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H G Beger

Publications and source records attributed to H G Beger.

At least 217 records · Page 12Linked to original sources
PubMed1997

Altered expression of insulin-like growth factor II receptor in human pancreatic cancer.

The insulin-like growth factor-II (IGF-II) receptor (IGF-IIR) is a single-chain transmembrane protein identical to the mannose-6-phosphate receptor. In the present study we examined IGF-IIR expression in normal and cancerous human pancreatic tissues. In the normal pancreas, moderately strong IGF-IIR immunoreactivity was present in the cytoplasm of islet cells, and mild cytoplasmic immunoreactivity was evident occasionally in ductal and acinar cells. Some ductal cells also exhibited nuclear IGF-IIR immunoreactivity. In the pancreatic cancers, regions of strong IGF-IIR immunoreactivity were present in the duct-like cancer cells within the tumor mass, often exhibiting nuclear localization. Expression of IGF-IIR mRNA in the cancer cells was confirmed by in situ hybridization. By comparison with normal pancreatic tissues, 7 of 12 pancreatic cancers exhibited a 5.6-fold increase in IGF-IIR mRNA levels, whereas in 3 cancers the IGF-IIR transcript was below the level of detection. Furthermore, all six tested cultured human pancreatic cancer cell lines expressed the IGF-IIR mRNA transcript. Our data indicate that IGF-IIR is overexpressed in a significant number of human pancreatic cancers, where it has a tendency to localize in the nucleus, and raise the possibility that IGF-IIR may contribute to the pathobiology of pancreatic cancer.

Adolescent↗
PubMed1997

Time-scale of interleukin-6, myeloid related proteins (MRP), C reactive protein (CRP), and endotoxin plasma levels during the postoperative acute phase reaction.

During goitre surgery (25 patients) and after major abdominal surgery (52 patients), we studied the plasma levels of endotoxin, interleukin-6 (IL-6), C reactive protein (CRP), and the so called myeloid-related proteins (MRP), MRP8, MRP14, and the heterocomplex of both single proteins, MRP8/MRP14 in three intervals: pre-, intra-, and postoperative. We observed that CRP levels began to increase on the first postoperative day, reaching a maximum on day 2 (median levels of 185 mg/L after major surgery and 77 mg/L after goitre surgery). IL-6 levels peaked at the end of the operation, remaining elevated for 6 h following abdominal surgery (299 pg/mL) and peaked on day 1 after goitre surgery (63 pg/mL). An increase in MRP8/MRP14 levels began toward the end of abdominal surgery, and maximum levels were recorded until 5 days after the operation (5,695 micrograms/L). Plasma levels were significantly elevated 2 and 6 h after minor surgery (3,619 micrograms/L), while no changes were observed in the plasma levels of MRP8 and MRP14. Evidence of significant endotoxemia was found after the induction of anesthesia in the abdominal surgery group (.13 endotoxin units (EU)/mL) and after skin incision (.07 EU/mL) in the thyroid surgery group. The observed time sequence, starting with the release of bacterial products at an early stage, followed by the secondary stimulation of factors inherent to the acute phase led us to conclude that certain bacterial compounds, probably deriving from the gastrointestinal tract, trigger the postoperative acute phase reaction and are responsible for the activation of monocytes/macrophages and granulocytes.

Abdomen↗
PubMed1997

The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis.

