[Identification of elevated carbohydrate-deficient transferrin (CDT) serum level as transferrin (Tf)-D-variant by means of isoelectric focusing]. / Identifizierung eines mittels Immunturbidimetrie nach Anionenaustausch-Chromatographie erhöhten Carbohydrate-Deficient-Transferrin-(CDT-)Serumspiegels als Transferrin (Tf)-D-Variante.

Many studies have shown carbohydrate-deficient transferrin (CDT) to be a sensitive and specific marker of chronic alcohol abuse. We present the case of a 23-year-old, healthy professional soccer player who caused a car accident due to alcohol consumption. Several CDT test results were elevated above the laboratory reference range and were considered to be caused by alcohol intake at a level commensurate with misuse and thus license reapplication was refused. In addition, assuming chronic alcohol abuse, the young man suffered from increasing social isolation. He was finally referred to our out-patient clinic for further evaluation on the assumption of a liver disease. Since chronic alcohol consumption was denied, and there was no evidence of liver disease, a qualitative characterization of the transferrin isoforms was performed. Isoelectric focusing of serum transferrin revealed a pattern atypical for chronic alcohol intake but detected a genetically determined transferrin (Tf)-D-variant. The changed amino acid sequence caused an overlapping of transferrin isoforms with different degrees of sialylation, thus revealing false-positive serum CDT values. Determination of this Tf-D-variant heterozygosity resulted in his social rehabilitation and license reinstatement. Thus, where the evidence for alcohol dependency is either uncertain or uncorroborated, qualitative isoelectric focusing of transferrin is a useful method for analyzing unexplained CDT elevations, thus increasing the value of CDT as a marker for chronic alcoholic abuse.

Bioengineered human bone tissue using autogenous osteoblasts cultured on different biomatrices.

Surgical treatment of critical-size posttraumatic bone defects is still a challenging problem, even in modern bone and joint surgery. Progress in cellular and molecular biology during the last decade now permits novel approaches in bone engineering. Recent conceptual and technical advances have enabled the use of mitotically expanded, bone-derived cells as a therapeutic approach for tissue repair. Using three different tissue carrier systems, we successfully cultivated human osteoblasts in a newly developed perfusion chamber. We studied cell proliferation and the expression of osteocalcin, osteopontin, bone morphogenetic protein-2A, alkaline phosphatase, and vascular endothelial growth factor as parameters for osteoblast function and viability. Adherence of highly enriched human osteoblasts had already started after 1 h and resulted in completely overgrown human bone pieces after 10 days. Expression analysis of bone-specific alkaline phosphatase indicated differentiating osteoblasts, whereas the high mRNA expression of osteocalcin and osteopontin revealed terminally differentiated osteoblasts and the process of mineralization. Additionally, gene expression was significantly higher when demineralized bone was used as biomatrix, compared to autoclaved bone and hydroxyapatite ceramics. We conclude that with our newly developed perfusion culture system, vital autogenous bone implants of clinically applicable size can be generated within 17 days in order to manage critical-size bone defects.

Epidemiological trends in pancreatic neoplasias.

Primary prevention is the most effective approach to reduce the incidence of pancreatic cancer. Epidemiological studies have contributed to the identification of risk factors for pancreatic cancer, suggesting an association with age, various medical conditions, environmental and lifestyle risk factors, and occupational and genetic conditions. Age is the strongest risk factor. The most consistently identified environmental risk factor is smoking, but there is less certainty concerning dietary factors. Studies have suggested a positive association with high energy intake, cholesterol and meat, while vegetable and fruit intakes are probably protective. Patients with chronic pancreatitis and new onset of diabetes mellitus have a low but increasing risk of having or developing pancreatic cancer. There is strong evidence for the association of hereditary pancreatitis or cystic diseases of the pancreas and pancreatic cancer. A family history of pancreatic cancer is an important risk factor, but only a small proportion can be linked with known familial cancer syndromes. Thus, additional yet unidentified predisposing risk factors have to be assumed.

