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Biomedical subjects

U Pichlmeier

Publications and source records attributed to U Pichlmeier.

47 records · Page 3Linked to original sources

Long-term follow-up of cytostatic intravesical instillation in patients with superficial bladder carcinoma. Is short-term, intensive instillation better than maintenance therapy?

OBJECTIVES: Comparisons of two 3-year protocols, one 20-week protocol of mitomycin C instillation and one 3-year protocol of doxorubicin instillation for the prevention of recurrent tumors and progression in patients whose superficial bladder tumors had been removed by transurethral resection. METHODS: A prospective, randomized parallel group multicenter trial was conducted. 419 patients were evaluated after a median follow-up of 57 months. Cox proportional hazards analysis was performed. RESULTS: An overall recurrence rate of 22.7% and an overall progression rate of 9.8% was found. For time to progression a significant overall treatment effect was detected dependent on the recurrence status before entry into the study (p = 0.0059). Pairwise comparisons showed the mitomycin protocol with short-term intensive (weekly) combined with long-term maintenance instillation to have a highly beneficial effect compared to long-term maintenance instillation only especially for patients entering the study with recurrent tumors (RR = 0.06, 95% CI: [0.008, 0.506]. CONCLUSION: These results show that intensive therapeutic instillation may have an advantage over less intensive, prophylactic regimens.

Administration, Intravesical↗

Autoradiographic mapping of beta-adrenoceptors in human skin.

A high density of beta 2-adrenoceptors has been found in human skin. Using autoradiographic mapping we investigated the distribution of beta 1- and beta 2-receptors in normal and diseased human skin. Cryostat sections of human skin obtained at biopsy were incubated with [125I]-iodocyanopindolol and nonspecific binding was identified by incubation of adjacent sections with 200 microM (-)-isoproterenol; beta 2-receptors were visualized using CGP 20712A and beta 1-receptors using ICI 118,551 as competing agents. The epidermis was densely labelled with an even distribution throughout all layers. Most of the beta-receptors were of the beta 2-subtype, with practically no beta 1-receptors. beta-Receptors were also localized to eccrine sweat glands, dermal blood vessels, and perivascular inflammatory cells, but there was no labelling of sebaceous glands. Topical glucocorticoids caused an increase in the density of epidermal beta-receptors. We conclude that keratinocytes and eccrine sweat glands express high densities of beta 2-receptors, suggesting that they may have a physiological role in the regulation of these cells.

Autoradiography↗

[Validity of fiber optic cerebral vein oximetry during extracorporeal circulation].

INTRODUCTION: This study investigates the accuracy of continuous jugular bulb venous oximetry during different conditions of hypothermic cardiopulmonary bypass (CPB) (27 degrees C) for coronary artery bypass graft. METHODS: 38 ASA III patients were studied following Ethical Care Committee approval and informed consent. Patients were anaesthetized with fentanyl, midazolam, continuous infusion of etomidate and pancuronium. Ventilation was performed with oxygen in air. CPB was managed according to alpha-stat conditions under moderate hypothermia (27 degrees C). SjO2 (%) and jugular bulb temperature (degree C) were measured by a fiberoptic thermodilution catheter (Opticath F 5.5, Abbott Critical Care Systems) placed in the jugular bulb via the internal jugular vein. Appropriate catheter position was x-ray controlled prior to the measurements. The fiberoptic data were compared to co-oximetric data of blood samples after induction of anaesthesia, 2 min following start of CPB, during cooling, stable hypothermia and rewarming of CPB. STATISTICS: Assessing of agreement (Bland/Altman and Bartko). RESULTS: Jugular venous oximetry correlated closely with the co-oximeter determinations after induction of anaesthesia. However, following start of CPB accuracy was decreased. During cooling, stable hypothermia and rewarming oximetric data correlated well with co-oximetry, however, over-estimating the SjO2 by 1.4 to 2%. CONCLUSION: The present data show that continuous jugular bulb venous oximetry is accurate and reliable for continuous SjO2 monitoring during hypothermic CPB for cardiac surgery. Induction of CPB and hemodilution affect accuracy slightly, but changes are well detected. Before clinical intervention SjO2 should be confirmed by laboratory co-oximetry.

Adult↗

Long-term outcome and quality of life after thymectomy for myasthenia gravis.

