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Biomedical subjects

B Kremer

Publications and source records attributed to B Kremer.

At least 91 records · Page 5Linked to original sources

[Characterization of spontaneous transplant tolerance exemplified by orthotopic liver transplantation: significance of Fas ligand induced programmed cell death].

For the first time, this study provides strong evidence that hepatocytes express functional Fas-ligand protein after orthotopic liver transplantation in specific allogeneic strain combinations. Fas-L expression correlates with intra-graft elimination of alloreactive T cells and subsequent tolerance induction. Thus, detection of Fas-L offers the possibility to be used as a marker protein for tolerized liver transplants.

Animals↗

[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↗

Onset of action, effectiveness and tolerance of levocabastine and nedocromil in topical therapy of seasonal allergic rhinoconjunctivitis. The Deutsche Rhinitis-Studiengruppe.

This study evaluated the effectiviness and the onset of action of levocabastine (CAS 79547-78-7) nasal spray and eyedrops as well as of nedocromil (CAS 69049-74-7) nasal spray and eyedrops in practical relevant circumstances. The study was designed as an open observational study with parallel groups in 10 centres and comprised 102 patients. All patients presented with seasonal allergic rhinitis and evidenced conjunctival symptoms requiring therapy. The patients as well as the investigators were required to rate the symptoms using symptom scores in order to evaluate the effectiveness of the used drugs. The effectiveness according to symptom scores did not differ significantly between investigator's and patient's judgment. Onset of action was within the first hour in 81.6% of the patients treated with levocabastine and in 82.9% of the patients treated with nedocromil. Symptoms were evaluated on a visual analogue scale ranging from 0 to 100. The use of both substances reduced the severity of the reported symptoms by 50% within the first hour. Thus, no significant difference in the onset of action could be observed even though a later onset of action was expected of the stabiliser of mast cell membranes. Both drugs were tolerated well.

Administration, Intranasal↗

[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↗

[Esophageal carcinoma: guidelines in surgical therapy].

According to oncological criteria, resections for esophageal cancer require a combined abdominal and thoracic approach and should include two-field lymphadenectomy. The value of a three-field lymphadenectomy is still under discussion, because this extended lymph node dissection may provide better survival rates for patients with proximal esophageal cancer and positive lymph node stages on the one hand, but will cause increased morbidity, on the other. A neoadjuvant radio- and/or chemotherapy allows down staging in about 50% of patients with advanced esophageal cancer (stage IIB, III or IV). This leads to higher resectability rates, but is not necessarily associated with better survival rates.

Adenocarcinoma↗

[Fractionated, interstitial postoperative HDR-/PDR-brachytherapy with intraoperatively placed probes--initial experiences with a new radiotherapy modality in treatment of recurrent or non-resectable colorectal carcinomas].

Twenty-eight patients with recurrent (82.1%) and/or noncuratively resected (71.4%) colorectal cancer underwent fractionated interstitial BT (20.1 Gy) by using median 5.6 (3-11) afterloading tubes placed directly on the tumor bed intraoperatively. HDR/PDR BT started 2-3 weeks after multivisceral resection (50%) and was combined with external beam radiation therapy in 96% and with chemotherapy (5-FU/Leucoverin) in 86% of the patients. Though the R0-resection rate before BT was only 28.6% multimodality treatment resulted in a local tumor control rate of 64.3%, a survival rate of 53.6%, and a tumor-free survival rate of 42.9%, in an average of 19.8 months (2-43 months) after BT.

Brachytherapy↗

Cytokine-mediated enhancement of epidermal growth factor receptor expression provides an immunological approach to the therapy of pancreatic cancer.

