Biomedical subjects

H G Beger

Publications and source records attributed to H G Beger.

At least 181 records · Page 10Linked to original sources

PubMed1998

FDG PET: elevated plasma glucose reduces both uptake and detection rate of pancreatic malignancies.

UNLABELLED: The aim of the study was to evaluate the effects of elevated plasma glucose levels on tumor detection. METHODS: One-hundred and seventy-one fasted patients (100 malignant pancreatic tumors, 46 chronic pancreatitis and 25 patients with other benign pancreatic lesions) were studied with 18F-fluorodeoxyglucose (FDG) PET before planned resective pancreatic surgery. Nineteen of 171 patients had elevated plasma glucose levels above 130 mg/dl, and 24 of 171 had diabetes mellitus. Standard uptake values (SUVs) with and without glucose correction, tumor-to-muscle ratios and tumor-to-liver ratios were measured of the pancreatic lesion respective of the area with the highest uptake within the pancreas. The original qualitative PET reports concerning the dignity of the pancreatic lesion were translated into a five-point malignancy scale. Tumor detection rates and SUVs were compared according to plasma glucose levels above and below 130 mg/dl, the presence of diabetes and by using receiver operating characteristic (ROC) analysis. RESULTS: The detection rates (and mean SUVs) for pancreatic malignancies were 86% and 42% (4.2 and 2.3) if fasted plasma glucose levels were below and above 130 mg/dl, respectively. The sensitivities (and mean SUVs of malignant tumors) were 83% and 69% (3.3 and 2.5) for patients without and with known diabetes. Areas under ROC curves were nearly equal for glucose corrected SUV and visual qualitative results (0.86 and 0.85), followed by uncorrected SUV (0.83), tumor-to-liver ratios (0.80) and tumor-to-muscle ratios (0.79). SUVs for chronic pancreatitis, muscle and liver had a tendency to increase with elevated plasma glucose levels. CONCLUSION: Negative PET results of patients with elevated plasma glucose should be interpreted with caution.

Blood Glucose↗

PubMed1998

Nitric oxide-induced apoptosis in human pancreatic carcinoma cell lines is associated with a G1-arrest and an increase of the cyclin-dependent kinase inhibitor p21WAF1/CIP1.

Nitric oxide (NO) is a messenger molecule with various biological activities including DNA damage. In the present study, we examined the influence of endogenously produced NO on human pancreatic cell lines. In response to cytokine stimulation (tumor necrosis factor alpha, IFN-gamma, and interleukin 1beta), human pancreatic carcinoma cell lines expressed the inducible NO synthase that synthesizes NO, detectable as nitrate and nitrite in the culture supernatants. Endogenously produced NO induced apoptosis in all of the tested pancreatic carcinoma cell lines. In cell cycle analysis, endogenous production of NO revealed a G1-arrest in all of the tested cell lines. This G1-arrest was blockable by addition of NG-monomethyl-L-arginine. These data indicate that NO induces a G1-arrest followed by apoptosis in pancreatic carcinoma cell lines.

Apoptosis↗

PubMed1998

Surgical treatment of acute pancreatitis.

The most important diagnostic step in the management of patients with severe acute pancreatitis is discrimination between interstitial-oedematous and necrotizing pancreatitis. Surgical decision-making is based on clinical, bacteriological and contrast-enhanced CT-data. Persisting or progressive systemic or local organ complications occurring despite ICU-treatment are indicators for surgical management. Patients suffering from sepsis syndrome, cardiovascular shock, multisystemic organ failure syndrome, surgical acute abdomen and persisting or progressing ileus should be treated surgically. The surgical technique is based on careful necrosectomy or debridement in combination with continuous or repeated surgical evacuation of necrotic tissue, bacteria and biologically active compounds. Necrosectomy and postoperative continuous local lavage resulted in a hospital mortality of 17% in necrotizing pancreatitis, conservative management of necrotizing pancreatitis in a hospital mortality of 6.3%. In 1442 patients treated in a 14-year period the overall hospital mortality was 4.4%.

Acute Disease↗

PubMed1998

[Cystic neoplasms of the pancreas: surgical therapy and chances for cure].

