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Biomedical subjects

D M Cooper

Publications and source records attributed to D M Cooper.

At least 199 records · Page 11Linked to original sources
PubMed1986

Abnormal pancreatic electrolyte secretion in cystic fibrosis. Reliability as a diagnostic marker.

We performed pancreatic function tests on sixty-five cystic fibrosis (CF), and eleven control children. The technique used continuous IV infusion of cholecystokinin and secretin, with duodenal juice collection over a 90 min period, and was made quantitative by continuous duodenal infusion and distal collection of an unabsorbable marker (bromosulphthalein). Some CF patients had near normal pancreatic enzyme outputs, some had impaired but measurable levels, but most (79%) had almost absent trypsin secretion. CF children with better pancreatic function, were younger and more likely to be male. All controls showed a large increase in bicarbonate concentration and secretion rate per kilogram body weight during the test, but most children with CF (96.5%) did not. Because two of our CF patients had water and bicarbonate secretion within the control range, this finding does not exclude the diagnosis of CF. Sodium, potassium and chloride ion secretion in CF patients was lower than controls but overlap occurred. We found a linear correlation between acinar and tubular secretion in CF patients which indicates that there is probably not a primary genetic defect in pancreatic bicarbonate secretion in CF.

Adolescent↗
PubMed1986

Glucose turnover in response to exercise during high- and low-FIO2 breathing in man.

The purpose of this study was to assess whether breathing high or low concentrations of O2 could affect glucose turnover during exercise in man. Ten healthy subjects performed two constant work-rate exercise tests, one when the fraction of inspired O2 (FIO2) was 0.15 and the other at the same work rate but when the FIO2 was 0.80. The work rate for each subject was chosen so that blood lactate would be elevated during hypoxia, but would be lower during hyperoxia. Glucose appearance (Ra) and disappearance (Rd) were measured using the primed, constant infusion of [3-3H]glucose. Although the work rate was the same during hypoxia and hyperoxia in each subject, hypoxic exercise was accompanied by a significantly larger rest to exercise increase in Rd (delta Rd) compared with hyperoxia by 265%. Similarly, delta Ra was greater during hypoxia than during hyperoxia by 188%. Lactate to pyruvate ratios were significantly higher during hypoxic exercise suggesting a shift in the cell redox to a more reduced state. Insulin and glucagon were not affected by the FIO2, but both epinephrine and norepinephrine were increased during hypoxic exercise, which may explain the increase in Ra. The regulation of blood glucose during exercise in vivo appears to be dependent on the availability of oxygen to the working muscle cells.

Adult↗
PubMed1986

Dynamics of oxygen uptake during exercise in adults with cyanotic congenital heart disease.

The dynamic increase in oxygen uptake (VO2) at the start of exercise reflects the circulatory adjustments to metabolic changes induced by the exercise. Because VO2 measured at the lungs is the product of pulmonary blood flow and arteriovenous oxygen difference, pathologic conditions affecting the capacity of these factors to change would be expected to alter VO2 kinetics. To determine whether measurement of VO2 kinetics can detect conditions in which the pulmonary blood flow response to exercise is abnormal, VO2 was measured, breath-by-breath, during the transition from rest to exercise in 13 adults with cyanotic congenital heart disease (central venoarterial shunting) and in nine normal subjects. The increase in VO2 above baseline during the first 20 sec of exercise (phase I), reflecting the immediate increase in pulmonary blood flow, was diminished in the patients compared with that in normal subjects (14.8 +/- 10.9 vs. 49.8 +/- 19.2 ml of oxygen) (p less than .001). The patients' phase I responses correlated with their reported physical activity tolerance (p less than .01). In addition, the second phase of the VO2 response kinetics was prolonged in patients compared with normal subjects (half-time = 63 +/- 13 vs 15 +/- 13 sec) (p less than .001). We conclude that striking disturbances in VO2 kinetics occur in patients with cyanotic congenital heart disease and that these measurements provide a useful noninvasive means of evaluating the degree to which the increase in pulmonary blood flow is constrained in response to exercise.

Adult↗
PubMed1986

Dopamine, acting through D-2 receptors, inhibits rat striatal adenylate cyclase by a GTP-dependent process.

