Search PubMed⌕ Search

Biomedical subjects

H G Beger

Publications and source records attributed to H G Beger.

At least 235 records · Page 13Linked to original sources

Serum phospholipase A2 in patients with multiple organ failure.

Multiple organ failure (MOF) is the most common cause of death in the surgical intensive care unit. We studied the relation of MOF to changes in the concentration of group II phospholipase A2 (PLA2) in serum. Altogether, 215 surgical intensive care patients with multiple injuries, diffuse peritonitis, or sepsis and control patients, who were at a high risk for postoperative sepsis after various surgical interventions, were included in the present prospective study. The clinical performance of the MOF score and the concentrations of group II PLA2 and C-reactive protein (CRP) in serum were studied using receiver operating characteristic (ROC) curves. The group II PLA2 level was considerably above normal in all groups of patients during the first week of observation. There was a highly significant difference in group II PLA2 levels between patients with severe infections (peritonitis and sepsis) and the other patients studied (multiple injuries and elective surgery) (ROC 0.931, P < 0.0001). The concentration of group II PLA2 had a significant positive correlation to the CRP level and body temperature, which indicates that group II PLA2 is an acute phase reactant and that the determination of group II PLA2 is a useful measurement to diagnose severe infections. It was concluded that the concentration of group II PLA2 in serum effectively predicts lethal MOF in patients with multiple injuries after the second day (ROC 0.739, P < 0.01) and in patients with diffuse peritonitis after the fourth day (ROC 0.750, P < 0.02).

Adolescent↗

Intraperitoneal regional chemotherapy with mitroxantrone.

Pharmacokinetic considerations and tests with cell lines and individual cell suspensions from metastatic human solid tumor biopsies suggested testing the efficacy of mitoxantrone (NOV) in intraperitoneal regional chemotherapy (IPRC). Twenty-seven patients with intraperitoneal metastatic disease of various solid tumors received cyclic IPRC with NOV for treatment of malignant ascites (N = 16) or of peritoneal carcinomatosis (N = 11) at a NOV instillate concentration of 10 micrograms/ml. A total of 125 cycles (1-5 per patient) were applied. Response and toxicity were registered according to WHO criteria. The response rate (CR+PR) was 56 percent in malignant ascites, 45 percent in peritoneal carcinomatosis, and 52 percent overall. There were no systemic toxicities. Regional side effects were bacteriemia (4 of 125 cycles), pain (2 of 125 cycles), small bowel stricture (1 of 27 patients), and small bowel perforation (1 of 27 patients). From these results we can conclude that NOV appears to be effective in IPRC for malignant ascites and peritoneal carcinomatosis at tolerable toxicities.

Antineoplastic Agents↗

In vitro pharmalogic rationale for intraperitoneal regional chemotherapy.

We performed basic in vitro studies on cell lines and individual tumor cell suspensions to support the concept of intraperitoneal regional chemotherapy, and to improve the rationale for drug selection in this regional chemotherapeutic method. We defined the concentration-response behavior and the dependence of drug cytotoxicity on time using the two human colorectal carcinoma cell lines HT29 and NMG 64/84. In addition, the drugs concentration-response behavior and cytotoxic potency for IPRC after a single drug exposure at 10 micrograms/ml (5-FU at 100 micrograms/ml) was preclinically defined with in vitro phase II studies using single cell suspensions of human solid tumor biopsies in the human tumor colony assay (HTCA). The drugs doxorubicin (ADM), cisplatin (CDDP), epidoxorubicin (EPI), 5-fluorouracy (5-FU), 5-fluorodeoxyuridine (5-FUDR), melphalan (LPAM), mitomycin C (MMC), and mitroxantrone were incubated at increasing concentrations up to 1000 micrograms/ml at 10, 30, 60, 360, and 1440 minutes with the cell lines. These drugs, as well as vindesine (VDS) and mafosfamide (MAF) were also tested in the HTCA at increasing concentrations. The HTCA response rates at 10 micrograms/ml (5-FU and MAF at 100 micrograms/ml) were used for in vitro phase II comparisons of potential drug clinical activities. All test drugs showed a time- and concentration-dependent cytotoxic activity against the cell lines. Based on the cytotoxicity test results with HT29 and NMG 64/84, specific times were recommended for clinical therapy with each drug. In the HTCA, the drugs showed different cytotoxic concentration responses. The concentration-response behavior of each drug varied in individual tumor biopsies of the same histology. Comparing the response rates at 1 microgram/ml (5-FU and MAF 10 micrograms/ml) and 10 micrograms/ml (5-FU and MAF 100 micrograms/ml), an overall increase of in vitro response by a factor of 2.1 +/- 0.7 (1.1-3.7) was noted. We were able to prove this principle qualification of various test drugs in our in vitro studies and to suggest the optimal exposure times for their use in intraperitoneal chemotherapy. Based on these results, NOV was successfully used in an IPRC clinical study.

