PubMed HealthSearch

Biomedical subjects

I Vogel

Publications and source records attributed to I Vogel.

At least 19 recordsLinked to original sources

A human carcinoma model in athymic rats reflecting solid and disseminated colorectal metastases.

We studied the metastatic properties of human tumor cells and tumor cell dissemination in a xenograft tumor model for human colorectal carcinoma in athymic rats which shows a reproducible pattern of metastases similar to the clinical situation. Such a model is also attractive for evaluating several therapeutic approaches. The tumor cell lines HT-29 and WiDr which are derived from the same colorectal tumor and exhibit a similar tumorigenic potential after subcutaneous injection were injected into the portal venous system of 4-week-old male nude rats. After injection of WiDr cells no liver metastases were observed; however, 50% of the rats developed liver metastases 4-12 weeks after injection of HT-29. Immunostaining of the liver cryosections at different times after injection revealed a total disappearance of WiDr cells within the first 12 h. A subpopulation of HT-29 (HT29-b) with increased metastatic activity was isolated by double selection and recultivation of cells from induced liver metastases. After a 6- to 12-week period rats injected with HT-29b showed a pattern of metastases with additional lung metastases and in some cases peritoneal carcinosis. In addition to immunohistochemistry cytokeratin 20 reverse transcriptase-polymerase chain reaction was confirmed to be a sensitive and specific tool for the detection of disseminated tumor cells in different compartments.

Animals

The retroperitoneal resection margin and vessel involvement are important factors determining survival after pancreaticoduodenectomy for ductal adenocarcinoma of the head of the pancreas.

The prognosis of ductal adenocarcinoma of the pancreas is still poor. We analysed the factors that have a major influence on the survival of patients. Surgical specimens from 51 patients with ductal adenocarcinoma of the head of the pancreas were examined for tumour size, histological type, grade and local extension. In 7 patients the retroperitoneal resection margin was involved either macroscopically or histologically. Their mean survival was 10.6 months (1-17 months), compared with 22.7 months for the 44 patients with curative R0 resection. In 10 patients large vessels (portal and/or mesenteric vein) had to be resected; they survived for only 2-11 months, with a mean of 5 months (P<0.05). Non-R0-resected patients and patients in whom tumour-invaded vessels had to be resected constitute a high-risk group with a significantly shorter mean survival of 8.8 months, compared with 24.3 months for R0 resected patients without vessel invasion (P<0.05). Lymph node metastases were seen in 35 of 51 patients. Survival analysis based on nodal status revealed a mean survival of 33 months for patients staged as N0, 21.4 for N1a patients and 14 month for N1b patients. The differences were not statistically significant, however. Our data suggest that tumour invasion of the retroperitoneal resection margin and large vessel involvement are the major factors determining survival in patients with pancreatic cancer.

Aged

Clear cell carcinoma of the pancreas: an adenocarcinoma with ductal phenotype.

AIMS: Primary clear cell carcinoma of the pancreas resembling metastatic renal carcinoma has only rarely been described. To date it has been poorly characterized as a distinct tumour entity. METHODS AND RESULTS: We report a case of clear cell carcinoma in a 53-year-old man involving the head of the pancreas and which had a small intraductal papillary component. The clear cell portion comprised about 90% of the tumour mass. It showed predominantly a solid growth pattern with a few scattered tubular structures. Immunocytochemically the tumour cells stained positively for cytokeratins 7, 8, 18 and 19, whereas the reaction for vimentin and neuroendocrine markers was negative. K-ras analysis revealed a point mutation at codon 12 with mutation of GGT to GAT. CONCLUSION: The intraductal tumour component of this clear cell carcinoma as well as the cytokeratin pattern and the K-ras mutation suggest that this rare type of pancreatic cancer has a ductal phenotype.

Adenocarcinoma, Clear Cell

Effect of octreotide, captopril or insulin on renal changes and UAE in long-term experimental diabetes.

Renal and glomerular growth is inherent in early human and experimental diabetes frequently followed by later increase in urinary albumin excretion (UAE). Treatment with angiotensin converting enzyme (ACE) inhibitors has proven effective in delaying progression of human and experimental diabetic renal changes, and so has somatostatin analog treatment in experimental diabetes. The aim of the present study was to investigate three weeks of octreotide and captopril treatment alone or in combination following three months of untreated experimental diabetes, and compare the effects to those of insulin treatment. Diabetes induced significant increases in renal and glomerular growth and urinary albumin excretion. Octreotide and captopril alone and in combination reduced renal but not glomerular size, and the combined administration reduced UAE. None of these schedules affected blood glucose levels. Insulin treatment inducing euglycemia significantly reduced renal and glomerular size and UAE. In conclusion, insulin treatment with normalization of the diabetic metabolic derangement nearly normalizes renal and glomerular growth and UAE after three months of untreated diabetes. The combined treatment of octreotide and captopril was also followed by a significant decrease in renal growth and reduction in UAE compared to placebo treatment without affecting the metabolic control of the diabetic animals.

