PubMed Health⌕ Search

Biomedical subjects

E Fisher

Publications and source records attributed to E Fisher.

At least 19 recordsLinked to original sources
PubMed1992

New nonpeptide angiotensin II receptor antagonists. 2. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)quinoline derivatives.

A novel series of nonpeptidic angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylcarboxylic acid or biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 2-alkyl quinoline. When evaluated in an in vitro binding assay using a guinea pig adrenal membrane preparation, compounds in this series generally gave IC50 values in the range 0.01-1 microM. Structure-activity studies showed the quinoline nitrogen atom and a short alkyl chain at the quinoline 2-position to be essential for receptor binding. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-2.0 mg/kg. One of the compounds, 2-ethyl-4-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methoxy]quinoline (5g), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg in AII-infused, normotensive rats, the compound exhibited a dose-related inhibition of the pressor response with a good duration of action at the higher doses. In a renal hypertensive rat model, compound 5g showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg. On the basis of its profile, this compound, designated ICI D8731, has been selected for clinical evaluation.

Angiotensin II↗
PubMed1991

Racial differences in social support and mental health in men with HIV infection: a pilot study.

The mediating role of social support in the mental health and behaviours of persons coping with life-threatening chronic illness is of potentially great importance in determining the quality of life of persons with HIV infection (PWHs). As part of a biracial pilot study of the ways black and white men manage the stresses of sexually acquired HIV infection, we have examined the relationship between social support and mental health and behaviours. Forty homosexual/bisexual men (20 white and 20 black) attending a Detroit hospital-based HIV outpatient clinic were recruited for the study and underwent physical and mental health (HSCL-59 and NIMH DIS interview), behavioural and psychosocial evaluations, and a neuropsychologic screening test battery. The black and white men did not differ in terms of age, education, sexual behaviours, physical or mental health status. However, the black men were less likely to be open about their sexuality to their primary social support network, and to report that their social support was less affirmative than did the white men. When correlations between the six-dimensional social support measures (Wortman & O'Brien, 1987) and HSC-L distress scores were examined, both availability of material social support and affirmation were correlated negatively with distress among the white men but positively among the black men. Similarly, the previously observed positive relationship between perceived adequacy of social support and adoption of safer sexual practices was observed among white but not black participants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Psychological↗
PubMed1991

Changes in hepatic glutathione metabolism in diabetes.

Glutathione is important in the regulation of the redox state, and a decline in its tissue level has often been considered to be indicative of increased oxidative stress in diabetes. In this study of diabetic rats, the level of hepatic glutathione was normal unless food intake was restricted. Thus, the previous report of a reduction in hepatic glutathione in diabetes is likely to be the result of food deprivation rather than diabetes alone. In contrast to changes characteristic of oxidative stress, the efflux of glutathione in bile from diabetic animals was significantly decreased, whereas hepatic mixed disulfides were unchanged, and the hepatic gamma-glutamyltransferase activity was considerably increased. These changes were not reproduced by food deprivation. The decrease in biliary excretion of glutathione in diabetes may reflect an attempt to conserve glutathione by activation of the hepatic gamma-glutamyl cycle. We conclude that the disturbances of glutathione metabolism in diabetes are not typical of those seen in oxidative stress or food restriction.

Animals↗
PubMed1991

Interaction of ascorbic acid and glucose on production of collagen and proteoglycan by fibroblasts.

Collagen and proteoglycans are two major constituents of the extracellular matrix, and their abnormalities have been incriminated in the pathogenesis of diabetic complications. A decrease of plasma ascorbic acid has been reported in diabetes and thus may play a role in the collagen and proteoglycan abnormalities in diabetes. Ascorbic acid and glucose share structural similarity, and their metabolism may interact at the level of membrane transport and cellular action. In this study, we used a fibroblast culture system to explore this possibility. Ascorbic acid increased collagen and proteoglycan both in the culture medium and the cell layer. This stimulatory action of ascorbic acid was inhibited by the presence of glucose at a concentration of 25 mM. The effect of high glucose concentration was not mediated by inhibition of ascorbic acid uptake by fibroblasts. Insulin is able to abolish this inhibitory action of glucose on collagen production, but the precise mechanism is unclear. These results show that the high glucose concentration in diabetes can impair the action of ascorbic acid at the cellular level. This may further accentuate the problem of decreased availability of this vitamin as a result of its low plasma concentration.

