Increased short- and long-term mortality in 8146 hospitalised peptic ulcer patients.

BACKGROUND: Incidence and complications of peptic ulcer disease (PUD) have declined, but mortality from peptic ulcer bleeding has remained unchanged. The few recent studies on mortality associated with both uncomplicated and complicated patients with peptic ulcer disease provide contradictory results. AIMS: To evaluate short- and long-term mortality, and the main causes of death in peptic ulcer disease. METHODS: In this retrospective epidemiologic cohort study, register data on 8146 adult patients hospitalised with peptic ulcer disease during 2000-2008 were collected in the capital region of Finland. All were followed in the National Cause of Death Register until the end of 2009. The data were linked with the nationwide Drug Purchase Register of the Finnish Social Insurance Institution. RESULTS: Mean follow-up time was 4.9 years. Overall mortality was substantially increased, standardised mortality ratio 2.53 (95% CI: 2.44-2.63); 3.7% died within 30 days, and 11.8% within 1 year. At 6 months, the survival of patients with perforated or bleeding ulcer was lower compared to those with uncomplicated ulcer; hazard ratios were 2.06 (1.68-2.04) and 1.32 (1.11-1.58), respectively. For perforated duodenal ulcers, both the short- and long-term survival was significantly impaired in women. The main causes of mortality at 1 year were malignancies and cardiovascular diseases. Previous use of statins was associated with significant reduction in all-cause mortality. CONCLUSIONS: One-year mortality in patients hospitalised with peptic ulcer disease remained high with no change. This peptic ulcer disease cohort had a clearly decreased survival rate up to 10 years, especially among women with a perforated duodenal ulcer, most likely explained by poorer survival due to underlying comorbidity.

Incidence and complications of peptic ulcer disease requiring hospitalisation have markedly decreased in Finland.

BACKGROUND: The characteristics of peptic ulcer disease (PUD) are changing. AIM: To evaluate time trends in the incidence of PUD and its complications in hospitalised patients at the beginning of the 21st century, drug therapies in out-patient care as a risk factor for recurrent PUD, and medication used by PUD patients compared with the background population. METHODS: In this retrospective epidemiologic cohort study, data from the years 2000-2008 came from The Hospital District of Helsinki and Uusimaa, and the Finnish Care Register. All hospitalised adult patients with PUD in the capital region of Finland were included. The data were linked with nationwide Prescription Register of the Finnish Social Insurance Institution allowing detailed individual medicine purchase data. RESULTS: A total of 9951 peptic ulcers were detected among 8146 individual patients during the study period. The mean annual incidence of all peptic ulcers decreased from 121/100,000 (95% CI: 117-125) in 2000-2002, to 79 (95% CI: 76-82) in 2006-2008 [Incidence rate ratio = 0.62 (95% CI: 0.58-0.64), P < 0.001 after age and sex adjustment]. Decrease in incidence was seen in all age groups and in both sexes. The overall rate of severe complications of PUD was reduced. One-year cumulative incidence of recurrent ulcers was 13%. Use of several drugs was associated with increased risk for recurrence. The purchases of various drugs were more common among PUD patients compared with background population. CONCLUSIONS: Both the incidence and complication rates have markedly decreased during the study period. Recurrent peptic ulcer disease was associated with polypharmacy.

Gastrointestinal complaints among subjects with depressive symptoms in the general population.

BACKGROUND: Patients with depression have irritable bowel syndrome (IBS) more often than do nondepressed patients, but the comorbidity of depression and gastrointestinal (GI) symptoms in the general population has received little study. AIM: To study the co-occurrence of depressive and GI symptoms in a general population sample and to assess the rate of health-care utilization particularly for GI reasons among subjects with depressive symptoms. METHODS: A questionnaire containing the Finnish version of the Beck Depression Inventory Short Form and questions covering GI symptoms according to Rome II criteria was mailed to 5000 randomly selected adults. RESULTS: Response rate was 73%. Prevalence of depressive symptoms was 17% (95% CI: 15.7-18.2). Frequent abdominal pain, diarrhoea, constipation, dyspepsia or IBS were present in 54% of those with depressive symptoms and in 29% of nondepressed controls (P < 0.0001). Of those with depressive symptoms, 24% had visited a physician at least once because of abdominal symptoms during the previous year, compared to 13% of controls (P < 0.0001). CONCLUSIONS: Depressive symptoms are prevalent in the general population. They are associated with a high rate of GI symptoms, leading to increased use of health-care services and work absenteeism because of abdominal complaints.

