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[Paraneoplastic hypouricemia in Hodgkin's lymphoma secondary to a renal tubular reabsorption defect of uric acid (author's transl)].

A patient is reported with stage IV-B Hodgkin's lymphoma, lymphocyte depletion type, and associated hypouricemia (1,7 mg/dl). In the few cases described of this association hypouricemia was secondary to a high renal clearance of urate, but in no case was the involved tubular level precisely delimited. In the present case the pyrazinamide and the probenecid tests were performed, disclosing the existence of a possible defect in the postsecretory reabsorptive phase which was improved by therapy. The different pathogenetic mechanisms described to explain this transitory tubular defect are reviewed.

Adult↗

Monitoring regularity of drug intake in tuberculous patients by means of simple urine tests.

A study was undertaken to evaluate simple, reliable urine spot tests suitable for detection of the major anti-tuberculosis (TB) drugs rifampicin, isoniazid and pyrazinamide. The discrepancy between the actual ingestion of anti-TB tablets and prescribed medication was investigated in 234 hospitalized male and female patients as well as in 85 male and female outpatients with pulmonary tuberculosis. Several factors implicated in patient non-compliance are discussed, namely the degree of supervision, the independent administration of rifampicin before the other TB medication, and patient preference for certain TB medicines because of tablet size.

Color↗

Oxidative stress during antituberculous therapy in young and elderly patients.

Using allantoin (ATN) as a marker for reactive oxygen species (ROS), oxidative stress during antituberculous (anti-TB) therapy was compared in 10 young and 9 elderly patients. Before treatment, ATN plasma concentrations in patients were similar to that of volunteers. Administration of a combination of isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) increased plasma ATN in both groups of patients. ATN concentrations (M +/- SE) at six hours were higher (P < 0.05) in elderly than in young patients on day one, 8.22 +/- 1.50 vs 1.89 +/- 0.98 microgram/mL); day 30, (5.85 +/- 0.82 vs 0.87 +/- 0.57 microgram/mL; and day 90, (4.84 +/- 1.24 vs 0.52 +/- 0.50 microgram/mL). Because total amount of ATN excreted was similar in both groups on the three occasions, more ATN was formed in elderly than young patients. In conclusion, there was more oxidative stress in elderly than young patients. It is thereby suggested that Anti-TB drugs induce formation of ROS and elderly patients are at a greater risk of toxicity probably because of poor antioxidant mechanisms.

Adult↗

[Analysis of course and treatment results after treatment of pulmonary tuberculosis with early introduction of interrupted observation--preliminary report].

The results of the treatment 33 patients for smear-positive pulmonary tuberculosis with Isoniazid, Rifampicin, Pyrazinamide and Streptomycin administrated during first two weeks daily, from 3 to 8 week also with these four drugs but in a little higher doses twice weekly and next Isoniazid and Rifampicin during 9-26 weeks also twice weekly as in standard Polish model were described. After therapy with above described regimen all patients became smear-negative and radiological improvement was observed. Drugs in higher doses were well tolerated. Only abnormality in laboratory findings was temporary elevated level of uric acid, which recovered to normal values before the end of therapy. Costs of antituberculous drugs were used in this regimen is approximately 35% lower than standard model in Poland.

Adult↗

Ethambutol-induced pulmonary infiltrates with eosinophilia and skin involvement.

A 67 year old woman presented with miliary tuberculosis. She was treated with streptomycin, isoniazid, rifampicin, ethambutol and pyrazinamide. However, she developed rifampicin-induced thrombocytopenia after 6 weeks of treatment, and skin rash, blood eosinophilia and pulmonary infiltrates after 8 weeks of therapy. The latter was found to be ethambutol related. Additional evidence, including blood and sputum eosinophilia and the rapidity of its response to corticosteroid, suggested that the pulmonary infiltrates might also be eosinophilic in nature. To the best of our knowledge, this constitutes the first report of such adverse drug reaction, induced by ethambutol.

Aged↗

Anti tubercular treatment induced hepatotoxicity: does acetylator status matter?

Anti tubercular drug related hepatotoxicity is common. The mechanism of injury and factors predisposing to its development are not fully understood. Forty patients with anti tubercular drugs related hepatotoxicity were studied to see the clinical and biochemical profile of these patients and to find out the significance of acetylator phenotype in the development of hepatotoxicity. Mean age of patients with liver damage (37.82 +/- 10.0 years) was similar to those without liver damage (36.48 +/- 12.5 years). Pyrazinamide appeared to increase the hepatotoxicity of isoniazid and rifampicin. The percentage of rapid acetylators and slow acetylators among patients with hepatotoxicity (70% and 30% respectively) was similar to controls (66.6% rapid and 33.3% slow acetylators). Acetylator phenotype probably has no role in anti tubercular drugs induced hepatotoxicity.

