Classification of pancreatitis--Cambridge and Marseille.
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England↗
Biomedical subjects
I Ihse
Publications and source records attributed to I Ihse.
Sequential studies on the development of nitrosamine-induced pancreatic carcinoma in the Syrian golden hamster.
An attempt was made to define the importance of accumulated carcinogen dose and of induction-time on the development of pancreatic tumors after administration of N-nitrosobis(2-hydroxypropyl)amine (BHP) to Syrian golden hamsters. The development and progression of ductal hyperplasia, the number of tumor-bearing animals, the number of cancer-bearing animals, the number of tumors per tumor-bearing animal, and the grade of histological differentiation were found to be related to the accumulated dose of the carcinogen given, as was survival-time. The duration of the period between the carcinogen administration and examination was another factor of importance for the same changes except for the grade of histological differentiation of cancers and for survival-time. Once ductal hyperplasia and tumor development had started, there were no signs of regression - but rather progression - even after cessation of carcinogen administration. It is concluded that the development (progression) of induced pancreatic cancer in the Syrian golden hamster is influenced by the accumulated carcinogen (BHP) dose and the duration of the experiment. The results emphasize the need for a strict standardization of the experimental design as well as for the histological evaluation when animal models are used for studies of the effect of factors or procedures with a possible influence on the rate of tumor development.
Animals↗
Lysosomal enzymes, alkaline phosphatase, and bilirubin in plasma after bile duct transection in the rat.
Plasma levels of the lysosomal enzymes beta-glucuronidase and beta-hexosaminidase were studied for 6 weeks after permanent bile duct occlusion (19 animals) or sham operation (5 animals). The bile duct-occluded animals had a stable bilirubinemia throughout the observation period. The median level of beta-glucuronidase in controls was 0.45 U/l. In jaundiced animals the median level was 1.09 at 0.5 weeks, 1.28 at 2 weeks, and 1.58 at 6 weeks after bile duct occlusion. The median level of beta-hexosaminidase in controls was 18.5 U/l. In jaundiced animals the median level was 18.0 at 0.5 weeks, 20.8 at 2 weeks, and 53.3 at 6 weeks after operation. Compared with beta-glucuronidase, prominent elevation of the beta-hexosaminidase level appeared much later after bile duct obstruction, which might suggest a closer association with reticuloendothelial system function for the latter enzyme.
Alkaline Phosphatase↗
Influence of bile duct occlusion on the exocrine pancreas in rats.
The exocrine pancreas was studied in the rat after both prolonged permanent and transient biliary obstruction. Double ligation, transection, and transposition of the distal end of the bile duct rendered the animal permanently jaundiced, whereas simple ligation led to a transient jaundice followed by restitution within 15-20 days. In permanent cholestasis pancreatic mass and protein, DNA, amylase, and trypsinogen content were increased. Transient cholestasis probably had only transient effects, since no significant changes in pancreatic mass, protein, DNA or enzymes could be found at 3-5 weeks after surgery. The results show that obstructive jaundice with absence of bile flow to the intestine causes enlargement of the pancreas due to parenchymatous hyperplasia and interstitial edema.
Alkaline Phosphatase↗
A method to prevent recanalization of the transected bile duct in the rat.
The purpose of this study was to develop a surgical technique for bile duct occlusion in the rat which would prevent restoration of biliary drainage. In three successive series of animals the surgical technique was modified from ligation and transection to ligation and transection with resection and, finally, to ligation and transection with transposition of the distal end behind the stomach-duodenum. In these three groups recanalization was observed in 4 out of 9, 1 out of 9, and 0 out of 19 animals, respectively. Bilirubin levels in plasma monitored in the last group showed that a stable cholestatic jaundice was maintained for at least 6 weeks. The results suggest that transposition of the distal transected end of the bile duct below the stomach-duodenum will effectively reduce the chance of recanalization and thus make study of long-term extrahepatic cholestasis in the rat more practical.
