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Biomedical subjects

G Kundt

Publications and source records attributed to G Kundt.

At least 19 recordsLinked to original sources
PubMed2001

Simultaneous immunohistochemical detection of tumor cells in lymph nodes and bone marrow aspirates in breast cancer and its correlation with other prognostic factors.

PURPOSE: We studied the prognostic and predictive value of immunohistochemically detected occult tumor cells (OTCs) in lymph nodes and bone marrow aspirates obtained from node-negative breast cancer patients. All were classified as distant metastases-free using conventional staging methods. PATIENTS AND METHODS: A total of 484 patients with pT1-2N0M0 breast cancer and 70 with pT1-2N1M0 breast cancer and a single affected lymph node participated in our trial. Ipsilateral axillary lymph nodes and intraoperatively aspirated bone marrow were examined. All samples were examined for OTCs using monoclonal antibodies to cytokeratins 8, 18, 19. Immunohistological findings were correlated with other prognostic factors. The mean follow-up was 54 +/- 24 months. RESULTS: OTCs were detected in 180 (37.2%) of 484 pT1-2N0M0 patients: in the bone marrow of 126 patients (26.0%), in the lymph nodes of 31 patients (6.4%), and in bone marrow and lymph nodes of 23 (4.8%) patients. Of the 70 patients with pT1-2N1MO breast cancer and a single involved lymph node, OTCs were identified in the bone marrow of 26 (37.1%). The ability to detect tumor cells increased with the following tumor features: larger size, poor differentiation, and higher proliferation. Tumors of patients with OTCs more frequently demonstrated lymph node invasion, blood vessel invasion, higher urokinase-type plasminogen activator levels, and increased PAI-1 concentrations. Patients with detected OTCs showed reduced disease-free survival (DFS) and overall survival (OAS) rates that were comparable to those observed in patients who had one positive lymph node. Multivariate analysis of prognostic factors revealed that OTCs, histological grading, and tumor size are significant predictors of DFS; OTCs and grading of OAS. CONCLUSION: OTCs detected by simultaneous immunohistochemical analysis of axillary lymph nodes and bone marrow demonstrate independent metastatic pathways. Although OTCs were significantly more frequent in patients with other unfavorable prognostic factors, they were confirmed as an independent prognostic factor for pT1-2N0M0, R0 breast cancer patients.

Adult↗
PubMed2001

Ultrasonographic detection of asymptomatic endometrial cancer in postmenopausal patients offers no prognostic advantage over symptomatic disease discovered by uterine bleeding.

The aim of this study was to investigate whether endometrial carcinoma (EC) screening by transvaginal sonography (TVS) has a prognostic advantage over symptomatic EC. In a retrospective study, 190 postmenopausal patients with symptomatic EC and 123 asymptomatic patients with suspicious endometrium detected by TVS were analysed regarding clinical, socio-economic and histopathological findings. Total bleeding time and the International Federation of Gynecology and Obstetrics (FIGO) tumour stage were evaluated with respect to their effect on survival. In 123 asymptomatic patients with suspicious endometrium, 16 (13%) EC, 61 (50%) polyps, 21 (17%) hyperplasias, 23 (19%) atrophias, 1 (0.8%) myoma and 1 (0.8%) metastasis were found. TVS findings in asymptomatic patients resulted in unnecessary operations, which were associated with considerable costs totalling at least 116256. Compared with screened asymptomatic patients, symptomatic patients were significantly (P<0.05) older, more frequently obese, and hypertensive, had a larger proportion of cases living in rural areas and visited their gynaecologists rarely. The bleeding time of symptomatic patients strongly correlated with the tumour stage (P<0.0001). Depending on the bleeding time, the 5-year disease-free survival and overall survival rates were 77% and 86% (no bleeding), 83% and 98% (<8 weeks), 74% and 90% (8-16 weeks), and 62% and 69% (>16 weeks), respectively. The corresponding tumour stage-related data for disease-free and overall survival were 100% (Ia; both rates), 87% and 95% (Ib), 66% and 93% (Ic), 63% and 78% (II) and 36% (III/IV; both rates), respectively. Postmenopausal vaginal bleeding represents an early symptom of EC, but it is not always perceived as problematic by the patients. There is no prognostic advantage for screened compared with symptomatic patients, who had bleeding of shorter than 8 weeks. Moreover, patients who are at a high risk for EC tend to avoid TVS screening. Finally, endometrial screening often results in unnecessary operations, which are associated with increased morbidity and costs.

