Antituberculosis drugs and hepatotoxicity.
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Antitubercular Agents↗
Biomedical subjects
S K Sharma
Publications and source records attributed to S K Sharma.
A stepped approach for prediction of obstructive sleep apnea in overtly asymptomatic obese subjects: a hospital based study.
BACKGROUND AND PURPOSE: Prevalence of obstructive sleep apnea (OSA) is high in obese subjects, many of whom may not be overtly symptomatic. Polysomnography (PSG) is a costly and time-consuming investigation. Since it is not feasible to subject all obese individuals to PSG, it is useful to define predictors of OSA among these subjects. PATIENTS AND METHODS: One hundred and eighteen obese subjects [body mass index (BMI)> or =25 kg/m(2)] presenting to the hospital with non-sleep related complaints were included, of which 53 subjects with PSG evidence of OSA [apnea-hypopnea index (AHI)> or =15/h] were defined as cases and 65 subjects without any evidence of OSA (AHI<15/h) were defined as controls. Anthropometry, biochemical investigations, blood gas analysis, pulmonary function tests, and PSG were performed for all subjects. RESULTS: Waist hip ratio (WHR) (as percentage of a standard) [odds ratio (95% CI): 1.07 (1.00-1.14); P = 0.049] male gender [odds ratio (95% CI): 3.97 (0.99-15.81); P = 0.046] and neck circumference (NC) [odds ratio (95% CI): 1.23 (1.03-1.47); P = 0.023] were found to be independent predictors of OSA. Overnight oxygen desaturation data were evaluated in patients selected as having OSA on the basis of these clinical markers, and the best cut-off for level of desaturation (10%) was defined. The stepped approach had a specificity, sensitivity, positive and negative predictive value of 89.2, 88.5, 86.8 and 90.6%, respectively, for the diagnosis of OSA. CONCLUSIONS: Male gender, WHR and NC are independent predictors of OSA in overtly asymptomatic obese subjects. A stepped approach to diagnose OSA should be used, as it is accurate and cost-effective.
Adult↗
Pharmacokinetics and dosage regimen of ceftriaxone in buffalo calves.
The pharmacokinetics and dosage regimen of ceftriaxone were investigated in buffalo calves (n = 6) following a single intravenous administration of ceftriaxone (10 mg/kg). The elimination rate constant was 0.18 +/- 0.01 h(-1) and the elimination half-life was 3.79 +/- 0.09 h. The apparent volume of distribution (Vd(area)) was 1.40 +/- 0.01 L/kg and the total plasma clearance was 0.26 +/- 0.01 L/(kg h). Approximately 43% of total administered dose of ceftriaxone was excreted in urine within 8 h. To maintain a minimum therapeutic concentration of 1 microg/ml, a satisfactory intravenous dosage regimen of ceftriaxone in buffalo calves is 13 mg/kg repeated at 12 h intervals.
Animals↗
Diagnostic utility of pleural fluid IFN-gamma in tuberculosis pleural effusion.
Pleural fluid interferon-gamma (IFN-gamma) levels are increased in patients with tuberculosis (TB) pleural effusion. Recent studies from the west have found that estimation of pleural fluid IFN-gamma levels is an excellent diagnostic strategy for these patients. The diagnostic utility of pleural effusion IFN-gamma level estimation has not been evaluated in patients from developing countries, however. This work was carried out to study the diagnostic utility of IFN-gamma level estimation in patients with TB pleural effusion and to define the best cutoff of IFN-gamma for diagnosis TB pleural effusion. We studied 101 patients with pleural effusion. Of these, 64 were found to have a TB etiology, established by means of various conventional modalities. Measurement of pleural fluid IFN-gamma levels was done by ELISA technique. The median value of pleural fluid IFN-gamma levels in patients with TB (1480 pg/ml, range 3-14,000 pg/ml) was significantly higher (p < 0.001) compared with the non-TB group (3 pg/ml, range 0-900 pg/ml). The receiver operator characteristic (ROC) curve for IFN-gamma showed an area under the curve (AUC) value of 0.954, and the best cutoff was computed to be 138 pg/ml. Using this cutoff for IFN-gamma levels in pleural fluid for the diagnosis of TB, sensitivity, specificity, negative predictive value, and positive predictive value were found to be 90.2%, 97.3%, 85.7%, and 98.3%, respectively. Estimation of IFN-gamma levels in pleural fluid is a useful diagnostic modality for TB pleural effusion. A cutoff of 138 pg/ml provides the best sensitivity and specificity for diagnosis of TB.
