Naveed Nazir Shah

Mediastinal hydatid cyst rupturing into the pleural cavity associated with pneumothorax: case report and review of the literature.

Hydatid disease remains a serious health problem in Mediterranean countries. Living in a rural area is an important risk factor for the disease. Hydatid cysts are usually located in the liver, lungs and brain. Mediastinal hydatid disease is very rare and has been noted only anecdotally in the literature. The present article reports a case of a mediastinal hydatid cyst rupturing into the pleural cavity, which was associated with pneumothorax of the same side. The patients previous chest x-rays (posteroanterior and left lateral views) showed a well-defined mediastinal mass on the left side, and contrast-enhanced computed tomography of the thorax (taken a few days after the chest x-ray) showed multiple round-to-oval soft tissue opacities with partial collapse of the left lung. An indirect hemagglutination test for echinococcus was positive. Even after two weeks of intercostal tube drainage, the patients condition did not improve. During thoracotomy, multiple daughter cysts were found in the pleural cavity, and the diagnosis of a hydatid cyst was confirmed after histopathological examination.

Alpha-1-antitrypsin deficiency: Genetic variations, clinical manifestations and therapeutic interventions

Alpha-1-antitrypsin (AAT) is an acute phase secretory glycoprotein that inhibits neutrophil proteases like elastase and is considered as the archetype of a family of structurally related serine-protease inhibitors termed serpins. Serum AAT predominantly originates from liver and increases three to five fold during host response to tissue injury and inflammation. The AAT deficiency is unique among the protein-misfolding diseases in that it causes target organ injury by both loss-of-function and gain-of-toxic function mechanisms. Lack of its antiprotease activity is associated with premature development of pulmonary emphysema and loss-of-function due to accumulation of resultant aggregates in chronic obstructive pulmonary disease (COPD). This in turn markedly reduces the amount of AAT that is available to protect lungs against proteolytic attack by the enzyme neutrophil elastase. The coalescence of AAT deficiency, its reduced efficacy, and cigarette smoking or poor ventilation conditions have devastating effect on lung function. On the other hand, the accumulation of retained mutant proteins in the endoplasmic reticulum of hepatocytes in a polymerized form rather than secreted into the blood in its monomeric form is associated with chronic liver disease and predisposition to hepatocellular carcinoma (HCC) by gain- of- toxic function. Liver injury resulting from this gain-of-toxic function mechanism in which mutant AAT retained in the ER initiates a series of pathologic events, eventually culminating at liver cirrhosis and HCC. Here in this review, we underline the structural, genetic, polymorphic, biochemical and pathological advances made in the field of AAT deficiency and further comprehensively emphasize on the therapeutic interventions available for the patient.

Novel variants of SERPIN1A gene: Interplay between alpha1-antitrypsin deficiency and chronic obstructive pulmonary disease

Alpha1-antitrypsin (AAT) is one of the major circulating anti-protease whose levels in circulation are raised during excessive amount of proteases, especially neutrophil elastase (NE) released during the course of inflammation. Proteolytic attack of NE on peripheral organs, more exclusively on lung parenchyma has severe consequence that may precipitate pulmonary emphysema. Normally, human body has its own molecular and physiological mechanisms to synthesize and regulate the production of anti-protease like AAT to mitigate the extent of inflammatory damage. AAT coded by serine-protease inhibitor (SERPINA1) is predominantly expressed in hepatocytes and to some extent by macrophages, monocytes, lung tissue etc. The observation that persons with AAT deficiency developed chronic obstructive pulmonary disease (COPD) and early-onset of emphysema proposed a role for pathways connecting AAT in pathogenesis. Extensive studies have been done till now to bridge a connection between numerous genetic polymorphisms of SERPINA1 gene and the early onset of COPD. Here in this review, we have comprehensively discussed some of the variants of SERPINA1 gene discovered till date and their association with the exacerbation of obstructive pulmonary disease.

