[Primary sclerosing cholangitis with itching treated during pregnancy with ursodeoxycholic acid]. / Primaer skleroserende cholangitis med kløe behandlet under graviditet med ursodeoxykolsyre.

A 23-year old woman with primary sclerosing cholangitis was being treated with ursodeoxycholic acid (URSO). When pregnancy was diagnosed, she was already through the first trimester. The treatment was discontinued, but her symptoms including severe pruritus recurred immediately, and the biochemical markers of bile duct obstruction worsened. It was necessary to start URSO-treatment again, which relieved her symptoms and improved the biochemistry. The remaining part of the pregnancy was uncomplicated, there were no malformations and so far, the baby is doing fine. URSO may be a possible treatment for severe intrahepatic cholestasis and pruritus during pregnancy.

Continuous end-tidal carbon dioxide monitoring during normofrequent jet-ventilation.

BACKGROUND: Continuous end-tidal carbon dioxide (ETCO2) monitoring during normofrequent jet-ventilation (NFJV) has not previously been successful and no correspondence between ETCO2 and arterial carbon dioxide (PaCO2) demonstrated. METHODS: During NFJV jet-ventilation in 19 healthy volunteers, continuous ETCO2 was measured and compared to PaCO2 values. The original ETCO2 sampling line from our Datex CO2 measuring equipment was placed longitudinally against a suction catheter and both were wrapped with aluminium foil. They were placed 4-5 cm above the carina and the position was verified with a fiberoptic bronchoscope. RESULTS: The correlation between methods gave a Pearson's product moment correlation (r value) of 0.836, significant at the P < 0.001 level, indicating a close correlation between methods. A difference against mean scatter diagram confirmed that ETCO2 and PaCO2 measurements are of equal value in monitoring healthy patients during NFJV. CONCLUSION: A valuable method of continuous ETCO2 monitoring during NFJV is presented.

The influence of halothane on spermatogenesis in surgical patients.

Seventeen male patients delivered a sperm sample before and 80-90 days after halothane anaesthesia, acting as their own control. The sample was tested according to WHO criteria. There was no difference before and after anaesthesia. We conclude that halothane used in normal anaesthetic concentration in combination with nitrous oxide during arthroscopic knee surgery had no certain effect on the quality of sperm.

Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse. Double-blind comparative trial.

In a double-blind, parallel-group clinical trial of 195 patients with duodenal ulcers who after a short-term study had relief of pain and healed ulcers proved endoscopically, 65 were randomized to receive 20 mg omeprazole 3 days a week (once in the morning from Friday to Sunday), 64 to receive 10 mg omeprazole once daily in the morning, and 66 to receive placebo for up to 6 months. The patients underwent repeat endoscopy with biopsy of the gastric fundic mucosa (qualitative assessment of argyrophilic cell population), assessment of symptoms, and laboratory screening with measurement of basal serum gastrin concentrations at 3 and 6 months or more often if indicated by recurrence of symptoms. At 3 months, endoscopically proved ulcer relapse occurred in 16% receiving 20 mg omeprazole 3 days a week; 21% receiving 10 mg omeprazole daily; and 50% receiving placebo. At 6 months, corresponding rates were 23%, 27%, and 67% with 95% confidence intervals of difference between the placebo group and omeprazole groups of 28%-60% and 24%-56% (P less than 0.00001), respectively, and between omeprazole groups of -19%-11% (NS). No major clinical or laboratory side effects were noted. Thus both omeprazole regimens are effective and safe in preventing duodenal ulcer relapse.

Effect of 10 mg and 20 mg omeprazole daily on duodenal ulcer: double-blind comparative trial.

One-hundred and seventy-one patients with endoscopically proven duodenal ulcers were allocated at random to double-blind treatment with 10 or 20 mg of omeprazole in the morning for up to 4 weeks. Patients completed the study if ulcer healing and pain relief had occurred at 2 weeks. A total of 155 patients completed the trial. Patients treated with 20 mg of omeprazole daily responded significantly more rapidly than those treated with 10 mg of omeprazole daily (P less than 0.001; Cochran-Mantel-Haenszel test covering both time points), cumulative healing rates at 2 and 4 weeks were 74% (58/78) and 91% (71/78), respectively. The corresponding rates in the group treated with 10 mg daily were 48% (39/81) and 75% (58/77). Pain relief was again more pronounced during treatment with the larger dose (P less than 0.05; stratified Wilcoxon test). No major clinical or biochemical side effects were noted. An omeprazole dose of 20 mg daily is preferable to a lower dose for the treatment of duodenal ulcer disease in the short term.