BACKGROUND: Infection of pancreatic necrosis has a major impact on clinical course, management, and outcome in acute pancreatitis. Currently, guided fine needle aspiration is the only means for an early and accurate diagnosis of infected necrosis. Procalcitonin (PCT), a 116 amino acid propeptide of calcitonin, and interleukin 8 (IL-8), a strong neutrophil activating cytokine, are markers of severe inflammation and sepsis. AIMS: To analyse the clinical value of PCT and IL-8 as biochemical parameters for predicting infected necrosis in acute pancreatitis. PATIENTS AND METHODS: Fifty patients with acute pancreatitis entered this prospective study and were stratified into three groups according to morphological and bacteriological findings: 18 patients with oedematous pancreatitis (group I), 14 patients with sterile necrosis (group II), and 18 patients who developed infected necrosis a median of 13.5 days after the onset of symptoms (group III). After admission serum samples were drawn daily for two weeks. Concentrations of PCT and IL-8 were measured by chemoluminescent immunoassays (upper reference range 0.5 ng/ml for PCT and 70 pg/ml for IL-8). The routine parameter C-reactive protein was determined by laser nephelometry (upper reference range 10 mg/l). RESULTS: Median concentrations of PCT and IL-8 were significantly higher in patients with infected necrosis than in those with sterile necrosis during the observation period, whereas there was no difference in C-reactive protein. In oedematous pancreatitis overall median concentrations of all three parameters were low. By receiver operating characteristics best cut off levels for predicting infected necrosis or persisting pancreatic sepsis were 1.8 ng/ml for PCT and 112 pg/ml for IL-8. If these cut off levels were reached on at least two days, sensitivity, specificity, and accuracy for the prediction of infected necrosis were 94%, 91%, and 92% for PCT and 72%, 75%, and 74% for IL-8, respectively. After surgical treatment of infected necrosis median PCT and IL-8 values continued to be significantly higher in patients with persisting pancreatic sepsis (n = 11) compared with those having an uneventful postoperative course (n = 7). For the preoperative differentiation between infected necrosis and sterile necrosis guided fine needle aspiration was performed in 24 patients with necrotising pancreatitis and reached a diagnostic accuracy of 84% compared with 87% for PCT, and 68% for IL-8. There was no correlation between the aetiology of acute pancreatitis or the extent of necrosis and PCT or IL-8. CONCLUSION: PCT and IL-8 are found in high concentrations in infected necrosis and associated systemic complications in patients with acute pancreatitis. The course of PCT shows the closest correlation with the presence of infected necrosis. Monitoring of serum PCT is a potential new marker for the non-invasive and accurate prediction of infected necrosis as well as for the selection of patients with persisting septic complications after surgical debridement.

Adolescent↗
PubMed1997

pH-dependent changes of nitric oxide, peroxynitrite, and reactive oxygen species in hepatocellular damage.

Low arterial blood pH and sustained nitric oxide (NO) production are critical parameters in inflammatory events such as sepsis, and appropriate treatment is still under debate. Because the stability of nitrogen and oxygen intermediates is dependent on the surrounding pH, we investigated whether the relationship among NO, peroxynitrite (ONOO-), and reactive oxygen species production also depends on the pH value, particularly with respect to their effects on hepatocellular damage. Our studies demonstrate that the extracellular pH influences NO and hydroxyl radical (OH) production in hepatocytes. Acidification (pH 7.0) of the medium revealed a significant increase (P < 0.05) of OH-like radicals, enhanced hepatocellular damage, and a sharp drop in cellular glutathione (GSH) content compared with levels measured at physiological or alkaline pH conditions. Furthermore, inhibition of NO synthesis at all pH conditions resulted in decreased NO production and cellular GSH levels but a simultaneous increase of OH-like radicals and hepatocellular damage with a maximum seen at pH 7.0. Our results suggest that hepatocellular damage is in part regulated by the surrounding pH and that inhibition of NO synthesis at acidic conditions (e.g., in sepsis) leads to increased reactive oxygen-mediated cell injury.

Animals↗
PubMed1997

Regional celiac artery infusion as adjuvant treatment after pancreatic cancer resection.

BACKGROUND/AIMS: The dismal course of pancreatic adenocarcinoma patients after resection is determined by the biology of the disease preventing R-0 resections. In the spontaneous course after resection, patients frequently develop either local recurrences, liver metastases and/or peritoneal metastases. Postoperative radiochemotherapy may extend survival and reduce local recurrences without influence on hepatic progression. We performed adjuvant celiac artery infusion in pancreatic cancer, to find out whether this treatment prolongs survival and changes the biology of the disease after resection, especially by reducing liver metastasis. METHODS: 20 patients received cyclic celiac artery infusions (CAI) after resection of their pancreatic cancer (18 ductal, 2 cystadenocarcinoma). The treatment consisted of 6 cycles intraarterial infusion using Seldinger's technique with mitoxantrone (Novantron, Wyeth-Lederle, Germany) 10 mg/m2 dl, 5-fluorouracil + folinic acid (Fluroblastin, Farmitalia, Germany + Leucovorin, Wyeth-Lederle) 600 mg/m2 + 170 mg/m2 d2-4, and cis-platinum (Cisplatin, Bristol, München, Germany) 60 mg/m2 d5. The patients were monitored for toxicity, development of disease progression and survival. RESULTS: The median survival time was 21 months, and only 15% of the patients developed liver metastases. The median survival time of the CAI-treated patient group compared favorably to the median survival of 9.3 months in a matched historical control group. CONCLUSION: Adjuvant celiac artery infusion seemed to prolong median survival and the occurrence of liver metastases appeared to be delayed or reduced.

