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Biomedical subjects

M L Fisher

Publications and source records attributed to M L Fisher.

At least 37 records · Page 2Linked to original sources
PubMed1994

Increased resting metabolic rate in patients with congestive heart failure.

OBJECTIVE: To examine resting metabolic rate in patients with congestive heart failure as a cause of cardiac cachexia and associated weight loss. DESIGN: Cross-sectional study. SETTING: Baltimore Veterans Affairs Medical Center. PATIENTS: 20 men with heart failure (mean age +/- SD, 69 +/- 7 years) and reduced ejection fraction (mean, 0.24 +/- 0.10) and 40 healthy men (mean age, 69 +/- 7 years). RESULTS: Patients with heart failure had smaller fat-free mass than did controls (53 +/- 8 kg compared with 56 +/- 6 kg; P < 0.09), but no difference in fat mass existed (21 +/- 8 kg compared with 19 +/- 8 kg). Measured resting metabolic rate was 18% higher in patients with heart failure than in controls (1828 +/- 275 kcal/d compared with 1543 +/- 219 kcal/d; P < 0.01); no difference in caloric intake existed (2144 +/- 479 kcal/d compared with 2174 +/- 826 kcal/d). The difference in resting metabolic rate between the two groups was even more striking when indexed per kilogram of fat-free mass. CONCLUSIONS: Higher resting metabolic rate in patients with heart failure at least partially accounts for otherwise unexplained weight loss. Present caloric guidelines, which were established in healthy elderly persons, substantially underestimate the resting caloric needs of elderly persons with heart failure.

Aged↗
PubMed1994

Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial.

OBJECTIVES: This clinical trial was performed to determine the safety and clinical impact of titrated metoprolol therapy in patients with heart failure, documented coronary artery disease and a low ejection fraction. BACKGROUND: Despite known cardiodepressant effects, long-term use of beta-adrenergic antagonists appears to be beneficial in patients with idiopathic dilated cardiomyopathy. However, this therapy has not been critically evaluated in patients with heart failure and coronary artery disease. METHODS: In 50 patients with heart failure, known coronary artery disease and an ejection fraction < or = 0.40, we examined the impact of metoprolol therapy in a 6-month double-blind, placebo-controlled randomized trial, assessing the frequency of heart failure exacerbations and changes in symptoms (New York Heart Association functional class), ejection fraction and exercise duration. Placebo-treated patients who completed 6-month follow-up studies then underwent a trial with metoprolol therapy (crossover group). RESULTS: Metoprolol was titrated to a mean maximal dose of 87 mg/day (range 25 to 100) without serious adverse reactions. During double-blind therapy, use of a beta-blocker was associated with a significant reduction in the number of hospital admissions (4% vs. 32%, p < 0.05), overall improved functional class (p = 0.02), increased ejection fraction (4 +/- 7% [mean +/- SD] compared with 0 +/- 6%, p < 0.05) and a greater increase in exercise duration (193 +/- 276 vs. 38 +/- 213 s with placebo, p < 0.01). Crossover outcome paralleled the favorable impact seen during randomized metoprolol therapy. CONCLUSIONS: Cautious use of titrated metoprolol appears to be safe and beneficial when added to standard heart failure therapy in patients with dilated cardiomyopathy associated with coronary artery disease.

Coronary Disease↗
PubMed1994

Selected predictors of registered nurses' intent to stay.

This paper reports initial findings from a longitudinal study of autonomy, willingness to risk, exit/voice (E/V) and managerial environment (ME) as predictors of registered nurses' intent to stay (ITS) that is being conducted at eight Midwestern hospitals in the USA. In this two-stage study, initial findings are based on responses from 524 staff nurses. Due to the nature of the ITS variable, two logistic regression analyses were computed to test the predictive relationships of the independent variables. In the first, subjects with neutral ITS scores were grouped with subjects who had no intent to stay. Both ME and E/V were predictive of ITS. In the second analysis, the subjects with neutral ITS scores were grouped with subjects who intended to stay. In this case, only ME was predictive. While the per cent variance accounted for by these variables is not as high as some other variables reported in previous research, these variables are amenable to managerial interventions.

Adult↗
PubMed1993

Kinetic studies on the peroxidase activity of selenosubtilisin.

