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Biomedical subjects

G Modin

Publications and source records attributed to G Modin.

13 recordsLinked to original sources

Amiloride improves hemodynamics in patients with chronic congestive heart failure treated with chronic digoxin and diuretics.

Potassium-sparing diuretics have been reported to decrease the positive inotropic effect of digoxin. We studied the hemodynamic effects of amiloride in patients taking digoxin for chronic heart failure. Eleven men with a history of congestive heart failure were studied in a double blind, cross-over, placebo controlled trial with the patients on digoxin alternating placebo with amiloride. After 7 days on the trial drug, a Swan-Ganz catheter was placed in the pulmonary artery and measurements made at rest and with increasing degrees of supine bicycle exercise. Right-sided and pulmonary artery wedge pressures and systemic arterial pressures, as well as cardiac outputs, were measured. After a 7 day washout period, placebo (P) and Amiloride (A) were switched and after 7 days on the therapy, a second hemodynamic study at rest and varying degrees of supine bicycle exercise was repeated. At rest there were no significant differences in the right-sided, pulmonary arterial wedge pressure or cardiac outputs between the patients on Amiloride (A) versus placebo (P). During exercise there were significant differences between (P) and (A) at the 50 watt-second stage of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride

[Reocclusion following thrombolytic treatment in acute myocardial infarct].

Currently there are five thrombolytic substances undergoing evaluation: streptokinase, tissue plasminogen activator, acylated plasminogen streptokinase activator complex, urokinase and single chain urokinase plasminogen activator. Equal results for mortality reduction (25 per cent) and reocclusion (6-24 per cent) has been reported in the literature for the five substances. Reocclusion can be divided into an early (greater than 24 hours) and a late phase. The early phase is most likely due to an imbalance between thrombolysis and the formation of a thrombus. During late reocclusion there is formation of a thrombus on the underlying coronary plaque or residual thrombotic mass, following thrombolytic therapy. The residual stenosis following thrombolysis seems to be the most important prognostic factor for reocclusion. A residual stenosis of over 75 per cent is unfavourable. Early reocclusion is prevented through simultaneous antithrombotic and thrombolytic therapy. Patients with a residual stenosis of over 75 per cent should be considered for some sort of active intervention to prevent late reocclusion.

Acute Disease

Sialosyl-Tn. A novel mucin antigen associated with prognosis in colorectal cancer patients.

Colon cancers typically produce mucin. However, it is not known whether tumor mucin plays a biological role in cancer cell behavior. To address this issue, the expression of a mucin-associated antigen, sialosyl-Tn, was examined by immunohistochemical study in 128 primary colorectal carcinoma specimens from 137 patients who underwent curative surgical resection. Antigen expression was correlated with disease-free and overall 5-year survival. Sialosyl-Tn antigen expression occurred in 112 (87.5%) tumors, and was independent of age, gender, tumor location, Dukes' stage, depth of invasion, degree of differentiation, and ploidy status. Survival at 5 years for patients with sialosyl-Tn-negative versus sialosyl-Tn-positive tumors was 100% versus 73% (P less than 0.05) and disease-free survival was 94% versus 73%, respectively (P = 0.12). Although more advanced Dukes' stage, deeper invasion, and aneuploidy were all associated with poorer overall 5-year survival, antigen-negative tumors within each of these groups had much better prognoses than antigen-positive tumors. Multivariate regression analysis revealed that tumor ploidy (P less than 0.001) and sialosyl-Tn expression (P less than 0.05) were the two variables of most importance for predicting both disease-free and overall survival. The authors conclude that sialosyl-Tn expression is an independent predictor of poor prognosis in colon cancer, and therefore suggest that qualitative mucin alterations may reflect important differences in the biological behavior of these neoplasms.

Aged

Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone.

BACKGROUND: Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic. METHODS: In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P. carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day). RESULTS: The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3). Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025). With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs. one). Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations. Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient. Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone. CONCLUSIONS: In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P. carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.

Acquired Immunodeficiency Syndrome

Comparative efficacies of ciprofloxacin, pefloxacin, and vancomycin in combination with rifampin in a rat model of methicillin-resistant Staphylococcus aureus chronic osteomyelitis.

The efficacies of the quinolones ciprofloxacin and pefloxacin alone and in combination with rifampin were compared with those of vancomycin alone and in combination with rifampin in a rat model of chronic osteomyelitis caused by methicillin-resistant Staphylococcus aureus. Neither the quinolones nor vancomycin alone was effective in reducing titers of organisms in bone after therapy, while rifampin alone was effective. All combination regimens with rifampin were more effective than the regimen with rifampin alone was, although these differences did not achieve statistical significance. Rifampin-resistant isolates were detected rarely. Quinolone-rifampin combination regimens may offer a nonparenteral option for the treatment of chronic osteomyelitis caused by methicillin-resistant S. aureus.

