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Objective The cause for shortness of breath among systemic sclerosis (SSc) patients is often lacking. We sought to characterize the hemodynamics of these patients by using simple isotonic arm exercise during cardiac catheterization. Methods Catheterization was performed in 173 SSc patients when resting echocardiographic pulmonary systolic pressures were 40 mmHg post stress. Patients with resting mean pulmonary arterial pressures (mPAP) ≤ 25 and pulmonary arterial wedge pressures (PAWP) ≤ 15 mmHg exercised with 1-pound hand weights. Normal exercise was defined as a change in mPAP divided by the change in cardiac output (CO) (ΔmPAP/ΔCO) ratio ≤ 2 for patients 50). An abnormal ΔmPAP/ΔCO ratio, an exercise transpulmonary gradient (TPG) ≥ 15, a PAWP ΔPAWP and a pulmonary vascular resistance (PVR) which increased defined exercise-induced pulmonary arterial hypertension (EIPAH). An abnormal ΔmPAP/ΔCO ratio, an exercise TPG

This study compared serum antibody titers and granzyme B (GrzB) levels in virus-stimulated peripheral blood mononuclear cells following influenza vaccination. Twelve of 239 older adults who subsequently developed laboratory-diagnosed influenza illness (LDI) had significantly lower GrzB levels compared to subjects without LDI (P=0.004). Eight subjects with LDI in the previous year showed an enhanced GrzB response to vaccination (P=0.02). Serum antibody titers following vaccination did not distinguish those older adults who developed LDI from those who did not. These results suggest that GrzB levels could be combined with antibody titers to more effectively predict vaccine efficacy in older adults.

Objectives We sought to determine the incidence of stress-induced pulmonary artery (PA) systolic hypertension in a referral population of patients with scleroderma, and to examine the relation between stress-induced pulmonary systolic hypertension and exercise capacity in this population. Background Early detection of patients with scleroderma at risk for pulmonary hypertension (PHTN) could lead to more timely intervention and thus reduce morbidity and improve mortality. The change in PA systolic pressure (PASP) with exercise provides a possible tool for such detection. Methods Sixty-five patients with scleroderma (9 men and 56 women; mean age 51 ± 12 years [SD]), normal resting PASP, and normal resting left ventricular function underwent exercise Doppler echocardiography using a standard Bruce protocol. Tricuspid regurgitation velocity was measured before and after exercise. Exercise variables including workload achieved in metabolic equivalents (METS), total exercise time, percentage of target heart rate achieved, and PASP at rest and within 60 s after exercise were recorded. Results Thirty patients (46%) demonstrated an increase in PASP to > 35 mm Hg plus an estimated right atrial pressure of 5 mm Hg. Postexercise PASP inversely correlated to both the maximum workload achieved ( r = − 0.34, p = 0.006) and exercise time ( r = − 0.31, p = 0.01). In women, the correlation was more significant ( r = − 0.38, p = 0.003). Patients in the lowest quartile of exercise time, with the least cardiac workload achieved, produced the highest postexercise PASP. Conclusion Stress-induced PHTN is common in patients with scleroderma, even when resting PASP is normal. Stress Doppler echocardiography identifies scleroderma patients with an abnormal rise in PASP during exertion. Peak PASP is linearly related to exercise time and maximum workload achieved. Measurement of PASP during exercise may prove to be a useful tool for the identification of future resting PHTN.