The increased expression of epidermal growth factor receptor induced by tumor necrosis factor alpha renders pancreatic cancer cells more susceptible to antibody-dependent cellular cytotoxicity by a mAb specific for this receptor. Laboratory studies with athymic mice bearing xenografts of human pancreatic cancer cells demonstrated a cytokine-induced ability of the mAb to cause significant tumor regression. In a phase I/II clinical trial, 26 patients with unresectable pancreatic cancer were enrolled into three cohorts receiving variable amounts of the antibody together with a constant amount of tumor necrosis factor alpha. With increasing doses of antibody, the growth of the primary tumor was significantly inhibited. This was reflected by a longer median survival, with one complete remission lasting for 3 years obtained with the highest dose of antibody employed. Thus, a combination of the cytokine, tumor necrosis factor alpha, with a mAb to the epidermal growth factor receptor offers a potentially useful approach for the treatment of pancreatic cancer.

Animals↗

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↗

Frequent expression of complement resistance factors CD46, CD55, and CD59 on gastrointestinal cancer cells limits the therapeutic potential of monoclonal antibody 17-1A.

BACKGROUND: One reason for the failure of monoclonal antibody (mab) trials in most cancer patients might be the presence of complement resistance factors that inhibit complement dependent cytotoxicity (CDC) and the release of inflammatory mediators (e.g., anaphylatoxins). METHOD: We have determined the expression of CD46, CD55, and CD59 in five gastric, three colon, and seven pancreatic human cancer cell lines by immunostaining. The complement activating properties of mabs and conjugates with cobra venom factor (CVF) were studied in a 51Cr-release toxicity assay and in an ELISA to determine the release of C3a. RESULT: Virtually all tumor cell lines strongly expressed CD46, CD55, and CD59, except KATOIII gastric cancer cells (CD55 and CD59 negative). In accordance with other studies we could confirm that expression of CD55 and CD59 inhibits a complement activation by mabs. Whereas 17-1A was able to induce a cytotoxic complement activation on KATOIII cells, neither a CDC nor an anaphylatoxin release (C3a) was observed on MKN28 cells (strong expression of CD55 and CD59). Conjugation with CVF, a strong activator of the alternative pathway of complement, could partially restore the complement activation by mabs. A 17-1A-CVF conjugate, although still nontoxic, induced the release of the anaphylatoxin C3a on both cell lines. The same observations were made in PancTuI pancreatic cancer cells treated with a conjugate of the mab CA19-9 and CVF. CONCLUSIONS: Our study shows that complement resistance is a frequent event in gastrointestinal cancer, limiting the potential of monoclonal antibodies. Mabs, when conjugated with CVF, partially retain complement activating properties by releasing C3a, which in vivo will support a cellular immune response.

Antibodies, Monoclonal↗

Pathological association and dissociation of functional systems in multiple sclerosis and Huntington's disease.

This study examined pathological associations and dissociations of functional cognitive systems in patients with multiple sclerosis and Huntington's disease. Using the subtests of the WAIS-R, two motor tests, and the word fluency test, the interest correlations showed distinct patterns. In comparison to normals, the two clinical groups exhibited a greater degree of association among the tests. Subsequently, word fluency performance was predicted from these tests. For the normals, the overall predictive power was quite low (7%). For the MS group, the predictive power rose to 28%. For the HD group, the predictive power was 50%. These results suggest that pathological association of functional systems may be a marker of brain dysfunction and that the affected systems may be delineated by these methods.

Adult↗

Non-alcoholic duct destructive chronic pancreatitis.

BACKGROUND: The pathology of non-alcoholic chronic pancreatitis has not yet been sufficiently studied. AIMS: To identify the major changes of pancreatic tissue in patients surgically treated for non-alcoholic chronic pancreatitis. PATIENTS: Pancreatectomy specimens from 12 patients with non-alcoholic chronic pancreatitis, including four patients with autoimmune or related diseases (Sjögren's syndrome, primary sclerosing cholangitis, ulcerative colitis, and Crohn's disease), were reviewed. METHODS: Morphological changes were studied histologically and immunohistochemically (to type inflammatory cells) and compared with the pancreatic alterations found in 12 patients with alcoholic chronic pancreatitis. RESULTS: In patients with non-alcoholic chronic pancreatitis, with or without associated autoimmune or related diseases, pancreatic inflammation particularly involved the ducts, commonly resulting in duct obstruction and occasionally duct destruction. None of these features was seen in alcoholic chronic pancreatitis which, however, showed pseudocysts and calcifications. CONCLUSION: The pancreatic changes in patients with non-alcoholic chronic pancreatitis clearly differ from those with alcoholic chronic pancreatitis. The term chronic duct destructive pancreatitis is suggested for this type of pancreatic disease.

