Ulrik Tage-Jensen

Effect of omeprazole and cimetidine on duodenal ulcer. A double-blind comparative trial.

We conducted a double-blind randomized study of 132 patients to determine whether the new, investigational proton-pump inhibitor, omeprazole (30 mg per day), would accelerate healing and pain relief, as compared with cimetidine (1 g per day), in patients with duodenal ulcer. After two weeks of treatment, which was completed by all patients, the healing rates were 73 per cent in the omeprazole group and 46 per cent in the cimetidine group (P less than 0.01). After four weeks of treatment, which was completed by 118 patients, the corresponding figures were 92 and 74 per cent (P less than 0.05). In the omeprazole group 55 per cent of the patients were free of pain after the first week, as compared with 40 per cent of those treated with cimetidine (P greater than 0.05). No major clinical or biochemical side effects of omeprazole or cimetidine were noted. A six-month follow-up study revealed no significant difference between the recurrence rates after omeprazole and after cimetidine treatment. In May 1984 clinical trials with omeprazole were temporarily suspended, since a study of long-term toxicity in rats had shown the development of gastric carcinoid tumors.

Hepatobiliary Dysfunction and Primary Sclerosing Cholangitis in Patients with Crohn's Disease

BACKGROUND Only a few studies have attempted to determined the prevalence of long-standing abnormal liver function and primary sclerosing cholangitis (PSC) in patients with Crohns disease (CD). The aim of the study was to determine the prevalence of long-standing abnormal liver function test results and to describe the clinical, biochemical, and histologic findings in patients with large-duct classic PSC and small-duct PSC (that is, normal cholangiogram) in patients with CD during a 15-year period. METHODS Patients with CD and long-standing abnormal liver function results were investigated individually with endoscopic retrograde cholangiography and liver biopsy. RESULTS Of 262 consecutive patients with CD, 38 (15%) had long-standing increased alkaline phosphatase (ALP) values (mean, 1065 U/l; range, 321-4165 U/l). Of these, 10 patients were classified as having hepatic disease (4%), of which 9 had PSC and 1 had a non-specific reactive hepatitis. Of nine patients with PSC (3.4%), three were classified as having large-duct PSC; five, small-duct PSC; and one, unclassified. In patients with large-bowel CD (n = 102) the prevalence of PSC was 9%. Mean age at diagnosis of PSC was 35 years (22-46 years), and the female to male ratio, 7:2. All PSC patients had large-bowel involvement (P < 0.00015), and two of them developed colonic carcinoma of the large bowel (P < 0.01). All cases of small-duct PSC were stage 1, whereas large-duct PSC were stage 2-3. During the observation period (mean, 5.4 years) no PSC patients died. CONCLUSIONS The results of our study indicate that PSC is the major hepatic disease in patients with CD and long-standing abnormal liver function tests and is approximately as prevalent as in ulcerative colitis. Patients with PSC and CD may have a milder liver disease than patients with PSC and ulcerative colitis, perhaps because large-duct PSC is less common in patients with CD. Cholangiograms and liver biopsies are both needed to evaluate the extent of the disease.

Risk of hospitalization resulting from upper gastrointestinal bleeding among patients taking corticosteroids: A register-based cohort study

PURPOSE We assessed the risk of hospitalization for upper gastrointestinal bleeding among patients using systemic corticosteroids, accounting for the use of other drugs that may increase the risk of bleeding. SUBJECTS AND METHODS We conducted a population-based cohort study in North Jutland County, Denmark. Data on the use of corticosteroids, nonsteroidal anti-inflammatory drugs, aspirin, and anticoagulants during 1991 to 1995 were obtained from a countywide prescription database. All hospitalizations because of upper gastrointestinal bleeding were identified through the Hospital Discharge Registry. The observed numbers of patients with gastrointestinal bleeding in various exposure categories among corticosteroid users were compared with the expected number based on the North Jutland population who did not receive prescriptions for any of the drugs under study. RESULTS A total of 45,980 patients accrued 18,379 person-years of corticosteroid use. There were 109 hospital admissions for gastrointestinal bleeding among corticosteroid users, compared with 26 expected, yielding a relative risk of 4.2 [95% confidence interval (CI): 3.4 to 5.0]. Among corticosteroid users who did not use other drugs associated with gastrointestinal bleeding, the relative risk was 2.9 (95% CI: 2.2 to 3.7). The relative risk decreased further to 1.9 (95% CI: 1.4 to 2.5) when current corticosteroid usage was compared with former usage. CONCLUSION We observed an increased risk of hospitalization because of upper gastrointestinal bleeding among patients prescribed corticosteroids, especially among those who use other medications. Confounding from the underlying disease may also have contributed to the observed increase in risk.