Animals↗
Long term results of pancreaticojejunostomy in chronic pancreatitis.
Fifty-one consecutive pancreaticojejunostomies for pain in chronic pancreatitis performed during the years 1964 to 1983 have been reviewed. Mean observation time was 8.2 years. Information on alcohol consumption, pain intensity and clinical signs of pancreatic dysfunction was recorded at regular intervals. Operative mortality was nil. Analysis showed no difference between alcohol abusers and other patients with regard to calcification, ductal dilation or exocrine and endocrine insufficiency. Good to excellent pain relief was achieved in 65 per cent of abusers and 88 per cent of nonabusers and was stable for at least five years. Patients who are heavy and unremitting abusers did not get much pain relief as a result of the operation. Patency of the anastomosis does not seem to be crucial for pain relief after pancreaticojejunostomy.
Adult↗
Preoperative and operative diagnosis of pancreatic cancer.
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Biopsy, Needle↗
Influence of intraluminal trypsin activity on the course of acute experimental pancreatitis.
In short-term experiments (25 or 72 h) oral trypsin inhibitor administration to pancreatitic rats significantly decreased survival rate, whereas oral trypsin administration had no effect in this respect. Neither treatment influenced the activities of amylase in serum, pancreatic tissue or ascites. Trypsin given in excess together with the trypsin inhibitor abolished the deleterious effects on survival caused by the trypsin inhibitor. In a long-term experiment in healthy rats oral trypsin inhibitor ingestion caused a significant increase in pancreatic wet weight, protein concentration and activities of amylase, lipase and trypsinogen in pancreatic tissue; again, trypsin administration had no effect. The data support the idea that oral trypsin inhibitor administration causes release of cholecystokinin (CCK) or CCK-like factors from the intestine by interfering with the negative feedback regulation exerted by intraluminal trypsin. The results of the short-term experiments further indirectly suggest that even small amounts of trypsin within the intestine - as in acute pancreatitis - can exert the feedback regulation. Finally, the results of the long-term experiment suggest that oral administration of trypsin does not exert any suppressive effects on pancreatic wet weight and pancreatic enzyme content.
Acute Disease↗
Effects of pectin and wheat bran on intraluminal pancreatic enzyme activities and on fat absorption as examined with the triolein breath test in patients with pancreatic insufficiency.
In totally pancreatectomized patients breath 14CO2 excretion after ingestion of 14C-labeled triolein was significantly increased by a granulated pancreatic enzyme preparation and was reduced when pectin was added to the enzyme supplement. In the same patients pectin reduced trypsin, lipase, and amylase activities of jejunal aspirates after a test meal supplemented with pancreatic enzyme substitution, which was shown to give good enzyme activities in the intestine. In patients with chronic pancreatitis, breath 14CO2 excretion was reduced by wheat bran, which also caused a reduction in lipase and amylase activities of duodenal aspirates after a test meal. The findings demonstrate the efficiency of treatment with a granulated pancreatic enzyme preparation in restoring intraluminal enzyme activities and fat absorption in patients with pancreatic insufficiency. They also show that pectin and wheat bran may induce fat malabsorption and inhibit digestive enzyme activities in vivo.
Adult↗
Pancreatic carcinoma: diagnosis and treatment.
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Adolescent↗
Studies of the effect of cerulein administration on experimental pancreatic carcinogenesis.
