Biomedical subjects
Publications and source records attributed to A Clark.
A method is presented which maintains mean arterial blood pressure at predetermined values during cerebrovascular occlusion studies in a rat model. The system consists of a pressure measurement apparatus, a pump capable of infusing and withdrawing fluids, and a personal computer to control the infusion and withdrawal rate. An evaluation of the system is presented, and potential advantages and difficulties are discussed.
Our study examined whether urinary tract infections (UTIs) would cause false-positive results when urine sediment was tested with the Chlamydiazyme (CZ) system. Thirty-six infected urine samples and fifteen controls were studied. All controls were negative. Forty-seven percent of Escherichia coli UTIs (n = 30) and 100% of Klebsiella pneumoniae UTIs (n = 4) were positive on CZ testing of urine sediment. Nine E. coli UTIs positive by CZ were negative by direct fluorescent-antibody staining. When suspensions of the pure cultures were analyzed, 47% of E. coli and 100% of K. pneumoniae samples were CZ positive. False-positive results were not related to organism biotype or urine characteristics, including pH, specific gravity, and leukocyte count. We conclude that the presence of a UTI and also bacterial contamination must be ruled out prior to urine sediment testing.
Distribution of O2 within and among arterioles and venules was determined in dog and rat gracilis muscles with a cryospectrophotometric method. Saturation in 40-microns arterioles was not demonstrably different from saturation in the aorta even when flow was abnormally low. Arterioles greater than 40 microns ran parallel to venules. Measurements and a mathematical model indicate that diffusive shunting is negligible for typical separation distances between arterioles and venules. Most separation distances were greater than 30 microns. In some venule segments less than 15 microns from an arteriole, saturation within 10 microns of the wall facing the arteriole was higher than at other locations within the venule. However, saturation in the population of venules did not increase with venule diameter, and mean venular saturation was not different from saturation in effluent blood. We make the following conclusions: 1) a small arteriovenous diffusive O2 flux exists in postural muscles; 2) contribution of this flux to O2 mass balance is negligible; 3) O2 diffusivity of the arteriolar wall and surrounding tissue in vivo cannot be much higher than O2 diffusivity determined in vitro; and 4) effluent PO2 closely approximates mean end-capillary PO2.
To determine whether serum 3 alpha-androstanediol glucuronide (3AG) reflects the overall effect of integrated adrenal androgen secretion in the virilizing form of congenital adrenal hyperplasia (CVAH), circadian levels (0800, 1200, 1600, and 2000 h) of serum 3AG and 17-hydroxyprogesterone (17OHP) or 11-deoxycortisol (S), androstenedione (A), testosterone (T), and 24-h urinary 17-ketosteroids (17KS) were examined in seven patients (pts) with classical 21-hydroxylase deficiency (21OHD) and one pt with classical 11 beta-hydroxylase deficiency (11 beta OHD). Hormonal studies were conducted during the second day of dexamethasone (Dex) administration (2 mg/day). In five poorly controlled CVAH pts, including the 11 beta OHD pt, highly elevated baseline morning (AM) serum 17OHP or S as well as A levels, and elevated AM T levels in three pts decreased markedly in the evening (PM), while elevated serum 3AG showed no significant circadian changes; 17KS levels were markedly elevated for age. During Dex, moderately or slightly elevated AM 17OHP, A, or T in two to four pts with 21OHD decreased to the normal range in the PM. In the pt with 11 beta OHD, S, A, and T levels were suppressed. 3AG levels were modestly elevated or normal, without circadian changes, in these pts; 17KS levels were elevated or normal. In two other 21OHD pts, modestly elevated AM baseline 17OHP and A levels decreased in the PM; elevated AM T decreased in one pt in the PM; modestly elevated 3AG levels showed no circadian changes; 17KS levels were modestly elevated. During Dex, normal or slightly elevated serum steroids and 17KS levels were associated with normal or high normal 3AG levels without circadian changes. In one postpubertal female with 21OHD, modestly elevated AM baseline 17OHP levels decreased at 2000 h; normal A and T levels throughout the day and low normal 17KS were associated with slightly low 3AG levels, without circadian variation. During Dex treatment, normal 17OHP, A, T, and low 17KS levels were associated with low 3AG levels without circadian variation. In all pts as a group, an excellent correlation (r = 0.9) was found between either 0800 h or mean, or 2000 h serum 3AG levels and 17KS. In addition, AM and PM serum 3AG levels in five normal women were similar. We conclude that the high correlation between serum 3AG and urinary 17KS and the absence of a significant circadian variation in 3AG indicate that serum 3AG, regardless of sample time, is a useful metabolic index of integrated adrenal androgen secretion in CVAH.
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DC cardioversion is a safe, simple procedure for the management of patients with tachyarrhythmias. Its great advantages in an emergency are its immediate effect and the avoidance of the potential side effects of drug therapy. It should be considered in the management of any patient with a tachyarrhythmia.