Adenocarcinoma↗
PubMed1997

International documentation system for pancreatic cancer (IDS). The future in pancreatic cancer evaluation.

Different classification systems for pancreatic cancer have evolved in western countries as compared to Japan. While the UICC classification which is focused on tumour size and distant metastasis has achieved widespread acceptance, the more complicated Japanese system seems to be superior in the estimation of local growth. The major drawback of the JPS system, however, is the complex structure and difficult handling. To overcome both the international barriers in classification systems and to achieve a universal prospective data acquisition, a uniform international Documentation System for Exocrine Pancreatic Cancer (IDS for EPC) has been developed by an international group of pancreatologists. The present form of IDS is supported by a software program (based on Microsoft Access) which allows simplified data acquisition and statistical analysis as well as automated stage grouping for the UICC and JPS classifications. From the first contact with the patient, through all diagnostic and therapeutic measures including follow-up, IDS enables a compact and easy-to-use tool for prospective data acquisition and exchange on an international basis.

Documentation↗
PubMed1997

Overexpression of glucose transporter 1 and increased FDG uptake in pancreatic carcinoma.

UNLABELLED: Increased glycolysis is a characteristic metabolic feature of a malignant transformed phenotype. In cultured cells transformed by viruses or activated oncogenes, enhanced glycolytic metabolism is mediated by the overexpression of glucose transporter 1 (Glut-1) and key regulatory glycolytic enzymes. Whether increased glucose metabolism in solid human malignant tumors is related to the overexpression of key regulatory proteins of glucose metabolism is presently unknown. We thus studied the expression of Glut-1 and glucose uptake, assessed with 2-fluorodeoxyglucose (FDG) and PET in human pancreatic carcinoma (PC) and chronic mass-forming pancreatitis (MFP). METHODS: Glucose uptake was measured in the fasting state with FDG and PET in 12 patients with PC and 15 patients with MFP. The standardized uptake value (SUV) of FDG was determined as a global quantitative measure of tissue glucose utilization in cancer tissue or MFP. The expression of Glut-1 and Glut-4 was analyzed from operatively removed cancer or MFP tissue by Northern analysis or semiquantitative reverse transcriptase-polymerase chain reaction. The count ratio of Glut-1 to Glut-4 transcripts was used as an indicator of selective Glut-1 up-regulation. RESULTS: The SUVs of FDG in patients with cancer and MFP were 2.98 +/- 1.23 and 1.25 +/- 0.51 (p < 0.01), respectively. Northern analysis showed intense Glut-1 expression in four of five patients with cancer but not in any of the five patients with MFP that were tested. In PC, Glut-1 and Glut-4 transcripts were found in five of five and three of 10 patients, respectively, using reverse transcriptase-polymerase chain reaction, whereas in MFP, Glut-1 was detected in one of five and Glut-4 was detected in all five patients. The Glut-1-to-Glut-4 transcript ratios were 6.17 +/- 1.27 in patients with cancer and 0.42 +/- 0.12 in patients with MFP. The mean Glut-1 concentration in eight patients with cancer was 1.71 nmol of Glut-1 mRNA/microg of mRNA (range, 0.0446-9.43) and 0.15 (range, 0-1.55) (p < 0.05) in 13 patients with MFP. CONCLUSION: The concomitant enhancement of glucose utilization and selective overexpression of Glut-1 mRNA in pancreatic cancer but not in MFP suggested constitutive activation of Glut-1 gene or decreased degradation of Glut-1 mRNA in human pancreatic cancer. These findings may imply a potential for the early detection of pancreatic cancer with FDG and PET and identify new targets for anticancer therapy.

Adult↗
PubMed1997

[Regionalization of surgical research in Germany].

Surgical research can only be effective if there is good cooperation between clinical and basic researchers. Surgeons should be given the opportunity to practise surgical research as a full-time job for several years. We present part of the data obtained from all surgical departments of German universities concerning the organisation of their surgical research.