Prevalence and distribution of gastric intestinal metaplasia and its subtypes.

BACKGROUND AND STUDY AIMS: Intestinal metaplasia, especially type III intestinal metaplasia is considered to be a precursor of gastric cancer and because of this it is suggested that these patients should be followed up by gastroscopy. Our aim was to find out the prevalence of intestinal metaplasia and its subtypes, the appearance of intestinal metaplasia in different parts of the stomach, and the correlation of intestinal metaplasia with other histological and endoscopic findings. PATIENTS AND METHODS: A total of 505 consecutive patients, with a mean age+/-S.D. of 54+/-16 years, had two biopsies taken from the antrum, two from the corpus, and, in 272 cases, two from the angulus of the stomach during routine upper gastrointestinal endoscopy. Histological specimens were examined according to the updated Sydney system and the ones with incomplete intestinal metaplasia were further stained for sulphomucin visualisation to divide these into types II and III. RESULTS: The overall prevalence of intestinal metaplasia was 19%. The prevalence of type III intestinal metaplasia was 2.8%, type II intestinal metaplasia was 4.4%, and complete intestinal metaplasia was 11%. Intestinal metaplasia was found most frequently in the antrum and also in the angulus. There was no type III intestinal metaplasia in the corpus. Intestinal metaplasia was found more frequently in patients with atrophic gastritis than in other patients (p < 0.01). The patients with type III intestinal metaplasia were older than the patients without intestinal metaplasia (mean age of 73 versus 51 years). None of the patients with a totally normal appearing stomach in upper gastrointestinal endoscopy had type II or type III intestinal metaplasia. CONCLUSION: The relatively high overall prevalence of intestinal metaplasia was found in patients referred for gastroscopy in a region of low prevalence of Helicobacter pylori infection and low incidence of gastric cancer. Intestinal metaplasia was most often found in the antrum and angulus. Type III intestinal metaplasia was more prevalent in older patients and intestinal metaplasia was more frequently found in patients with atrophic gastritis. Normal appearing endoscopic finding seems to exclude type II and III intestinal metaplasia.

The expression of 8-hydroxydeoxyguanosine in oesophageal tissues and tumours.

PURPOSE: The most common marker of oxidative DNA damage is 8-hydroxydeoxyguanosine (8-OHdG), which is linked with several malignancies. In the present study we investigated whether DNA damage linked to oxidative stress (as 8-OHdG) is present in Barrett's mucosa with or without associated adenocarcinoma or high-grade dysplasia and in normal controls' squamous mucosa. EXPERIMENTAL DESIGN: We measured 8-OHdG in 51 patients (13 Barrett's metaplasia, six Barrett's oesophagus with high-grade dysplasia, 18 adenocarcinoma of the distal oesophagus/oesophagogastric junction and 14 normal controls). The amount of DNA damage was determined by high-performance liquid chromatography in oesophagus samples obtained either from endoscopy or as samples from surgery. The median 8-OHdG concentration was expressed as the ratio of 8-OHdG per 10(5) deoxyguanosine. RESULTS: Analysis revealed that 8-OHdG was present in both Barrett's metaplasia with and without dysplasia as well as in adenocarcinoma of the oesophagus/oesophagogastric junction. Although the study group was small the amount of 8-OHdG was significantly increased in the distal oesophagus both in Barrett's epithelium 1.26 (0.08-29.47) and in high-grade dysplasia 1.35 (1.04-1.65) as well as in adenocarcinoma of oesophagus/oesophagogastric junction 1.08 (0.59-1.94) compared to controls 0.06 (0-4.08) (p=0.002, p=0.012, p=0.001, respectively). Barrett's patients had no significant difference in 8-OHdG levels between their distal and proximal oesophageal samples. CONCLUSIONS: Our results show the presence of oxidative DNA damage in the distal oesophagus of patients with Barrett's oesophagus and adenocarcinoma of the oesophagus/oesophagogastric junction. This may have a connection to carcinogenesis in Barrett's oesophagus.

The clinical value of taking routine biopsies from the incisura angularis during gastroscopy.

