Treatment outcome of multi-drug resistant tuberculosis in a tertiary care hospital in Karachi

Objective: To assess the outcomes of pulmonary multidrug-resistant tuberculosis (MDR-TB) patients treated at Ojha Institute of Chest Diseases (OICD), a reference hospital for TB in Karachi, Pakistan. Methods: Clinical study for the period 1996-2006, with follow-up until June 2007 was performed. All the culture and sensitivity proven cases of MDR pulmonary TB were initially admitted for 3-6 months till the sputum converted negative. Treatment regimen was decided on individual basis, and included 4-6 drugs. Supervised treatment was given to all patients during the hospitalization. After discharge from the hospital, patients were followed at monthly interval at the outpatient department of OICD for 18 months total. Results: Five hundred and seventy nine adult patients (59.93% male) with mean age of 32.44 ± 12.63 years were studied. All patients had a history of treatment with first line anti-tuberculosis drugs. Treatment was successful in 227 (39.2%). The mortality rate was 27(4.6%) during hospitalization. During admission 83(14.3%) left treatment and 239 (41.2%) were lost to follow-up during treatment. Treatment failure was observed in three patients. Conclusion: The treatment success rate in this study is satisfactory but high default rate is a challenge in the management of MDR tuberculosis (JPMA 59:694; 2009)

Primary drug resistance against Mycobacterium tuberculosis in Karachi

OBJECTIVE: To evaluate the primary drug resistance of new culture positive cases of pulmonary tuberculosis in Karachi. METHODS: All new suspected pulmonary tuberculosis patients were recruited initially. They were instructed to produce three-sputum samples for smear examination and on one of the specimen\u27s culture was applied. Bronchoscopy and bronchial wash was done in patients who were not expectorating. Bronchial wash was then applied for both smear and culture for Mycobacterium tuberculosis. RESULTS: Out of 79 cases recruited initially, 52 were able to produce sputum while bronchoscopy was performed in the remaining. AFB direct smear was positive in 32/52 sputum and 12/27 bronchial wash samples. Later, 02 sputums and 04 bronchial washes became culture positive which were initially smear negative. All cultures were of Mycobacterium tuberculosis species. These fifty culture positive cases were then included in the final analysis. Pyrazinamide was the most sensitive drug i.e. 49 isolates (98%). The resistance pattern is as follows: Streptomycin 13(26%), Isoniazid 08 (16%), Ethambutol 08 (16%), Rifampicin 04 (08%) and Pyrazinamide one (02%). Multi-Drug Resistant tuberculosis was observed in 02 (04%) patients. CONCLUSION: In this small study, the high prevalence of primary resistance against streptomycin, INH and Ethambutol raises an urgent need of a proper nationwide survey to evaluate the true picture of primary resistance

Drug Resistance Pattern in Multidrug Resistance Pulmonary Tuberculosis Patients

Objective: To evaluate accuracy of modified Kenneth Jones scoring criteria (MKJSC) as a screening tool to diagnose tuberculous meningitis in children. Study Design: Cross-sectional study. Place and Duration of Study: Paediatric Medicine, Unit-I, Bahawal Victoria Hospital, Bahawalpur, from May 2006 to March 2007. Methodology: A total of 100 children admitted through emergency in Paediatric Medicine, Unit-I, were included who were having fever and features suggestive of central nervous system (CNS) infection. Lumbar puncture was done in all patients after written consent. Findings of lumbar puncture were taken as gold standard for the diagnosis of TBM. MKJSC was applied on each patient and accuracy determined against the gold standard. Results: Out of 100 children, 47 were diagnosed as TBM on the basis of CSF results. All children had scored 0-7 or above according to MKJSC. A score 1-2, 3-4, 5-6 and 7 or more was obtained in 23, 25, 30 and 22 children respectively. Children who had scored 5 or more received ATT. Accuracy of MKJSC was calculated to be 91%. Conclusion: MKJSC is a simple and accurate tool to improve tuberculous meningitis case detection rate in children

