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Biomedical subjects

M D'Costa

Publications and source records attributed to M D'Costa.

32 records · Page 2Linked to original sources
PubMed1990

Hypogonadotropic hypogonadism in idiopathic hemochromatosis: evidence for combined hypothalamic and pituitary involvement.

Hypogonadism is a common finding in idiopathic hemochromatosis. Most studies have localized the defect to either the pituitary gland or the testes. We describe a case with evidence that favors the likely concomitant involvement of the hypothalamus as a factor in the observed hypogonadism. A clinically hypogonadal male with hemochromatosis had a low testosterone concentration with inappropriately normal serum LH levels. Leydig cell function was intact, as demonstrated by a normal increase in serum testosterone following HCG administration. However, although the pituitary secretion of LH was normal in response to GnRH stimulation, clomiphene administration did not produce an increase in LH and FSH, suggesting that there was a defect in the hypothalamic GnRH response. Since the FSH and prolactin responses to stimulatory testing were inadequate, coexisting pituitary dysfunction was likely also present. We conclude that this man had hypogonadism with laboratory evidence for a combined defect in hypothalamic and pituitary function.

Chorionic Gonadotropin↗
PubMed1990

Perinatal factors associated with the respiratory distress syndrome.

Perinatal factors related to the incidence of respiratory distress syndrome were analyzed by the multiple logistic regression statistical method in 263 mothers and their 298 offspring delivered between 24 and 35 weeks' gestation in a 1-year period in a regional referral perinatal center. The risk of respiratory distress syndrome in white infants rose with decreasing gestational age (p less than 0.0001) while prolonged rupture of membranes of greater than 24 hours in the absence of maternal infection (28% of cases) was highly protective (p less than 0.0001). Compared with vaginal delivery, cesarean delivery without labor increased the risk of respiratory distress syndrome (p = 0.03). The administration of tocolytic drugs was unrelated to the incidence of respiratory distress syndrome, but corticosteroid therapy given at least 72 hours before delivery was protective (p = 0.03). Male and female infants were equally at risk for respiratory distress syndrome as were black and white infants, but other races had a lower incidence (p = 0.004). Infants with respiratory distress syndrome were on mechanical ventilators longer than those with other respiratory illnesses.

Adrenal Cortex Hormones↗
PubMed1990

Effect of caffeine on ventilatory responses to hypercapnia, hypoxia, and exercise in humans.

The effect of oral caffeine on resting ventilation (VE), ventilatory responsiveness to progressive hyperoxic hypercapnia (HCVR), isocapnic hypoxia (HVR), and moderate exercise (EVR) below the anaerobic threshold (AT) was examined in seven healthy adults. Ventilatory responses were measured under three conditions: control (C) and after ingestion of either 650 mg caffeine (CF) or placebo (P) in a double-blind randomized manner. None of the physiological variables of interest differed significantly for C and P conditions (P greater than 0.05). Caffeine levels during HCVR, HVR, and EVR were 69.5 +/- 11.8, 67.8 +/- 10.8, and 67.8 +/- 10.9 (SD) mumol/l, respectively (P greater than 0.05). Metabolic rate at rest and during exercise was significantly elevated during CF compared with P. An increase in VE from 7.4 +/- 2.5 (P) to 10.5 +/- 2.1 l/min (CF) (P less than 0.05) was associated with a decrease in end-tidal PCO2 from 39.1 +/- 2.7 (P) to 35.1 +/- 1.3 Torr (CF) (P less than 0.05). Caffeine increased the HCVR, HVR, and EVR slopes (mean increase: 28 +/- 8, 135 +/- 28, 14 +/- 5%, respectively) compared with P; P less than 0.05 for each response. Increases in resting ventilation, HCVR, and HVR slopes were associated with increases in tidal volume (VT), whereas the increase in EVR slope was accompanied by increases in both VT and respiratory frequency. Our results indicate that caffeine increases VE and chemosensitivity to CO2 inhalation, hypoxia, and CO2 production during exercise below the AT.

Administration, Oral↗
PubMed1990

Sensitive time-resolved fluorescence immunoassay of somatotropin in serum.

We describe a new "sandwich"-type non-isotopic immunoassay for human somatotropin (GH, growth hormone) in serum. In the assay, GH is captured by a monoclonal antibody immobilized in a white microtiter well and simultaneously reacted with a second biotinylated monoclonal antibody. The degree of binding of biotinylated antibody, which increases with increasing amount of GH in the sample, is quantified by adding streptavidin labeled with the europium chelate of 4.7 - bis(chlorosulfophenyl) - 1.10 - phenanthroline - 2.9 - dicarboxylic acid. The fluorescent complex on the solid phase is then measured by excitation at 337.1 nm (nitrogen laser) and monitoring the emission at 615 nm in a gated fluorometer/analyzer. The proposed procedure has short incubation times (less than 4 h protocol), uses only 25 microL of serum per microtiter well, and gives precise and accurate results. The method was clinically evaluated with samples obtained from pediatric patients undergoing investigation for growth abnormalities and from a patient with acromegaly.