Albuminuria

Isolated tumor cells are frequently detectable in the peritoneal cavity of gastric and colorectal cancer patients and serve as a new prognostic marker.

OBJECTIVE: To evaluate the prognostic significance of isolated tumor cells detected by a panel of various monoclonal antibodies. SUMMARY BACKGROUND DATA: Previously, we showed by using immunocytology that cancer cells are frequently found in bone marrow and peritoneal cavity samples of gastrointestinal cancer patients. METHODS: Findings in bone marrow and peritoneal cavity samples were compared and correlated with the 4-year survival rate of 84 gastric and 109 colorectal patients with cancer. RESULTS: Although positive results in the bone marrow showed little prognostic significance, the peritoneal cavity results correlated with the 4-year survival rate (gastric cancer: p = 0.0038; colorectal cancer: p = 0.0079). Additionally, in subgroups of patients with early (gastric cancer: p = 0.02, colorectal cancer: p = 0.48) and advanced (gastric cancer: p = 0.02, colorectal cancer: p < 0.0001) tumor stages, a correlation of immunocytologic findings and the survival rate was seen. CONCLUSIONS: The detection of minimal residual disease in the peritoneal cavity serves as a new prognostic marker.

Colorectal Neoplasms

Comparison of injectable anesthetic combinations in free-ranging two-toed sloths in French guiana.

Immobilization was studied in 202 free-ranging two-toed sloths (Choloepus didactylus). All the sloths were in good condition with a body weight > 2 kg, and were anesthetized for a variety of minor clinical procedures. Intramuscular anesthetic combinations included 0.1 mg/kg acepromazine + 10 mg/kg ketamine (A/K, n = 30), 1 mg/kg xylazine + 10 mg/kg ketamine (X/K, n = 89), 10 mg/kg tiletamine/zolazepam (T/Z, n = 37), and 0.04 mg/kg medetomidine + 3 mg/kg ketamine (M/K, n = 46) antagonized by 0.2 mg/kg atipamezole. The animals were quiet during the induction stage and complete recumbency was reached in (mean +/- SD) 2.5 +/- 2.0 min with A/K, 2.7 +/- 1.7 min with X/K, 1.8 +/- 0.6 min with T/Z, and 2.5 +/- 5 with M/K. Utilization of A/K was not satisfactory because of poor anesthetic level and lack of muscle relaxation. T/Z induced immobilization was characterized by deep anesthesia and good myorelaxation, but often was associated with irregular respiration and low relative oxyhemoglobin saturation values (SpO2). Ketamine in combination with alpha2-agonists, xylazine or medetomidine, provided suitable anesthesia, with good to excellent muscular relaxation, good analgesia, high SpO2 values, moderate bradycardia, but strong bradypnea with medetomidine. Anesthesia with M/K was reversed after 41.6 min of immobilization with atipamezole. Calm recoveries were obtained and the animals were able to hang up after 10.0 +/- 7.9 min. The first signs of arousal were observed within an average of 43 to 51 min after the injection of the three other combinations. Recoveries from X/K immobilization were quiet; sloths held on after 34 min. With T/Z, recovery duration was long and very irregular at 76.7 +/- 31.3 min, some animals required 3 hr before being able to hang up. Finally, ketamine in association with an alpha2-agonist appeared to give the best chemical immobilization in wild two-toed sloths for 40 min procedures including minor surgery.

Acepromazine

[Cystic liver, an indication for liver transplantation or decompressive resection?].

In patients suffering from polycystic liver disease sclerosing therapy, decompressive hepatic resection and liver transplantation represent the main therapeutic options. Since 1987, 10 females with highly symptomatic polycystic liver disease underwent hepatic resection for decompression (five left lateral bisegmentectomies, one left hemihepatectomy, one right central and three bilateral atypical resections). Despite of a 0% lethality 3 patients developed complications, in two cases an abscess had to be drained and in one case a postoperatively increasing hepatic insufficiency required urgent liver transplantation. Patient's symptoms were remarkably improved in 8 cases, but only 6 patients had a long lasting benefit over years. One patient was resected a second time three years after the first operation and is free of symptoms for another five years. 6/96 the "European Liver Transplant Registry" has listed 81 patients after liver transplantation because of polycystic liver disease. 5-year survival is 78.2%. So liver transplantation offers a therapeutic alternative for patients severely suffering from symptoms or increasing hepatic insufficiency.

Cysts

[Resection of liver metastases--possibilities for a cure].

