Acute lung involvement in RA is not always ILD

Rheumatoid arthritis is a systemic inflammatory disorder with diverse extra-articular manifestations including vasculitis,lung disease, inflammatory eye disease and subcutaneous nodule formation. Among these manifestations, lung diseasehas been identified as a primary contributor of morbidity and mortality. The predominance of non-specific interstitialpneumonia pattern has been observed in most forms of connective tissue-associated ILD. Studies have demonstratedthat the usual interstitial pneumonia (UIP) pattern is more prevalent among patients with RA-associated ILD. The extraarticular manifestations have been noted in nearly 50% of the patients, and the lung involvement in majority of thecases.8, 9 This study details the occurrence of lung involvement of viral etiology in RA, which could be misdiagnosed asRA-associated ILD

Structure based virtual screening, docking and molecular dynamic simulation studies to identify potent mdm2-p53 inhibitors: Future implications for cancer therapy

Objective: To identify the p53 binding pocket as well as active residues in mdm2 protein, and search for similar (or) better compounds to inhibit mdm2-p53 interactions in comparison to FDA approved drug (Nutlin) by ligand and structure based virtual screening methods, docking, and molecular dynamic simulation studies. Methods: A structure and ligand based virtual screening for mdm2 protein; targeting the key residues involved in their active binding of p53 peptide was conducted after obtaining structurally suitable compounds similar to Nutlin from ZINC database. These compounds are virtually screened onto the mdm2 protein targeting its active binding site where p53 binds. The best compound with highest binding affinity was taken up for further analysis using molecular dynamic simulations for further validating the docking studies and to reveal interactions during the conformational changes Results: We discovered several compounds that are potentially able to block the interaction between active residues of mdm2 and p53 complex, suggesting their capability to act as anti-cancer agents. As proven by our structure based virtual screening studies coupled with semi-flexible and flexible docking studies, compound ZINC59256947 was found to be the strongest inhibitors for mdm2 protein amongst all of those isolates from ZINC database. Conclusion: Our results suggest that, a simple, selective and reliable inhibition assay can be performed to search for novel inhibitors of p53-mdm2 interaction. Therefore this study provides a rationalization to the ability of a ZINC59256947, an isolate from ZINC database with strong binding affinity towards mdm2 protein, for future implications as anti-cancer agent.

Polymyositis presenting with respiratory failure.

Polymyositis is a systemic autoimmune disorder characterised by inflammatory myopathy of the skeletal muscles predominantly affecting the proximal muscles and associated with extra-muscular manifestations like dysphagia and skin involvement. In this case report, we describe the occurrence of diaphragmatic weakness and respiratory failure due to polymyositis with relatively well preserved power in limb muscles.

Translocations used to generate chromosome segment duplications in Neurospora can disrupt genes and create novel open reading frames.

In Neurospora crassa, crosses between normal sequence strains and strains bearing some translocations can yield progeny bearing a duplication (Dp) of the translocated chromosome segment. Here, 30 breakpoint junction sequences of 12 Dp-generating translocations were determined. The breakpoints disrupted 13 genes (including predicted genes), and created 10 novel open reading frames. Insertion of sequences from LG III into LG I as translocation T(UK8- 18) disrupts the eat-3 gene, which is the ortholog of the Podospora anserine gene ami1. Since ami1-homozygous Podospora crosses were reported to increase the frequency of repeat-induced point mutation (RIP), we performed crosses homozygous for a defi ciency in eat-3 to test for a corresponding increase in RIP frequency. However, our results suggested that, unlike in Podospora, the eat-3 gene might be essential for ascus development in Neurospora. Duplication–heterozygous crosses are generally barren in Neurospora; however, by using molecular probes developed in this study, we could identify Dp segregants from two different translocation–heterozygous crosses, and using these we found that the barren phenotype of at least some duplication–heterozygous crosses was incompletely penetrant.

Mitral leaflet separation index-a simple novel index to assess the severity of mitral stenosis.

BACKGROUND: Mitral leaflet separation (MLS) index is a recently recognized method to assess the severity of mitral stenosis. The aim of this study is to assess the severity of mitral stenosis (MS) using the MLS index. METHODS AND RESULTS: One hundred and fifty consecutive patients with MS who underwent 2D echo were studied. In each patient the severity of MS was assessed using 2D mitral valve area, pressure half time and MLS index. The mitral leaflet separation was measured in diastole, as the maximal separation at the tips in long axis and apical 4 chamber views. There were 34 (22.7%) patients with mild MS, 52 (34.7%) patients with moderate MS and 64 (42.7%) patients with severe MS. One hundred and ten (73.3%) patients were in sinus rhythm and 40 (26.7%) patients were in atrial fibrillation. The MLS index correlated very well with MVA by planimetry (r = 0.87, P < 0.0001) and pressure half time (r = 0.86, P < 0.0001). Good correlation was found even in atrial fibrillation (r = 0.87 and r = 0.87, respectively). ROC curve demonstrates that MLS index of 0.80cm or less identified severe MS with 92% sensitivity and 92% specificity. MLS index of >1.11 cm identified mild MS with 97% sensitivity and 97% specificity. CONCLUSION: The MLS index can be used as a screening method to semi quantify patients with mitral stenosis. This should be added into yet another method to assess the severity. This index will complement the other methods in our practice.

Prevalence of asthma in urban and rural children in Tamil Nadu.

