Efficacy of systemic and intratympanic corticosteroid combination therapy versus intratympanic or systemic therapy in patients with idiopathic sudden sensorineural hearing loss: a randomized controlled trial.

OBJECTIVE: The present study was conducted to compare the rates of recovery from idiopathic sudden deafness after the treatment with oral and intratympanic corticosteroids in both mono and combination therapies. STUDY DESIGN: Triple-blind randomized clinical trial. SETTINGS: Tertiary referral hospital. SUBJECTS AND METHODS: A total of 112 patients who were admitted to the ENT emergency department randomly divided into three groups: an oral corticosteroid plus intratympanic placebo (systemic corticosteroid monotherapy group); an intratympanic corticosteroid plus oral placebo group (IT monotherapy group); and a combination therapy group (IT plus systemic combination group). All patients were treated additionally with antiviral and proton pomp inhibitor. An audiometry was performed once before beginning the therapies and again at the end of the therapy. RESULTS: Of the total of 112 patients, 32 received intratympanic (IT) corticosteroids, 45 were receiving systemic corticosteroids, and 35 were receiving a combination of the two. A total of 74 patients (66.1%) responded positively [response to treatment was calculated as gain of at least 10 dB in 10 dB in average threshold or with the minimum improvement of 15% in speech discrimination scores (SDS)] to corticosteroid therapy. No significant differences were observed between the three groups (IT, systemic group, and combination therapy group) in their overall response to treatment (p = 0.5). Patients who suffered from concomitant tinnitus and dizziness responded less positively to the treatment (p < 0.002). Positive family history of SSNHL seems to be negative prognostic factors in the response to treatment (p < 0.001). The response to treatment was not related to the pattern (p = 0.04) and initial severity of hearing loss (p = 0.9). CONCLUSION: This study did not find any difference in the rate of hearing improvement between systemic, intratympanic, and combined corticosteroid therapy for sudden hearing loss. LEVEL OF EVIDENCE: 1b.

Significance of Response to Hepatitis B Recombinant Vaccine in Subjects with Isolated Antibody to Hepatitis B Core Antigen.

BACKGROUND It is important to differentiate whether isolated anti-HBc is due to false positive results or the prior exposure to hepatitis B virus, because individuals with false-positive anti-HBc can benefit from vaccination and their blood can be safely transfused. To distinguish between these two conditions, we evaluated the serologic response to hepatitis B vaccine. METHODS Ninety subjects with isolated anti-HBc (cases) and 100 subjects with totally negative hepatitis B serologic markers (controls) were recruited to receive three doses of hepatitis-B (HB) vaccine. Thirty days after the first dose of the vaccine, anti-HBs titers were checked and individuals with anti-HBs titer >50 mIU/mL did not receive additional doses of the vaccine. However, others completed the vaccination course, and another blood sample was collected 30 days after the third dose to measure anti-HBs level. RESULTS Nineteen (21.1%) cases and three (3%) controls had no sero-conversion (anti-HBs titers <10 mIU/mL) 30 days after the third dose (p<0.0001). Primary response, defined as the development of anti-HBs antibody titers ≥10 mIU/mL 30 days after the third dose, was observed in 43 (47.8%) cases and 92 (92%) controls (p<0.0001). Also, 31.1% of cases developed anti-HBs titers ≥ 50 mIU/mL 30 days after the first dose of vaccine, but the rate was significantly lower (5%) in the control group (p<0.0001). Furthermore, half of the individuals with positive isolated anti-HBc developed protective levels of anti-HBs after three doses of HB vaccination. CONCLUSION More than 75% of individuals with positive isolated anti-HBc can benefit from vaccination and can be included in donor pool. Also, one fifth seemed to have occult HBV infection. So HB vaccination may be used as a diagnostic tool for clarifying the situation of the subjects with isolated anti-HBc.

Time trend analysis and demographic features of inflammatory bowel disease in Tehran.

