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Biomedical subjects

J A Sbarbaro

Publications and source records attributed to J A Sbarbaro.

At least 19 recordsLinked to original sources
PubMed1992

The combined effect of rifampin and pyrazinamide within the human macrophage.

A recent study in the murine model suggested that a combination of rifampin and pyrazinamide used as preventive therapy might shorten the duration of treatment time. Clinical trials using this combination have been initiated, but significant results will not be available for many years. The ex vivo human macrophage model has been instructive in expanding our knowledge of the activity of chemotherapeutic agents against intracellular virulent tubercle bacilli. Prior studies have shown rifampin to have a bactericidal effect in this model while even at clinically unachievable levels, pyrazinamide had only a bacteriostatic impact. This study finds an enhanced bacteriostatic effect when low, nonbactericidal levels of rifampin are combined with clinically achievable levels of pyrazinamide but not with higher bactericidal levels of rifampin. Adding pyrazinamide 2 days after the introduction of rifampin clearly enhanced the combined killing effect. However, reversing the order and adding rifampin 2 days after the introduction of pyrazinamide produced a result weaker than introducing the agents simultaneously. Our findings do not support the use of these agents as a potentially effective preventive therapy combination, but they suggest that the timing of the administration of these chemotherapeutic agents could be an important factor in their effectiveness.

Colony Count, Microbial↗
PubMed1990

A 62-dose, 6-month therapy for pulmonary and extrapulmonary tuberculosis. A twice-weekly, directly observed, and cost-effective regimen.

STUDY OBJECTIVE: To evaluate the efficacy and toxicity of a 62-dose, four-drug, 6-month, and directly observed regimen for treatment of pulmonary and extrapulmonary tuberculosis. DESIGN: An open, nonblinded clinical trial, with intended follow-up of patients for 36 months after the completion of therapy. SETTING: A metropolitan tuberculosis clinic in a public health department. PATIENTS: From March 1981 through April 1989, we enrolled 160 patients with suspected or known tuberculosis; 35 of these patients were excluded from the analysis. INTERVENTIONS: Isoniazid, rifampin, pyrazinamide, and streptomycin were administered daily for 2 weeks; these drugs were then given in higher doses twice weekly for 6 weeks, followed by isoniazid and rifampin twice weekly for 6 weeks, followed by isoniazid and rifampin twice weekly for 18 weeks. A total of 62 doses were administered, and all therapy was directly observed by a nurse or an outreach worker. MEASUREMENTS AND MAIN RESULTS: Of the 125 evaluable patients, 101 (81%) had pulmonary tuberculosis, 7 (6%) had both pulmonary and extrapulmonary involvement, and 17 (13%) had extrapulmonary disease only. Seventy-one (57%) patients had a history of recent alcoholism. There were two relapses (1.6% +/- 2.2%), occurring 6 and 56 months after the completion of therapy. The time at which sputum samples became culture negative in pulmonary patients ranged from 1 to 19 weeks (median, 4.6 weeks); 40% +/- 9.6% of patients were culture-negative after 4 weeks of therapy, 75% +/- 8.5% after 8 weeks, 94% +/- 4.7% after 12 weeks, 97% +/- 3.3% after 16 weeks, and 100% after 20 weeks. Adverse drug reactions included hyperuricemia (greater than 178 mumol/L [3 mg/dL] above normal) secondary to pyrazinamide in 80 patients (64%), twofold or greater elevations of aspartate aminotransferase in 21 patients (17%), 1.5-fold or greater elevations of alkaline phosphatase in 33 patients (27%), cutaneous abnormalities in 8 patients (6%), nausea in five patients (4%), and dizziness in 1 patient (1%). CONCLUSIONS: This 62-dose, largely twice-weekly tuberculosis treatment regimen is efficacious and relatively nontoxic and is especially useful for patients in whom directly observed therapy is indicated.

Adolescent↗
PubMed1990

Community-based short-course treatment of pulmonary tuberculosis in a developing nation. Initial report of an eight-month, largely intermittent regimen in a population with a high prevalence of drug resistance.

A community-based tuberculosis case-finding and short-course chemotherapy program was conducted in a suburb of Manila and featured 1 month of daily isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA) followed by 7 months of twice-weekly, high dose, directly observed INH + EMB + PZA. Church-affiliated lay workers obtained 1,990 sputum specimens from subjects who complained of chronic cough or wasting symptoms; 207 of the specimens were positive on Ziehl-Neelsen smears. On culture, 176 yielded a significant growth of M. tuberculosis. Of these 176 patients, 144 were selected to enter the study; 10 were lost because of withdrawal or death and four (2.7%) because of drug toxicity. This left 130 patients who were followed long-term. Remarkably, 80% (104) were initially shedding drug-resistant organisms; 26% (34) were resistant to one drug, 30% (40) were resistant to two drugs, and 24% (30) were resistant to three or more drugs. Responses to therapy corresponded closely to the extent of drug resistance: 80% (48 of 60) of patients with drug-susceptible or single resistance had a favorable outcome; 43% (28 of 65) were resistant to two or three drugs, and 0% (0 of 5) of those were resistant to four or more drugs. Notable findings of this study were the success of a community-based program in conducting prolonged, directly observed treatment, the unexpectedly high prevalence of multiple-drug-resistant organisms in this population, and the inadequacy of INH + PZA + EMB during the continuation phase of therapy in this setting.

