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Biomedical subjects

M L Fisher

Publications and source records attributed to M L Fisher.

At least 19 recordsLinked to original sources
PubMed1992

Renal response to indomethacin in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

The impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on renal function has not been evaluated in patients with congestive heart failure. Therefore, the renal effects of indomethacin were examined in patients with chronic heart failure, and the relation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration was assessed. Twenty-five patients with congestive heart failure and an ejection fraction less than 40% were evaluated. At baseline, renal plasma flow and glomerular filtration rate were measured, using disappearance from the serum of intravenously injected 131I-orthodihippurate and urinary accumulation of intravenously injected technetium-99m diethylenetriamine pentaacetic acid, respectively. After 3 days, 75 mg of sustained release indomethacin were administered, and repeat renal function tests were performed. Mean glomerular filtration rate decreased from 40 +/- 21 to 32 +/- 16 ml/min/1.73 m2 (p less than 0.05), and mean renal plasma flow decreased from 242 +/- 122 to 222 +/- 110 ml/min/1.73 m2 (p less than 0.05). There was no correlation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration. It is concluded that 1 dose of an NSAID may cause marked and clinically important alterations in renal function in patients with heart failure. However, the decrease in glomerular filtration rate does not merely reflect a decrease in renal plasma flow, but probably the effects of NSAIDs on the intraglomerular actions of prostaglandins.

Adult↗
PubMed1992

Different patterns of gene expression of topoisomerase II isoforms in differentiated tissues during murine development.

The expression of DNA topoisomerase II alpha and beta genes was studied in murine normal tissues. Northern blot analysis using probes specific for the two genes showed that the patterns of expression were different among 22 tissues of adult mice. Expression levels of topoisomerase II alpha gene were high in proliferating tissues, such as bone marrow and spleen, and undetectable or low in 17 other tissues. In contrast, high or intermediate expression of topoisomerase II beta gene was found in a variety of tissues (15) of adult mice, including those with no proliferating cells. Topoisomerase II gene expression was also studied during murine development. In whole embryos both genes were expressed at higher levels in early than late stages of embryogenesis. Heart, brain and liver of embryos two days before delivery, and these same tissues plus lung and thymus of newborn (1-day-old) mice expressed appreciable levels of the two genes. Interestingly, a post-natal induction of the beta gene expression was observed in the brain but not in the liver; conversely, the expression of the alpha gene was increased 1 day after birth in the liver but not in the brain. However, gene expression of a proliferation-associated enzyme, thymidylate synthase, was similar in these tissues between embryos and newborns. Thus, the two genes were differentially regulated in the post-natal period, and a tissue-specific role may be suggested for the two isoenzymes in the development of differentiated tissues such as the brain and liver. Based on the differential patterns of expression of the two isoforms, this analysis indicates that topoisomerase II alpha may be a specific marker of cell proliferation, whereas topoisomerase II beta may be implicated in functions of DNA metabolism other than replication.

Aging↗
PubMed1992

Determinants of the renal response to ACE inhibition in patients with congestive heart failure.

The objective of the present study was to determine whether pretreatment neurohormonal and renal hemodynamic parameters predict the change in renal function with the administration of quinapril, a new angiotensin-converting enzyme (ACE) inhibitor. Twenty patients with New York Heart Association (NYHA) class III and IV heart failure were evaluated. Following pretreatment determination of renal function and plasma neurohormones, patients were treated daily with 10 mg of quinapril. Measurements of glomerular filtration rate (GFR) and renal plasma flow (RPF) were repeated after 7 weeks to assess changes in function (delta GFR and delta RPF). Mean GFR increased from 49 +/- 6 to 56 +/- 7 ml/min/1.73 m2 (p = 0.10), but decreased in five patients. Mean RPF increased from 235 +/- 23 to 252 +/- 23 ml/min/1.73 m2 (p = 0.08), but decreased in five patients. There was no relation between delta GFR and baseline determinations of GFR, RPF, plasma renin activity, plasma angiotensin II, or serum Na. Only a high filtration fraction (GFR/RPF) predicted a decreased GFR (r = 0.61, p less than 0.005). In contrast, no baseline renal hemodynamic parameter correlated with delta RPF. We conclude that poor renal function does not increase the risk of renal deterioration with quinapril. However, dependence of renal function upon the renin-angiotensin system may be predicted by a high filtration fraction.

Angiotensin II↗
PubMed1990

Prognostic importance of the serum magnesium concentration in patients with congestive heart failure.