Between 1986 and 1997 we treated 67 patients with 68 cystic tumors of the pancreas including 17 mucinous cystadenocarcinomas, four serous cystadenocarcinomas, 15 mucinous cystadenomas, 18 serous cystadenomas, ten intraductal papillary-mucinous tumors, three solid-pseudopapillary tumors, and one cystic neuroendocrine tumor. Regarding surgical therapy our results reveal a differentiated management with respect to the histological findings. While in benign tumors a local resection is adequate the cystadenocarcinomas require an extended resection. In general there is an indication for surgical therapy in all cystic tumors of the pancreas--not only in malignant neoplasias. A nonoperative management is not justified. With a mean follow-up of 35 months the prognosis of the patients with a benign cystic tumor was excellent revealing a mortality of 0% whereas survival of the patients with a cystadenocarcinoma was 67% at five years.

Adult↗

PubMed1998

Multimodal therapy in rectal cancer.

The possibilities and results of multimodal treatment in rectal cancer were reviewed with respect to the results of surgical treatment only. Based on the results of 4 studies, reducing local relapse rates and increasing long-term survival rates significantly, postoperative radiochemotherapy (RCT) + chemotherapy (CT) should remain the recommended standard for R0 resected UICC II and III rectal cancers. Preoperative neoadjuvant radiotherapy (RT) reduced local relapse rates in 8 studies, and extended survival in one study that evaluated all eligible patients. Preoperative RT may evolve as standard, if the patient selection is improved and postoperative morbidity and long-term toxicity are reduced. Postoperative adjuvant RT reduced local relapses significantly in a single trial, and no impact on survival time is reported. Since postoperative RT is inferior to preoperative RT, this treatment cannot be recommended, if RT is chosen as a single treatment modality as an adjunct to surgery. Preoperative RCT + CT downstages resectable and nonresectable tumors and induces a higher sphincter preservation rate. This treatment may be routinely applied in nonresectable primary tumors or local relapses. Intraoperative RT could be added to this concept or be used together with preoperative/postoperative RT with the same indications. The results of local tumor excisions may be improved with pre- or postoperative RCT + CT.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

[Diagnosis and therapy of pancreatic pseudocysts in chronic pancreatitis].

Cystojejunostomy is the operation of choice in patients with pancreatic pseudocysts with pain and/or local complications if no resection procedure is necessary. This procedure can be performed safely after 6 weeks with a low morbidity and mortality and good long-term results compared to conservative treatment.

Chronic Disease↗

PubMed1998

[Radical surgery in cystadenoma of the pancreas--long-term experiences with 35 patients].

We report on 15 patients with mucinous and 19 patients with serous cystadenoma of the pancreas. Cystadenomas were more common in female patients (22/12), and CT was the most sensitive diagnostic tool. There was no mortality in the short or the long term (median 6 years); however, mucinous cystadenomas tend to recur when not treated by radical resection.

Aged↗

PubMed1997

Low serum levels of soluble CD44 variant 6 are significantly associated with poor prognosis in patients with pancreatic carcinoma.

BACKGROUND: Variant CD44 splice products, especially CD44 variant 6 (CD44v6), are expressed on activated lymphocytes and tumor cells. The soluble forms of CD44 standard (CD44s) and CD44v6 are present in the serum of normal individuals. The aim of the current study was to evaluate the concentrations and the prognostic potential of soluble CD44s and CD44v6 in patients with pancreatic carcinoma. METHODS: The serum CD44s and CD44v6 levels were determined quantitatively by enzyme-linked immunosorbent assay. The molecular mass of CD44v6 isoforms was determined by immunoprecipitation and Western blot analysis. CD44 mRNAs were analyzed by reverse transcriptase polymerase chain reaction followed by exon specific analysis. RESULTS: Both serum CD44s and serum CD44v6 were significantly reduced in patients with pancreatic carcinoma (n = 93, P < 0.001 and P < 0.00005). The median survival in the group with CD44v6 serum concentrations below 100 ng/mL was significantly decreased compared with that in the group with serum concentrations higher than 100 ng/mL (6.7 vs. 15.1 months, P < 0.0005). The isoforms containing soluble CD44v6 (sCD44v6) that were detected in the sera of pancreatic carcinoma patients showed molecular masses comparable to the sCD44v6 isoforms detected in the supernatant of lymphocytes activated by phorbol myestral acetate, whereas the sCD44v6 isoforms detected in the supernatant of pancreatic carcinoma cell lines exhibited higher molecular masses. CONCLUSIONS: These results suggest that serum CD44v6 is significantly reduced in pancreatic carcinoma patients and could serve as a good prognostic marker for patients with this disease.

