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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 37 records · Page 2Linked to original sources
PubMed1979

Studies on pregnancy-associated plasma protein A in the third trimester of pregnancy.

The plasma concentration of pregnancy-associated plasma protein A (PAPP-A) was measured in 34 women during the last 10 weeks of pregnancy. From 30 to 36 weeks the concentration of this protein increased steadily. Thereafter the concentration of PAPP-A rose more steeply, the highest amounts being found in early labour. The concentration of PAPP-A in peripheral venous blood and in the uterine vein was much the same. It was less in the retroplacental blood and a great deal less in the peritoneal fluid. The day-to-day variation was small; the coefficient of variation at 38 weeks was only 7.3 per cent. After delivery, the concentration of PAPP-A fell more slowly than other placental proteins and steroids, the average half-life being 51 hours. Although there is no doubt that PAPP-A is a product of the syncytiotrophoblast, our findings suggest that it is not simply secreted by the chorionic villi directly into the intervillous space but makes its way into the maternal circulation by a more circuitous route.

Ascitic Fluid↗
PubMed1979

Suppression of chronic ventricular arrhythmias with propranolol.

The antiarrhythmic efficacy of propranolol was evaluated in 32 patients with chronic high frequency ventricular arrhythmias in a placebo-controlled protocol. After a placebo control period, propranolol was begun and the dosage increased sequentially until arrhythmia suppression was achieved, side effects appeared, or a maximum dosage of 960 mg/day was reached. Computerized analysis of ambulatory recordings was used to quantify the arrhythmias. Twenty-four patients had 70--100% arrhythmia suppression at plasma levels ranging from 12--1100 ng/ml (end of dosing interval). Eight patients in this group had frequent episodes of ventricular tachycardia that were totally suppressed at or below the dosage that produced greater than or equal to 70% suppression of ventricular ectopic depolarizations (VEDs). A biphasic dose-response curve was seen in five patients who responded with a decrease in arrhythmia frequency in the lower ranges of dosages but had increased frequency of ectopic rhythms as the dosage was increased above the optimal level. Only one-third of patients responded at doses less than or equal to 160 mg/day. However, with dosages of 200--640 mg/day, an additional 40% responded. Propranolol appears to control ventricular arrhythmias safely and effectively in many patients. The finding that the antiarrhythmic effect in many patients required plasma concentrations greater than those that produce substantial beta-adrenergic blockage raises a question whether blockade of cardiac beta receptors can directly account for all of the antiarrhythmic actions of propranolol.

Adult↗
PubMed1979

Whole body hyperthermia: a phase-I trial of a potential adjuvant to chemotherapy.

Fourteen patients with a variety of neoplasms not responsive to standard forms of therapy underwent whole body hyperthermia for a maximum 4 h at 41.8 degrees C. This was a phase-I cancer trial designed to develop whole body hyperthermia as an adjuvant to systemic chemotherapy. Intravenous analgesia was used to sedate patients, obviating the need for general endotracheal anesthesia. Hyperthermia was induced by means of a high-flow water perfusion suit. Cardiovascular performance was evaluated using a flow-directed pulmonary artery catheter. Patients developed a twofold mean increase in cardiac index without evidence of cardiac damage by ECG or creatine phosphokinase (CPK) isoenzymes. An acute fall in serum magnesium and phosphate and an acute rise in arterial pH, serum CPK values, and granulocyte count occurred in all patients. There were no clotting abnormalities. Toxicity included fatigue, diarrhea, nausea, and transient elevations in liver enzymes. Four patients were febrile for 36 h after initial defervescence. Peripheral neuropathy developed in four. These results show that with carefully monitored conditions whole body hyperthermia is feasible.

Adolescent↗
PubMed1979

Renal anomalies in mice prenatally exposed to ethanol.

The current observations confirm and extend earlier data demonstrating the deleterious effects of ethanol in the C57BL/6J mouse. Ethanol given to pregnant mice from gestation-day 5 to gestation-day 11 reduced the number of mice going to full term, decreased the number of pups per litter, and lowered the birthweight of the live pups. Prenatal exposure to ethanol also produced a high incidence of hydronephrosis in the offspring.

Abnormalities, Drug-Induced↗
PubMed1979

Treatment of renal bone disease with 1 alpha-hydroxylated derivatives of vitamin D3. Clinical, biochemical, radiographic and histological responses.

