Non-ulcer Patients Research Articles

Anorectal Manometry in Patients With Fecal Incontinence After Ileal Pouch–Anal Anastomosis for Ulcerative Colitis: A Cohort Study

Abstract Background Fecal incontinence commonly occurs in patients with ulcerative colitis and ileal pouch–anal anastomosis. There is a paucity of manometric data in pouch patients. We aimed to better define manometric parameters in pouch patients with fecal incontinence. Methods We compared clinical and manometric variables in ulcerative colitis patients with pouch and fecal incontinence to ulcerative colitis patients with pouch without fecal incontinence and to non-ulcerative colitis patients with fecal incontinence. Manometric data for the 3 cohorts were compared to established normative data. An independent-samples t-test was performed for continuous variables, and chi-square test was used for categorical variables. Logistic regression was performed to identify predictors of incontinence in pouch patients (P < .05). Results Among 26 pouch patients with fecal incontinence (73% female), 26 pouch patients without fecal incontinence (35% female), and 84 patients with fecal incontinence without ulcerative colitis (68% female), there were no differences in anorectal pressures between patients with fecal incontinence. Lower pressures were observed in pouch patients with fecal incontinence compared to those without fecal incontinence. Resting pressure was similar between pouch patients with fecal incontinence and healthy controls (60.9 ± 36.1 mmHg vs. 66.9 ± 3.2 mmHg, P = .40). Female sex (P = .019) and defecatory disorders (P = .033) each independently predicted fecal incontinence in pouch patients. Conclusions Pouch patients with fecal incontinence have lower anorectal pressures compared to pouch patients without incontinence, though have similar pressures to non-ulcerative colitis patients with fecal incontinence. Pouch patients with fecal incontinence have similar resting pressures as healthy controls. Distinct manometric normative values for pouch patients are needed.

Integrated mRNA-miRNA transcriptome analysis of bladder biopsies from patients with bladder pain syndrome identifies signaling alterations contributing to the disease pathogenesis

BackgroundInterstitial cystitis, or bladder pain syndrome (IC/BPS), is a chronic bladder disorder characterized by lower abdominal pain associated with the urinary bladder and accompanied by urinary frequency and urgency in the absence of identifiable causes. IC/PBS can be separated into the classic Hunner’s ulcerative type and the more prevalent non-ulcerative disease. Our aim was to unravel the biological processes and dysregulated cell signaling pathways leading to the bladder remodeling in non-ulcerative bladder pain syndrome (BPS) by studying the gene expression changes in the patients’ biopsies.MethodsWe performed paired microRNA (miRNA) and mRNA expression profiling in the bladder biopsies of BPS patients with non-Hunner interstitial cystitis phenotype, using comprehensive Next-generation sequencing (NGS) and studied the activated pathways and altered biological processes based on the global gene expression changes. Paired mRNA-miRNA transcriptome analysis delineated the regulatory role of the dysregulated miRNAs by identifying their targets in the disease-induced pathways.ResultsEIF2 Signaling and Regulation of eIF4 and p70S6K Signaling, activated in response to cellular stress, were among the most significantly regulated processes during BPS. Leukotriene Biosynthesis nociceptive pathway, important in inflammatory diseases and neuropathic pain, was also significantly activated. The biological processes identified using Gene Ontology over-representation analysis were clustered into six main functional groups: cell cycle regulation, chemotaxis of immune cells, muscle development, muscle contraction, remodeling of extracellular matrix and peripheral nervous system organization and development. Compared to the Hunner’s ulcerative type IC, activation of the immune pathways was modest in non-ulcerative BPS, limited to neutrophil chemotaxis and IFN-γ-mediated signaling. We identified 62 miRNAs, regulated and abundant in BPS and show that they target the mRNAs implicated in eIF2 signalling pathway.ConclusionsThe bladders of non-ulcerative BPS patients recruited in this study had alterations consistent with a strong cell proliferative response and an up-regulation of smooth muscle contractility, while the contribution of inflammatory processes was modest. Pathway analysis of the integrated mRNA-miRNA NGS dataset pinpointed important regulatory miRNAs whose dysregulation might contribute to the pathogenesis. Observed molecular changes in the peripheral nervous system organization and development indicate the potential role of local bladder innervation in the pain perceived in this type of BPS.