Acetylation↗

[Contemporary methods in the diagnosis and treatment of intrathoracic tuberculosis in children].

Reduced chemotherapy courses (6-10 months) were studied for effectivity in 108 children with advanced intrathoracic tuberculosis. Intramuscular isoniazid, pyrazinamide+rifampicin produced a complete response in 87.9% of the cases who suffered side effects 2 times less frequently. The overall treatment course became shorter by 2-3 months. The treatment of 157 children with destructive pulmonary tuberculosis required long-term (12 months and more) treatment with employment of all the tuberculostatic armory and surgical intervention in 15.3% of the cases.

Administration, Oral↗

Evaluation of the 3-drug combination, Rifater, versus 4-drug therapy in the ambulatory treatment of tuberculosis in Cape Town.

The subjective impression among clinicians that the use of Rifater was causing delayed sputum conversion and increased drug resistance was tested in a prospective study. Adults in the Cape Town municipal area with a first episode of pulmonary tuberculosis were treated either with Rifater or a regimen consisting of isoniazid, rifampicin, pyrazinamide and ethambutol. All patients who took the treatment as prescribed (67 Rifater, 39 the 4-drug regimen) converted to a negative sputum culture by the time 90 doses had been taken. The rates of inadequate compliance and of side-effects were similar in the two groups. Drug sensitivity testing of bacteria cultured from pre-treatment sputum specimens revealed an overall primary resistance rate of 4.84% in the population studied, sufficiently low to preclude any necessity for routine pre-treatment drug sensitivity testing.

Antitubercular Agents↗

Drug resistance of Mycobacterium tuberculosis strains isolated from HIV-infected Italian patients: preliminary report from a multicentric study. The Italian Tuberculosis Drug Resistance Study Group.

A multicentric prospective study started in March '93 to describe both initial and acquired resistance of Mycobacterium Tuberculosis in Italian HIV+ patients (pts.) to first line drugs: Rifampin (R), Isoniazid (I), Pyrazinamide (P), Ethambutol (E), Streptomycin (S). All tuberculosis (TB) cases diagnosed in HIV+ patients (pts.) were included, along with clinical-anamnestical data. Drug-susceptibility tests were performed centrally. Preliminary results indicate an overall low frequency of TB resistance to first line drugs: R = 2%, P = 4%, S = 9%, I/E = none. However, a relevant nosocomial outbreak of multiple drug resistant (DR) TB was detected. This finding, along with some previous Italian reports of DR-TB clusters, may herald a further spread of DR-TB. Surveillance, therefore, is mandatory in Italy from now on.

Antitubercular Agents↗

[Compliance and tolerance of new antitubercular short-term chemopreventive regimens in childhood--a pilot project].

Efficacy of preventive chemotherapy in tuberculosis-infected children depends to a great extend on medical compliance and drug tolerability. Two new short-course chemoprevention-regimes of tuberculosis--four months Rifampin (A) and two months Rifampin plus Pyrazinamide (B)--were compared with the well established regimen of six months Isoniacid (C). 150 children (mean age 3.6 years with Tb conversion) were randomly allocated to these three regimens. 13 patients were non-compliant, in terms of interview, urinary INH-test strips, urine colour and prescription frequency: 7 in group C and 3 in group A and B, respectively. Adverse effects were observed in 5 patients: 3 in group C and 1 in group A and B. 1 child (group B) developed tuberculosis two years after stopping short course chemoprevention. Good compliance (94%) as well as neglectable risks of adverse effects (2%) justify further controlled studies to evaluate the efficacy of short course chemoprevention in childhood.

Adolescent↗

[Pulmonary tuberculosis in infants. Apropos of 6 cases].

BACKGROUND: The present increased incidence of tuberculosis in children can be explained by contacts with infected adults and/or late BCG vaccination. PATIENTS: Six infants, 3 to 18 months-old (mean: 8 months), were admitted from November 1990 to May 1992 for various reasons; only two were admitted with a diagnosis of tuberculosis based on tuberculin test and only one was given a BCG vaccine. The disease produced a broad range of symptoms. Diagnosis was based on tuberculin test and radiographic examination showing lymph node enlargement of mediastinum and segmental consolidation lesions. Mycobacterium tuberculosis was found in two cases. The patients were given isoniazid, rifampin, ethambutol and/or pyrazinamide; corticosteroids were added in five patients. Each patient received four or three drugs for 2-4 months and two drugs (isoniazid plus rifampin) beyond, for a mean total duration of 13 months (range: 9-17 months). Repeated CT scan of thorax was performed to evaluate the efficacy of treatment. Tuberculosis was diagnosed in 11 subjects in contact with these children. CONCLUSION: Tuberculosis in children is not rare, and BCG vaccination of neonates should be seriously considered.

