Allelic frequency of the MCP-1 promoter −2518 polymorphism in the Turkish population and in Turkish patients with juvenile rheumatoid arthritis

Although genetic and environmental factors contribute to the pathogenesis of juvenile rheumathoid arthritis (JRA), the etiology and pathogenesis remain controversial. The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene −2518 (G/A) polymorphism in the healthy Turkish population and patients with JRA. Genomic DNA was collected from 66 JRA patients and 150 healthy individuals. To evaluate the association of the −2518 (G/A) MCP-1 gene polymorphism with the outcome of JRA, we analyzed the types of JRA and the score on the childhood health assessment questionnaire (C-HAQ score). In the healthy Turkish population, the frequencies of A and G alleles were 71 and 29%, respectively. No significant difference was observed between the JRA patients and healthy subjects in the distribution allelic and genotypic frequencies of the −2518 (G/A) MCP-1 gene polymorphism (p>0.05). However, the AG genotype was found to be higher and the AA genotype was found to be lower in the patients with systemic type JRA compared to those with the other types of JRA (p=0.019). When the JRA patients were evaluated according to the C-HAQ score, we found that the −2518 (G/A) MCP-1 gene polymorphism did not relate the prognosis (p>0.05). AG genotype was found to be higher in the systemic type of JRA. The results indicate that MCP-1 gene polymorphism might slightly associate with patients with systemic JRA. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of JRA in various populations because this polymorphism has a functional significance and an ethnic difference.     

Guidance on the development and validation of diagnostic tests that depend on nucleic acid amplification and detection

In order to comply with national and international clinical laboratory accreditation standards (e.g. the ISO 15189, Clinical Pathology Accreditation standards) and with the joint code of practice for research, there must be a method of assessing that test methods are “fit for purpose”. This document gives guidance on development and describes how a validation file is produced. A test method may be a commercial kit, an in-house assay or reagent or a set of reagents bought separately and used to prepare an in house assay.A validation file is needed for both current and new test procedures. The file may refer to data recorded in workbooks, papers and reports. Modifications to assays (including commercially available assays) necessitate either an update to the validation file or creation of a new file.This paper is intended to provide a generic framework for in-house assay development and validation of new nucleic acid amplification assays including real-time polymerase chain reaction (PCR).     

Ear,nose and throat involvement in patients with pemphigus vulgaris: correlation with severity,phenotype and disease activity

Background Pemphigus vulgaris (PV) is the most common clinical form of pemphigus that is characterized by easily ruptured or loose bulla formation on skin and/or mucosa. The frequency of the ear, nose and throat involvement of PV is not clearly defined. Objectives To evaluate the frequency of ear, nose and throat (ENT) involvement in patients suffering from PV who had been recently diagnosed or exacerbated under follow up and to determine the association with ENT symptoms, clinical involvement, severity and duration of pemphigus vulgaris. Materials and Methods The study group included a total of 38 PV patients comprising 24 new patients and 14 patients who showed exacerbations while on complete remission or under treatment. All patients were asked about ENT symptoms and endoscopic examination were performed to evaluate the presence of nasal, pharynx, larynx and ear involvement. Results Of the 38 patients, 33 (87%) had active PV lesions on endoscopic evaluation. Twenty‐five patients (66%) had lesions on pharynx, twenty‐one (55%) on larynx, twenty‐nine (76%) on nasal mucosa and four (10%) on the ear mucosa. ENT involvement was not associated with the severity and the clinical involvement of the disease. Pharyngeal and nasal involvement was significantly associated with symptoms, while laryngeal and ear involvement was not found to be significantly associated with symptoms. Nasal and ear involvement was not associated with the duration of the disease while pharyngeal and laryngeal involvement favored newly diagnosed patients. Conclusions Our results revealed that high number of patients with PV may present with active ENT lesions, furthermore patients with ear, nose and throat involvement may be asymptomatic and active lesions may be found in patients without any ENT symptoms. Therefore it should be considered that to understand the real extent of PV involvement, endoscopic ENT evaluation should be performed in patients with or without symptoms.     

Do the laryngopharyngeal symptoms and signs ameliorate by empiric treatment in patients with suspected laryngopharyngeal reflux?

Objectives

In clinical practice, antireflux medication is given almost always empirically without pH monitorization. We aimed to evaluate the improving effect of empiric antireflux treatment on layngopharyngeal symptoms and signs in patients with gastroesophageal reflux (GER) and suspected laryngopharyngeal reflux (LPR) according to reflux symptom index (RSI) and reflux finding score (RFS).

Methods

GER was determined by esophagogastroduedonoscopy and biopsy in 127 patients. RSI and RFS were calculated for each patient. The patients with a pathology other than LFR which may be responsible from laryngopharyngeal symptoms and signs were excluded from the study. Fifty patients whom were thought to have LPR according to RSI and RFS comprised the study group. After 12-weeks of antireflux treatment, RSI and RFS were calculated again. The statistical analyses were made according to the changes in the severity and frequency of each symptom and sign.

Results

There was statistically significant improvement in RSI and RFS after treatment when compared with initial scores. There was statistically significant improvement in severity of all symptoms and signs. Although there was quantitively decrease in frequency of some signs and symptoms, complete resolution of the disease was not observed generally.