This report demonstrates that the D-2 dopamine receptors that are present in rat striatum can directly inhibit the activity of adenylate cyclase in a GTP-dependent manner. N-n-propylnorapomorphine evoked a more pronounced inhibition than did dopamine. However, in the presence of the D-1-selective antagonist, SCH 23390, dopamine was also observed to inhibit the enzyme. Forskolin facilitated the detection of D-2 receptor-mediated inhibition by markedly stimulating striatal adenylate cyclase activity. The inhibition was antagonized in a dose-dependent manner by the D-2 receptor antagonist spiperone (Ki value = 70 pM) and was absolutely dependent on the presence of both GTP and sodium ions. Inhibition produced via D-2 receptors was additive with that produced via opiate or adenosine A1 receptors. The nonhydrolyzable GTP analogue, 5'-guanylylimidodiphosphate [Gpp(NH)p], did not substitute for GTP in promoting the D-2 receptor-mediated inhibition. It thus appears that D-2 receptors mediate adenylate cyclase inhibition by processes that have been observed for other neurotransmitters in the striatum and elsewhere. In addition, Gpp(NH)p displayed a Ca2+/calmodulin dependency for its inhibitory effects that was not shared by receptor-mediated, GTP-dependent inhibition.

Adenylyl Cyclase Inhibitors↗
PubMed1985

Cholera toxin ADP-ribosylates the islet-activating protein substrate in adipocyte membranes and alters its function.

In adipocyte membranes, cholera toxin may ADP-ribosylate the islet-activating protein (IAP) substrate, under certain conditions. Covalent modification is maximal in the absence of a guanosine triphosphate; in the presence of 5'-guanylylimidodiphosphate, incorporation of [32P]ADP-ribose is markedly reduced. ADP-ribosylation by cholera toxin has similar functional consequences as does IAP-mediated modification, i.e. the biphasic response of isoproterenol-stimulated adenylate cyclase to GTP and the inhibition by N6-phenylisopropyladenosine is abolished, and only the stimulatory phase remains. In contrast, membranes treated with cholera toxin in the presence of GTP display both the stimulatory and inhibitory responses to GTP. The binding of the adenosine analog [3H]N6-phenylisopropyladenosine is increased in the presence of GTP. Treatment of the membranes with IAP, but not with cholera toxin in the absence of GTP, reverses this GTP effect on [3H]N6-phenylisopropyladenosine binding. However, [3H]N6-phenylisopropyladenosine binding is still sensitive to GTP in membranes treated with cholera toxin in the presence of GTP. In adipocyte and cerebral cortical membranes, the IAP substrate appears as a 39,000/41,000-Da doublet which does not appear to reflect protease activity. On two-dimensional polyacrylamide gels, these two proteins migrate with approximate pI values 6.0 and 5.6, respectively. Although both behave similarly under all conditions explored in this study, it is unknown whether both, or only one, are involved in inhibition of adenylate cyclase activity. These results extend the already striking homology between the adenylate cyclase complex and the visual system. Ni, as well as transducin, may be ADP-ribosylated by cholera toxin and by IAP, and, in all cases, there are functional consequences.

Adenosine Diphosphate Ribose↗
PubMed1985

Magnesium ion exerts a central role in the regulation of inhibitory adenosine receptors.

Guanine nucleotides and Mg2+ differentially regulate agonist binding to adenosine (Ri) receptors in fat-cell plasma membranes. GTP alone decreases binding of the agonist ligand [3H]N6-cyclohexyladenosine (CHA) by increasing the dissociation constant (Kd). Mg2+ alone also decreases [3H]CHA binding, which is associated with a decrease in the number of receptors and in the dissociation constant. In the presence of Mg2+, the effect of GTP is to increase [3H]CHA binding by increasing the total number of receptors. It thus appears that Mg2+ acts specifically at a bivalent-cation site which, with GTP, regulates agonist binding. This putative Mg site is highly sensitive to alkylating agents. Mild treatment with N-ethylmaleimide (NEM) abolishes the characteristic GTP effect on agonist binding in the presence of Mg2+. In addition, the effect of Mg2+ alone is also eliminated. The effect of GTP alone is largely unaltered. Studies of the adenylate cyclase activity indicate that this NEM treatment also abolishes the inhibition of basal activity by adenosine analogues, whereas guanylyl imidodiphosphate inhibition of forskolin-stimulated activity is only slightly impaired at this NEM concentration. These observations indicate that a Mg2+ 'site' or 'component' is required for the integration of receptor (Ri) occupancy with regulation of catalytic activity (C). The regulatory role of Mg2+ is more demonstrable in receptor-GTP-regulatory-protein (Ri-Ni) interactions than in GTP-regulatory-protein-catalytic-unit (Ni-C) interactions.

