Effects of diltiazem on recurrent myocardial infarction in patients with non-Q wave myocardial infarction.

Diltiazem has been reported to reduce the short-term in-hospital reinfarction rate in patients with a non-Q wave myocardial infarction. In the long-term Multicenter Diltiazem Postinfarction Trial, there were 514 patients with non-Q wave myocardial infarction; 279 patients were randomized to the placebo group and 235 to the treatment group. The average follow-up period was 25 months. There was no difference in baseline clinical characteristics between the two groups. Early reinfarction (less than or equal to 6 months) occurred in 17 patients in the placebo group and in 2 patients in the diltiazem group (p less than 0.001). Late reinfarction (greater than 6 months) occurred in 13 patients in the placebo group and in 14 patients in the diltiazem group (p = NS). Initial and reinfarction electrocardiograms (ECGs) were analyzed by using a coding system that permitted identification of standard anatomic areas involved in the infarction process. Thirty-one of the 46 patients had a localized infarction on index and reinfarction ECGs. In the early reinfarction group, 10 (77%) of 13 infarctions occurred in the same ECG region in which the initial infarction had occurred; all 10 were in patients in the placebo group. Among the 18 patients with late reinfarction, the site of the second infarction was the same as that of the first in 9 patients and differed in 9. There was no difference between the placebo and diltiazem groups with respect to location of the infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between beta-adrenergic blocker use, various correlates of left ventricular function and the chance of developing congestive heart failure. The Multicenter Diltiazem Post-Infarction Research Group.

This study examined the relations among beta-adrenergic blocker use, various correlates of left ventricular function and the chance of developing congestive heart failure in patients after myocardial infarction. The study was performed with the placebo group of the Multicenter Diltiazem Post-Infarction Trial. Ejection fraction data were available in 1,084 patients; of these, 557 were receiving a beta-blocker and 527 were not. In addition to ejection fraction, other correlates of left ventricular function included the presence or absence of pulmonary rales, chest X-ray film evidence of pulmonary congestion and the presence of an S3 gallop. Beta-blocker use was less frequent in patients with an ejection fraction less than 30%, rales, an S3 gallop and pulmonary congestion on chest X-ray film. Twenty-one percent of patients with an ejection fraction less than 30%, 42% of patients with rales, 28% of patients with an S3 gallop and 28% of patients with pulmonary congestion were receiving beta-blocker therapy. For every correlate of left ventricular function, the chance of developing congestive heart failure was greater in patients with diminished left ventricular function than in those without. For each level of left ventricular function, the chance of developing congestive heart failure requiring treatment was greater in patients not taking a beta-blocker.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocarditis with myocardial abscesses and pericarditis in an adult: group B Streptococcus as a cause.

Group B beta-hemolytic Streptococcus, S agalactiae, is an uncommon cause of endocarditis in adults. We present the clinical, laboratory, and postmortem findings of an adult patient with group B streptococcal endocarditis and major arterial emboli. What to our knowledge are previously unreported features are purulent pericarditis and myocardial abscesses. Twenty-five cases of endocarditis caused by group B Streptococcus that are reported in the literature are reviewed.

Digoxin bioavailability during quinidine administration.

Digoxin serum concentration rises in the presence of quinidine. To determine whether quinidine alters digoxin bioavailability, six subjects received 1.0 mg of digoxin intravenously alone and by mouth on alternate weeks during steady-state oral quinidine administration. The area under the digoxin concentration:time curves (AUC) and the amount of digoxin excreted in the urine (Xxu) were determined for the 96 hr after each of the four experiments. Values for digoxin bioavailability relative to the corresponding intravenous study in the absence and presence of quinidine were (+/- S.D.) 73.5 +/- 8.6% and 79.5 +/- 22.6% (P greater than 0.05) for serum and 69.8 +/- 6.8% and 70.2 +/- 10.5% (P greater than 0.05) for urine. There was no difference in the steady-state quinidine serum concentration during the 4 days after intravenous and oral digoxin. We conclude that quinidine does not alter digoxin bioavailability and therefore that altered absorption does not explain the rise in digoxin serum concentration in the presence of quinidine.

Effects of chronic cetamolol therapy on resting, ambulatory, and exercise blood pressure and heart rate.

