Type 1 diabetes mellitus and celiac disease: endothelial dysfunction

Many reports indicate a hypercoagulative state in diabetes mellitus as result of endothelial damage. Experimental evidence suggests that a metabolic derangement triggers a cascade of biochemical events that lead to vascular dysfunction. The net effect is to convert the endothelium from thromboresistant to thrombogenic surface. In literature, a strong association between type 1 diabetes mellitus (DM1) and celiac disease (CD) has been reported. We do not have information about the hemostatic system in these associated conditions. Our study aims at evaluating whether the presence of CD in a group of DM1 patients is associated with a different expression of some hemostatic factors and with a different manifestation and/or progression of microvascular complications of DM1 in comparison with patients with only diabetes. Ninety-four adult DM1 patients were enrolled in the study and subsequently screened for CD. Anti-endomysial antibodies (EMA) were positive in 13 of 94 DM1 patients (13.8%). CD diagnosis was confirmed by histology and organ culture. The mean age and duration of DM1 of patients also affected by CD were similar to those of only diabetic patients, but the metabolic control and the hemocoagulative parameters were significantly different between the two groups: DM1 patients also affected by CD presented significantly lower concentrations of glycosylated hemoglobin (HbA1c) (P < 0.05), cholesterol (P < 0.001), triglycerides (P < 0.001), factor VII antigen (FVII:ag) (P < 0.005), factor VII coagulant activity (FVII:c) (P < 0.05), and prothrombin degradation fragments (F1+2) (P < 0.001), as well as higher values of activated C protein (APC) (<0.001). No retinal abnormalities and no signs of renal damage were observed in DM1 patients also affected by CD. Our results suggest a potential protective role of CD in the prothrombotic state of DM1.     

i-Scan high-definition white light endoscopy and colorectal polyps: prediction of histology, interobserver and intraobserver agreement

Purpose

Aim of the study was the evaluation of high-definition white light (HDWL) i-Scan endoscopy for diagnostic prediction of histology, inter- and intraobserver agreement for colorectal polyps.

Methods

In this prospective single-center cohort study, a skilled endoscopist, with HDWL i-Scan, predicted on real-time the histology of 150 polyps from 78 patients undergoing colonoscopy. Subsequently, four endoscopists, not involved in the collection of cases, predicted the polyps' histology (neoplastic vs nonneoplastic) and repeated the assessment after 6 months.

Results

Real-time assessment of the lesions predicted a correct histology in 138/150 cases with a sensitivity, specificity, and accuracy of 95, 82, and 92 %, respectively. Sensitivity, specificity, and accuracy of post-acquisition evaluation were 87.7, 61.7, and 82.2 %, respectively. The κ values of inter- and intraobserver agreement of prediction of histology were 0.462 (0.373–0.537) and 0.657 (0.523–0.917). Among the subset of polyps (n?=?82) with good/excellent quality image, sensitivity and accuracy of HDWL i-Scan improved (97 %, p?=?0.003 and 94 %, p?=?0.002, respectively) as well as κ value of interobserver agreement (0.699).

Conclusions

HDWL i-Scan technology helps for characterization of polyps of the colon with good accuracy even if it cannot replace, at the moment, the histopathological examination. Reproducibility among operators is supported by a moderate substantial interobserver and intraobserver agreement.     

