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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↗
PubMedDate not supplied

[Resistance of Mycobacterium tuberculosis in Mexican patients. I. Clinical features and risk factors].

OBJECTIVE: To determine the clinical manifestations associated with resistant M. tuberculosis infection and the antimicrobial resistance in isolates from Mexican patients. STUDY DESIGN: Epidemiological surveillance. PATIENTS: Tuberculosis confirmed cases. METHODS: Primary resistance: no history of treatment prior to diagnosis. The following critical concentrations (micrograms/mL) were used for susceptibility: isoniazid 0.2 and 1; rifampin 1 and 5; ethambutol 5 and 10; streptomycin 2 and 10; ethionamide 5; kanamycin 6; and para-aminosalicylic acid (PAS) 2 and 10. RESULTS: Eighty-four patients with a mean age of 44.7 years were included; 54 men (64%) and 30 women (36%); most patients were from the Mexico City metropolitan area. In 34 patients there was clinical information available, 26 presented fever and weight loss and 8 respiratory symptoms. Fifty-nine patients (70%) were infected by pan-susceptible M. tuberculosis, and 25 (30%) by a resistant isolate; 17 (68%) of them were resistant to at least two drugs, 16 (64%) to isoniazid and rifampin. The proportion of resistance was: isoniazid 24%, rifampin 19%, streptomycin 12%, ethambutol 10%, PAS 9%, etionamide 7%, and kanamycin 6%. Of 47 patients without previous treatment, eight had a resistant microorganism (17%): 9% resistant to isoniazid, 6% to rifampin, 2% to streptomycin, 6% to PAS and 6% multiresistant. Of 37 patients with history of previous treatment for tuberculosis, 17 (46%) had a resistant isolate; 44% were resistant to isoniazid, 35% to rifampin, 24% to streptomycin, 19% to ethambutol, 12% to PAS and 35% multiresistant. Of the 84 patients, four were physicians infected by a resistant isolate, and seven HIV-infected patients, one with a multiresistant isolate, and another with isoniazid resistance. CONCLUSIONS: Antimicrobial resistance among M. tuberculosis is alarmingly high in Mexico City; these results emphasize the importance of case detection and early isolation of patients.

Adolescent↗
PubMed1997

Multidrug-resistant tuberculosis in Denmark 1993-1995.

SETTING: All bacteriologically confirmed new cases of tuberculosis and treatment relapses in Denmark are examined for drug resistance. In the years 1993-1995, nine cases of multidrug-resistant tuberculosis (MDR-TB), all acquired outside Denmark, were identified among 1354 cases of tuberculosis. OBJECTIVE: To examine incidence, treatment and prognosis for patients with tuberculosis due to MDR Mycobacterium tuberculosis. DESIGN: Retrospective evaluation of routine data. RESULTS AND CONCLUSION: Multidrug resistance was present in less than one present of patients with tuberculosis. One patient died from tuberculosis without revision of treatment, and eight patients responded favourably to a regimen of pyrazinamide, streptomycin or amikacin, ofloxacin and cycloserine. In two patients, this regimen was supplemented with para-aminosalicylic acid and thiacetazone respectively. All patients needed prolonged hospitalization and had observed treatment. It is possible to cure such patients, but it is a lengthy and expensive process. It is expected that similar cases will be imported into the country and that they will occur within Denmark in the future.

AIDS-Related Opportunistic Infections↗
PubMed1984

Plasma and lipoprotein lipid responses to four hypolipid drugs.

The responses of 14 hyperlipidemic subjects to 4 hypolipidemic agents were compared by measuring cholesterol and triglyceride in whole plasma, very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL) monthly for 2 months before and 3 months during treatment with each of 4 drugs: clofibrate, 2 g/d; colestipol, 20 g/d; para-aminosalicylic acid-ascorbate (PAS-C), 6-8 g/d; and oxandrolone, 7.5 mg/d. Lipid responses proved to be stable by the first monthly evaluation both off and on each drug. Mean adherence was high and similar for all agents (81-92% of the prescribed dose). Clofibrate was associated with significant decreases in mean plasma cholesterol (-16%, p less than .01), plasma triglyceride (-51%, p less than .005), VLDL-cholesterol (-61%, p less than .005) and VLDL-triglyceride (-61%, P less than .005), while HDL cholesterol increased (+20%, p less than .01), and the LDL-cholesterol/HDL ratio declined (-24%, p less than .05). Colestipol was associated with decreases in mean plasma cholesterol (-15%, p less than .01) and LDL-cholesterol (-22%, p less than .05), while VLDL-triglyceride increased (+41%, p less than .05), and the LDL-cholesterol/HDL-cholesterol radio declined (-25%, p less than .05). PAS-C was associated with decreases in VLDL-cholesterol (-30%, p less than .05), and VLDL-triglyceride (-29%, p less than .05), while the LDL-cholesterol/HDL-cholesterol ratio remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1976

Effect of sodium para-aminosalicylate on oxygen affinity in normal, sickle and fetal human blood.

