The shared epitope hypothesis in rheumatoid arthritis: evaluation of alternative classification criteria in a large UK Caucasian cohort

OBJECTIVE: Many classification systems for the HLA-DRB1 allelic association with rheumatoid arthritis (RA) have been reported, but few have been validated in additional populations. We sought to evaluate 3 different DRB1 allele classification systems in a large cohort of Caucasian RA patients and control subjects in the UK. METHODS: HLA-DRB1 typing was undertaken in 1,325 Caucasian RA patients and 462 healthy Caucasian controls who were residents of the UK. Logistic regression analyses were performed to investigate the different classification systems. RESULTS: We confirmed the association between the susceptibility alleles S2 and S3P, as proposed by Tezenas du Montcel, and the presence of RA in UK Caucasians. A significant hierarchy of risk was observed within the S3P allele group. There was no evidence of a significant association between DRB1*1001 and RA. Our data did not support the hypothesis that an isoleucine at position 67 conferred protection against RA, other than in contrast to the susceptibility alleles. However, the presence of an aspartic acid at amino acid 70 did appear to confer some degree of protection. CONCLUSION: We were unable to fully substantiate any of the 3 recent revisions of the shared epitope hypothesis in this large cohort of Caucasian RA patients and control subjects in the UK. This reinforces the importance of evaluating disease susceptibility alleles in different Caucasian populations as well as in other ethnic groups. In particular, it will be important to clarify the precise DRB1 association in a given population before DRB1 genotyping is incorporated into clinical diagnostic or treatment algorithms.     

Bacteriological study of diabetic foot infections

AIMS: The polymicrobial nature of diabetic foot infection has been well documented in the literature. Patients with diabetic foot infection not exposed to antibiotics are not well studied before. The relative frequency of bacterial isolates cultured from community-acquired foot infections that are not exposed to antimicrobial agents for 30 days is studied. In addition, the bacterial comparative in vitro susceptibility to the commonly used antibacterial agents is assessed. METHODS: This is a prospective study in which the infected wounds of 86 consecutive diabetic patients seen in the diabetic foot clinic in Adan Teaching Hospital were cultured when visiting the clinic. The patients did not receive antimicrobial therapy 30 days prior to taking the cultures. The specimen was cultured using aerobic and anaerobic microbiological techniques. Isolates were tested for susceptibility to commonly used antimicrobial therapy. RESULT: Staphylococcus aureus was the most common isolate, being recovered from 38.4% of cases. Other organisms were Pseudomonas aeruginosa (17.5%) and Proteus mirabilis (18%), anaerobic gram-negative organisms (10.5%), mainly Bacteroides fragilis. Imipenem, meropenem, and cefepime were the most effective agents against gram-negative organisms. Vancomycin was the most effective against gram-positive organisms. CONCLUSION: S. aureus and P. aeruginosa were the most common causes of diabetic foot infections. Anaerobic organisms are still a common cause for infection, although the prevalence is less. These wounds may require use of combined antimicrobial therapy for initial management.     

Prevalence and Impact of Hepatic Steatosis on the Response to Antiviral Therapy in Saudi Patients with Genotypes 1 and 4 Chronic Hepatitis C

Background

Hepatic steatosis in hepatitis C virus (HCV)-infected patients has been shown to enhance the progression of liver fibrosis and decrease the response to antiviral therapy.

Aims

We aimed to determine the role of HCV genotype 4 (HCV-G4) in the prevalence of hepatic steatosis, its impact on antiviral therapy, and its associations and predictive factors in comparison to HCV-G1-infected patients.

Methods

Treatment-naïve HCV patients who were started on pegylated interferon a-2b plus ribavirin therapy in two centers in Saudi Arabia were included. The severity of steatosis was assessed using the METAVIR and NAS (non-alcoholic fatty liver disease [NAFLD] activity score) scoring systems. Sustained virological response (SVR) was studied in relation to the degree of steatosis. Associations between steatosis and multiple demographic, laboratory, and virological factors were examined. HCV-G1 and HCV-G4 patients were compared.