Adenocarcinoma↗

PubMed1997

Fibroblast growth factor-5 stimulates mitogenic signaling and is overexpressed in human pancreatic cancer: evidence for autocrine and paracrine actions.

Fibroblast growth factor (FGF)-1 and -2 are overexpressed in human pancreatic cancer. In this study the role of FGF-5 in human pancreatic cancer was investigated, as FGF-5 has a classical signal sequence for secretion not found in FGF-1 or -2. Northern blot analysis with a 306 bp FGF-5 cDNA revealed the presence of 4.0 kb and 1.6 kb FGF-5 mRNA transcripts in both normal and cancerous pancreatic tissues. Densitometric analysis indicated that 4.0 kb and 1.6 kb FGF-5 mRNA transcripts levels were increased 2.4- and 2.7-fold in the cancers by comparison with normal tissues, respectively (P < 0.002, P < 0.0001). Immunohistochemistry and in situ hybridization demonstrated that FGF-5 localized in the cancer cells, stromal fibroblast and inflitrating macrophages. FGF-5 mRNA was also detected in COLO-357 human pancreatic cancer cells. Furthermore, secreted FGF-5 protein was present in conditioned medium of COLO-357 cells. Exogeneous FGF-5 (0.37 nM) increased the growth of COLO-357 cells by 48% (P < 0.0001) and increased mitogen-activated protein kinase activity. COLO-357 cells expressed the IIIc isoform of the type I FGF receptor, the preferred FGF receptor for FGF-5. These observations suggest that FGF-5 may participate in autocrine and paracrine pathways promoting pancreatic cancer cell growth in vivo.

Adenocarcinoma↗

PubMed1997

Thymidylate synthase is a predictor for response and resistance in hepatic artery infusion chemotherapy.

The value of intratumoral thymidylate synthase (TS) quantitation as a predictive parameter for hepatic artery infusion (HAI) chemotherapy in patients with colorectal liver metastases was investigated. Relative TS mRNA levels were determined in 29 tumor samples using a quantitative RT-PCR amplification method. The median level of expression was 3.0 x 10(-3) (no units) and varied considerably among the tumors over a range of 135-fold. Patients with low TS levels were 4.1-fold more likely to respond (P < 0.03) compared to patients with high TS levels. Our results indicate that TS quantitation is a valuable predictive marker for tumor response to HAI therapy.

Adult↗

PubMed1997

Exogenous, but not endogenous, nitric oxide increases proliferation rates in senescent human fibroblasts.

We investigated the effects of endogenously produced and exogenously applied nitric oxide (NO) on cell proliferation rates and cell cycle regulation in senescent human fibroblasts (WI38). Induction of inducible nitric oxide synthase by tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta inhibited cell proliferation and led to a G1 arrest. These effects were partially reversible by N(G)-monomethyl-arginine (NMA). Addition of the NO donors sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP) increased cell proliferation rates as well as the S/G2 fraction. This points to a functional role of NO in cell cycle regulation and cell proliferation in human fibroblasts which depends on the mode of NO generation as well as the culture conditions used.

Apoptosis↗

PubMed1997

Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein.

In a previous large scale screen for differentially expressed genes in pancreatic cancer, we identified a gene highly overexpressed in cancer encoding a novel protein with four K-homologous (KH) domains. KH-domains are found in a subset of RNA-binding proteins, including pre-mRNA-binding (hnRNP) K protein and the fragile X mental retardation gene product (FMR1). By fluorescence in situ hybridization (FISH) the identified gene named koc (KH domain containing protein overexpressed in cancer) was assigned to chromosome 7p11.5. Two pseudogenes were localised on chromosome 6 and 11. The cloned koc cDNA has a 250 bp 5'-UTR, a 1740 bp ORF and a 2168 bp 3'-UTR. The AU-rich 3'-untranslated region of koc contains eight AUUUA and four AUUUUUA reiterated motifs. The deduced koc protein with 580 amino-acids has a relative molecular mass (Mr) of approximately 65,000 (65 K). The koc transcript is highly overexpressed in pancreatic cancer cell lines and in pancreatic cancer tissue as compared to both, normal pancreas and chronic pancreatitis tissue. High levels of expression were as well found in tissue samples of other human tumours. As the KH domain has been shown to be involved in the regulation of RNA synthesis and metabolism, we speculate that koc may assume a role in the regulation of tumour cell proliferation by interfering with transcriptional and or posttranscriptional processes. However, the precise role of koc in human tumour cells is unknown and remains to be elucidated.

