Search PubMed⌕ Search

Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 55 records · Page 3Linked to original sources
PubMed2003

Actions of endothelin and corticotropin releasing factor in the guinea-pig ileum: no evidence for an interaction with capsaicin-sensitive neurons.

Both endothelins and corticotropin releasing factor (CRF) appear in capsaicin-sensitive neurons. We have investigated the effects of human endothelin-1 (ET-1) and CRF in the guinea-pig ileum longitudinal and circular preparations and sought for ways of specific antagonism. With the aid of tachyphylaxis to capsaicin (i.e., rendering capsaicin-sensitive neurons functionally impaired) it was tested if these neurons played a mediating role in the effects of ET-1 or CRF. We also tried to find out whether endogenous endothelin or CRF plays a role in the excitatory and inhibitory effects of capsaicin in the ileum. In preparations at basal tone, both exogenous ET-1 (1-100 nM) and CRF (3-100 nM) caused contraction. These responses were not influenced by capsaicin tachyphylaxis. The contractile effect of ET-1 was not affected by tetrodotoxin (1 microM), atropine (1 microM), methysergide (100 nM), chloropyramine (100 nM) or SR140333 (100 nM) but was significantly inhibited or even abolished by the receptor antagonist BQ123 (3 microM) or BQ788 (3 microM). CRF caused contraction that was fully sensitive to tetrodotoxin (1 microM), tachyphylaxis to CRF or to atropine (1 microM) plus the tachykinin NK1 receptor antagonist SR140333 (200 nM). Atropine alone had a weak inhibitory effect on the contractile action of CRF. Neither the antagonist BQ123 (3 microM) nor CRF tachyphylaxis inhibited the contractile action of capsaicin (2 microM), even in the presence of a mixture of GR82334 (3 microM) and SR142801 (100 nM), for blocking tachykinin NK1 and NK3 receptors, respectively--a treatment that by itself significantly reduced the effect of capsaicin. Exogenous ET-1 (0.3-5 nM), but not CRF (30-100 nM), caused relaxation of the atropine-treated, histamine-precontracted ileum. This effect of ET-1 was significantly inhibited or abolished by BQ123 (10 microM), or BQ788 (3 microM), but was not influenced by capsaicin tachyphylaxis. Likewise, relaxation of the atropine-treated, histamine-precontracted ileum in response to capsaicin was not influenced by the endothelin receptor antagonist BQ788 (3 microM) or BQ788 (3 microM) plus BQ123 (3 microM). Apamin (300 nM) was also without effect on the capsaicin-induced relaxation. In circular muscle strips ET-1 inhibited the indomethacin-induced spontaneous activity. This effect was abolished by BQ123 (3 microM) or BQ788 (3 microM). CRF caused a stimulation of the circular muscle. This stimulatory effect was not influenced by atropine (1 microM) alone, but was inhibited by atropine plus tachykinin NK1 and NK2 receptor antagonists (SR140333 (200 nM) and SR48968 (200 nM)) and also by tetrodotoxin (1 microM). It is concluded that capsaicin-sensitive neurons do not play a role in the effects of exogenous ET-1 or CRF in the guinea-pig ileum. ET-1 can both contract and relax the ileal longitudinal smooth muscle directly, probably via both ETA and ETB receptors. CRF acts by specifically stimulating excitatory (but not inhibitory) neurons of the myenteric plexus. Neither endogenous ET-1 nor CRF seems to play a role in the excitatory or inhibitory effects of capsaicin.

Animals↗
PubMed2003

A retrospective analysis of the outcome of patients who have received two prior chemotherapy regimens including platinum and docetaxel for recurrent non-small-cell lung cancer.

