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PubMed1988

Sulfasalazine and 5-aminosalicylic acid inhibit contractile leukotriene formation.

Sulfasalazine, used therapeutically in the treatment of ulcerative colitis, is cleaved in vivo to form 5-aminosalicylic acid (5-ASA) and sulfapyridine. In an isolated preparation of rat peritoneal cells both sulfasalazine (IC50 = 0.15 mM) and 5-ASA (IC50 = 2.3 mM), but not sulfapyridine, inhibited calcium ionophore-stimulated formation of contractile leukotriene activity. This activity, although not identified directly, is attributable to a mixture of leukotriene C4 and leukotriene D4 (commonly referred to as SRS-A, or slow-reacting substance of anaphylaxis). Reference compounds evinced expected activities (IC50 = 0.024 mM for phenidone, IC50 = 0.3 microM for nordihydroguaiaretic acid, IC50 = 0.033 mM for BW 755C), whereas para-aminosalicylic acid and thiosalicylic acid were inactive. These properties of sulfasalazine may contribute to its therapeutic efficacy in vivo.

Aminosalicylic Acids↗

PubMed1988

[Cold agglutinin disease].

Cold agglutinin disease is a normo- or macrocytic anemia due to antibodies, active under body temperature, mostly belonging to the immunoglobulin class M. Initially the agglutination of erythrocytes with acrocyanosis is reversible at body temperature. High antibody activity or long lasting period of coldness lead to intravascular or intrahepatic hemolysis, but high risk anemia is rare. Beside the idiopathic form, infection induced (especially infectious mononucleosis, cytomegalovirus, Mycoplasma pneumoniae, Klebsiella), and drug induced (especially quinidine, alpha methyldopa, penicillin, para-aminosalicylic acid, various analgetics, sulfonylurea), tumor associated (especially malignant lymphomas), and autoimmune disease associated (especially systemic lupus erythematosus) cold agglutinin anemias are discribed. "Cross reacting antigenity" to the hemolysing agent and the membrane of erythrocyte, exogenous induced changing of erythrocytic antigenity, and diversification concerning the production of antibodies are discussed as pathophysiological explanations.

Agglutinins↗

PubMed1979

Tuberculosis of the male urethra.

Tuberculosis of the male urethra is a rare lesion, with only 21 cases reported in the literature. Two patients with tuberculosis of the urethra, who presented with multiple periurethral fistulas and a periurethral abscess, are described. In both patients there was associated genitourinary tuberculosis. Mycobacterium tuberculosis could be isolated from the urine and the exudate of the perineal ulcers. Biopsy from the perineal ulcers demonstrated tuberculous granulation tissue with tuberculous bacilli. Treatment consisted of suprapubic cystostomy and a 2-year course of antituberculous drugs, consisting of streptomycin, para-aminosalicylic acid and isoniazid. The urethral fistulas healed with this treatment. The urethral strictures were treated with repeated urethral dilations.

Adult↗

PubMed1986

Papulonecrotic tuberculid: a neglected disease in Western countries.

Papulonecrotic tuberculid was diagnosed in twelve young patients demonstrating symmetric scattered papulopustular necrotic lesions of the extremities. The diagnosis was supported by a strongly positive Mantoux reaction in all cases, evidence of preexisting or past tuberculosis in eight patients, characteristic histologic findings, and a prompt resolution with antituberculosis therapy. Recurrence of the skin lesions in three patients treated only with isoniazid or with para-aminosalicylic acid and isoniazid indicates the necessity for combination treatment with several antituberculosis drugs. A detailed study of twenty biopsies indicates that the primary lesion is a subacute lymphohistiocytic vasculitis that causes thrombosis and destruction of small dermal vessels. These changes lead to an infarctlike lesion with coagulation necrosis of dermal tissue. In eleven instances a well-marked palisaded histiocytic reaction was seen around necrotic areas, calling into question the differential diagnosis of granuloma annulare or Churg-Strauss granulomatosis.

Adolescent↗

PubMed1976

Some bacteriologic aspects of the epidemiology of pulmonary and extrapulmonary tuberculosis.

