Prerequisites and initial experience for the noninvasive routine evaluation of viability of experimental and human organ transplants by magnetic resonance spectroscopy.
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Biomedical subjects
Publications and source records attributed to H G Beger.
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Once a diagnosis of acute pancreatitis is established it is necessary to discriminate between an edematous-interstitial and a necrotizing course of the disease, to determine the extent and location of necroses by contrast-enhanced CT and to detect early infection by ultrasound guided needle aspiration. In chronic pancreatitis it is imperative to ascertain the severity by ERCP, and to use imaging techniques to determine degree of functional impairment and the extent to which the inflammatory process has extended to the peripancreatic tissues by means of imaging techniques. Based on clinical data pancreatic carcinoma can not usually be detected until it is already in a late stage, but it can then be confirmed with great reliability by ERCP, contrast-enhanced CT, tumor marker tests and fine needle aspiration.
From 3/1982 to 12/1989 773 patient underwent an elective Cholezystectomy at the Surgical University Hospital of Ulm. In 87% of cases the indication was a symptomatic cholelithiasis, the mean age being 55.4 years for females and 56.6 years for males. Intraoperative complications were rare (2.8%) and of a technical nature. Postoperative morbidity was 15.2%. General disturbances occurred in 10.3% and were age-depended. Local postoperative problems (4.9%) did not show this age-dependent distribution. Residual stones were detected in 0.8% of cases; they were removed operatively or endoscopically or crushed by shock waves. 1.3% of patients had to be re-operated. In the age group under 70 years as well as over 70 years lethality was 0%. In 9 cases (1.16%) a gallbladder carcinoma was found incidentally during the operation. We think that elective cholecystectomy is a safe therapeutic procedure in gallbladder stone disease, which also considers the association of chronic cholelithiasis and gallbladder carcinoma.
Since 1972, resection of the head of the pancreas with preservation of the duodenum has been carried out in 141 patients with chronic pancreatitis and an inflammatory mass in the head of the gland. One patient died in hospital (0.7%), and seven further patients died during the median follow-up period of 3.6 years (range 0.5-16). In contrast to the Whipple procedure, this operation spares the patient a gastric resection, a duodenectomy, and resection of the common bile duct. In terms of long lasting relief of pain and preservation of the endocrine function of the pancreas, the limited resection with preservation of the duodenum is highly effective and the mortality and late morbidity are low.
Regional chemotherapy with floxuridine was undertaken in 50 patients (32 men and 18 women, mean age 57 years) with colorectal carcinoma with metastases only to the liver. In 25 patients (group I) the drug (0.2 mg/kg) was administered exclusively intraarterially into the hepatic artery, while in the remaining 25 (group II) it was given both intraarterially (0.21 mg/kg) and intravenously (0.09 mg/kg) via the inferior vena cava. The remission rate in group I was 56% (14 of 25), in group II it was 64% (16 of 25). It was subsequently discovered that 4 of the 25 in group II already had extrahepatic metastases at the time of implantation of the infusion catheter. The difference in remission rate between the two groups is not significant. Extrahepatic tumour recurrence occurred after a median period of 16 months in 17 patients of group I (68%) and six of 21 of group II (29%, P less than 0.01). Over an observation period of 34 months the survival rates of the two groups were not significantly different. However, these results suggest that over a longer period a higher survival rate is to be expected for the intraarterially plus intravenously treated group.
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A position-specifically labelled phosphatidylcholine is the substrate for the selective determination of Phospholipase A2 in serum, ascites and tissue samples. Optimal reaction conditions and simplifications of handling are discussed. A control group of human serum samples ranged up to 2.1 U/l. The maximum serum activity in samples of patients with acute pancreatitis was 126 U/l. In human ascites activities up to 380 U/l were measured. The method described here turned out to be a practicable instrument for the determination of phospholipase A2 activity using only commercially available reagents.
We investigated the effect of gabexate mesilate on the catalytic activity of phospholipase A2 in homogenized porcine pancreatic tissue. Gabexate mesilate is a potent inhibitor of serine proteases. There is no direct inhibition of phospholipase A2 catalytic activity in concentrations up to 6 mmol/l. Preincubation of homogenized pancreatic tissue with gabexate mesilate leads to a reduction of phospholipase A2 activity even in concentrations as low as 6 mumol/l. The activation of purified porcine prophospholipase A2 added to pancreatic tissue can be completely inhibited. Thus gabexate mesilate might influence the activation of phospholipase A2 administered in therapeutic concentrations in inflamed pancreatic tissue.
