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Biomedical subjects

R Simon

Publications and source records attributed to R Simon.

At least 73 records · Page 4Linked to original sources
PubMed1999

Different genetic pathways in the evolution of invasive breast cancer are associated with distinct morphological subtypes.

Invasive breast cancer shows a wide range of morphological differentiation, associated with differences in prognosis, but as yet, the underlying genetic mechanisms cannot be accounted for. In order to establish a model of the possible progression from the different subtypes of ductal carcinoma in situ (DCIS) to invasive breast cancer, 77 selected cases of invasive breast cancer representing distinct morphological subtypes were investigated by means of comparative genomic hybridization (CGH). There was a high degree of genetic homology between tubular and tubulo-lobular carcinoma and well-differentiated DCIS, and between ductal invasive carcinoma G3 and poorly differentiated DCIS. Highly differentiated invasive breast cancers were characterized by a loss of 16q and a low average number of aberrations per case. In high-grade tumours, losses of this chromosomal region were seen with a much lower frequency in cases with evidence of an aneuploid tumour status. These data demonstrate the close genetic similarity of well-, intermediately, and poorly differentiated DCIS and distinct morphological types of invasive breast carcinoma, providing further evidence that DCIS is a direct precursor lesion of invasive breast cancer and that various evolutionary genetic pathways exist.

Adenocarcinoma↗
PubMed1999

Interactions of hydroxy-s-triazines with sodium dodecyl sulfate-micelles investigated by micellar capillary electrophoresis.

The electrophoretic behavior of fourteen 4,6-diamino-s-triazines was investigated in the presence of an anionic surfactant (sodium dodecyl sulfate, SDS) using micellar capillary electrophoresis (MCE). The measurements were performed at the pH of zero charge of the hydroxytriazines and the existence of strong ionic and H-bond interactions of hydroxy-s-triazine species with the anionic micelles could be shown. Their migration behavior was compared to the n-octanol-water partition coefficients (log Kow) measured with reverse-phase HPLC and calculated with different fragment contribution methods. A partition model was proposed to understand the interactions of the three major hydroxy-s-triazine species: cationic, anionic and neutral (presenting enol and keto forms) with the charged SDS micelles taken as model for charged natural polyelectrolytes like humic substances. These results strongly indicate that hydroxy-striazines are polarized in the presence of the charged micelles and that they are essentially present in their keto form in the micellar phase (and enol form in the water phase), confirming previous studies suggesting the presence of zwitterionic resonance structures at a neutral pH around their isoelectric point.

Algorithms↗
PubMed1999

The ARTS study (Arterial Revascularization Therapies Study).

The rising costs of health care have forced policy makers to make choices, and new treatments are increasingly assessed in terms of the balance between additional costs and additional effects. The recent recognition that stenting has a major and long-lasting effect enhancing balloon PTCA procedure has made it imperative to compare in patients with multivessel disease the standard surgical procedure with multiple stenting in a large scale multinational and multicentre approach (19 countries, 68 sites). Selection and inclusion of patients is based on a consensus of the cardiac surgeon and interventional cardiologist on equal 'treatability' of patients by both techniques with analysis of clinical follow-up (event-free survival) on the short (30 day), medium (1 year), and long-term (3 and 5 year) with analysis of cost-effectiveness and quality of life (EuroQol and SF-36). Of the entire trial, the primary null hypothesis which needs to be rejected is that there will be no difference in event-free survival or effectiveness (E), at 1 year and also that the direct and indirect costs (C) per event-free year are not different between surgery or stenting. For this to become significant with a power of 90% one needs 1200 patients. Between April 97 and June 98, 1205 patients have been randomized with a monthly recruitment of 83 patients. Expected costs, effects and cost-effectiveness ratio (CE ratio) are: Stent high costs 2 VDStent high costs 3 VDStent low costs 2 VDStent low costs 3 VDCABG costs (C)$19.297$24.566$16.638$20.456$21.350 effects (E)81%81%81%81%88% CE ratio$23.876$30.397$20.586$25.322$24.348 Clinically, stenting is not expected to be more effective than CABG, but should be cost effective in both the 2- and 3-VD group when using the lower cost estimate and in the 2 VD group when using the higher cost assumptions.

