Study of HLA DR and DQ Types in Patients with Pemphigus Vulgaris as Compared to that in Healthy Subjects

OBJECTIVES: Pemphigus is an acquired immunobullous disease of the skin and mucosa with genetic predisposition and autoimmune aetiology. HLA Class II genes are associated with pemphigus. IgG1 and IgG4 antibodies are the pathogenic antibodies in pemphigus of which IgG4 is associated with active disease. The primary objective of this study was to find out the HLA DR and DQ types in pemphigus vulgaris in India, and to compare it to that in normal healthy controls. Secondary objective was to look at the correlation between disease severity in terms of PDAI score and serum IgG4 levels. METHODS: A hospital based cross-sectional study done over a period of 10 months. The diagnosis of pemphigus was established by clinical examination, biopsy, DIF and anti-Dsg ELISA. Pemphigus vulgaris patients were enrolled for HLA DR and DQ typing by PCR-SSOP method. Renal transplant donors were taken as controls. Clinical examination and PDAI score was done in pemphigus vulgaris and foliaceus patients with active disease and it was correlated with serum total IgG4 levels in them. Chi-square test was applied to analyze the frequencies of HLA DR and DQ types in cases versus controls. Spearman Rho was used to correlate serum IgG4 levels and PDAI scores. Mann-Whitney U test was used to look for the association between HLA types and disease severity. RESULTS: The study included 72 patients, 54 (75%) pemphigus vulgaris and 18 (25%) pemphigus foliaceus. Mean age at disease onset for pemphigus vulgaris patients was 39.2 ±13.3 years, M : F ratio 1 : 1.45. In pemphigus foliaceus group mean age at disease onset was 44.3 ± 12.9 years, M:F ratio 3.5:1. The mean PDAI score was 23.5 in pemphigus vulgaris and 33.8 in foliaceus patients. Typical features on histopathology was seen in 88.4% pemphigus vulgaris cases and 100% foliaceus cases. DIF was positive in 91.4% vulgaris and 100% foliaceus cases. HLA typing was done in 50 patients and compared with 50 controls. HLA DRB1*14 was present in 94% cases versus 36% controls (p<0.001). HLA DQB1*05 was present in 94% cases versus 48% controls (p<0.001). The haplotype DRB1*14, DQB1*05 was present in 88% cases versus 28% controls (p<0.001). Negative association was found with DRB1*15 (14% cases versus 32% controls, p<0.05) and DQB1*06 (16% cases versus 38% controls, p<0.05). HLA DQB1*03 was associated with more severe disease. Mean serum IgG4 was 1114.4mg/L in pemphigus vulgaris patients and 1147.1mg/L in foliaceus patients. Positive correlation between PDAI and IgG4 levels was present in pemphigus vulgaris patients, but did not reach significance levels. This correlation was not observed in pemphigus foliaceus group

Clinical Findings and Pro-Inflammatory Cytokines in Dengue Patients in Western India: A Facility-Based Study

BACKGROUND: Descriptions of dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from Pune, Western India, with respect to clinical profile and pro-inflammatory cytokines. METHODOLOGY/PRINCIPAL FINDINGS: In 2005, 372 clinically suspected dengue cases were tested by MAC-ELISA and RT-PCR for dengue virus (DENV) aetiology. The clinical profile was recorded at the hospital. Circulating levels of IFN-gamma, TNF-alpha, IL-6, and IL-8 were assessed by ELISA and secondary infections were defined by IgM to IgG ratio. Statistical analysis was carried out using the SPSS 11.0 version. Of the 372 individuals, 221 were confirmed to be dengue cases. Three serotypes, DENV-1, 2 and 3 were co-circulating and one case of dual infection was identified. Of 221 cases, 159 presented with Dengue fever (DF) and 62 with Dengue hemorrhagic fever (DHF) of which six had severe DHF and one died of shock. There was a strong association of rash, abdominal pain and conjunctival congestion with DHF. Levels of IFN-gamma were higher in DF whereas IL-6 and IL-8 were higher in DHF cases (p<0.05). The mean levels of the three cytokines were higher in secondary compared to primary infections. Levels of IFN-gamma and IL-8 were higher in early samples collected 2-5 days after onset than late samples collected 6-15 days after onset. IFN-gamma showed significant decreasing time trend (p = 0.005) and IL-8 levels showed increasing trend towards significance in DHF cases (interaction p = 0.059). There was a significant association of IL-8 levels with thrombocytopenia and both IFN-gamma and IL-8 were positively associated with alanine transaminase levels. CONCLUSIONS/SIGNIFICANCE: Rash, abdominal pain and conjunctival congestion could be prognostic symptoms for DHF. High levels of IL-6 and IL-8 were shown to associate with DHF. The time trend of IFN-gamma and IL-8 levels had greater significance than absolute values in DHF pathogenesis

