[Development and actual status of animal welfare legislation].
The author informs on the status of animal welfare legislation in the EU as well as in the Federal Republic of Germany.
Animal Welfare↗
Biomedical subjects
G Baumgartner
Publications and source records attributed to G Baumgartner.
Evaluation of Cyfra 21-1 as a marker for lung cancer.
The sensitivity and specificity of Cyfra 21-1 as marker for lung cancer was evaluated in comparison with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). Patients with histologically verified lung cancer and different groups without lung cancer were investigated. Sensitivity of Cyfra 21-1 (cut-off level 2.9 micrograms/l) was 40% for non-small cell lung cancer (NSCLC), 60% for rare histological types and 21% for small cell lung cancer (SCLC). In NSCLC sensitivity of Cyfra 21-1 was 35% for squamous cell carcinoma and 41% for adenomous carcinoma. The highest sensitivity for CEA was 45% in NSCLC, with 57% in the subtype of adenomous cell carcinoma; for SCC 30% was achieved in squamous cell carcinoma and for NSE 66% sensitivity was reached in SCLC. In our patients Cyfra 21-1 and CEA appeared equally useful for evaluating patients with NSCLC.
Adult↗
Distribution of K ions in intermediate KC60.
Explore the source record for details and available documents.
Journal Article↗
The diagnostic value of urinary pyridinium cross-links of collagen, serum total alkaline phosphatase, and urinary calcium excretion in neoplastic bone disease.
Bone metastases strongly affect skeletal metabolism by both their growth and their paracrine activities. However, so far no specific laboratory marker has been found to signal the spread of neoplastic disease to bone. We performed a cross-sectional study of 153 cancer patients and an equal number of healthy controls matched for sex and age, in which we determined serum levels of calcium and total alkaline phosphatase (TAP) as well as the fasting urinary excretion of calcium (uCa) and of the collagen cross-links pyridinoline (uPYD) and deoxypyridinoline (uDPD). The aim of the study was to analyze the diagnostic validity of the biochemical parameters measured with regard to neoplastic bone involvement. In the cancer group, 98 patients had overt bone metastases, as judged from radiographic and radioisotopic bone imaging. The remaining 55 patients were also in an advanced stage of disease, but there was no evidence of malignant bone involvement. In comparison to healthy controls, patients both with and without metastatic bone disease had significantly higher levels of TAP, uPYD, and uDPD (P < 0.0001). Only in cancer patients with bone metastases was the median serum calcium level higher than in the healthy controls (P < 0.02). uCa was the same in cancer patients and the control group. Within the collective of cancer patients, individuals with skeletal metastases had higher levels of serum calcium (P < 0.05), TAP (P < 0.01), and uPYD and uDPD (both P < 0.0001), than patients without evidence of malignant bone disease. uCa did not differ between the 2 groups of cancer patients. The cancer patients were then stratified into 4 subgroups according to the serum calcium level (< or = 2.6 mmol/L >) and the absence or evidence of bone metastases. This stratification revealed that in patients with bone metastases, uPYD and uDPD levels were similar in normocalcemic and hypercalcemic subjects, whereas in hypercalcemic patients, uCa levels significantly exceeded those in normocalcemic patients. When the efficacy of TAP, uCa, uPYD, and uDPD in discriminating between patients with and without bone metastases was evaluated by use of receiver-operating characteristic curves and stepwise multivariate regression analysis, uPYD was found to have the highest diagnostic validity. Using 50 mumol PYD/mol creatinine (i.e. the upper limit of normal range) as the cut-off level, the sensitivity of uPYD was 88.7%, whereas the specificity was only 41.8% (odds ratio, 5.598; 95% confidence interval, 2.547-12.306).(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
[High frequency catheter ablation in AV-nodal reentry tachycardia: clinical significance of slow pathway potentials and junctional tachycardia].