With the availability of chemotherapy agents for first- and second-line treatment of advanced non-small-cell lung cancer (NSCLC), the patient population that requires subsequent chemotherapy is increasing. This retrospective analysis was performed to describe the clinical course after two standard or approved chemotherapy agents in patients with good overall performance status. Data were selected from patients with advanced NSCLC who had received third- or fourth-line chemotherapy after two prior chemotherapy regimens that included platinum and docetaxel given concurrently or sequentially. Prior regiments had failed due to discase progression within 90 days of chemotherapy, or unacceptable toxicity. Examination of over 700 patient records between January 1993 and January 2000 at one US and one European cancer centre revealed 43 patients that fulfilled the inclusion criteria. Response rates decreased with each line of treatment: first line, 20.9%; second line, 16.3%; third line, 2.3%; and fourth line, 0%. The disease control rate (response plus stable disease) also decreased dramatically from first- to fourth-line treatment, although it was higher for second-line treatment (74.4%) than for first-line treatment (62.8%). The median overall survival time from diagnosis was 16.4 months. The median overall survival time from the start of the last treatment (either third or fourth line) was 4 months. Patients with stage III disease at diagnosis had a longer overall survival from diagnosis than patients with stage IV disease (P=0.02). This review highlights the need for novel therapy approaches for patients with recurrent NSCLC who have failed second-line therapy and provides a baseline for the statistical design of such studies.

Adult↗
PubMed2003

Treatment of patients with advanced mycosis fungoides and Sézary syndrome with alemtuzumab.

OBJECTIVES: Alemtuzumab (anti-CD52, Campath-1H) has recently been shown to be effective in the treatment of a range of hematological malignancies, including B-cell chronic lymphocytic leukemia and T-cell prolymphocytic leukemia. We undertook a phase II study to evaluate the safety, tolerability and efficacy of alemtuzumab in patients with relapsed or refractory advanced stage cutaneous T-cell lymphoma. PATIENTS AND METHODS: A total of eight patients were enrolled, seven with mycosis fungoides/Sézary syndrome (MF/SS) and one with large-cell transformation of MF. Seven patients had disease refractory to multiple previous therapies. Alemzumab (30 mg) was administered intravenously three times per week for 12 wk or until maximum response. RESULTS: The overall response rate was 38%, with three patients achieving partial remission, two patients with stable disease and three patients with progressive disease (PD) during treatment. The time to progression was short, with all patients developing PD within 4 months of starting alemtuzumab. Response duration in the three PR patients was also brief, with responses lasting less than 3 months in all three cases. Significant hematological and immunosuppressive toxicity was observed, with both grade 3-4 cytopenias and significant infectious complications occurring in a majority of cases. CONCLUSIONS: Our findings suggest that in heavily pretreated, refractory, advanced stage MF/SS, although alemtuzumab has biological activity, it is associated with significant toxicity and only modest clinical utility. As such, combination regimens incorporating alemtuzumab merit further investigation in this difficult to treat patient group.

Adult↗
PubMed2003

Drosophila melanogaster and D. simulans rescue strains produce fit offspring, despite divergent centromere-specific histone alleles.

The interaction between rapidly evolving centromere sequences and conserved kinetochore machinery appears to be mediated by centromere-binding proteins. A recent theory proposes that the independent evolution of centromere-binding proteins in isolated populations may be a universal cause of speciation among eukaryotes. In Drosophila the centromere-specific histone, Cid (centromere identifier), shows extensive sequence divergence between D. melanogaster and the D. simulans clade, indicating that centromere machinery incompatibilities may indeed be involved in reproductive isolation and speciation. However, it is presently unclear whether the adaptive evolution of Cid was a cause of the divergence between these species, or merely a product of postspeciation adaptation in the separate lineages. Furthermore, the extent to which divergent centromere identifier proteins provide a barrier to reproduction remains unknown. Interestingly, a small number of rescue lines from both D. melanogaster and D. simulans can restore hybrid fitness. Through comparisons of cid sequence between nonrescue and rescue strains, we show that cid is not involved in restoring hybrid viability or female fertility. Further, we demonstrate that divergent cid alleles are not sufficient to cause inviability or female sterility in hybrid crosses. Our data do not dispute the rapid divergence of cid or the coevolution of centromeric components in Drosophila; however, they do suggest that cid underwent adaptive evolution after D. melanogaster and D. simulans diverged and, consequently, is not a speciation gene.

Animals↗
PubMed2003

[Efficacy of Arnica in varicose vein surgery: results of a randomized, double-blind, placebo-controlled pilot study].