Acromegaly↗
PubMed1988

Selective determination of urinary free cortisol by liquid chromatography after solid-state extraction.

We have developed a selective and precise high-performance liquid chromatographic method for urinary free cortisol with an improved and efficient sample clean-up using C18 Sep-Pak cartridges. The urine sample (2 ml), with 11-deoxycortisol as internal standard, is applied to the Sep-Pak, which is then sequentially washed with acetone-water (1:4, v/v), water and hexane. Cortisol is eluted with diethyl ether, evaporated to dryness and redissolved in 2 ml of water. The wash cycle is repeated once using the same Sep-Pak cartridge. This double extraction greatly improves sample clean-up and allows modification of the mobile phase (tetrahydrofuran-methanol-water) so that cortisol is rapidly eluted as a single well resolved peak at 13 min. Chromatography is performed isocratically on a reversed-phase column with detection at 254 nm. Detection limits for urinary free cortisol by this procedure were two or three times lower than those obtained with two commercial radioimmunoassay kits. The chromatographic method was used successfully in the diagnosis of patients with hypercortisolism and Cushing's syndrome.

Chromatography, High Pressure Liquid↗
PubMed1988

Serum pituitary and steroid hormone levels in the adult male: one value is as good as the mean of three.

The result of the hormone concentration of one blood sample was used to determine the accuracy of predicting not only the hormone concentrations of a second and third sample drawn 15 minutes apart, but also the mean value of the three samples. Three blood specimens from 73 men involved in two previously reported studies (A and B) were assayed individually for luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, androstenedione, dehydroepiandrosterone sulfate, estradiol, and cortisol. The predictive correlation of one single hormone value, when compared with the mean of three values, was 0.90 or greater, except for prolactin in study A (0.86) and testosterone in study B (0.86). Since the hormone level obtained for one sample has such a high predictive value for the hormone levels of the other two samples, drawing more than one sample is redundant.

Adult↗
PubMed1988

Improved receptor assay for measuring digoxin activity.

We describe a receptor assay of digoxin activity involving Na+/K+-ATPase (EC 3.6.1.37) derived from human heart tissue. The procedure requires 500 microL of serum or plasma and incorporates one purification step, with Sep-Pak C18 cartridges (Waters). The method appears to be considerably more specific for digoxin and its cardio-active metabolites than are conventional immunoassays. Cardio-inactive metabolites and several digoxin-like factors cross react only slightly. The between-day coefficient of variation for the procedure ranged from 8.10% to 1.37% for digoxin concentrations between 0.5 and 5.0 nmol/L.

Animals↗
PubMed1987

Lecithin/sphingomyelin ratios in tracheal aspirates from newborn infants.

A sensitive and rapid high-performance liquid chromatography method for determining lecithin/sphingomyelin (L/S) ratios in small volume tracheal aspirates has been evaluated in 115 infants sampled within 3 h of delivery. Respiratory distress syndrome was present in 41 infants and all had L/S ratios of less than or equal to 15 (sensitivity 100%). Respiratory distress syndrome was absent in 74 infants, 67 of whom had L/S ratios of greater than 15 (specificity 91%). Serial tracheal aspirates (n = 68) in 27 infants showed little change in nine respiratory distress syndrome infants with L/S ratio less than or equal to 15 over 3 h while 18 nonrespiratory distress syndrome infants with L/S greater than 15 were more variable. In two infants initial immature ratios rose to maturity rapidly after birth. Comparison of amniotic fluid L/S ratios obtained within 2 h of delivery correlated with the corresponding tracheal aspirate L/S in 24 infants (r = 0.81, p less than 0.001) although the latter were three times higher. This method may have potential routine application in the assessment of surfactant replacement and mechanical ventilator therapies.

Amniotic Fluid↗
PubMed1985

Validation of a simple rapid high performance liquid chromatographic method for amniotic fluid lecithin/sphingomyelin ratios.

A simple, rapid and sensitive HPLC method for the determination of L/S ratios in amniotic fluids is described. The method is based on isocratic separation in the normal phase with UV detection. The procedure has good precision and was validated clinically and by comparison with a routine TLC method. Although L/S ratios differed from those obtained by TLC, the clinical correlation between these methods was good. In single and serial samples from 39 mothers (42 babies) the HPLC method predicted respiratory distress syndrome (RDS) in all 9 babies with L/S ratios less than 7. No babies with ratios above 7 developed RDS. This method has potential clinical usefulness for the assessment of fetal lung maturity.

Amniotic Fluid↗
PubMed1983

Lactic acidosis in a patient with acute leukemia.

