Snorri Olafsson

Altered dopamine D2 receptor function in fibromyalgia patients: a neuroendocrine study with buspirone in women with fibromyalgia compared to female population based controls

BACKGROUND To what extent fibromyalgia belongs to affective spectrum disorders or anxiety spectrum disorders remains disputed. Buspirone induces a hypothermic response, which most likely is due to 5-HT(1A) autoreceptor stimulation, and growth hormone (GH) release, which probably is related to postsynaptic 5-HT(1A) receptor stimulation. The prolactin response to buspirone has been suggested to be mediated through dopamine (DA) antagonistic effects. OBJECTIVES Based on the assumption that fibromyalgia is more strongly related to stress and anxiety than affective spectrum disorders, we hypothesized that compared to population controls, fibromyalgia patients should demonstrate an increased prolactin response (DA sensitivity) to buspirone challenge test, but no difference in hypothermic response or GH release (5HT sensitivity). METHOD A 60-mg dose of buspirone was given orally to 22 premenopausal women with fibromyalgia and 14 age and sex matched healthy control subjects. Core body temperature, growth hormone and prolactin levels were analyzed at baseline and after 60, 90, and 150 min. RESULTS Fibromyalgia patients showed an augmented prolactin response to buspirone compared to controls. Temperature and growth hormone responses did not differ from controls. CONCLUSIONS Dopaminergic rather than serotonergic neurotransmission is altered in fibromyalgia, suggesting increased sensitivity or density of dopamine D(2) receptors in fibromyalgia patients. Stress and anxiety is an important modulator of dopaminergic neurotransmission. Our results suggest that fibromyalgia is related to anxiety and associated with disturbance in the stress response systems.

Fibromyalgia is associated with panic disorder and functional dyspepsia with mood disorders: A study of women with random sample population controls

BACKGROUND We compared ICD-10 psychiatric disorders in female patients with fibromyalgia (n=45) or functional dyspepsia (n=18) with age-matched random sample controls (n=49). METHOD Version 2 of The Schedules for Clinical Assessment in Neuropsychiatry (SCAN) was used for present state examination and lifetime diagnoses. RESULTS Current psychiatric disorders (somatoform pain disorder and specific phobia omitted) were diagnosed in 80% of fibromyalgia patients (OR=8.3), 83% of functional dyspepsia patients (OR=10.3) and 33% controls. Among fibromyalgia patients 27% had lifetime panic disorder. Lifetime mood disorders were found in 83% of functional dyspepsia patients. First-degree relatives with psychiatric disorder were found in 16% of the fibromyalgia patients, 50% of functional dyspepsia patients and 20% of controls. CONCLUSIONS Fibromyalgia is associated with panic disorder and functional dyspepsia with mood disorders in substantial subgroups. Psychiatric symptoms and somatic complaints are closely related in these disorders.

In vitro evaluation of three-dimensional ultrasonography based on magnetic scanhead tracking

The objective of this study was to evaluate the accuracy and precision of a magnetic position sensor system for acquisition of three-dimensional (3D) ultrasound images in volume estimation of phantoms in vitro. Installation of either 0.9% solution of saline at 37 degrees C or distilled water at 20 degrees C to a condom was performed. Scanning was performed either by a continuous or stepwise acquisition. This 3D ultrasound system demonstrated good correlation (r = 0.99-1.0, n = 8) between estimated (EV) and true volumes (TV). The errors were in the range 1.3%+/-0.3% (SEM) to 1.9%+/-0.6%, independent of sound velocity. Scanning through a porcine abdominal wall positioned at the fluid surface yielded a systematic underestimation of the volume: mean (EV - TV) = -7.2+/-0.8 ml. Eight repeated scans of the same volume yielded a coefficient of variation of 1.1%. Interobserver error of the tracing procedure was 2.6%+/-0.9%. This 3D ultrasound system gave high accuracy and precision in volume estimation in vitro, and yielded low interobserver error. A change in ultrasound velocity of approximately 60 m/s did not influence the accuracy significantly. Scanning through an abdominal wall underestimated volumes slightly.