Hyperthermia, inducing pancreatic heat-shock proteins, fails to prevent cerulein-induced stress kinase activation.

The dually phosphorylated c-jun kinase and p38 mitogen-activated protein (MAP) kinase, also termed stress kinases, are members of the MAP kinase family. They are activated early during cerulein pancreatitis induction and have been proposed as regulators during pancreatitis development by us and others. We recently showed that hyperthermia preconditioning induces expression of pancreatic heat-shock proteins (HSP) and protects against cerulein pancreatitis. Because it was further reported that HSP70 can prevent activation of stress kinases in lymphoid tumor cells, we investigated whether hyperthermia preconditioning might reduce hyperstimulation-mediated activation of pancreatic stress kinases. Pancreatic HSP expression was induced by whole-body hyperthermia preconditioning. Without prior HSP induction, cerulein led to a rapid and dose-dependent increase in serum lipase and amylase levels, pancreatic wet weight through edema formation, and activation of pancreatic MAP kinases. Hyperthermia preconditioning, although strongly inducing HSP70 and almost completely preventing edema formation, as well as the increase of serum amylase and lipase, did not reduce cerulein-mediated stress kinase activation. This indicates that in the pancreas, cerulein can strongly activate MAP kinases even when pancreatitis development is greatly inhibited, and that pancreatic HSPs do not inhibit activation of pancreatic stress kinases in vivo.

GLP-1 release in man after lower large bowel resection or intrarectal glucose administration.

BACKGROUND: This study addresses the question whether the insulinotropic gut hormone, glucagon-like peptide-1 (GLP-1), is released from the lower large bowel upon oral or rectal glucose uptake. METHODS: It was evaluated whether rectum or sigmoid colon resection alters glucose homeostasis or the plasma levels of the insulinotropic gut hormone, gastric inhibitory polypeptide (GIP), or GLP-1. Six men and 3 women (age 63 +/- 8 years, BMI 25.4 +/- 4.0 kg/m2) with normal preoperative fasting glucose values were treated before and after resection of large bowel segments. Fasting oral glucose tolerance (OGT, 75 g glucose/300 ml) tests were performed both before and 10 days postoperatively. Another approach aimed to clarify whether luminal glucose stimulation in the rectum/sigmoid colon increases GLP-1 plasma levels. Ten healthy volunteers (4 males, 6 females, age 25 +/- 2 years, BMI 22.1 +/- 2.4 kg/m2) received enemas with both saline and, 7 days later, 1 g/kg body weight glucose (70% glucose solution) intrarectally. RESULTS: Neither rectum nor sigmoid colon resection led to significant changes in the pre- and postoperative glucose responses to OGT testing, or insulin, GIP and GLP-1 release. Intrarectal glucose instillation increased blood glucose by about 10 mg/dl with parallel small elevations in immunoreactive insulin and immunoreactive C peptide. However, plasma GLP-1 levels remained unaltered. CONCLUSION: Our data make it unlikely that GLP-1 derived from the lower large bowel contributes significantly to maintain normal glucose tolerance.

[Conservative and interventional therapy of acute diverticulitis with reference to pathophysiology]. / Konservative und interventionelle Therapie der akuten Divertikulitis unter Berücksichtigung der Pathophysiologie.

Diverticular disease is most common in the sigmoid colon. Its etiology is multifactorial and probably related to low-fiber diets, age dependent changes of the colonic wall, hypermotility and myochosis with subsequent increase in intraluminal pressure. Acute diverticulitis results from inflammation of a pseudo-diverticulum. It can progress to pericolitis and perforation with abscess formation. Therapy of uncomplicated diverticulitis is a conservative regimen with bowel rest and intravenous broad spectrum antibiotics. In subjects with complicated diverticulitis, preoperative percutaneous image-guided catheter drainage of diverticular macroabscesses is indicated. This aims at resolving intra-abdominal sepsis thereby avoiding the need for temporary colostomy and multiple-stage surgery. Interval single stage sigmoid resection with primary anastomosis should then be performed. Generalized peritonitis, with or without evidence of free perforation, should be treated surgically. Long-term cereal fiber supplementation and physical activity may prevent complications and inflammatory recurrences in diverticular disease.