Selenosubtilisin, a semisynthetic selenoenzyme produced by chemical modification of the serine protease subtilisin, acts as a mimic of glutathione peroxidase, catalyzing the reduction of tert-butyl hydroperoxide by 3-carboxy-4-nitrobenzenethiol. To clarify the mechanism of action of this catalyst, detailed kinetic studies have been carried out. Thiol-mediated reduction converts the seleninic acid form of selenosubtilisin (ESeO2H) into a selenenyl sulfide (ESeSAr). Investigations into the reduction of ESeO2H by the aromatic thiol revealed saturation kinetics and were consistent with a significant lowering of the pKa of the seleninic acid in the enzyme active site. While the reduction of ESeO2H was slow compared with a simple model system, the reduced selenoenzyme (ESeSAr) exhibited a much greater peroxidase activity than model compounds. The enzymic selenocysteine residue was shown to be crucial for this activity, and ping-pong kinetics were observed. A catalytic cycle involving interconversion of the ESeSAr, ESeH, and ESeOH forms of the enzyme has been proposed that is consistent with all the available data. The pH-rate profile for the peroxidase activity indicates the involvement of the active site histidine (His64) in the rate-determining step, which these investigations suggest is attack of ArS- on ESeSAr. The results presented here correlated well with crystallographic and spectroscopic data and provide more detailed information about crucial interactions within the active site of selenosubtilisin.

Binding Sites↗
PubMed1993

Abnormal Valsalva blood pressure response in dilated cardiomyopathy: association with "pseudonormalization" of echocardiographic Doppler transmitral filling velocity pattern.

In patients with dilated cardiomyopathies, the presence of an abnormal blood pressure response to the Valsalva maneuver has been shown to correlate well with increased left-sided filling pressures. The presence of a "pseudonormalized" early peak to late peak velocity (E/A) ratio on echocardiographic Doppler transmitral filling pattern has also been correlated with increased left ventricular end-diastolic pressures in these patients. Since both abnormal blood pressure response to the Valsalva maneuver and a "pseudonormalized" Doppler transmitral E/A ratio probably represent elevated left ventricular filling pressure, we postulated that there would be a positive correlation between the two in a group of patients with dilated cardiomyopathy and abnormal systolic function. Twenty-five consecutive male patients with New York Heart Association (NYHA) class II to IV heart failure and dilated cardiomyopathy were included. Patients with abnormal blood pressure responses to Valsalva had significantly larger peak early (E) velocities, smaller peak late (A) velocities, and larger E/A ratios compared with patients with normal responses. E/A ratio < 1.0 was present in eight (100%) of the eight patients with a normal blood pressure response to the Valsalva maneuver and E/A ratio > 1.0 was present in 12 (71%) of 17 patients with an abnormal response (p < 0.01). This correlation supports the hypotheses of the physiologic mechanisms of these phenomena and also provides two noninvasive methods of evaluating left-sided filling pressures useful in the diagnosis and treatment of congestive heart failure caused by dilated cardiomyopathy.

Adult↗
PubMed1993

Effects of intravenous magnesium sulfate on arrhythmias in patients with congestive heart failure.

Intravenous magnesium is an effective treatment for ventricular tachycardia of some etiologies, and in patients with congestive heart failure low serum magnesium concentrations are associated with frequent arrhythmias and high mortality. This suggests that magnesium administration may decrease the frequency of ventricular arrhythmias in patients with heart failure. We therefore assessed the impact of an intravenous magnesium infusion upon the frequency of ventricular premature depolarizations in 40 patients with New York Heart Association (NYHA) class II to IV heart failure and serum magnesium < or = 2.0 mg/dl. Within 1 week of a baseline 6-hour ambulatory electrocardiographic recording, an infusion of 0.2 mEq/kg of MgSO4 was given over 1 hour and a repeat 6-hour recording was obtained. There was an inverse relationship between the change in magnesium concentration and the change in frequency of premature ventricular depolarizations; premature ventricular depolarizations declined by 134 +/- 207 hr-1 in patients in whom serum magnesium concentration increased > or = 0.75 mg/dl, but increased by 72 +/- 393 hr-1 in patients with a change < 0.75 mg/dl (p < 0.05). For all patients, the frequency of premature ventricular depolarizations was 283 +/- 340 hr-1 pretreatment and 220 +/- 269 hr-1 following magnesium infusion (p = 0.21). Patients with > or = 300 premature ventricular depolarizations hr-1 demonstrated a decrease from 794 +/- 309 to 369 +/- 223 hr-1 (p < 0.001). Intravenous magnesium administration decreased the frequency of couplets from 233 +/- 505 to 84 +/- 140 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Sustained hemodynamic response to flosequinan in patients with heart failure receiving angiotensin-converting enzyme inhibitors.

