Search PubMed⌕ Search

Biomedical subjects

G Reynolds

Publications and source records attributed to G Reynolds.

At least 73 records · Page 4Linked to original sources

Haemodynamic dose-response effects of intravenous nisoldipine in coronary artery disease.

The circulatory consequences of slow-calcium channel blockade with a new dihydropyridine nisoldipine were evaluated at rest and during exercise-induced angina in 16 patients with angiographically proven coronary artery disease. In 10 patients resting cardiac stroke output (thermodilution) and pulmonary artery occluded pressure were determined following four intravenous nisoldipine injections (cumulative dosage of 1, 2, 4 and 8 micrograms kg-1). The exercise effects of nisoldipine were evaluated by comparing the effects of the 8 micrograms kg-1 cumulative dosage with a control exercise period at the same workload. At rest nisoldipine reduced systemic vascular resistance and mean arterial pressure, and increased heart rate, cardiac and stroke volume indices. During 4 min supine-bicycle exercise nisoldipine reduced systemic mean arterial pressure and vascular resistance; this resulted in augmented cardiac and stroke volume indices at an unchanged pulmonary artery occluded pressure. In six additional patients rest and exercise ejection fractions were measured using a nonimaging nuclear probe. Nisoldipine (4 micrograms kg-1) resulted in a small trend to increase left ventricular rest and exercise ejection fraction. These data demonstrated improved rest and exercise cardiac performance following nisoldipine in patients with severe coronary artery disease.

Adult↗

A study of the long-term efficacy and tolerability of oral nicardipine in hypertensive patients.

This study was designed to evaluate the efficacy of oral nicardipine in 91 patients with uncomplicated essential hypertension over a period of 12 months. All patients started on a fixed nicardipine dose of 30 mg three times daily which was adjusted in the range 10-40 mg three times daily, where necessary to achieve a target diastolic blood pressure less than 95 mm Hg. At 6 weeks, blood pressure (mean +/- s.e. mean) was reduced from an average of 190 +/- 22/112 +/- 8 to 167 +/- 23/96 +/- 11 mm Hg supine and from 180 +/- 21/113 +/- 7 to 154 +/- 17/95 +/- 11 mm Hg standing and remained controlled in all patients throughout the study. A total of 96 unwanted experiences were reported by 49 patients (54%); 17 (19%) reported a single symptom once and two (2%) reported a single symptom more than once. The most frequently reported adverse experiences were peripheral oedema in 27 (28%) and headaches in 15 patients (16%). The majority of the adverse experiences occurred in the first 3 months of treatment. Ten patients (11%) withdrew from the study during this time and eight (9%) in the subsequent 9 months because of drug-related side effects; five others (5%) withdrew for unrelated reasons. The incidence of adverse experiences was dose-related. Three patients reported unwanted effects on 10 mg three times daily, eight on 20 mg three times daily, 36 on 30 mg three times daily, and 12 on 40 mg three times daily oral nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Comparative haemodynamic effects of nicardipine and verapamil in coronary artery disease.

The haemodynamic relevance of the disparate electrophysiological and structural differences between agents blocking the slow-calcium channels in patients with exercise-induced angina pectoris is controversial. We therefore evaluated the effects of single intravenous and equivalent hypotensive doses of nicardipine (7.5 mg) or verapamil (16 mg) in a randomized single-blind study of 30 patients with angiographically documented coronary artery disease. The randomization process achieved comparable distribution of 15 patients with similar demographic data and cardiac function to each drug. Patients were evaluated at rest and during four minutes upright bicycle exercise at an individually titrated symptom-limited load in both control and post-drug assessments; the reproducibility of the haemodynamics during such tests has been previously demonstrated. Both nicardipine and verapamil induced similar reductions in systemic mean arterial blood pressure and vascular resistance; the reduction in afterload resulted in increased resting cardiac index and stroke volume index on each agent. The magnitude of the former increase was greater following nicardipine (p less than 0.05). The pulmonary artery occluded pressure (PAOP) increased following verapamil (p less than 0.01) without change following nicardipine. During dynamic exercise, neither drug improved cardiac stroke volume index, the PAOP was significantly higher following verapamil compared with nicardipine (p less than 0.05). Analysis of the cardiac performance curve demonstrated its significant depression following verapamil but not following nicardipine. Thus clear haemodynamic advantages were present, both at rest and during exercise-induced angina, for nicardipine; whether such haemodynamic effects will be reflected in symptomatic terms should be critically evaluated.

Adult↗

Is the intrinsic sympathomimetic activity (ISA) of beta-blocking compounds relevant in acute myocardial infarction?

