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T Fischer

Publications and source records attributed to T Fischer.

At least 145 records · Page 8Linked to original sources
PubMed1999

Nitric oxide synthase activity and Doppler parameters in the fetoplacental and uteroplacental circulation in preeclampsia.

OBJECTIVE: We investigated the hypothesis that changes in blood flow in the uteroplacental and fetoplacental circulation in preeclampsia are associated with an abnormality of placental or uterine placental bed nitric oxide (NO) synthesis. METHODS: We measured pulsatility indices on Doppler waveform analysis from uterine and umbilical arteries in 20 patients with preeclampsia and 14 healthy pregnant controls before elective cesarean section. During cesarean section, biopsies from the uterine placental bed and the placenta were taken and the nitric oxide synthase (NOS) activity was measured by the [3H] L-arginine-[3H] L-citrulline conversion assay in these samples. RESULTS: The NOS activity was significantly lower in the uterine placental bed in comparison to the placental tissue (p < 0.01). Placental NOS activity was similar between patients with preeclampsia and healthy controls and in the groups with either a pathological or a normal Doppler flow in the umbilical artery. In the uterine placental bed however, NOS activity from patients with preeclampsia was significantly lower (p < 0.01), whereas the blood flow resistance in the uterine arteries was elevated (p < 0.01) in comparison to healthy controls. CONCLUSIONS: Our data show that pathological Doppler waveforms in the uterine arteries of patients with preeclampsia are paralleled by diminished NOS activity in the uterine placental bed. Therefore, the compromised NO production in the uterine placental bed may play an important role in the impaired uteroplacental blood flow and potentially in some pathological features of preeclampsia such as intervillous thrombosis formation and fetal growth retardation.

Adult↗
PubMed1999

Drug metabolizing capacity of cryopreserved human, rat, and mouse liver parenchymal cells in suspension.

The phase I and phase II drug-metabolizing capacity of freshly isolated and cryopreserved parenchymal cells (PC) from human, rat, and mouse liver held in suspension at 37 degrees C for up to 120 min after thawing was compared. Although 7-ethoxycoumarin-O-deethylase activity was strongly reduced in freshly isolated as well as in cryopreserved PC from human, rat, and mouse liver after 120 min, 7-ethoxyresorufin-O-deethylase activity as well as the profile and formation rates of hydroxylated testosterone metabolites in general remained constant throughout the 2-h incubation period in cryopreserved PC from all three species and was similar to that measured in freshly isolated PC. The activity of glutathione S-transferase (GST) and that of UDP-glucuronosyltransferase (UDP-GT) toward 4-methylumbelliferone significantly decreased, whereas the activities of UDP-GT activity toward 4-hydroxybiphenyl and sulfotransferase in cryopreserved human PC were similar to those measured in freshly isolated PC. The activities of GST, UDP-GT toward 4-methylumbelliferone, and sulfotransferase in cryopreserved rat PC showed a significant decrease when compared with the activities in freshly isolated PC. The phase II enzyme activities in cryopreserved mouse PC proved to be far more stable, being similar to the activities of freshly isolated mouse PC at all four time points measured with the exception of GST, which showed a decay from t = 60 min onward. In conclusion, phase I drug-metabolizing enzyme activities in cryopreserved human, rat, and mouse PC are very similar to those of freshly isolated PC, whereas phase II enzyme activities are affected by cryopreservation.

Animals↗
PubMed1999

[Synthesis of tumor affinity label Yb-169- and Y-90- porphyrin complexes and animal experimental investigations with various Yb-169-porphyrins].

AIM: It should be shown, that it is possible to insert radioactive isotopes of Yb and Y into some selected porphyrins. Besides, first informations about the biodistribution of Yb-169-por-phyrin-complexes should be obtained. METHODS: Carrier added radioactive isotopes were used for the synthesis of the metal porphyrin complexes. The animal experiments were done with mamma carcinoma bearing mice. The activity of the organs was determined 5 and 24 h after i.v. injection in a well counter. RESULTS: Four Yb-169-porphyrin complexes and Y-90-porphyrin complexes could be synthesized in non-carrier-free form. This was verified by absorption spectra, TLC and HPLC. Depending on the complex, the average tumour/background ratios were between 2 and 20. CONCLUSION: The synthesized radioactive metal-porphyrin complexes showed a clear tumour-affinity which could be used for tumour scintigraphy or perhaps therapy if the synthesis is improved (goal: reduction of carrier, other radionuclides).

