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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 955 records · Page 53Linked to original sources

Effect of insulin on renal potassium metabolism.

The effect of insulin on renal potassium excretion was examined by employing the euglycemic insulin clamp technique in combination with renal clearance measurements. While euglycemia was maintained, insulin was infused at rates of 4.8 (n = 7) and 12 (n = 5) mU X kg-1 X min-1. Steady-state plasma insulin levels of 164 +/- 8 and 370 +/- 15 microU/ml were achieved in the low- and high-dose studies, respectively. Base-line plasma potassium concentration declined progressively by a mean of 0.14 +/- 0.09 (P less than 0.05) and 0.40 +/- 0.05 meq/liter (P less than 0.01) during the low- and high-dose insulin infusion protocols. Urinary potassium excretion did not change significantly from base line with either insulin dose. Because the decline in plasma potassium concentration could have masked a stimulatory effect of insulin on UKV, six rats received a 12-mU X kg-1 X min-1 euglycemic insulin clamp in combination with an exogenous potassium infusion to maintain the plasma potassium concentration constant at the basal level (4.03 +/- 0.03 vs. 4.05 +/- 0.05 meq/l). Under these conditions of normokalemia, insulin augmented UKV 2.4-fold, from 0.20 +/- 0.05 to 0.48 +/- 0.04 meq/l (P less than 0.001).

Animals↗

Experience with the Pelorus stereotactic system.

The Pelorus stereotactic system, by its unique approach, alleviates the need for the traditional head frame and computer-generated coordinates which are common to most other systems. Despite its simplicity, it sacrifices nothing in terms of the range of problems for which it can be used to diagnose and treat. In fact, its unencumbered design may make it more appropriate for advanced procedures than conventional systems.

Humans↗

Disparity between ejection and end-systolic indexes of left ventricular contractility in mitral regurgitation.

To examine left ventricular function in mitral regurgitation (MR), we compared the ejection phase indexes of left ventricular contractility with maximal systolic elastance (Emax) in an experimental preparation of MR. In eight anesthetized open-chest dogs, pressure-volume loops were derived during afterload manipulation with methoxamine and nitroprusside from simultaneous left ventricular pressure and dimensional (sonomicrometry techniques) data before and after creation of MR. From these data maximal systolic elastance (Emax), the end-systolic pressure-volume relationship (ESPVR), and the end-systolic stress-volume relationship (ESSVR) were determined by linear regression analysis. After creation of MR, end-diastolic volume increased significantly (40 +/- 13 to 53 +/- 18 ml, p less than .001); likewise end-systolic volume increased (28 +/- 11 to 33 +/- 15 ml, p less than .05). Ejection fraction increased after MR (35 +/- 6% to 44 +/- 8%, p less than .005), as did the mean velocity of fiber shortening (0.62 +/- 0.20 to 1.02 +/- 0.39 sec-1, p less than .02). In contrast, Emax declined significantly (4.63 +/- 2.5 to 3.54 +/- 1.94 mm Hg/ml, p less than .05); ESPVR and ESSVR showed similar directional changes. An inverse relationship was found between systolic elastance and end-diastolic volume in both control and MR states. When Emax, ESPVR, and ESSVR were normalized to end-diastolic volume, they were unchanged after MR. These results suggest that either there was a decline in left ventricular contractile state after MR, or that contractility was unchanged (if elastance is normalized for increased contractility, but occurred as a consequence of increased preload with no significant change in afterload.

Animals↗

Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats.

Insulin resistance is characteristic of the diabetic state. To define the role of hyperglycemia in generation of the insulin resistance, we examined the effect of phlorizin treatment on tissue sensitivity to insulin in partially pancreatectomized rats. Five groups were studied: group I, sham-operated controls; group II, partially pancreatectomized diabetic rats with moderate glucose intolerance; group III, diabetic rats treated with phlorizin to normalize glucose tolerance; group IV, phlorizin-treated controls; and group V, phlorizin-treated diabetic rats restudied after discontinuation of phlorizin. Insulin sensitivity was assessed with the euglyemic hyperinsulinemic clamp technique in awake, unstressed rats. Insulin-mediated glucose metabolism was reduced by approximately 30% (P less than 0.001) in diabetic rats. Phlorizin treatment of diabetic rats completely normalized insulin sensitivity but had no effect on insulin action in controls. Discontinuation of phlorizin in phlorizin-treated diabetic rats resulted in the reemergence of insulin resistance. These data demonstrate that a reduction of beta-cell mass leads to the development of insulin resistance, and correction of hyperglycemia with phlorizin, without change in insulin levels, normalizes insulin sensitivity. These results provide the first in vivo evidence that hyperglycemia per se can lead to the development of insulin resistance.

Animals↗

Quantitative analysis of glycogen repletion by nuclear magnetic resonance spectroscopy in the conscious rat.

