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Biomedical subjects

E M Gilbert

Publications and source records attributed to E M Gilbert.

At least 73 records · Page 4Linked to original sources
PubMed1988

OKT3 monoclonal antibody in heart transplantation.

OKT3 monoclonal antibody (OKT3) has already proved to be a valuable edition to the immunosuppression armamentarium available in cardiac transplantation. It is highly effective in treating refractory rejection, where approximately 90% of subjects may be salvaged. It may be even more valuable in prophylaxis, where in combination with an antibody suppression strategy and low-dose, "delayed" cyclosporine it appears to afford near complete protection against rejection. Moreover, OKT3-based prophylaxis seems to impact favorably on the rejection rate after the prophylaxis course has been completed. Adverse reactions are common and generally manageable, although occasional serious clinical events do occur.

Antibodies, Monoclonal↗
PubMed1988

Echocardiographic evaluation of potential cardiac transplant donors.

Since the initiation of the UTAH Cardiac Transplant Program, echocardiography has been used to evaluate 74 potential donors including 65 of 71 hearts ultimately used for transplantation. Of these 65 donors, 46 had normal studies, nine had pericardial effusions, five had mild septal hypokinesia with otherwise normal function, four had equivocal mitral valve prolapse, and only one heart could not be visualized. All transplants were successful and all donor hearts exhibited satisfactory hemodynamic function immediately after transplantation, including the hearts that were mildly abnormal before transplantation. These hearts included 21 (29%) that could have been excluded by conventional screening criteria. Nine potential donor hearts with grossly abnormal echocardiograms were not used for transplantation, including eight hearts with severe hypokinesia and one heart with significant mitral and tricuspid regurgitation. Inspection or histologic analysis confirmed the presence of severe dysfunction or morphologic damage in those hearts subjected to these additional measures. We conclude that echocardiographic screening is a useful method of evaluating potential cardiac transplant donors. It can identify potential donors that would otherwise have been excluded and it can identify potential donors with severe cardiac dysfunction without the need for direct surgical inspection.

Adult↗
PubMed1987

Acute hemodynamic response to low dose enoximone (MDL 17,043): an oral dose-range study.

The efficacy of low dose oral enoximone (MDL 17,043) was evaluated in the treatment of congestive heart failure (CHF). Fourteen male patients with stable, moderately severe CHF (New York Heart Association functional class II or III) and mean left ventricular ejection fraction of 0.21 +/- 0.02 were randomized to receive 50, 75, 100, 150 or 200 mg of enoximone (mean dose 1.46 +/- 0.16 mg/kg). Hemodynamic data were measured before and during the first 24 hours of therapy. An oral dose was given in the first 24 hours, and then every 8 hours. Acute administration of enoximone resulted in significant improvement in cardiac index (2.07 +/- 0.18 to 2.36 +/- 0.16 liters/min/m2, p less than 0.05), mean pulmonary arterial pressure (35 +/- 4 to 30 +/- 4 mm Hg, p less than 0.02), mean pulmonary artery wedge pressure (22 +/- 3 to 18 +/- 2 mm Hg, p less than 0.05) and systemic vascular resistance (1,712 +/- 148 to 1,384 +/- 82 dynes s cm-5, p less than 0.02). Neither hypotension nor tachycardia was observed. Although there was a trend toward a dose-response relation, hemodynamic responses to doses less than 1.5 mg/kg and greater than 1.5 mg/kg were not significantly different. Clinical symptoms improved with long-term therapy, but left ventricular ejection fraction and exercise treadmill time did not change. In patients with moderate and severe CHF, low doses of enoximone result in significant acute hemodynamic improvement.

Administration, Oral↗
PubMed1987

Heterogeneous regulatory changes in cell surface membrane receptors coupled to a positive inotropic response in the failing human heart.

The failing human ventricular myocardium undergoes heterogeneous changes at the receptor level that have some impact on the ability of the failing myocardium to respond to inotropic stimuli. In the failing human ventricular myocardium the beta 1-adrenergic receptor is profoundly down-regulated, the beta 2-adrenergic receptor is only slightly decreased, alpha 1-adrenergic receptors are unchanged and VIP receptors appear to be increased in density or affinity. These changes have implications for therapeutic strategies for heart failure and for the natural history and pathogenesis of heart muscle disease.

