Henry Nyhlin

Serum biomarkers provide an accurate method for diagnosis of atrophic gastritis in a general population: The Kalixanda study

Objective. Serological biomarkers can be used for non-invasive diagnosis of gastritis and atrophic gastritis. The aim of this study was to compare the validity of serum levels of pepsinogen I (PGI) and II (PGII), gastrin-17 (G-17) and Helicobacter pylori antibodies (Hpab) with that of the gold standard histology for diagnosis of atrophic gastritis in a population sample from Northern Sweden. Material and methods. In all, 1000 subjects underwent endoscopies with biopsies. Serum biomarkers were available in 976 subjects for independent diagnosis of gastric mucosal status using a predetermined diagnostic algorithm. Results. Overall agreement between histology and serological biomarkers in diagnosing corpus atrophy was 96% (CI 95%: 95–97%). Sensitivity and specificity of markers for atrophic gastritis were 71% (CI 68–74%) and 98% (CI 97–99%) respectively, corresponding to 69% (CI 95%: 66–72%) and 98% (95% CI 97–99%) positive and negative predictive values. The positive likelihood ratio was 35.5 (95% CI: 35.0–36.0%). In subgroups with normal stomachs, H. pylori non-atrophic gastritis and H. pylori-negative gastritis by histology, the prevalence of corpus atrophy diagnosed with the biomarkers was 0.8% and 4.9%, respectively. In total, 6.6% of subjects in the study population had corpus atrophy according to the serological biomarkers. Conclusions. Serological biomarkers show a high degree of accuracy as a non-invasive method to diagnose corpus atrophy, which is common in the general population.

Serum 7α-hydroxy-4-cholesten-3-one and selenohomocholyltaurine (sehcat) whole body retention in the assessment of bile acid induced diarrhoea

Objective: To assess the reliability of serum 7α-hydroxy-4-cholesten-3-one (7α-3ox-C) in the differential diagnosis of bile acid induced diarrhoea by comparison with 75selenohomocholyltaurine whole body retention (SeHCAT WBR). Design: One hundred and sixty-four patients with chronic diarrhoea were investigated prospectively in two centres (Edinburgh and Sweden) by two different tests which measure bile acid loss or synthesis: the SeHCAT test which measures the 7-day SeHCAT WBR and serum 7α-3ox-C which reflects the rate of bile acid synthesis. Results: Forty-six patients had SeHCAT WBR of less than 10% (19 with ileal disease or resection, nine with idiopathic bile acid induced diarrhoea and 18 with miscellaneous causes for bile acid induced diarrhoea). All patients with ileal or idiopathic disease showed a favourable response to treatment as did 13 of the miscellaneous group. Serum 7α-3ox-C was raised in all subjects with ileal disease/resection, seven patients with idiopathic disease and all subjects in the miscellaneous group who responded to treatment. Sixteen out of 118 patients with SeHCAT WBR greater than or equal to 10% had raised serum 7α-3ox-C. Conclusion: The positive predictive value of serum 7a-3ox-C was 74%. The high negative predictive value (98%) of serum 7α-3ox-C indicates the possible use of this test for excluding bile acid malabsorption in this population. All but two subjects who responded to treatment had raised serum 7a-3ox-C concentrations. The possibility that the sensitivity of the test can be improved by repeat testing needs to be further investigated. There was a significant correlation between fractional catabolic rate (FCR) SeHCAT and serum 7α-3ox-C (r = 0.63, P< 0.0001). Further data are required to validate the reference range in women over 70 years of age.

Spectral analysis of heart rate variability in patients with irritable bowel syndrome

BACKGROUND Autonomic dysfunction, both adrenergic and cholinergic, has been associated with the irritable bowel syndrome (IBS). The accuracy of the methods in use, however, has been limited by the need for active co-operation by the patients, with consequent difficulties in standardization. The aim of this study was to investigate the function of the autonomic nervous system in patients with IBS by using spectral analysis of the heart rate variability, an accurate method depending very little on patient cooperation. METHODS Eighteen patients with IBS were compared with 36 sex- and age-matched controls. Spectral analysis of heart rate variability was performed to quantify sympathetic and parasympathetic nerve activity. RESULTS The patients with IBS had significantly higher sympathetic activity than controls (P = 0.005). There was no significant (P = 0.308) increase in parasympathetic activity. There were no significant differences in heart rate or blood pressure between the patients and controls. CONCLUSION Spectral analysis of heart rate variability has been used to assess the function of the autonomic nervous system in patients with IBS. IBS patients have significantly increased symphathetic activity, whereas parasympathetic activity does not differ from that of controls.

