Determination of the cut-off value of serum alanine aminotransferase in patients undergoing hemodialysis, to identify biochemical activity in patients with hepatitis C viremia.

BACKGROUND: Elevated liver enzymes are infrequent in patients with hepatitis C virus (HCV) infection undergoing chronic hemodialysis (HD), suggesting that the alanine aminotransferase (ALT) is a poor predictor of hepatocellular damage in this population. OBJECTIVE: To establish a more appropriate cut-off value of ALT to identify biochemical activity due to HCV infection in HD patients. STUDY DESIGN: A total of 217 patients, with an average age of 51.2 years, were evaluated between January and October 2002; 130 were males (60%). Serum ALT was measured by a kinetic method in five consecutive monthly blood samples, from which an average was obtained and divided by the upper limit of normal (ULN). HCV antibodies were determined using an enzyme immunoassay, the serum HCV-RNA by nested-PCR and HCV genotype by hybridization of the amplified sequence from the 5'-non-coding region. The cut-off value of ALT was obtained from a ROC curve. RESULTS: Within the 217 patients, 18 (8.3%) were anti-HCV-positive, 17 (7.8%) of whom were also HCV-RNA-positive. Genotype distribution was: 1a=47%; 1b=18%; 3a=35%. Mean ALT/ULN (0.77+/-0.57) of the 18 anti-HCV-positive cases was higher (p<0.001) than the negative group (0.38+/-0.23). The mean ALT/ULN (0.81+/-0.57) of the 17 HCV-RNA-positive cases was also higher (p<0.0001) than the negative cases (0.37+/-0.23). The cut-off value of ALT to distinguish the anti-HCV-positive from negative patients was 0.50% or 50% of the ULN (sensitivity=67%; specificity=83%). According to the HCV-RNA, the cut-off value of ALT was 0.45% or 45% of the ULN (sensitivity=71%; specificity=80%). CONCLUSION: Reducing the cut-off of ALT by half, enables a better identification of biochemical activity in patients with HCV infection on chronic HD.     

Degradation of extracellular matrix proteins (fibronectin, vitronectin and laminin) by serine-proteinases isolated from Lonomia achelous caterpillar hemolymph.

Lonomia achelous is a caterpillar distributed in southern Venezuela and in northern Brazil that causes an acute hemorrhagic syndrome in people who have contact with its bristles. The effect of the crude hemolymph and its chromatographic fractions (FDII, Lonomin V and Lonomin V-2) on extracellular matrix proteins was studied. The chromatographic fractions show activities similar to plasmin and urokinase. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, both lonomins appear as a protein band of 25 kDa under reduced conditions. By exclusion chromatography, the molecular weights of Lonomin V and Lonomin V-2 were 26.5 and 24.5 kDa, respectively. Fibronectin, laminin and vitronectin were degraded by all venom components. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, under reduced conditions, shows that lonomins degrade fibronectin in four main fragments of 116, 60, 50 and 30 kDa. Molecular exclusion chromatography in native conditions shows that the molecular masses of these fragments are > or = 300, 62 and 27 kDa. The proteolytic effect of lonomins was abolished by benzamidine/HCl, iodoacetic acid and aprotinin. The extracellular matrix protein degradation together with the fibrino(geno)lytic activity of hemolymph and its fractions could explain, in part, the hemorrhagic syndrome, and the wound dehiscence in persons who have had contact with the L. achelous caterpillar.     

The Role of Instructional Set on Alcoholic Performance

This study was conducted to determine whether alcoholic and control subjects respond differently to manipulations that either enhance personal involvement (PI) or reduce negative affect (R, relaxation) on tests of neuropsychological function. In Phase 1, 48 male alcoholics and 36 male control subjects completed neuropsychological tasks under standard instructional sets. In Phase 2, subjects completed equivalent forms of these tests under one of three randomly assigned conditions; the PI condition in which subjects were encouraged to identify specific ways of improving their performance, the R condition in which subjects participated in a short relaxation exercise designed to reduce anxiety, or a No Treatment (NT) condition in which no attempt to manipulate the subjects' involvement or affect was made. Alcoholics were inferior to controls in both Phase 1 and Phase 2 [Fs (1,82) > 5.03, ps < 0.03]. The experimental manipulation differentially affected measures of negative affect and effort in the predicted direction. There were no group x condition interactions. Alcoholic and control subjects responded comparably to the experimental manipulations. This investigation, in combination with others using related manipulations, reinforces the hypothesis that alcohol-related cognitives dysfunction reflects an underlying deficit in brain states.     

Progressive knowledge loss: a longitudinal case study.

The evolution of the progressive loss of semantic knowledge of a patient, VZ, with lesions mainly affecting the infero-medial temporal lobes, was followed for two years. At the beginning of the study VZ's performance was mainly characterized by a category-specific deficit for living things and a modality-specific deficit for perceptual attribute knowledge. As time went on, VZ's disorder affected all categories by changing the relationship between category and attribute knowledge. Data show that dissociations may change in the course of progressive cognitive breakdown, depending on both degeneration stage and task demands. VZ's performance is discussed in the light of the most influential theoretical accounts. Methodological suggestions regarding longitudinal studies of degenerative patients are also put forward.     

Cholesterol-sensing receptors, liver X receptor alpha and beta, have novel and distinct roles in osteoclast differentiation and activation.