Aged↗
PubMed2000

Effects of adjuvant tamoxifen on the endometrium in postmenopausal women with breast cancer: a prospective long-term study using transvaginal ultrasound.

PURPOSE: To study the value of transvaginal ultrasound (TVS) in endometrial screening of postmenopausal breast cancer patients treated with tamoxifen. PATIENTS AND METHODS: In 247 tamoxifen-treated (20 to 30 mg/d for >/= 2 years) women and 98 controls, the endometrium was prospectively followed-up by means of TVS every 6 months for up to 5 years. Patients with homogeneous endometrium of more than 10-mm thickness were then scanned repeatedly every 3 months. RESULTS: The mean endometrial thickness was 3.5 +/- 1.1 mm before treatment and increased to a maximum of 9. 2 +/- 5.1 mm after 3 years of tamoxifen application (P: <.0001), which was significantly (P: <.0001) thicker compared with controls. Fifty-two asymptomatic patients with thickened or morphologically suspect endometrium underwent hysteroscopy and dilatation and curettage (D&C), resulting in four uterine perforations. Histopathologically, atrophy was found in 38 patients (73.1%), polyps in nine, hyperplasia in four, and endometrial cancer in one case. In 20 screened patients who reported vaginal bleeding, five atrophies (25%), five polyps, four hyperplasias, and two endometrial cancers were found. Before hysteroscopy and D&C were performed, 36 (69.2%) of 52 asymptomatic and four (20%) of 20 symptomatic patients were scanned by repeated TVS over 2 to 30 months. Invasive diagnostic procedures were significantly (P: <.05) more frequent in younger and obese patients. In the controls, one asymptomatic polyp and one symptomatic hyperplasia were found. CONCLUSION: In tamoxifen-treated patients, TVS offered a high false-positive rate, even with a cutoff value of 10 mm for endometrial thickness and repeated TVS scans. Increased iatrogenic morbidity and only one asymptomatic endometrial carcinoma do not warrant endometrial screening by TVS in tamoxifen-treated patients.

Adult↗
PubMed2000

p53 mutational spectra are different between squamous-cell carcinomas of the lip and the oral cavity.

We studied the p53 mutational spectra of 34 lip and 60 intra-oral squamous-cell carcinomas and examined possible etiological and prognostic correlations for these tumor sites. For the p53 analysis of exons 5-8, we used PCR/TGGE screening followed by DNA sequencing. Mutations were found in 18/34 (53%) lip and 22/60 (38%) intra-oral carcinomas. The p53 mutational spectrum of the intra-oral carcinomas comprised transitions and transversions in nearly equal frequency (11 to 10). In comparison, transitions were 3.5 times more frequent than transversions (14 to 4) in carcinomas of the lip. The predominant types of base change found in intra-oral tumors were G:C-to-T:A transversions and G:C-to-A:T transitions (32% each), while in lip tumors G:C-to-A:T transitions (70%) were the most frequent. The rate of lip tumors with mutations was higher in non-smokers (8/13) than in smokers (9/20). In contrast, p53 mutations in intra-oral tumors clustered in smokers (18/47 vs. 2/10). G:C-to-T:A transversions, regarded as tobacco smoke-associated in lung cancer, were found in 2 moderate and 4 heavy smokers with intra-oral cancer. This base substitution was found in none of our lip cancers. In lip tumors, a high rate of mutations occurred at dipyridine sites (13/18); among these were 8 C-to-T transitions and 1 CC-to-TT tandem base transition. These changes are characteristic of DNA damage caused by UV light. The presence of mutational events at the DNA-binding surface of the p53 protein may correlate with poor clinical outcome. However, we could not find any statistically significant correlations between p53 status and survival. Only the recurrence-free interval was significantly shortened in cases with mutations affecting residues of the DNA-binding surface of the p53 protein.

Alcohol Drinking↗
PubMed2000

Comparison of several approaches of therapeutic drug monitoring of cyclosporin A based on individual pharmacokinetics.

