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Biomedical subjects

H G Beger

Publications and source records attributed to H G Beger.

At least 19 recordsLinked to original sources

Human pancreatic tissue concentration of bactericidal antibiotics.

Pancreatic infection represents the most important cause of fatal outcome in human acute pancreatitis. In a comparative analysis, human pancreatic tissue concentrations of 10 different bactericidal antibiotics were determined in 89 patients undergoing pancreatic surgery. Concentrations of the antibiotics were determined in the blood and pancreatic tissue using high-pressure liquid chromatography. Pancreatic tissue concentrations 120 minutes after intravenous administration were as follows: mezlocillin, 19.0 mg/kg; piperacillin, 20.3 mg/kg; cefotaxime, 9.1 mg/kg; ceftizoxime, 7.9 mg/kg; netilmicin, 0.4 mg/kg; tobramycin, 0.4 mg/kg; ofloxacin, 1.7 mg/kg; ciprofloxacin, 0.9 mg/kg; imipenem, 6.0 mg/kg; metronidazole, 3.5 mg/kg. Three groups of antibiotics were established: group A, substances with low tissue concentrations (netilmicin, tobramycin), which were below the minimal inhibitory concentrations of most bacteria found in pancreatic infection; group B, antibiotics with pancreatic tissue concentrations which were sufficient to inhibit some but not all bacteria in pancreatic infection (mezlocillin, piperacillin, ceftizoxime, cefotaxime); group C, substances with high pancreatic tissue levels as well as high bactericidal activity against most of the germs present in pancreatic infection (ciprofloxacin, ofloxacin, imipenem). These data could serve as the basis for adequate antibiotic prophylaxis or treatment of pancreatic infection.

Adult

The role of oxygen radicals in experimental acute pancreatitis.

Oxygen-derived free radicals mediate an important step in the initiation of experimental acute pancreatitis. Thereby, it seems that these reactive oxygen metabolites are generated at an early stage of disease. The source of the enhanced production of oxygen radicals still remains unclear. Experimentally, the efficiency of scavenger treatment varied between different models, whereby these differences depended on the experimental model and not on the form of pancreatitis which was induced. Most studies pretreated the experimental animals before inducing acute pancreatitis. This does not mirror the clinical reality, since patients are admitted to the hospital after onset of the disease. It was shown in Cerulein pancreatitis, however, that scavenger treatment also mitigated the pancreatic tissue damages after induction of acute pancreatitis. Moreover, antioxidant treatment also attenuated the extrapancreatic complications, thus improving the final outcome of the disease. The first indirect observations also suggest that in human acute recurrent and chronic pancreatitis, oxygen free radicals are generated and add to the damages seen. Therefore, well-defined controlled clinical studies with patients suffering from acute pancreatitis are needed to validate the role of oxygen radicals in this disease.

Acute Disease

Changes in peptidergic innervation in chronic pancreatitis.

We sought to identify characteristics of peptidergic innervation that altered in patients with chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed by immunohistochemistry using antisera against neuropeptide Y, tyrosine hydroxylase, vasoactive intestinal polypeptide, peptide histidine isoleucine, calcitonin gene-related peptide, and substance P, respectively. In accordance with recent findings, the number and diameter of intralobular and interlobular nerve bundles were found to be increased as compared with control pancreas from organ donors. The striking change in the peptidergic innervation pattern in chronic pancreatitis concerned these altered nerves. It consisted of an intensification of the immunostaining for calcitonin gene-related peptide and substance P in numerous fibers contained in these nerves. Adjacent sections showed that immunoreactive substance P and immunoreactive calcitonin gene-related peptide coexisted in these fibers. Because both of these peptides are generally regarded as pain transmitter candidates, our findings provide further evidence that changes in pancreatic nerves themselves might be responsible for the long-lasting pain syndrome in chronic pancreatitis.

Adult

Treatment of duct carcinoma of the pancreas with the LH-RH analogue buserelin.

Thirty-six patients (21 male, 15 female) with ductal pancreatic cancer were treated with the long-acting synthetic luteinizing hormone releasing hormone (LH-RH) analogue buserelin. All patients had advanced tumor stages (stage II: 7 patients; stage III: 11 patients; stage IV: 18 patients). A monthly follow-up including clinical status, computed tomography scan, or ultrasonography and the tumor markers carcinoembryonic antigen (CEA) and H carbohydrate antigen 19-9 (CA19-9) was carried out. There were no severe side effects apart from impotency in men and hot flashes and outbreaks of perspiration in three patients. No partial or complete remission was seen. Twenty-six patients showed tumor progression with a median survival time of 4 months (range 0.5-11 months). In 10 patients a "no change" evaluation with a median survival time of 10 months (range 8-17 months) was registered. In only two of these patients there was no increase in the serum tumor markers CA19-9 and CEA during this time. In conclusion, LH-RH analogue treatment cannot be recommended in this selected group of patients suffering from advanced tumor stages of pancreatic cancer.