Effects of gut-directed hypnotherapy on IBS in different clinical settings-results from two randomized, controlled trials.

OBJECTIVES:Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome (IBS). However, randomized, controlled studies are rare and few have been performed outside highly specialized research centers. The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical settings outside the traditional research units.METHODS:The study population included IBS patients refractory to standard management. In study 1, patients were randomized to receive gut-directed hypnotherapy (12 sessions, 1 h/week) in psychology private practices or supportive therapy, whereas patients were randomized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2. Gastrointestinal symptom severity and quality of life were evaluated at baseline, at 3 months follow-up and after 1 year.RESULTS:We randomized 138 IBS patients refractory to standard management, 90 in study 1 and 48 in study 2. In both the studies, IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups (P<0.05), but not in the control groups (ns). In study 1, a significantly greater improvement of IBS-related symptom severity could be detected in the gut-directed hypnotherapy group than in the control group (P<0.05), and a trend in the same direction was seen in study 2 (P=0.17). The results seen at 3 months were sustained up to 1 year.CONCLUSIONS:Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS, but the effectiveness is lower when the therapy is given outside the highly specialized research centers.

Evaluation of ileal function using 23-selena-25-homotaurocholate, a-gamma-labeled conjugated bile acid. Initial clinical assessment

23-Selena-25-homotaurocholate is a synthetic bile acid labeled with a gamma-ray-emitting radioisotope 75Se. It is readily measured using external detectors and is thus suitable for whole-body counting. Whole-body retention was measured at 0, 4, and 7 days after oral administration to normal controls and to patients with disease of the small intestine, colon, or ileocecal region. Whole-body retention of less than 25% of the administered radioactivity within 4 days is definitely abnormal, but there was overlap between normal and abnormal groups at this time. At 7 days, whole-body retention less than 12% is abnormal and greater than 19% is normal. Between these limits, values may represent minimal ileal dysfunction not demonstrable by older techniques. Excretion of 23-selena-25-homotaurocholate follows a biexponential curve. The faster component has a half-life similar to that of natural bile acid. It is uncertain whether the slower component represents a hitherto unrecognized slowly turning over pool of bile acid or is a metabolic product of 23-selena-25-homotaurocholate not yet identified in vitro. There is a significant relationship between the whole-body retention of 23-selena-25-homotaurocholate and total fecal and primary bile acids. 23-selena-25-homotaurocholate is simple and acceptable for investigating ileal function.

A negative Helicobacter pylori serology test is more reliable for exclusion of premalignant gastric conditions than a negative test for current H. pylori infection: a report on histology and H. pylori detection in the general adult population.

Objective. Corpus-dominant gastritis, gastric mucosal atrophy and intestinal metaplasia (IM) associated with Helicobacter pylori infection are all known potential risk markers for the development of gastric cancer. As the accuracy for finding cases at risk in the general population is unknown, we aimed to determine the prevalence of current and/or past H. pylori infection and associated gastric mucosal findings by means of histological survey of a random adult population. Material and methods. A random Swedish sample (n=3000, age 20–81 years) was surveyed using a validated gastrointestinal symptom questionnaire with 74% response rate. One-third of the responders were selected at random for esophago-gastro-duodenoscopy with biopsies and H. pylori serology. Results. Of those endoscoped (n=1000, mean age 53.5, 51% women), 43.0% were H. pylori+ by serology (seropositive), 33.9% had signs of current infection on either histology or culture (gold standard+), and 9.3% were seropositive, but gold standard negative. Corpus atrophy was found in 10% and IM in 13% when gold standard positive, and in a significantly higher number (17% and 21%, respectively) of those with only a serological sign of past infection. Among those who were seronegative, values were 1% and 2%, respectively. Corpus-dominant gastritis was found in 4.1%, all seropositive. Conclusion. One-third had an ongoing H. pylori infection, and a further 10% had signs of past infection. Corpus-dominant gastritis was found mostly among the former, while detection of those with corpus atrophy and IM also required a test for past infection. Seronegativity almost excludes precancerous conditions in a screening situation.

Antimicrobial Susceptibility of Helicobacter pylori Strains in a Random Adult Swedish Population

Background and Aim:  Antimicrobial resistance in Helicobacter pylori is a growing problem and has become an important factor leading to eradication failure. Information on antimicrobial susceptibility is important for selection of an optimum treatment regimen. The resistance rate in a random population has not been studied previously.