Distribution of the Highest Plantar Pressure Regions in Patients with Diabetes and Its Association with Peripheral Neuropathy, Gender, Age, and BMI: One Centre Study.

The abnormal plantar pressure distribution and value play a key role in the formation of plantar calluses and diabetic foot ulcer. The prevalence of the highest pressure different distribution and its association with various factors among patients with diabetes is not well known. The study purpose was to evaluate the prevalence of different regions for the highest pressure on the sole and its association with selected factors among patients with diabetes. Medical records of nonulcer patients were retrospectively analysed. The relationship between pressure patterns on the sole obtained during a pedobarographic test as a semiquantitative assessment with colourful print analysis and neuropathy, gender, age, and BMI was searched. The most common location of the highest pressure was the central part of the forefoot. No association was found between the different highest pressure regions and age, sensory neuropathy, calluses, and foot deformities. The highest pressure on the lateral part of the foot and midfoot was observed more often in females and in patients with a BMI ≥ 35. The prevalence of the highest pressure on the forefoot was more common in patients with a BMI < 35. Conclusions. The most frequent regions of the highest pressure on the sole in patients with diabetes were the central part of the forefoot (2-3 metatarsal heads) with no simple relationship to the assessed variables other than BMI < 35. Female gender and higher BMI seem to be responsible for shifting the place of the highest pressure to other places of the foot.

Mitochondrial DNA Mutations are Associated with Ulcerative Colitis Preneoplasia but Tend to be Negatively Selected in Cancer

The role of mitochondrial DNA (mtDNA) mutations in cancer remains controversial. Ulcerative colitis is an inflammatory bowel disease that increases the risk of colorectal cancer and involves mitochondrial dysfunction, making it an ideal model to study the role of mtDNA in tumorigenesis. Our goal was to comprehensively characterize mtDNA mutations in ulcerative colitis tumorigenesis using Duplex Sequencing, an ultra-accurate next-generation sequencing method. We analyzed 46 colon biopsies from non-ulcerative colitis control patients and ulcerative colitis patients with and without cancer, including biopsies at all stages of dysplastic progression. mtDNA was sequenced at a median depth of 1,364x. Mutations were classified by mutant allele frequency: clonal > 0.95, subclonal 0.01-0.95, and very low frequency (VLF) < 0.01. We identified 208 clonal and subclonal mutations and 56,764 VLF mutations. Mutations were randomly distributed across the mitochondrial genome. Clonal and subclonal mutations increased in number and pathogenicity in early dysplasia, but decreased in number and pathogenicity in cancer. Most clonal, subclonal, and VLF mutations were C>T transitions in the heavy strand of mtDNA, which likely arise from DNA replication errors. A subset of VLF mutations were C>A transversions, which are probably due to oxidative damage. VLF transitions and indels were less abundant in the non-D-loop region and decreased with progression. Our results indicate that mtDNA mutations are frequent in ulcerative colitis preneoplasia but negatively selected in cancers. IMPLICATIONS: While mtDNA mutations might contribute to early ulcerative colitis tumorigenesis, they appear to be selected against in cancer, suggesting that functional mitochondria might be required for malignant transformation in ulcerative colitis.

Up-regulated Th17 cell function is associated with increased peptic ulcer disease in Helicobacter pylori-infection

BackgroundDuring Helicobacter pylori (H. pylori) infection CD4+ T cells in the gastric lamina propria are hyporesponsive and polarized by Th1/Th17 cell responses controlled by Treg cells. The objective of this study was to determine the number of Th17 cells in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Th17 cells. Methods and materialsA total of 89 H. pylori-infected gastritis patients, 63 H. pylori-infected peptic ulcer patients and 48 H. pylori-negative non-ulcer dysplasia patients were enrolled in this study. The number of Th17 was determined by immunohistochemistry. IL-8 and IL-17A expressions were determined by real-time polymerase chain reaction (qPCR). Also, the grade of chronic and active inflammation was investigated for involvement according to the density of neutrophils and mononuclear in gastric mucosal crypts, from one to all crypts. ResultsThe number of Th17 cells and the expression of IL-8 and IL-17A in infected patients were significantly higher than uninfected subjects. The number of Th17 cells and the expression of IL-8 and IL-17A in infected patients with peptic ulcer were significantly higher than patients with gastritis. Additionally, the numbers of Th17 cells as well as the expression of IL-8 and IL-17A were positively correlated with the degree of H. pylori density in infected patients with peptic ulcer, while this correlation was negative in infected patients with gastritis. The numbers of Th17 cells as well as the expression of IL-8 and IL-17A were positively correlated with the degree of chronic inflammation. ConclusionThe predominant Th17 cell responses may play a role in the pathogenesis of peptic ulcers disease in infected patients.

