Leprosy and BCG in southern Vietnam.
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Adult↗
Biomedical subjects
J Grosset
Publications and source records attributed to J Grosset.
[Bacteriologic basis for the treatment of tuberculosis].
To be fully effective, short-course chemotherapy for tuberculosis should take into account the slow growth rate, high oxygen requirement and high drug-resistant mutant emergence rate of Mycobacterium tuberculosis, as well as the type of the lesions observed and the specific activity of each antituberculous drug. Due to their unique sterilizing activities against bacilli that are not actively metabolizing, rifampicin and pyrazinamide are the key drugs for short-course chemotherapy. To prevent the selection of drug-resistant mutants and the occurrence of therapeutic failures, a combination of isoniazid, rifampicin, pyrazinamide and ethambutol should be given during the first two months of treatment. To kill persisting M. tuberculosis, and thus avoid posttreatment relapses, the isoniazid-rifampicin combination should be prescribed for à further four months.
Antibiotics, Antitubercular↗
mRNAs newly synthesized by tobacco mesophyll protoplasts are wound-inducible.
We have used 2-dimensional (2D) non-equilibrium pH gradient gel electrophoresis (NEPHGE) of in vitro synthesized proteins and northern hybridization with labelled cDNAs coding for three pathogenesis related (P.R.) proteins, to analyze the shift in mRNA content induced by the isolation and culture of tobacco mesophyll protoplasts. The in vitro protein pattern of mRNAs from freshly isolated protoplasts is characterized by the absence of most leaf spots and the appearance of 19 new spots. After 6 hours of culture, the mRNAs coding for the P.R. proteins become detectable and after 12 hours the protoplasts contain an mRNA population almost typical of callus cells. The different steps involved in the isolation and culture of protoplasts were analysed. Cutting off the leaf and sterilization do not change the mRNA set. In contrast, the mechanical injury applied to the leaf in order to facilitate the penetration of the enzymatic mixture induces a modification of the mRNA content identical to that resulting from protoplast isolation. Wounding is the essential event inducing dedifferentiation. Varying the culture medium and conditions leads to only limited modifications of the mRNA pattern. These results are discussed on the basis of present knowledge of the reaction of the plant to wounding and we suggest that wound healing callus and in vitro callus correspond to the same differentiation state.
Cell Differentiation↗
Tobacco Mesophyll Protoplasts Synthesize 1,3-beta-Glucanase, Chitinases, and "Osmotins" during in Vitro Culture.
Tobacco (Nicotiana tabacum) mesophyll protoplasts synthesize six basic proteins (a, a', a(1), b, b', and c) which are undetectable in the leaf and whose synthesis is reduced by auxin (Y Meyer, L Aspart, Y Chartier [1984] Plant Physiol 75: 1027-1033). Polypeptides a, a', and a(1) were shown to have similar mobilities on two-dimensional electrophoresis as one 1,3-beta-glucanase and two chitinases from tobacco mosaic virus-infected leaves. In immunoblotting experiments, polypeptide a was recognized by specific antibodies raised against the 1,3-beta-glucanase and a' and a(1) reacted with anti-chitinase antibodies. Similarly, b and b' comigrated with osmotin and its neutral counterpart, two proteins characteristic of salt-adapted tobacco cells, and reacted with anti-osmotin antibodies. In addition it has been shown that 1,3-beta-glucanase and chitinase activities increased at the same time as a, a', and a(1) accumulated in cultivated protoplasts. Finally, polypeptide c was also detected in tobacco mosaic virus-infected leaves but could not be identified as any of the pathogenesis-related proteins characterized so far in tobacco. Thus, cultivated tobacco protoplasts synthesize and accumulate typical stress proteins.
Journal Article↗
Activities of clarithromycin, sulfisoxazole, and rifabutin against Mycobacterium avium complex multiplication within human macrophages.
