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Biomedical subjects

A Zimmermann

Publications and source records attributed to A Zimmermann.

449 records · Page 25Linked to original sources

Long-term follow-up of serum N-terminal propeptide of collagen type III levels in patients with chronic liver disease.

To evaluate the diagnostic and prognostic significance of the N-terminal propeptide of collagen Type III (Col 1-3) in chronic liver disease, the peptide level was measured in the serum of 4 patients with primary biliary cirrhosis, 5 with chronic persistent hepatitis, 12 with chronic active hepatitis, and 1 with autoimmune hepatitis, for a period of 2 to 10 years and compared with liver function and histology. In primary biliary cirrhosis, Col 1-3 peptide levels were always elevated, regardless of medical therapy; however, after liver transplantation in one patient, the Col 1-3 peptide level decreased. In chronic persistent hepatitis, the peptide level fluctuated around the upper limit of normal. Among patients with chronic active hepatitis, the Col 1-3 peptide level normalized in 2 patients during remission, but was elevated in 7 patients who developed cirrhosis. Only in a patient with autoimmune hepatitis was the Col 1-3 peptide level normal, although the patient developed cirrhosis during prednisone therapy. When prednisone was withdrawn, the Col 1-3 peptide level increased. The data suggest that the serum Col 1-3 peptide may estimate the course of liver fibrosis in chronic liver disease and has prognostic value, particularly in chronic active hepatitis. Persistent elevation suggests ongoing fibrosis and development of cirrhosis; normalization suggests remission.

Adult↗

The evolution of changes in quantitative liver function tests in a rat model of biliary cirrhosis: correlation with morphometric measurement of hepatocyte mass.

The aim of this study was to determine the prognostic significance of functional changes in the liver during progression of cirrhosis. Liver function was quantitated weekly by the aminopyrine breath test (measuring microsomal function) and the galactose breath test (measuring cytosolic function) in rats made cirrhotic by bile duct ligation (n = 14) and in sham-surgery controls (n = 9). Nine rats died spontaneously of cirrhosis. Both the aminopyrine breath test and galactose breath test were sensitive (89%) predictors of death within 1 week, but the galactose breath test was more specific (83%). Morphometric measurements of livers from surviving cirrhotic animals and controls (n = 5 each) showed that mean hepatocyte mass was maintained in the cirrhotic livers [cirrhosis (17.0 +/- 2.0) vs. controls (13.9 +/- 0.9 gm)]. The galactose breath test was also maintained, whereas the aminopyrine breath test was significantly decreased in the surviving cirrhotics. The galactose breath test, but not the aminopyrine breath test, correlated with hepatocyte mass (r = 0.67). The aminopyrine breath test correlated with microsomal aminopyrine N-demethylase activity (r = 0.78). Serial use of quantitative liver tests allows prediction of time of death from cirrhosis in this model.

Aminopyrine↗

Vaginal Ureaplasma urealyticum colonization: influence on pregnancy outcome and neonatal morbidity.

The effects of Ureaplasma urealyticum colonization on pregnancy and neonatal outcome was prospectively studied in women with impending term or preterm delivery. One hundred and seventy women colonized with U. urealyticum as the only pathogenic microorganism and 83 women with negative cultures were enrolled for study. Compared to the controls, U. urealyticum colonization was associated with a significantly increased rate of amnionitis (2% vs 35%; p < 0.001), chorioamnionitis (0% vs 10%; p < 0.05), premature rupture of membranes (12% vs 35%; p < 0.001) and preterm delivery (10% vs 41%; p < 0.001). The rate of vertical transmission ranged from 38% in term infants to 95% in very low birth weight infants. U. urealyticum colonization at birth was associated with an increased risk for the development of respiratory distress syndrome (9% vs 51%), intraventricular hemorrhage (1% vs 7%) and bronchopulmonary dysplasia (4% vs 17%) in very low birth weight infants (< 1500 g). It is concluded that maternal U. urealyticum colonization is associated with amnionitis, chorioamnionitis and preterm delivery, and that tracheal colonization with U. urealyticum increases the risk for respiratory and neurological complications in very low birth weight infants.

Adult↗

Bak expression and cell death occur in peritumorous tissue but not in pancreatic cancer cells.