INTRODUCTION: In homeopathy ARNICA is widely used as a woundhealing medication and for the treatment of hematomas. OBJECTIVE: In this pilot study the efficacy and safety of ARNICA D12 in patients following varicose vein surgery were investigated. DESIGN: Prospective, randomized, double-blind, placebo-controlled pilot trial according to ICH GCP guidelines. SETTING: The study was conducted by a surgeon at the Angiosurgical Clinic, Berlin- Buch. INTERVENTION: After randomized allocation, 60 patients received either ARNICA D12 or placebo. Start of medication occurred the evening before operation with 5 globules. On the operation day one preoperative and hourly postoperative dosages after awakening were given. On days 2-14 of the study 5 globules 3 times a day were given. OUTCOME CRITERIA: Surface (in cm(2) and using a three-point verbal rating scale) and intensity of hematomas induced by operation, complications of wound healing, and intensity of pain (five-point verbal rating scale) as well as efficacy and safety of the study medication were assessed. RESULTS: Hematoma surface was reduced (from day 7 to day 14) under ARNICA by 75.5% and under placebo by 71.5% (p = 0.4726). The comparison of hematoma surface (small, medium, large) using the verbal rating scale yielded a value of p = 0.1260. Pain score decreased by 1.0 +/- 2.2 points under ARNICA and 0.3 +/- 0.8 points under placebo (p = 0.1977). Remission or improvement of pain was observed in 43.3% of patients in the ARNICA group and in 27.6% of patients in the placebo group. Tolerability was rated as very good in all cases. CONCLUSION: The results of this pilot study showed a trend towards a beneficial effect of ARNICA D12 with regard to reduction of hematoma and pain during the postoperative course. For a statistically significant proof of efficacy of ARNICA D12 in patients following varicose vein surgery a larger sample size is necessary.

Arnica↗
PubMed2002

Results of the safety and efficacy of iobitridol in more than 61,000 patients.

We present results of a postmarketing surveillance study with iobitridol (Xenetix, Sulzbach, Germany) in more than 61,000 patients from 1996 until 2000. The purpose of this study was the assessment of safety and diagnostic efficacy of the non-ionic contrast agent iobitridol in the setting of a post-marketing surveillance study. Iobitridol (Xenetix) has been registered in Germany since 1996. Between 1996 and 2000 207 radiologists have documented in a questionnaire the routine use of Xenetix in 61,754 patients that have received Xenetix for diagnostic procedures. On each questionnaire parameters regarding demographic data, safety, and diagnostic efficacy were assessed. The data were statistically evaluated and analysed. The examination allowed for a diagnosis in 99% of cases. Image quality was rated as "excellent" or "good" in 89.8% of cases. In obese patients there was a significantly higher percentage ( p<0.001) of poor image quality. In 0.1% poor contrast was noted. Of patients, 28.8% had at least one risk factor, and 3.1% had three or more. Adverse events were noted in 2.3% of the examinations, but nearly half of them (1.1%) presented with "feeling of warmth" as the only symptom. Of adverse events, 0.2% were non-transient, and 1 patient died. In 0.2% of patients the procedure was stopped due to adverse events. In 0.9% of patients the causal relationship with the contrast agent was rated as probable (probable+possible=1.1%). The percentage of adverse events (excluding warmth) was independent of iodine concentration and of dose, and was higher in young patients. Xenetix is an efficient contrast agent for radiological procedures and is associated with a low rate of adverse events.

Contrast Media↗
PubMed2002

Ultrafast dynamics of electron localization and solvation in ice layers on Cu(111).

The femtosecond dynamics of localization and solvation of photoinjected electrons in ultrathin layers of amorphous solid H2O and D2O have been studied by time- and angle-resolved two-photon-photoelectron spectroscopy. After electron transfer from the metal substrate into the conduction band of ice, the excess electron localizes within the first 100 fs in a state at 2.9 eV above E(F), which is further stabilized by 300 meV on a time scale of 0.5-1 ps due to molecular rearrangements in the adlayer. A pronounced change of the solvation dynamics at a coverage of approximately 2 bilayers is attributed to different rigidity of the solvation shell in the bulk and near the surface of ice.

Journal Article↗
PubMed2002

Surfactant protein B gene variations enhance susceptibility to squamous cell carcinoma of the lung in German patients.