The activities of clarithromycin, sulfisoxazole, and rifabutin against three virulent strains of Mycobacterium avium complex isolated from patients with acquired immunodeficiency syndrome were evaluated in a model of intracellular infection. Human monocyte-derived macrophages were infected at day 6 of culture with M. avium complex. Intracellular bacteria were counted 60 min after inoculation. Extra- and intracellular bacteria were counted at days 4 and 7 after inoculation. The concentrations used were 4 micrograms of clarithromycin per ml (MICs for the three strains, 4, 4, and 4 micrograms/ml), 50 micrograms of sulfisoxazole per ml (MICs, 50, 25, and 25 micrograms/ml), and 0.5 micrograms of rifabutin per ml (MICs, 2, 0.5, and 0.5 micrograms/ml). Compared with controls, clarithromycin and rifabutin slowed the intracellular replication of the three strains (at day 7 after inoculation, P was less than 0.01 for the first strain and less than 0.001 for the two others). Sulfisoxazole was ineffective against the three strains. Clarithromycin was as effective as rifabutin. Clarithromycin plus rifabutin was as effective as each single agent. Clarithromycin plus sulfisoxazole was as effective as clarithromycin alone.
Acquired Immunodeficiency Syndrome↗
[Norfloxacin: a broad-spectrum quinolone for superficial eye infections].
Norfloxacin is a synthetic antibiotic belonging to the fluoroquinolone class. At present, an oral formulation is available and indicated for the treatment of urinary tract infections. Because of the properties of norfloxacin, a 0.3% norfloxacin ophtalmic solution may be used by ophtalmologists. The molecular target of norfloxacin is DNA gyrase that regulates DNA replication. Norfloxacin is a broad spectrum antibiotic. A flurin atome in position 6 is responsible for the broad spectrum of activity as compared with the first generation quinolones. MICs of norfloxacin against Haemophilus influenzae, Neisseria gonorrhoeae, Staphylococcus aureus, Pseudomonas aeruginosa, and enterbacteriaceae are low or intermediate. Norfloxacin is a bactericidal drug of which MBCs are equivalent to or twice as high as MICs against the majority of organisms. The proportion of norfloxacin resistant strains is limited and, at present, no plasmid resistance has been observed. This explains the activity of norfloxacin against clinical isolates whose drug resistance is plasmid-mediated. Norfloxacin resistance is chromosomic, but the mutation rate is low. There is no cross-resistance between quinolones and other classes of drug, with the exception of drug resistance related to changes in the bacterial outer membrane proteins. A low decrease in norfloxacin susceptibility is observed in case of resistance to first generation quinolones. The above-mentioned properties make norfloxacin in ophtalmic solution a first line drug for treatment of superficial ocular infections and a second line drug for treatment of infections due to organisms resistant to other drugs.
Anti-Bacterial Agents↗
Results of blood cultures for detection of mycobacteria in AIDS patients.
Since the advent of the acquired immunodeficiency syndrome (AIDS) numerous M. avium intracellulare disseminated infections have been recognised. Blood culture is a convenient method for diagnosing these infections. At Pitié-Salpêtrière hospital AIDS patients with persistent unexplained fever each had three blood cultures. The blood samples, taken on 3 consecutive days without taking in account fever peaks, were collected in the Isolator-10 lysis-centrifugation system and inoculated onto Löwenstein-Jensen medium with and without 0.25% sodium pyruvate. From February 1986-September 1987, 564 samples taken from 165 patients were cultivated for the detection of mycobacteria. Sixty one (10.8%) taken from 19 patients (11.5%) were positive. M. avium intracellulare was the most frequently isolated mycobacterial species. In 10 patients, the positive blood culture was the only or the first positive culture for mycobacteria.
Acquired Immunodeficiency Syndrome↗
In-vitro activity of FCE 22101 and other beta-lactam antibiotics against Enterobacteriaceae resistant to third generation cephalosporins.