A study was carried out to investigate the drug resistance patterns of the prevalent tubercle bacilli in pulmonary and extrapulmonary tuberculosis in and about the city of Lahore, Pakistan. This report includes 168 strains of Mycobacterium tuberculosis isolated from the same number of pulmonary tuberculosis cases (100 untreated cases, defined as patients either having no history of anti-tuberculous therapy or having had chemotherapy for not more than 10 days; 68 treated, defined as having had chemotherapy for more than 10 days), and 162 strains from the same number of extrapulmonary tuberculosis cases (77 untreated, 38 treated and 47 doubtful). The proportion method of drug susceptibility assay was employed. According to the procedures used in this study and with 1% as the critical proportion for resistance, bacterial resistance was found to be very prevalent in pulmonary tuberculosis. Even among those cases in which no history of previous treatment was elicited, 46% were found to be excreting populations of tubercle bacilli having some degree of resistance to one or more of the primary drugs--isoniazid, streptomycin and para-aminosalicylic acid. In treated cases, 86.8% were found to have some resistance to one or more drugs. Overall, resistance to streptomycin was found to be commonest. Drug resistance was observed to be somewhat less common in extrapulmonary than in pulmonary tuberculosis, with streptomycin resistance predominating. Although both catalase-positive and catalase-negative isoniazid-resistant strains of M. tuberculosis were isolated from patients with pulmonary disease, no catalase-negative strains were isolated from patients with extrapulmonary disease, suggesting limited pathogenic potentialities of catalase-negative strains for man. Epidemiologic aspects of these observations are discussed.

Adult↗

PubMed1986

Contact dermatitis to antituberculosis drugs.

The literature has been reviewed for contact dermatitis occurring to antituberculosis agents. Of the 12 known drugs, 6 (isoniazid, rifampicin, ethambutol, para-aminosalicylic acid, streptomycin and kanamycin) have been documented by patch test to cause this type of dermatitis in certain individuals. Cross sensitization has been observed to contribute significantly to the allergic reactions noted from isoniazid, streptomycin, and kanamycin. Hyposensitization has also been discussed in this review.

Aminosalicylic Acid↗

PubMed1976

A continuing survey of primary drug resistance in tuberculosis, 1961 to 1968. A U.S. Public Health Service cooperative study.

From 1961 through 1968 the incidence of primary drug resistance was monitored among patients admitted to 22 participating hospitals. The patients were believed to have newly diagnosed, previously untreated, bacteriologically proved pulmonary tuberculosis. During the study period the level of primary resistance to isoniazid, streptomycin, and para-aminosalicylic acid remained very low; there was no indication that primary resistance to these drugs was increasing. Investigation of patient histories revealed that a significant proportion of persons initially believed to have been previously untreated actually had received prior chemotherapy. Resistance rates to both isoniazid and streptomycin were significantly higher among younger patients than among older patients. No relationship was found between race or sex and primary resistance rates. The low incidence of drug resistance found in this survey suggests that disease caused by virulent resistant organisms occurs infrequently.

Adult↗

PubMed1978

Primary antituberculous drug resistance in Hawaii, 1957 to 1977.

A study of primary antituberculous drug resistance in Hawaii was conducted from 1957 to 1977 to determine the incidence of primary resistance with respect to time. A total of 1,869 initial cultures of Mycobacterium tuberculosis submitted to Leahi Hospital in Honolulu were screened to identify drug resistance. Of 256 patients who excreted resistant bacilli, only 55 had no history of previous antituberculous chemotherapy. The frequencies of primary drug resistance from July 1957 to July 1977 were as follows: streptomycin, 0.86 per cent; isoniazid, 1.2 per cent; para-aminosalicylic acid, 1.5 per cent. No strains were resistant to ethambutol or rifampin. A slight decrease in the incidence of drug resistance during a 20-year period was observed. This was especially significant because Hawaii's tuberculosis problem is principally confined to its foreighn-born population. Although no serious primary drug resistance problem was discovered, Hawaii possesses both the highest immigration rate and the highest incidence of tuberculosis in the United states. Therefore, there is a need for continued periodic monitoring of drug resistance in Hawaii.

Aminosalicylic Acid↗

PubMed1979

Primary drug resistance in children. Drug susceptibility of strains of Mycobacterium tuberculosis isolated from children during the years 1973 through 1977 at the Kings County Hospital Center of Brooklyn.

A continuing study of the frequency of primary drug resistance among children treated at the Kings County Hospital Center of Brooklyn during the years 1973 through 1977 showed a high incidence of primary drug resistance to isoniazid (8.8 per cent) and to streptomycin (12.3 per cent). In contrast, there were no strains resistant to cycloserine, viomycin, ethambutol, or rifampin, and only one of 57 strains (1.8 per cent) was resistant to ethionamide, and one (1.8 per cent) was resistant to para-aminosalicylic acid. Comparison with previous studies begun in 1961 showed no significant increase in resistance to isoniazid during 3 prior periods of study and no increase in resistance to streptomycin during the last 2 periods of study. It must be emphasized that these findings relate only to the children of a local community, and do not reflect the prevalence of primary drug resistance elsewhere in this country or among different age groups.

