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Biomedical subjects

P Fritz

Publications and source records attributed to P Fritz.

At least 73 records · Page 4Linked to original sources
PubMed1996

Identification of N2 as a metabolite of acetylhydrazine in the rat.

In the pathogenesis of isoniazid-induced hepatic injury, cytochrome P450-dependent metabolic activation of the metabolite, acetylhydrazine (AcHz), is the crucial step. Exhalation of [14C]-carbon dioxide has previously been used to quantify indirectly this pathway. In contrast, according to the current concept of AcHz bioactivation, molecular nitrogen is produced directly, but has not yet been identified. Here, we measured [15N]-nitrogen and 14CO2 exhalation, after the administration of [15N2]-[14C]-AcHz, in rats. Laser magnetic resonance (LMR) spectroscopy, a new sensitive and specific technique for the measurement of 15N and 14N in gas samples, was used. To demonstrate the involvement of cytochrome P450, rats were treated with phenobarbital (PB) or PB+cobalt(II) chloride (CoCl2) (n = 3 in each group). Time-dependent 15N2 exhalation differed significantly between treatment groups (p < 0.001). At 240 min, cumulative exhalation of 15N was 1.92 +/- 0.43% (mean +/- SE) of the dose in the control group, 2.53 +/- 0.23% in the PB group, and 1.00 +/- 0.15% in the PB+CoCl2 group (p < 0.05 compared to controls, p < 0.01 compared to PB). Cumulative exhalation of 14CO2 in 24 h ranged from 15.1 to 21.9%, with no significant difference between treatment groups. In conclusion, N2 is a metabolite of AcHz. N2 formation reflects the cytochrome P450-mediated activation of AcHz and can be used as an index of this pathway. Generally, LMR spectroscopy is valuable for monitoring any N2-liberating process in vivo.

Animals↗
PubMed1996

Differential effects of dose rate and superfractionation on survival and cell cycle of V79 cells from spheroid and monolayer culture.

Recent developments concerning brachytherapy suggest conditions for an equivalence between the common continuous low dose rate (CLDR) exposure and pulsed irradiation regimens (PDR), provided that total dose is administered in the same overall time. The respective theoretical considerations have been based solely on the phenomenon of sublethal damage recovery. The present study, therefore, aimed to assess a possible influence of growth state/cell cycle progression when CLDR and different super fractionation protocols are compared. The respective experiments were performed with V79 cells that can be grown as a rapidly proliferating monolayer culture or as small spheroids (without hypoxia) where most of the cells are out of cycle. Differential changes in cell cycle distribution occurring during the compared exposure schemes and their impact on cell survival were expected to be expressed most clearly with this model system because of the short G1 phase. Cell irradiations were performed with brachytherapy sources either continuously (137Cs) or with high dose rate pulses (192Ir) at different (1 h and 4 h) pulse repetitions whereby the overall dose rate was kept constant to approximately 1 Gy/h. Cell survival curves were generated by sampling cells at different exposure times or number of pulses, respectively. For spheroid cells an unequivocal decrease of effectivity was demonstrated with decreasing dose per pulse, and the dose effect relation obtained with hourly pulses of 1 Gy was indistinguishable from the CLDR response. For monolayer cells, on the contrary, the scheme of hourly pulses was significantly more effective than the CLDR irradiation. As measured by flow cytometry, this different behaviour could be attributed to the accumulation of cycling cells in the radiosensitive G2/M phase (G2 block) during protracted exposure which was drastically more pronounced for the pulsed scheme compared to the CLDR condition. The observed principle phenomenon of a block to cell cycle progression from high dose rate pulses (at low overall dose rate) may be less expressed in (human) cells having a long G1 period, but if applicable to a clinical situation, an increase of acute effectiveness of a superfractionated brachytherapy protocol has to be considered.

Animals↗
PubMed1996

The ex-vivo isolated, perfused human lung model: description and potential applications.