Small intestinal bacterial overgrowth and warfarin dose requirement variability

The dose of warfarin needed to obtain a therapeutic anticoagulation level varies widely among patients and can undergo abrupt changes for unknown reasons. Drug interactions and genetic factors may partially explain these differences. Intestinal flora produces vitamin K₂ (VK₂) and patients with small intestinal bacterial overgrowth (SIBO) rarely present reduced INR values due to insufficient dietary vitamin K. The present study was undertaken to investigate whether SIBO occurrence may affect warfarin dose requirements in anticoagulated patients. Based on their mean weekly dose of warfarin while on stable anticoagulation, 3 groups of 10 patients each were defined: low dose (LD, ≤ 17.5 mg/wk of warfarin); high dose (HD, from 35-70 mg/wk); and very high dose (VHD ≥ 70 mg/wk). Each patient underwent a lactulose breath test to diagnose SIBO. Plasma levels of warfarin and vitamin K-analogues were also assessed. Patients with an altered breath test were 50% in the VHD group, 10% in the HD group, and none in the LD group (P = 0.01). Predisposing factors to SIBO were more frequent in the VHD group, while warfarin interfering variables were not. VHD patients were younger and had a higher plasma vitamin K₁ (VK₁) concentration (P > 0.05). On the contrary, the plasma VK₂ levels tended to be lower. This pilot study suggests that SIBO may increase a patient's warfarin dose requirement by increasing dietary VK₁ absorption through the potentially damaged intestinal mucosa rather than increasing intestinal VK₂ biosynthesis. Larger studies are needed to confirm these preliminary data and to evaluate the effects of SIBO decontamination on warfarin dosage.     

Appropriateness of colonoscopy： Diagnostic yield and safety in guidelines

AIM: To evaluate if the guidelines for the appro-priateness of performing colonoscopy by American Society for Gastrointestinal Endoscopy (AGSE) and Italian Society of Digestive Endoscopy (SIED) yield a good diagnostic efficacy and do not present risks of missing important colonic pathologies in an Italian population sample.METHODS: A total of 1017 consecutive patients (560 men and 457 women; mean age 64.4 ± 16 years) referred to an open-access endoscopy unit for colonoscopy from July 2004 to May 2006 were evaluated according to ASGE and SIED guidelines for appropriateness of performing the procedure. Diagnostic yield was defined as the percentage of relevant colonic pathologies of the total number of colonoscopies performed.RESULTS: About 85.2% patients underwent colono-scopy that was considered appropriate based on at least one ASGE or SIED criterion, while it was considered inappropriate for 14.8% of patients. The diagnostic yield of colonoscopy was significantly higher for appropriate colonoscopies (26.94% vs 10.6%, P < 0.001) than for inappropriate colonoscopies (5.3%). There was no missed colorectal cancer following the ASGE/SIED criteria.CONCLUSION: ASGE/SIED guidelines have shown a good diagnostic yield and the rate of missing relevant colonic pathologies seems very low. Unfortunately, the percentage of inappropriate referrals for colonoscopy in an open-access endoscopy system is still high, despite the number of papers published on the issue and the definition of international guidelines. Further steps are required to update and standardize the guidelines to increase their diffusion and to promote educational programs for general practitioners.     

Audit of Constipation in a Gastroenterology Referral Center

This study was designed to assess the various subtypes of functional constipation in a referral gastrointestinal center of a Latino-American country. All patients referred for evaluation of constipation during a 10-year period were audited, and those with functional constipation according to Rome I criteria classified by physiologic tests of colonic transit, as well as tests of anorectal and pelvic floor function. More than 70% of patients with functional constipation had evidence of pelvic floor dysfunction, whereas those with slow transit and constipation-predominant irritable bowel syndrome subtypes were less frequently represented. Even in a setting different from those most frequently reported in the literature, pelvic floor dysfunction represents the most common cause of functional constipation. Simple, physiologic testing is needed and useful for the diagnosis. This fact has therapeutic implications, especially because many such patients may benefit from biofeedback.     

