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At least 19 recordsLinked to original sources

Inhibition of multiplication of Mycobacterium leprae by several antithyroid drugs.

Multiplication of Mycobacterium leprae in the mouse footpad was inhibited when mice were fed, mixed in their diet, 0.05 per cent methimazole, 0.066 per cent USP thyroid powder, methimazole plus thyroid powder, 0.15 per cent 5-n-heptyl-2-thioxo-4-thiazolidinone, 0.1 per cent propylthiouracil, and 0.1 per cent thambutosine for 154 days, beginning on the day of inoculation. All of the treatment regimens, except for the 2 containing thyroid powder, decreased the plasma concentrations of thyroxine and protein-bound iodine. It is suggested that the 2 antithyroid drugs, methiomazole and propylthiouracil, and the 2 antimicrobial agents, heptylthioxothiazolidinone and thiambutosine, all of which possess structural features in common, may exert the antithyroid and antimicrobial effects through a common mechanisms.

Aniline Compounds

Chromatographic-fluorometric analysis of antileprotic sulfones.

Modifications to the power supply system of a spectrophotofluorometer are described. These modifications stabilize the output of the xenon are lamp and permit the determination of nanogram quantities of antileprotic sulfones. The sulfones are removed from plasma by a single extraction with ethyl acetate, then separated by high-pressure liquid chromatography on silica, and detected in the effluent by their fluorescence. The method is specific, rapid, and reproducible.

Autoanalysis

A cost-effective conventional endpoint PCR assay for HLA-B*13:01 genotyping to guide personalized dapsone therapy in leprosy in low-resource settings.

BACKGROUND: Dapsone is a drug used to treat leprosy. Dapsone causes a highly morbid and potentially fatal severe drug hypersensitivity reaction (DHS) in 1-3% of leprosy cases. The allele HLA-B*13:01 is a known genetic risk factor for DHS. However, resource-intensive genotyping methods preclude its testing in resource-limited settings. This study aimed to develop an endpoint PCR assay to detect the presence of HLA-B*13:01. RESEARCH DESIGN AND METHODS: DNA was extracted from blood samples of leprosy patients at Anandaban Hospital, Nepal (2022-24). A duplex endpoint PCR was optimized and validated against a previously validated commercial qPCR method and NGS (next‑generation sequencing). RESULTS: In 113 samples, duplex PCR showed 100% (95% CI: 79.4-100%) sensitivity and 100% specificity (95% CI: 96.2-100%) compared to the validated qPCR method. The same accuracy was confirmed in 58 NGS-typed samples (concordance 98.3%, 95% CI: 90.7-99.9%). The assay reliably differentiated HLA-B*13:01 from closely related allele. Analytical sensitivity reached a lower detection limit of 100 genome equivalents (0.67 ng DNA/reaction). CONCLUSION: The developed duplex endpoint PCR offers a simple and affordable method for detecting HLA-B*13:01, suitable in low-resource settings. Its use may significantly reduce the risk of DHS by guiding safer drug choices prior to MDT initiation.

Humans

Combined therapy in leprosy. Background and findings.

This report is based on data obtained from 64 lepromatous cases. Despite many years of DDS monotherapy, the homogenates from biopsies of these patients revealed 10(4) or more bacteria. From the beginning of combination therapy with synergistic-acting substances (rifampicin + isoprodian (INH + PTH + DDS) the logarithms of the number of bacteria in the homogenates decreased, both during treatment period and during treatment-free observation period (Figs. 3--8). During the whole time biopsies were taken almost monthly. A considerable regression of the bacterial mass or even "negativity" could be observed within a relatively short time. Once started, the process of reduction of bacteria continued also after termination of therapy. To be able to evaluate a medication, therapy-free observation periods (for a minimum of 5 years) are indispensable.

Dapsone

Evaluation of treatment of lepromatous leprosy patients in the Netherlands.

The results of treatment of the group of leprosy patients at the lepromatous side of the leprosy spectrum registered at the Department of Dermatology of the University of Amsterdam in the years 1950-1976 were studied. The average duration of treatment to obtain bacteriologically negative skin biopsies in patients who were untreated at the time of registration, was 5 years. A substantial number of patients suffered a relapse; the main reasons for these relapses were discontinuation of treatment and DDS treatment in low dosage.

Clinical Trials as Topic

Activity of some antileprosy compounds against Mycobacterium intracellulare in vitro.