Adenylyl Cyclases↗
PubMed1987

Long-term experience with sotalol in the treatment of complex ventricular arrhythmias.

Sotalol was given for extended therapy to 22 of 29 patients with frequent (greater than or equal to 30/hour) complex premature ventricular complexes (PVCs) who had participated in a short-term study of sotalol vs placebo. Open-label sotalol was given in individually titrated divided doses of 160 to 800 mg/day (median 323, mean 386 mg/day). Response was assessed at approximately 1, 6, and 12 months or until patient discontinuation. The period of sotalol therapy averaged 9 months (range, 0.2 to 22.7). At about 1 month, 13 (59%) of 22 patients showed effective control of arrhythmia. The median percentage change in total PVCs for individual patients at 1 month was -70% and for repetitive PVCs it was -95%. At about 6 months, 10 (45%) of the 22 patients continued to be successfully treated; at about 12 months, seven patients continued on sotalol, six (27%) successfully treated according to Holter criteria. Reasons for discontinuation included lack of efficacy in nine, adverse effects in four (fatigue in three, bradycardia with sinus pauses in one), and miscellaneous reasons in two. ECG PR and especially QTc intervals increased significantly during therapy (p less than 0.02, p less than 0.01, respectively). In summary, sotalol is a moderately effective antiarrhythmic agent in patients with complex PVCs, but during long-term therapy a rather high dropout rate was observed because of arrhythmia recurrence or adverse effects.

Administration, Oral↗
PubMed1987

Treatment of refractory cardiac allograft rejection with OKT3 monoclonal antibody.

OKT3 monoclonal antibody is a murine monoclonal antibody specific for the T lymphocyte T3 cell surface receptor that mediates antigen recognition. The use of OKT3 monoclonal antibody for the treatment of cardiac allograft rejection refractory to conventional therapy with high-dose steroids and antithymocyte globulin is described. Seven patients received 5 mg of OKT3 monoclonal antibody intravenously per day for 10 to 14 days. Diagnosis of moderate or severe rejection was made in all seven from right ventricular endomyocardial biopsy. Biopsy was repeated 48 to 72 hours and seven to 10 days after OKT3 monoclonal antibody was begun. With treatment, four patients had a complete response, with improvement on both early and late biopsy. Two patients had partial responses, with improvement on early biopsy followed by worsening rejection on late biopsy. One patient died of graft failure six hours after receiving OKT3 monoclonal antibody. Adverse events were common in the first two days of therapy but were well tolerated. It is concluded that OKT3 monoclonal antibody is useful in the treatment of refractory cardiac allograft rejection.

Adult↗
PubMed1987

Age-associated decline in cardiac allograft rejection.

The influence of age on cardiac allograft rejection was studied in 57 consecutive recipients. Twenty-one subjects were 54 years of age or older (mean, 57.7 +/- 0.6 years [+/- SEM]; range, 54 to 63 years) and 36 subjects were 52 years of age or younger (mean, 39.9 +/- 1.8 years; range, 16 to 52 years; p less than 0.001). The older recipients had fewer rejection episodes during the first four months following cardiac transplantation (0.24 +/- 0.05 episodes per month versus 0.72 +/- 0.09 episodes per month; p less than 0.001) and during the total duration of follow-up (0.20 +/- 0.03 episodes per month versus 0.40 +/- 0.07 episodes per month; p = 0.045), and experienced their first rejection episode later (50.4 +/- 4.0 days versus 27.7 +/- 8.5 days; p = 0.008). Younger age was found to add significantly as a predictor of rejection in a multivariate analysis that controlled for sex, immunosuppressive agents, cause of heart failure, and pretransplantation lymphocyte cross-match status (r = 0.64, p less than 0.05). Decreased rejection frequency occurred without a concomitant increase in the serious infection rate (67 percent in both groups). The 12-month actuarial survival was 100 percent in the older group and 94 percent in the younger group (p = NS). Decreased rejection in the older recipients is likely a manifestation of an age-associated decline in immune function and might represent an advantage in transplantation for carefully selected older patients.