Six-Minute Walk Test Performance in Healthy Adult Pakistani Volunteers

Objective: To determine the six-minute walking distance (6MWD) for healthy Pakistanis, identify factors affecting 6MWD, compare published equations with the local data and derive an equation. Study Design: Cross-sectional study. Place and Duration of Study: Two medical institutes of Karachi, from January to May 2011. Methodology: Subjects between 15 and 65 years were prospectively enrolled after screening. A standardized 6MWT was administered. SpO2, HR, BP and dyspnoea scores were determined pre- and post-test. Results: Two hundred and eleven (71%) men and 85 (29%) women participated. Mean 6MWD was 469.88 ± 101.24 m: men walked 502.35 ± 92.21 m and women walked 389.28 ± 74.29 m. On univariate analysis, gender, height, weight and age showed a significant relationship with the 6MWD. Gender and age were identified as independent factors in multiple regression analysis, and together explained 33% of the variance. The gender-specific prediction equations were: 6MWD (m) for men = 164.08 + (78.06*1) - (1.90*age in years) + (1.95*height in cms) 6MWD (m) for women = 164.08 - (1.90*age in years) + (1.95*height in cms). Conclusion: 6MWDs among the volunteer subjects were shorter than predicted by reference equations in literature. Height, gender and weight combined explained 33% of the variance. The moderate over-estimation of the 6MWD in Pakistani subject. The proposed equation gives predicted (mean) 6MWDs for adult Pakistani naïve to the test when employing standardized protocol

Abdul Aziz Khan

Objective:  Pituitary lesions cause morbidity and mortality in all age groups due to their hormonal hypersecretion, its mass effects, and post-surgery complications. The present study determined the frequency of functional and non-functional pituitary adenomas. Materials & Methods:  The study included patients (n = 114) presenting with functional and non-functional pituitary adenoma. Pituitary adenomas were diagnosed based on MRI brain with contrast and the size of the tumor was noted a tumor having a size of 10 mm or more was labeled as macro adenoma and a tumor having a size less than 10 mm was labeled as microadenoma. Pituitary adenomas were stratified among age, gender, duration of symptoms, types of adenomas, types of functional adenoma, and type of the tumor on a size basis. Results:  Most of the patients had TSH- secreting adenoma (21.9%). 52.6% were found with microadenoma and 47.4% had macro adenoma. Patients with functional adenoma were 30.7% and with non-functional adenoma 32.5% were male while patients with functional adenoma were 26.3% and with non-functional adenoma 10.5%were female (p = 0.018). Patients with functional adenoma (43.9%) and non-functional adenoma (8.8%) were found to have microadenoma, whereas patients with functional adenoma (13.2%) and non-functional adenoma (34.2%) were found to have macroadenoma (p = 0.000). Patients with functional adenoma having a duration of symptoms below 1 year were 11 (9.6%), 1 to 3 years were 25 (21.9%), 17 (14.9%) were 4 to 6 years, and 12 (10.5%) above 6 years duration of symptoms. Conclusion:  Patients with pituitary adenomas should be diagnosed early to receive successful therapy

Computational Seismic Analysis of Dry-Stack Block Masonry Wall

In this research the computational modeling of Dry-Stack Block Masonry (DSM) walls subjected to cyclic monotonic loading testing is done. The analytical results were compared with experimental test results of the unreinforced and unconfined DSM cantilever walls subjected to lateral loading along with a constant axial load. ABAQUS has been used for Finite Element Modeling and analysis of the wall. Various material properties are defined for the wall in the software and modeled as a homogeneous material. The proposed numerical models had a good correlation with the experimental data. The test results discussion includes failure moods, load displacement curves, and stress/strain profile. Doi: 10.28991/cej-2021-03091668 Full Text: PD

Interplay of chemo attractant peptides (cathelicidin and chemerin) with vitamin-D in patients with pulmonary tuberculosis

Aim: Both Cathelicidin and Chemerin are chemoattractant proteins and possess antimicrobial activity.Sufficient level of Vitamin D is important for optimum response of Cathelicidin for its antimycobacterial activity. Studies on the role of these antimicrobial peptides and their relationship withVitamin D level are limited in tuberculosis. The aim of this study was to investigate an associationof Vitamin D with antimicrobial peptide (Cathelicidin) and an adipokine (Chemerin) in patients with pulmonary tuberculosis (TB). Methods: In a case control study we estimated level of Vitamin D, Chemerin, Cathelicidin and TNFα in pulmonary TB patients (n=22) and healthy endemic controls (n=17) using sandwich ELISA methodology. The study was conducted at Aga Khan University Karachi during 2011. Results: TB group had higher proportion of subjects above median level of Cathelicidin (median test; p=0.034) and fewer number of subjects with Chemerin (median test; p=0.001).Pairwise comparison also showed significant differences between average ranks of Vitamin D vs.Cathelicidin (p\u3c0.0001), Chemerin vs. Cathelicidin (p=0.04) and Vitamin D vs.TNFα(p\u3c0.0001). Cathelicidin was identified as most discriminatory marker between TB disease and healthy group(ROC,AUC 0.780; p=0.007). Conclusion: Our results highlight the role of Cathelicidin as a potential biomarker of active TB disease. The role of Cathelicidin and Chemerin as plausible biomarkers requires further studies in both inflammatory and non inflammatory condition

