Abnormal gut motility in inflammatory bowel disease: an update.

BACKGROUND: There is substantial evidence linking disturbed gastrointestinal motility to inflammation. Thus, it is not surprising that abnormalities of gastrointestinal motility play a role in inflammatory bowel disease (IBD), affecting patient outcomes. We performed a review of the literature to investigate the relationship between abnormal gut motility and IBD. METHODS: With an extensive literature search, we retrieved the pertinent articles linking disturbed gut motility to IBD in various anatomical districts. RESULTS: The evidence in the literature suggests that abnormal gastrointestinal motility plays a role in the clinical setting of IBD and may confuse the clinical picture. CONCLUSIONS: Abnormal gut motility may be important in the clinical setting of IBD. However, additional data obtained with modern techniques (e.g., magnetic resonance imaging) are needed to individuate in a more precise manner gastrointestinal motor dysfunctions, to understand the nature of clinical manifestations and properly tailor the treatment of patients.

Helicobacter pylori CagA antibodies and thyroid function in latent autoimmune diabetes in adults.

OBJECTIVE: H. pylori infection is reportedly associated with autoimmune diseases such as chronic thyroiditis and autoimmune diabetes. The aim of this study is to determine the association between H. pylori infection and its virulent strain CagA with antibodies against thyroperoxidase (TPO Ab) and thyrotropin (TSH) in a cohort of latent autoimmune diabetes in adult (LADA) patients. PATIENTS AND METHODS: We included 234 LADA patients (53.8% women). Antibodies against H. pylori whole antigens and CagA, TPO Ab and TSH were assessed in all patients. RESULTS: Prevalence of IgG against H. pylori and GagA was 52.1% and 20.9% respectively. Antibodies against H. pylori were not associated with TPO Ab and TSH (rho = 0.067, p = 0.620 and rho = 0.156, p = 0.099, respectively). Antibodies against CagA showed a positive association with TSH and TPO Ab (respectively rho = 0.309, p = 0.036 and rho = 0.419, p = 0.037). Subjects with hypothyroidism (TSH ≥ 3.5 µU/ml) had an increased frequency of Ab anti CagA (p = 0.059). CONCLUSIONS: The infection by H. pylori strains expressing CagA is associated with increased TPO Ab and TSH levels in LADA patients, suggesting a possible mechanism involved in thyroid autoimmunity and dysfunction of the gland. Further research is needed to test this hypothesis.

Risk factors associated with colonic diverticulosis among patients from a defined geographic area.

BACKGROUND: Only a few data regarding colonic diverticulosis are available in Italy. We examined the frequency of colonic diverticulosis and its associations with risk factors in a homogeneous Northern Sardinian population undergoing colonoscopy for any reason in the last decades. METHODS: This was a retrospective single-center study. Medical records of patients undergoing colonoscopy for any indication between 1995 and 2013 were reviewed. Demographic information including age, gender, geographic area (urban, rural), marital status, smoking habit, occupation, body mass index, and comorbidities were collected. Presence, number, and extension of diverticula were assessed by colonoscopy. The diagnosis of diverticulosis was defined by the presence of more than five diverticula. RESULTS: A total of 4458 records were collected (39.8 % males). Analysis by birth cohorts showed a significant progressive age-related increase in the prevalence of diverticulosis. The average prevalence was 18.9 % without significant variation across the 19-year observation period. In 101 (12.1 %) subjects diverticula were single or few. Seventy-one percent of diverticula were located predominantly in the left side, 2 % in the right side, and 14.3 % were spread throughout the colon. There was a significant association with obesity but not with smoking habits, marital status, or urban versus rural environment. A strong association was observed between the presence of diverticulosis and cardiovascular and other gastrointestinal and lung disease (p < 0.0001). These associations were also confirmed by the logistic regression analysis. CONCLUSIONS: In this endoscopic study, colonic diverticulosis in Northern Sardinia showed prevalence similar to other series in Western countries, and it was predominantly left sided and age related.

The PNEI holistic approach in coloproctology.

The psycho-neuroendocrine-immune approach relies on the concept of considering diseases from a holistic point of view: the various components (psyche, nervous system, endocrine system, and immune system) control the diseased organ/apparatus and in turn are influenced by a feedback mechanism. In this article, we will consider the psycho-neuroendocrine-immune approach to coloproctological disorders, by providing clinical cases and discussing them in light of this approach.