A prospective study on quality of life in patients with pulmonary tuberculosis at a tertiary care hospital in Kashmir, Northern India

BACKGROUNDnPulmonary Tuberculosis (PTB) is a contagious, airborne infection that destroys when M. tuberculosis primarily attacks the lungs. PTB is curable with an early diagnosis and antibiotic treatment. Stigmatization and negative emotions resulting from the illness could result in long term impairment of patients psychological well being which may result in work absenteeism resulting in loss of productivity and reduced monthly income.nnnMETHODSnThis was a prospective study which was conducted over a period of one and half year. A total of 198 patients were recruited for the study. Quality Of Life (QOL) was assessed at baseline and at the end of intensive phase. For QOL WHO based QOLBREF was used.nnnRESULTSnIn the present study patients scored lowest in the baseline physical (8.36xa0±xa01.60) followed by the psychological domain (10.40xa0±xa01.72) however at the end of intensive phase both physical (11.98xa0±xa01.70) and psychological (12.75xa0±xa01.) domains improved very much and the difference was statistically significant.nnnCONCLUSIONnWe conclude that HRQOL is significantly reduced in patients with PTB, and that it improves rapidly and significantly with DOTS-based intensive phase of treatment. Special focus on reduction of stigmatization should be given in the management of TB to reduce the psychological distress.

SERPINA1 Hepatocyte-Specific Promoter Polymorphism Associate with Chronic Obstructive Pulmonary Disease in a Study of Kashmiri Ancestry Individuals

PurposeDifferent mutations in coding and non-coding sequences of the SERPINA1 gene have been implicated in the pathogenesis of COPD. However, −u200910T/Cxa0mutation in the hepatocyte-directed promoter region has not been associated with COPD pathogenesis so far. Here, we report an increased frequency of −u200910C genotype that is associated with decreased levels of serum alpha1-antitrypsin (α1AT) in COPD patients.MethodsThe quantification of serum α1AT was done by ELISA, the phenol–chloroform method was used for DNA extraction, PCR products were directly sequenced. The IBM SPSS Statistics v21 software was used for statistical analyses of the data.ResultsThe mean serum α1AT level was found to be 1.203+0.239 and 3.162+0.160 g/L in COPD cases and in control, respectively. The −u200910C allele is associated with an increased risk of COPD [OR, 3.50 (95%CI, 1.86-6.58); p < 0.001]. The combined variant genotype (TT+CC) was significantly found associated with an increased risk of COPD [OR, 3.20 (95% CI, 1.47-6.96); p = 0.003]. A significant association of the family history with COPD (overall p value= 0.0331) suggests that genetics may play an important role in the pathogenesis of COPD.ConclusionThe polymorphism associated with hepatocyte-specific promoter region (−u200910T/C) is likely to be associated withxa0the pathogenesis of COPD. It is quite possible that the change of the base in thexa0hepatocyte-specific promoterxa0of the SERPINA1 gene can modulate its strength, thereby driving the reduced expression of α1AT.

To study the effectiveness of DOTS at J N Medical College Aligarh

Background: Tuberculosis remains the major cause of morbidity and mortality in India and affects largely the most productive members of the society. The major concern is increasing number of MDR TB cases due to inadequate and improper treatment of primary and post primary TB cases. However Directly observed therxadapy, short course (DOTS) is emerging as standard of care for the majority of TB patients and results from various parts of country are encouraging. Objective: To study the effectiveness of directly observed therapy and to compare it with self administered therapy in patients with tuberculosis. Design: Prospective randomized uncontrolled study The study was conducted on the patients attending the OPD or indoor patients at J N Medical College and hospital A M U Aligarh from October2004 to June 2006. Patients included pulmonary and extra-pulmonary TB cases diagnosed on the baxadsis of sputum smear, culture, chest radiograph, cytological and histopathological examination. Patients were assigned into two groups to receive either treatment under DOTS or self administered treatment. We compared the treatment outcomes in these patients between the two groups. Results: Patients treated by directly observed therapy DOT (n=495) had a similar cure rate compared with patients treated by self- administered therapy (n=450) (81% vs 81.6%, p > 0.05). The overall default rate was significantly more in the self administered group when compared to DOT (7.5% vs 5.3%, p Conclusion: Patients treated by DOT have excellent cure rates with lesser default rates. Thus we conclude that treatment plans that emphasize directly observed therapy from the start of treatment, have greatest success in improving tubercuxadlosis treatment outcomes, thereby preventing the transmission of disease in comxadmunity.