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R Simon

Publications and source records attributed to R Simon.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1999

Differential effects of mibefradil, verapamil, and amlodipine on myocardial function and intracellular Ca(2+) handling in rats with chronic myocardial infarction.

Mibefradil is a selective T-type Ca(2+) channel blocker that exerts a potent vasodilating but weak inotropic action. The present study compared mibefradil with traditional L-type Ca(2+) channel blockers in regard to the effects of chronic oral administration on hemodynamics, contractility, and intracellular Ca(2+) handling in failing myocardium from postinfarction rats. Male Wistar rats with ligation-induced myocardial infarction were assigned to placebo or treatment with mibefradil (10 mg/kg/day), verapamil (8 mg/kg/day), or amlodipine (4 mg/kg/day) by oral gavage starting 7 days before the induction of myocardial infarction. Six weeks after myocardial infarction, hemodynamic measurements were performed in conscious animals. In addition, isometric force and free [Ca(2+)](i) were determined in isolated left ventricular papillary muscles. Placebo-treated rats exhibited a decreased mean atrial pressure, an increased left ventricular end-diastolic pressure, and a reduced rate of pressure rise compared with sham-operated animals. Mibefradil treatment significantly improved all of these parameters, whereas both amlodipine and verapamil exerted only minor effects. beta-Adrenergic stimulation with isoproterenol (ISO) enhanced contractility and Ca(2+) availability in papillary muscles from sham-operated rats, whereas the ISO-induced inotropic effect in muscles from placebo-treated rats was severely blunted. Chronic mibefradil treatment significantly improved the inotropic response to ISO stimulation, although the Ca(2+)(i) availability appeared to be less than in muscles from placebo-treated animals. In contrast, both verapamil and amlodipine did not restore the inotropic and Ca(2+)(i) modulating effect of ISO in remodeled myocardium. Thus, T-type Ca(2+) current appears to be of pathophysiological relevance in postischemic reperfused myocardium.

Adrenergic beta-Agonists↗
PubMed1998

Gene expression profiling of alveolar rhabdomyosarcoma with cDNA microarrays.

Several forms of human sarcoma, lymphoma, and leukemia are characterized by somatically acquired chromosome translocations that result in fusion genes that encode chimeric transcription factors with oncogenic properties. We have used cDNA microarrays containing 1238 cDNAs to investigate the gene expression profile of a group of seven alveolar rhabdomyosarcoma (ARMS) cell lines characterized by the presence of the PAX3-FKHR fusion gene. Using the method of multidimensional scaling to represent the relationships among the cell lines in two-dimensional Euclidean space, we determined that ARMS cells show a consistent pattern of gene expression, which allows the cells to be clustered together. By searching across the seven ARMS cell lines, we found that 37 of 1238 genes were most consistently expressed in ARMS relative to a reference cell line. Only three of these genes have been previously reported to be expressed in ARMS. Among these 37 were genes related to both primary (PAX3-FKHR) and secondary (CDK4) genetic alterations in ARMS. These results in ARMS demonstrate the potential of cDNA microarray technology to elucidate tumor-specific gene expression profiles in human cancers.

Chromosomes, Human, Pair 13↗
PubMed1998

The Antirrhinum ERG gene encodes a protein related to bacterial small GTPases and is required for embryonic viability.

Small GTPases have diverse roles in animals and yeast, including signal transduction, regulation of secretion, organisation of the cytoskeleton, and control of cell division. Similar GTPases have also been found in bacteria, such as the Escherichia coli GTPase ERA, which is involved in regulating metabolism and cell division [1,2]. Many small GTPases have been cloned from plants but their functional analysis has largely been limited to complementation of mutations in corresponding yeast genes, and antisense experiments which have implicated these proteins in processes such as root nodulation [3,4]. No mutations in plant GTPases have been reported, and thus their true importance in plant growth and development is unknown. Here we report the isolation of a gene from Antirrhinum majus encoding a protein from an entirely novel class of eukaryotic GTPases showing strongest similarity to the prokaryotic protein ERA. We have named this gene ERG (for ERA-related GTPase). The ERG gene is expressed in dividing or metabolically active cells. We generated a deletion allele of ERG by site-selected transposon mutagenesis and have shown that seeds containing embryos and endosperm homozygous for this deletion arrest soon after fertilisation. We conclude that ERG has a crucial role in plant growth and development, possibly by influencing mitochondrial division.

