Effects of naloxone on glucagon and insulin concentrations after injection of endotoxin in rats.

OBJECTIVE: To find out how infusions of endotoxin and endotoxin plus naloxone affected glucose, glucagon, and insulin concentrations in rats. DESIGN: Random control study. SETTING: University hospital, Norway. MATERIAL: 27 Male Wistar rats. INTERVENTIONS: 8 Rats were given Escherichia coli endotoxin 0.25 mg in saline; 5 were given a naloxone infusion (0.4 ml of 0.04 mg/ml for the first half hour and continued at a rate of 0.4 ml/hour for a total of 80 minutes) starting 10 minutes before the same dose of endotoxin; 6 were given saline alone for 70 minutes, and 8 saline alone for 10 minutes. Blood was taken for analysis after 70 minutes in the first three groups and at the end of the infusion in the 10 minute group. MAIN OUTCOME MEASURES: Serum concentrations of glucose, glucagon, and insulin compared with baseline (10 min group). RESULTS: Median (interquartile) concentrations of all three substances rose significantly 70 minutes after the injection of endotoxin compared to basal values: 9.8 (8.2-10.9) compared with 6.0 (4.8-7.5) mmol/l for glucose (p < 0.01); 53.1 (44.6-56.0) compared with 3.6 (3.1-5.1) ng/l for glucagon; and 39.4 (38-50.4) compared with 16.7 (11.2-25.5) pmol/l for insulin. When naloxone was combined with endotoxin glucagon and insulin concentrations were significantly lower: 24.3 (23.9-37.5) ng/l (p < 0.01), and 30.6 (24.5-31.6 pmol/l (p < 0.05), respectively. The concentration of glucose in venous blood was unchanged. CONCLUSIONS: The rise in glucagon and insulin concentrations after endotoxin infusions may be partly mediated by opioids. Naloxone in the dose given did not abolish the increase in glucagon after endotoxin. The high glucagon:insulin ratio after both endotoxin alone and endotoxin plus naloxone may be important in the aetiology of the hyperglycaemia seen.

Peptic ulcer patterns in Arctic Norway.

While there are four times as many duodenal as gastric ulcers in Europe and the United States, previous studies have shown gastric ulcers to be more common in the Arctic regions of Norway. To investigate a possible change in the duodenal-to-gastric ulcer ratio, the incidence rate of first-time peptic ulcer in a well defined population in Northern Norway was studied by registration of all examinations of the upper digestive tract from 1983 to 1984. In this population, 5.3% were examined by endoscopy (52.5%) or a barium meal (47.5%). The incidence rates of duodenal and gastric ulcers were 1.4 and 0.8 per 1,000 per year, resulting in a duodenal-to-gastric ulcer ratio of 1.7:1. Although this ratio is higher than in a previous study (1.1:1), the pattern of peptic ulcer disease in northern Norway is still different from that in the rest of Europe.

Aetiology of peptic ulcer: a prospective population study in Norway.

STUDY OBJECTIVE: To analyse simultaneously the effect of several risk factors for peptic ulcer. DESIGN: Cohort study where all patients with new or incident peptic ulcers in a well defined population were registered for a seven year period. The follow up started with a comprehensive health survey including a questionnaire on diet, lifestyle, psychological and social conditions, and health. Relative risks, both sex specific and separate, for gastric and duodenal ulcers were estimated from proportional hazard regression analysis. SETTING: A population based survey conducted in the municipality of Tromsø, northern Norway. PARTICIPANTS: In 1980, a total of 21,440 men and women, aged 20 to 54 years and 20 to 49 years respectively, were invited to participate. A total of 14,667 people attended and returned the questionnaire. MAIN RESULTS: A total of 328 people had their first peptic ulcer in the follow up period. Age, cigarette smoking, first degree relatives with peptic ulcer, and low educational level were shared risk factors for peptic ulcer in both men and women. In men, frequent upper respiratory infections increased the risk of gastric ulcer and drinking a great deal of milk increased the risk of duodenal ulcer. None of the other dietary variables, including coffee and alcohol consumption, contributed significantly to the risk. Use of analgesics was not a risk factor, and none of the psychological indicators analysed carried any significant risk. CONCLUSIONS: Age, inheritance, and cigarette smoking are all important risk factors for peptic ulcer. The increased risk associated with low educational background indicate that social strains, comprising lifestyle and diet habits, are part of the multifactorial aetiology of peptic ulcer. No support was found for the assumption that peptic ulcer disease is a psychosomatic disorder. This study did not support the view that duodenal and gastric ulcers have different aetiologies-rather it showed a similarity in risk patterns.

