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PubMed1997

Mechanism of hypouricemia in a child with the normotensive form of Gordon's syndrome.

The mechanism of renal tubular urate transport disorder was studied by the pyrazinamide and probenecid tests in a 12-year-old hypouricemic boy suffering from the normotensive form of Gordon's syndrome, with increased distal tubular reabsorption of NaCl (confirmed by the hypotonic saline diuresis test). The aim of the study was to determine the impact of oral hydration during the tests on the phases of renal tubular urate transport: before (I), and during long-term hydrochlorothiazide therapy (0.5 mg/kg BW/day) (II). In both periods (I,II), presecretory reabsorption of urate was within normal limits. Hypouricemia in our patient was caused by decreased postsecretory reabsorption, with or without simultaneous increase of tubular urate secretion. The degree of overhydration determines which of these mechanisms is responsible for increased renal urate clearance.

Blood Pressure↗
PubMed1984

Renal handling of uric acid in patients with recurrent calcium nephrolithiasis and hyperuricosuria.

Hyperuricosuria is a frequent finding in patients with recurrent calcium nephrolithiasis (RCN) that has been related to purine overingestion . The influence of diet and the renal handling of uric acid were investigated in patients with RCN to assess the pathogenic mechanism of excessive urate excretion. Among 50 patients with recurrent nephrolithiasis 42 formed renal stones containing calcium and 9 of these 42 patients demonstrated concomitant asymptomatic hyperuricosuria while on a self-selected diet. Ingestion of a purine-free diet normalized the uric acid excretion in 4 of these 9 patients. The other 5 patients showed persistent hyperuricosuria while on a purine-free diet. In order to assess a possible dysfunction in the renal handling of uric acid, pharmacological tests were undertaken in these 9 patients. Pyrazinamide administration almost completely suppressed urate excretion, excluding a presecretory reabsorption defect. Urate excretion in response to probenecid administration was decreased in 4 patients and increased in 1. This finding is in accordance with a postsecretory reabsorption defect in the former and an augmented tubular secretion of urate in the latter. This study proves that both dietary factors and tubular transport defects are involved in patients with recurrent calcium nephrolithiasis and hyperuricosuria.

Adult↗
PubMed1987

Rapidly progressive glomerulonephritis associated with rifampicin therapy for pulmonary tuberculosis.

Two months after commencing continuous treatment with rifampicin, isoniazid, streptomycin and pyrazinamide for pulmonary tuberculosis a patient developed a nephrotic syndrome, acute nonoliguric renal failure and evidence of intravascular hemolysis. Renal biopsy revealed a severe crescentic nephritis with mild interstitial changes. The use of rifampicin has been associated with various renal abnormalities and this report documents the occurrence of a rapidly progressive crescentic glomerulonephritis presenting as nephrotic syndrome in a patient receiving continuous treatment with rifampicin.

Acute Disease↗
PubMed1988

Mechanism of hypouricemia in Hodgkin's disease. Isolated defect in postsecretory reabsorption of uric acid.

We present a patient with hypouricemia associated with Hodgkin's disease. Serum uric acid level ranged from 1.4 to 2.2 mg/dl and fractional excretion of uric acid was 26.5%. No other renal tubular abnormalities were found. The pyrazinamide suppression test came off normal. However, during the benzbromarone test, the uricosuric response was reduced. The abnormal renal handling of urate became normal following therapy of Hodgkin's disease. The findings suggest that hypouricemia in Hodgkin's disease is caused by an impairment of postsecretory tubular reabsorption of uric acid.

Female↗
PubMed1991

Evaluation of renal handling of uric acid in essential hypertension: hyperuricemia related to decreased urate secretion.

The tubular transport of urate was studied in 40 hypertensive patients and in 20 normal subjects by means of pyrazinamide and benzbromarone tests. There was a marked decrease in urate excretion per nephron in hyperuricemic patients with essential hypertension. Serum uric acid correlated inversely with fractional excretion of urate (r = -0.7450, p less than 0.001). Presecretory and postsecretory reabsorption of urate did not significantly differ between hypertensive patients with high uric acid levels and control subjects. Urate secretion was significantly reduced in hypertensive patients and in those with hyperuricemia showed a twofold decrease. Serum uric acid correlated inversely with tubular secretion of urate (r = -0.7091, p less than 0.001) in hypertensive patients. These findings indicate that impaired tubular secretion of urate is a potential mechanism of hyperuricemia in essential hypertension.

