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Biomedical subjects

G Acocella

Publications and source records attributed to G Acocella.

At least 19 recordsLinked to original sources

Tuberculosis and HIV infection association in a rural district of northern Uganda: epidemiological and clinical considerations.

59 (18.3%) of 323 patients with tuberculosis (TB) tested for HIV-1 antibody by ELISA technique (Wellcozyme) were seropositive. In the control group selected among the health personnel working in the Arua Hospital, 7.7% were found positive for HIV-1 antibody, thus showing a significantly lower prevalence compared with the TB patients (P < 0.005). The prevalence of HIV infection was 50% in the urban TB patients, 7% in TB patients living in rural areas surrounding Arua town and 1.6% in the peripheral rural setting. Of 27 TB patients with clinical AIDS, 18 died during the course of the study. The AIDS patients' survival rate was 46.4% 6 months after diagnosis, and 21.4% after 16 months, the median period of survival being 5.0 months. Risk factors, sputum conversion rate, clinical and radiological findings were analysed. No significant difference was found between seropositive and seronegative TB patients for clinical drug-related toxicity (P > 0.05).

Adolescent

Proposal of an improved score method for the diagnosis of pulmonary tuberculosis in childhood in developing countries.

210 children aged less than 5 years, referred to the Arua Regional TB Centre (Uganda) for suspected pulmonary tuberculosis (PTB), were examined by anamnesis, clinical examination, Mantoux test, gastric washing, chest X-ray. The response to treatment criterion was applied to the patients treated. According to the score method suggested by Ghidey and Habte, 31 children were diagnosed as PTB patients. 30 of the 31 children with PTB tested positive for alcohol acid-fast bacilli (AAFB) in the aspirated juice. The Mantoux test and X-rays gave a minor contribution to diagnosis. The clinical results are commented. A statistical analysis was carried out to evaluate the role of gastric washing in the diagnosis of PTB in children under 5 years of age (sensitivity, 96.8%; specificity, 92.2%; positive predictive value, 68.2%; negative predictive value, 99.4%). The response to treatment was also evaluated. A modified enlarged score method (based on gastric washing and including response to treatment) is proposed to be applied in developing countries where chest X-ray and other facilities are often lacking.

Antitubercular Agents

Comparison of three different regimens in the treatment of acute brucellosis: a multicenter multinational study.

The present study was undertaken to evaluate efficacy, safety and patient acceptability of three antibiotic regimens for the treatment of acute brucellosis. Six different centres were involved: three in France, one in Greece and two in Spain. The regimens were: oral rifampicin 900 mg/day plus oral doxycycline 200 mg/day for 45 days (A), oral doxycycline 200 mg/day for 45 days plus im streptomycin 1 g/day for 21 days (regimen B) [corrected] and the WHO regimen (C) combining oral tetracycline 2 g/day for 21 days plus im streptomycin, 1 g/day, for 14 days. Regimens A and B were randomly allocated in all centres, while regimen C was allocated only in two centres. All patients were suffering from acute brucellosis clinically and biologically proven. 143 patients were allocated for treatment and analysed. Their mean age was 41 years (range 13-70), 49 were female and 94 male, and their mean weight was 64 kg (range 35-98). Among these patients, 14% had localized disease (nine orchitis, eight osteo-articular involvement and one pleural effusion), but there was no statistical difference between the three regimens in regard to this localized disease. Forty-five per cent of the patients had positive blood cultures. The cure rate with regimen A was 95%, 96% with regimen B and 59% with regimen C. Thus regimen A presented the same efficacy rate as regimen B, but regimen C cannot be regarded as the treatment of choice for acute brucellosis.

Acute Disease

Comparative bioavailability of isoniazid, rifampin, and pyrazinamide administered in free combination and in a fixed triple formulation designed for daily use in antituberculosis chemotherapy. I. Single-dose study.

A comparative bioavailability study of the antituberculosis drugs isoniazid, rifampin, and pyrazinamide was carried out in a group of 10 healthy volunteers after administration of the three compounds, once in individual association and once in a combined, fixed preparation. The investigation was designed as an open, crossover study where each subject received five tablets of a preparation containing 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide (corresponding to a total dose of 250 mg isoniazid, 600 mg rifampin, and 1,500 mg pyrazinamide). The same doses were administered in the session where the drugs were combined using the individual formulations. For each subject and experimental session, 15 blood samples were collected over a period of 24 h, and the plasma concentrations of the three drugs were assessed. The results indicated the absence of negative pharmacokinetic interactions between the drugs when administered in both free and this new, fixed combination.

Adult

Comparative bioavailability of isoniazid, rifampin, and pyrazinamide administered in free combination and in a fixed triple formulation designed for daily use in antituberculosis chemotherapy. II. Two-month, daily administration study.

The time course of the plasma concentrations of isoniazid, rifampin, and pyrazinamide was assessed in a group of 13 patients with lung tuberculosis treated over a period of 2 months on a continuous daily basis with a fixed triple combination of the same drugs. The blood kinetics of the three antituberculosis drugs were determined on Days 1, 15, 30, and 60 of treatment. The triple combination employed in this study contained 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide per tablet, the number of tablets ranging from four to seven per day according to the body weight of the patients. Almost superimposable plasma concentration curves for isoniazid were observed during the 4 days of the study. For rifampin, a fall in the plasma concentrations at the time intervals after the peak was observed comparing the data on Day 1 with those on Days 15, 30, and 60, which did not differ from each other. This finding is thought to be due to the well-known phenomenon of self-induction, which leads to an increased rate of disposal of the antibiotic from the blood compartment within the first and second weeks of continuous treatment. For pyrazinamide, an equilibrium in the opposite sense as that of rifampin seemed to take place within the 2 months of the study. Because of the relatively high plasma levels observed 24 h after each administration, an increase in plasma concentrations with respect to those observed on Day 1 was found on Days 15, 30, and 60, the levels on these days no differing from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Short-course chemotherapy of pulmonary tuberculosis: a new approach to drug dosage in the initial intensive phase.

