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Biomedical subjects

G B Phillips

Publications and source records attributed to G B Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1992

The variability of the serum estradiol level in men: effect of stress (college examinations), cigarette smoking, and coffee drinking on the serum sex hormone and other hormone levels.

The results of studies carried out to evaluate the relationship of estradiol to coronary heart disease and its risk factors in men have been conflicting. Three possible causes of these conflicting results are (a) an inherent variability of the estradiol level within individual men; (b) the confounding effects on the estradiol level of certain common exogenous factors such as psychological stress, cigarette smoking, and coffee drinking; and (c) methodology and study design. The present study was conducted to test in men the inherent variability of the serum estradiol level and the effects of psychological stress (college examinations), cigarette smoking, and coffee drinking on the serum estradiol level. Subsets of 41 men, 19-57 years of age, were studied. A highly significant correlation in the estradiol levels was found between two fasting samples taken 30 minutes, 19.1 (mean) days, 2-6 months, and 10-89 months apart. Neither the stress of college examinations nor 30 minutes of cigarette smoking or coffee drinking had any apparent effect on the serum estradiol level, even in the presence of a two- to fivefold increase in the level of other hormones in four subjects with an autonomic reaction (three to smoking and one to venipuncture). It appears that the serum estradiol level is remarkably stable in men when taken under controlled conditions and that neither inherent fluctuation in this level nor the effects of the exogenous factors as studied are responsible for the conflicting results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Synthesis and cardiac electrophysiological activity of aryl-substituted derivatives of the class III antiarrhythmic agent sematilide. Potential class I/III agents.

Twelve novel derivatives of the selective class III antiarrhythmic agent sematilide were prepared in an attempt to incorporate both class I and class III electrophysiological properties into a single molecule. Electrophysiological activity was determined by standard microelectrode techniques in canine cardiac Purkinje fibers. Initial assessment of class I efficacy was carried out in a ouabain-induced arrhythmia model in guinea pigs. All of the compounds prolonged action potential duration in Purkinje fibers (class III activity), and three were active against ouabain-induced arrhythmias (class I activity). Selected compounds were evaluated further in dogs for efficacy against arrhythmias occurring 24 h following coronary ligation (automatic arrhythmias) and induced by using programmed electrical stimulation techniques (reentrant arrhythmias). The most effective compounds from the series are 3g and -j, which were effective in both canine models. Molecular modeling and structure-activity relationships are discussed.

Action Potentials↗
PubMed1990

Synthesis and cardiac electrophysiological activity of N-substituted-4-(1H-imidazol-1-yl)benzamides--new selective class III agents.

The synthesis and cardiac electrophysiological activity of 18 N-substituted imidazolylbenzamides or benzene-sulfonamides are described. Compounds 6a,d,f-k and 11 exhibited potency in the in vitro Purkinje fiber assay comparable to that of N-[2-(diethylamino)ethyl]-4- [(methylsulfonyl)amino]benzamide (1, sematilide), a potent selective class III agent which is undergoing clinical trials. These data indicate that the 1H-imidazol-1-yl moiety is a viable replacement for the methylsulfonylamino group for producing class III electrophysiological activity in the N-substituted benzamide series. N-[2-(Diethylamino)ethyl]-4-(1H-imidazol-1-yl)benzamide dihydrochloride (6a) was further studied in two in vivo models of reentrant arrhythmias and showed potency and efficacy comparable to those of 1.

Animals↗
PubMed1990

Synthesis of novel (aryloxy)propanolamines and related compounds possessing both class II and class III antiarrhythmic activity.

Several (aryloxy)propanolamines and related compounds (i.e. 5-13, 16-18, 20-24, 27-33, 35, 37-39, 41, and 42) were synthesized and investigated for their class III electrophysiological activity and class II (beta-blocking) effects with use of in vitro and in vivo models. Structure-activity relationships are discussed for a series of 30 compounds. A number of these compounds prolonged the action potential duration at 95% repolarization of isolated canine cardiac Purkinje fibers by 20% (C20APD95) at concentrations of less than 1.0 microM, with no significant effects on cardiac conduction. beta-Adrenergic receptor binding studies showed that some of these compounds were 2-20 times more potent for cardiac beta 1 receptors than for beta 2 receptors. In particular, compounds 32, 41, 1, and especially (S)-1 were found to be orally active class III agents in anesthetized mongrel dogs (1 or 3 mg/kg, id) and efficacious at suppressing programmed electrical stimulation induced arrhythmias in halothane-anesthetized dogs. The profile of these compounds was similar to that found for sotalol. Compound (S)-1, which was more potent than sotalol in the PES study and equieffective in the halothane/epinephrine dog model, is being investigated further as a combined class III/II antiarrhythmic agent.

Action Potentials↗
PubMed1988

Serum sex hormone levels and myocardial infarction in the Honolulu Heart Program. Pitfalls in prospective studies on sex hormones.