Extensive darier’s disease with pityriasis amiantacea, alopecia and congenital facial nerve palsy

We present a 65-year-old man with Darier disease with pityriasis amiantacea on the scalp, alopecia, and congenital facial nerve palsy

Extensive darier’s disease with pityriasis amiantacea, alopecia and congenital facial nerve palsy

We present a 65-year-old man with Darier disease with pityriasis amiantacea on the scalp, alopecia, and congenital facial nerve palsy

A study of safety and efficacy of dexmedetomidine in cystoscopy

Introduction: Outpatient performance of minimally invasive transurethral procedures, such as cystoscopy, will have a substantial effect on the protection of financial and workforce capital, but they must be tolerable. By providing sedation coupled with analgesia/anesthesia, normally induced by an anesthesiologist, the discomfort, restlessness and patient movements that can lead surgeon’s discomfort during the procedure can be solved. Aim: To study the efficacy and safety of&nbsp; Dexmedetomidine given at a dose of 0.5 µg /kg 10 minutes&nbsp; before &nbsp;cystoscopy. Material and methods: Prospective randomized controlled study done at Osmania General Hospital for a period of 2 months in Sixty patients presenting for cystoscopy in urology operation theatre were randomly assigned into two groups either Group-A or Group-B. Results:0.5 μ/kg of dexmedetomidine was administered 10 minutes prior to the procedure that was not accompanied by maintenance infusion and had no hemodynamic changes along with VAS of 3.78 intraoperatively (mild to moderate pain score) and VAS 2.89 (mild pain) postoperatively compared to the Placebo group sample, in which VAS was 7.2 intraoperatively and postoperatively 4.4 suggesting moderate to severe pain in the group.While in the dexmedetomidine group&nbsp; the OAA/S scale was 5 both intraoperatively and postoperatively indicating patient alertness during and after cystoscopy. Conclusion:Dexmedetomidine infusion even without loading dose provides safe, effective adjunct analgesia, without undesirable hemodynamic effects in cystoscopy

Asp299Gly and Thr399Ile polymorphism of TLR-4 gene in patients with prostate cancer from North India

Background: The etiological factors associated with prostate cancer (CaP) have not been completely understood as yet. Genetic predisposition and inflammation is fast emerging as risk factors for CaP is a key player in the innate immune response and plays role in immune- surveillance and inflammation. The present study was conducted to evaluate TLR-4 gene polymorphism in patients with CaP. Material and Methods: DNA was isolated from blood samples of 198 patients with CaP, 200 cases of Benign Prostatic Hyperplasia (BPH) and 119 controls. TLR-4 gene polymorphisms Asp299Gly and Thr399Ile were determined by Restriction Fragment Length Polymorphism (RFLP) technique using Nco1 and Hinf 1 restriction enzymes. All statistical calculations were performed using SPSS for windows, version 13 (SPSS Inc., Chicago, Illinois, USA) Results: A significantly high proportion of patients with CaP had AG genotype (16.6%) as compared to control (4.2%) [OR-4.4, 95% CI (1.57-13.26), P =0.0013] with respect to Asp299Gly single nucleotide polymorphism (SNP). AA genotype showed a protective effect towards CaP development [OR-0.39, 95% CI (0.18-0.83), P=0.007). A trend was observed towards development of BPH with respect to AG genotype (P=0.06). Thr399Ile SNP was not significantly different among the population groups studied. Conclusions: This finding highlights the genetic predispositions to CaP with respect to TLR-4 gene. Individuals with Asp299Gly polymorphism having AG genotype appear to have four fold higher risk for development of Prostate cance