Female↗
PubMed1997

Pulmonary infection due to Mycobacterium gordonae in an adolescent immunocompetent patient.

We report the case of 17-year-old male adolescent immunocompetent patient with an operated transposition of the great arteries after the Mustard technique admitted to our hospital because of a cough and hemoptysis. Two nodules and an area of ground glass appearance located in the lower lobe of the left lung were diagnosed by ultrafast computed tomography (UF-CT) after ruling out cardiovascular complications. The gastric aspirate revealed acid-fast bacilli despite a repeatedly negative tuberculin skin test identified as Mycobacterium gordonae by the Gen-Probe Rapid Diagnostic Test. After an initial standard antimycobacterial therapy with isoniazid, rifampin and pyrazinamide the therapy was changed to clarithromycin and after a treatment course of 14 days, the UF-CT revealed a normal scan of both lungs. The case described suggests that one has to consider M. gordonae as a rare cause of infection even in immunocompetent patients.

Adolescent↗
PubMed1987

Effects of anti-tuberculosis drugs on the production of prostaglandin E2 and on mononuclear leucocyte transformation.

The effects of the anti-tuberculosis (TB) drugs isoniazid, rifampicin, streptomycin, pyrazinamide and ethambutol on the synthesis of prostaglandin E2 (PGE2) by polymorphonuclear leucocytes were investigated. Only rifampicin at a concentration of 100 micrograms/ml caused statistically significant stimulation of PGE2 production whereas the other compounds had no effect. Immunomodulatory properties of the compounds individually and in combination were investigated using phytohaemagglutinin-stimulated mononuclear leucocyte transformations. Rifampicin caused dose-dependent inhibition of blastogenesis and combinations containing this agent also had an inhibitory effect. The prostaglandin synthesis inhibitor indomethacin caused stimulation of phytohaemagglutinin responsiveness and this effect was not influenced by the presence of the anti-TB drugs.

Antitubercular Agents↗
PubMed1992

Chlorpromazine: a drug potentially useful for treating mycobacterial infections.

Chlorpromazine (CPZ) is one of several phenothiazines known to have antimicrobial properties. It can inhibit mycobacteria, and was reported in the early literature to improve tuberculosis clinically. CPZ was tested here for its ability to inhibit the replication of Mycobacterium tuberculosis and Mycobacterium avium in cultured normal human macrophages, as determined by counts of viable bacteria at 0, 4, and 7 days after bacterial infection of the macrophages. CPZ inhibited the intracellular bacteria at a concentration range of 0.23-3.6 micrograms/ml, and was more effective intracellularly than extracellularly. It was further tested for its ability to cooperate with isoniazid, streptomycin, pyrazinamide, rifampin, rifabutin, penicillin and ethambutol (EMB) against intramacrophage M. tuberculosis and M. avium. CPZ enhanced the effectiveness of most of the drugs tested against intracellular mycobacteria. However, the combination of CPZ and EMB did not result in augmented antimycobacterial activity.

Antitubercular Agents↗
PubMed1996

Treatment of multidrug-resistant tuberculosis in Thailand.

Tuberculosis (TB) has remained the 5th leading cause of death in Thailand for several years. There has been a slight change in the total number of TB cases notified since 1985 when the first case of HIV infection was reported. Although there is an increase in the incidence of TB in HIV-infected cases, the percentage of multidrug-resistant tuberculosis (MDR-TB) in this group is the same as in the HIV-negative group (2.7%). The percentages of total initial drug resistance, four-drug resistance and MDR-TB have increased to 22.4, 1.4 and 4.8%, respectively. Comparable figures for acquired resistance are up to 2.5-, 10- and 6-fold, respectively. The rapid diagnosis and susceptibility pattern of MDR-TB are essential for improving therapeutic outcome. At present there is no defined standard regimen for MDR-TB and clinical practice has been to select a regimen of three to four sensitive or not previously exposed anti-TB drugs. Duration of treatment for 24-30 months depends on severity, previous therapy and the number of drug resistances. Surgery is suggested for persistent positive cases with localized lesions and a good cardiopulmonary reserve. The quinolone, ofloxacin, is a promising drug for MDR-TB, achieving a sputum conversion rate of 59-79%. A prospective study showed a success rate of 67% with no adverse effects. The current Bangkok multicenter trials on ofloxacin 600 mg daily combined with pyrazinamide, p-aminosalicylate, amikacin and ethambutol are ongoing. Good organization of ambulatory TB management combined with directly observed therapy will probably help to reduce the incidence of MDR-TB.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Tuberculosis verrucosa cutis which remained undiagnosed for forty-three years.