Genetic factors are thought to influence the risk for lung cancer. Since pulmonary surfactant mediates the response to inhaled carcinogenic substances, candidate genes may be among those coding for pulmonary surfactant proteins. In the present matched case-control study a polymorphism within intron 4 of the gene coding for surfactant specific protein B was analysed in 357 individuals. They were divided into 117 patients with lung cancer (40 patients with small cell lung cancer, 77 patients with non small cell lung cancer), matched controls and 123 healthy individuals. Surfactant protein B gene variants were analysed using specific PCR and cloned surfactant protein B sequences as controls. The frequency of the intron 4 variation was similar in both control groups (13.0% and 9.4%), whereas it was increased in the small cell lung cancer group (17.5%) and the non small cell lung cancer group (16.9%). The gene variation was found significantly more frequently in patients with squamous cell carcinoma (25.0%, P=0.016, odds ratio=3.2, 95%CI=1.24-8.28) than in the controls. These results indicate an association of the surfactant protein B intron 4 variants and/or its flanking loci with mechanisms that may enhance lung cancer susceptibility, especially to squamous cell carcinoma of the lung.

Adult↗
PubMed2002

MR imaging of the lungs with hyperpolarized helium-3 gas transported by air.

Hyperpolarized noble gas MRI shows promise in the functional imaging of the pulmonary air spaces. The production of hyperpolarized (HP) gas requires specialized laser optical pumping apparatus, which is not likely to be home built in the majority of clinical MRI radiology centres. There are two routes through which HP gas will be made available to hospitals for clinical use: either the apparatus will be installed locally at a considerable expense to the centre, or a central facility will produce the gas and then deliver it to remote MRI sites as and when required. In this study, the feasibility of transporting large quantities of HP gas for in vivo MR imaging from a remote production facility in Mainz, Germany, by airfreight to Sheffield, UK, was successfully demonstrated.

Air↗
PubMed2002

[Function and responsibility of an interdisciplinary tumor center. Need for a "cancer center" for multimodal therapy concepts].

BACKGROUND AND OBJECTIVE: Cancer will be the leading cause of death in industrialized countries within the next few years. A successful treatment represents a great challenge within the next years and requires multimodality treatment approaches. An multidisciplinary tumour center is essential for coordination and communication between different departments and institutions and is important to maintain standards in diagnostic and therapeutic procedures. METHODS: Two years ago, a cancer center was founded in Marburg. The central facility of its work is a twice weekly tumour conference, where patients requiring multimodality treatment approaches are presented and treatment procedures are fixed and documented. Furthermore, guidelines for diagnosis and treatment of the various cancer diseases will be established and the transfer of clinical and experimental research to the actual patient treatment is intended. RESULTS: A total of 407 patients were discussed within the first year. Leading cancer entities were lung cancer, colorectal cancer and tumours of the upper GI-tract. The tumour conference has improved the communication between all involved disciplines. The process of standardisation of diagnostic and therapeutic procedures is ongoing. The next step will be the documentation of the further follow up of all patients discussed in the tumour conference. CONCLUSIONS: In the communication between all disciplines involved in cancer patient care, success, be it a survival benefit or an improvement in quality of life, is most likely. All the described tasks are best organized within a cancer center.

Adolescent↗
PubMed2002

Portal or hepatic vein thrombosis as the first presentation of a myeloproliferative disorder in patients with normal peripheral blood counts.

Myeloproliferative disorders (MPD) are associated with an increased risk of thrombotic complications. We describe three patients with portal or hepatic vein thrombosis and normal peripheral blood counts who had MPD on bone marrow morphology and growth factor-independent megakaryocyte or erythroid colony growth in vitro. The peripheral blood counts have become abnormal subsequently in two patients. Patients presenting with unexplained portal or hepatic vein thrombosis should be investigated systematically for the presence of a MPD, which may not be apparent using conventional diagnostic criteria.

Adult↗
PubMed2002

["Rabies odontologica" Analysis of communications among dentists by legal means].

The present study examines developments in the language used in protests, appeals and objections as lodged by patients and by attending dentists in regard to formal legal aspects and contents. The study is based on about 15,000 expert reports prepared by the Dental Services Department of the City of Wuppertal during the period from 1990 to 2001. The investigation reveals a considerable and growing discrepancy between the neutral and objective language qua legal proviso of the expert reports and the diction used in the objections, above all on the part of dentists. The authors propose a set of instruments to be used for legal analysis of texts and discuss possible reasons, including non-medical reasons, for the documented deplorable drop in standard of controversies among dentists in particular.

