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Biomedical subjects

H G Beger

Publications and source records attributed to H G Beger.

At least 253 records · Page 14Linked to original sources

Inhibition of nitric oxide synthesis does not improve interleukin-2-mediated antitumor effects in vivo.

Nitric oxide (NO) decreases cytotoxicity and proliferation of cytotoxic lymphocytes (CTLs) in vitro. Both can be prevented by inhibitors of the NO synthase (NOS). To elucidate whether inhibition of the IL-2-induced NOS could boost efficacy of IL-2-stimulated CTLs in vivo, we assessed lung metastases in mice injected with IL-2, the NOS inhibitor aminoguanidine (AG), their combination and the diluent. No improvement was observed for IL-2 + AG compared to IL-2 while NO production was normalized. Since NO causes one of the two major side effects of IL-2 treatment, hypotension, we further studied whether capillary leak could be attributed to NO, too. While IL-2-inducible NO was reduced to control levels by AG, pulmonary edema was unaffected. Thus a decrease in NO does not improve antitumor effects of IL-2-stimulated CTLs nor does it attenuate IL-2-associated capillary leak.

Animals↗

[Adjuvant regional chemotherapy in resected advanced pancreas carcinoma].

Systemic chemotherapy in patients who underwent resection of pancreatic carcinoma has not been significantly improved median survival times. We investigated whether regional chemotherapy administered via celiac trunc infusion increases survival rates in patients with locally advanced pancreatic carcinoma after resection of the primary. From 12/1992 to 2/1995 we treated 18 patients with regional chemotherapy consisting of mitoxantrone (d1), 5-FU + folinic acid (d2-4) and CDDP (d5) on five consecutive days. This cycle was repeated up to 6 times. Besides non-symptomatic GI-ulcerations (3/18) no severe side effects were observed. The median survival is actually 17.8 months (regression analysis). Compared to a historical control of our department survival times are significantly prolonged (17.8 vs. 9.3 months, p < 0,0003). In conclusion we state that adjuvant regional chemotherapy in patients with advanced pancreatic cancer is well tolerated and prolongs survival significantly.

Aged↗

[Pancreatic carcinoma in chronic pancreatitis with inflammatory tumor of the head of the pancreas].

Whether chronic pancreatitis is a risk factor for the development of pancreatic cancer is still under discussion. 395 patients operated for chronic pancreatitis with enlargement of the head of the pancreas between 1982 and 1994 were evaluated retrospectively. The frequency of pancreatic cancer in pre-existing chronic pancreatitis was 3.8% (n = 15). This frequency was significantly elevated in comparison to the estimated cancer frequency of the normal population (p < 0.001). The time interval between first diagnosis of chronic pancreatitis and diagnosis of pancreatic carcinoma was 33.3 month in the mean. 474 patients with pancreatic carcinoma without pre-existing chronic pancreatitis were operated in the same period. Histological examination revealed signs of chronic obstructive pancreatitis due to tumor obstruction of the main pancreatic duct in 11.1% (n = 53). The relative risk of patients suffering primarily from chronic pancreatitis to develop pancreatic carcinoma is elevated by a factor of more than 50 in comparison to normal population.

Adult↗

The risk of pancreaticointestinal anastomosis can be predicted preoperatively.

The risk of developing postoperative complications following pancreatic resection depends mainly on how difficult it is to perform a proper pancreaticointestinal anastomosis. We have evaluated the serum pancreolauryl test, a rapid tubeless pancreatic function test, as a simple preoperative predictor of the degree of pancreatic fibrosis. Degree of fibrosis in turn provides an indirect parameter for the difficulties of performing a proper and safe pancreaticointestinal anastomosis. In 35 patients (21 chronic pancreatitis, 14 pancreatic tumors) undergoing major pancreatic resection, we found a negative correlation (r = -0.75, p < 0.001) between the degree of fibrosis at the resection margin and the serum pancreolauryl test results. Patients with chronic pancreatitis had a significantly higher degree of fibrosis at the resection margin (59 +/- 22 vs. 34 +/- 25%; X +/- SD; p < 0.01) and lower fluorescein serum concentrations (2.6 +/- 1.9 vs. 4.3 +/- 2.1 micrograms/ml; X +/- SD; p < 0.01) in comparison with patients with pancreatic tumors. These findings indicate that the degree of pancreatic fibrosis, the difficulties of performing a proper pancreaticointestinal anastomosis, and subsequently the potential risk of postoperative complications can easily be predicted preoperatively.