Bak is a pro-apoptotic member of the Bcl-2 family whose genes are involved in regulation of programmed cell death. Using in situ hybridization, immunohistochemistry, and Northern blot analysis, we studied the expression of Bak in specimens from 12 normal pancreata and 26 primary pancreatic cancers, and correlated the findings with the clinical and histopathologic data of the patients. By comparison with normal pancreas, Northern blot analysis demonstrated a 2.5-fold increase of Bak messenger RNA expression in the tumor samples (P <0. 001). Elevated levels were found in 15 of the 26 pancreatic cancer tissue specimens. In these samples Bak expression was increased 4.3 fold (P <0.001). No association was detected between Bak expression and tumor stage. In situ hybridization and immunohistochemistry revealed that the tumor cells themselves and the stroma cells expressed only low levels of Bak. In contrast, in regions adjacent to the tumor, which showed chronic inflammation, there was always high expression in the acinar and inflammatory cells, explaining the increased Bak levels found in the tumor samples by means of Northern blot analysis. In the normal pancreas the expression of Bak was generally moderate in the acinar cells and low in the ductal and islet cells. In situ analysis using the terminal deoxynucleotidyl transferase method further showed that there was extensive cell death in the peritumorous areas with chronic inflammation. Taken together, these results suggest that in pancreatic cancer Bak expression and programmed cell death are present in cells that are localized in regions of chronic inflammation surrounding the pancreatic cancer cells but not in the tumor cells themselves, a situation that may facilitate tumor growth and spread.

Adolescent↗

Speech evaluation and swallowing ability after intra-oral cancer.

In this study, four methods of postoperative speech evaluation are compared for 19 persons with oral cancers who have undergone oral surgery and/or radiotherapy. The Munich Intelligibility Profile was used for intelligibility testing and semiquantitative scoring by novice listeners. Expert ratings were done on the Therapy Outcome Measure (TOM) Phonological Disability form. For self-evaluation, the EORTC QLQ-C30 and the Head and Neck module was used. Swallowing function was scored on the TOM Dysphagia form. There was a high intercorrelation between the results of subjective speech evaluation by experts and non-experts and the intelligibility test, but no correlation with any of these methods could be shown for the self-evaluation by the participants. Voice quality seemed to have an influence on non-expert scores. Swallowing was a more severe problem for our group than speech impairment.

Aged↗

Perioperative infection prophylaxis and risk factor impact in colon surgery.

BACKGROUND: A prospective observational study was undertaken in 2, 481 patients undergoing elective colon resection in 114 German centers to identify optimal drug and dosing modalities and risk factors for postoperative infection. METHODS: Patients were pair matched using six risk factors and divided into 672 pairs (ceftriaxone vs. other cephalosporins, group A) and 400 pairs (ceftriaxone vs. penicillins, group B). End points were local and systemic postoperative infection and cost effectiveness. RESULTS: Local infection rates were 6.0 versus 6.5% (group A) and 4.0 versus 10.5% (group B); systemic infection rates in groups A and B were 4.9 versus 6.3% and 3.3 versus 10.5%, respectively. Ceftriaxone was more effective than penicillins overall (6.8 vs. 17.8%, p < 0.001). Length of postoperative hospital stay was 16.2 versus 16.9 days (group A) and 15.8 versus 17.6 days (group B). Of the six risk factors, age and concomitant disease were significant for systemic infection, and blood loss, rectum resection and immunosuppressive therapy were significant for local infection. Penicillin was a risk factor compared to ceftriaxone (p < 0.0001). Ceftriaxone saved 160.7 EUR versus other cephalosporins and 416.2 EUR versus penicillins. CONCLUSION: Clinical and microbiological efficacy are responsible for the cost effectiveness of ceftriaxone for perioperative prophylaxis in colorectal surgery.

Aged↗

Solitary plasmocytoma of the larynx.

Solitary plasmocytoma of the larynx is a rare tumor. To our knowledge there are only 73 cases reported in the world literature. We present 2 more supraglottic plasmocytomas and give a review of the relevant literature.

Aged↗

Nuclear mitotic apparatus protein (NuMA) in benign and malignant diseases.

