Bodil Ohlsson

Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: A nationwide study

Objective. Autoimmune hepatitis (AIH) is a chronic liver disease, which if untreated can lead to cirrhosis and hepatic failure. The aim of the study was to investigate the incidence, prevalence, diagnostic tradition and clinical initial presentation of AIH. Material and methods. Analyses were performed in 473 patients identified as having probable or definite AIH. Results. The incidence of AIH was 0.85/100,000 (95% CI 0.69–1.01) inhabitants, which is somewhat lower than reported previously. The point prevalence amounted to 10.7/100,000 (95% CI 8.8–13.1), and 76% of the cases were females. The age-related incidence curve was bimodal but men were found to have only one incidence peak in the late teens, whereas women had a peak after menopause. AIH was presented as a spectrum of clinical settings from detected “en passant” to acute liver failure. Almost 30% of patients already had liver cirrhosis at diagnosis. Autoantibodies indicative of AIH type 1 were found in 79% of cases. Other concomitant autoimmune diseases were frequently found (49%). Conclusions. The incidence and prevalence figures confirm that AIH is a fairly uncommon disease in the Swedish population. Symptoms at presentation were unspecific, but almost half of the patients were jaundiced, with around 30% having liver cirrhosis. The majority of Swedish AIH patients had AIH type 1.

Development and psychometric testing of the Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS).

BackgroundThe aim of this study was to develop and psychometrically test a short, patient-reported questionnaire to be used in clinical practice for patients with Irritable Bowel Syndrome (IBS). The Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS) questionnaire was designed to measure the treatment response of symptoms and well-being in patients suffering from IBS.MethodsThe VAS-IBS was psychometrically tested for content and criterion validity, scale acceptability, item-reduction, internal reliability consistency, simplicity, and speed. Two samples were used. One expert panel (five physicians and four registered nurses), who gave their opinion on the content validity, and one of 71 patients with IBS (mean age 38 years SD +13, range 19–65), who completed the VAS-IBS, as well as the Gastrointestinal Symptom Rating Scale and the Psychological General Well-Being Index for criterion validity.ResultsThe items in the VAS-IBS capture the main physical concerns women with IBS might present and the psychometric testing confirmed that the VAS-IBS is an acceptable homogeneous patient-reported questionnaire indicated by Cronbachs alpha internal consistency reliability coefficient, with a value of 0.85. All correlations to test the criterion validity performed by using Pearsons correlation test, were statistically significant (p < 0.0001) and in the expected directions. The VAS-IBS is easy to complete and unproblematic to calculate.ConclusionThe VAS-IBS appears to be reliable and user-friendly, for patients as well as for health professionals. The final version of the VAS-IBS including nine items needs to be further tested in clinical practice cross-culturally in women as well as in men.

Effects of long-term treatment with oxytocin in chronic constipation; a double blind, placebo-controlled pilot trial.

Abstractu2002 Background:u2002 Oxytocin and its receptor have been found throughout the gastrointestinal (GI) tract, where it affects gut function. Clinically, we have noticed an improvement of bowel habits during lactation in constipated women. The aim of this study was to examine whether oxytocin has an effect on bowel symptoms and psychological well being in women with refractory constipation.

Oxytocin and oxytocin-receptor mRNA expression in the human gastrointestinal tract: a polymerase chain reaction study

BACKGROUND/AIMnOxytocin (OT) has a wide range of effects throughout the body. However, the role of OT on the gastrointestinal (GI) tract has to be settled. So far, the few studies performed reveal no conclusive results. The aim of this study was to examine the expression of OT and OT-receptor mRNA in the human GI tract.nnnMATERIAL AND METHODSnFull-thickness biopsies from all segments of the GI tract and the gallbladder were collected during operations at the Department of Surgery, Malmö University Hospital. Biopsies were taken and put immediately into fluid nitrogen and stored at -70 degrees C until total RNA was extracted after mechanical tissue homogenization. Subsequently, poly A(+) mRNA was isolated from the total RNA extract using an automated nucleic acid extractor and converted into single-stranded cDNA. PCR amplifications were carried out using gene-specific OT and OT-receptor primers. The specificity of the PCR amplicons was further confirmed by Southern blot analyses using gene specific OT and OT-receptor hybridization probes.nnnRESULTSnExpression of OT and OT-receptor mRNA was detected in nearly all segments of the GI tract analyzed. In most of the biopsy specimens analyzed, co-expression of both OT and OT-receptor mRNA appeared to take place.nnnCONCLUSIONnThe present study demonstrates that OT and OT-receptor mRNAs are expressed throughout the GI tract. A possible physiological and/or pathophysiological role of OT and OT-receptor expression in the human GI tract and the cellular location of its expression remain to be shown.