Communication↗
PubMed2002

Isolex 300i CD34-selected cells to support multiple cycles of high-dose therapy.

BACKGROUND: We have previously reported that repeated cycles of high-dose therapy (HDT), can be supported by unmanipulated autologous PBPC. Here we investigate whether purified CD34+ cells, obtained by immunomagnetic separation using the Isolex 300i device, can support such therapy. METHODS: Twenty-nine consecutive patients with metastatic breast cancer had PBPC mobilized and harvested following chemotherapy and G-CSF (10 microg/kg per day). Patients with > 4.0 x 10(6)/kg CD34+ cells in the apheresis product underwent CD34-selection using the Isolex 300i (v2.0) device. All cells collected were equally divided into three aliquots and cryopreserved. Patients who did not achieve this threshold had unmanipulated cells collected and stored. Patients subsequently received three cycles of HDT with paclitaxel (175 mg/m2), thiotepa (300 mg/m2) and either ifosfamide (10 g/m2) or cyclophosphamide (4 g/m2). It was intended for patients to receive CD34-selected cells to support each of the three cycles of HDT (i.e 1/3 for each cycle) and to compare hemopoietic recovery between patients receiving CD34-selected cells or unmanipulated cells. RESULTS: Thirteen of the 29 patients (45%) did not mobilize sufficient CD34+ cells to undergo CD34-selection. The remaining 16 patients underwent CD34-selection with a median purity of 84.3% (range: 16.3-96.1%) and yield of 34% (range: 1-60%). Fifteen of these patients proceeded to HDT and 42 of the planned 45 cycles were administered. Nine patients had all three HDT cycles supported by CD34-selected cells. The median number of CD34-selected cells (x 10(6)/kg) infused per cycle was 1.5 (range: 0.04-3.01). Three of the 15 patients required infusion of 'back-up' unmanipulated cells because of delayed neutrophil recovery. Of the 13 patients whose PBPCs did not undergo CD34+ cell selection, 11 proceeded to HDT with a median of 3.2 x 10(6)/kg (range: 2.0-4.4) unselected cells infused per cycle and 31 of 33 planned cycles were delivered. When hemopoietic recovery was compared between cycles of HDT supported by CD34-selected (n = 34) and unmanipulated cells (n = 31), there was a modest slowing in the patients receiving CD34-selected cells; time to ANC > 1.0 x 10(9)/L = 11 days versus 10 days (P = 0.0122) and platelets > 20 x 10(9)/L = 14 days versus 13 days (P = 0.0009). No difference in recovery to 50 x 10(9)/L was observed (P = 0.54). CONCLUSION: We have demonstrated that Isolex 300i CD34-selected cells are capable of supporting multiple cycles of HDT. However, we were unable to acquire sufficient CD34+ cells to perform this processing in 45% (13/29) of patients and further improvements in yield are required to overcome the modest delay in neutrophil and platelet recovery.

Adult↗
PubMed2002

CliniMACS CD34-selected cells to support multiple cycles of high-dose therapy.

