The incidence of other gastroenterological disease following diagnosis of irritable bowel syndrome in the UK: a cohort study

BACKGROUND: Guidelines recommend Irritable Bowel Syndrome (IBS) diagnosis and management in primary care with minimal investigations; however little evidence exists regarding risk of organic gastrointestinal conditions following diagnosis of IBS and how such risks vary over the long term. This study assesses excess incidence of coeliac disease, inflammatory bowel disease (IBD) and colorectal cancer (CRC) and variation with age and time after IBS diagnosis. METHODS: IBS patients and controls were identified within the UK Clinical Practice Research Dataset. Incidence rates were calculated and stratified by age and time since IBS diagnosis with incident rate ratios generated. RESULTS: Fifteen years after IBS diagnosis there is a significant cumulative excess incidence of coeliac disease, IBD and CRC in IBS of 3.7% compared to 1.7% in controls. For every 10000 patient years, IBS patients experienced an additional 4 diagnoses of coeliac disease, 13 of IBD and 4 CRCs. In each condition peak excess incidence was in the 6 months following diagnosis. After one year, increased incidence of coeliac disease remained consistent without variation by age. IBD incidence fell slowly, with higher rates in those under 30. CRC incidence was increased only in patients aged 30 to 74 during the first 5 years. CONCLUSION: Some IBS patients later receive organic gastrointestinal diagnoses, with the early excess incidence likely detected during diagnostic investigation at the time of IBS diagnosis. More than 5 years after IBS diagnosis there is no increased risk of CRC compared to the general population, but a small excess risk of coeliac disease and IBD persists. Overall, though our findings provide reassurance that non-specialists, especially those in primary care, are unlikely to be missing an organic condition in the majority of their patients. This suggests that current guidelines suggesting avoidance of universal referral for these patients are appropriate

Helicobacter pylori (H pylori) infection in Greece: the changing prevalence during a ten-year period and its antigenic profile

BACKGROUND: To evaluate changes in H pylori infection prevalence in Greece during a ten-year period, and to examine its antigenic profile. METHODS: Three groups of patients were studied. Group O-87: Banked serum samples of 200 consecutive adult outpatients, from the Hepato-Gastroenterology clinic of a teaching hospital at Athens, collected in 1987. Group O-97: Serum samples of 201 similarly selected outpatients from the same Unit, collected in 1997. Group BD-97: Serum samples of 120 consecutive blood donors from the same hospital, collected in 1997. H pylori IgG antibody seroprevalence was studied by a quantitative ELISA. Antigenic profile was studied by western-blot IgG assay, in 62 IgG positive patients of O-97 and BD-97. Results were analyzed by conventional statistics and multivariate regression analysis. RESULTS: The H pylori seroprevalence increased with age in the three tested groups. In O-97, seroprevalence did not differ from that, in BD-97. On the contrary, there was a significant decrease in seropositivity between O-87 and O-97 (59.5% vs 49.2%, p = 0.039). Multiple regression analysis showed that age over 35 years (OR:3.45, 95% CI:1.59–7.49, p = 0.002) and year of patients' selection – that is 1987 or 1997 – (OR:1.73, 95% CI:1.14–2.65 for 1987, p = 0.010), were independent risk factors of H pylori infection. The seroprevalence of CagA+ and VacA+ strains was 77.4% and 58.5%, respectively, and type I(CagA+/VacA+) strains were significantly more common than type II(CagA-/VacA-) strains (59.7% vs 22.6%, p < 0.001). CONCLUSIONS: During a ten-year period, we found a significant decrease of H pylori infection in Greece and our data support the birth cohort phenomenon as an explanation for the age-dependent increase of H pylori infection. The prevalence of CagA and/or VacA positive strains is relatively high, in a country with low incidence of gastric cancer

H. pylori Seropositivity before Age 40 and Subsequent Risk of Stomach Cancer: A Glimpse of the True Relationship?

Stomach carcinogenesis involves mucosal and luminal changes that favor spontaneous disappearance of Helicobacter pylori. Therefore, the association between the infection and cancer risk might typically be underestimated. As acquisition of the infection almost invariably occurs before adulthood, the serostatus at age 16–40 should best reflect the lifetime occurrence of the infection. We therefore conducted a case-control study nested within a historic cohort of about 400,000 individuals who donated sera before age 40 to either of two large Swedish Biobanks between 1968 and 2006, and whose records were linked to complete nationwide registers. For each stomach adenocarcinoma case occurring at least 5 years after serum donation 2 controls were selected matched on age, sex and year of donation and biobank. Serum immunoglobulin G antibodies against H. pylori cell-surface antigens (Hp-CSAs) were measured with an enzyme–linked immunosorbent assay and antibodies against CagA with an immunoblot assay. Conditional logistic regression models were used to estimate odds ratios (ORs) for stomach adenocarcinoma among H. pylori infected relative to uninfected. We confirmed 59 incident cases of stomach adenocarcinoma (41 non-cardia tumors) during follow-up. ORs for non-cardia stomach adenocarcinoma among subjects with Hp-CSA antibodies (regardless of CagA serostatus), antibodies against CagA (regardless of Hp-CSA serostatus), and antibodies to both, relative to those who were seronegative to both, were 17.1 (95% confidence interval [CI] 4.0–72.9), 10.9 (95% CI 3.2–36.9), and 48.5 (95% CI 5.8–407.4), respectively. H. pylori infection is a much stronger risk factor for non-cardia stomach adenocarcinoma than initially realized. However, further studies are needed to answer whether it is a necessary cause, as the possibility of misclassification of H. pylori status could not be ruled out in our study