Characteristics and long-term outcome of patients with autoimmune hepatitis related to the initial treatment response

Abstract Objectives. Autoimmune hepatitis (AIH) is a liver disease which, if untreated, may lead to liver cirrhosis and hepatic failure. Limited data exist regarding factors predicting the long-term outcome. The aims of this study were to investigate symptoms at presentation, prognostic features, management and treatment in relation to long-term outcome of AIH. Material and methods. A cohort of 473 Swedish patients with AIH was characterized regarding initial symptoms and signs, factors predicting death and future need for liver transplantation. Survival and causes of death were retrieved from Swedish national registers. Results. At diagnosis, fatigue was a predominant symptom (69%), 47% of the patients were jaundiced and 30% had liver cirrhosis. Another 10% developed cirrhosis during follow-up. Markedly elevated alanine aminotransferase levels at presentation were correlated with a better outcome. A high international normalized ratio (INR) at diagnosis was the only risk factor predicting a need for later liver transplantation. Histological cirrhosis, decompensation and non-response to initial treatment were all factors that correlated with a worse outcome. Overall life expectancy was generally favourable. However, most deaths were liver-related, e.g. liver failure, shock and gastrointestinal bleeding. Conclusions. Cirrhosis at diagnosis, a non-response to initial immune-suppressive treatment or elevated INR values were associated with worse outcome and a need for later liver transplantation. In contrast, an acute hepatitis-like onset with intact synthetic capacity indicated a good response to treatment and favourable long-term prognosis. Lifetime maintenance therapy is most often required.

Oesophageal dysmotility, delayed gastric emptying and autonomic neuropathy correlate to disturbed glucose homeostasis

Aims/hypothesisAmong diabetic patients, glucose homeostasis may be affected by abnormal gastrointestinal motility and autonomic neuropathy. This study analysed whether oesophageal dysmotility, delayed gastric emptying or autonomic neuropathy affect glucose homeostasis.Materials and methodsOesophageal manometry and gastric emptying scintigraphy were performed in 20 diabetic patients. Heart-rate variation during deep breathing (expiration/inspiration [E/I] ratio) and continuous subcutaneous glucose concentrations for a period of 72xa0h were also monitored in the same patients.ResultsOesophageal dysmotility was found in eight of 14 patients. Eleven of 20 patients had delayed gastric emptying (abnormal gastric emptying half-time [T50]) and nine of 18 had an abnormal E/I ratio. Complaints of abdominal fullness were predictive of delayed gastric emptying. A low peristaltic speed of the oesophagus was associated with impaired T50 (rs=−0.67; p=0.02). One hour after breakfast, subcutaneous glucose levels decreased in patients with delayed gastric emptying but continued to rise in those with normal emptying. Consequently, the median glucose level 2.5xa0h after breakfast was lower in the former (9.1 [4.2–12.5] vs 14.3 [11.2–17.7]xa0mmol/l; p<0.05). Glucose fluctuations during the 72xa0h were significantly higher in patients with an abnormal E/I ratio than in those with a normal E/I ratio (coefficient of variation: 41 [46–49] vs 28 [27–34]%; p=0.008).Conclusions/interpretationAbdominal fullness predicted delayed gastric emptying that was associated with diminished glucose uptake after breakfast. Low oesophageal peristaltic speed was associated with slow gastric emptying whereas parasympathetic neuropathy was associated with increased glucose variations.

The oxytocin/vasopressin receptor antagonist atosiban delays the gastric emptying of a semisolid meal compared to saline in human

BackgroundOxytocin is released in response to a meal. Further, mRNA for oxytocin and its receptor have been found throughout the gastrointestinal (GI) tract. The aim of this study was therefore to examine whether oxytocin, or the receptor antagonist atosiban, influence the gastric emptying.MethodsTen healthy volunteers (five men) were examined regarding gastric emptying at three different occasions: once during oxytocin stimulation using a pharmacological dose; once during blockage of the oxytocin receptors (which also blocks the vasopressin receptors) and thereby inhibiting physiological doses of oxytocin; and once during saline infusion.Gastric emptying rate (GER) was assessed and expressed as the percentage reduction in antral cross-sectional area from 15 to 90 min after ingestion of rice pudding. The assessment was performed by real-time ultrasonography. At the same time, the feeling of satiety was registered using visual satiety scores.ResultsInhibition of the binding of endogenous oxytocin by the receptor antagonist delayed the GER by 37 % compared to saline (p = 0.037). In contrast, infusion of oxytocin in a dosage of 40 mU/min did not affect the GER (p = 0.610). Satiation scores areas in healthy subjects after receiving atosiban or oxytocin did not show any significant differences.ConclusionOxytocin and/or vasopressin seem to be regulators of gastric emptying during physiological conditions, since the receptor antagonist atosiban delayed the GER. However, the actual pharmacological dose of oxytocin in this study had no effect. The effect of oxytocin and vasopressin on GI motility has to be further evaluated.