Adenosine↗
PubMed1985

Kinetics of oxygen uptake and heart rate at onset of exercise in children.

Requirements for cellular homeostasis appear to be unchanged between childhood and maturity. We hypothesized, therefore, that the kinetics of O2 uptake (VO2) in the transition from rest to exercise would be the same in young children as in teenagers. To test this, VO2 and heart rate kinetics from rest to constant work rate (75% of the subject's anaerobic threshold) in 10 children (5 boys and 5 girls) aged 7-10 yr were compared with values found in 10 teenagers (5 boys and 5 girls) aged 15-18 yr. Gas exchange was measured breath to breath, and phases I and II of the transition and phase III (steady-state exercise) were evaluated from multiple transitions in each child. Phase I (the VO2 at 20 s of exercise expressed as percent rest-to-steady-state exercise VO2) was not significantly correlated with age or weight [mean value 42.5 +/- 8.9% (SD)] nor was the phase II time constant for VO2 [mean 27.3 +/- 4.7 (SD) s]. The older girls had significantly slower kinetics than the other children but were also found to be less fit. When the teenagers exercised at work rates well below 75% of their anaerobic threshold, phase I VO2 represented a higher proportion of the overall response, but the phase II kinetics were unchanged. The temporal coupling between the cellular production of mechanical work at the onset of exercise and the uptake of environmental O2 appears to be controlled throughout growth in children.

Adolescent↗
PubMed1985

Gas exchange during exercise in children with thalassemia major and Diamond-Blackfan anemia.

The two main goals of this study were: to determine how O2 uptake, ventilation, and CO2 production during exercise were acutely affected by transfusion in children with congenital anemia (thalassemia major and Diamond-Blackfan syndrome) requiring hypertransfusion and chelation therapy and to compare gas exchange responses to exercise of the anemic patients to normal values. Thirteen patients (age range 7-27) performed cycle ergometry with a progressively increasing work rate. Gas exchange was measured breath-by-breath. Tests were done before and after routine transfusion (mean increase in hematocrit 22%). The results were compared to 10 age-matched normal children who performed the same protocol on two occasions separated by a 2-day interval, and to the results of 109 normal children studied in this laboratory. Transfusion resulted in: a small, but significant increase in the anaerobic threshold (9%) and an increase in the slope of the relationship between O2-uptake and heart rates. Despite these improvements, the majority of the patients had abnormally low values of maximal O2 uptake, anaerobic threshold, and slope of the O2 uptake-heart rate relationship. The abnormalities were more marked in the older patients. Measurement of gas exchange during exercise may be helpful in determining an optimal hematocrit for patients on hypertransfusion regimens.

Adolescent↗
PubMed1984

Mycoplasma pneumoniae: acute illness, antibiotics, and subsequent pulmonary function.

One hundred and eight children presenting with Mycoplasma pneumoniae infection were assessed during the acute illness and followed for three years. The incidence of wheezing with the acute infection (40%) was greater than expected in a normal childhood population. The initial illness precipitated wheezing for the first time in some subjects but others wheezed only with the acute illness. In non-asthmatic subjects significant bronchodilator responsiveness was present one month after infection. Children given erythromycin during the first seven days of their illness had a significantly shorter fever duration compared with those treated inappropriately. No significant effects of treatment were noted on pulmonary function three years later but non-asthmatic children had abnormal mean forced expiratory volume in one second and forced expiratory flow after 50% of the expired vital capacity compared with 64 healthy controls. These findings indicate impaired function three years after initial infection.

Adolescent↗
PubMed1984

Aerobic parameters of exercise as a function of body size during growth in children.