Angioplasty, Balloon, Coronary↗
PubMed1999

[In Process Citation]

To optimise the microsurgical training in our clinic we organized a permanent possibility to practice microsurgical techniques of vascular anastomosis. This includes step-wise education by means of plastic materials, human placenta and the rat model. The most important role in this concept is played by the placenta. It supplies a realistic simulation of different in vivo situations concerning microvascular anastomosis. As to availability, handling and costs the placenta is superior to animal models and has replaced them almost completely in our educational concept.

Journal Article↗
PubMed1999

[Determination of torsion angle after shaft fractures of the lower extremity--clinical relevance and measurement techniques].

In the treatment of femoral and tibial fractures the frontal and sagittal planes are controlled and documented by conventional X-ray films. Computed tomography permits exact measurement of the coronal plane. Between June 1993 and December 1997, 161 computed tomographic measurements of femoral torsion and 55 of tibial torsion after shaft fracture were carried out. The results were analyzed in a clinical study. A CT examination was carried out if the clinical examination aroused suspicion of a difference in torsion. 28.5% of the patients examined with femoral fractures and 23.8% of those with tibial fractures and torsion differences of more than 20 degrees. Between June 1993 and June 1997, 30 corrective derotating osteotomies of the femur and 9 of the tibia were carried out. The average preoperative difference of torsion of the femur was 29 degrees and of the tibia 25 degrees. After the operation the average femur difference was 7 degrees and of the lower leg 6.5 degrees, which are inside normal physiological limits. The osteotomies were carried out in the metaphysis near the fracture. Additional corrections in other planes were necessary on the femur in 27% and on the lower leg in 46%. With the aim of avoiding torsion differences, or at least to recognize them at an early stage, CT measurements of torsion after osteosythetic treatment of fresh unilateral femur-shaft fractures were carried out in 49 patients between October 1996 and December 1997. The torsion measurements during the operations had to be carried out clinically. No sufficiently exact method of measurement is available in the operating room. Three patients with increased differences of 28 degrees, 26 degrees or 19 degrees had their osteosyntheses corrected. The measurements after correction were inside the normal spread.

Adult↗
PubMed1999

Chromosomal imbalances in primary lymphomas of the central nervous system.

Twenty-two primary central nervous system lymphomas of immunocompetent adults were studied by comparative genomic hybridization. All were high-grade diffuse large B cell lymphomas. Comparative genomic hybridization revealed an average of 5.5 chromosomal changes per tumor, with gains being more common than losses (3.5 vs. 2.0). The most frequent DNA copy number changes were gains on chromosomes 1, 12, 18 (41% each), 7 (23%), and 11 (18%) and losses involving chromosomes 6 (59%), 18, and 20 (18% each). Commonly involved regions were +12q (41%), +18q (36%), +1q (32%), and +7q (23%), as well as -6q (50%), -6p (18%), -17p, and -18p (14% each). High-level gains were found on 7 chromosomes, mainly involving chromosomes 18q (23%), 12q (18%), and 1q (14%). Minimal common regions of over- and underrepresentation were found on +1q25-31, -6q16-21, +7q11.2, +12p11.2-13, +12q12-14, +12q22-24.1, and +18q12.2-21.3. A significant correlation between loss of DNA copy numbers on chromosome 6q and shorter survival could be established (10.2 vs. 22.3 months; P < 0.05). Our findings suggest that chromosomal imbalances of primary central nervous system lymphomas are similar to those of diffuse large B cell lymphomas at other locations and are probably not related to cerebral presentation; however, they may be prognostically relevant.