Animals↗
PubMed1999

Oxygenation and lung morphology in a rabbit pediatric ARDS- model under high peak pressure ventilation plus nitric oxide and surfactant compared with veno-venous ECMO.

UNLABELLED: The aim of the study is to investigate which of two treatment options of saline lavage induced ARDS in rabbits is better in terms of oxygenation and prevention of barotrauma: combined high peak pressure ventilation with surfactant administration and inhaled nitric oxide or veno-venous ECMO combined with low peak inspiratory pressure ventilation. MATERIALS AND METHODS: After saline lavage (10 cc/kg repeated as long as foamy retrieval was observed) two combined therapeutic strategies were examined: ventilation with high inspiratory pressures (35 cm H2O) with additional exogenous surfactant administration (100 mg/kg) and inhaled nitric oxide (10 PPM) (n=5, group 1) and low inspiratory pressure (20 cm H2O) ventilation under veno-venous ECMO support (n=5, group 2). The FiO2 was maintained at 1.0 in both groups. The paO2/FiO2 ratio was calculated in 30 minute intervals for 4 hours. After that the animals were sacrificed and the lungs examined macro- and microscopically. Aeration was described in a semiquantitative method using the alveolar expansion index. Oxygenation in group 1 was significantly better than in group 2, it increased significantly after surfactant but not after additional nitric oxide administration. However, the lungs in group 1 showed severe signs of baro/ergotrauma (Hyaline membranes, air leaks, infiltration of polymorphonuclear (PMN) granulocytes and macrophages, break down of alveolar capillary membranes) after 4 hrs of combined therapy, whereas the lungs in group 2 appeared normal. Adding surfactant and NO to a high tidal volume ventilation improved oxygenation, but did not prevent baro/ergotrauma. Ventilation with low inspiratory pressures combined with ECMO caused little baro/ergotrauma but adequate oxygenation could not be achieved, probably due to anatomical features of the rabbit which do not allow appropriate blood flow within the ECMO-circuit.

Animals↗
PubMed1999

[The autonomic nervous system and pre-eclampsia].

Alterations in the autonomic cardiovascular control have been implicated to play an important etiologic role in preeclampsia. Earlier assessments of sympathetic nervous system activity by measurements of urinary and plasma levels of catecholamines showed contradictory results, due to serious methodological problems. The microneurographic technique enables the assessment of sympathetic outflow to the vascular bed of skeletal muscles. By the use of this technique it has been shown that preeclampsia represents a state of sympathetic overactivity as compared to healthy pregnant women. Other studies have shown that exogenous stimulation of the celiac ganglion causes a HELLP-syndrome-like disease in pregnant rats and that preeclamptic human plasma increases norepinephrine release in isolated sympathetic neurons of chicken embryos. These data suggest that the autonomic nervous system may play a fundamental role in the etiology of preeclampsia.

Animals↗
PubMed1998

[Benign symmetrical lipomatosis ("peripheral lipodystrophy") during antiretroviral therapy of HIV infection].

HISTORY AND ADMISSION FINDINGS: A 29-year-old hemophiliac with HIV infection for which he was receiving antiretroviral treatment (ART) with indinavir, zidovudine and zalcitabine reported increasing swelling of the neck. Physical examination noted a soft to doughy swelling, not sensitive to pressure, extending from the neck to between the shoulder blades. INVESTIGATIONS: Ultrasonography and magnetic resonance imaging revealed the swelling to consist of an accumulation of subcutaneous fat without capsule. Cytology demonstrated benign fatty tissue. Blood triglycerides totalled 667 mg/dl. DIAGNOSIS, TREATMENT AND COURSE: The typical location, absence of a capsule and the cytological finding confirmed the clinical diagnosis of drug-induced benign symmetrical lipomatosis (BSL, also called peripheral lipodystrophy) in ART. A connection with the hyperlipoproteinaemia is supported by the observation that the patient used to have a normal fat metabolism; the onset of BSL coincided with a massive increase in triglyceride levels. The hyperglyceridaemia and clinical signs improved on a low-fat diet. CONCLUSIONS: BSL can occur in the course of ART in HIV infection, when reverse-transcriptase inhibitors or protease inhibitors are being taken. Medication should not be changed, when antiretroviral treatment is adequate. To reduce the symptoms low-fat diet should be tried, as well as administration of HMG-CoA-reductase inhibitors or, if necessary, surgical liposuction.