Antineoplastic Agents↗

Adjuvant treatment of colon and rectal cancer: impact of chemotherapy, radiotherapy, and immunotherapy on routine postsurgical patient management. Forschungsgruppe Onkologie Gastrointestinaler Tumoren (FOGT).

Colon cancer patients with UICC stage III or T4 N0 M0 stage II should receive postoperative adjuvant therapy, since relapse rates are high and surgical outcome has been improved by adjuvant treatment. The standard treatment is 5-fluourouracil plus levamisole; an alternative option is the combination of 5-fluourouracil and folinic acid. Stage II (T3 N0 M0) colon cancer patients should not receive adjuvant treatment outside of studies. Rectal cancer patients of stage II or III should receive postoperative radiochemotherapy with 45-54.4 Gy and 5-fluourouracil as standard treatment. Patients not eligible for radiotherapy may receive adjuvant chemotherapy only. Studies need to be conducted to improve adjuvant therapy in colorectal cancer. All qualified patients should be treated within these studies requiring sufficient patient numbers, as well as comparable surgical procedures, proper patient selection and stratification criteria, drug and dose intensities. Intraportal infusion may be as effective as systemic adjuvant treatment; the tumor type and stage for which benefit from this kind of treatment is consistently significant needs to be defined, since intraportal infusion of all resectable colorectal cancers is overtreatment. Both surgery and histopathological staging may be improved in some centers, and these require standardization and quality control.

Colonic Neoplasms↗

Molecular oncology in pancreatic cancer.

Cancer of the pancreas still has a very poor prognosis despite improved diagnostic methods and therapeutic regimens. The reasons for the aggressiveness of this cancer are not known, and the molecular mechanisms that govern the growth of pancreatic cancer cells are still not clearly defined. During the past two decades the development of new molecular biological techniques has offered new perspectives for a better understanding of pancreatic cancer. Tumor markers such as CA19-9 and CEA are used for diagnosis and for following the postoperative course of cancer patients. Characterization of pancreatic cancer cells using several molecular biological techniques has revealed overexpression or altered expression of growth factors and adhesion molecules, implying altered cell-cell and growth-regulatory interactions. In pancreatic cancer mutations in oncogenes and tumor suppressor genes are frequently detected in p53 and K-ras. This article reviews the possible molecular approaches for diagnosis, prognosis, or even therapy of pancreatic cancer.

Biomarkers, Tumor↗

Release of histamine in whole blood by oxygen radicals: division between specific and unspecific processes.

Oxygen derived free radicals are involved in many pathological processes such as postischemic reperfusion injuries, hepatotoxicity of drugs and inflammatory processes. Thereby these oxygen radicals induce lipid peroxidation and perturbation of cellular membranes. The aim of our present study was to determine whether oxygen radicals generated by the xanthine oxidase/ hypoxanthine system cause a release of histamine in human blood cell cultures. Stimulation of blood cell cultures with oxygen radicals induced a histamine liberation which was mainly due to calcium independent processes during the first 30 min, whereas then calcium requiring processes took part in the release of histamine. The regulation of the leukocyte selection LECAM-1 was altered by oxygen radicals whereas histamine, which is known to modulate vascular selectin expression, did not affect the expression of LECAM-1. Our data indicate that oxygen radicals induce a direct calcium independent release of histamine which is due to membrane pertubating processes during the first phase but also induce a specific reaction leading to a further indirect histamine liberation which is probably mediated by PAF.

Cell Adhesion Molecules↗

The role of anti-p53-autoantibodies in pancreatic disorders.