Nuclear mitotic apparatus protein (NuMA) is a 239 kDa internal nuclear matrix protein described to be elevated in cancer patients, especially in colorectal carcinoma and early colorectal cancers. We tested the significance of NuMA as tumour marker in colorectal cancer and also the sensitivity/specificity profile in general. Therefore, we investigated in a retrospective clinical study 507 sera from patients suffering from solid tumours, with the main emphasis on colorectal carcinoma, and 418 sera from patients with benign diseases and healthy individuals. Testing was done with a double monoclonal enzyme immunoassay detecting head and rod domain of NuMA and results were compared to the established tumour associated antigens. Based on a specificity of 95% versus the benign reference group of gastrointestinal diseases, we found--at the time of primary diagnosis--a sensitivity for colorectal cancer of 8% for NuMA, 36% for CEA and 17% for CA 19-9. Regarding T-stages of colorectal cancer no marker detected T1 when regarding 95% specificity-cut-off value but NuMA showed little more sensitivity when based on a 95% specificity cut off value versus healthy. This could not be shown in Dukes' stages. Regarding all other solid tumours tested--all based on a specificity of 95% for the corresponding benign reference groups--no advantage of NuMA in sensitivity for all other solid tumours investigated was found. No additional sensitivity could be observed. Based on our results, the NuMA-assay in its present form has no clinical relevance.

Antigens, Nuclear↗

CA 242 in comparison with established tumour markers in colorectal, pancreatic and lung cancer.

In a prospective study (N = 566) we investigated the tumour associated carbohydrate-protein CA 242, focusing on the question whether CA 242 (CaNAG, Sweden) expression in carcinoma patients is distinctly higher than in benign disorders, especially when compared to CA 19-9 (EIA Roche Germany). A second point of interest was if CA 242 is expressed to a higher extent in early stages of colorectal cancer than CEA (MEIA Abbott, USA) and CA 19-9 are, and third its behavior in pancreatic and lung cancer. We found CA 242 values comparable in healthy individuals and benign gastrointestinal disorders, thus CA 19-9 remains the marker of first choice for pancreatic cancer and CEA for colorectal cancer. CA 242 shows no advantage in lung cancer as compared to the established markers (CEA, CYFRA 21-1 (EIA Roche Germany) and NSE (EIA Hoffmann LaRoche, Switzerland) and no clearly higher expression in early colorectal cancer. Overall, the combination of CEA and CA 242 shows the best sensitivity in colorectal cancer.

Antigens, Tumor-Associated, Carbohydrate↗

CYFRA 21-1 in the early diagnosis of recurrent disease in non small cell lung carcinomas (NSCLC).

UNLABELLED: Due to its high specificity and sensitivity CYFRA 21-1 was found to be the leading marker in NSCLC. We focused our interest on the diagnostic value of CYFRA 21-1 in the detection of recurrent disease of 86 patients suffering from NSCLC following R0-resection (median follow up: 22.7 months). Preoperatively, CYFRA 21-1 was positive (cut off 3.3 ng/mL) in 38 of the 86 patients (45%). 48 hours after surgery all 38 patients had CYFRA 21-1-concentrations within the reference range corresponding to a R0-resection. During further follow up 22 of these patients developed local recurrence and/or distant metastases. All 22 patients showed elevated CYFRA 21-1-values at time of detection of relapse, in 8 patients the CYFRA 21-1-increase preceded the detection of recurrence by 2 to 15 months. 16 patients remained disease free and had stable low CYFRA 21-1-values all the time. Out of the 48 preoperatively CYFRA 21-1-negative patients 15 developed recurrent disease. 7 of the 15 patients proved to express cytokeratin 19-fragments at this time. CONCLUSION: CYFRA 21-1 possesses a high specificity and sensitivity in the detection of recurrent disease of patients suffering from NSCLC and with elevated values at time of primary diagnosis. Thus CYFRA 21-1 could contribute to an economical follow up care. Even if there is not the possibility of curative therapy at time of relapse the early use of systemic therapy could be considered.

Adenocarcinoma↗

Down-regulation of nerve growth factor in poorly differentiated and advanced human esophageal cancer.