Quality of life in patients with subjective food hypersensitivity: Applicability of the 10-item short form of the Nepean Dyspepsia Index

The aim of this study was to investigate quality of life and applicability of the 10-item short form of the Nepean Dyspepsia Index (SF-NDI) in patients with subjective food hypersensitivity. Fifty-two adult patients and 120 controls were examined using three questionnaires: Quality of life Nepean Dyspepsia Index (NDI), Gastrointestinal Symptom Rating Scale (GSRS), and Ulcer Esophagitis Subjective Symptoms Scale (UESS). To document psychometric properties, 20 of the patients filled in the SF-NDI questionnaire once more 4 weeks later. Patients had poor quality of life compared with controls from health care workers or general population (P < 0.001). Scores on SF-NDI were significantly correlated with scores on the GSRS (r = 0.34, P = 0.02) and UESS (r = 0.41, P = 0.003). The SF-NDI performed very satisfactorily, with a high reliability, construct validity, and responsiveness. Patients with subjective food hypersensitivity have considerably reduced quality of life. The SF-NDI provides reliable, responsive, and clinically valid measures of quality of life in these patients.

Pain attacks in non-complicated and complicated gallstone disease have a characteristic pattern and are accompanied by dyspepsia in most patients: The results of a prospective study

Objective. The cardinal indication for surgical treatment of gallstones is pain attacks. However, following cholecystectomy, 20% of patients remain symptomatic. It is unclear to what extent post-cholecystectomy symptoms can be ascribed to persistence of preoperative symptoms or to new pathology. The pain and digestive pattern in gallstone patients has not been defined in a recent setting with ultrasonography as the diagnostic method. The aim of this study was to characterize a pain pattern that is typical for gallstone disease and to describe the extent of associated dyspepsia. Material and methods. A total of 220 patients with symptomatic gallstone disease including complicated disease (acute cholecystitis and common bile duct stones) were interviewed using detailed questionnaires to disclose pain patterns and symptoms of indigestion. Results. All patients had pain in the right upper quadrant (RUQ) including the upper midline epigastrium. The pain was localized to the right subcostal area in 20% and to the upper epigastrium in 14%, and in the rest (66%) it was more evenly distributed. An area of maximal pain could be defined in 90%. Maximal pain was located under the costal arch in 51% of patients and in the epigastrium in 41%, but in 3% behind the sternum and in 5% in the back. The pain was referred to the back in 63% of the patients. The mean visual analogue scale (VAS) score was very high: 90 mm on a 0–100 scale. A pattern of incipient or low-grade warning pain with a subsequent relatively steady state until subsiding in the same fashion was present in 90% of the patients. An urge to walk around was experienced by 71%. Pain attacks usually occurred in the late evening or at night (77%), with 85% of the attacks lasting for more than one hour and almost never less than half an hour. Sixty-six percent of the patients were intolerant to at least one kind of food, but only 48% to fatty foods. Symptoms of functional indigestion (gastroesophageal reflux, dyspepsia or irritable bowel symptoms) were seen in the vast majority in association with attacks. Conclusions. Gallstone-associated pain follows a certain pattern in the majority of patients. The pain is located in a defined area with a point of maximum intensity, is usually referred, and occurs mainly at night with duration of more than one hour. The majority of patients experience functional indigestion, mainly of the reflux type or dyspepsia.