Lactic acidosis is a rare but potentially fatal complication of acute leukemia. The terminal phase of acute leukemia in a 22-year-old woman, heralded by lactic acidosis, is described in order to focus attention on the occurrence of this metabolic disturbance in the absence of overt manifestations of acute leukemia. As reported in other cases, the lactic acidosis in our patient responded poorly to bicarbonate therapy but dramatically to antileukemic chemotherapy. The pathogenesis of the lactic acidosis is unclear but it may be the result of an undefined 'paraneoplastic' metabolic disturbance induced by the leukemic cells.

Acidosis↗
PubMed1983

Ultrafiltrable calcium and magnesium in ultrafiltrates of serum prepared with the Amicon MPS-1 system.

We evaluated the Amicon micropartition system (MPS-1) for preparing ultrafiltrates of serum for use in evaluating ultrafiltrable Ca and Mg. We found no adsorption of either to the filter and 99.6% retention of serum proteins on the membrane. Ultrafiltrate volumes recovered (100-450 microL) varied with centrifugation time (10-30 min) and temperature. Centrifugation time did not affect the measured concentration of ultrafiltrable calcium and magnesium, and pH change in the 1-mL serum specimen during a 30-min centrifugation at room temperature was negligible. There was an inverse relationship between temperature and ultrafiltrable Ca and Mg concentrations. The precision (CV) between filters ranged from 1.2 to 5.1% for ultrafiltrable Ca and 1.5 to 2.7% for ultrafiltrable Mg. The correlation between ultrafiltrable Ca (y) and ionized Ca (x) in samples from 115 patients with calcium-related metabolic disorders was good (y = 1.04x + 0.18; r = 0.9128). We find the MPS-1 to be a simple and convenient tool for the rapid production of serum ultrafiltrates.

Adult↗
PubMed1977

Insulin-like effects of fluoroacetate on lipolysis and lipogenesis in adipose tissue.

Hormone-stimulated lipolysis in adipose tissue was inhibited by fluoroacetate and there was a concomitant decrease in both the basal and hormone-stimulated cyclic AMP levels. Adenylate cyclase (EC 4.6.1.1) activity in membrane preparations was inhibited by fluoroacetate. There was no influence of fluoroacetate on the low Km cyclic AMP phosphodiesterase (EC 3.1.4.17) activity. The rate of glucose conversion to fatty acids was increased when adipose tissue was incubated in the presence of fluoroacetate. The outputs of pyruvate and lactate into the incubation medium were decreased at this time, suggesting decreased tissue pyruvate levels and a site of activation of lipogenesis distal to pyruvate formation. Pyruvate dehydrogenase (EC 1.2.4.1) activity was increased twofold in adipose tissue incubated in the presence of fluoroacetate. This was attributed to a fluoroacetate-induced inhibition of pyruvate dehydrogenase kinase, the enzyme responsible for inactivating the pyruvate dehydrogenase complex. Glucose transport was increased to a small but significant degree by fluoroacetate. In addition, both the tissue content of citrate and its release into the incubation medium were increased, suggesting that fluoroacetate resulted in an inhibition of aconitase (EC 4.2.1.3). The tissue ATP content was unchanged. Because the antilipolytic and lipogenic effects of fluoroacetate parallel those of insulin, they may share a common mechanism.

Adipose Tissue↗
PubMed1975

Uncoupling of lipolysis from cyclic AMP by procaine: a tool for studying the mechanism of action of antilipolytic agents.

The initial rate of net glycerol release in norepinephrine-stimulated adipose tissue fragments was inhibited (40-78%) by procaine-HCl (1-5mM), whereas basal (unstimulated) lipolysis was unaffected. A dose-related inhibition of norepinephrine-induced lipolysis by procaine-HCl (0.1-1 mM) also occurred in adipocytes. Procaine-induced antilipolysis was associated with an augmented rather than a reduced hormone-stimulated increment in intracellular cyclic AMP. The dissociation of lipolysis from cyclic AMP accumulation has been termed the uncoupling effect of procaine. This effect of procaine was employed to define the precise mechanism of action of the antilipolytic drug clofibrate (Atromid-S) which inhibits lipolysis by reducing cyclic AMP. A reduction in cyclic AMP by clofibrate was demonstrated in norepinephrine-stimulated cells exposed to procaine (uncoupled system). Thus, the inhibitory effect of clofibrate on cyclic AMP could not be attributed to accumulation of products of lipolysis. Because neither procaine-HCl nor clofibrate had any effect on the low Km 3':5'-cyclic-AMP phosphodiesterase (EC 3.1.4.17) activity in hormone stimulated cells, the clofibrate-induced reduction in cyclic AMP was attributed to its direct action on adipocyte adenylate cyclase.

3',5'-Cyclic-AMP Phosphodiesterases↗