Conclusion

Empiric antireflux treatment according to RSI and RFS is an effective method. Antireflux treatment has a significant improving effect on laryngopharyngeal symptoms and signs. There may be needed longer times of treatment for complete resolution of symptoms and signs.     

Vascular malformation in the infrapatellar (Hoffa's) fat pad

A 16-year-old girl presented with pain and swelling of her right knee for 2 years. Magnetic resonance imaging disclosed a mass in the infrapatellar fat pad. Arthroscopic removal of the lesion led to a histopathologic diagnosis of vascular malformation, which has not been reported exclusively in this location.     

Identification of frequency and distribution of the nine most frequent mutations among patients with 21-hydroxylase deficiency in Turkey

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders mainly due to defects in the steroid 21-hydroxylase (CYP21A2) gene. METHODS: To determine the mutational spectrum in the Turkish population, the CYP21A2 active gene was analyzed in 100 unrelated patients with the classical form of 21-hydroxylase deficiency using PCR and RFLP. RESULTS: Mutations were detected in 78 patients: 64 patients were homozygous for one mutation, seven patients were compound heterozygous with different mutations on each chromosome, two patients were homozygous for two different mutations, five patients were heterozygous, and 22 patients harbored none of the tested mutations. The most frequent mutation was IVS2-13A/C (28.5%), followed by large gene deletion (17%), Q318X (11.5%), I172N (4%), V281L (3.5%), R356W (3.5%), 8-bp (3%), complex alleles (2%), P30L (1%) and E6 cluster (1%). CONCLUSION: The distribution of mutation frequencies in our study was slightly different from those previously reported in Turkey and in other parts of the world.     

Interactive role of endothelial nitric oxide synthase gene polymorphisms in T2D with CAD and CAD patients of Punjab (North-West India)

Dysregulation of endothelial nitric oxide synthase (eNOS) activity causes the reduction in the production of nitric oxide (NO) which is an early indicator of type 2 diabetes (T2D) and cardiovascular complications. The present study evaluates the association of ?786 T?>?C, 894 G?>?T, and 4a/b polymorphisms of eNOS gene in total of 1223 individuals enrolling 307 coronary artery disease (CAD) cases, 486 T2D cases with (n?=?170) and without (n?=?316) CAD as the secondary macrovascular complication, and 430 healthy controls from Punjab (North-West India). Genotyping of ?786 T?>?C and 894 G?>?T polymorphisms was done with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the genotyping of 4a/b insertion/deletion polymorphism was done by PCR. The minor allele frequency (MAF) of ?786 T?>?C polymorphism was higher in CAD (21.8 %), T2D + CAD (22.4 %), and T2D cases (18.4 %) as compared to healthy controls (17.6 %). However, in single-locus analysis, no significant results were obtained for eNOS polymorphisms in any of the studied groups. Significant association of C-b-G haplotype with the risk of both CAD [P?=?0.003, odds ratio (OR)?=?1.89 (1.04–3.45)] and T2D [P?=?0.019, OR?=?1.69 (0.92–3.13)] was observed. Diplotype analysis showed that TbG/CbG haplotype combination conferred risk towards CAD and T2D [P?=?0.01, OR?=?2.04 (1.18–3.57); P?=?0.006, OR?=?2.13 (1.22–3.57), respectively]. Furthermore, phenotypic parameters like waist circumference, high-density lipoprotein, and waist to height ratio are significantly associated with 894 G?>?T genotypes among CAD patients. In conclusion, the eNOS polymorphisms did not provide any conclusive result individually; however, their interactive effect gives some insights towards eNOS role in the population of Punjab.     

Comparative Analysis of Mutational Profile of Sonic hedgehog Gene in Gallbladder Cancer

Digestive Diseases and Sciences - Gallbladder cancer has high incidence in northeastern India; mortality too is high as the disease is often diagnosed late. Numerous studies have shown the role of...     

Association of macrophage migration inhibitory factor gene −173 G/C polymorphism with prognosis in turkish children with juvenile rheumatoid arthritis

The objectives of this study were to determine genotypic and allelic frequencies of macrophage migration inhibitory factor (MIF) gene −173 G/C polymorphism in patients with juvenile rheumatoid arthritis (JRA) and to evaluate the association of the MIF −173 C allele with the outcome of JRA. Genomic DNA was collected from 67 JRA patients and 153 healthy individuals. To evaluate the association of the MIF −173 polymorphism with the outcome, we analyzed the data concerning the treatment regimen, duration of glucocorticoid treatment, score on the childhood health assessment questionnaire (C-HAQ) and the number of joints with active arthritis. Nonsignificant differences were observed between the study and control groups in the distribution of genotype and allele frequencies of the MIF gene −173 G/C polymorphism. In JRA patients, carrying a MIF −173 C allele, the number of disease modifying antirheumatic drugs required for the treatment was more, the duration of glucocorticoid treatment was significantly longer, and at the last visits the C-HAQ scores and the number of joints with active arthritis were significantly higher. MIF gene −173 C allele frequency did not differ between the controls and JRA patients. MIF −173 C allele did not confer increased susceptibility to JRA in our study group. Carriage of the MIF −173 C allele was found to be a strong predictor of poor outcome in all types of JRA.