The liver X receptor (alpha,beta) is responsible for regulating cholesterol homeostasis in cells. However, our studies using the LXRalpha-/-, LXRbeta-/-, and LXRalpha-/-beta-/- mice show that both LXRalpha and beta are also important for bone turnover, mainly by regulating osteoclast differentiation/activity. Introduction: The liver X receptors (alpha,beta) are primarily responsible for regulating cholesterol homeostasis within cells and the whole body. However, as recent studies show that the role for this receptor is expanding, we studied whether the LXRs could be implicated in bone homeostasis and development. MATERIALS AND METHODS: pQCT was performed on both male and female LXRalpha-/-, LXRbeta-/-, LXRalpha-/-beta-/-, and WT mice at 4 months and 1 year of age. Four-month-old female mice were additionally analyzed with reference to qPCR, immunohistochemistry, histomorphometry, transmission electron microscopy, and serum bone turnover markers. RESULTS: At the mRNA level, LXRbeta was more highly expressed than LXRalpha in both whole long bones and differentiating osteoblast-like MC3T3-E1 and osteoclast-like RAW 264.7 cells. Four-month-old female LXRalpha-/- mice had a significant increase in BMD because of an increase in all cortical parameters. No difference was seen regarding trabecular BMD. Quantitative histomorphometry showed that these mice had significantly more endosteal osteoclasts in the cortical bone; however, these cells appeared less active than normal cells as suggested by a significant reduction in serum levels of cross-linked carboxyterminal telopeptides of type I collagen (CTX) and a reduction in bone TRACP activity. Conversely, the female LXRbeta-/- mice exhibited no change in BMD, presumably because a significant decline in the number of the trabecular osteoclasts was compensated for by an increase in the expression of the osteoclast markers cathepsin K and TRACP. These mice also had a significant decrease in serum CTX, suggesting decreased bone resorption; however, in addition presented with an increase in the expression of osteoblast associated genes, bone formation markers, and serum leptin levels. CONCLUSIONS: Our findings show that both LXRs influence cellular function within the bone, with LXRalpha having an impact on osteoclast activity, primarily in cortical bone, whereas LXRbeta modulates trabecular bone turnover.     

Gender differences in informal caring

Men have hitherto largely been invisible in research on informal care. This paper examines gender differences in informal caring, focusing on gender differences according to the relationship between the carer and care-recipient and the location of caring. The paper uses secondary analysis of the 1990–91 General Household Survey, which identified over 2700 adults as informal carers. Four per cent of men and women provide care for someone living in the same household. More women than men, 13% compared with 10%, provide care for someone living in another household. Men carers are less involved in care provision than women, providing fewer hours of care each week, and are less likely to be the main carer. However, gender differences are most marked among married carers, apart from those caring for their spouse, and least among unmarried carers. Married men can often rely on their wives to perform caring roles rather than performing them personally. Women carers are more likely to provide personal care than men carers, but the gender difference is least among those caring for their spouse or for disabled children. Cross-sex personal care is performed within the marital relationship and by parents caring for disabled children, but seldom by adult children caring for their parents or in more distant caring relationships. Evidence of cross-sex taboos in giving personal care is largely restricted to care provided in another household. Since the majority of elderly people in need of care are women, such cultural taboos may reinforce the pressure on mid-life women to care for mothers and mothers-in-law.     

Postoperative ST-segment elevation: was vasospasm caused by anaphylaxis or by its treatment with epinephrine?

BACKGROUND: Anaphylaxis must be recognized and treated promptly to avoid significant morbidity and mortality. In this clinical setting, electrocardiographic changes can be multifactorial. OBJECTIVE: To discuss vasospasm as a cause of myocardial ischemia and its possible triggering by anaphylaxis itself or by the administration of epinephrine. METHODS: We describe a patient with multiple previous allergies who received intravenous epinephrine to treat suspected anaphylaxis. She immediately developed crushing chest pain with ST-segment elevations in the inferior leads. Throughout the discussion, we address differential diagnoses, physiologic features, and treatment. RESULTS: Her symptoms and electrocardiographic changes were consistent with vasospasm, which resolved after treatment with sublingual nitroglycerin. However, the reaction was sufficient to cause an elevation in the troponin T level and, therefore, myocardial damage on the cellular level. CONCLUSIONS: Cardiovascular complications, including electrocardiographic changes, may be induced by anaphylactic mediators or by medications used for its treatment.     

Stapled Hemorrhoidopexy: A Prospective Study From Pathology to Clinical Outcome

Stapled hemorrhoidopexy is widely accepted to treat hemorrhoids, but serious complications have been reported. In this prospective audit, we correlated clinical outcome with pathological findings. From January 2003 to April 2007, 94 patients underwent hemorrhoidopexy. Macroscopic appearance of the specimen (shape, size, and depth) was recorded. Microscopically, the presence of columnar, transitional, and squamous epithelium, the involvement of circular/longitudinal smooth muscle, and features of mucosal prolapse were assessed. Clinical outcome was evaluated by a validated questionnaire. Postoperative pain, secretion, and bleeding durations were 12.7 +/− 10.6, 5.6 +/− 9.6, and 6.3 +/− 8.4 days. Patient’s return to work averaged 16.7 +/− 10.7 days. Fissure, skin tags, and anal strictures were observed in 23.4%. Seven patients experienced pain for a significantly longer period of time. All specimens contained columnar mucosa, but 29.8% contained columnar and transitional epithelium and 12.8% contained columnar, anal transitional, and stratified squamous epithelium. Smooth muscle was observed in 62.7%. Pain was significantly increased if transitional epithelium was present in the specimen. No correlation or differences were observed if smooth muscle was present, although postoperative bleeding was more frequent. Hemorrhoidopexy is safe and effective. The specimen should always be sent for pathology examination. Only columnar epithelium should be present and, although the presence of smooth muscle does not influence the outcome in terms of functional results, its presence may play a role in postoperative bleeding. Presented as poster at the Digestive Disease Week, May 2007, Washington, USA