Retrieval of Context-Associated Memory is Dependent on the Cav3.2 T-Type Calcium Channel

Among all voltage-gated calcium channels, the T-type Ca2+ channels encoded by the Cav3.2 genes are highly expressed in the hippocampus, which is associated with contextual, temporal and spatial learning and memory. However, the specific involvement of the Cav3.2 T-type Ca2+ channel in these hippocampus-dependent types of learning and memory remains unclear. To investigate the functional role of this channel in learning and memory, we subjected Cav3.2 homozygous and heterozygous knockout mice and their wild-type littermates to hippocampus-dependent behavioral tasks, including trace fear conditioning, the Morris water-maze and passive avoidance. The Cav3.2 −/− mice performed normally in the Morris water-maze and auditory trace fear conditioning tasks but were impaired in the context-cued trace fear conditioning, step-down and step-through passive avoidance tasks. Furthermore, long-term potentiation (LTP) could be induced for 180 minutes in hippocampal slices of WTs and Cav3.2 +/− mice, whereas LTP persisted for only 120 minutes in Cav3.2 −/− mice. To determine whether the hippocampal formation is responsible for the impaired behavioral phenotypes, we next performed experiments to knock down local function of the Cav3.2 T-type Ca2+ channel in the hippocampus. Wild-type mice infused with mibefradil, a T-type channel blocker, exhibited similar behaviors as homozygous knockouts. Taken together, our results demonstrate that retrieval of context-associated memory is dependent on the Cav3.2 T-type Ca2+ channel

Evaluation of guided imagery as treatment for recurrent abdominal pain in children: a randomized controlled trial

BACKGROUND: Because of the paucity of effective evidence-based therapies for children with recurrent abdominal pain, we evaluated the therapeutic effect of guided imagery, a well-studied self-regulation technique. METHODS: 22 children, aged 5 – 18 years, were randomized to learn either breathing exercises alone or guided imagery with progressive muscle relaxation. Both groups had 4-weekly sessions with a therapist. Children reported the numbers of days with pain, the pain intensity, and missed activities due to abdominal pain using a daily pain diary collected at baseline and during the intervention. Monthly phone calls to the children reported the number of days with pain and the number of days of missed activities experienced during the month of and month following the intervention. Children with ≤ 4 days of pain/month and no missed activities due to pain were defined as being healed. Depression, anxiety, and somatization were measured in both children and parents at baseline. RESULTS: At baseline the children who received guided imagery had more days of pain during the preceding month (23 vs. 14 days, P = 0.04). There were no differences in the intensity of painful episodes or any baseline psychological factors between the two groups. Children who learned guided imagery with progressive muscle relaxation had significantly greater decrease in the number of days with pain than those learning breathing exercises alone after one (67% vs. 21%, P = 0.05), and two (82% vs. 45%, P < 0.01) months and significantly greater decrease in days with missed activities at one (85% vs. 15%, P = 0.02) and two (95% vs. 77%. P = 0.05) months. During the two months of follow-up, more children who had learned guided imagery met the threshold of ≤ 4 day of pain each month and no missed activities (RR = 7.3, 95%CI [1.1,48.6]) than children who learned only the breathing exercises. CONCLUSION: The therapeutic efficacy of guided imagery with progressive muscle relaxation found in this study is consistent with our present understanding of the pathophysiology of recurrent abdominal pain in children. Although unfamiliar to many pediatricians, guided imagery is a simple, noninvasive therapy with potential benefit for treating children with RAP

Lactate Produced by Glycogenolysis in Astrocytes Regulates Memory Processing

When administered either systemically or centrally, glucose is a potent enhancer of memory processes. Measures of glucose levels in extracellular fluid in the rat hippocampus during memory tests reveal that these levels are dynamic, decreasing in response to memory tasks and loads; exogenous glucose blocks these decreases and enhances memory. The present experiments test the hypothesis that glucose enhancement of memory is mediated by glycogen storage and then metabolism to lactate in astrocytes, which provide lactate to neurons as an energy substrate. Sensitive bioprobes were used to measure brain glucose and lactate levels in 1-sec samples. Extracellular glucose decreased and lactate increased while rats performed a spatial working memory task. Intrahippocampal infusions of lactate enhanced memory in this task. In addition, pharmacological inhibition of astrocytic glycogenolysis impaired memory and this impairment was reversed by administration of lactate or glucose, both of which can provide lactate to neurons in the absence of glycogenolysis. Pharmacological block of the monocarboxylate transporter responsible for lactate uptake into neurons also impaired memory and this impairment was not reversed by either glucose or lactate. These findings support the view that astrocytes regulate memory formation by controlling the provision of lactate to support neuronal functions

Neurogenic mechanisms in bladder and bowel ageing

The prevalence of both urinary and faecal incontinence, and also chronic constipation, increases with ageing and these conditions have a major impact on the quality of life of the elderly. Management of bladder and bowel dysfunction in the elderly is currently far from ideal and also carries a significant financial burden. Understanding how these changes occur is thus a major priority in biogerontology. The functions of the bladder and terminal bowel are regulated by complex neuronal networks. In particular neurons of the spinal cord and peripheral ganglia play a key role in regulating micturition and defaecation reflexes as well as promoting continence. In this review we discuss the evidence for ageing-induced neuronal dysfunction that might predispose to neurogenic forms of incontinence in the elderly