Adult

Role of oxygen radicals in experimental acute pancreatitis.

A growing body of evidence suggests that oxygen radicals are generated in all forms of experimental pancreatitis at an early stage of disease. Moreover, first indirect observations assume that also in human acute recurrent and chronic pancreatitis oxygen free radicals are generated and add to the damages seen. The source of the enhanced production of oxygen radicals remains still unclear. Experimentally, the efficiency of scavenger treatment varies between three different models, whereby these differences depend more on the design of the experimental models than on the form of pancreatitis which was induced. Antioxidant treatment with radical scavengers should therefore interrupt these deleterious pathomechanisms or at least mitigate the damages normally seen. Most studies, however, pretreated the experimental animals before inducing acute pancreatitis, which does not mirror the clinical reality. Patients, however, are admitted after onset of the disease. Therefore, well-defined, controlled clinical studies are needed to validate the involvement of oxygen radicals in acute and chronic pancreatitis and the effect of scavenger treatment in patients with pancreatitis.

Acute Disease

Clinical relevance of experimental acute pancreatitis.

There are several well-standardized models of experimental acute pancreatitis such as the closed duodenal loop technique, cholecystokinin or cerulein stimulation, duct injection and diet-induced acute experimental pancreatitis. With regard to human acute pancreatitis, experimental models in animals have a considerable high clinical relevance if the subject of investigation concerns pathogenetic, morphological and diagnostic approaches to the disease; as regards the treatment modalities and causative therapy of acute pancreatitis, experimental models in animals up to now seem to be far away from the clinical situation and therefore these protocols have low clinical relevance. The reasons for this discrepancy are outlined in this paper.

Acute Disease

Acute pancreatitis: when and how to operate.

Patients with proved necrotizing pancreatitis should be treated in an intensive care unit. Surgical management of necrotizing pancreatitis is indicated if an acute abdomen or persistent or increasing signs of organ complications develop, such as pulmonary or renal insufficiency, cardiocirculatory dysfunction or metabolic disorders, and these do not respond to maximum intensive care treatment over at least 72 h. Besides these so-called non-responders to ICU treatment, operative management is clearly indicated in patients who develop signs of sepsis on the basis of a bacteriologically positive fine-needle aspiration of pancreatic necroses. In patients with minor necroses without any bacterial contamination and without extensive retroperitoneal fatty tissue necroses intensive care therapy can be successful without the necessity of a surgical intervention. The gold standard of surgical management of necrotizing pancreatitis is careful removal of necrotic tissue, drainage of bacterially infected area, elimination of the pancreatogenic ascites in order to prevent systemic spread of vasoactive and toxic substances and interruption of the inflammatory process. For the treatment of pancreatic necrosis we strongly support surgical debridement (necrosectomy), supplemented by postoperative closed continuous lavage of the lesser sac and the adjacent necrotic cavities. In 152 patients suffering from severe necrotizing pancreatitis the hospital mortality was 12.5% (19/152) by this surgical approach.

Acute Disease

Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha.

The epidermal growth factor (EGF) receptor is activated by both EGF and transforming growth factor-alpha (TGF-alpha). Using immunohistochemical and immunoblotting techniques we now report that the EGF receptor, EGF, and TGF-alpha are found in both pancreatic acini and ducts in the normal human pancreas, and that all three proteins are expressed at higher levels in human pancreatic cancer tissues. Using in situ hybridization techniques, we also report that the mRNA encoding the EGF receptor, EGF, and TGF-alpha colocalize with their respective proteins. Northern blot analysis of total RNA indicates that, by comparison with the normal pancreas, the pancreatic tumors exhibit a 3-, 15-, and 10-fold increase in the mRNA levels encoding the EGF receptor, EGF, and TGF-alpha, respectively. Furthermore, by in situ hybridization, there is a marked increase in these mRNA moieties within the tumor mass. These findings suggest that EGF and TGF-alpha may participate in the regulation of normal pancreatic exocrine function, and that overexpression of the EGF receptor and its two principal ligands may contribute to the pathophysiological processes that occur in human pancreatic cancer.

Adult

[The effect of duodenum-preserving pancreatic head resection on the endocrine pancreas function in patients with chronic head pancreatitis].