BACKGROUND AND STUDY AIMS: The incisura angularis is considered to be a typical site for Helicobacter pylori colonization, glandular atrophy, intestinal metaplasia, gastric ulcer, and gastric carcinoma. Our aim was to clarify whether it is necessary to biopsy the incisura angularis routinely during gastroscopy, in addition to obtaining biopsies of the corpus and antrum. PATIENTS AND METHODS: A total of 272 consecutive patients, with a mean age +/- SD of 53.8 +/- 15.5 years, had two biopsies taken from the angulus, two from the antrum, and two from the corpus of the stomach during routine upper gastrointestinal endoscopy. Histological specimens were examined according to the updated Sydney System for the classification and grading of gastritis. RESULTS: Of the 272 patients, 11 (4.0 %) showed chronic inflammation in the angulus biopsy only. Similarly, the angulus was the only biopsy site which showed neutrophil polymorph infiltration (or "activity") in two patients (0.7 %), intestinal metaplasia in 13 patients (4.7 %), atrophy in three patients (1.1 %), and H. pylori colonization in one patient (0.4 %). Dysplasia (intraepithelial neoplasia) was not found in any of the biopsied sites in any of the 272 patients. H. pylori was found in 39 of the 272 patients (14 %). Of the 272 patients, 120 patients showed abnormalities at the incisura angularis, 101 having gastropathy or erosions, and only 19 showing more specific macroscopic changes, the main ones being ulcer, ulcer scarring, and atrophy. Of the 152 patients with a normal-looking mucosa at the angulus, only six (3.9 %) showed the histological changes of chronic inflammation in the angulus alone. Similarly, the angulus was the only biopsy site which showed neutrophil polymorph infiltration in one patient (1/152, 0.7 %), and intestinal metaplasia in five patients (5/152, 3.3 %). Atrophy and H. pylori colonization were not seen exclusively at the angulus in any of the patients with a macroscopically normal-looking angulus. CONCLUSION: Based on our data, routine biopsy of the incisura angularis would provide little additional clinical information to that obtainable from antrum and corpus biopsies.

First-line eradication therapy for Helicobacter pylori in primary health care based on antibiotic resistance: results of three eradication regimens.

AIM: To determine the efficacy of three Helicobacter pylori eradication regimens and factors affecting the eradication results in Finland. METHODS: A total of 342 H. pylori-positive adult patients from primary health care referred for gastroscopy at 23 centres in different parts of Finland were randomized to receive either (i) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and metronidazole 400 mg t.d.s. (LAM), (ii) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC), or (iii) ranitidine bismuth citrate 400 mg b.d., metronidazole 400 mg t.d.s. and tetracycline 500 mg q.d.s. (RMT). A (13)C-urea breath test was performed 4 weeks after therapy. RESULTS: The eradication result could be assessed in 329 cases. Intention-to-treat cure rates of LAM, LAC, and RMT were 78, 91 and 81%. The difference was significant between LAM and LAC (P = 0.01) and between LAC and RMT (P = 0.04). The eradication rates in cases with metronidazole-susceptible vs. -resistant isolates were for LAM 93% vs. 53% (P = 0.00001), for LAC 95% vs. 84%, and for RMT 91% vs. 67% (P = 0.002). Previous antibiotic use, smoking, and coffee drinking reduced the efficacy of therapy. CONCLUSIONS: In unselected patients in primary health care, LAC was the most effective first-line eradication.

Prevalence of irritable bowel syndrome according to different diagnostic criteria in a non-selected adult population.

BACKGROUND: Prevalence of irritable bowel syndrome shows great variation among epidemiological studies, which may be due to different diagnostic criteria. AIM: To assess prevalence of irritable bowel syndrome according to various diagnostic criteria and to study differences in symptom severity, psychopathology, and use of health care resources between subjects fulfilling different diagnostic criteria. METHODS: A questionnaire was mailed to 5000 randomly selected adults. Presence of irritable bowel syndrome was assessed by four diagnostic criteria: Manning 2 (at least two Manning symptoms), Manning 3 (at least three Manning symptoms), Rome I and Rome II. RESULTS: Response rate was 73%. Prevalence of irritable bowel syndrome by Manning 2, Manning 3, Rome I and Rome II criteria was 16.2%, 9.7%, 5.6%, and 5.1% respectively. Of those fulfilling Rome II criteria, 97% fulfilled Manning 2. Severe or very severe abdominal pain was reported by 27-30% of Manning-positive subjects, and 44% of Rome-positives. Prevalence of depression in Manning 2, and Rome II groups was 30.6 and 39.3%. CONCLUSIONS: Prevalence of irritable bowel syndrome by Rome II criteria is considerably lower than by Manning criteria. Subjects fulfilling Rome criteria form a subgroup of Manning-positive subjects with more severe abdominal symptoms, more psychopathology, and more frequent use of the health care system.