Results

A total of 116 patients (HCV-G4 85 [73.3%]; HCV-G1 31 [26.7%]) were included. The mean age was 50.4 ± 10.7 years and 56.9% were males. In terms of steatosis grading using the NAS scoring system, 50% had steatosis grade 0, 26.7% grade 1, 14.7% grade 2, and 8.6% grade 3, while the overall staging of steatosis revealed that 43.1% had mild steatosis, 42.2% moderate, and 14.7% severe. Gamma-glutamyl transpeptidase (GGT), platelet count, body mass index (BMI), cholesterol level, presence of hyperlipidemia, liver histology stage, and grade were significantly correlated with hepatic steatosis in one or more of the statistical analyses. Twenty-two out of 55 patients (40.0%) had an SVR in the mild steatosis group, compared to 52.7% in the moderate group and 7.3% in the severe group (P = 0.03). The HCV genotype did not correlate with steatosis or SVR.

Conclusion

Our study confirms the high prevalence of steatosis in HCV-G4 and HCV-G1 patients, but with no difference in the grade or score of steatosis between the two genotypes. The grade of steatosis correlates with GGT, platelet count, and BMI, while the NAS score of steatosis correlates with response to antiviral therapy.     

Testosterone or 17{beta}-estradiol exposure reveals sex-specific effects on glucose and lipid metabolism in human myotubes

Changes in sex hormone levels with aging or illness may lead to metabolic disorders. Moreover, the ratio changes in men versus women may have distinct pathological responses. Since little is known about sex hormone action on muscle metabolism, we examined the role of testosterone or 17β-estradiol (E(2)) in metabolism and investigated whether either hormone may mediate a sex-specific effect. Myotubes from postmenopausal women and age-matched male donors were treated with 10?nM testosterone or E(2) for 4 days, and assays were performed to measure metabolic readouts, signal transduction, and mRNA expression. Testosterone and E(2) treatment enhanced insulin-stimulated glucose incorporation into glycogen and AKT phosphorylation in myotubes from female donors, highlighting a sex-specific role of sex hormone in glucose metabolism. Testosterone treatment increased palmitate oxidation in myotubes from both female and male donors, while E(2) enhanced palmitate oxidation in myotubes from male donors only. Testosterone-mediated increase in palmitate oxidation was attenuated at the presence of androgen receptor antagonist, which may indicate a role of nuclear steroid receptor in muscle lipid oxidation. Testosterone treatment increased mRNA expression of the insulin receptor substrate 2 in myotubes from male and female donors, whereas it increased mRNA expression of glycogen synthase 1 only in myotubes from male donors. E(2) treatment increased pyruvate dehydrogenase kinase 4 mRNA expression in myotubes from female donors. Thus, our data suggest that testosterone or E(2) modulates muscle glucose and lipid metabolism and may play a role in metabolism in a sex-dependent manner.     

Melena： A rare complication of duodenal metastases from primary carcinoma of the lung

Small bowel metastases from primary carcinoma of the lung are very uncommon and occur usually in patients with terminal stage disease. These metastases are usually asymptomatic, but may present as perforation, obstruction, malabsorption, or hemorrhage. Hemorrhage as a first presentation of small bowel metastases is extremely rare and is related to very poor patient survival. We describe a case of a 61- year old patient with primary adenocarcinoma of the lung, presenting with melena as the first manifestation of small bowel metastasis. Both primary tumor and metastatic lesions were diagnosed almost simultaneously. Upper gastrointestinal endoscopy performed with a colonoscope revealed active bleeding from a metastatic tumor involving the duodenum and the proximal jejunum. Histological examination and immunohistochemical staining of the biopsy specimen strongly supported the diagnosis of metastatic lung adenocarcinoma, suggesting that small bowel metastases from primary carcinoma of the lung occur usually in patients with terminal disease and rarely produce symptoms. Gastrointestinal bleeding from metastatic small intestinal lesions should be included in the differential diagnosis of gastrointestinal blood loss in a patient with a known bronchogenic tumor.     

Assessing clinical communication skills in physicians: are the skills context specific or generalizable

Background  

Communication skills are essential for physicians to practice Medicine. Evidence for the validity and domain specificity of communication skills in physicians is equivocal and requires further research. This research was conducted to adduce evidence for content and context specificity of communication skills and to assess the usefulness of a generic instrument for assessing communication skills in International Medical Graduates (IMGs).