The purpose of this study was to assess the involvement of oxygen radicals and phospholipase A2 in acute pancreatitis. Acute pancreatitis was induced in rats by the CCK-analogue cerulein (5 micrograms/kg.h) for 30 min, 3.5 h, and 12 h. At the end of the infusion, serum enzymes and the lipid peroxidation products conjugated dienes and malondialdehyde in the tissue were measured. Moreover, tissue samples underwent lightmicroscopical examination. After 3.5 h cerulein, an interstitial edema and a beginning accumulation of granulocytes in the pancreatic gland is observed. These changes are aggravating within 12 h, leading to tissue necrosis and migration of the granulocytes into the tissue. Concomitantly amylase and lipase increased by 15 and 35 times, respectively. Conjugated dienes and malondialdehyde increase already after 30 min cerulein and reach their highest levels after 3.5 h cerulein. At the same time the tissue activity of phospholipase A2 is elevated three fold. Rats were treated with superoxide dismutase and catalase before cerulein infusion. Treatment significantly prevents tissue necrosis, granulocyte accumulation, and edema formation. The enhanced activity of phospholipase A2, however, is unaffected by the treatment. Oxygen radicals seem to be instrumental in the development of the disease.
Serum from 48 patients with acute pancreatitis (21 with interstitial-edematous and 27 with necrotizing pancreatitis) was monitored for immunoreactive (IR) phospholipase A2 (PLA2) protein concentration and PLA catalytic activity. In both groups within 48 h after start of acute pancreatitis an up to tenfold increase of IR-PLA2 was demonstrable. Determination of IR-PLA2 revealed no differences between the groups. In contrast, determination of PLA catalytic activity allowed us to differentiate between patients with interstitial-edematous and necrotizing pancreatitis.
To study the source and role of circulating phospholipase A2 (PLA2) catalytic activity we monitored the serum from patients with necrotizing pancreatitis (n = 8), diffuse peritonitis (n = 6), and multiple injuries (n = 11). Immunoreactive PLA2 serum protein concentration was analysed using a fluoroimmunoassay based on an antibody against human pancreatic PLA2. Serum PLA2 catalytic activity was analysed using a radiochemical method based on a substrate with tritiated palmitic acid in beta position. In necrotizing pancreatitis immunoreactive PLA2 and PLA2 catalytic activity both increased. Obviously, in necrotizing pancreatitis the major part of serum catalytic activity stems from the pancreas. In patients with diffuse peritonitis and multiple injuries, as a rule, immunoreactive phospholipase A2 serum concentration appears to be within the normal range. In contrast, in these patients we demonstrated high serum catalytic PLA2 activity comparable to that in necrotizing pancreatitis. The source of catalytic PLA2 activity in peritonitis and multiple injuries seems not to be the pancreas. There was a correlation between pulmonary insufficiency and serum PLA2 catalytic activity in patients with necrotizing pancreatitis, peritonitis, and multiple injuries.
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In rats, total gastrectomy (TG) has been shown to induce pancreatic hyperplasia and increased tissue concentrations of pancreatic trypsin and amylase, whereas lipase concentration was decreased. We performed total gastrectomy with the additional insertion of a duodenal tube in 17 rats. A central venous catheter was placed after 3 wk. The control groups consisted of sham-operated rats with a gastrotomy plus duodenal tube and a group of rats with only a duodenal tube. The rats received meal stimulation with a 6 mL liquid diet (3 mL oil, 2 mL amino acid solution, and 1 mL glucose) via duodenal tube upon recuperation. Blood samples were taken before as well as 5, 15, 30, and 60 minutes after the meal and analyzed for insulin, pancreatic glucagon, gastrin, and CCK by specific RIA techniques. Glucose tolerance was found to be impaired after total gastrectomy. Though insulin release was delayed compared to the controls, the integrated postprandial output was unchanged. The pancreatic glucagon release after the meal increased 83% in TG rats, compared to control rats. The baseline and postprandial gastrin values diminished 70% compared to control animals. Neither group exhibited a postprandial increase in gastrin levels. TG led to an increased postprandial CCK output of 72% compared to controls. The trophic changes of rat exocrine pancreas following total gastrectomy, therefore, could be based on an elevated postprandial release of CCK.
