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Biomedical subjects

J Widerhorn

Publications and source records attributed to J Widerhorn.

14 recordsLinked to original sources
PubMed1994

Risks of angiotensin-converting enzyme inhibition during pregnancy: experimental and clinical evidence, potential mechanisms, and recommendations for use.

OBJECTIVE: To review reports on the use of angiotensin-converting enzyme inhibitors (ACE-I) during pregnancy in order to determine the incidence, nature, and potential mechanisms of fetal complications in an attempt to establish recommendations related to the use of these drugs during gestation. DATA SOURCES: Relevant English-language articles identified through a Medline search and bibliographies found in recent articles. STUDY SELECTION: Large number of reports both on animals and on humans have consistently shown a high degree of morbidity and even mortality in fetuses or newborns exposed to ACE-I during pregnancy. The reported complications include oligohydramnios, intrauterine growth retardation, premature labor, fetal and neonatal renal failure, bony malformations, limb contractures, persistent patent ductus arteriosus, pulmonary hypoplasia, respiratory distress syndrome, prolonged hypotension, and neonatal death. A high incidence of fetal complications was related to the use of ACE-I at all trimesters of pregnancy. CONCLUSION: The gestational use of ACE-I may be associated with a high degree of fetal and newborn morbidity and even mortality. The use of these drugs should be avoided at all trimesters of pregnancy.

Abnormalities, Drug-Induced↗
PubMed1993

Electrophysiological evaluation of moricizine in patients with sustained ventricular tachyarrhythmias: low efficacy and high incidence of proarrhythmia.

In patients with history of sustained ventricular tachycarrhythmias, the efficacy and safety of moricizine have not been systematically evaluated by electrophysiological studies. We performed electrophysiological testing in these patients in the drug-free state and then after moricizine loading, and evaluated the safety profile of moricizine during in-hospital loading and follow-up. The study population comprised of 31 patients with clinically sustained ventricular tachyarrhythmia. The underlying heart disease was coronary in 25 patients, cardiomyopathy in 5 patients, and none in 1 patient. The left ventricular (LV) ejection fraction ranged from 15%-69% (mean 39 +/- 15%). During the baseline drug-free electrophysiological testing, sustained ventricular tachycardia was inducible in 27 patients, ventricular fibrillation in 1 patient, and reproducible, nonsustained ventricular tachycardia (15-25 sec) in 3 patients. All 31 patients received moricizine to the maximum tolerated dose (851 +/- 185 mg) over a period of 2-7 days. Six patients developed ventricular proarrhythmia within the first 4 days. Proarrhythmia required multiple cardioversions in three patients, was not associated with QT prolongation, and spontaneously resolved 6-24 hours after withdrawal of moricizine. Of the remaining 25 patients, 24 underwent electrophysiological testing on moricizine and 4 patients (16%) were rendered noninducible. The VT cycle length in the other 20 patients slowed from 243 +/- 30 msec to 299 +/- 60 msec (P < 0.09). Four noninducible patients, two patients with inducible but slowed VT and one patient who had refused further testing were discharged on moricizine.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1992

Prognostic significance of programmed ventricular stimulation in patients surviving complicated acute myocardial infarction: a prospective study.

In survivors of complicated myocardial infarction, the inducibility of sustained ventricular tachycardia may help identify a subset that is at increased risk for subsequent sudden cardiac death or spontaneous sustained ventricular tachycardia. We performed prehospital discharge programmed ventricular stimulation in 86 survivors of acute myocardial infarction complicated by heart failure, angina pectoris, or nonsustained ventricular tachycardia. These patients also underwent cardiac catheterization with coronary angiography and 24-hour ambulatory ECG recording. Programmed ventricular stimulation induced sustained ventricular tachycardia in 19 patients (22%) and ventricular fibrillation in six (7%) and did not induce these arrhythmias in 61 patients (71%). During an average follow-up of 18 +/- 13 months, 11 patients had arrhythmic events (seven sudden death and four nonfatal spontaneous sustained ventricular tachycardia) and 10 patients had nonsudden cardiac death. The total cardiac mortality rate was 20%. Arrhythmic events occurred in 32% of the 19 patients with inducible sustained ventricular tachycardia compared with 7% of the remaining 67 patients (p less than 0.003). By multivariate analysis the occurrence of arrhythmic events was independently predicted by both inducible sustained ventricular tachycardia and Killip class III or IV heart failure. The risk of arrhythmic events was 4.4% in the absence of both variables versus 38.4% (p less than 0.001) when both variables were present. The total cardiac mortality rate was best predicted by low left ventricular ejection fraction (less than 30%). Thus programmed ventricular stimulation is useful in risk stratification of survivors of complicated acute myocardial infarction. The prognostic utility appears to be particularly high in patients with infarction complicated by Killip class III or IV heart failure.