BACKGROUND: There are very few community-based studies on the prevalence of asthma in Indian children. We aimed to estimate the prevalence of asthma in children under 12 years of age and to study possible differences in the prevalence of childhood asthma in urban and rural areas of Tamil Nadu. METHODS: A total of 584 children from Chennai and 271 children from 25 villages around Chennai formed the urban and rural groups, respectively. From November 1999 to February 2000, data were collected using a simplified version of the ISAAC questionnaire, which was administered by trained students. Symptoms suggestive of asthma or hyperreactive airways disease in children under 12 years of age were recorded from the selected urban and rural populations by questioning the parents. The results were analysed separately for children 0-5 and 6-12 years of age. RESULTS: Of the 855 children studied, the overall prevalence of breathing difficulty (including asthma) was 18% and the prevalence of 'diagnosed' asthma was 5%. Twenty-two per cent of urban and 9% of rural children 6-12 years of age reported breathing difficulty 'at any time in the past' (p < 0.01). A significantly higher proportion of 6-12-year-old urban children also reported nocturnal drycough (28.4% v. 18.7%, p < 0.05). Urban children reported recent wheeze more often than rural children (92% v. 77%, p = 0.01). CONCLUSIONS: Symptoms suggestive of asthma were present in 18% of children under 12 years of age. Though the prevalence of diagnosed childhood asthma was about 5% in both urban and rural areas, the prevalence of 'breathing difficulty' and nocturnal cough was significantly higher among urban children in the age group of 6-12 years. Children living in urban areas also reported 'recent wheeze' more often than rural children. Our data suggest that the actual prevalence of asthma and other 'wheezy' illnesses may be higher than that previously documented. Further studies are needed to confirm the difference in prevalence between urban and rural children and also to identify possible causes that could account for the higher urban prevalence of asthma in Tamil Nadu.

Acquired drug resistance in tuberculosis in Harayana, India.

Sputa of 200 treatment failure cases of pulmonary tuberculosis over a period of 1991-1995 were subjected to culture and sensitivity testing against commonly used anti-tuberculosis drugs. Out of 200 cases, 75% revealed resistance to one or more anti-TB drugs, resistance to isoniazid was observed in 72% cases, it was 49% for rifampicin, and 37% for streptomycin, while the resistance rate for other drugs was low. Majority of patients had resistance to two or three drugs concomitantly while resistance to 4, 5 and 6 drugs was of very low order and resistance to reserved drugs like kanamycin, ethionamide and cycloserine was encountered infrequently (1%). Out of 200 treatment failure patients multidrug resistance (MDR) was seen in 59% cases as 16% revealed resistance to isoniazid alone and strains in 22% cases were sensitive to all drugs. The study concludes that acquired MDR against first line antituberculosis drugs had increased as significant resistance against 3 drug combinations was observed although resistance against 2 drugs concomitantly was insignificant. Most ominous acquired drug resistance was seen against rifampicin in our region. The trends of drug resistance in the country and Haryana State are compared and their implications on outcome of chemotherapy are discussed.

Omental plug closure of large duodenal defects--an experimental study.

This study was conducted to evaluate the efficacy of omental plugging in the management of large duodenal defects and analyse the serial histopathological changes occurring in the omental plug and the edges of the defect until healing occurred as evidenced by complete mucosal cover. The study was conducted in 12 dogs. Through a laparotomy wound a 20 mm diameter defect was created in the first part of the duodenum. The abdomen was closed, leaving the defect open, for a period of three hours to allow peritonitis to set in. Subsequently the abdomen was reopened and the perforation was plugged with omentum pulled into the duodenal lumen and fixed to the edges. They were randomly sacrificed two at a time on the first week, second week, fourth week, sixth week and eight week post operatively. The morphology of the perforation site, adequacy of the duodenal lumen, and the histological picture at each stage were studied. There was no morbidity except in one dog which showed signs of high intestinal obstruction that resolved after conservative management. There was one mortality due to sepsis unrelated to the procedure. The omentum was firmly adherent and there was no evidence of leak from the site of closure. The omental plug underwent inflammation, necrotic changes, granulation, reduction in size and fibrosis. The defects decreased rapidly in size and healing was complete at eight weeks with the mucosa taking a normal histological appearance. None of the dogs exhibited luminal obstruction on autopsy. This study reaffirms the reliability of the omental plug in safely occluding large duodenal defects and producing healing through a process of inflammation, granulation, vascularisation and fibrosis eventually providing a normal duodenal mucosal cover to the perforation site.

Pyopneumothorax associated with pneumopericardium.

An unusual association of pneumopericardium with pyopneumothorax is presented. Pneumopericardium responded after intercostal drainage.

Branchiogenic cyst of larynx.

An extremely rare case of branchiogenic cyst of the larynx in young adult male is reported. Relevant literature is reviewed.

An epidemiological study of hepatitis B virus amongst blood donors.

The study was carried out on 186 professional blood donors. A detailed-socio economic profile of these donors was taken and the serum was tested for HBs. Ag. Majority (63.4 per cent) of the donors were in the age bracket of 30-40 years with an average age of 34 years. About 83.3 per cent were illiterate and belonged to the lowest rung of the socio economic scale. The average length of blood donation was observed to be 4 years with blood letting frequency of 4.4 within a stipulated period of three months. Most of them were anaemic with an average haemoglobin level of 8.2 gm per cent. The HBs Ag prevalence was observed to be 15.59 per cent. HBs Ag positivity was found to be significantly associated with the length and the frequency of blood donation (P less than .05). Remedial measures for prevention of viral hepatitis-B through professional blood donors was emphasized.