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OBJECTIVE: To assess the relations between breast feeding and infant illness in the first two years of life with particular reference to gastrointestinal disease. DESIGN: Prospective observational study of mothers and babies followed up for 24 months after birth. SETTING: Community setting in Dundee. PATIENTS: 750 pairs of mothers and infants, 76 of whom were excluded because the babies were preterm (less than 38 weeks), low birth weight (less than 2500 g), or treated in special care for more than 48 hours. Of the remaining cohort of 674, 618 were followed up for two years. INTERVENTIONS: Detailed observations of infant feeding and illness were made at two weeks, and one, two, three, four, five, six, nine, 12, 15, 18, 21, and 24 months by health visitors. MAIN OUTCOME MEASURE: The prevalence of gastrointestinal disease in infants during follow up. RESULTS: After confounding variables were corrected for babies who were breast fed for 13 weeks or more (227) had significantly less gastrointestinal illness than those who were bottle fed from birth (267) at ages 0-13 weeks (p less than 0.01; 95% confidence interval for reduction in incidence 6.6% to 16.8%), 14-26 weeks (p less than 0.01), 27-39 weeks (p less than 0.05), and 40-52 weeks (p less than 0.05). This reduction in illness was found whether or not supplements were introduced before 13 weeks, was maintained beyond the period of breast feeding itself, and was accompanied by a reduction in the rate of hospital admission. By contrast, babies who were breast fed for less than 13 weeks (180) had rates of gastrointestinal illness similar to those observed in bottle fed babies. Smaller reductions in the rates of respiratory illness were observed at ages 0-13 and 40-52 weeks (p less than 0.05) in babies who were breast fed for more than 13 weeks. There was no consistent protective effect of breast feeding against ear, eye, mouth, or skin infections, infantile colic, eczema, or nappy rash. CONCLUSION: Breast feeding during the first 13 weeks of life confers protection against gastrointestinal illness that persists beyond the period of breast feeding itself.
The purpose of this study was to determine whether the excitotoxin N-methyl-d-aspartate (NMDA) could be used to make lesions within the lateral hypothalamus and what effect they had on regulatory behaviour. Larger doses of NMDA were effective in the lateral hypothalamus but tended to spread into adjacent structures; smaller doses made lesions which were contained within the lateral hypothalamus and zona incerta. Lesions which damaged the lateral hypothalamus and surrounding tissue had no effect on the concentration of dopamine (or its metabolites) in the dorsal or ventral striatum. The large lesions, including extrahypothalamic damage, were associated with long-term deficits in lab chow and water intake, but rats with lesions restricted to the lateral hypothalamus made good recoveries, eating and drinking normally from around the tenth day post-operation. Body weight gain was normal in these rats, though there was a long-term loss of body weight compared to controls. Unoperated rats with food intake yoked to lesioned rats showed identical long-term changes in body weight, suggesting that the changes in body weight of lesioned rats may be a reflection of changes in eating and drinking rather than a disruption of a body weight set-point mechanism. Motor deficits were not found; all rats were able to consume without difficulty saccharin solutions. All lateral hypothalamic lesioned rats failed to respond to dehydrating, dipsogenic or glucoprivic challenges. It is concluded that NMDA is an effective toxin in the rat lateral hypothalamus, sparing ascending dopamine fibres, and that the main effect of such lesions is an impairment in responding to physiological challenges.
Islet amyloid may have a pathological role in the development of Type 2 (non-insulin-dependent) diabetes mellitus. The prevalence of islet amyloid has been investigated on post-mortem pancreatic tissue from both diabetic and non-diabetic Pima Indian subjects who had previously been assessed by oral glucose tolerance tests. Islets were examined for amyloid deposits and for cellular immunoreactivity to pancreatic hormones and islet amyloid polypeptide, the constituent peptide of islet amyloid. Twenty of 26 diabetic subjects (77%) had islet amyloid, compared with one of 14 non-diabetic subjects (7%). Twelve of the diabetic subjects (46%) had amyloid in more than 10% of their islets, whereas only 4% of islets were affected in a single non-diabetic subject. Positive immunoreactivity for islet amyloid peptide was present in the islet amyloid and in islet cells in 54% of the diabetic and 50% of the non-diabetic subjects. Islet amyloid in diabetic Pima Indians may indicate a primary Beta-cell defect which interacts with insulin resistance to produce diabetes, or may develop as a result of Beta-cell dysfunction induced by insulin resistance and hyperglycaemia.
The effect of intravenous infusion of islet amyloid polypeptide (IAPP/amylin) and calcitonin gene-related peptide (CGRP) on blood glucose and plasma insulin in the basal and glucose-stimulated state was investigated in the anaesthetized rat. Both peptides had no effect on basal blood glucose or plasma insulin but following an intravenous bolus of glucose, CGRP-treated rats were hyperglycaemic and hyperinsulinaemic compared with control animals which were similar to IAPP-treated rats. IAPP had no effect on glucose-stimulated islet insulin secretion. These results suggest that CGRP, but not IAPP, alters glucose removal in vivo.