BCG Vaccine↗

Pharmacologic evaluation of the renal handling of uric acid and oxypurines.

The effect of drugs that alter the renal tubular transport of urate in the renal excretion of the oxypurines, hypoxanthine (Hx) and xanthine (X), was used to analyze the tubular mechanisms involved in oxypurine excretion in normal subjects and in patients with idiopathic renal hypouricemia. In healthy subjects, administration of the drugs, benzbromarone (Bb) and probenecid (Pb), brought a marked uricosuric effect, but did not alter oxypurine excretion. One of 2 hypouricemic patients exhibited no uricosuric effects with Bb and the other showed a slight uricosuric effect with the drug. Bb administration, however, produced no increase in oxypurine excretion in either patient. In healthy subjects, administration of pyrazinamide (PZA) suppressed the excretion of urate and oxypurines to varying degrees: relative to the baseline values, the fraction excretion of urate was reduced by 95% or more, that of Hx by about 24%, and that of X by about 64%. In patients with hypouricemia, the effects of PZA on urate and oxypurine excretion were impaired. According to these findings, we can speculate that the oxypurines have the same renal secretory mechanism as uric acid. However, the reabsorptive mechanisms of oxypurines at the postsecretory site are likely to differ from that of uric acid.

Adult↗

Renal hypouricemia: incomplete combined defect.

A 20-year-old man with hypouricemia with markedly increased renal uric acid clearance is described. He also exhibited idiopathic hypercalciuria and lipoid nephrosis on hospital admission. Urate excretion was minimally suppressed by pyrazinamide and minimally increased after administration of probenecid, whereas it decreased after administration of benzbromarone. These results suggest that not only presecretory reabsorption, but also postsecretory reabsorption of urate was incompletely defective and indicate that the latter is more defective than the former. The relationship between hypouricemia and hypercalciuria or lipoid nephrosis in this case is not clear. However, since the hypouricemia persisted despite the remission of minimal change nephrotic syndrome, it appears that at least his nephrosis was incidental.

Adult↗

Controlled clinical trial of five short-course (4-month) chemotherapy regimens in pulmonary tuberculosis. First report of 4th study. East African and British Medical Research Councils.

Five 4-mo regimens of chemotherapy for tuberculosis are compared. The two regimens in which rifampicin was given throughout the 4 mo were associated with bacteriological-relapse rates of 8% in the first 6 mo after stopping chemotherapy, but the three regimens in which rifampicin was given for only the first 2 mo had relapse-rates of 24-32%. There was no evidence that the addition of pyrazinamide in the second 2 mo of chemotherapy reduced the bacteriological-relapse rate. Removal of the streptomycin from the first 2 mo appeared to reduce the bactericidal and sterilising activity of the regimen, although the differences were not statistically significant. The incidence of adverse reactions was very low with all five regimens.

Adolescent↗

Clinical features, diagnosis, and treatment of tuberculosis in infants.

OBJECTIVE: Despite the recent resurgence of tuberculosis among children in the United States, no series of infants < 1 year of age with tuberculosis has been reported in the last 20 years. This study was undertaken to describe the epidemiology, clinical, and radiographic manifestations, and response to therapy in infants < 1 year of age with tuberculous disease. METHODS: The medical records were reviewed for all infants age 12 months or less with a diagnosis of tuberculosis and cared for at the Children's Tuberculosis Clinic at Ben Taub General Hospital in Houston, Texas between January 1, 1985 and June 30, 1992. RESULTS: Of the 47 infants identified, 51% were female. The median age at diagnosis was 8 months (range 3.5 to 12 months). Fifty-one percent of the infants were African-American and over one-third were Hispanic. All patients were born in the United States. Diagnosis resulted from the examination of an ill infant in 79% of cases, a case contact investigation of an adult suspected of having tuberculosis in 19%, and routine tuberculin skin testing in 2%. An adult with infectious tuberculosis who had contact with the infant was identified in 68% of cases. Intrathoracic disease alone was present in 70% of cases. Fourteen (30%) infants had extrapulmonary tuberculosis (11 central nervous system disease, 2 disseminated disease, and 1 cervical adenitis). Gastric aspirate cultures yielded Mycobacterium tuberculosis from 75% of the infants with isolated intrathoracic disease. Forty-five infants successfully completed therapy and only one death was directly related to tuberculosis. Forty-eight percent of the infants with pulmonary tuberculosis were treated with a 6-month regimen consisting of isoniazid and rifampin supplemented during the first 2 months by pyrazinamide. Eighteen infants received some twice weekly directly observed therapy mainly due to documented or suspected nonadherence. Treatment was well-tolerated; one patient (2%) developed hepatotoxicity due to isoniazid. No infant had a relapse or recurrence of disease in 6 months to 7 years follow-up for a median of 3 years (range, 6 months to 7 years). CONCLUSION: Most infants with tuberculosis are symptomatic at the time of diagnosis, and bacteriologic confirmation was obtained in 70% of cases. A contact investigation of the household should be initiated immediately when an infant is suspected of having tuberculosis because valuable information needed to establish the diagnosis and guide therapy in the infant may be obtained. Intensive 6-month and twice weekly directly observed therapy appear to be well-tolerated and effective for the treatment of pulmonary tuberculosis in infants.