Male longevity in Sardinia, a review of historical sources supporting a causal link with dietary factors.

The identification of a hot spot of exceptional longevity, the Longevity Blue Zone (LBZ), in the mountain population of Sardinia has aroused considerable interest toward its traditional food as one of the potential causal factors. This preliminary study on the traditional Sardinian diet has been supported by the literature available, which has been carefully reviewed and compared. Up to a short time ago, the LBZ population depended mostly upon livestock rearing, and consumption of animal-derived foods was relatively higher than in the rest of the island. The nutrition transition (NT) in urbanized and lowland areas began in the mid-1950s, fueled by economic development, whereas in the LBZ it started later owing to prolonged resistance to change by a society organized around a rather efficient pastoral economy. Even nowadays a large proportion of the population in this area still follows the traditional diet based on cereal-derived foods and dairy products. The LBZ cohorts comprising individuals who were of a mature age when NT began may have benefited both from the high-quality, albeit rather monotonous, traditional diet to which they had been exposed most of their life and from the transitional diet, which introduced positive changes such as more variety, increased consumption of fruits and vegetables and moderate meat intake. It could be speculated that these changes may have brought substantial health benefits to this particular aging group, which was in need of nutrient-rich food at this specific time in life, thereby resulting in a decreased mortality risk and, in turn, life-span extension.

Is aphallic vas deferens development in females related to the distance from organotin sources? A study with Stramonita haemastoma.

Imposex, a syndrome characterized by the appearance of a penis and/or vas deferens in female gastropods due the presence of organotins in environment, is still observed in Brazilian gastropod populations, as in other countries, even after the tributyltin (TBT) ban. Nevertheless, the progressive controls on the use of organotins in antifouling systems at national and international levels and the consequent reduction of their environmental concentrations have led to changes in the characteristics of imposex development observed in Stramonita haemastoma. Populations of this species were analyzed on the coast of Rio de Janeiro (Brazil) between 2007 and 2008, and the developmental pathways associated with the syndrome were identified. Compared with previous works, it was noted that imposex expression was reduced in most of Guanabara Bay. Aphallic imposex development, on the other hand, showed a marked increase. The pathways of imposex development were also evaluated in a temporal data series from a fixed sampling station at Vermelha beach, and the incidence of aphallic imposex development was found to show a marked increase from 1998 onward. Furthermore, the observation of either the presence or absence of a penis in imposex-affected females may indicate that penis development is related to the contaminant exposure level and that the decreasing TBT concentrations in the local environment result in the predominance of an aphallic route of imposex development. These findings support the idea that imposex female aphally in this species could be a dose-dependent response, rather than a genetic anomaly.

Proteomic characterization of hepatitis C eradication: enzyme switch in the healing liver.

Lipid pathway impairment, decrease in the antioxidant pool and downregulation in amino-acid metabolism are just some of the metabolic variations attributed to chronic HCV infection. All of them have been studied separately, mainly in animal models. Thanks to proteomic analysis we managed to describe (for the fist time to the best of our knowledge), in vivo and in humans, the metabolic alterations caused by HCV, and the recovery of the same alterations during HCV treatment. We performed proteomic analysis on liver specimens of a 28-year-old woman affected by hepatitis C genotype 1a, alcoholism and diabetes mellitus type 1, before and after antiviral treatment with pegylated interferon alpha 2b and ribavirin. The subject, thanks to a patient-tailored therapy, reached Sustained Virological Response. Throughout the treatment period the patient was monitored with subsequent biochemical, clinical and psychological examinations. The data obtained by the patient's close monitoring suggest a direct interaction between insulin resistance and an active HCV genotype 1 infection, with a leading role played by the infection, and not by insulin resistance, as demonstrated by the sharp fall of the insulin units needed per day during treatment. The proteomic analysis showed that after therapy, a downregulation of enzymes involved in amino acid metabolism, glycolysis/gluconeogenesis and alcohol catabolism takes place, the latter probably due to cessation of alcohol abuse. On the contrary, the metabolic pathways linked to metabolism of the reactive oxygen species were upregulated after therapy. Finally, a significant alteration in the pathway regulated by peroxisome proliferator-activated receptor alpha (PPARA), a major regulator of lipid metabolism in the liver, was reported. These "real time" data confirm in vivo, in humans, that during HCV infection, the pathways related to fatty acids, glucose metabolism and free radical scavenging are inhibited. The same enzyme deficit is completely recovered after HCV eradication.

