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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 1,045 records · Page 58Linked to original sources

Compliance to treatment for hypertension in elderly patients: the SHEP pilot study. Systolic Hypertension in the Elderly Program.

Assessing the compliance of people over 60 years of age and older with an antihypertensive treatment regimen was a major objective of the Systolic Hypertension in the Elderly Program (SHEP) pilot study. The study randomized 551 men and women over the age of 60 (mean age = 72 years) to a stepped care treatment that included chlorthalidone or placebo in a double-blind trial. Three measures of compliance to treatment protocol--pill count, self-report, and a urine chlorthalidone assay--all indicated high levels of compliance in 80 to 90% of participants at 3 months and 1 year after randomization. Pill-taking compliance was similar in the active and placebo groups, although the rate of discontinuance from study medications at 1 year was higher in the placebo than in the active group. Compliance was high in all age categories, including those over age 80. These data suggest that elderly patients can achieve high levels of compliance with antihypertensive medications.

Age Factors↗

Joint mobility and mitral valve prolapse in an Arab population.

The association of joint laxity and mitral valve prolapse (MVP) has been disputed. In this study of an Arab population, the joint mobility scores of 29 subjects with MVP, 10 of whom were asymptomatic, were compared to 60 normal controls. It was found that the joint mobility score was significantly higher in both the asymptomatic and the symptomatic subjects with MVP when compared to the controls. This suggests that both mitral valve prolapse and joint laxity may be due to the same abnormality of connective tissue structure.

Adult↗

Effect of lung volume on in vivo contraction characteristics of human diaphragm.

We performed transcutaneous bilateral phrenic nerve stimulation at varying lung volumes between residual volume (RV) and total lung capacity (TLC) in six normal male volunteers. Peak twitch transdiaphragmatic pressure declined from 49.1 +/- 9.1 (SD) cmH2O at RV to 19.6 +/- 5.97 (SD) cmH2O at TLC. Twitch contraction time fell from 91.8 +/- 11.3 (SD) ms at RV to 57.7 +/- 7.4 (SD) ms at TLC. There was a good correlation between changes in contraction time and transdiaphragmatic pressure (r = 0.7). The fall in transdiaphragmatic pressure was almost all due to a fall in pleural pressure, with little change in gastric pressure between RV and TLC. At TLC the pleural pressure in response to phrenic nerve stimulation was -0.58 cmH2O. We conclude that, as lung volume increases and the diaphragm shortens, it becomes less effective as a pressure generator and that pressure it generates is less well converted into useful inspiratory pressure. At a lung volume close to TLC, the diaphragm ceases to act as an inspiratory muscle.

Adult↗

Total respiratory system compliance in asymptomatic infants with cystic fibrosis.

Total respiratory system compliance (Crs) was assessed by the weighted spirometer method in 11 asymptomatic infants (mean age, 11.1 months) with cystic fibrosis (CF) who had normal chest radiographs. In addition to Crs, functional residual capacity (FRC), respiratory rate (RR), and mixing index (MI) were measured. There was no significant difference in FRC between normal controls (n = 36) and CF infants (190 +/- 69 versus 186 +/- 63 ml; p less than 0.8), although the CF group had a higher RR (32 +/- 7 versus 37 +/- 7 BPM; p less than 0.05) and a lower MI (45 +/- 7 versus 40 +/- 8%; p less than 0.05), reflecting an abnormal distribution of ventilation. The lower Crs (9.0 +/- 3.4 versus 5.7 +/- 2.8 ml/cm H2O; p less than 0.01) and the lower specific compliance, Crs/FRC (0.049 +/- 0.013 versus 0.029 +/- 0.007 1/cm H2O; p less than 0.0001), in the CF group were the parameters that best distinguished the normal control and CF infants. We conclude that the measurement of Crs represents a noninvasive method for detecting early pulmonary function abnormalities in CF infants.

Cystic Fibrosis↗

Validation of doubly labeled water for assessing energy expenditure in infants.

