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T Zimmermann

Publications and source records attributed to T Zimmermann.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Ciprofloxacin levels in pleural fluid and serum during systemic administration after pneumonectomy].

Postpneumonectomy empyema represents a frequently lethal complication. It remains unsolved whether prophylactic antibiotics achieve a bactericidal concentration in the pleural cavity after pneumonectomy. 12 patients undergoing pneumonectomy received ciprofloxacin intravenously (2 x 200 micrograms/d) and orally (2 x 500 micromilligrams/d) during the first and second postoperative week, respectively. 1, 6, 9 and 14 days after the operation the ciprofloxacin concentration was measured in the pleural fluid and serum. Already after 24 hours bactericidal levels (0.56 microgram/ml) were found in the pleural fluid, rising to 1.11 micrograms/ml on day 14 under the higher oral dosage. Thus, it could be demonstrated that during the first two weeks after pneumonectomy high concentrations of an antibiotic similar to the levels in the serum can be achieved in the pleural fluid.

Administration, Oral↗
PubMed1999

[Molecular biology studies of a multicenter phase III study (SIC Study)].

Transcription factors adjust the up- and downregulation of inflammatory genes. Within the bounds of the SIC-study (Selenium in Intensive Care) the authors will investigate the role of transcription factors NF-kappa B and AP-1 in S.I.R.S/septic patients. The goal of these investigations is the corroboration of therapy of septic patients with sodium selenite at the molecular biological level.

Critical Care↗
PubMed1999

[Significance of selenium in regulation of inflammatory response by transcription factors in polytrauma patients. A clinical study].

The authors have investigated the relationship between selenium and transcription factors (NF-kappa B and AP-1) in the field of pathogenesis of polytrauma. Correlations between plasma selenium content and transcription factor binding activity have been found. The measured connecting capacitances of transcription factors have been associated with the severity of disease. To harden the results of this research a randomized double blind study with sodium selenite substitution is necessary next. This study will be to establish the therapy with sodium selenite in the treatment of polytrauma.

APACHE↗
PubMed1999

[Low T3 syndrome in multiple trauma patients--a phenomenon or important pathogenetic factor?].

BACKGROUND: Many nonthyroidal illnesses, such as major trauma, severe burn injury, sepsis or immune deficiency are associated with a reduced T3 concentration without increased serum TSH secretion. The pathopysiologic meaning of this phenomenon was controversely discussed since its investigation 20 years ago. The identification of the Type I 5-iodthyronine-deiodinase as a selenoenzyme brought many new aspects into this discussion. PATIENTS AND METHODS: To investigate the correlation of T3 blood levels and the selenium concentrations in consideration of the severity of the nonthyroidal illness 20 patients with major trauma where included in this study. In all these patients frequently T3, T4, fT3, fT4, TSH, Se (whole blood), Se (plasma) and Glasgow-Coma-Scale (GCS), APACHE II and MOF-Score where measured until the 28th day of illness. RESULTS: Five patients (20%) died during the study until the 8th day of measurement. Survivors and nonsurvivors initial showed a low T3 and fT3 level in serum. While the T3 serum concentrations of nonsurvivors remained on a low level the thyronine concentrations of survivors distinctly increased. The measured thyroid hormone concentrations were significantly correlated with MOF-score, APACHE II and inversely with GCS. There was no significant correlation between low T3/fT3 blood levels and low selenium concentrations in all observed patients. CONCLUSION: The selenium deficiency in all patients with major trauma seems to be not the single cause of the low T3 syndrome. The distinctly suppression of TSH could be caused by the action of various cytokines such as IL-6 and TNF-alpha. Further investigations should improve the effectivity of substitution of selenium and/or thyroid hormones in the therapy of patients with severe nonthyroidal illness.

APACHE↗
PubMed1999

[Redox sensitive behavior of selenite in the presence of reactive oxygen species. Are there nonenzymatic direct reaction pathways].