OBJECTIVES: We evaluated the short- and long-term effects of flosequinan in 47 patients with severe heart failure despite ongoing captopril treatment. BACKGROUND: There have been no previous evaluations of the long-term hemodynamic effects of any direct-acting vasodilator in patients with heart failure receiving an angiotensin-converting enzyme inhibitor. Flosequinan is an arterial and venous vasodilator with actions similar to those of the hydralazine-isosorbide dinitrate combination. METHODS: After baseline hemodynamic measurements using balloon-tipped pulmonary artery and radial arterial catheters, patients were randomized to receive 50, 100 or 150 mg of flosequinan daily. Hemodynamic variables were measured immediately before and after short-term flosequinan administration and after 8 weeks of therapy. RESULTS: With short-term flosequinan administration, mean arterial, right atrial and left ventricular filling pressures decreased by 6.4 +/- 1.1, 3.8 +/- 0.5 and 7.3 +/- 0.7 mm Hg, respectively (all p < 0.001). Cardiac index increased by 0.5 +/- 0.1 liters/min per m2, systemic vascular resistance decreased by 616 +/- 105 dynes.s.cm-5 and heart rate increased by 4 +/- 1 beats/min (all p < 0.001). After 8 weeks of long-term flosequinan administration, the vasodilator effect of a dose of flosequinan persisted. Compared with pretreatment baseline values, mean arterial, right atrial and left ventricular filling pressures at the peak effect of flosequinan were decreased by 3.5 +/- 1.3, 2.8 +/- 0.7 and 5.1 +/- 1.3 mm Hg, respectively (all p < 0.01). Systemic vascular resistance had decreased by 585 +/- 95 dynes.s.cm-5, cardiac index had increased by 0.5 +/- 0.1 liters/min per m2 and heart rate had increased by 10 +/- 2 beats/min (all p < 0.001). CONCLUSIONS: The arterial and venous vasodilator flosequinan exerts both short- and long-term sustained hemodynamic effects in patients with heart failure receiving angiotensin-converting enzyme inhibitors.

Adult↗
PubMed1993

The evaluation and management of known or suspected stones of the common bile duct in the era of minimal access surgery.

Laparoscopic cholecystectomy (LC) has rapidly become the procedure of choice for symptomatic cholelithiasis. The perioperative diagnosis and modern treatment of suspected stones of the common bile duct (CBD) remains controversial. A database of 573 patients undergoing LC was compiled during an 11 month period. Sixty-seven patients (47 females, 20 males) (13 percent) were suspected of having CBD stones based upon clinical, laboratory and roentgenographic evidence. Fifty-two patients underwent endoscopic retrograde cholangiopancreatography (ER-CP) (45 preoperative and seven postoperative). Seventeen patients were studied with intraoperative cholangiogram (IOC). The indications for cholangiography (either ERCP or IOC) included pancreatitis (group 1), clinical history suggestive of CBD stones, but normal preoperative liver function tests (LFT) (group 2), cholangitis (group 3), grossly abnormal LFT (group 4) and dilated CBD (greater than 7 millimeters on sonogram) (group 5). The incidence of CBD stones was three of 14 (21 percent) in group 1, six of 20 (30 percent) in group 2, two of three (67 percent) in group 3, 16 of 26 (62 percent) in group 4 and two of four (50 percent) in group 5. Overall, 29 patients (23 females and six males) had stones retrieved from the CBD. Of the 52 ERCP, 20 endoscopic sphincterotomies were performed for documented CBD stones. Of the group that had pre-LC ERCP, three (6 percent) ultimately required an open procedure. There were three instances of post-ERCP pancreatitis (6 percent) and ERCP was not able to opacify or clear the CBD in four instances. Seven patients had postoperative ERCP with successful retrieval of retained CBD stones (100 percent). Of the 17 IOC, eight were positive--two patients underwent laparoscopic clearance of the CBD and six required conversion to an open procedure. There were no deaths or extensive complications. Total and direct bilirubin, alkaline phosphatase and serum glutamic pyruvic transaminase were independently related to the presence of a CBD stone, while demographic data, past medical history, preoperative symptoms, leukocyte count, vital signs, amylase, serum glutamic-oxalacetic transaminase nuclear scintigraphic visualization of the duodenum or size of CBD on sonography, were not. No patient with biliary pancreatitis had CBD stones without abnormalities in the LFT or the preoperative sonogram. ERCP is a useful technique to clear the CBD pre-LC. However, ERCP in patients with biliary pancreatitis, but otherwise normal preoperative tests, has a low yield. In this group of patients, IOC is an appropriate alternative to pre-LC ERCP.

Adult↗
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↗