OBJECTIVE: The clinical outcome of patients after organ transplantation is correlated with cyclosporin A (CyA) exposure. It is generally accepted that the area under the concentration-time curve (AUC) provides a reliable means for drug exposure. However, in routine therapeutic drug monitoring (TDM) of CyA, trough levels are mostly used. Currently, a number of different new concepts of CyA-TDM, including approaches such as single, double or triple time-point and abbreviated AUC determinations, have been introduced. The purpose of this study was to compare the predictive value of the different strategies of TDM. METHODS: Calculations were based on 40 individual concentration time profiles after oral administration of CyA to patients who had been included into an ongoing prospective clinical trial. Non-compartmental analysis was used to calculate the AUC0-12h. Multiple linear regression was performed to describe the relationship between the different sets of blood concentrations and the respective AUC0-12h as well as to evaluate their predictive value regarding AUC. Predictive performance was assessed by prediction bias and prediction precision, which were estimated as the mean prediction error and root mean squared error, respectively. RESULTS: When comparing the various combinations of time points, it was found that one-point approaches showed the strongest differences with regard to the predictive value; the associated r2 values differed from 0.203 to 0.792. The two and three time-point approaches showed lower differences - r2 0.802-0.972. The four-point and five-point approaches (r2 0.942-0.982) were the strongest predictors for CyA AUC0-12h. Relative bias ranged from -27.7% to 63.8% and changed significantly when multiple-point predictors were used. In those cases, the predictive performance improved. Considering the predictive performance as well as the smallest bias and highest prediction precision, C3, C1 + C3, C1 + C3 + C6 and C1 + C2 + C3 + C6 were the best predictors. CONCLUSION: The results of this study indicate that in kidney transplant patients a clinically sufficient precise estimation of the CyA AUC is possible using two or three concentration time points.

Adult↗
PubMed2000

[Analysis of the dynamics of the ciliary muscle during accommodation].

BACKGROUND: The magnitude of anterioaxial shift of the human ciliary muscle during accommodation and its ceasing of ciliary function with advanced age are still unknown. PATIENTS AND METHODS: A total 105 patients (aged 10-91 years) were examined by high-resolution ultrasound biomicroscopy during disaccommodation and voluntary accommodation. Accommodative changes in the total area of the ciliary muscle and in the outer contour were quantified with a specially developed software program for automatic contour determination. RESULTS: A significant anterior shift independent of age was observed in the total area of the ciliary muscle and defined points on the outer contour of the muscle in the range of 56-121 microns, while the inward displacement was less obvious. A decrease in the magnitude of configurational changes during accommodation was observed with age. CONCLUSION: The new software program could be useful in further investigations of the accommodative process and evaluation of the potential causes of presbyopia.

Accommodation, Ocular↗
PubMed2000

[Skin sparing mastectomy with autologous immediate reconstruction: oncological risks and aesthetic results].

OBJECTIVE: Is the oncological safety of skin sparing mastectomy (SSM) with immediate autologous reconstruction and improved aesthetic results comparable to postoperative findings in patients treated with modified radical mastectomy (MRM)? MATERIAL AND METHODS: Sixty patients with T1-2 breast carcinomas and contraindications for breast conserving therapy were treated by SSM and compared to 81 patients of the same age groups and MRM with regard to oncological and aesthetic data. In 33 (55%) patients the nipple areola complex (NAC) could be spared. For autologous tissue TRAM- and Latissimus dorsi-flaps were used. The mean follow-up was 40 (range 20-71) months. RESULTS: The observed local recurrence rates were not significantly different (p = 0.443) after SSM (n = 3; 5.0%) or MRM (n = 5; 6.2%). Distant metastases and death were seen in 26.7% and 15.0% (SSM), respectively, and in 25.9% and 13.5% (MRM), respectively. Body mass index, operation time and postoperative haemoglobin concentration differed between both groups significantly (p < 0.001) but not the rate of complications (p = 0.232). Aesthetic results of SSM were judged as excellent or good in 90.0% of patients and in 83.4% of surgeons. Nine patients (11.1%) underwent a secondary breast reconstruction after MRM. Furthermore, 12 (14.8%) patients with MRM would prefer a SSM with immediate reconstruction in a similar situation. CONCLUSION: Skin-sparing mastectomy improves aesthetic results to a high degree without increasing of local or distant recurrence rates. Skin-sparing mastectomy should be offered to selected patients with breast cancer as an alternative to modified radical mastectomy.

