Clinical significance of elevated alanine aminotransferase in blood donors: a follow-up study.

Alanine aminotransferase (ALT) elevation in blood donors can be related to many variables such as viral hepatitis, overweight and ethanol consumption. BACKGROUND/AIMS: This study aims to define factors associated with ALT elevation in candidates for blood donation, to evaluate ALT levels during follow-up, and to establish a histological diagnosis of hepatic disease. METHODS: Alcoholism, obesity, drug-induced liver disease, diabetes, hemochromatosis and alpha 1-anti-trypsin deficiency were investigated in 119 subjects (113 males, six females, aged 33.4+/-8.4 years) who were hepatitis B surface antigen/anti-hepatitis C virus negative and had been rejected as blood donors as a result of elevated ALT (>1.5 times the upper normal limit (UNL) in two determinations). During follow-up, ALT was determined every 8 weeks and liver biopsy recommended in cases with persistently elevated ALT levels. RESULTS: Obesity (30.2%) and alcoholism (28.6%) were most frequently associated with ALT elevation and in 9.2% of cases no association was found. ALT levels decreased significantly, regardless of the associated factor. Liver histology in 40 patients showed steatosis (35%), steatohepatitis (30%), non-specific reactive hepatitis (12.5% of cases), normal liver (15% of cases) and alcoholic cirrhosis, hemochromatosis and non-specific portal fibrosis in three cases. CONCLUSION: ALT levels usually dropped during follow-up and although severe hepatic lesions can be found in asymptomatic blood donors, mild hepatic damage is the rule.     

Types of clinical studies. II. Cohort studies.

Cohort studies include groups of patients that are followed over time to determine the incidence or natural history of a disease, together with the risk factors for specific outcomes. These studies can be used to determine disease characteristics as well as the causal relationship between exposure and disease. They are, however, very expensive, because they need large patient samples. Cohort studies can be classified as prospective (the investigator defines the sample and measures predictive variables before outcomes arise) or retrospective (the investigator defines the sample and measures predictive variables after outcomes arise). Cohort studies are susceptible to various types of bias (systematic errors) that must be eliminated in order to ensure the validity of the results. To increase the validity of cohort studies the investigator has to consider exposure, outcome, sample selection and the statistical analysis (risk ratios and/or differences, absolute and relative risks, etc.).     

Late outcome after successful balloon dilatation of Blalock-Taussig variant shunt stenosis

Complications after successful angioplastic dilatation of pulmonary artery narrowings have been well documented, and are known to include rupture and death.¹ Transient unilateral pulmonary edema, resolving within a few days after dilatation has occurred.² Successful dilatation of stenosed Blalock-Taussig (B-T) shunts, both classic and modified, has been performed for palliation in selected patients.^2–4 This report notes a late complication of shunt angioplasty—the development of excessive pulmonary blood flow.     

Immunoglobulin E antibody reactivity to the major shrimp allergen, tropomyosin, in unexposed Orthodox Jews

BACKGROUND: Assessment of allergic (IgE antibody-mediated) reactions to foods may become complicated by cross-reactivity that can occur among certain food families and between foods and seemingly unrelated allergens. OBJECTIVE: The allergenic properties of tropomyosin (muscle-derived protein) have been recently demonstrated in invertebrates such as cockroaches, dust mites, and shrimp. In view of a possible cross-reactivity between food allergens and related allergens from animal sources, we designed a study to assess IgE antibody reactivity to the major shrimp allergen, Pen a 1, in an unexposed population of Orthodox Jews, who observe Kosher dietary laws that prohibit eating shellfish. METHODS: Nine subjects, who reacted positively by skin tests to shrimp (Penaeus setiferous), were selected for the study. Subjects (two females, seven males) ranged in age from 14 to 32 years (mean 20.4). All subjects were strictly observant of Jewish tradition and had no prior exposure to seafood (regarded as a non-Kosher food). Serum was obtained from all the subjects and tested for IgE antibody reactivity to shrimp and dust mite. RESULTS: All subjects reported symptoms of perennial allergic rhinitis, five had history of asthma, atopic dermatitis, and/or sinusitis. All had positive skin prick tests to shrimp and house dust mite (HDM) (Dermatophagoides farinae, D. pteronyssinus, or both); 2/7 subjects were positive to cockroach mix (Blattella germanica and Periplaneta americana). Sera of 4/9 subjects demonstrated specific IgE antibodies by RAST to shrimp (7.0-20.0%), 3/9 to Pen a 1 (6.3-24.1%), and 3/9 to shrimp or Pen a 1 by immunoblot. IgE binding to Pen a 1 was inhibited with either mite or cockroach extracts as demonstrated by RAST and/or immunoblot inhibition analysis. CONCLUSIONS: These studies indicate that IgE antibody reactivity to a major food allergen, shrimp, can occur in an unexposed population of individuals; some subjects allergic to HDM and/or cockroach show substantial IgE antibody reactivity to the major shrimp allergen Pen a 1 (tropomyosin). Based on inhibition with cockroach and/or dust mite extracts, this reactivity appears to be due to cross-reacting tropomyosins.     