Morphine effects on the release of glucagon, insulin and somatostatin from the isolated, perfused rat pancreas.

The pancreatic glands from six male Wistar rats weighing between 200 and 250 g were isolated and perfused. After 30-min equilibration and 20-min basal periods, perfusion with 0.2 mg/ml of morphine for 20 min resulted in a significant (P < 0.05) increase in insulin release, with no changes in release of gucagon or somatostatin. After a recovery period of 20 min, a higher morphine concentration of 2 mg/ml was introduced for another 20-min period. With this morphine dose there were significant increases in release of insulin (P < 0.05), glucagon (P < 0.01) and somatostatin (P < 0.05). This shows that morphine induces the release of insulin, glucagon and somatostatin from pancreas in a dose-dependent way, and that release of insulin and glucagon is not primarily affected by regulation of somatostatin levels.

Morphine and morphine/naloxone modification of glucose, glucagon and insulin levels in fasted and fed rats.

In rats weighing 200-250 g catheters were placed in the internal jugular vein and carotid artery. After 1 week of accommodation the training for the experimental situation, morphine (10 mg kg-1) was injected intravenously alone or in combination with naloxone (0.04 mg ml-1, 0.8 ml h-1). Otherwise no form of anaesthesia was used during the experiments. In control fed and fasted rats, there were no significant differences in blood glucose. In fed rats, morphine increased blood glucose as compared to control rats (p < 0.001). This was not seen in the fasted rats. The morphine induced increase in blood glucose in the fed rats was abolished by naloxone (p < 0.001). Glucagon was significantly higher in fasted than in fed control rats (p < 0.01). It was significantly increased after morphine in fed (p < 0.05), but not in fasted rats. The morphine induced increase in glucagon in fed rats was abolished by naloxone (p < 0.01). Insulin was significantly higher in fed than in fasted control rats (p < 0.05). Morphine increased insulin levels significantly in fed and fasted rats (p < 0.001), p < 0.01). The morphine induced increase in insulin in the fed rats was abolished by naloxone treatment. It is concluded that morphine stimulates glucose and glucagon release in fed but not fasted rats, and that these increases are caused by opioid action. Insulin increases after morphine were proved to be opioid-mediated only in the fed state.

Comparison of the modifying effects of somatostatin and propranolol on morphine-induced changes in glucose, glucagon and insulin levels in fed rats.

Twenty-eight rats in four different groups were used. Catheters were implanted in the carotid artery and jugular vein one week before the experiments were performed. The rats were trained to the experimental situation daily, and allowed food and water ad libitum. One group of rats was used to establish control values; a second was injected with morphine (10 mg/ml, 1 ml/kg); a third group got morphine injection (10 mg/ml, 1 ml/kg) combined with somatostatin infusion (0.01 mg/ml, 1 ml/h); and the fourth group was injected with morphine (10 mg/ml, 1 ml/kg) combined with propranolol (0.4 ml, 1 mg/ml). Blood samples for venous glucose and arterial insulin and glucagon were drawn 15 min after start of stimulation. Glucose, insulin and glucagon levels were significantly higher in morphine treated than in control rats. When morphine was combined with somatostatin, the increase in glucose, insulin and glucagon was significantly reduced. However, after the morphine and propranolol stimulation the increase in glucose and glucagon was significantly reduced, whereas the insulin levels were as high as when morphine was given alone. The combined reduction of both glucagon and glucose after somatostatin or propranolol treatment in morphine exposed rats, points to glucagon as a potential link between opioid stimulation and hyperglycemia. Beta-receptor stimulation seems to contribute to the glucagon but not to the insulin release after morphine.

Changing incidence of peptic ulcer--facts or artefacts? A cohort study from Tromsø.