Objectives: The risks and benefits of β-blockade with bucindolol were assessed in heart failure (HF) patients with Class IV symptoms within the Beta-blocker Evaluation of Survival Trial (BEST). Background: β-blockade is accepted therapy for mild to moderate HF, but its safety and efficacy in advanced HF have not been established. Methods: BEST recruited 2708 HF patients; of these, 226 with Class IV symptoms (n = 114 randomized to bucindolol, n = 112 to placebo) formed the basis of this study. All-cause death, HF hospitalization, and drug discontinuations occurring early during therapy (≤6 months) and overall during follow-up were assessed. Compared with Class III, Class IV patients were older and had higher plasma norepinephrine levels, prevalence of coronary disease, S3 gallops, and lower ejection fractions, but characteristics of the 2 Class IV treatment groups were similar. Results: During a mean of 1.6 years, 49% Class IV patients died, and 54% were hospitalized for HF. Bucindolol increased the combined endpoint of death or HF hospitalization within the first 6 months (hazard ratio [HR] = 1.7, 95% confidence interval [CI] = 1.1-2.7) and did not result in benefit overall (HR = 1.2, 95% CI = 0.9-1.6). HF hospitalization alone within 6 months was increased by bucindolol (HR = 1.7), and an early adverse trend for death was seen (HR = 1.6) with no benefit overall (HR = 1.1). Bucindolol was discontinued more frequently than placebo for worsening HF (11% versus 4%) and hypotension (3% versus 0%). Conclusions: Class IV HF patients in BEST were at high risk. Bucindolol did not reduce death or HF hospitalization and was associated with early hazard.

Bacterial contamination of the operative site is a common occurrence in obstetrics and gynecology. The widespread use of antibiotic prophylaxis has reduced but not eliminated serious postoperative infections. For most operations, a single dose of a limited-spectrum drug has been as effective as a multidose regimen. In the differential diagnosis it is important to consider cellulitis, abscess, necrotizing fasciitis and septic pelvic thrombophlebitis. Abscess and necrotizing fasciitis are expected to require invasive therapy in addition to antibiotics, while cellulitis and septic pelvic thrombophlebitis should respond to medical management alone. Although a postoperative fever is a warning sign of possible infection, it may also be caused by the antibiotics that are given for treatment. The use of prolonged courses of antibiotics once the patient is clinically well is discouraged. While clinical guidelines are provided for use in the diagnosis and management of postoperative infections, these recommendations are intended for general direction and not as an exclusive management plan.

Objective Our purpose was to measure the effect of ventricular pacing in patients with atrial fibrillation (AF) on stroke volume and cardiac output. Background Unceasing variation in cycle length in AF decreases stroke volume and cardiac output. Because ventricular-inhibited pacing after atrioventricular node ablation has been reported to improve left ventricular performance, we tested the hypothesis that overdrive pacing would produce a similar benefit by regularizing cycle length. Methods and Results We studied 18 patients with chronic AF and permanent pacemakers. The aortic time velocity integral (TVI) was measured with continuous-wave Doppler and was used as a surrogate measure of stroke volume (stroke volume = TVI × aortic valve area, and aortic valve area is constant whether in AF or during pacing). For each patient, the linear relation between preceding cycle length and TVI in AF was used to estimate relative stroke volume (TVI compared within each patient) at a preceding cycle length of 666 ms in AF, and a similar comparison between AF and pacing was made at the minimum allowable pacing rate. Relative stroke volume in AF was then compared with relative stroke volume at both the fixed cycle (666 ms) and the minimum allowable rate. During pacing at 666 ms, relative stroke volume increased significantly by 18% ( t = 2.8, P =.048), but there was no difference in cardiac output during pacing at the minimum possible rate and the corresponding preceding cycle length in AF. Conclusion Our data suggest that regularization of ventricular rhythm by overdrive pacing in patients with AF only improves stroke volume (and by extension, cardiac output) at pacing rates at the outer limit of and above the normal physiologic range. (Am Heart J 2002;143:827-32.)

Metronidazole-resistant Trichomonas vaginalis has been reported across the United States. Some reports have suggested that clinically resistant cases could be increasing. Currently, metronidazole is the only drug available to treat trichomoniasis, including resistant cases. In such cases, treatment usually consists of giving higher and more prolonged doses of metronidazole, which patients are often unable to tolerate. Tinidazole, a second-generation nitroimidazole currently under development in the United States, has been shown to be an effective therapy in resistant T. vaginalis. Tinidazole appears to have several advantages over metronidazole, including greater in vitro potency against both sensitive and resistant strains of T. vaginalis, a more prolonged duration of action, and improved patient tolerability. This report describes the successful use of tinidazole in 3 cases of clinically metronidazole-resistant trichomoniasis.