Adult↗
PubMed2000

Cartographic mapping of health data.

Health is a primary, individual interest of the population. The observation of health standard and health risks requires the consideration of geographical information. The cartographic visualization of health data is used to show spatial relations and correlations. A presupposition is that health data has local references. There are various local references: the local reference by domicile is most important in investigating the spatio-temporal occurrence, the geographically spread, the intensity and temporal periodicity of diseases. Cartographic visualization allows a quick and intuitive recognition of the situation in a geographical region.

Data Collection↗
PubMed1999

Detection of residual aneuploid leukemic cells by "continuous gating".

BACKGROUND: A new method for the detection of residual aneuploid leukemic cells in bone marrow by flow cytometry is described. This method is based on the analysis of FCM derived list-mode-datasets with a new software called "Continuous Gating". The program is able to decrease the detection level of aneuploid tumor cells by analyzing groups of cells with comparable antigen density and scatter properties. METHODS: Aneuploid acute lymphocytic leukemia cells with a known CD34 expression were diluted with diploid bone marrow cells to a concentration of 10, 1, 0.1, 0.05, and 0.01%. Each sample was measured in a FACScan flow cytometer, after staining with CD34 Moab and propidium iodide. Listmode-data were analyzed with the new "Windows"-based "Continuous Gating" software. A gate was set in the DNA parameter, defining the channels in which the aneuploid G0/G1-peak of possible residual tumor-cells should be found. Ten thousand overlapping gates of size 200 x 200 channels (out of 1,023 x 1,023 channels) were set automatically by the program into the side-scatter (SSC)/CD34 dot-plot, calculating the percentage of aneuploid G0/G1-phase cells for every specific gate. RESULTS: The results are plotted in a contour-plot. In dot-plot gates with less than 20 cells, the calculation of the percentage of aneuploid cells was declared invalid and the area in the contour-plot was marked. Detection of residual aneuploid cells, based on a defined expression of CD34 and granularity (SSC), was possible down to a contamination of 0.1%. CONCLUSIONS: The new "Continuous Gating" software can be used for the automated detection of aneuploid leukemic cells, if the density of a certain surface-marker is slightly different from normal cells.

Adult↗
PubMed1999

[Simultaneous radiochemotherapy with carboplatin in patients with inoperable advanced stage III and IV head and neck tumors].

BACKGROUND: The results of treating advanced tumors in the head and neck region with radiotherapy alone are disappointing. Concurrent radiotherapy and chemotherapy may improve this situation. The treatment results of concurrent radiochemotherapy at the University of Rostock were analyzed retrospectively. PATIENTS AND METHODS: From 1991 to 1996 92 patients with head and neck tumors were treated with concurrent radiochemotherapy (1.8 to 63 Gy; 70 mg/m2 carboplatin day 1 to 5 and 29 to 33) with palliative tumor resection (n = 37) or without surgical treatment (n = 55). Remission rate, overall survival and disease-free survival, local control and acute toxicity were analyzed. RESULTS: Six weeks after radiochemotherapy 56.5% of patients had a complete remission, 36% a partial remission and 7.5% "no change". With a median follow-up of 42 months (6 to 74 months) overall survival, disease-free survival and local control were 24.3%, 28.9%, 18.0% 5 years after treatment. All these criteria were significantly better in patients with palliative tumor resection compared to no surgical treatment (uni- and multivariate) and in patients with Stage III than in patients with Stage IV carcinomas (univariate), overall survival was significantly better in patients with Stage III (multivariate). A pretherapeutic Hb level below 7.0 mmol/l (11.27 g/dl) reduced the local control significantly (uni- and multivariate). Grade III and IV mucositis was detected in 10%, Grade III leucopenia in 12% of treated patients. Grade IV leucopenia and Grade III thrombopenia were observed in 1 patient each. CONCLUSION: The toxicity of this treatment is tolerable. However, additional trials must be conducted before considering the palliative tumor resection as standard therapy.

Adult↗
PubMed1999

Disturbances of palatogenesis and their prophylaxis in animal experiments.