During slow pathway-ablation of AV nodal reentrant tachycardia (AVNRT) with a mean cycle length of 355 +/- 70 ms the clinical significance of slow pathway electrograms (SP-EGM) and junctional tachycardias (JT) was evaluated in 39 patients (9 male, 30 female; mean age 57 +/- 15 years). After two patients were excluded from further investigation because of inadvertent procedural complete heart block, typical SP-EGM were recorded in 30/37 patients (81%) before successful RF administration in the posteroseptal portion of the right atrium. Signals were recorded 61 +/- 22 and 34 +/- 24 ms after atrial activation in the His bundle and proximal coronary sinus catheter, respectively. Additionally, timing was noted 15 +/- 10 ms before the His spike; the duration of SP-EGM was 27 +/- 7 ms, and the A/V relation of the SP-EGM was calculated as 0.59 +/- 0.51 in the ablation bipole. JT was observed in 24/37 patients (78%), with a mean cycle length of 511 +/- 92 ms. The first tachycardia beat appeared initially 4.1 +/- 3.8 s after delivery of the successful RF administration and lasted 18 +/- 8 s. In 14/37 patients (38%) either SP-EGM or JT was missing; in one patient neither of these two was recorded despite successful ablative therapy. The success rate, defined by noninducibility of AVNRT, was 95% (35/37). In 11% (4/37) AVNRT recurred during a mean follow-up of 5 +/- 4 months. In summary, SP-EGM and JT were recorded reproducibly and proved to be a useful tool as electrographic mapping approach of slow pathway ablation in AVNRT.
Adult↗
[CYFRA 21-1: initial experiences in bronchus carcinoma and other tumors].
CYFRA 21-1 (CYFRA) is a new tumor-associated marker which appears to be useful in monitoring non-small cell bronchial carcinoma. We examined 193 sera from tumor patients (92 of whom had bronchial carcinoma), and 62 patients with benign lung disease. Sensitivity and specificity of CYFRA was compared with that of CEA, TPA, TPS and SCC in squamous cell bronchial carcinoma and with that of NSE in small cell bronchial carcinoma. The sensitivity of CYFRA in other tumor localizations was also assessed. In squamous cell bronchial carcinoma CYFRA proved to be the best marker with respect to sensitivity (58%) and specificity (98%). In gastrointestinal tumors CYFRA had a similar sensitivity to CEA. Since the two markers do not correlate their sensitivity is additive. In conclusion, CYFRA is confirmed as marker of first choice in squamous cell bronchial carcinoma. In other tumors CYFRA displayed a similar sensitivity to CEA.
Adult↗
High-dose intravenous melphalan in a patient with multiple myeloma and oliguric renal failure.
A kappa light-chain myeloma was diagnosed as the underlying disease in a 52-year-old woman with acute oliguric renal failure. The patient was erroneously treated with high-dose intravenous melphalan (60 mg/m2). Because of this overdose treatment with granulocyte colony-stimulating factor was initiated, but pronounced absolute leukopenia (white blood cell count < 0.5 x 10(9)/l) developed and lasted for 13 days. Following melphalan treatment a continuous increase in urine volume was accompanied by a decrease of serum creatinine and blood urea nitrogen. Within 10 days after the administration of melphalan the patient no longer required hemodialysis. We conclude that high-dose chemotherapy in combination with hematopoietic growth factors should be considered in individual cases with newly diagnosed light-chain nephropathy.
Acute Kidney Injury↗
Successful radiofrequency ablation of adenosine-sensitive right ventricular outflow tract tachycardia.
We report on a patient without evidence of structural heart disease who presented with adenosine-sensitive sustained ventricular tachycardia with left bundle branch block and right axis QRS morphology. Endocardial catheter mapping revealed the origin of ventricular tachycardia to be located in the right ventricular outflow tract, where the earliest endocardial activation during ventricular tachycardia was registered 30-40 ms prior to onset of QRS complex in the surface ECG. Pace-mapping provided no additional information; we found a good match between 12 lead surface ECGs registered during spontaneous episodes of ventricular tachycardia and those recorded during pacing in a relatively large area in the right ventricular outflow tract. The 10th application of radiofrequency current abolished ventricular tachycardia temporarily, but it recurred within 30 min. After the 28th radiofrequency current delivery ventricular tachycardia was permanently abolished.