Previous studies show that the doubly labeled water method is accurate for measuring energy expenditure in the adult human. To validate this method in infants, carbon dioxide production rate and energy expenditure were measured for 5 to 6 days by doubly labeled water (DLW) and periodic open circuit respiratory gas exchange (RGE) in 10 blinded studies in nine infants following abdominal surgery. Infants were maintained on consistent oral or parenteral nutrition prior to and during study. This avoided diet-related changes in baseline isotopic enrichment of body water which could theoretically contribute to significant errors in calculation of carbon dioxide production rate. For DLW, insensible water loss was assumed to be proportional to respiratory volume and body surface area, where the former was predicted from carbon dioxide production rate. Insensible water loss thus calculated averaged 18% of water turnover. Rates of carbon dioxide production measured by DLW were not significantly different from that of RGE (10.4 +/- 1.1 and 10.5 +/- 0.9 l/kg/day, mean +/- SD, respectively). Energy expenditure was calculated using respiratory quotients from dietary intake (DLW:DIET) and RGE (DLW:RGE) data. There was no significant difference between energy expenditure determined by DLW (DLW:DIET and DLW:RGE) and that measured by RGE (58.5 +/- 6.1, 56.8 +/- 6.1, and 57.3 +/- 5.1 kcal/kg/day, mean +/- SD, respectively). Rate of carbon dioxide production, DLW:diet, and DLW:RGE calculated by DLW differed from corresponding RGE values by -0.9 +/- 6.2, -1.1 +/- 6.1, and 1.6 +/- 6.2%, mean +/- SD, respectively. These findings demonstrate the validity of the doubly labeled water method for determining energy expenditure in infants without concurrent water balance studies.

Absorption↗

The origin of Ia antigen-expressing cells in the rat kidney.

The lineage of Ia antigen expressing (Ia+) cells that have been detected in the parenchyma and interstitium of the rat kidney has not been defined. The authors have studied the origins of Ia+ cells in chimeric rats using monoclonal antibodies to define cells of bone marrow and parenchymal origin. PVGc RTI rats (recipients) received intravenously 2 X 10(6) bone marrow cells from F1 hybrid PVG RTIc/RTIu rats (donors) 1 day after 1000 rads whole body irradiation. Ia chimerism was monitored in blood and isolated glomeruli by immunofluorescence and in frozen sections by immunoperoxidase, using monoclonal antibodies MRC OX3 (anti-Ia RTIu), MRC OX4 (anti-RTIc and u), and MRC OXI (anti-rat leukocyte common antigen). In normal F1 hybrid kidneys, glomerular cell counts were as follows: OXI+, 7.19 +/- 0.23/gl; OX4+, 3.03 +/- 0.14; OX3+, 2.34 +/- 0.1 (76% detectable expression of RTIu). OXI+, OX4+, and OX3+ cells were codistributed in cells in the interstitium between renal tubules. Proximal tubules were weakly OX4+, OX3+. In chimeric rats 5 days after irradiation, blood leukocytes, and renal OX1+ and OX4+ cells were depleted; OX3+ cells were not detected; by 4 weeks blood leukocytes were restored to normal numbers, and 85% of Ia+ cells were OX3+. By 6 weeks OXI+ and OX4+ cells were restored in glomeruli and interstitium, with increasing expression of OX3+ cells; at 10 weeks 75% of glomerular Ia+ cells were OX3+ (equivalent to detectable level of OX3+ cells in normal F1 hybrids) and OX1+, OX4+, and OX3+ cells appeared in equivalent numbers in the interstitium. Groups of proximal tubules were OX4+ and OX3-. These results in established bone marrow chimeras show that in the normal rat kidney bone marrow derived leukocytes expressing Ia antigen are present in the glomerulus and interstitium. Ia antigen is also expressed on some proximal tubular cells. There is no evidence for endothelial Ia positivity.

Animals↗

Leukotriene B4 production in normal rat glomeruli.

The production of the lipoxygenase metabolite of arachidonic acid, leukotriene B4 (LTB4) by normal rat glomeruli has been studied. Isolated glomeruli from saline-perfused rat kidneys were incubated in Kreb's buffer for 15 min at 37 degrees C. The concentrations of LTB4 and other eicosanoids in cell-free supernatants were determined by direct radioimmunoassays (RIA). Mean basal syntheses of eicosanoids were: thromboxane B2 (TXB2) 0.77 +/- 0.13, prostaglandin (PG) E2 0.40 +/- 0.05, 6-keto-PGF1 alpha 0.38 +/- 0.06 ng/mg glomerular protein (mean +/- SEM n = 8). In these assays immunoreactive LTB4 synthesis was 0.12 +/- 0.02 ng/mg. In samples incubated with BW755C, 50 micrograms/ml, an inhibitor of arachidonate metabolism via both the cyclo-oxygenase and lipoxygenase pathways, there was more than 80% inhibition of the synthesis of TXB2, PGE2 and 6-keto-PGF1 alpha. However, immunoreactive LTB4 was only reduced by 44%, suggesting the presence of other materials which cross-react in the RIA. The presence of authentic LTB4 in the supernatants was confirmed after extraction and high-pressure liquid chromatography (HPLC). This material represented 25% of the original material detected by RIA. Although the physiological role of LTB4 in the normal state is unknown, its chemotactic activity may be of great significance during glomerular inflammation.