AIM: This retrospective study is aimed to review demographic and clinical characteristics of IBD to elucidate the probable factors associating with IBD development in Taleghani Hospital in Iran since 2001 during a 12-year-period. BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are two major idiopathic entities of inflammatory bowel disease (IBD). Previous studies have reported an increased incidence of IBD in Middle East countries. PATIENTS AND METHODS: In the present study 1914 patients with UC, 318 patients with CD and 25 with indeterminate colitis (IC) were included. Demographic information, clinical features, extraintestinal manifestations, complications and extension of disease were collected and interpreted for all participants. According to the time of registration, patients were divided into seven groups. Statistical analysis was performed using the chi-square test. RESULTS: In seven groups of IBD patients, disease registry was estimated for UC, CD, and total IBD during a 12-year-period. From 2001 to 2005, a relative increased registry was observed among UC patients. However, in the years 2006 and 2007 a ​​significant reduction in the number of patients was reported. Then an increasing trend was observed in UC patients. UC presented mostly with diarrhea, hematochezia and bloody diarrhea, while most of CD patients complained of abdominal pain. CONCLUSION: Evaluation of data related to registered IBD patients in Iran shows that probable incidence and prevalence of IBD (UC and CD) is increasing compared to previous decades.

Target antigens for perinuclear antineutrophil cytoplasmic antibodies in Iranian patients with ulcerative colitis.

UNLABELLED: BACKGROUND Patients with ulcerative colitis (UC) carry autoantibodies such as perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). OBJECTIVE: The aim of the present study was to evaluate the target antigens for p-ANCA in Iranian patients with UC. METHODS p-ANCA target antigens including elastase, lactoferrin, cathepsin G, myeloproxidase, lysozyme, and bactericidal permeability increasing protein (BPI) were determined in 113 patients with UC using enzyme-linked immunosorbent assay (ELISA). RESULTS 59.2% of the patients were positive for at least one antigen and p-ANCA directed against lactoferrin, elastase, lysozyme, cathepsin G, Bactericidal permeability increasing protein, and myeloproxidase in 31.5%, 25.9%, 8.3%, 7.4%, 5.6%, and 0% of the patients, respectively. CONCLUSION The highest prevalence of p-ANCA was observed against lactoferrin and elastase. Also, myeloproxidase was not an antigen for p-ANCA among our patients.

Association of Tumor Necrosis Factor Alpha Gene Polymorphisms with Inflammatory Bowel Disease in Iran.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology, in which genetic factors, seem to play an important role in the disease predisposition and course. Assessment of tumor necrosis factor (TNF-α) gene polymorphisms in many populations showed a possible association with IBD. Considering the genetic variety in different ethnic groups, the aim of the present study was to investigate the association of five important single nucleo-tide polymorphisms (SNPs) in the promoter region of (TNF-α) gene with IBD in Iran. METHODS: In this case-control study, 156 Ulcerative colitis (UC) patients, 50 Crohn's disease (CD) patients and 200 sex and age matched healthy controls of Iranian origin were enrolled. The study was performed during a two year period (2008-2010) at Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. DNA samples were evaluated for (TNF-α) gene polymorphisms (including -1031, -863, -857, -308 and -238) by PCR and RFLP methods. RESULTS: The frequency of the mutant allele of -1031 polymorphism was significantly higher in Iranian patients with Crohn's disease compared to healthy controls (P=0.01, OR=1.92; 95% CI: 1.14-3.23). None of the other evaluated polymorphisms demonstrated a significant higher frequency of mutant alleles in Iranian IBD patients compared to controls. CONCLUSION: Among the five assessed (SNPs), only -1031 polymorphism of (TNF-α) gene may play a role in disease susceptibility for Crohn's disease in Iran. This pattern of distribution of (TNF-α) gene polymorphisms could be specific in this population.

Modified retro-tubercle opening-wedge versus conventional high tibial osteotomy.

