Enalapril versus bendroflumethiazide in type 2 diabetes complicated by hypertension

In a double-blind, double-dummy, randomized, multi-centre study, the effects of bendroflumethiazide vs. enalapril on blood pressure, glycaemic control, lipoprotein concentrations and albuminuria were compared in non-proteinuric, hypertensive type 2 diabetic patients; they were treated for 20 weeks with either bendroflumethiazide 2.5-5.0 mg (n = 59) or enalapril 10-20 mg (n = 55). Age, fasting plasma glucose, HbA1c and BMI were similar in the groups. Systolic and diastolic blood pressure were reduced in both groups. Bendroflumethiazide was accompanied by minor but significant elevations in fasting plasma glucose and serum C-peptide. HbA1c was increased during both treatments. Lipoproteins and urinary albumin/creatinine ratio were stable. Bendroflumethiazide caused a decrease in serum potassium and an increase in serum urate. No significant correlations were observed between the decline in blood pressure and changes in the metabolic risk factors. Baseline levels of age, sex, BMI, blood pressure or urinary albumin/creatinine ratio were not related to changes in blood pressure, metabolic parameters or urinary albumin/creatinine ratio.     

Activated dissociative chemisorption of methane on Ni(100): a direct mechanism under thermal conditions?

The dissociative chemisorption of methane on a Ni(100) single crystal has been studied under thermal conditions as a function of pressure and temperature. The initial sticking coefficient was measured in the pressure range of 0.010–7.0 mbar at temperatures ranging from 375 to 500 K. A strong pressure dependence was observed, consistent with a direct dissociation mechanism under these thermal conditions. This was further confirmed by experiments where the gas at a low pressure was heated by a thermal finger facing the crystal surface. With the thermal finger at the same temperature as the surface, it was possible to ensure that the methane was fully equilibrated to the crystal and an activation energy of 59±1.5 kJ/mol was determined under isothermal conditions.     

Personal Exposure in Displacement Ventilated Rooms

Personal exposure in a displacement ventilated room is examined. The stratified flow and the considerable concentration gradients necessitate an improvement of the widely used fully mixing compartmental approach. The exposure of a seated and a standing person in proportion to the stratification height is examined by means of full-scale measurements. A breathing thermal manikin is used to simulate a person. It is found that the flow in the boundary layer around a person is able to a great extent to entrain and transport air from below the breathing zone. In the case of non-passive, heated contaminant sources, this entrainment improves the indoor air quality. Measurements of exposure due to a passive contaminant source show a significant dependence on the flow field as well as on the contaminant source location. Poor system performance is found in the case of a passive contaminant released in the lower part of the room close to the occupant. A personal exposure model for displacement ventilated rooms is proposed. The model takes the influence of gradients and the human thermal boundary layer into account. Two new quantities describing the interaction between a person and the ventilation are defined.     

Influence of HIV-related immunodeficiency on the histopathology of chronic hepatitis C

OBJECTIVE: There is substantial evidence demonstrating the aggravating effect of human immunodeficiency virus (HIV) infection on the progression of chronic hepatitis C virus (HCV) infection. There is however, little data on the affect of certain factors which could affect liver pathology findings in patients with concomitant HIV infection such as the duration of HIV infection or T-cell subpopulation counts. We examined pathology findings in patients with concomitant HIV and HCV infections to determine the impact of immunodepression. PATIENTS AND METHODS: We reviewed liver pathology data collected in patients with concomitant HIV and HCV infections grouping patients according to severity of the liver pathology: group 1 = cirrhosis or active hepatitis; group 2 = minimally active hepatitis or histologically normal liver. Transparietal liver biopsies were obtained for the work-up of viral hepatitis or because of long-term unexplained fever or suspected lymphoma. Epidemiological and biological data were obtained from medical files. The duration of the liver disease was estimated from the date of exposure to risk of immunodepression as determined by the peripheral CD4+ and CD8+ counts. All pathology specimens were read by two pathologists who established the Knodell score for each patient. RESULTS: Fifty patients were included: 23 were classed in group 1 and 28 in group 2. The Knodell score was significantly different between the two groups, 11 +/- 4 and 4 +/- 3 respectively (p < 0.0001). Disease duration was similar for the two groups: mean 8 years. Mean CD4+ count was significantly higher in group 1: 312/mm3 versus 110/mm3 for group 2 (p = 0.0057); as was the mean CD8+ count (758/mm3 versus 360/mm3, p = 0.0013). For the entire study population, there was a significantly negative correlation (p < 0.05) between the Knodell score and the CD4+ count (r = 0.31) and for the CD8+ count (r = 0.41). CONCLUSION: HCV-related liver pathology in patients co-infected with HIV depends on the level of immunodepression. CD8+ counts are better correlated with pathology findings than with CD4+ counts.     

