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Biomedical subjects

H Worning

Publications and source records attributed to H Worning.

At least 37 records · Page 2Linked to original sources

Exocrine pancreatic function in patients with progressive systemic sclerosis.

The exocrine pancreatic function was investigated in 16 patients with progressive systemic sclerosis by means of a meal test (Lundh test) and in 9 of the patients by the secretin-cholecystokinin test as well. Gastrointestinal involvement with progressive systemic sclerosis was evaluated by esophageal manometry and by routine roentgenographic series of the small bowel. Fecal fat excretion measurement, the D-xylose absorption test, and a small-intestinal biopsy procedure were carried out. Duodenal juice was cultured and bacterial counts were estimated. One-third of the patients had reduced exocrine pancreatic function, but only four patients had unequivocally a reduction that could be of clinical importance. The results obtained with the meal test were in accordance with the secretin-cholecystokinin test, indicating a preserved capacity for endogenous stimulation.

Adult↗

Etiologic aspects of chronic pancreatitis. Review of current theories and experimental evidence.

The recent increase in incidence of chronic pancreatitis is difficult to explain. Alcohol consumption, although the prime precipitating factor, is not the only factor involved in the etiology. Differences in risk, presentation, and mortality in various areas of the world warrant investigation of the basic pathophysiologic mechanisms that are operative, and studies to determine if they are identical in all cases of chronic inflammatory diseases of the pancreas. Satisfactory animal models for human chronic pancreatitis have not yet been produced and it is still not known if the basic mechanism(s) leading to chronic pancreatitis are identical in all cases. The only theory concerning the etiopathogenesis of chronic pancreatitis that seems to have therapeutic merit involves the aberrant effects of mixed function oxidases, cytochrome P-450 induction, free radicals of oxygen, lipid peroxidation, and so on.

Chronic Disease↗

Decomposition of wheat bran and ispaghula husk in the stomach and the small intestine of healthy men.

Decomposition of dietary fibers in the stomach and small bowel was studied in 13 healthy male volunteers. Liquid control meals were compared with test meals, which in addition contained a source of fiber (wheat bran or ispaghula husk) in random order. Aspirations were collected from the stomach, the proximal jejunum, the mid gut and the terminal ileum. Radiolabeled polyethylene glycol-4000 was used as nonabsorbable water-phase marker, and the formation of free arabinose was used to quantify the hydrolysis of dietary fibers. Ingested fibers, aspirates and urine specimens were analyzed for monosaccharides, either free or fiber-bound, by gas-liquid chromatography. Both types of fiber were hydrolyzed in the stomach, but not in the small bowel. Of ispaghula husk, 1-6% was hydrolyzed, as was 5-8% of wheat bran. Intestinal absorption of free arabinose was 85-93%, but excretion of arabinose in the urine was not greater than after control meals. For further evaluation of gastric hydrolysis six additional healthy male volunteers were studied by serial aspirations from the antral part of the stomach. Hydrolysis was instantaneous for both fibers, and was significantly more pronounced for wheat bran than for ispaghula husk.

Adult↗

Pancreatic hormone secretion in chronic pancreatitis without residual beta-cell function.

Hormonal responses (glucagon, pancreatic polypeptide and somatostatin) to iv glucagon, iv arginine, and ingestion of a mixed meal were investigated in 6 patients with insulin-dependent diabetes secondary to chronic pancreatitis without beta-cell function, in 8 Type I (insulin-dependent) diabetics without beta-cell function, and 8 healthy subjects. No significant differences were found between the two diabetic groups regarding glucagon responses to arginine and meal ingestion. In the patients with diabetes secondary to chronic pancreatitis compared with Type I diabetics and normal controls, the pancreatic polypeptide concentrations were significantly lower and somatostatin concentrations were significantly higher after glucagon, arginine and a mixed meal. Thus, pancreatic glucagon secretion was preserved in patients with insulin-dependent diabetes secondary to chronic pancreatitis, having no residual beta-cell function. These findings suggest that pancreatic glucagon deficiency is not absolute in insulin-dependent diabetes secondary to chronic pancreatitis. A high level of somatostatin may contribute to a lower blood glucose level in patients with chronic pancreatitis.

Adult↗

Effect of trypsin on the hormonal regulation of the fat-stimulated human exocrine pancreas.