It has been hypothesized that hyperestrogenemia may underlie myocardial infarction. As a test of this hypothesis, the serum estradiol and testosterone levels were estimated in samples collected prospectively from 96 male patients aged 52-74 years [mean age 60.8 +/- 6.3 (SD)] who had had a myocardial infarction and from 96 matched control subjects in the Honolulu Heart Program. Established risk factors for myocardial infarction were measured prospectively. No significant difference between patients and control subjects in mean estradiol or testosterone level was observed. The only established risk factor that was significantly different was blood pressure, which was higher in the patients. Thus, the data did not confirm the hypothesis. However, two major pitfalls for prospective studies of estradiol in myocardial infarction, which might have affected the validity of the results, were observed, namely, deterioration of estradiol values with prolonged storage (8.5-12 years in this study) and intervention. The value of this study, therefore, may lie in pointing out difficulties in carrying out prospective studies on sex hormones.

Aged↗
PubMed1985

Levels of serum sex hormones and risk factors for coronary heart disease in exercise-trained men.

On the basis of previous findings, it has been hypothesized that hyperestrogenemia may be the major predisposing factor for coronary heart disease and that an elevation in the estradiol-to-testosterone ratio, or a closely related hormonal alteration, may cause the expression of risk factors for coronary heart disease. The present study was carried out to investigate whether exercise training, which has been reported to reduce risk factors for coronary heart disease, affects the serum sex hormone levels. The serum sex hormone levels, established risk factors for coronary heart disease, and physical fitness were measured in 10 men who had undergone at least six months of intensive exercise training and in 10 sedentary men of similar age. Despite evidence for a strikingly higher level of physical fitness and a lower level of risk factors in the trained group, no significant difference in mean serum estradiol level was found. Nor did three subjects from the sedentary group show a decrease in estradiol level after three to four months of exercise training. The mean estradiol-to-testosterone ratio, however, was significantly lower in the trained group and might account for the lower level of risk factors in that group. If the hypothesis is correct, exercise training may decrease established risk factors for coronary heart disease without decreasing the risk of coronary heart disease.

Adult↗
PubMed1984

Evidence for hyperestrogenemia as the link between diabetes mellitus and myocardial infarction.

The previous findings of hyperestrogenemia in men with myocardial infarction and of a correlation between the ratio of serum estradiol to testosterone and the glucose-insulin-lipid defect have led to the hypothesis that hyperestrogenemia may be responsible for the increased incidence of atherosclerosis and its complications in patients with diabetes. The hypothesis predicts that the mean serum level of estradiol and the ratio of serum estradiol to testosterone are elevated in patients with diabetes. To test this hypothesis, the serum levels of estradiol and testosterone were measured in 21 nonobese men with diabetes and in 19 apparently healthy men of similar age and weight. A higher mean serum estradiol level (p less than 0.001) and estradiol-to-testosterone ratio (p less than 0.005) were observed in the patients with diabetes, whereas the mean serum testosterone level was not significantly different. The findings are consistent with the hypothesis.

Adult↗
PubMed1983

Association of hyperestrogenemia and coronary heart disease in men in the Framingham cohort.

The serum levels of estradiol and testosterone as well as established risk factors for coronary heart disease were estimated in 61 men (mean age 70.0 +/- 6.4 [SD] years) with coronary heart disease and in 61 matched control subjects enrolled in the Framingham Heart Study. The mean serum estradiol level was significantly higher in the subjects with coronary disease (p = 0.011). This difference in estradiol level increased with the exclusion of subjects older than 75 years (p less than 0.001). The mean serum testosterone level was not significantly different. None of the established risk factors for coronary heart disease was different between subjects with coronary disease and control subjects except blood glucose level, which was higher in the subjects with coronary disease (p = 0.025). We conclude that hyperestrogenemia is an important correlate of coronary heart disease in men.

Adult↗
PubMed1982

Acute myelomonocytic leukemia presenting as a primary cutaneous lymphoma of true histiocytes.

Malignant histiocytic and monocytic infiltrates of the skin are seen in true histiocytic lymphomas, in malignant histiocytosis, and in monocytic leukemias. Occasionally such cutaneous lesions constitute the presenting manifestation of the underlying malignancy. We report here a patient whose first manifestation of acute myelomonocytic leukemia was a malignant histiocytic infiltrate in the skin. Cytochemical and electron microscopic data confirmed the histiocytic nature of the skin tumor, and cytochemical data documented the myelomonocytic nature of the subsequent leukemia. Purely histiocytic skin tumors do not often presage myelomonocytic leukemias, although they have developed into monocytic leukemias, and monocytic leukemias have been transformed into myelomonocytic leukemias.

Aged↗
PubMed1981

Gastric cytomegalovirus infection in bone marrow transplant patients: an indication of generalized disease.

Cytomegalovirus infection in immunosuppressed patients is well known. It usually appears as an interstitial pneumonitis that may progress to a disseminated viral infection. The authors report on two patients who, after bone marrow transplantation, had signs and symptoms of gastric ulceration as the initial manifestation of cytomegalovirus infection. Both died with disseminated cytomegalovirus infection. Though gastric presentation is unusual for cytomegalovirus infection, epigastric pain and gastrointestinal hemorrhage in a bone marrow transplant patient may herald a potentially lethal viral infection.

Acute Disease↗