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Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 19 recordsLinked to original sources
PubMed2006

Randomised phase II study comparing topotecan/carboplatin administration for 5 versus 3 days in the treatment of extensive-stage small-cell lung cancer.

BACKGROUND: Topotecan is an active drug in small-cell lung cancer (SCLC). In our previous study, a combination of topotecan with cisplatin was associated with a median overall survival of 7.6 or 8.7 months, depending on the duration of treatment. We have replaced cisplatin by carboplatin in this trial, with the objective of creating a more convenient schedule for our patients. Furthermore, we have also compared the standard 5-day schedule with an experimental 3-day schedule. PATIENTS AND METHODS: A total of 100 patients with metastatic disease were included. Patients were randomly assigned to receive either topotecan 0.75 mg/m2, days 1-5, and carboplatin AUC 5, day 5 (arm A) or topotecan 1.25 mg/m2, days 1-3, and carboplatin AUC 5, day 3 (arm B). Six cycles were given at a 3-week interval. RESULTS: A total of 91 patients were assessable for response. The response during therapy was 86.9% in arm A and 80.0% in arm B. Median survival in arm A was 11.8 months and in arm B 11.6 months (P=0.37). CONCLUSIONS: The combination of topotecan and carboplatin is active in extensive-disease SCLC. Toxicity and median survival were comparable in both arms. Three days of treatment seems to be similar to the 5-day regimen.

Adolescent↗
PubMed2006

Post-transplant hypophosphatemia: Tertiary 'Hyper-Phosphatoninism'?

Hypophosphatemia is a common complication of kidney transplantation. Tertiary hyperparathyroidism has long been thought to be the etiology, but hypophosphatemia can occur despite low parathyroid hormone (PTH) levels and can persist after high PTH levels normalize. Furthermore, even in the setting of normal allograft function, hypophosphatemia, and hyperparathyroidism, calcitriol levels remain inappropriately low following transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor-23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed a prospective, longitudinal study of 27 living donor transplant recipients to test the hypotheses that excessive FGF-23 accounts for hypophosphatemia and decreased calcitriol levels following kidney transplantation. Hypophosphatemia <2.5 mg/dl developed in 85% of subjects, including one who had previously undergone parathyroidectomy; 37% developed phosphate < or =1.5 mg/dl. The mean pre-transplant FGF-23 level was 1,218+/-542 RU/ml. Within the first week following transplantation, mean levels decreased to 557+/-579 RU/ml, which were still above normal. FGF-23 was independently associated with serum phosphate (P < 0.01), urinary excretion of phosphate (P < 0.01), and calcitriol levels (P < 0.01); PTH was not independently associated with any of these parameters. We calculated area under the curve for FGF-23 and PTH between the pre- and first post-transplant levels as a summary measure of early exposure to these phosphaturic hormones. An area under the FGF-23 curve greater than the median was associated with a relative risk of developing hypophosphatemia < or =1.5 mg/dl of 5.3 (P = 0.02) compared with lower levels. Increased area under the PTH curve was not associated with greater risk of hypophosphatemia. Excessive FGF-23 exposure in the early post-transplant period appears to be more strongly associated with post-transplant hypophosphatemia than PTH.

Adult↗
PubMed2006

Time evolution of the electronic structure of 1T-TaS2 through the insulator-metal transition.

Femtosecond time-resolved photoemission is used to investigate the time evolution of electronic structure in the Mott insulator 1T-TaS2. A collapse of the electronic gap is observed within 100 femtoseconds after optical excitation. The photoemission spectra and the spectral function calculated by dynamical mean field theory show that this insulator-metal transition is driven solely by hot electrons. A coherently excited lattice displacement results in a periodic shift of the spectra lasting for 20 ps without perturbing the insulating phase. This capability to disentangle electronic and phononic excitations opens new directions to study electron correlation in solids.

Journal Article↗
PubMed2006

[An internet connecting bridge between specialized institution and the daily routine].