To study the effects of trypsin on the pancreaticobiliary secretion and the release of secretin and cholecystokinin (CCK) to plasma, seven normal subjects were stimulated twice with duodenal perfusates containing 20 mM oleic acid (pH 6.0) with and without 1 g of bovine trypsin added per liter. In addition, six patients with advanced pancreatic insufficiency who received only the oleic acid were compared with eight normal subjects. The concentrations of secretin and CCK in plasma and the pancreatic enzyme and volume secretions were unaffected by the addition of trypsin, but the initial bile acid output and the bicarbonate secretion in the period after gallbladder emptying were reduced during perfusion with trypsin. The severely reduced enzyme secretion in chronic pancreatitis did not influence the basal or oleic acid-stimulated concentrations of the hormones in plasma. The study does not support the hypothesis of a trypsin-mediated negative feedback control of human pancreatic enzyme secretion. Furthermore, the reduced duodenal output of bicarbonate found in response to trypsin is not explained by changes in the release of secretin or CCK.

Adult↗

Metabolic control and B cell function in patients with insulin-dependent diabetes mellitus secondary to chronic pancreatitis.

Among 88 unselected patients with chronic pancreatitis 35% (95% confidence limits 25 to 46) had insulin-dependent diabetes, 31% (21% to 41%) had non-insulin-dependent diabetes or impaired glucose tolerance (by intravenous glucose tolerance test), and 34% (24% to 45%) had normal glucose tolerance. B cell function measured by C-peptide concentration after 1 mg glucagon IV correlated with the pancreatic enzyme secretion (meal stimulated duodenal lipase content). B cell function was preserved to a greater extent (P less than .01), and glycosylated hemoglobin and fasting level of glucose were lower (P less than .01 to .05) in the 31 patients with pancreatogenic diabetes than than in 35 otherwise comparable patients with type I (insulin-dependent) diabetes, yet daily insulin dose was similar in the two groups. Glucagon stimulated C-peptide was inversely correlated to glycosylated hemoglobin in insulin-dependent patients with pancreatogenic diabetes and in type I diabetes. Since body mass indices were identical in the two groups, better glucoregulation was not due to reduced food intake or malabsorption in pancreatogenic diabetes. Rather residual B cell function and/or different secretion of other pancreatic hormones in pancreatogenic diabetes may account for different metabolic control in type I IDDM compared with insulin-dependent pancreatogenic diabetes.

Adult↗

Exocrine pancreatic function in dyspepsia.

The prevalence of pancreatic diseases as the cause for dyspepsia differs in clinical materials between 0 and 25-30%. In parallel, the incidence rate of chronic pancreatitis varies between 0.7 and 10 per 100,000 inhabitants per year. The correct figures are unsettled. The main reason for the great variability in figures for frequency of chronic pancreatitis is probably the different clinical awareness and variable practice for performing morphological and functional studies of the pancreas in patients with dyspepsia. Epidemiologic data indicate, but do not prove, an increasing frequency of chronic pancreatitis at least valid for the alcoholic chronic pancreatitis. Pancreatic function and pancreatic disease are probably connected to different gastro-intestinal diseases (duodenal ulcer, inflammatory bowel diseases, malabsorption syndromes, subtotal and total gastrectomy and to some extent in patients with hepatobiliary diseases). The prevalence of chronic pancreatitis can be calculated to around 70 per 100,000 inhabitants in the Western world. Around one-third of these present with exocrine pancreatic insufficiency. The demand for enzyme substitution based on marked exocrine pancreatic insufficiency in patients with chronic pancreatitis, pancreatic cancer and mucoviscidosis can be calculated to approximately 150 patients per 1 million inhabitants. The question concerning the analgetic effect of pancreatic enzyme substitution is still unsettled.

Chronic Disease↗

Estimation of the 3-day faecal fat excretion and fat concentration as a differential test of malabsorption and maldigestion.

The diagnostic efficiency of estimating the faecal fat excretion and faecal fat concentration in uncontrolled 3-day collections was estimated from a prospective series of 87 consecutive patients. The diagnoses were established on the basis of morphologic criteria, and the assimilation was established from the faecal 14C-triolein/3H-oleic acid test. These investigations showed the diagnostic sensitivity of the 3-day faecal fat excretion to be 90%. The 3-day mean faecal fat concentration was less than or equal to 5.1% w/w in patients with normal lipid assimilation. Of the patients with malassimilation 90% had a faecal fat concentration greater than or equal to 5.1% w/w. The faecal fat concentration was especially high in patients with maldigestion. When 10% w/w was used as the discrimination level between malabsorption and maldigestion, the faecal fat concentration correctly distinguished between these in 66% of the patients with malassimilation. The day-to-day variation of the faecal fat concentration was modest. Diagnosis of the lipid assimilation as estimated by the 1-day faecal fat concentration agreed with the diagnosis of the mean 3-day faecal fat concentration in 115 of the 122 1-day samples. The 1-day faecal fat concentration seems useful as a first screening test when malassimilation is suspected.