Drug Therapy, Combination↗

[Evaluation of uric acid transport in nephrons of patients with calcium nephrolithiasis and hyperuricosuria].

Renal excretion of uric acid was studied in 48 patients with recurrent calcium nephrolithiasis. Hyperuricosuria was found in 16 patients (33%) and among them 10 patients had increased values of urate clearance and fractional excretion. The tubular transport of urate was evaluated by means of pharmacological tests with pyrazinamide (PZA) and benzbromarone (BB) in these 11 patients with hyperuricosuria of renal origin. PZA suppression test was normal in 10 patients while in one case uric acid excretion was not suppressed sufficiently by PZA. Maximal uricorusirc response to BB was increased in two patients, normal in one patient and impaired in eight patients. PZA and BB tests revealed isolated defect of uric acid postsecretory reabsorption in seven patients, impaired reabsorption at both pre- and postsecretory site in one case and enhanced tubular secretion of uric acid in two patients. This study indicates that different defects of uric acid transport in nephron are the frequent cause of hyperuricosuria in patients with recurrent calcium nephrolithiasis.

Absorption↗

[A study on uric acid excretion in patients with hypouricemia].

We studied four patients with hypouricemia and almost normal renal function. Two patients are idiopathic renal and familial. The other two cases are secondary to diabetes mellitus. The study of the uricosuric mechanism with pyrazinamide (PZA) and benzbromarone (Bb) test shows that two patients have a defect of pre-secretory reabsorption of urate, the other one a incomplete combined defect of pre-and post-secretory reabsorption, and the other one a enhanced secretion of urate. The fact that two patients have the history of acute renal failure (ARF) suggested that strenuous exercise or dehydration would be responsible for ARF in patients with renal hypouricemia.

Acute Kidney Injury↗

Pharmacokinetics of isoniazid in pulmonary tuberculosis--a comparative study at two dose levels.

OBJECTIVES: To compare the pharmacokinetic parameters and the clinical efficacy of isoniazid, administered in 10 mg/kg or 5 mg/kg to children suffering from pulmonary tuberculosis. DESIGN: A randomized, open, controlled clinical trial. SETTING: Teaching hospital in New Delhi. SUBJECTS: Twenty children suffering from pulmonary tuberculosis in the age group 6-12 years. INTERVENTIONS: A three drug antitubercular regimen comprising of rifampicin (10 mg/kg), pyrazinamide (30 mg/kg) and isoniazid in a dose of either 10 mg/kg (Group I) or 5 mg/kg (Group II) was administered for fourteen days. On day fifteen serial blood samples were collected at 0,1,2,3,6 and 24 h of isoniazid administration and analyzed spectrofluorometrically. MAIN OUTCOME MEASURES: Serum isoniazid concentrations and clinical response in both the groups. RESULTS: In both the groups, serum concentration of isoniazid were above the therapeutic range (0.5-2 micrograms/ml) at 6 h following drug administration. The minimum serum concentration of isoniazid was within or above minimum inhibitory concentration of the drug at 24 h in both the groups. The time to achieve maximum serum concentration, elimination half life, elimination rate constant, mean residence time, volume of distribution at steady state and plasma drug clearance were also comparable. At the end of 6 months follow up, all children showed comparable clinical and radiological improvement. CONCLUSION: Isoniazid in a dose of 5 mg/kg administered with other antitubercular drugs appears adequate for treatment of pulmonary tuberculosis in children.

Antibiotics, Antitubercular↗