Annacinzia Amoruso

Slow-transit constipation: Solitary symptom of a systemic gastrointestinal disease

INTRODUCTION: Autonomic neuropathy is thought to play a role in the pathogenesis of slow-transit constipation, but other gastrointestinal organs may also be involved, even if they are symptom-free. We investigated whether motility in gastrointestinal organs other than the colon was impaired in patients with slow-transit constipation and whether the autonomic nervous system was involved. METHODS: Twenty-one consecutive patients (18 females; median age, 46 years) with severe chronic constipation (≤2 defecations/week and delayed colonic transit time) were studied. Autonomic neuropathy function was tested with esophageal manometry, gastric and gallbladder emptying (fasting and postprandial motility) by ultrasonography, orocecal transit time (H2-breath test), colonic transit time (radiopaque markers), and anorectal volumetric manometry. The integrity of the autonomic nervous system was assessed by a quantitative sweat-spot test for preganglionic and postganglionic fibers, tilt-table test, and Valsalva electrocardiogram R-R ratio. RESULTS: Esophageal manometry showed gastroesophageal reflux or absence of peristalsis in five of the seven patients examined. Gallbladder dysmotility (i.e., increased fasting, postprandial residual volume, or both) was observed in 6 of 14 (43 percent) patients. Gastric emptying was decreased in 13 of 17 (76 percent) patients. Orocecal transit time was delayed in 18 of 20 (90 percent) patients; median transit time was 160 (range, 90–200) minutes. Median colonic transit time was 97 (range, 64–140) hours. Anorectal function showed abnormal rectoanal inhibitory reflex and decreased rectal sensitivity in 11 of 19 (58 percent) patients. Signs of autonomic neuropathy of the sympathetic cholinergic system were found in 14 of 18 (78 percent) patients. Only one of nine patients had vagal abnormalities detected with the Valsalva test and four of five patients with a history of orthostatic hypotension had a positive tilt-table test. CONCLUSIONS: Slow-transit constipation may be associated with impaired function of other gastrointestinal organs. More than 70 percent of patients with slow-transit constipation present some degree of autonomic neuropathy. Severe constipation may be the main complaint in patients with a systemic disease involving several organs and possibly involving the autonomic nervous system. This should be considered in the management of such cases.

Primary clarithromycin resistance in Italy assessed on Helicobacter pylori DNA sequences by TaqMan real-time polymerase chain reaction

Helicobacter pylori clarithromycin resistance is increasing worldwide and different mutations are involved in its mechanisms. Recently, molecular methods have been proposed to assess these mutations.

Lamivudine and alpha-interferon in combination long term for precore mutant chronic hepatitis B

BACKGROUND/AIMS Alpha-interferon (alpha-IFN) and lamivudine are the two licensed drugs for patients with chronic hepatitis B, however, their efficacy in precore mutant chronic hepatitis B is limited. The aim of this study was to investigate the efficacy of 1 year alpha-IFN-lamivudine combination therapy for anti-HBe/hepatitis B virus- (HBV)-DNA positive patients. METHODS Between 1997 and 1999, 29 consecutive anti-HBe/HBV-DNA positive patients entered this prospective pilot study. Patients received 100mg lamivudine orally daily and alpha-IFN 6 million units (MU) three times weekly for 52 weeks. All patients were followed-up for 12 months after stopping therapy. Primary end points were loss of serum HBV-DNA and alanine transaminase normalization at week 52. RESULTS Overall, the end-treatment biochemical and virological response was 93% while the sustained response at week 104 was 14%. HBV-DNA negative patients did not experience a viral breakthrough during treatment; no tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase (YMDD) variant emerged. At week 52, 46% of patients with paired liver biopsies slides available, showed an histological improvement (histological activity index > or =2). CONCLUSIONS Combination of lamivudine and interferon for 1 year is followed by high end-treatment virological and biochemical response rates, by improvement of liver histology and by the prevention of the emergence of YMDD mutation; however, the sustained response rate remains low.

Proliferative activity of gastric epithelium in progressive stages of Helicobacter pylori infection

Helicobacter pylori (HP) infection is the main etiopathogenetic agent responsible for inflammatory and ulcerative changes in gastroduodenal mucosa and the basis for both intestinal and diffuse types of gastric carcinoma. In this latter case, intestinal metaplasia is the intermediary between gastritis and cancer. In this study we describe the proliferative activity of gastric epithelium in the progressive stages of HP infection. The expression of proliferating cell nuclear antigen (PCNA), which has proven to be a reliable method for this evaluation, was used as a marker. The study was performed on endoscopic biopsies of the gastric antrum of 40 patients, who were divided into five groups, eight in each group: normal histology and endoscopy, HP−; histological HP+ gastritis with normal endoscopy; histological HP+ gastritis with endoscopic evidence of chronic erosions; complete and incomplete intestinal metaplasia in a HP+ stomach. PCNA was detected by immunohistochemistry and expressed as labeling index, ie, percentage of positive nuclei either in the whole or upper third of foveolae. Our data show a progressive increase of epithelial proliferation in the successive stages of HP infection ranging from gastritis alone to the development of incomplete intestinal metaplasia, a well-known precancerous condition. The proliferative pattern tended to expand towards the upper foveolar third, which in normal conditions does not represent a site of epithelial renewal. These alterations may be related to the development of neoplastic transformations of gastric epithelium. It is well known that genetic mutations are facilitated in proliferating cells. Therefore, our results indicate that the high epithelial turnover, expressed by PCNA LI, may be an indicator of increased risk of neoplastic changes in long-standing untreated HP+ chronic gastritis.