The cause for shortness of breath among systemic sclerosis (SSc) patients is often lacking. We sought to characterize the hemodynamics of these patients by using simple isotonic arm exercise during cardiac catheterization.Catheterization was performed in 173 SSc patients when resting echocardiographic pulmonary systolic pressures were40 but40 mmHg post stress. Patients with resting mean pulmonary arterial pressures (mPAP) ≤ 25 and pulmonary arterial wedge pressures (PAWP) ≤ 15 mmHg exercised with 1-pound hand weights. Normal exercise was defined as a change in mPAP divided by the change in cardiac output (CO) (ΔmPAP/ΔCO) ratio ≤ 2 for patients50 years (≤3 for50). An abnormal ΔmPAP/ΔCO ratio, an exercise transpulmonary gradient (TPG) ≥ 15, a PAWP20, a ΔTPGΔPAWP and a pulmonary vascular resistance (PVR) which increased defined exercise-induced pulmonary arterial hypertension (EIPAH). An abnormal ΔmPAP/ΔCO ratio, an exercise TPG15, a PAWP ≥ 20, a ΔTPGΔPAWP and a drop in PVR defined left ventricular diastolic dysfunction (DD). Twelve patients without SSc served as controls.Pulmonary pressures increased with exercise in 53 patients. Six had EIPAH and 47 had DD. With exercise, mPAP and PAWP were 20 ± 4 and 13 ± 2 in controls, 36 ± 3 and 12 ± 4 in EIPAH and 34 ± 6 and 26 ± 4 in DD. Control ΔmPAP/ΔCO was 0.8 ± 0.7, 7.5 ± 3.9 in EIPAH and 9.1 ± 7.2 in DD. Rest and exercise TPG was normal for control and DD patients but increased (12 ± 4 to 23 ± 4) in EIPAH (P0.0001). PVR decreased in DD but increased in EIPAH with exercise.Exercise during catheterization elucidates the pathophysiology of dyspnea and distinguishes EIPAH from the more common DD in SSc patients.

A simple traction-countertraction technique using common and readily available materials was successfully used to remove infected pacemaker leads from two patients. The specific methodology is presented. Although somewhat technically demanding, this approach appears safe and cost-effective. This method provides another way to remove pacemaker leads without resorting to thoracotomy.

Idiopathic pulmonary arterial hypertension (IPAH) is increasingly being diagnosed in patients of advanced years. We sought to investigate observed vs expected mortality among geriatric IPAH patients treated with specific pulmonary arterial hypertension (PAH) therapy.From the University of Connecticut's Pulmonary Vascular Disease Program database, 20 IPAH patients over 65 years of age were identified. Patient demographics, cardiopulmonary hemodynamics, PAH therapy, and mortality were retrospectively analyzed. Based on observed follow-up time, the probability of death was calculated for each subject using a prediction formula for PAH patients developed by the National Institutes of Health (NIH). Byar's method for Poisson counts was used to compare observed and expected tallies of deaths within the study sample. A P valueor = 0.05 was considered statistically significant.The mean age of the 20 geriatric IPAH patients was 77 years (+/- 6.6) of which 70% were female. The mean cardiopulmonary hemodynamic values for the cohort were: right atrial pressure: 10 mmHg (+/- 4); mean pulmonary artery pressure: 45 mmHg (+/- 9); pulmonary artery occlusion pressure: 11 mmHg (+/- 3); cardiac output: 4.1 L/min (+/- 1.2); cardiac index: 2.3 L/min (+/- 0.5); and pulmonary vascular resistance: 712 dynes / sec / cm-5 (+/- 319). Fourteen subjects received PAH monotherapy with bosentan, sildenafil, or epoprostenol. Six subjects received PAH combination therapy with bosentan, sildenafil, iloprost, or treprostinil. Total follow-up across the 20 subjects was 58.7 years, with average follow-up of 2.9 yrs (+/- 1.7) per subject. Based upon the NIH formula, the expected number of deaths for this cohort was 9.4. During follow-up, three deaths actually occurred. Thus, observed mortality was only 31.9% of expected (P = 0.03, 95% C.I. = [6.4%, 93.2%]).Geriatric patients are increasingly being diagnosed with IPAH. Efficacy of PAH therapy in geriatric patients is unknown. In this cohort of subjects, the outcomes of older adults treated with specific PAH therapy demonstrates improved survival relative to that predicted by the NIH formula.