Adult↗
PubMed1999

The potential for improved teamwork to reduce medical errors in the emergency department. The MedTeams Research Consortium.

This article describes emergency department care work teams designed to improve team communication and coordination and reduce error. The core of this teamwork system is the teaching of teamwork behaviors and skills, development of teamwork habits, and creation of small work teams, all of which are key teamwork concepts largely drawn from successful aviation programs. Arguments for enculturating teamwork into ED practice are drawn from a retrospective study of ED malpractice incidents. Fifty-four incidents (1985-1996), a sample of convenience drawn from 8 hospitals, were identified and judged mitigable or preventable by better teamwork. An average of 8.8 teamwork failures occurred per case. More than half of the deaths and permanent disabilities that occurred were judged avoidable. Better teamwork could save nearly $3.50 per ED patient visit. Caregivers must improve teamwork skills to reduce errors, improve care quality, and reduce litigation risks.

Communication↗
PubMed1999

Dantrolene sodium improves the force-frequency relationship and beta-adregenic responsiveness in failing human myocardium.

BACKGROUND: Failing human myocardium is characterized by a negative force-frequency relationship and impaired beta-adrenergic responsiveness which have been related to alterations of the intracellular Ca2+ homeostasis. Dantrolene sodium is a clinically used drug that modulates myocardial [Ca2+]i handling in animal models. This study investigated the effects of dantrolene sodium on intracellular Ca2+ handling and contractile function in failing human myocardium. METHODS AND RESULTS: Twenty-three muscle strips from human left ventricular trabeculae were obtained from patients undergoing heart transplantation for end-stage heart failure caused by idiopathic dilated cardiomyopathy (n = 15). Isometric contraction and intracellular Ca2+ transients (Ca2+ indicator: aequorin) were recorded simultaneously. The experiments were performed in three separate groups exposed to control condition (n = 8), addition of dantrolene (10 micromol/l; n = 8), or addition of verapamil (1 micromol/l; n = 7). Isoproterenol induced a moderate positive inotropic effect in the control group with a maximal increase of developed tension from 10.8 +/- 2.9 to 23.4 +/- 4.7 mN/mm2 and a parallel rise in peak systolic [Ca2+]i to a maximum of 1.36 +/- 0.20 micromol/l. Dantrolene significantly improved (10.2 +/- 3.8 to 32.4 +/- 0.9 mN/mm2) and verapamil blunted (8.3 +/- 2.8 to 17.1 +/- 4.3 mN/mm2) the inotropic response to isoproterenol. The diastolic and systolic [Ca2+]i during isoproterenol stimulation were slightly lower in the dantrolene group but significantly depressed in the verapamil group as compared to the control group. Similarly, analyses of force-frequency relationships revealed an improvement of developed tension in dantrolene-treated as compared to control preparations whereas the peak systolic [Ca2+]i was almost identical. CONCLUSION: Dantrolene improves the negative force-frequency relationship and beta-adrenergic responsiveness in failing human myocardium. These effects are not accompanied by an additional increase in intracellular [Ca2+]i but might be related to modifications of the diastolic [Ca2+]i homeostasis.

Adrenergic beta-Agonists↗
PubMed1999

Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease.

Elucidating the cellular immune response to infectious agents is a prerequisite for understanding disease pathogenesis and designing effective vaccines. In the identification of microbial T-cell epitopes, the availability of purified or recombinant bacterial proteins has been a chief limiting factor. In chronic infectious diseases such as Lyme disease, immune-mediated damage may add to the effects of direct infection by means of molecular mimicry to tissue autoantigens. Here, we describe a new method to effectively identify both microbial epitopes and candidate autoantigens. The approach combines data acquisition by positional scanning peptide combinatorial libraries and biometric data analysis by generation of scoring matrices. In a patient with chronic neuroborreliosis, we show that this strategy leads to the identification of potentially relevant T-cell targets derived from both Borrelia burgdorferi and the host. We also found that the antigen specificity of a single T-cell clone can be degenerate and yet the clone can preferentially recognize different peptides derived from the same organism, thus demonstrating that flexibility in T-cell recognition does not preclude specificity. This approach has potential applications in the identification of ligands in infectious diseases, tumors and autoimmune diseases.

