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Biomedical subjects

T Wagner

Publications and source records attributed to T Wagner.

At least 19 recordsLinked to original sources
PubMed2006

Metronomic trofosfamide inhibits progression of human lung cancer xenografts by exerting anti-angiogenic effects.

BACKGROUND: Recent studies of conventional chemotherapeutic drugs administered in metronomic therapy schedules showed remarkable inhibitory effects on tumor angiogenesis. Subsequent and prolonged tumor regression was achieved moreover by circumventing acquired drug resistance. In this study, metronomic and conventional trofosfamide were compared on human NSCLC xenograft "LX-1." MATERIALS AND METHODS: In vitro cytotoxicity of trofosfamide on tumor and human umbilical cord endothelial cells was determined under normoxic and hypoxic conditions. Additionally fractions and duration of cell cycles were analyzed by flow cytometry. In vivo LX-1 xenotransplanted nude mice were treated with trofosfamide in conventional and metronomic schedules (i.p./p.o.). Tumor sections were evaluated for microvessel density (MVD), relative growth fraction and apoptosis. RESULTS: In contrast to the rapid growth of conventionally treated lung cancer, long lasting tumor growth retardation over the total treatment period was achieved with metronomic treatment. While growth fraction and apoptotic rate of LX-1 cells remained unchanged, the MVD was significantly reduced (50%). CONCLUSION: Our results show advantages of a metronomic trofosfamide schedule compared to a conventional bolus therapy mainly due to inhibition of angiogenesis. In vitro data show that this mechanism works under normoxic and hypoxic conditions and suggest that this is in part a direct cytotoxic effect on endothelial cells.

Angiogenesis Inhibitors↗
PubMed2006

[Laparoscopic treatment of para-esophageal hernias].

AIM: This retrospective study aims at analyzing the functional results obtained in patients operated by laparoscopy for a para-esophageal hernia. PATIENTS AND METHODS: From 1994 to 2004, 38 patients underwent a laparoscopic procedure for a symptomatic para-esophageal hiatal hernia of at least 3/4 of the proximal stomach: 27 females and 11 males, mean age 65 years (extreme: 22-84). There was no case on emergency, 4 patients had have at least one episode of intrathoracic volvulus. The operation consisted in gastric reduction into the abdominal cavity, excision of the sac, suture of the crura reinforced with a mesh in 6 patients and the construction of a gastric wrap. A postoperative barium swallow was performed on POD 3 in order to confirm the anatomical result. RESULTS: Mean operating time was 157 minutes (75-480), no case was converted into laparotomy. Four postoperative complications were observed (morbidity 10.8%): one gastric perforation diagnosed on POD 1, 2 severe dysphagias linked to the wrap, and one atelectasia. There was no death in this series. Functional results were evaluated by the mean of a questionnaire in 33 patients who had a follow up more than 6 months. Thirty-three questionnaires have been sent, 3 patients were lost and one was dead. Among the 29 patients analyzed, 14 were very satisfied, 11 were satisfied and 3 were deceived by the operation. Best results are obtained in patients with GERD, dysphagia or postprandial cardiothoracic symptoms. CONCLUSION: These results compared to the published data allow us to discuss about indications of surgery, the necessity to removal the hernia sac, and the advantages to reinforce the crura by the mean of a non absorbable mesh.

Adult↗
PubMed2006

[Bronchial obstruction in intensive care].

Bronchial obstruction due to one of the major pulmonary diseases asthma, COPD, or emphysema are a common problem in intensive care medicine as the leading cause or as comorbidity. While in pharmacological therapy no major changes have occurred during the last few years, two major advances have been reached in ventilation therapy which are in the focus of this review. First the non invasive ventilation (NIV) has been shown to prove efficient in treating acute on chronic respiratory failure in COPD patients and is capable of shortening the duration of hospital stay. In addition NIV can be used successfully in weaning after long time ventilator therapy and improve prognosis in COPD patients. Secondly the strategy of invasive ventilation therapy has changed significantly. "Permissive hypercapnia" is unequivocally established in severe bronchial obstruction in situations of limited ventilation. When intrinsic PEEP and elevated airway resistance are present PEEP may be useful and the upper limit of airways peak pressure that we are used to in "protective ventilation" of ARDS patients can be necessary and useful to exceed.

Airway Obstruction↗
PubMed2006

[Sentinel lymph node dissection in prostate cancer. Experience after more than 800 interventions].