Beta 1-6 branched oligosaccharides as a marker of tumor progression in human breast and colon neoplasia

Malignant transformation of murine and human cells is commonly associated with increased--GlcNAc beta 1-6Man alpha 1-6Man beta--branching in asparagine-linked oligosaccharides. Somatic mutations and drugs which block expression of the beta 1-6 branched oligosaccharides are potent inhibitors of tumor cell invasion and metastasis in animal models. This suggests that the oligosaccharides are required for metastasis to occur and therefore their increased presence in primary tumors may be diagnostic of metastatic disease. Although antibodies to the beta 1-6 branched portion of the oligosaccharides are not available, a plant lectin leukoagglutinin (L-PHA) has been shown to bind specifically to this structure. L-PHA lectin histochemistry was performed on paraffin sections of human breast and colon tissues. All breast carcinomas and epithelial hyperplasia with atypia showed significantly increased L-PHA staining compared to fibroadenomas and hyperplasia without atypia. In histological sections of colon, adenomas showed a small but significant increase in L-PHA staining compared to normal colonic epithelium, while carcinomas showed greatly increased reactivity. In addition, Dukes stage C tumors showed higher levels of L-PHA staining than stage A tumors. These results demonstrate that L-PHA-reactive beta 1-6 branched N-linked oligosaccharides are consistently increased in neoplasias of human breast and colon and that the level of L-PHA staining correlates with the pathological staging of the diseases.     

Evidence that the median raphé nucleus – dorsal hippocampal pathway mediates diazepam withdrawal-induced anxiety

On the basis of our previous series of experiments we had postulated that the increased anxiety that occurred during diazepam withdrawal was mediated by increased 5-HT release in the hippocampus. The present series of experiments provide evidence for a major role of the median raphé nucleus (MRN) dorsal hippocampal pathway. Rats were treated once daily for 21 days with diazepam (2 mg/kg IP) and then tested after 24 h withdrawal in the social interaction test of anxiety. Relative to chronically vehicle treated animals, those withdrawn from diazepam were significantly more anxious and had significantly greater K⁺-evoked release of [³H]-5-hydroxytryptamine (5-HT) from slices of dorsal and of ventral regions of the hippocampus. Estimation of extracellular concentrations of 5-HT within the dorsal hippocampus, using in-vivo microdialysis, showed doubling in the levels of 5-HT in the rats withdrawn from chronic diazepam treatment. This just failed to reach significance, but 33% of the rats showed dramatic increases (650%). It was not possible to test these animals in the social interaction test, but it is proposed that only the diazepam-withdrawn rats with raised extracellular levels of 5-HT would have displayed increased anxiety. 5-HT_1A receptor agonists injected into the MRN decrease the MRN firing rate, and hence the release of 5-HT in the dorsal hippocampus. As a further test of our hypothesis, we examined the effects of MRN injection of the 5-HT_1A receptor agonist, 8-OH DPAT, on animals withdrawn from diazepam and tested in the low light familiar condition of the social interaction test. 8-OH DPAT (50–200 ng) dose-dependently reversed the anxiogenic effect of diazepam withdrawal, while having no effects in chronic vehicle-treated animals. These results provide clear evidence that the MRN-dorsal hippocampal 5-HT pathway is at least one of the pathways playing an important role in mediating diazepam withdrawal-induced anxiety. Received: 10 May 1996 / Final version: 15 October 1996     

Emphysematous cystitis.

Case A 39-year-old homeless man presented with weight loss, urinaryfrequency and urinary incontinence. On examination he had apalpable bladder and extensive peripheral neuropathy. Initialblood glucose level was 43.5 mmol/l, serum creatinine was 107µmol/l and Hb_A1c was 16.2%. He     

Cloning and in vivo expression of the pig MyoD gene

Summary The complete sequence of the pig MyoD gene has been determined through the isolation and characterization of a 17 kb genomic clone. The deduced amino acid sequence shows relative conservation of about 90% with the MyoD sequences determined in other mammalian species, though there are several non-conservative changes scattered throughout the C-terminus. In situ hybridization on pig embryos (20–30 days post coitum) showed that MyoD expression was confined to myotomes and skeletal muscle masses.