Caerulein pancreatitis increases mRNA but reduces protein levels of rat pancreatic heat shock proteins.

We have recently reported that preconditioning through hyperthermia induces expression of pancreatic heat shock proteins (HSPs) and protects against caerulein pancreatitis. Here, we investigate caerulein-mediated effects on pancreatic HSPs without prior hyperthermia. Caerulein time and dose dependently increased pancreatic mRNA levels of the constitutive isoform of HSP70 (HSC70). However, pancreatic HSC70 protein levels were decreased, as were HSP60 protein levels. Also, in contrast to hyperthermia preconditioning, caerulein did not induce measurable levels of mRNA or protein of the inducible isoform of HSP70. Thus the pancreas reacts to different kinds of stress (hyperthermia vs. hyperstimulation) with differential induction of HSP mRNAs. Clearly, hyperthermia leads to induction of HSP protein expression, whereas caerulein treatment does not. Therefore, our current study further supports the idea that hyperthermia-induced protection against caerulein pancreatitis may be mediated through increased protein levels of pancreatic HSPs. It is further tempting to hypothesize that failure to appropriately increase HSP protein levels in response to high doses of caerulein might be a factor in the development of pancreatitis.

Small bowel lengthening by mechanical distraction.

To evaluate whether the small bowel can be distracted by mechanical stress in analogy to limb lengthening by osteodistraction, a gut-lengthening apparatus was designed. This distractor was placed at the antimesenterical side of a defined jejunum segment in rabbits. Distraction was performed by 1 mm lengthening of the distractor once daily using extracorporal screws. An effective gut lengthening was achieved of 9.9 +/- 0.5 mm (approximately 100%) within 3 weeks. Treated animals gained weight and remained in good general condition. Fasting plasma levels of cholecystokinin, neurotensin, glucagon-like peptide-1, gastric inhibitory polypeptide, and insulin remained unaffected. Postoperative factor XIII levels were significantly diminished and gastrin was elevated during gut distraction. DNA and protein concentrations in the mucosa of the distracted gut segments corresponded to controls. Mucosal lactase and saccharase activities were reduced. In the distracted bowel segments total tunica muscularis thickness was more than doubled due to muscle cell hypertrophy. In distracted segments villous width was increased. Detection of proliferating mucosal crypt cells utilizing BrdUrd labeling revealed no effects. In conclusion, small gut lengthening by mechanical distraction is possible without major changes in gut morphology. This technique may hint a novel experimental approach for the treatment of short bowel syndrome.

No apparent benefit of liquid formula diet in NIDDM.

We have studied the impact of liquid diets formulated for complete or supplemental enteral nutrition of type II, non insulin-dependent (NIDDM) diabetics on carbohydrate homeostasis. To achieve this, liquid formula tolerance tests were performed in NIDDM patients under an oral treatment regimen with a combination of diet plus glibenclamide (7 men, 3 women, age: 56 +/- 11 years; mean body mass index of 26.2 +/- 3.6 kg/m2). After an overnight fast, each patient received the usual morning medication and, thereafter, ingested formula diet in randomized order with 10 day intervals between tests. 500 ml were administered of either a standard liquid diet (Biosorb Sonde), a fibre containing diet (Biosorb Plus Sonde), or a carbohydrate modified, fructose containing "diabetes" diet (Fresubin Diabetes) (carbohydrate contents of approximately equal to 60 g, respectively). Blood samples were collected over 180 min. Considering minor variations in the nutritional values of the diets, IR-insulin, IR-C-peptide, IR-glucose-dependent insulinotropic polypeptide (GIP), and IR-glucagon-like peptide. 1 (GLP-1) in plasma did not significantly differ between the study groups. After ingestion of Biosorb Sonde area under the curve glucose was greater than that seen after uptake of fibre containing or carbohydrate modified, i.e. fructose containing "liquid diabetes diets". All diets challenged the entero-insular axis in non-insulin dependent diabetics to a comparable extent. This data does not support the contention to employ special "diabetes" formulas for enteral nutrition of patients with NIDDM.