The influence of the cholecystokinin analogue cerulein on induced pancreatic cancer in the Syrian golden hamster was investigated. Of hamsters given weekly subcutaneous injection of N-nitrosobis(2-hydroxypropyl)amine (BHP) in initial experiments 50% succumbed within 30 weeks when a dose of 125 mg BHP per kg body weight was used and within 25 weeks after the double dose. An induction time of at most 24 weeks was therefore used in the subsequent experiments. Administration of cerulein (2 micrograms twice daily for 5 days a week) for 18 or 22 weeks caused an increase of pancreatic wet weight by about 100% and of pancreatic protein content by 73% (18 weeks). BHP did not influence the pancreatic weight either in hamsters given cerulein or in those given saline injections. BHP (125 mg/kg) caused tumors in 44% of the animals after 18 weeks and in 73% after 22 weeks. When BHP was given in a dose of 250 mg/kg, 100% of the animals had pancreatic tumors after 22 weeks. At neither dose and neither time interval did cerulein influence the number of tumor-bearing animals, number of cancer-bearing animals, or number of tumors per tumor-bearing animal or cancers per cancer-bearing animal. No morphological differences were found within the lesions of animals given only BHP as compared with those given cerulein in addition. All lesions were of ductal appearance. The distribution of tumors was also similar irrespective of the treatment given. The results show that cerulein does not influence experimental pancreatic carcinogenesis in the Syrian golden hamster, possibly reflecting that cerulein and BHP primarily act on different target cells.
Animals↗
Bile reflux and pancreatic cancer.
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Animals↗
Pain reduction by an oral pancreatic enzyme preparation in chronic pancreatitis.
In a double-blind study on 19 patients with the diagnosis of chronic pancreatitis, the effects of treatment with a granulated pancreatic enzyme preparation (Pankreon) were compared with those of placebo administration. One week of treatment with each preparation was preceded by one week without any medication. The patients kept daily records of their symptoms, plotting the severity of pain on an analog scale. Weekly assessments of the mean pain level were also made by an examiner questioning the patients. Recordings of body weights and pancreas and liver laboratory tests were done weekly. Fifteen of 19 patients noted less pain during the week of treatment with pancreatic enzymes as compared to that of placebo treatment (P less than 0.05). The average reduction of pain, as calculated for all patients, was 30% as evaluated by both patients (P less than 0.01) and the examiner (P less than 0.05). No differences were found in other parameters examined. A possible explanation of the findings could be an effect on the intraductal pressure by intraluminal trypsin.
Adult↗
Hormonal and cholinergic effects on amylase and lysosomal enzyme activities in pancreatic tissue and ascites of rats with acute experimental pancreatitis.
The effects of hormonal or cholinergic stimulation on survival and on activities of lysosomal enzymes and amylase in pancreatic tissue and ascites were studied in rats with induced pancreatitis. Pancreatitis per se caused an increase of the activities of cathepsin D, N-acetyl-beta-D-glucosaminidase and amylase, and a decrease of acid phosphatase in pancreatic tissue. Pancreatic protein concentration was not influenced. In pancreatitic rats administration of cerulein or carbachol markedly decreased survival rate. Cerulein increased the activities of cathepsin D and amylase in ascites and cathepsin D and acid phosphatase in pancreatic tissue. Carbachol increased the activities of cathepsin D and amylase in ascites and acid phosphatase in pancreatic tissue. Both cerulein and carbachol decreased the activity of amylase in pancreatic tissue. Administration of secretin or the anticholinergic drug Pro-Banthine did not influence survival rate or the activities of lysosomal enzymes and amylase in ascites. In pancreatic tissue the activity of acid phosphatase was slightly increased by secretin or Pro-Banthine. In conclusion, the results show a nonparallel alteration of lysosomal enzyme activities in pancreatic tissue in rats with pancreatitis. Cerulein and cholinergic stimulation decreased survival rate and brought about a marked increase of cathepsin D activity in ascites and, in the case of cerulein, also in pancreatic tissue. The implication of lysosomes and especially the catheptic proteases in the pathogenesis and outcome of acute pancreatitis deserves further attention.
Acetylglucosaminidase↗
Factors influencing survival after total pancreatectomy in patients with pancreatic cancer.
