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Biomedical subjects

A Gill

Publications and source records attributed to A Gill.

At least 73 records · Page 4Linked to original sources
PubMed1988

2-Ethynylbenzenealkanamines. A new class of calcium entry blockers.

A series of 2-(aryl- or alkylethynyl)benzenealkanamines were synthesized. They exhibit antihypertensive activity in spontaneously hypertensive rats and coronary vasodilator activity with minimal negative inotropic activity in the "Langendorff" guinea pig heart in vitro. They have been shown to exert their activity by inhibition of Ca2+ influx across cell membranes. Optimal activity is found among the N-(arylethyl)-5-methoxy-alpha-methyl-2-(phenylethynyl)ben zeneethanamines and -propanamines.

Alkynes↗
PubMed1988

Effects of the novel calcium channel blocker, McN-5691, on cardiocirculatory dynamics and cardiac output distribution in conscious spontaneously hypertensive rat.

The purpose of this study was to characterize the cardiocirculatory effects of McN-5691 in the conscious spontaneously hypertensive rat (SHR) and in age matched Wistar-Kyoto (WKY) control rats. Animals were instrumented under halothane anesthesia for right atrial, left ventricular arterial, and venous pressure recordings. The radioactive microsphere technique was used to estimate regional blood flow and cardiac output before (control) and during intravenous (i.v.) infusion of either McN-5691 at three dosage levels (0.3, 1.0, 3.0 mg/kg), or vehicle (VH) at an infusion rate of 0.0408 ml/min. The predominant hemodynamic effect of McN-5691 (cumulative dose = 0.3-4.3 mg/kg i.v.) in conscious SHR was dose-related reduction in mean arterial pressure with normalization occurring at a cumulative dose of 1.3 mg/kg i.v. The antihypertensive effect of McN-5691 was accompanied by reductions in left ventricular peak systolic pressure (cumulative dose = 1.0-4.3 mg/kg i.v.), arterial pressure-rate product (1.3-4.3 mg/kg i.v.), and systemic vascular resistance (4.3 mg/kg i.v.). McN-5691 had no statistically significant effect on heart rate or cardiac contractility as measured by dP/dt/peak left ventricular pressure. The predominant peripheral vascular effects of McN-5691 were increases in skeletal muscle blood flow (4.3 mg/kg i.v.) and reductions in skeletal muscle (1.3-4.3 mg/kg i.v.), renal (1.3-4.3 mg/kg i.v.), gastrointestinal (4.3 mg/kg i.v.), and coronary (1.3-4.3 mg/kg i.v.) vascular resistances. Despite the fall in renal vascular resistance, renal blood flow was not changed by McN-5691. McN-5691 did not have major effects on other regions of the peripheral circulation. Thus, McN-5691 is an antihypertensive agent as defined by its ability to normalize blood pressure in the SHR, and the hemodynamic mechanism leading to this effect is reduction in peripheral vascular resistance. This antihypertensive effect is not accompanied by reflex tachycardia and is not associated with negative inotropic activity or detrimental peripheral circulatory changes in the conscious SHR.

Animals↗
PubMed1987

cDNA clone encoding a high molecular weight antigen of Babesia bovis.

An expression library was constructed by inserting cDNA copied from mRNA of the blood stages of Babesia bovis isolate KA into bacteriophage lambda gt11-amp3. An antigen-positive cDNA clone detected by screening the library with antibodies from cattle vaccinated with the KA isolate was shown to encode part of a high-molecular weight polypeptide antigen of B. bovis. This molecule was a dominant immunogen and was found by immunofluorescence to be within the parasite in infected erythrocytes.

Animals↗
PubMed1986

Postnatal growth in infants born before 30 weeks' gestation.

The postnatal weight pattern up to 14 weeks after birth was determined in 184 singleton survivors born at 23 to 29 weeks' gestation in whom routine parenteral nutrition was used before milk feeding was established. A mean postnatal weight loss of 14% of birth weight occurred at a mean of 6 days. The more immature infants had significantly higher postnatal weight loss and longer time to regain birth weight despite a higher volume intake in the first week. From the fourth postnatal week all gestational subgroups had a mean weight gain at above intrauterine growth rate. As a result of the initial period of weight loss, however, the mean body weight remained below the 10th percentile of the intrauterine growth curve. The early growth rate in infants small for gestational age was higher than those who were appropriate weight for gestation, although the mean body weight of the former group remained significantly lower at 2 years.

Aging↗
PubMed1986

Effects of bepridil hydrochloride on calcium-induced responses in guinea pig Langendorff heart.