An unusual case of tuberculosis verrucosa cutis of the left lower limb in a 65-year-old woman is reported. The disease, arising on the plantar aspect of the foot in 1950, was correctly diagnosed by culture of Mycobacterium tuberculosis complex from a skin biopsy only in 1993. A spectacular improvement of the cutaneous lesions was achieved using combined therapy with isoniazide, rifampicin, ethambutol and pyrazinamide.

Aged↗
PubMed1994

Tuberculous chancre in the partner of an intravenous drug abuser.

We report a 26-year-old housemaid whose partner was an intravenous drug abuser with undiagnosed pulmonary tuberculosis. The patient presented with a painless chin ulcer with an elevated irregular border and a firm, nontender submandibular adenopathy. The lesion had been present for 2 months and did not respond to antibiotic therapy. The tuberculin test was positive, and a biopsy and Löwenstein culture confirmed the diagnosis of cutaneous chancre. The patient was treated with rifampicin, isoniazid and pyrazinamide and, after 6 months of treatment, she developed scrofuloderma which had to be surgically removed. After 1 year of follow-up, the lesions had totally cleared.

Adult↗
PubMed1994

Adenosine deaminase and carcinoembryonic antigen in pericardial effusion diagnosis, especially in suspected tuberculous pericarditis.

BACKGROUND: Adenosine deaminase (ADA) and carcinoembryonic antigen (CEA) have been measured in pleural fluid to help distinguish malignant from benign effusions, especially in tuberculous pleurisy. We investigated ADA and CEA levels in patients with moderate to large pericardial effusions of different etiologies. METHODS AND RESULTS: We performed diagnostic and therapeutic pericardiostomy with drainage and biopsy. We measured ADA and CEA levels in the pericardial fluid in 26 patients with moderate to large pericardial effusion and 19 control patients. Patients were included in a prospective protocol from August 1991 to August 1993. Patients were grouped as follows: group 1, 9 patients with tuberculous pericarditis (TP) confirmed by bacteriologic culture or histology of pericardial biopsy; group 2, 5 patients with clinically strongly suspected TP; group 3, 12 patients with malignancy (8) and acute pericarditis (4); group 4, 19 control patients without pericardial disease. We treated patients with TP with isoniazid, rifampin, and either streptomycin or ethambutol for 12 months and pyrazinamide for 2 months. We observed for symptoms and signs of recurrent pericarditis or constrictive pericarditis on follow-up. In group 1 the ADA activity was significantly higher (101 +/- 14 U/L) than that in group 3 (22 +/- 5 U/L) or that in group 4 (17 +/- 2 U/L) (P < .05). There was no significant difference between ADA activity in group 1 (101 +/- 14 U/L) and that in group 2 (100 +/- 26 U/L). With a cutoff value for ADA activity of 40 U/L, sensitivity was 93% and specificity 97% in the diagnosis of TP. In benign diseases, the CEA level was significantly lower (1.0 +/- 0.3 ng/mL) than that in malignant diseases (135.1 +/- 79.7 ng/mL) (P < .05). With a cutoff value for CEA level of 5 ng/mL, sensitivity was 75% and specificity 100% in the diagnosis of malignant pericarditis. Follow-up study (mean, 12.9, 19.8, and 11.8 months in groups 1, 2, and 3, respectively, showed no symptoms or signs of constrictive pericarditis, except for 1 patient. CONCLUSIONS: Pericardial fluid ADA and CEA are useful for the differential diagnosis of pericardial effusion of various causes. They also have great value in early diagnosis of TP, particularly when the results of other clinical and laboratory tests are negative.

Adenosine Deaminase↗
PubMed1996

Predictors of survival in human immunodeficiency virus-infected patients with pulmonary tuberculosis. The Makerere University-Case Western Reserve University Research Collaboration.