The in-vitro activity of FCE 22101 was compared with those of imipenem, aztreonam, cefotaxime, ceftriaxone and latamoxef against 225 Enterobacteriaceae (209 clinical isolates and 16 derivatives of Escherichia coli K12) chosen for their resistance (MIC greater than or equal to 8 mg/l) to third-generation cephalosporins. The beta-lactamases produced by the strains of Enterobacter cloacae, Klebsiella pneumoniae and Esch. coli were identified. The mean MICs of FCE 22101 were 2-8 mg/l for Ent. cloacae, Citrobacter freundii and Morganella morganii. For Ent. cloacae, the MICs were slightly higher for the cephalosporinase non overproducing (5.5-8 mg/l) than for the cephalosporinase overproducing (4.5 mg/l) strains. The mean MIC was 9 mg/l for Serratia spp. but for half of the strains the MICs were greater than or equal to 16 mg/l. The MICs of FCE 22101 were 0.5-1 mg/l for the resistant clinical isolates or isogenic derivatives of K. pneumoniae and Esch. coli producing extended broad-spectrum beta-lactamases (SHV-2, SHV-3 or CTX-1), whether measured in the presence of clavulanate or not, and against the sensitive controls. This showed that the compound was not affected by these new beta-lactamases. The MICs of imipenem, on the average four to five times lower than those of FCE 22101, were found to be very similar for resistant and sensitive strains. The MICs of aztreonam were high (32-128 mg/l) for C. freundii, K. oxytoca and cephalosporinase overproducing strains of Ent. cloacae. There was cross-resistance between the third-generation cephalosporins, but the MICs of latamoxef remained low (1 mg/l) against M. morganii, Klebsiella spp. and Esch. coli.
Carbapenems↗
A prospective study of protected bronchoalveolar lavage in the diagnosis of nosocomial pneumonia.
The value of a new technique of protected bronchoalveolar lavage not requiring bronchoscopy was prospectively evaluated for the diagnosis of nosocomial pneumonia in two groups of critically ill patients. The control group was comprised of 29 patients free of any pulmonary disease whose lungs were ventilated for a mean time of 14 +/- 9 days (mean +/- SD). The pneumonia group was comprised of 30 patients with histologically proven nosocomial pneumonia whose lungs were ventilated for a mean time of 11 +/- 8 days. All patients of the pneumonia group died, and postmortem lung biopsies were taken for bacteriologic and pathologic examination. Twice a week in the control group or within the day preceding death in the pneumonia group, distal bronchial samples were obtained by a technique of protected bronchoalveolar lavage performed at the bedside. Fifty-one distal bronchial samples were bacteriologically analyzed in the control group and 30 in the pneumonia group. The sensitivity of a positive protected bronchoalveolar lavage for diagnosing nosocomial pneumonia was 80%, whereas the specificity was 66%. In 73% of the patients of the pneumonia group, the microorganisms isolated in the protected bronchoalveolar lavage and in the lung culture were partially (16%) or completely in agreement (57%). Among the 43 microorganisms isolated in the lung cultures, 74% were recovered by the protected bronchoalveolar lavage technique. This study shows that the protected bronchoalveolar lavage is an accurate technique for the diagnosis of nosocomial pneumonia. Because the technique is simple, noninvasive, easily repeatable at the bedside, and enables gram staining, it represents an attractive alternative to the fiberoptic bronchoscopy technique using a plugged double-sheathed brush.
Biopsy↗
Relapses after stopping chemotherapy for experimental tuberculosis in genetically resistant and susceptible strains of mice.