An ex-vivo isolated, perfused, and ventilated human lung (IPHL) model is well suited for many kinds of physiological, pharmacological, and surgical studies, when the physiological and biochemical conditions in the lung can be maintained near to those in vivo. The aim of this work was to develop such a model. The lung preparations used were available after resection because of bronchial carcinoma. Since the tumor remains intact in these anatomical preparations, this model is particularly suitable for investigation of the pharmacokinetics and effects of anticancer agents. Carrying out a series of 52 IPHL experiments (with 11 whole-lung preparations and 41 lobe preparations), we have established an IPHL model which allows extracorporeal perfusion and ventilation of the resected lungs in physiological conditions for 2-3 hours. The net weight gain during the experiment, wet-to-dry weight ratio for lung tissue, angiography of the pulmonary artery, pulmonary vascular resistance, color and fluorescence of the lung surface, and alveolar gas diffusion into the perfusate proved to be useful parameters to assess the stability of the preparations and the quality of the experiments. To confirm that an intraparenchymal tumor was perfused via the pulmonary artery, methods to detect avidin and dextran-biotin in tumor tissue after administration into the perfusion solution were employed. Histological examination of bronchial as well as tumor tissue, a computerized histoanalyzation, and a tumor grading program demonstrated that IPHL experiments did not interfere with the grading and staging of the tumors-an important ethical precondition for the use of human preparations in an extracorporeal perfusion model.

Carcinoma, Bronchogenic↗
PubMed1996

Immunohistochemical assessment of human microsomal epoxide hydrolase in primary and secondary liver neoplasm: a quantitative approach.

1. Epoxide hydrolases form an enzyme family involved in the metabolism of a variety of xenobiotics including cytostatic drugs and carcinogens. Whether human microsomal epoxide hydrolase--one of the main members of the epoxide hydrolase family--is expressed in neoplasia of the liver has been the subject of a controversial discussion. 2. We therefore developed a quantitative immunohistochemical assay and monitored epoxide hydrolase expression in hepatocellular carcinomas (HCC, n = 20), cholangio-cellular carcinomas (CCC, n = 2) and liver metastases (n = 57) of tumours of various origins, and compared the expression intensities and patterns to normal liver tissue. 3. In normal liver tissue microsomal epoxide hydrolase displays expression of the constitutive type with non-zonal staining of all hepatocytes. 4. When using a quantitative immunohistochemical approach statistically significant differences in microsomal epoxide hydrolase expression were observed between normal tissue, hepatocellular carcinoma and liver metastases (mean optical density 2.35, 1.63 and 0.21 respectively, p = 2.9, 6.3 and 18.9). These data indicate differential expression in different types of liver neoplasm. 5. As microsomal epoxide hydrolase is involved in metabolism of different xenobiotics our findings may have implications for tumour progression.

Aged↗
PubMed1996

Breast carcinoma. Correlations between visual diagnostic criteria for histologic grading and features of image analysis.

OBJECTIVE: To investigate the relevance of image analysis for grading breast carcinomas. STUDY DESIGN: The results of histologic grading were correlated with 18 features of image analysis, including SD. "Simple" characteristics, like area and perimeter, shape indices, optical density and textural features of nuclei from cancer cells, were analyzed. Hematoxylin-eosin-stained tissue sections of 67 cancer specimens were routinely used for the study. RESULTS: We found statistically significant correlations between overall histologic grading and the sum of its subscores and features of image analysis, especially nuclear area, nuclear perimeter and the diameter of the circumscribing circle (diametercirc), including their SDs. The visually and therefore subjectively assessed subscore of the nuclear pleomorphism of histologic grading significantly correlated with the features of image analysis, like nuclear area, nuclear perimeter, diametercirc, integrated optical density and correlation (and their SDs). There were significant relationships between the absolute numbers of mitoses per 10 high-power fields and nuclear area, nuclear perimeter and diametercirc (and their SDs). We did not observe a significant correlation between the subscore of tubule formation of histologic grading and any of the features of the image analysis studied. Furthermore, the correlations between the features of image analysis and the subscores of the visual histologic grading system were analyzed with respect to each other. The subscore of nuclear pleomorphism of histologic grading correlated best with overall grading (r = .72), whereas no significant correlation could be found between the subscores of nuclear pleomorphism and mitotic activity. CONCLUSION: Image analysis provides objectivity and reproducibility to the grading of breast carcinomas and thus could contribute to more individualized prognostication of the disease.

Breast Neoplasms↗
PubMed1995

Immunohistochemical localization of cytochrome P450 2E1 in human pulmonary carcinoma and normal bronchial tissue.