Adult↗

Plasma concentrations of endotoxin and antiendotoxin antibodies in patients with multiple injuries: a prospective clinical study.

OBJECTIVE: To investigate the time course of endotoxaemia and its effects on the synthesis of antiendotoxin antibodies in patients with multiple injuries. DESIGN: Prospective clinical study. SETTING: University hospital, Germany. PATIENTS: 40 Patients with multiple injuries and 20 healthy volunteers who served as controls. INTERVENTIONS: Blood samples were collected up to 10 days after injury and the concentrations of endotoxin, antiendotoxin antibodies to four endotoxins, and for anti-alpha-haemolysin of Staphylococcus aureus were measured. The kinetics of endotoxaemia and antiendotoxin antibodies were investigated. RESULTS: Endotoxaemia peaked 0-3 hours after injury at 0.425 EU/ml and decreased thereafter to 0.04 EU/ml within five days. Total concentrations of IgM, IgA, and IgG increased continuously after day 3 (p < 0.05), but the specific IgM response to all endotoxins was only temporary and the relative content of specific antibodies to all endotoxins peaked at day 3 (p < 0.05). Antiendotoxin antibodies of IgM class cross-reacted among themselves. There was no general increase in specific antiendotoxin antibodies of IgA and IgG class. The relative content of specific antibodies to alpha-haemolysin of S aureus of all classes of immunoglobulins (IgM, IgA, IgG) remained on the same level from day 0-10. CONCLUSION: Multiple injuries are associated with early and temporary endotoxaemia which causes specific increases in antiendotoxin antibodies of the IgM-class. IgM antibodies to endotoxins cross-react among themselves.

Adolescent↗

[Duodenum preserving pancreatic head resection in chronic pancreatitis with inflammatory tumor in the pancreas head].

15 to 30% of the patients with chronic pancreatitis develop an inflammatory mass in the pancreatic head. The leading symptoms of these patients are severe upper abdominal pain and complications of the surrounding organs. From 1969 to 1995, 380 patients were treated with a duodenumpreserving pancreatic head resection. The cause of the disease was alcohol abuse in 81%. 93% of the patients suffered from severe pain with recurrent pain attacks. CT-scan revealed enlargement of the pancreatic head (> 4 cm in diameter) in 79% of the patients. 83% of the patients had an impaired exocrine pancreatic function; 48% of the patients had an impaired glucose tolerance or were diabetic. The hospital mortality was 0.8%; 5% of all patients had to be reoperated. The mean duration of the hospitalization was 13.9 days. 89% of the patients showed an unchanged endocrine function in the early postoperative course. The glucose metabolism was improved in 9%, 2% had a deteriorated function. The duodenum-preserving pancreatic head resection is a procedure with a low postoperative mortality and morbidity without deterioration of the endocrine pancreatic function.

Adolescent↗

[Cattell-Warren anastomosis in soft pancreatic remnant after q pancreas resection].

The high morbidity and mortality after resection of the pancreas are mostly due to pancreas anastomosis. Cattell-Warren anastomosis is a technique of pancreaticojejunostomy with low complications. Cattell-Warren anastomosis, combined with octreotide therapy, is a safe method to decrease the morbidity after resection of the pancreas.

Anastomosis, Surgical↗

[Indications for total parenteral nutrition or small intestine transplantation?--Prognostic factors in short bowel syndrome].