Status of Helicobacter pylori cag pathogenicity island (cagPAI) integrity and significance of its individual genes

One of the most important virulence factors of H. pylori is the intact cagPAI.The aim of the present study is to investigate cagPAI intactness among Bulgarian H. pylori isolates, its associations with clinical outcomes and vacA alleles, and to evaluate the significance of individual cagPAI genes. Material and methodsTotally, 156 isolates from 156 patients with endoscopic findings for duodenal or gastric ulcer (33 subjects), non-ulcer disease (121) and other diseases, such as Crohn's disease and hepatitis (2) were tested. Polymerase chain reaction (PCR) was used to detect 14 essential cagPAI genes, including cagA, as well as vacA s, i and m alleles. ResultsCagA positive were 81.4% of all H. pylori isolates. Intact cagPAI was found in 64.1% of the all isolates, 16.7% and 19.2% showed complete and partial cagPAI absence, respectively. The prevalence of all cagPAI genes and intact cagPAI was significantly higher in isolates from ulcer patients compared with those from non-ulcer patients (p = 0.001). The most frequently missing genes among the isolates with partially deleted cagPAIs were cagE or/and cagY (28 of 30 isolates). Overall prevalence of vacA s1a allele was 80.1% and that of vacA i1 was 64.1%. The vacA s1a, m1 and i1 alleles were more prevalent in H. pylori isolates from ulcer patients (p = 0.03, p = 0.009, and p = 0.0003, respectively) and were associated with isolates with intact cagPAI. ConclusionsIn Bulgaria the prevalence of intact cagPAI was high. cagE or/and cagY absence was the most important predictor of cagPAI status.

Long-term satisfaction and complications in women with interstitial cystitis undergoing partial cystectomy and augmentation enterocystoplasty

Objective: Interstitial cystitis (IC) is a chronic syndrome without effective definite treatment. Partial cystectomy with augmentation enterocystoplasty (AE) is considered a treatment of last resort for ulcer-type IC. This study investigated the long-term satisfaction and complications of IC patients undergoing AE. Methods: Fifteen IC (12 ulcer-type and 3 nonulcer-type) patients who underwent AE at a single medical center from 2010 to 2016 were retrospectively reviewed. The clinical symptoms and urodynamic study results of each patient were recorded before the operation. The long-term satisfaction of each patient was then evaluated using the global response assessment (GRA), and the postoperative symptoms were graded on a 4-point scale. The complications of AE were also recorded. Results: The mean age of the patients was 58.7 ± 12.7 years, and the mean follow-up period was 36.9 ± 23.1 months. The complications associated with AE included bladder stones, hydronephrosis, acute pyelonephritis, acute urinary retention, and recurrent bladder ulcers. The patients with ulcer-type IC who underwent AE reported better GRA results compared to those with nonulcer IC. The postoperative symptoms of bladder pain, dysuria, frequency, and urinary tract infection (UTI) were present in both groups of patients. No benefit was reported in all nonulcer IC patients. Conclusions: Although AE can improve bladder symptoms in ulcer-type IC patients, postoperative dysuria and UTI remain problems, and IC patients might have complications related to AE. Meanwhile, most of the patients with nonulcer IC reported no benefit from AE and hence AE should not be recommended.

MP29-07 DEVELOPMENT OF THE ULCERATIVE INTERSTITIAL CYSTITIS RISK SCORE (ICUS): A URINE-BASED MULTIPLE PROTEIN ASSAY TO PREDICT ULCERATIVE INTERSTITIAL CYSTITIS

