APACHE III study design: analytic plan for evaluation of severity and outcome in intensive care unit patients. Introduction.
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Biomedical subjects
Publications and source records attributed to D Wagner.
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The proportion of oligosaccharide chains on the Fc fragment of IgG which terminate with N-acetylglucosamine and not galactose (%GO) has previously been shown to be raised in rheumatoid arthritis (RA), Crohn's disease (CD) and tuberculosis (Tb), but to be normal in sarcoidosis (SA), and in both lepromatous and tuberculoid leprosy. However we have now studied %GO in sequential serum samples collected from lepromatous leprosy patients undergoing episodes of erythema nodosum leprosum (ENL). During ENL %GO is transiently raised, and this rise parallels an increase in circulating interleukin 2 receptors (IL-2R). These findings confirm that changes in T cell function occur during ENL. Moreover it appears that %GO rises when there is, simultaneously, T-cell-mediated tissue damage and an acute phase response (RA, CD, Tb, ENL), but not when there is an acute phase response without major T cell involvement, or chronic T cell activity alone (SA, and tuberculoid leprosy). We suggest therefore that %GO is an indicator of a type of T cell activity with broad immunopathological implications.
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Advances in molecular biology over the last few years have made it possible to extend studies concerned with the role of renin in blood pressure regulation and fluid balance to the genetic level. Epidemiological data from cross-sectional population studies as well as experimental findings in spontaneously hypertensive rats suggest a greater disposition towards hypertension in males than in females. Testosterone (T) is known to raise blood pressure in female and castrated male SH-rats, while concomitantly increasing tissue renin activities. The availability of recombinant DNA technology and of a 32P labeled mouse submandibular gland renin cRNA as a hybridization probe enabled us to quantitatively assess whether this increase is paralleled by enhanced renin gene expression. In groups of female NMRI mice injected with DHT, we were able to show, that cardiac renin activity was significantly increased after 2 hours (1.6 fold) and 21 days (1.9 fold) of dihydrotestosterone (DHT) treatment compared to controls. DHT had no effect on renin mRNA concentration in the uterus, whereas in the ovary it resulted in a 50% decrease. We conclude that enhanced renin-activity and mRNA levels in peripheral organs and in the central nervous system are due to direct or indirect effects (cis, transacting) of T on renin gene expression. Thus, T may participate in the development of hypertension by stimulating the activity of tissue renin-angiotensin systems.
A new solution hybridization assay was established for the measurement of renin mRNA. The assay makes use of a radioactively labelled renin complementary RNA as hybridization probe and allows rapid and sensitive detection of renin mRNA in amounts as low as 0.5 pg. With this assay it was possible to quantify renin mRNA in tissues with low-gene expression such as brain and heart as well as in testis, kidney and the submandibular gland (SMG) of mice. The concentrations in these organs were 0.03, 0.07, 1, 5.2 and 164 pg renin mRNA/micrograms RNA, respectively. These results are in agreement with Northern blotting experiments. The general applicability and ease of the solution hybridization assay described here should greatly improve the rapidity of mRNA measurements in future functional studies.
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Both membrane (p55) and soluble (p45) forms of TAC-reactive interleukin-2 receptor (IL-2R) are expressed and/or released by activated lymphocytes or monocytes. Previous work has detected increased levels of circulating, TAC-soluble IL-2R (soluble TAC antigen) in the serum of most B-cell chronic lymphocytic leukemia (B-CLL) patients. We detected soluble TAC antigen in B-CLL patients (mean of 3,332 U/mL v 410 for controls). Serum soluble TAC antigen levels increased with stage (mean value of 1,187 U/mL for stage 0 v 2,527 for stage 2 and 5,410 for stages 3 and 4). We next attempted to determine whether the elevated serum levels of soluble TAC antigen in B-CLL patients might result from shedding or secretion of the receptor from the circulating, malignant B cells. Purified, malignant B cells from B-CLL patients were capable of producing easily detectable soluble TAC antigen after 48 hours of in vitro culture (range of 60 to 1,563 U/mL). IL-2R production by CLL B cells was dose dependent in most patients over a concentration of 10 x 10(6) to 60 x 10(6)/mL. In contrast, there was little or no detectable soluble TAC antigen when highly purified T cells from the same patients were cultured. Finally, despite elaboration of soluble IL-2R by CLL B cells, membrane expression of B-cell IL-2R was detected in only six of 11 patients. Thus, the cellular source of the elevated serum IL-2R levels is the malignant CLL B cell. Taken together these data suggest that (a) the malignant CLL B cell is "activated" in terms of release of soluble IL-2R and may serve as a tumor marker in this disease and (b) the elevated levels of circulating IL-2R may be an associated factor in the cellular immunodeficiency noted in B-CLL patients.
