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Biomedical subjects

D Kindermann

Publications and source records attributed to D Kindermann.

18 recordsLinked to original sources

Frequency of hereditary non-polyposis colorectal cancer among unselected patients with colorectal cancer in Germany.

INTRODUCTION: Hereditary non-polyposis colorectal cancer (HNPCC) is a major form of familial colorectal cancer (CRC). It is diagnosed when either the Amsterdam criteria (AC) are fulfilled or mutations in one of the mismatch repair (MMR) genes have been identified. This project aims at estimating the proportion of HNPCC among unselected patients with CRC. PATIENTS AND METHODS: During a period of 2 years, a total of 351 non-selected patients with CRC were registered prospectively. 92 patients met the Bethesda criteria (9 of them fulfilled the AC) and 259 did not. 348 tumours were examined for microsatellite instability (MSI) and expression of MMR proteins. RESULTS: MSI-H and MSI-L were identified in 17 and 6%, respectively. Loss of MSH2 or MLH1 was found in 1.5 and 8.8%, respectively. Based on the results of tumour tissue analyses, 80 patients with MSI and/or loss of MSH2 or MLH1 expression were identified as candidates for germline mutation screening. DNA of 40/80 patients was available. These patients were screened for MSH2 and MLH1 mutations; 19/40 patients with MSI and normal MSH2 or MLH1 expression were screened for mutations in MSH6. Three patients had relevant MMR gene mutations and six variants of unknown functional relevance were detected. CONCLUSIONS: After adjusting for the cases not evaluable for germline mutations, 1.7% of the CRC patients had HNPCC proven by molecular genetics.

Adaptor Proteins, Signal Transducing↗

Population-based registration of unselected colorectal cancer patients: five-year survival in the region of Bonn/Rhine-Sieg, Germany.

INTRODUCTION: Epidemiological data of colorectal cancer are sparse and often incomplete. Therefore, we initiated a population-based examination of five-year survival of colorectal cancer patients. METHODS: For complete registration, diagnosis and tumour stage of all patients in the region of Bonn/Rhine-Sieg were assessed independently according to reports of medical practitioners and pathologists. Each patient was followed by a standardised questionnaire during a period of five years. RESULTS: Between June and November, 1994 348 patients were registered. Median age at diagnosis was 69 years for males (n = 160) and 72 years for females (n = 188). According to the UICC classification 18, 26, 23 and 26 % had stage I-IV tumours, respectively; the tumour stage remained unclear in 7 %. Adjuvant (radio)-chemotherapy was indicated in 89 patients, but only 49 % of these were treated. Five-year overall survival (OS) and relative overall survival were 41 and 54 %, respectively. Although disease-free survival (DFS) was significantly better for early stage colorectal cancer, OS did not differ significantly between stage I and stage III tumours. Young patients diagnosed before the age of 50 had a significantly lower DFS. These data were comparable with other European countries but were lower than data reported in the USA. DISCUSSION: The high rate of patients with stage IV colorectal cancer and the low proportion of patients receiving adjuvant (radio)-chemotherapy according to international or national consensus recommendations were disappointing. Although data were comparable with other European countries more efforts are necessary to establish effective screening programs for asymptomatic patients and to increase the willingness for standardised adjuvant treatment.

Adult↗

Lack of prognostic relevance of alterations in the epidermal growth factor receptor-transforming growth factor-alpha pathway in human astrocytic gliomas.

Alterations in the epidermal growth factor receptor (EGFR) and its main ligand, transforming growth factor-alpha (TGF alpha), were investigated for a possible prognostic relevance in 125 astrocytic gliomas (44 World Health Organization (WHO) Grade II, 19 WHO Grade III, and 62 WHO Grade IV tumors). The TGF alpha and EGFR proteins were detected immunohistochemically using monoclonal antibodies. A positive immunoreaction to TGF alpha was detected in 33 (75%) of 44 WHO Grade II astrocytomas, 18 (95%) of 19 WHO Grade III astrocytoma, and 50 (81%) of 62 WHO Grade IV glioblastomas. No correlation between TGF alpha immunoreaction and duration of survival could be found. A positive EGFR immunoreaction was detected in seven (16%) of 44 WHO Grade II astrocytomas, five (26%) of 19 WHO Grade III astrocytomas, and 32 (52%) of 62 WHO Grade IV glioblastomas. Of these gliomas, 97 (26 WHO Grade II, 17 WHO Grade III, and 54 WHO Grade IV gliomas) were examined for EGFR gene amplification using a differential polymerase chain reaction assay. Amplification of the EGFR gene was detected in none of the WHO Grade II astrocytomas, one (6%) of 17 WHO Grade III astrocytomas, and 18 (33%) of 54 WHO Grade IV glioblastomas. Twenty-two of the tumors investigated showed a positive EGFR immunoreaction without detectable gene amplification (five WHO Grade II, four WHO Grade III, and 13 WHO Grade IV tumors). Gene amplification was invariably associated with a positive EGFR immunoreaction. For the entire study group, a strong correlation between EGFR alterations (gene amplification and positive immunoreaction) and survival could be found. However, this correlation only reflected the higher percentages of cases with EGFR alterations in malignant gliomas and was not an independent prognostic factor as determined by multifactorial analysis. These data demonstrate that EGFR alterations are frequent events in astrocytic gliomas and are largely restricted to glioblastomas. However, within one tumor grade they do not provide prognostic information.