Retrospective analysis of 167 liver resections in patients with liver metastases of colorectal carcinoma revealed the following prognostic factors: UICC stage of the colorectal carcinoma (stage I/II vs III/IV), number of liver metastases (1-3 vs > 3 metastases), size of liver metastases (< or = 5 cm vs > 5 cm). Most important for long-term survival was the curative (R0) resection with a histologically proven tumor-free resection margin of more than 1 cm (P = 0.0496). Simultaneous resection of liver metastases and the primary colorectal carcinoma did not influence lethality and morbidity or long-term survival.

Colorectal Neoplasms

Comparative analysis of bone marrow and venous blood isolates from gastrointestinal cancer patients for the detection of disseminated tumor cells using reverse transcription PCR.

We investigated 141 bone marrow and 104 venous blood isolates from gastrointestinal cancer patients with a cytokeratin (CK) 20-specific nested reverse transcription PCR for the detection of disseminated tumor cells at time of primary tumor resection. In colorectal cancer patients, 20 of 65 (31%) bone marrow and 9 of 52 (17%) venous blood isolates yielded a CK 20 mRNA-positive result in a stage-dependent manner. The detection rates for gastric cancer patients were 11 of 49 (22%) and 5 of 30 (17%) for bone marrow and venous blood, respectively. In pancreatic cancer patients, positive signals were found in advanced tumor stage. A duplex PCR system improved the feasibility of the test. After analyzing 70 sets of bone marrow and venous blood isolates from colorectal, gastric, and pancreatic cancer patients, we observed a higher detection rate in bone marrow isolates. Survival of patients with CK 20 mRNA-positive findings was significantly shorter than that of negatively tested patients.

Biomarkers, Tumor

Primary stable anterior instrumentation or dorsoventral spondylodesis in spondylodiscitis? Results of a comparative study.

The operative results of 23 patients with a specific or unspecific spondylodiscitis were documented over 2 years after the focus of the inflammation had been eradicated, bone chip had been interposed and a CDH instrumentation had been performed by an anterior approach only. These outcomes were compared with the results of 32 patients in whom the focus had been removed and the defect had been filled with bone graft from an anterior approach, followed by stabilisation with CD instrumentation through an additional dorsal approach. In the cases where CDH instrumentation was applied, the range of fusion averaged 1.3 segments. This was clearly less extensive than in dorsoventral stabilisation, in which on average 3.5 segments were fused. In 47 of 55 cases mobilisation was achieved without orthesis. Eight months after the operations bony fusion could be observed radiologically in all patients. The mean preoperative kyphotic angle of the affected segments was 14.4 degrees, compared to 4 degrees after the operation. The mean loss of reposition was measured to be about 2.7 degrees in both groups. Average operation time and blood loss were about 50% higher in the patients treated dorsoventrally. We conclude that even in the case of florid spondylodiscitis, a short-range anterior fusion of the affected spinal segment may be performed by use of a stable-angle implant without an increased risk of infection-related loosening.

Bone Transplantation

No effects of human relaxin on the active and passive biomechanical properties of isolated cervical specimens from nonpregnant women.

OBJECTIVE: To evaluate the effect of human relaxin (hRLX-2) on the active and passive biomechanical properties of cervical tissue in vitro. MATERIAL: Cervical samples were obtained from the middle part of the cervix in 22 nonpregnant women undergoing hysterectomy. METHODS: The effect of hRLX-2 (10(-7) M) on the active biomechanical properties was studied on vasopressin (10(-8) M) induced smooth muscle contractions in an organ bath model. The effect on the passive biomechanical properties were studied after incubation of the strips for 48 h with hRLX-2 (10(-8) M and 10(-9) M). Subsequently, the specimens were stretched in a material testing machine until they broke. The load applied and the elongation were simultaneously recorded and the results translated into stress-strain curves. RESULTS: hRLX-2 did not influence the vasopressin-induced contractility of cervical strips from nonpregnant women in this study. No synergistic effect of progesterone could be demonstrated. The passive biomechanical properties (tensile strength, extensibility, stiffness of failure energy) did not change significantly after relaxin incubation. The results obtained in vitro do not suggest an important physiological effect of relaxin on the human nonpregnant cervix.

Adult

Overexpression of p53 protein during pancreatitis.

Overexpression of p53 correlates with neoplasia in many cytological specimens. To test the specificity of overexpressed p53 as a tumour marker for the detection of pancreatic cancer, we analysed cytological specimens of pancreatic juice samples from patients with pancreatitis or pancreatic carcinoma (n = 42) for p53 protein overexpression. p53 protein overexpression was found in 59% of patients with pancreatitis and 67% of patients with pancreatic carcinoma. Thus, the assessment of p53 protein overexpression is not useful in the diagnosis of pancreatic cancer. Overexpressed p53 during pancreatitis appears to be wild-type p53. Overexpression of p53 may result from DNA damage occurring during chronic inflammation. It is well established that p53 can induce apoptosis upon DNA damage. Consequently, we found apoptotic cell death in five out of five tested cytological preparations from patients with pancreatitis as well as in one out of one pancreatic carcinoma specimen.