Presentation of Acute Lymphoblastic Lymphoma and Colorectal Carcinoma in the Context of Constitutional Mismatch Repair Deficiency Syndrome (CMMRD): a Case Report with Literature Review

Introduction: Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive disease-carrying an increased risk of cancers (pediatric tumors of central nervous system, haemato-lymphoid malignancies along with gastrointestinal (GI) cancer(s), which are usually seen in the second and third decade) leading to syndromic presentation. Causal mutations are detected in DNA mismatch repair (MMR) genes, including MLH1, PMS2, MSH2, and MSH6 that are also known for their established role in Lynch syndrome. We describe a case of CMMRD with an earlier (first decade of life) presentation of mediastinal acute lymphoblastic lymphoma and colorectal malignancy. Case Presentation: A five-year-old boy presented with respiratory complaints, bilateral cervical lymphadenopathy, multiple café au lait macules (CALMs) on the lower back, history of parental consanguinity with the death of three sisters due to brain tumor within 6 months of diagnosis. Computerized tomographic (CT) scan chest revealed a huge mediastinal mass. The patient underwent a trucut-biopsy of the mass. The results were significant for a pre T-cell acute lymphoblastic lymphoma. Suspicion of CMMRD was raised based on a combination of factors described above. A panel of mismatch repair (MMR) proteins was applied on the biopsy tissue that revealed loss of nuclear expression of MLH1 and PMS2 immunostaining in tumor cells with positive external controls. While on maintenance therapy for lymphoma, about a year later, the patient developed sub-acute intestinal obstruction due to a stenosing polypoidal circumferential tumor in the mid-sigmoid colon found on flexible sigmoidoscopy that was followed by endoscopic biopsies and insertion of a fully-covered self-expanding metallic adult biliary stent with a diameter of 10 mm and length of 6 cm leading to immediate relief of obstruction. Biopsies revealed adenocarcinoma with neuroendocrine differentiation. Metastatic tumor deposits were seen in the omentum, anterior abdominal wall, and the left peritoneal wall. Practical Implications: Earlier (first decade) presentation of gastrointestinal malignancy warrants that an earlier screening through radiological scans for any possible tumors and MMR protein expression analysis (loss in tumor plus normal non-tumor cells) are essential in patients having CALMs and family history of pediatric tumors

The Apolipoprotein E Polymorphism And Dyslipidemia In Elderly Patients Of Calcific Aortic Stenosis: A Case Control study

Objective: This study aimed to investigate the impact of the Apo E polymorphisms on plasma lipid profile and to identify the polymorphism of the apo-E gene as genetic predictor of calcific AS in Pakistani population.   Methodology: This was a case control study conducted in Dow University of Health Sciences and National Institute of Cardiovascular Disease, Karachi. It included total of 100 individuals, 50 echocardiographically identified calcific AS cases and 50 age and gender matched controls. Apo E allele frequencies were computed, lipid profiles were estimated and Apo E gene polymorphism was identified by the techniques of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).   Result: Apo E 2, 3, and 4 allele frequencies were 16%, 52%, and 32% in calcific AS cases, and 10%, 52%, 28% in controls respectively (p=0.622). Out of 50 cases, 18% presented with mild AS, 22% moderate AS and 60% lied in severe calcific AS. It was observed that levels of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) were higher in Apo E4 allele as compared to other genes in both cases and control.   Conclusion: The findings of this study suggested that Apo E4 allele of Apo E gene is an impotent risk factors for dyslipidemia while Apo E4 allele is not associated with calcific AS contemplates distinctive genetic backgrounds of CAD and AS