BACKGROUND: Traditionally, following high-dose therapy (HDT), unmanipulated autologous PBPC are infused. Alternatively, purified CD34+ cells can now be obtained by immunomagnetic separation using the CliniMACS device. Limited data currently exist examining hemopoietic recovery with such cells. METHODS: Ten patients with advanced breast cancer had PBPC mobilized with docetaxel (100 mg/m2) and G-CSF (10 microg/kg per day), harvested and processed using the CliniMACS CD34-selection device and equally divided into three aliquots for cryopreservation. Unmanipulated 'back-up' cells were also collected on a separate day of the same mobilization, divided into three and cryopreserved. Patients subsequently received three cycles of HDT with cyclophosphamide (4 g/m2), thiotepa (300 mg/m2) and paclitaxel (175 mg/m2). The intent was for patients to receive CD34-selected cells to support each of the three cycles of HDT (i.e., 1/3 for each cycle). If, however, hemopoietic recovery was delayed after Cycle 1, 1/3 of the unmanipulated cells were infused following Cycle 2 and the remaining CD34-selected cells (2/3) were used to support Cycle 3. RESULTS: PBPC from 10 patients underwent CD34-selection with a resulting median purity of 93% (range: 76-98%) and yield of 62% (range: 16-93%). Of the 10 patients, only two were able to be supported with CD34-selected cells for all three cycles of HDT. The remaining eight patients required unmanipulated 'back-up' cells to support Cycle 2. Three patients also required infusion of 'back-up' unmanipulated cells because of persistent neutropenia (n = 1) or thrombocytopenia (n = 2) following cycles initially supported by CD34-selected cells. The median number of CD34-selected cells (x 10(6)/kg) infused per cycle was 1.5 (0.7-2.6) (n = 20) and unselected cells was 1.7 (1.4-2.8) (n = 10). Comparing hemopoietic recovery between cycles of HDT supported by CD34-selected (n = 20) and unmanipulated cells (n = 10) there was a significant slowing with the CD34-selected cells; time to ANC > 1.0 = 13 days versus 10 days, platelets > 20 = 17 days versus 13 days, > 50 = 25 versus 17 days (all P values < 0.001). There was no correlation between the dose of CD34-selected cells infused and neutrophil/platelet recovery. DISCUSSION: We have demonstrated that, although unmanipulated PBPC achieve rapid hemopoietic recovery (at modest CD34 doses of < or = 2.8 x 10(6)/kg), CliniMACS-selected CD34+ cells (in the doses utilized in this study of < or = 2.6 x 10(6)/kg) result in significantly prolonged recovery.

Adult↗
PubMed2002

Plasminogen activation by blood monocytes and alveolar macrophages in primary pulmonary hypertension.

The pathophysiology of primary pulmonary hypertension (PPH) remains poorly understood. Vascular wall remodeling and endothelial dysfunction reflected by modifications in plasma fibrinolytic proteins and von Willebrand factor have been well documented in PPH. We hypothesize that endothelial mediators, produced in excess in PPH patients, may stimulate migrating mononuclear cells and thereby modulate alveolar macrophage function; in particular, the plasminogen activation system. Components of the fibrinolytic system were therefore studied in plasma, blood monocytes and alveolar macrophages obtained from bronchoalveolar lavage in 10 patients with PPH and in four controls. Compared with controls, PPH patients had elevated plasma levels of tissue-type plasminogen activator (15.6 +/- 9.9 versus 5.5 +/- 3 ng/ml) and plasminogen activator inhibitor-1 (27.8 +/- 23 versus 16.4 +/- 12 ng/ml). In contrast, binding and activation of plasminogen by single-chain urokinase-type plasminogen activator (scu-PA) at the surface of blood monocytes and alveolar macrophages were not different from those of control values. Dissociation constants (K(d)) for binding of scu-PA and plasminogen to alveolar macrophages were similar in both PPH (4.7 +/- 1.5 and 0.88 +/- 0.3 micromol/l, respectively) and control (6.7 +/- 0.1 and 1.02 +/- 0.12 micromol/l, respectively) groups. These results indicate that in PPH patients the fibrinolytic activity of alveolar macrophages is normal, whereas endothelial fibrinolytic proteins are abnormally elevated in plasma.

Adult↗
PubMed2002

BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives.

This study investigated whether patients developing pulmonary arterial hypertension (PAH) after exposure to the appetite suppressants fenfluramine and dexfenfluramine have mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene, as reported in primary pulmonary hypertension. BMPR2 was examined for mutations in 33 unrelated patients with sporadic PAH, and in two sisters with PAH, all of whom had taken fenfluramine derivatives, as well as in 130 normal controls. The PAH patients also underwent cardiac catheterisation and body mass determinations. Three BMPR2 mutations predicting changes in the primary structure of the BMPR-II protein were found in three of the 33 unrelated patients (9%), and a fourth mutation was found in the two sisters. No BMPR2 mutations were identified in the 130 normal controls. This difference in frequency was statistically significant. Moreover, the mutation-positive patients had a somewhat shorter duration of fenfluramine exposure before illness than the mutation-negative patients, a difference that was statistically significant when the two sisters were included in the analysis. In conclusion, the present authors have detected bone morphogenetic protein receptor 2 mutations that appear to be rare in the general population but may combine with exposure to fenfluramine derivatives to greatly increase the risk of developing severe pulmonary arterial hypertension.

Adolescent↗