From extensive research over the last decade it has been known that selenium is essential as necessary component of selenoaminoacids and of specific enzymes. Among others, the redoxpair GSH/GSSG is closely connected with antioxidative processes. Moreover it inhibits and/or activates molecular key reactions with the involvement of various small reactive O- and N-species. We investigated the direct interaction of selenite with components of the respiratory burst of human blood cells, considering the redoxamphoterie of alkali-selenite. Selenite tend to redox-disproportation depending on the pH-value. Whether selenite leads to oxidation or reductation is dependent not only on the pH-value, but also on the redox-potential of the reaction partners. In in-vivo adapted in-vitro conditions (ph = 7.4; mumolar concentrations of reaction partners) we observed the following results: 1. SeO3(2-) is not oxidized by H2O2/NO or triplet-oxygen, when the oxidatives are applied alone; 2. SeO3(2-) is quantitatively oxidized from SeO4(2-) by the combination H2O2/NO2- or O2-/NO; 3. SeO3(2-) is semiquantitatively oxidized by singlett oxygen to SeO4(2-). The composition of reaction products was measured by 77Se-NMR-spectroscopy. The reactive intermediate product for the 2. reaction should be peroxynitrite (HOONO). One cannot rule out the possibility that HOONO reacts on a large scale with H2O2 to singlett oxygen. Subsequently singlett oxygen oxidizes selenite. The pathophysiological impact of singlett oxygen in processes like arteriosclerosis is now being investigated. It has been supposed, that singlett oxygen is participating in processes of lipidperoxidation invivo. Further investigations have to show, to what extent selenite is effective as direct 1O2-scavanger.

Arteriosclerosis↗
PubMed1999

[Selenium administration in children with SIRS].

PATIENTS AND METHOD: At the Clinic for Paediatric Surgery of the University of Dresden, in a time period ranging from 5/1994 to 12/1996, all patients aged between 1 and 16 years with severe inflammatory surgical diseases or extended scalded skin, were given an adjuvant selenium substitution. As control group, all patients with the same diagnosis and age treated during the months 1/1997 to 12/1998, did not receive this adjuvant selenium substitution. All these patients fulfilled the criteria of "Systemic Inflammatory Response Syndrome" (SIRS). The selenium-therapy group consisted of 34 patients and the control group without substitution consisted of 31 patients. The following laboratory parameters were measured on the 1st, 2nd, 3rd, 6th and last treatment day: white blood cell count, interleukin 6, C-reactive protein, fibrinogen, malondialdehyde, activity of glutathione peroxidase in plasma and level of selenium in plasma and whole blood. RESULTS: The initially high interleukin 6 rates declined significantly in both groups from the 2nd day on. The acute phase proteins, i.e. the C-reactive protein and fibrinogen, normalized in both groups after the 3rd day of treatment. The initial low rates of selenium in plasma and blood gained more rapidly a normal level in the therapy group than in the control group. On the 1st day of therapy the glutathione peroxidase activity in plasma was in both groups at the inferior limit of norm range and remained at this level in the control group for the whole observation period. In the selenium-substitution group on the contrary, these initial low values raised to the double as an expression of an elevated cell membrane protection. The initial significant elevated malondialdehyde rates in both groups, expressing a raised lipidperoxidation, fell down to a normal level in the selenium-substitution group, whereas they remained at their initial high level in the control group during the whole observation period. CONCLUSION: The substitution of selenium in children with SIRS is a supportive therapy.

Adolescent↗
PubMed1999

Frequency- and structure-dependent inhibition of normal and epileptiform activity by 6-benzoyldeltamine in rat hippocampal slices.

The present study investigated the effects of the Aconitum alkaloids 6-benzoyldeltamine and the structurally related eldeline on neuronal activity in rat hippocampal slices. 6-Benzoyldeltamine (1-30 microM) decreased the orthodromic field potentials recorded in area CA1 in a concentration-dependent manner. The inhibitory effect of eldeline (3-100 microM) was lower. The attenuation of the postsynaptic population spike was accompanied by a simultaneous decrease in the presynaptic fibre spike evoked by electrical stimulation of the Schaffer collaterals. The input-output relationship of the presynaptic fibre spike as function of the stimulation intensity, and for the postsynaptic population spike as function of the presynaptic fibre spike was shifted to the right. Thus, electrophysiologically, these alkaloids seem to inhibit predominantly the excitability of the afferent fibres and, in consequence, neurotransmission between Schaffer collaterals and the CAI neurons, thereby suppressing the firing of the latter. The inhibitory action of 6-benzoyldeltamine revealed use-dependence as obvious by an enhanced attenuation of the antidromic spike when stimulation frequency was increased. 6-Benzoyldeltamine inhibited stimulus-triggered epileptiform population bursts in area CA1 elicited by omission of Mg2+, as well as spontaneously occurring epileptiform discharges in area CA3 elicited by omission of Mg2+ and elevation of K+. Complete suppression of spontaneous activity was observed at 1 microM 6-benzoyldeltamine, which reduced the population spike only by about 20% of control. It is concluded that the inhibitory and antiepileptiform effect of 6-benzoyldeltamine is mediated by a frequency-dependent decrease in excitability, which might be important for filtering high frequency bursts of action potentials characteristic for epileptiform activity in the hippocampus.