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II1 Apr 2017MP29-07 DEVELOPMENT OF THE ULCERATIVE INTERSTITIAL CYSTITIS RISK SCORE (ICUS): A URINE-BASED MULTIPLE PROTEIN ASSAY TO PREDICT ULCERATIVE INTERSTITIAL CYSTITIS Laura Lamb, Joseph Janicki, Sarah Bartolone, Interstitial Cystitis Association, Bernadette Zwaans, Kenneth Peters, and Michael Chancellor Laura LambLaura Lamb More articles by this author , Joseph JanickiJoseph Janicki More articles by this author , Sarah BartoloneSarah Bartolone More articles by this author , Interstitial Cystitis AssociationInterstitial Cystitis Association More articles by this author , Bernadette ZwaansBernadette Zwaans More articles by this author , Kenneth PetersKenneth Peters More articles by this author , and Michael ChancellorMichael Chancellor More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.919AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial syndrome of severe pelvic and genitalia pain and compromised urinary function. A fraction of IC patients who are the most severe present with Hunner's ulcers or patches on their bladder walls, termed ulcerative IC (UIC). UIC is diagnosed by cystoscopy, however this is a painful and expensive procedure. The objective of this study was to determine if a calculated Interstitial Cystitis Ulcerative Risk Score (ICUS) based on non-invasive urinary cytokines could discriminate UIC patients from controls and non-ulcerative IC patients. METHODS A national crowdsourcing effort targeting IC/BPS patients resulted in 442 urine samples consisting of 153 IC patients (146 female, 7 male), 155 female controls, and 134 male controls were collected. Controls were age-matched. This consisted of 52 UIC patients (48 females, 4 male). Urinary cytokine levels were determined using Luminex assay. A predictive classification model was generated from this data using the scikit-learn machine learning library and the Python programming language. It provides a probability of ulcerative IC when the algorithm is supplied with the levels of three different proteins found in the urine. RESULTS A defined ICUS Score of 0 to 1 was calculated to predict UIC, or a bladder permeability defect etiology (Figure 1). If the ICUS is ≥ 0.5, then there is an 87% chance that the patient has ulcerative IC. If the ICUS is <0.5, there is an 87% chance that the patient does not have ulcerative IC. The three protein levels combined provide a much better prediction model versus any of the individual protein levels alone. CONCLUSIONS The ICUS Score quantifies UIC risk, indicative of a bladder permeability defect etiology, in a subset of IC patients. This provides a new clinical tool to improve diagnosing patients with suspected IC symptoms. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e382 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Laura Lamb More articles by this author Joseph Janicki More articles by this author Sarah Bartolone More articles by this author Interstitial Cystitis Association More articles by this author Bernadette Zwaans More articles by this author Kenneth Peters More articles by this author Michael Chancellor More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effectiveness of 7-Day and 14-Day Moxifloxacin-Dexlansoprazole Based Triple Therapy and Probiotic Supplement for Helicobacter Pylori Eradication in Thai Patients with Non-Ulcer Dyspepsia: A Double-Blind Randomized Placebo-Controlled Study

Background:Helicobacter pylori (H. pylori) is important cause of peptic ulcer and gastric cancer. Moxifloxacin is effective antibiotic for treatment for H. pylori. However, there were limited studies as first line therapy. Probiotics had been shown to decrease therapy-related side-effect and increase eradication rate. Aim of this study was to evaluate the efficacy of moxifloxacin-dexlansoprazole based triple therapy with probiotic for H. pylori treatment in Thailand.Methods:Patients with H. pylori infected gastritis were randomized to receive 7- or 14-day moxifloxacin-dexlansoprazole based triple therapy with probiotic or placebo. Regimen consisted of 60 mg dexlansoprazole twice daily, 400mg moxifloxacin once daily, 1g clarithromycin MR once daily. Probiotic used in this study was 282.5mg Saccharomyces boulardii (S. boulardii) in capsule prescribed twice daily. CYP2C19 genotyping, antibiotic susceptibility tests, and CagA genotyping were also done. Successful eradication was defined as a negative 13C-urea breath test at least 4 weeks after treatment.Results:Total of 108 subjects was enrolled (27 each to 7- and 14-day regimens with probiotic or placebo). Antibiotic susceptibility tests showed 29% fluoroquinolone, 19% metronidazole and 4% clarithromycin resistance. CYP2C19 genotyping demonstrated 43%, 47% and 11% were rapid, intermediate and poor metabolizers, respectively. CagA genes were positive in all patients. Eradication rates of 7-day and 14-day regimens with probiotic were 100%, and 93% respectively. There were no significant differences between eradication rate of 7-day and 14-day regimen with or without probiotics. Regarding side-effects, incidence of nausea, abdominal discomfort, bitter taste, and diarrhea were significantly lower in regimen with probiotic group compared with placebo(7.4%vs. 22.2%; p=0.028, 0.00%vs.14.8%; p=0.003, 35.2%vs.70.4%; p=0.0002, and 0.00%vs.9.3%; p=0.028, respectively).Conclusions:7-day moxifloxacin-dexlansoprazole therapy plus S. boulardii provide an reliable cure rate of H. pylori in non-ulcer dyspeptic patients in Thailand, independent of CYP2C19 genotype. Probiotic adding also decreased side effects during the treatment.