Adenocarcinoma

[Surgical oncology: possible methods for financing complex oncological therapy procedures].

The AOK Schleswig-Holstein actually finances the evaluation of treatment costs for the project "Operative Oncology". After the primary conceptual phase, the project will be financed for several years and will be accompanied by quality-control studies. In addition to the procedure of the BMG, the costs of psychological support/therapy as well as for new molecular biological tests for the detection of micrometastases are calculated. The reason for this calculation is that these additional costs might be included into a specific, oncological resource-based value system of payment.

Cost-Benefit Analysis

Variations in serum relaxin (hRLX-2) concentrations during human pregnancy.

STUDY OBJECTIVE: To study variations in serum relaxin concentrations during normal and abnormal human pregnancy and parturition and in umbilical cord blood. DESIGN AND PATIENTS: Diurnal variations were determined in samples collected every 2 hours for 24 hours (n = 4). Variations during pregnancy were studied in samples taken every 4th week from normal pregnant women (n = 26). Additionally samples were collected once a week from the 37th week of pregnancy and until spontaneously delivery (n = 5). Changes in relaxin during early pregnancy (gestational age: 30 to 97 days) were studied in serum from 12 normal pregnant women, 13 with spontaneous abortion and 38 with an ectopic pregnancy. Fetal serum was obtained at delivery from the umbilical vein (n = 20). All samples were analysed for relaxin by an ELISA based on human relaxin antibodies. MAIN RESULTS: No diurnal variation in relaxin concentrations were found. In normal pregnant women relaxin concentrations increased during the first 14 weeks of pregnancy. From week 14 to 24 a gradual decrease was found and the concentrations remained constant during the last part of pregnancy. No changes in concentrations were found immediately before or during spontaneous delivery. Women with abnormal pregnancies had lower serum relaxin values than normal early pregnant women. The relaxin concentration was significantly correlated to the serum HCG concentration in early pregnancy but not to the serum HPL levels after week 28. In the umbilical vein relaxin concentrations were low. CONCLUSION: The variation in circulating levels of relaxin during human pregnancy differs markedly from those found in other species. This suggests a different role for relaxin in human pregnancy.

Abortion, Spontaneous

[Results of liver resection in 113 patients with metastases of colorectal carcinomas].

Between 1985-1991 and 1991-1994 118 liver resections in 113 patients with colorectal liver metastases were performed by our group at the University hospitals of Hamburg and Kiel. The data of 106 patients were analysed regarding the prognostic factors: age, sex, localisation--stage--grading of the primary tumor, localisation--number--size--synchronous/metachronous appearance of metastases, extent and radicality of the liver resection. The results showed, that a significant prognostic influence regarding the long-term survival rate could only be achieved in patients, in which a R0-resection with a histologically proven tumor free margin of more than 1 cm was performed. In these cases (n = 46) a median survival time of 38 months was observed. In patients with histologically proven tumor free resection margins < 1 cm (n = 38) the median survival time was 24 months, in patients with R1-resections (n = 7) 26 months and in patients with R2-resections (n = 15) 20 months respectively.

Adult

Relaxin (hRLX-2)-induced weakening of human fetal membranes in vitro.

We examined the effect of human relaxin (hRLX-2) on the biomechanical properties of human fetal membranes in vitro. Intact chorioamniotic membranes were obtained from twelve elective cesarean sections before the onset of labor. Membrane strips with a fixed width were biomechanically tested after incubation for 20 h with hRLX-2 in concentrations of 10(-7) mol/l and 10(-9) mol/l. Incubation with hRLX-2 (10(-9) mol/l) changed the load-strain values as the membrane stiffness was decreased by 19% when compared with controls: median 2.45 N (range, 0.81-4.31) versus 3.03 N (1.28-5.46), P = 0.02 (Mann-Whitney test). For description of the membrane material as such, the stress-strain values were calculated by dividing the load-strain values with the cross sectional area of the membranes. Incubation with hRLX-2 (10(-9) mol/l) decreased the tensile strength of the membranes by 30%-0.817 N/mm2 (0.282-1.139) vs. 0.575 N/mm2 (0.101-1.150), P = 0.03--and reduced the elastic modulus by 31%--2.26 N/mm2 (0.82-5.08) versus 1.57 N/mm2 (0.51-3.71), P = 0.002. Less pronounced effects were found after incubation with hRLX (10(-7) mol/l). No quantitative or qualitative changes of the membrane collagen were found after relaxin incubation. Although the mechanism for rupture of the fetal membranes remains unknown, the present results suggest that relaxin might be involved in the process leading to rupture of the membranes.

Amnion