There is no consensus on which prostate cancer patients should undergo lymph node removal and which lymph nodes should be included. Therefore, most clinicians rely on nomograms and dispense with lymph node dissection in patients with low-risk disease. Meanwhile, there are some studies which prove that there are also lymph node metastases in patients with low-risk prostate cancer and that lymph node metastases are predominantly localized outside the region of standard lymphadenectomy. In more than 800 men we could show that lymph node metastases were found more often than shown in the Partin tables. These lymph node metastases were detected by sentinel lymph node dissection outside the region of standard and extended lymphadenectomy. Because of insufficient preoperative diagnostics it is unclear which patients have positive lymph nodes. Therefore, it is useful to perform lymph node dissection in every patient. Men with positive nodes could have a better prognosis, when sentinel and extended lymph node dissection are performed.

Biomarkers, Tumor↗
PubMed2005

Pharmacokinetics and efficacy of ifosfamide or trofosfamide in patients with intraocular lymphoma.

BACKGROUND: The prognosis of intraocular lymphoma (IOL) is poor, and the optimal treatment has not yet been defined. The study assesses ifosfamide (IFO) and trofosfamide (TRO) for treating IOL. PATIENTS AND METHODS: We prospectively evaluated the efficacy and aqueous penetration of intravenous IFO, oral TRO and their active 4-hydroxy (4-OH) metabolites in 10 patients with IOL. Doses varied from 1500 to 2000 mg/m2/day on days 1-3 for IFO and from 150 to 400 mg/day (continuous or intermittent administration) for TRO. Four patients had newly diagnosed disease, and six had relapsed after pretreatment. RESULTS: All patients responded to first treatment with IFO or TRO, and both of two patients responded to re-treatment with IFO on ocular relapse. Progression-free survival from the first treatment with IFO or TRO was > or = 6-18 months. In six of six patients, 4-OH metabolites were detected in the aqueous humor at a concentration of 0.32-1.56 microM immediately after IFO infusion with an aqueous/serum ratio of 0.19-0.54. 4-OH metabolites could be detected in one of three patients at a concentration of 7.2 microM 3-16 h after ingestion of TRO. CONCLUSIONS: IFO and TRO are active in IOL. IOL patients evidence aqueous penetration of 4-OH metabolites after intravenous administration of IFO.

Aged↗
PubMed2005

The light-addressable potentiometric sensor for multi-ion sensing and imaging.

The light-addressable potentiometric sensor (LAPS) is a semiconductor-based chemical sensor with an electrolyte-insulator-semiconductor structure. The LAPS can have many measuring points integrated on the sensing surface, which are individually accessed by a light beam. By modifying the measuring points with different materials, a single sensor plate can be used as a multi-analyte sensor. In this paper, instrumentation and application of LAPS to multi-ion sensing and imaging are described. As a new application of LAPS, potentiometric imaging of a microfluidic channel is proposed.

Biosensing Techniques↗
PubMed2005

Effects of formulation and process variables on the release of a weakly basic drug from single unit extended release formulations.

A new commercially available extended release matrix material, Kollidon SR, composed of polyvinylacetate (PVA) and polyvinylpyrrolidone (PVP), was evaluated with respect to its ability to modulate the in vitro release of the weakly basic drug ZK 811 752. The effect of different formulation and process parameters on the release kinetics of ZK 811 752 from PVA/PVP based matrix tablets was investigated as a function of the (i) nature of excipient added to the drug-polymer mixtures, (ii) method of manufacturing (direct compression versus wet granulation), and (iii) effect of a post-compression curing step. ZK 811 752 containing extended release matrix tablets were successfully prepared by using Kollidon SR. The drug release from the matrix tablets increased by the addition of excipients such as maize starch, lactose and calcium phosphate. Addition of the highly swellable maize starch and the water-soluble lactose accelerated the drug release in a more pronounced manner compared to the water-insoluble calcium phosphate. Compound release from matrix tablets prepared by wet granulation was faster compared to the drug release from tablets prepared by direct compression. Post compression curing did not influence the drug release rate from drug-lactose-Kollidon SR formulations. Stability studies demonstrated no degradation of the drug substance and reproducible drug release patterns for matrix tablets stored at 25 degrees C/60% RH and 30 degrees C/70% RH for up to 6 months.

Calcium Phosphates↗
PubMed2005

Development of a multi particulate extended release formulation for ZK 811 752, a weakly basic drug.