Role of routine small intestinal biopsy in adult patient with irritable bowel syndrome-like symptoms.

AIM: The clinical evaluation of patients with chronic diarrhea and/or abdominal pain requires a complex work-up. The aim of the study was to evaluate whether routine duodenal biopsy sampling of macroscopically normal mucosa of patients with irritable bowel syndrome-like symptoms undergoing upper endoscopy assists in diagnosis and management. METHODS: Consecutive adults scheduled for upper endoscopy for evaluation of uninvestigated dyspepsia and abdominal pain and/or chronic diarrhea based upon the history, were enrolled. Gastric biopsies and 3 duodenal biopsies were taken for histological evaluation. RESULTS: A total of 786 sets of biopsies from 262 consecutive patients (200 females and 62 males, mean age 46 years; range: 15-82), were analyzed. Microscopic damage was observed in 212 of 262 patients (81%) with normal mucosa. Mild to moderate and severe duodenitis or villi atrophy was histologically confirmed in 65%, 26% and 8% of 212 patients respectively. The negative predictive value of a normal appearing duodenal mucosa was 19%. Additional tests confirmed celiac disease in 12 patients. Lactose malabsorption was present in 42%, bacterial overgrowth in 14%, and H. pylori infection in 28%. Colonoscopy performed in 92 patients revealed non specific colitis (25%), microscopic colitis (28%), Crohn's disease (1%), and diverticulosis (15%). CONCLUSION: Duodenal biopsies revealed abnormalities in the majority of adults with chronic diarrhea and/or abdominal pain despite macroscopically normal gross findings. These results suggest that duodenal biopsies could be helpful in patients with chronic diarrhea and/or abdominal pain for the following work up.

Correlation between nasal mucociliary clearance time and gastroesophageal reflux disease: our experience on 50 patients.

OBJECTIVES: It is increasingly suggested that gastroesophageal reflux disease (GERD) could play an important role in chronic rhinosinusitis. The aim of our study was to evaluate the nasal mucociliary clearance time in GERD patients and if any correlations could be assumed. METHODS: Fifty GERD patients endoscopically diagnosed underwent an ear, nose and throat evaluation. The saccharin test and the 20-Item Sino-nasal Outcome Test (SNOT-20) were administered to 50 participants who correspond to our inclusion criteria. The saccharin test is a validated proof to verify the nasal mucociliary clearance time and the SNOT-20 is a disease-specific, health-related quality of-life questionnaire widely used for the assessment of rhinosinusitis. RESULTS: Thirty-seven (74%) patients showed a significant increment in their saccharin test values in comparison with the others subjects (23.79+/-5.58 vs 8.15+/-2.06min; P=0.0001). This group of patients reported only typical gastroesophageal symptoms (GES) without any other complaint. Gastroesophageal endoscopic findings revealed some interesting and unexpected results in this subgroup. The remainder of patients considered (13/50; 26%) showed normal values for nasal mucociliary clearance time and they referred only typical extraesophageal symptoms (EES). In any case and in both groups rhinosinusitis complaints were present. The SNOT-20 test results were normal in all patients even if a significant difference for GES group could be highlighted (19.3 vs 7.4; P<0.005). CONCLUSION: This study supports the assumption of possible and important correlations between nasal mucociliary clearance time and GERD. GERD could be an altering factor for nasal function also in absence of laryngo-pharyngeal symptoms although to verify this interesting hypothesis more validated data are necessary.

Gastritis, dyspepsia and peptic ulcer disease.

Peptic ulcer disease remains a common problem and it most frequently due to the presence of an Helicobacter pylori infection or use of non-steroidal anti-inflammatory drugs (NSAIDs). Dyspepsia is neither sensitive or specific for diagnosing peptic ulcer disease. The approach to patients with dyspepsia is to arrive at a definitive diagnosis without unnecessary exposure to invasive or costly diagnostic procedures. Non-invasive testing is preferred with endoscopy being reserved for those with alarm markers or above a specified age (e.g., 55 years in Western countries). Patients negative for H. pylori infection should receive an empiric trial of acid suppression for 4 to 8 weeks and if beneficial it can be continued.

Twice daily (mid-day and evening) quadruple therapy for H. pylori infection in the United States.

