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At least 1,117 records · Page 62Linked to original sources
PubMed1990

Renal tubular hypouricemia: evidence for defect of both secretion and reabsorption.

Two patients had hypouricemia due to increased uric acid clearance. They showed no decrease of urate clearance to creatinine clearance ratio (Cua/Ccr) following pyrazinamide administration, and no increase of Cua/Ccr after probenecid. One patient showed a limited decline in Cua/Ccr after intravenous furosemide. In the other patient, neither acetylsalicylate nor furosemide produced any noticeable change in Cua/Ccr. Both showed a normal diuretic response after intravenous furosemide. The results indicate that they had massive defects in urate transport along the nephron, probably including both secretion and reabsorption.

Aged↗
PubMed1991

Insulin-dependent diabetes and renal hypouricemia.

We studied 14 patients (11 women and 3 men) from 18 to 33 years old, suffering from type I diabetes mellitus with normal renal function (creatinine clearance 106.91 +/- 28.73 ml/min) and serum uric acid below 2.5 mg/dl (2.34 +/- 0.11 mg/dl) as well as a high uric acid clearance (23.04 +/- 5.92 ml/min) and fractional urate excretion (21.4 +/- 2.6) versus urate clearance 9.82 ml/min and fractional urate excretion 8.80 +/- 1.3 in 14 normal control subjects. The study of the uricosuric mechanisms was conducted by the combination of probenecid (PB) test which inhibits the reabsorption of secreted urate, and pyrazinamide (PZA) test, which inhibits its tubular secretion. The results of studies indicate that the increase in urate clearance was accounted for by increased PZA-nonsuppressible urate suggesting a decreased reabsorption of filtered urate. Increased PZA-suppressible urate excretion combined with impaired response to a uricosuric drug is consistent with impaired reabsorption of secreted urate. According to our findings, increased urate excretion in diabetic patients may be attributed to the inhibition of both filtered and secreted reabsorption. This reabsorptive tubular abnormality is consistent with the view of an interference of tubular reabsorption of glucose with the tubular capacity for uric acid reabsorption.

Adolescent↗
PubMed1992

Decreased renal clearance of xanthine and hypoxanthine in a patient with renal hypouricemia: a new defect in renal handling of purines.

Renal handling of urate, xanthine and hypoxanthine was studied in a hypouricemic patient who had increased plasma concentrations of xanthine and hypoxanthine. The patient, a 50-year-old man, had been suffering from Parkinson's disease, while neither systemic disorders nor particular renal diseases known to affect plasma purine levels were found. His serum urate level was 58 +/- 6 mumol/l (healthy controls for males, 310 +/- 48 mumol/l, mean +/- SD) and the renal uric acid clearance was 3 times higher than that of the controls, establishing a diagnosis of renal hypouricemia. Xanthine and hypoxanthine concentrations in the plasma were elevated to 1.3 +/- 0.1 mumol/l (controls, 0.5 +/- 0.3) and 5.9 +/- 3.5 mumol/l (controls, 1.6 +/- 0.4), respectively. Both renal xanthine and hypoxanthine clearance was only half the value of the controls, indicating reduced urinary excretion of xanthine, and hypoxanthine appears to be responsible for their elevation in plasma. A probenecid loading test revealed no response of urinary urate excretion but normal responses of xanthine and hypoxanthine excretion. However, urinary excretion of urate, xanthine or hypoxanthine did not respond at all to pyrazinamide administration. These findings indicate that the patient had a defective renal handling of xanthine and hypoxanthine as well as urate.

Humans↗
PubMed1993

Renal hypouricemia with both drug-insensitive secretion and defective reabsorption of urate: a novel type of renal hypouricemia.

Renal handling of urate in the hypouricemic patient with increase in both urate clearance (Cur) and Cur/creatinine clearance (Ccr) and normal urinary excretion of urate was studied according to the pharmacological evaluation. In the present case there was no response of urate excretion to either pyrazinamide or probenecid. Both furosemide and prednisolone could not alter Cur and Cur/Ccr. Administration of inosine could have increased Cur, which was greater than Ccr. These results suggest that the present case had the defect of both pre- and postsecretory reabsorption of urate, accompanied by the existence of drug-insensitive secretion of urate, which is different from hitherto known types of renal hypouricemia, i.e. a novel type of renal hypouricemia.