A spontaneously beating guinea pig Langendorff heart preparation was used to evaluate and compare the effects of bepridil hydrochloride (BP) and other Ca blockers. Cardiac contractile force was measured in isolated hearts perfused at constant pressure with nonrecirculating Krebs-Henseleit physiological salt solution (PSS). The calcium-induced inotropic response was assessed by measuring contractile force during stepwise increases in PSS Ca concentration. The results suggest that the effects of BP on cardiac muscle are different from those of the other Ca blockers tested and may involve multiple cellular mechanisms of action.

Animals↗
PubMed1986

[Preventive chemotherapy of superficial tumors of the bladder].

A retrospective study of 135 patients with superficial transitional cancer of bladder (pTa - pT1) was conducted after follow-up for at least 3 years following treatment for 2 years at the "Instituto de Urología, Nefrología y Andrología (Fundación Puigvert)". Patients had been randomly allocated for treatment with: RTU alone, RTU + instillation of Thiotepa and RTU followed by instillations of Adriamycin. Chemotherapy was administered preventively. Recurrence after 3 years and possible progression towards infiltration during this period were evaluated, and the usefulness of this type of treatment questioned because of the cost/benefit ratio and small intergroup differences found.

Administration, Topical↗
PubMed1983

Sustained concurrent blood pressure and salt/water balance in unrestrained rats.

Methodology is detailed that provides sustained concurrent measurement of fluid volume and electrolyte intake and output with direct measurement of arterial pressure in unrestrained, unanesthetized spontaneously hypertensive rats (SHR). This method employs an all-Teflon arterial pressure conduction system, an air-pressurized infusion system, and standard rat metabolism cages. Blood pressure-salt/water balance studies comparing SHR unoperated, sham operated, and infused at several infusion rates and saline normalities indicated that infusion of 0.25 N saline at 0.5 ml/h sustained a patent system for high-fidelity recording of systolic and diastolic blood pressure without distortion of homeostasis over a 3-week period. Studies of basal SHR blood pressure and salt/water balance suggested that the SHR primarily used renal water-conserving mechanisms to dilute net acquired salt over an 11-day period. This methodology for sustained blood pressure measurement appears to represent a significant improvement for direct blood pressure measurement in unrestrained, unanesthetized rats.

Animals↗
PubMed1982

Reduced sympathetic nervous system responsivity associated with the relaxation response.

Sympathetic nervous system activity was assessed in experimental and control subjects who were exposed to graded orthostatic and isometric stress during monthly hospital visits. After the first session, the experimental subjects practiced a technique that elicited the relaxation response. Their concentrations of plasma norepinephrine during subsequent graded stresses were significantly higher. No such changes were noted in the control group. These results were than replicated in the control group in a crossover experiment. The groups did not differ in their heart rate and blood pressure responses. These observations are consistent with reduced norepinephrine end-organ responsivity after regular elicitation of the relaxation response.

Adult↗
PubMed1982

Metabolic interactions of glucagon and cortisol in man--studies with somatostatin.

The metabolic response to pathophysiologic concentrations of glucagon, induced by glucagon infusion, has been examined in normal man before and after 36-60 hr hypercortisolaemia, induced by administration of tetracosactrin-depot. Glucagon alone increased serum insulin levels twofold but blood glucose was unaltered. Plasma NEFA and blood ketone body concentrations were decreased by glucagon infusion. Tetracosactrin produced a threefold rise in serum cortisol levels and caused mild fasting hyperglycemia and hyperinsulinaemia. Subsequent glucagon infusion had no effect on circulating insulin, glucose, NEFA or ketone body concentrations. Simultaneous infusion of somatostatin, to produce partial insulin-deficiency, unmasked a hyperglycemic action of glucagon (+ 3.8 +/- 0.2 mmol/l at 90 min, p less than 0.02). This glucagon-induced rise in blood glucose was diminished by prior tetracosactrin administration. Tetracosactrin revealed a mild lipolytic action of glucagon in partial insulin deficiency, not apparent in the euadrenal state. Glucagon was equally hyperketonemic during somatostatin infusion before and after tetracosactrin. Thus the hyperglycemic and hyperketonemic actions of glucagon at pathophysiologic levels are restricted to insulin deficiency. Hypercortisolaemia reveals a lipolytic action of glucagon in insulin-deficient man but does not potentiate the hyperglycemic or hyperketonemic effects.

Adult↗
PubMed1982

Metabolic effects of cortisol in man--studies with somatostatin.