UNLABELLED: Four probes for the acquisition of rumen fluid in adult cattle were tested with regard to their usefulness (pump capacity): probe I = original instrument of Schambye-Sørensen, probe II = modified Schambye-Sørensen instrument, probe III = guidable instrument of Dirksen, probe IV = a simple "home made" plastic instrument with a metal suction head. In a first step bovine saliva was added in increasing quantities (in increments of 5% up to 50%) to normal rumen fluid samples collected via rumen fistula. Some relevant parameters of the rumen fluid were analyzed with these mixtures. The experiments were carried out in order to obtain data for the calculation of saliva inflow in samples collected by orally introduced probes. In a second step a sample of rumen fluid was aspirated from the ventral rumen sac via the fistula before each introduction of the rumen sound. Saliva inflow was calculated on the basis of the in vitro changes in pH and in Na+ and K+ concentrations noted with each 5% addition of saliva. RESULTS: The pH value increased with the addition of saliva more markedly for samples with a lower initial value. The sodium concentration in the rumen fluid increased almost linearly by an average of 2.5 mmol/l, while potassium concentration decreased by approximately 1.4 mmol/l with each 5% increase of saliva. Chloride concentration of the physiologic rumen fluid was essentially unaffected by addition of saliva (up to 30%). The methylene blue reaction was slightly enhanced by admixture of 5 to 10% saliva and prolonged by greater volumes.(ABSTRACT TRUNCATED AT 250 WORDS)
9295 smears, obtained from women attending three gynaecological hospitals for routine screening, were examined for human papillomavirus (HPV) types 6 and 11 and HPV 16 and 18 infections by filter in-situ hybridisation. The data were compared with cytological findings. In women with normal cytological smears HPV infection was identified in about 10% of women aged between 15 and 50 years and in less than 5% of those aged over 50. In women with abnormal smears (cervical intraepithelial neoplasia [CIN] I, II, and III and invasive cancer) HPV infection was detected in 35-40%; this rate seemed to be age-independent. the Peak incidence of CIN appeared several years after that of HPV infection. In women aged greater than 30 years it also declined earlier than did HPV positivity. The age-group distribution of women with CIN I, II, and III differed significantly from that of patients with invasive cancer. Only about a third of HPV-positive patients remained virus-positive, probably because of fluctuations in virus production and the insensitivity of the test system used. It is possible that filter in-situ hybridisation underestimates the total rate of HPV infections by a factor of 2 to 3.
The kinetics of leucine, phenylalanine, and tyrosine metabolism following orthotopic human liver transplantation in end-stage liver disease in hospitalized patients were evaluated and compared to controls. The investigation was carried out by protein turnover studies using 13C leucine, D5-phenylalanine, and [U-14C] tyrosine by continuous infusion and employing a stochastic model in 32 patients with end-stage liver disease, 17 of whom went on to receive an hepatic allograft, and 7 controls without significant liver disease who underwent elective abdominal surgery. Mean tyrosine flux in the liver disease group was 3,242 +/- 811 (n = 32) v 2,899 +/- 688 mumol/h in controls (n = 7) (P less than .001), while the tyrosine oxidation was 328 +/- 179 v 422 +/- 185 mumol/h (P less than .001). Tyrosine clearance in pretransplant patients was 719 +/- 345 (n = 17) v 1,193 +/- 568 mL/min (P less than .005) in posttransplant patients (n = 17) with virtually no overlap. There was a significant correlation between serum albumin levels and the tyrosine clearance (r = .60, P less than .05), but correlations with other conventional liver function tests were of a low order. Leucine and phenylalanine kinetics in liver disease patients did not show any significant differences from controls. Leucine and tyrosine fluxes in controls did exhibit a significant correlation (r = .70, P less than .05), but no correlation was observed in patients with liver disease. These findings indicate that the kinetics of the amino acid tyrosine are substantially altered by end-stage liver disease, with the most profound effect on tyrosine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)