Effectiveness and pharmaceutical cost of sequential treatment for Helicobacter pylori in patients with non‐ulcer dyspepsia

Background : A novel 10‐day sequential treatment regimen recently achieved a significantly higher eradication rate than standard 7‐day therapy in both peptic ulcer disease and non‐ulcer dyspepsia. Its higher performance has recently been confirmed using a halved clarithromycin dose in peptic ulcer disease.

Helicobacter pylori and nonulcer dyspepsia in childhood: clinical pattern, diagnostic techniques, and bacterial strains.

BACKGROUND This is a report of the results of a multicenter study performed in children with dyspepsia from five pediatric centers in Puglia, a region in southern Italy. In the study, clinical features of Helicobacter pylori infection, the reliability of diagnostic techniques, and the involvement of bacterial strains were examined. METHODS Fifty-three outpatients with dyspepsia enrolled in our study and compiled a diary recording clinical symptoms in patients before they underwent the following diagnostic techniques: endoscopy, biopsy for histologic analysis, rapid urease test, 13C urea breath test, serology specific for immunoglobulin (Ig)G and anti-CagA and VacA. RESULTS H. pylori showed a prevalence of 30.2% (n = 16). Histologic positivity was seen in all patients at the antral level (H. pylori-associated chronic gastritis). In the gastric body, bacterial chronic active gastritis was present only in six patients (H. pylori-associated chronic pangastritis). Clinical evaluation showed a significant difference in favor of subjects positive for H. pylori only for epigastric burning and/or pain (p < 0.001). The comparison of results of diagnostic tests, using histology as the gold standard, showed sensitivity and specificity of more than 93% for 13C urea breath test and more than 85% for rapid urease test and serology. Anti-CagA antibodies were found in 64.3% and anti-VacA antibodies in 42.8% of H. pylori-positive patients. CONCLUSIONS H. pylori prevalence in children with dyspepsia from the geographic area studied is comparable with that found in other developed countries. Approximately 50% of the studied patients were infected by cytotoxic strains. The urea breath test was the most reliable noninvasive diagnostic tool and is suitable for routine use, although endoscopy with histologic assessment remains the definitive investigation and is particularly important in patients with positive serology for CagA and VacA. Finally, the frequency of aggressive strains in our region seems to affect the clinical pattern; this emphasizes the importance of definitive diagnosis in children and offers a new role for serology.

Functional modification of CD11c+ liver dendritic cells during liver regeneration after partial hepatectomy in mice†

Local immunosuppression within the liver and sex steroid changes, in both blood and tissue during liver regeneration, are well‐recognized events. Dendritic cells (DC) play pivotal roles in the induction and regulation of immune responses. Their numbers are expanded markedly in vivo by fms‐like tyrosine kinase 3 ligand (Flt3L) administration, without modification of their maturation state. Recent evidence suggests that estrogen can modulate DC function and promote a Th2‐type immune response. Few data are available concerning the role of DC in liver regeneration. After 75% partial hepatectomy (PH) in male C57BL/6 mice, CD11c+ liver (L)DC increased significantly within 6 hours and maintained an immature phenotype. Numbers returned to pre‐hepatectomy levels by 24 hours. The expanded LDC population showed increased IL‐10 and reduced IFN‐γ gene transcription. Using these DC compared with control LDC as T cell stimulators in 72‐hour mixed leukocyte cultures, IL‐10 production was enhanced and IFN‐γ production reduced. LDC isolated 6 hours after 75% PH exhibited enhanced estrogen receptor (ER) expression, concomitant with increased serum estrogen levels. By contrast, spleen (S)DC isolated before and after PH showed no significant changes in their function (maturation state, T cell stimulatory activity, cytokine production, and ER expression). Increased liver regeneration (more than 50%) was observed 48 hours after 40% PH in the Flt3L‐pretreated compared with the PBS group. In conclusion, interstitial LDC may play a key role in local immune regulation during liver regeneration, possibly linking estrogen‐mediated immune modulation and hepatocyte proliferation. (HEPATOLOGY 2006;43:807–816.)