Amino Acids↗
PubMed1990

Abnormalities of ascorbic acid metabolism and diabetic control: differences between diabetic patients and diabetic rats.

Ascorbic acid is required in the synthesis of collagen and is also an important anti-oxidant. In a previous study, plasma ascorbic acid concentration was found to be decreased in diabetic patients but there was no relationship with blood glucose level. In the current study of diabetic patients, both plasma ascorbic acid and its urinary excretion correlated inversely with glycosylated hemoglobin level. Plasma ascorbic acid was also lower in diabetic rats but urinary ascorbic acid was elevated. The divergent trend in urinary ascorbic acid excretion observed in diabetic patients and diabetic rats may be due to difference in the ability of these two species to synthesize ascorbic acid. Difference in renal reabsorption of ascorbic acid may also be a relevant factor. The lower plasma and urinary ascorbic acid levels in diabetic patients with more severe hyperglycaemia indicates that this group of patients is particularly at risk of developing deficiency of this vitamin. As ascorbic acid has many important functions in the body, it may be necessary to supplement this vitamin in patients with chronically poorly controlled diabetes.

Adult↗
PubMed1979

Gestational age and indomethacin elimination in the neonate.

The disposition of oral indomethacin was studied in 9 premature infants with significant patent ductus arteriosus (sPDA) with birth weights ranging from 800 to 1,960 gm and gestational ages of 28 to 36 wk. Peak plasma concentrations in most of the subjects were not observed until 3 to 4 hr after administration and ranged from 0.027 to 0.31 microgram/ml. Plasma half-life (t1/2) of indomethacin ranged from 11 to 20 hr and correlated with gestational age. Plasma protein binding studies, in samples from the premature infant using radiolabeled indomethacin, showed no difference in binding from values obtained with adult plasma (greater than 98%). Absorption of orally administered indomethacin appears to be incomplete and plasma clearance much longer than in the adult.

Blood Proteins↗
PubMed1979

The compromised host and Legionnaires' disease.

Pneumonia caused by Legionnaires' disease bacterium was recognized in eight patients during a 7-month period. The patients were immunosuppressed by their underlying illness, corticosteroid therapy, and other exogenous immunosuppressive agents. Five of the patients had received immunosuppressive therapy for less than 16 days. Clinical presentation was similar to that of other bacterial pneumonias in compromised patients. Legionnaires' disease progressed to necrotizing pneumonia with abscess formation and respiratory failure in two patients. Diagnosis was made by [1] culture of lung tissue and bronchial washings; [2] direct fluorescent antibody staining of lung tissue, sputum, and bronchial washings; and [3] serologic evidence of infection. Therapy with oral erythromycin was ineffective. Intravenous erythromycin was given to six patients, with a good response. However, two patients showed further clinical improvement after rifampin was added. Because this illness may be more severe in compromised hosts, open lung biopsy and special microbiologic tests should be done when Legionnaires' disease is suspected.

Adrenal Cortex Hormones↗
PubMed1979

Disposition of indomethacin in preterm infants.

Indomethacin is currently used for the pharmacologic closure of PDA in preterm infants with respiratory distress syndrome. However, the response to the drug has been variable and the disposition of the drug in preterm infants is not well understood. We studied the pharmacokinetics of indomethacin in nine preterm infants with birth weights ranging from 800 to 1,960 gm and gestational ages of 28 to 36 weeks. Three different dose schedules (0.1, 0.25, 0.3 mg/kg dose) were used. The plasma half-life of indomethacin ranged from 11 to 20 hours. Peak levels were achieved within four hours and ranged from 0.027 to 0.310 microgram/ml. The half-life in infants less than 32 weeks' gestation was significantly prolonged compared to that in infants greater than 32 weeks. Protein-binding studies with 14C indomethacin showed that 98% of indomethacin was protein bound. Absorption of orally administered indomethacin appears to be poor and incomplete. No immediate major complications could be correlated to indomethacin therapy in this study.

Birth Weight↗
PubMed1978

Polymicrobial infective endocarditis: an increasing clinical entity.