Adult↗
PubMed1998

[Costs of intensive insulin therapy in type 1 diabetes mellitus. Experiences from the DCCT study].

Diabetes mellitus is one of the most common metabolic diseases in many countries of the world. Its prevalence in Germany has increased 7- to 8-fold over the past 30 years. The clinical and economical importance of diabetes is determined by the frequent occurrences of such serious complications as neuropathy, retinopathy and nephropathy. Intensive insulin therapy with regular monitoring of blood glucose (up to 4 measurements daily) and adjustment of the insulin dose accordingly may achieve virtually normal levels of blood glucose and thus decrease the risk of these complications. The present cost-effectiveness-study shows that the higher costs of invasive insulin therapy are offset by savings of 8.114 German marks per patient resulting from the reduction in morbidity and mortality. On the basis of an estimated 5% to 10% type 1 diabetes among the total diabetic population (prevalence 4.9%), potential saving of 1.62 to 3.24 billion marks are calculated for Germany.

Blood Glucose↗
PubMed1998

Long term use of megestrol acetate by cancer survivors for the treatment of hot flashes.

BACKGROUND: Hot flashes are often a troublesome symptom in breast carcinoma survivors and men with prostate carcinoma who have undergone androgen deprivation therapy. A previous clinical study demonstrated that, on a short term basis, low dose megestrol acetate markedly reduced hot flashes and was well tolerated. Little information has been available regarding the long term use of low dose megestrol acetate for hot flashes. METHODS: Patients previously enrolled on a randomized placebo-controlled trial that evaluated the short term use of megestrol acetate for hot flashes were contacted and interviewed by telephone. RESULTS: A total of 132 persons were contacted. Nine percent of the patients discontinued megestrol acetate after resolution of their hot flashes. Forty-five percent of the patients contacted were continuing to utilize megestrol acetate approximately 3 years beyond the conclusion of the 1992 study. Three-quarters of these patients were utilizing < or =20 mg of megestrol acetate per day. Potential toxicities attributed to megestrol acetate included episodes of chills, appetite stimulation/weight gain, vaginal bleeding, and carpal tunnel syndrome symptoms. CONCLUSIONS: A substantial proportion of patients continue to use megestrol acetate for periods of up to 3 years or longer with continued control of hot flashes. This treatment appears to be relatively well tolerated.

Breast Neoplasms↗
PubMed1998

Cost-effectiveness analysis of paclitaxel and cisplatin versus cyclophosphamide and cisplatin as first-line therapy in advanced ovarian cancer. A European perspective.

Paclitaxel is a new cytotoxic agent that has demonstrated significant activity in advanced ovarian cancer. The aim of this study was to determine the cost structure of advanced ovarian cancer and the cost-effectiveness of paclitaxel-cisplatin (PC) combination therapy compared with a standard cyclophosphamide-cisplatin (CC) regimen at first-line therapy. The analysis was performed separately for six European countries: Germany, Spain, France, Italy, The Netherlands and the U.K. The study was conducted from the national health service payer's perspective. The total cost of treatment per patient (six cycles of chemotherapy) in the six European countries varied between a minimum of US$4,926 in the U.K. and US$12,578 in Germany for the CC regimen and between US$13,038 and US$24,487 for the PC regimen (April 1996). Since the new regimen improved life expectancy by 1.283 years compared with CC, the incremental cost-effectiveness of PC was calculated to be between US$6,403 per 5-year saved in the U.K. and US$11,420 per life-year saved in Italy. Overall, the cost-effectiveness of PC compares favourably with other oncological interventions. The findings of this study suggest that healthcare decision makers should consider paclitaxel, in combination with cisplatin, as a cost-effective first-line therapy for patients with advanced ovarian cancer.

Adult↗
PubMed1998

Calculation of left ventricular outflow tract area using three-dimensional echocardiography. Influence on quantification of aortic valve stenosis.