Effect of probiotic or prebiotic supplementation on antibiotic therapy in the small intestinal bacterial overgrowth: A comparative evaluation

UNLABELLED Bacterial intestinal overgrowth syndrome (SIBO) treatment is based on antibiotics. Probiotics have been shown to give similar results, whilst no study is available about prebiotics. This study evaluated the addition of probiotics or prebiotics to antibiotics on SIBO symptoms in a 6-month follow-up. We enrolled 40 patients (14 males and 26 females) reporting abdominal compliant without gastrointestinal diseases/alarm symptoms. SIBO was diagnosed by the agreement of lactulose and glucose breath tests. Patients were randomly divided into two groups homogeneous for sex and age: group 1 received Rifaximin 400 mg/day for 7 days/month followed by Lactobacillus casei for 7 days more and group 2 antibiotic followed by short chain fructo-oligosaccharides. All patients recorded a questionnaire for subjective symptom evaluation according to Rome III criteria and Bristol scale for stool characters before the study and after 6 months. STATISTICS Students t and Fishers exact tests. In group 1, a significant improvement was obtained in 5 out of 6 symptoms, whilst in group 2 in 4 out of 6 symptoms (nausea and number of bowel movements failed to improve). Despite we observed a trend of probiotics to be more effective than prebiotics, the difference in the percentage of improved symptoms was not significant (83,3% vs 66.6%; p= 0.57). Our preliminary data show a good outcome with sequential antibioticprobiotic/ prebiotic administration in patients with SIBO.

A comparison of the nutritional status between adult celiac patients on a long-term, strictly gluten-free diet and healthy subjects

Background/Objectives:There are conflicting data on the effect of a gluten-free diet (GFD) on the nutritional status of celiac patients. In the present study, we evaluated, in adult celiac patients, the influence of a long-term, strictly GFD on their nutritional status and compared it with matched healthy volunteers.Subjects/Methods:Our study included 39 celiac patients and 39 healthy volunteers. The body mass index (BMI) of patients and controls was evaluated at enrollment, while the patients’ BMI before the GFD was retrieved from clinical records. In addition, at enrollment, in both groups, we compared BMI, fat mass (FM), bone mineral density (BMD), as well as their dietary intake, recorded on a 7-day diary.Results:At the time of diagnosis, the majority of celiac patients (82.0%) had a normal BMI or were overweight, while 10.3% were malnourished. After the GFD, patients with a normal BMI showed a significant weight increase (P=0.002), but none of them switched in the overweight or obese category. Two (50%) of the four malnourished patients achieved a normal BMI. Controls and patients on a GFD had a similar BMI, FM, BMD and total calorie intake, but the amount of lipids and fiber intake was significantly different in the two groups (P=0.003 and P<0.0001, respectively).Conclusions:Our study demonstrates that a GFD is able to improve the nutritional status of celiac patients without inducing overweight or obesity. Our findings are related to a celiac population adopting a GFD based on a Mediterranean-type diet.

Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up.

AIM To assess the evolution of duodenal lymphocytosis (DL), a condition characterized by increased intraepithelial lymphocytes (IELs), over 2 years of follow-up. METHODS Consecutive patients undergoing upper endoscopy/histology for abdominal pain, diarrhea, weight loss, weakness or other extraintestinal features compatible with celiac disease (CD) were included. Evaluation of IELs infiltrate in duodenal biopsy samples was carried out by CD3-immunohistochemistry and expressed as number of positive cells/100 enterocytes. Diagnostic agreement on the IELs count was tested by calculating the weighted k coefficient. All patients underwent serological detection of autoantibodies associated with CD: IgG and IgA anti-tissue transglutaminase and endomysium. Each patient underwent further investigations to clarify the origin of DL at baseline and/or in the course of 2 years of follow-up every six months. Autoimmune thyroiditis, intestinal infections, parasitic diseases, bacterial intestinal overgrowth, hypolactasia and wheat allergy were detected. Colonoscopy and enteric magnetic resonance imaging were performed when necessary. Risk factors affecting the final diagnosis were detected by multinomial logistic regression and expressed as OR. RESULTS Eighty-five patients (16 males, 69 females, aged 34.1 ± 12.5 years) were followed up for a mean period of 21.7 ± 11.7 mo. At baseline, endoscopy/duodenal biopsy, CD3 immunohistochemistry revealed: > 25 IELs/100 enterocytes in 22 subjects, 15-25 IELs in 37 and < 15 IELs in 26. They all had negative serum anti-transglutaminase and anti-endomysium, whilst 5 showed IgG anti-gliadin positivity. In the course of follow-up, 23 developed CD seropositivity and gluten sensitivity (GS) was identified in 19. Other diagnoses were: 5 Helicobacter pylori infections, 4 jejunal Crohns disease, 1 lymphocytic colitis and 1 systemic sclerosis. The disease in the remaining 32 patients was classified as irritable bowel syndrome because of the lack of diagnostic evidence. At multivariate analysis, the evolution towards CD was associated with an IELs infiltrate > 25 (OR = 1640.4) or 15-25 (OR = 16.95), human leukocyte antigen (HLA) DQ2/8 (OR = 140.85) or DQA1*0501 (OR = 15.36), diarrhea (OR = 5.56) and weakness (OR = 11.57). GS was associated with IELs 15-25 (OR = 28.59), autoimmune thyroiditis (OR = 87.63), folate deficiency (OR = 48.53) and diarrhea (OR = 54.87). CONCLUSION DL may have a multifactorial origin but the IELs infiltrate and HLA are strong predictive factors for CD development and a clinical diagnosis of GS.