Adult↗
A_16_C haplotype in the FcepsilonRIbeta gene confers a higher risk for atopic asthma in the Indian population.
We conducted a case-control study aimed at identifying polymorphisms and haplotypes in the FcepsilonRIbeta gene associated with asthma and its associated phenotypes such as serum IgE levels. A G/A polymorphism in intron 2, a (CA)n repeat polymorphism in intron 5, and a C/T polymorphism in 3'-UTR, encompassing a length of 8.74 Kb, were genotyped, and haplotypes were generated for unrelated patients and healthy volunteers in two independent cohorts. A significant association was observed at the level of alleles and genotypes studied with asthma independently in the two cohorts (p < 0.05). A change in CC_AA genotype combination to a non-CC_AA genotype was associated with reduced risk for asthma. Interestingly, a three-locus haplotype, A_16_C, was found to be significantly associated with asthma (p = 10(-5) in cohort A and p = 0.004 in cohort B). On the other hand, the haplotype G_18_T was found to be negatively associated with asthma (p = 0.007 in cohort A and p = 0.0004 in cohort B). This is the first study identifying a haplotype A_16_C that predisposes individuals to asthma in the Indian population.
Adolescent↗
Molecular genotyping of a large, multicentric collection of tubercle bacilli indicates geographical partitioning of strain variation and has implications for global epidemiology of Mycobacterium tuberculosis.
Tuberculosis continues to be a major killer disease, despite an all-out effort launched against it in the postgenomic era. We describe here the population structure of Mycobacterium tuberculosis strains, as revealed by a chromosome-wide scan of fluorescent amplified fragment length polymorphisms (FAFLPs), for more than 1,100 independent isolates from 11 different countries. The bacterial strains were genotyped based on a total of 136 +/- 1 different FAFLP markers at the genome sequence interface, with details on IS6110 profiles, drug resistance status, clinicopathological observations, and host status integrated into the analysis process. The strains were found to cluster with possible geographic affinities, including the parameters of host species type, IS6110 profile, and drug susceptibility status. Of the five most commonly amplified fragment sets (or amplitypes), type A predominated in strains of mixed origin, deposited in The Netherlands; type B was exclusively observed for Indian isolates; type C was found mainly in strains from Peru and Australia; and types D and E predominated in European strains from France and Italy. The amplitypes were independent of certain large sequence polymorphisms representing two important deletions, TbD1 and Rd9. It appears that M. tuberculosis has a high genomic diversity with a possible geographic evolution. This may have occurred due to specific genomic deletions and synonymous substitutions selected rigorously against host defenses and environmental stresses on an evolutionary timescale. The genotypic data reported here are additionally significant for genotype-phenotype correlations and for determining whether pathogen diversity is a reflection f the host population diversity.
DNA Transposable Elements↗
Primary transitional cell carcinoma of the prostate presenting as a rectal ulcer.
Primary transitional cell carcinoma of the prostate is a rare clinicopathological entity. It is an aggressive tumor with a poor prognosis. Presentation is usually late, with obstructive voiding complaints. Radical surgery offers locoregional control of the disease. We report a case with an atypical presentation of bleeding per rectum and associated obstructive voiding symptoms. Examination revealed a rectal ulcer overlying an enlarged prostate and fixed to it. Histopathology showed a picture of transitional cell carcinoma of the prostate infiltrating the rectum. Imaging studies revealed an enlarged prostate with altered echo pattern with locoregional spread, infiltrating the rectum. Bladder involvement and distant metastases were not evident. External beam radiotherapy achieved good local control. At 3 months of follow-up, the patient was free of urinary symptoms and his rectal ulcer had healed. The patient declined subsequent treatment.
Carcinoma, Transitional Cell↗
Malarial morbidity in tribal communities living in the forest and plain ecotypes of Orissa, India.