The metabolic effects of chronic hypercortisolaemia were studied by administration of tetracosactrin-depot, 1 mg I.M. daily for 36-60 hr to normal subjects. Partial insulin and glucagon deficiency were induced at the end of the period by infusion of somatostatin, 100 micrograms/h for 210 min. Tetracosactrin alone induced a three fold rise in basal serum cortisol levels and fasting blood glucose concentration rose from 5.2 +/- 0.2 to 7.2 +/- 0.2 mmole/l (p less than 0.01) with a rise in fasting serum insulin from 5.2 +/- 1.2 to 13.1 +/- 1.9 mU/l (p less than 0.02). Concentrations of the gluconeogenic precursors lactate, pyruvate and alanine were also raised, but non-esterified fatty acid, glycerol and ketone body levels were unchanged. Somatostatin infusion caused a 30%-50% decrease in serum insulin and a 20%-60% decrease in plasma glucagon concentrations both before and after tetracosactrin administration. A similar rise in blood glucose concentration, relative to the saline control, occurred over the period of somatostatin infusion both with and without elevated cortisol levels. However, prior tetracosactrin administration caused a 100% greater rise in blood ketone body concentrations during infusion of somatostatin than was seen in the euadrenal state, despite similar plasma NEFA concentrations. Hypercortisolaemia causes hyperglycaemia and elevated gluconeogenic precursor concentrations but the associated rise in serum insulin concentrations limits lipolysis and ketosis. In insulin deficiency, a ketotic effort of glucocorticoid excess is evident which may be independent of lipolysis and occurs despite concurrent glucagon deficiency. These catabolic actions of cortisol are likely to be of major importance in the metabolic response to stress.

Adult↗
PubMed1980

Ongoing outcome research on short-term dynamic psychotherapy.

In this paper short-term dynamic psychotherapy (STAPP) is described briefly in terms of its selection criteria and technique, and the preliminary findings of an ongoing outcome study are presented. Of 22 experimental patients who were treated with STAPP, 14 were rated as 'recovered' by two evaluators, 4 were 'much better', 3 'little better' and 1 was 'unchanged'. Of 8 controls who waited a period of 2--5 months, 5 were 'unchanged' and 3 'a little better' at the end of their waiting period. When they were treated subsequently, 4 had 'recovered', 2 were 'much better' and 2 withdrew having moved from the Boston area. The complexities inherent in psychotherapy evaluation are described, and the 3 patients who improved 'a little' and the 1 who was 'unchanged' are discussed briefly.

Anxiety↗
PubMed1978

Hormonal regulation of ketone-body metabolism in man.

The main hormones involved in ketone-body metabolism are the anabolic hormone insulin and the primarily catabolic hormones, glucagon, cortisol, catecholamines and growth hormone. These hormones may regulate ketone-body metabolism at three sites: adipose tissue, by regulating fatty acid supply to the liver; the liver itself, by determining the relative activities of the re-esterification and fatty acid oxidation pathways; and the periphery, by influencing the rate of extrahepatic utilization of ketone bodies. The first two are quantitatively the most important. Insulin acts on all three regulatory sites. In adipose tissue lipolysis is inhibited and re-esterification enhanced with consequent decrease of fatty acid release. Both these processes are extremely insulin-sensitive. In the liver insulin increases fatty acid synthesis and esterification. At the same time malonyl-CoA formation is increased, which inhibits the acylcarnitine transferase system and thus decreases the transport of fatty acids into mitochondria and hence fatty acid oxidation and ketogenesis. Insulin also has a small stimulatory effect on extrahepatic ketone-body utilization. The effects of glucagon depend on whether insulin is present. In normal man glucagon stimulates insulin secretion and the predominant effect is that of insulin, i.e. decreased ketogenesis. In insulin deficiency glucagon has a mild stimulatory effect on lipolysis, increasing fatty acid supply to the liver. The main effects of glucagon are, however, on the liver. It activates the carnitine acyltransferase system through inhibition of malonyl-CoA synthesis. Fatty acid oxidation is increased and ketogenesis enhanced. The overall effect on the liver depends on the relative amounts of insulin and glucagon present. Studies with somatostatin show that glucagon can increase ketogenesis acutely when insulin secretion is inhibited in normal man, but the effects are short-lived. Cortisol has similar effects to glucagon. In the presence of insulin there is a small increase in fatty acid mobilization from adipose tissue, secondary to impaired glucose entry, and perhaps a small effect on lipolysis itself. This fatty acid is, however, directed to triacylglycerol in the liver. In insulin deficiency, again demonstrated by somatostatin infusion, the incoming fatty acidstone-body formation. The mechanism remains obscure. Catecholamines, in contrast, have their most potent effects on adipose tissue, stimulating lipolysis and fatty acid release even in the presence of insulin. They thus act mainly by enhancing precursor supply and have only minor effects on liver and no effect on peripheral utilization. Growth hormone, like glucagon, has little effect in the presence of insulin, but can enhance ketogenesis in insulin deficiency, although again the mechanism is unknown. Thus in normally fed man the effects of insulin will be overriding and little ketogenesis occurs because of limited fatty acid availability in the liver...

Adipose Tissue↗