Helicobacter pylori Peptidyl Prolyl Isomerase Expression Is Associated with the Severity of Gastritis.

Helicobacter pylori secretory peptidyl prolyl isomerase, HP0175, is progressively identified as a pro-inflammatory and pro-carcinogenic protein, which serves to link H. pylori infection to its more severe clinical outcomes. Here, we have analyzed host HP0175-specific antibody responses in relation to the severity of gastritis. The HP0175 gene fragment was PCR-amplified, cloned, expressed and purified by Ni-NTA affinity chromatography. Serum antigen-specific antibody responses of non-ulcer dyspeptic patients (N=176) against recombinant HP0175 were detected by western blotting. The infectionstatus of these subjects was determined by rapid urease test, culture, histology, and serology. The grade of inflammation and stage of atrophy were scored blindly according to theOLGA staging system. The recombinant HP0175 (rHP0175)was expressed as a ~35kDa protein and its identity was confirmed by western blotting using anti-6X His tag antibody and pooled H. pylori-positive sera. Serum IgG antibodies against rHP0175 segregated our patients into two similar-sized groups of sero-positives (90/176, 51.1%) and sero-negatives (86/176, 48.9%). The former presented with higher grades of gastric inflammation (OR=4.4, 95% CI=1.9-9.9, P=0.001) and stages of gastric atrophy (OR = 18.3, 95 %CI = 1.4-246.6, P=0.028). Our findings lend further support to the pro-inflammatory nature of H. pyloripeptidyl prolyl isomerase (HP0175) and recommends this antigen as a non-invasiveserum biomarker of the severity of H. pylori-associated gastritis.

The Role of Immunoglobulin E in the Pathogenesis of Ketamine Related Cystitis and Ulcerative Interstitial Cystitis: An Immunohistochemical Study

Background: A previous study revealed elevated serum Immunoglobulin E (IgE) in ketamine related cystitis (KC) patients. IgE might participate the pathogenesis of different types of bladder pain syndromes, including KC and interstitial cystitis (IC). Objectives: To investigate the IgE expression in KC and IC bladder tissue. Study Design: Prospective evaluation. Setting: The study was conducted in a tertiary teaching hospital, Hualien Tzu Chi Hospital. Methods: We investigated the bladder IgE with immunofluorescence staining and quantification. The active mast cells were measuring using tryptase. The symptoms and urodynamic study results were recorded. Double immunofluorescence staining of tryptase and IgE was also performed. Sixteen KC patients, 10 ulcerative IC patients, and 20 non-ulcerative IC patients participated. The history and urodynamic parameters were investigated in these patients. The bladder mucosa was biopsied during cystoscopic hydrodistention. Bladder biopsies were also taken from 22 patients with bacterial cystitis and 12 healthy controls. Results: Bladder IgE was positive in 15 (93.8%) KC patients, 9 (90%) ulcerative IC patients, one (5%) non-ulcer IC patient, 8 (36.4%) bacterial cystitis patients, and 2 (16.7%) controls (P &lt; .001). The bladder IgE was greater in the patients with KC than in the others (P &lt; .001). After excluding KC patients, bladder IgE was significantly higher in the patients with ulcerative IC than the others (P &lt; .001). The bladder IgE was significantly correlated with pain on a visual analogue scale (r2 = 0.156, P = .017) and maximum bladder capacity (r2 = 0.423, P &lt; .001). Tryptase expression did not show a significant difference between KC, ulcer IC, and non-ulcer IC (P = 0.222). Double immunofluorescence staining showed co-expression of tryptase and IgE. Conclusions: IgE-mediated inflammation played a significant role in the pathogenesis of KC and ulcerative IC. Key words: Immunoglobulin E, ketamine cystitis, interstitial cystitis

Raised serum 25-hydroxyvitamin D levels in patients with active diabetic foot ulcers.