Primary Helicobacter pylori resistance to metronidazole and clarithromycin in the Finnish population.

AIM: To systematically determine Helicobacter pylori primary antimicrobial resistance in Finland and the associated demographic and clinical features. METHODS: A total of 342 adult patients referred for gastroscopy at 23 centres in different parts of Finland and positive for the rapid biopsy urease test were recruited. Clinical and demographic data were collected via a structured questionnaire. Patients with positive H. pylori culture and successful antibiotic sensitivity determination by the E-test method (n = 292) were included in the present analysis. RESULTS: The study population consisted of 134 men and 158 women, mean age 56 years (95% CI, 55-58 years). Resistance to metronidazole was 38% (110 of 292) and to clarithromycin 2% (seven of 292). Resistance to metronidazole was higher in women than in men (48% vs. 25%, P < 0.001). Previous use of antibiotics for gynaecological infections predicted metronidazole resistance (P = 0.01), and previous use of antibiotics for respiratory (P = 0.02) and dental infections (P = 0.02) the clarithromycin resistance. We observed no major geographical variations in metronidazole resistance. CONCLUSIONS: The primary metronidazole resistance of H. pylori was 38% and was common in women previously treated for gynaecological infections. Primary clarithromycin resistance was uncommon (2%) and may associate with previous dental and respiratory infections.

Duodenal disaccharidase activities in the follow-up of villous atrophy in coeliac disease.

BACKGROUND: In active coeliac disease, mucosal atrophy is associated with a marked decrease in intestinal disaccharidase enzyme activities. We investigated the value of duodenal mucosal disaccharidases to predict the severity of mucosal villous atrophy and its recovery in 50 patients with coeliac disease. METHODS: Duodenal mucosal histology and disaccharidase activities were studied at least twice with a mean interval of 9 months. Histology of specimens from all patients was examined by the same pathologist blinded to the data on disaccharidase activities. Mucosal damage was scored into four groups as follows: Grade 0 = normal mucosa; grade I = slight villous atrophy, that is, cryptic component 30%-50%; grade 2 = moderate villous atrophy, that is, cryptic component 50%-90%; grade 3 = severe villous atrophy, that is, cryptic component >90%. The enzyme activities of the disaccharidases were determined as U/g protein. RESULTS: Duodenal mucosal disaccharidase activities were good predictors of the grade of mucosal villous atrophy. Positive predictive values for moderate or severe villous atrophy were 90% for maltase (maltase activity <150 U/g protein), 86% for sucrase (<40 U/g protein) and 71% for lactase (<20 U/g protein). Accordingly, negative predictive values, that is, none or only minimal villous atrophy (grades 0 or 1) with normal disaccharidase activities, were 71% for maltase, 70% for sucrase and 63% for lactase. CONCLUSIONS: The increase in duodenal disaccharidase activities correlated with recovery of the mucosa based on histology. Besides the histological examination, measurement of disaccharidase activities offers an additional tool to evaluate response to a gluten-free diet in patients with coeliac disease.

Oesophageal acid exposure: higher in Barrett's oesophagus than in reflux oesophagitis.

