A decade of clinical trial developments in postmyocardial infarction, congestive heart failure, and sustained ventricular tachyarrhythmia patients: from CAST to AVID and beyond. Cardiac Arrhythmic Suppression Trial. Antiarrhythmic Versus Implantable Defibrillators

Multiple trials using antiarrhythmic drugs, pharmacologic therapy, and implantable cardioverter defibrillators have been performed in an attempt to improve survival in patients: (1) postmyocardial infarction; (2) with congestive heart failure, with and without nonsustained ventricular tachycardia; and (3) with sustained ventricular tachycardia and those who have survived an out-of-hospital cardiac arrest. This article reviews some of the key findings and limitations of completed and ongoing trials. We also make recommendations for the current treatment of such patients based on the results of these trials.     

An immune complex selective affinity column utilizing site-specific attachment of bovine conglutinin

Established leukemic cell lines have been useful models for studying the biology of leukemia. Analysis of the actions of differentiating agents on leukemic cell lines in vivo has been limited by an inability to unambiguously distinguish host hematopoietic elements from differentiated leukemic cells. In order to identify and quantify leukemic cells during in vivo studies, a derivative of the murine myelomonocytic leukemia cell line WEHI-3B D+, which stably expresses beta-galactosidase, was constructed utilizing retroviral vector gene transfer. This cell line, termed WEHI-3B D+/lacZ 2.8, demonstrated in vitro growth and differentiation properties similar to the parental cell line. WEHI-3B D+/lacZ 2.8 expressed high levels of beta-galactosidase following prolonged in vitro growth and following differentiation in suspension cultures and clonogenic assays. In vivo, WEHI-3B D+/lacZ 2.8 was leukemogenic and high level expression of beta-galactosidase was maintained. Quantification of tissue involvement with WEHI-3B D+/lacZ 2.8 leukemia was performed utilizing staining with the fluorogenic beta-galactosidase substrate fluorescein di-beta-galactoside and fluorescence-activated cell sorting analysis. In vivo differentiation efficiency following granulocyte colony-stimulating factor (G-CSF) administration was determined using a simultaneous nuclear and cytoplasmic staining procedure. Results indicate that treatment of mice inoculated with WEHI-3B D+/lacZ 2.8 cells with G-CSF administration causes detectable but limited differentiation.     

Predictors of the early development of advanced metachronous colon adenomas

BACKGROUND/AIMS: In order to reduce the number of colonoscopies performed for the surveillance of patients after polypectomy, suitable predictors of adenomas recurrence are needed. The aim of this study was to find predictors of the early development of metachronous adenomas and specifically of advanced ones. MATERIALS AND METHODS: Forty-four patients underwent total colonoscopy 24-26 months after initial endoscopic polypectomy. All polyps were endoscopically removed and an adenoma was considered as advanced if the diameter was > 1 cm and/or villous component and/or severe dysplasia were present. RESULTS: Metachronous adenomas were detected in 16 (36.4% patients. Five (11.4%) of them had advanced metachronous adenomas. Early recurrence of adenomas was significantly correlated with the total number of indices adenomas (p = 0.027). On the contrary, the presence of metachronous adenomas was not related to any of the patients' characteristics nor to the site and the histology of the indices adenomas. The development of advanced metachronous adenomas during the same period was significantly correlated with patients' age, as it was observed only in patients aged > or = 60 years (5/21 or 23.8%) and in none of the patients aged < 60 years (Odds ratio: 15.7, p = 0.02). Logistic regression analysis revealed that patient's age was the only significant predictor of the early development of advanced metachronous adenomas (beta = 0.40, p = 0.02) and that the number of the indices adenomas was the only significant predictor for the recurrence of all adenomas (beta = 1.59, p = 0.02). CONCLUSIONS: 1. Only patients aged > or = 60 years seem to develop advanced metachronous adenomas two years after polypectomy and 2. The likelihood for developing metachronous adenomas during the same period is related to the number of indices adenomas.     

Antianginal response to once-daily diltiazem CD in patients receiving concomitant beta-blockers, long-acting nitrates, or both. Diltiazem CD Study Group

STUDY OBJECTIVE: To determine the safety and efficacy of diltiazem CD 180 mg administered once/day in patients with chronic stable angina inadequately controlled with P-blockers, long-acting nitrates, or both. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. SETTING: Medical clinics in the private and academic sectors. PATIENTS: Of 172 patients, 170 completed the 2-week double-blind treatment period. INTERVENTION:. Patients received either diltiazem CD 180 mg or placebo once/day in combination with existing antianginal therapy. MEASUREMENTS AND MAIN RESULTS: The time to termination of exercise tolerance testing, 24 hours after the dose increased significantly in the diltiazem CD group (37.2 sec) compared with the placebo group (21.3 sec, p=0.0438). Time to onset of angina during exercise testing also increased (57.6 vs 35.0 sec, respectively, p=0.0324), as did time to moderate angina (37.5 vs 20.6 sec, respectively, p=0.0354). The rates of total angina attacks and of angina attacks on exertion were significantly reduced in the diltiazem CD group versus placebo (p<0.05). Significant reductions in systolic and diastolic blood pressures and heart rate-blood pressure product measured at rest, submaximum exercise, and exercise termination were observed in diltiazem CD-treated patients compared with placebo (p<0.05). The frequency of treatment-related adverse events was identical in the two groups, 15.1%. CONCLUSION: Diltiazem CD 180 mg once/day is an effective, safe, and beneficial initial dosage when added to existing antianginal therapy.     

Management of posttransplant lymphoproliferative disease in pediatric liver transplant recipients receiving primary tacrolimus (FK506) therapy

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) after pediatric liver transplantation has been associated with high mortality rates. METHODS: The present study examined 282 consecutive pediatric liver transplant recipients from October 1989 to June 1996 who received primary tacrolimus immunosuppression. The aim was to determine the incidence of PTLD, management strategies, and patient outcome. RESULTS: The incidence of PTLD was 13% (361282) with a mean age of 5.5+/-0.7 years (range 0.6 to 15) at diagnosis. The average time from transplantation to PTLD was 10.1+/-2.1 months. Initial treatment of PTLD consisted of reduction (3 patients) or discontinuation (33 patients) of tacrolimus and initiation of antiviral therapy (intravenous ganciclovir, 14 patients; intravenous acyclovir, 22 patients; or both, 5 patients). Alpha-interferon was used in four patients (two successfully). One patient also received gamma-interferon, chemotherapy, and radiation for a central nervous system lesion. Chemotherapy was also used in one patient with Burkitt's, whereas one patient with a pulmonary lesion received additional radiation therapy. Three patients received supportive surgery for gastrointestinal involvement, and one patient had a splenectomy for hemolysis. Overall mortality was 22% (8/36) with 5 (14%) PTLD-related deaths (disseminated disease, 4 patients; bowel perforation, 1 patient). Of 31 survivors, 23 had acute rejection at a median time of 24 days after PTLD, with 2 patients developing chronic rejection. One patient required retransplantation. Present immunosuppression consists of tacrolimus monotherapy in 14 patients, tacrolimus/prednisone in 8 patients, and none in 6 patients. CONCLUSION: In summary, PTLD can be successfully treated with reduction of immunosuppression and administration of antiviral agents in most patients. The management of rejection after PTLD requires reassessment of disease status and judicious reintroduction of immunosuppression therapy.