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Biomedical subjects

T S Rector

Publications and source records attributed to T S Rector.

53 records · Page 3Linked to original sources
PubMed1989

Association of coronary artery disease in cardiac transplant recipients with cytomegalovirus infection.

Coronary artery disease (CAD) is now the major limitation to long-term survival after cardiac transplantation. Its etiology remains unclear. The possible role of viral infection in the genesis of CAD stimulated the review of 102 patients transplanted since the introduction of triple drug immunosuppression (cyclosporine, azathioprine and prednisone) to assess the importance of posttransplant cytomegalovirus infection in the development of CAD in the cardiac graft. CAD occurred in 16 patients (16%). Recipient age and sex, donor age, pretransplant diagnosis, frequency of acute rejection episodes, HLA mismatch, cytomegalovirus infection, incidence of posttransplant systemic hypertension and diabetes mellitus, and mean triglyceride, cholesterol and cyclosporine levels were analyzed to assess their influence on the development of CAD. Only the occurrence of cytomegalovirus infection was found to be a significant factor (p = 0.007): infection occurred in 62% of patients with CAD and in only 25% of those without. These data support the existence of an association between cytomegalovirus infection and CAD after cardiac transplant. It is possible that the virus contributes to the initial injury to the coronary endothelium.

Adult↗
PubMed1989

Alpha 2-receptor-mediated vasoconstriction in patients with congestive heart failure.

alpha 2-Adrenoceptors exist postsynaptically to subserve vasoconstriction and presynaptically to modulate norepinephrine release into the synaptic cleft. Because adrenoceptors may down-regulate in response to chronic stimulation, we investigated the activity of alpha 2-receptor-mediated vasoconstriction in patients with congestive heart failure, who had increased levels of plasma norepinephrine. We used the isolated forearm model and intra-arterial infusions of subsystemic doses of yohimbine, a specific alpha 2-blocker, in 11 patients with heart failure and in 15 normal subjects. Yohimbine produced a dose-related increase in forearm blood flow and decrease in forearm vascular resistance. These findings were consistent with a direct vasodilator effect mediated by blockade of the postsynaptic alpha 2-vascular receptor. Furthermore, the vasodilator responses in patients with heart failure were similar to the normal subjects in terms of the percent increase in forearm blood flow, the dose-response relation, and the fractional response to hyperemia and phentolamine; thus, alpha 2-receptor-mediated vasoconstriction is neither enhanced nor down-regulated in heart failure. In addition, in patients with heart failure and in normal subjects, yohimbine produced an increase in the forearm venous norepinephrine concentration, consistent with an inhibition of the presynaptic alpha 2-receptor resulting in an augmented release of norepinephrine into the synaptic cleft. Thus, these data suggest that the postsynaptic alpha 2-receptor is an important mediator of vasoconstriction in patients with heart failure. Despite chronic elevations in plasma norepinephrine in patients with heart failure, alpha 2-receptor mechanisms subserving vasoconstriction and inhibition of norepinephrine release into the synaptic cleft are still functional in heart failure.

Female↗
PubMed1988

Prognosis of congestive heart failure and predictors of mortality.

The interaction of physiologic variables that appear to be predictive of prognosis in patients with severe congestive heart failure was examined in a series of 139 patients referred to a heart failure service. Left ventricular ejection fraction, peak oxygen consumption during a progressive maximal exercise test and resting plasma norepinephrine concentration were identified as the strongest univariate predictors of prognosis. Examination of their interaction was accomplished by stratifying each variable into quartiles and then pooling quartiles for bivariate analysis. The data demonstrate that ejection fraction has the most profound effect on survival calculated from maximal oxygen consumption and norepinephrine concentration, but that each of the variables provides additional independent prognostic information when added to survival estimated from any of the other variables. Therefore, ventricular function, exercise tolerance and sympathetic nervous system activation appear to provide independent insight into the prognosis of patients with heart failure.

Female↗
PubMed1988

OPC-8212 in the treatment of congestive heart failure: results of a pilot study.

To characterize the effects of OPC-8212, a quinolone inotropic agent, in patients with heart failure, we utilized invasive hemodynamics, exercise testing, 24-hour ambulatory electrocardiograms, and two patient self-assessment questionnaires, before and after 1 month of treatment with OPC-8212, in 17 patients with moderate to severe congestive heart failure. There were no significant changes from baseline in heart rate (83 +/- 8 beats/min), mean arterial pressure (70 +/- 15 mmHg), pulmonary wedge pressure (18 +/- 7 mmHg), or cardiac index (2.3 +/- 0.4 L/min/m2) following treatment with OPC-8212. Both exercise duration (5.3 +/- 1.6 min) and peak oxygen consumption (12.0 +/- 2.9 mL/kg/min) were unchanged by OPC-8212. Two independent patient self-assessment scores, the Sickness Impact Profile and the Minnesota Living with Heart Failure Questionnaire, showed improvements from 6.8 to 5.4 and 49 to 38, respectively (both p less than .05), suggesting that the patients reported an improvement in daily functioning. The median ventricular premature contraction count and frequency were reduced from 1,118 beats to 243 beats (p less than 0.05) and 11/1,000 beats to 2.4/1,000 beats (0.05 less than p less than 0.10), respectively. Two patients developed agranulocytosis during longer-term treatment following this 1-month study. These data demonstrate that OPC-8212 did not have significant effects on hemodynamics or exercise tolerance. However, the improvement in patient self-assessment scores and the trend for improvement in ventricular arrhythmia profiles suggest that OPC-8212 may have some benefit for patients with congestive heart failure, but additional placebo-controlled, double-blind studies are necessary.