The relevance of the intrinsic sympathomimetic activity (ISA) of beta-blocking compounds to the clinical therapeutics of acute myocardial infarction was evaluated in 20 patients with an uncomplicated acute myocardial infarction by comparing the haemodynamic effects of equivalent beta-blocking doses of propranolol (non-cardioselective; no ISA) and pindolol (non-cardioselective; 50% ISA). Consecutive eligible male patients admitted to a Coronary Care Unit were randomised following a 1 h control period to two separate studies. In Study 1 the short-term dose-response effects of propranolol (1-8 mg) or pindolol (0.1-0.8 mg) were assessed. In Study 2 comparison of the effects of single i.v. propranolol (8 mg) and pindolol (0.8 mg) doses was undertaken over 6 h. Haemodynamic variables and thermodilution cardiac output were subsequently recorded to compare the effects of each drug on the circulation. The plasma concentrations of propranolol and pindolol were in the recognised therapeutic range. Both drugs were clinically well-tolerated, the changes induced in haemodynamic variables following each drug demonstrated effective beta-blockade. Within the limits of the experimental protocol, these data did not suggest definite haemodynamic advantage for ISA of pindolol in acute myocardial infarction. These findings are perhaps due to sympathetic activation in acute myocardial infarction attenuating the haemodynamic impact of ISA.

Adrenergic beta-Antagonists↗

Haemodynamic effects of intravenous nicardipine during upright exercise in patients with stable angina pectoris.

The immediate haemodynamic effects, at rest and during exercise, of 2.5 and 10mg intravenous nicardipine were measured in 20 male patients with uncomplicated angina pectoris due to angiographically confirmed coronary artery disease. At rest, both doses of nicardipine resulted in reductions in the systemic arterial pressure and vascular resistance and increases in heart rate and cardiac output. The changes were greater after the larger than after the smaller dose of nicardipine. During exercise, neither dose of nicardipine resulted in a substantial change in the haemodynamic profile, except that after the larger dose heart rate and cardiac output were higher than in the control study. These results indicate that the major overall haemodynamic effect of intravenous nicardipine is dilatation of the systemic arteriolar resistance vessels associated with reflex increase in cardiac pumping activity.

Adult↗

Haemodynamic effects of nicardipine in acute myocardial infarction.

The haemodynamic dose-response effects of the slow-calcium channel blocker nicardipine were evaluated in fifteen male patients with uncomplicated acute myocardial infarction. Following a 1 hr control period, during which the stability of base-line control haemodynamic variables was confirmed, four i.v. boluses of 1.25, 1.25, 2.5 and 5.0 mg of the drug (cumulative dosage 1.25, 2.5, 5.0 and 10.0 mg) were administered at 15 min intervals. The plasma concentrations achieved are within the previously described therapeutic range (greater than 20 micrograms/l). Nicardipine resulted in linear reductions in systemic arterial pressure and vascular resistance, and dose-related increases in heart rate, cardiac and stroke output without change in the left heart filling pressure. Intravenous nicardipine did not induce any depression of left ventricular pumping performance in our patients in the early stages of uncomplicated myocardial infarction.

Blood Pressure↗

Hepatitis B in homosexual men: prevalence of infection and factors related to transmission.

Of 3,816 homosexual men examined in five sexually transmitted disease clinics in the United States, 6.1% had hepatitis B surface antigen, 52.4% had antibody to hepatitis B surface antigen, and 3.0% of the men who had no other indicator of infection with hepatitis B virus (HBV) had antibody to hepatitis B core antigen. The rate of seropositivity for HBV indicated by the presence of one or more of these serologic markers was 61.5%; seropositivity was significantly related to the duration of regular homosexual activity and to the number of nonsteady male sexual contacts in the four months before the patients were interviewed. Anal-genital intercourse, oral-anal intercourse, and rectal douching were significantly related to evidence of HBV infection, but oral-oral contact and oral-genital contact were not. Trauma to the rectal mucosa is a feature common to the practices that were significantly related to seropositivity for HBV.

Adolescent↗

Metastatic duodenojejunal carcinoma from ovarian primary.

A 55-year-old woman presented with symptoms of progressive sub-acute high gastrointestinal obstruction. Barium studies, upper gastrointestinal endoscopy, ultrasound and ERCP were normal. Diagnosis was therefore delayed. At laparotomy, malignant tumours were found at the duodenojejunal flexure and left ovary, which were histologically identical and consistent with an ovarian primary. Endoscopic techniques for visualization of the third and fourth parts of the duodenum should be employed after barium studies, including careful screening in this area, have failed to reveal pathology.

Adenocarcinoma↗

Regulation of collagen synthesis by ascorbic acid.

After prolonged exposure to ascorbate, collagen synthesis in cultured human skin fibroblasts increased approximately 8-fold with no significant change in synthesis of noncollagen protein. This effect of ascorbate appears to be unrelated to its cofactor function in collagen hydroxylation. The collagenous protein secreted in the absence of added ascorbate was normal in hydroxylysine but was mildly deficient in hydroxyproline. In parallel experiments, lysine hydroxylase (peptidyllysine, 2-oxoglutarate:oxygen 5-oxidoreductase, EC 1.14.11.4) activity increased 3-fold in response to ascorbate administration whereas proline hydroxylase (prolyl-glycyl-peptide, 2-oxoglutarate:oxygen oxidoreductase, EC 1.14.11.2) activity decreased considerably. These results suggest that collage polypeptide synthesis, posttranslational hydroxylations, and activities of the two hydroxylases are independently regulated by ascorbate.