In a prospective clinical-experimental study, 15 patients with chronic pancreatitis operated consecutively due to severe pain were examined for the effects of a duodenum-preserving resection of the pancreas head on endocrine pancreas function. This was done by means of oral and intravenous glucose tolerance testing before the operation, on the 10th or 11th postoperative day, and three months after the operation. In addition to glucose levels in the peripheral venous blood, levels of insulin, C-peptide, glucagon, somatostatin, and pancreatic polypeptide were determined. As indicated by the k-value, glucose tolerance improved postoperatively in 11 patients; two patients showed no change, and one patient was worse. Only one patient developed evident diabetes mellitus immediately postoperatively. The pre- and postoperative levels of insulin and C-peptide showed no significant differences. The fasting levels of glucagon were significantly lower postoperatively than before the operation (2p less than 0.01). Duodenum-preserving pancreas head resection led to improvement of the glucose tolerance in the majority of patients; a deterioration was observed only in two cases.

Adult

[Cryotherapy in rectal cancer. A palliative local tumor treatment].

Cryotherapy was applied to 182 rectal cancer patients in the Department of General Surgery, University of Ulm, between 4/1982 and 4/1991. Recipients of this tumor freezing therapy were patients whose general condition was bad, patients with an advanced inoperable carcinoma, patients with tumor recurrence and patients refusing operation. Rectal carcinomas, mostly in an advanced stage, were usually freezed several times. Only 4 patients with general inoperability reached the survival time margin of 5 years. In 18 patients local tumor destruction was possible by application of cryotherapy. In 80% of cases disagreeable tumor symptoms like tenesma, mucous discharge and oozing hemorrhages could be reduced or completely removed. Perianal pain and intense tumor bleeding could be relieved temporarily or definitely in only 50% of patients. An artificial anus could be avoided in 80% of cases by local tumor destruction/reduction or arrest of tumor growth. The mean survival time of patients with tumor recidivation was 11 months after onset of the recurrence. Tumor progression, incontinence and iatrogenic rectal perforation made an artificial anus necessary in 14 patients.

Aged

[Oxygen radicals and acute pancreatitis].

Oxygen-derived free radicals mediate an important step in the initiation of experimental acute pancreatitis. Thereby these reactive oxygen metabolites are generated at an early stage of disease. The source of the enhanced production of oxygen radicals remains unclear. Experimentally, the efficiency of scavenger treatment varied between different models, whereby these differences were depending on the experimental model and not on the form of pancreatitis which was induced. Most studies pretreated the experimental animals before inducing acute pancreatitis. This does not mirror the clinical reality, since patients are admitted to the hospital after onset of the disease. It was shown in Cerulein-pancreatitis, however, that scavenger treatment also mitigated the pancreatic tissue damages after induction of acute pancreatitis. Moreover, antioxidant treatment also attenuated the extrapancreatic complications, thus improving the final outcome of the disease. The first indirect observations also suggest that in human acute recurrent and chronic pancreatitis oxygen free radicals are generated and add to the damages seen. Therefore, well-defined controlled clinical studies with patients suffering from acute pancreatitis are needed to validate the role of oxygen radicals in this disease.

Acute Disease

[Surgical therapy of acute cholecystitis--advantages of early operation].

229 patients with an acute cholecystitis were operated on at the Surgical University Hospital of Ulm between 3/1982 and 6/1990. 42.3% of the patients were older than 70 years, the mean age being 64.3 years. 51.5% suffered from a complicated form of the disease. Intercurrent diseases were preoperatively found in 76%. Intraoperative complications of a technical nature occurred in 3.1%. The overall postoperative morbidity rate was 54%, with 9.4% of local problems, and showed a clear dependency on age and the number of preexisting risk factors. 31% had to undergo reoperation. The overall mortality rate was 2.6%, with a 0% mortality for patients under 65 years. The number of preexisting risk factors clearly correlated the period of hospitalisation, which was 16.1 days on average. In symptomatic gallstone diseases an early elective cholecystectomy should be strongly considered, especially in aged and multimorbid patients.

Acute Disease

[Surgical therapy of acute pancreatitis].

