Wilson disease (WD) is an autosomal recessive disorder of copper metabolism, characterized by its accumulation in tissues which results in hepatic, neurological, and/or psychiatric symptoms. The aim ...of this study was to investigate the genetics of WD in Croatian patients.
Correlation of the clinical presentation subtype and the age at onset of the diagnosis of WD with the ATP7B genotype was investigated in a group of Croatian WD patients. DNA from peripheral blood samples was tested for the p.His1069Gln by direct mutational analysis and other polymorphisms were identified by sequence analysis of coding and flanking intronic regions of ATP7B gene.
In the group of 75 WD patients of Croatian origin, 18 different mutations in ATP7B gene were detected, three of which were novel. The p.His1069Gln mutation was most frequent, being detected in 44 Croatian WD patients (58.7%). Most ATP7B mutations (90.4%) were located in exons 5, 8, 13, 14, and 15.
Clinical diagnosis of WD was confirmed in 59 patients by detecting mutations on both ATP7B alleles. The age at onset of WD and the type of WD clinical presentation showed no significant correlation with the ATP7B genotype.
The term inflammatory bowel disease (IBD) denotes a genetically, immunologically and histopathologically heterogeneous group of inflammatory bowel disorders classified at present time as ulcerative ...colitis (UC), Crohn's disease (CD) and indeterminate colitis (IC). Diagnosis of IBD is based on a non-strictly defined combination of clinical and diagnostic parameters. In order to guide the treatment, patients must be assessed by determining IBD phenotype, disease extension and distribution, extraintestinal manifestations, disease behavior, disease severity and drug responsiveness. Each element of the diagnostic process cannot be looked at alone, but has to be incorporated into general clinical assessment, bearing in mind that different phenotypes and age groups require specific diagnostic solutions. Advances in technology provided the possibility for the assessment of the entire digestive system with endoscopy leading the way. Sophisticated imaging methods made the analysis of the bowel wall with its vascularity and adjacent mesentery possible. The challenge is still the small bowel, where a combination of endoscopy and imaging methods is used. The use of imaging methods should be, among other things, guided by level of irradiation which is especially important in young patients and in patients requiring repeated investigations. Using abdominal ultrasound as a low-cost, noninvasive procedure, one has to take into account that it is very operator-dependent method. In UC, endoscopy is used for the evaluation of the extent and activity of the disease and to assess complications like stricture, dysplasia and cancer. UC is classified by the disease extent into proctitis, left-sided colitis and extensive colitis beyond the splenic flexure. Pediatric patients with UC have more extensive disease than adults with rectal sparing in up to 30% of patients. The severity of mucosal changes are reported as Baron endoscopic score. Endoscopic findings correlate well with clinical activity and are commonly incorporated into Mayo index, combination of clinical Truelove Witts index and Baron score. Complications like strictures require imaging methods as supplement to endoscopy. The incidence of CD, particularly in children and adolescents, has risen during the past decade, with children often having extensive and severe disease The nature of CD requires the use of wide array of endoscopic and imaging methods, placed properly in the diagnostic algorithms for specific disease phenotypes and complications and adapted for specific age groups. Endoscopic features of CD are very variable and can be quantified as Crohn's Disease Endoscopic Index of Severity (CDEIS) or Simple Endoscopic Score for CD (SES-CD). Disease activity is most commonly assessed by CDAI. Perianal disease activity should be measured by PDAI due to low CDAI scores in these patients. The activity of CD in children should be assessed by the Pediatric Activity Index. IC is part of the IBD spectrum where chronic colitis cannot be defined as either UC or CD after sequential colonoscopies and colonic biopsies or at colectomy.
Upalne bolesti crijeva, osobito Crohnova bolest, karakterizirane su intermitentnim tijekom bolesti, gdje svaki relaps bolesti dovodi do dodatnog oštećenja crijeva s rezultirajućim komplikacijama i ...potrebom za čestim hospitalizacijama i kirurškim zahvatima. Stoga se današnja terapija bazira na akceleriranom “step-up” pristupu gdje se što ranije nastoje uključiti najdjelotvorniji lijekovi kako bi rano zaustavili destruktivni upalni proces i prevenirali komplikacije. Ključni uvjet za postizanje duge stabilne remisije jest mukozno cijeljenje koje se definira kao endoskopska remisija, odnosno odsutnost mukoznih ulceracija. Mukozno cijeljenje samo je inicijalni, ali bitan događaj u supresiji upale u dubljim slojevima stijenke crijeva. U radu se opisuju mehanizmi procesa mukoznog cijeljenja te djelotvornost danas dostupnih lijekova u postizanju mukoznog cijeljenja. Ostaju mnoga otvorena pitanja poput izbora trenutka prekida biološke terapije te razvoja lijekova s alternativnim mehanizmima djelovanja važnih za bolesnike koji ne reagiraju na anti-TNF-terapiju.