Three strains of mice (Swiss albinos, C57BL/6,C3H/OuJ) were injected intravenously with 3.7 x 10(6) colony forming units (CFU) of M. tuberculosis, H37RV, sensitive and resistant to antibiotics (90% of bacilli sensitive, 9% resistant to Streptomycin and 0.9% resistant to Kanamycin). Two weeks later, chemotherapy was started 6 days a week for a 6-month period with isoniazid (INH) and rifampicin (RMP). Twenty mice of each strain were killed at the end of the chemotherapy and the others were kept without antibiotics for a second 6-month follow-up period before being killed. The early multiplication of bacilli during the first 2 weeks following infection and before chemotherapy, was similar in the three strains of mice. Chemotherapy had the same apparent efficacy in the three strains of mice, nearly all the mice being cured as assessed by a negative spleen culture on Loewenstein-Jensen medium at the end of chemotherapy. But after the 6-month follow-up period, the C3H strain presented a statistically significantly higher level of positive spleen culture ('relapse') than seen in the C57BL/6 strain, and an increased number of mycobacteria per relapsing mouse spleen. It has been estimated with the help of resistant and sensitive bacilli that the relapses were due in most of the cases to the regrowth of one or very few bacilli, giving a clone. It seems that the C3H strain of mice, known to carry the Bcg-r allele of the Bcg gene, might be less able to develop a specific acquired resistance capable of stopping the delayed development of a highly virulent strain of mycobacteria.
Animals↗
Preparation by two-dimensional electrophoresis of proteins for antibody production: antibodies against proteins whose synthesis is reduced by auxin in tobacco mesophyll protoplasts.
Using phenol extraction from tobacco callus, we have prepared extracts with a high protein content. These proteins were separated in cylindrical non-equilibrium pH gradient gels and visualized by dipping in sodium dodecyl sulfate (SDS)-containing solution. Three gel sections, each containing proteins previously detected as abundantly synthesized in tobacco mesophyll protoplasts and whose synthesis is reduced by auxin application, were excised from each gel and collected. These proteins were further separated on slab SDS gels and protein bands were excised after Coomassie Brilliant Blue R-250 staining and used to inject three rabbits. After one booster, highly specific antibodies were detected in their sera by ELISA and immunoblotting. Using these sera we have confirmed that the corresponding proteins are identical in callus and mesophyll protoplast and demonstrated that they are abundantly accumulated in tobacco roots but are undetectable in aerial organs and seeds.
Antibody Formation↗
New antibacterial drugs for the treatment of mycobacterial disease in man.
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Animals↗
[Study of the minimal inhibitory concentration of rifabutine (Ansamycin LM 427) for Mycobacterium tuberculosis, Mycobacterium xenopi and Mycobacterium avium-intracellulare].
Ansamycin LM 427 (or rifabutine) is a spiropiperidyl-rifamycin which has been proposed as a treatment for tuberculosis and mycobacterial infections resistant to rifampicin. The minimal inhibitory concentration (MCI) of rifabutine and of rifampicin for 10 strains of M. tuberculosis sensitive to rifampicin, 15 strains of M. tuberculosis resistant to rifampicin, 10 strains of M. xenopi and 15 of M. avium-intracellulare have been measured in a comparative fashion on gel DIFCO 7H11 medium and also on a Loewenstein-Jensen medium. The MCI of rifampicin and of rifabutine inhibiting 90% of the strains (MCI 90) of M. tuberculosis sensitive to rifampicin have been 0.06 mg/l on 7H11 media and 1 mg/l on Loewenstein-Jensen media respectively. For strains of M. tuberculosis resistant to rifampicin they were respectively 256 and 8 mg/l on 7H11 and of 1024 and 128 Loewenstein-Jensen, for the strains of M. xenopi they were 8 and 0.5 on 7H11 and 64 and 4 mg/l on Loewenstein-Jensen respectively, and finally for strains of M. avium-intracellulare they were 64 and 2 mg on 7H11 and 256 and 16 on Loewenstein-Jensen media. With rare exceptions for proven mycobacterial infections there was a link of the order of 20:1 between the values for CMI of rifampicin and rifabutine measured on Loewenstein-Jensen medium and on 7H11; the MCIs were ten times more elevated on the first than on the second and the liaison between the MCI of rifampicin and the MCI of rifabutine tended to show that these two antibiotics have the same mode of action.(ABSTRACT TRUNCATED AT 250 WORDS)
Antitubercular Agents↗
[Tuberculosis and pregnancy].