Cytochrome P450 2E1 (CYP2E1) is a major xenobiotic-metabolizing enzyme but data concerning its extrahepatic expression are few. CYP2E1 can metabolically activate many procarcinogens and therefore its presence in the lung might play a role in bioactivation of procarcinogens, so we studied the expression and localization of CYP2E1 in primary pulmonary carcinomas and surrounding normal bronchial tissue from 28 patients. Seromucous glands showed expression of CYP2E1 in 19 and bronchial epithelium in 18 of the 28 samples of normal bronchial tissue. Thirteen of the corresponding cases of primary pulmonary carcinoma showed staining for CYP2E1. In 11 of these 13 cases, CYP2E1 was also present in normal bronchial tissue. There was no statistically significant difference in the expression of CYP2E1 between adenocarcinomas and squamous cell carcinomas. No association was observed between the expression of CYP2E1 in tumour tissue and normal bronchial tissue. However, there was a significant correlation between the expression of CYP2E1 in seromucous glands and bronchial epithelium (r = 0.61, P < 0.01) of normal tissue. We conclude that CYP2E1 can be present in both normal and neoplastic bronchial tissue.

Adenocarcinoma↗
PubMed1995

Immunohistochemical localization of cytochrome P450 3A in human pulmonary carcinomas and normal bronchial tissue.

The cytochrome P450 (CYP) enzymes metabolize drugs and other xenobiotics in liver and also in some extrahepatic tissues. We have studied the expression and localization of CYP3A in primary lung tumours and normal lung tissue from the same patients. Thirty-two patients undergoing partial or total lung resection for therapy of primary pulmonary carcinoma were included in this study. Immunohistochemical staining for CYP3A was performed with a modification of the ABC technique. Eight of the 32 cases of primary pulmonary carcinoma showed expression of CYP3A. In 12 of the 32 cases of normal tissue, the seromucous glands were positive for CYP3A. The bronchial epithelium was positive for CYP3A in 11 cases. We observed no correlation between CYP3A expression in tumour tissue and that in seromucous glands or bronchial epithelium. We conclude that CYP3A is present in both normal and cancerous lung tissue. Our findings suggest, however, no co-expression of CYP3A in lung cancer.

Adult↗
PubMed1995

Inadequate response to H2-receptor antagonists. Absence of parietal cell cAMP-stimulating autoantibodies.

In peptic ulcer patients with adequate (AR; N = 16) and inadequate response (IR; N = 20) to H2-receptor antagonists, the presence of parietal cell cAMP-stimulating autoantibodies was studied. Serum Ig fractions from these patients and 10 control subjects were examined to test whether they could stimulate cAMP production in a gastric cell line model. The human cell line HGT-1 was found to be a sensitive in vitro model for the cAMP stimulation assay as histamine (10 microM) increased by 11-fold the production of cAMP. Neither IgG (4 mg/ml) nor IgG-free Ig fractions (1 mg/ml) isolated from the blood of AR or IR affected cAMP production in the HGT-1 cells. The results obtained with the cAMP stimulation assay were confirmed by indirect immunofluorescence measurements based on frozen sections of rat stomach and kidney. No specific staining of rat parietal cells could be observed with patient sera. In addition, human gastric biopsies of the oxyntic mucosa from the same patients were studied for immunoreactive cell populations to assess organ-specific autoimmune processes. Biopsy specimens from AR and IR showed increased lymphocytic infiltrates, usually associated with gastritis. However, no significant differences in location of various cell populations between AR and IR could be observed. Our findings do not support a recent hypothesis that poor response to treatment with H2-receptor antagonists is due to the presence of autoantibodies.

Animals↗
PubMed1995

Expert consultation by use of telepathology--the Heidelberg experiences.

The benefits and constraint using visual telecommunication in pathology (telepathology) are described based upon the experiences of the authors for more than 4 years. The experiences include first trials in visual telecommunication to analyze image quality, transfer rates, handling of commercially available equipment, and need for routinely diagnostic work followed by routinely expert consultations in frozen sections. A quality control study on diagnostic reliability of bronchial carcinomas was performed later, and the diagnosticly different cases were reclassified by a panel of pathologists using visual telecommunication. The latest experiences are based upon routinely expert consultations in morphologically difficult cases by ISDN-based telecommunication. As a result, image quality and transfer rates are sufficient to permit efficient expert contribution to diagnostically difficult cases in 30-50% of transmitted cases in both common telephone lines and ISDN connections. No influence of various staining procedures, immunohistology, or in situ hybridization on image quality or transfer rates were observed. The area of transmitted images is still too small, and the reliability of ISDN lines is still not sufficient for remote control service in Germany. The handling of commercially available equipment needs to be improved; however, as a general result, telepathology will probably improve the diagnostic quality and access in histopathology within the coming years.