Hyperthermia induces heat shock protein expression and protection against cerulein-induced pancreatitis in rats.

BACKGROUND & AIMS: Heat shock proteins (HSPs) are part of the cellular stress response machinery. HSPs are expressed in the pancreas, but their protective potential has not been thoroughly investigated. The aim of this study was to characterize the pancreatic heat shock response both in vitro and in vivo and to study whether this response has protective effects. METHODS: For in vitro experiments, rat pancreatic acini were exposed to heat and protein expression was analyzed through 35S-methionine labeling or Western blots. In vivo, cerulein pancreatitis was induced after whole body hyperthermia (42 degrees C). RESULTS: After thermal stress (42 degrees C), acini increasingly expressed five proteins of 92, 72, 59, 58, and 30 kilodaltons, with HSP. 70 the most strongly induced 72-kilodalton protein. In vivo, increased expression of four isoforms of pancreatic HSP-70 was found. Isoform-specific antibodies identified the inducible and constitutively expressed (HSC-70) isoform of HSP-70. HSP-60 was also weakly induced after hyperthermia. Concomitantly, cerulein-induced pancreatic organ damage was greatly reduced after whole-body hyperthermia. The time course and strength of HSP induction correlated well with the time course and degree of protection against cerulein-induced pancreatitis. CONCLUSIONS: A causal relation between hyperthermia-induced HSP expression and organ protection seems possible.

"Human pancreas-specific protein" (procarboxypeptidase B): a valuable marker in pancreatitis?

Human pancreas-specific protein (PASP) has been characterized previously as a serum marker for pancreatitis. It was then identified as pancreatic procarboxypeptidase B (PCB). The aim of the present study was to verify the usefulness of PASP (PCB) as a serum marker in patients with acute (n = 20) and chronic (n = 12) pancreatitis and in those following endoscopic retrograde cholangiopancreaticography (ERCP) (n = 44). Serum PASP values were analyzed by radioimmunoassay, with a range of normal values between 15 and 111 ng/ml. Between April 1992 and September 1992, 20 subjects (19-86 years of age) with acute pancreatitis (alcoholic, 8; biliary, 8; other, 4) were studied. We found edematous pancreatitis in 17 cases and severe hemorrhagic pancreatitis in three cases. At admission, peak levels of PASP (average value, 1,976 +/- 329 ng/ml), pancreatic isoamylase (942 +/- 151 U/L) and lipase (2,946 +/- 534 U/L) were detected in 15 of 20, 16 of 20, and 12 of 20 cases, respectively. The etiology of the pancreatitis had no influence on the PASP values. Furthermore, 10 patients with alcoholic and two patients with nonalcoholic chronic pancreatitis (29-67 years of age) were studied. The average peak level of PASP was 1,229 +/- 434 ng/ml. In this group, PASP paralleled the time course of amylase and lipase. Maximal PASP, amylase, and lipase levels were found in 11 of 12, nine of 12, and five of 12 patients, respectively, on the day of admission. ERCP was performed in 44 patients (36-87 years of age), demonstrating common bile duct stones in 16 and bile or pancreatic ductal tumors in 15 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of synthetic cyclic AMP analogs on amylase exocytosis from rat pancreatic acini.