The goal of this study using experimental animals was to induce disturbances of palatogenesis which are comparable to human maxillary clefts. Simultaneously, an in vivo method of testing presumed antiteratogenic substances is presented. 13 gravid Wistar rats bearing 98 fetuses received 200 mg/kg of procarbazine on day 14 post conception (p. c.) to induce malformations. 7 of these gravid animals, bearing 48 fetuses, additionally received 200 mg/kg thiamine daily from day 13-19 p. c. to prevent malformations. On day 20 p. c., the fetuses were teratologically screened: all fetuses were externally examined, the skeletons of 1/3 were visualized using cartilage/bone staining methods, and the heads of 2/3 were histologically examined in 24 sequential frontal sections. At birth, the procarbazine-damaged fetuses exhibited a high rate of cleft palate, primarily involving the secondary palate (94%), which was accompanied by retardation and delayed ossification of the viscerocranium. 66% of the fetuses showed pronounced brachygenia. The disturbances of palatogenesis were frequently accompanied by disturbed odontogenesis, which chiefly manifested itself near the cleft of the frontal maxilla as a reduction in size (63%), retardation (38%) or absence (31%) of the tooth germ. In the trial group additionally treated with thiamine, the findings did not differ significantly from these. The animal model presented here proved suitable for studying palatogenesis and localization-specific testing of substances presumed to have antiteratogenic effects. A prophylactic effect of thiamine initially tested as a highly-dosed monotherapy was not verifiable.

Abnormalities, Drug-Induced↗
PubMed1998

[Corneal penetration of various aminoglycosides and quinolones].

BACKGROUND: Penetration of the aminoglycosides gentamicin and tobramycin and chinolones ciprofloxacin and ofloxacin applied as eyedrops and soaked disposable lenses (ACUVUE), used as antibiotic prophylaxis, was investigated. MATERIALS AND METHODS: 217 patients received before undergoing cataract extraction 0.3% solutions of these antibiotics as eyedrops or by soaked ACUVUE-lenses. During surgery 50-100 microliters aqueous humor was aspirated; concentration of gentamicin and tobramycin was analysed by fluorescence polarisation immuno assay, concentration of ciprofloxacin and ofloxacin was analysed by high pressure liquid chromatography. RESULTS: After application of gentamicin and ofloxacin as eyedrops and via soaked ACUVUE-lenses as drug delivery system (DDS) we found higher concentrations than after application of tobramycin and ciprofloxacin by the same modes. After using of soaked lenses as DDS the aqueous humor concentrations of all tested substances were higher than the concentrations after the frequent instillation of eyedrops. CONCLUSIONS: Penetration of gentamicin through normal human cornea is higher than penetration of tobramycin; penetration of ofloxacin through normal human cornea is higher than penetration of ciprofloxacin. The aqueous humor concentrations of ofloxacin applied as eyedrops and DDS, of ciprofloxacin and gentamicin applied as DDS allow their use as antibiotic prophylaxis in cataract surgery.

Anti-Bacterial Agents↗
PubMed1998

Morphometric measurements to quantify the cerulein induced hyperstimulatory pancreatitis of rats under the protective effect of lectins.

In preceding papers we demonstrated an inhibitory effect of wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA) on the cholecystokinin (CCK) binding to the CCK receptor of rat pancreatic cells and also on the CCK induced Ca2+ release and alpha-amylase secretion in vitro as well as on pancreatic secretion of intact rats in vivo. In the present study we show the same inhibitory effect of both lectins on the cerulein pancreatitis of rats. This acute pancreatitis was induced by supramaximal injections (5 microg/kg/h i.v. or 10 microg/kg/h i.p.) of the CCK analogue cerulein in rats every hour. To monitor the degree of pancreatitis, we measured the number and diameter of injury vacuoles in the pancreatic acinar cells as one of the most important signs of this type of pancreatitis by light microscopic morphometry with two different systems on paraffin sections. Furthermore, the serum alpha-amylase activity was measured biochemically. We found a correlation between the diameter of vacuoles inside the acinar cells and the serum enzyme activity up to 24 h. The simultaneous i.p. administration of cerulein and WGA or UEA in a dosage of 125 microg/kg/h for 8 h led to a reduction of vacuolar diameter from 13.1+/-2.0 microm (cerulein) to 7.5+/-1.1 microm (cerulein + WGA) or 7.2+/-1.3 microm (cerulein + UEA). The serum amylase activity was reduced from 63.7+/-15.8 mmol/l x min (cerulein) to 37.7+/-11.8 (cerulein + WGA) or 39.4; +52.9; -31.1 (cerulein + UEA-I). Both parameters allow the grading this special type of pancreatitis to demonstrate the protective effect of the lectins.