STUDY OBJECTIVE: The aim was to estimate the age and sex specific incidences of duodenal and gastric ulcers censored for death and migration. DESIGN: A population based cohort was followed seven years through records of x ray examinations, endoscopies, and operations in the only hospital serving the area. SETTING: The study was conducted in the municipality of Tromsø, Northern Norway, where all men aged 20 to 54 years and women aged 20 to 49 years in 1980, a total of 21,440, were included. MAIN RESULTS: We found an incidence of 1.47 (95% CI 1.21-1.76) and 0.88 (0.67-1.14) per 1000 person-years for gastric and 1.98 (1.69-2.31) and 0.85 (0.64-1.11) for duodenal ulcers in men and women, respectively. A small and insignificant sex difference for gastric ulcer was noted. The duodenal preponderance in men was only recognised among the ulcers identified by x ray, not among ulcers diagnosed by endoscopy. CONCLUSIONS: This population based study has, in contrast to recent studies from other areas, revealed an unchanged high incidence of gastric and duodenal ulcer in both sexes. Compared to earlier studies from this area it indicates a preponderance of duodenal ulcers. The study also shows the impact of attendance rate, death, and migration, and of diagnostic methods on the incidence estimates. Ignoring these potential biases may lead to conclusions on peptic ulcer trends that reflect artefacts rather than real changes in peptic ulcer occurrence.

Sorbitol in isolation of rat pancreatic islets. Effects on islet yield, insulin secretion and accumulation of inositol phosphates.

Tissue aggregation and exocrine contamination are problems encountered in gradient separation of pancreatic islets. Here we report that sorbitol used as an osmotic component in Percoll gradients gives a low ionic strength gradient with improved purity of islet fraction, less islet aggregation and reduced time for final manual rinsing following separation in gradients with NaCl as osmotic component. Previous reports have indicated that long-term (weeks) exposure to high sorbitol concentrations leads to low intracellular levels of inositol phosphates and subsequent effects on the intracellular signal transduction in cells. In our model, short-term exposure to high sorbitol concentrations had no effect on the accumulation of the inositol phosphates or insulin secretion caused by glucose. On the other hand, sorbitol increased the basal insulin secretion three-fold, apparently via a non-stimulatory mechanism. Therefore, we conclude that sorbitol is preferable to NaCl as the osmotic component in Percoll gradient separation of rat pancreatic islets, although long-term exposure should be avoided due to potential toxic effects.

Is Helicobacter pylori the cause of dyspepsia?

OBJECTIVE: To determine the association between infection with Helicobacter pylori and dyspepsia. DESIGN: Cross sectional study of dyspeptic subjects and age and sex matched controls identified by a questionnaire survey of all inhabitants aged 20-69. (Endoscopy, histological examination, and microbiological examinations of biopsies from the gastric mucosa were performed blind.) SETTING: Population based survey in Sørreisa, Norway. SUBJECTS: All 782 dyspeptic subjects (excluding those with a previous history of peptic ulcer, gall stones or kidney stones, and coronary heart disease) and controls were offered an endoscopy, of whom 309 dyspeptic subjects and 310 controls attended. MAIN OUTCOME MEASURES: Prevalences of endoscopic and histological diagnoses and of cultures positive for H pylori. RESULTS: A high prevalence of positive cultures, increasing with age, was found in both dyspeptic subjects (48%) and non-dyspeptic controls (36%) (p = 0.004). Positive cultures in both dyspeptic subjects and controls were strongly associated with histological gastritis (70%, 95% confidence interval 65.5 to 85.3; 60%, 52.7 to 67.7, respectively) and peptic ulcer (92%, 61.5 to 99.8; 64.1, 9.4 to 99.2, respectively). Only 3% of subjects with a histologically non-inflamed gastric mucosa had this infection (dyspeptic subjects 2%, 0.2 to 7.0; controls 4%; 1.2 to 8.8). CONCLUSIONS: The relation between dyspeptic symptoms and H pylori is dubious; H pylori seems to have a pathogenetic role in gastritis and may be a contributing factor but not a cause of peptic ulcer.

Glucagon mediates arginine-induced somatostatin secretion from isolated rat pancreatic islets.

Glucagon has been suggested to be a mediator of intra-islet paracrine effect of insulin and somatostatin during nutritive stimulation. The aim of this study was to reveal possible intra-islet interactions between insulin, somatostatin and glucagon in a batch stimulation model with isolated pancreatic islets. Such interactions may influence stimulus-secretion experiments in this experimental model. In our hands arginine stimulated somatostatin secretion only in the presence of insulin antiserum. Furthermore, arginine-induced glucagon secretion was greatly increased following addition of insulin antiserum. The addition of glucagon antiserum inhibited these effects of insulin antiserum on somatostatin secretion. In conclusion, glucagon apparently represents the central mediator of arginine effects on somatostatin secretion in isolated rat pancreatic islets in batch stimulation experiments.