Diastereomers of adenosine 3',5'-phosphorothioate activate cAMP-dependent protein kinases (cAMP-PK) in vitro. We found that these compounds are highly selective tools to monitor cAMP-dependent PKA activation and its effect on amylase exocytosis from pancreatic acini. In permeabilized rat acinar cells, (Sp)-cAMPS dose-dependently stimulated amylase secretion, while (Rp)-cAMPS inhibited (Sp)-cAMPS-induced amylase release. In intact rat acini, 8-Br-(Rp)-cAMPS reduced the secretory responses to secretin, vasoactive intestinal polypeptide (VIP), 8-Br-cAMP, and 8-Br-(Sp)-cAMPS, but not to cerulein. Another derivative, dibutyryl-(Rp)-cAMPS, induced a small inhibitory effect against 8-Br-(Sp)-cAMPS and VIP, which was overlapped by an unspecific stimulatory effect on amylase exocytosis induced by the degradation product butyrate. Furthermore, (Sp)-5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3',5'- monophosphorothioate ((Sp)-5,6-DCl-cBIMPS), a specific cAMP-PK activator, induced a maximal induction of cAMP-PK activity, but its stimulation of amylase secretion was less than that by secretin. (Sp)-5,6-DCl-cBIMPS regulated the phosphorylation of several proteins, which were also affected by secretin. However, secretin had additional effects. Its action was most likely mediated by a dual effect on the cAMP and the calcium pathway. Our results indicate that the cAMP-dependent pathway is involved in amylase exocytosis from rat pancreatic acini.

[Routine intravenous urography before colorectal resections?]. / Routinemässige intravenöse Urographie vor kolorektalen Resektionen?

The value of preoperative intravenous urography (IVU) to prevent iatrogenic damage to the urogenital tract was investigated in a series of 236 females and 188 males (mean age 54 [5-87] years) who underwent an operation on the colon or rectum between April 1988 and March 1992. The operations were: 101 right and 49 left hemicolectomies, 125 sigmoid resections, 74 anterior rectum resections, 58 abdomino-perineal rectum amputations and 17 total colectomies. Preoperative IVU was performed in 279 patients (65.8%), while in 145 (34.2%) urgency of the operation or intolerance to contrast medium prevented the procedure being done. The results were abnormal in 75 of the 279 IVUs (26.9%). Of the latter, only 19 (6.8%) of the abnormalities were related to the colorectal disease (renal obstruction due to tumour: 9, malignant invasion of the bladder: 5, ureter displacement: 5). Other diagnostic procedures had given abnormal results in six patients, although the preoperative IVU had been unremarkable. Iatrogenic damage to a ureter occurred in only one patient: the IVU had been normal. No ureteral damage occurred in any of the patients who had not had an IVU. These data indicate that the decisive factor in preventing intraoperative damage to a ureter is not a preoperative IVU but careful intraoperative dissection and visualization of the ureter. There is, therefore, no need for routine preoperative IVU in these cases.

[Pancreatitis in primary hyperparathyroidism (pHPT) is a complication of advanced pHPT]. / Die Pankreatitis beim primären Hyperparathyreoidismus (pHPT) ist eine Komplikation des fortgeschrittenen pHPT.

Pancreatitis occurred in 13 (5.6%) of 234 patients (76 men, 158 women; mean age 63 [2-83] years) who were operated on for primary hyperparathyroidism (pHPT) between 1987 and 1992. The pancreatitis patients had a significantly higher median level of parathormone (340 pg/ml), of serum calcium (3.2 mmol/l) and of thyroid weight (1.7 g) than the remaining 221 patients (135 pg/ml; 2.9 mmol/l; 1.0 g, respectively: P < 0.05 for each). In ten patients pHPT had been diagnosed during an attack of pancreatitis: pancreatitis had been the diagnostic clue to pHPT. After conservative treatment of the pancreatitis and parathyroidectomy seven of the ten patients were free of symptoms during the follow-up. In one patient pancreatitis recurred postoperatively and two patients died of the consequences of haemorrhagic necrotizing pancreatitis. Cholelithiasis, as another possible causative factor for pancreatitis, was present in five of the 13 patients (38%). None of the patients was an alcoholic. These data indicate that there is a positive correlation between advanced pHPT and pancreatitis. Pancreatitis may be the expression of much advanced hyperparathyroidism which has been diagnosed too late.