Arrhythmias, Cardiac↗
PubMed1992

Effect of loading conditions on Doppler-derived transmitral flow indices in normal subjects and patients with coronary artery disease.

The influence of alterations in preload and afterload on left ventricular diastolic filling using echocardiography was examined in nine normal volunteers (NLS) and nine patients (PTS) with coronary artery disease. The sequential interventions used were handgrip to increase afterload, nitroglycerin to decrease preload, and nifedipine to decrease afterload. Transmitral flow was measured using pulsed-Doppler echocardiography. Measurements were made pre- and post interventions. With increase in afterload using handgrip, the A and E wave velocities and the A/E ratio increased in both groups: 0.62 +/- 0.14 versus 0.86 +/- 0.17 in NLS; 0.75 +/- 0.45 versus 0.84 +/- 0.50 in PTS (P less than 0.05). Following administration of nitroglycerin to reduce preload, the A wave velocities increased, the E wave velocity decreased in both groups, and the A/E ratio increased 0.57 +/- 0.11 versus 0.67 +/- 0.13 in NLS; 0.78 +/- 0.40 versus 0.91 +/- 0.44 in PTS (P less than 0.05). Following use of nifedipine, the A and E wave velocities decreased in both groups with an increase in the A/E ratio in the patient group 0.83 +/- 0.13 versus 0.89 +/- 0.11 (P = NS). Thus, both normal subjects and patients with coronary artery disease had similar changes in Doppler-derived indices of left ventricular filling following interventions that changed left ventricular preload and afterload.

Adult↗
PubMed1991

A prospective evaluation of the immediate reproducibility of the signal-averaged ECG.

The purpose of this investigation was to prospectively evaluate the immediate reproducibility of the signal-averaged electrocardiogram (SAECG). A total of 114 patients undergoing evaluation for ventricular arrhythmias were enrolled in this protocol. Two consecutive SAECG's (40 Hz bidirectional high-pass filtering with a computer-automated system) were performed 10 minutes apart. Abnormal SAECG parameters were defined as (1) vector QRS duration more than 120 msec, (2) terminal root mean square (RMS) voltage less than 20 microV, and (3) low-amplitude signal (LAS) duration more than 40 msec. An SAECG was defined as abnormal if at least one vector parameter was abnormal. There was close correlation between vector parameters during the two SAECG observations: QRS duration had the highest reproducibility (r2 = 0.97, p less than 0.001) followed by terminal RMS voltage (r2 = 0.92, p less than 0.001), and LAS duration (r2 = 0.90, p less than 0.001). The mean (+/- SD) percentage of change between the two recordings was 2% +/- 2% of the QRS duration, 13% +/- 22% for terminal RMS voltage, and 7% +/- 11% for LAS duration. The reproducibility of an initially normal SAECG was 92% and of an initially abnormal SAECG, 96%. Seventeen patients (15%) had a change in one of the three vector parameters between the two recordings. There were no clinically significant differences between the 17 patients in whom the SAECG was nonreproducible and the 97 patients in whom the SAECG was reproducible. However, reproducibility was significantly higher in patients with an initially normal versus an initially abnormal SAECG (92% vs 76%, p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1991

The role of combination therapy with mexiletine and procainamide in patients with inducible sustained ventricular tachycardia refractory to intravenous procainamide.

This study evaluated the role of serial electropharmacological testing on combination therapy with mexiletine and procainamide in 20 patients with inducible sustained ventricular tachycardia (VT) refractory to intravenous procainamide. The clinical arrhythmias were cardiac arrest in five patients, sustained VT in 11 patients, and recurrent syncope of presumably arrhythmic origin in four patients. The mean left ventricular ejection fraction (LVEF) was 0.40 +/- 0.12 (mean +/- SD). All patients had inducible sustained VT at baseline and after administration of intravenous procainamide. All 20 patients underwent electropharmacological testing on combination therapy with mexiletine and procainamide. The mean cycle length of inducible sustained VT was 251 +/- 48 ms at baseline, 324 +/- 81 ms on intravenous procainamide (P less than 0.014 vs baseline), and 365 +/- 82 ms on combination therapy (P less than 0.0001 vs baseline, P = NS vs intravenous procainamide). Combination therapy did not suppress VT inducibility, nor did it make VT more difficult to induce in 19 of 20 patients. The remaining one patient had a partial response (runs of nonsustained VT, longest 10 seconds). Furthermore, combination therapy did not significantly prolong the VT cycle length over and above that observed during testing with intravenous procainamide. Therefore, in patients with inducible sustained VT refractory to procainamide during initial electropharmacological testing, mexiletine in combination with procainamide appears to be of little or no value and serial electropharmacological testing on these drugs is of limited usefulness. Early initiation of alternative therapy may be the preferred clinical option.