To identify relationships between anabolic hormones, inflammatory markers, and physical function.Cross-sectional.Outpatient university heart failure program in Connecticut.Sixty patients with an ejection fraction of 40% or less.The 6-minute walk distance and frailty phenotype were measured. The relationship between physical measures of hormones and inflammatory mediators were examined. Linear and ordinal logistic regression analyses were performed for the physical measures.Forty-three men (mean age 77 +/- 9) and 17 women (mean age 78 +/- 12) participated. Longer 6-minute walk distance was correlated with higher 25-hydroxyvitamin D (25OHD) level, and a shorter walk was correlated with higher cortisol: dehydroepiandrosterone sulphate (DHEAS) ratio, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), and intact parathyroid hormone (PTH) (all P.05). Percentage of free testosterone, DHEAS alone, and N-terminal pro-brain natriuretic peptide (NTpro-BNP) did not correlate with 6-minute walk distance. Higher frailty phenotype score (more frail) was correlated with higher high-sensitivity CRP, higher IL6, and lower 25OHD levels (all P.05). Linear regression with the 6-minute walk distance as the dependent variable and independent variables of age, sex, percentage of free testosterone, DHEAS, 25OHD, intact PTH, hsCRP, IL6, cortisol/DHEAS ratio, and NTpro-BNP, revealed age, sex, 25OHD and hsCRP to be significant (coefficient of determination=53.5%). Ordinal logistic regression with the frailty phenotype and hormonal levels revealed that age, 25OHD, and hsCRP also predicted frailty status.Twenty-five-hydroxyvitamin D and hsCRP levels may contribute to lower aerobic capacity and frailty in patients with heart failure. A longitudinal study will further define the role of 25OHD and hsCRP on muscle strength and functional decline.

It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination. This study prospectively evaluated the relationship between the development of influenza illness, and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure (CHF). Adults age 60 years and older (90 subjects), and 10 healthy young adult controls received the 2003-04 trivalent inactivated influenza vaccine. Laboratory diagnosed influenza (LDI) was documented in 9 of 90 older adults. Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness (LDI subjects) and those who would not (non-LDI subjects). In contrast, PBMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects. The mean IFN-γ:IL-10 ratio in influenza A/H3N2-stimulated PBMC was 10-fold lower in LDI vs non-LDI subjects. Pre-and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI. In non-CHF subjects with LDI, granzyme B levels increased to high levels at the time of influenza infection. In conclusion, measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people. Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults.

This paper summarizes the proceedings of a workshop convened in June 2000 by four federal agencies to evaluate the published evidence establishing the effectiveness of latex male condoms in preventing HIV/AIDS and other sexually transmitted diseases. It reviews a discussion of other factors that influence condom effectiveness.

Intrauterine infection with syphilis was diagnosed by reactive maternal serologic studies, ultrasonographic findings, and exclusion of other causes in three hydropic fetuses at 31, 34, and 35 weeks' gestation. With penicillin therapy and preterm delivery all infants survived through the perinatal period. Intrauterine infection that follows syphilis is a potentially treatable cause of nonimmune hydrops.