BACKGROUND: Quadruple therapy provided inadequate eradication rate when given twice-a-day at breakfast and evening meals. AIM: To test twice daily (mid-day and evening) quadruple therapy for Helicobacter pylori eradication. METHODS: This was a single-centre pilot study in which H. pylori-infected (positive histology and culture and RUT) patients were given 2 x 250 mg of metronidazole and 2 x 250 mg of tetracycline, two Pepto-Bismol tablets, plus one 20 mg rabeprazole tablet twice-a-day for 14 days. H. pylori status was confirmed 4 or more weeks after the end of therapy. RESULTS: Thirty-seven patients including 3 with peptic ulcer disease, 19 asymptomatic infected, 4 GERD, and 11 with NUD. Mid-day quadruple therapy was successful in 92.3% (95% CI: 79-98%) including 96.2% of those with metronidazole-susceptible strains, and in 83.3% (10/12) of those with metronidazole-resistant H. pylori. Compliance was 100% by pill count except in one individual who stopped medication after 12 days because of side-effects and who failed therapy. Moderate or greater side-effects were experienced by five patients. CONCLUSION: Twice-a-day, mid-day, quadruple therapy proved effective using the combination of bismuth subsalicylate and rabeprazole instead of bismuth subcitrate and omeprazole. Detailed studies of different formulations (e.g. 2 x 250 mg versus 1 x 500 mg of metronidazole or tetracycline) and timing of administration (breakfast and evening meal versus mid-day and evening meals) may result in significant improvements in H. pylori eradication regimens.

Ulcers and gastritis.

Significant advances continue to be made in the area of gastritis and ulcer disease. Studies to identify the most appropriate use of capsule endoscopy have now confirmed that it is superior to other methods for identifying small-bowel mucosal pathology and sites of obscure gastrointestinal bleeding. It has increasingly been recognized that the complications of ulcer disease are secondary to the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and to interactions between NSAIDs and Helicobacter pylori. Effective prophylaxis for NSAID ulcers in H. pylori-negative individuals continues to be a challenge, as it has become clear that conclusions from studies focusing on "endoscopic ulcers" in patients whose H. pylori status was unknown provided a false sense of security. The concept of multifocal atrophic gastritis has been challenged. The precursor lesion to gastric cancer now appears to be a sheet of pseudopyloric metaplasia advancing into the gastric body with islands of intestinal metaplasia embedded within it. Multifactorial models such as those proposed for understanding periodontal disease, including the organism, environmental factors, and host factors, appear particularly applicable to understanding the pathogenesis of H. pylori-associated gastric cancer.

High-level beta-lactam resistance associated with acquired multidrug resistance in Helicobacter pylori.

Four clinical Helicobacter pylori isolates with high-level resistance to beta-lactams exhibited low- to moderate-level resistance to the structurally and functionally unrelated antibiotics ciprofloxacin, chloramphenicol, metronidazole, rifampin, and tetracycline. This pattern of multidrug resistance was transferable to susceptible H. pylori by natural transformation using naked genomic DNA from a clinical multidrug-resistant isolate. Acquisition of the multidrug resistance was also associated with a change in the genotype of the transformed multidrug-resistant H. pylori. DNA sequence analyses of the gene encoding penicillin binding protein 1A (PBP 1A) showed 36 nucleotide substitutions resulting in 10 amino acid changes in the C-terminal portion (the putative penicillin binding domain). Acquisition of beta-lactam resistance was consistently associated with transfer of a mosaic block containing the C-terminal portion of PBP 1A. No changes of genes gyrA, rpoB, rrn16S, rdxA, and frxA, and nine other genes (ftsI, hcpA, llm, lytB, mreB, mreC, pbp2, pbp4, and rodA1) encoding putative PBPs or involved in cell wall synthesis were found among the transformed resistant H. pylori. Antibiotic accumulations of chloramphenicol, penicillin, and tetracycline were all significantly decreased in the natural and transformed resistant H. pylori compared to what was seen with susceptible H. pylori. Natural transformation also resulted in the outer membrane protein profiles of the transformed resistant H. pylori becoming similar to that of the clinical resistant H. pylori isolates. Overall, these results demonstrate that high-level beta-lactam resistance associated with acquired multidrug resistance in clinical H. pylori is mediated by combination strategies including alterations of PBP 1A and decreased membrane permeability.

Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or salvage therapy for Helicobacter pylori infection.