Actuarial Analysis↗
PubMed1986

Occurrence of ventricular arrhythmias in patients receiving acute and chronic infusions of milrinone.

Milrinone is a promising new inotrope, but its arrhythmogenic potential has not been defined. We monitored ventricular arrhythmias during a 24-hour baseline and 48-hour milrinone infusion period in 12 patients with chronic heart failure. Patients were characterized by a mean age of 58 years and a left ventricular ejection fraction of 21%. Nine (75%) were male, nine had primary idiopathic dilated cardiomyopathy, and three had coronary artery disease. None had a history of cardiac arrest or sustained ventricular tachyarrhythmia. Milrinone was given as a loading dose (mean 53 micrograms/kg/10 min; range 37.5 to 75) followed by a 48-hour maintenance infusion (mean 0.53 micrograms/kg/min; range 0.25 to 0.75). Acutely, cardiac index increased by 27% and pulmonary wedge pressure decreased by 30% during milrinone; changes were maintained during continued therapy. Ventricular arrhythmia response was variable, with no significant overall difference. However, a trend toward increased ectopic activity was noted. No sustained tachyarrhythmias occurred. Mean frequency of premature ventricular complexes (PVCs) was 87 +/- 48 PVCs/hr (x +/- SEM) during baseline monitoring and 141 +/- 69/hr following infusion of the drug (p = 0.08). Mean frequency of couplets was 6.0 +/- 4.9/hr before drug infusion and 14.3 +/- 11.0/hr during infusion (p = 0.21). Mean frequency of runs was 0.9 +/- 0.8/hr before and 2.7 +/- 2.4/hr during drug infusion (p = 0.29). Two patients met criteria for proarrhythmia (increased PVCs of greater than 4x and/or repetitive forms of greater than 10x. However, neither proarrhythmia patient required reduction in the dosage of milrinone or additional antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Multicenter trial of sotalol for suppression of frequent, complex ventricular arrhythmias: a double-blind, randomized, placebo-controlled evaluation of two doses.

Sotalol is a unique beta-adrenergic blocking agent with additional actions characteristic of Vaughn-Williams class III antiarrhythmic agents in experimental models. To test the efficacy of sotalol to suppress ventricular arrhythmias, a 6 week parallel, placebo-controlled out-patient study of two doses (320 and 640 mg/day, in two divided doses) was performed in four hospitals in 56 patients with chronic premature ventricular complexes at a frequency of 30/h or more (mean +/- SE, 528 +/- 60/h) on 48 hour ambulatory electrocardiographic recording. During a placebo week, no change occurred in arrhythmia frequency (532 +/- 76/h). Subsequent sotalol therapy significantly reduced median arrhythmia frequency in patients receiving both low (n = 19) and high (n = 18) doses compared with that in patients receiving placebo (by 77 and 83%, respectively, versus 6%; p less than 0.001). Twenty-two (59%) of 37 sotalol-treated patients, 11 in each group, reached the prospectively defined criterion of efficacy (greater than or equal to 75% arrhythmia reduction) versus 2 (11%) of 19 placebo control patients (p less than 0.001). Sotalol reduced the median frequency of couplets by 94% (p less than 0.0001) and that of runs by 89% (p less than 0.0007). The electrocardiographic effects of sotalol included reductions in heart rate (by 17 to 27%) and increases in the QTc (by 6 to 9%) and PR (by 6%) intervals. Ejection fraction was unchanged. The most common adverse side effect was fatigue, but drug discontinuation was required in only three patients taking 640 mg/day. No proarrhythmic events or biochemical abnormalities were observed. In summary, sotalol displays significant antiarrhythmic activity of moderately high degree with good tolerance in doses of both 320 and 640 mg/day. Its antiarrhythmic actions are distinguished from those reported for other beta-blockers by its effects on the QTc interval and its moderately high degree of antiarrhythmic activity.