Serum cathodic trypsin-like immunoreactivity, pancreatic lipase, and pancreatic isoamylase as diagnostic tests of chronic pancreatitis or pancreatic steatorrhea.

We compared serum concentrations of cathodic trypsin-like immunoreactivity, pancreatic lipase, and pancreatic isoamylase as diagnostic tests of chronic pancreatitis (and of pancreatic steatorrhea in the 41 patients with steatorrhea) in 105 patients (57 men, 48 women) consecutively investigated because of clinical suspicion of chronic pancreatitis. Chronic pancreatitis (36 patients), pancreatic steatorrhea (24 patients), and other diseases were diagnosed without knowledge of the serum levels of the three enzymes. When evaluated by means of receiver operating characteristic curves, no differences were found in diagnostic performance of the enzymes with regard to chronic pancreatitis or pancreatic steatorrhea. The sensitivity and specificity for recognition of chronic pancreatitis ranged from 0.306 to 0.444 and from 0.942 to 0.986 when the discrimination values were chosen to give highest efficiencies. The similar ranges for pancreatic steatorrhea were 0.500-0.708 and 0.882-0.941. In conclusion, none of the three enzymes had any advantage over the others as diagnostic tests of chronic pancreatitis or of pancreatic steatorrhea. Only positive test results have clinical importance because of the low sensitivities of the three enzymes.

Postanaesthetic arousal time in elderly patients. A double-blind study of glycopyrrolate and atropine.

Postanaesthetic arousal time was studied in elderly patients given either glycopyrrolate 0.01 mg kg-1 or atropine 0.02 mg kg-1 before antagonism of neuromuscular blockade. Forty patients (age greater than or equal to 65 yr) undergoing elective hip replacement were included in a double-blind study. Arousal was scored for 2 h after recovery using a modified scoring system. No difference in arousal time was found between the two groups.

Residual curarisation: a comparative study of atracurium and pancuronium.

Sixty patients (17-78 years old, ASA group I-II) were included in the study, which was triple-blind, randomised, stratified and controlled. Patients were selected in pairs according to sex and type of operation, and randomly allocated to one of two groups, atracurium or pancuronium. Anaesthesia was achieved with thiopentone, pethidine and nitrous oxide in oxygen, and patients were then given atracurium 0.1 mg kg-1 or pancuronium 0.6 mg kg-1. Incremental doses were administered when clinically indicated. On recovery, residual curarisation was evaluated clinically and with the train-of-four method by a doctor who was unaware of the neuromuscular blocking agents used. Residual curarisation was found to be less after neuromuscular blockade with atracurium in the doses used in this study. Atracurium has advantages in this respect when neuromuscular monitoring is not used during operation.

Omeprazole and ranitidine in treatment of reflux oesophagitis: double blind comparative trial.

One hundred and sixty two patients with endoscopically proved reflux oesophagitis stratified for severity, 66 with grade 1 disease (erythema and friability) and 96 with grade 2 or 3 disease (including erosions or ulcerations), were allocated at random to double blind treatment with omeprazole 40 mg in the morning or ranitidine 150 mg twice daily for up to 12 weeks. A patient could be evaluated sooner if symptomatic relief and endoscopically normal mucosa (grade 0) were noted after four to eight weeks' treatment. Patients treated with omeprazole responded significantly more rapidly than those treated with ranitidine (p less than 0.0001), cumulative healing rates at four, eight, and 12 weeks being 90%, 100%, and 100% respectively for those with grade 1 disease and 70%, 85%, and 91% respectively for those with grade 2 or 3 disease in the omeprazole group. Corresponding rates in the ranitidine group were 55%, 79%, and 88% (grade 1) and 26%, 44%, and 54% (grade 2 or 3). Relief of the major symptoms of heartburn, regurgitation, and dysphagia and improvements in the histological appearance of the mucosa occurred earlier and were again more pronounced during treatment with omeprazole than with ranitidine. This observed superiority of omeprazole 40 mg in the morning over ranitidine 150 mg twice daily in the short term treatment of reflux oesophagitis was obtained without major clinical or biochemical side effects, but further research is needed into longer term use of omeprazole and the effects of the acid inhibition it induces.

Medical treatment of peptic ulcer disease.