After massive intestinal resection resulting in short bowel syndrome it is often unclear if the patient will remain on total parenteral nutrition (TPN) or regain enteral autonomy. Small bowel transplantation or bowel-lengthening procedures could potentially be a therapeutic option for patients confined to life-long parenteral nutrition. Initiated early in the course of the disease this could prevent frequent serious complications of long-term parenteral nutrition. However, it is unclear which factors determine the outcome of these patients. For further information on the long-term prognosis, data of 33 patients with short bowel syndrome operated in our institution from 1982 to 1995 were retrospectively analyzed and the present status of all living patients evaluated. Gender, age or underlying disease had no influence on the adaptation of the small intestine or the duration of TPN in the surviving patients. Return to enteral autonomy mainly depended upon the length of the remaining small and large bowel. Thus the further course of the disease can be predicted and necessary measures can be taken as this information is always available at the time of initial surgery.

Adult↗

Regional chemotherapy directed by individual chemosensitivity testing in vitro: a prospective decision-aiding trial.

A prospective decision-aiding trial was performed to select drugs for regional chemotherapy of various liver tumors (n = 36) by individual drug testing. The drugs were chosen for hepatic artery infusion according to the individual chemosensitivity of tumor biopsies in the human tumor colony-forming assay (HTCA). In vitro HTCA sensitivity correlated with complete response (CR) + partial response (PR) + no change (NC) 93% of the time and with CR + PR 55% of the time. The test sensitivity was 90%, and the specificity was 67% for CR + PR + NC versus progressive disease (PD), whereas the sensitivity and specificity were 89% and 28%, respectively, for CR + PR versus NC + PD. The overall predictive accuracy of the test was 86% for CR + PR + NC versus PD and 58% for CR + PR versus NC + PD. Overall, 83% of this heterogenous patient group with various tumors achieved CR + PR + NC and a 50% clinical response (CR + PR). In vitro-sensitive patients showed a significantly lower intrahepatic progression rate (7% PD) than in vitro-resistant patients (57%; P < 0.05). These results indicate that the HTCA could identify active drugs for individualized hepatic artery infusion, and patients may profit from the use of in vitro-sensitive drugs.

Adult↗

Differential expression of CD44 splice variants in human pancreatic adenocarcinoma and in normal pancreas.

Immunohistochemical screening of pancreatic adenocarcinomas from 24 different patients and 9 pancreatic carcinoma cell lines revealed variant CD44 expression in all specimens tested. In contrast to normal pancreatic tissue, carcinomas were strongly positive for epitopes encoded by variant exons v5, whereas v6 was expressed on carcinoma cells as well as normal ductal pancreatic cells. Analysis of RNA expression revealed clear differences between normal pancreatic tissue and tumor specimens. In normal pancreas, v6 and v3 solely and one major chain consisting of v6-v10 were expressed, whereas in pancreatic carcinoma, multiple splice variants were detected. In about 80% of all carcinoma cases and all cell lines tested, the exon v5 appeared in the chain containing at least v4-v10. These data thus far suggest that not the presence alone but the chain composition of the CD44 variant chains could be important for their altered function because one of the major differences between normal and cancer tissue is the linkage of CD44v5 to the CD44v6-containing chain.

Adenocarcinoma↗

[Regional chemotherapy in advanced pancreatic carcinoma].

BACKGROUND: Even after resection median survival times in advanced pancreatic carcinoma are seldom more than one year. The aim of our study was to evaluate the effectivity of regional chemotherapy in patients suffering from unresectable pancreatic cancer. PATIENTS AND METHODS: From 2/92 until 11/94 32 patients with unresectable pancreatic cancer (17 patients stage III, 15 patients stage IV) were treated by celiac trunc infusion. One cycle consisted of mitoxantrone (d 1), 5-FU, folinic acid (d 2 to 4) and cisplatinum (d 5). RESULTS: Besides a few severe complications, therapy was well tolerated in 101 cycles. In unresected patients with stage III tumors the median survival is 12 months compared to 4.8 months in patients with biliodigestive bypasses (p < 0.006) and 4 months in regionally infused patients stage IV compared to 2.7 months in untreated patients (n.s.). CONCLUSION: Regional chemotherapy in advanced pancreatic carcinoma is well tolerated and increases median survival in patients with stage III tumors.