BACKGROUND: Binding of nerve growth factor (NGF) to its receptor TrkA leads to intracellular tyrosine kinase activation and regulates the growth and differentiation of various non-neuronal tumours. PATIENTS AND METHODS: In the present study NGF and TrkA were analysed by Northern blot analysis, in situ hybridisation and immunohistochemistry in 41 esophageal cancer samples in comparison to normal controls. RESULTS: NGF mRNA (P < 0.01), but not TrkA mRNA was down-regulated in esophageal cancer samples compared with normal tissues. In the normal esophagus, NGF mRNA and protein was present in epithelial cells of the entire epithelial layer and TrkA mRNA and protein was present in epithelial cells of the basal layer. In esophageal cancer NGF and TrkA mRNA and protein were present in the cancer cells. Down-regulation of NGF correlated with poor differentiation (P < 0.01) and advanced tumour stage (P < 0.01). Low TrkA expression was related to advanced tumour stage (P < 0.05). CONCLUSION: A loss of activation of the NGF/TrkA pathway occurs during tumour progression and may contribute to loss of tumour differentiation in esophageal cancer.

Adenocarcinoma↗

Flow-cytophotometry of nuclear DNA in biopsies of 45 human gliomas and after primary culture in vitro.

DNA distribution in biopsies and cell cultures of human gliomas was examined by flow-fluorescence-cytometry using ethidium bromide staining. Glioblastomas (n = 25) showed "polyploid", "marked tetraploid", or "hypertetraploid" aneuploid karyograms, comparable to subtypes previously proposed by Japanese authors. "Diploid-hyperdiploid" DNA patterns were manifest in 3 cases plus 1 sarcoma--glioblastoma, containing abundant rapidly growing mesenchymal cells. Most tumors showed S-phase increment. "Near-diploid" patterns could be a result of aggregated cells, and small 4 C peaks could be due to non-representative specimens (3 cases). During cultivation, the DNA distribution usually remained stable, but maxima occasionally shifted. Oligodendrogliomas (n = 11) and astrocytomas (n = 9) of low-grade showed low 4 c peaks. High-grade gliomas, however, showed abnormal DNA patterns. Thus, one case of an oligodendroglioma--I developed an abnormal "marked tetraploid" glioblastoma after a 3-year interval presenting its malignant transformation. DNA distribution can obviously vary during tumor evolution. However, it may well support the assessment of grading and more closely define the prognosis in gliomas.

Adolescent↗

[Prenatal diagnosis of osteogenesis imperfecta, type II, following AID].

Osteogenesis imperfecta is a severe disorder of skeletal formation with nonuniform mode of inheritance. Insufficient bone formation in severe cases (Type II and III) leads to spontaneous intrauterine fractures with shortening of the extremities and thoracic deformities. Sonographical, radiological, pathological-anatomical and clinical data are presented and discussed in a case which was diagnosed at the 19. week of pregnancy.

Adult↗

Shape changes and chemokinesis of Walker carcinosarcoma cells: effects of protein kinase inhibitors (HA-1004, polymyxin B, sangivamycin and tamoxifen) and an inhibitor of diacylglycerol kinase (R 59022).

Previous work has shown that PMA and diacylglycerols, activators of protein kinase C (PKC) can suppress cell polarity and locomotor activity of Walker carcinosarcoma cells in vitro, suggesting that PKC activation may result in a stop signal for tumor cell locomotion. This hypothesis was further analysed. The present results show that the DAG kinase inhibitor, R 59022, suppressed tumor cell polarity and strongly inhibited cell locomotion at a concentration of 10(-4), thus supporting the earlier finding that an increased availability of DAGs can suppress the locomotor activity of Walker carcinosarcoma cells. The results support the stop-signal hypothesis of PKC activation insofar as DAG kinase inhibition mimics the effects of DAGs and PMA. In order to clarify further the effects of protein kinase modulation on locomotion, we now extended our studies on structurally different inhibitors of protein kinases. In contrast to H-7, HA-1004 had no effect on cell polarity and did not reduce cell locomotion in the presence of colchicine, but reduced the proportion of spontaneously locomoting cells by 70% at 3 x 10(-4) M. Polymyxin B suppressed cell polarity and locomotion only at concentrations that proved to be toxic. Tamoxifen had no significant effect on cell polarity and locomotor activity. Sangivamycin did not suppress cell polarity and spontaneous locomotion at a concentration range of 10(-9) M to 10(-4) M. However, at 10(-4) M it decreased the proportion of migrating, colchicine-stimulated cells by 50%. The diverse responses to structurally different PKC inhibitors may be explained by their limited and variable specificity for PKC and different mechanisms of action on PKC.

Animals↗