Forty patients with severe bone disease and chronic renal failure were treated with 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) or 1,25-dihydroxycholecalciferol (1,25(OH)2D3) for 7--49 months (total = 738 patient months). There were symptomatic, biochemical and radiographic improvements in the majority of patients (greater than 70 per cent). Paired bone biopsies, taken before and during treatment in 26 patients, showed no change in bone matrix area, whereas matrix area decreased in a control group of 26 patients over the same period. There were small but consistent decreases in bone marrow fibrosis and in bone cell (osteoblast and osteoclast) counts in treated patients but not in controls. However, the proportion of patients who showed histological 'cure', in the sense of complete reversal of marrow fibrosis or excess osteoid was no greater in the treated than in the control group...

Adolescent↗
PubMed1979

Diurnal intraocular pressure in juvenile open-angle glaucoma.

Outpatient diurnal intraocular pressures were obtained on 10 patients with juvenile open-angle glaucoma at approximately 6 hour intervals. There were 8 males and 2 females with an age range of 19 to 38 years. All glaucomatous medications were stopped 24 hours before recording the tensions. The peak intraocular pressure was recorded at the 6 PM interval in 6 of the 10 patients. Three patients recorded their highest pressures at the 12 AM (midnight) interval. Extraordinarily wide angles were observed in all cases and myopia was a common refractive error. Although the family history was not known in 3 patients, there was a positive family history of glaucoma in 7 of the 10 patients, which suggests an autosomal dominant mode of inheritance.

Adult↗
PubMed1978

Is 24,25-dihydroxycholecalciferol a calcium-regulating hormone in man?

Small doses (1-10 microgram daily) of 24,25-dihydroxycholecalciferol (24,25-(OH)2D3), a renal metabolite of vitamin D of uncertain function, increased intestinal absorption of calcium in normal people and in patients with various disorders or mineral metabolism, including anephric subjects. In five of six patients studied, calcium balance increased, but, unlike 1,25-dihydroxycholecalciferol, 24,25-(OH)2D3 did not increase plasma or urinary calcium concentrations. These results suggest that 24,25-(OH)2D3 may be an important regulator of skeletal metabolism in man with potential value as a therapeutic agent.

Adult↗
PubMed1978

Cross-linking of lipid bilayers by central nervous system myelin basic protein: aggregation of free and vesicle-bound protein.

Central nervous system myelin basic protein binds to the zwitterionic lipid, egg diacylphosphatidylcholine, over a wide range of pH and ionic strength. Lipid vesicles containing the protein have been observed to increase in size and to aggregate. The size increase is most marked at very low ionic strengths whereas aggregation is evident at ionic strengths from 0.001 to 0.35. The pH and ionic-strength dependence of this aggregation closely follows that of the self-association of the protein, suggesting that vesicle association is mediated by binding between polypeptides attached to different vesicles. Basic protein is monomeric at low pH but above pH 6 self-associates yielding primarily small oligomers (probably dimers) and minor amounts of higher species. It is envisaged that each protein molecule possesses two distinct binding sites, one capable of association with lipid bilayers and the second with another protein molecule. Basic protein is found predominantly on the intracellular surface of the myelin membrane. Given the ability of the protein to act as a bridge between lipid bilayer vesicles in vitro it is proposed that it may perform a similar function in vivo, serving to cross-link the inner surfaces of the oligodendroglial cell membrane. This protein function could lead to formation of the long cellular processes which encircle the nerve cell axon and could assist in stabilizing the highly ordered myelin structure which results.

Animals↗
PubMed1978

Physiological and pharmacological aspects of 24,25-dihydroxycholecalciferol in man.

The present study describes the response to small oral doses (1--10 microgram/day) of 24,25-DHCC in man. Contrary to expectation, 24,25-DHCC was as potent as 1,25-DHCC in increasing intestinal absorption of calcium both in normal persons and in patients with a variety of disorders of calcium metabolism. Despite this increase in intestinal absorption, plasma and urine calcium did not increase after 24,25-DHCC as they did after 1,25-DHCC. Metabolic balance studies showed calcium balances to increase by 1.6 to 11.5 mmoles/day in 5 of the 6 patients studied. 24,25-DHCC increased intestinal absorption of calcium equally well in anephric patients, suggesting that conversion of 24,25-DHCC to 1,24,25-trihydroxycholecalciferol by the kidney cannot be the sole mechanism by which 24,25-DHCC expresses biological activity, even though in vitamin D deficient rats nephrectomy does abolish the ability of large doses of 24,25-DHCC to increase calcium absorption. It is concluded that 24,25-DHCC may be a calcium-regulating hormone in man. In view of the effects demonstrated here and its relatively high concentration in plasma and slow turnover rate, 24,25-DHCC has the properties that might be ideal for a long-acting stimulator of bone mineralisation. Further work is needed to explain why 24,25-DHCC has effects in man which are not readily seen in other species.

Bone Development↗