Despite the fact that common surgical techniques for the treatment of genu varum usually correct the malalignment in the affected knee, these methods have significant complications and cause problems in the long term. Retro-tubercle opening-wedge high tibial osteotomy is among the newer techniques for the treatment of genu varum. The goal of this study was to compare the results of retro-tubercle opening-wedge high tibial osteotomy with those of medial opening-wedge osteotomy. In a randomized, controlled trial, 72 patients with varus knees who were scheduled for surgery were assigned into either the retro-tubercle opening-wedge high tibial osteotomy (n=34) or medial opening-wedge osteotomy groups (n=38). Groups were matched for age and sex. The position of the patella was compared with respect to the tuberosity and the upper tibial slope pre- and postoperatively. Patients were followed for an average of 13 months (range, 10-21 months). In the retro-tubercle opening-wedge high tibial osteotomy group, the length of the patellar tendon did not significantly differ pre- and postoperatively (P≥.5); however, in the medial opening-wedge osteotomy group, a statistically significant shortening was noted in patellar tendon postoperatively (P≤.05). Similarly, the tibial plateau inclination showed a statistically significant difference postoperatively in the medial opening-wedge osteotomy group, while the difference in the retro-tubercle opening-wedge high tibial osteotomy group did not reach statistical significance.

NOD2 exonic variations in Iranian Crohn's disease patients.

PURPOSE: The NOD2 gene is known to have a strong association with Crohn's disease, but different trends were reported in occurrence of NOD2 variants in distinct ethnicities. The aim of this study was to assess all exonic sequences of the NOD2 gene in Iranian Crohn's disease patients and healthy controls to identify any existing variation and evaluate their association with Crohn's disease. METHODS: A total of 90 non-related Crohn's disease patients and 120 sex- and age-matched healthy controls of Iranian origin were enrolled in this study. The participants were referred to a tertiary center in a 2-year period (2006-2008). The exonic regions of the NOD2 gene were amplified by polymerase chain reaction and evaluated by direct sequencing. RESULTS: A total of 21 sequence variations were identified among all exonic regions of the NOD2 gene, of which eight had an allele frequency of more than 5%. Eight new mutations (one in exon 2 and seven in exon 4) were observed. The three main variants (R702W, G908R, and 1007fs) showed allele frequencies of 13.3%, 2.2%, and 1.7%, respectively. Three new variations (P371T, A794P, and Q908H) and R702W mutation were significantly more frequent in Crohn's disease patients compared to controls. CONCLUSIONS: Eight novel mutations were identified in the NOD2 exons, but the pathophysiological importance of these variants remains unclear. Iranian patients with their different genetic reservoirs may demonstrate some novel characteristics for disease susceptibility.

Prevalence of celiac disease among blood donors in Sistan and Balouchestan Province, Southeastern Iran.

BACKGROUND: The prevalence of celiac disease is common in Iran. The aim of the present study was to determine the prevalence of celiac disease in apparently healthy blood donors of Sistan and Balouchestan Province, southeastern Iran. METHODS: Serum samples of 1600 consecutive apparently healthy blood donors at Zahedan Blood Donation Center were assayed for anti-tissue transglutaminase (tTG) antibody. The levels of IgG antibodies against tTG were screened for all subjects with IgA deficiency. All subjects with positive anti-tTG IgA or IgG were offered upper gastrointestinal endoscopy and duodenal mucosal biopsies. RESULTS: IgA deficiency was found in 28:1600 (1.8%) of the subjects, among whom 4 cases were positive for IgG-class tTG antibody. Meanwhile, 10 blood donors were positive for anti-tTG IgA antibody. With the exception of 2 subjects who had normal small bowel biopsies, the remainder of the subjects' biopsy findings were compatible with celiac disease. The prevalence of celiac disease was found to be 0.88% (1/114) based on tTGA positivity. CONCLUSION: The prevalence of celiac disease among the southeastern Iranian population is high and comparable with other parts of Iran as well as many other countries.

Diagnostic value of antineutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibody in Iranian patients with inflammatory bowel disease.