Adolescent↗

[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↗

[Instrumental diagnosis for therapy decision making--what is possible and desirable, what is indispensible and what is superfluous in tumors of the pancreas?].

The spectrum of diagnostic procedures in patients with pancreatic malignancies today includes the patient's report and history, laboratory parameters, and modern techniques ranging from ERCP, EUS, CT, angiography, MRCP, and PET to molecular biology and parameters such as the cytological detection of ki-ras mutations. Anamnesis, laboratory parameters, tumor markers, ultrasound investigation, and ERCP are the relevant procedures for establishing the basic diagnosis of a pancreatic malignancy. MRCP will replace ERCP in most cases in future. EUS shows the highest accuracy in the diagnosis of vascular involvement by a pancreatic tumor.

Diagnostic Imaging↗

[Gastrectomy with radical D2 lymph node excision--effective and economically standardized therapy of adenocarcinoma of the stomach].

In a retrospective single center study, the impact of radical D2-lymph adenectomy and splenectomy on operativ course, morbidity, mortality and long-term survival, in 243 patients who underwent radical surgical therapy for gastric cancer, was analyzed. D2-lymph node dissection during gastrectomy or gastric resection did not influence blood loss, artificial respiration time, ICU days or surgical morbidity, whereas splenectomy correlated with a higher hospital mortality, leakage and abscess rate. Due to routinely performed D2-lymphadenectomy long term survival rate (5 years) was 40.6% for all (in detail: 96% in stage IA; 68.5%/IB; 61.2%/II; 35.8%/IIIA; 17.3%IIIB; and 2.6% in stage IV and 58.1% for curative resected patients.

Adenocarcinoma↗

The detection of disseminated tumor cells in bone marrow from colorectal-cancer patients by a cytokeratin-20-specific nested reverse-transcriptase-polymerase-chain reaction is related to the stage of disease.

The dissemination of cancer cells is a prerequisite in the development of micrometastases and solid metastases. Our previous examinations of these cells were based on immunocytological staining of tumor-associated antigens and cytokeratins. We have now developed a highly sensitive and specific detection method based on a nested reverse-transcriptase-polymerase-chain reaction (RT-PCR) of cytokeratin-20 (CK-20) mRNA. Using this method, we examined the bone marrow of 57 patients with colorectal cancer and detected increasing numbers of CK-20-positive samples, depending on the UICC stage. Some 35% of all bone-marrow samples tested positive for CK-20: none were found in colorectal cancer stage 1, 24% were in stage II, 31% in stage III and 71% in stage IV. Investigation of bone-marrow specimens of patients with pancreatic cancer showed that 4 out of 11 patients were positive for CK-20 mRNA. To confirm that sample positivity for CK-20 expression was due to disseminated tumor cells, we examined bone marrow from a control group (n = 16) without apparent carcinoma. In this group, 15 out of 16 donors were CK-20-negative, while one donor with familial adenomatous polyposis showed a CK-20-specific signal.

Base Sequence↗

[Gastrectomy with radical lymphadenectomy--standard therapy of adenocarcinoma of the stomach].

From January 1992 to December 1995, 208 patients with adenocarcinoma of the stomach were admitted for surgical treatment; total gastrectomy was performed in 152 patients. Improvement of survival rates in comparison to earlier European studies could be obtained by radical resection and routinely performed D2-lymphadenectomy without an increase in morbidity or hospital lethality. The results from Japanese researchers could not be reached.

Adenocarcinoma↗