Only a decade ago surgery was the preferred treatment of recurrent peptic ulcer. With the introduction of cimetidine in 1976 effective and safe medical treatment could be offered to the patient. H2-receptor antagonists are still the basic drugs in ulcer healing, but in recent years mucosa protective agents as sucralfate and colloidal bismuth have been increasingly used. Complete inhibition of acid secretion may be achieved by the new proton pump inhibitor omeprazole. In ulcer resistant to treatment with H2-receptor antagonists either a mucosa protective agent, as colloidal bismuth or a potent acid inhibitor (omeprazole) may be used. In recurrent duodenal ulcer a systematic and prolonged maintenance therapy with H2-receptor antagonists is indicated. This treatment is safe and it reduces the incidence of a relapse to one third compared with placebo. Surgery is no longer indicated in the majority of patients with uncomplicated recurrent peptic ulcer. In most patients this disease can now be controlled by effective and cheap anti-ulcer drugs. Although medical treatment of peptic ulcer has been used for centuries, surgery was still the main treatment of recurrent peptic ulcer in the nineteen seventies. Up to that time the surgical management of ulcer disease had made major progress, while medical treatment had failed to offer effective cure. Thus, as late as in 1975 the medical treatment of peptic ulcer consisted of antacids, bed rest and carbenoxolone. With the important side effects of carbenoxolone in mind, it is no wonder that medical treatment was no alternative to surgery in patients suffering from recurrent peptic ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary tumors containing cholecystokinin.

We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained increased amounts of cholecystokinin, the concentrations being extremely high in two: 8281 and 13,453 pmol per gram as compared with less than 30 pmol per gram in normal pituitary glands. The cholecystokinin concentrations were moderately increased in adenomas from another 12 patients, of whom 5 had Cushing's disease and 7 acromegaly with adenomas containing ACTH. The cholecystokinin peptides from the tumors were smaller and less sulfated than cholecystokinin from normal pituitary glands. We conclude that ACTH-producing pituitary cells may also produce an altered form of cholecystokinin.

Molecular forms of gastrin in antrum and duodenum after parietal cell vagotomy.

We examined whether parietal cell vagotomy (PCV) changed the distribution between the different molecular forms of gastrin. Serum, antrum, and duodenum from PCV patients, unoperated duodenal ulcer (DU) patients and control subjects were studied. PCV was followed by a twofold increase in the serum gastrin concentration, while the distribution between small and large gastrins were unaffected. However, sulfation of antral gastrins was reduced from 45 percent in unoperated DU patients to 34 percent in PCV patients (p less than 0.01). We conclude that gastrin sulfation is diminished after PCV. Diminished sulfation seems to be correlated to hypergastrinaemia of antral origin and not to specific diseases.

Relations between circulating gastrin and endocrine cell proliferation in the atrophic gastric fundic mucosa.

It has been suggested that gastrin may be a causative factor in the proliferation of gastric fundic mucosal endocrine cells, as seen in the Zollinger-Ellison syndrome and in atrophic gastritis with hypergastrinemia of antral origin. In the present study, morphometrically determined densities of endocrine cells in fundic mucosal biopsy specimens were related to basal levels of serum gastrin in 10 normal controls and 60 patients with achlorhydric fundic atrophic gastritis, of which 45 had pernicious anemia (5 with fundic mucosal carcinoid) and 15 had atrophic gastritis without pernicious anemia. The densities of fundic mucosal endocrine cells were positively related to the levels of serum gastrin (atrophic gastritis, rs = 0.65; atrophic gastritis and normal controls, rs = 0.72). The highest levels of serum gastrin were found in patients with carcinoid tumors (mean, 1659.3 pmol/l), followed by those in patients with focal hyperplasias (cluster formation) of endocrine cells (mean, 503.2 pmol/l) and those in patients without focal hyperplasias (mean, 304.4 pmol/l) (p = 0.03 and p = 0.04, respectively).

Complete tyrosine O-sulfation of gastrin in adult and neonatal cat pancreas.

We have found gastrin in both the adult and neonatal cat pancreas. In contrast with the main production sites, antrum and duodenum, gastrin in the pancreas occurs in a single molecular form, tyrosine O-sulfated gastrin-17. Since tyrosine sulfation increases the pancreozymic effect of gastrin, the complete sulfation seems functionally expedient.

Development of cimetidine resistance in the Zollinger-Ellison syndrome.