BACKGROUND AND STUDY AIMS: Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) and anti-Saccharomyces Cerevisiae antibody (ASCA) are potential markers for diagnosis of inflammatory bowel disease (IBD). The aim of the present study was to evaluate the diagnostic value of pANCA and ASCA in Iranian patients with IBD. PATIENTS AND METHODS: Serum samples were collected from 144 patients with IBD (113 ulcerative colitis and 31 Crohn's disease) and patients with non-IBD problems were assayed for ASCA by Enzyme-Linked Immunosorbent Assay (ELISA) and for pANCA by indirect immunofluorescence assay. RESULTS: Sensitivity and specificity of pANCA in UC were 39.8% and 82.1%, respectively. For CD, pASCA test provided the sensitivity of 58% and specificity of 70%. A combination of pANCA+/ASCA- for diagnosis of UC showed a sensitivity of 31.9% and specificity of 89.1%. In addition the combination of pANCA-/ASCA+ showed a sensitivity of 35.5% and specificity of 79.8% for diagnosis of CD. CONCLUSION: Due to low sensitivity of pANCA and ASCA alone or in combination, they are not valuable serological markers for diagnosis of UC or CD.

Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease.

BACKGROUND AND AIMS: The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be linked to inflammatory bowel disease (IBD). Many studies have recognized the relation of VDR gene polymorphisms with inflammatory and autoimmune disorders. Determining the frequency of these polymorphisms and their possible relation with IBD can improve understandings about the genetic background of these diseases. The objective of this study was to assess the association of VDR gene polymorphisms (Apa I, Taq I, Bsm I, Fok I) with IBD in Iran. METHODS: In this case control designed study 150 patients with ulcerative colitis, 80 patients with Crohn's disease and 150 Age and Sex matched healthy controls from Iranian origin were enrolled. These patients were referred to a tertiary center during a two-year period (2004-2006). Assessment of VDR gene polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype-phenotype association for these polymorphisms was analyzed. RESULTS: Only the frequency of the Fok I polymorphism was significantly higher in ulcerative colitis and Crohn's groups. The frequency of the polymorphic allele f was higher in ulcerative colitis and Crohn's patients comparing with controls (P = 0.011 and P < 0.001, respectively). The f/f genotype was also significantly more frequent (P < 0.001), while the F/F genotype was less presented in Crohn's patients compared to controls (P < 0.001). No genotype-phenotype association was observed with any mutations. CONCLUSIONS: This study suggests a probable association of the Fok I polymorphism in VDR receptor gene and Crohn's susceptibility in Iranian population.

Frequency of three common mutations of CARD15/NOD2 gene in Iranian IBD patients.

BACKGROUND: The CARD15/NOD2 gene, located on the pericentromeric region of chromosome 16 (IBD1) has been reported to have an association with IBD, especially Crohn's disease. Three common mutations of CARD15 are variably associated with Crohn's disease in different ethnic groups. We evaluated the frequency of these mutations (R702W, G908R and 1007fsinsC) in Iranian IBD patients and compared it with the healthy control population. METHODS: One hundred patients with ulcerative colitis, 40 patients with Crohn's disease, and 100 sex- and age-matched controls were enrolled from a tertiary center during a one-year period (2005-2006). The three mutations were assessed in DNA of leukocytes by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of R702W mutation was significantly higher in Iranian patients with Crohn's disease (p< 0.001; OR 19.21; 95% CI 4.23-87.32) compared to healthy controls. No association was observed between the other mutations and Crohn's disease and none of these mutations was associated with ulcerative colitis. CONCLUSION: The R702W mutation of CARD15 gene was associated with Crohn's disease in the Iranian population.

A decision tree-based approach for determining low bone mineral density in inflammatory bowel disease using WEKA software.

BACKGROUND: Decision tree classification is a standard machine learning technique that has been used for a wide range of applications. Patients with inflammatory bowel disease (IBD) are at increased risk of developing low bone mineral density (BMD). This study aimed at developing a new approach to select truly affected IBD patients who are indicated for densitometry, hence, subjecting fewer patients for bone densitometry and reducing expenses. MATERIALS AND METHODS: Simple decision trees have been developed by means of WEKA (Waikato Environment for Knowledge Analysis) package of machine learning algorithms to predict factors influencing the bone density among IBD patients. The BMD status was the outcome variable whereas age, sex, duration of disease, smoking status, corticosteroid use, oral contraceptive use, calcium or vitamin D supplementation, menstruation, milk abstinence, BMI, and levels of calcium, phosphorous, alkaline phosphatase, and 25-OH vitamin D were all attributes. RESULTS: Testing showed the decision trees to have sensitivities of 65.7-82.8%, specificities of 95.2-96.3%, accuracies of 86.2-89.8%, and Matthews correlation coefficients of 0.68-0.79. Smoking status was the most significant node (root) for ulcerative colitis and IBD-associated trees whereas calcium status was the root of Crohn's disease patients' decision tree. CONCLUSION: BD specialists could use such decision trees to reduce substantially the number of patients referred for bone densitometry and potentially save resources.