Adult↗
PubMed1999

Long-term outcome in children with fractures of the proximal femur after high-energy trauma.

BACKGROUND: Fractures of the femoral head and neck in children have a risk of severe complications, especially femoral head necrosis. We performed a long-term follow-up study of patients treated at our institution. METHODS: Patients were reexamined at least 3 years after trauma and were included if they were younger than 17 years old at the time of injury, if there was no history of previous fracture, and if there was no history of underlying bone disease. Fractures were classified according to Delbet, and outcome was graded according to Ratliff. Anterior capsulotomy was not performed, and stabilization devices were placed short of the epiphysis except for type I fractures. RESULTS: Of 32 patients, 28 were reexamined. Among these patients, the mean age at the time of injury was 11.8 years and the mean follow-up time was 11.1 years (range, 3-21 years). There were 3 patients with type I fractures, 8 patients with type II fractures, 12 patients with type III fractures, and 5 patients with type IV fractures. Thirteen patients had Injury Severity Scores > 18. At last follow-up, 20 patients presented with good function, 5 with fair outcome, and 3 with poor results; all of the latter suffered type I fractures. Eighteen patients had no restrictions in activities of daily living or during sports activities. In six other patients, the inability to participate in sports was attributable to head trauma, amputation, or peripheral neurologic damage. CONCLUSION: We found favorable long-term outcome in type II to type IV fractures. In these patients, restrictions of function were usually caused by other associated injuries. All patients with type I fractures presented with poor outcome secondary to their proximal femoral fractures, and not because of other associated injuries. Type I fractures during childhood and adolescence represent an unsolved problem.

Accidents↗
PubMed1999

Bayesian design and analysis of active control clinical trials.

We consider the design and analysis of active control clinical trials, i.e., clinical trials comparing an experimental treatment E to a control treatment C considered to be effective. Direct comparison of E to placebo P, or no treatment, is sometimes ethically unacceptable. Much discussion of the design and analysis of such clinical trials has focused on whether the comparison of E to C should be based on a test of the null hypothesis of equivalence, on a test of a nonnull hypothesis that the difference is of some minimally medically important size delta, or on one or two-sided confidence intervals. These approaches are essentially the same for study planning. They all suffer from arbitrariness in specifying the size of the difference delta that must be excluded. We propose an alternative Bayesian approach to the design and analysis of active control trials. We derive the posterior probability that E is superior to P or that E is at least k% as good as C and that C is more effective than P. We also derive approximations for use with logistic and proportional hazard models. Selection of prior distributions is discussed, and results are illustrated using data from an active control trial of a drug for the treatment of unstable angina.

Angina, Unstable↗
PubMed1999

Demonstration of high-fidelity simulation team training for emergency medicine.

Emergency medicine (EM) presents many cognitive, social, and systems challenges to practitioners. Coordination and communication under stress between and among individuals and teams representing a number of disciplines are critical for optimal care of the patient. The specialty is characterized by uncertainty, complexity, rapidly shifting priorities, a dependence on teamwork, and elements common to other risky domains such as perioperative medicine and aviation. High-fidelity simulators have had a long tradition in aviation, and in the past few years have begun to have a significant impact in anesthesiology. A national, multicenter research program to document the costs of teamwork failures in EM and provide a remedy in the form of an Emergency Team Coordination Course has developed to the point that high-fidelity medical simulators will be added to the hands-on training portion of the course. This paper describes an evolving collaborative effort by members of the Center for Medical Simulation, the Harvard Emergency Medicine Division, and the MedTeams program to design, demonstrate, and refine a high-fidelity EM simulation course to improve EM clinician performance, increase patient safety, and decrease liability. The main objectives of the paper are: 1) to present detailed specifications of tools and techniques for high-fidelity medical simulation; 2) to share the results of a proof-of-concept EM simulation workshop introducing multiple mannequin/ three-patient scenarios; and 3) to focus on teamwork applications. The authors hope to engage the EM community in a wide-ranging discussion and handson exploration of these methods.