We studied blood pressure (BP) and heart rate (HR) responses in 12 patients with hypertension who were receiving cetamolol, a cardioselective beta-blocker with intrinsic sympathomimetic activity. The BP and HR parameters were evaluated at rest (casual, office readings), with ambulatory BP monitoring, and after treadmill exercise testing. At a mean (+/- SD) dose of 46 +/- 21 mg/day, casual supine BP decreased by 10/12 mm Hg (P less than 0.05 for systolic; P less than 0.01 for diastolic) compared with placebo, while HR decreased 4 bpm. Cetamolol resulted in a significant reduction in the mean 24-hour systolic BP. The most striking reduction occurred in the BP at work (23 mm Hg), with almost no decrease in the BP during sleep. Ambulatory HR reductions occurred while the subjects were at work (9 bpm; P less than 0.05) but not while at home (awake) or during sleep. The mean duration of exercise was the same during cetamolol and placebo phases, but both HR and BP fell significantly at peak performance after cetamolol. These data suggest that cetamolol reduces BP without lowering HR at rest. During periods of increased adrenergic activity such as work and dynamic exercise, both HR and BP are reduced.

The effects of the long-acting angiotensin-converting enzyme inhibitor cilazapril on casual, exercise, and ambulatory blood pressure.

We assessed blood pressure (BP) and heart rate (HR) responses in a double-blind, randomized study comparing cilazapril, a long-acting, nonsulfhydryl-group converting enzyme inhibitor, with placebo in 18 patients with mild to moderate (sitting diastolic BP, 95 to 114 mm Hg) essential hypertension. The BP and HR parameters were evaluated at rest (casual, 24 hours after administration), during treadmill exercise testing (Bruce protocol), and with 24-hour noninvasive ambulatory BP monitoring. These assessments were made after a 4-week drug washout period and after 8 to 12 weeks of therapy. After 8 weeks of therapy with cilazapril (mean dose 3.6 +/- 0.9 mg/day), casual BP decreased 19/11 mm Hg (p less than 0.01), whereas placebo lowered BP by 4/5 mm Hg (difference not significant) compared with the baseline period. The casual HR was modestly (7 beats/min) but significantly (p less than 0.05) lowered by cilazapril monotherapy. Exercise BP was reduced by cilazapril (reduction at peak HR, 23/11 +/- 10/5 mm Hg; p less than 0.05), and exercise HR was unchanged. Compared with baseline, the duration of exercise was improved with cilazapril but not with placebo (1.0 minute vs -0.2 minute; p less than 0.05). Twenty-four-hour mean, awake, and sleep BPs were reduced with cilazapril with the most impressive reduction occurring during the awake period (19/12 mm Hg; p less than 0.01). These data demonstrate that cilazapril lowers casual, exercise, and ambulatory BP with a modest but significant improvement in exercise time. Thus cilazapril may be particularly effective in the physically active hypertensive patient.

Digoxin-quinidine-spironolactone interaction.

Digoxin kinetics are substantially altered by quinidine and by spironolactone. We evaluated the effect of the combination of quinidine and spironolactone on digoxin kinetics and compared it to the effect on digoxin of each drug alone. Six normal subjects each received a 1.0-mg intravenous dose of digoxin alone, digoxin with quinidine, digoxin with spironolactone, and digoxin with both quinidine and spironolactone. Spironolactone and quinidine, alone and in combination, reduced digoxin systemic, renal, and nonrenal clearances and prolonged digoxin elimination t 1/2. A greater alteration in digoxin kinetics was induced by quinidine than by spironolactone, and an even greater effect resulted from the combination. We did not assess clinical consequences of the interaction. We advise reduction in digoxin dose, careful clinical evaluation, and measurement of serum digoxin concentrations when digoxin is used in combination with quinidine and spironolactone.

Assessment of beta blockade with propranolol.