A detailed epidemiological study of malarial morbidity was carried out in 13 'tribal' villages in the forest or plain ecotypes of Sundargarh district, Orissa, India. Longitudinal and cross-sectional, parasitological surveys were conducted in all the villages, to determine the incidence of malaria and the prevalence of malarial infection. The annual numbers of malaria cases/1000 were much higher in the forest (347.9) than on the plain (61.0). In the forest clinical malaria occurred more frequently in children than in adults but on the plain all age-groups were equally affected. In cross-sectional surveys, 14.1% of the subjects from the forest but only 2.8% of those from the plain were found smear-positive for malarial infection. The prevalences of infection in the forest area were highest in the young children (aged 1-5 years) and gradually declined with increasing age. The highest incidence of Plasmodium falciparum malaria (0.90 episode/person-year) was also recorded in the subjects from the forest who were aged 1-5 years. In the forest and plain communities surveyed, 78.5%-81.5% and 36.0%-52.0% of the children aged 2-9 years had detectable splenomegaly, respectively, indicating that the forest was hyper-endemic and the plain meso-endemic for malaria. Malaria is clearly a major problem among the tribal communities of Sundargarh, causing great morbidity and, consequently, considerable economic losses.
Adolescent↗
Differentiation of members of the Anopheles fluviatilis species complex by an allele-specific polymerase chain reaction based on 28S ribosomal DNA sequences.
Anopheles fluviatilis, one of the major vectors of malaria in India, is a complex of at least three cryptic species provisionally designated as species S, T, and U. Identification of the cryptic species of An. fluviatilis complex is of paramount importance in disease control program due to contrasting differences in their vectorial efficiency, preference for feeding on humans, and resting behavior. Species S, T, and U are morphologically indistinguishable at any stage of their life cycle and can be identified only by the examination of species-specific fixed inversions in the polytene chromosomes. We report an allele-specific polymerase chain reaction assay for the differentiation of members of An. fluviatilis complex, which is based on differences in nucleotide sequences in D3 domain of 28S ribosomal DNA. The assay was evaluated against chromosomally examined individuals from different localities with different sympatric associations and was found to differentiate unambiguously all the members of the complex.
Alleles↗
The prevention of contrast-induced nephropathy in patients undergoing percutaneous coronary intervention.
Contrast-induced nephropathy (CIN) is a leading cause of morbidity and mortality in high-risk patients undergoing percutaneous coronary intervention (PCI) or other radiocontrast procedures. Approximately 25% of all patients selected for these procedures are at risk for its development. Patients who experience this complication have higher rates of mortality, longer hospital stays and poorer long-term outcomes. The occurrence of CIN is directly related to the number of co-existing clinical risk factors. Among the many risk factors, preexisting renal impairment, advanced age, the presence of diabetes mellitus and both the volume and type of the contrast agent administered are among the most important. While the precise pathophysiological mechanisms responsible for this condition are complex and incompletely understood, experimental studies suggest that the pathogenesis involves a combination of renal ischemia and direct tubular epithelial cell toxicity. At the present time, adequate periprocedural hydration and the selection of low-osmolar and, more recently, iso-osmolar contrasts agents are the only available tools to the operator for reducing the risk of this complication. Several other modalities, such as the use of NaHCO3 and hemofiltration, also appear promising in preventing the development of this complication. This article reviews the epidemiology, pathophysiology, and consequences of CIN. It also reviews the risk factors for the development of CIN, as well as the history of the various modalities studied in its prevention.
Algorithms↗
Extrapulmonary tuberculosis.
Extrapulmonary involvement can occur in isolation or along with a pulmonary focus as in the case of patients with disseminated tuberculosis (TB). The recent human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic has resulted in changing epidemiology and has once again brought extrapulmonary tuberculosis (EPTB) into focus. EPTB constitutes about 15 to 20 per cent of all cases of tuberculosis in immunocompetent patients and accounts for more than 50 per cent of the cases in HIV-positive individuals. Lymph nodes are the most common site of involvement followed by pleural effusion and virtually every site of the body can be affected. Since the clinical presentation of EPTB is atypical, tissue samples for the confirmation of diagnostic can sometimes be difficult to procure, and the conventional diagnostic methods have a poor yield, the diagnosis is often delayed. Availability of computerised tomographic scan, magnetic resonance imaging laparoscopy, endoscopy have tremendously helped in anatomical localisation of EPTB. The disease usually responds to standard antituberculosis drug treatment. Biopsy and/or surgery is required to procure tissue samples for diagnosis and for managing complications. Further research is required for evolving the most suitable treatment regimens, optimal duration of treatment and safety when used with highly active antiretroviral treatment (HAART).