A patient with the Zollinger-Ellison syndrome was followed with multiple gastric secretion tests and serum gastrin analyses for six years. During this period cimetidine requirement increased to a daily dose of 8 g, but it reversed spontaneously after two years. The altered cimetidine effectiveness was not associated with reduced oral bioavailability and serum calcium was unchanged. Total serum gastrin was very high at all times, and fractionation of gastrins in serum by gel filtration showed varying proportion of big to small gastrins, but not in a mode which explained the parietal cell resistance to cimetidine.

Complete sulfation of jejunal gastrin in the human fetus.

The degree of tyrosine-O-sulfation and the ratio between large (gastrin-34 and component I) and small (gastrin-17 and -14) molecular forms of gastrin were studied in extracts of human fetal (n = 14) and adult (n = 9) antrum, duodenum, jejunum and pancreas. Boiled water extracts were applied to gel- and ion-exchange chromatography before and after treatment with trypsin and arylsulfatase. The fractions were monitored with sequence-specific radioimmunoassays that distinguish sulfated from non-sulfated gastrins. In antrum and duodenum about half the gastrins were sulfated at all stages of development. In the fetal jejunum gastrin occurred in sulfated form only while in the adult 72% (range, 64-88%) of the jejunal gastrins were sulfated. The larger molecular forms of gastrin predominated in the fetal compared with the adult antrum. In duodenum and jejunum, however, the ratio between small and large forms was the same in fetus and adult. Gastrin was undetectable in both fetal and adult pancreas. The results show that the degree of sulfation of gastrin varies substantially in the different parts of the gut at different stages of development. The differences may have functional significance, since sulfation increases the pancreozyminic and cholecystokinetic potency of gastrin.

Species variation in the tyrosine sulfation of mammalian gastrins.

The degree of tyrosine sulfation and the distribution between gastrin-17- and gastrin-34-like immunoreactivity (LI) were studied in the antra of ten mammalian species. Specific radioimmunoassays, gel-, and ion-exchange chromatography as well as enzymatic cleavage with trypsin and arylsulfatase were used. The percentage of sulfation varied from 24.4 +/- 4.2 (mean +/- SEM) in dogs to 80.1 +/- 2.6 in sheep, 46.8 +/- 3.3 in humans, 50.1 +/- 3.2 in cows, 55.9 +/- 2.3 in rats, 57.4 +/- 3.1 in pigs, 61.3 +/- 2.2 in guinea pigs, 64.1 +/- 4.7 in cats, 64.8 +/- 2.1 in mice and 68.2 +/- 2.8 in rabbits. Gastrin-34-LI in antral extracts could be converted to gastrin-17-LI by trypsin in all species. Five percent of antral gastrins eluted as gastrin-34-LI in all species. We conclude that while the ratio of gastrin-34-LI to gastrin-17-LI varies little in mammals, large differences occur in the degree of sulfation.

Decreased sulfation of serum and tissue gastrin in hypergastrinemia of antral origin.

The sulfation of gastrin in serum, antrum and duodenum was studied in 22 normo- and 20 hypergastrinemic patients. The ratio between gastrin-17 and gastrin-34 was measured in antrum and duodenum. The degree of sulfation was reduced in the antrum of hypergastrinemic patients (35.3 +/- 1.3%, mean +/- SEM) compared with 48.0 +/- 2.1% in normo-gastrinemic patients (p less than 0.001). The degree of sulfation in serum and duodenum was similar to that of the antral gastrins in all patients. The percentage of gastrin-34 in antrum was increased (7.3 +/- 0.7%) in hypergastrinemic compared with 4.9 +/- 0.3% in normogastrinemic patients (p less than 0.01). In the duodenum the percentage of gastrin-34 was similar in normo- and hypergastrinemia. When classified according to clinical diagnosis, sulfation of antral gastrin was normal in duodenal ulcer (47.6 +/- 4.5%) but decreased in gastric ulcer (36.7 +/- 1.6%, p less than 0.01) and pernicious anemia (31.3 +/- 1.9%, p less than 0.001) compared with 48.2 +/- 2.2% in control patients. In pernicious anemia a larger proportion of antral gastrins occurred as gastrin-34 (8.2 +/- 0.9%) compared with 4.8 +/- 0.4% in control patients (p less than 0.01). Our study suggests that both sulfation and proteolytic processing of the gastrin precursor is diminished in hypergastrinemia of antral origin.