Amino Acid Sequence↗

PubMed1997

Overexpression of cyclin D1 in human pancreatic carcinoma is associated with poor prognosis.

We have investigated the expression of cyclin D1 in adenocarcinoma of the pancreas and the relevance of cyclin D1 expression to clinical outcome. In comparison to normal pancreas, Southern blot analyses revealed amplification of the cyclin D1 coding gene in 25% of the cases, whereas with reverse transcription-PCR, overexpression of mRNA was observed in 82% of the examined tissues. Immunohistochemically, we could demonstrate nuclear overexpression in tumor cells in 68.4%, and this protein accumulation correlated significantly with poor prognosis [median survival, 18.1 versus 10.5 months; P < 0.01 (chi2 test)].

Adult↗

PubMed1997

[Clinical value of the CA 19-9 tumor marker with special reference to the Lewis phenotype].

BACKGROUND: Because of structure and biosynthesis of CA 19-9, it was postulated that patients with the Lewis phenotype Le(a-b-) are not able to synthesize CA 19-9. But some patients with Le(a-b-) on red blood cells showed elevated levels of this tumor marker. PATIENTS AND METHOD: In 164 patients suffering from benign or malignant diseases both CA 19-9 and the Lewis phenotype were determined in sera. In addition in 51 patients red blood cells were tested for Lewis substances. RESULTS: The frequencies of the different Lewis phenotypes on red blood cells were compared with the results found in sera. The prevalence of the phenotype Le(a-b-) on erythrocytes was significantly higher than in sera. In 51 patients both determinations were performed. These results were compared additionally. The phenotype Le(a-b-) found on red blood cells agreed with the results found in sera only in 30% of the cases. A loss of Lewis substances on erythrocytes could be seen both in malignant and benign diseases. Only in patients with Lewis substances found in sera elevated levels of CA 19-9 could be seen. CONCLUSION: Considering only the Lewis phenotype in sera, it could be confirmed that patients with the genotype Le(a-b-)are not able to express elevated concentrations of CA 19-9.

Aged↗

PubMed1997

[Antibiotic use in necrotizing pancreatitis. Results of a controlled study].

BACKGROUND AND OBJECTIVE: The clinical course and death rate in acute necrotizing pancreatitis (ANP) are largely determined by septic complications as part of bacterial invasion of the necrotic tissues. It remains unclear whether antibiotic prophylaxis reduces bacterial invasion of the necroses or septic complications. It was, therefore, the aim of this study to evaluate the effect of prophylactic administration of antibiotics to patients with ANP. PATIENTS AND METHODS: In a prospective randomized study 13 patients with ANP and sterile necroses (quantified by contrast-enhanced computed tomography) were given twice daily 200 mg ofloxacin and twice daily 500 mg metronidazole intravenously. The results were compared to those in a control group of patients with ANP (n = 13) who had not initially received antibiotics. In both patient groups fine-needle biopsies of the necrotic areas were performed on days 1, 3, 5, 7 and 10. If there was evidence of infection, antibiotics were then also given to patients of the control group. RESULTS: The extent of the necroses was the same, 40%, in both groups. These necroses became infected in a median of 9.5 (treated group) and 10 days (untreated group). The clinical course, documented by the APACHE II score, showed significant improvement under antibiotic treatment (days 1-5-10: scores 15-13.0-9.5). In the (initially untreated) control group the clinical condition deteriorated significantly (days 1-5-10: score 11.5-15.0-16.0). The changes from days 1 to 5, 5 to 10 and 1 to 10 were highly significant (Wilcoxon test, P < 0.01). None of the patients in the antibiotic group died within the first 3 weeks, but 2 of the 13 in the control group died. CONCLUSION: Antibiotic prophylaxis neither prevented nor delayed bacterial infection of the necrotic pancreas. But it significantly improved the clinical course if started before the onset of infection of the pancreatic necroses.