The "Internet-Brücke" is intended to facilitate the patient's return from a specialist institution for psychotherapy and psychosomatics to the everyday setting. Participants meet once a week in an internet chat room. The open group sessions are accompanied by a group therapist, and their overall availability is limited to 12-15 weeks. This option was greatly welcomed by the patients, and from the technical point of view proved reliable, secure and easy to use. In a prospective, controlled study, the "Internet-Brücke" turned out to be an effective means of maintaining the health improvements achieved during institutionalized treatment.This option would appear to be strongly indicated when continued, post-institution treatment either cannot be provided at all, or only after too long a delay.

Aftercare↗
PubMed2006

Femtosecond laser induced associative desorption of H2 from Ru(0001): comparison of "first principles" theory with experiment.

A three dimensional model based on molecular dynamics with electronic frictions is developed to describe the femtosecond laser induced associative desorption of H2 from Ru(0001)(1 x 1)H. Two molecular coordinates (internuclear separation d and center of mass distance to surface z) and a single phonon coordinate are included in the dynamics. Both the potential energy surface and the electronic friction tensor are calculated by density functional theory so that there are no adjustable parameters in the comparison of this model with the wide range of experiments available for this system. This "first principles" dynamic model gives results in semiquantitative agreement with all experimental results; nonlinear fluence dependence of the yield, isotope effect, two pulse correlation, and energy partitioning. The good agreement of theory with experiment supports a description of this surface femtochemistry in terms of thermalized hot electron induced chemistry with coupling to nuclear coordinates through electronic frictions. By comparing the dynamics with the analytical one dimensional frictional model used previously to fit the experiments for this system, we show that the success of the one dimensional model is based on the rapid intermixing of the z and d coordinates as the H-H climbs out of the adsorption well. However, projecting the three dimensional dynamics onto one dimension introduces a fluence (adsorbate temperature) dependent "entropic" barrier in addition to the potential barrier for the chemistry. This implies that some caution must be used in interpreting activation energies obtained in fitting experiments to the one dimensional model.

Journal Article↗
PubMed2006

Identification of target genes in laryngeal squamous cell carcinoma by high-resolution copy number and gene expression microarray analyses.

Molecular mechanisms contributing to initiation and progression of head and neck squamous cell carcinoma are still poorly known. Numerous genetic alterations have been described, but molecular consequences of such alterations in most cases remain unclear. Here, we performed an integrated high-resolution microarray analysis of gene copy number and expression in 20 laryngeal cancer cell lines and primary tumors. Our aim was to identify genetic alterations that play a key role in disease pathogenesis and pinpoint genes whose expression is directly impacted by these events. Integration of DNA level data from array-based comparative genomic hybridization with RNA level information from oligonucleotide microarrays was achieved with custom-developed bioinformatic methods. High-level amplifications had a clear impact on gene expression. Across the genome, overexpression of 739 genes could be attributed to gene amplification events in cell lines, with 325 genes showing the same phenomenon in primary tumors including FADD and PPFIA1 at 11q13. The analysis of gene ontology and pathway distributions further pinpointed genes that may identify potential targets of therapeutic intervention. Our data highlight genes that may be critically important to laryngeal cancer progression and offer potential therapeutic targets.

Carcinoma, Squamous Cell↗
PubMed2006

Ultrafast dynamics of delocalized and localized electrons in carbon nanotubes.

We report on the dynamics of the dielectric function of single-wall carbon nanotubes in the 10-30 THz frequency range after ultrafast laser excitation. The absence of a distinct free-carrier response is attributed to the photogeneration of strongly bound excitons in the tubes with large energy gaps. We find a feature of enhanced transmission caused by the blocking of optical transitions in small-gap tubes. The rapid decay of a featureless background with pronounced dichroism is associated with the increased absorption of spatially localized charge carriers before thermalization is completed.

Journal Article↗
PubMed2006

[Respiratory sinus arrhythmia as predictor of blood pressure stability during anaesthetic induction in diabetics].