OBJECTIVE: The authors identify criteria suitable to predict long-term clinical improvement and evaluate quality of life after thymectomy for myasthenia. DESIGN: Retrospective analysis with long-term follow-up (mean 92 months) was conducted for 86 patients and questionnaire interviews were performed for 65 patients who underwent thymectomy between 1976 and 1993. MAIN OUTCOME MEASURES: The authors used the Osserman Score and the European Organization for Research and Treatment of Cancer quality-of-life questionnaire. RESULTS: After thymectomy, lasting benefits were achieved predominantly by patients with moderate and severe myasthenia, and this association was significant (p < 0.001) in both bivariable and multiple analyses. No correlation was observed between outcome and thymic pathology, patient age or gender, duration of disease, preoperative plasmapheresis, and medication. Restitution to normal was complete at most recent follow-up as to physical status, working ability, and cognitive and social functions, but some emotional and vegetative deficits remained. CONCLUSION: Future patient selection for thymectomy should-apart from those with suspected thymoma-concentrate on patients with moderate and severe myasthenia unresponsive to conservative management.

Adult↗

Serum interleukin-6 levels during bone marrow transplantation: impact on transplant-related toxicity and engraftment.

The biological properties of IL-6 include the induction of acute phase proteins, stimulation of hematopoietic stem cell growth and thrombopoiesis. Serum levels of IL-6 were closely monitored in 66 patients before and after allogeneic (n = 37), autologous bone marrow transplantation (n = 8) or autologous peripheral blood stem cell transplantation (n = 21). Almost every patient showed elevated IL-6 serum levels during the aplastic phase. Patients then suffered from mucositis, had elevated C-reactive protein (CRP) and usually body temperatures of above 38 degrees C. It was investigated whether IL-6 serum levels, apart from inducing acute phase reactions, correlated with transplant-related complications or leukocyte and thrombocyte engraftment. By statistical analysis, a correlation was found between IL-6 and CRP and between IL-6 and fever. In contrast, no correlation was found between IL-6 and elevated serum bilirubin as a marker for hepatotoxicity. IL-6 showed a weak negative correlation with leukocyte or platelet counts. In contrast, the day of platelet engraftment correlated with the day of peak serum IL-6 value, possibly indicating an influence of IL-6 on platelet engraftment.

Bilirubin↗

Prevention of experimental endotoxin shock by a monocyte activator.

In patients with polytrauma or major surgery, severe bacterial infections leading to septic shock and multiorgan failure are still a major cause of death. Prevention of septic shock in patients at risk would be an alternative to treatment of patients with overt septic shock. We therefore conducted a trial with the monocyte activator muramyl tripeptide phosphatidylethanolamine (MTP-PE) in an experimental pig model. Liposome encapsulated MTP-PE (50 micrograms/kg of body weight) or liposomes alone were given intravenously at 72 or 24 h before endotoxemia was induced by lipopolysaccharide (LPS), simultaneously with the induction of endotoxin shock, or 1 h thereafter. Pretreatment with MTP-PE at 72 and 24 h before endotoxemia was induced resulted in a reduction of endotoxin shock-induced mortality from 81.8% (9 of 11 animals) in the control group to 8.3% (1 of 12 animals) of the MTP-PE-pretreated animals (P < 0.001). The administration of MTP-PE 24 h before the induction of endotoxin shock was more effective (P < 0.01) than administration of MTP-PE 72 h before endotoxemia was induced (P = 0.05). The pretreated animals did not develop fever or cardiovascular complications, and pulmonary function was significantly improved. Furthermore, the alpha-form of the soluble CD14 LPS receptor in pig serum showed a marked decrease in LPS-treated animals, and this decrease was reduced by MTP-PE pretreatment at 24 h before endotoxemia was induced. When MTP-PE was given simultaneously with the induction of septic shock or 1 h thereafter, it did not influence either mortality or morbidity. In conclusion, pretreatment of pigs with MTP-PE improves several parameters of endotoxin shock and it reduces mortality. Patients with high risk of developing septic complications might benefit from a pretreatment with this monocyte-activating substance.

Acetylmuramyl-Alanyl-Isoglutamine↗

[The significance of regional lymphatic tumor cell dissemination in patients with resectable non-small cell bronchial carcinoma. Results of a prospective study].