Amino Acid Sequence↗
PubMed1998

Trends in reported incidence of primary malignant brain tumors in children in the United States.

BACKGROUND: The reported incidence of primary malignant brain tumors among children in the United States increased by 35% during the period from 1973 through 1994. The purpose of our study was twofold: 1) to determine whether the reported incidence rates for this period are better represented by a linear increase over the entire period ("linear model") or, alternatively, by a step function, with a lower rate in the years preceding 1984-1985 and a constant higher rate afterward ("jump model"); and 2) to identify the specific brain regions and histologic subtypes that have increased in incidence. METHODS: Incidence data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the period from 1973 through 1994 for primary malignant brain tumors in children were used to model the number of cases in a year as a random variable from a Poisson distribution by use of either a linear model or a jump model. RESULTS/CONCLUSIONS: The increase in reported incidence of childhood primary malignant brain tumors is best explained by the jump model, with a step increase in incidence occurring in the mid-1980s. The brain stem and the cerebrum are the primary sites for which an increase in tumor incidence has been reported. The increase in reported incidence of low-grade gliomas in the cerebrum and the brain stem (unaccompanied by an increase in mortality for these sites) supports the substantial contribution of low-grade gliomas to the overall increase in reported incidence for childhood brain tumors. IMPLICATIONS: The significantly better fit of the data to a jump model supports the hypothesis that the observed increase in incidence somehow resulted from changes in detection and/or reporting of childhood primary malignant brain tumors during the mid-1980s.

Adolescent↗
PubMed1998

Chromosomal aberrations associated with invasion in papillary superficial bladder cancer.

Non-invasive and invasive papillary transitional cell carcinomas of stages pTa and pT1 represent the first steps of tumour progression in bladder cancer. In order to analyse different chromosomal alterations of pTa and pT1 superficial bladder cancer, 46 tumour specimens were examined by comparative genomic hybridization (CGH). Losses of chromosome 9 material (11/20) and gains of chromosome 17 material (6/20) were frequently found in pTa tumours. Stage pT1 tumours were characterized by gains of chromosome 1q (14/26; including amplification at 1q21-q24 in three cases) and chromosome 17 material (15/26), as well as by losses of 11p (15/26) and 11q (13/26). Other loci frequently showing losses in pT1 tumours were 2q (9/26), 4q (10/26), 5q (9/26), 8p (10/26), 9p (9/26), 9q (12/26), 10q (8/26), 17p (7/26), and 18q (8/26). Amplifications were detected at 8q21/22, 5q21, 7q36, 10p14, 10p12, 10q25, 12q12, and 12q14. The most striking differences between grade 2 pTa and pT1 tumours were gains of 1q (P < 0.01) and losses at 2q (P < 0.025), 10q (P < 0.05), 11p (P < 0.01), 11q (P < 0.01), and 17p (P < 0.05), as well as the total number of aberrations (pTa grade 2: 4.1; pT1 grade 2: 8.6 aberrations per tumour). These data show characteristic chromosomal aberrations associated with invasion in superficial bladder cancer.

Carcinoma, Transitional Cell↗
PubMed1998

Effects of angiotensin II on inotropy and intracellular Ca2+ handling in normal and hypertrophied rat myocardium.

The direct inotropic effect of angiotensin II on the myocardium is still controversial and little information exists as to its potential modification by heart disorders. Therefore, this study performed simultaneous measurements of isometric force and intracellular Ca2+ concentrations ([Ca2+]i) in left ventricular papillary muscles from sham-operated and aortic-banded rats at 10 weeks post-surgery. Angiotensin II (10(-6) M) induced a reduction of peak systolic [Ca2+]i (0.56 +/- 0.03 to 0.48 +/- 0.04 microM; P<0.05) and a parallel but insignificant diminution of developed tension (10.5 +/- 1.3 to 9.6 +/- 0.8 mN/mm2) in normal papillary muscles from sham-operated animals. Hypertrophied papillary muscles from aortic-banded rats demonstrated a significant decline in both peak systolic [Ca2+]i (0.51 +/- 0.02 to 0.44 +/- 0.01 microM; P<0.05) and developed tension (8.4 +/- 1.1 to 6.8 +/- 1.7 mN/mm2; P<0.05) after addition of angiotensin II. The time courses of the mechanical contraction and the intracellular Ca2+ signal were prolonged by angiotension II in both groups. Isoproterenol dose-dependently increased developed tension and peak systolic [Ca2+]i in papillary muscles from sham-operated rats. In contrast, the positive inotropic response to isoproterenol was markedly reduced in hypertrophied muscles despite a seemingly unimpaired increase in peak systolic [Ca2+]i. Pretreatment with angiotensin II (10(-6) M) resulted in a significant attenuation of the systolic [Ca2+]i response to isoproterenol stimulation in both normal and hypertrophied papillary muscles. Neither the bradykinin B2 antagonist icatibent (10(-6) M) nor the nitric oxide (NO) inhibitor L-NMMA (10(-6) M) abolished the depressant effects of angiotension II. Thus, ANG II induces a parallel decline of the mechanical performance and Ca2+ availability in rat myocardium. These effects are more distinct in hypertrophied than in normal muscle and become accentuated during beta-adrenergic stimulation. The underlying mechanism is not associated with the NO pathway but might involve a negative functional coupling between the angiotensin and beta-adrenergic-receptor complex.

Angiotensin II↗
PubMed1998

Plasmodium falciparum polyoximes: highly immunogenic synthetic vaccines constructed by chemoselective ligation of repeat B-cell epitopes and a universal T-cell epitope of CS protein.

Effective immunoprophylaxis directed against the pre-erythrocytic stages of the malaria parasite requires a vaccine that can elicit humoral and cell mediated immunity in individuals of diverse genetic background. In order for a synthetic peptide malaria vaccine to meet these requirements, problems associated with genetic restriction, peptide chemistry, adjuvant formulation and physiochemical characterization of the final synthetic vaccine product must first be overcome. To address these issues, five polyoxime vaccine candidates have been constructed by ligating purified peptide epitopes of the P. falciparum CS protein to a branched template via oxime bonds. All five constructs, including two based on templates containing the synthetic adjuvant tripalmitoyl-S-glyceryl cysteine (Pam3Cys), were of sufficient purity for characterization by mass spectrometry. The immunogenicity of the malaria polyoximes in different murine strains was compared to that of multiple antigen peptide (MAP) constructs synthesized by standard step-wise synthesis. A tri-epitope polyoxime-Pam3Cys construct, based on the repeats and a universal T-cell epitope that contains both helper and CTL epitopes of the CS protein, was shown to be a precisely-defined synthetic malaria vaccine candidate that was highly immunogenic in murine strains of diverse H-2 haplotypes.

Adjuvants, Immunologic↗
PubMed1998

Evidence that childhood acute lymphoblastic leukemia is associated with an infectious agent linked to hygiene conditions.

OBJECTIVES: The incidence of acute lymphoblastic leukemia (ALL) in children has shown temporal and geographic variation during the 20th century, with higher rates in developed nations appearing in the first half of the century, but with persisting low rates in developing nations. We sought to assess the relation of childhood ALL with hygiene conditions, an aspect of socioeconomic development affecting rates of exposure to infectious agents. METHODS: Infection patterns for hepatitis A virus (HAV), an agent with a fecal-oral route of transmission, were used to indicate hygiene conditions in different populations, with emphasis on instructive United States and Japanese data. A catalytic model was fit to these data, estimating the HAV force of infection and age-specific seroprevalence rates over time. These analyses were used to assess the temporal relationship of changes in HAV infection rates to changes in childhood leukemia mortality and incidence rates. RESULTS: We observed an inverse relationship between HAV infection prevalence and rates of childhood leukemia. Further, decreases in the HAV force of infection in the United States and Japan appear to have preceded increases in childhood leukemia rates. We describe a model based on a putative leukemia-inducing agent with a change in infection rate over time correlated with that of HAV that describes well the temporal trends in childhood leukemia rates for White children in the US and for Japanese children. CONCLUSION: The data suggest that improved public hygiene conditions, as measured by decreased prevalence of HAV infection, are associated with higher childhood ALL incidence rates. The model that we present supports the plausibility of the hypothesis that decreased childhood exposure to a leukemia-inducing agent associated with hygiene conditions leads to higher rates of ALL in children by increasing the frequency of in utero transmission caused by primary infection during pregnancy (or by increasing the number of individuals infected in early infancy because of lack of protective maternal antibodies).