Animals

Electrophysiologic effects of cigarette smoking in patients with and without chronic beta-blocker therapy.

After refraining from smoking for at least 8 hours, 22 adult male habitual smokers underwent baseline electrophysiologic study including atrial and ventricular burst pacing and programmed premature stimulation with single extrastimuli. After smoking 2 of their usual brand of cigarettes in rapid succession, the electrophysiologic protocol was repeated. Nicotine, catecholamine and carbon monoxide concentrations all increased significantly. Smoking increased heart rate and improved atrioventricular conduction in the 13 patients receiving chronic beta-blocker therapy (mostly for angina pectoris); increases in heart rate and improvement in atrioventricular conduction were not different statistically from those seen in patients not receiving beta-blocker therapy, suggesting the possibility of a direct effect of nicotine or other components of tobacco smoke. Ventricular refractoriness was not altered and atrial and ventricular arrhythmias were not increased by smoking. Persistent sympathomimetic actions of cigarette smoking may explain in part the failure of beta-blocking drugs to reduce cardiac mortality risk in smokers after myocardial infarction.

Adrenergic beta-Antagonists

Survival in severe left ventricular failure treated with the new nonglycosidic, nonsympathomimetic oral inotropic agents.

Survival in severe left ventricular failure is poor but has not been widely assessed since the introduction of several new nonglycosidic, nonsympathomimetic oral inotropic agents for long-term therapy. We examined retrospectively the survival of 82 patients with severe left heart failure during long-term treatment with oral milrinone (17 patients), posicor (12 patients), enoximone (47 patients), and piroximone (6 patients). Sixty-five patients were in New York Heart Association (NYHA) functional class 4, 15 patients were in class 3, and two patients were in class 2. There were 57 patients with ischemic and 25 patients were in class 2. There were 57 patients with ischemic and 25 patients with nonischemic etiology of left heart failure. Most patients were referred for inotropic therapy after failing to respond to conventional agents, including vasodilators. However, in almost all patients, marked hemodynamic and clinical improvement occurred initially. Overall survival was 36 percent at six months, the majority of deaths occurring during the first three months. Survival in relation to etiology of heart failure showed a trend toward increased mortality in patients associated with ischemic heart disease vs non-ischemic dilated cardiomyopathy. Sudden death mortality was also higher in the ischemic group (28 percent at six months vs 5 percent at six months; p less than 0.05). There was a trend toward reduced sudden death mortality in patients on antiarrhythmic agents during inotropic therapy (p = 0.06). We conclude that overall survival in symptomatic patients with severe left ventricular failure remains very low during long-term therapy with several new oral inotropic agents. Sudden death appears higher in patients with an ischemic etiology during therapy with these agents.

Administration, Oral

Cocaine use and the risk for endocarditis in intravenous drug users.

Endocarditis is a relatively frequent infection in intravenous drug users. We compared features in the cases of 102 patients with those in intravenous drug users with other causes of fever to identify risk factors predictive of endocarditis. Logistic regression analysis showed cocaine use to be strongly associated with endocarditis. This special risk involving cocaine use has not been reported previously; the explanation for it may provide insight into the pathogenesis of endocarditis.

Adult

Graded exercise testing in patients with sinus node dysfunction.

Serial measurements of heart rate and oxygen uptake were obtained before and during maximal upright graded bicycle stress testing in 16 patients, 10 to 77 years old (mean 46 years), with sinus node dysfunction; five had permanent and two had temporary demand ventricular pacemakers. In 15 patients, including those with pacemakers, maximal exercise was performed before and after the intravenous administration of 1 mg atropine. Maximal exercise was terminated because of cerebral symptoms in seven (three had effort-induced tachyarrhythmias and one had autonomic insufficiency), fatigue in five (one had effort-induced heart block), heart failure in three and angina pectoris in one. With maximal exercise, patients with sinus node dysfunction were unable to obtain maximal heart rates or oxygen uptakes comparable to age- and sex-matched control subjects. Additionally, maximal oxygen uptake did not differ significantly between patients with or without pacemakers even when ventricular pacing rates were increased (two instances). The administration of atropine increased the resting heart rate, but the maximal heart rate and oxygen uptake achieved during maximal exercise did not differ significantly from those obtained before the administration of atropine in the patient and control groups. Physically active patients with sinus node dysfunction have diminished exercise capacity due in part to cardiac arrhythmia, latent or overt cardiac failure, or autonomic dysfunction.