In a prospective clinical trial, 85 patients with acute pancreatitis, including 50 with acute interstitial-edematous pancreatitis and 35 with necrotizing pancreatitis, were recruited. Serum pancreatic immunoreactive phospholipase A2 (IR-PLA2), serum phospholipase A catalytic activity (CA-PLA), and serum phospholipase A2 catalytic activity (CA-PLA2) were determined daily between day 1 and day 10 after the onset of the disease. The serum course of IR-PLA2 values for patients with acute interstitial-edematous pancreatitis was comparable to that for patients with necrotizing pancreatitis. In contrast, the determination of CA-PLA and of CA-PLA2 specific activity in the serum revealed a high differentiation between patients with interstitial edematous and those with necrotizing pancreatitis. The overall accuracy for differentiating patients with necrotizing pancreatitis from those with the interstitial-edematous type was 79% for CA-PLA and 77% for CA-PLA2 (cut-off level: CA-PLA, 15 U/L, day 1-5; CA-PLA2, 3.5 U/L, day 1-5). Patients with pancreatitis-associated pulmonary complications showed significantly higher CA-PLA and CA-PLA2 values in the serum. This study demonstrates the role of serum catalytic phospholipase A2 in human acute pancreatitis where the development of pancreatic necrosis and pulmonary failure is concerned.
The most important diagnostic step in the management of patients with severe acute pancreatitis is the discrimination between acute interstitial and necrotizing pancreatitis. Measurement of C-reactive protein, lactic acid dehydrogenase, alpha-1-antitrypsin, and alpha-2-macroglobulin and contrast-enhanced CT are useful in detecting the necrotizing course of acute pancreatitis. C-reactive protein, lactic acid dehydrogenase, and contrast-enhanced CT offer detection rates of 85 per cent to more than 90 per cent for pancreatic necrosis. Surgical decision-making in necrotizing pancreatitis should be based on clinical, morphologic, and bacteriologic data. Patients with focal pancreatic necrosis, in general, respond well to medical treatment and do not need surgery. Extended (50 per cent or more) pancreatic necroses, infected necroses, and intrapancreatic parenchymal necroses plus extrapancreatic fatty tissue necroses are indicators for surgical management. The decision for the timing of operation in patients with proved necrotizing pancreatitis should be based on clinical criteria: the development of an acute surgical abdomen, generalized sepsis, shock, persisting or increasing organ dysfunction, or some combination thereof despite maximum intensive care treatment for at least 3 days. Major pancreatic resection for the treatment of necrotizing pancreatitis appears disadvantageous. Necrosectomy and continuous local lavage allow debridement of devitalized tissue and preservation of vital pancreatic tissue. Postoperative local lavage thus results in an atraumatic evacuation of necrotic tissue, the bacterial material, and biologically active substances. The hospital mortality rate of patients treated with necrosectomy and continuous local lavage (the Ulm protocol) is below 10 per cent. Nevertheless, controlled prospective clinical trials should be performed in order to bring more precision to our clinical decisions in respect to the role of surgery for this disease.
In 128 patients with severe chronic pancreatitis and inflammatory enlargement of the head of the pancreas, a duodenum-preserving resection of the pancreatic head was performed. Median post-operative hospitalization was 15.5 days, and the frequency of reoperation was 5.5%. One patient died during the early post-operative phase, and hospital mortality amounted to 0.8%. After a median follow-up period of 3.6 years (range of 7 months to 16 years), six of 127 patients died (late mortality of 4.7%). Seventy-seven per cent of the patients were completely free of abdominal pain, 67% returned to their former occupations. During the late follow-up period, the glucose metabolism was unchanged in 80.7% of the patients, in 13.7% it deteriorated, and in 5.5% it improved permanently; 80% of the patients experienced a marked increase in weight averaging 8.7 kg. Compared with the Whipple procedure, the duodenum-preserving resection of the head of the pancreas spares the patient with chronic pancreatitis a gastrectomy, duodenectomy, and resection of the extrahepatic biliary ducts. In terms of a subtotal resection, the limited operative intervention at the head of the pancreas and the preservation of the duodenum explain the low early and late postoperative morbidity and mortality.
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