CONCLUSION: Anti-p53-autoantibodies (a-p53-aabs) may suppress the development of distant metastases, but not lymph node metastases. This could explain the significantly prolonged survival of patients with UICC stage III tumors who have a-p53-aabs compared to those without a-p53-aabs. BACKGROUND: Mutation within the tumor suppressor gene p53 leads to increased intracellular p53 protein levels and an increased antibody formation against this molecule. Altered p53 has been proposed to be associated with poor prognosis, and the present study investigated whether the detection of a humoral response to p53 gives evidence for a prognostic or diagnostic parameter in pancreatic disorders. METHODS: We screened 145 patients with pancreatic cancer and 95 patients with chronic pancreatitis for the development of a-p53-aab via ELISA and Western-blotting. p53 expression was examined by immunohistochemistry. RESULTS: We found that 41% of the tissues of patients suffering from pancreatic carcinoma overexpressed p53, and 15.9% of the patients suffering from pancreatic cancer developed a-p53-aab. In pancreatic cancer, we could exhibit a significant correlation between grading, p53-overexpression, survival, and antibody response against p53. A-p53-aabs were significantly more frequent in patients with stage III tumors (tumors with lymph node metastases, but not distant metastases, p < 0.02).

Adult↗

CA 19-9 serum course and prognosis of pancreatic cancer.

CONCLUSION: CA 19-9 measurement is a simple test that can be used for diagnosis as well as for prediction of resection, survival rate after surgery, and recurrences. METHODS: Serum expression of the tumor marker CA 19-9 was studied in 2119 patients. RESULTS: The discriminating capacity between benign and malignant disease was high for CA 19-9, especially in patients with pancreatic cancer (n = 347). The sensitivity of CA 19-9 was 85%. In patients who were Lewis blood type positive, the sensitivity increased to 92%. CA 19-9 levels were significantly lower in patients with resectable tumors (n = 126) than in those with unresectable tumors (n = 221, p < 0.0001) (sensitivity 74 vs 90%). CA 19-9 dropped sharply after resection, but normalized only in 29, 13, and 10% in patients with stage I, II, and III, respectively. In unresectable tumors no significant decrease of CA 19-9 after laparotomy or bypass operation was found. In patients of the same tumor stage, the median survival time in those whose CA 19-9 levels returned to normal after resection was significantly longer than in those with postoperative CA 19-9 levels that decreased, but did not return to normal (in stage I, 33 vs 11.3 mo, in stage II, 41 vs 8.6 mo, and in stage III, 28 vs 10.8 mo). In patients with recurrent disease, 88% had an obvious rise in CA 19-9 levels.

CA-19-9 Antigen↗

Serous cystadenocarcinoma of the pancreas.

The mucinous type of cystadenoma of the pancreas is known to have malignant potential, whereas the serous type is believed to be benign. Therefore, the therapeutic strategies for serous cystadenomas are less aggressive than in mucinous cystadenoma, where complete operative resection is the procedure of choice. A patient with a biopsy-proven serous cystadenocarcinoma with a lymph node metastasis is reported. Considering the reported case and a review of the literature, the origin of serous cystadenocarcinoma appears to be from cystadenoma lesions. Even if this development of cystadenocarcinoma in pre-existing serous cystadenoma lesions is a rare entity, a less aggressive treatment of this lesion should be avoided in favor of resection procedures because of the good chance of cure.

Aged↗

[Solid pseudopapillary tumors of the pancreas].

We report on three female patients with solid pseudopapillary tumors of the pancreas. The histogenetic origin of this entity is still unclear. The tumor, usually occurring in young women, forms large masses (up to 10 cm in diameter) before becoming symptomatic. Metastases have very rarely been reported. In contrast to other pancreatic tumors, the main pancreatic duct was displaced, but of normal caliber without stenosis, in all our patients. Despite the large size of the tumors, they were curatively resected in all three cases. Two of the tumors infiltrated the parenchyma or adipose tissue of the pancreas but did not spread into the lymph nodes or other organs. All of the patients are alive and without signs of tumor recurrence up to 8 years after surgical resection.

Adult↗

Importance of the duodenal passage and pouch volume after total gastrectomy and reconstruction with the Ulm pouch: prospective randomized clinical study.