Sodium para-aminosalicylate (sodium salt of 2-hydroxy-4-aminobenzoic acid, Na-PAS) lowers the oxygen affinity of normal adult human placental, heterozygous and homozygous sickle cell anemic whole blood at 37 degrees C. The reduction of oxygen affinity is related to the type of hemoglobin in the blood. The mean P50 +/- S.E. at pH 7.40 for normal, placental, heterozygoud and homozygous sickle cell anemic blood in 26.2 +/- 0.1, 20.8 +/- 0.3, 26.8 +/- 0.3 and 31.0 +/- 0.5 mm Hg; in the presence of 5.7 mmol of Na-PAS per liter of blood the P50 values are increased to 28.0 +/- 0.3, 22.9 +/- 0.8, 30.5 +/- 0.6 and 33.9 +/- 0.3 mm Hg, respectively. The Bohr effect in normal and placental blood at this Na-PAS concentration is essentially unchanged: in heterozygous and homozygous sickle cell anemic blood, the Bohr factor (deta log P50/deta pH) is reduced from -0.48 +/- 0.02 to -0.41 +/- 0.01 and from -0.53 +/- 0.03 to -0.48 +/- 0.01. The Hill constants (n) of normal and placental blood are not affected by Na-PAS. In homozygous and heterozygous sickle blood, high concentrations of Na-PAS (22.9 mmol/l) decrease the Hill constant from 2.55 to 2.35 and from 2.56 to 2.28, respectively. Na-PAS is more firmly bound to red blood cells than to plasma. The binding of Na-PAS is probably primarily ionic in nature since the drug can be almost completely removed from blood components by dialysis. The changes in oxygen affinity caused by Na-PAS are consistent with conformational changes (R leads to T) which enhance the presence of deoxyhemoglobin.

Adult↗
PubMed1982

Short-term inhibition of fatty acid biosynthesis in isolated hepatocytes by mono-aromatic compounds.

An overview is presented of a selected number of mono-aromatic derivatives and their short-term effects on hepatic fatty acid biosynthesis. The compounds discussed in this paper are ortho-hydroxybenzoate (salicylate), meta-hydroxybenzoate, para-hydroxybenzoate, benzoate, para-t-butylbenzoate, para-aminosalicylate, clofibrate, halofenate, alpha-cyano-4-hydroxycinnamate and benfluorex. All of these drugs inhibit fatty acid biosynthesis by isolated rat liver cells, albeit with different effectiveness. In contrast, the compounds have differential effects on fatty acid esterification and oxidation by isolated hepatocytes. An attempt is made to describe in molecular terms the underlying mechanisms of the acute inhibitory effects of the mono-aromatic derivatives on hepatic lipogenesis. It is proposed that all of the drugs exert an inhibitory action at the level of acetyl-CoA carboxylase, the enzyme generally considered to catalyse the rate-limiting step in hepatic fatty acid synthesis. This inhibitory effect may be either direct, i.e. by an alteration of the enzyme's structure as a result of interaction between drug and enzyme, or indirect, i.e. through a drug-induced change in the cellular levels of allosteric effectors of acetyl-CoA carboxylase.

Acetyl-CoA Carboxylase↗
PubMedDate not supplied

Fractionated precipitation of acid macropolyanions by dialysis, a simple method for the estimation of DNA in complex biological samples.

After efficient extraction by para-aminosalicylate, chopping, grinding and eventual sonication, the macropolyanions are transformed into their cetyltrimethylammonium salts. These have differing solubilities, strongly depending on ionic strength. The cationic detergent-macropolyanionic salts are solubilized by high salt concentration. Salt is then dialysed out, rendering the polyanions highly insoluble in a sequential fashion. The insolubilized components are determined quantitatively by monitoring turbidity, which in case of DNA is strictly proportionate to its concentration. This relation is not affected by other components. This makes DNA determination possible even in crude aqueous extracts. The method has been applied to different objects, such as bacteria, plants, animals, soil and activated sludge. The method may prove to be especially useful in research of environmental poisons e.g. in rivers, lakes or clarifiers.

Animals↗
PubMed1977

P-aminosalicylate metabolism in cancer patients sensitive and resistant to chemotherapy.