Aged↗
PubMed1988

Hemodynamic, renal, and neurohumoral effects of a selective oral DA1 receptor agonist (fenoldopam) in patients with congestive heart failure.

Fenoldopam mesylate (SK&F 82526-J) is a novel benzazepine derivative. It has selective agonist activity at post-junctional (DA1) vascular dopaminergic receptors, which normally subserve renal artery vasodilation. Previous studies in normal subjects and in patients with hypertension indicate that fenoldopam increases renal blood flow and promotes a sodium diuresis. Drug efficacy was clinically evaluated in eight patients with chronic congestive heart failure (CHF) after a single oral dose of 100 mg of fenoldopam and following 3 days of therapy (100 mg four times daily). Stroke volume index acutely increased from 26 +/- 7 (mean +/- SD) to 30 +/- 4 ml/beat/m2 (p less than 0.05) and left ventricular filling pressure decreased from 26 +/- 13 to 23 +/- 11 mm Hg (p less than 0.05). Systemic vascular resistance decreased from 1513 +/- 159 to 1128 +/- 319 (p less than 0.05). Hemodynamic changes were seen as early as 30 minutes following fenoldopam and returned to control levels by 4 hours. Forearm blood flow, hepatic blood flow, and venous capacitance did not significantly change acutely, but renal blood flow index was significantly reduced (34 +/- 4 to 30 +/- 3 min-1 X 1000, p less than 0.01). Plasma norepinephrine, plasma renin activity, plasma arginine vasopressin, and plasma aldosterone did not significantly change acutely. After 3 days of treatment, 100 mg of fenoldopam again reduced the renal blood flow index (35 +/- 7 to 26 +/- 7 min-1 X 1000, p less than 0.01) and tended to increase plasma renin activity (11.7 +/- 8 to 21.2 +/- 19.4 ng/ml/hr, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Sequential neurohumoral measurements in patients with congestive heart failure.

Patients with chronic congestive heart failure are known to have increased plasma norepinephrine and plasma renin activity. In order to evaluate neurohumoral changes over time, we measured plasma norepinephrine and plasma renin activity at baseline and sequentially during follow-up in 49 patients with chronic, stable congestive heart failure. All patients were treated with digitalis and diuretics. Converting enzyme inhibitor therapy was prescribed as adjunctive therapy in 22 patients, while 10 patients were taking hydralazine and/or isosorbide dinitrate, seven were taking prazosin, and 10 had no adjunctive therapy. Patients were divided into those taking converting enzyme inhibitors (group I, n = 22) and those not taking converting enzyme inhibitors (group II, n = 27). Group I was followed for a median (25th to 75th percentiles) of 24.3 (18 to 27.9) months, while group II was followed for 18.7 (11.9 to 36.5) months. Results indicate that patients in group I demonstrate a significant positive trend for rise in plasma norepinephrine of 11.7 pg/ml per month (7.8 to 15 pg/ml per month, 95% confidence interval). Patients in group II also demonstrated a significant positive trend in plasma norepinephrine over time of 6.6 pg/ml per month (2.2 to 11.1 pg/ml per month). Moreover, there was a progressive trend upward in plasma renin activity over time in group II (median 0.34 ng/ml/hr per month; range 0.13 to 0.54). The data indicate that there is a significant trend of neurohumoral activation over time in patients with chronic, clinically stable congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Reduced atrial natriuretic factor after ligation of the left coronary artery in rats.

The diuretic-natriuretic responses of eight assay rats to extracts of atrial tissue obtained 3 months after left coronary ligation were less than the responses to extracts of tissue from sham-operated controls. The mean difference in diuresis (sham-operated response minus ligated response) was 370 (range 22 to 656) microliter/20 minutes (p less than 0.01) and in natriuresis 56 (range -92 to 222) microEq/20 minutes (p = 0.19). The differences in diuretic responses to these extracts was directly related to the severity of elevation of left ventricular end-diastolic pressure in these rats (r = -0.82, p = 0.01). These results in a model with varying degrees of left ventricular dysfunction suggest that myocardial damage is associated with a chronic decrease in atrial natriuretic factor. Reduced circulating atrial natriuretic factor therefore could contribute to the previously observed impaired ability of coronary ligated rats to excrete a saline load and to the sodium retention observed in clinical heart failure. Conclusive evidence will depend on the development of techniques to measure plasma levels of this hormone.