Infection with the human immunodeficiency virus (HIV) has changed both the epidemiology and natural history of tuberculosis. Despite a generally good response to effective antituberculous therapy, the prognosis remains poor. The objective of this analysis was to determine the independent predictors of survival in HIV-infected Ugandan adults with smear-positive pulmonary tuberculosis. A total of 191 HIV-infected Ugandan adults with smear-positive pulmonary tuberculosis were enrolled into a clinical trial of chemotherapy for tuberculosis. The subjects received either rifampin, isoniazid, and pyrazinamide for two months, followed by rifampin and isoniazid for six months (n = 101) or streptomycin, thiacetazone, and isoniazid for two months followed by thiacetazone and isoniazid for eight months (n = 90). After standard measurements were made at baseline, the group was followed at regular intervals for a mean of 16 months to determine survival. During the course of follow-up, 82 (43%) of the patients died, six within the first month of therapy. The one-year survival proportion was 68% with an estimated median survival of 26 months and did not differ according to treatment regimen. The hazard for death was biphasic, high early in the course of therapy, and then again after about one year. After controlling for the treatment regimen, four independent predictors of survival were found: anergy to purified protein derivative, atypical chest roentgenogram, previous HIV-related condition, and lymphopenia. In this cohort of Ugandan adults, four simple and inexpensive predictors of survival were found. These factors suggest that the degree of immunosuppression was a major determinant of survival.

AIDS-Related Opportunistic Infections↗
PubMed1996

Six-month supervised intermittent tuberculosis therapy in Haitian patients with and without HIV infection.

We enrolled 427 consecutive patients with tuberculosis diagnosed in Cité Soleil, Haiti in a trial of short-course intermittent therapy. All patients received supervised therapy with isoniazid, rifampin, pyrazinamide, and ethambutol thrice weekly for 8 wk, followed by isoniazid and rifampin thrice weekly for 18 wk. At entry, the 177 human immunodeficiency virus (HIV)-infected patients (42%) were found significantly more likely to have extrapulmonary tuberculosis and negative tuberculin skin tests (p < 0.05). Treatment was well tolerated by both groups of patients, and adherence to the treatment regimen was over 90%. Among patients with pulmonary or intrathoracic tuberculosis, 9% of HIV-seropositive and 1% of HIV-seronegative patients died during therapy (p < 0.001), whereas 81% and 87%, respectively, of those in the two groups were cured. Relapses occurred in 5.4% of HIV-seropositive and 2.8% of HIV-seronegative patients who completed treatment (p = 0.36). Survival after tuberculosis was poorer in HIV-seropositive patients, whose probability of dying was 33% at 18 mo after diagnosis as compared with 3% for HIV-seronegative patients (p < 0.001). HIV-seropositive patients who died had significantly lower median CD4 lymphocyte counts than did HIV-seropositive patients who survived (p < 0.001). Treatment of tuberculosis with short-course, thrice-weekly, supervised therapy in the setting of a developing country is highly efficacious in both HIV-seropositive and -seronegative patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

Efficacy and safety of rifabutin in the treatment of patients with newly diagnosed pulmonary tuberculosis.

The efficacy and safety of rifabutin (RBT) and rifampicin (RMP) were compared in 298 patients with newly diagnosed pulmonary tuberculosis. In the initial 8-wk phase, all patients received isoniazid 400 mg/d, ethambutol 1200 mg/d, and pyrazinamide 2 g/d and were randomly allocated to receive either RMP 600 mg/d or RBT 300 mg/d. In the 16-wk continuation phase, patients received intermittent treatment (twice weekly) with isoniazid 600 mg/d, ethambutol 2400 mg/d and either RMP 600 mg/d or RBT 300 mg/d. Two hundred twenty-five (RMP = 118; RBT = 107) patients completed the 24-wk treatment period (evaluable patient population). Bacteriologic conversion rates in the RMP and RBT groups were 87.7 versus 92.0% at Week 8, 99.1 versus 99.0% at Week 12, 93.5 versus 93.8% at Week 24, and 89.8 versus 95.3% at the last valid observation. The mean time to first bacteriologic conversion was 14.1 wk in the RMP group and 14.3 wk in the RBT group. None of these differences was significant. Adverse events were reported by four patients (five events) in the RMP group and six patients (six events) in the RBT group. Those events thought to be associated with RMP were increased SGOT and leucopenia and, with RBT, increased SGOT and thrombocytopenia. Two hundred four patients entered the follow-up phase, and, of these, 95 (RMP = 49; RBT = 46) completed the scheduled 24-mo period. The overall rate of relapse was 3.8% (4/106) for the RMP group and 5.1% (5/98) for the RBT group. These differences were not significant. All relapsed patients, except for two who could not be traced, were successfully retreated. We conclude that the efficacy and tolerability of RBT is equivalent to that of RMP in the treatment of newly diagnosed uncomplicated tuberculosis, and that RBT can be effectively administered in a part-daily, part-intermittent dosage schedule.

Adolescent↗
PubMed1998

Once-weekly rifapentine-containing regimens for treatment of tuberculosis in mice.