A series of 12 compounds, consisting of 3 known antileprosy drugs (dapsone, B663, and Ciba 1906) and 9 structural derivatives of dapsone, were tested for their antimycobacterial activity against 50 strains of Mycobacterium intracellulare. Detailed investigations of B663, the only compound showing considerable in vitro activity, were carried out. All of the strains of M. intracellulare were inhibited by a B663 concentration of 1.6 mug per ml, and 88% were inhibited by a drug concentration of 0.8 microng per ml. The rate of emergence of in vitro resistance was similar to that of M. tuberculosis against streptomycin and isoniazid. Preliminary experiments indicated that the action of the drug on M. intracellulare may be bacteriocidal in nature.

Clofazimine

Leprosy relapse after multidrug therapy: Systematic review and meta-analysis.

OBJECTIVE: To synthesize the scientific evidence regarding the prevalence of leprosy relapse following multidrug therapy. METHOD: A systematic review was conducted following the JBI methodology for prevalence studies and reported according to the guidelines, with the registration number CRD42020177141. The inclusion criteria were based on the mnemonics (Population, Condition, Context). Population: Individuals of any age or sex diagnosed with leprosy relapse and previously treated with paucibacillary or multibacillary multidrug therapy. Conditions: Leprosy relapse after multidrug therapy, measured as the proportion of cases. Context: Studies conducted within the healthcare service settings. The databases searched included Medline, Latin American and Caribbean Health Sciences Literature (LILACS), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, WoS, and Caribbean Public Health Agency (CARPHA). The references were managed using Mendeley. A random-effects meta-analysis model was employed, and heterogeneity was assessed using Higgins' I² statistics. RESULTS: Of 26 studies (a combined sample of 71,385 participants), 19 were included in the meta-analysis. A higher prevalence of relapse was observed in working-age males, multibacillary cases with a high bacillary load, and those with established physical disabilities. The estimated prevalence of relapse across studies ranged from 0% to 10%, with a pooled estimate of 4% in India (95% CI: 0.03-0.05). The overall point estimate for relapse using regular multidrug therapy was 0.04 (95% CI: 0.02-0.05). CONCLUSION: The prevalence of relapse varied according to the geographic location and type of multidrug therapy, with substantial heterogeneity across studies. These findings suggest that factors such as individual patient characteristics, treatment adherence, and capacity for healthcare services may have influenced the outcomes observed in this review.

Humans

Some aspects of tuberculoid leprosy and chemotherapeutic trials.

The author describes the progress made in our knowledge of tuberculoid leprosy since the original case of Jadassohn in 1898. The numerical importance of T patients in different parts of the world is reviewed and their role in the transmission of the disease discussed. An analysis is made of the subgroups into which T leprosy is divided according to the clinical symptoms, bacteriology, histopathology and immunology in the Madrid classification as well as in the Souza-Lima-Souza Campos and Ridley-Jopling studies. The author concludes that a majority of T patients are immunologically stable and belong to two well defined groups, the first called T annular in the Souza-Lima-Souza Campos study and TT in the Ridley-Jopling classification and the second called T reactional by S.L.-S.C. and BT by R.J. Taking into account the high proportion of T cases in most epidemiological situations, their generally accepted good prognosis under treatment and the present availability of several drugs of proved efficacy, the author suggests to carry out in T leprosy under controlled conditions a trial of a number of therapeutic regimens of not more than 12 months duration. Follow-up periods will make possible medium and long-term evaluation of results after 3 and 5 years respectively of the initiation of the chemotherapeutic regimens. The practical implications of effective and well tolerated short-term therapy in T leprosy is stressed. Its widespread use in field programmes will represent among other advantages a considerable economy in personnel and drugs costs. The use of a single protocol is recommended. The one worked out by THELEP for therapeutic trials in lepromatous leprosy could be adopted with a few changes made necessary because of the morphological and bacteriological differences between L and T leprosy. It is suggested that, if the results of the trial are successful, similar regimens could be tried in indeterminate leprosy.

Clinical Trials as Topic

Mycobacterium leprae: atypical and unclassified.

Once M. leprae is grown on artificial media in the test tube, it might prove to have a great variety of characteristics quite different to those expected from our knowledge of M. leprae isolated from the susceptible host. The cultures might be slow or fast growing, pigmented or colorless, pathogenic for the armadillo, or not; they might produce limited disease in the foot pad of mice, or the contrary. The in vitro M. leprae culture might or might not provoke a lepromine reaction; the culture might grow at a lower or higher temperature. It is well documented that mycobacteria show great differences in elasticity and adaptability to cultivation conditions. It is absolutely certain that once grown in a test tube, M. leprae will behave as an atypical species. However, each individual culture of M. leprae obtained in vitro will have the same drug sensitivity pattern as in the lepromatous leprosy patient from whom it was cultivated.

Adaptation, Physiological