Diagnosis, Differential↗

Cholecystokinetic and pancreozymic effect of O-sulfated gastrin compared with nonsulfated gastrin and cholecystokinin.

To assess whether sulfated gastrin contributes to the cholecystokinetic and pancreozymic activity of plasma in humans, 8 healthy subjects on separate days received a mixed meal, graded i.v. infusions of synthetic human tyrosine-O-sulfated gastrin 17 (10.9, 32.7, and 98.1 pmol/kg X h), which was compared with nonsulfated gastrin 17 (12.2, 36.6, and 109.8 pmol/kg X h) and O-sulfated cholecystokinin-octapeptide (5.5, 16.5, and 49.5 pmol/kg X h). Gallbladder volumes were measured by ultrasonography, and the concentrations of gastrin and cholecystokinin in the circulation were determined by specific radioimmunoassays. Neither of the gastrins induced changes in gallbladder volume at serum concentrations occurring postprandially, whereas cholecystokinin-octapeptide produced a significant reduction in gallbladder volume even at a plasma cholecystokinin concentration lower than observed postprandially. Another 8 subjects received the same infusions in combination with a background infusion of synthetic secretin (0.3 CU/kg X h). Gastric and duodenal juice was continuously aspirated using a double-marker perfusion technique. Neither of the gastrins caused an increase in the output of amylase, lipase, trypsin, chymotrypsin, or bilirubin, but both induced a modest increase in the output of bicarbonate and duodenal juice, the former only significantly during infusion of sulfated gastrin 17. The output of all parameters was significantly elevated during all doses of cholecystokinin-octapeptide. The results indicate that neither of the gastrins stimulates gallbladder contraction and pancreatic enzyme secretion in humans under physiologic conditions. However, gastrin may, like cholecystokinin, potentiate the effect of secretin on pancreatic secretion of juice and bicarbonate.

Adult↗

Plasma cholecystokinin concentrations in patients with advanced chronic pancreatitis.

Plasma concentrations of cholecystokinin (CCK) have been reported to be elevated in patients with chronic pancreatitis. The elevations are suggested to be due to increased release of CCK from the upper small intestine secondary to the absence of protease activity (trypsin and chymotrypsin) in the intestinal lumen. We have studied plasma CCK levels before and after liquid as well as solid meals in eight patients with pancreatic insufficiency due to advanced chronic pancreatitis and in eight healthy controls. CCK concentrations were measured with a sensitive and specific radioimmunoassay using an antibody directed against the sulfated tyrosyl region of CCK. No differences in basal or maximal postprandial plasma CCK levels between patients and controls were observed. In the liquid meal study, basal CCK concentrations in patients and controls were 2.2 +/- 0.7 and 2.5 +/- 0.4 pM, respectively, with maximal postprandial concentrations of 9.6 +/- 2.2 and 11.2 +/- 1.4 pM. In the solid meal study, basal CCK concentrations in patients and controls were 2.5 +/- 0.6 and 2.6 +/- 0.4 pM, respectively, with maximal postprandial concentrations of 9.4 +/- 1.6 and 8.6 +/- 1.4 pM. The only difference observed was a significantly longer time interval to maximal plasma CCK levels in patients as compared with controls after the liquid meal. Two patients with no detectable trypsin activity in the small intestinal lumen during a Lundh test meal had basal CCK levels of 1.3 and 1.8 pM. Thus, the present study does not support the hypothesis that trypsin is involved in the regulation of CCK release.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholecystokinin↗

Symptomatic effect of pancreatic enzyme therapy in patients with chronic pancreatitis.

The symptomatic effect of pancreatic enzyme substitution therapy was examined in a 4-week double-blind crossover study. Twenty patients, 11 with and 9 without steatorrhoea, were examined. Pancreatic steatorrhoea was reduced from a median of 24 g/day to 10 g/day by the enzyme therapy (P less than 0.01). No significant pain reduction was found in either of the two groups, although there was a tendency to reduction in pain and analgetic consumption in the patients with steatorrhoea when treated with pancreatic enzymes. It is concluded that pancreatic steatorrhoea is still the only indication for pancreatic enzyme therapy.

Adult↗

Results of long-term treatment with cimetidine.