Adult↗

TP53 alterations and clinical outcome in low grade astrocytomas.

Thirty-eight WHO grade II astrocytomas and 10 malignant recurrent gliomas in these patients were examined for the presence of TP53 alterations. Seventeen/38 low grade astrocytomas and 6/10 malignant recurrent tumors harbored mutations of the gene detected by SSCP analysis and direct sequencing of PCR products. TP53 mutations in five out of six high grade mutant tumors were already present in the corresponding low grade astrocytomas. In two cases, TP53 mutations present in the low grade astrocytoma could not be demonstrated in the recurrent glioma. Immunohistochemistry with two different antibodies to the human TP53 protein revealed nuclear immunoreaction of tumor cells in 11/38 low grade and in 8/10 recurrent tumors. There was no correlation between the presence of TP53 alteration and clinical course. We conclude that, although TP53 mutations are detectable in a substantial fraction of WHO grade II astrocytomas, they do not appear to play a role in the malignant progression of these tumors and they are not of prognostic significance.

Amino Acid Sequence↗

Glare-correction in DNA image cytometry.

We tested the reproducibility of a simple method for glare correction in a modern video-based optical densitometer (CYDOK) by performing repeated measurements of the DNA content on identical sets of different rat hepatocyte DNA-classes and lymphocytes. Using a computer-controlled scanning stage of the microscope we were able to re-localize each nucleus of air-dried Feulgen-stained preparations with different microscope settings. The proposed microscope-adjusted glare-correction algorithm is based on the measurement of the transmittance of opaque bars a standard micrometric glass. The procedure gives local glare errors and allows calculation of the mean glare error which is applicable for the entire view field. Subtraction of this mean glare transmittance from each object and normalization of the background allows the user to eliminate errors due to different nuclear Feulgen-staining intensities. The method eliminates the need to use cell-type-dependent constants to correct the known DNA disproportionalities in air-dried, Feulgen-stained preparations. An additional advantage of the glare correction algorithm is the low coefficients of variation (CV, < 3%) within each nuclear DNA-class which reflect the highly reproducible DNA measurements.

Algorithms↗

Histological findings in a falloposcopically retrieved isthmic plug causing reversible proximal tubal obstruction.

We present the case of a 33-year-old woman with a 10 year history of infertility. Transvaginal falloposcopy revealed a proximal tubal occlusion (PTO) on the right due to a tissue plug. The plug was removed during dilatation of the tubal lumen. After the procedure patency for dye was restored. Histological and immunohistochemical findings--for the first time, to the best of our knowledge, performed in a falloposcopically retrieved plug--revealed the diagnosis of an inflammatory polyp arising from the tubal mucosa with focal calcifications. Local obstructive inflammatory residues of a previously treated tubal endometriosis, which was accompanied by features of salpingitis isthmica nodosa, are considered the most likely cause for this condition. Other possible aetiological factors responsible for PTO are discussed.

Adult↗

[Cytomegalovirus infections of the gastrointestinal tract].

Histopathological findings in 8 cases of CMV infections of the gastrointestinal tract including 5 cases with AIDS are presented. The cytomegalic cells were irregularly distributed and were predominantly found in esophagus, small bowel and colon. Viral inclusions were detected in "stromal" cells and in endothelial cells, sometimes associated with lesions of the vascular wall. Cytomegalic smooth muscle cells and glandular epithelia were also observed. No correlation was found between the number of cytomegalic cells per mm2 of tissue and the inflammatory response. Monoclonal CMV antibodies reacted immunohistologically not only with cytomegalic cells but also with a few normally appearing cells. The in-situ-hybridization detected CMV-DNA also in cells which were negative for CMV antigens. Notwithstanding the new immunohistological techniques the searching for cytomegalic cells and their recognition still belong to the most important steps required for the diagnosis of CMV infection.

AIDS-Related Opportunistic Infections↗

Endoscopic fetal surgery by excimer laser. An experimental study in premature lambs.