OBJECTIVE: Diabetics with cardiovascular autonomous neuropathy (CAN) can show severe hypotension during the course of anaesthesia. To improve the safety of anaesthesia, pre-operative evaluation of this concomitant disorder is recommended. The conventional test battery described by Ewing and Clarke to diagnose CAN is relatively time-consuming and complex. The aim of this study was to evaluate whether patients at risk could be reliably identified with less diagnostic effort. METHODS: Fifty patients with diabetes mellitus undergoing an ophthalmosurgical procedure were investigated. To evaluate their cardiovascular reflex status, the following tests were performed one day before surgery: determination of heart rate variation (HRV) under deep respiration (6 breaths/min), and the response of heart rate (max/min 30:15 ratio) and blood pressure after getting up from a supine position. Anaesthesia was induced with thiopental and fentanyl and maintained with enflurane/N (2)0; vecuronium was administered for tracheal intubation. Patients whose systolic blood pressure fell below 90 mm Hg during the induction phase were assigned to Group H (hypotensive), the remaining patients to Group N (non-hypotensive). The groups were compared regarding the pre-operatively collected variables. RESULTS: The demographic data were comparable in the two groups with exception of the length of diabetes. Regarding blood pressure reaction during orthostatic load, there was no significant difference between the groups. In contrast, the parameters of HRV under deep respiration (with exception of the "mean circular resultant") and the max/min 30 : 15 ratio were significantly lower in patients of Group H than in Group N. The best differentiation between the groups offered the E/I ratio (= quotient resulting from the longest R-R interval during expiration (E) and the shortest R-R interval during inspiration (I) under deep breathing) as a measure of respiratory sinus arrhythmia. The incidence of hypotension during anaesthetic induction in patients with a normal E/I ratio was 8.7 %, but in patients with a pathologically reduced E/I ratio 51.9 % ( P = 0.0019). The sensitivity of this test concerning hypotension that occurred was 87.5 %, the specificity 61.7 %. CONCLUSION: The available results prove the close connection between the pre-operatively measured breadth of respiratory sinus arrhythmia and blood pressure response during anaesthetic induction. Patients at risk of hypotension can be identified reliably and quickly during pre-operative screening with the help of a single, simple test procedure.

Adult↗
PubMed2006

Prognostic value of inhibitory anti-ADAMTS13 antibodies in adult-acquired thrombotic thrombocytopenic purpura.

In order to assess the prognostic value of inhibitory anti-ADAMTS13 antibodies in thrombotic thrombocytopenic purpura (TTP), we performed a multicentre prospective study of 33 adult patients with idiopathic acquired TTP. Patients were treated with high-dose plasma infusion and therapeutic plasma exchange. Patients without (group 1, n = 12) and with (group 2, n = 21) detectable inhibitory anti-ADAMTS13 antibodies were compared for clinical presentation, treatment and outcome. Both groups were comparable for clinical presentation. All patients in group 1 achieved a sustained complete remission within a median of 7 d [95% confidence interval (CI), 4-18], which required a median plasma volume of 235 ml/kg (range, 131-1251). In group 2, 17 patients achieved a durable complete remission within a median of 23 d (95% CI, 11-32) (P = 0.001). Median plasma volume was 718 ml/kg (range, 219-3107) (P = 0.02). In group 2, there was a trend for more episodes of flare-up than in group 1 (13 vs. 3, respectively, P = 0.07). Four patients, all from group 2, died (P = not significant). The relapse rate was comparable between both groups. We suggest that TTP with detectable inhibitory anti-ADAMTS13 antibodies displays a worse prognosis, relative to a delayed platelet count recovery, a higher plasma volume requirement to achieve complete remission, and a trend for more frequent episodes of flare-up.

ADAM Proteins↗
PubMed2005

Femtosecond electron and spin dynamics in Gd(0001) studied by time-resolved photoemission and magneto-optics.

Femtosecond electron and spin dynamics of the Gd(0001) surface are investigated by time-resolved photoemission and second harmonic generation. Upon optical excitation the spin polarization of the surface state is reduced by half while its exchange splitting remains nearly unchanged. Electron-magnon interaction is proposed to facilitate electron-spin-flip scattering among spin-mixed surface and bulk states, which provides a mechanism for ultrafast demagnetization.

Journal Article↗
PubMed2005

The effect of the Hyper-CVAD chemotherapy regimen on fertility and ovarian function.

