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Biomedical subjects

R Simon

Publications and source records attributed to R Simon.

At least 37 records · Page 2Linked to original sources
PubMed2004

Prognostic value of Doppler transmitral filling patterns in patients with chronic heart failure.

BACKGROUND: Chronic heart failure is a significant cause of cardiovascular morbidity and mortality. This study tested the hypothesis that restrictive filling pattern may provide useful prognostic data for identifying patients with chronic heart failure at high risk of all-cause cardiac death. METHODS: Ninety patients with chronic heart failure [70 men and 20 women, mean age (58.1 +/- 11.6) years] were investigated and followed for (18.8 +/- 7.9) months. During this period, 14 patients died of progressive pump failure, 12 patients underwent heart transplantation, 5 patients died suddenly, and 2 patients died of acute myocardial infarction. A new criterion, the restrictive filling index (RFI), was designed to subgroup patients into a restrictive and a nonrestrictive group. RESULTS: Patients with restrictive filling pattern had a more severe left ventricular dysfunction and a higher cardiac mortality. Analysis by the Kaplan-Meier method revealed that patients in the RFI > or = 1 and RFI < 1 groups had a cardiac events-free survival rate of 52% versus 94% at 1 year, and 27.5% versus 92% at 2 years, respectively. The multivariate Cox proportional hazard model selected RFI as the most powerful prognostic factor (chi(2) = 8.8017, P = 0.0030) for all-cause cardiac death. CONCLUSION: These results indicate that RFI is a simple, noninvasive, and specific clinical predictor for adult chronic heart failure patients who are at a high risk for all-cause cardiac death.

Chronic Disease↗
PubMed2004

[Surgical treatment of pulmonary metastases--long-term results].

A group of 103 patients operated for lung metastases in the Surgical clinic of the FNsP of L. Dérer and in the II Surgical clinic of L. Pasteur is assessed in this work. Minor operations of atypical resection prevailed among the resections. The postoperative mortality in the whole group was 1.9%. The best long-term survival rates were reached in tumors primarily treated by chemotherapy and followed by the lung metastasectomy. All patients in this group suffered from testical tumors and their long-term survival rate was 69%. In tumor cases, where the metastasis was primarily removed by surgery, the long-term survival rate correlated with the literature data of 30%. When the prognostic factors were considered, the number of removed metachrone metastases being less than 3, appeared statistically significant from the point of view of the patient survival. Based on the evaluated results, it can be concluded that surgical treatment of the lung metastases performed within the interdisciplinary oncological concept, currently remains a generally accepted therapeutic procedure.

Adolescent↗
PubMed2004

[Analysis of gene expression profiles among 3 epithelial ovarian tumor subtypes using cDNA and tissue microarrays].

BACKGROUND & OBJECTIVE: Ovarian cancer is the leading cause of death among the gynecological malignancy mainly due to lacking of effective early diagnostic methods. To identify novel candidate genes and further explore their clinical significance of epithelial ovarian tumors, we developed a new method in our laboratory by combining cDNA microarray with RNA in situ hybridization in frozen tissue microarray. METHODS: cDNA microarrays were used to seek differentially expressed genes among 3 subtypes of ovarian tumors (serous borderline ovarian tumors, serous ovarian cancers, and endometrioid ovarian carcinomas). RNA in situ hybridization in frozen tissue microarray was used to further confirm the findings from cDNA microarrays. RESULTS: In the study of cDNA microarray, 40 genes and ESTs showed significant differential expression between low and high-malignancy, as well as serous and endometrioid carcinomas. EPHB6, PTPRF, GFER, ERG25, PLRP1, FLJ22060, and WISP2 were further validated by RNA in situ hybridization in tissue microarray. CONCLUSIONS: cDNA microarray combined with RNA in situ hybridization in frozen tissue microarray is an ideal choice for identifying novel oncogenes. EPHB6, PTPRF, GFER, ERG25, PLRP1, FLJ22060, and WISP2 might become the new candidate oncogenes for epithelial ovarian cancer.

CCN Intercellular Signaling Proteins↗
PubMed2003

Diagnostic and prognostic prediction using gene expression profiles in high-dimensional microarray data.

DNA microarrays are a potentially powerful technology for improving diagnostic classification, treatment selection and therapeutics development. There are, however, many potential pitfalls in the use of microarrays that result in false leads and erroneous conclusions. This paper provides a review of the key features to be observed in developing diagnostic and prognostic classification systems based on gene expression profiling and some of the pitfalls to be aware of in reading reports of microarray-based studies.

Algorithms↗
PubMed2003

Statistical design of reverse dye microarrays.

MOTIVATION: In cDNA microarray experiments all samples are labelled with either Cy3 dye or Cy5 dye. Certain genes exhibit dye bias-a tendency to bind more efficiently to one of the dyes. The common reference design avoids the problem of dye bias by running all arrays 'forward', so that the samples being compared are always labelled with the same dye. But comparison of samples labelled with different dyes is sometimes of interest. In these situations, it is necessary to run some arrays 'reverse'-with the dye labelling reversed-in order to correct for the dye bias. The design of these experiments will impact one's ability to identify genes that are differentially expressed in different tissues or conditions. We address the design issue of how many specimens are needed, how many forward and reverse labelled arrays to perform, and how to optimally assign Cy3 and Cy5 labels to the specimens. RESULTS: We consider three types of experiments for which some reverse labelling is needed: paired samples, samples from two predefined groups, and reference design data when comparison with the reference is of interest. We present simple probability models for the data, derive optimal estimators for relative gene expression, and compare the efficiency of the estimators for a range of designs. In each case, we present the optimal design and sample size formulas. We show that reverse labelling of individual arrays is generally not required.