Adolescent

Prognostic value of infranodal conduction time in patients with chronic bundle branch block.

His bundle recordings were obtained in 121 patients with chronic bundle branch block and the patients were followed for a mean period of 18 months. Seventy-nine patients had an infranodal conduction time (H-Q) less than 70 msec while 42 had H-Q greater than or equal to 70 msec. There was no significant difference in mean age, smoking history, diabetes, syncope, dizziness, blood pressure, and serum cholesterol or triglyceride levels between the two groups. There was a significantly greater incidence of progresssion to second degree or third degree atrioventricular block (9/42, 21%), and of severe congestive heart failure (16/42, 38%) in patients with H-Q greater than or equal to 70 compared with those with H-Q less than 70 (1/79, 1.3%; and 13/79, 16%, respectively). The risk of sudden death was significantly greater only in the group with H-Q greater than or equal to 70 and severe congestive heart failure. There was no correlation between the presence of first degree atrioventricular block and/or any particular type of bundle branch block pattern with sudden death and/or progression to second degree or third degree atrioventricular block. Analysis of the surface electrocardiogram is only of limited value in predicting high risk patients with chronic bundle branch block. Electrophysiologic studies are of greatest value in patients with bundle branch block with transient neurologic symptoms in whom no cause for the symptoms is evident.

Bundle-Branch Block

Atrial pacing in patients with sinus node dysfunction.

Sinus nod recovery time (SNRT) at paced atrial rates of 100 (SNRT100) and 120 (SNRT120) beats/min, atrial effective refractory periods at spontaneous heart rates (AERP) and at paced rates of 100 (AERP100) and 120 (AERP120) beats/min, and premature atrial stimulation were among the studies in evaluating 33 patients with symptomatic sinus node disease and 42 normal subjects. Although mean SNRT100 and SNRT120 were statistically significantly greater in patients than in control subjects, there was a significant overlap between patient and control groups, and SNRT100 or SNRT120 was associated with a 30.3 per cent false-negative and 5 per cent false-positive incidence. Correction for heart rate (SNRT-spontaneous cycle length) failed to improve the sensitivity or specificity of this test. There was no significant difference in mean AERP, AERP100 or AERP120, or in sinoatrial conduction time in patients compared with control subjects. Analyses of curves derived from plots of test and return cycles showed abnormal curves in only five of the 24 patients studied by progressively premature atrial stimulation. Two of these five patients showed normal zone I and II phenomena followed by a progressive linear increase in the return cycle that was thought to be due to abnormal refractoriness of the perinodal fibers.

Adult

Echocardiography in serial evaluation of left ventricular systolic and diastolic function: importance of image acquisition, quantitation, and physiologic variability in clinical and investigational applications.

Quantitative echocardiography is frequently used for serial evaluation of left ventricular performance. This prospective study was designed to determine the extent to which the acts of image acquisition and quantitation, and the subjects themselves, affect total variability in two-dimensional and Doppler echocardiographic indexes of left ventricular morphology and performance. Therefore, two technicians and two readers acquired and analyzed 60 echocardiograms from 15 normal subjects, each of whom was studied four times (twice on each of two visits). Analysis of variance based on generalizability theory was used to estimate the magnitude of these variability sources by calculating standard deviations (SD) and used to estimate their contribution to total variability. Of the two-dimensional echocardiographic indexes tested, ejection fraction varied least (SD, 6.6%) and left ventricular mass varied most (SD, 35.3 gm). Of the Doppler indexes, normalized early diastolic filling velocity integral varied least (SD, 8.4%) and deceleration time varied most (SD, 48.6 msec). Technical (image acquisition and quantitation) variability contributed most (and subject variability least) to total variability of stroke volume (68%) and deceleration time (67%). Technical variability contributed least (and subject variability most) to variability of ejection fraction (43%) and diastolic filling time (25%). The acts of image acquisition and quantitation varied more between than within technicians and readers. Peak atrial filling velocity and the ratio of peak early to atrial filling velocity significantly differed between technicians. Left ventricular ejection fraction, left ventricular mass, peak atrial filling velocity, early filling integral, and deceleration of early filling differed significantly between readers. Therefore the acts of image acquisition and quantitation, and subject variability itself, all contribute to total variability in echocardiographic indexes. Changes seen on clinical studies should be interpreted as abnormal only when exceeding the total variability originating from these sources. Generalizability theory allows one to tailor strategies to reduce variability. These strategies include increasing the number of observations, readers, and technicians for any given "baseline" study and using the same readers and technicians for sequential follow-up studies.

Adult