The objective of this randomized study was to examine which reconstruction method and which pouch volume offer the best preconditions for a good quality of life and extensive physiologic regulation of gastrointestinal hormones after total gastrectomy. Up to now there is no general agreement with regard to the ideal reconstruction after total gastrectomy. The importance of the duodenal passage, the need for a pouch reconstruction, and the ideal pouch volume are matters of controversy. A total of 60 patients underwent the following reconstructions: Ulm pouch (pouch reconstruction with preservation of the duodenal passage), Hunt-Lawrence-Rodino pouch, or Roux-en-Y reconstruction without pouch. The clinical course, quality of life, and regulation of gastrointestinal hormones in correlation to reconstruction type and pouch volume were documented. Quality of life was assessed by means of a standardized specific questionnaire. Blood glucose, insulin, cholecystokinin, motilin, secretin, and pancreatic polypeptide were measured after stimulation by a standardized test meal. Six months after total gastrectomy those patients with an Ulm pouch were found to have a significantly better life quality (p < 0.01), higher body weight, and better physiologic regulation of gastrointestinal hormones; moreover, they developed (in contrast to all other reconstruction types) no pathologic glucose tolerance. Our conclusion is that all patients with a postoperative life expectancy of at least 6 months (i.e., tumor stages UICC I and II) should undergo pouch reconstruction with preservation of the duodenal passage.

Aged↗

CAM 17.1--a new diagnostic marker in pancreatic cancer.

CAM 17.1-Ab is a recently described monoclonal antibody that detects a mucus glycoprotein with high specificity for intestinal mucus, particularly in the colon, small intestine, biliary tract and pancreas. We investigated the expression and release of CAM 17.1 in pancreatic carcinoma cell lines and tissue specimens of normal pancreas, chronic pancreatitis and pancreatic cancer. CAM 17.1 was weakly expressed on normal ductal cells and chronic pancreatitis, whereas it was overexpressed in pancreatic cancer. Serum analysis using a new enzyme-linked antibody sandwich assay (CAM 17.1/WGA) of patients with chronic pancreatitis, pancreatic cancer or other gastrointestinal cancer and of healthy blood donors revealed a high sensitivity (67%) and excellent specificity (90%) of CAM 17.1/WGA assay in pancreatic cancer. In comparison with the tumour marker CA19-9, the sensitivity of the CAM 17.1/WGA assay was similar to the sensitivity of CA 19-9 (67% and 76%, P = 0.22), whereas the specificity of CAM 17.1/WGA assay was higher than in CA 19-9 (90% compared with 78% in chronic pancreatitis, P > 0.05).

Adult↗

[Clinical relevance of mammography in men].

PURPOSE: During a period of four years 104 mammograms were performed in 89 men. Mastectomies were carried out on 23 men (group 1). 66 patients (group 2) were followed up clinically and in 15 patients serial mammograms were obtained. MATERIAL AND METHOD: In group 1 there were 5 patients with bilateral gynaecomastia, 9 with unilateral gynaecomastia and two with pseudogynaecomastia and there were 7 patients with malignancies. In group 2 there were 46 patients with bilateral gynaecomastia and 10 patients with unilateral gynaecomastia. Pseudogynaecomastia was found in 25 patients. There were 7 malignancies, of which 5 had been suspected clinically and one had been diagnosed as gynaecomastia by mammography. Two carcinomas in situ were missed clinically and also by mammography. CONCLUSION: When malignancy is not suspected on clinical grounds the first examination should be sonography, mammography being reserved for cases of doubt. Where, however, malignancy is suspected, and for follow-up, mammography retains its primary position.

Adolescent↗

Total gastrectomy. Updated operative mortality and long-term survival with particular reference to patients older than 70 years of age.

OBJECTIVE: The authors conducted a study of patients who underwent total gastrectomy for gastric malignancy to elucidate contributing factors that lead to successful management of this disease in geriatric patients. SUMMARY BACKGROUND DATA: The average mortality rate for patients undergoing stomach surgery due to carcinoma is 7.8% according to the literature overview, still relatively high. Even higher mortality rates are observed for geriatric patients after a total gastrectomy. Because of epidemiologic changes, a total gastrectomy is required with growing frequency in these high-risk patients. METHODS: The study involved 380 patients with a gastric malignancy. Risks and benefits of a total gastrectomy with radical lymphadenectomy at an advanced age were analyzed retrospectively in 163 patients older than 70 years of age. The results achieved in these patients were compared with those observed in 217 younger patients. RESULTS: The 30-day mortality and morbidity rates for the elderly patients were 3% and 33.7%, respectively; for the younger patients, they were 0.46% and 21.2%, respectively. A statistically significant correlation was found between the presence of risk factors, the occurrence of complications, and the mortality rate. No difference was seen between the two age groups when risk factors were absent. The 5-year survival rate was 30%, with no difference between young and elderly patients. CONCLUSIONS: The data prove that a total gastrectomy with a radical lymphadenectomy can be carried out safely in older patients, with long-term results comparable to those achieved in younger patients.