Aged↗
PubMed1986

The effect of fluid loading, blood transfusion, and catecholamine infusion on oxygen delivery and consumption in patients with sepsis.

Fifty-four patients with systemic sepsis and signs of circulatory shock were prospectively investigated immediately before and after 1 of 3 therapeutic interventions chosen to increase systemic oxygen delivery (DO2): colloidal fluid loading (Group I, n = 20), blood transfusion (Group II, n = 17), or catecholamine infusion (dopamine or dobutamine, Group III, n = 17). Patients in Groups I and II with normal blood lactate concentrations (less than 2.2 mmol/L) exhibited no significant increases in systemic oxygen consumption (VO2) in response to the increases in DO2. However, significant increases in VO2 were noted in patients in Groups I and II with elevated lactate concentrations (greater than 2.2 mmol/L). In contrast to patients in Groups I and II, patients in Group III with and without lactic acidosis exhibited significant increases in VO2 after catecholamine administration. Lactic acidosis, a clinical marker of anaerobic metabolism or oxygen debt, appears to predict increases in VO2 in response to increases in DO2 in septic patients receiving fluid and catecholamines increase VO2 without regard for the presence or absence of anaerobic metabolism. The results of this clinical trial therefore suggest that catecholamines may exert a direct effect on oxidative metabolism.

Biological Availability↗
PubMed1985

A randomized trial of low-dose beta-blockade therapy for idiopathic dilated cardiomyopathy.

Beta-blockade therapy to improve survival in idiopathic dilated cardiomyopathy (IDC) has been both advocated and criticized. However, randomized studies have not been performed. Thus, 50 patients with IDC were randomized in pairs to standard therapy (C) alone or with beta blockade (BB). Beta-blockade therapy with metoprolol was titrated from 12.5 to 50 mg twice daily as tolerated (final average dose, 61 mg/day). Groups were comparable in age (C, 50 +/- 15 years; BB, 51 +/- 13 years), gender (C, 76% male; BB, 56% male), entry functional class (C, 2.8 +/- 0.8; BB, 2.7 +/- 0.7), and left ventricular ejection fraction (C, 27 +/- 12%; BB, 29 +/- 10%). Follow-up averaged 19 months (range 1 to 38). One subject in each group was lost to follow-up. There were 3 early BB dropouts (within 2 days) due to low-output syndrome (2 patients) or fatigue (1 patient). Eleven patients died. By intention to treat, 5 BB and 6 C patients died (difference not significant). By actual treatment, 3 BB patients died, including 2 late dropouts (at 0.2, 10 and 17 months), and 8 C patients died (at 2, 9, 9, 15, 18, 24, 29 and 32 months, p = 0.12). In additional, functional evaluation on follow-up (functional class, San Diego questionnaire and exercise time) all tended to favor those receiving BB. Low-dose BB is tolerated in 80% of IDC patients on a long-term basis. Those continuing to take BB have a good prognosis. Mortality in C patients, however, is less than in some retrospective studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1985

Fluid loading increases oxygen consumption in septic patients with lactic acidosis.

We prospectively evaluated 20 patients with systemic sepsis and signs of circulatory failure to determine if fluid loading was associated with increases in systemic oxygen delivery (DO2) and consumption (VO2). Fluid loading led to an increase in DO2 in 14 patients (70%). Patients who demonstrated increased DO2 with a corresponding increase in VO2 (Group A, n = 8) had significantly higher (p less than 0.05) initial blood lactate levels (4.9 +/- 2.9 mmol/L, mean +/- SD) than did patients without an increase in VO2 (Group B, n = 6, 1.9 +/- 1.0 mmol/L). A decrease in DO2 that was attributed to hemodilution was noted in the remaining 6 patients (Group C). Group C exhibited elevated lactate levels (5.1 +/- 2.4 mmol/L) and no significant changes in VO2. We conclude that lactic acidosis, a marker of anaerobic metabolism, predicts increases in VO2 in septic patients who respond to fluid loading with an increase in DO2.

Acidosis↗