Each of seven subjects received on a weekly basis placebo or 10, 20, 40, 80, or 160 mg propranolol orally four times daily. The effect of propranolol on the resting heart rate and the heart rate responses to the Valsalva maneuver, tilt, isoproterenol, and maximal exercise were measured. Coefficients of determination were calculated from the individual dose-response curves. The results indicate that the resting heart rate and the tachycardiac response to the Valsalva maneuver and tilt cannot be used to estimate beta blockade. Propranolol concentrations correlated well (mean r2 = 0.80) with the isoproterenol dose ration minus one, but isoproterenon challenges appear clinically inapplicable. Reduction in maximal exercise tachycardia correlated best with propranolol concentrations (mean r2 = 0.89) but, to the extent that exercise could not be performed, there was no reliable way of clinically documenting beta blockade and only the serum concentration of propranolol was available as an indicator of appropriate therapy.

Effect of quinine on digoxin kinetics.

Six subjects were evaluated for the effect of quinine, the l-isomer of quinidine, on digoxin pharmokinetics. A 1.0-mg intravenous digoxin dose was given before and during quinine administration, followed by the measurement of digoxin serum and urine concentrations for 96 hr after each dose. Quinine reduced digoxin total body clearance by 26% from 2.98 to 2.22 ml/min/kg (p < 0.03). Digoxin elimination half-life (t 1/2) was lengthened from 34.2 to 51.8 hr, reflecting a 32% decrease in digoxin elimination rate constant (p < 0.003). Quinine did not reduce digoxin renal clearance or any volumes of distribution. The amount of digoxin excreted into the urine increased from x = 628. 29 micrograms to x = 772.52 micrograms (p < 0.02). Digoxin nonrenal clearance decreased an average of 55% from 1.2 to 0.55 ml/min/kg (p < 0.05). These results suggest that quinine alters digoxin metabolism or biliary secretion, reducing digoxin total body clearance by a mechanism that is qualitatively similar, but quamtitatively different, from quinidine.

Cellular actions and pharmacology of the calcium channel blocking drugs.

The calcium channel blockers represent a group of diverse chemical structures that block calcium-selective channels in the plasma membranes of a variety of excitable cells. As the calcium fluxes carried by these channels allow the calcium ion (Ca2+) to gain access to the cell interior, where calcium serves as an activator messenger, calcium channel blockers generally act to inhibit cell function. By reducing the depolarizing currents caused by the entry of positively charged Ca2+ into the negatively charged interior of resting cells, the calcium channel blockers also inhibit excitatory processes that depend on calcium entry across the plasma membrane. These principles account for most of the effects of calcium channel blockers on the cardiovascular system. The calcium channel blockers inhibit contractile function in the heart and vascular smooth muscle and, because the initial depolarizing currents in the sinoatrial and atrioventricular nodes are carried by calcium channels, slow the heart rate and prolong atrioventricular conduction. The negative inotropic and vasodilatory effects of the calcium channel blockers, both of which can reduce systemic blood pressure, offer a theoretic basis for their potential use in the treatment of hypertension. The tissue specificity exhibited by some of the calcium channel blockers may enhance their therapeutic value in selected hypertensive patients. Of the three calcium channel blockers now available for use in the United States (diltiazem, nifedipine, and verapamil), diltiazem and verapamil are approximately equipotent in inhibiting calcium channel function in the heart and vascular smooth muscle, whereas nifedipine is more potent in smooth muscle. This tissue specificity can be used to advantage in the management of hypertension. These pharmacologic principles underlie the growing appreciation of the potential value of the calcium channel blockers in the treatment of hypertension.

Creatine kinase MB isoenzyme in the evaluation of myocardial infarction.

The measurement of serum CK-MB isoenzyme is a very sensitive and specific indication of myocardial injury since only myocardium has substantial amounts of CK-MB. Serum CK-MB levels are most helpful clinically when the total creatine kinase is nonspecifically elevated, as with intramuscular injections, cardiac catheterization, stroke, noncardiac surgery and electric cardioversion. Elevations of serum CK-MB occurring in Duchenne's muscular dystrophy and other neuromuscular disorders may be due to the presence of abnormal regenerative skeletal muscle fibers, which are known to contain large amounts of CK-MB isoenzyme. These examples emphasize that under normal, nonregenerative conditions, elevations of serum CK-MB are rare in the absence of myocardial injury.

Amyloid heart disease manifested by systemic arterial thromboemboli.