Design of an isolated pig heart preparation for positron emission tomography and magnetic resonance imaging

RATIONALE AND OBJECTIVES: Validation of new positron emission tomography (PET) tracers or magnetic (MR) imaging contrast agents is based on isolated rodent heart preparations. The use of larger animals could provide a more direct validation using the devices used for humans. METHODS: An isolated pig heart preparation has been developed and adapted to the technical constraints of whole body PET and MR imaging. This preparation could be used either in the Langendorff or working mode after selective cannulation of both coronary arteries. RESULTS: The authors showed that quantification of regional kinetics of PET tracers was possible using this preparation by measuring fluorine-18-labeled deoxyglycose (18FDG) kinetics in remote and ischemic territories. Experiments using MR imaging contrast agents, for myocardial perfusion, demonstrated the ability of this preparation to accurately validate these contrast agents over a wide range of flow rates. CONCLUSIONS: An isolated pig heart preparation could be developed to fulfill the constraints of PET and MR imaging, and proved useful for the study of the distribution of different tracers or contrast media developed for functional cardiac imaging in humans.     

Analysis of the human factor VIII A2 inhibitor epitope by alanine scanning mutagenesis

Antibodies directed to the A2 domain of factor VIII (fVIII) are usually an important component of the polyclonal response in patients who have clinically significant inhibitory antibodies to fVIII. A major determinant of the A2 epitope has been located by homolog scanning mutagenesis using recombinant hybrid human/porcine fVIII molecules to a sequence bounded by Arg484-Ile508 (Healey, J. F. , Lubin, I. M., Nakai, H., Saenko, E. L., Hoyer, L. W., Scandella, D. , and Lollar, P. (1995) J. Biol. Chem. 270, 14505-14509). Within this region, human residues Arg484, Pro485, Tyr487, Ser488, Arg489, Pro492, Val495, Phe501, and Ile508 differ from porcine fVIII. We stably expressed in mammalian cells nine active B-domainless human fVIII molecules containing single alanine substitutions at these sites. Their inhibition by a murine anti-A2 monoclonal antibody, monoclonal antibody (mAb) 413, and by three A2-specific alloimmune and two A2-specific autoimmune human inhibitor plasmas was measured by the Bethesda assay. The inhibition of Arg484 --> Ala, Tyr487 --> Ala, Arg489 --> Ala, and Arg492 --> Ala by mAb413 was reduced by greater than 90% compared with wild-type, B-domainless human fVIII. mAb413 inhibited the most severely affected mutant, Arg489 --> Ala, 0.01% as well as wild-type fVIII. For all five patient plasmas, the Tyr487 --> Ala mutant displayed the greatest reduction in inhibition. The inhibition of the Tyr487 --> Ala mutant by these antibodies ranged from 10% to 20% that of wild-type fVIII. The inhibition of the Ser488 --> Ala, Arg489 --> Ala, Pro492 --> Ala, Val495 --> Ala, Phe501 --> Ala, and Ile508 --> Ala mutants by most of the plasmas also was significantly reduced. In contrast, the Arg484 --> Ala and Pro485 --> Ala mutants were relatively unaffected. Thus, although mAb413 binds to the same region as human A2 inhibitors, it recognizes a different set of amino acid side chains. The side chains recognized by human A2 inhibitors appear to be similar, despite the differing immune settings that give rise to fVIII alloantibodies and autoantibodies.