Gastroparesis is associated with oxytocin deficiency, oesophageal dysmotility with hyperCCKemia, and autonomic neuropathy with hypergastrinemia

BackgroundGastrointestinal (GI) dysmotility and autonomic neuropathy are common problems among diabetics with largely unknown aetiology. Many peptides are involved in the autonomic nervous system regulating the GI tract. The aim of this study was to examine if concentrations of oxytocin, cholecystokinin (CCK), gastrin and vasopressin in plasma differ between diabetics with normal function and dysfunction in GI motility.MethodsNineteen patients with symptoms from the GI tract who had been examined with gastric emptying scintigraphy, oesophageal manometry, and deep-breathing test were included. They further received a fat-rich meal, after which blood samples were collected and plasma frozen until analysed for hormonal concentrations.ResultsThere was an increase in postprandial oxytocin plasma concentration in the group with normal gastric emptying (p = 0.015) whereas subjects with delayed gastric emptying had no increased oxytocin secretion (p = 0.114). Both CCK and gastrin levels increased after the meal, with no differences between subjects with normal respective delayed gastric emptying. The concentration of vasopressin did not increase after the meal. In patients with oesophageal dysmotility the basal level of CCK tended to be higher (p = 0.051) and those with autonomic neuropathy had a higher area under the curve (AUC) of gastrin compared to normal subjects (p = 0.007).ConclusionReduced postprandial secretion of oxytocin was found in patients with delayed gastric emptying, CCK secretion was increased in patients with oesophageal dysmotility, and gastrin secretion was increased in patients with autonomic neuropathy. The findings suggest that disturbed peptide secretion may be part of the pathophysiology of digestive complications in diabetics.

Evaluation of gastrointestinal symptoms in different patient groups using the visual analogue scale for irritable bowel syndrome (VAS-IBS)

BackgroundIrritable bowel syndrome (IBS) and gastrointestinal (GI) dysmotility disorders have a similar clinical picture, although dysmotility disorders require the attention of a specialist. Patients with primary Sjögrens syndrome (pSS) have also been described to suffer from IBS-like symptoms. No objective marker is available to distinguish between the patients. A visual analogue scale has been developed for IBS patients (VAS-IBS) to measure treatment response of GI symptoms and well-being in patients with IBS. The aim of the present study was to examine if VAS-IBS could be used to compare the degree of GI complaints in different patient populations, to get an objective marker to differentiate between the patients.MethodsThe VAS-IBS consists of 7 VAS scales, namely, abdominal pain, diarrhoea, constipation, bloating and flatulence, vomiting and nausea, psychological well-being and the intestinal symptoms influence on daily life. Consecutive female patients suffering from IBS, dysmotility disorders and pSS were asked to complete the VAS-IBS questionnaire when visiting the out-patient clinics. In addition, a control population consisting of healthy female volunteers was included.ResultsHealthy volunteers had almost no GI symptoms, whereas all 3 patient groups expressed symptoms. There was no statistical significant difference between IBS and dysmotility in any of the scales besides vomiting and nausea (p = 0.044). Except for constipation, patients with pSS had less severe symptoms than the others.ConclusionThe VAS-IBS questionnaire could be used to assess the level of GI symptoms. However, VAS scores do not help the clinicians to differentiate between IBS and other dysmotility disturbances.

Subclinical sympathetic neuropathy appears early in the course of Crohn's disease.

BackgroundWe have previously demonstrated that patients with Crohns disease (CD) of long duration have signs of autonomic neuropathy. The aim of this study was to examine whether autonomic neuropathy is an early manifestation of CD, or a sign appearing late in the course.MethodsTwenty patients, median age 40 years, with a short duration of CD were included. Examination of autonomic reflexes included heart rate reaction to tilt (acceleration index – AI, brake index – BI) and heart rate variation to deep-breathing (expiration/inspiration index-E/I). Seven years later the same examinations were repeated, and in addition we examined the vasoconstriction response to indirect cooling by laser Doppler (vasoconstriction-index – VAC-index). The results were compared with healthy individuals.ResultsThere was no difference in the blood pressure between controls and the patients with CD at rest, but eight minutes after tilt, the systolic blood pressure was lowered in patients compared to controls, both at the first assessment (p = 0.016) and after seven years (p = 0.042). The change in systolic blood pressure between rest and eight minutes after tilt was not significant at the first assessment, while a significant change compared to controls was observed seven years later (p = 0.028). This indicates a progressive dysfunction. There were no differences in E/I, AI, BI or VAC indexes between patients and controls.ConclusionPatients with CD suffer from autonomic neuropathy early in their disease, suggesting involvement of many different organ systems in this entity.