Tuberculosis is neither more frequent, nor more serious in pregnant than non-pregnant women. The risks for the child are threefold: a doubling in the mortality level on account of the illness in the mother if she is not treated; a risk of toxicity linked to the anti-tuberculous drugs and a risk of tuberculous infection at birth. Isoniazid (INH) and ethambutol have a weak toxicity. These two antibiotics can be prescribed during pregnancy (after confirming the absence of Vitamin B6 deficiency in the mother). Rifampicin is teratogenic in high doses in animals, but epidemiological studies do not reveal any notable risk in man. For prudence it is only prescribed in the first trimester of pregnancy, in confirmed cases of tuberculosis. The data on the teratogenicity of pyrazinamide is insufficient and it should not be used in pregnancy. Thus the treatment of tuberculosis in pregnancy will be rifampicin + isoniazid + ethambutol (the ethambutol being stopped after two months and the isoniazid and rifampicin after 9 months of treatment). At the moment of confinement, if maternal tuberculosis is confirmed bacteriologically at the time of microscopy, chemoprophylaxis will be started in the new born with isoniazid, in a dose of 5 mg/kg until the mother is bacteriologically negative on microscopic examination, the new born should then be vaccinated with BCG. If the treatment of the mother is correctly prescribed and followed breast-feeding is possible and no isolation of either mother or child is necessary. The amount of antibiotic that passes in the mothers milk is minimal and such specific nourishment should not be dispensed with if the treatment is necessary.
Antitubercular Agents↗
[Tuberculosis in the Department of Seine-Saint Denis. I. Cases under treatment in 1984].
A prospective study of notified cases of tuberculosis started on treatment during 1984 in the department of Seine-Saint-Denis situated in the northern suburb of Paris was undertaken with the help of the Ministry of Health, and the National Committee for the Prevention of Tuberculosis. Fifty-seven hospitals were involved as were 42 sanatoria, 19 clinics and private hospitals and 157 doctors enabled 578 cases of tuberculosis to be registered. For these 578 cases there were 884 notifications coming principally from the control services of the Social Security and public hospitals. Although several sources of notification had declared the same patient, no source had registered all the patients of whom they had knowledge. The notifications made on 12 different forms were often incomplete and sometimes erroneous. Of the 578 patients declared there were 34 different nationalities, of whom 190 were French, approximately 33%; 87 were Algerian, or 15%; 83 came from Mali, or 14%. The study compared the level of notification of tuberculosis in the French, Algerians and those from Mali and has shown that they are six times higher amongst Algerians than the French population and 39 times higher in those from Mali than in the French population. The proportion of patients already treated were 11% and those patients suffering from exclusively extra-respiratory tuberculosis was 16%. A bacteriological and/or histological confirmation was obtained in 70% of cases. The study of the socio-demographic characteristics of the patients has enabled a portrayal of the representation of unskilled workers and the unemployed in comparison to the general population of the department.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Transurethral surgery and persistent urinary infection: effect of a single preoperative dose of cefuroxime].
To evaluate the efficacy of cefuroxime, a second generation cephalosporin, in minimizing the risk of per and postoperative infection complications in patients with urinary tract infection undergoing transurethral surgery, 86 patients (ASA I, II) with persistent urinary tract infection despite antibiotic therapy were studied. A double blind protocol was followed. Patients were randomly assigned to receive 10 minutes before surgery either I.V. cefuroxime (1.5 g) (group C, n = 39) or placebo (group P, n = 47) the incidence of positive peroperative systematic blood cultures was lower in group C (9.7%) than in group P (25.2%) (p less than 0.001). The incidence of postoperative blood cultures taken when clinical septic signs were present, was significantly lower in group C (0%) than in group P (21.7%) (p less than 0.05). However neither the incidences of both postoperative urinary tract infection at the 48th postoperative hour and the clinical signs of bacteraemia including fever nor the average length of hospitalization were significantly different in the 2 groups. This lack of significant clinical benefit was not explained by the pharmacokinetic properties of this antibiotic. Thus, preoperative administration of a single dose of cefuroxime, reduces the incidence of per and postoperative bacteraemias in ASA I-II patients with persistent urinary tract infection.