Studies have emerged to demonstrate bidirectional changes in circulating cytokines of inflammation in active diabetic foot ulcers (DFU). To further expand the understanding of inflammatory status present in chronic active DFU, we comparatively assessed the associations of selected pro-inflammatory cytokines and 25-hydroxyvitamin D (25(OH)D) with the presence of DFU. In a cross-sectional setting, thirty patients with type 2 diabetes and active DFU matched with thirty control non-ulcerative patients with type 2 diabetes and twenty-eight healthy subjects underwent anthropometric and biochemical assessment of study parameters. Recruited patients with DFU were selected from the grade II active chronic DFU at the time of hospitalisation according to the University of Texas wound classification system. Patients with DFU and controls had comparable age, sexual distribution, diastolic blood pressure and TAG, LDL-cholesterol and glycated Hb. The trend changes from healthy controls towards DFU showed a significant increase for serum monocyte chemoattractant protein-1, IL-6, 25(OH)D and highly sensitive C-reactive protein and a decrease for IL-8. In the multivariate adjusted logistic regression model, 25(OH)D emerged as the only independent correlate of DFU (OR 2·194; 95 % CI 1·003, 4·415). Unprecedented increase of serum 25(OH)D in chronic active DFU is possibly related to a selective alteration in the inflammatory status. In particular, 25(OH)D and IL-8 seem to share a common pathway in the pathogenesis of diabetic foot.

Determination of relative frequency of eosinophils and mast cells in gastric and duodenal mucosal biopsies in adults with non-ulcer dyspepsia.

To determine eosinophil and mast cell populations in gastric and duodenal mucosal biopsies of adults with nonulcer dyspepsia (NUD) as compared to non-dyspeptic adults. A case control study. Shahid Sadoughi University of Medical Sciences, Yazd, Iran, from January 2010 to June 2011. A total of 52 (25 non-ulcer dyspeptic patients as case and 27 non-dyspeptic patients as control) patients underwent endoscopy. All patients had a minimum of 2 forceps biopsies obtained from stomach and duodenum. Routine histological evaluation was performed and additionally evaluated to determine eosinophil and mast cell counts. The statistical analysis was performed on SPSS version 17.0, using Mann-Whitney test with significance at p < 0.05. The mean age in the case and control groups was 31.72 ± 12.17 and 35.74 ± 12.42 years respectively. The median eosinophil density in gastric mucosa in case group was 5.0 (ranging from 1 to 20) and 4.0 in control group (ranging from 0 to 16; p = 0.140). The median eosinophil density in duodenal mucosa in case group was 16.0 (ranging from 2 to 24) and 13 in control group (ranging from 2 to 45; p = 0.147). The median mast cell density in gastric mucosa in case group was 4.0 (ranging from 0 to 33) and 4.0 in control group (ranging from 0 to 26; p = 0.827). The median mast cell density in duodenal mucosa in case group was 4.0 (ranging from 0 to 31) and 3.0 in control group (ranging from 1 to 23; p = 0.704). The frequency of Helicobacter pylori infection in both the groups was similar. Although there were not statistically significant differences in eosinophil and mast cell densities between case and control groups, there was a trend toward mild eosinophilia in gastric and duodenal mucosa. The specific role of eosinophils and mast cells in NUD is yet to be completely defined.

Significance of Helicobacter pylori vacA intermediate region genotyping—a Bulgarian study

The significance of the intermediate (i) region of the Helicobacter pylori vacA gene as a virulence factor associated with the severity of gastric disease is still disputable. The aim of the present study was to evaluate the prevalence and significance of vacA i alleles alone or in combination with other vacA alleles in symptomatic Bulgarian patients and to find out possible associations between vacA i genotype and patients' disease, age, sex, and other H. pylori virulence factors. Unlike vacA s1 and m1, vacA i1 prevalence was significantly higher (75.0%) in strains from peptic ulcer patients than in strains from nonulcer patients with gastric diseases (58.6%) (P = 0.022). Less virulent vacA s1 i2 m2 strains were more prevalent in females (P = 0.03), and cagA+ was associated with vacA i1, s1, m1, and their combinations. In conclusion, vacA i status is a better predictor for the strain virulence than other vacA alleles.