ZK 811 752, a potent candidate for the treatment of autoimmune diseases, demonstrated pH-dependent solubility. The resulting release from conventional mini matrix tablets decreased with increasing pH-values of the dissolution medium. The aim of this study was to overcome this problem and to achieve pH-independent drug release. Mini matrix tablets were prepared by direct compression of drug, matrix former (polyvinylacetate/polyvinylpyrrolidone; Kollidon SR) and excipients (lactose, calcium phosphate or maize starch). To solve the problem of pH-dependent solubility fumaric acid was added to the drug-polymer excipient system. The addition of fumaric acid was found to maintain low pH-values within the mini tablets during release of ZK 811 752 in phosphate buffer pH 6.8. Thus, micro environmental conditions for the dissolution of the weakly basic drug were kept constant and drug release was demonstrated to be pH-independent. Incorporation of water-soluble (lactose) or highly swellable (maize starch) excipients accelerated drug release in a more pronounced manner compared to the water-insoluble excipient calcium phosphate. Stability studies demonstrated no degradation of the drug substance and reproducible drug release patterns for mini matrix tablets stored at 25 degrees C/60% RH and 30 degrees C/70% RH for up to 6 months.

Calcium Phosphates↗
PubMed2005

A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients.

The authors investigated the use of slow-frequency repetitive transcranial magnetic stimulation (rTMS) to the unaffected hemisphere to decrease interhemispheric inhibition of the lesioned hemisphere and improve motor function in patients within 12 months of a stroke. Patients showed a significant decrease in simple and choice reaction time and improved performance of the Purdue Pegboard test with their affected hand after rTMS of the motor cortex in the intact hemisphere as compared with sham rTMS.

Adult↗
PubMed2005

Assessing methane emissions from global space-borne observations.

In the past two centuries, atmospheric methane has more than doubled and now constitutes 20% of the anthropogenic climate forcing by greenhouse gases. Yet its sources are not well quantified, introducing uncertainties in its global budget. We retrieved the global methane distribution by using spaceborne near-infrared absorption spectroscopy. In addition to the expected latitudinal gradient, we detected large-scale patterns of anthropogenic and natural methane emissions. Furthermore, we observed unexpectedly high methane concentrations over tropical rainforests, revealing that emission inventories considerably underestimated methane sources in these regions during the time period of investigation (August through November 2003).

Journal Article↗
PubMed2005

Development of a single unit extended release formulation for ZK 811 752, a weakly basic drug.

ZK 811 752, a potent candidate for the treatment of autoimmune diseases, demonstrated pH-dependent solubility. The resulting release from conventional matrix tablets decreased with increasing pH-values of the dissolution medium. The aim of this study was to overcome this problem and to achieve pH-independent drug release. Three different polymers were used as matrix formers, the partly water-soluble and poorly swellable mixture of polyvinylacetate/polyvinylpyrrolidone, the water-insoluble and almost unswellable ethylcellulose (EC) and the water-soluble and highly swellable hydroxypropyl methylcellulose (HPMC). To solve the problem of pH-dependent solubility different organic acids, such as fumaric, tartaric, adipic, glutaric and sorbic acid were added to the drug-polymer system. The addition of organic acids to all three matrix formers was found to maintain low pH-values within the tablets during release of ZK 811 752 in phosphate buffer pH 6.8. Thus, the micro-environmental conditions for the dissolution of the weakly basic drug were kept almost constant. An extended release matrix tablet for ZK 811 752 consisting of drug, polymer and organic acid providing the desired pH-independent drug release has been developed.

Chemistry, Pharmaceutical↗
PubMed2005

Multi axis differential optical absorption spectroscopy (MAX-DOAS) of gas and aerosol distributions.

We present and demonstrate a relatively simple algorithm, which converts a set of slant column density measurements of oxygen dimers (O4) and NO2 at several different elevation angles to determine the atmospheric aerosol extinction and the absolute concentration and mixing ratio of NO2 within the atmospheric boundary layer. In addition the height of the atmospheric boundary layer can usually be derived, also the technique can be readily extended to determine the concentration of several other trace gases including SO2, CH2O, or glyoxal. The algorithm is based on precise radiation transport modelling determination, taking into account the actual aerosol scenario as determined from the O4 measurements. The required hardware is simple encompassing essentially a miniature spectrometer, a small telescope, a pointing mechanism, and a Personal Computer (PC). Effectively the technique combines the simplicity of a passive MAX-DOAS observation with the capability of a much more complex active DOAS instrument to determine path-averaged, absolutely calibrated mixing ratios of atmospheric trace gases at relatively high accuracy.

Aerosols↗
PubMed2004

[New pharmaceutical and invasive approaches in cancer pain therapy].