Adult↗
PubMed1993

Hypouricemia due to increased tubular secretion of urate in children with Amanita phalloides poisoning.

The tubular transport of urate was studied in 20 children poisoned with Amanita phalloides and in control group. The aim of this study was to investigate the cause of repeatedly observed episodes of hypouricemia in patients after A. phalloides poisoning. A significant negative correlation between serum uric acid concentration and fractional excretion of urate in poisoned and control groups (r = 0.73, p < 0.001) was found. The results of pyrazinamide and probenecid tests performed in patients after A. phalloides poisoning indicated that hyperuricosuria was most likely due to an increment in renal tubular urate secretion, and not due to decreased presecretory and postsecretory reabsorption of uric acid. These findings indicate that hypouricemia found after A. phalloides poisoning in children is of renal origin due to an increase in tubular urate secretion.

Adolescent↗
PubMed1995

Impairment of tubular secretion of urate in renal transplant patients on cyclosporine.

The prevalence of hyperuricemia was investigated in 214 kidney allograft recipients, 81 were on azathioprine and steroids and 133 on cyclosprine (CyA) and low-dose steroids or on triple therapy. All had stable renal function, serum creatinine < 2.5 mg/dl, and a follow-up between 12 and 120 months. At the time of the study, blood and urine samples were obtained to perform tests of renal function. The renal handling of urate was evaluated by a combined pyrazinamide and probenecid test in 35 selected patients (12 normouricemic on azathioprine, 9 normouricemic on CyA and 14 hyperuricemic on CyA). The prevalence of hyperuricemia was higher in the group of patients on CyA (19.7 vs. 66.9%, p < 0.001), as well as the concentration of serum urate (6.1 +/- 1.9 vs. 7.6 +/- 1.7, p < 0.001), and serum creatinine (1.2 +/- 0.3 vs. 1.4 +/- 0.4, p < 0.001). In patients on CyA, multivariate analysis showed that the most important predictive variables of hyperuricemia were: serum creatinine, FEurate, diuretic use and CyA blood levels (r = 0.73, p < 0.0001). Thirteen patients on CyA (9.9%) had at least one episode of gouty arthritis. Those patients were older than the hyperuricemic patients without gout (45.7 +/- 6.7 vs. 37.1 +/- 13.5 years, p < 0.01), had worse renal function (serum creatinine 1.9 +/- 0.4 vs. 1.5 +/- 0.4 mg/dl, p < 0.01), and higher prevalence of hypertension (100 vs. 63.1%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Hypouricemia and cancer. A study of the mechanisms of renal urate wasting in two cases.

Two cases of hypouricemia in association with malignant diseases are presented. One patient had metastatic breast cancer and the other an undifferentiated retroperitoneal sarcoma of the childhood. Uric acid renal handling was studied with the pyrazinamide and benzbromarone tests. Both patients had reduced postsecretory reabsorption of uric acid. The increase of serum uric acid levels in both patients, after a partial response to chemotherapy, indicates the possible paraneoplastic origin of hypouricemia. Our results are discussed and compared with other reports in the literature.

Adolescent↗
PubMed1985

Six-month chemotherapy for urogenital tuberculosis.

Rifampicin (RMP, 600 mg), isoniazid (INH, 300 mg) and pyrazinamide (PZA, 1,000 mg) administered daily in the hospital for a duration of 2 months was followed at home by daily administration of 600 mg RMP and 300 mg INH for a duration of 4 months. 113 patients with previously untreated and bacteriologically proven urogenital tuberculosis were admitted to the study. Therapy was completed and evaluated in 106 (94%) patients. No failure of chemotherapy was observed during the treatment; one bacteriologically proven relapse occurred after completion of treatment within the 45- to 63-month follow-up. This 6-month chemotherapy seems as efficient as the standard treatment which lasted for 18-24 months.

Adult↗
PubMed1994

Preventive therapy of tuberculosis with rifapentine in immunocompetent and nude mice.

The effectiveness of intermittent administration of rifapentine (RPT), with or without isoniazid (INH), for preventive therapy of tuberculosis was evaluated in immunocompetent (normal) and nude mice. After infection with a small inoculum of Mycobacterium tuberculosis H37Rv, normal mice developed a chronic and nonfatal infection, and the bacterial population became relatively stable after an initial period of limited multiplication. On the other hand, nude mice developed an acute and fatal infection, and all untreated mice died within 5 wk, with very high colony-forming-unit (CFU) counts in their organs. Various degrees of bactericidal activity were shown in normal mice after daily treatment with rifampin (RMP) plus pyrazinamide (PZA) for 13 wk, INH daily for 26 wk, or RPT once weekly for 13 or 26 wk or once fortnightly for 26 wk. The activity of RPT was significantly enhanced when INH was added at the same dosing frequency. In nude mice the response of M. tuberculosis infection to certain regimens was less favorable than that in normal mice, suggesting that preventive therapy may be less effective in severely immunodeficient hosts even during treatment. After chemotherapy was stopped, virtually all nude mice relapsed within 12 wk regardless of the regimen administered, whereas no or very few relapses were observed in normal mice that had been treated with RMP+PZA daily for 13 wk, or RPT alone or RPT+INH once weekly for 26 wk. The latter three regimens and RPT+INH once weekly for 13 wk may be applied for fixed-duration preventive therapy in human immunodeficiency virus (HIV)-negative subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

A prospective evaluation of antituberculosis therapy in patients with human immunodeficiency virus infection.

The purpose of this study was to determine the efficacy and toxicity of a standard antituberculosis regimen in patients with human immunodeficiency virus (HIV) infection. We prospectively evaluated 89 patients with tuberculosis and HIV infection at an urban medical center. Eighty-two patients received isoniazid, rifampin, and pyrazinamide, with or without ethambutol, for 2 mo, followed by isoniazid and rifampin for 7 mo. Seven patients received other regimens because of drug resistance or intolerance. Therapy was self-administered in 57 patients and directly observed in 32 cases. All patients showed rapid clinical improvement during the first month of therapy, and sputum cultures reverted to negative after 3 mo in 52 of 54 patients from whom specimens were obtained. Adverse reactions to isoniazid or rifampin prompted alterations in antituberculosis regimens in five patients (6%). Forty patients (45%) died during follow-up, and tuberculosis was a potential contributory cause of death in three cases. Treatment failure occurred in five patients (6%), four of whom were noncompliant with therapy. The fifty patient had an isoniazid-resistant organism. No relapses occurred in 916 patient-months of follow-up posttreatment. We thus conclude that the 9-mo regimen used for treatment of drug-susceptible tuberculosis in HIV-infected patients is effective and well tolerated.

AIDS-Related Opportunistic Infections↗
PubMed1999

Four-month, four-drug preventive therapy for inactive pulmonary tuberculosis.

Standard preventive therapy for inactive pulmonary tuberculosis (TB) is 12 mo of isoniazid. Shorter multiple-drug preventive regimens have been proposed. From December 1993 through January 1996 we evaluated a 4-mo, four-drug regimen of preventive therapy for patients with inactive TB, mostly newly arriving immigrants from countries with high rates of TB and of isoniazid resistance. Fifty-three evaluable patients received a 4-mo regimen of isoniazid, rifampin, ethambutol, and pyrazinamide. We compared their completion rate, side effects, and cost of treatment with those of 108 age-matched patients who had received 12 mo of isoniazid at an earlier time. Sixty-eight percent of patients on the 4-mo regimen completed treatment; 69% of those on the 12-mo regimen completed treatment (p = 0.9393). Side effects were more frequent for the 4-mo regimen (30.2%) compared with 12 mo of isoniazid (11.1%) (p = 0. 0027). The cost of providing an uncomplicated, self-supervised regimen was estimated to be almost four times greater for the four-drug regimen compared with isoniazid. These results show that, in terms of compliance, a four-drug, 4-mo regimen had no advantage over standard preventive therapy for persons with inactive pulmonary TB. On the other hand, the shorter, more intensive regimen was associated with more frequent adverse effects and was more costly.

Adult↗
PubMed2000

Antituberculosis activity of once-weekly rifapentine-containing regimens in mice. Long-term effectiveness with 6- and 8-month treatment regimens.

The effectiveness of various once-weekly 10 mg/kg rifapentine (P)- containing regimens for treatment of tuberculosis was assessed in mice infected intravenously with 4.3 x 10(6) colony-forming units (cfu) of Mycobacterium tuberculosis H37Rv, and treated 14 d later with various combinations of rifampin (R), P, isoniazid (H), pyrazinamide (Z), ethambutol (E), or streptomycin (S). Control mice treated daily with either 2-mo HRZ + 4-mo HR or 2-mo HRZ + 6-mo HE were rendered spleen and lung culture-negative at 6 mo and 8 mo, respectively. Treatment failure with emergence of R-resistant bacilli occurred in all mice given once-weekly monotherapy with P for 6 mo. Once-weekly PH treatment was successful at 6 mo when it was preceded by a 2-mo daily phase with HRZ. When the initial daily phase was reduced to 2 wk, once-weekly PH-containing treatment was successful, at 6 mo, only if it was supplemented with S during the initial daily and the once-weekly phases, and at 8 mo if it was supplemented with daily H during the once-weekly phase. Without these supplements, once-weekly treatment failed in some mice with selection of R-resistant or H-resistant mutants.

Animals↗
PubMed1987

Short-course chemotherapy of pulmonary tuberculosis in pneumoconiotic patients.

This is the first prospective clinical trial recorded to date of short-course chemotherapy in pulmonary tuberculosis complicated by pneumoconiosis. Forty-eight anthrasillicotic and 11 silicotic patients with previously untreated pulmonary tuberculosis completed 9-month, short-course chemotherapy regimens: 2 months of daily streptomycin, isoniazid, rifampicin, and pyrazinamide followed by daily isoniazid and rifampicin for 7 months (2SHRZ/7HR). There were 3 treatment failures (5%). The remaining 56 patients (95%) all had their sputum converted within 4 months (mean, 1.5 months). Bacteriologic relapses were noted in 3 patients (5%) after 18 to 40 months of follow-up (mean, 28.4 months). The relapses occurred within 7 months after chemotherapy was stopped. There were 2 deaths from nontuberculosis causes during the follow-up period. Fifty-one patients (90%) remained bacteriologically sterile for 28.4 +/- 6.1 months. These results suggest that the 2SHRZ/7HR regimen is satisfactory in treating anthrasilicotic or silicotic patients with pulmonary tuberculosis, though antituberculosis chemotherapy seemed less effective in patients with pneumoconiosis than in those without pneumoconiosis.

Adult↗
PubMed1988

Five-year follow-up of a clinical trial of three 6-month regimens of chemotherapy given intermittently in the continuation phase in the treatment of pulmonary tuberculosis. Singapore Tuberculosis Service/British Medical Research Council.

In a study in Singapore, patients of Chinese, Malay, and Indian ethnic origin with sputum-smear-positive pulmonary tuberculosis were allocated at random to daily treatment with streptomycin, isoniazid, rifampin, and pyrazinamide for 2 months (2SHRZ), for 1 month (1SHRZ), or for 2 months without streptomycin (2HRZ), followed, for all patients, by 3-times-weekly isoniazid and rifampin (H3 R3) up to 6 months. As previously reported, all except 1 of 319 patients with drug-susceptible tubercle bacilli pretreatment had a favorable bacteriologic status at the end of chemotherapy, and among the 300 patients assessed up to 30 months (24 months after the end of chemotherapy), there was only 1 bacteriologic relapse in each series, giving an overall therapeutic failure rate of only 1.3%. Follow-up has been continued at 6-month intervals up to 5 yr. During the 5 yr, the total relapse rate for patients with drug-susceptible strains pretreatment was 2.4% of 297 patients (95% confidence limits, 1.0 to 4.8%). Among the 31 patients with strains resistant to isoniazid, streptomycin, or both drugs pretreatment, there were no failures during chemotherapy and 4 (13%) subsequent relapses.

Antitubercular Agents↗
PubMed1989

A controlled trial of 3-month, 4-month, and 6-month regimens of chemotherapy for sputum-smear-negative pulmonary tuberculosis. Results at 5 years. Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council.

Of 1,710 Chinese patients with radiologically active pulmonary tuberculosis but with sputum negative for acid-fast bacilli on four or more initial microscopic examinations who were studied for 5 yr, 592 (35%) had one or more initial sputum cultures positive for Mycobacterium tuberculosis. These 592 patients were randomly allocated to receive streptomycin, isoniazid, rifampin, and pyrazinamide daily for 4 months or 3 times a week for either 4 or 6 months. The remaining 1,118 patients with all their initial cultures negative were randomly allocated to receive the same four drugs daily for 3 months or 3 times a week for either 3 or 4 months. There were no bacteriologic failures during chemotherapy, and the relapse rates for the 4-month regimens during the 5 yr were 2% in 293 patients with drug-susceptible cultures initially (95% confidence limits, 1 to 5%); 8% in 59 patients with cultures resistant to isoniazid, streptomycin, or both drugs, but susceptible to rifampin initially; and 4% in 325 patients with all their cultures negative initially (95% confidence limits, 1 to 7%). The combined relapse rate for the 3-month regimens was 7% in 709 patients with all their cultures negative initially (95% confidence limits, 5 to 9%). In Hong Kong, 4 months of chemotherapy is now used routinely in the treatment of patients with smear-negative pulmonary tuberculosis, whether their initial sputum cultures are positive or negative.

Adolescent↗
PubMed1993

Early bactericidal and sterilizing activities of ciprofloxacin in pulmonary tuberculosis.

The early bactericidal and sterilizing activities of ciprofloxacin were evaluated in the treatment of adult patients with smear positive pulmonary tuberculosis. Two randomized prospective studies were performed in Northern Tanzania. In study 1, ten patients received either 750 mg ciprofloxacin or 300 ng isoniazid daily for 7 days. Counts of colony-forming units (cfu) of Mycobacterium tuberculosis in early morning sputum were performed. In study 2, twenty patients received either a standard regimen of rifampin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) (regimen HRZE) or a trial regimen of ciprofloxacin (C), isoniazid (H), and rifampin (R) (regimen HRC). Sputum colony counts were performed for 8 wk. Patients were tested for antibodies to human immunodeficiency virus (HIV)-1. The results demonstrate that ciprofloxacin alone has useful early bactericidal activity, resulting in a mean daily fall of 0.20 log10cfu/ml/day during 7 days compared with 0.25 log10cfu/ml/day for isoniazid. When HRZE and HRC regimens were compared, the HRC regimen appeared to be inferior in its sterilizing ability, with a culture conversion rate of 67% at 2 months compared with 100% for HRZE. The difference in outcome was most marked in HIV-1 positive patients. The role of ciprofloxacin in combination regimens may be as a bactericidal rather than a sterilizing agent.

Adult↗
PubMed1981

Shortest possible acceptable, effective ambulatory chemotherapy in pulmonary tuberculosis: preliminary report I.

In two 4.5-month regimens and one 3-month regimen the four most potent antituberculous drugs (isoniazid, rifampin, pyrazinamide, and streptomycin) were given for the initial 3 months of chemotherapy. Acceptance by the patients was high, and bacillary sterilization was achieved in 96% of cases within 2 months. Addition of a fifth drug, ethionamide, during the initial 3 months was neither acceptable nor useful. No relapses were observed during a 12-month follow-up period after completion of the 4.5-month regimens. A relapse rate of 5% followed the 3-month regimen. The toxicity and side effects of antituberculous drugs were observed in 16% of patients during the initial 3-month period. In 3.4% of patients, toxicity necessitated cessation of treatment. In the remaining 13% of patients, adverse side effects could be managed without cessation of treatment. Even when patients were ambulatory and outpatient attendance was required for drug administration, the noncompliance rate was only approximately 10%. With the current over-all cost of drugs being limited to 100 United States dollars, the patients with moderately extensive disease must be treated for 100 days, or a maximum of 100 doses.

Ambulatory Care↗
PubMed1982

Drug-resistant Mycobacterium tuberculosis in Korean isolates.

Tuberculosis is a common disease in developing countries. An increasing incidence of resistance to isoniazid (INH) and streptomycin in organisms isolated from patients who contracted their disease in these countries, particularly in the Far East, is well recognized. This drug resistance has led to the recommendation of empirically beginning a regimen in patients with tuberculosis from the Far East of INH, ethambutol, and rifampin. This report documents the increasing incidence of resistance in isolates from Korea to ethambutol and rifampin in addition to INH and streptomycin. It suggests that the empiric use of INH, ethambutol, and rifampin in this group of patients could potentially lead to resistance to all of these drugs because of a significant amount of multidrug resistance. A regimen of INH, rifampin, pyrazinamide, and capreomycin is suggested as appropriate initial therapy in these patients based on the in vitro sensitivity data presented and initial clinical experience.

Adult↗