Amylases↗
PubMed1997

[Influence of reduction of radiation dosage on the incidence of radiation-induced pneumonitis, pulmonary fibrosis and pericarditis after mediastinal irradiation in the treatment of lymphogranulomatosis].

BACKGROUND: The amount of radiation dose applied in the treatment of Hodgkin's disease is associated with the incidence of complications including radiation-induced pneumonitis, lung fibrosis and pericarditis. Therefore, from the beginning of 1986, we have started to apply a radiation therapy approach with reduced doses in order to minimize complications while maintaining effective treatment. PATIENTS AND METHOD: From 1983 through 1992 141 patients suffering from Hodgkin's disease were included in the present study. All of them were treated by radiation of mediastinum. In 126 cases polychemotherapy was applied before radiation. From 1986 we used a reduced radiation dose in cases that were treated by radiation alone (affected nodal regions with 40 Gy instead of 45 Gy and unaffected nodal regions with 36 Gy instead of 40 Gy) as well as after application of chemotherapy (affected nodal regions 36 Gy instead of 40 Gy and unaffected nodal regions with 30 Gy instead of 36 Gy). Ninety-five patients were treated according to the new therapy protocol. Forty-six patients had been treated with the higher dosages and served as the historical control group. Radiation therapy included Co-60, 15-MV and 9-MV photons, and 15-MeV and 9-MeV electrons. Serial thoracic X-ray controls were performed. CT scans, echocardiographic and electrocardiographic investigations were added in selected cases. RESULTS: During the period from 1983 to 1992, we diagnosed radiation-induced pneumonitis in 31% of the patients who underwent radiation therapy of the mediastinum. In addition, 16% demonstrated lung fibrosis and 10% pericarditis. After implementation of the reduced radiation dosages, the incidence of pneumonitis decreased from 35% to 24% (nearly significant in the 5% range), lung fibrosis from 24% to 12% (p < 0.05) and pericarditis from 26% to 2% (p < 0.01). The efficacy of treatment remained unaffected by the new therapy approach as has been demonstrated for cumulative survival data and recurrence-free intervals. CONCLUSIONS: Reduction of radiation dose in patients with Hodgkin's disease who undergo mediastinal radiation leads to a decrease in the incidence of radiation-induced complications (pneumonitis, lung fibrosis, pericarditis) whereas treatment efficacy remains unchanged.

Evaluation Studies as Topic↗
PubMed1997

Application of thiamine in preventing malformations, specifically cleft alveolus and palate, during the intrauterine development of rats.

OBJECTIVE: Animal experiments were conducted to test the reproducibility of previously documented antiteratogenic effects of thiamine on cleft formation in the craniofacial system. DESIGN: Thirteen gravid Wistar rats carrying 98 fetuses were given the hydrazine derivative procarbacine (200 mg/kg BW) on the fourteenth day postconception (PC) to induce malformations, chiefly cleft alveolus and palate (day of determining presence of sperm was called the first day PC). Seven of the treated gravid rats carrying 48 fetuses were additionally given a daily dose of 200 mg/kg thiamine from the thirteenth to the nineteenth day PC. OUTCOME MEASURES: A comparative analysis of the fetuses in both experimental groups was conducted externally and, for the skeleton, macroscopically using special staining techniques; the heads were analyzed using successional histologic sections; bodies were examined stereomicroscopically using the razor-blade sectioning technique. RESULTS: In 12 of the 16 parameters evaluated, no statistically significant differences were found between experimental groups. In some cases, we even observed an amplifying effect of thiamine on the development of malformations in the rat strain used in our study. CONCLUSIONS: Because several previous authors have repeatedly described treatment with thiamine as one of the sufficient prophylactic measures in slowing the development of viscerocranial malformations, especially cleft alveolus and palate, it is of utmost importance that the timing of treatment and dosage of thiamine be taken into consideration not only in animal experiments but also when applying results to humans.

Abnormalities, Drug-Induced↗