Plasma concentrations of motilin and somatostatin are increased in late pregnancy and postpartum.

OBJECTIVE: To examine plasma levels of motilin and somatostatin throughout pregnancy. DESIGN: Prospective observational study. SETTING: University Hospital, Norway. SUBJECTS: Eight healthy pregnant women (aged 24-38 years) six of them primigravidae and eight healthy non-pregnant women of similar age with ovulatory menstrual cycles. INTERVENTIONS: In the pregnant women blood samples were obtained at 4-week intervals from 8 weeks gestation throughout pregnancy and again at 5 days and 28 days postpartum. In the non-pregnant controls blood samples were obtained on cycle days 4, 7, 10, 13, 14, 15, 18, 21 and 24. MAIN OUTCOME MEASURES: Plasma levels of motilin and somatostatin. RESULTS: Plasma concentrations of both motilin and somatostatin rose continuously during pregnancy, and motilin levels increased still further to a peak of 165.1 (SE 35.8) pmol/l at 5 days postpartum. Plasma motilin levels were significantly higher during the third trimester and at 5 days postpartum compared with non-pregnant controls (P less than 0.0001). The highest plasma somatostatin levels were found at 40 weeks gestation and at 5 days postpartum (mean 32.1 SE 1.1 pmol/l). Somatostatin levels were significantly higher during the second and third trimester and the postpartum period compared with levels in the follicular phase of the non-pregnant controls (P less than 0.0001). CONCLUSIONS: Circulating levels of motilin cannot play a major role in the relaxation of the gut in pregnancy, but somatostatin may play a part in regulating motility.

Increments in glucose, glucagon and insulin after morphine in rats, and naloxone blocking of this effect.

In awake rats adapted to experimental conditions and allowed food ad libitum, hyperglycemia was induced by the administration of morphine 10 mg/kg through indwelling catheters in the external jugular vein. High glucose values were measured at 5, 15 and 25 min. Glucagon values were high at 5 and 15 min, and again at basal level at 25 min. Insulin was increased after morphine both at 5, 15 and 25 min, whereas somatostatin levels did not change after morphine. When morphine was administered together with naloxone after an initial 10 min period of naloxone administration, there was no increment in glucose, insulin or somatostatin values; neither at 5, 15 or 25 min. There was a remarkable glucagon decrease after naloxone and morphine remaining from 5 to 25 min. Then, one of the possible mechanisms for the hyperglycemic response after morphine may be an opioid effect on pancreas, stimulating glucagon and thereby causing hepatic glucose output.

Erosive prepyloric changes in dyspeptics and non-dyspeptics in a defined population. The Sørreisa Gastrointestinal Disorder Study.

In this population-based endoscopic survey we found erosive prepyloric changes (EPC) in 38.5% of dyspeptics and 35.1% of non-dyspeptics. EPC were observed more frequently in men than in women in both groups. Occurrence of Helicobacter pylori was not associated with EPC. No common gastrointestinal symptoms were found to be associated with EPC. Endoscopic duodenitis of the duodenal bulb was found more frequently in subjects with EPC of the two highest grades than in subjects without EPC. Only the highest grade of EPC was associated with chronic gastritis. EPC were associated with cigarette smoking and, among women, also use of alcohol. We conclude that EPC constitute an endoscopic finding without relation to specific symptoms. These changes therefore do not represent a clinical entity, and it is doubtful whether this finding will give the clinician a better understanding of dyspepsia.

Somatostatin inhibition of phospholipase C activity in isolated rat pancreatic islets.