A retrospective analysis of factors influencing short-term and long-term survival after total pancreatectomy for pancreatic cancer was done in 86 patients. Among the 41 factors studied, hospital mortality was significantly affected by age over 70 years, preoperative diabetes, pain as presenting symptom, S-bilirubin, preoperative bile drainage, prophylactic antibiotic treatment, stage of the tumor, and experience of the surgeon. The only factors which had a statistically significant influence on long-term survival were stage of the tumor and sex of the patient. It is concluded that improvement of long-term survival can mainly be achieved by earlier identification and removal of the tumors and by introduction of more efficient adjuvant therapy. Whereas these goals probably will require a long time to be reached, the majority of factors associated with worsening of hospital mortality may be avoided by a strict selection of the patient, the tumor and the surgeon.
Adenocarcinoma↗
Influence of pancreatic duct ligation on endocrine and exocrine rat pancreas.
A parallel investigation into endocrine and exocrine pancreatic function, after duct-ligation in the rat, was performed to study the effect of reduced intestinal trypsin levels on insulin secretion and glucose tolerance. Animals with only a slight exocrine insufficiency displayed a normal insulin secretion and a normal glucose tolerance 4 weeks after operation. At 4-5 month s these animals showed a slight increase in glucose-induced insulin release when compared with control rats. However, animals operated on with a more complete ligation of the pancreatic ducts, who showed a marked exocrine insufficiency accompanied by decreased levels of intestinal trypsin, displayed a markedly increased insulin secretory response to intravenous glucose and an increased glucose tolerance. The results lend further support to our previous suggestion that, in the rat, the levels of intestinal trypsin may influence insulin secretory processes via complex feed-back mechanisms which may involve cholecystokinin and/or other intestinal hormones.
Amylases↗
Effects on the exocrine and endocrine pancreas of duct occlusion with two different tissue glues in the rat.
Exocrine and endocrine pancreatic function was studied in the rat after occlusion of the pancreatic ducts with acrylate or prolamine, respectively. After 5 months the effect of these procedures was a clear-cut exocrine insufficiency as evidenced by reduced enzyme activities in pancreatic tissue and in intestinal content, while the endocrine function was not impaired. The insulin secretory response to an intravenous glucose load was rather increased in duct-occluded rats, and the glucose tolerance was improved. The liver glycogen levels in duct occluded rats were decreased. As judged from the present investigation there was no striking difference between the effects of acrylate and prolamine on either exocrine or endocrine pancreas. The results suggest that long-term duct occlusion in the rat by acrylate or prolamine is harmless to the endocrine pancreas. The improvement of the glucose-induced insulin response and the glucose tolerance is probably due to an enteropancreatic feedback mechanism elicited by low levels of intestinal trypsin.
Animals↗
Hormonal and cholinergic influences on pancreatic lysosomal and digestive enzymes in rats.
Hormonal and cholinergic influences on lysosomal and digestive enzyme activities in pancreatic tissue were studied in normal adult rats. Hormonal stimulation by the cholecystokinin analogue, caerulein, induced a marked enhancement of the activities of cathepsin D and N-acetyl-beta-D-glucosaminidase in pancreatic tissue, whereas the activities of amylase and lipase tended to decrease. Acid phosphatase activity was not affected. Further, caerulein was found to induce a significant increase of cathepsin D output in bile-pancreatic juice. This output largely parallelled that of amylase. Cholinergic stimulation by the muscarinic agonist carbachol, at a dose level giving the same output of amylase as caerulein, did not affect pancreatic activities of cathepsin D and N-acetyl-beta-D-glucosaminidase. Further, cholinergic stimulation induced an increase of amylase activity and a slight decrease of acid phosphatase activity in pancreatic tissue. Lipase activity was not affected. No apparent effect on cathepsin D output in bile-pancreatic juice was encountered after cholinergic stimulation. The activities of neither the digestive nor the lysosomal enzymes were influenced by the administration of secretin. The results suggest a possible lysosomal involvement in caerulein-induced secretion and/or inactivation of pancreatic digestive enzymes, whereas cholinergic stimulation seems to act through different mechanisms.
Acetylglucosaminidase↗