Amyloid heart disease characteristically produces a stiff heart syndrome whereby diastolic filling is impaired yet systolic function is well preserved. We report two patients with this pattern of amyloid heart disease, both of whom developed cardiogenic thromboemboli. The rarity of this complication is striking given the pathophysiologic bases of amyloid heart disease. Investigation of contributing causes revealed that the phenomena appeared to represent the cumulative effects of disorders producing stasis, endothelial disturbance, and probable abnormalities in blood coagulability, the classic Virchow's triad revisited. Understanding of the pathophysiologic basis of this event leads to specific suggestions for workup and management in this patient population.

Follow-up of patients with tubo-ovarian abscess(es) in association with salpingitis.

The medical records of 143 patients hospitalized with a diagnosis of salpingitis over a five-year period were reviewed. Ninety-three patients had salpingitis without clinical evidence of a tubo-ovarian abscess. Seven (7.5%) of these women had surgical treatment; five of the seven were found to have tubo-ovarian abscesses which had not been detected clinically. Eighty-six of 93 (92.5%) patients with a clinical diagnosis of salpingitis and no abscess responded to medical management alone. Fifty patients had salpingitis and clinical evidence of a tubo-ovarian abscess(es); five of these patients had medical management only, 27 had medical treatment followed by surgery, and 18 had surgery initially before receiving antibiotics. There was a significant difference in age but not in parity between patients with evidence of a tubo-ovarian abscess that was managed medically and those who had surgery. There was no significant difference in surgical procedure performed, chronic symptoms, subsequent gynecologic surgery, or subsequent pregnancy among the groups with an abscess. There was a trend toward more surgical complications among women who had delayed surgical intervention for an abscess. Among women with a unilateral tubo-ovarian abscess, those who had a unilateral salpingo-oophorectomy had a higher pregnancy rate than those who received antibiotics alone. In this study, women with a tubo-ovarian abscess in association with salpingitis did not respond well to antibiotic treatment alone. This may be the most reliable way of distinguishing these patients from women with salpingitis alone or salpingitis in association with a tubo-ovarian inflammatory complex, who, as a group, did respond well to medical management alone.

Fetal tachycardia as an indicator of maternal and neonatal morbidity.

Presented is a prospective, controlled study to determine if intrapartum fetal tachycardia is reliable as an indicator of maternal and fetal infectious morbidity. Thirty neonates with defined intrapartum tachycardia were matched by gestational age and weight with 30 control subjects without defined tachycardia. There was a significant difference in maternal febrile morbidity and a trend toward a difference in maternal infectious morbidity between the two groups. There was no significant difference in maternal complications at delivery or administration of antibiotics to the mother. Among the neonates, there was a significant difference in administration of antibiotics and the incidence of respiratory distress syndrome (RDS) between the two groups; however, both of these were significantly related to birth weight. There was no significant difference between the two groups in duration of ruptured membranes, duration of labor, number of vaginal examinations, or antepartum anemia. Only one study infant had a bacteremia. The data confirm an increased risk of neonatal complications, such as RDS, asphyxia, and meconium aspiration, in association with intrapartum fetal tachycardia.

Efficacy of oral antibiotics following parenteral antibiotics for serious infections in obstetrics and gynecology.

Patients with serious soft-tissue infections in obstetrics and gynecology are frequently treated with parenteral antibiotics until afebrile and clinically well for 48-72 hours, and then discharged on a broad-spectrum oral antibiotic. To evaluate the efficacy of this type of management, we designed a prospective, randomized single-blinded study comparing a group of patients who received oral antibiotics after hospital discharge (N = 80) with a group who did not (N = 83). No significant differences in age, race, parity, diagnosis, or pathogen isolated were observed between the patients in the two groups. No significant difference was noted in delayed morbidity between those who did and those who did not take oral antibiotics (P greater than .06). In light of the cost of oral antibiotics and the chance of drug-induced side effects, the data suggest that oral antibiotics after parenteral antibiotics are not indicated.

Prevention of perinatal group B streptococcal infection: current controversies.