Germany↗
PubMed1997

[PET in pancreatic tumor of unknown origin--luxury or value?].

18FDG-positron emission tomography (PET) was performed preoperatively in 159 patients (89 pancreatic cancers, 48 inflammatory pancreatic tumors, 22 benign tumors) with pancreatic mass of unknown origin and its diagnostic value (ROC analysis) was compared with ERCP and computed tomography. In patients with normal fasted blood glucose level (< 130 mg%) and without active inflammation (n = 126), diagnostic value of PET was equal to ERCP (0.94) and higher than CT (0.84; p < 0.02); PET showed in 88% of cases no prediction of resectability or local tumor infiltration, no influence on explorative celiotomies, in 93% no increase of preoperative hospital stay, in 4% influence on surgical strategy, in 5% metastases as additional information. Though its additional information gain for the surgeon remains limited, PET is certainly a diagnostic achievement with high diagnostic value in preselected patients.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1997

[Risk of gastrectomy for stomach carcinoma in relation to reconstruction methods].

Between 1982 and 1996 we performed 452 total gastrectomies due to gastric cancer. 108 patients underwent a pouch reconstruction called Ulm pouch with preservation of the duodenal passage. In 251 patients, the reconstruction was made according to Hunt-Lawrence-Rodino and in 93 patients, a Roux-en-Y reconstruction without pouch was performed. In the Ulm pouch group, the rate of anastomotic leakage as well as the 30-day mortality was 0.8% and its relative risk was 2.6 times lower than in the other reconstruction groups (n = 452) and therefore, this type of reconstruction can be recommended for all curatively resected patients also with regard to morbidity and mortality.

Adult↗
PubMed1997

[Duodenum preserving resection of the head of the pancreas: a new standard operation in chronic pancreatitis].

Between 1972 and 1993, 298 patients with chronic pancreatitis underwent a duodenum-preserving pancreatic head resection (DPPHR). The early and late outcomes were prospectively analyzed. An operative mortality rate of 1%, a postoperative morbidity rate of 28.5% and a relaparotomy rate of 5.7% for the DPPHR were competitive with the rates for Whipple resection. After a median late follow-up of 6 years (range: 1 to 22 years), late mortality was 9%; 88% of the patients had no or infrequent episodes of pain and 63% were completely rehabilitated professionally. Only 6 patients developed diabetes mellitus early postoperatively. Our study proves that the duodenum-preserving pancreatic head resection provides better results than the Whipple resection. Therefore, this operation should be adopted as a new standard operation in patients with chronic pancreatitis.

Adult↗
PubMed1996

Increased angiogenin expression in pancreatic cancer is related to cancer aggressiveness.

We have investigated the expression of angiogenin (ANG) in pancreatic cancer and the relevance of ANG expression to the progression of pancreatic cancer. In comparison to normal pancreas, increased ANG mRNA expression was observed in 80.0% of the cases of pancreatic cancer by in situ hybridization, and increased ANG protein expression was observed in 86.7% of the cases of pancreatic cancer using Western blot analysis. The mean serum ANG concentration of pancreatic cancer patients (566.6 +/- 191.9 ng/ml) was significantly higher (P < 2.0 x 10(-8)) than that of healthy volunteers (359.0 +/-t 59.9 ng/ml). Increased ANG mRNA expression as well as elevated serum ANG concentration correlated with poor prognosis. These findings suggest that ANG expression is up-regulated in pancreatic cancer patients and that ANG contributes to the aggressiveness of pancreatic cancer.

Adult↗
PubMed1996

Increased expression of insulin receptor substrate-1 in human pancreatic cancer.

Insulin receptor substrate-1 (IRS-1) is a multisite docking protein implicated in mitogenic signaling following activation of the insulin and insulin-like growth factor I receptors. In the present study we characterized IRS-1 expression in human pancreatic cancer. Northern blot analysis revealed high levels of IRS-1 mRNA transcripts in ASPC-1 and MIA PaCa-2 human pancreatic cancer cell lines, and lower levels in COLO-357, PANC-1, and T3M4 cells. Immunoblotting with anti-IRS-1 antibodies indicated that IRS-1 protein levels paralleled IRS-1 mRNA levels. Analysis of RNA isolated from normal and cancerous human pancreatic tissues indicated that 7 of 16 pancreatic cancer samples overexpressed IRS-1 mRNA transcripts by comparison with the normal pancreas and that insulin mRNA levels were abundant in many tumors. These data suggest that IRS-1 contributes to the signaling pathways that lead to excessive growth stimulation in human pancreatic cancer.