The bactericidal activities of several once-weekly rifapentine (P)-containing combination regimens against Mycobacterium tuberculosis, and their ability to prevent the selection of rifampin (R)-resistant mutants, were compared with those of the standard six-times-weekly regimen consisting of R, isoniazid (H), and pyrazinamide (Z) in a mouse experiment. Mice were infected intravenously with 1.3 x 10(7) cfu of M. tuberculosis strain H37Rv, and 8 wk of treatment began on Day 14 after infection, when mice were randomly allocated to an untreated control group and nine treatment groups of 30 mice each. At the end of 8 wk of treatment, all the tested regimens showed promising bactericidal activities. Once-weekly P alone was less bactericidal than six-times-weekly R alone; likewise, the once-weekly P-containing combined regimens were less bactericidal than the six-times-weekly standard regimen. However, the difference in killing was about 1 log10, which represented only a fraction of the overall 4 log10 to 5 log10 magnitude of killing effects. The addition of streptomycin (S) improved the bactericidal effect of once-weekly PHZ, and the effect of once-weekly PHZS was further enhanced when it was preceded by 2 wk of daily HZS. The latter regimen achieved the same level of activity as the standard six-times-weekly regimen. All of the once-weekly P-containing combined regimens were able to prevent the selection of R-resistant mutants, whereas monotherapy with R or P selected resistant mutants in approximately 50% of animals.

Animals↗
PubMed1989

Tuberculosis control policies in major metropolitan health departments in the United States. IV. Standards in 1988.

Twenty-eight metropolitan health departments reporting greater than 250 cases annually in 1978 were surveyed to determine the standard of practice in the control of pulmonary tuberculosis and the factors affecting treatment policy. The results were compared to previous surveys in 1978, 1980, and 1984 to determine the impact of policies recommended by the Centers for Disease Control, state health departments, and other agencies. A high degree of uniformity again was demonstrated in chemoprophylaxis and hospitalization policies. However, screening, drug toxicity monitoring, and post-treatment follow-up varied widely among programs. A major trend toward short-course chemotherapy (mean duration of treatment, 20.8 +/- 2.34 months in 1980 versus 7.59 +/- 1.02 months in 1988) accompanied inclusion of pyrazinamide in first-line treatment of 59.4% of all patients in 1988 versus none in 1980. The prevalence of acquired immune deficiency syndrome (AIDS) in association with tuberculosis was estimated to be 7.72% in 1988 versus 2.52% in 1984; nine programs identified AIDS + tuberculosis in greater than 5% of all new cases in 1988 versus only two programs in 1984. Health departments identified the recommendations of the Centers for Disease Control and their respective state health departments as the major source of treatment policy; recommendations of the World Health Organization, American Academy of Pediatrics, and peer-reviewed literature had little effect upon treatment policies. This survey identifies substantial departures from prior treatment policies, some of which are attributed to reduction in available funding, development of shorter-course technology, and recognition of new groups of patients at risk to develop tuberculosis in the major cities in the major cities in the United States.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Controlled clinical trial of levamisole in short-course chemotherapy for pulmonary tuberculosis. A Kenyan/Zambian/British Medical Research Council Collaborative Study.

The effect of adding a once-weekly dose of levamisole for 4 or 8 wk to a 6-month antituberculosis chemotherapy regimen has been studied in a double-blind, placebo-controlled clinical trial. All patients received the same daily chemotherapy regimen of streptomycin, isoniazid, rifampin, and pyrazinamide for 8 wk followed by thiacetazone and isoniazid for 18 wk, the first 10 wk being given fully supervised on an inpatient basis in hospital and the remainder to be self-administered at home. In 504 patients with fully susceptible strains pretreatment assessed at the end of chemotherapy, there was no evidence of an advantage to the patients receiving levamisole for 8 wk (L8 series) or 4 wk (L4 series) when compared with those receiving placebo only (L0 series) in terms of the rate of achievement of sputum culture negativity or of radiographic improvement at independent assessment. The bacteriologic relapse rates in 2 yr of follow-up were also similar in the three series, namely, 8% for the 144 patients in the L8, 5% for the 152 in the L4, and 8% for the 160 in the L0 series. There was thus no evidence of benefit from levamisole in the dosage schedule studied. The frequency of adverse reactions to the antituberculosis drugs was unaffected by levamisole. None of 424 patients receiving levamisole had adverse reactions attributable to the drug.

Adolescent↗