In patients with proven acute pancreatitis which is not necrotizing conservative therapy leads to a rapid pain release; after sanitation of the basic disease, complete healing is achieved. In case of a biliary pancreatitis with incarcerated gallstones in the papilla an EPT with removal of the choledochal stones is carried out within the first 12 hours after onset of incarceration symptoms; after disappearance of the symptoms of acute pancreatitis an endoscopic or minilap.-cholecystectomy is performed. Conservative therapy leads to a complete cure in patients with minor necroses without any bacterial contamination and without extensive retroperitoneal fatty tissue necroses. Surgery is indicated if a surgical acute abdomen or a sepsis develops, if patients do not respond to maximum intensive care treatment over at least 72 hours, or if organ complications, such as pulmonary/renal insufficiency, cardiocirculatory dysfunction/shock and metabolic disorders grow worse under ICU treatment. The choice procedure against bacterially contaminated necrosis is their careful removal by necrosectomy or débridement. Resectional techniques should be avoided. A third of patients needs reoperation because of extensive inflammatory processes in the retroperitoneum and around the pancreas. Treatment centres report a hospital mortality rate of clearly below 20%.

Acute Disease

[Laparoscopic cholecystectomy versus mini-lap-cholecystectomy. Results of a prospective, randomized study].

Laparoscopic cholecystectomy (LCCE) was gaining acceptance rapidly, when several institutions could demonstrate the safety of this minimal invasive treatment modality. Nevertheless prospective randomised studies still are missing to prove the advantages of this new treatment modality in contrast to open cholecystectomy. 77 patients with symptomatic cholelithiasis were treated by LCCE (n = 40) or mini-lap CCE (n = 37) in a prospective, randomised study. As preliminary results, there were no differences in duration of anesthesia and operation time, perioperative complications or postoperative need for analgetics. Patients with LCCE had significant less postoperative pain, less restriction of total vital capacity and a shorter postoperative hospital stay as parameters of a diminished operative trauma.

Cholecystectomy

[What is confirmed in chemo- and immunotherapy of solid tumors. Standard protocols, studies and new developments].

Reviewing the treatment perspectives with chemo- and immunotherapy in carcinomas and sarcomas to be treated by general or orthopedic surgeons, the following indications are regarded as recommendable: Adjuvant chemotherapy in breast cancer, neoadjuvant chemotherapy with radiation in anal carcinoma and neoadjuvant/adjuvant chemotherapy of high-grade malignant osteosarcoma. Isolation perfusion currently is the treatment of choice in melanoma metastasis limited to an extremity. With several indications, recent developments have produced promising results that should be urgently confirmed in appropriate studies. Therefore the following studies have a high priority: Neoadjuvant chemotherapy in esophageal carcinoma and in locally advanced breast and stomach cancer, adjuvant chemoimmunotherapy in colon carcinoma UICC III and chemoradiation in rectal carcinoma UICC II and III, systemic chemotherapy of metastasized stomach-, colorectal-, breast cancer and sarcomas. Isolated non-resectable liver metastases of colorectal origin and hepatocellular carcinoma should be included in studies evaluating the treatment advantage of regional chemotherapy. Those malignant "surgical" tumors not listed above should receive chemotherapy within experimental studies, after consideration of individual risk factors, or no chemotherapy. Immunotherapy with its various modalities is still in the experimental stage.

Antineoplastic Agents

The involvement of oxygen radicals in acute pancreatitis.

The purpose of this study was to assess the involvement of oxygen radicals in acute edematous and hemorrhagic pancreatitis. Acute pancreatitis was induced in rats by the CCK-analogue cerulein (5 micrograms/kg/h) and by retrograde injection of 5% sodium taurocholate for 30 min, 3.5 h, and 12 h. At the end of the infusion and observation time, serum enzymes, conjugated dienes, and malondialdehyde in the tissue were measured. Moreover, the tissue samples underwent light microscopical examination. In cerulein pancreatitis, an interstitial edema and intravascular margination of granulocytes in the pancreatic gland were observed after 3.5 h. After 12 h, the histological evaluation revealed a pronounced zymogen degranulation, extensive tissue necrosis and migration of granulocytes into the tissue. Parallelly, amylase and lipase increased by 15 and 35 times, respectively. In contrast, conjugated dienes and malondialdehyde increased in cerulein pancreatitis and reached their highest level after 3.5 h and decreased to normal levels after 12 h. The development of the histological damages and serum enzyme levels with sodium taurocholate pancreatitis was similar as compared to the cerulein pancreatitis, however, the development was faster and more traumatic. Already after 3.5 h an extensive zymogen degranulation and cell necrosis was observed. Concomitantly, the amylase and lipase levels increased by 90 and 30 times, respectively. Treatment with superoxide dismutase (100,000 U/kg/h) and catalase (400,000 U/kg/h) prevented lipid peroxidation and reduced zymogen degranulation and tissue necrosis. Tissue edema and inflammatory response were not affected in both models of acute pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease