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M Kurz

Publications and source records attributed to M Kurz.

At least 37 records · Page 2Linked to original sources
PubMed2000

A cell-kinetic model of CD34+ cell mobilization and harvest: development of a predictive algorithm for CD34+ cell yield in PBPC collections.

BACKGROUND: Mobilization and homing of PBPCs are still poorly understood. Thus, a sufficient algorithm for the prediction of PBPC yield in apheresis procedures does not yet exist. STUDY DESIGN AND METHODS: The decline of CD34+ cells in the peripheral blood during apheresis and their simultaneous increase in the collection bag were determined in a prospective study of 18 consecutive apheresis procedures. A cell-kinetic, four-compartment model describing these changes was developed. Retrospective data from 136 apheresis procedures served to further improve this model. A predictive algorithm for the yield was developed that considered the sex, weight, and height of the patient, the number of CD34+ cells in peripheral blood before apheresis, the inlet flow, and the duration of the apheresis. The accuracy of this algorithm was evaluated by comparison of the predicted and the observed yields of CD34+ cells in 105 prospective autologous and 148 retrospective allogeneic apheresis procedures. RESULTS: The correlation between predicted and observed yields was good for the autologous and allogeneic groups with a correlation coefficient (r) of 0.8979 and 0.8311 (p<0.0001), respectively. The regression is described by the equations log (measured value [m]) = 1.0118 + 0.8595 x log (predicted value [p]) for the autologous and log (m) = 2.226 + 0.7559 x log (p) for the allogeneic group. The respective equations for the zero-point regression are log (m) = 1.014 x log (p) and log (m) = 1.026 x log (p). The probability that the measured value was 90 percent or more of the predicted value was 83.8 percent for the autologous and 90.5 percent for the allogeneic apheresis procedures. CONCLUSION: The predictive accuracy of the algorithm and the slope of the zero-point regression curve were higher for allogeneic than autologous PBPC collections. The predictive algorithm may be a useful tool in PBPC harvest, enabling the adaptation of the size of the apheresis to the needs of each patient.

Algorithms↗
PubMed2000

Selection bias in clinical trials with antipsychotics.

Although the selection of patients is known to be a powerful factor affecting the results of clinical trials, little is known about recruitment issues. Many patients with schizophrenia who are screened for a clinical trial of an investigational antipsychotic are ultimately not included in the study. Therefore, the question arises of whether the results obtained by studying a selected group of patients are really representative of the general population of patients with schizophrenia. The authors studied possible reasons for selective sampling in 200 patients who were consecutively admitted to inpatient units of Innsbruck's Department of Psychiatry with a diagnosis of schizophreniform or schizophrenic disorder over a time period of 33 months. Apart from demographic data and a psychopathologic rating (using the Brief Psychiatric Rating Scale), the authors recorded whether or not a patient was included in a phase III study and whether or not those were not included would have theoretically been eligible for such a study. Twenty-seven patients were finally recruited for a clinical trial. These patients were younger, on average, had a more recent onset of illness, and had experienced fewer psychotic episodes in the past. A history of noncompliance with previous treatment and the refusal of consent were the most common reasons for not including theoretically eligible patients in a clinical trial.

Adolescent↗
PubMed2000

Friulimicins: novel lipopeptide antibiotics with peptidoglycan synthesis inhibiting activity from Actinoplanes friuliensis sp. nov. II. Isolation and structural characterization.

Four novel lipopeptide antibiotics, friulimicins A, B, C, and D, were isolated from cultures of Actinoplanes friuliensis HAG 010964 after fermentation in different nutrient media. The new compounds were separated by ion-exchange chromatography from the acidic lipopeptides of the amphomycin type also present in the culture fluid, compounds A-1437 A, B, E, and G. The principal constituent friulimicin B, C59H94N14O19, was structurally characterized by mass spectrometric investigations of its hydrolysis and partial degradation products and by sequencing of the cyclic acyl peptide. The NMR data of friulimycin B and the amphomycin constituent A-1437 B were completely assigned by a variety of 2-D experiments, and confirmed the structures determined by mass spectrometry. All 8 lipopeptides possess an identical peptide macrocycle as their central element, linked via a diaminobutyric acid N-terminal either to an acylated asparagine residue or, in the case of the amphomycin series, to an acylated aspartic acid residue. The structures of the amphomycins have now been revised to take account of the peptide framework described herein and the determined cis-configuration of the exocyclic double bond. As a consequence of their higher isoelectric points, the new compounds friulimicin A, B, C, and D have different properties than the amphomycins.

Actinomycetales↗
PubMed1999

G-CSF versus GM-CSF for stimulation of peripheral blood progenitor cells (PBPC) and leukocytes in healthy volunteers: comparison of efficacy and tolerability.

This study compared two recombinant human (rh) hematopoietic growth factors in healthy volunteers for stem cell stimulation. Granulocyte colony-stimulating factor (G-CSF, n=9) or granulocyte-macrophage colony-stimulating factor (GM-CSF, n=8) was given subcutaneously for 5 days (5 microg/kg/day). Controls (n=5) received no growth factor. Laboratory parameters and side effects were monitored for 8 days. Within 24 h, both cytokines led to a rapid increase of leukocytes, the majority of which were granulocytes. Compared with the controls (n=5), the increase on day 5 in the G-CSF/GM-CSF groups was 37-/10-fold (CD34+ cells), 5.2-/2.4-fold (leukocytes), 7.2-/3.0-fold (granulocytes), 7.4-/4.4-fold (monocytes), 1.7-/1.1-fold (lymphocytes), 9.8-/2.7-fold (basophils), 2.3-/9.6-fold (eosinophils), and 1.9-/1.6-fold (reticulocytes). The mobilization of myeloblasts, promyelocytes, myelocytes, and metamyelocytes coincided with the pronounced increase of CD34 + PBPC observed on day 4. Serum levels of uric acid (UA) and lactic dehydrogenase (LDH) increased under G-CSF, and platelets decreased after G-CSF discontinuation. Rash at the injection site occurred in 50% of the GM-CSF-treated volunteers. Seven volunteers in the GM-CSF group and six in the G-CSF cohort complained of flu-like symptoms, including musculoskeletal pain. We conclude that, in terms of tolerance and mobilization of CD34+ cells and leukocytes, G-CSF is superior to GM-CSF, but higher levels of UA and LDH and late decrease in platelets make monitoring of these parameters necessary.

Adult↗
PubMed1999

Azide reduces the hydrophobic barrier of the bacteriorhodopsin proton channel.

The sensitivity of a nitroxide spin label to the polarity of its environment has been used to estimate the hydrophobic barrier of the proton channel of the transmembrane proton pump bacteriorhodopsin. By means of site-specific mutagenesis, single cysteine residues were introduced at 10 positions located at the protein surface, in the protein interior, and along the proton pathway. After reaction with a methanethiosulfonate spin label, the principle values of the hyperfine tensor A and the g-tensor were determined from electron paramagnetic resonance spectra measured at 170 K. The shape of the hydrophobic barrier of the proton channel is characterized in terms of a polarity index, DeltaA, determined from the variation of the hyperfine coupling constant Azz. The maximum of the hydrophobic barrier is found to be close to the retinal chromophore in the proton uptake pathway. The effect of the asymmetric distribution of charged and polar residues in the proton release and uptake pathways is clearly reflected in the behavior of the hydrophobic barrier. The presence of azide reduces the barrier height of both the cytoplasmic and extracellular channels. This finding supports the view of azide and other weakly acidic anions as catalysts for the formation of hydrogen-bonded networks in proton pathways of proteins.

Azides↗
PubMed1999

Low transplant-related mortality in patients receiving unrelated donor marrow grafts for leukemia.

Transplantation with unrelated donor (UD) marrow has been shown to potentially cure patients with leukemia. Between January 1991 and April 1998, 54 patients with leukemia have received an UD BMT at our institution. Five patients received their UD BMT as a second transplant after a preceding autologous or syngeneic BMT and were excluded from further analysis. Forty-nine patients with leukemia (acute leukemia n = 26; CML n = 23) and a median age of 36 years (range 19-51) were analyzed. For conditioning, all patients received a combination of fractionated TBI and CY. GVHD prophylaxis consisted of MTX and CsA in all patients. As of 30 April 1998, 27 of 49 (55%) patients survive after a median observation time of 18 months. The probability of overall survival for standard risk and high risk patients is 54% and 31% (P = 0.05). Probability of transplant-related mortality (TRM) is 27%, 24% in standard risk and 31% in high risk patients (P = 0.44). Patients younger than 40 years (n = 33) had a similar TRM as patients 40 years and older (n = 16). The probability of relapse is 41% for the whole group, 29% for standard risk and 55% for high risk pts (P<0.05). Our data confirm that UD BMT is an effective treatment for patients with leukemia. TRM is almost similar to related sibling BMT, most probably due to improvements in HLA typing technology, conditioning regimen and supportive patient care.

Adult↗
PubMed1999

Five-year-survey of invasive aspergillosis in a paediatric cancer centre. Epidemiology, management and long-term survival.

The epidemiology, management, and long-term survival of invasive aspergillosis was assessed in a prospective, 5-year observational study in 346 unselected paediatric cancer patients receiving dose-intensive chemotherapy for newly diagnosed or recurrent malignancies. Invasive aspergillosis occurred exclusively in the context of haematological malignancies, where it accounted for an incidence of 6.8% (n = 13 of 189). The lung was the primary site in 12 cases, and dissemination was present in three of those. Prior to diagnosis, the overwhelming majority of patients had been profoundly neutropenic for at least 14 days (n = 11 of 13) and were receiving systemic antifungal agents (n = 10 of 13). Clinical signs and symptoms were nonspecific but always included fever. All 11 patients who were diagnosed and treated during lifetime for a minimum of 10 days responded to either medical or combined medical and surgical treatment, and seven were cured (64%). Nevertheless, the overall long-term survival was merely 31% after a median follow-up of 5.68 years after diagnosis. Apart from refractory or recurrent cancer, the main obstacles to successful outcome were failure to diagnose IA during lifetime and bleeding complications in patients with established diagnosis. The frequency of invasive aspergillosis of greater than 15% in paediatric patients with acute myeloblastic leukaemia and recurrent leukaemias warrants the systematic investigation of preventive strategies in these highly vulnerable subgroups.

Adolescent↗
PubMed1999

IgG titer, subclass, and light-chain phenotype of pregnancy-induced HPA-5b antibodies that cause or do not cause neonatal alloimmune thrombocytopenia.

BACKGROUND: The most common pregnancy-induced platelet-specific antibody is HPA-5b. Neonatal alloimmune thrombocytopenia that results from anti-HPA-5b may cause severe hemorrhage in only a few infants, but the sequelae for the affected children can be severe. It is therefore essential that infants at risk for neonatal alloimmune thrombocytopenia are identified. STUDY DESIGN AND METHODS: The IgG titer, subclass, and light-chain composition of pregnancy-induced anti-HPA-5b were determined by the monoclonal antibody-specific immobilization of platelet antigens assay. Sera were from 12 mothers, who among them had 16 pregnancies that resulted in an HPA-5-mismatched fetus (positive for HPA-5b). Eight mothers gave birth to an infant with a normal platelet count. Three maternal sera were obtained after delivery of a severely thrombocytopenic infant. Three alloimmunized women were followed repeatedly during the course of a subsequent pregnancy, again with an HPA-5-mismatched infant. RESULTS: There was no difference in the antibody titer or its subclass in mothers who had a thrombocytopenic child and the titer or subclass in mothers compared with those who had a child with a normal platelet count. All pregnancy-induced HPA-5b antibodies were of a predominant, lambda, light-chain type. The IgG subclass did not change during pregnancy. CONCLUSION: Neither the antibody titer nor the subclass composition predict the occurrence of thrombocytopenia in a newborn whose mother is alloimmunized against HPA-5b.

Antigens, Human Platelet↗
PubMed1999

Biogenesis of Tim proteins of the mitochondrial carrier import pathway: differential targeting mechanisms and crossing over with the main import pathway.

Two major routes of preprotein targeting into mitochondria are known. Preproteins carrying amino-terminal signals mainly use Tom20, the general import pore (GIP) complex and the Tim23-Tim17 complex. Preproteins with internal signals such as inner membrane carriers use Tom70, the GIP complex, and the special Tim pathway, involving small Tims of the intermembrane space and Tim22-Tim54 of the inner membrane. Little is known about the biogenesis and assembly of the Tim proteins of this carrier pathway. We report that import of the preprotein of Tim22 requires Tom20, although it uses the carrier Tim route. In contrast, the preprotein of Tim54 mainly uses Tom70, yet it follows the Tim23-Tim17 pathway. The positively charged amino-terminal region of Tim54 is required for membrane translocation but not for targeting to Tom70. In addition, we identify two novel homologues of the small Tim proteins and show that targeting of the small Tims follows a third new route where surface receptors are dispensable, yet Tom5 of the GIP complex is crucial. We conclude that the biogenesis of Tim proteins of the carrier pathway cannot be described by either one of the two major import routes, but involves new types of import pathways composed of various features of the hitherto known routes, including crossing over at the level of the GIP.

Amino Acid Sequence↗
PubMed1999

Sexual disturbances during clozapine and haloperidol treatment for schizophrenia.

OBJECTIVE: The aim of this study was to evaluate the frequency and course of sexual disturbances associated with clozapine and haloperidol and their potential influence on compliance with medication regimens in patients with schizophrenia. METHOD: The authors prospectively investigated 153 patients with schizophrenia who received clozapine (N = 100) or haloperidol (N = 53) in a drug monitoring program. RESULTS: The frequency of sexual disturbances was lower in female patients than in male patients. There was no statistically significant difference between the patients taking haloperidol and those taking clozapine in the frequency of these disturbances. Clozapine plasma levels had a significant effect on diminished sexual desire and functional disturbances in male patients. Functional disturbances and diminished sexual desire did not have any influence on compliance in patients taking either haloperidol or clozapine. CONCLUSIONS: There was no statistically significant difference between haloperidol and clozapine in regard to their propensity to induce sexual side effects.

Adult↗
PubMed1999

Ala(0)-actagardine, a new lantibiotic from cultures of Actinoplanes liguriae ATCC 31048.

The actagardine-producing strain Actinoplanes liguriae ATCC 31048, forms an additional lantibiotic when it is cultured on mannitol and soya meal. The new compound, Ala(0)-actagardine (1), has been isolated by solid-phase extraction followed by a two-step chromatographic separation. The molecular formula of 1 is C84H129N21O25S4. Its chemical structure was determined by 2D-NMR analysis and was further confirmed by an amino acid analysis, Edman degradation, and partial synthesis from actagardine. 1 exhibits a slightly higher biological activity than the parent compound actagardine. The synthetic analogs Lys(0)-actagardine (2) and Ile(0)-actagardine (3) demonstrate also antibacterial activities and emphasize the importance of the N-terminus for further derivatization.

Actinomycetales↗
PubMed1999

Autologous blood donation for surgery in inflammatory bowel disease--a report of six cases.

BACKGROUND: Surgery in inflammatory bowel disease (IBD) is frequently associated with need for perioperative blood transfusions carrying the potential risk of infection. Autologous blood donation is often limited by IBD-associated anemia which is reversible by intravenous iron and erythropoietin. We therefore tested the feasibility of autologous blood donation in IBD. METHODS: Six patients (five Crohn's disease, one ulcerative colitis) with indication for elective bowel resection were treated after informed consent was obtained. Two to four blood donations were scheduled during four weeks prior to surgery. Once a week 350-450 ml of blood were collected from patients with a hemoglobin level above 11.0 g/dl. After each donation 200 mg of iron saccharate diluted in 0.9% saline were given to all patients intravenously as substitute for donation-related iron loss. Patients with preexisting anemia or C-reactive protein above 2.0 mg/dl received concomitant erythropoietin. RESULTS: The scheduled number of packed red cells was donated successfully by four patients. Due to low hemoglobin levels two patients donated one unit less than intended. Four patients received autologous blood transfusions intra- or postoperatively. No patient needed homologous blood. No serious adverse events were observed during blood donations, perioperatively, and during the one year follow-up period. CONCLUSION: Preoperative autologous blood donation is save and feasible in IBD patients with elective bowel resection.

Adult↗
PubMed1998

Three-dimensional structure of moenomycin A--a potent inhibitor of penicillin-binding protein 1b.