Fetal malformations are detected early in pregnancy by means of ultrasound challenging fetal therapy. While open fetal surgery has been preformed during preliminary clinical trials we evaluated fetoscopic therapy avoiding laparotomy and uterotomy. We used a laser fibre (900 mu) which was introduced into the uterus by an endoscope. During animal experiments in five fetal lambs with a gestational age of 120-122 days we used an excimer laser (Technolas, x) with a wave-length of 308 nm. Laser incisions were compared with the conventional cutting technique using a scapel. During histological evaluation the tissue effect was morphometricly analysed. The zone of devitalisation was characterized by pycnosis of the nuclei and in a change of cytoplasma volume. The excimer laser incisions using a frequency of 40 HZ had a mean zone of devitalisation of 50.3 +/- 4.5 mu. Using the excimer laser with a frequency of 10 HZ we found a tissue alteration of only 11.2 +/- 3.4 mu. The incisions by scapel showed a extended traumatisation with a mean tissue effect of 153.2 +/- 16.3 mu. From these results we conclude, that endoscopic surgery may be come a usefull additional tool for fetal therapy.

Animals↗

An approach to fetal surgery: endoscopic use of excimer laser.

Recent progress in the area of prenatal diagnosis by means of ultrasound forces the improvement of surgical techniques for intra-uterine fetal therapy. By the use of short, intense pulses of ultraviolet laser light (20-200 ns long) a photoablation of defined samples of biological tissue is performed with no substantial thermal side effects. The experimental set-up applied in this study included endoscopic operation on five fetal lambs. Macroscopically, a sharp edge in the incision area was observed at both prechosen laser frequencies of 10 and 40 Hz. The clinical application of pulsed ultraviolet laser systems with the characteristics of guided photoablation and atraumatic incisions avoiding thermal side-effects opens new perspectives for fetal surgery.

Animals↗

Effects of propane-2, 2-diphosphonate (PDP) on matrix-induced ectopic bone formation in comparison to ethane-1-hydroxy-1, 1-diphosphonate (EHDP).

The most prominent effect of propane-2, 2-diphosphonate (PDP) and ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on matrix-induced ectopic bone in the rat was a dose-dependent inhibition of osteogenesis in the early phases of development. The delay was seen as a consequence of osteoprogenitor cell inhibition. Additionally, later phases of bone maturation were disturbed by interference with the mineralization and remodeling processes. However, direct effects on the calcium phosphates of bone are only of minor additional value, which remains of lesser importance in comparison to the cellular impairment. After withdrawal of diphosphonates, the effects were nearly completely remitted. Neither PDP nor EHDP, even given in high doses, resulted in a lasting reduction in ectopic mass. The remission may be referred to the recovery of cell activities, whereas the mineral impregnation of osteoidosis was, if at all, of little importance. For treatment of ectopic osteogenesis PDP proved inefficient.

Animals↗

[Pisotriquetral osteoarthritis].

Isolated osteoarthritis of the pisotriquetral joint is rare and can be as disabling as osteoarthritis of any other joint. The authors report on two cases, one in both hands. With typical anamnesis, exact clinical investigation, proper positioning during radiological examination and intraarticular application of anaesthetics, the diagnosis can be easily confirmed. If conservative therapy is unsuccessful, relief of pain can be obtained by excision of the pisiform bone. The biomechanical importance of the pisiform bone in its relation to the flexor carpi ulnaris is discussed.

Aged↗

[Effects of mellitic acid on matrix-induced, ectopic osteogenesis in the rat].

Similar to diphosphonates mellitic acid is characterized by its high affinity to Calcium-phosphate-minerals. Mellitic acid inhibits the crystallization of hydroxyapatite in vitro and in vivo. Local application of mellitic acid (concentration 1 mmol/l) proved not to impair osteoinduction and development of nature bone in the matrixinduced ectopic osteogenesis. But in the course of osteogenesis prominent masses of cartilage developed. Higher local concentrations of mellitic acid may be efficient in the therapy of ectopic ossification, but also may be accompanied by formation of crystal deposition.

Animals↗

[Control of the re-epithelialization of skin defects and burns].

In an experimental study an attempt was made to compare the effect of the tetrachlorodekaoxygen anion complex (TCDO) with an aqueous KCl/CaCl2 solution of a defined molar concentration in hydrogel on the basis of skin defects, irradiated skin defects, and necrectomized burns of the skin of the back of naked euthymic guinea pigs. The wound healing of the irradiated skin defects and the necrectomized burns was found to be generally delayed. The use of the Kcl/CaCl2 solution in hydrogel, however, brought about a faster repair of the defects than the application of TCDO.

Animals↗