Effects of ethanol on temporal recovery of auditory-evoked potentials in individuals at risk for alcoholism

The present investigation examined the effects of placebo (P), low dose (LD), and high dose (HD) ethanol on auditory event-related potential (AEP) recovery functions in a group of males at high risk to develop alcoholism (HR; n = 23, mean = 22.3 years) and a low risk (LR; n = 27, mean = 23.0 years) control group. Condition order was randomized, with one condition (P, LD, or HD) per day and a minimum 1-day interval between conditions. For each subject, both blood alcohol levels (BALs) measured via breathalyzer, and event-related potentials recorded with the entire 10/20 International System, were assessed prior to and at mean intervals of 20, 60, 90, and 130 min after P, LD, or HD administration. A series of binaural auditory stimuli with randomly interposed interstimulus intervals of 0.5, 1.0, and 10.0 sec were used to elicit the N100 and P200 components of the AEP. Between-groups comparisons indicated that ethanol elicited risk group differences in recovery functions not present at baseline. The differences were manifested in the HR group as larger decrements in P200 amplitude during the ascending blood alcohol curve (acute sensitivity) and more rapid returns of both N100 and P200 to baseline levels during the descending blood alcohol curve (acute tolerance). These findings support Newlin and Thomson's (1990) Differentiator Model, suggesting that LR and HR individuals are differentially sensitive to the effects of ethanol.     

Fasting plasma glucose in screening for diabetes in the Taiwanese population

OBJECTIVE: To reveal the relationship between fasting and 2-h postload plasma glucose and to examine the appropriate fasting glucose cutoff as the primary screening test for diabetes. RESEARCH DESIGN AND METHODS: We recruited 5,303 subjects from preventive services of the National Cheng Kung University Hospital. Exclusion criteria were age <20 years, pregnancy, known diabetes, and a history of recent surgery, trauma, or illness. All subjects received the 75-g oral glucose tolerance test. The relationship between fasting and 2-h glucose was examined. Sensitivities, specificities, efficiency, and predictive values were assessed at different cutoffs of fasting glucose for prediction of diabetes. RESULTS: The best fit model for the relationship between fasting and 2-h glucose was fasting glucose = 4.914-0.060 x (2-h glucose) + 0.0144 x (2-h glucose)2. From this model, the fasting glucose was 6.0 mmol/l when 2-h glucose was 11.1 mmol/l. A fasting glucose with 6.25 mmol/l gave the same diabetes prevalence as the World Health Organization 2-h glucose criterion. When 7.8 mmol/l was the fasting glucose cutoff, the sensitivity was 28.5%. Lowering the cutoff from 7.8 to 7.0 mmol/l increased the sensitivity by 11.2% and slightly reduced the specificity and positive predictive value. If the cutoffs were 6.25 and 6.0 mmol/l, the sensitivity increased and the specificity and the positive predictive value decreased accordingly. CONCLUSIONS: Our results suggest that fasting glucose as a screening criterion for diabetes could be revised downward to 7.0 mmol/l, because the slight reduction of positive predictive value was more than balanced by an apparent increase of sensitivity and insignificant change of specificity.     

Quantitative analysis of microvascular changes in diffuse astrocytic neoplasms with increasing grade of malignancy

BACKGROUND: Despite concerns about its prevalence and ramifications, harassment has not been well quantified among physicians. Previous published studies have been small, have surveyed only 1 site or a convenience sample, and have suffered from selection bias. METHODS: Our database is the Women Physicians' Health Study, a large (4501 respondents; response rate, 59%), nationally distributed questionnaire study. We analyzed responses concerning gender-based and sexual harassment. RESULTS: Overall, 47.7% of women physicians reported ever experiencing gender-based harassment, and 36.9% reported sexual harassment. Harassment was more common while in medical school (31% of gender-based and 20% for sexual harassment) or during internship, residency, or fellowship (29% for gender-based and 19% for sexual harassment) than in practice (25% for gender-based and 11% for sexual harassment). Respondents more likely to report gender-based harassment were physicians who were now divorced or separated and those specializing in historically male specialties, whereas those of Asian and other (nonwhite, nonblack, non-Asian, non-Hispanic) ethnicity, those living in the East, and those self-characterized as politically very conservative were less likely to report gender-based harassment. Being younger, born in the United States, or divorced or separated were correlated with reporting ever experiencing sexual harassment; those who were Asian or who were currently working in group or government settings were less likely to report it. Those who felt in control of their work environments, were satisfied with their careers, and would choose again to become physicians reported lower prevalences of ever experiencing harassment. Those with histories of depression or suicide attempts were more likely to report ever having been harassed. CONCLUSIONS: Women physicians commonly perceive that they have been harassed. Experiences of and sensitivity to harassment differ among individuals, and there may be substantial professional and personal consequences of harassment. Since reported rates of sexual harassment are higher among younger physicians, the situation may not be improving.     

Danazol for systemic lupus erythematosus with refractory autoimmune thrombocytopenia or Evans' syndrome

OBJECTIVE: To determine the efficacy of danazol for refractory autoimmune thrombocytopenia or Evans' syndrome complicating systemic lupus erythematosus (SLE). METHODS: We studied 16 consecutive patients with SLE and corticosteroid refractory autoimmune thrombocytopenia; 3 patients had coexisting autoimmune hemolysis (Evans' syndrome). Five patients had undergone splenectomy. Danazol was commenced at 200 mg/day, and increased stepwise (maximum 1200 mg/day) until benefit or toxicity was observed. After remission the danazol dose was gradually reduced to 200-400 mg/day. RESULTS: All 16 patients achieved a complete remission (platelet count >100 x 10(9)/l, hematocrit >39%) 2 months after starting danazol (range 6 weeks-8 months). Remission persisted during continued danazol therapy (mean followup 18.2 months, range 2-49 months). One patient with Evans' syndrome required discontinuation of danazol because of jaundice and biopsy proven minimal hepatic necrosis: hemolysis recurred after discontinuation of danazol. CONCLUSION: Danazol is effective for the treatment of autoimmune thrombocytopenia or Evans' syndrome complicating SLE irrespective of splenectomy status. Longer followup will be needed to determine whether the remission persists after withdrawal of danazol.     