Hyper-CVAD is a dose intensive chemotherapy regimen that has been used successfully in lymphoblastic lymphoma and leukaemia. However, the effect on ovarian function has not been evaluated. Thus, we undertook a retrospective analysis of patients under 40 years of age who had Hyper-CVAD as initial therapy and documented ovarian function as defined by regular menstruation off hormonal agents or naturally conceiving. Of the 12 patients identified, 7 were evaluable. Median age was 25. Six patients had resumption of regular menstruation and three of these women have conceived naturally. In conclusion, resumption of normal fertility is probable post-treatment with Hyper-CVAD.

Adult↗
PubMed2005

Quantum theoretical study of electron solvation dynamics in ice layers on a Cu(111) surface.

Recent experiments using time- and angle-resolved two-photon photoemission (2PPE) spectroscopy at metal/polar adsorbate interfaces succeeded in time-dependent analysis of the process of electron solvation. A fully quantum mechanical, two-dimensional simulation of this process, which explicitly includes laser excitation, is presented here, confirming the origin of characteristic features, such as the experimental observation of an apparently negative dispersion. The inference of the spatial extent of the localized electron states from the angular dependence of the 2PPE spectra has been found to be non-trivial and system-dependent.

Journal Article↗
PubMed2005

Automated segmentation of the optic nerve head for diagnosis of glaucoma.

Glaucoma is the second most common cause of blindness worldwide. Low awareness and high costs connected to glaucoma are reasons to improve methods of screening and therapy. A well-established method for diagnosis of glaucoma is the examination of the optic nerve head using scanning-laser-tomography. This system acquires and analyzes the surface topography of the optic nerve head. The analysis that leads to a diagnosis of the disease depends on prior manual outlining of the optic nerve head by an experienced ophthalmologist. Our contribution presents a method for optic nerve head segmentation and its validation. The method is based on morphological operations, Hough transform, and an anchored active contour model. The results were validated by comparing the performance of different classifiers on data from a case-control study with contours of the optic nerve head manually outlined by an experienced ophthalmologist. We achieved the following results with respect to glaucoma diagnosis: linear discriminant analysis with 27.7% estimated error rate for automated segmentation (aut) and 26.8% estimated error rate for manual segmentation (man), classification trees with 25.2% (aut) and 22.0% (man) and bootstrap aggregation with 22.2% (aut) and 13.4% (man). It could thus be shown that our approach is suitable for automated diagnosis and screening of glaucoma.

Algorithms↗
PubMed2005

[Pre-operative measurement of heart rate variability in diabetics: a method to estimate blood pressure stability during anaesthesia induction].

BACKGROUND: In diabetics severe hyopotension can occur during anaesthesia as a consequence of cardiovascular autonomic neuropathy (CAN). A simple approach to recognize CAN is heart rate variability (HRV) measured at rest. The aim of this study was to determine the relationship between pre-operatively measured HRV and blood pressure stability during induction phase of anaesthesia. PATIENTS AND METHODS: A total of 35 diabetics undergoing an ophthalmosurgical procedure under general anaesthesia were investigated. HRV was examined one day before surgery by the following parameters: coefficient of variation (CV), root mean squared successive difference (RMSSD), and power spectrum. Anaesthesia was induced with thiopental and fentanyl and maintained with enflurane/N(2)O; tracheal intubation was performed after relaxation with vecuronium. Patients who developed a drop in systolic blood pressure below 90 mmHg during anaesthesia induction were assigned to group H (hypotensive), the other patients to group N (normotensive). The groups were compared regarding HRV and other variables. RESULTS: Of all patients 13 developed hypotension during anaesthesia induction (group H). The groups were comparable regarding the demographic data. Parameters of HRV, with the exception of spectral power in low frequency (LF) band of power spectrum, were significantly lower in group H. The groups differed mainly in relation to spectral power in the mid-frequency (MF) band of the power spectrum, and especially regarding CV. In patients with normal CV incidence of hypotension after anaesthesia induction was 11%, but in patients with abnormally reduced CV, 65% (p=0.002). CONCLUSION: The results confirm a significant relationship between HRV pre-operatively measured at rest and blood pressure stability during anaesthesia induction in diabetics. Particularly examination of CV, a simple test feasible within few minutes, may be useful in pre-operative risk stratification of these patients. Application of the time consuming traditional test combination to identify CAN seems to be unnecessary.