Adenosine↗
Parathyroid hormone-related protein and life expectancy in hypercalcemic cancer patients.
We determined the effect of raised serum levels of midregional (53-84) parathyroid hormone-related protein (PTHrP) on life expectancy in 59 cancer patients with first presentation of hypercalcemia. The patients were stratified according to the serum PTHrP levels measured on day 0 after fluid repletion prior to bisphosphonate therapy. Twenty-nine patients were assigned to group N (PTHrP < or = 21 pmol/L) and 30 to group E (PTHrP > 21 pmol/L). Breast cancers were more common in group N, squamous cell cancers predominated in group E (p < 0.02). More patients with normal PTHrP had skeletal metastases, whereas group E was characterized by a higher incidence of prognostically unfavorable visceral involvement (p < 0.001). Bisphosphonates (pamidronate or BM.210955) were administered on day 0. Within one week, normocalcemia (serum calcium < or = 2.6 mmol/L) was restored in 96% of patients in group N, compared to 70% of patients in group E (p < 0.01). On day 12, 7 patients with elevated PTHrP were still hypercalcemic. Although a comparable number of patients in the two groups received cytostatic treatment after day 12, objective tumor responses were seen only in group N (n = 6; p < 0.05). Calculated from the first occurrence of hypercalcemia, the median survival was 66 days in group N and 33 days in group E (log-rank test: p = 0.0456; Wilcoxon-Breslow test: p = 0.0475). We conclude that in hypercalcemia of malignancy raised serum levels of PTHrP indicate a reduced hypocalcemic response to bisphosphonates, a more advanced tumor state and, therefore, an extremely poor prognosis.
Adult↗
[Remaining developments and status of animal welfare legislation].
The author reports that in Germany animal welfare gets increasing importance in public opinion. He informs on the status of animal welfare legislation in the EU as well as in the Federal Republic of Germany.
Animal Welfare↗
Role of the MDR-1-encoded multiple drug resistance phenotype in prostate cancer cell lines.
The treatment of advanced metastatic prostate cancer by hormone manipulation or orchiectomy is frequently followed by the appearance of hormone-insensitive and highly chemoresistant tumor cells. In this study we have investigated the contribution of the P-glycoprotein-mediated drug efflux (multidrug-resistance; MDR) to the cellular resistance of prostate carcinoma-derived cell lines to diverse cytotoxic drugs by detection of P-glycoprotein (P-gp) measurement of P-gp-mediated drug transport and reversal of MDR by chemosensitizers. The in vitro chemosensitivity of three prostate cancer cell lines (PC-3, DU-145 and LNCaP) to doxorubicin was measured in a thymidine incorporation proliferation assay. Growth of the partially hormone-sensitive cell line LNCaP is inhibited by low doses of doxorubicin (IC50:27 ng./ml.), but PC-3 and DU-145 are highly resistant to the drug, with IC50 values of 10 micrograms./ml. and 7.5 micrograms./ml., respectively. The chemosensitivity of the PC-3 and DU-145 cells is increased in response to 1 microM. verapamil, 1 micrograms./ml. cyclosporine A and 2 microM. tamoxifen, which are known to partially reverse the MDR phenotype in other resistant tumors. A verapamil-sensitive drug efflux has been demonstrated for the PC-3 and Du-145, but not for the LNCaP, cell lines, using flow cytometric measurements of the P-gp substrate rhodamine 123 efflux from preloaded cells. In agreement with the functional measurements, the expression of the P-glycoprotein was detected in the PC-3 and Du-145 cell lines in Western blots using the monoclonal C 219 antibody. In conclusion, the chemoresistant and hormone-insensitive PC-3 and Du-145 cell lines express P-gp and exhibit verapamil-sensitive drug efflux, indicative of MDR. However, the low MDR-reversal rates observed in these cell lines in response to chemosensitizers in clinically achievable concentrations (approximately 2- to 3-fold reversal), point to non-MDR-associated cellular mechanisms as dominant factors of chemoresistance in prostate cancer.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Calcium antagonists as modulators of multi-drug resistant tumor cells].