Animals↗

Immunological reconstitution after bone marrow transplant with Campath-1 treated bone marrow.

Immunological reconstitution after allogeneic bone marrow transplant (BMT) was studied in 20 patients who received Campath-1 treated bone marrow. The peripheral blood lymphocyte phenotype was analysed with a panel of monoclonal antibodies at 3, 6 and 12 months. T cell proliferative capacity was evaluated by stimulation with PHA and Con A and in the mixed lymphocyte reaction (MLR). Natural killer (NK) cell activity was analysed against the K562 cell line at specified times after BMT in nine patients. Absolute numbers of T lymphocytes were reduced in all patients at 3 and 6 months. A marked decrease in the number of CD4+ cells persisted beyond 12 months. CD8+ cells regenerated more rapidly and reached normal at 6 months. No correlation was found between changes in lymphocyte subpopulations and the presence of graft-versus-host disease or cytomegalovirus infection. B cells recovered rapidly and maintained normal numbers throughout the study. A moderate increase in HNK1+ (Leu7) cells was observed at 3 and 6 months simultaneously with a low expression of NK15 (Leu11) and OKM1 antigens at 3 and 6 months, suggesting the presence of immature NK cells early after the transplant. A profound decrease of T cell proliferative capacity was observed both after mitogen stimulation and in the mixed lymphocyte reaction. NK cell activity was raised during the first month after transplant in all but one patient but no correlation was found with the presence of GVHD or cell marker analysis.

Adolescent↗

Differing effects of carbohydrate, fat and protein on the rate of ethanol metabolism.

The rate of metabolism of ethanol in humans has been assessed by intravenous infusion of ethanol/saline under feedback control to maintain a constant blood alcohol concentration. After equilibration, meals consisting predominantly of carbohydrate, fat or protein were eaten and changes in ethanol metabolic rate were found. Carbohydrate caused a significant increase in this rate and fat or protein caused small but non-significant decreases. Infusion of ethanol/saline resulted in a temporary fall in plasma free fatty acid levels and a steady rise in plasma triglycerides. The changes in alcohol metabolism following carbohydrate cannot be accounted for by changes in insulin, free fatty acid or lactate/pyruvate levels.

Adult↗

Isolation and characterization of inflammatory leukocytes from glomeruli in an in situ model of glomerulonephritis in the rat.

Inflammatory cell populations in glomerulonephritis (GN) are not well characterized. A method is reported for isolating leukocytes from glomeruli. GN was induced in rats by perfusing left kidneys (LKs) with cationized human IgG followed by intravenous rat anti-human IgG serum. Acute GN developed in LKs with proteinuria, deposition of human and rat IgG and C3, leukocyte infiltration, and capillary wall electron-dense deposits. Glomeruli (GL) isolated at 24 hours were digested with collagenase, trypsin, and DNase, and the resulting cells were as follows (mean +/- SEM): LK, 354 +/- 25/GL; RK, 214 +/- 32/GL. Cells were labeled with monoclonal antibody MRCOX1 (anti-rat leukocyte common [LC] antigen) followed by FITC F(ab')2 rabbit anti-mouse Ig: LK, 170 +/- 11 leukocytes/GL;RK, 8 +/- 2 leukocytes/GL (P less than 0.001). Isolated cells were sorted by flow cytometry to 98% pure LC+ cells with greater than 80% viability (Giemsa staining: 86% mononuclear cells, 14% neutrophils); the ultrastructure was that of maturing macrophages and neutrophils. This method quantitates leukocyte infiltration and provides leukocytes from nephritic glomeruli suitable for in vitro studies.

Animals↗