Age Distribution↗

Influence of etiology on the course and outcome of acute pancreatitis.

It has been supposed that there are differences with regard to clinical course and outcome due to the underlying etiological factor in acute pancreatitis. Therefore, the objective of this study was to analyze the severity of the disease, serum enzymes, indicators of necrosis, systemic complications, and mortality in acute pancreatitis with regard to the etiology. One hundred ninety patients with acute pancreatitis (127 male, 63 female) were studied prospectively and subdivided into three etiological groups: (i) alcohol, (ii) gallstones, and (iii) other causes and idiopathic acute pancreatitis. Severity scores (Ranson and Bank) and findings by contrast-enhanced computed tomography were similar in all three groups. Analysis of serum enzymes [lipase, aspartate aminotransferase (ASAT)] and indicators of necrosis (C-reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin, and lactate dehydrogenase) showed only for ASAT within 24 h significantly higher levels in biliary acute pancreatitis in comparison with the other groups. There were no differences in the rate of infected pancreatic necrosis and mortality in alcohol-related acute pancreatitis (31 and 5.3%), biliary acute pancreatitis (38 and 10%) and acute pancreatitis due to other etiological factors (43 and 5.5%). In conclusion, this study clearly showed that once the pathogenetic mechanisms have initiated the disease, the course and outcome of acute pancreatitis are not influenced by the underlying etiological factor.

Acute Disease↗

Endotoxin-induced release of interleukin 6 and interleukin 1 beta in human blood is independent of tumor necrosis factor alpha.

It has been suggested that tumor necrosis factor alpha (TNF alpha) acts not only by direct toxicity, but also as a proximal mediator which is able to induce the production of other cytokines, especially interleukin 6 (IL-6) and interleukin 1 beta (IL-1 beta). In order to test the dependence of the release of these two cytokines from leukocytes upon induction by TNF alpha, we stimulated whole blood in vitro with TNF alpha and compared the cytokine levels with those induced by endotoxin. The cytokine release was also determined after stimulation by endotoxin with added TNF alpha and by endotoxin with monoclonal antibodies against TNF alpha (anti-TNF alpha) added in order to reduce TNF alpha. Unstimulated blood samples were used as controls. The plasma levels of both IL-6 and IL-1 beta were significantly higher after stimulation with endotoxin than after stimulation with TNF alpha. TNF alpha did not induce cytokine levels significantly higher than controls. The cytokine levels were the same whether or not anti-TNF alpha was included together with the endotoxin. Plasma from samples with added anti-TNF alpha had no detectable TNF alpha. Our results indicate that the leukocyte-derived production of IL-6 and IL-1 beta in whole blood is stimulated directly by endotoxin and is not mediated by TNF alpha.

Antibodies, Monoclonal↗

Determination of endotoxin-neutralizing capacity of plasma in postsurgical patients.

In 92 patients who underwent abdominal and goiter surgery endotoxin and endotoxin-neutralizing capacity (ENC) were determined in plasma preoperatively and daily postoperatively. Endotoxin plasma levels started to increase on day 1 in patients who were laparotomized. Correspondingly ENC was reduced during the 1st postoperative week. Even on the 1st postoperative day determination of ENC made the differentiation between patients possible who showed an uneventful course and patients who developed pneumonia, pulmonary failure, or mental disorders. Furthermore the need for diuretics in order to maintain sufficient renal function was associated with lower ENC during days 1-3. Endotoxin plasma levels were significantly elevated in patients who developed pneumonia during days 1-4, whereas the occurrence of pulmonary failure was only correlated with elevated endotoxin levels on day 3. Endotoxemia was pronounced in patients needing diuretics on days 1, 4, and 5. In patients who underwent goiter surgery ENC changed significantly as found for endotoxin plasma values during the postoperative course. Determination of endotoxin and especially ENC with the use of the limulus amebocyte lysate test turned out to be a reliable method correlating with impending complications at least in postsurgical patients.

Adult↗