Adult↗
PubMed1990

Prospective evaluation of parenteral magnesium sulfate in the treatment of patients with reentrant AV supraventricular tachycardia.

This study prospectively assessed the electrophysiologic effects of parenteral magnesium sulfate administration on paroxysmal atrioventricular (AV) reentrant supraventricular tachycardia and the efficacy of magnesium to terminate these arrhythmias. Eleven normomagnesemic patients, seven with orthodromic reentrant supraventricular tachycardia that used an accessory AV pathway, and four with typical AV nodal reentry were examined. All patients had a history of sustained supraventricular tachycardia requiring pharmacologic therapy or electrical cardioversion for termination of tachycardia. After baseline electrophysiologic study, including documentation of sustained supraventricular tachycardia that was reproducibly induced, parenteral magnesium sulfate (a bolus of 0.3 mEq/kg of elemental magnesium infused over a 10-minute period followed by a maintenance infusion of 0.2 mEq/kg/hr) was administered during sustained supraventricular tachycardia. The serum magnesium concentration increased from (mean +/- standard deviation) 1.9 +/- 0.2 mg/dl to 4.0 +/- 0.6 mg/dl (p = 0.0001). Except for flushing and mild diaphoresis during infusion of the magnesium sulfate bolus, and dry heaves in one patient, there were no untoward effects or significant changes in systolic blood pressure. During administration of magnesium, the tachycardia cycle length increased from 319 +/- 39 msec to 348 +/- 43 msec (p = 0.0001). Slowing of the tachycardia occurred predominantly in the antegrade limb of the circuit at the level of the AV node with the AH interval increasing from 171 +/- 66 msec to 197 +/- 68 msec (p = 0.0001), whereas there was no significant change in the HV interval (43 +/- 3 msec to 43 +/- 4 msec, p = NS) or the VA interval (106 +/- 43 msec to 110 +/- 47 msec, p = NS) during tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Central and renal hemodynamic effects of a new agonist at peripheral dopamine- and beta-2 adrenoreceptors (dopexamine) in patients with heart failure.

The effect of dopexamine, a new dopamine analogue, on central and renal hemodynamics was evaluated in nine patients with chronic, congestive heart failure caused by severe left ventricular (LV) systolic dysfunction. The administration of the maximally tolerated dose (7.2 +/- 4 micrograms/kg/min) resulted in a significant increase in cardiac index from 1.9 +/- 0.4 L/min/m2 to 2.6 +/- 0.9 L/min/m2 (p less than 0.05). This increase in cardiac index was largely a result of increase in heart rate (from 88 +/- 20 beats/min to 104 +/- 24 beats/min, p less than 0.05), because stroke volume index demonstrated only a small change (from 23 +/- 10 ml/m2 to 27 +/- 11 ml/m2, p not significant) in spite of a significant fall in systemic vascular resistance from 1992 +/- 717 dynes.sec.cm-5 to 1361 +/- 524 dynes.sec.cm-5 (p less than 0.05) and diastolic blood pressure (from 89 +/- 15 mm Hg to 80 +/- 17 mm Hg, p less than 0.05). No change was seen during dopexamine infusion in systolic blood pressure, right and left ventricular filling pressures, and LV stroke work index. Both renal blood flow and glomerular filtration rate were impaired at baseline in most patients. Dopexamine administration resulted in a significant increase (2x coefficient of variation) in renal blood flow in two patients only. Mean values of both renal blood flow and glomerular filtration rate did not show significant change (485 +/- 183 ml/min vs 563 +/- 221 ml/min and 89 +/- 39 ml/min vs 93 +/- 34 ml/min, respectively, p not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Strongyloides stercoralis hyperinfection in a patient with the acquired immune deficiency syndrome.

Severe infections with Strongyloides stercoralis occur in immunocompromised patients. Strongyloides hyperinfection syndrome complicated by gram-negative bacteremia and meningitis in a bisexual man with the acquired immune deficiency syndrome (AIDS) is described. Increased awareness of this infection, which may also be sexually transmitted, is recommended when caring for patients with AIDS who are homosexual, or have resided in areas endemic for strongyloidiasis. Multiple stool examinations should be performed routinely for such patients. Examination of sputum for the parasite is recommended if pneumonia is present. Prompt diagnosis and therapy are essential for prevention of fatal dissemination.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Cardiovascular drugs in pregnancy.

Cardiovascular drugs are often used in pregnancy for the treatment of maternal and fetal conditions. The complex physiologic changes occurring during pregnancy may significantly affect the pharmacokinetics of many drugs and, consequently, the toxicity and therapeutic response. Of special concern are the effects of maternal therapy on the fetus and the undesired translactal passage of drugs to newborns. Although the body of information regarding cardiovascular therapy in pregnancy is incomplete, some of the available data are summarized in this article.

Adrenergic beta-Antagonists↗