Clinical Laboratory Techniques↗
PubMed1995

Aspects of telepathology in routinary diagnostic work with specific emphasis on ISDN.

Histopathological diagnosis is based upon visual information and additional clinical and environmental factors. Information can be transmitted over long distances in real time without difficulties. Thus, telecommunication is a technique which may be used in pathology. Several approaches have been performed to introduce telepathology into the daily work of pathologists. Histopathological images of intraoperative sections were transmitted between the Department of Pathology, Thoraxklinik, and the Institute of Pathology, Klinikum Baumgärtner Höhe, Vienna. The transfer time of one image lasted 1-2 minutes depending upon the time of the day; i.e. during telephone "rush" hours the transmission time increased from 1.1 min to more than 2.4 min. As an average, 2 different sections of the image at usually 2 different magnifications were transmitted. Parallel discussion of the images, and acoustic assistance in diagnostic classification or advice lasted for an additional average 3 min. A substantial assistance in the intraoperative classification of the diseases was achieved in 35-40% of cases. No breakdown of telephone lines or communication was observed, while this was the case for the telepathology trials performed by ISDN between the Department of Pathology, Thoraxklinik and the Department of Pathology, Robert Bosch Krankenhaus, Stuttgart. These trials included expert consultation of difficult paraffin embedded cases of various lung diseases. The transmission time of 1 image lasted an average 10 sec was the transfer of non average 4-6 images of the same case was required for substantial assistance in diagnostic classification. The value of the diagnostic assistance was confirmed by submission of the corresponding slides to the partner after termination of the telepathology conference.(ABSTRACT TRUNCATED AT 250 WORDS)

France↗
PubMed1995

Quantitation in immunohistochemistry. A research method or a diagnostic tool in surgical pathology?

Quantification of immunohistochemical methods is feasible by two ways, namely microscope photometry and TV densitometry. The rapid progress of computer technology argues largely in favour of the second system. From the immunohistochemical methods either ABC, the PAP or the APAAP method should be chosen. Diaminobenzidine is the H2-donor of choice for the peroxidase mediated systems, whereas Fast Red TR or Neufuchsin can be used with the APAAP system. The test efficiency, and the precision of measurements should be investigated in each laboratory doing quantitative immunohistochemistry. Low levels of coefficients of variation (CV) should be reached for one field of interest. Examples of introducing the method of quantitative immunohistochemistry in a routine laboratory are discussed. The demonstration of either a steroid receptor or a proliferation marker, such as PCNA or Ki67, are seemingly of the greatest clinical interest.

Humans↗
PubMed1994

Combined external beam radiotherapy and intraluminal high dose rate brachytherapy on bile duct carcinomas.

PURPOSE: The aim of this study was to investigate the effectiveness and complications of combined external beam and intraluminal high dose rate irradiation and various adjuvant biliary drainage techniques on patients with bile duct carcinomas. METHODS AND MATERIALS: Eighteen patients with carcinomas of the hepatic duct bifurcation and 12 patients with carcinomas of the choledochus duct or the common hepatic duct were treated with combined external beam radiotherapy and intraluminal high-dose rate brachytherapy. Nine patients received radiotherapy after palliative tumor resection and 21 patients were primarily irradiated. Twenty-five patients completed the full course of radiotherapy. On these patients, the reference doses for the external beam varied from 30 to 45 Gy and for brachytherapy from 20 to 45 Gy. Biliary drainage after radiotherapy was achieved either with percutaneous catheters, endoprosthesis, or stents. RESULTS: The median survival for the entire group was 10 months. The actuarial survival was 34% after 1 year, 18% after 2 and 3 years, and 8% after 5 years. The subgroup with palliative tumor resection exhibit a significantly better survival (median: 12.1 months vs. 7.9 months). Three patients are still living without evidence of disease since 35 to 69 months. Major complications like bacterial cholangitis could be lowered from 37% to 28% through exchange of percutaneous transhepatic catheters to endoprosthesis or stents. The longest lasting drainages were achieved through stents. The frequency of radiogenic ulcera were lowered from 23% to presently 7.6% after the total dose of the high dose rate afterloading boost was reduced to 20 Gy. CONCLUSIONS: The present standard treatment schedule 40 Gy for the external beam and 20 Gy (fourfold 5 Gy) for the afterloading boost seems to be appropriate and well tolerated. After radiotherapy, a permanent supply of drainage should be made with a stent.