Cellular ultrastructure of the ruptured anterior cruciate ligament. A transmission electron microscopic and immunohistochemical study in 55 cases.

To evaluate the cellular ultrastructure following injury, we examined the anterior cruciate ligaments in 55 patients with complete tears in different phases after the injury and compared them to a control group of 39 cadaver knees. Samples were analyzed by electron microscopy, immunofluorescence, and ultramorphometry. After an invasion of inflammatory cells into the stumps of the ruptured ligaments, a marked proliferation of fibroblasts was found at the end of Phase 1 (2-3 days after the ligament injury), that was even more pronounced at the beginning of Phase II (4-17 days). These cells were initially highly metabolically active and secreted Type III collagen precursors. In Phase III (4-45 days), fibroblast degeneration occurred with increasing frequency. Furthermore, some fibroblasts showed signs of cell death. Our findings suggest that the structural alterations of the intraligamentous fibroblasts diminish their function and, consecutively, disorganization of the developing repair tissue occurs. This mechanism might contribute to the poor healing potential of the ruptured anterior cruciate ligament.

[Diagnostic and therapeutic procedures in splenic and hepatic artery aneurysms]. / Diagnostische und therapeutische Vorgehensweisen beim Milz- und Leberarterienaneurysma.

The diagnosis and therapy of splenic and hepatic artery aneurysms is besides clinical findings based on ultrasound and selective arteriography. Surgical treatment depends on the exact localization of the aneurysm. Because of postsplenectomy sepsis preservation of spleen should be reached. Otherwise splenectomy with resection of the aneurysm must be performed. If the aneurysm is localized at the common hepatic artery ligation of the vessel is possible. The interposition of an autologous vein graft is the most favorable proceeding in aneurysms of proper hepatic artery. Those of intrahepatic arteries should be treated just as aneurysms in high risk patients by selective percutaneous embolization.

Protective effects of therapy with a protease and xanthine oxidase inhibitor in short form pancreatic biliary obstruction and ischemia in rats.

The current study was done to evaluate the effects of short term (60 minutes) pancreatic biliary duct obstruction (PBDO) with intraductal hypertension (IDH) stimulated by secretin (0.2 clinical unit per kilogram per hour) and caerulein (0.2 microgram per kilogram per hour) plus 30 minutes of temporary pancreatic ischemia (ISCH) produced by ligation of celiac and superior mesenteric artery on the exocrine pancreas and protective effects of a new potent protease inhibitor, ONO3307 in combination with xanthine oxidase inhibitor, allopurinol, in this multifactor related model of acute pancreatitis in rats. Twelve hours after PBDO with IDH plus ISCH, we observed hyperamylasemia (23 +/- 3 units per milliliter) (p < 0.01); moderate pancreatic histologic changes; pancreatic edema (water content--81 +/- 2 percent) (p < 0.02), as well as the impaired amylase (2,889 +/- 328 units per kilogram per hour) (p < 0.01) and cathepsin B output (7 +/- 3 units per kilogram per hour) (p < 0.01) into the pancreatic juice of rats stimulated by caerulein (control group--serum amylase levels, 6 +/- 1 units per milliliter; pancreatic water content, 74 +/- 1 percent. Furthermore, PBDO with IDH plus ISCH caused the redistribution of lysosomal enzyme from lysosomal fraction (12 kilo times gravity pellet; 40 +/- 3 percent; p < 0.01) to zymogen fraction (1.3 kilo times gravity pellet; 38 +/- 3 percent; p < 0.01) (control group--12 kilo times gravity pellet, 59 +/- 2 percent; 1.3 kilo times gravity pellet, 24 +/- 2 percent) and the impaired pancreatic adenylate energy metabolism (0.79 +/- 0.02, p < 0.02) (control group--energy charge equals 0.88 +/- 0.01). Only PBDO with IDH caused no significant changes. Although only ONO3307 or allopurinol therapy showed the partial significant protective effects against pancreatic injuries, improving serum amylase levels, the administration of ONO3307 in combination therapy with allopurinol showed almost complete protective effects against the pancreatic injuries induced by PBDO with IDH plus ISCH (serum amylase levels, 9 +/- 2 units per milliliter; pancreatic water content, 76 +/- 2 percent; amylase and cathepsin B output, 7,127 +/- 946 and 18 +/- 3 units per kilogram per hour; 1.3 kilo times gravity pellet, 28 +/- 2 percent; 12 kilo times gravity pellet, 54 +/- 2 percent, and energy charge equals 0.85 +/- 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)