Vagal tone and meal-induced abdominal symptoms in healthy subjects

Background/Aims: Patients with functional dyspepsia often have meal-induced dyspeptic symptoms and low vagal tone. We examined whether these variables are related in healthy subjects. Methodology: In 40 healthy subjects vagal tone and abdominal symptoms were recorded before and after a 500-ml soup meal ingested in 1 and 4 min on separate visits. Vagal tone was indexed by respiratory sinus arrhythmia (RSA). Results: Scores for nausea and discomfort were higher when the soup was ingested in 1 min as compared with 4 min (nausea: p = 0.02; discomfort: p = 0.04). There was no difference in fullness or abdominal pain. RSA was unrelated to meal-induced symptom scores. RSA varied with respiration and body position: It was highest while breathing deeply in the sitting position (24.0 beats/min). With normal breathing RSA was highest in the supine position (9.0 beats/min), lower while sitting (7.0 beats/min) and lowest while standing (6.2 beats/min). Conclusions: Epigastric discomfort in response to rapid ingestion of a test meal in healthy subjects was not related to vagal tone as indexed by RSA. Vagal tone varied with breathing pattern and body position. It is possible that increasing vagal tone by such measures can be beneficial in the treatment of patients with functional dyspepsia.

Controversies in dyspepsia

Even in the absence of visible lesions like an ulcer, cancer or oesophagitis, patients with functional dyspepsia may complain of severe dyspeptic symptoms and have a poor quality of life. Characteristically, these patients also often have a low estimate of their own health and have complaints from several organ systems. The cause of the disease is not known. Both central nervous system and gastric disturbances appear to be involved, and their relative importance is controversial. There is no clear beneficial effect of acid suppression or H. pylori eradication although effects of such therapy may be seen in minor subgroups. New findings emphasise the importance of distinguishing between functional dyspepsia and gastro-oesophageal reflux disease, which exhibit completely different gastric accommodation patterns to a meal and have very different therapeutic potential. The effect of drugs like glyceryl trinitrate, glucagon, sumatriptan and buspirone which all concomitantly improve symptoms and gastric accommodation support the important role of abnormal gastric accommodation to meals in patients with functional dyspepsia. A hypothetical model for the pathogenesis of functional dyspepsia is presented. It incorporates four established abnormalities: various psychological abnormalities, low vagal tone, impaired gastric relaxation, and visceral hypersensitivity, in a logical interplay along the brain-gut axis.

Common pathogenetic mechanisms in symptomatic, uncomplicated gallstone disease and functional dyspepsia: volume measurement of gallbladder and antrum using three-dimensional ultrasonography.

Following cholecystectomy for uncomplicatedgallstone disease (GS) some patients experiencepersistent symptoms suggesting an underlying functionaldisorder. To study this phenomenon, we have comparedsymptomatic GS with functional dyspepsia (FD) patients andhealthy individuals (C) with respect to putativepathogenetic mechanisms. Gallbladder and gastric antrumvolumes were estimated with three-dimensional (3D) ultrasonography before and 10 min afteringestion of 500 ml meat soup in 18 patients with GS.Volume estimation was performed digitally afterinteractive manual tracing and organ reconstruction inthree dimensions. Respiratory sinus arrhythmia (RSA)was calculated to index vagal tone. Abdominal symptomswere assessed by interview. The results were compared topreviously published data in patients with FD and C investigated with the exact samemethods. No significant differences were found betweengroups with respect to fasting gallbladder orgallbladder emptying. Antral volumes both fasting (P< 0.05) and postprandially (P < 0.01) were larger inGS and FD than in C. The soup meal induced dyspepticsymptoms in 2/18 (11% ) of C, 12/18 (67% ) of GS and15/17 (88%) of FD patients (P < 0.001). Compared with C, both GS and FD patients had significantlydecreased vagal tone (P < 0.001). There was nosignificant difference between GS and FD patients withrespect to antral volume, vagal tone, or symptoms. Weconcluded that both gallstone and functional dyspepsiapatients are characterized by dyspeptic symptoms inresponse to ingestion of 500 ml of meat soup, a widegastric antrum, low vagal tone, but normal gallbladder size and emptying. Thus, patients withsymptomatic, uncomplicated gallstone disease andfunctional dyspepsia seem to have common pathogeneticmechanisms.