Child↗
PubMed1998

Data management and analysis for gene expression arrays.

Microarray technology makes it possible to simultaneously study the expression of thousands of genes during a single experiment. We have developed an information system, ArrayDB, to manage and analyse large-scale expression data. The underlying relational database was designed to allow flexibility in the nature and structure of data input and also in the generation of standard or customized reports through a web-browser interface. ArrayDB provides varied options for data retrieval and analysis tools that should facilitate the interpretation of complex hybridization results. A sampling of ArrayDB storage, retrieval and analysis capabilities is available (www.nhgri.nih.gov/DIR/LCG/15K/HTML/ ), along with information on a set of approximately 15,000 genes used to fabricate several widely used microarrays. Information stored in ArrayDB is used to provide integrated gene expression reports by linking array target sequences with NCBI's Entrez retrieval system, UniGene and KEGG pathway views. The integration of external information resources is essential in interpreting intrinsic patterns and relationships in large-scale gene expression data.

Computer Communication Networks↗
PubMed1998

Comparative genomic hybridization and telomerase activity analysis identify two biologically different groups of 4s neuroblastomas.

Chromosomal aberrations of 20 stage 4s neuroblastomas were analysed by comparative genomic hybridization (CGH). In a subset of 13/20 tumours, telomerase activity was evaluated by the telomeric repeat amplification protocol (TRAP). The CGH data were compared with the CGH results of ten stage 1 and 2 (stage 1/2) and 22 stage 3 and 4 (stage 3/4) neuroblastomas. A total of 17/20 stage 4s neuroblastomas did not progress clinically, whereas tumour progression with lethal outcome occurred in 3/20 cases. The CGH data of clinically non-progressing stage 4s tumours revealed a high rate of whole-chromosome aberrations (73.4%) with an overrepresentation of mainly chromosomes 2, 6, 7, 12, 13, 17, 18 and an underrepresentation of mainly chromosomes 3, 4, 11, 14. MYCN amplification or 1p deletion was observed in only 1/27 or 2/17 clinically non-progressing stage 4s tumours respectively, whereas all three progressive stage 4s neuroblastomas showed MYCN amplification, 1p deletion and, in 2/3 cases, distal 17q gains. Except for one case, telomerase activity was not observed in non-progressing stage 4s neuroblastomas. In contrast, 4s tumours with lethal outcome revealed elevated telomerase activity levels. Our data suggest that stage 4s neuroblastomas belong to two biologically different groups, one of which displays the genetic features of localized stage 1/2 tumours, whereas the other mimics advanced stage 3/4 neuroblastomas.

Blotting, Southern↗
PubMed1998

The relationship of packed cell transfusion to red blood cell deformability in systemic inflammatory response syndrome patients.

RBC deformability (RBCD) is decreased in critically ill patients. This is thought to impede the passage of the RBC through the microcirculation. The cell transit analyzer (CTA) provides an evaluation of RBCD. RBCD was examined in 16 patients admitted to the surgical intensive care unit. CTA analysis was conducted within 24 h of admission to the surgical intensive care unit or as soon as possible thereafter, and then repeated every 72 h. Counts per second (C/s) was the parameter used as an index of RBCD. Patients were classified as Septic/SIRS or nonseptic at the time of each blood collection by standard clinical criteria. There were 34 total specimens, 22 septic/SIRS and 12 nonseptic. The C/s for the SIRS samples (41.7 +/- 3.4 was significantly (p < .05) lower than that of the non-SIRS samples (54.3 +/- 5.3). Seventeen of the Septic/SIRS samples were obtained following blood transfusion. Pearson's test calculated for the C/s and the total number of packed RBC transfusions showed a positive correlation (r = .594) that was statistically significant (p < .02). CTA was also performed on 10 U of banked packed RBC in vitro. Deformability was maintained at a constant level until the very end of the storage period, at which time there was a statistically significant decrease in C/s (p < .0001). These data suggest that packed RBC transfusion is associated with a significant improvement in the abnormally low RBCD seen in critically ill patients. This may be due to replacement of previously rigidified cells by cells with a more normal RBCD.

Adult↗
PubMed1998

Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma.

PURPOSE: Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. PATIENTS AND METHODS: Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. RESULTS: The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. CONCLUSION: The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.

Adult↗