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The efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients (68% men, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Patients with sitting diastolic blood pressure (BP) > or =110 mm Hg during the placebo run-in received HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan cilexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. After 1 week of double-blind treatment, patients with sitting diastolic BP > or =90 mm Hg were uptitrated to candesartan cilexetil 16 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitration. Primary efficacy measurement was a change in trough (24+/-3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to double-blind week 4. Mean changes in systolic and diastolic BP were significantly greater with candesartan cilexetil than with placebo, -11.3/-9.1 mm Hg versus -4.1/-3.1 mm Hg, p <0.001/p <0.001, respectively. Patients with higher sitting diastolic BP at the end of the HCTZ run-in tended to have greater decreases in BP (p <0.05). Most patients (53%) receiving candesartan cilexetil were responders (diastolic BP <90 mm Hg or > or =10 mm Hg decrease) and 32% were controlled (diastolic BP <90 mm Hg). Tolerability and safety profiles were similar in the candesartan and placebo groups. In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effective and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in the United States.

Background: Diversion of the fecal stream with or without primary repair has been the mainstay of therapy for rectal injuries. Because primary repair has replaced colostomy as the treatment of choice for most colon injuries, we reviewed our experience with primary repair of rectal injuries in order to determine if primary repair without diversion is a feasible option in selected patients., Materials and Methods: All traumatic rectal injuries over the past 48 months were reviewed for mechanism of injury, diagnosis, treatment, and outcome., Results: Thirty consecutive patients with extraperitoneal rectal injuries were identified. Six of the 30 patients underwent primary repair without diversion. Five were repaired transanally, and 1 was repaired at celiotomy. There was no morbidity related to the rectal repair in patients who underwent primary repair without diversion, and there were no deaths., Conclusions: Based on a small number of patients, these data suggest that primary repair of rectal injuries in selected patients may be feasible. Further prospective investigation is needed to determine which patients may be successfully treated in this fashion.

This prospective multicenter study was conducted under the Food and Drug Administration Investigational Device Exemption to evaluate the safety and efficacy of the combination of the Cadence implantable defibrillator (Ventritex, Inc.) and 60-series Endotak C leads (Cardiac Pacemakers, Inc.). Implantation was attempted in 148 patients with hemodynamically compromising ventricular tachycardia or fibrillation (VF), or with pace-terminable ventricular tachycardia. The system was successfully implanted in 97% of patients, with 96% of implants in a transvenous-lead-alone configuration. At implantation, the defibrillation threshold was 455 +/- 94 V (14 +/- 6 J) for lead-alone patients and 532 +/- 40 V (19 +/- 3 J) for those requiring a subcutaneous patch. VF conversion efficacy was reconfirmed in patients who underwent a 3-month chronic induction study. The system successfully detected all 763 induced arrhythmias and terminated 99.5% of them; after system modification, successful conversion was demonstrated in the 2 patients who initially had induced episodes requiring external defibrillation (1 lead revision; 1 reprogramming). All spontaneous episodes were terminated with an implantable-cardioverter defibrillator. Postshock VF redetection times were significantly shorter than initial detection times (4.5 +/- 1.8 seconds detection, 2.1 +/- 0.7 seconds redetection; p<0.0001). During an 8-month mean follow-up (range 1 to 31 months), 2 unwitnessed deaths were classified as sudden cardiac deaths, and 11 patients experienced a total of 12 complications, none of which was associated with the Cadence-Endotak combination.

Because the automatic internal cardioverter defibrillator's long-term ability to reduce arrhythmic mortality in patients with ventricular tachycardia/fibrillation is unknown, it is important to determine whether the threshold for defibrillation changes over time. Serial defibrillation thresholds were measured in 23 patients over a mean replacement time of 24.8 +/- 7.5 months. In all cases the lead system was a superior vena cava coil to a left ventricular epicardial patch. The defibrillation threshold for the entire group increased from 12.3 +/- 4.7 J to 16.9 +/- 5.9 J (p less than 0.05). Striking increases in the defibrillation threshold were seen in the subgroup of patients taking amiodarone (from 10.9 +/- 4.3 J at implantation to 20.0 +/- 4.7 J at replacement, p less than 0.05). Defibrillation threshold decreased in patients taking no antiarrhythmic drugs or taking class I agents. Thus, the increase in mean defibrillation threshold was the result of an increase in the patients taking amiodarone. These data suggest that at initial implantation lead systems associated with the lowest defibrillation threshold should be used and the defibrillation threshold should be measured at generator change to guarantee an adequate margin of safety.

Purpose: Amiodarone has proven to be effective in many cases of cardiac arrhythmias, refractory ventricular tachycardia, and ventricular fibrillation. Pulmonary toxicity is a possible side effect of the drug, with a reported incidence of 2 to 15 percent per year. To determine the effect of amiodarone on lung function, we prospectively studied serial lung function tests in a cohort of 91 patients with refractory cardiac arrhythmias treated with this agent., Patients and Methods: Spirometry and carbon monoxide diffusing capacity (DLCO) were measured at zero, three, six, 12, 18, and 24 months, with a mean follow-up of 351 days., Results: For the whole population taking a mean dose of amiodarone of 367 mg daily (range: 136 to 512 mg), there was no accelerated rate of decline in spirometric indices or DLCO. Analysis of lung function changes by multivariate analysis demonstrated that an accelerated decline in DLCO values occurred in elderly patients (p less than 0.05) but not in patients with pre-existing lung disease or cigarette smokers. In four patients (4.5 percent), clinical evidence of amiodarone pulmonary toxicity developed that was associated with a fall in DLCO of greater than 20 percent. All four patients recovered after the drug was stopped. Another 15 patients, without clinical evidence of pulmonary toxicity, had a sustained decline in DLCO of greater than 20 percent. These 15 patients remained asymptomatic over the next 11 months without interruption of therapy. A greater than 20 percent fall in DLCO was a sensitive test for clinically evident amiodarone pulmonary toxicity, but had a positive predictive value of only 21 percent., Conclusion: An isolated fall in DLCO, in the absence of clinical evidence of toxicity, does not necessitate stopping amiodarone. An unchanged DLCO value appears to be a reliable negative predictor of pulmonary toxicity.