To report serious cardiac dysrhythmias in two patients whose bulimia nervosa was not revealed during preoperative screening.Case #1: A 25-yr-old woman with preoperative hypokalemia (K+ = 3.1 mEq x l(-1)) required anesthesia for removal of a wrist ganglion. She claimed the hypokalemia was of unknown etiology, and denied other medical problems. Shortly after induction of anesthesia with thiopental and isoflurane, the ECG revealed two runs of torsades de pointes. This was successfully treated by decreasing pulmonary ventilation, allowing P(ET)CO2 to increase from 32 to 45 mm Hg. Case #2: A 39-yr-old woman who denied any medical problems received propofol, rocuronium sevoflurane and N2O during general anesthesia for breast augmentation. In the PACU, the patient complained of light-headedness, and the ECG revealed a heart rate of 44 bpm with P-R interval of 0.42 sec. Following 0.5 mg atropine, the heart rate increased but the P-R interval remained prolonged (0.36 sec) and the corrected Q-T interval was 0.51 sec. Treatment with 2.5 g MgSO4, 20 mEq KCl, and 9.4 mEq calcium gluconate i.v. normalized the Q-T interval, and decreased the P-R interval to 0.22 sec. Upon specific questioning, she admitted to a remote history of bulimia, but denied any bulimic behavior for the last 16 yr.Two patients with histories of eating disorders failed to disclose this information during preoperative evaluation. Perioperative cardiac dysrhythmias developed in these patients, even though they claimed that eating behavior had returned to normal.

Left atrial diameter was measured by echocardiography in 107 patients in atrial fibrillation. The etiology of atrial fibrillation was rheumatic heart disease with predominant mitral valve involvement (RHD) in 51 patients and idiopathic atrial fibrillation (IAF) in 56. The left atrial diameter was correlated to the patient's response to therapy. The mean left atrial diameter was 3.4 cm in patients with paroxysmal atrial fibrillation, 3.8 cm in those requiring direct current (DC) cardioversion, and 4.4 cm in patients with persistent atrial fibrillation. However, in each of these therapeutic response groups, the left atrial diameter was signficantly smaller in patients with idiopathic atrial fibrillation. In the group with paroxysmal atrial fibrillation, the mean left atrial diameter was 4.3 +/- .7 cm in patients with RHD, compared to 3.1 +/- .6 cm in those with IAF (p less than .001). In the group requiring DC cardioversion, the left atrial diameter was 4.7 +/- .8 cm in patients with RHD compared to 3.6 +/- .5 cm in those with IAF (p less than .01). In patients with persistent atrial fibrillation, the left atrial diameter was 5.2 +/- .9 cm in patients with RHD and 4.0 +/- 1.0 cm in IAF (p less than .001). Left atrial diameter as well as the etiology of the heart disease are important in determining the response of atrial fibrillation to therapy.

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.

These complications can be broken down into three major categories: the direct effects of ischemia, the effects of myocardial rupture or similar structural loss secondary to ischemic insult, and the effects of inhibitory autonomic reflexes triggered by infarction. It is critical to correlate the hemodynamic problem with its etiology in order to choose the appropriate treatment.

Six subjects were evaluated for the effect of quinine, the 1-isomer of quinidine, on digoxin pharmacokinetics. 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 (t½) 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 μg to x = 772.52 μg (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 quantitatively different, from quinidine. Clinical Pharmacology and Therapeutics (1980) 28, 425–430; doi:10.1038/clpt.1980.183

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.

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 calcium-channel blockers represent a diverse group of chemical structures that block calcium-selective channels in the plasma membrane of a variety of excitable cells. As the calcium fluxes carried by these channels allow ionic calcium (Ca2+) to gain access to the cell interior, where Ca2+ 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. In vivo, 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. However, in vivo in human studies, there are differences among the calcium-channel blockers. The vasodilatory effects of the calcium channel blockers, which can reduce systemic blood pressure, offer a primary 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 cardiac and vascular smooth muscle, whereas nifedipine is more potent in vascular smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated the efficacy of an intravenous infusion of procainamide in 26 consecutive candidates for cardioversion of atrial fibrillation. Procainamide was administered at a rate of 15 to 20 mg/min up to a maximum of 1000 mg. The treatment was considered effective only if cardioversion occurred during the procainamide infusion. Conversion to sinus rhythm occurred in 15 patients. Converters had a significantly shorter mean duration of atrial fibrillation (6 +/- 7 days, mean +/- S.D.) compared to nonconverters (79 +/- 88 days) (p less than 0.01). The mean left atrial size of converters (4.3 +/- 0.6 cm) did not differ significantly from that of nonconverters (4.7 +/- 0.9 cm). The dose of procainamide required for cardioversion ranged from 3.6 to 16.4 mg/kg. Two patients developed nonsustained ventricular tachycardia, and there was one episode of bifascicular block during the infusion. Intravenous procainamide is an effective form of therapy for conversion of atrial fibrillation of new onset.