Adrenal Cortex Hormones↗
Multidrug-resistant tuberculosis.
Multidrug-resistant tuberculosis (MDR-TB) caused by Mycobacterium tuberculosis resistant to both isoniazid and rifampicin with or without resistance to other drugs is among the most worrisome elements of the pandemic of antibiotic resistance. Globally, about three per cent of all newly diagnosed patients have MDR-TB. The proportion is higher in patients who have previously received antituberculosis treatment reflecting the failure of programmes designed to ensure complete cure of patients with tuberculosis. While host genetic factors may probably contribute, incomplete and inadequate treatment is the most important factor leading to the development of MDR-TB. The definitive diagnosis of MDR-TB is difficult in resource poor low income countries because of non-availability of reliable laboratory facilities. Efficiently run tuberculosis control programmes based on directly observed treatment, short-course (DOTS) policy is essential for preventing the emergence of MDR-TB. Management of MDR-TB is a challenge which should be undertaken by experienced clinicians at centres equipped with reliable laboratory service for mycobacterial culture and in vitro sensitivity testing as it requires prolonged use of expensive second-line drugs with a significant potential for toxicity. Judicious use of drugs, supervised individualised treatment, focussed clinical, radiological and bacteriological follow up, use of surgery at the appropriate juncture are key factors in the successful management of these patients. In certain areas, currently available programme approach may not be adequate and innovative approaches such as DOTS-plus may have to be employed to effectively control MDR-TB.
Causality↗
Drug susceptibility of Mycobacterium tuberculosis to primary antitubercular drugs by nitrate reductase assay.
BACKGROUND & OBJECTIVES: Rapid susceptibility testing of Mycobacterium tuberculosis strains is imperative for therapy selection but traditional drug susceptibility tests take weeks or are expensive. In this study we evaluated nitrate reductase assay which utilizes the detection of nitrate reduction as an indication of growth and therefore results can be obtained faster than by visual detection of colonies. METHODS: One hundred clinical isolates of M. tuberculosis were tested for four first line antitubercular drugs by nitrate reductase assay (NRA) and were compared with standard proportion method. The bacteria were inoculated on Lowenstein-Jensen (LJ) medium with primary antitubercular drugs and potassium nitrate was incorporated. After incubation for 7- 14 days, nitrate reduction indicating growth could be detected by colour change when reagents were added. RESULTS: Resistance of isolates as determined by both methods for isoniazid, rifampicin, streptomycin and ethambutol was 32, 35, 62 and 15 per cent respectively. Agreement between NRA and proportion method was 99 per cent for isoniazid and ethambutol. Complete agreement (100%) was found for rifampicin and streptomycin. Results were available in 7-14 days by NRA as compared to proportion method which takes 4-6 wk. INTERPRETATION & CONCLUSION: Nitrate reductase assay is a rapid and inexpensive method for susceptibility testing of M. tuberculosis for primary antitubercular drugs and could be an appropriate alternative to existing methods, particularly in resource-poor settings.
Antitubercular Agents↗
Uncommon manifestations of sarcoidosis.