Effects of acute and chronic morphine on rotational behavior in nigral-lesioned rats

Stimulation of mu-opioid receptors located on dopaminergic neurons in the striatum and the nucleus accumbens increases dopamine release, which may account for some of the behavioral effects of morphine. In this study, we examined the effects of acute and chronic morphine treatment on rotational behavior in rats with unilateral 6-hydroxydopamine dopamine (6-OHDA)-induced lesions of the nigrostriatal pathway. Rats receiving morphine acutely (0.3-10 mg/kg) did not show a significant bias toward contralateral or ipsilateral turning. Mini osmotic pumps dispensing morphine continuously (20-24 mg/kg/day) were implanted s.c. in these animals. This treatment induced tolerance to the behavioral depression produced by the highest dose of morphine (10 mg/kg) when it was given acutely. A slight but significant increase in ipsilateral turning occurred over the range of morphine doses examined. The effects of morphine on rotational behavior are slight, and do not correlate well with the reported increase in locomotor activity or extraneural dopamine in the striatum that are produced by doses of morphine similar to the ones tested in this study.     

Effect of alcohol consumption on adult and aged bone: composition, morphology, and hormone levels of a rat animal model

To determine the effect of life-long alcohol consumption on the adult and aged rat model, 4-week-old, female Sprague-Dawley rats were divided into three diet groups. Alcohol-treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35% ethanol-derived calories, whereas the pair-fed animals (weight-matched to ethanol rats) received an isocaloric liquid diet in which maltose-dextrin substituted calories supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Proximal tibiae (primarily cancellous bone) and femora (primarily cortical bone) were removed for analysis after 3, 6, 9, 12, or 18 months on the diets. Serum was collected for analysis of calcium levels, the calcium regulating hormones; parathyroid hormone, 25-hydroxyvitamin D, calcitonin, corticosterone, estradiol, testosterone, and IGF-1. Creatinine, SGOT/AST, and SGPT/ALT levels were measured to determine kidney and liver integrity. Previous studies, with young animals, showed that chronic alcohol consumption during the age of bone development reduced bone density and bone mass in both cortical and cancellous bone. The present study demonstrates that these reductions last throughout life, whereas morphological values, such as length and diameter, attain control levels. Calcium regulating hormones and sex hormones are essentially normal and do not appear to be the primary causative agent for adult alcohol-induced osteopenia, but it appears to be due to a more direct effect of alcohol on bone cells.     

Functional modulation of P2X2 receptors by cyclic AMP-dependent protein kinase

It is generally believed that protein phosphorylation is an important mechanism through which the functions of voltage- and ligand-gated channels are modulated. The intracellular carboxyl terminus of P2X2 receptor contains several consensus phosphorylation sites for cyclic AMP (cAMP)-dependent protein kinase (PKA) and protein kinase C (PKC), suggesting that the function of the P2X2 purinoceptor could be regulated by the protein phosphorylation. Whole-cell voltage-clamp recording was used to record ATP-evoked cationic currents from human embryonic kidney (HEK) 293 cells stably transfected with the cDNA encoding the rat P2X2 receptor. Dialyzing HEK 293 cells with phorbol 12-myristate 13-acetate, a PKC activator, failed to affect the amplitude and kinetics of the ATP-induced cationic current. The role of PKA phosphorylation in modulating the function of the P2X2 receptor was investigated by internally perfusing HEK 293 cells with 8-bromo-cAMP or the purified catalytic subunit of PKA. Both 8-bromo-cAMP and PKA catalytic subunit caused a reduction in the magnitude of the ATP-activated current without affecting the inactivation kinetics and the value of reversal potential. Site-directed mutagenesis was also performed to replace the intracellular PKA consensus phosphorylation site (Ser431) with a cysteine residue. In HEK 293 cells expressing (S431C) mutant P2X2 receptors, intracellular perfusion of 8-bromo-cAMP or purified PKA catalytic subunit did not affect the amplitude of the ATP-evoked current. These results suggest that as with other ligand-gated ion channels, protein phosphorylation by PKA could play an important role in regulating the function of the P2X2 receptor and ATP-mediated physiological effects in the nervous system.     

Vaginal colonization with Group B beta-hemolytic streptococcus as a risk factor for post-cesarean section febrile morbidity

Vaginal colonization of mothers with Group B beta-hemolytic streptococcus (GBS) has been recognized as a risk factor for neonatal morbidity. The relationship of GBS colonization to risks for the mother who undergoes cesarean section has not been defined. In this study, we found that, among patients who underwent cesarean section, the 19% of them who were colonized with GBS had a higher incidence of standard fever (66.6% vs. 30.5%), clinical diagnosis of endomyometritis (61.1% vs. 12.5%), and use of antibiotics (61.1% vs. 26.3%) in relationship to a significantly increased frequency of premature rupture of the membranes (50.0% vs. 14.8%). Reasons for the association between vaginal colonization and increased morbidity are discussed.