Replication and meta-analysis of 13,000 cases defines the risk for interleukin-23 receptor and autophagy-related 16-like 1 variants in Crohn��s disease

BACKGROUND/OBJECTIVE:

Variants in the interleukin-23 receptor (IL23R) and the autophagy-related 16-like 1 (ATG16L1) genes have been associated with an increased risk of Crohn’s disease (CD). Both genes were identified through genome-wide association scans and subsequent studies have validated these associations. To assess the effect size of these variants, an independent case-control association study and meta-analysis were performed.

METHODS:

British Caucasian subjects with inflammatory bowel disease (n=500) and 877 ethnically matched controls were genotyped for the disease-associated variants in IL23R and ATG16L1. In addition, meta-analyses of 12,991 patients and 14,598 controls, and 11,909 patients and 15,798 controls, were conducted on independently published data for the associations between IL23R and ATG16L1 variants and CD, respectively.

RESULTS:

In the present cohort, both susceptibility variants showed highly significant associations, including IL23R (rs11209026, P=0.0006; OR 0.37; 95% CI 0.21 to 0.67) and ATG16L1 (rs2241880, P=0.0017; OR 1.36; 95% CI 1.12 to 1.66). The meta-analysis based on the random effects model showed similar combined effects for rs11209026 (n=26, OR 0.41; 95% CI 0.37 to 0.46) and rs2241880 (n=25, OR 1.33; 95% CI 1.28 to 1.39). There was no statistically significant gene-gene interaction between caspase recruitment domain (CARD15) variants and the IL23R or ATG16L1 polymorphisms (P=0.44 and P=0.24, respectively).

CONCLUSION:

The present cohort and meta-analysis provides strong evidence that, in addition to CARD15, polymorphisms in both IL23R and ATG16L1 alter susceptibility to CD and that these effects are consistent across all populations of European ancestry; however, only ATG16L1 is relevant to inflammatory bowel disease in the Asian population.     

Spectrum of Acute Viral Hepatitis in Southern India

Background

The incidence of hepatitis-A among adults in India is on the decline as majority develops protective immunity to it by late adolescence. Most of these studies are from northern India. Clinical spectrum of sporadic acute viral hepatitis from southern India has not been well documented.

Methods

A prospective hospital based study was conducted in a large military hospital in southern India. 224 consecutive patients with acute viral hepatitis were studied for their presentation, etiology and clinical features.

Result

Hepatitis-E was detected in 102 (45.4%), hepatitis A in 74 (33%) and hepatitis B in 28 (12.5%) patients. Acute hepatitis C was detected in two patients. 15 patients had a mixed infection. Hepatitis A constituted 41.2% and 31.3% of all cases in the age groups 11-20 and 21-30 years respectively. Cholestasis was present in 68 (30.4%) patients with hepatitis E accounting for most (61.8%) cases. There were four (1.8%) cases of acute liver failure. Two cases were due to hepatitis E and one case each was due to hepatitis A and hepatitis B. A relapsing course was seen in four cases due to hepatitis-A.

Conclusion

Hepatitis A remains a significant cause of sporadic acute viral hepatitis in young adults in southern India.Key Words: Viral hepatitis, Hepatitis A     

Impact of Body Mass Index on Left Ventricular Function

Background

Obesity is associated with increased cardiovascular morbidity and mortality. A direct effect of isolated obesity on cardiac function is not well established. The study was designed to determine the direct effect of various grades of isolated obesity on echocardiographic indices of systolic and diastolic left ventricular function.

Methods

Fifty one obese and 25 normal weight, serving personnel without any other pathological condition were studied. Group I (n=25) consisted of subjects with normal weight and body mass index (BMI <25kg/m²), Group II (n=34) of overweight subjects (BMI 25-29.9 kg/m²) and Group III (n=17) of obese subjects (BMI >30 kg/m²). Echocardiographic indices of systolic and diastolic function were obtained and dysfunction was assumed when at least two values differed by ≥ 2 SD from the normal weight group.

Result

Ejection fraction, fractional shortening were increased (p<0.05) in Group II and III. Left ventricular dimensions were increased (p< 0.001) but relative wall thickness was unchanged. Systolic dysfunction was not observed in any of the obese patients. The mitral valve pressure half time (p< 0.01), left atrial diameter (p < 0.01) and the deceleration time were increased (p< 0.01) in obese subjects, while other diastolic variables were unchanged. No difference were found between obesity subgroups. Subclinical diastolic dysfunction was more prevalent among obese subjects. BMI correlated significantly with indices of left ventricular systolic and diastolic function.

Conclusion

Subclinical left ventricular diastolic dysfunction was noted in all grades of obesity which correlates with BMI.Key Words: Obesity, Systolic function, Diastolic function, Echocardiography     

Virulence of major periodontal pathogens and lack of humoral immune protection in a rat model of periodontal disease

Oral Diseases (2010) 16 , 686–695 Objective: This study was designed to test the hypothesis that periodontal pathogens Tannerella forsythia and Porphyromonas gingivalis are synergistic in terms of virulence potential using a model of mixed‐microbial infection in rats. Materials and methods: Three groups of rats were infected orally with either T. forsythia or P. gingivalis in mono‐bacterial infections or as mixed‐microbial infections for 12 weeks and a sham‐infected group were used as a control. This study examined bacterial infection, inflammation, immunity, and alveolar bone loss changes with disease progression. Results: Tannerella forsythia and P. gingivalis genomic DNA was detected in microbial samples from infected rats by PCR indicating their colonization in the rat oral cavity. Primary infection induced significantly high IgG, IgG2b, IgG1, and IgG2a antibody levels indicating activation of mixed Th1 and Th2 immune responses. Rats infected with the mixed‐microbial consortium exhibited significantly increased palatal horizontal and interproximal alveolar bone loss. Histological examinations indicated significant hyperplasia of the gingival epithelium with moderate inflammatory infiltration and apical migration of junctional epithelium. The results observed differ compared to uninfected controls. Conclusion: Our results indicated that T. forsythia and P. gingivalis exhibit virulence, but not virulence synergy, resulting in the immuno‐inflammatory responses and lack of humoral immune protection during periodontitis in rats.     

<Emphasis Type="Italic">TP53</Emphasis>mutation status and gene expression profiles are powerful prognostic markers of breast cancer

Introduction  

Gene expression profiling of breast carcinomas has increased our understanding of the heterogeneous biology of this disease and promises to impact clinical care. The aim of this study was to evaluate the prognostic value of gene expression-based classification along with established prognostic markers and mutation status of the TP53 gene (tumour protein p53) in a group of breast cancer patients with long-term (12 to 16 years) follow-up.     

A multicentre (double-blind) comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea corporis and tinea cruris

In a double-blind, parallel group study we compared fluconazole 150mg once weekly with griseofulvin 500 mg once daily for 4–6 weeks in the treatment of tinea corporis or tinea cruris. Eighty-four of 114 patients (74%) (39% after 3 weeks) were clinically cured in the fluconazole group compared with 72 of 116 (62%) (39% after 3 weeks) in tbe griseofulvin group (P = 0·06). In tbe fluconazole group 78% were mycological cured compared with 80% in the griseofulvin group. In the fluconazole group nine patients (7·5%) had treatment related adverse events and in tbe griseofulvin group 15 patients (12·5%) had adverse events. Fluconazole 150 mg once weekly for 6 weeks is botb clinically and mycologically effective in the treatment of tinea corporis and tinea cruris and few side-effects were reported.