Adenocarcinoma↗

New aspects concerning the regulation of the post-operative acute phase reaction during cardiac surgery.

During a cardio-pulmonary bypass, as well as post-operatively, high levels of endotoxin, interleukin-6 (Il-6) and C-reactive protein (CRP) were measured in 30 patients. A significant increase in endotoxin plasma level occurred during surgery, culminating in a peak during reperfusion. Plasma levels of endotoxin continued to be slightly raised until the fifth day after surgery, whereas those of Il-6 rose at the time the operation came to an end and were at their highest 6 h later. CRP levels were also high, post-operatively, and were markedly raised on day 2. A definite, statistically significant correlation between the plasma levels of endotoxin and Il-6 during the operation was established, leading us to conclude that the endotoxin liberated during cardiac surgery acts as the main trigger in the release of Il-6 and thus induces the post-operative acute phase reaction. There was no evidence of a correlation between CRP and endotoxin or Il-6 plasma levels.

Acute-Phase Reaction↗

Insulin-like growth factor I overexpression in human pancreatic cancer: evidence for autocrine and paracrine roles.

We assessed the potential roles of insulin-like growth factor-I (IGF-I) and the IGF-I receptor (IGF-IR) in human pancreatic cancer. IGF-I enhanced the growth of ASPC-1 and COLO-357 human pancreatic cancer cells, and this effect was significantly inhibited by a highly specific monoclonal anti-IGF-IR antibody (alpha IR3). Both cell lines expressed mRNA transcripts for IGF-IR, and basal cell growth was significantly reduced by an IGF-IR antisense oligodeoxynucleotide. IGF-I mRNA transcripts were not detected in either cell line or in two additional pancreatic cancer cell lines. In contrast, analysis of 12 pancreatic cancers revealed a 32-fold increase (P < 0.01) in IGF-I mRNA levels by comparison with the low levels observed in the normal pancreas. By in situ hybridization, IGF-I mRNA grains were present in both the cancer cells and in the surrounding connective tissue. Six of the cancers exhibited a 4.4-fold increase in IGF-IR mRNA levels. These findings suggest that IGF-I may participate in aberrant autocrine and paracrine activation of IGF-IR in pancreatic cancer in vivo.

Adolescent↗

[The role of oxygen radicals in acute pancreatitis. Clinical and experimental results of therapy with free radical scavengers].

Numerous studies support the theory that oxygen free radicals (OR) are involved in the development of tissue damage in all forms of experimental acute pancreatitis. OR are generated in an early phase of the disease before tissue damage is detectable by histology. The pathomechanism that leads to this oxidative stress is not fully understood. The efficacy of scavenger treatment was clearly proven in most models of experimental acute pancreatitis. In first clinical trials applying antioxidant treatment with selenium show favorable results in reducing the lipidperoxidation and improving the antioxidant status. However these preliminary results but must be supported in a larger series of patients to allow proper evaluation of patient outcome.

Free Radicals↗

Randomized controlled multicentre study of the prevention of complications by octreotide in patients undergoing surgery for chronic pancreatitis.

A randomized double-blind placebo-controlled multicentre trial was carried out in 247 patients undergoing major elective surgery for chronic pancreatitis to clarify whether the perioperative application of octreotide prevents postoperative complications. Eleven complications were defined, including death, anastomotic leakage, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency and postoperative pancreatitis. A total of 124 patients underwent pancreatic head resection, 55 left resection, 61 pancreaticojejunostomy and seven had other procedures. The overall mortality rate was 1.2 per cent (octreotide group 1.6 per cent, placebo group 0.8 per cent [corrected] (P not significant)). The postoperative complication rate in the octreotide group was 16.4 per cent (20 of 122 patients) and in the placebo group 29.6 per cent (37 of 125) (P < 0.007). The perioperative application of octreotide substantially reduces the risk of postoperative complications in patients undergoing major pancreatic surgery for chronic pancreatitis.

Adult↗