In 23 patients with aortic valve stenosis (14 male, 9 female, mean age 66 +/- 21.5 years) left ventricular outflow tract cross-sectional area was determined in planimetric fashion using three-dimensional echocardiography. The 3-D data-set for each patient had been acquired in the course of a multiplane transesophageal examination. Aortic valve area was determined using the continuity equation. Results obtained were compared to those calculated by continuity equation using to the conventionally determined LVOT area (a = pi [d/2]2). As reference method the results were compared to invasive measurements. 3-D planimetric determination of LVOT cross-sectional area was possible in 20 of 23 patients. In three patients, this method failed due to artefacts. The mean difference to the conventionally calculated LVOT area amounted to 0.18 cm2 (SD = 0.46). The comparison of AVA determined by continuity equation and by invasive measurement showed a mean difference of -0.074 cm2 (SD = 0.21) for the conventionally calculated LVOT area; for the planimetrically determined LVOT area the mean difference of AVA amounted to -0.03 cm2 (SD = 0.14) (p < 0.05). Planimetric determination of LVOT area using 3-D echocardiography improves the agreement of the continuity equation with invasive measurement.

Aged↗
PubMed1998

Chemotherapy-induced mobilization of karyotypically normal PBSC for autografting in CML.

High-dose chemotherapy with autologous transplantation of in vivo purged PBSC is a new and interesting therapeutic option for CML patients not eligible for allogeneic transplantation. We investigated the feasibility and toxicity of this approach in 57 patients with Ph-positive CML. For mobilization of Ph-negative PBSC, patients were treated either with '5 + 2/7 + 3'- type chemotherapy or with 'mini-ICE/ICE' chemotherapy followed by administration of G-CSF. Fourteen patients were in early chronic phase, 30 patients in late chronic phase and 13 patients in accelerated phase (AP) or blast crisis (BC). Cytogenetic responses in the PBSC harvests were dependent on both disease stage and type of chemotherapy: in late chronic phase and AP/BC, a complete or major cytogenetic response could be obtained in nine out of 13 patients treated with 'mini-ICE/ICE' but only in three out of 23 patients treated with '5 + 2/7 + 3' chemotherapy. However, in early chronic phase a Ph-negative autograft could be obtained in three out of eight patients upon mobilization with '5 + 2' chemotherapy. Thirty-one patients underwent PBSC transplantation and all of them successfully engrafted. Post-transplant cytogenetic analysis was available on 21 cases, of whom seven achieved a complete or major cytogenetic response, with two minor cytogenetic remissions. One patient (1/57) in blast crisis died during mobilization therapy (1.8%). Transplantation related mortality was 0%. This study demonstrates that mobilization of Ph-negative PBSC after myelosuppressive chemotherapy is feasible in CML patients and is associated with acceptable toxicity. Autologous transplantation of in vivo purged PBSC is a safe procedure with rapid and complete hematopietic recovery.

Adult↗
PubMed1998

Bcr-Abl kinase promotes cell cycle entry of primary myeloid CML cells in the absence of growth factors.

Cell cycle control of both immature and differentiated primary myeloid normal and chronic-phase chronic myeloid leukaemia (CML) cells to growth factor deprivation was studied. CD34+ cells were cultured in liquid culture. After removal of growth factors for 48 h normal cells were very efficiently arrested with the fraction of cells in S phase reduced by 70.8 +/- 6.5% in CD34+ and 50.5 +/- 4.2% in CD34- cells. In contrast, a significantly higher proportion of leukaemic cells remained in S phase. The fraction of S-phase cells was reduced by only 29.3 +/- 5.7% in CD34+ CML cells and 21.2 +/- 3.8% in CD34- cells. This abnormal negative cell cycle control in leukaemic cells was specific for growth factor deprivation. Reaction to IFN-alpha and TNF-alpha treatment was identical both in normal and CML cells. Equal quantities of the cytokines TNF-alpha, IL-1alpha, IL-1RA and IL-6 were produced by CML and normal cells. However, production of GM-CSF, with a median of 11 +/- 5 pg/ml, was found only in the supernatants of CML cells. But antibodies to GM-CSF did not restore growth factor dependence of the leukaemic cells. The defect was completely corrected by the abl-specific tyrosine kinase inhibitor CGP 57148 without effecting cell cycle control of normal cells. Our results demonstrate a directly Bcr-Abl-dependent defective response of both immature and differentiated primary myeloid CML cells to growth factor deprivation.