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 S3gallop.Beta-blocker use was less frequent in patients with an ejection fraction

Digoxin scrum 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 ± 22.69c (P > 0.05) for serum and 69.8 ± 6.8% and 70.2 ± 10.5% (P > 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. Clinical Pharmacology and Therapeutics (1981) 30, 594–599; doi:10.1038/clpt.1981.209

This paper delineates the results of analysis of 234 Rh-sensitized pregnancies. It is now possible to predict the outcome in an Rh-isoimmunized pregnancy based only on the mean amniotic fluid, Δ 450 ¯ . This is an improvement over past methods since it does not depend upon calculation of weeks of pregnancy.

We studied blood pressure (BP) and heart rate (HR) responses in 12 patients with hypertension who were receiving cetamolol, a cardioselective β-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 < 0.05 for systolic; P < 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 < 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. Clinical Pharmacology and Therapeutics (1986) 39, 664–668; doi:10.1038/clpt.1986.116

The demonstration of normal coronary arteries at cardiac catheterization has been considered adequate definition of normal myocardial perfusion. To examine this, we have utilized intracoronary injections of technetium-99 m labeled albumin microspheres in 11 patients with valvular heart disease, and in 13 patients with chest pain syndrome or constrictive pericarditis. Eight patients with valvular heart disease had large, patchy, irregular perfusion deficits noted on the scintiphotos. Only one of thirteen control patients had a perfusion deficit. Caution, therefore, must be used in attributing such perfusion deficits to atherosclerotic disease when valvular disease is present.

Rest and exercise thallium-201 scintigraphy (201Tl stress test), 90% submaximal treadmill exercise test (ECG stress test), and coronary angiography were performed on 49 patients with suspected coronary artery disease. When technically unsatisfactory and uninterpretable scintiphotos were excluded, the sensitivity (true positives/true positives + false negatives) of the 201Tl stress test in detecting coronary artery stenosis ≥70% was 81%. The sensitivity of the 201Tl stress test in detecting coronary artery stenosis ≥50% was 84&‰ However, when technically unsatisfactory and uninterpretable studies were considered as failures of the test to detect disease, the sensitivity of the 201Tl stress test in detecting coronary artery stenosis ≥50% was 71%. The sensitivity of the ECG stress test was 92% in detecting stenosis ≥70% and 85%. in detecting stenosis ≥50% when non-diagnostic tests were excluded. However, when 11 non-diagnostic ECG stress tests were considered as a failure of the test to detect disease, the sensitivity of the ECG stress test in detecting coronary artery stenosis ≥50% was 64%. The sensitivity of the combined stress test in detecting coronary artery stenosis ≥50% was high whether or not technically unsatisfactory and uninterpretable studies were (89%) or were not (94%) included in the analysis. The specificity (true negatives,/true negatives + false positives) for ≥50% coronary artery stenosis was 90% for the 201Tl stress test, 75% for the ECG stress test and 80% for the combined stress test. Combined ECG and 201Tl stress testing detects a number of patients with significant coronary artery disease missed by ECG stress testing alone, primarily in those cases where the ECG stress test is non-diagnostic.

A DDD pacemaker utilizing an atrial J electrode was implanted in a patient whose right atrial appendage had been removed 7 years prior during aortic valve replacement. Alternating QRS morphologies produced by pacemaker stimulus artifacts occurred as a consequence of atrial lead dislodgement. The screw-in atrial electrode has superior stability in patients with right atrial appendage removal; stability of the atrial J electrode cannot be obtained in such cases.

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.

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 response 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 ratio minus one, but isoproterenol 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. Clinical Pharmacology and Therapeutics (1981) 30, 283–290; doi:10.1038/clpt.1981.161