Role of gastritis pattern on Helicobacter pylori eradication

Helicobacter pylori eradication rate following standard triple therapy is decreasing. Identification of predictive factors of therapy success would be useful for H. pylori management in clinical practice. This study aimed to evaluate the role of different gastritis patterns on the efficacy of the currently suggested 14-day triple therapy regimen. One-hundred and seventeen, consecutive, non-ulcer dyspeptic patients, with H. pylori infection diagnosed at endoscopy, were enrolled. All patients received a 14-day, triple therapy with lansoprazole 30 mg, clarithromycin 500 mg and amoxicillin 1 g, all given twice daily. Bacterial eradication was assessed with (13)C-urea breath test 4-6 weeks after completion of therapy. H. pylori infection was cured in 70.1% at ITT analysis and 83.7% at PP analysis. The eradication rate tended to be lower in patients with corpus-predominant gastritis as compared to those with antral-predominant gastritis at both ITT (66.1 vs 74.5%) and PP (80.4 vs 87.2%) analyses. The multivariate analysis failed to identify factors associated with therapy success. However, 14-day triple therapy does not achieve acceptable H. pylori cure rate in Italy, and should be not recommended in clinical practice.

Benefits of Helicobacter pylori cagE genotyping in addition to cagA genotyping: a Bulgarian study

Associations of Helicobacter pylori cagE status with complex patient characteristics remain to be elucidated in Eastern Europe. The aim of this study was to assess the frequencies of cagE gene and cagA/cagE combinations in H.pylori strains from symptomatic Bulgarian patients and to improve cagA detection. cagA and cagE genotypes were evaluated in 219 patients with single-strain infections. In total, 84.9% of strains were cagA (+), while 68.5% were cagE (+). cagA (+), cagE (+), and cagA (+)/cagE (+) strains were more prevalent in peptic ulcer (93.8%, 84.4%, and 84.4%) compared with nonulcer patients (81.3%, 61.9%, and 61.3%, respectively). In elderly patients, cagE (+) and cagA (+)/cagE (+) strains were 1.9-fold more common than in the 12 children evaluated. Only 10% of the elderly subjects harbored low-virulence cagA (+)/cagE (-) strains compared with 16.8% of adults and 41.7% of children. Intriguingly, prevalence of the cagA (+)/cagE (-) genotype was 2.1-fold lower in men than in women, suggesting a higher frequency of more virulent strains in men. The presence of both cag genes and combinations was not linked to strain susceptibility to clarithromycin or metronidazole, place of residence, or prior therapy. Use of an extra primer pair increased cagA detection in 14.7% of 31 cagA (-) strains. In conclusion, use of a second primer pair for the cagA gene can be recommended in countries with common cagA (+) strains. Although both cag genes were linked to severe diseases in Bulgarian patients, the best discrimination of virulent strains was obtained by the cagA/cagE combination or by the cagE gene alone. cagE prevalence increased gradually with patient age, while the cagA (+)/cagE (-) genotype, implying a disrupted cag pathogenicity island, was associated with both younger age and female gender.

Expressions of Uroplakin gene family in interstitial cystitis

Objective To detect gene expressions of Uroplakin (UP) family in interstitial cystitis (IC). Methods Gene expression of UP Ia, Ib, II, III, and III-δ4 was quantitatively measured in bladder biopsy samples from patients with IC (n=29) and control subjects (n=16) using real-time RT-PCR. Results UP III-delat4, a splicing variant of UP III, was significantly up-regulated to 4.80 in IC samples (P<0.001). When IC patients were divided into two groups, one with and one without ulcerative changes, the UP Ia, UP Ib, UP II, UP III and III-δ4 genes were significantly up-regulated to 4.99, 3.31, 2.75, 15.38, 11.48 in nonulcerative IC patients, but decreased to 0.04, 0.29, 0.09, 0.11, 0.34 in ulcerative IC patients (P<0.01). The up-regulation of UP III-δ4 was more prominent than that of UP III: 26.5-fold versus 5.6-fold compared to the median values of normal subjects. Conclusion Although the clinical implications of the over-expression of UP III and III-δ4 in non-ulcerative IC bladders remain to be clarified, from the diagnostic viewpoint, UP III-δ4 is a potential marker for identifying nonulcerative IC. Key words: Cystitis, interstitial; Uroplakin genes

Variations of plantar thermographic patterns in normal controls and non-ulcer diabetic patients: Novel classification using angiosome concept

