Role of metabolism in ethyl carbamate-induced suppression of antibody response to sheep erythrocytes in female Balb/C mice

A possible role of metabolism by cytochrome P450 (P450) in ethyl carbamate-induced suppression of the antibody response to a T-cell-dependent antigen, sheep erythrocytes (SRBCs), was investigated in female Balb/C mice. When mice were treated with ethyl carbamate intraperitoneally for 14 consecutive days at 25, 50, 100, 200 and 400 mg/kg, the antibody response was significantly suppressed from 200 mg/kg. These doses also caused a decrease in thymus weight. An acute dosing of ethyl carbamate at 1 g/kg also caused not only a significant suppression of the antibody response, but also a decrease in thymus weight. The antibody response was most likely to be the IgM antibody response, which was demonstrated in a haemagglutination study. When mice were pretreated with phenobarbital (80 mg/kg) for 3 days to induce P450 enzymes, followed by administration of ethyl carbamate intraperitoneally for 7 consecutive days, the antibody response was more suppressed than in saline-pretreated controls. Moreover, a study using aminoacetonitrile, a P450 inhibitor, showed that the antibody response suppressed by ethyl carbamate was completely recovered by the inhibitor. The present results suggest that metabolism of ethyl carbamate by P450 may be the critical pathway to produce metabolites capable of suppressing the antibody response.     

Vagal regulation during bottle feeding in low-birthweight neonates: support for the gustatory-vagal hypothesis

BACKGROUND AND PURPOSE: Linear accelerators equipped with multileaf collimators (MLCs) are becoming more common and are widely available from most commercial manufacturers. There is a need to ensure they retain their commissioning specification using a preventative maintenance and quality control (QC) programme. This paper considers the design criteria of the Philips MLC which are important to the production of a comprehensive quality control programme. MATERIALS AND METHODS: The specific QC problems related to MLCs are identified as the positional accuracy of the leaves and their relationship to the back-up collimators, leakage considerations, the relationship of X-ray to light field and the influence of gravity on the positioning and leakage characteristics of the leaves. These problems are considered in relation to the general design considerations of the MLC, and methods of performing routine quality control checks are discussed. RESULTS AND CONCLUSIONS: The introduction of MLCs into clinical use results in new QC procedures being developed but it can be concluded that for the Philips MLC only an extra 30 min of QC time is needed per month and that its use has added little to the general down-time of this department.     

Sodium pump isoform specificity for the digitalis-like factor isolated from human peritoneal dialysate

We have isolated a labile, specific sodium pump inhibitor or digitalis-like factor from the peritoneal dialysate of volume-expanded renal failure patients whose levels correlated closely with volume status and blood pressure. This study characterizes the inhibitory profile of this agent compared with that of ouabain against the three alpha-isoforms of the sodium pump. We prepared microsomal Na,K-ATPase from rat tissues representing the highest proportion of one of the alpha-isoforms. Both Northern and Western blot analyses confirmed that kidney had predominantly the alpha1-isoform, skeletal muscle the alpha2-isoform, and fetal brain the alpha3-isoform. Ouabain (5 x 10(-6) mol/L) produced little inhibition of kidney Na,K-ATPase (3.4+/-2.0%) but significant inhibition of skeletal muscle (37.2+/-3.7%, P<.001) and fetal brain (38.8+/-3.5%, P<.001) activity. In contrast, the labile digitalis-like factor, causing comparable inhibition of fetal brain Na,K-ATPase activity (33.3+/-4.7%), produced markedly greater inhibition of kidney (42.5+/-5.6%, P<.001) and moderately greater inhibition of skeletal muscle pump activity (57.7+/-6.3%, P<.05). In addition, the labile digitalis-like factor produced a marked concentration-dependent inhibition of the alpha2- and alpha3-isoforms (r=.79, P=.00005). Experiments combining the labile digitalis-like factor and ouabain confirmed that digitalis-like factor, unlike ouabain, was an effective inhibitor of all three isoforms in rat, in particular alpha2. The different pattern of isoform sensitivity displayed by the labile digitalis-like factor and ouabain further differentiates the two agents and raises some interesting possibilities about the functional implications of the endogenous factor.     

Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure

INTRODUCTION: In CAPD patients serum albumin is frequently used as an index of nutritional status, although it is recognized that hypoalbuminaemia may be caused by many factors. We have further examined the relationship between serum albumin and nutrition. METHODS: Nutritional status was assessed by biochemistry, anthropometry, mid-arm muscle circumference, muscle strength (hand grip and back), and lean body mass (from anthropometry, creatinine kinetics and bioimpedance) in a group of 76 stable CAPD patients. Correlations between biochemical and nutritional parameters were sought and data were compared between patient groups defined by serum albumin (> or = 37 vs < 37 g/l on two occasions 2 months apart) and separately according to subjective global assessment score (normal nutrition, A vs mild to moderate, B, and severe, C, malnutrition). RESULTS: In patients with a low SGA score, actual body weight, body mass index, mid-arm muscle circumference, lean body mass, subscapular skinfold thickness, hand grip strength (males and females) and iliac and triceps skinfold thicknesses and back strength (females only) were all significantly less than in patients with a normal SGA score. In contrast, none of these variables differed in either gender when patients were compared according to serum albumin. Serum albumin was correlated with serum creatinine (r = 0.45, P = 0.01), daily urine protein excretion (r = -0.42, P = 0.02) and uncorrected weekly creatinine clearance (r = -0.39) in females, but not with any index of body composition in either gender. CONCLUSION: Whilst SGA identified a patient group with significantly abnormal body mass, muscle mass and muscle strength, serum albumin did not. Serum albumin is not a useful marker of malnutrition in stable patients on CAPD.     

Developmental instability and cerebral lateralization

On the basis of prior studies of handedness, it was predicted that variations from modal asymmetry scores on cognitive tasks, in either direction from the mean, would be associated with an elevated incidence of classic markers of developmental instability (minor physical anomalies and fluctuating anatomic asymmetries). University students (N = 146) were administered 4 tasks that typically reveal functional asymmetries: the fused rhymed words dichotic listening task, the line bisection task, the chimeric faces task, and the cartoon faces task. A composite measure of developmental instability was computed from minor physical anomalies and fluctuating asymmetries. Participants with greater evidence of developmental instability had more atypical lateralization scores, deviating more from the sample mean, in either direction. Directional asymmetries were unrelated to developmental instability. These results suggest that developmental instability influences variation in the lateralization of cognitive skills as well as handedness.     

Clinical relevance of parvovirus B19 as a cause of anemia in patients with human immunodeficiency virus infection

Parvovirus B19 (B19) DNA was detected by dot blot hybridization in sera from 5 (17%) of 30 human immunodeficiency virus (HIV)-infected patients with hematocrits (HCT) of < or =24 and 4 (31%) of 13 HRV-infected patients with HCT of < or =20, suggesting that B19 is a reasonably common cause of severe anemia in HIV infection. The anemia promptly remitted after immunoglobulin therapy in 3 of 4 treated patients. The presence of IgM to B19, the clinical circumstance in which anemia developed, and the marrow morphology were poor predictors of chronic B19 infection. DNA hybridization studies of sera from 191 HIV-infected and 117 HIV-seronegative homosexual males attending a clinic in the Seattle area revealed that 1 (0.5%) and 2 (2%) samples, respectively, from the 2 groups contained B19. However, when assayed by polymerase chain reaction (PCR), 5% of the serum samples from HIV-infected persons and 9% from uninfected persons contained B19, although each had an HCT of > or =40. The data argue that anemia results from chronic high-titer B19 infection. Although a negative PCR assay excludes this diagnosis, DNA hybridization may be the more specific serum test.     

Diagnostic value of p53 protein and flow cytometric DNA analysis in the study of serous effusions

OBJECTIVE: To investigate the diagnostic value of p53 protein and DNA analysis in the study of serous effusions. STUDY DESIGN: A total of 76 samples of serous effusions were studied by immunohistochemistry for p53 protein and flow cytometric (FCM) DNA analysis. The results were correlated with final cytologic diagnoses, which were confirmed by immunohistochemistry using antibodies against cytokeratin, carcinoembryonic antigen, epithelial membrane antigen and fibronectin. RESULTS: Final cytologic diagnoses included 28 malignant effusions and 48 benign effusions. No expression of p53 protein was seen in benign effusions. In contrast, p53 protein expression was seen in 19/28 (sensitivity 68%) malignant effusions. FCM detected aneuploid cells in 12/28 (43% sensitivity) of malignant and 0/46 of benign effusions. Immunohistochemical determination of p53 protein combined with FCM DNA analysis increased sensitivity to 79%. CONCLUSION: Immunohistochemical determination of p53 protein and FCM DNA analysis can aid in making an accurate and specific diagnosis of serous effusions, but the principal limitation of these tests is their relatively low sensitivity.     

Arthroscopic-assisted reduction of distal radius fractures

The outcomes of seven patients with severe comminuted intraarticular fractures of the distal radius treated by arthroscopic reduction and percutaneous external fixation (ARPEF) were retrospectively reviewed. All of the fractures were classified as C3 types using the AO classification scheme. Outcomes were evaluated using the Gartland and Werley functional criteria, an objective wrist examination, a radiographic analysis, and a self-assessment outcome form at an average follow-up of 27 months (range, 12 to 45 months). All patients were free of pain and had returned to their prior occupations. No patient had articular incongruency of greater than 1 mm, and there was no evidence of radiocarpal degenerative change. Active range of motion and maximal grip strength averaged 92% and 98%, respectively, of the uninjured wrist. The technique of arthroscope-assisted reduction and percutaneous external fixation yielded excellent results in a small group of patients, with minimal complications.