Group B streptococcus (GBS) is the most frequent cause of neonatal sepsis in the United States. The Centers for Disease Control and Prevention (CDC) issued guidelines for its prevention in 1996. This article details areas of controversy with those guidelines and offers recommendations for resolution. We recommend that a prevention policy be adopted by all hospitals. If a screening-based policy is chosen, compliance is essential. Penicillin is the antibiotic of choice for GBS prevention. Increasing resistance to clindamycin and erythromycin might eliminate them as alternative choices in patients allergic to penicillin. Group B streptococcal prophylaxis might not be necessary in women who have repeat elective cesarean delivery. In asymptomatic women, a positive urine culture for GBS should be considered clinically equivalent to a positive vaginal or rectal sample for screening. Neonatal sepsis caused by organisms other than GBS must be monitored carefully by all hospitals providing obstetrics services.

A survey of practices in infectious diseases by obstetrician-gynecologists.

OBJECTIVE: To survey current practices among obstetricians and gynecologists concerning a wide range of infectious diseases to guide future efforts in continuing medical education. METHODS: A survey questionnaire of multiple-choice questions was mailed to 2500 physicians, under age 65, randomly selected from the American Medical Association specialty list of obstetrician-gynecologists. The first 500 returns constituted the data set and were analyzed by computer. RESULTS: We found many clinical areas in which practice patterns were deemed appropriate, including antibiotic selection, universal screening for hepatitis B, and follow-up of urinary tract infection in pregnancy. In other areas, marked by controversy among "experts," practice patterns varied widely. These areas included management of premature rupture of the membranes and premature labor, and universal screening for group B streptococci. Areas in need of further continuing medical education efforts include management of perinatal viral infections and diagnosis and treatment of sexually transmitted diseases. CONCLUSIONS: Although this survey indicated that practice patterns of American obstetricians and gynecologists are appropriate in many clinical areas relevant to infectious diseases, there are other clinical conditions requiring future efforts in continuing medical education.

Evaluation of various methods of digoxin dosing.

The ability to precisely predict serum digoxin concentrations using 12 published methods in a group of 85 patients was undertaken. Two methods of estimating creatinine clearance and two estimates of ideal body weight were employed as input variables using the 12 dosing methods. This resulted in 40 relationships from which correlation coefficients and linear regression constants were derived for predicted versus measured serum digoxin concentrations. The correlation coefficients between predicted and measured serum digoxin ranged from -0.393 to 0.389. Possible explanations for the low correlation coefficients are interpatient variability in the kinetics of digoxin, the small number of subjects used to generate some of the digoxin dosing methods, undetected patient noncompliance in the present study, the use of empirically derived dosing methods, and/or the use of rather homogeneous patient populations to develop a given method while this study is comprised of a heterogeneous group of patients. The methods studied tend to overpredict serum digoxin concentrations and therefore generally allow safe, first approximations for digoxin dosing.

The endomyocardial biopsy.

Endomyocardial biopsy (EMB) provides a safe, simple method of gathering unique information. Although the role of EMB continues to evolve rapidly, present consensus includes the following indications, based on the ability of EMB to provide diagnoses unobtainable by other means: assessment of early rejection following cardiac transplantation; determination of myocarditis as etiology of clinically obscure cardiac dysfunction; quantification of chemotherapeutic (especially anthracycline) cardiotoxicity; and distinction between constrictive and restrictive heart disease. Each of these indications carries major therapeutic as well as prognostic implications. Methods of processing EMB are presented, complications listed, artifacts described, findings and uses illustrated, and suggestions for future development addressed briefly.

Metronidazole.

Metronidazole has proven to be a useful and inexpensive antibiotic for the treatment of T. vaginalis and bacterial vaginosis. Few alternatives exist for these two specific indications, and metronidazole will continue to play a primary role in therapy. Oral metronidazole continues to be a very inexpensive alternative to oral vancomycin for the treatment of C. difficile-induced pseudomembranous colitis. For the treatment of moderate to severe mixed aerobic/anaerobic pelvic infections, metronidazole should be considered secondarily in patients who have failed other multiple- or single-drug regimens or in patients who are infected. with anaerobic organisms resistant to other commonly used agents including clindamycin, cefoxitin, cefotetan, or ampicillin/sulbactam. Metronidazole is not a first line drug of choice for antibiotic prophylaxis in obstetric and gynecologic patients.