Adolescent↗

PubMed1986

Primary drug-resistant tuberculosis in children. Emergence of primary drug-resistant strains of M. tuberculosis to rifampin.

A prospective study of primary drug-resistant strains of Mycobacterium tuberculosis among children was begun at the Kings County Hospital Medical Center of Brooklyn in 1961 and reported at 5 4-yr periods through 1980. The present report extends our observations of primary drug-resistant tuberculosis in children through 1984. The salient finding in the present report was the increase in primary drug resistance to rifampin, 3 of 19 strains resistant in the last period of study (1981 to 1984) as compared with 1 of 96 strains isolated in the previous 3 periods of study (1969 to 1980). This increase was significant (p less than 0.02) even though the number of strains isolated was small. There were continued low resistance rates to ethambutol and para-aminosalicylic acid and stable resistance rates for isoniazid and streptomycin.

Adolescent↗

PubMedDate not supplied

Pharmacokinetic interactions with rifampicin.

Rifampicin, a potent antituberculosis agent, is frequently combined with other antituberculosis drugs, or with drugs belonging to entirely different classes which may be required during a long period of antituberculous treatment, and therefore has a potential for drug interactions of practical clinical importance. The absorption of rifampicin is markedly decreased when it is simultaneously administered with para-aminosalicylic acid granules, due to adsorption by an excipient, bentonite. Several clinical observations and investigations have indicated that rifampicin itself accelerates the metabolism of various other compounds, including oral anticoagulants, the contraceptive pill, oral hypoglycaemic agents and digitoxin. Rifampicin seems to be a potent inducer of drug metabolism in humans and it causes a proliferation of the smooth endoplasmatic reticulum and an increase of cytochrome P450 content in the liver. It also increases its own rate of desacetylation. However, of the test compounds hexobarbitone and tolbutamide, the metabolic clearance increased 2-to 3-fold following rafampicin treatment, whereas antipyrine clearance was unaltered. This indicates that there is a certain selectivity in the enzyme induction effect of rifampicin, although it reamins unclear which compound will and which will not be affected. Rifampicin may also possibly interfere with hepatic uptake of other compounds, but the clinical significance of this type of interaction has not been clearly demonstrated; On the other hand, oral probenecid significantly increases the serum level of rifampicin, probably due to a similar depression of hepatic uptake.

Absorption↗

PubMed1979

Canadian survey to determine the rate of drug resistance to isoniazid, PAS and streptomycin in newly detected untreated tuberculosis patients and retreatment cases.

In 1975, a survey was carried out in Canada to determine the primary and acquired drug resistance of M. tuberculosis isolates to isoniazid (INH), para-aminosalicylic acid (PAS) and streptomycin. The results of this investigation were compared with those of the primary drug resistant study of Armstrong, undertaken in 1963-64. It revealed that primary drug resistance has increased from 4.9% to 6.3%. The increase is mainly due to immigrants having arrived in this country during the last 12 years. In these newcomers the primary resistance rate was 11.5%. Moreover, 57.8% of the immigrants examined in the survey were of Asian origin, with a drug resistance rate of 11.7%, while 15.6% had arrived from South Europe with a resistant ratio of 16.7%. In retreatment cases, the national average of drug resistance was 26.4%. Among the Canadian provinces, the highest drug resistance rate in retreatment patients (40%) was found in Quebec. While in primary resistance Streptomycin exhibited the highest incidence, in retreatment cases isoniazid resistance proved to be more frequent. In natives, the rates and patterns of primary and acquired resistance were very similar to those observed in other Canadian born patients.

Aminosalicylic Acid↗

PubMed1991

Correspondence with a pioneer, Jürgen Lehmann (1898-1989), producer of the first effective antituberculosis specific.

Correspondence between the author and Lehmann provided evidence that the latter evolved the first effective antituberculosis drug, para-aminosalicylic acid (PAS), contrary to accepted belief that this honour belonged to Nobel Prize-winner Selman A. Waksman for his production of streptomycin. While both drugs appeared in 1943, successful animal and clinical trials of PAS preceded those of streptomycin. PAS has been discarded in modern treatment regimens because of gastric side-effects, but was available at a critical time to demonstrate the principle of multiple therapy in prevention of bacterial resistance in tuberculosis therapy. It probably saved streptomycin, which causes bacterial resistance and clinical regression within 3 months when used alone, from being discarded as an unsuitable drug of temporary benefit and a public health hazard.

Aminosalicylic Acid↗

PubMed1987

Augmentation of hepatic uridine-diphosphate glucuronyl transferase activity by antituberculous drugs in hamsters in vivo.