Multidrug-resistance (MDR) is a cellular mechanism, which in certain tumors reduces the chemosensitivity of cells to a characteristic group of structural different cytostatic drugs, as anthracyclines, Vinca alkaloids and others, and correlates with a unfavourable clinical prognosis. In MDR-cells the intracellular concentration of cytostatic drugs is reduced due to the action of the mdr-1-gene-encoded P-glycoprotein (P-gp/gp 170), which functions as drug efflux pump with broad substrate specificity. Many calcium channel blockers of all subclasses (phenylalkylamine, dihydropyridine and benzothiazepine type) and other calcium antagonists inhibit the P-gp-mediated drug efflux and represent modulators of MDR (resistance modifiers, chemosensitizers). Since the sensitized tumor cells express no voltage-gated calcium channels, the induction of changes in intracellular free calcium showed no effect on MDR and the MDR-activity of antagonists is not correlated with their cardiovascular effects, the chemosensitization by these drugs is independent from their action on calcium channels and Ca(++)-regulation. Photoaffinity labelling with reactive derivatives proved the direct competitive interaction of calcium antagonists with the binding site of P-gp for cytostatic drugs as mechanism of action. The MDR-modulation of the doxorubicin or Vinca alkaloid resistance of tumor cells in vitro by verapamil and other calcium channel blockers was confirmed in vivo as increased survival length in mice with tumor transplants in combination with cytostatic therapy. The clinical application of calcium antagonists is limited by their severe cardiovascular side effects associated with the high concentrations required for successful reversal of MDR.(ABSTRACT TRUNCATED AT 250 WORDS)
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Effect of clodronate treatment on bone scintigraphy in metastatic breast cancer.
Because of their high affinity for bone, bisphosphonates are used both in the treatment of benign and malignant bone disease and in radiopharmaceutical bone imaging. A prospective study was undertaken to evaluate whether intravenous clodronate (dichloromethylene bisphosphonate) therapy might affect the results of bone scintigraphy with 99mTc-labeled methylene diphosphonate (MDP). In 11 female patients with breast cancer and metastatic bone disease, quantitative bone scans were obtained using a region of interest (ROI) method on Days 0 and 22. After intravenous clodronate therapy from Day 1 to Day 21, all metastatic bone lesions were still detectable, and median ROI ratios did not differ to a statistically significant extent from baseline values. Serum calcium levels decreased (p = 0.0449), whereas parathyroid hormone concentrations showed an increase (p = 0.0053). Mean serum levels of creatinine, inorganic phosphorus, osteocalcin, gamma glutaminyl-transpeptidase and alkaline phosphatase remained unchanged. However, a more than twofold rise in the serum activity of alkaline phosphatase was measured in three patients. We conclude that 3 wk of intravenous clodronate treatment did not impair the sensitivity of 99mTc-MDP bone scintigraphy in detecting bone lesions in patients with metastatic breast cancer.
Bone Neoplasms↗
[Are amendments to the German animal welfare law necessary?].
The author gives a survey on the actual discussions and negotiations to amend the German Animal Welfare Act. Additionally, he reports about preparations to amend existing and to implement new animal welfare regulations.
Animal Welfare↗
[Recurrent hypoglycemia and lactate acidosis in non-Hodgkin's lymphoma].