Recent developments of newer opioids are now alternatives to morphine hydrochloride. Fentanyl and buprenorphine can be administered as trans dermal therapeutic systems. Hydromorphone and oxycodone can be given orally with different adverse profiles compared to morphine hydrochloride. Invasive therapeutic options should be kept in mind for patients refractory or resistant to conventional analgesic approaches. These approaches are presented and discussed, especially the neurolytic blockade of the celiac plexus which is important in the therapy of visceral pain. Epidural and intrathecal morphine administration can be used in the treatment of severe cancer pain.

Administration, Cutaneous↗
PubMed2004

Learning a new behavioral strategy in the shuttle-box increases prefrontal dopamine.

Using microdialysis from medial prefrontal cortex of gerbils during aversive auditory conditioning in the shuttle-box we have previously shown a transient increase of dopamine efflux correlated with the establishment of avoidance behavior. We hypothesized that the acquisition of a new behavioral strategy is generally accompanied by this extra prefrontal dopamine release. The present experiment aimed at further testing this hypothesis. In a pre-training period in the shuttle-box the gerbils acquired an active avoidance response by generalizing two different tone signals to a GO-meaning (change of shuttle-box compartment). Thereafter, they were subjected in relearning sessions to differentially associate the known tone stimuli with GO- and NOGO- (no change of shuttle-box compartment) conditions, respectively. The following formation of discrimination behavior led to a similar extra dopamine increase as found during establishment of the avoidance strategy. This significant enhancement was limited to rapidly relearning individuals. Furthermore, the dopamine increase attenuated in these animals with increasing performance during the course of the discrimination training, similar to the retrieval stage of the avoidance strategy. Therefore, the dopamine system seems to be critically involved in the initial formation of associations for new behavioral strategies, i.e. learning. We assume that the prefrontal dopamine increase during initial learning of the complex discrimination behavior indicates an involvement of working memory principles and a goal-directed formation of a behavioral strategy.

Animals↗
PubMed2004

Moxonidine in the treatment of overweight and obese patients with the metabolic syndrome: a postmarketing surveillance study.

Moxonidine is a centrally active imidazoline receptor agonist that effectively lowers blood pressure and has been shown to have beneficial effects on lipid and carbohydrate metabolism. We assessed the efficacy of moxonidine in a postmarketing surveillance study (CAMUS) conducted in 772 practices in Germany, documenting 4005 patients with hypertension, who were overweight and/or suffered from metabolic syndrome. Patients were treated with moxonidine (Cynt) for the first time following the baseline visit for 8 weeks. Mean blood pressure decreased from 168/97 to 141/83 mmHg for all patients and from 168/96 to 141/83 mmHg for patients with metabolic syndrome. Blood pressure reduction was particularly pronounced in patients with severe hypertension at baseline. The response rate (DBP< or =90 mmHg or reduction > or =10 mmHg) of antihypertensive treatment with moxonidine was 94.0% for all patients and 93.8% for patients with metabolic syndrome. The recommended targets for antihypertensive treatment of the German Diabetes Society/German Hypertension Society were reached by 30.5% of nondiabetics (goal: <140/90 mmHg) and by 3.6% of diabetics (goal: <130/80 mmHg) observed. After 8 weeks of treatment, patients achieved a mean weight loss of 1.4 kg, which was particularly pronounced in obese patients. The rate of patients receiving antihypertensive combination therapy was 81.1% for those with metabolic syndrome, and 63.3% for all other patients. Patients with metabolic syndrome were preferentially treated with ACE inhibitors and diuretics. We conclude that moxonidine effectively reduces blood pressure in patients with metabolic syndrome while simultaneously reducing body weight in obese patients.

Adult↗
PubMed2004

Thermal stability of Ti and Pt nanowires manufactured by Ga+ focused ion beam.

Ti and Pt nanowires have been produced by ultra high-vacuum molecular beam epitaxy deposition of Ti thin films and focused ion beam (FIB) deposition of Pt thin films, followed by cross-sectional FIB sputtering to form electron-transparent nanowires. The thermal stability of the nanowires has been investigated by in situ thermal cycling in a transmission electron microscope. Epitaxial single crystal Ti nanowires on (0001)Al(2)O(3) substrates are microstructurally stable up to 550-600 degrees C, above which limited dislocation motion is activated shortly before the Ti-wires oxidize. The amorphous FIB-deposited Pt wires are stable up to 580-650 degrees C where partial crystallization is observed in vacuum. Faceted nanoparticles grow on the wire surface, growing into free space by surface diffusion and minimizing contact area with the underlying wire. The particles are face-centred cubic (fcc) Pt with some dissolved Ga. Continued heating results in particle spheroidization, coalescence and growth, retaining the fcc structure.

Journal Article↗