A reduced response of a tumour to chemotherapy may be due to the host's drug metabolism. To test this hypothesis, we measured the metabolism of a model drug, para-aminosalicylate (PAS). Volunteers and cancer patients ingested a single oral dose (2 g) of PAS and we measured the plasma disappearance curve of the drug and its metabolite. In 7 patients suffering from lymphosarcoma, acute or chronic leukaemia and resistant to cancer chemotherapy, we observed low plasma PAS concentrations, an increase in PAS acetylation and an increased number (and a higher frequency) of abnormal liver-function tests. In 14 patients with malignant blood disease, yet responding well to chemotherapy, the metabolism of PAS is similar to that of healthy controls of the same age and sex. The plasma half-life of PAS is similar in sensitive and resistant patients, but slightly longer than in volunteers. Finally, in urine collected 120 min after drug administration, we observed the same results as in plasma. In conclusion, cancer patients resistant to chemotherapy do not metabolize the model drug PAS as volunteers or sensitive patients do, and this might be relevant to the terminal stage of the disease.

Acute Disease↗
PubMed1969

Intermittent chemotherapy for tuberculosis in an urban community.

A regimen designed for effective foolproof antituberculosis treatment, acceptable on a routine basis, was applied to all patients newly diagnosed at the Chest Clinic, Hammersmith Hospital, in 1963, 1964, and 1965. During the first three months of treatment patients received daily (six days a week) streptomycin 0.75 g. plus isoniazid 300 mg. plus sodium para-aminosalicylate (P.A.S.) 12 g. The P.A.S. was usually stopped when bacterial sensitivity reports made this possible. For a further 15 months streptomycin 1 g. plus isoniazid 600 mg. was given on three alternate days each week to complete a total of 18 months' treatment.Of the total of 140 patients (66% sputum-positive) 112 (80%) completed the planned 18 months with intermittent streptomycin plus isoniazid and a further eight completed treatment on alternative regimens (a total of 85%). The equivalent figures for one year are 88% and 94%. Excellent clinical and radiological results, together with sputum conversion, were achieved in 138 of the 140 patients (99%). Only two patients were lost from surveillance, because of failure to co-operate, before quiescence was obtained.It is concluded that the total efficiency of supervised intermittent treatment is greater than that of unsupervised daily regimens. Since 100% arrest of tuberculosis is possible with co-operative patients, less should not be accepted in developed countries.

Adolescent↗
PubMed1996

The effect of 5-aminosalicylate and para-aminosalicylate on the synthesis of prostaglandin E2 and leukotriene B4 in isolated colonic mucosal cells.

The effect of 5-aminosalicylate (5-ASA) and para-aminosalicylate (PAS) on the synthesis of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) was studied in 24 healthy volunteers. Both drugs are successfully used in the treatment of chronic inflammatory bowel disease, but the biochemical pathway of their anti-inflammatory action is still unknown. Biopsies were taken from the descending colon and were isolated biochemically. 5-ASA, PAS and a control were added to the suspension of isolated colonic mucosal cells and incubated over 0-45 min. Both 5-ASA and PAS did not alter the PGE2 production but, compared with PAS and the control, 5-ASA decreased the LTB4 synthesis in a dose-related fashion. As a result, the LTB4/PGE2 ratio was significantly diminished by 10(-4) mol/l 5-ASA. These findings are consistent with those of other authors, indicating that 5-ASA, at least in part, modulates the colonic eicosanoid synthesis. In contrast, PAS did not influence the mucosal production of PGE2 and LTB4 and therefore must exert some other biochemical action in order to explain its therapeutic effects in the treatment of Crohn's disease or ulcerative colitis.

Adult↗
PubMed1994

[Enhancement of rectal absorption of rifampicin by sodium para-aminosalicylate dihydrate in human subjects].

The suppositories of rifampicin (RFP) containing sodium para-aminosalicylate dihydrate (PAS-Na) were prepared in order to enhance the rectal absorption of RFP. By the addition of PAS-Na, the in vitro release of RFP from the suppositories was enhanced and the hardness of the suppositories decreased. The rectal absorption of RFP from the suppositories containing no PAS-Na (control suppositories) was significantly lower compared to oral administration of it (26%) in human subjects. When PAS-Na was added to the suppository (300 mg), both the area under the plasma concentration-time curve (AUC) and the maximum plasma concentration (Cmax) increased significantly compared to those of the control suppositories. The rectal absorption of PAS-Na itself from the suppositories seemed to be fast. PAS-Na might increase the absorption of RFP dissolved in the rectal fluid from the suppositories, but not affect the undissolved RFP.

Administration, Oral↗