Adenocarcinoma↗
PubMed1994

Paradiaphyseal calcific tendinitis with cortical bone erosion.

OBJECTIVE: To determine the clinical, radiologic, and histologic features of calcific tendinitis with cortical bone erosion. METHODS: The records of 6 patients with paradiaphyseal calcific tendinitis and adjacent bone cortex erosion were reviewed. RESULTS: Calcific tendinitis involved the linea aspera in 4 patients, the bicipital groove in 1 patient, and the deltoid insertion in another. Calcium deposits were associated with cortical bone erosions, revealed on plain radiographs in 4 patients and computed tomography scans in 2. Bone scans were performed in 2 patients and showed local hyperfixation of the isotope. In 4 patients, suspicion of a neoplasm led to a biopsy. Calcium deposits appeared to be surrounded by a foreign body reaction with numerous giant cells. Apatite crystals were identified by transmission electron microscopy and elemental analysis in 1 surgical sample. CONCLUSION: Paradiaphyseal calcific tendinitis with cortical bone erosion is an uncommon presentation of apatite deposition disease.

Adult↗
PubMed1994

Characterization of bile ducts in primary biliary cirrhosis and other liver diseases by immunohistochemical demonstration of Lewis(a) or b antigen.

We investigated Lewis(a) and Lewis(b) expression of bile ducts in 68 specimens from various kinds of liver disease. In addition, the number of IgM and IgG synthesizing plasma cells in the hepatic inflammatory reactions were immunostained and counted. We found a statistically significant decrease in the number of bile ducts in PBC (primary biliary cirrhosis) in comparison with either chronic active or persistent hepatitis (CAH/CPH). Bile ducts could be detected easily and constantly by their Lewis antigen expression. Isolated bile duct epithelial cells not apparent in H&E sections could be identified by Lewis(a) and b immunostaining. The number of plasma cells in PBC was significantly different than in (CAH/CPH). A large number of IgM plasma cells was a characteristic feature of PBC. However, neither counting of Lewis(a) and b positive bile ducts nor counting of IgM plasma cells was of definite diagnostic significance in the individual clinical case, since no cut-off value could be determined above or below which a PBC was ruled out or proven.

Bile Ducts↗
PubMed1994

Two-dimensional cryostat section electrophoresis: a novel method and its application to the diseased synovial membrane.

A two-dimensional electrophoresis technique for analysing sections of human tissue is described. Cryostat sections, 10 microns thick, are placed on an isoelectric focusing gel and then transferred to an SDS gel in the second dimension. The protein pattern is visualized by silver staining and is thought to represent soluble proteins. The silver-stained proteins were found to be both reproducible and, to the extent tested, organ-specific. This method was used to analyse 43 synovial membranes from patients suffering from rheumatoid arthritis or degenerative joint diseases. The analysis did not reveal any specific protein pattern for rheumatoid arthritis. The protein spot number was not related to the cause of arthritis. However, the total protein spot number was related to the histomorphological synovitis type, with those exhibiting either an exudative or proliferative synovitis pattern possessing significantly higher protein spot numbers than those specimens exhibiting a sero-fibrous or lympho-plasmacytic pattern of synovitis.

Arthritis, Rheumatoid↗
PubMed1993

[Lethal Salmonella enteritidis meningoencephalitis in an adult with a carcinoma of an unknown primary site].

A 71-year-old man with an aortobifemoral bypass graft had experienced several episodes of severe pain in the thoracic and lumbar spine, followed by severe abdominal pain, during the preceding two weeks. Physical examination, chest X-ray, ultrasonography and computed tomography of the abdomen provided no specific pointers to a diagnosis. He was anaemic (haemoglobin 95 g/l), but had a normal WBC count with neutrophilia (up to 91%) and thrombocytopenia (up to 24,000/microliters). The transaminase and lactate dehydrogenase activities were raised, as were the bilirubin level and the retention values. There was a metabolic acidosis (pH 7.20). Because of suspected septicaemia ciprofloxacin (twice daily 200 mg) was administered intravenously. But the patient gradually lost consciousness, required mechanical ventilation and died 24 hours after admission in circulatory failure. Autopsy revealed a meningoencephalitis, carcinoma of unknown primary with bone marrow carcinomatosis as well as widespread carcinomatosis of blood and lymph vessels. The findings of blood, urine and sputum cultures, available only postmortally, revealed growth of tetracycline-resistant Salmonellae enteritidis.

Aged↗