Aconitine↗
PubMed1999

The pharmacokinetics of extended-release formulations of calcium antagonists and of amlodipine in subjects with different gastrointestinal transit times.

The influence of gastrointestinal (GI) transit times on the pharmacokinetics (PK) of three calcium channel blockers (CCBs), recommended for once-daily dosing, was investigated. In a three-way crossover design, the single-dose PK of a controlled-delivery formulation of 240 mg diltiazem (DIL), an extended-release formulation of 10 mg felodipine (FEL), and 5 mg amlodipine (AML) were compared in two groups of healthy subjects, with either slow (> 35 h) or rapid (< 15 h) GI transit, as assessed by the metal detector method (EAS II). GI transit significantly affected the PK of DIL. Mean PK parameters in the rapid versus slow transit group were the following: trough levels (C24 h): 22.8 +/- 8.3 versus 49.5 +/- 35.7 ng/ml, p < 0.05; AUC 1134.4 +/- 512.7 versus 1704.7 +/- 1185.6 hng/ml, p < 0.05 (one-sided). Neither AUC nor trough levels of FEL and AML were significantly influenced by transit times, nor was Cmax after any of the three treatments. Variations in PK parameters, as indicated by coefficients of variation, were about twofold higher for both DIL and FEL, compared to AML. Variations in mean residence times were significantly lower for AML compared to DIL and FEL (7% vs. 30% and 17%, p < 0.001 and p < 0.002, respectively). Peak-to-trough ratios (Cmax/C24 h mean) were 1.8 +/- 0.9 for DIL, 7.6 +/- 3.5 for FEL, and 1.7 +/- 0.2 for AML. In conclusion, the predictability of pharmacokinetic behavior both in conditions of rapid or slow GI transit is optimized in drugs with intrinsically slow elimination such as amlodipine. The pharmacokinetics of the CCBs with formulation-based once-a-day characteristics are sensitive to GI transit if these processes are rapid enough to interfere with the formulation-specific release profile.

Adult↗
PubMed1999

[Therapy of deep leg vein thrombosis. When is surgical therapy indicated?].

In spite of quite a few clinical trials the benefit of venous thrombectomy is seen controversially. The primary objectives of treating venous thrombosis are survival rate, prevention of pulmonary embolism and of postthrombotic syndrome. We report our experience with 47 patients who underwent venous thrombectomy. The mortality rate was 0%. We did not observe clinically relevant pulmonary embolism. After two years 90% of thrombectomised veins were patent. The mortality rates given in the literature of conservative treatment with heparin and following oral anticoagulation are 0.4 to 1.6%. Fibrinolysis shows mortality rates of 1 to 2.4, and thrombectomy of 3.8%, respectively. Venous thrombectomy is an effective treatment to prevent pulmonary embolism. In our own experience we saw no clinically significant pulmonary event. The danger of embolism rises with the proximity of the venous thrombus. Therefore those patients may have the greatest potential benefit from thrombectomy who present with a mobile inguinal thrombus or a thrombus in the iliac vein. So far there are no statistically sufficient data to support the indication of thrombectomy to prevent a postthrombotic syndrome.

Adult↗
PubMed1999

[An unusual trauma in labor: diaphragmatic rupture].

We present a case of a delayed diagnosed traumatic diaphracmatic rupture and herniation in a 49-year-old woman. The rupture was secondary to trauma sustained 26 years ago during delivery, when the obstetrician pressed his hands against the upper abdominal wall of the patient. She perceived a sudden violent pain in her left belly. In the following years the pain never disappeared. But only after the period of more than two decades, diagnosis was made when abdominal organs prolapsed into the thoracic space. After the operation, the patient was free of pain. We believe this to be the first reported case of traumatic diaphragmatic rupture due to delivery.

Diagnosis, Differential↗
PubMed1999

The uptake of fluconazole in finger and toe nails.