Forty-two patients, 35 with duodenal ulcer, 6 with prepyloric ulcer, and 1 with gastric ulcer, were, in accordance with their own choice, allocated to either maintenance therapy with cimetidine or intermittent therapy in connection with symptoms and endoscopically proven relapse. Dosage during maintenance therapy was kept as low as possible to keep patients free of symptoms. Patients receiving maintenance therapy were mostly free of symptoms, but 6 out of 24 patients had from one recurrence every 2nd year to 3 recurrences per year. Patients receiving intermittent therapy had two recurrences per year (median). The yearly dose of cimetidine in maintenance therapy was high (219 g; range, 73-292 g) compared with 59 g (range, 42-84 g) in intermittent therapy. To conclude, we cannot recommend the use of maintenance therapy for years in the routine management of ulcer patients.

Cimetidine↗

Exocrine pancreatic substitution: facts and controversies.

The effect on intraluminal postprandial concentrations of different pancreatic enzymes and on fat absorption were studied in 35 patients with advanced chronic pancreatitis with pancreatic insufficiency. Different regimes were studied: commercial Pankreatin (III) alone or in combination with Cimetidine, Pancrease, dispensed in microspheres, and commercial Pankreatin III compared to an equivalent uncoated preparation (Pankreatin I). Pankreatin induced significant increase in the intestinal concentration of amylase, lipase, and trypsin. Pretreatment with Cimetidine did not increase the enzyme concentrations further. The amount of enzymes in Pancrease capsules are rather small, no effect on concentrations of enzymes could be detected but treatment with Pancrease decreased significantly the fat excretion in faeces. The uncoated Pankreatin I induced a significantly higher increase in enzyme concentrations in the intestine compared to Pankreatin III but the overall effect tested on faecal fat excretion was identical with the two preparations. The results indicate that the estimation of concentration of enzyme at one level of the small intestine without and with enzyme substitution not necessarily gives information on the therapeutical effect of the enzymes.

Adult↗

Bioavailability of D-penicillamine in a patient with gastrointestinal progressive systemic sclerosis.

D-penicillamine pharmacokinetics were studied in a patient with gastrointestinal progressive systemic sclerosis possibly complicated by malabsorption. D-penicillamine bioavailability was examined after oral, duodenal, intravenous and rectal administration. No D-penicillamine was detectable in plasma after administration to the gastrointestinal tract. The pharmacokinetics after intravenous administration agreed closely with the corresponding situation in healthy volunteers.

Administration, Oral↗

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.

Adult↗

Evaluation of the marker technique for measurement of exocrine pancreatic secretion rate.

A secretin-cholecystokinin test was performed in 103 patients, representing both normal and reduced exocrine pancreatic function. The duodenum was intubated with a triple-lumen tube. The gastric and duodenal contents were aspirated separately and sampled in 10-min periods. An inert, water-soluble marker (58Co-vitamin B12 dissolved in isotonic saline) was infused at a constant rate into the duodenum. Exocrine pancreatic secretion was stimulated by continuous intravenous infusion of secretin for 60 min and a combination of secretin and cholecystokinin for another 60 min. The total recovery of the infused marker was 80%. The concentration of marker in the aspirate did not vary significantly between consecutive 10-min periods during the last 20 min of the secretin stimulation period or during the last 50 min of the combined secretin-cholecystokinin stimulation period, indicating a steady secretion rate into the duodenum. By means of the marker concentrations in the aspirate, the duodenal volumes were calculated and found to vary significantly less than the aspirated volumes. This finding demonstrates that the duodenal volume calculated from the recovery of an inert marker is a closer estimate of the true volume than that obtained by the usual aspiration technique without a volume indicator.

Cholecystokinin↗

Chronic pancreatitis: pathogenesis, natural history and conservative treatment.

Chronic pancreatitis is a serious disease with high morbidity and high mortality. It mostly affects young adults and specifically people with long-term alcohol intake. The diagnosis must be suspected in patients with abdominal pain of unknown origin and in patients with diarrhoea and/or weight loss, particularly if they regularly use alcohol or present with a mild diabetes developed after the age of 30 years. Fundamental problems, such as the aetio-pathogenesis and the mechanism for the abdominal pain, are still unanswered. Contradictory observations concerning the natural history have been reported and further studies are needed to characterize the long-term course of symptoms and complications. The long-term management of patients requires careful attention to medical abuse and to complications (pseudocysts, duodenal ulcer, overt diabetes, and exocrine insufficiency). The high risk for malignant diseases also has to be taken into consideration.

Adolescent↗