Colonic propulsive and postprandial motor activity in patients with ulcerative colitis in remission

BACKGROUND: Although it is known that colon motility is abnormal in ulcerative colitis, data are still scarce with regard to the underlying mechanisms. Recent evidence suggests that the propulsive activity is highly increased during the active phase of the disease, probably contributing to the diarrhoea. However, data are even scarcer in the quiescent phase of the disease. AIMS: To assess the colonic high-amplitude and low-amplitude propulsive activity and the colonic motor response to eating in patients with ulcerative colitis in remission. PATIENTS AND METHODS: Fourteen patients were recruited, all with the disease in remission as documented by clinical and endoscopic criteria. Twenty-four hour manometric recordings were obtained in these patients, and compared to those of 16 healthy controls. RESULTS: The high-amplitude propagated contractions were similar in both groups (5.8+/-2.6 events in ulcerative colitis patients and 5.5+/-0.8 in controls (P=0.13)), whereas patients tended to display a higher number of low-amplitude propagated events (134.4+/-34 vs. 60.9+/-16 in controls (P=0.058)). No differences were found in the colonic motor response to eating between patients and controls. CONCLUSIONS: Colonic propulsive activity in ulcerative colitis in remission is almost normal, even though the low-amplitude propagated activity tends to be similar to that observed in patients with the irritable bowel syndrome, thus possibly contributing to the persistence of abdominal symptoms in a subgroup of patients.     

Non-surgical treatment of esophageal achalasia

INTRODUCTION Esophageal achalasia is a rare neuromuscular disorder characterized by degenerative changes of myenteric plexus leading to a selective loss of inhibitory nerve endings. The consequences of this damage are the irreversible loss of peristaltic …     

Pharmacokinetic profile of a new modified release formulation of zolpidem designed to improve sleep maintenance

The aim of this study was to compare the relative bioavailability and the pharmacokinetic profile of a single oral dose of a zolpidem modified-release (MR) 12.5-mg formulation with those of the standard 10-mg zolpidem immediate-release (IR) formulation. Absolute bioavailabilities of oral formulations were evaluated using intravenously (i.v.) administered zolpidem as a reference. Twenty-four healthy, Caucasian, male volunteers (18-45 years old) received single doses of three oral formulations (zolpidem-MR 12.5 mg, zolpidem-IR 10 mg and an experimental form) and zolpidem i.v. infusion (8 mg) in a randomized, open-label, crossover trial. Blood samples (18 time-points) were collected up to 16 h post-dose after oral administration and up to 12 h post-dose after i.v. administration. Pharmacokinetic parameters were determined by non-compartmental analysis, allowing comparisons between treatments based on estimated ratios and differences, with 90% confidence intervals. The initial absorption phase of the zolpidem-MR formulation was as fast as that of zolpidem-IR with no significant difference in t(max). With zolpidem-MR 12.5 mg, C(max) was moderately lower than with zolpidem-IR (ratio of 0.82), and plasma zolpidem concentrations were maintained above those observed with zolpidem-IR for a longer period of time, particularly from 3 to 6 h post-dose. This was confirmed by an increase in half-value duration (HVD) from 2.3 h with zolpidem-IR to 4.6 h with zolpidem-MR 12.5 mg. The mean terminal half-life was similar between formulations. Zolpidem-MR 12.5 mg provides the appropriate pharmacokinetic characteristics to extend plasma zolpidem concentrations into the middle of the night (3-6 h post-dose), while retaining the same t(max) and terminal half-life.     

Immunocytochemical Assessment of p53 Protein to Detect Malignancy in Increased Cell-Yield Brush Cytology from the Biliopancreatic Tree

Background Malignancies arising from the biliopancreatic tree are often diagnostic challenges for the gastroenterologist and the pathologist, especially when strictures without masses are present. Aim To evaluate the diagnostic yield of p53 immunocytology for the detection of malignancies in material obtained by biliopancreatic tree brushing by means of an increased cell-yield procedure. Patients and Methods Cytologic specimens obtained from biliary and pancreatic tree brushing in 24 patients with biliary strictures suspected for malignancy were assessed by conventional Papanicolau staining and p53 immunocytochemistry. Results Papanicolau staining detected 67% and p53 87% of the malignancies in the study group. p53 immunocytology displayed excellent sensitivity, specificity, and diagnostic accuracy. Conclusions p53 immunocytology may represent a useful diagnostic tool in the detection of malignancies from biliary and pancreatic tree brushing, especially when using an increasing cell-yield procedure.