Oesophageal acid exposure at different pH intervals between 0 and 8 in patients with Barrett's oesophagus (n = 24) was compared with that in patients with reflux oesophagitis (n = 19) by using 24-h pH monitoring. Prior to the monitoring, the position and pressure of the lower oesophageal sphincter was measured by manometry. Columnar epithelium with intestinal metaplasia and goblet cells was verified histologically in all Barrett patients and grade I-III oesophagitis in patients with reflux oesophagitis. Acid exposure (percentage of total time at pH < 4) in the Barrett group was significantly greater than in the oesophagitis group: 21.5+/-20.0% SD vs 11.1+/-11.7% SD (P < 0.01). The number of reflux episodes lasting longer than 5 min (representing oesophageal body clearance function) was also significantly greater in the Barrett group (8.3+/-5.9 SD) than in the oesophagitis group (4.5+/-4.7 SD) (P < 0.01). In the Barrett group the acid exposure time was greater at all pH intervals 0-1, 1-2, 2-3 and 3-4, (P < 0.01) but in the oesophagitis group the exposure time was greater at pH interval 5-6 (P < 0.01). There was no significant difference in exposure at pH values above 7. The mean lower oesophageal sphincter pressure was equal in both groups (11.0 vs 11.9 mmHg). In conclusion, oesophageal acid exposure was significantly greater in Barrett's oesophagus than in reflux oesophagitis, and this was associated with decreased oesophageal clearance function. In addition, the results indicated the need for special attention and perhaps higher dosages of drugs to suppress acid production in patients with Barrett's oesophagus.

Endoscopic ultrasonography in the preoperative staging of adenocarcinoma of the distal oesophagus and oesophagogastric junction.

BACKGROUND: Endoscopic ultrasonography is considered to be the most accurate procedure in the preoperative staging of oesophageal carcinoma. Its accuracy was evaluated in the preoperative staging of adenocarcinoma of the distal oesophagus and oesophagogastric junction. METHODS: Thirty-two consecutive patients with adenocarcinoma of the distal oesophagus and oesophagogastric junction were preoperatively examined and staged by means of endoscopic ultrasonography. All patients underwent radical en bloc resection of the oesophagus and proximal stomach (or total gastrectomy) with standard lymphadenectomy including thoracic duct and mediastinal fat tissue. The postoperative histopathologic TNM stage was taken as reference. RESULTS: An endoscopic ultrasonography examination could be completed in 26 of the patients; the other 6 had obstructive tumour. In two patients infiltration of the tumour into the vital organs (in one patient aortic infiltration and in a second patient pericardial infiltration) was incorrectly suspected. The ability to predict T stage was 65.6%. T stage was overstaged in 31.2% and understaged in 3.1% of the cases. The ability to predict N stage was 71.9%. N stage was overstaged in 25.0% and understaged 3.1% of the cases. CONCLUSIONS: In adenocarcinoma of the oesophagus and oesophagogastric junction endoscopic ultrasonography helps in predicting resectability, but the exact TN staging is not accurate. Since early detection of tumour and aggressive surgical intervention constitute the only curative treatment, caution must be exercised when judging a patient to be inoperable solely on the basis of endoscopic ultrasonography findings without proven distant metastases.

Long-term treatment of ulcerative colitis with ciprofloxacin: a prospective, double-blind, placebo-controlled study.

BACKGROUND & AIMS: Although bacterial bowel flora may be one of the contributing factors in the pathogenesis of chronic mucosal inflammation, antibiotic treatment has no established role in ulcerative colitis. The aim of the study was to evaluate the role of ciprofloxacin in the induction and maintenance of remission in ulcerative colitis in patients responding poorly to conventional therapy with steroids and mesalamine. METHODS: Ciprofloxacin (n = 38; 500-750 mg twice a day) or placebo (n = 45) was administered for 6 months in a double-blind, randomized study with a high but decreasing dose of prednisone and maintenance treatment with mesalamine including follow-up for the next 6 months. Clinical assessment and colonoscopic evaluation were performed at 0, 3, 6, and 12 months. Treatment failure, the primary end point, was defined as both symptomatic and endoscopic failure to respond. RESULTS: During the first 6 months, the treatment-failure rate was 21% in the ciprofloxacin-treated group and 44% in the placebo group (P = 0.02). Endoscopic and histological findings were used as secondary end points and showed better results in the ciprofloxacin group at 3 months but not at 6 months. CONCLUSIONS: Addition of a 6-month ciprofloxacin treatment for ulcerative colitis improved the results of conventional therapy with mesalamine and prednisone.

Treatment of Barrett's esophagus by endoscopic laser ablation and antireflux surgery.