We have assessed the effect of somatostatin on the phospholipase C activity in isolated rat pancreatic islets. The phospholipase C activity was measured as the generation of inositol 1,4,5-trisphosphate and its metabolite inositol 1,3,4-trisphosphate from the hydrolysis of polyphosphoinositides. Inositol phosphates were measured using anion-exchange fast protein liquid chromatography analysis of extracts from islets prelabelled with myo-[3H]inositol. Somatostatin (1-1000 nmol l-1) significantly inhibited the glucose-induced (12 mmol l-1) phospholipase C activity in a concentration-dependent manner. The Ca2+ channel blocker verapamil (25 mumol l-1) also inhibited the glucose-induced (12 mmol l-1) phospholipase C, whereas the combination of somatostatin and verapamil did not induce any additional inhibition. At 3.3 mmol l-1 glucose, the hypoglycaemic sulphonylurea, tolbutamide (1 mmol l-1), increased the phospholipase C activity. This effect was reversed by somatostatin (100 nmol l-1). Tolbutamide did not further increase the glucose-induced (12 mmol l-1) phospholipase C activity. However, the somatostatin inhibition of glucose-induced (12 mmol l-1) phospholipase C was reversed by tolbutamide. The activator of adenylyl cyclase, forskolin (20 mumol l-1), did not exert any effect on the PLC-inhibition of somatostatin, whereas forskolin alone inhibited the phospholipase C activation at 12 mmol l-1 glucose. Our study demonstrates that somatostatin inhibits the hydrolysis of polyphosphoinositides in pancreatic islets, apparently via a mechanism dependent on Ca2+ and not on cAMP.

Medium-associated luteinization expressed as progesterone release in granulosa-luteal cells isolated from patients undergoing in-vitro fertilization.

The present study describes the effect of culture medium components on progesterone release from human granulosa-luteal cells isolated from patients undergoing in-vitro fertilization (IVF). Progesterone release was selectively measured as a central parameter of in-vitro luteinization, a process believed to decrease the success rate of IVF treatments. Ten different media of relevance to embryo culture were investigated for their effect on progesterone release in unstimulated granulosa cell cultures and in cultures stimulated with human chorionic gonadotrophin (HCG) (1 IU/ml) during 4 days in vitro. Culture media supplemented with human serum yielded the greatest secretion of progesterone. Supplementation with fetal calf serum caused an intermediate pattern of progesterone release. Substitution of serum with a synthetic replacement (Medi-CultR SSR 1 and 2), lacking hormones, cholesterol and growth factors, led to a minimal output of progesterone from granulosa-luteal cells. Complex media (RPMI 1640 and Ham's F10) generally caused a greater progesterone release than simple salt solution (EBSS). No effect of insulin was detected when added to serum-free media.

The interaction between cAMP-dependent and cAMP-independent mechanisms in mediating the somatostatin inhibition of insulin secretion in isolated rat pancreatic islets.

To characterize the intracellular mechanisms by which somatostatin modulates the insulin secretion, studies were performed with isolated rat pancreatic islets at 12 mmol l-1 glucose. Somatostatin (0.1-1000 nmol l-1) inhibited the glucose-induced insulin secretion concentration-dependently. Increasing intracellular cAMP concentration either with dibutyryl-cAMP (1 mmol l-1) or by the adenylate cyclase activator forskolin (20 mumol l-1) partly reversed the inhibition by somatostatin (100 nmol l-1). Neither somatostatin (100 nmol l-1) nor dibutyryl-cAMP (1 mmol l-1 were able to affect the low insulin secretion observed in the absence of extracellular Ca2+. To study cAMP-independent mechanisms of somatostatin, the experiments were performed with and without dibutyryl-cAMP (1 mmol l-1) present. Both somatostatin (100 nmol l-1) and the Ca(2+)-channel blocker verapamil (25 mumol l-1) inhibited the insulin secretion both with and without dibutyryl-cAMP present. An additional inhibition of the insulin secretion was observed when somatostatin was combined with verapamil in the absence, but not in the presence of dibutyryl-cAMP. We conclude that somatostatin inhibits the glucose-induced insulin secretion both by cAMP-dependent mechanism which requires extracellular Ca2+, and by cAMP-independent/verapamil-sensitive Ca(2+)-channel-dependent mechanism.

Increased plasma levels of vasoactive intestinal polypeptide in pre-eclampsia.

OBJECTIVE: To investigate the plasma vasoactive peptide (VIP) levels in pregnancies complicated by pre-eclampsia. DESIGN: A prospective clinical study. SETTING: University Department of Obstetrics, Tromsø, Norway. SUBJECTS: 18 women with untreated gestational proteinuric hypertension between 32 and 40 weeks gestation (13 primigravid) and 8 women with normal pregnancies of similar gestational age. INTERVENTIONS: Fasting blood samples on two occasions, 10 min apart. MAIN OUTCOME MEASURES: Plasma VIP measured by radioimmunoassay. RESULTS: Mean maternal plasma VIP was 13.9 (SEM 1.7) pmol/l in those with pre-eclampsia and 4.4 (SEM 0.5) pmol/l in normal pregnancies (P less than 0.0001). CONCLUSION: The increased levels of VIP in pre-eclampsia may represent a powerful compensatory mechanism to restore vascular perfusion of various organs, including the uterus and placenta.

