Enhanced performance feedback to strengthen biofeedback treatment outcome with childhood migraine

The activity of rifabutin (LM 427) against Mycobacterium leprae was evaluated in armadillos inoculated earlier with human-derived M. leprae. Rifabutin was administered daily at a dose of 6 mg/kg body weight/day. The effect of rifabutin on M. leprae harvested from armadillos was determined by measuring the intracellular levels of ATP (an indicator of metabolic activity) of M. leprae and also their ability to multiply in the mouse footpads and in vitro in DH medium. Within 2 weeks of initiating the treatment, ATP levels declined to 21% of the original (pre-treatment level) and these M. leprae failed to multiply in the footpads of mice as well as in the in vitro culture system. This suggests that rifabutin was able to kill all M. leprae within 2 weeks. After 8 weeks the treatment was terminated and results showed that M. leprae from the treated armadillos remained non-viable in the mouse footpad system as well as in the in vitro system, indicating bactericidal action of rifabutin. The results suggest that rifabutin can be a substitute for rifampin in the leprosy multi-drug therapy regimen.     

Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors

Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.     

Prevalence of gastrointestinal symptoms in obese and normal weight binge eaters

OBJECTIVES: Disturbances in gastrointestinal function may result from disordered eating and may lead to increases in gastrointestinal (GI) symptoms. We compared GI symptoms in obese and non-obese binge eaters and non-binge eaters. METHODS: One hundred nineteen obese and 77 normal-weight females completed a questionnaire on bowel symptoms and binge eating behaviors for the previous 3 months. Based on binge behaviors and body mass index (> 30 kg/m2), individuals were grouped as obese binge eaters (n = 73), obese non-binge eaters (n = 43), non-obese binge eaters (n = 14), and normal-weight controls (n = 61). RESULTS: Obese binge eaters reported more upper GI symptoms than normal controls or obese non-binge eaters (p < 0.001). Compared with normal controls, nausea, vomiting, and bloating was 2-4 times more prevalent in both binge eating groups. Indigestion was more prevalent in both obese groups. Obese binge eaters reported more lower GI symptoms than normal-weight controls (p < 0.05). Binge eating in both weight groups was associated with more frequent abdominal pain and dyschezia. Obesity was associated with more frequent constipation, diarrhea, straining, and flatus, whether or not subjects reported binge eating. Chi-square showed a significant association between obesity, binge eating, and symptoms of irritable bowel syndrome, using the Manning criteria. CONCLUSIONS: Specific GI symptoms were associated with binge eating and obesity. Overall, symptoms were more prevalent and more severe in obese binge eaters. The high prevalence of GI symptoms in obese patients who indulge in binge eating should be considered in their evaluation and treatment.     

Becker muscular dystrophy with bundle branch reentry ventricular tachycardia

This report describes a case of Becker muscular dystrophy presenting with recurrent symptomatic wide complex tachycardia. Electrophysiologic testing demonstrated the mechanism to be bundle branch reentry ventricular tachycardia. It is important to consider this potential mechanism in patients with ventricular arrhythmias who have this particular clinical entity, since radiofrequency catheter ablation can represent a curative treatment.     

Chicken oviductal ecto-ATP-diphosphohydrolase. Purification and characterization

An ecto-ATP diphosphohydrolase (ATPDase) was purified to homogeneity from vesiculosomes shed from chicken oviduct. First, the ecto-ATPDase-enriched vesiculosomes were concentrated by filtration, differential centrifugation, and exclusion chromatography. Next, the nonionic detergent, Nonidet P-40, was used to extract the ecto-ATPDase from vesiculosomal membranes, and the solubilized enzyme was further purified by ion exchange (DEAE-Bio-Gel) and lentil-lectin-Sepharose 4B chromatography. In the final stage, immunoaffinity chromatography was utilized to obtain purified ecto-ATPDase. More than 25,000-fold purification was achieved. Specific activity of the purified enzyme was greater than 800 micronol/min/mg of protein with MgATP as the substrate, the highest ever reported for an ATPDase. The enzyme also hydrolyzed other nucleoside triphosphates in the presence of magnesium at similar rates and CaATP and MgADP at lower rates. The molecular mass of the purified glycoprotein was 80 kDa as determined by SDS-polyacrylamide gel electrophoresis and Western blot analysis. Based on its enzymatic properties, the relationship of the chicken oviduct ecto-ATPDase with other reported ATPDases and ecto-ATPases is discussed.     

Embryotoxic doses of vitamin A to rabbits result in low plasma but high embryonic concentrations of all-trans-retinoic acid: risk of vitamin A exposure in humans

Retinoid pharmacokinetics were examined in plasma, placenta and embryos of gestational d 12 rabbits following application of an embryotoxic dosing regimen (10 mg retinyl palmitate/kg body wt per day from gestational d 7 to 12). Vehicle-treated or untreated rabbits served as controls. Physiological concentrations of all-trans-retinoic acid (all-trans-RA) and 13-cis-RA in rabbit plasma (5-8.33 nmol/L) were very close to the endogenous levels in human plasma. In addition, we identified endogenous all-trans-RA, 3,4-didehydroretinol and 3,4-didehydroretinoic acid in rabbit embryo. Following the last retinyl palmitate administration, apparent steady-state concentrations of all retinoids were reached in the examined compartments of rabbits. The major polar retinoid in plasma was 9, 13-di-cis-RA, but its embryonic concentrations were only about 6% of those in plasma. In the embryo, retinol and its esters were found at high concentrations; lower amounts of all-trans-4-oxo-RA and the newly identified 14-hydroxy-4, 14-retro-retinol could also be measured. Embryonic concentrations of all-trans-RA were about 100% higher than endogenous levels. The overall exposure of the embryo to this retinoid was, however, substantial. Embryonic area under the concentration time curve values strongly suggest that the embryotoxicity of the applied dosing regimen is mainly due to the action of all-trans-RA. A very remarkable finding of this study is the marginal increase of plasma concentrations of all-trans-RA over their endogenous levels, which is comparable to the human situation after vitamin A intake. This analogy indicates that high vitamin A intake may be associated with a higher risk for teratogenic effects in humans even in the absence of high elevation of plasma all-trans-RA levels.     

Gestational choriocarcinoma metastatic to the brain treated successfully by stereotactic radiosurgery and chemotherapy

This report analyzes the intracorporal lengths of 236 consecutive organically impotent men who underwent insertion of a penile prosthesis. The average right or left intracorporal length in this series was 20.9 cm, with a standard deviation of 2.2 cm. Intracorporal length ranged from 14-27 cm. This data may be used as reference ranges for penile prosthesis manufacturers, and for Urologists who implant prostheses or perform penile lengthening procedures.