OBJECTIVE: The regeneration of intestinal metaplasia by squamous epithelium in 17 patients with Barrett's esophagus after endoscopic laser ablation in a reflux-free environment after successful antireflux surgery was prospectively examined. METHODS: All patients had antireflux surgery, and healing of reflux was verified at postoperative endoscopy and 24-hour esophageal pH monitoring. Thereafter, in 11 patients, the whole Barrett's epithelium was ablated using endoscopic Nd-YAG laser energy in 1 to 8 sessions (mean, 4). The needed energy was 965 to 11,173 joules (mean 4709), or about 1000 joules per centimeter of Barrett's esophagus. Six patients had no laser ablation but were treated by antireflux surgery and served as a control group. RESULTS: In all laser-treated patients, the regenerated epithelium was histologically of squamous type in the tubular esophagus, but two patients still had intestinal metaplasia in the gastric cardia. In controls, the length of Barrett's esophagus and intestinal metaplasia remained unchanged. The length of follow-up was 26 months after the last laser session and 21 months in the control group. CONCLUSIONS: The regenerated esophageal epithelium arising after laser ablation in reflux-free environment surgery is of squamous type. This treatment may have a role in preventing the development of esophageal adenocarcinoma arising in Barrett's esophagus.

Undiagnosed coeliac disease is common in Finnish adults.

BACKGROUND: Large-scale screening for coeliac disease has suggested that the disease is more prevalent than anticipated. In the screening studies published, only a minor proportion of those with a positive result have undergone jejunal biopsy to confirm the diagnosis. Our aim was to search for previously undiagnosed patients with coeliac disease by means of antiendomysium antibodies, which are more specific for the disease than serum antigliadin antibodies, and to study jejunal histology in each with a positive titre. METHODS: Serum from 1070 adults working at Helsinki University Central Hospital were screened for untreated coeliac disease with IgA antiendomysium antibodies. All adults with positive titres underwent jejunal biopsy for villous structure analysis and counting of CD3-positive cells and cells bearing the gamma/delta T-cell receptor. RESULTS: Coeliac disease was confirmed in a jejunal biopsy specimen from 8 of the 11 subjects with positive antiendomysium titres--that is, a frequency of 1 in 130. Seven of these eight coeliac patients had had minor abdominal discomfort for years, and one patient had a diagnosis of hyperthyroidism. None of the patients had osteoporosis, four had low iron storages, but only two were anaemic; no other nutritional deficiencies were found. The three other adults had a positive antiendomysium titre but a normal villous structure. One of these three was regarded as a false-positive case (titre, 1 in 5). The two other subjects (titres, 1 in 400) had increased numbers of CD3-positive T cells and gamma/delta T-cell receptor-bearing cells, suggesting a predisposition for coeliac disease. CONCLUSIONS: Undiagnosed coeliac disease is common in the adult population in Finland; in this study the prevalence was 1 in 130. Screening for coeliac disease is recommended on minor suspicion.

Colorectal dysplasia and carcinoma in patients with ulcerative colitis and primary sclerosing cholangitis.

BACKGROUND: The aim of this study was to evaluate the role of primary sclerosing cholangitis (PSC) as a cofactor in the dysplasia-carcinoma sequence in ulcerative colitis (UC). METHODS: Forty-five patients with UC and concomitant PSC and 45 pair-matched control patients with UC only were examined for colorectal dysplasia and carcinoma. RESULTS: The median duration of UC was 11 years in the group with UC and PSC and 15 years in the control group. Thirteen of the 45 patients (29%) with UC and PSC had colorectal neoplasia: 4, carcinoma; 2, high-grade dysplasia; and 7, low-grade dysplasia. Four of the 45 control patients (9%) had neoplastic findings: 1, carcinoma; 1, high-grade dysplasia, and 2, low-grade dysplasia (P < 0.05). CONCLUSION: The results suggest that the risk of colorectal dysplasia and carcinoma in patients with UC is increased by concomitant PSC.

Plasma lathosterol as a screening test for bile acid malabsorption due to ileal resection: correlation with 75SeHCAT test and faecal bile acid excretion.