Two weeks after partial resection of the small intestine for an intra-abdominal stenosing centroblastic non-Hodgkin lymphoma, a 65-year-old man began to experience recurrent attacks of hypoglycaemia (down to 30 mg/dl) together with lactic acidosis (lactate 5.13 mmol/l), tachycardia and sensations of heat. Very high parenteral glucose input (up to 750 g/day) was necessary to maintain normal blood sugar levels. There was close correlation between the level of glucose consumption and the degree of lactic acidosis. After chemotherapy the abnormalities improved, but recurred as the neoplasm proliferated once more. An endocrine mechanism for the hypoglycaemic attacks was excluded by the low serum concentrations of insulin and of "insulin-like growth factors" I and II and by the fact that the levels of glucagon, glucocorticoids, growth hormone and thyroid hormone were within the normal ranges. There were pleural and peritoneal effusions containing large numbers of tumour cells. Investigated in vitro, the fluids showed a decline in glucose and a rise in lactate concentration. Studies with an artificial pancreas also showed that glucose utilization rate in vivo was increased to four times the normal and that it could be raised still further by insulin stimulation. These findings provide evidence of direct consumption of glucose by the tumour cells in the form of abnormally increased anaerobic glycolysis.
Acidosis, Lactic↗
[PTH-related protein (PTHrP) in serum of patients with tumor hypercalcemia].
Parathyroid hormone-related protein (PTHrP) is a recently described hormone, that was isolated from malignant tumors. It shows many properties of parathyroid hormone (PTH) and is related to the pathogenesis of humoral hypercalcemia of malignancy. Therefore, we analyzed PTHrP in the sera of 30 patients with hypercalcemia of malignancy and compared the values with those obtained in patients with primary hyperparathyroidism, Paget's disease of bone, and normal subjects. PTHrP was quantitated with radioimmunoassay (RIA) using aminoterminal antibodies without and with chromatographical sample purification applying SEP-PAK C18 cartridges. Measurements of PTHrP without sample purification yielded high values in all patient groups. There was no differentiation between patient groups. However, quantitation of PTHrP after SEP-PAK C18 purification of the samples resulted in values above the normal range only in tumour patients. In 30 normal subjects PTHrP levels were 110 +/- 75 pg-eq/ml. Eight out of 30 patients with malignant tumours displayed PTHrP-concentrations above 335 pg-eq/ml. PTHrP levels in patients with primary hyperparathyroidism or Paget's disease of bone were within the normal range. PTHrP concentrations were not affected from renal function. We conclude, that determination of PTHrP after sample purification may contribute to the differential diagnosis of malignant disease.
Aged↗
Synergistic effect of coumarin (1,2 benzopyrone) and endotoxin in the induction of human interleukin-1.
Coumarin as well as its derivatives 7-OH coumarin and 4-OH coumarin were found to stimulate interleukin-1 beta (IL-1 beta) release from freshly isolated human mononuclear cells (MNC) if the culture medium contained fetal calf serum. Under serum-free conditions, almost no induction of IL-1 beta release was observed and the former effect could be completely eliminated by polymyxin B. Therefore, the combined action of endotoxin and coumarin was tested on MNC IL-1 beta production. The coumarins were able to potentiate human MNC IL-1 beta production by lipopolysaccharide (LPS) in a dose-dependent manner. That the effect was due to the presence of coumarins and not endotoxin contamination was shown by negative Limulus amebocyte lysate tests and pre-incubation of the coumarins with polymyxin B-agarose. The latter procedure was able to block endotoxin induced IL-1 beta production but the synergism between coumarin and endotoxin was not influenced by pre-incubating the coumarins with polymyxin B-agarose. Cycloheximide as well as actinomycin D eliminated the induction of IL-1 release by coumarin and LPS demonstrating that the cytokine was newly synthesized after MNC stimulation. In addition, both the total amount of MNC IL-1 beta (cell-associated + extracellular) and the extracellular portion of the cytokine were synergistically decreased if coumarin or its derivatives were added to endotoxin-stimulated cultures. Synergism of coumarin and endotoxin in the induction of interleukin-6 or tumour necrosis factor-alpha could be observed in a smaller percentage of donors. These findings demonstrate an immunomodulatory effect of coumarin on cytokine production by monocytes in vitro which might help to explain some of the biological activities attributed to the drug upon its application in tumour patients.
4-Hydroxycoumarins↗