Thermometry of the plantar skin temperature has been one of the important parameters for assessing ulceration risks in diabetic patients. Recent progress of infrared thermographic technology allows us to obtain imaging of temperature distribution of the whole plantar skin. However, it has not been fully elucidated to what extent the individual variation of the plantar thermographic patterns shows different trends between normal controls and diabetics. In this study, we made a novel framework of conceptual classification with 20 different categories of plantar thermographic patterns according to the foot angiosome concept. The thermographic images from 32 normal volunteers and 129 non-ulcer diabetic patients, recruited from Diabetes Foot Outpatient Clinic of the University of Tokyo Hospital, were allocated to the above-mentioned framework categories. In the normal group, thermographic patterns of more than 65% of feet were allocated to the two typical categories, including the 'butterfly pattern' among the 20 categories, whereas 225 feet (87.2%) of the diabetic groups were variously allocated to 18 out of the 20 categories. This is the first study, which describes detailed plantar thermographic patterns, showing wider variations in the diabetic patients than in the normal subjects. Thermography will be one of the screening options to assess circulatory status in both daily foot care and surgical intervention.

Comparison of 7- and 14-day first-line therapies including levofloxacin in patients with Helicobacter pylori positive non-ulcer dyspepsia

Because of the increasing resistance to clarithromycin and metronidazole, the most frequently used antibiotics in the first-line therapy of Helicobacter pylori eradication, new therapeutic alternatives are needed. The aim of this study was to compare the efficacy of 7- and 14-day triple therapy including lansoprazole, levofloxacin and amoxicillin for Helicobacter pylori eradication as a first-line therapy. Ninety-one non-ulcer dyspeptic patients infected with Helicobacter pylori as diagnosed by both histology and a rapid urease test were included in this study. Patients were randomized to receive either 7- (Group 1; 51 patients) or 14-day (Group 2; 40 patients) therapy with lansoprazole (30 mg b.i.d.), plus levofloxacin (500 mg o.i.d.) and amoxicillin (1000 mg b.i.d.) and they were followed for six weeks. Eradication was assessed by 14C-urea breath test four weeks after completing the treatment protocols. In Group 1, 41 patients completed the treatment and the eradication rate was 34.15%. In group 2, 36 patients completed the treatment and the eradication rate was 72.2% (p= 0.001 vs group 1). Triple therapy with lansoprazole, levofloxacin and amoxicillin for 14 days was effective for Helicobacter pylori eradication, but 7-day therapy with the same protocol had a lower and unacceptable cure rate and should not be used.

Comparative study of Nigella Sativa and triple therapy in eradication of Helicobacter Pylori in patients with non-ulcer dyspepsia

Background/Aim:A large number of diseases are ascribed to Helicobacter pylori (H. pylori), particularly chronic active gastritis, peptic ulcer disease and gastric cancer. Successful treatment of H. pylori infection with antimicrobial agents can lead to regression of H. pylori–associated disorders. Antibiotic resistance against H. pylori is increasing, and it is necessary to find new effective agents. Nigella sativa seed (NS), a commonly used herb, possesses in vitro anti-helicobacter activity. The present study was undertaken to evaluate the efficacy of NS in eradication of H. pylori infection in non-ulcer dyspeptic patients.Materials and Methods:The study was conducted on 88 adult patients attending King Fahd Hospital of the University, Al-Khobar, Saudi Arabia, from 2007 to 2008, with dyspeptic symptoms and found positive for H. pylori infection by histopathology and urease test. Patients were randomly assigned to four groups, receiving i) triple therapy (TT) comprising of clarithromycin, amoxicillin, omeprazole [n= 23], ii) 1 g NS + 40 mg omeprazole (OM) [n= 21], iii) 2 g NS + OM [n= 21] or iv) 3 g NS + OM [n= 23]. Negative H. pylori stool antigen test four weeks after end of treatment was considered as eradication.Results:H. pylori eradication was 82.6, 47.6, 66.7 and 47.8% with TT, 1 g NS, 2 g NS and 3 g NS, respectively. Eradication rates with 2 g NS and TT were statistically not different from each other, whereas H. pylori eradication with other doses was significantly less than that with TT (P < 0.05). Dyspepsia symptoms improved in all groups to a similar extent.Conclusions:N. sativa seeds possess clinically useful anti-H. pylori activity, comparable to triple therapy. Further clinical studies combining N. sativa with antibiotics are suggested.