OBJECTIVE: To study the uncommon manifestations in patients of sarcoidosis. METHODS: This is a prospective study of uncommon manifestations observed in 93 of the 210 biopsy proved patients (mean age 43.8 +/- 6.4 years; 58 males) of sarcoidosis seen by us over the last 22 years at the All India Institute of Medical Sciences, New Delhi. RESULTS: Clinical presentation of acute sarcoidosis in the form of Löfgren's syndrome (n = 5) was uncommonly observed. Rare pulmonary manifestations included seasonal dyspnoea with audible wheezing mimicking bronchial asthma (n = 30); narrowing of main bronchi, fixed upper airways obstruction (n = 1); pleural involvement (n = 7); bullous lung disease (n = 2); chronic respiratory failure (n = 2); and vocal cord involvement (n = 4). Other notable features were glaucoma (n = 4); digital clubbing (n = 3); sarcoid nephritis (n = 1); and sicca syndrome (n = 1). Uncommon neurological manifestations included bilateral sequential facial nerve palsy (n = 2); optic atrophy (n = 2); optic neuritis, proximal myopathy, multiple brainstem lesions, pituitary stalk lesion (one patient each). Cardiac involvement occurred in 15 patients. This included complete heart block (n = 2); congestive heart failure (n = 4); supraventricular ectopics (n = 6); ventricular ectopics (n = 2); and recurrent ventricular tachycardia requiring radiofrequency ablation (n = 1). Contrast-enhanced computerised tomographic scan (CECT scan) of the abdomen revealed intrabdominal lymphadenopathy (n = 5); infiltrates in the liver and spleen (n = 3). Portal hypertension was observed in four patients with grade IV (n = 2) and grade II oesophageal varices (n = 2). One of the patients with grade IV oesophageal varices had recurrent haematemesis and successfully underwent endoscopic sclerotherapy while another patient with grade IV varices succumbed to massive haematemesis. CECT scan was found to be useful in localising the lesions in patients with extrapulmonary sarcoidosis. CONCLUSION: Awareness regarding uncommon manifestations of sarcoidosis will facilitate early confirmation of diagnosis.
Adult↗
Dengue: current trends and challenges--an Indian perspective.
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Dengue↗
Significance and characterisation of pseudomonads from urinary tract specimens.
Pseudomonads are commonly encountered in clinical samples. Usually ignored as contaminants, these organisms are known to cause nosocomial opportunistic infections like urinary tract infections (UTI). One hundred and two pseudomonads obtained in pure culture and significant numbers from 8400 consecutive urinary tract (UT) specimens were biochemically characterised upto species level by a battery of biochemical tests. Modified Stoke's disk diffusion method was followed for testing antibiotic susceptibility. Beta-lactamase production was checked by nitrocefin disk method. Minimum Inhibitory Concentration for some of these strains against imipenem was done by agar dilution method of NCCLS. Etiological significance of isolating these organisms from UT specimens was also assessed. P. aeruginosa was the commonest (76) followed by B. pickettii (10), P. putida (6), P.fluorescence (2), P. stutzeri (20) P. vesicularis (2), S. putrefaciens (2) and Stenotrophomonas maltophilia (2). Seventy six per cent of P. aeruginosa produced beta-lactamases as compared to 45% of other pseudomonads. The frequency of antibiotic resistance was gentamicin and ciprofloxacin (68.6%) followed by netilmicin (60.7%), ceftazidime (58.8%), amikacin (43.1%) and piperacillin (39.2%). In 42 patients (51.2%) the etiological significance of isolating a pseudomonad could be confirmed. Risk factors for development of UTI were present in 62(75%). Obstructive uropathy (20) followed by post operative period and surgery on urinary tract were the commonest risk factors involved. A high level of resistance was observed for imipenem (P. aeruginosa 43.7% and other pseudomonads 25%).
Adolescent↗
Concentration of a potent calcium oxalate monohydrate crystal growth inhibitor in the urine of normal persons and kidney stone patients by ELISA-based assay system employing monoclonal antibodies.
Standardized calcium oxalate monohydrate (COM) crystal growth assay system was employed to study the ability of various test samples to influence growth rates of COM crystals. The inhibitory activity (IA) of various samples was expressed in terms of inhibitory units. Urine samples obtained from normal persons and kidney stone patients were found to have IA of 3.18 +/- 0.62 and 1.02 +/- 0.08, respectively. A potent inhibitor having molecular weight between 14.2 and 16.2 kDa was found to be primarily responsible for the differences observed in the urinary IAs between normal persons and kidney stone patients. The potent inhibitor was found to be tightly associated with a chromophore resembling Urobilirubin. An ELISA based assay system, using monoclonal antibodies against the above most potent inhibitor confirmed the difference observed in the urinary IA between the normal persons and kidney stone patients. This assay system has the potential to be routinely used to screen human beings for potential stone formers.
Adult↗