Adolescent↗
[BCG vaccination in France].
First used in 1921 and obligatory since 1950, BCG vaccination is a part of the classical arsenal in the struggle against tuberculosis in France. The progressive reduction in the incidence of tuberculosis leads one to wonder what to expect now and in the future, so much so that the degree of protection conferred by BCG is continually discussed. In animal experiments, BCG vaccination is efficacious but there is no absolute protection conferred. In man, the results of 9 prospective studies performed with control groups have thrice shown an 80% protection, thrice a 30% protection and thrice no protection (in the case of studies from Southern India). On the grounds that there were large differences in the methodology of the 9 studies and that the best methodology was found in the 3 studies which showed good protective efficacy of BCG, it is justifiable to consider that the protection conferred against tuberculosis by a correct BCG vaccination is of the order of 80% and lasts 15 years (direct effect of BCG). Equally, a similar protection has been observed in numerous retrospective studies. But it is not accompanied by a reduction in the transmission of tuberculous bacilli in the population vaccinated with BCG. Since one does not observe any reduction in the incidence of tuberculosis in non-vaccinated subjects who live in contact with the vaccinated population (indirect effect of BCG).(ABSTRACT TRUNCATED AT 250 WORDS)
BCG Vaccine↗
[In vitro effect of piperacillin on aerobic bacteria. Variations according to the phenotypes of resistance to beta-lactam antibiotics].
In a first study the MICs of piperacillin (PIP), mezlocillin (MEZ), azlocillin (AZL), carbenicillin (CARB) and ticarcillin (TIC) against 563 strains of aerobic bacteria were compared. The MIC50 of PIP against E. coli and P. mirabilis was 0.5 to 1 mg/l, that is equal to those of MEZ and TIC but 2 or 3 times lower than those of AZL and CAR. The MIC50 of PIP and MEZ against Klebsiella, a species that is naturally resistant to TIC and CAR, was 4 mg/l. Enterobacter, Serratia and Citrobacter showed two populations of strains: the first was sensitive to the five penicillins tested (MIC50 of PIP: 1 to 2 mg/l); the second was resistant to all of them. PIP and AZL were more active (MIC50 8 mg/l) against Ps. aeruginosa than MEZ, TIC and CAR. All five penicillins had limited activity against Acinetobacter (MIC50 less than 16 mg/l). PIP, MEZ and AZL were more active than TIC and CAR against enterococci. In a second study, the activity of PIP was evaluated by standard sensitivity tests on 4993 strains of enterobacteria, Ps. aeruginosa and Acinetobacter classified according to their phenotype of resistance to beta-lactam antibiotics. PIP was regularly active against enterobacteria and Ps. aeruginosa strains devoid of acquired resistance. The activity of PIP was significantly reduced against enterobacteria strains with a phenotype suggesting induced penicillinase production. However, the inhibition zone diameters, although reduced, remained within what is now considered the sensitivity range (notably with E. coli and Proteus spp), which raises the problem of in vitro tests interpretation. PIP was active against E. coli strains with a "cephalosporinase" phenotype, but inactive against cefotaxime resistant strains of: Enterobacter, Citrobacter and Serratia. The activity of PIP on CAR-resistant Ps. aeruginosa strains was significantly reduced, but the inhibition zone diameter in one quarter of them was still within limits of sensitivity.
Azlocillin↗