In order to directly determine the amount of label exchange that occurs in the tricarboxylic cycle from labeled alanine and lactate after the ingestion of a glucose load [1-13C]glucose was administered by continuous intraduodenal infusion to awake catheterized rats to achieve steady state jugular venous glycemia (160 mg/dl) for 180 min. Liver was freeze-clamped at 90 and 180 min, and perchloric acid extracts of the liver were subjected to 13C and 1H nuclear magnetic resonance analysis. Dilution in the oxaloacetate pool was determined by comparing the intrahepatic 13C enrichments of C2, C3 positions of glutamate with the C2, C3 positions of alanine and lactate. In addition steady state flux equations were derived for calculation of relative fluxes through pyruvate dehydrogenase/TCA cycle flux and pyruvate kinase flux/total pyruvate utilization. After glucose ingestion in a 24-h fasted rat direct conversion of glucose was responsible for 34% of glycogen. The intrahepatic dilution factor for labeled pyruvate in the oxaloacetate pool was 2.4. Using this factor, alanine and lactate contributed approximately 55% to glycogen formation. Pyruvate dehydrogenase flux ranged between 24 and 35% of total acetyl-coenzyme A (CoA) production and pyruvate kinase flux relative to total pyruvate utilization was approximately 40%.

Amino Acids↗

AIDS and self-organization among intravenous drug users.

Gays and intravenous (i.v.) drug users are the two largest risk groups for AIDS. Gays, unlike drug users, have formed many organizations to deal with AIDS. Data are presented indicating that gay individuals have more risk-reducing behavioral changes than have i.v. drug users. It is also shown that i.v. drug users are more likely to protect themselves if their acquaintances do so. It is suggested that collective self-organization can lead to peer support for risk reduction and that this can help i.v. drug users to reduce their risks on an ongoing basis. Difficulties that face i.v. drug users' attempts to organize collectively and examples of i.v. drug user collective organization to deal with AIDS and other problems are discussed.

Acquired Immunodeficiency Syndrome↗

Crack.

Explore the source record for details and available documents.

Adult↗

Multicenter study of trilostane: a new hormonal agent in advanced postmenopausal breast cancer.

Trilostane, an inhibitor of the production of adrenal estrogens, was administered, together with dexamethasone, to 97 eligible postmenopausal women with advanced breast cancer. Seventy-four patients who had either received trilostane for a minimum of 10 weeks or whose disease had progressed while on trilostane before this period were assessed for tumour response. Eighteen patients (25%) had objective responses (two complete, 16 partial); a further 21 patients had stable disease. The response rate among all 97 patients, including those not treated for a minimum 10-week period, was 19%. Thirty-two of 97 patients reported adverse reactions which were attributed to trilostane and/or dexamethasone. Therapy was stopped for 15 patients, and the dose of trilostane was reduced for ten. Diarrhea was the commonest side effect, being reported in 16 patients, of whom nine stopped treatment. Trilostane, given with a corticosteroid, is an effective alternative hormonal agent acting by adrenal blockade for postmenopausal women with advanced breast cancer.

Breast Neoplasms↗

Pneumococcal vaccine prevents death from acute lower-respiratory-tract infections in Papua New Guinean children.

In three double-blind placebo-controlled trials of pneumococcal capsular polysaccharide vaccines against death from acute lower-respiratory-tract infections (ALRI), children were vaccinated at 6 months to 5 years of age. The efficacy of the vaccines against ALRI as the sole cause of death was estimated at 59% in children vaccinated when younger than 5 years (p = 0.008) and 50% in children vaccinated when younger than 2 years (p = 0.043). Mortality from all causes was 19% less in the vaccinated group.

Acute Disease↗

Products of cells cultured from gliomas. IV. Extracellular matrix proteins of gliomas.

Five primary and 3 established human glioma cell lines were cultured with ascorbate and examined for expression of extracellular matrix components. All lines except C6 expressed collagen as assessed by silver impregnation, immunofluorescence and lectin staining and expressed laminin and fibronectin. None expressed a lectin marker for endothelial cells. Both epithelial and mesenchymal collagens were expressed. While extracellular components of glioma lines resembled those of fibroblasts more closely than other cell types, subtle differences between gliomas and fibroblasts were present. These included more laminin and collagen type-IV antigenic reactivity and more 11-12 nm diameter extracellular fibrils from individual gliomas, and slight differences in spectra of low-molecular-weight extracellular proteins assessed by gel electrophoresis. One primary and two established glioma lines analysed for DNA content were aneuploid in contrast to diploid fibroblasts. Simultaneous expression of mesenchymal and epithelial markers suggests a dual differentiation potential of glioma cells. Results do not support an endothelial origin for cells cultured from gliomas.

Carbohydrates↗

P NMR evaluation of hypoxic stress in brain of animal models.

Quantification by NMR of hypoxic stress is best afforded by the ratio of phosphocreatine (PCr) to inorganic phosphate (Pi). The thin cranium and sternum of neonates affords ideal conditions for NMR evaluation of impaired oxidative metabolism. Brains of animal models (dog and cat) are best studied with muscles retracted with the rf coil placed on the bare skull. 31P and 1H (lactate) signals are time shared with a doubly tuned coil. Servo-stabilized hypoxia gives simplified steady state analysis. Hypoxic insults of the brain are evaluated by the integral of the deviation of the PCr/Pi ratio from the normoxic values. Generally, a deviation of 1 unit of PCr/Pi for an interval of 3 hr will lead to a severe metabolic damage and recovery from hypoxia is often 30-fold delayed. Comprehensive monitoring of energy metabolism (PCr/Pi), respiratory chain redox states, intracellular pH and lactate accumulation allow the calculation of integrated pH and lactate "insults" and thus offer new insights on the effects of hypoxia on brain oxidative metabolism.

Animals↗