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M Koller

Publications and source records attributed to M Koller.

At least 19 recordsLinked to original sources
PubMed2001

Inorganic iron complexes derived from the nitric oxide donor nitroprusside: competitive N-methyl-D-aspartate receptor antagonists with nanomolar affinity.

Aquopentacyanoferrate(II), [Fe(II)H2O(CN)5]3-, is one of the photodegradation products of the vasodilator and nitric oxide donor nitroprusside. Earlier observations concerning the light dependence of N-methyl-D-aspartate (NMDA) receptor blockade by nitroprusside prompted us to examine the effects of this iron complex on the NMDA receptor. [Fe(II)H2O(CN)5]3- and two other related species, aminopentacyanoferrate(II) and aminopentacyanoferrate(III), were found to be highly potent, competitive, and selective NMDA receptor antagonists. In a binding assay for the transmitter recognition site on the NMDA receptor, these iron complexes displaced the radioligand [3H]CGP 39653 with nanomolar affinities. They did not displace radioligands labeling the channel ([3H]MK-801) or the glycine co-agonist ([3H]glycine) sites of the NMDA receptor, nor did they have any relevant affinities for a number of other neurotransmitter (alpha-adrenergic, 5-hydroxytryptamine, dopamine, opiate) receptors. The iron complexes blocked NMDA-induced depolarizations in rat cortical slices at submicromolar concentrations, whereas responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate were not affected. In another functional receptor assay (potentiation of [3H]MK-801 binding by glutamate under non-equilibrium conditions), Schild analysis demonstrated the competitive nature of the NMDA receptor antagonism. The pA2 values obtained from these experiments were similar to the pK(i) values derived from radioligand ([3H]CGP 39653) binding assays. To explain the high affinity and selectivity of these compounds for the NMDA receptor, a novel mechanism of antagonist-receptor interaction is proposed, involving a ligand exchange process in which a loosely bound species (here H2O or NH3) in the coordination sphere of the iron complex is replaced by a functional group of an amino acid side chain placed at the glutamate recognition site of the NMDA receptor, thereby hindering agonist binding.

2-Amino-5-phosphonovalerate↗
PubMed2001

[Outcome of minimally invasive surgery. Qualitative analysis and evaluation of the clinical relevance of study variables by the patient and physician].

INTRODUCTION: Mechanistic study endpoints, evaluated exclusively by the physician, are mostly used in clinical studies evaluating new treatment modalities (e.g. laparoscopic cholecystectomy). Those endpoints often lack clinical relevance. The patient's opinion concerning the importance of a study endpoint is particularly important in the evaluation of minimally invasive procedures, which place special emphasis on patient comfort. METHODS: In a first step it was evaluated by meta-analysis, which clinical endpoints have been used for comparison of laparoscopic and conventional cholecystectomy. Furthermore, using a qualitative analysis it was investigated how important the individual study endpoints are for patients and physicians. Ten patients and five surgeons were questioned in a structured interview. RESULTS: Of all outcome variables used world-wide, approximately one third were hermeneutic study endpoints, depending on the quality of the study, but often the method of evaluation was insufficient. Only three of 215 endpoints (< 2%) were quality of life scores, an integrated concept of outcome was missing completely. The qualitative analysis confirms the claimed difference between isolated and integrated evaluation of treatment goals. The importance of postoperative death is underestimated by patients and physicians; postoperative pain is overestimated. Patients ranked the outcome variable "restoration of full physical fitness" as the most important study endpoint after avoidance of complications and death. It is underestimated in isolated evaluation and has not been used in the world literature at all. CONCLUSION: The analysis of clinical relevance of study endpoints should be the first and not the last step of studies to evaluate surgical technology. It cannot be based purely on intuition; it must make use of scientifically accepted techniques (e.g. qualitative analysis).

Attitude of Health Personnel↗
PubMed2000

Lack of effect of LY314582 (a group 2 metabotropic glutamate receptor agonist) on phencyclidine-induced locomotor activity in metabotropic glutamate receptor 2 knockout mice.

In metabotropic glutamate receptor 2 (mGlu(2)) knockout mice, the group 2 metabotropic glutamate receptor agonist LY314582 (20 mg/kg, i.p.), a racemate of LY354740, inhibits neither spontaneous nor phencyclidine (PCP)-induced (2.5 mg/kg, s.c.) locomotor activity. Since LY314582 attenuated spontaneous and PCP-induced locomotor activity in wild-type control mice, these data indicate that the effects of LY314582 are mediated via the mGlu(2) receptor and not via the mGlu(3) receptor.

Analysis of Variance↗
PubMed2000

Pyrrolo[3,4-c]-beta-carboline-diones as a novel class of inhibitors of the platelet-derived growth factor receptor kinase.

Members of the structurally diverse family of beta-carbolines have previously been shown to exhibit a wide range of biological activities. A novel synthetic strategy for generation of beta-carbolines was developed, allowing imido-beta-carbolines to be created in three steps from known compounds. The compounds were screened for inhibition of platelet-derived growth factor (PDGF)-stimulated tyrosine phosphorylation in Swiss 3T3 fibroblasts. A number of the newly synthesized beta-carbolines with moderate to potent inhibitory activity were revealed. The most active derivative, 2,3-dihydro-8,9-dimethoxy-5-(2-methylphenyl)-1H,6H-pyrrolo[3, 4-c]pyrido¿3,4-bĭndole-1,3-dione 2ee, inhibited purified PDGF receptor kinase and PDGF-receptor autophosphorylation in intact cells with IC(50) values of 0.4 and 2.6 microM, respectively. Dione 2ee also inhibited PDGF-stimulated DNA synthesis in Swiss 3T3 fibroblasts with an IC(50) of 3.2 microM. The compound had no effect on Src or epidermal growth factor (EGF) receptor kinase activity and a six-seven-fold higher IC(50) for inhibition of basic fibroblast growth factor (bFGF)-stimulated tyrosine phosphorylation or Kit/stem cell factor (SCF) receptor autophosphorylation, indicating a reasonable extent of kinase specificity. Thus, beta-carbolines present a new lead of tyrosine kinase inhibitors with the capacity to selectively interfere with PDGF receptor signal transduction and PDGF-dependent cell growth.

Animals↗
PubMed2000

[Evaluation of therapy of patients with rectal carcinoma. Goals of healing (outcome) and implementation of the quality of life concept in total medical care].

Quality of life (QL) assessment by means of standardised scales allows a valid representation of an individual's subjective sense of well-being in three dimensions: somatic (intensity and frequency of symptoms), psychological (anxiety, depression) and social (family life, employment, sexuality). The question, however, whether routine measurement, documentation and analysis of QL-data could lead to an improvement of patient care is still unsolved. Studies with a clearly defined practical goal in collaboration with physicians and patients should help to resolve this issue. The introduction of the QL concept into everyday clinical practice first requires that this tool is understandable and valuable to the clinician. In this respect, we propose to integrate the factor QL into a broader outcome-concept in parallel to the classical quality indicators (outcome-criteria), to demonstrate individual patient's clinical and therapeutical course in the form of QL-profiles and to correlate the patient's actual clinical and psychosocial situation with the results of QL measurement. We illustrate the feasibility of a stepwise concept of implementation of the QL concept by demonstrating interim results of our field trial on regional management and care of patients with rectal carcinoma in the county of Marburg-Biedenkopf.

Germany↗
PubMed2000

How asymptomatic is asymptomatic primary hyperparathyroidism?

We observed several cases of patients who believed they were free of symptoms or signs of primary hyperparathyroidism (pHPT) preoperatively. reported a change of complaints following parathyroidectomy (PTX). We, therefore, decided to examine a larger group of patients to discover if these findings were incidental or of more general significance. The role of PTX in these patients with asymptomatic pHPT remains controversial. In 1991 criteria were defined at a NIH-consensus conference, according to which patients qualify for either operative therapy or long term medical surveillance. Until now, it was generally believed that the majority of asymptomatic patients would never develop symptoms. In a epidemiological cohort-study, the perioperative data of 582 consecutive patients with pHPT, including 116 asymptomatic patients (20.9%), who underwent parathyroidectomy between 1987 and 1998 were evaluated by uni- and multivariate analysis. At a median of 72 months postoperatively, all patients underwent a planned follow-up which included a standardised, validated questionnaire, physical examination and laboratory investigations. Eighty-six patients who were asymptomatic preoperatively were available for follow-up. Only eight (9.3%) were definitely asymptomatic, 4.6% of the entire, representative cohort. Postoperative improvement was reported in 81.4% of the "asymptomatic" patients. Multivariate analysis did not reveal a single or a set of preoperative measurements, that would allow to predict the retrospectively definitely asymptomatic patient. PTX resulted in normocalcaemia in 98.8% of preoperatively asymptomatic patients, with an operative morbidity of 1.2% and no mortality. Many apparently asymptomatic patients with pHPT will only realise that they did in fact have preoperative symptoms in retrospect, following PTX. This study suggests that using an up-to-date definition of asymptomatic pHPT, there are only a small number of truly asymptomatic patients and that these cannot be predicted preoperatively, as their symptoms may become apparent only after PTX. "Asymptomatic" patients with pHPT may share the same objective and subjective benefits from PTX as symptomatic patients. They should be operated as soon as the diagnosis is established.

Calcium↗
PubMed2000

Expectations and quality of life of cancer patients undergoing radiotherapy.

Expectations, real or false, affect the way patients respond to their illnesses. We assessed therapy-related expectations in relation to global quality of life in 55 cancer patients before and after radiotherapy. Factor analysis indicated that therapy-related expectations come into three broad categories--pain/emotional control, healing and tumour/symptom control. 35 patients expected 'healing' even though curative treatment was intended in only 19 and all patients had been fully informed. The expectation of healing was associated with high quality of life, and the same was true of perception of healing after radiotherapy. In the group as a whole, quality of life was little altered by radiotherapy, but it became substantially worse in those patients who had expected healing but perceived that this had failed, even though physician-assessed Karnofsky status did not change. These findings indicate that the expectation of healing, in cancer patients, is a component of a good global quality of life, whereas more limited expectations (pain control, tumour control) relate to lower quality of life. Patients' expectations deserve further study as a novel approach to improving care.

Analysis of Variance↗
PubMed1999

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with type A-resistant cervical dystonia (CD). BACKGROUND: Local intramuscular injections of BoNT are an effective therapy for CD. After repeated use, some patients become resistant to therapy. BoNT/B, effective in type A toxin-responsive patients, is proposed as an alternative therapy for type A-resistant patients. METHODS: The authors performed a 16-week, double-blind, placebo-controlled trial of BoNT/B in type A-resistant patients with CD. After resistance to therapy was confirmed with the frontalis-type A test, placebo or 10,000 U BoNT/B was administered in a single session into two to four clinically involved muscles. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was the primary efficacy measurement. TWSTRS-Total, three visual analog scales (Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, Patient Analog Pain Assessment), and adverse events were assessed at baseline and weeks 2, 4, 8, 12, and 16. RESULTS: A total of 77 patients participated (38 placebo, 39 active). Improvements in severity, disability, and pain were documented in the BoNT/B-treated group. TWSTRS-Total scores were improved in the BoNT/B-treated group at weeks 4 (p = 0.0001), 8 (p = 0.0002), and 12 (p = 0.0129). All three visual analog scales demonstrated improvements at week 4 (p < 0.0001, 0.0001, and 0.001). A Kaplan-Meier analysis supported a duration of effect of 12 to 16 weeks in the active group. Dry mouth and dysphagia were self-limited adverse effects, reported more commonly in the BoNT/B group. CONCLUSIONS: Botulinum toxin type B (BoNT/B) (NeuroBloc) is safe and efficacious for the management of patients with type A-resistant cervical dystonia with an estimated duration of treatment effect of 12 to 16 weeks.

Adult↗
PubMed1999

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with cervical dystonia (CD). BACKGROUND: BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD. METHODS: The authors performed a 16-week, randomized, multicenter, double-blind, placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A. Placebo, or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinically in CD. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure. Clinical assessments and adverse events were recorded for treatment day 1 and at weeks 2, 4, 8, 12, and 16. RESULTS: A total of 109 patients were enrolled randomly across all three treatment groups. The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 (placebo), 9.3 (5,000 U), and 11.7 (10,000 U). For the prospectively defined primary contrast (10,000 U versus placebo), highly significant differences were noted for the primary (TWSTRS-Total, baseline to week 4, p = 0.0004) and supportive secondary (Patient Global Assessment, baseline to week 4, p = 0.0001) outcome measures. Improvement in pain, disability, and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients. Overall, improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose. The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses. CONCLUSION: Botulinum toxin type B (NeuroBloc) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia.

Adult↗
PubMed1999

Symptom reporting in cancer patients II: relations to social desirability, negative affect, and self-reported health behaviors.

BACKGROUND: Patients' appraisal of somatic symptoms is correlated with their negative affect. The authors have investigated whether social desirability is associated with patients' symptom and health behavior reporting. METHODS: One hundred fourteen surgical cancer patients who participated in either an outpatient or an inpatient follow-up care program filled out the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the New Social Desirability Scale, and a health behavior checklist. RESULTS: Patients' reports of somatic symptoms were correlated inversely with social desirability (r = -0.50) and positively with negative affect (r = 0.72). When objective health and demographic variables (e.g., prognosis, adjuvant therapy prior to follow-up, and gender) were entered first in hierarchical multiple regression analyses, social desirability and negative affect accounted for an additional 16% and 36% of the symptom variance, respectively. Similar results were found when global quality of life was the dependent variable. Self-reported health behaviors were explained only through the set of health and demographic variables (14%), and social desirability and negative affect did not account for additional variance. On the average, patients reported that they had a median of 4.7 (out of a list of 21) self-initiated health behaviors, and 11% of the patients admitted to having used unproven therapies. CONCLUSIONS: Symptom reports do not give a pure picture of patients' health status, but they are strongly correlated with social desirability and negative affect. Detection of such psychologic variables is essential to understanding the dynamics of quality of life. In applied settings, quality-of-life measures should be used together with conventional criteria. As practical experience and scientific understanding grow, the relative positioning of these patient-oriented versus clinic-oriented endpoints will become clear.

Adaptation, Psychological↗
PubMed1999

A safety and pharmacokinetic study of intravenous natalizumab in patients with MS.

A phase 1, randomized, placebo-controlled, five-level dose escalation safety and tolerability and pharmacokinetic study of a single IV dose of natalizumab was performed. Doses of 0.03 to 3.0 mg/kg natalizumab or placebo were studied in 28 stable relapsing-remitting or secondary-progressive MS. All doses were safe and well tolerated in MS. Serum concentrations of natalizumab are detectable for 3 to 8 weeks after a single 1- or 3-mg/kg IV dose and justify controlled efficacy studies.

Adult↗
PubMed1999

Positive margins of breast biopsy: is reexcision always necessary?

BACKGROUND AND OBJECTIVES: Breast-conserving surgery requires excision of all gross tumor and subsequent radiation therapy. It is generally accepted that the presence of microscopically positive margins requires reexcision. The goal of this study was to identify characteristics that distinguish breast biopsy specimens with positive margins that when reexcised are free from residual tumor. This population of patients may benefit from breast irradiation only, without the need for another surgical procedure. METHODS: One hundred and fifteen of 395 cancer-proven biopsies had positive surgical margins and were treated with reexcision or mastectomy. Sixty-seven of these were negative for residual tumor and 48 were positive for residual tumor. Evaluation for tumor type, tumor size, grade, presence of vascular invasion, volume of the biopsy specimen, true positivity and the number of positive margins, multifocality of the tumor, and type of anesthesia was done by univariate and multivariate analysis. RESULTS: Univariate and multivariate analysis revealed that factors associated with a positive reexcision included margin status, method of detection, histologic appearance, and type of anesthesia used. CONCLUSION: These results suggest that small, clinically detectable unifocal tumors could be treated without the need for a further excision. Eradication of microscopic residual tumor could be done by irradiation only, sparing the patient an additional surgical procedure.

Aged↗
PubMed1999

beta-Carbolinedione derivatives as topoisomerase I inhibitors.

Pyrrolo[3,4-c]-beta-carbolinedione dimers 5-14 were synthesized from furo[3,4-c]-beta-carbolinediones and diamines by solvent-free TaCl5/silica catalyzed reaction under microwave irradiation. The inhibitory property of these target compounds, the starting materials 2, 31, 32, and the N-alkylated pyrrolo[3,4-c]-beta-carbolinediones 16, 17, 20-30 was tested against the relaxation of supercoiled pRB322 DNA by calf thymus topoisomerases I and II. Some of these compounds, especially 7 and 23 proved to be selective inhibitors of topoisomerase I.

Carbolines↗
PubMed1999

[A scale for measuring symptoms related to degenerative diseases of the cervical spine. A reference in determining indications and evaluating surgical outcome].

A scale for measuring symptoms related to degenerative diseases of the cervical spine is presented. Twenty typical symptoms are listed, e. g., neck pain, dysesthesia, and reduced mobility. Responses are assessed via a 6-point scaling ("did not have symptom" - "had symptom and suffered very strongly".) The cervical spine scale was tested in three samples: patients having undergone cervical spine surgery (n = 70), patients with other orthopedic diagnoses (n = 104), and healthy students (n = 100). The single items of the scale were aggregated into four scores: total number of symptoms, degree of overall symptom distress, functional disability, and pain/psychological distress. Statistical analyses proved the high reliability (Cronbach's alpha = 0.85 to 0.95) and validity (content, convergent, discriminant) of all scores. The scale differs clearly between cervical spine patients, other orthopedic patients and healthy individuals, and between cervical spine patients with different subjective operative outcomes. For applied clinical purposes the cervical spine scale can be included in a quality of life profile (QL-profile); this allows for a readily understandable graphic depiction of individual patients' QL-status.

Activities of Daily Living↗
PubMed1999

Successful treatment of a patient with ARDS after pneumonectomy using high-frequency oscillatory ventilation.

High frequency oscillatory ventilation (HFOV) was used in a patient who developed the acute respiratory distress syndrome 5 days following a right pneumonectomy for bronchogenic carcinoma. When conventional pressure-controlled ventilation failed to maintain adequate oxygenation, HFOV dramatically improved oxygenation within the first few hours of therapy. Pulmonary function and gas exchange recovered during a 10-day period of HFOV. No negative side effects were observed. Early use of HFOV may be a beneficial ventilation strategy for adults with acute pulmonary failure, even in the postoperative period after lung resection.

Airway Resistance↗
PubMed1999

Second step: testing-outcome measurements.

Despite worldwide enthusiasm for endoscopic surgery, this new technology is now on the top of McKinlay's "product life circle curve." Critical questions are being asked about its benefits and burdens, but the concepts applied and the methodologies used for technology assessment are in a similar position as endoscopic surgery and need a critical evaluation. (1) There are incorrect and outdated concepts for the scientific basis of surgery (surgical theory) including the basic sciences involved; biomedicine still dominates, but assessment of outcome after operations is no longer possible without clinical epidemiology and social psychology. (2) Based on an outdated scientific theory for surgery, an outdated concept of disease is still propagated. It is denoted as mechanical and is based solely on biomedicine. Human subjects are reduced to biologic machines, and outcomes measurement excludes most dimensions of functioning and well-being. To achieve a valid result for outcome measures, a hermeneutic approach must be combined with the mechanical approach. (3) Based on an outdated model of disease, the outcomes used in endoscopic surgery rely too much on traditional measures, such as mortality rate, complication rate, hospital stay, and especially an endless list of biochemical mediators. Their alterations during the perioperative period have not yet been shown to be related to clinical or hermeneutic outcomes. A new method of assessment for clinical trials in endoscopic surgery and for other surgical problems is outlined, such as for surgical infections and for surgical oncology. It includes an index of recovery and objective health status assessed by the doctor, a quality-of-life self-report by the patient, and the true endpoint concept as a critical weighting of both types of outcome by patients and doctors.

Endoscopy↗