1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2. Plasma lathosterols and other non-cholesterol sterols were determined by GLC. Faecal bile acids were measured by GLC, and SeHCAT retention times by gamma camera. The study subjects were divided into two groups according to the degree of bile acid malabsorption: controls (faecal bile acids < 10 mg day-1 kg-1, n = 9) and bile acid malabsorption (faecal bile acids > 10 mg day-1 kg-1, n = 13). 3. Faecal bile acid excretion was 5.9 +/- 1.0 mg day-1 kg-1 in control subjects and 45.7 +/- 6.1 mg day-1 kg-1 in the bile acid malabsorption group. The biological half-life of 75SeHCAT (T1/2) was 95.6 +/- 16.3 h and 14.1 +/- 4.1 h, respectively. Plasma lathosterol levels were significantly elevated in patients with bile acid malabsorption (742 +/- 84 micrograms/ml compared with 400 +/- 59 micrograms/ml in control subjects) and correlated closely with faecal bile acid levels (r = 0.779, P < 0.001), with 75SeHCAT T1/2 (r = -0.524, P < 0.05) and with Schilling test (r = -0.591, P < 0.05). Significant correlations were also obtained for delta 8-cholestenol with faecal bile acids (r = 0.784, P < 0.001) and 75SeHCAT (r = -0.505, P < 0.05). The biological half-life of SeHCAT correlated with faecal bile acid excretion (r = -0.702, P < 0.001). Using mean+2 SD of lathosterol (In micrograms/ml cholesterol) as a cut-off value and 10 mg day-1 kg-1 as the upper limit for faecal bile acid excretion, the test gives 100% sensitivity and 82% specificity for plasma lathosterol determination to detect bile acid malabsorption. 4. The results indicate that both the 75SeHCAT test and plasma lathosterol detect bile acid malabsorption in patients with ileal resections for Crohn's disease. However, plasma lathosterol is a simpler and less expensive method.

Globus pharyngis, commonly associated with esophageal motility disorders.

OBJECTIVES: To evaluate the role of gastrointestinal and psychiatric etiology in globus sensation. METHODS: The study population consisted of 32 consecutive patients with globus sensation without dysphagia referred to the Department of Otorhinolaryngology in Helsinki University Hospital. Eleven patients were excluded from the study: two because of advanced age, one prisoner, and six patients refused further studies. Only two patients (6%) were found to have abnormal otorhinolaryngological status. These patients were also excluded from the study. Esophagogastroduodenoscopy, 24-h pH recording, esophageal manometry, and Bernstein acid perfusion test were carried out in 21 patients (13 females, eight males, mean age 49 yr). Psychiatric evaluation was done in 20 patients; one patient refused the psychiatric consultation. RESULTS: Abnormal endoscopy was found in 12/21 (57%) of the patients, with antral gastritis and hiatal hernia being the most common findings. Two patients had esophagitis. Sixty-seven percent demonstrated abnormalities in esophageal manometry, the most frequent finding being a nonspecific esophageal motility disorder (29%). pH monitoring was normal in 16/21 of patients (76%), whereas the Bernstein test showed positive results in 13/21 (62%). With DSM IIIR as the diagnostic tool, five of 20 patients (25%) received a psychiatric diagnosis. CONCLUSIONS: Globus sensation has a multiple etiology, and local reasons are rare but should first be ruled out. Abnormalities in esophageal motility are commonly found, and these patients seem to be sensitive to esophageal acidity. Esophageal manometry and ambulatory 24-h pH recording should be included in the evaluation of a globus patient. The number of psychiatric disorders does not differ from that in the general population. Treatment of globus sensation should be directed toward the abnormality found behind the symptom.

Disturbance of the water and electrolyte balance during high-dose interferon treatment.

Ten patients with amyotrophic lateral sclerosis were treated during 5 consecutive days with intravenous infusion of high-dose human leukocyte interferon-alpha (IFN-alpha) or placebo in a single-blinded randomized trial. To assess the effect of IFN on the water and electrolyte balance, serum electrolytes, creatinine, and antidiuretic hormone as well as urine excretion of electrolytes, aldosterone, and cortisol were measured before the trial and during the fourth day of IFN infusion. Compared with placebo the results showed a significant reduction of the mean serum calcium level (from 2.28 +/- 0.03 mmole/liter to 2.01 +/- 0.06 mmole/liter; p less than 0.01), that of the mean serum osmolality (from 296 +/- 9.9 mosm/kgH2O to 281 +/- 2.5 mosm/kgH2O; p less than 0.05) and that of the mean urinary excretion of magnesium (from 5.32 +/- 2.04 mmoles/liter to 2.65 +/- 1.68 mmoles/liter; p less than 0.05). Careful observation of water and electrolyte balance is emphasized during high-dose IFN treatment.