Population-based study of the risk and short-term prognosis for bacteremia in patients with liver cirrhosis

We examined the risk of bacteremia in patients with liver cirrhosis (compared with the risk for all Danish citizens >20 years of age who were living in North Jutland County, Denmark), as well as the type of bacteremia and the 30-day case-fatality rate. We used the Danish National Registry of Patients to identify 1339 patients with liver cirrhosis, and we used the North Jutland County Bacteremia Database to identify episodes of bacteremia. We observed 117 cases of bacteremia in patients with liver cirrhosis (11.0 cases were expected), which yielded a standardized incidence ratio of 10.5 (95% confidence interval [CI], 8.8-12.7). Sixty-two cases of bacteremia were nosocomial infections. There were 53 cases of gram-positive bacteremia, 55 cases of gram-negative bacteremia, and 8 cases of polymicrobial bacteremia (1 case of candidemia was excluded from the analysis). The most common cause of death was bleeding from gastroesophageal varices; the second most common cause of death was infection in the respiratory system. The 30-day case-fatality rate was 0.53 (95% CI, 0.39-0.73). Patients with liver cirrhosis had an increased risk of bacteremia and a poor prognosis.

Gut pain reactions in man: an experimental investigation using short and long duration transmucosal electrical stimulation.

Abstract Visceral pain is a substantial, clinical problem but unfortunately few experimental models are available to study this phenomenon in man. In the present study we inserted a stimulation catheter 5–10 cm into the ileo‐sigmoidostomy of nine patients. The catheter contained six small, flexible electrodes separated by 4 mm. The gut was stimulated by single burst, repeated burst (five stimuli delivered at 2 Hz), or continuous burst stimuli (4 Hz for 30, 60, 90, and 120 s). The sensation (ST), pain detection (PDT), and pain tolerance (PTT) thresholds to single/repeated burst stimuli were determined. The location/size/sensitivity of referred pain after repeated/continuous stimulation were characterized. The brain potentials to single burst stimuli and to increasing stimulus intensity were measured. ST to single burst stimuli was easy to determine (8 mA) and to reproduce. The patients found it difficult to determine the PDT and PTT to single burst stimuli, however both thresholds were easily determined for repeated burst stimuli. The pain thresholds to single burst stimuli were twice as high as the thresholds to repeated burst stimuli, indicating the importance of central temporal summation for visceral pain. Minor changes in the stimulus location resulted in changes of the referred pain projection site. The words most frequently selected (78%) from the McGill Pain Questionnaire to describe repeated burst stimulations were shooting, pricking, flashing, and boring. The amplitude of the brain potentials increased at increasing stimulus intensity. A stimulus intensity giving an initial pain rating of around 5 on a 0–10 visual analog scale (VAS) was used for continuous stimulation. A general increase of the pain intensity and the area of referred pain was found during this stimulation. It was concluded that electrical stimulation of the human gut provokes pain and especially long sequences of visceral stimuli are adequate to evoke referred pain mimicking pain profiles of pathologic origin.

Experimental pain in the stomach: a model based on electrical stimulation guided by gastroscopy

Background—Abdominal pain is often variable in intensity and difficult to characterise due to its referred pain pattern. Clinical pain is furthermore confounded by various emotional and cognitive factors. Aims—To develop and apply an experimental model to induce localised gastric pain. Subjects—Twelve healthy male volunteers. Methods—Stimulating electrodes were mounted on a biopsy forceps and electric stimuli were delivered during gastroscopy. Single, five repeated, and continuous stimuli were given at four locations in the stomach. Pain detection thresholds and pain intensities were assessed together with localisation of the referred pain area. Results—Pain detection thresholds were higher in the prepyloric region compared with those obtained at the lesser and greater curvature. Increasing stimulus intensity resulted in augmented pain perception and repeated stimuli elicited pain at a lower stimulus intensity than single stimuli. Continuous stimuli evoked constant (33%), increasing (33%), or decreasing (33%) pain. The localisation of referred pain varied considerably in the subjects. Conclusions—The model seems relevant to study basic pain mechanisms elicited by localised stimuli in the stomach. The experimental data support the premise that a gastric focus should always be suspected in patients referred with different kinds of abdominal pain.