Changes in uridine-diphosphate glucuronyl transferase activity (UDP-GT) in liver homogenates of hamsters treated with different doses of isoniazid (INH), rifampicin (RMP), para-aminosalicylic acid (PAS) and hydrocortisone for several periods of time were studied and expressed as mg of bilirubin conjugated per g of protein per h. INH, RMP, PAS and hydrocortisone induced UDP-GT activity to a statistically significant degree. The optimum dose for high induction was 20 mg for INH, RMP and hydrocortisone, and 200 mg for PAS per kg of body weight. The optimum time of treatment for high induction was 10 consecutive days of intraperitoneal administration for all drugs examined. Such data, particularly for INH and RMP, indicate why patients who receive these drugs show no clinical jaundice, although they develop an hepatitis-like disease with elevation of serum transaminase of hepatic origin. This could be the result of stimulation of the hepatic smooth endoplasmic reticulum which produces rapid conjugation and therefore excretion of bilirubin. Similarly, the antituberculous drugs may cause liver dysfunction by inducing other liver enzymes.

Aminosalicylic Acid↗

PubMed1987

Neuromuscular abnormalities associated with hypothyroidism and lymphocytic thyroiditis in three dogs.

Various degrees of persistent or paroxysmal paresis involving only the hindlimbs or all four limbs were observed in 3 dogs with hypothyroidism and lymphocytic thyroiditis. Clinical features included lethargy, obesity, alopecia, insidious and progressive paresis, hypotonia, and slow segmental reflexes in 2 dogs. Obesity, alopecia, paroxysmal paresis, and behavior change were observed in the third dog. Laboratory tests indicated that thyroid function was less than normal in all 3 dogs. Abnormal electromyographic potentials and slow motor nerve conduction velocities were found in each dog. Muscle biopsy specimen abnormalities included selective type-II myofiber atrophy in all dogs, whereas one dog had angular atrophy of type-I and type-II myofibers indicative of denervation. A substance that stained with para-aminosalicylic acid was observed within vacuoles of type-I myofibers in one dog. Lymphocytic thyroiditis characterized by lymphocytic infiltration of excised thyroid glands was observed in all dogs.

Animals↗

PubMed1985

[Resistance of Mycobacterium tuberculosis. An 8-year survey in the Poitiers area].

We have studied in Poitiers area from 1977 to 1984 the resistance of 853 Mycobacterium tuberculosis strains to the main anti-tuberculosis drugs. The overall rate of drug resistance was showed to be steady over the years while the primary resistance rate has decreased. The only one drug resistance has concerned para-aminosalicylic acid, streptomycin and isoniazid. Foreigners, most of them Asian people or North-African people, often bear resistant tubercle bacilli (29,03%) compared with French people (9,29%). We encountered drug resistance phenomena essentially among less than 60 years old patients. Drug susceptibility tests remain indispensable for a good epidemiologic supervision at the time of relapses and among patients possibly infected with multiresistant germs.

Adult↗

PubMedDate not supplied

[Effect of theophylline and isoprenaline on N-acetylation activity in the rat liver].

The activity of N-acetyltransferase is shown to significantly rise after administration of theophylline and isoprenaline, but not of propranolol and N-acetylderivate of para-aminosalicylic acid to form during 30 minutes at a constant rate that increases following addition of cyclic AMP to the incubation medium. The capacity of the rat to acetylate paraaminosalicylic acid did not change under the effect of the mentioned agents.

Acetylation↗

PubMed1976

Chemoprophylaxis in inactive tuberculosis: long-term evaluation of a Canadian trial.

A trial of chemoprophylaxis to prevent reactivation of tuberculosis in persons with inactive disease who had never had adequate chemotherapy was conducted in Canada in the mid-1960s. Preventive drug treatment consisted of either isoniazid (INH) alone or INH plus para-aminosalicylic acid (PAS), for a maximum of 18 months. Long-term evaluation in 1974 of 1571 treated patients and 834 control patients demonstrated clearly the substantial and sustained value of adequate chemoprophylaxis in reducing the risk of reactivation. Among those who took INH alone for 6 months or more the annual reactivation rate was 1.2 per 1000 persons, while among those who took INH plus PAS the rate was 0.38/1000. These rates were, respectively, 70 and 90% less than the average rate in the controls, 3.9/1000. Among those who underwent chemoprophylaxis for less than 6 months the annual reactivation rate was 3.7/1000, similar to that in the controls. Cost-benefit analysis showed chemoprophylaxis to be economically sound. Despite the recent increasing application of this preventive measure, there are still many persons living in Canada who could benefit substantially from a course of chemoprophylaxis.

Aminosalicylic Acids↗