Changes in food tolerance and lifestyle after eradication of Helicobacter pylori

Background: It is known that patients with peptic ulcer disease (PUD) often have an unhealthy lifestyle that results in increased mortality because of smoking-related diseases. No thorough study has been done to see what changes, if any, the patient makes to lifestyle after eradication of Helicobacter pylori. Methods: One-hundred-and-eighty-three patients were enrolled in an open-endoscopy setting; 58% had PUD and 42% gastritis and/or duodenitis (G/D). They filled out a lifestyle questionnaire before the start of ant-Helicobacter therapy and again 1 year later. Results: The prevalence of food intolerance decreased from 71% to 44% among patients with PUD (P < 0.0001) and from 76% to 63% among patients with G/D (P = 0.09). Tolerance improved for coffee, orange juice, fried foods, spicy foods and fruits. There was no significant change in smoking or alcohol consumption after eradication. Coffee and tea consumption was unchanged. Milk consumption decreased from 4.2 dL/day to 3.3 (P = 0.01). The number of meals decreased from 3.5/day to 3.4 (P = 0.005) and snacking from 1.3 snacks/day to 1.1 (P = 0.02). Consumption of fruit increased from 4.0 to 4.3 times/week (P = 0.04), but the frequency of meat, fish, vegetables, spicy foods, salty foods, sweets and cakes did not change. The time spent on each meal was unchanged. There was no change in the time spent exercising. There were few significant differences between PUD and G/D patients. Conclusions: Food was better tolerated, but there were no major changes in lifestyle after eradication of H. pylori. Patients therefore do not abuse the privilege of a more tolerant digestion by indulging in a more unhealthy lifestyle.

Patients with Endoscopic Gastritis and/or Duodenitis Improve Markedly Following Eradication of Helicobacter pylori, Although Less So Than Patients with Ulcers

Background: It is well documented that dyspepsia in patients with peptic ulcer disease (PUD) improves markedly after eradication of Helicobacter pylori, while rarely does it improve in patients with functional dyspepsia. There is a large group of H. pylori -infected patients who do not qualify for either diagnosis, but in whom eradication may be considered. The aim of this study was to compare symptom severity, change in gastrointestinal symptoms 1 year after eradication and satisfaction with therapy between PUD patients and patients with endoscopic diagnoses of gastritis and/or duodenitis (G/D patients). Methods: The patients were randomized to one of four triple regimens containing ranitidine bismuth and metronidazole, and either oxytetracycline or spiramycine. Eradication was assessed with the 14 C-urea breath test. GI symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) and the Ulcer Esophagitis Subjective Symptoms Scale (UESS) questionnaires. Results: One-hundred-and-eighty-three patients were recruited from GI outpatient clinics. Patients with PUD and G/D had similar severity of symptoms before eradication therapy. One year after H. pylori eradication, 99% of the PUD patients and 75% of the G/D patients felt better regarding their main upper GI complaint. Abdominal pain score decreased by 48% as measured by GSRS and by 78% as measured by UESS in the PUD group and by 25% and 47%, respectively, in the G/D group. Reflux symptoms decreased by 41% and 63% in PUD patients and by 28% and 45% in G/D patients; indigestion by 30% and 47% in PUD and by 20% and 34% in G/D; eating discomfort by 60% in PUD and by 35% in G/D. Sleep quality score improved by 68% in PUD and by 41% in NU patients. Constipation decreased by 22% in the PUD group. All these differences in symptoms were highly significant compared to baseline. Diarrhoea was unchanged. Conclusions: Abdominal pain, reflux symptoms, indigestion and the ability to eat and sleep improved in both PUD and G/D patients 1 year after H. pylori eradication. Chronic diarrhoea was not induced. Abdominal pain improved significantly more in PUD than in G/D patients. Further study of the effect of H. pylori eradication in G/D patients is warranted.