Animals↗
PubMed1979

Steady-state plasma concentrations as a function of the absorption rate and dosing interval for drugs exhibiting concentration-dependent clearance: consequences for phenytoin therapy.

Model-dependent relationships describing the effects of absorption rate and dosing interval on steady-state phenytoin plasma concentrations are presented and discussed. Utilizing a range of operative Michaelis-Menten parameters that characterize phenytoin elimination via a single capacity-limited pathway, a situation assuming instantaneous absorption (case I) is compared with the situation in which continuous constant-rate absorption occurs (case II). The results of these comparisons demonstrate that average steady-state concentrations do not differ significantly between the two cases. Ratios (case I/case II) of areas under the curve during a steady-state dosing interval substantially deviating from unity are associated with high plasma clearances and clinically low phenytoin concentrations. When the same daily dose is maintained, but the dosing interval is altered (0.25, 0.33, 0.50, 1.0 day), little difference in the average steady-state levels is observed even when absorption is instantaneous. Differences between steady-state maximum and minimum concentrations increase with prolonged dosing intervals as well as faster absorbed phenytoin formulations, but for most patients these fluctuations are therapeutically insignificant. A dimensionless parameter, Q, which is a function of the individual patient's parameters and the dosing regimen, is introduced, and its relationship with steady-state phenytoin concentrations is discussed. Formulation-related differences in phenytoin dissolution rates that may result in significantly altered absorption rates should not affect average steady-state levels unless the extent of absorption is altered. More frequent dosing is not necessary to avoid increases in the average steady-state levels when rapidly absorbed phenytoin products are administered, but may be desirable if the required daily dose is high or the individual patient exhibits a narrow therapeutic range for this drug.

Drug Administration Schedule↗
PubMedDate not supplied

Drug kinetics in burn patients.

Thermal trauma reportedly induces a spectrum of intricate physiological alterations that often involve cardiovascular, hepatic, renal, and dermatological functions. Individual responses to varying degrees of burn and secondary complications may produce unpredictable changes in the pharmacokinetics of drugs. A number of reports describing the disposition of aminoglycoside antibiotics in burn patients have demonstrated clinially significant alterations in the pharmacokinetics of this class of drugs. Several authors have found significantly reduced serum half-lives in burn patients as compared with average values in non-burned subjects. Increased aminoglycoside clearances in some burn patients have been attributed to increased glomerular filtration secondary to elevated cardiac output, prostaglandin formation, and glucagon secretion: others attribute this to enhanced elimination of drug across damaged skin tissue. Monitoring of serum aminoglycoside concentrations is recommended because of the low therapeutic index of these agents and the variable course of renal function following burn injury. Topical application of mafenide acetate, providone iodine, and gentamicin to burn wounds has resulted in varying amounts of systemic absorption. Various systemic toxicities have been attributed to these topical therapies, especially in patients with compromised renal function. The extent and area of the burn, degree of hydration, and the amount of drug applied are factors influencing transcutaneous absorption. Sulphonamide derivatives are excreted in the urine subsequent to the application of silver sulphadiazine cream, but silver ions appear to be localised on surface tissue and are thus unavailable to the subeschar space. Additional studies are needed to characterise the pharmacokinetics of medications commonly administered to burn patients. Unfortunately, the marked variability and fluctuations in pathophysiological status following burn trauma often confound the interpretation of such kinetic investigations.

Administration, Topical↗
PubMedDate not supplied

Health status of heart transplant recipients versus patients awaiting heart transplantation: a preliminary evaluation of the SF-36 questionnaire.

Measures of the effects of health care on patients' lives are being requested to evaluate heart transplantation programs. A relatively short, 36-item, questionnaire (SF-36) designed to measure health status is being evaluated as an outcome measure for a variety of conditions. The SF-36 was sent to all adults awaiting heart transplantation (n = 48) and heart transplant recipients (n = 177) at the University of Minnesota as a pilot study of the SF-36 applied to heart transplantation. Response rates were 88% and 81%, respectively. Heart transplant recipients had significantly (p < 0.0001) better scores for general health perceptions (70 +/- 21 versus 33 +/- 21), vitality (62 +/- 19 versus 39 +/- 2), physical function (71 +/- 22 versus 36 +/- 24), ability to perform roles without physical limitations (62 +/- 41 versus 27 +/- 35), and social function (85 +/- 18 versus 63 +/- 31) compared with patients awaiting heart transplantation. Mental function and ability to perform roles without emotional problems were good in both groups and not significantly different. Mean SF-36 scores for the heart transplant recipients were uniformly not as high as scores for a historical group with only minor medical problems. These preliminary data suggest that the SF-36 is sensitive to the effects of heart transplantation. Additional studies of the SF-36 as an outcome measure for heart transplantation are warranted and should include methods to control for extraneous variability and to provide unbiased data collection.

Female↗