Long-term effects of hypnotherapy in patients with refractory irritable bowel syndrome

Abstract Objective. Gut-directed hypnotherapy is considered to be an effective treatment in irritable bowel syndrome (IBS) but few studies report the long-term effects. This retrospective study aims to evaluate the long-term perceived efficacy of gut-directed hypnotherapy given outside highly specialized hypnotherapy centers. Methods. 208 patients, who all had received gut-directed hypnotherapy, were retrospectively evaluated. The Subjective Assessment Questionnaire (SAQ) was used to measure changes in IBS symptoms, and patients were classified as responders and non-responders. Patients were also asked to report changes in health-care seeking, use of drugs for IBS symptoms, use of alternative non-pharmacological treatments, and if they still actively used hypnotherapy. Results. Immediately after hypnotherapy, 103 of 208 patients (49%) were responders and 75 of these (73%) had improved further at the follow-up 2–7 years after hypnotherapy (mean 4 years). A majority of the responders still used hypnotherapy on a regular basis at follow-up (73%), and the responders reported a greater reduction in health-care seeking than non-responders. A total of 87% of all patients reported that they considered gut-directed hypnotherapy to be worthwhile, and this differed between responders and non-responders (100% vs. 74%; p < 0.0001). Conclusion. This long-term follow-up study indicates that gut-directed hypnotherapy in refractory IBS is an effective treatment option with long-lasting effects, also when given outside highly specialized hypnotherapy centers. Apart from the clinical benefits, the reduction in health-care utilization has the potential to reduce the health-care costs.

Assessment of normal bowel habits in the general adult population: the Popcol study.

Abstract Objective. Defining normal stool habit is important when evaluating diarrhoea or constipation, but common confounders such as irritable bowel syndrome (IBS) or the intake of medications with gastrointestinal side effects have not been considered in earlier population based studies defining what is normal. We hypothesized that the exclusion of subjects with common confounders would help to better understand what are “normal bowel habits”. We aimed to prospectively study bowel habits in a carefully studied random sample of the general population. Material and methods. Two hundred and sixty-eight randomly selected subjects between 18 and 70 years completed symptom diaries for one week and were clinically evaluated by a gastroenterologist. They also had a colonoscopy and laboratory investigations to exclude organic disease. Results. One hundred and twenty-four subjects had no organic gastrointestinal abnormality, IBS, or relevant medication; 98% of them had between three stools per day and three per week. Seventy-seven percent of all stools were normal, 12% hard, and 10% loose in consistency. Urgency was reported by 36%; straining by 47% and incomplete defecation by 46%. After the exclusion of subjects with organic abnormalities, women had significantly more symptoms than men in terms of abdominal pain, bloating, constipation, urgency, and feeling of incomplete evacuation but these gender differences disappeared after excluding subjects with IBS. Conclusions. This study confirms that normal stool frequency is between three per week and three per day. We could not demonstrate any gender or age differences in terms of stool frequency, defecatory symptoms or abdominal bloating. Some degree of urgency, straining, and incomplete evacuation should be considered normal.

Prevalence of colonic neoplasia and advanced lesions in the normal population : a prospective population-based colonoscopy study.

Abstract Objective. There are few prospective studies of the prevalence of colonic neoplasia in the normal population. In order to properly evaluate screening-protocols for colorectal cancer in risk groups (e.g., older subjects or those with a family history), it is essential to know the prevalence of adenomas and cancer in the normal population. Methods. A prospective population-based colonoscopy study on 745 individuals born in Sweden aged 19–70 years was conducted (mean age 51.1 years). All polyps seen were retrieved and examined. Results. Out of the 745 individuals 27% had polyps, regardless of kind. Adenomas were found in 10% of the individuals and finding of adenomas was positively correlated to higher age. Men had adenomas in 15% and women in 6% of the cases. Women had a right-sided dominance of adenomas. Hyperplastic polyps were seen in 21% of the individuals. The presence of hyperplastic polyps was significantly positively correlated to the presence of adenomas. Advanced adenomas were seen in 2.8% of the study participants, but no cancers were detected. Conclusion. One in 10 healthy subjects had an adenoma but advanced adenomas were uncommon. Men and women have a different adenoma prevalence and localization. The results provide baseline European data for evaluating colonoscopy screening-protocols for colorectal cancer risk groups, and the findings may have implications for colon cancer screening in the normal, otherwise-healthy population.