Prevalences of endoscopic and histological findings in subjects with and without dyspepsia.

OBJECTIVE: To examine the association between dyspeptic symptoms and endoscopic and histological diagnoses. DESIGN: Cross sectional study of people with dyspepsia and controls matched for age and sex identified by questionnaire survey of all inhabitants aged 20 to 69. Endoscopy and histological examination was performed with the examiner blind to whether or not the patient had dyspepsia. SETTING: Population based survey in Sørreisa, Norway. SUBJECTS: All people with dyspepsia and age and sex matched people without dyspepsia were offered endoscopy. A total of 309 people with dyspepsia and 310 without dyspepsia underwent endoscopy, giving 273 matched pairs. MAIN OUTCOME MEASURES: Prevalences of endoscopic and histological diagnoses made according to internationally accepted standards. RESULTS: In all, 1802 of 2027 (88.9%) people returned the questionnaire. Of the 163 subjects who refused endoscopy, 114 were controls. Of five endoscopic and four histological diagnoses only peptic ulcer disease, endoscopic duodenitis, and active chronic gastritis were diagnosed significantly more often in people with dyspepsia. In all, 30% to 50% of the diagnoses of mucosal inflammation and peptic ulcer disease were made among subjects without dyspepsia, and only 10% of both those with and those without dyspepsia had normal endoscopic findings. CONCLUSIONS: The diagnostic findings, with possible exceptions of peptic ulcer disease and endoscopic duodenitis, showed no association of clinical value with dyspeptic symptoms. The small number of "normal" endoscopic findings in both those with and those without dyspepsia challenge well accepted endoscopic and histological diagnostic criteria with relation to the upper gastrointestinal tract.

Prolactin response to secretin during the spontaneous menstrual cycle in women.

The effect of an intravenous infusion of secretin (2.0 CU/kg/h) on serum prolactin (PRL) and estradiol levels and plasma levels of vasoactive intestinal polypeptide and somatostatin (SRIH) was studied in 8 healthy and normally cycling women during the midfollicular phase (cycle day 7), at midcycle (day 14), and during the midluteal phase (day 21) of the menstrual cycle. When compared to basal preinfusion levels, a significant decrease in serum PRL levels was observed at steady state concentrations of plasma secretion (+30 to +60 min) both during the follicular (p less than 0.03) and the luteal (p less than 0.0001) phases. At midcycle a nonsignificant decrease was observed. A significant and negative correlation existed between serum PRL and plasma secretin levels in the follicular phase (r = -0.33; p less than 0.05) and in the luteal phase (r = 0.73; p less than 0.0001). The plasma concentrations of SRIH increased significantly at steady state conditions of secretin at midcycle (p less than 0.02) and in the luteal phase (p less than 0.04), while no effect was found during the follicular phase. A significant and positive correlation between plasma levels of SRIH and secretin was observed at midcycle (r = 0.63; p less than 0.002) and in the luteal phase (r = 0.46; p less than 0.02). No effect of secretin on plasma vasoactive intestinal polypeptide and serum estradiol concentrations was demonstrated. These results suggest that the suppression of PRL in the follicular phase of the spontaneous menstrual cycle can be ascribed to an effect of secretin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of ulcerative colitis in Northern Norway from 1983 to 1986. The Northern Norwegian Gastroenterology Society.

In a 3-year prospective epidemiologic multicentre study in Northern Norway the average annual incidence of ulcerative colitis was 12.8 per 100,000. Both inpatients and outpatients were included. There was a significant sex difference in annual incidence in the health region (15.1 per 100,000 in males versus 10.4 per 100,000 in females), which was most pronounced Nordland county (16.6 per 100,000 in males versus 10.4 per 100,000 in females). The highest incidence was seen in the age group 20-29 years, with an incidence of 30.3 in men and 20.3 in women per 100,000 per year. A family history of first-degree relatives with inflammatory bowel disease was obtained in 10.1%. The pathologic changes were equally distributed among the rectum and the distal and total colon. Ulcerative colitis located to the distal colon seemed more associated with extraintestinal manifestations.