Benzamides↗
PubMed1998

Patients with visual display unit-related facial symptoms are stingers.

Thirty patients without obvious skin disease but with subjective skin symptoms related to work with visual display units (VDUs) and 32 healthy persons were single-blind-tested with a solution of 5% lactic acid and pure water on their cheeks. Thirteen of the patients and 6 control persons reacted positively as "stingers" (p < 0.05) in this objective test of sensitive skin. The reason why some patients react with subjective symptoms like itching, burning, stinging, prickling or tingling is unclear. The result of this study, that patients with VDU-related skin symptoms have sensitive skin, does not tell anything about the aetiology of the symptoms. Former studies speak against the role of electric and magnetic fields and indicate that "techno-stress", cognitive factors or flickering from the VDUs or fluorescent tubes could be of importance, as could the Swedish mass media debate.

Adult↗
PubMed1998

Induction of the pro-myelocytic leukaemia gene by type I and type II interferons.

The physiological role of the pro-myelocytic leukaemia (PML) gene product is poorly defined. Among other functions, PML is involved in haematopoietic differentiation and in control of cell growth and tumorigenesis. We investigated the regulation of human PML expression by interferons (IFNs) and IL-1 in various human haematopoietic lines (U937, THP1, HL60, NB4), in human diploid fibroblasts and in human peripheral blood leukocytes. Cytokine-induced modulation of PML expression was assessed by Northern blot analyses, flow cytometry studies and in situ immunolabelling. Our data show that IFNs and IL-1 upregulate PML transcript and protein expression in a time and dose-dependent manner. In situ immunolabelling revealed that upregulation of protein expression by IFN-alpha is a consequence of a marked increase in both the number and the intensity of the staining of so-called PML nuclear bodies. Our data suggest that stimulation of PML expression by interferons and IL-1 may account for upregulation of PML proteins observed in inflammatory tissues and in proliferative states.

Cell Nucleus↗
PubMed1998

RGS-GAIP, a GTPase-activating protein for Galphai heterotrimeric G proteins, is located on clathrin-coated vesicles.

RGS-GAIP (Galpha-interacting protein) is a member of the RGS (regulator of G protein signaling) family of proteins that functions to down-regulate Galphai/Galphaq-linked signaling. GAIP is a GAP or guanosine triphosphatase-activating protein that was initially discovered by virtue of its ability to bind to the heterotrimeric G protein Galphai3, which is found on both the plasma membrane (PM) and Golgi membranes. Previously, we demonstrated that, in contrast to most other GAPs, GAIP is membrane anchored and palmitoylated. In this work we used cell fractionation and immunocytochemistry to determine with what particular membranes GAIP is associated. In pituitary cells we found that GAIP fractionated with intracellular membranes, not the PM; by immunogold labeling GAIP was found on clathrin-coated buds or vesicles (CCVs) in the Golgi region. In rat liver GAIP was concentrated in vesicular carrier fractions; it was not found in either Golgi- or PM-enriched fractions. By immunogold labeling it was detected on clathrin-coated pits or CCVs located near the sinusoidal PM. These results suggest that GAIP may be associated with both TGN-derived and PM-derived CCVs. GAIP represents the first GAP found on CCVs or any other intracellular membranes. The presence of GAIP on CCVs suggests a model whereby a GAP is separated in space from its target G protein with the two coming into contact at the time of vesicle fusion.

Animals↗
PubMed1998

Objective assessment of nickel sulfate patch test reactions with laser Doppler perfusion imaging.

The laser Doppler perfusion scanning technique was used to assess the superficial blood flow of nickel sulfate hexahydrate patch test reactions. There was good agreement between laser Doppler and visual assessments when the highest assessment values of reactions were studied. Earlier detection of reactions was possible with the laser technique. There was great inter-individual variance in perfusion between identically tested patients. 4 patients were visually negative when a TRUE Test patch test dose of 0.20 mg/cm2 was applied for 48 h and the test area read 4x up to 168 h. These 4 showed a dose-related increase in perfusion and visually positive reactions using longer application times. The instrument allowed a dose reduction not possible for visual assessments. Reading transparent patches in contact with the skin through transparent semi-occlusive plastic foil or through windows in the tape strip over the patches, allowed us to detect perfusion at 48 h, where a longer application would have been needed using tape and visual assessments.

Adult↗