An analysis carried out on the dosage schemes adopted in several controlled clinical trials in tuberculosis has indicated that preestablishing the daily doses of isoniazid, rifampicin, and pyrazinamide in the initial intensive phase results in large deviations of the doses administered from those considered appropriate in mg/kg body weight. This is due partly to the variations in the patients' body weight and partly to the restrictions in terms of fine adjustments of dosage imposed by the unitary content of active principle in the available individual preparations of the drugs. The availability of a fixed-triple combination of the same 3 drugs where the content of each component is established multiplying the mg/kg requirement of each drug by 10, allows a complete coincidence between the appropriate and the administered dose simply administering 1 tablet every 10 kg of body weight. The implications of the large overdosing in light patients if the conventional approach is followed are discussed in terms of toxicity and drug purchasing cost, both being of great relevance for Third World countries where the majority of patients are of low body weight.

Antitubercular Agents

Pharmacokinetic studies on antituberculosis regimens in humans. I. Absorption and metabolism of the compounds used in the initial intensive phase of the short-course regimens: single administration study.

The absorption and metabolism of streptomycin, isoniazid, rifampicin, and pyrazinamide were evaluated after administration of each drug alone and in combination. In the combination sessions, isoniazid, rifampicin, and pyrazinamide were administered orally, either individually or in a single fixed-ratio triple preparation. The results have shown that the pattern of absorption and metabolism (acetyl-isoniazid, desacetyl-rifampicin, and pyrazinoic acid) found after administration of each drug alone did not differ from that found after administration of the drugs in free and fixed combination. The 3 orally administered drugs given in a fixed combination resulted in a reduction of the order of 50% of the total number of tablets to be ingested.

Absorption

The penetration of rifampicin, pyrazinamide, and pyrazinoic acid into mouse macrophages.

The degree of penetration of rifampicin, pyrazinamide, and its metabolite pyrazinoic acid in mouse macrophages was evaluated over a period of 24 h. Cell cultures were exposed to 14C-labeled drugs at concentrations corresponding to peak, trough, and intermediate serum concentrations observed in humans after administration of therapeutic doses. The study was carried out with dead, resident, and stimulated peritoneal macrophages. The results indicated that the 3 compounds penetrate macrophages rapidly. At the lower concentrations, uptake of the 3 drugs is practically complete. With increasing concentrations, the absolute amount in the intracellular compartment increased. Comparison of the degree of penetration of the 3 drugs into dead, resident, and stimulated macrophages seems to suggest that the process of transfer through the macrophage wall is of a passive nature and not related to the metabolic state of the cells. Analysis of the binding of the 3 drugs to intracellular proteins indicated that more binding sites are probably available for rifampicin than for the other 2 drugs.

Animals

Killing of macrophage-ingested mycobacteria by rifampicin, pyrazinamide, and pyrazinoic acid alone and in combination.

A study was undertaken with the aim of assessing the killing capacity of rifampicin, pyrazinamide, and pyrazinoic acid on macrophage-ingested, live Mycobacterium tuberculosis. The 3 drugs were used at concentrations corresponding to the average peak levels observed in humans after administration of therapeutic doses that had been found to penetrate into macrophages in a previous study. The degree of killing was studied after exposure of the cell cultures to the individual drugs and their combinations for 3, 18, 24, 48, and 72 h. Comparing the degree of killing in the control, drug-free cultures with that observed in the drug-containing systems, over a period of 3 to 24 h, indicated that in these a greater, more rapid, although not statistically significant, killing of intracellular mycobacteria took place. At 48 h the degree of killing was similar in the control and in the drug-containing cell cultures. Between 48 and 72 h, however, a marked growth of intracellular mycobacteria was observed in the control cultures. This phenomenon was much less evident in the drug-containing cultures. No major increase in the killing effect with respect to that observed with the individual drugs was found after exposure of the macrophages to all possible combinations of the 3 drugs.

Animals

Can rifampicin use be safely extended? Evidence for non-emergence of resistant strains of Mycobacterium tuberculosis.

Data on the incidence of primary resistance to rifampicin in Mycobacterium tuberculosis strains have been collected from various countries. Strains isolated from those countries where rifampicin is used for both tuberculous and non-tuberculous conditions (Italy, Argentina, Brazil, and Spain) did not show a higher incidence of primary resistance than did strains from other countries (France, U.K., and U.S.A.) where rifampicin use is confined to tuberculosis. It is concluded that there is no evidence to justify fears of an increased incidence of resistance to rifampicin in M. tuberculosis if rifampicin were used discreetly for treating non-tuberculous infections.

Antitubercular Agents

Serum and urine concentrations of rifampicin administered by intravenous infusion in man.

Two studies were carried out in man with the aim of assessing the serum and urine concentrations of rifampicin administered by i.v. infusion. In patients suffering from various diseases, a dose of 600 mg i.v. proved to be equieffective with a 600 mg oral dose. Repeated administration of a 600 mg dose by i.v. infusion for a week produced serum levels corresponding to those achieved by oral administration. With the i.v. preparation the drop in serum rifampicin levels during continuous administration was less marked than with the oral administration. The recovery of antibiotic in the urine seems to be lower with i.v. than with the oral preparation. The i.v. preparation was very well tolerated by all the patients.

Administration, Oral