Factors influencing success rate of leukocyte immunization and anti-paternal antibodies in spontaneous recurrent miscarriage.

PROBLEM: Paternal leukocyte immunotherapy has been used as treatment for spontaneous recurrent miscarriage; however, controversies have raged against the factors influencing its success. METHODS: Five hundred and forty-nine women with three or more unexplained pregnancy losses were offered immunization. Two weeks after the second immunization, serum was tested for anti-paternal cytotoxic antibody (APCA) by cross matching and if revealed positive she was advised pregnancy. Meanwhile, decision trees have been developed by Waikato Environment for Knowledge Analysis package to predict factors influencing APCA production and pregnancy. RESULTS: Of 549 subjects, 93 (16.9%) revealed to have positive APCA, among whom 49(52.7%) had clinically successful pregnancy (> or =28 weeks). Patient's age, consanguinity between couples and previous history of surgery, and infectious, endocrine, immunologic, uterine and cervix disorders were inversely associated with APCA production and clinically successful pregnancy, whilst, number of children was a potent positive predictor. CONCLUSION: Leukocyte immunization could be borne in mind as a therapeutic approach in selected subjects. Younger females with negative past medical history who are not frequent aborters are more likely to take benefit from this therapeutic approach if they do not have any familial relationship with their spouse.

The frequency of C3435T MDR1 gene polymorphism in Iranian patients with ulcerative colitis.

BACKGROUND AND AIMS: The MDR1 (multidrug resistance) gene, located on chromosome 7, is in one of the inflammatory bowel disease susceptibility loci. It produces P-glycoprotein, a transmembrane efflux pump, transferring drugs and toxins from intracellular to extracellular domains. In the human gastrointestinal (GI) tract, P-glycoprotein is found in high concentrations on the epithelial cells of the colon and small intestine. MDR1 gene polymorphisms such as C3435T are associated with lower P-glycoprotein expression, and thus it is suggested to have an association with ulcerative colitis. We tried to determine the frequency of C3435T polymorphism of the MDR1 gene in Iranian patients with ulcerative colitis and to compare it with a healthy control population. MATERIALS AND METHODS: In this case-control-designed study, 300 unrelated ulcerative colitis patients and 300 sex-and-age-matched healthy controls were enrolled. They were visited at a tertiary center during a 2-year period (2003-2005). DNA of patients and controls was amplified by polymerase chain reaction with specific primers, and C3435T polymorphism was detected by the restriction fragment length polymorphism method. RESULTS: The frequency of the 3435T allele was significantly higher in ulcerative colitis patients compared to the controls (p < 0.001). The frequency of homozygote T/T and heterozygote C/T genotypes were also significantly higher in Iranian patients with ulcerative colitis (p = 0.044 and 0.041, respectively). CONCLUSION: This study suggests that C3435T polymorphism of the MDR1 gene has an association with ulcerative colitis in Iranian population as previously reported in western countries.