Adult↗

PubMed1997

The induction of apoptosis in proliferating human fibroblasts by oxygen radicals is associated with a p53- and p21WAF1CIP1 induction.

The role of reactive oxygen species (ROS) generated by hypoxanthine/xanthine oxidase (HX/XO) in the induction of apoptosis was studied in the human fibroblast cell line WI38. Apoptosis but not necrosis was observed in proliferating fibroblasts after 48 h incubation with 1 mM HX and 0.05 U/ml XO. Induction of apoptosis was hindered by catalase. Cell-cycle analysis revealed a reduction of cells in the S/G2 phase 24 and 48 h after stimulation, suggesting that ROS induce a G1 arrest in proliferating fibroblasts. This was supported by an accumulation of p53 and the cdk inhibitor p21WAF1/CIP1. Since apoptosis was not inducible in senescent fibroblasts our data indicate that ROS mainly induces apoptosis in proliferating cells.

Apoptosis↗

PubMed1997

Thermo-controlled device for inducing deep coagulation in the liver with the Nd:YAG laser.

BACKGROUND AND OBJECTIVE: To increase the effectiveness of laser-induced interstitial thermotherapy (LITT), a new thermo-controlled application system for minimal invasive intervention was designed. Our system consists of a laser applicator of 2.5 mm in diameter, insertion equipment, and a Nd:YAG-laser source. STUDY DESIGN/MATERIALS AND METHODS: A cylindrical light emitting fiber (1-6 cm in length) was placed in the center of the applicator. The surrounding tissue was irradiated through a Duran window at the distal end of the applicator. The power of the laser source was controlled dynamically by thermosensors in a water-cooling system of the laser applicator. The temperature at the surface of the Duran window was kept constant at approximately 60 degrees C, without charring the surrounding tissue. RESULTS/CONCLUSION: We obtained homogeneous coagulation zones. In in vitro experiments with pig livers, we reached ellipsoid coagulation volumes of 3 and 5 cm in diameter within 10 minutes, corresponding to a volume of approximately 25 cm3.

Animals↗

PubMed1997

Improved methods to measure end products of nitric oxide in biological fluids: nitrite, nitrate, and S-nitrosothiols.

The aim of this study was to compare and improve standard methods to determine nitrite (NO2-), nitrate (NO3-) and S-nitrosothiol (RSNO) levels in cell culture supernatants, sera, and urine. We modified the conventional Griess reaction by replacing sulfanilamide with dapsone (4,4'-diamino-diphenylsulfone) and compared the NO2- levels in our study samples with a commercially available NO2- assay kit. Our modification, along with ultrafiltration of the samples, resulted in an enhanced sensitivity to measure NO2- down to 0.2 microM. The detection limit was further improved to 0.02 microM when NO2- was identified by the fluorochrome 2,3-diaminonaphthalene (DAN). To measure the stable end product NO3- by the Griess reaction or the DAN method, this anion must be reduced to NO2-. We compared the capacity of bacterial nitrate reductase with the reducing metal cadmium to convert NO3- to NO2-. After reduction, NO2- levels were determined either by the DAN method or by our modified Griess reaction. We found that there was a high correlation (r2 = 0.998) in total NO2- concentrations in the study samples using both methods for reducing NO3- to NO2-. The simultaneous determination of NO2- and NO3- was achieved by using anion-exchange chromatography (HPLC; Polyspher IC AN-1 column). The detection limit of this assay for each anion is 0.5 microM, and it can be applied equally well to sera, urine, and culture media. We also adapted the DAN method to determine RSNO levels in our study samples. Using this approach, we were able to measure RSNO levels down to 0.15 microM. As result we discovered that RSNO levels were markedly increased in urine from septic patients and in supernatants from cytokine-stimulated human tumor cell lines. L-Citrulline, a coproduct of NO biosynthesis, was measured using a colorimetric assay with a sensitivity limit of 3.0 microM. Increased L-citrulline levels in media from cultured cells, but not in sera or urine, correlated with increased NO production. Although all methods studied were suitable for quantifying end products of NO in biological fluids and media, the use of bacterial reductase and the modified Griess reaction proved successful to provide the greatest sensitivity and linear range for routine measurements of NO2- and NO3-.

Body Fluids↗