ABSTRACT
SETTING: Hypothyroidism is an adverse effect of certain anti-tuberculosis drugs. DESIGN: This is a prospective study of the frequency and possible pathomechanisms associated with hypothyroidism due to second-line treatment of multidrug-resistant tuberculosis. Fifty human immunodeficiency virus negative patients and 20 controls were included. All participants underwent ultrasonography of the thyroid and measurement of thyroid stimulating hormone (TSH). TSH levels were checked every 3 months. If hypothyroidism was present, T3, T4 and thyroid peroxidase autoantibodies were measured, and imaging extended to scintigraphy and repeated ultrasonography. RESULTS: Before treatment, 7 patients (14%) and 1 control (5%) were hypothyreotic. During the first 6 months of treatment, TSH levels increased in 41 patients (82%), 39 (78%) had values above the normal range and 19 (38%) had overt hypothyroidism. As none of the patients had signs of autoimmune thyroiditis, interaction with anti-tuberculosis drugs was assumed to be the cause of hypothyroidism. Nine patients died during treatment, all of whom had developed hypothyroidism. In seven, the metabolic situation at their death was known, and they had become euthyreotic following levothyroxine substitution. CONCLUSION: TSH levels should be checked before initiating anti-tuberculosis treatment and after 3 and 6 months to start timely replacement of levothyroxine. Further studies are needed to elucidate the exact pathomechanism involved in hypothyroidism and whether hypothyroidism can be used as predictor of treatment failure.
Subject(s)
Antitubercular Agents/adverse effects , Hypothyroidism/chemically induced , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/drug therapy , Adolescent , Adult , Autoantibodies/blood , Autoantigens/immunology , Biomarkers/blood , Case-Control Studies , Female , Humans , Hypothyroidism/blood , Hypothyroidism/diagnostic imaging , Iodide Peroxidase/immunology , Iron-Binding Proteins/immunology , Male , Middle Aged , Prospective Studies , Risk Factors , Thyrotropin/blood , Thyroxine/blood , Treatment Outcome , Triiodothyronine/blood , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/microbiology , Ultrasonography , Young AdultABSTRACT
BACKGROUND: Genetic predisposition to psoriasis, an inflammatory skin disease affecting 0·2-4% of the world population, is well established. Thus far, 41 psoriasis susceptibility loci reach genome-wide significance (P ≤ 5 × 10(-8) ). Identification of genetic susceptibility loci in diverse populations will help understand the underlying biology of psoriasis susceptibility. OBJECTIVES: The primary objective of this study was to examine psoriasis susceptibility associations previously reported in Chinese and caucasian populations in a Pakistani cohort. METHODS: Blood samples and phenotype data were collected from psoriasis cases and controls in Islamabad, Pakistan. DNA was isolated and genotypes of selected susceptibility markers were determined. The data were analysed using χ(2) tests or logistic regression for psoriasis association. RESULTS: HLA-Cw6 showed the strongest association [odds ratio (OR) 2·43, P = 2·3 × 10(-12) ]. HLA-Cw1 showed marginally significant association (OR 1·66, P = 0·049), suggesting that the HLA-Cw1-B46 risk haplotype may be present in the Pakistani population. Three other loci (IL4/IL13, NOS2, TRAF3IP2) showed nominally significant association (P < 0·05). CONCLUSIONS: HLA-Cw6 is strongly associated with psoriasis susceptibility in the Pakistani population, as has been found in every other population studied. In addition, HLA-Cw1 showed marginal association, reflecting the relative geographical proximity and thus likely genetic relatedness to other populations in which the HLA-Cw1-B46 haplotype is known to be associated. A larger cohort and a denser marker set will be required for further analysis of psoriasis associations in the South Asian population.
Subject(s)
Genetic Loci/genetics , Psoriasis/genetics , Adaptor Proteins, Signal Transducing , Adult , Age of Onset , Female , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Genotype , HLA-C Antigens/genetics , Haplotypes , Humans , Interleukin-13/genetics , Male , Nitric Oxide Synthase Type II/genetics , Pakistan/ethnology , Polymorphism, Single Nucleotide , Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/geneticsABSTRACT
PURPOSE: The objective was to establish the parameters for reversible electroporation of murine embryos. METHODS: In Trial 1, murine presumptive zygotes received an electrical pulse of 5, 10, or 20-micros duration, and one of five voltages (100, 200, 250, 300, or 400 V). In Trial 2, embryo orientation within the electroporation chamber was evaluated with 250 or 400 V at a pulse period of 10 micros. RESULTS: Presumptive zygotes that received 400 V at each pulse length and zygotes exposed to 20 micros at each voltage had the lowest embryonic development (P < 0.05). Presumptive zygotes that received 250 V had higher development compared to 400 V, irrespective of orientation (P < 0.01), but development was lower than the controls (P < 0.01). CONCLUSIONS: Electrical stimulation of presumptive zygotes can have a detrimental impact on early embryo development, but low amounts of stimulation may allow for potential gene transfer in transgenic experimentation.