Partial hepatectomy affects pancreatic size and function in rats.

The effect of partial hepatectomy (62 +/- 2% of liver mass) or sham laparotomy on the pancreas was studied in rats. Pancreatic contents of DNA, protein, and digestive enzymes were measured 14 days postoperatively. Pancreatic acini were prepared to study exocrine pancreatic function after hormonal stimulation. Islet hormone release was investigated in the isolated perfused pancreas. Liver regeneration reached 93 +/- 1% within 14 days. Water contents in liver and pancreas remained unaltered. Simultaneously, the pancreatic weight increased significantly. Pancreatic enzymes showed a parallel elevation, whereas DNA remained unaffected. Amylase secretion from pancreatic acini was unaltered. Stimulated insulin and somatostatin release from the perfused pancreas were both increased. Plasma cholecystokinin levels were elevated, whereas neurotensin was decreased. Insulin and gastrin remained unchanged. In conclusion, after partial hepatectomy, enhanced cholecystokinin and decreased neurotensin blood levels are suggested to contribute to a hypertrophic effect on the exocrine pancreas and an adaptive regulation of the endocrine gland.

Intraoperative ultrasonography in surgery for chronic pancreatitis.

We report our experience with intraoperative ultrasonography in 49 patients undergoing surgery for chronic pancreatitis. Among drainage procedures, there were 14 laterolateral pancreaticojejunostomies, 15 pseudocystojejunostomies, and 2 pseudocystoduodenostomies. Under the guidance of intraoperative ultrasonography, left sided partial resection of the pancreas was performed in 7 patients, whereas a Whipple-type procedure was necessary in 6 cases. All preoperatively diagnosed pseudocysts, abscess formations, and dilated pancreatic ductal systems could be easily localized with the assistance of intraoperative ultrasound. Additionally to diagnoses already made preoperatively, intraoperative ultrasonography revealed a second, smaller pseudocyst in one patient and pancreaticolithiasis in another case. However, significant assistance and comfort to the operating surgeon was provided in all cases by intraoperative ultrasound imaging. This technique, which is cost effective and minimally invasive, proved to be extremely helpful in localizing pancreatic fluid collections and the course of the pancreatic duct. It facilitates the operation by reducing tissue traumatization and operative time. In experienced hands, intraoperative ultrasonography is a reliable method and a useful adjunct to the surgeon.

Cytotoxic effects of cyclosporin A on the exocrine pancreas in rats.

The current study was done to evaluate the subacute toxic effects of cyclosporin A (CS) on the exocrine pancreas and the protective effect of potent protease inhibitor camostate (FOY-305). CS administration (15 milligrams, twice a day) for 14 days caused a significant increase in serum amylase levels, pancreatic amylase and cathepsin B content and mild acinar cell vacuolization and interstitial edema. CS also caused the redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction, indicating colocalization of lysosomal enzyme with pancreatic digestive enzymes. The administration of camostate (150 milligrams per kilogram, twice a day for 14 days) almost completely prevented the toxic changes induced by CS. These results indicate that CS induces exocrine pancreatic injury and that lysosomal enzymes play important roles in the pathogenesis of the injury. The results also suggest the usefulness of camostate in protecting the exocrine pancreas in patients treated with CS after organ transplantation, because it can inhibit some proteases that are closely involved in the fragility of the subcellular organelles.