Aged↗
PubMed2005

Randomized phase II study comparing topotecan/cisplatin administration for 5 days versus 3 days in the treatment of extensive stage small cell lung cancer (SCLC).

BACKGROUND: Topotecan (T) is an active drug in SCLC. A combination of topotecan with cisplatin (DDP) was suggested to be highly synergistic. This phase II trial was initiated to assess the activity of T/DDP in chemotherapy-naive patients suffering from extensive disease small cell lung cancer (SCLC) and to compare the conventional 5-day regime with an experimental 3-day schedule. PATIENTS AND METHODS: A total of 86 patients were included. Patients were randomized to receive either T 1.0 mg/m2 d 1-5 and DDP 75 mg/m2 d 5 (arm A) or T 1.5 mg/m2 d 1-3 and DDP 75 mg/m2 d 3 (arm B). Six cycles were given at a 3-week interval. RESULTS: Data of 84 evaluable patients (67 males and 17 females) were analysed. All patients had metastatic disease. The best response rate was 61.9% in arm A and 59.5% in arm B. Median overall survival was 8.7 months in arm A and 7.6 months in arm B (p=0.6809). CONCLUSIONS: Combination of T and DDP is active in ED SCLC. Toxicity and median survival were comparable in both arms. Three days treatment seems to be similar to the 5 days regime.

Adult↗
PubMed2005

Extra-placental expression of vascular endothelial growth factor receptor-1, (Flt-1) and soluble Flt-1 (sFlt-1), by peripheral blood mononuclear cells (PBMCs) in normotensive and preeclamptic pregnant women.

The soluble VEGF receptor, sFlt-1 (otherwise referred to as sVEGFR-1), has been implicated in the pathogenesis of preeclampsia. The preeclamptic placenta has been previously demonstrated to produce high levels of the soluble VEGF receptor. Here we tested the hypothesis that peripheral blood mononuclear cells (PBMCs) may also represent an additional source for circulating sFlt-1 during normal and preeclamptic pregnancies. We first demonstrate that preeclamptic placentae show five-fold increased Flt-1 and sFlt-1 mRNA levels. We also show that the Flt-1 and sFlt-1 levels are eight-fold higher in preeclamptic placentae if we collect biopsies without rinsing them in saline to remove excess blood. Cultured villous explants from women with preeclampsia failed to show the increased amount of Flt-1 and sFlt-1 mRNA that was observed in the placental biopsies of normal pregnancy and preeclampsia. Under normoxic conditions the Flt-1 and sFlt-1 mRNA levels in the explants were 3.11+/-0.6 fold in normal pregnancy and 3.6+/-0.4 fold in women with preeclampsia (p = NS by ANOVA). However, the same villous explants showed hypoxic induction of Flt-1 mRNA (NP 3.96+/-0.4 fold, p = NS and PE 5.24+/-0.6 fold, p < 0.05 by ANOVA). We analyzed Flt-1 and sFlt-1 protein levels in the peripheral blood mononuclear cells (PBMCs) to analyze the possibility of an extra-placental sFlt-1 source. Our results indicate that PBMCs of pregnant women are capable of expressing variable amounts of Flt-1 proteins. PBMCs from pregnant women exposed to hypoxia show up-regulation of HIF-1alpha and Flt-1 proteins. PBMCs obtained from women with preeclampsia (n = 9) produced significantly higher amounts of sFlt-1 under normal tissue culture conditions (104.6+/-14.3 pg/ml vs. 46.23+/-5.03 pg/ml, p < 0.05 by ANOVA) and much higher concentrations under hypoxia (196.74+/-26.3pg/ml vs. 83.3+/-13.6pg/ml, p < 0.05 by ANOVA) than PBMCs from normal pregnant women (n = 11). Moreover, analysis of PBMCs from a different group of women with a history of preeclampsia showed persistent abnormality of Flt-1 women one year post-partum. The present study indicates that Flt-1 dysregulation in PBMCs of pregnant women resulting in over-expression of sFlt-1 could be an additional (extra-placental) source of sFlt-1 that contributes to the pathogenesis of preeclampsia.

Adult↗