OBJECTIVE: Helicobacter pylori (H. pylori) eradication rates in northern Sardinia using standard 1-wk triple therapies (i.e., a proton pump inhibitor and two antibiotics) are typically <60%, primarily because of antibiotic resistance. The aim of this study was to test b.i.d. quadruple therapy as primary and as salvage therapy in this population. METHODS: This was a prospective, single center study of consecutive dyspeptic H. pylori-infected patients. Therapy consisted of omeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg, all b.i.d. with the midday and evening meals for 14 days. H. pylori status was evaluated by 13C-urea breath test and histology before and 4-6 wk after therapy. Eradication was defined as no positive test. RESULTS: We enrolled 118 consecutive dyspeptic patients (mean age 46 yr; 73 men, including 15 with peptic ulcer disease). Of the patients, 42 (38%) had failed prior therapy: twice in 21 cases, three times in 12, and four or more times in nine. The intention-to-treat cure rate was 95% (110 of 116) (95% CI = 90-98%) overall, and 98% per protocol, irrespective of diagnosis, age, prior treatment failure, or smoking status. Moderate or severe side effects were experienced by only 5% of patients. CONCLUSIONS: Bismuth subcitrate-based b.i.d. quadruple therapy was an excellent primary and salvage therapy and should be considered as first line therapy.

Genotypic characterization of clarithromycin-resistant Helicobacter pylori strains.

UNLABELLED: Helicobacterpylori (Hp) resistance to clarithromycin, one of the antibiotics most used to eradicate infection, is connected with the presence of a point mutation on the level of adenine at position 2143 or 2144 of 23S rRNA. AIM: The aim of the study is to evaluate of the presence of these mutation vs control clarithromycin resistant Hp strains present in North Sardinia; to verify the real association between the type of mutation and the resistance-level; to use easier molecular biology methods to quickly locate the resistance-associated mutations beginning with the bioptic material. The clarithromycin susceptibility of Hp isolates was tested by the E-test method (antibiotic assay). Genomic DNA of Hp strains was amplified using specific primers for the domain V. of ribosomic 23S rRNA and sequenced after the reaction with a primer within the fragment 23S. At the same time PCR-RFLP reliability was examined underlining the presence of these mutations with BsaI, BbsI, MboII restriction enzymes. Two mutations in 2143 (A- - G) and 2144 (A- - G) were found by domain V sequencing. The strains with mutation 2143 are characterized by a greater resistance level (MIC>64 g/ml) than those with mutation 2144 (MIC <64 g/ml). Restriction endonucleases BbsI and MboII recognise the site containing the mutation 2143 (A- - G), while BsaI recognise the mutation 2144 (A- - G). These methods might enable us to identify the presence of Hp directly from bioptic material and possible clarithromycin resistance and plan a suitable therapeutic strategy and consequently a better control of the infection.

Genomic instability in chronic viral hepatitis and hepatocellular carcinoma.

Chronic hepatitis may progress to cirrhosis and hepatocellular carcinoma (HCC). Progressive accumulation of mutations and genomic instability in chronic viral hepatitis might flag an increased risk of HCC development. Genomic instability at dinucleotide microsatellite loci in chromosomes 2, 13, and 17 and at 2 mononucleotide repeat loci was examined in liver tissues from 41 patients, including 30 without HCC (18 patients with chronic hepatitis and 12 with cirrhosis) and 11 with HCC. Genomic instability was detected in 51% of the 41 cases. Allelic imbalance at informative dinucleotide loci occurred in 37% of the cases. In 14 cases (34%), allelic imbalance was detected in chronic hepatitis or cirrhosis without HCC. Allelic imbalance at the chromosome 13 locus was detected in 50% of the cases of chronic hepatitis C. Allelic imbalance at the TP53 chromosome locus and/or at the chromosome 13 locus was significantly more frequent than alterations at the chromosome 2 locus (P =.026). Low-level microsatellite instability was found in 20% of all cases examined and high-level microsatellite instability in 3 patients (7.5%), including 2 cases of chronic hepatitis and 1 case of cirrhosis. Our results show that allelic imbalance occurs frequently in hepatitis-related HCC as well as in chronic hepatitis in patients without HCC. Allelic imbalance at the D13S170 chromosome 13 locus (13q31.2) occurs frequently in chronic hepatitis, suggesting that genomic alterations affecting the long arm of chromosome 13 might be used to monitor the natural progression of chronic hepatitis-associated liver carcinogenesis.