Polymicrobial endocarditis was very uncommon until ten years ago. However, since that time, at least 21 cases were reported, and 10 patients with this mixed infection were seen at our hospital. All, except one of these infections, occurred in patients who had undergone heart surgery or abused intravenous drugs. Although, generally clinically indistinguishable from mono-microbial endocarditis, these mixed infections carried a very high mortality rate (greater than 30 per cent), and an unusually large number of the patients (greater than 50 per cent) needed heart surgery either to control the infection or to repair cardiac defects resulting from the infection. The prognosis depended on the species rather than the number of organisms isolated and on aggressive antimicrobial and surgical therapy.

Adult↗
PubMed1977

A new prenatal cardiac diagnostic device for congenital heart disease.

A unique case of congenital heart disease and complete heart block diagnosed by fetal electrocardiogram (ECG) and phonocardiogram recorded initially at 32 weeks gestation is presented. The slow, regular fetal heart rate of approximately 50 beats/min with bizarre QRS and a diamond-shaped murmur beginning with the fetal QRS complex made a diagnosis of complete heart block (CHB) and associated congenital heart disease highly probable. Direct fetal electrocardiograms (FECG) recorded during labor and vaginal delivery at term confirmed the diagnosis of completel atrioventricular block. Cardiac catheterization at 1 day of age showed multiple congenital heart anomalies. The infant developed signs of congestive heart failure and transvenous pacemaker was successfully placed; however, he died at 9 days of age of sepsis and renal failure.

Adult↗
PubMed1977

Tuberculous meningitis in an urban general hospital.

We analyzed the clinical and laboratory findings of 19 patients with tuberculous meningitis seen between 1966 and 1974 at the Henry Ford Hospital. Eighteen patients were adults at the time of diagnosis. In eight patients, the history suggested that the infection with the tubercle bacillus had occurred in the remote past. Cerebrospinal fluid analysis was often typical for tuberculous meningitis; stains for Mycobacterium tuberculosis were usually negative. Of 16 patients who were treated, five died and five suffered permanent neurological sequelae. The addition to rifampin to isoniazid therapy did not improve either survival or permanent sequelae. We were not able to analyze the effect of steroids on the disease.

Adult↗
PubMed1976

Bennett's fracture in general practice.

A review of eight cases of Bennett's fracture is presented. The mechanism of injury appears well defined and a simple method of treatment is described. Uniformly good results have been achieved in all eight cases.

Adolescent↗
PubMed1976

Intramuscular clindamycin for therapy of infective endocarditis. Report of 23 cases and review of the literature.

Twenty-three patients with infective endocarditis received intramuscular clindamycin (Cleocin) for treatment. Thirteen had acute Staphylococcus (S.) aureus endocarditis but none had involvement of the aortic valve. Eleven of these 13 infections were heroin-related and involved the tricuspid valve.Twenty-one patients were successfully treated. Two patients with heroin-related S. aureus infection failed to respond to intramuscularly administered clindamycin, but responded to retreatment with methicillin. There have been 34 reported cases of endocarditis treated with clindamycin. Although 80 percent of all cases due to staphylococci responded favorably, almost all were heroin-related tricuspid valve infections. In addition 91 percent of cases due to aerobic streptococci responded but, surpisingly, treatment failed in three of four cases of anaerobic endocarditis. Although clindamycin can be useful in streptococcal endocarditis and in some cases of heroin-related S. aureus tricuspid endocarditis, caution should be exercised in its use. It is "less" bactericidal than the penicillins or cephalosporins, and organisms have become resistant during treatment. Furthermore, patients with anaerobic endocarditis have not responded well, and data are not available to recommend administration of clindamycin for acute S. aureus infections engrafted on the aortic or mitral valve.

Adolescent↗
PubMed1976

Interruption of patent ductus arteriosus in premature infants with respiratory distress syndrome.

In infants with respiratory distress syndrome (RDS) hypoxemia inhibits closure of the patent ductus arteriosus (PDA), resulting in increased pulmonary blood flow with subsequent increased hypoxemia. In an attempt to interrupt this cycle 42 consecutive premature infants with RDS and PDA, weighing between 550 and 2,000 gm (average, 1,383 gm) and with an average gestational age of 31 weeks, were arbitrarily treated either medically (13 patients) or by interruption of the PDA (20 patients). Eleven patients who were initially treated medically could not be weaned from the respirator and later underwent operation. There were no operative or anesthetic deaths; late survival was 65% (20 patients). The last 31 patients were randomly divided into operative and nonoperative groups. Preliminary results revealed no significant differences in late survival between the two groups. Since the operative risk is minimal, further investigative efforts are indicated to settle this issue.

Digoxin↗