclude certain social-professional groups (e.g. civil servants) from statutory coverage but cover these groups under alternative schemes. In terms of service coverage, excluded or restricted services include optical treatments, dental care, physiotherapy, reproductive health services, and psychotherapy. Early access to new and expensive pharmaceuticals is a concern, especially for rare diseases and cancers. As to cost coverage, some countries introduced protective measures for vulnerable patients in the form of exemptions or ceilings from user chargers, especially for deprived groups or patients with accumulation of out-of-pocket spending. For service access, common issues are low perceived quality and long waiting times, which are exacerbated for rural residents who also face barriers from physical distance. Some groups may lack physical or mental ability to properly formulate their request for care. Currently, available indicators fail to capture the underlying causes of gaps in coverage and access.     

Effect of diet on the single- and multiple-dose pharmacokinetics of sustained-release ketoprofen

The indirect effect of diet on the single-and multiple-dose pharmacokinetics of sustained-release ketoprofen was studied in 16 healthy male volunteers. In an open, cross-over design, 200 mg ketoprofen was administered as a gastric-juice-resistant, sustained-release tablet once daily during two periods of 5 days. A low-calorie/low-fat diet (LCFD) was given in the first period and a high-calorie/high-fat diet (HCFD) in the second period. The first meal on each day was given 4 h after drug intake. Ketoprofen plasma concentrations were measured over 24 h after the first dose on day 1 and over 36 h after the final dose on day 5 of each period.On average, plasma concentrations of ketoprofen were higher with the LCFD than with the HCFD. With the HCFD there was a tendency to longer absorption-lag times on day 5. The maximum concentration and the area under the curve over one 24-h dosage period (AUC_0–24) were significantly higher with the LCFD, both on day 1 and on day 5. For AUC_0–24 the differences were on average 15% (day 1) and 24% (day 5). The same tendency was observed for the amount excreted in urine over 24 h (A_e), but the difference was only significant on day 1 (14%). The elimination rate constant (K) and the mean residence time were similar for the two diets, both on day 1 and on day 5.From these results, we conclude that there was an acute indirect effect of diet when a meal was had 4 h after intake of the medication. This resulted in a greater extent of ketoprofen absorption with the LCFD than with the HCFD. The absorption rate was apparently not influenced by this acute effect. The longer gastric residence time of ketoprofen with the HCFD may be the result of a long-term indirect effect on gastric emptying rate. If the extreme difference between the diets in this study is taken into account, it seems unlikely that the observed indirect effects have implications for clinical practice.     

A series of articles on the usefulness and uselessness of physical diagnostics; comment

The sensitivity, specificity and reproducibility (especially the interassessor variation) of many physical diagnostic tests taught in the medical curricula appear not to have been established. Nevertheless, many of these tests are mentioned as end terms in the General plan 1994 medical education. A series of articles in this journal will be concerned with tests from physical diagnostics, with reference to usefulness and uselessness: sensitivity, specificity and reproducibility.