Clinical Competence↗
PubMed1999

The German monitoring and reporting system for the treatment of substance-related problems: a national system on the basis of aggregated data.

The German treatment monitoring and reporting system EBIS for out-patient centres treating clients with substance-related problems and disorders was set up in 1980. A parallel system for in-patient treatment was added in 1993 under the name of SEDOS. Together they are based nation-wide on more than 600 specialised treatment centres which collect diagnosis- and treatment-related data as well as information on socio-economic and family background. As part of the data relate to the end of treatment, also evaluative elements are included. In EBIS and SEDOS, aggregated data are the basis of the national and regional statistics produced, which offers a very high level of data protection for the clients treated. The revision of the national system implementing the Treatment Demand Indicator Protocol as the European Monitoring Centre for Drugs and Drug Addiction standard has already been started.

Ambulatory Care↗
PubMed1999

The EMCDDA/Pompidou Group treatment demand indicator protocol: a European core item set for treatment monitoring and reporting.

Over the last decades inside and outside of Europe, treatment-based data have been used in epidemiological research on drugs and drug abuse. They offer information on hidden populations and allow to follow socially stigmatised behaviour. As this type of research can be done on rather low budgets, there are long-term projects run in many countries. Experts from the national systems in several EU member states have been working together to develop a common standard on the basis of the Pompidou Group (PG) Definitive Protocol. The items and basic definitions of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)/PG Treatment Demand Indicator Protocol are described, which plays an important role in the process of harmonisation of data collection for the EMCDDA. Implementation strategies are described, and future steps are discussed.

Europe↗
PubMed1999

The role of statisticians in intervention trials.

The planning, conduct, analysis and reporting of randomized trials to reliably evaluate an intervention create a complex intellectual and logistical endeavour. Success generally requires active collaboration of a well-trained, experienced and committed statistician. A good intervention trial asks an important question, gets a reliable answer and is honestly reported. Many trials fail on one of these components and some of these failures could have been avoided with better statistical involvement. Many subject matter investigators do not understand how to effectively collaborate with statisticians. The objective here is to outline some of the important responsibilities of the statistician in intervention trials.

Clinical Trials as Topic↗
PubMed1999

Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress.

PURPOSE: All cooperative group studies performed in North America for patients with extensive-stage small-cell lung cancer (SCLC) were evaluated to determine the pattern of the clinical trials and the outcome of patients over the past 20 years. PATIENTS AND METHODS: Phase III trials for patients with extensive-stage SCLC were identified through a search of the National Cancer Institute Cancer Therapy Evaluation Program database from 1972 to 1993. Patients with extensive-stage SCLC treated during a similar time interval listed in the Surveillance, Epidemiology, and End Results (SEER) database were also examined. Trends were tested in the number of trials over time, the number and sex of patients entered onto the trials, and the survival time of patients treated over time. RESULTS: Twenty-one phase III trials for patients with extensive-stage SCLC were initiated between 1972 and 1990. The median of the median survival times of patients treated on the control arms of the phase III trials initiated between 1972 and 1981 was 7.0 months; for those patients enrolled onto control arms between 1982 and 1990, the median survival time was 8.9 months (P =.001). Analysis of the SEER database of patients with extensive-stage SCLC over the same time period shows a similar 2-month prolongation in median survival time. CONCLUSION: Analysis of 21 phase III trials initiated in North America and the SEER database from 1972 to 1994 demonstrates that there has been a modest improvement in the survival time of patients with extensive-stage SCLC.

Carcinoma, Small Cell↗