To examine the relationship between body weight in children and aerobic parameters of exercise, we determined the anaerobic threshold (AT), maximum O2 uptake (VO2max), work efficiency, and response time for O2 uptake (RT-VO2) in 109 healthy children (51 girls and 58 boys, range 6-17 yr old) using a cross-sectional study design. Gas exchange during exercise was measured breath by breath. The protocol consisted of cycle ergometry and a linearly increasing work rate (ramp) to the limit of the subject's tolerance. Both AT and VO2max increased systematically with body weight, whereas work efficiency and RT-VO2 were virtually independent of body size. The ratio of AT to VO2max decreased slightly with age, and its mean value was 60%. AT scaled to body weight to the power of 0.92, not significantly different from the power of 1.01 for VO2max. Thus both the AT and the VO2max increase in a highly ordered manner with increasing size, and as judged by AT/VO2max, the onset of anaerobic metabolism during exercise occurred at a relatively constant proportion of the overall limit of the gas transport system. We conclude that in children cardiorespiratory responses to exercise are regulated at optimized values despite overall change in body size during growth.

Adolescent↗
PubMed1984

Gas exchange response to exercise in children.

We measured the gas exchange response to exercise in 109 normal children (51 girls and 58 boys, ranging in age from 6 to 17 yr old) using noninvasive breath-by-breath techniques. The protocol consisted of cycle ergometry in which the work rate increased in a linear manner (ramp forcing function) until the limit of the subject's tolerance was reached. We measured the maximal oxygen uptake (VO2max) and the VO2 at the anaerobic threshold (AT). We found that both of these parameters were highly correlated with increasing height, and that for both the AT and VO2max, the values for boys were significantly higher than girls. We compared our results of VO2max to those obtained by Astrand over 30 years ago using different techniques. When boys and girls were considered together, there were no significant differences between our study and Astrand's; however, girls in our study had significantly lower values for VO2max than did girls in Astrand's study. These data provide normal values for both VO2max and AT and can be used to evaluate the exercise impairment resulting from disease in children.

Adolescent↗
PubMed1984

Respiratory mechanics in adolescents with idiopathic scoliosis.

Mechanisms causing the reduction in lung capacity commonly found in adolescents with idiopathic scoliosis (IS) have not been understood. In 29 patients with typical thoracic curvatures of mild to moderate degree (less than 60 degrees), total lung capacity (TLC) was a mean 75 +/- 13% (SD) of predicted. The patients could generate only -70 +/- 26 cm H2O (SD) maximal inspiratory airway pressure at function residual capacity, as compared with -102 +/- 28 cm H2O in 21 normal control subjects (p less than 0.001). Studies of lung mechanics in 15 of the patients showed that maximal transpulmonary pressure at TLC was also reduced. Static pressure volume curves were shifted to the right, and both static and dynamic lung compliance were significantly reduced. Although both upstream conductance per TLC and anatomic dead space per TLC were abnormally high, relationships between maximal expiratory flow and static lung recoil were appropriate for age, indicating a normal growth of airway dimensions. From results of the single-breath nitrogen washout procedure, amounts of trapped nitrogen were also normal, indicating that the low lung compliance is not caused by airway closure. After a 5-min period of positive pressure (25 cm H2O) breathing, dynamic compliance increased by a mean of 34% in subjects with low TLC, and by a significantly smaller (p less than 0.05) mean increase of 14% in subjects with normal TLC. The 15 patients were restudied 1 yr after corrective surgery by the Harrington procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Growth-related changes in oxygen uptake and heart rate during progressive exercise in children.

Although body size and muscle mass increase considerably during growth in children, certain aerobic responses to exercise appear to be regulated so that the delivery of oxygen to muscle is maintained at optimized levels. We proposed that the relationship between oxygen uptake, (VO2) and heart rate (HR) was one of the regulated responses. We further hypothesized that the increase in VO2 per increase in HR during progressive exercise would differ in subjects of different size, but when normalized to body weight would be constant since changes in muscle mass are highly correlated to changes in body mass. To test this, we performed a cross-sectional study of 107 normal children, 50 girls and 57 boys ranging in age from 6 to 17 years. The protocol consisted of a continuously increasing work rate on a cycle ergometer, to the limit of the child's tolerance (ramp forcing function). Gas exchange was measured breath-by-breath for the determination of VO2, and heart rate was measured beat-by-beat. We used linear regression techniques to determine M, the slope, and B, the y intercept of the equation: VO2 = M X HR - B. In both boys and girls, M increased significantly with body weight, but when normalized for body weight (M/kg), there was no systematic change with increasing weight or age, the mean value being 0.33 +/- 0.10 ml/min/kg (SD). The mean value for the boys was 0.37 +/- 0.10 which was significantly greater than that of the girls (0.29 +/- 0.08, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