OBJECTIVE: The uptake of the antimycotic agent fluconazole in finger and toe nail following various treatment schedules was investigated in order to characterize the pharmacokinetic basis for the systemic treatment of onychomycosis with fluconazole. SUBJECTS: Between 8 and 12 healthy, male and female Caucasian subjects were included in four separate studies. Mean age of the subjects in the single studies ranged between 34 years (study 4, group 2; n = 4 male and 4 female) and 38 years (study 4, group 1; n = 4 male and 4 female). METHODS: Fluconazole was administered orally over 4 weeks in all studies. The treatment schedules were 150 mg once weekly (study 1), 300 mg once weekly (study 2), 50 mg once daily (study 3) and 150 or 300 mg once weekly in a parallel group study (study 4). At fixed times samples of blood, nail cuttings and nail dust were taken, up to two months after end of treatment. Fluconazole was analyzed in blood plasma and in the nail samples using a highly specific and sensitive gas chromatographic procedure. RESULTS: High concentrations of fluconazole were found in distal nail clippings with all three treatments. Mean maximum concentrations which occurred in the third or fourth week of treatment amounted to 2.1 microg/g (150 mg/w), 5.4 microg/g (300 mg/w) and 6.5 microg/g (50 mg/d) in finger nails and to 9.6 microg/g (150 mg/w), 12.3 microg/g (300 mg/w) and 12.2 microg/g (50 mg/d) in toe nails. The nail concentrations were 1-2 times (finger) and 2-3 times (toe) higher than the corresponding fluconazole plasma levels and were within the MIC range for dermatophytes and yeasts occurring commonly in onychomycosis. The residence times of fluconazole in the nail plate after the end of treatment was long, with approximate half-lives of 33 days in finger nail and 30 days in toe nail. In pharmacokinetic terms there was no evidence of advantages of the daily dosage (50 mg) over the once-weekly (300 mg) dosage. Fluconazole was found to penetrate into both finger and toe nails at a very fast rate. On the first two days of the 150 mg/w and 300 mg/w treatments, i.e. after the first dosage, fluconazole concentrations in the distal nail plates amounted to 50-80% of the later observed peak levels. The initial concentrations in the upper dorsal plate were particularly high, with mean peak concentrations of 11.9 microg/g (150 mg) and 33.7 microg/g (300 mg) in finger nails and 5.7 microg/g (150 mg) and 24.4 microg/g (300 mg) in toe nails. CONCLUSIONS: Fluconazole is rapidly and highly distributed into finger and foot nail, reaching there higher concentrations than in the plasma. The rapid initial uptake of fluconazole in nail, which is unlike the uptake of other antifungal agents, suggests the existence of special routes of access to the nail for fluconazole, possibly based on high diffusion rates.

Adolescent↗
PubMed1999

The efficacy and tolerability of Valette: a postmarketing surveillance study.

OBJECTIVES AND METHODS: A postmarketing survey was carried out to determine the efficacy and tolerability of Valette (dienogest 2.0 mg and ethinylestradiol 0.03 mg) in routine gynecological practice. RESULTS: Valette had excellent contraceptive efficacy (unadjusted Pearl index 0.14), with 11 unplanned pregnancies from a total of 92 146 cycles of exposure, of which at least four were attributable to user failure. Cycle control was good, with spotting and breakthrough bleeding, which affected 5.0% and 3.4% of women, respectively, during the first cycle, becoming less frequent thereafter. Silent menstruation, i.e. the absence of withdrawal bleeding, affected on average 2.0% of women per cycle and 5.9% within the observation period. Valette was well tolerated. The most common adverse drug reactions were mastalgia (1.46% of all users), weight gain (1.11%), headache (0.98%), nausea/vomiting (0.96%), dysmenorrhea (0.35%), decreased libido (0.31%) and depressive moods (0.28%). The dropout rate due to adverse drug reactions was only 3.2%. Only six of the 16 267 women reported events which were considered to be serious adverse drug reactions; all recovered with appropriate treatment. CONCLUSIONS: These results confirm those from previous clinical trials, and demonstrate that Valette is highly effective, very well tolerated and produces excellent cycle control in routine practice.

Adolescent↗
PubMed1999

Disseminated Penicillium marneffei infection in an HIV-positive female from Thailand in Germany.

We report the case of a 33 year old Thai female, who was married in Germany for eight years and used to travel to Thailand every year for several weeks. She presented with abdominal and back pain, prolonged fever, generalized lymphadenopathy, and a recent history of oral thrush. She was diagnosed HIV positive with initial CD4 counts of 18/microliter and an HI virus load of 59,000 copies/ml. Antiviral therapy was installed with zidovudin, lamivudin, and efavirenz. Abdominal CT scans revealed greatly enlarged abdominal lymph nodes. Fine needle aspirates of cervical and retroperitoneal lymph nodes, sputum samples, blood samples, and a bone marrow biopsy were microscopically positive for Penicillium marneffei and grew P. marneffei. The isolates were sensitive to amphotericin B, flucytosine, itraconazole, and fluconazole. Both universal and specific fungal polymerase chain reaction assays were positive in various samples. Serum Aspergillus galactomannan antigen, which is known to crossreact with P. marneffei, was elevated and subsequently used for monitoring of therapy. With antifungal treatment (intravenous amphotericin B 0.6 mg/kg/d for two weeks, oral itraconazole 400 mg/d for 10 weeks and 200 mg/d as maintenance therapy), the fever declined in 6 days, the size of the enlarged lymph nodes gradually decreased in the CT scans, and the initial abdominal and back pain vanished.