Abstract Background Statin treatment was shown to be associated with improved outcomes in several inflammatory conditions. We wanted to evaluate the effects of statin therapy on the course and ...outcome of acute pancreatitis (AP). Methods A prospective cohort study included patients with acute pancreatitis divided into two groups according to statin use prior to hospitalization. Age, sex, etiology of AP, Ranson's score, APACHE II score and maximal CRP were recorded. Outcome measures were hospital length of stay and mortality. Matching of patients for matched analyses was done using individual matching and propensity score matching using variables a priori associated with course and outcome of acute pancreatitis. Results Inclusion criteria were met for 1062 patients of whom 92 were taking statins. Statin users were older and had higher body mass indexes. Severe disease was more common in the no-statin group than in statin group (20.6% vs. 8.7% respectively). All severity markers were also higher in the no-statin group. All cause mortality was not different, while cardiovascular mortality was higher in the statin group in the cohort analysis. After matching by either method, the severity of disease was greater for the patients without statins treatment. Pancreatitis related mortality was higher in the no-statin group after matching. Among patients who developed severe AP, statin users showed lower Ranson's and APACHE II scores and lower maximal CRP. Conclusions Prior statin treatment significantly reduces morbidity and mortality in acute pancreatitis. Further studies are needed to evaluate possible therapeutic use of statins in acute pancreatitis.
To analyze the distribution of SLC6A4 gene polymorphisms in Crohn's disease (CD) patients and their association with the disease.
We evaluated the presence/absence of promoter (5-HTTLPR, rs25531) and ...intron 2 (STin2 VNTR) polymorphic variants of SLC6A4 gene in a retrospective case-control study including 192 CD patients and 157 healthy controls (HC). Genotyping was performed by polymerase chain reaction. The association of polymorphisms with CD and its clinical subtypes was analyzed using χ2 and Fisher exact test, binary logistic regression, and haplotype analysis.
CD patients and healthy controls had similar sex (88 45.8% vs 84 53.5% women, respectively; P=0.154) and age (41.3±12.8 years vs 41.7±8.8 years, respectively, P=0.091) distribution. Significant differences were observed in the STin2 genotype and allele distribution between CD patients and healthy controls (P=0.003 and P=0.002, respectively) and between the corresponding female subgroups (P=0.004 and P=0.007, respectively), with a significant negative association of biallelic ss (STin2.9 and Stin2.10) STin2 genotype with CD (P=0.013, age- and sex-adjusted odds ratio OR 0.5, 95% confidence interval CI 0.29-0.86; women: P=0.006, age-adjusted OR 0.32, 95% CI 0.14-0.72) and a significantly higher S-STin2.12 (5-HTTLPR/rs25531: S-STin2: STin2.12) haplotype distribution in CD patients (P=0.004, OR 1.62, 95% CI 1.16-2.26). There was no significant association between 5-HTTLRP and rs25531 genotype or allele frequencies and CD and between any SLC6A4 polymorphic loci with clinical CD subtypes.
STin2 VNTR polymorphism of SLC6A4 gene may contribute to CD pathogenesis.
Background & Aims: Endoscopic screening of the colon with available instruments requires considerable training, is often painful, and carries a risk of perforation. New instrument platforms for ...endoscopic screening could be useful. The aim of this study was to evaluate the extent of colonic intubation by using a novel self-propelled, self-navigating endoscope (the Aer-O-Scope; GI View Ltd, Ramat Gan, Israel). Methods: Twelve young healthy volunteers underwent complete bowel preparation followed by a nonsedated examination using the novel device. Each examination was followed by a standard colonoscopy for safety evaluation. Cecal intubation was confirmed by endoscopic landmarks and fluoroscopy. Results: In 10 out of 12 subjects (83%) the cecum was successfully reached, whereas in 2 cases the Aer-O-Scope advanced to the hepatic flexure. The time to complete advancement to cecum averaged 14.0 ± 7 minutes, and the driving pressures averaged 34 ± 2.3 milibar. Two subjects requested analgesics during the procedures (in both cases the cecum was reached). Four subjects experienced sweating and a bloating sensation that resolved spontaneously. All subjects were followed up to 48 hours and then for 30 days postprocedure, and no complications were observed. Conclusions: In a preliminary pilot feasibility study of this new instrument, the Aer-O-Scope effectively intubated all or most of the colon. Further clinical studies are warranted.