The objective of this work is to theoretically model oxygen unloading in sickle red cells. This has been done by combining into a single model diffusive transport mechanisms, which have been well-studied for normal red cells, and the hemoglobin polymerization process, which has been previously been studied for deoxyhemoglobin-S solutions and sickle cells in near-equilibrium situations. The resulting model equations allow us to study the important processes of oxygen delivery and polymerization simultaneously. The equations have been solved numerically by a finite-difference technique. The oxygen unloading curve for sickle erythrocytes is biphasic in nature. The rate of unloading depends in a complicated way on (a) the kinetics of hemoglobin S polymerization, (b) the kinetics of hemoglobin deoxygenation, and (c) the diffusive transport of both free oxygen and oxy-hemoglobin. These processes interact. For example, the hemoglobin S polymer interferes with the transport of both free oxygen and unpolymerized oxy-hemoglobin, and this is accounted for in the model by diffusivities which depend on the polymer and solution hemoglobin concentration. Other parameters which influence the interaction of these processes are the concentration of 2,3-diphosphoglycerate and total hemoglobin concentration. By comparing our model predictions for oxygen unloading with simpler predictions based on equilibrium oxygen affinities, we conclude that the relative rate of oxygen unloading of cells with different physical properties cannot be correctly predicted from the equilibrium affinities. To describe the unloading process, a kinetic calculation of the sort we give here is required.
Enzyme immunoassays for the detection of chlamydial antigens are commonly used to diagnose Chlamydia trachomatis infection. As is true for all nonculture methods, the specificities of these tests are a concern. A confirmatory blocking assay (Abbott Laboratories, North Chicago, Ill.) was evaluated at four sexually transmitted disease test sites. This assay is designed to confirm true-positive Chlamydiazyme (CZ) specimens and to identify false-positive CZ reactions caused by cross-reacting bacteria. Cervical specimens were collected from 2,891 women. Chlamydia prevalence by tissue culture (TC) was 9.2% (266 of 2,891 specimens). Compared with TC, the sensitivity and specificity of CZ were 78.9% (210 of 266 specimens) and 98.2% (2,577 of 2,625 specimens), respectively. There were 48 CZ false-positive reactions. The direct fluorescent-antibody test (DFA) was positive for 31 of 48 false-positive reactions, indicating culture misses. Thus, when the standard was both TC and DFA, CZ sensitivity was 81.1% and CZ specificity was 99.3%. Of the 17 CZ-positive patients who were negative by both TC and DFA, 3 were negative on repeat CZ and 11 of 14 were identified as false positive by the confirmatory assay. The confirmatory test was positive for CZ-positive women who were positive by TC or DFA. Use of the confirmatory test, which increased the specificity to 99.9%, would increase confidence in positive CZ results and make the test more useful for screening populations with a low prevalence of C. trachomatis infection.
Adding kinetics to the model of the phosphate energy system [Connett. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R949-R959, 1988], we provide a framework for analyzing metabolic transients in muscle tissue. We modify the formalism of the earlier model and introduce a buffering factor, which measures buffering of adenine nucleotides by phosphocreatine. The time course of the phosphate energy state can be calculated given the following: 1) adenosinetriphosphatase (ATPase) rate, 2) pH, and 3) a mitochondrial driving function, i.e., ATP production in terms of the phosphate energy state. We use mitochondrial driving functions derived from steady-state measurements to predict the time courses for rest-work transitions. Predictions for transitions in the rat gastrocnemius muscle agree with published values. The model is used to test different existing hypotheses of oxygen consumption (VO2) regulation. Each hypothesis generates a specific mitochondrial driving function, which in turn generates a specific time course of phosphate energy state during transitions. A mitochondrial driving function based on enzyme kinetics with ADP as a substrate leads to time courses not matching the data. Mitochondrial driving functions that are linear with phosphocreatine, Pi, phosphorylation potential, or the pool of high-energy phosphate bonds (phosphate potential energy) gave good agreement with the data.
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Reported here are the results of the first effort to examine the effects of a dance-based aerobic exercise program for people with rheumatoid arthritis (RA). Forty-three subjects with RA completed a 16-week program that met twice weekly for 2 hours. One hour was devoted to exercise consisting of 15 to 20 minutes of warm-ups, 20 to 30 minutes of dance-based aerobic exercise, and 15 to 20 minutes of mat work for muscle strengthening and flexibility. The second hour was devoted to discussion that emphasized participant problem solving. The combined exercise/problem-solving discussion program was called EDUCIZE. Analyses of pretest to posttest changes indicated no deleterious effects on disease activity. In fact, physician-assessed articular pain and swelling decreased significantly, as did 50-foot walk time, pain, and depression. Participants reported significant improvement in lower extremity function. Changes in vigor and fatigue approached significance. Perceptions of general health as well as four of five quality of life indices improved significantly. This study adds to the as yet limited literature that indicates that weight-bearing vigorous exercise is beneficial for people with arthritis. Controlled studies to validate the findings of this study appear warranted. Also important for future research is investigation of the influence of the problem-solving discussion component on program effects.