Adult↗
PubMed1998

Accumulation of fluconazole in scalp hair.

The accumulation in scalp hair of the antimycotic triazole, fluconazole, was studied during and after administration. Fluconazole 50 mg was administered to 12 healthy subjects as a single capsule each day for 28 days. The concentration of fluconazole 5 hours after administration was measured in different 1-cm sections of scalp hair at intervals during treatment and for 6 months after the end of treatment. In each section of scalp hair the concentration of fluconazole increased during treatment and was consistently higher than values found in plasma. For example, the mean concentration in the first hair section on day 28, 19.8 micrograms/g, corresponded to a mean penetration ratio relative to plasma of 9.42. During administration, the maximal concentration of fluconazole was found in the first hair section. After cessation of administration, the measured concentrations of fluconazole decreased and greater concentrations were found in the distal hair sections, presumably as a result of hair growth. Fluconazole was detectable, however, in the hair of 9 of the 12 subjects even 6 months after treatment. The mean concentration of fluconazole in hair bulbs on day 28 was 12.1 micrograms/g (n = 6), corresponding to a mean penetration ratio of 5.99. In a second study, fluconazole was administered as a single oral 150-mg capsule per week for 4 weeks to a group of 8 healthy subjects. The mean fluconazole concentration in whole scalp hair 5 hours after the last dose was 3.2 micrograms/g.

Adult↗
PubMed1998

4D confocal microscopy of Dictyostelium discoideum morphogenesis and its presentation on the Internet.

Methods to present three-dimensional (3D) and time series of 3D datasets (4D) are demonstrated using the recent advances in confocal microscopy and computer visualization. The process of cell sorting during tip formation in the slime mould Dictyostelium discoideum is examined as an example by in vivo confocal microscopy of spectrally different green fluorescent protein (GFP) variants as reporters of cell-type specific gene expression. Also, cell sorting of the co-aggregating slime mould species D. discoideum and D. mucoroides is observed using a GFP variant and a spectrally distinguishable fluorescent vital stain. The confocal data are handled as 3D and 4D datasets, their processing and the advantages of different methods of visualization are discussed step by step. Selected sequences of the experiments can be viewed on the Internet, giving a much better impression of the complex cellular movements during Dictyostelium morphogenesis than printed photographs.

Animals↗
PubMed1998

Nitroglycerin to facilitate fetal extraction during cesarean delivery.

OBJECTIVE: To determine the efficacy of nitroglycerin in easing fetal extraction in elective cesarean deliveries in comparison with placebo and to collect maternal and fetal pharmacologic data after administration of nitroglycerin. METHODS: This randomized, double-blind clinical and descriptive pharmacokinetic study was carried out at the gynecology departments at Virchow Hospital and Charité Hospital (both university hospitals of Humboldt University, Berlin, Germany) between June 1994 and July 1996 in patients scheduled for elective cesarean delivery under general anesthesia. At the time of the uterine puncture incision, either 0.25 mg or 0.5 mg of nitroglycerin or a physiologic saline solution was administered as an intravenous bolus. Intraoperatively, maternal and neonatal pulse rates and blood pressure were monitored closely. The surgeons estimated reduction in uterine tone and the ease of fetal extraction by means of defined scales. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and from umbilical blood. RESULTS: Ninety-seven patients were included in the statistical evaluation of the study; 32 received 0.25 mg of nitroglycerin, 34 received 0.5 mg of nitroglycerin, and 31 received placebo. The evaluation of the surgeons' estimation revealed no significant difference in ease of fetal extraction (statistical power 0.7) and no significant reduction in uterine tone under treatment with both nitroglycerin dosages in comparison with placebo. Only substance-specific maternal side effects were noted. The neonates' conditions were not affected by administration of nitroglycerin. The median fetal-maternal ratio of venous nitroglycerin plasma levels was approximately 1:400 in the 0.25-mg nitroglycerin group and 1:160 in the 0.5-mg nitroglycerin group. Approximately 11-12 times more nitroglycerin was detected in the venous umbilical branch than in the arterial branch. CONCLUSION: Administration of nitroglycerin leads to no clinically relevant easing of fetal extraction, at least not in elective cesarean deliveries after the 34th week of gestation. With regard to pharmacokinetics, the measured median fetal-maternal venous nitroglycerin concentration was 1:400 in the 0.25-mg group and 1:160 in the 0.5-mg group.

Adult↗