Liver cirrhosis, other liver diseases, and risk of hospitalisation for intracerebral haemorrhage: A Danish population-based case-control study

BackgroundLiver diseases are suspected risk factors for intracerebral haemorrhage (ICH). We conducted a population-based case-control study to examine risk of ICH among hospitalised patients with liver cirrhosis and other liver diseases.MethodsWe used data from the hospital discharge registries (1991–2003) and the Civil Registration System in Denmark, to identify 3,522 cases of first-time hospitalisation for ICH and 35,173 sex- and age-matched population controls. Among cases and controls we identified patients with a discharge diagnosis of liver cirrhosis or other liver diseases before the date of ICH. We computed odds ratios for ICH by conditional logistic regressions, adjusting for a number of confounding factors.ResultsThere was an increased risk of ICH for patients with alcoholic liver cirrhosis (adjusted OR = 4.8, 95% CI: 2.7–8.3), non-alcoholic liver cirrhosis (adjusted OR = 7.7, 95% CI: 2.0–28.9) and non-cirrhotic alcoholic liver disease (adjusted OR = 5.4, 95%CI:3.1–9.5) but not for patients with non-cirrhotic non-alcoholic liver diseases (adjusted OR = 0.9, 95%CI:0.5–1.6). The highest risk was found among women with liver cirrhosis (OR = 8.9, 95%CI:2.9–26.7) and for patients younger than 70 years (OR = 6.1, 95%CI:3.4–10.9). There were no sex- or age-related differences in the association between other liver diseases (alcoholic or non-alcoholic) and hospitalisation with ICH.ConclusionPatients with liver cirrhosis and non-cirrhotic alcoholic liver disease have a clearly increased risk for ICH.

Cyclooxygenase-2, multidrug resistance 1, and breast cancer resistance protein gene polymorphisms and inflammatory bowel disease in the Danish population

Objective. Crohns disease (CD) and ulcerative colitis (UC) are characterized by an impaired mucosal defence to normal constituents of the intestinal flora and a dysregulated inflammatory response. The purpose of the study was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in these processes were associated with CD and UC. Material and methods. Allele frequencies of the cyclooxygenase 2 (COX-2/PTGS2/PGHS2) G-765C and breast cancer resistance protein (BCRP/ABCG2) C421A as well as allele and haplotype frequencies of multidrug resistance 1 (MDR1, ABCB1) SNPs G2677T/A, C3435T and G-rs3789243-A (intron 3) were assessed in a Danish case-control study comprising 373 CD and 541 UC patients and 796 healthy controls. Results. Carriers of the homozygous COX-2 and MDR1 intron 3 variant had a relatively high risk of CD, odds ratio (95% CI) (OR (95% CI))=2.86 ((1.34–5.88) p=0.006) and 1.39 ((0.99–1.92) p=0.054), respectively, and for UC of 2.63 ((1.33–5.26) p=0.005) and 1.28 ((0.96–1.51) p=0.093), respectively, assuming complete dominance. No association was found for BCRP or other MDR1 SNPs, or for selected MDR1 haplotypes. No effect-modification of smoking habit at the time of diagnosis was found. Conclusions. An effect of the COX-2 polymorphism on both CD and UC was shown which is compatible with the presence of a recessive allele in linkage equilibrium with the SNP marker in the COX-2 gene. The polymorphism located in intron 3 of the MDR1 gene showed a weak association with CD, and a marginally suggestive association with UC.

Duodenal Bulb Acidity in Patients With Duodenal Ulcer

Intraluminal pH was measured simultaneously in the human stomach and proximal duodenum with six small glass electrodes tied together at 1.5-cm intervals. Twenty-four healthy control subjects and 44 patients with duodenal ulcer disease were studied under fasting conditions and for 3 h after a standard liquid meal. Mean and median hydrogen ion activity, percentage of time with pH below 2 and 3, and the frequency of pH fluctuations were calculated from digital pH data sampled at a frequency of once per second from each electrode. None of these measurements of acidity differed significantly between the two groups or between subgroups of normosecretor controls and hypersecretor ulcer patients. At the time of pH study 15 of the patients had endoscopically verified active ulcer disease and 13 patients were without disease activity. Gastric as well as duodenal bulb acidity was the same in these two subgroups. We conclude that even though duodenal ulcer patients deliver more acid into the duodenum, this does not cause increased luminal acid aggression.

Pain evoked by electrical stimulation of the prepyloric region of the stomach: Cutaneous sensibility changes in the referred pain area

OBJECTIVE: To investigate the pain threshold and the referred pain areas to electrical stimulation of the prepyloric region of the stomach, and the cutaneous sensibility in the referred pain areas.