Thiopurine S-methyltransferase (TPMT) is an enzyme that converts thiopurine drugs into inactive metabolites. Over 20 variant TPMT-encoding alleles, which cause reduced enzymatic activity, have been ...discovered so far. Our aim was to investigate the frequencies of variant alleles, i.e. genotypes in inflammatory bowel disease (IBD) patients and healthy individuals and to compare these frequencies with selected world populations. The most common variant alleles TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C were analyzed with polymerase chain reaction-based assays and allele-specific polymerase chain reaction-based assays in 685 participants including 459 IBD patients and 226 healthy volunteers. Study results revealed 434/459 (94.55%) IBD patients and 213/226 (94.25%) healthy subjects to be homozygous for the wild-type allele (TPMT*1/*1). TPMT*1/*2 and TPMT *1/*3C genotypes were found in 4/459 (0.87%) and 7/459 (1.53%) IBD patients, respectively; in healthy volunteers they were not found. TPMT*1/*3A genotype was found in 14/459 (3.05%) IBD patients and 13/226 (5.75%) healthy subjects. Variant genotypes were statistically significantly more common in Crohn's disease subgroup than in ulcerative colitis subgroup. The prevalence of variant genotypes was 23/338 (6.80%) in Crohn's disease subgroup as compared with 2/121 (1.65%) in ulcerative colitis subgroup (χ2 = 4.59; p = 0.032). In conclusion, the most frequently occurring nonfunctional TPMT allele in Croatian population is TPMT*3A. The overall frequency of mutant alleles in our population is statistically nonsignificantly lower when compared with other populations of Caucasian origin. The Crohn's disease group had more mutant alleles than the ulcerative colitis group.
: Vanishing bile duct syndrome is a severe cholestatic disease associated with toxic effects of medications. Stevens‐Johnson syndrome is a hypersensitivity disorder that may also be caused by ...medications. We present a case of a 62‐year‐old male patient who developed vanishing bile duct syndrome a month after Stevens‐Johnson syndrome. These adverse drug reactions were associated with the use of azithromycin (500 mg daily for 3 days). The patient was initially treated for Stevens‐Johnson syndrome with steroids, antihistamines and proton pump inhibitors and fully recovered. However, a month after the beginning of Stevens‐Johnson syndrome, he developed vanishing bile duct syndrome and was treated with steroids, ursodeoxycholic acid, antihistamines and tacrolimus. Unfortunately, the treatment was unsuccessful and he was listed for liver transplantation which was performed 7 months after the beginning of jaundice. This is the first case of vanishing bile duct syndrome associated with the use of azithromycin and one of few that reports vanishing bile duct syndrome and Stevens‐Johnson syndrome co‐occurrence.
Using standard diagnostic algorithms it is not always possible to establish the correct phenotype of inflammatory bowel disease which is essential for therapeutical decisions. Endoscopic ultrasound ...elastography is a new endoscopic procedure which can differentiate the stiffness of normal and pathological tissue by ultrasound. Therefore, we aimed to investigate the role of transrectal ultrasound elastography in distiction between Crohn's disease and ulcerative colitis.
A total 30 Crohn's disease, 25 ulcerative colitis, and 28 non-inflammatory bowel disease controls were included. Transrectal ultrasound elastography was performed in all patients and controls. In all ulcerative coltis patients and 80% of Crohn's disease patients endoscopy was performed to assess disease activity in the rectum.
Significant difference in rectal wall thickness and strain ratio was detected between patients with Crohn's disease and controls (p = 0.0001). CD patients with active disease had higher strain ratio than patients in remission (p = 0.02). In ulcerative colitis group a significant difference in rectal wall thickness was found between controls and patients with active disease (p = 0.03). A significant difference in rectal wall thickness (p = 0.02) and strain ratio (p = 0.0001) was detected between Crohn's disease and ulcerative colitis patient group. Crohn's disease patients with active disease had a significantly higher strain ratio compared to ulcerative colitis patients with active disease (p = 0.0001).
Transrectal ultrasound elastography seems to be a promising new diagnostic tool in the field of inflammatory bowel disease. Further study on a larger cohort of patients is needed to definitely assess the role of transrectal ultrasound elastography in inflammatory bowel disease.
PDF