Encountering the high incidence of tumor recurrences in patients with apparently resectable non-small cell lung cancer it has to be assumed that in many patients already at the time of surgery a tumor cell dissemination has occurred, which is underestimated by current staging procedures. We therefore conducted a prospective study to assess the frequency and prognostic significance of a nodal tumor cell dissemination by using an immunohistochemical assay. Disseminated epithelial cells were demonstrated in 35 (6.2%) out of 565 lymph nodes staged as tumor free by conventional histopathology and in 27 (21.6%) out of 125 patients, respectively. In pN0 patients disseminated tumor cells were detected in 11/70 (15.7%) cases. In patients staged as pN1 and pN2 by conventional histopathology a tumor cell dissemination to additional lymph nodes was demonstrated by immunohistochemistry in 4/25 (16.0%) and in 12/30 (40.0%) patients, respectively (p = 0.019). Independent from tumor staging univariate survival analysis showed that the detection of a nodal tumor cell dissemination was associated with a reduced disease-free survival (p < 0.001). Multivariate analysis demonstrated that the detection of such cells is an independent prognostic parameter (p = 0.005). In conclusion, the use of immunohistochemistry enables to identify many patients with a widespread regional tumor cell dissemination at the time of surgery. This finding could represent a new criterion for an adjuvant therapeutic regime.

Aged↗

Deteriorating free radical-trapping capacity and antioxidant status in plasma during bone marrow transplantation.

Organ toxicity in BMT may in part be due to free radical damage. Therefore the 'Total Radical-trapping Antioxidant Parameter of plasma' (TRAP), individual plasma antioxidants, serum iron and linoleic acid, a main substrate of lipid peroxidation, were monitored before and after BMT, and they were compared with values obtained from healthy controls. Seven patients (3 AML, 3 CML, 1 multiple myeloma) receiving 16 mg/kg busulfan, 30-45 mg VP-16 and 120 mg/kg cyclophosphamide were investigated. TRAP values declined during chemotherapy by about 40% (day -9: 1019 +/- 245 mumol/l, mean +/- s.d.; day 0: 660 +/- 164 mumol/l; P < 0.05). The concentration of uric acid, one of the main antioxidants in plasma, decreased markedly (day -9: 339 +/- 108 mumol/l, day 0: 148 +/- 61 mumol/l; P < 0.05) and paralleled TRAP values. Vitamin E and bilirubin did not change from day -9 to 0 whereas vitamin C increased (day -9: 46 +/- 16 mumol/l, day 0: 89 +/- 44 mumol/l; P < 0.05). Serum iron rapidly increased within the pre-transplantation period, reaching values normally seen only in iron overload (day -9: 11.8 +/- 5.2 mumol/l, day 0: 40.6 +/- 6.5 mumol/l; P < 0.05). Linoleic acid levels were normal at the start and decreased substantially (27.0 +/- 1.6 wt% at day -9; 15.7 +/- 4.9 wt% at day 0; P < 0.05), indicating possible lipid peroxidation during high-dose chemotherapy. In conclusion, complex monitoring of the antioxidant status before and after BMT revealed a breakdown of plasma antioxidant defence and of radical-vulnerable lipids, which was associated with high circulating levels of iron.

Adult↗

Inhibition of CFU-C growth by VP-16 containing plasma samples obtained from patients after conditioning therapy for bone marrow transplantation.

The introduction of VP-16 into high-dose therapy regimens used for conditioning before BMT or PBSCT has resulted in higher remission rates and prolonged disease-free survival, even in high risk patients. VP-16 levels have been measured in plasma at the time of transplantation. The question is, is there a biological activity that corresponds with the risk of delayed engraftment or graft failure? We investigated the inhibitory effects of plasma samples obtained from patients under high-dose VP-16 therapy on the growth of human bone marrow progenitor cells. Bone marrow cells from healthy donors were exposed to the plasma samples and seeded into methylcellulose-culture (CFU-C-assay). We found a dose dependent CFU-C inhibition related to VP-16 plasma levels at the time of transplantation (k = 0.769, P < 0.01). There were signs of a correlation between CFU-C growth inhibition at the time of BMT and haematological recovery (k = 0.656, P < 0.05) between CFU-C inhibition and the time until leucocytes reached 0.2 x 10(9)/l. Patients with CFU-C growth inhibition at the time of BMT may show delayed engraftment of leucocytes and that there might be a correlation with VP-16 levels, but further investigation is necessary to determine the significance of the latter thesis and if VP-16 plasma levels could lead to failure of engraftment. We recommend a minimum time interval between VP-16 infusion and graft transplantation of 72 h.