Blotting, Northern↗
PubMed1996

[Multicentric gastric carcinoid in autoimmune gastritis].

HISTORY AND FINDINGS: A now 54-year-old woman was 32 years ago found to have immune thrombocytopenia and 3 years ago ANA-positive and HBsAg-negative hepatitis with cirrhotic metaplasia. Numerous small asymptomatic carcinoids with marked hypergastrinaemia (1626 ng/l) were also first found 3 years ago. No gastrinoma could be found. Severe arthralgia was the main symptom on admission. INVESTIGATIONS: Gastroscopy revealed a polypoid carcinoid, 1 cm in diameter. There was total achlorhydria. No pernicious anaemia or carcinoid syndrome was found. TREATMENT AND COURSE: Total gastrectomy with construction of a jejunal substitute stomach was performed. Histology showed typical chronic-atrophic gastritis type A, all stages of an argyrophilic endocrine cell hyperplasia, as well as microcarcinoidosis and multicentric carcinoid, in part with submucosal infiltration and lymph node metastases. Immunohistology revealed immune reaction for the global endocrine marker. No specific hormones were demonstrable in the carcinoid cells. The postoperative course was without complications. Serum gastrin levels have since been normal. CONCLUSIONS: The case confirms the possibility of an achlorhydria-hypergastrinaemia-carcinoid sequence. Now new stage-related therapeutic guidelines for this disease are needed.

Achlorhydria↗
PubMed1996

Evaluation of endotoxiuria for diagnosis of urinary tract infection after major surgical procedures.

In 148 patients after major surgical procedures urinary endotoxin levels were determined and compared with bacteriological results. The study was designed as a screening study. Urine samples were collected once by suprapubic or transurethral catheters. In a first series of 49 patients urine bacteriology was positive (mainly, Gram-negative rods were found) in 3 cases. However, endotoxin determination was positive in these 3 patients and in a further 10 patients receiving antibiotic therapy for other reasons. Therefore, the following 99 patients were studied also by urinalysis by reagent strips for leukocytes and nitrite. In the second series, 12 urine cultures positive for bacteria were observed. Eleven samples were also endotoxin positive. Five more patients were endotoxin positive and had pathological but unspecific reagent strip results. These patients were treated with antibiotics for other reasons. Patients with candida found in the urine culture (n = 5) were endotoxin negative. Thus, endotoxin determination in urine obtained by suprapubic or transurethral catheters proved to be a very sensitive method for diagnosis of bacterial contamination, even during antibiotic treatment.

Adult↗
PubMed1996

Effects of hepatocellular mitogens on cytokine-induced nitric oxide synthesis in human hepatocytes.

The synthesis of induced nitric oxide (NO) is regulated by several cytokines, including growth factors produced following hepatic injury and inflammation. However, little information is available on the role of growth factors in regulating the inducible NO synthase in human hepatocytes. The capacity of hepatocellular mitogens (HGF, EGF, and TGF-alpha) to regulate the inducible NO synthase (iNOS) was studied in human hepatocytes incubated with inflammatory cytokines and lipopolysaccharide (LPS). Furthermore, the effects of hepatic mitogens on NO-induced changes in DNA and protein synthesis was studied. It was found that NO-mediated decrease of protein and DNA synthesis were partially reversed by the mitogens. This was associated with a down-regulation in cytokine-mediated hepatocyte NO formation, iNOS mRNA expression, and NOS enzyme activity. Cytokine-induced NO formation or SNAP, an NO donor, added with cytokines increased hepatocyte chromatin condensation but no DNA fragmentation was observed. The increase in chromatin condensation was partially reversed by hepatic mitogens and corresponded with the inhibition of NO production. Thus, the hepatic mitogens, HGF, EGF, and TGF-alpha, all suppress iNOS expression and it is the suppression of iNOS that appears to be responsible for the mitogen-reduced preservation of DNA and protein synthesis and prevention of chromatin condensation.

Cells, Cultured↗