Magnesium abnormalities are common in patients with congestive heart failure but the clinical and prognostic significance of an abnormal serum magnesium concentration in this disorder has not been investigated. Therefore, the relation between serum magnesium concentration and the clinical characteristics and long-term outcome of 199 patients with chronic heart failure was evaluated. The serum magnesium concentration was less than 1.6 mEq/liter in 38 patients (19%), within the normal range in 134 patients (67%) and greater than 2.1 mEq/liter in 27 patients (14%). Patients with hypomagnesemia had more frequent ventricular premature complexes and episodes of ventricular tachycardia than did patients with a normal serum magnesium concentration (p less than 0.05). Even though the two groups were similar with respect to severity of heart failure and neurohormonal variables, patients with a low serum magnesium concentration had a significantly worse prognosis during long-term follow-up (45% versus 71% 1 year survival, p less than 0.05). Patients with hypermagnesemia had more severe symptoms, greater neurohormonal activation and worse renal function than did patients with a normal serum magnesium concentration but tended to have fewer ventricular arrhythmias. Hypermagnesemic patients had a worse prognosis than did those with a normal magnesium concentration (37% versus 71% 1 year survival, p less than 0.05). In conclusion, the measurement of serum magnesium concentration provides important clinical and prognostic information in patients with chronic heart failure.

Female↗
PubMed1989

gamma-Glutamylcyclotransferase: inhibition by D-beta-aminoglutaryl-L-alanine and analysis of the solvent kinetic isotope effect.

Spin-echo NMR spectroscopy was used to record the cleavage of a gamma-glutamyl--amino-acid by (5-L-glutamyl)-L-amino-acid 5-glutamyltransferase (cyclizing) (gamma-glutamylcyclotransferase) in human erythrocyte hemolysates. The Michaelis-Menten steady-state kinetic parameters were obtained by fitting the integrated Michaelis-Menten equation to the reaction time curves. The product, L-5-oxoproline, was shown to be an inhibitor of the reaction. The active site of the enzyme was probed by studies of the inhibition by D- and L-beta-aminoglutaryl-L-alanine which are the beta-amino-acid isomers of D- and L-gamma-glutamyl-L-alanine (the latter being a natural substrate of the enzyme); the D-isomer was the more potent inhibitor (Ki = 0.30 +/- 0.02 mmol/l water). When the alanyl alpha-carboxyl of the inhibitor was reduced to a hydroxyl (i.e. to give D-beta-aminoglutaryl-L-alaninol) the potency of inhibition was reduced. The previously reported kinetic isotope effect of solvent 2H2O on the enzyme-catalyzed reaction has been further studied using a proton inventory. We propose that the solvent kinetic isotope effect is due to an intramolecular proton transfer between the glutamyl amino group and the peptide bond nitrogen.

Acyltransferases↗
PubMed1988

Effect of postural changes, nitroglycerin and verapamil on diastolic ventricular function as determined by radionuclide angiography in normal subjects.

Whereas improvement in diastolic function indexes in response to therapeutic interventions has been attributed to a beneficial effect of the intervention, measurements of diastolic function appear to be influenced by changes in loading conditions, heart rate and sympathetic tone. To determine the effect of body position and short-term pharmacologic intervention on radionuclide angiographically determined left ventricular peak filling rate, high temporal resolution time-activity curves and absolute left ventricular volumes obtained by equilibrium-gated blood pool scans were evaluated in 12 normal subjects in the supine position at rest and in response to several postural and pharmacologic manipulations. This study confirmed the reproducibility of the technique and demonstrated that in normal subjects, peak filling rate varies in response to changes in body position and to short-term administration of sublingual nitroglycerin and intravenous verapamil. Peak filling rate ranged from 3.3 to 5.1 end-diastolic volumes (EDV)/s with a variability of 13.7% during five baseline supine measurements in the 12 subjects. Compared with values in the supine position (mean +/- SEM = 4.38 +/- 0.24 EDV/s), peak filling rate increased +16 +/- 6% to 4.75 +/- 0.27 EDV/s in the upright position (p less than 0.05) but did not change significantly with leg elevation. Peak filling rate at baseline and during postural changes correlated significantly with ejection fraction (r = +0.49), with stroke volume (r = +0.26) and inversely with end-systolic volume (r = -0.41), but did not correlate with heart rate or blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Electrophysiologic effects of cigarette smoking in patients with and without chronic beta-blocker therapy.

After refraining from smoking for at least 8 hours, 22 adult male habitual smokers underwent baseline electrophysiologic study including atrial and ventricular burst pacing and programmed premature stimulation with single extrastimuli. After smoking 2 of their usual brand of cigarettes in rapid succession, the electrophysiologic protocol was repeated. Nicotine, catecholamine and carbon monoxide concentrations all increased significantly. Smoking increased heart rate and improved atrioventricular conduction in the 13 patients receiving chronic beta-blocker therapy (mostly for angina pectoris); increases in heart rate and improvement in atrioventricular conduction were not different statistically from those seen in patients not receiving beta-blocker therapy, suggesting the possibility of a direct effect of nicotine or other components of tobacco smoke. Ventricular refractoriness was not altered and atrial and ventricular arrhythmias were not increased by smoking. Persistent sympathomimetic actions of cigarette smoking may explain in part the failure of beta-blocking drugs to reduce cardiac mortality risk in smokers after myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed1986

Changes in left ventricular function during recovery from upright bicycle exercise in normal persons and patients with coronary artery disease.

To characterize the hemodynamic changes during recovery after upright bicycle exercise, 56 normal subjects (group I) and 30 patients with documented myocardial ischemia (group II) were studied. Heart rate, blood pressure and radionuclide angiographically determined absolute left ventricular (LV) volumes were measured at baseline, peak exercise and 2 to 4.5 minutes and 4.5 to 7 minutes after upright bicycle exercise. Whereas ejection fraction and end-systolic volume responses at peak exercise differed between groups I and II, these parameters showed similar trends in both groups during recovery. Mean ejection fraction increased during 2 to 4.5 minutes in both groups, but remained elevated during 4.5 to 7 minutes only in normal subjects (group I). Elevation of cardiac output after exercise was accounted for predominantly by increased heart rate rather than increased stroke volume. Despite significantly decreased end-diastolic volume during recovery, stroke volume was maintained in both groups by a substantial decrease in end-systolic volume, suggesting the impact of decreased afterload or increased sympathetic tone during recovery. Thus, the Frank-Starling mechanism does not appear to be playing a major role during recovery after upright bicycle exercise, whereas enhanced contractility is evident in both normal subjects and patients with documented myocardial ischemia.

Adult↗
PubMed1986

Beta-blockers in congestive cardiomyopathy. Conceptual advance or contraindication?

The precise role of adrenergic activity in congestive cardiomyopathy has not been established. A number of mechanisms through which increased catecholamine levels may be harmful, along with the clinical and experimental evidence supporting this concept, are summarized in this review. In this context, the suggestion that beta blockers may be beneficial for patients with severe heart failure, despite their well-known propensity to decrease cardiac contractility, can be better understood. Published reports on the use of beta blocker therapy for congestive cardiomyopathy now include approximately 200 patients, but have yielded inconsistent results. Non-randomized trials in Sweden have suggested increased survival, with most patients having improved functional status while receiving beta blockade, although improvement may take three to six months to become evident. The Swedish group also reported clinical deterioration after discontinuation of beta blockade. Two recent randomized trials in America yielded promising results, but the unexpectedly low mortality in the placebo groups emphasizes the critical importance of concurrent controls. Unfavorable reports have involved small groups with short-duration therapy. Even in these reports, overt aggravation of clinical heart failure has been quite infrequent but sometimes profound. As large scale trials are undertaken, an obvious goal is the development of methods to differentiate the patients with congestive cardiomyopathy who will benefit in response to beta blocker therapy from the few patients who will have a serious adverse response.

Adrenergic beta-Antagonists↗
PubMed1986

Use of the Frank-Starling mechanism during submaximal versus maximal upright exercise.

To evaluate the extent to which the Frank-Starling mechanism is utilized during successive stages of vigorous upright exercise, absolute left ventricular end-diastolic volume and ejection fraction were determined by gated blood pool scintigraphy at rest and during multilevel maximal upright bicycle exercise in 30 normal males aged 26-50 yr, who were able to exercise to 125 W or greater. Left ventricular end-systolic volume, stroke volume, and cardiac output were calculated at rest and during each successive 3-min stage of exercise [25, 50, 75, 100, and 125-225 W (peak)]. During early exercise (25 W), end-diastolic and stroke volumes increased (+17 +/- 1 and +31 +/- 4%, respectively), with no change in end-systolic volume. With further exercise (50-75 W) end-diastolic volume remained unchanged as end-systolic volume decreased (-12 +/- 4 and -24 + 5%, respectively). At peak exercise end-diastolic volume decreased to resting level, stroke volume remained at a plateau, and end-systolic volume further decreased (-48 +/- 7%). Thus the Frank-Starling mechanism is used early in exercise, perhaps because of a delay in sympathetic mobilization, and does not appear to play a role in the later stages of vigorous exercise.

Adult↗
PubMed1986

Marketing: the creative advantage.

Success is celebrated best by sharing the process that led to its achievement. The marketing of nursing products at the 507-bed Akron General Medical Center is a success worth sharing with other nurse executives. The authors describe the marketing process that generated new sources of revenue to support staff education and clinical specialist services.

Hospital Bed Capacity, 500 and over↗
PubMed1985

Fiber optic probe cytometer.

An optical fiber probe is used to both excite and collect fluorescence from a suspension of cells. The configuration of the probe is such that one or a few cells are sensed at a time, with a convenient cell concentration. With fluorescently labeled antibodies to cellular antigens, the fiber optic cytometer is able to identify the presence of a specific set of cells with high sensitivity.

ABO Blood-Group System↗
PubMed1985

Transcutaneous temporary pacing in the operating room.

The safety and efficacy of transcutaneous temporary pacing were assessed in 21 patients undergoing elective surgical procedures under general anesthesia. Complete capture was achieved in all patients. The pacing threshold was 50 mamp in two patients, 100 mamp in nine, and 200 mamp in ten. The threshold was influenced by electrode position and also, possibly, by age, heart size, and chest size. No adverse effects of pacing were encountered. Transcutaneous pacing is a rapid, safe, and effective means of temporary pacing in the operating room.

Adult↗
PubMed1985

Value and limitations of exercise radionuclide angiography for detecting myocardial ischemia in healed myocardial infarction.

Exercise radionuclide angiography was performed in 65 normal subjects (group I), in 31 patients with exercise-induced transient thallium defects after acute myocardial infarction (AMI) (group II), and in 16 patients without exercise-induced transient thallium defects, angina or electrocardiographic changes after AMI (group III). Absolute left ventricular (LV) volumes were measured using a correction for attenuation in each patient. Similar peak heart rate-blood pressure products were achieved in groups II and III. Although the mean LV ejection fraction (EF) response to exercise in group III (increase of 0.11 +/- 0.10 units) closely resembled that of normal persons (increase of 0.14 +/- 0.09 units) and was significantly different from that of group II (decrease of 0.04 +/- 0.12), there was considerable individual variation. An abnormal EF response to exercise, defined as failure of EF to increase by at least 0.05 units, was found in 6 subjects (9%) in group I, 26 patients (84%) in group II, and 2 patients (13%) in group III. End-systolic volume failed to decrease in 10 subjects (15%) in group I, 25 patients (81%) in group II and 7 patients (44%) in group III. New regional wall motion abnormalities were found in no subject in group I, in 16 patients (52%) in group II and in only 1 patient (6%) in group III. Thus, although group responses of EF or end-systolic volume appeared to correlate with the presence or absence of ischemia, some patients with exercise-induced transient thallium defects after AMI responded normally to exercise radionuclide angiography stress testing and some patients without other evidence of exercise-induced ischemia after AMI responded to exercise radionuclide angiography testing abnormally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Routine preoperative exercise testing in patients undergoing major noncardiac surgery.

A prospective study of preoperative exercise testing was carried out in 200 patients older than 40 years scheduled for elective major noncardiac surgery under general anesthesia. The exercise test response was electrocardiographically positive in 32 patients (16%) (2 patients had a markedly positive test), equivocal in 11 patients (5.5%) and negative in 157 patients (78.5%). The patients were followed with serial pre- and postoperative electrocardiograms (ECGs) and determinations of serum creatine kinase (CK) and CK-MB. Six patients (3%) had primary endpoints: 3 (1.5%) died postoperatively and 3 (1.5%) had definite postoperative myocardial infarction. Secondary endpoints of suspected postoperative myocardial ischemia/injury diagnosed by ECG or elevation in CK-MB levels occurred in 27 patients (14%). Endpoint events were more common in patients aged 70 years or older. Endpoint events were also more common in patients with an abnormal (positive or equivocal) preoperative exercise test response than in those with a negative response (27% vs 14%); however, preoperative exercise results were not statistically significant independent predictors of cardiac risk. Using multivariate analysis, the only statistically significant independent predictor of risk was the preoperative ECG. Endpoint events were more common in patients with an abnormal than in those with a normal ECG (23% vs 7%, p less than 0.002). Because the results of exercise testing do not appear to add substantially to the risk separation provided by the ECG at rest, exercise testing is not recommended as a routine preoperative method for assessing perioperative risk in older patients who are being evaluated before major elective noncardiac surgery under general anesthesia.

Adult↗