Bone mineral density in Iranian patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk of developing osteopenia and osteoporosis. The aim of the study was to investigate the prevalence of decreased bone density and related risk factors in Iranian IBD patients. A total of 126 ulcerative colitis (UC) and 39 Crohn's disease (CD) patients were enrolled. Dual-energy x-ray absorptiometry technique was used to measure bone density, and blood samples were obtained to measure biochemical markers. To find predictive variables for bone mineral density (BMD), stepwise regression analysis was carried out. A total of 53 IBD patients (32.1%) had diminished bone mineral density at either lumbar spine (L1-L4) or femoral neck. Of these, 9 (5.4%) had osteoporosis; however, 44 (26.7%) were osteopenic. Femoral neck bone density was significantly decreased among CD patients (p<0.04). There was no significant difference in BMD between men and women. We have found significant differences in BMD T scores at lumbar L1-L4, L2-L4, and femoral neck in corticosteroid ever-users (p<0.002, p<0.001, p<0.003, respectively). There was no significant difference in biochemical markers between UC and CD patients, except that more CD patients were hypocalcemic (p<0.001). Stepwise regression analysis has revealed lumbar spine T score was predicted by age (p<0.0001), corticosteroid use (p<0.002), and body mass index (BMI) (p<0.005); however, femoral neck was predicted by age (p<0.0001), BMI (p<0.0001), smoking (p<0.009), and corticosteroid use (p<0.028). Low bone density in Iranian UC and CD patients is in accordance with Western societies. Treatment with corticosteroid has increased this possibility in both groups. Corticosteroid use, age, smoking, and BMI are predictive factors for low bone density.

Appendectomy, tonsillectomy, and risk of inflammatory bowel disease: a case control study in Iran.

There is some controversy about the prevalence of appendectomy and tonsillectomy among patients with Crohn's disease and a lower rate of appendectomy among patients with ulcerative colitis (UC). The objective of this study was to elucidate the role of appendectomy and tonsillectomy in Iranian patients with inflammatory bowel disease (IBD). Three hundred and eighty-two consecutive cases of UC and 46 cases of CD were included. Age and sex-matched controls were randomly selected. A total of 382 controls for UC and 184 controls for CD were enrolled. A standard record concerning smoking habit, history of appendectomy and tonsillectomy, OCP, and NSAID use was completed. Logistic regression analysis was used to evaluate potential confounding variables. Twelve patients (3.1%) with UC reported a previous history of appendectomy compared with 30 controls (7.9%) (OR=0.38, 95%CI=0.19-0.76, P<0.004). Appendectomy was reported by five patients (10.9%) with CD compared with four controls (2.2%) (OR=5.49, 95%CI=1.41-21.34, P<0.02). The logistic regression analysis showed that appendectomy is a risk factor in CD but has a modest protective effect for development of UC. No association with tonsillectomy was found for either disease. A statistically significant protective effect for smoking in UC was found (OR=0.2, 95%CI=0.13-0.32, P<0.0001). We have found an inverse association between OCP and NSAID use with UC, but not CD (P<0.0001 and P<0.001, respectively). Appendectomy is protective in UC, but a risk factor in CD among Iranian population. Tonsillectomy was not associated with either UC or CD disease. UC, but not CD, is a disease of non-smokers. The inverse association between ulcerative colitis and OCP or NSAID in the Iranian population is noted.

Inflammatory bowel disease in Iran: a review of 457 cases.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) was believed to be infrequent in Iran; however, unofficial reports have confessed the continuing rise in IBD in our country. METHODS: Demographic and clinical features, extraintestinal manifestations, extension of disease and complications of 401 patients with ulcerative colitis (UC), 47 with Crohn's disease (CD), and nine with indeterminatn colitis (IC) were assessed retrospectively. The exact course of physicians' visits of 250 IBD patient was asked through face-to-face interview. RESULTS: Mean age at diagnosis was 31.9 years in UC and 30.5 years in CD patients. The male to female ratio was 0.8 for UC and 1.3 for CD. The percentage of CD and UC patients who were non-smokers was 82.9 and 84.5%, respectively. Patients with UC presented with rectal bleeding (41.9%), whereas those with CD complained of abdominal pain (46.9%). Among UC patients, proctosigmoid was affected in 51.9%. Colorectal cancer was diagnosed in two patients. The mean lag time between the onset of symptoms and definite diagnosis was 13.9 and 17.7 months for UC and CD patients, respectively. A total of 32.4% of patients with IBD had at least one of the five major extra-intestinal diseases. CONCLUSION: The demographic and clinical picture of IBD is more or less the same as that of other developing countries; however, the rarity of CD in Iran is noted. Although the true epidemiologic profile of IBD in Iran is still unknown, it is not as rare as previously thought, and it seems as if gradual adoption of a Western lifestyle may be associated with the continuing rise in IBD.