Ascorbic Acid↗

Contractile basis of ameboid movement. VII. Aequorin luminescence during ameboid movement, endocytosis, and capping.

Aequorin luminescence has been utilized to determine the spatial and temporal fluctuations of the free calcium ion concentration [Ca++] in Chaos carolinensis during ameboid movement, pinocytosis, and capping. The [Ca++] increases above approximately 10(-7) M during normal ameboid movement. Three types of luminescent signals are detected in cells: continuous luminescence, spontaneous pulses, and stimulated pulses. Continuous luminescence is localized in the tails of actively motile cells, and spontaneous pulses occur primarily over the anterior regions of cells. We are sometimes able to correlate the spontaneous pulses with extending pseudopods, whereas stimulated pulses are induced by mechanical damage, electrical stimulation, concanavalin A-induced capping, and pinocytosis. The localization of both distinct actin structures and sites where [Ca++] increases suggests cellular sites of contractile activity. The independent evidence from localizing actin structures and the distribution of [Ca++] can also be viewed in relation to the solation-contraction coupling hypothesis defined in vitro.

Actins↗

Nonlinear pharmacokinetics of ethanol: the disproportionate AUC-dose relationship.

Whole venous blood concentrations of ethyl alcohol were measured following the constant rate intravenous infusion of ethanol to four Beagle dogs. Five different doses (0.1-0.8 g ethanol/kg body weight) were administered at scheduled intervals. The area under the blood ethanol concentration-time curves (AUC) was found to demonstrate a markedly nonlinear relationship with the administered dose. Simulations of one and two compartment open models with Michaelis-Menten elimination kinetics and zero-order input are presented with their theoretical AUC-dose relationships.

Animals↗

A potent contact allergen of Phacelia (Hydrophyllaceae).

The major contact allergen of Phacelia crenulata (Hydrophyllaceae) has been identified as geranylhydroquinone. A maximization test of geranylhydroquinone showed this to be a potent sensitizer comparable in degree to poison oak/ivy urushiol. Comparative patch testing on humans with urushiol established that the phacelia allergen does not cross-react with poison oak or ivy.

Allergens↗

Interaction of zinc and essential fatty acids in the rat.

Three experiments were performed to investigate the possibility of a physiological relationship between zinc and essential fatty acids (EFA). Male weanling rats were fed diets low in zinc, EFA or both and their growth rates, dermal scores and tissue fatty acid profiles determined. In experiment 1, a basal soybean protein diet containing 7 ppm of added zinc and approximately 300 ppm EFA was used in a 2 X 2 factorial design: low Zn-low EFA; adequate Zn-low EFA; low Zn-adequate EFA and adequate Zn-adequate EFA. The low zinc status accentuated signs of EFA deficiency, including dermal lesions and growth rate, but it had no significant effect on the fatty acid profile in plasma. In experiment 2, a basal casein diet containing approximately 25 ppm of EFA and less than 1 ppm of zinc, was used in a similar design. For 7 weeks two groups of weanling rats were fed ad libitum either a diet adequate in Zn and low in EFA or a diet adequate in all nutrients. From 7 to 12 weeks zinc was removed from one-half of each group and all were pair-fed to the intake of the low zinc-low EFA group. Zinc deficiency accentuated dermal lesions in the group deprived of EFA and caused enlarged joints suggestive of an arthritic-like syndrome. In experiment 3, an egg albumin based diet containing approximately 25 ppm EFA and less than 1 ppm of zinc was used in a 2 X 2 factorial design. No signs of fatty acid deficiency occurred in 5 weeks with adequate zinc. Zinc and EFA deficiency accentuated dermal scores and severely depressed growth. Zinc deficiency increased the proportion of arachidonic acid in foot skin especially in the EFA deficient group. It is concluded that there is a physiological interaction between Zn and essential fatty acids.

Animals↗

The phosphohydrolase activity in lamellar bodies and its relationship to phosphatidylglycerol and lung surfactant formation.

Phosphohydrolase activity of a lamellar body-enriched preparation from pig lung was examined to ascertain if two separate enzymes catalyze the hydrolysis of phosphatidic acid and phosphatidylglycerol 3-phosphate. From sulfhydryl inhibition, heat inactivation and substrate specificity studies, we suggest that one phosphohydrolase may account for the hydrolysis of both substrates. The relationship of the reported experiments to the biosynthesis of the glycerophospholipids present in surfactant is discussed.

Animals↗