The first three-dimensional structure of moenomycin A in aqueous solution based on NMR-derived distance constraints and molecular dynamics simulations is presented. The antibiotic moenomycin A was obtained from the FlavomycinR complex by ultrafiltration, chromatography on a DEAE-cellulose ion exchanger and reverse-phase chromatography in 98% purity. In contrast to the previously reported behaviour, the compound gave rise to well-resolved NMR spectra in standard solvents. Using several two-dimensional experiments, a complete assignment of proton and carbon chemical shifts was achieved in (CD3)2SO, CD3OD and H2O/D2O (9:1, pH 7.3). A total of 175 interproton distances were determined from 600-MHz rotating-frame NOE (ROE) spectra and were used as restraints in molecular dynamics calculations. These restraints included 84 ROEs between protons of the moenocinol part leading to a very well-defined structure of the lipid part of the molecule. The relative orientation of the subunits was determined by 66 ROEs among different sugar rings and between the sugar rings and moenocinol. As a result of the molecular dynamics calculation, rings D, E, and F as well as the moenocinol part are very well-defined (average rms deviation over all heavy atoms 0.48 A) whereas rings A, B and C display a higher degree of conformational flexibility which might be an artefact due to the lower number of ROEs in this part of the molecule. A three-dimensional pharmacophore hypothesis comprising functional groups of rings E and F and the carboxyl group of glyceric acid is presented on the basis of the degradation and derivatization studies of Welzel and coworkers [Welzel, P., Kunisch, F., Kruggel, F., Stein, H., Scherkenbeck, J., Hiltmann, A., Duddeck, H., Müller, D., Maggio, J. E., Fehlhaber, H.-W., Seibert, G., van Heijenoort, Y. & van Heijenoort, J. (1987) Moenomycin A: Minimum structural requirements for biological activity, Tetrahedron 43, 585-598; Welzel, P. (1993) Transglycosylase inhibition, in Antibiotics and antiviral compounds--Chemical synthesis and modifications (Krohn, K., Kirst, H. A. & Maag, H., eds) pp. 373-378, VCH Weinheim].

Bacterial Proteins↗
PubMed1998

Increase in endogenous thrombopoietin in healthy donors after automated plateletpheresis.

BACKGROUND: Thrombopoietin (TPO) is a key cytokine involved in the regulation of megakaryocytopoiesis and platelet production. The aim of the present study was to test whether platelet donation is associated with changes in the serum TPO levels in healthy donors undergoing plateletpheresis. STUDY DESIGN AND METHODS: The study group consisted of 23 healthy donors undergoing single-donor plateletpheresis for the first time. Serum TPO levels and platelet counts were determined before platelet collection, at the end of apheresis, and for 4 days thereafter. Serum TPO levels were determined by a TPO-specific enzyme-linked immunosorbent assay. RESULTS: In relationship to platelet donation, serum TPO levels showed a temporary increase from baseline levels of 69.2 +/- 7.1 pg per mL to 117 +/- 6.8 pg per mL 2 days after plateletpheresis (p < 0.05). Further evaluation revealed a decline in serum TPO levels as platelet counts increased. Female donors showed a delayed normalization of circulating platelet numbers and serum TPO levels as compared to male donors. There was no significant correlation between serum TPO levels and the absolute platelet number during normalization of the donors' platelet counts after plateletpheresis. CONCLUSION: Single-donor plateletpheresis results in a temporary increase in serum TPO levels in healthy platelet donors, which may be part of a compensatory response-boosting megakaryocytopoiesis after platelet collection.

Blood Donors↗
PubMed1998

Long-term pharmacokinetics of clozapine.

BACKGROUND: Previous studies of clozapine pharmacokinetics have shown a wide intra- and inter-individual variability of plasma levels in patients on stable clozapine doses. We investigated dose-plasma level relationships and intra-individual variability of plasma levels during maintenance treatment with clozapine. METHOD: Forty-one patients on clozapine were followed for 26 weeks with repeated plasma level measurements and assessments of co-medication and clinical symptoms. In a second step, 15 patients on stable clozapine doses between treatment Weeks 12 and 52 were followed in the same way. Coefficient of variation was used as a parameter of plasma level deviation. RESULTS: Dose-plasma level correlations stayed significant from Week 6 to Week 26 (n = 41). The group of patients followed up to Week 52 showed a mean intra-individual coefficient of variation of 52.8% (s.d. = 20.6), and remained stable psychopathologically. CONCLUSIONS: Even though clozapine plasma levels may show a significant degree of variation, this is not necessarily reflected in a change in psychopathology.

Adult↗
PubMed1998

A novel glycopeptide carrying a 3-oxazolin-5-one ring obtained by intra-molecular cyclization.

The structure of a product, isolated during the synthesis of the semisynthetic glycopeptide MDL 63,246, was elucidated on the basis of spectroscopic methods and proved to be a novel glycopeptide containing a 3-oxazolin-5-one ring between positions 36 and 38. Subjected to acid hydrolysis this compound gave the corresponding pseudo aglycone and aglycone derivatives which maintained the original oxazolinone structure. Tested for antibacterial activity, these compounds showed a moderate activity against Gram-positive and inactive against Gram-negative bacteria.

Anti-Bacterial Agents↗