Antitubercular Agents↗
PubMed1988

Effects of isoniazid and of ceforanide against virulent tubercle bacilli in cultured human macrophages.

Isoniazid (INH) is said to inhibit tubercle bacilli equally well in vivo and in vitro, and to be mycobactericidal. Ceforanide (CEF) can inhibit tubercle bacilli in vitro but has been found ineffective clinically. These two drugs were tested against virulent tubercle bacilli in cultured human macrophages (MP), partly to compare the results with clinical experience, and partly for a better understanding of antituberculosis activities of these drugs in human beings. INH had the same minimal inhibitory concentration (MIC) against tubercle bacilli in MP as in 7H9 broth cultures. It killed multiplying bacilli in MP but not nonmultiplying bacilli, even at 100 times MIC. It killed both multiplying and nonmultiplying bacilli in broth cultures. It interfered with its own effectiveness against intra-MP bacilli by preventing nonmultiplying bacilli from beginning to multiply and thus become susceptible to killing. These findings help explain why this demonstrably mycobactericidal drug produces relapses of tuberculosis when used alone. It was confirmed that CEF is able to inhibit growth in broth cultures (MIC = 10 micrograms/ml). However, it was not effective against either multiplying or nonmultiplying bacilli in MP at concentrations up to 50 micrograms/ml. These results with the drugs INH and CEF support the good record of correlation between the human MP model of tuberculosis and clinical experience in antituberculosis chemotherapy.

Adult↗
PubMed1979

Suppression of ventricular arrhythmias with intravenous disopyramide and lidocaine: efficacy comparison in a randomized trial.

Twenty-six patients with clinically significant ventricular arrhythmias were randomly assigned to treatment with either intravenous disopyramide or lidocaine; crossover to the other agent was permitted in nine cases of primary drug failure. In addition, disopyramide was administered nonrandomly to seven patients with ventricular arrhythmias not controlled by lidocaine in standard doses. Arrhythmia control (greater than 50 percent reduction of premature ventricular complexes) was achieved in all 22 trials with disopyramide and in 9 of 13 trails with lidocaine in the random study, whereas clinical efficacy (arrhythmia control with absence of side effects) occurred respectively in 15 of 22, and 8 of 13 trials. In all 11 patients (7 nonrandom, 4 random) whose arrhythmia was not controlled with lidocaine the arrhythmia was controlled with disopyramide. Thus, the clinical efficacy of intravenous disopyramide ran parallel to that of lidocaine in patients with ventricular arrhythmias. Furthermore, intravenous disopyramide was an effective alternative agent for patients with arrhythmia not controlled by lidocaine.

Acute Disease↗
PubMed1979

Thallium-201 imaging in assessment of aortocoronary artery bypass graft patency.

Fifteen patients with significant coronary artery disease confirmed by cardiac catheterisation were studied before and after aortocoronary artery bypass graft surgery by rest and exercise 201Tl myocardial scintigraphy in an attempt to predict graft status non-invasively. Segmental myocardial perfusion comparisons in pre- and postoperative exercise images allowed correct predictions of high (greater than or equal to 67%) or low (less than or equal to 50%) graft patency rates in 10 of 15 patients, while similar comparisons in postoperative rest and exercise images yielded 13 of 15 correct predictions. Furthermore, 20 of 21 myocardial segments with increased postoperative perfusion when compared with corresponding segments in preoperative exercise studies were supplied by patent grafts. Regional graft occlusion, however, was difficult to predict. It was also difficult to predict graft status when myocardial segments were shown to have unchanged perfusion postoperatively as compared with the preoperative segmental assessment. Despite these limitations, the non-invasive technique of 201Tl imaging can provide useful information regarding coronary artery bypass graft patency.

Adult↗
PubMed1979

A prospective study of mitral valvular prolapse in young men.

A cardiac history, a physical examination, an electrocardiogram, phonocardiograms in the supine and standing positions, and an M-mode echocardiogram were obtained in 100 randomly selected, presumably healthy, male medical students (mean age, 26 years). Four percent met standard echocardiographic criteria for mitral valvular prolapse. No midsystolic clicks or late systolic murmurs were appreciated in this group, and none complained of chest pain or palpitations. To elucidate further the clinical implication of the echocardiographic pattern of mitral valvular prolapse, 24-hour ambulatory ECGs, multistage exercise tests, and scintiscans of myocardial perfusion at rest and after exercise (using radioactive 13nitrogen-labelled ammonium) were obtained, with normal results. The absence of life-threatening arrhythmias and exercise-induced abnormalities in these four asymptomatic subjects without abnormal physical findings suggests that the echocardiographic pattern of mitral valvular prolapse in such individuals may represent a variant of normal which does not require extensive evaluation.

Adult↗
PubMed1978

Malignant fibrous histiocytoma of the heart presenting as an atrial myxoma.

A 37-year-old woman presented with signs and symptoms suggestive of mitral stenosis and insufficiency. Subsequent evaluation demonstrated a left atrial tumor which was suspected clinically and at the time of initial surgery to be an atrial myxoma. Histologic examination revealed that the tumor was actually a malignant fibrous histiocytoma. Despite near total removal at surgery and subsequent radiotherapy, the tumor recurred within six months in the left atrium. Re-excision was followed by a third recurrence in the same site.

Adult↗