Adolescent↗

Surgical stimulation induces changes in brain electrical activity during isoflurane/nitrous oxide anesthesia. A topographic electroencephalographic analysis.

BACKGROUND: The aim of this study was to investigate topographic changes in electroencephalographic (EEG) power and frequency induced by abdominal surgery during anesthesia with 0.6% or 1.2% isoflurane in 66% nitrous oxide. METHODS: Forty-six patients (aged 41 +/- 13 yr) scheduled for elective abdominal surgery were studied. The trachea of each patient was intubated and the lungs ventilated. Patients were randomly assigned to one of four groups: anesthesia was maintained with 0.6% (group 1, n = 12; group 2, n = 11) or 1.2% end-tidal isoflurane (group 3, n = 12; group 4, n = 11) in 66% nitrous oxide. Data were recorded over 20 min. Groups 1 and 3 were studied without surgery (as controls). In groups 2 and 4 recording was started 6 min before skin incision. The EEG was acquired via 17 scalp electrodes placed in standard International 10-20 locations (reference Cz). Absolute and relative power densities were calculated in selected frequency bands. EEG maps of spectral power densities were coded according to a continuous color spectrum. RESULTS: During baseline recordings, alpha activity was dominant at frontal areas in groups 1 and 2. In comparison, in groups 3 and 4, delta and theta activities were dominant at frontal leads. In group 2, the start of surgery resulted in increases in delta activity and decreases in alpha activity that were most dominant frontally (delta +181% and alpha -61%, F3). The delta shift was attenuated at 1.2% isoflurane (group 4, delta +44%, F3), but decreases in alpha activity (-53%, F3) were comparable to those in group 2. The EEG response in all frequency bands was attenuated at parietotemporal recording sites at both isoflurane concentrations. CONCLUSIONS: The current data demonstrate graded EEG responses induced by abdominal surgery during anesthesia with 0.6% or 1.2% isoflurane in 66% nitrous oxide. Spatial heterogeneities in absolute spectral power densities were reflected by color changes in the EEG maps. The topographic EEG analysis indicates that these changes were most dominant at frontal areas. The increases in delta and decreases in alpha activities may be related to intraoperative "paradoxical" electrophysiologic arousal phenomena.

Adult↗

Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small-cell lung cancer.

PURPOSE: This prospective study was designed to evaluate the prognostic relevance and biologic characteristics of a minimal lymphatic tumor load in non-small-cell lung cancer (NSCLC). METHODS: Frozen-tissue sections from 391 regional lymph nodes of 72 patients with completely resected NSCLCs, who were staged as free of metastases (pT1-3, pN0,M0,R0) by clinical tumor staging procedures and histopathologic examinations, were studied. For tumor-cell detection, we applied the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique with monoclonal antibody Ber-Ep4 against two glycoproteins of 34 and 49 kd present of the surface and cytoplasm of epithelial cells. RESULTS: Individual Ber-Ep4-positive cells were detected in 11 of 72 (15.2%) cancer patients, while positive staining was consistently absent in all sections from control nodes of 24 noncarcinoma patients. No correlation between a positive lymph node finding and either the size or differentiation grade of the primary tumor or the presence of micrometastatic tumor cells in bone marrow assessed by immunocytochemistry with antikeratin monoclonal antibody CK2 was observed. Following a median observation time of 26.0 months (range, 15 to 39), patients with lymph node micrometastases showed a significantly shorter disease-free survival duration than node-negative patients (log-rank test, P = .005). The independence of this prognostic significance was demonstrated by a multivariate analysis (Cox regression model, P = .005). CONCLUSION: Our results provide evidence that the presence of single lung carcinoma cells in lymph nodes is an independent indicator of the disseminatory capacity of an individual primary tumor. Immunohistochemical assessment of micrometastases in lymph nodes is recommended for current tumor staging in NSCLC, as it might lead to better stratification of patients for adjuvant therapy.

Carcinoma, Non-Small-Cell Lung↗