Algorithms↗
PubMed2002

Bypass surgery versus stenting for the treatment of multivessel disease in patients with unstable angina compared with stable angina.

BACKGROUND: Earlier reports have shown that the outcome of balloon angioplasty or bypass surgery in unstable angina is less favorable than in stable angina. Recent improvements in percutaneous treatment (stent implantation) and bypass surgery (arterial grafts) warrant reevaluation of the relative merits of either technique in treatment of unstable angina. Methods and Results- Seven hundred fifty-five patients with stable angina were randomly assigned to coronary stenting (374) or bypass surgery (381), and 450 patients with unstable angina were randomly assigned to coronary stenting (226) or bypass surgery (224). All patients had multivessel disease considered to be equally treatable by either technique. Freedom from major adverse events, including death, myocardial infarction, and cerebrovascular events, at 1 year was not different in unstable patients (91.2% versus 88.9%) and stable patients (90.4% versus 92.6%) treated, respectively, with coronary stenting or bypass surgery. Freedom from repeat revascularization at 1 year was similar in unstable and stable angina treated with stenting (79.2% versus 78.9%) or bypass surgery (96.3% versus 96%) but was significantly higher in both unstable and stable patients treated with stenting (16.8% versus 16.9%) compared with bypass surgery (3.6% versus 3.5%). Neither the difference in costs between stented or bypassed stable or unstable angina ($2594 versus $3627) nor the cost-effectiveness was significantly different at 1 year. CONCLUSIONS: There was no difference in rates of death, myocardial infarction, and cerebrovascular event at 1 year in patients with unstable angina and multivessel disease treated with either stented angioplasty or bypass surgery compared with patients with stable angina. The rate of repeat revascularization of both unstable and stable angina was significantly higher in patients with stents.

Acute Disease↗
PubMed2002

Identifying pre-post chemotherapy differences in gene expression in breast tumours: a statistical method appropriate for this aim.

Although widely used for the analysis of gene expression microarray data, cluster analysis may not be the most appropriate statistical technique for some study aims. We demonstrate this by considering a previous analysis of microarray data obtained on breast tumour specimens, many of which were paired specimens from the same patient before and after chemotherapy. Reanalysing the data using statistical methods that appropriately utilise the paired differences for identification of differentially expressed genes, we find 17 genes that we can confidently identify as more expressed after chemotherapy than before. These findings were not reported by the original investigators who analysed the data using cluster analysis techniques.

Antineoplastic Agents↗
PubMed2002

Iodine species and the endocrine system: thyroid hormone levels in adult Danio rerio and developing Xenopus laevis.

Recently a new approach for the analysis of iodinated organic species in human serum has been developed using liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS). This method enables quantification of iodide, T4 and T3, as well as reverse T3 (rT3) and the synthetic precursors of TH, monoiodotyrosine (MIT), and diiodotyrosine (DIT) in a single injection. In this work, the LC-ICP-MS approach was used to analyze whole-body homogenates of adult male and female zebrafish (Danio rerio) and tadpoles of the African clawed frog (Xenopus laevis) at two different developmental stages (NF58 and 61) according to Nieuwkoop and Faber. The data demonstrate that the LC-ICP-MS method was successful at measuring I-, MIT, DIT, T4, T3, and rT3 in these two species. Furthermore, the method also detected five additional iodinated compounds which are currently unidentified.

Animals↗
PubMed2002

[Pullback atherectomy. An alternative procedure in the treatment of coronary stenosis and in-stent restenosis].

Optimized directional coronary atherectomy (DCA) has shown significantly superior acute and long-term results compared to conventional balloon angioplasty (BA). Nevertheless DCA has remained a niche application due to specific procedural aspects. The pullback atherectomy catheter (PAC), developed to retrieve atheromatous plaque material, is an alternative debulking device. We report on clinical and angiographic experience in 55 consecutive patients, in whom de novo lesions (35 pts) as well as instent restenoses (17 pts) were treated. The minimal luminal diameter (MLD, mm) rose after PAC and additional BA from 1.06 +/- 0.53 to 2.68 +/- 0.48 and from 1.10 +/- 0.48 to 2.55 +/- 0.49 mm, respectively. A stenosis reduction from 69 +/- 13 to 19 +/- 16 and from 64 +/- 15 to 16 +/- 10%, resp., could be documented. After 3-6 months a complete angiographic follow-up showed MLD values of 2.01 +/- 0.69 and 1.88 +/- 0.61 mm. Nine of 35 (26%) vs. 5 of 17 (29%) pts developed significant restenosis at the treated site (diameter stenoses > 50%). Stent implantation was necessary to achieve an optimal acute angiographic result or due to dissection in 17 vs. 5 pts. Major cardiac events did not occur; however, two restenosed coilstents were removed by PAC. With the pullback atherectomy catheter, a safe and effective alternative device is available for the treatment of coronary lesions and also of in-stent restenosis. Promising short and acceptable long-term results are comparable to those of other debulking procedures.

Aged↗
PubMed2002

Neurophysiological and behavioral concomitants of mild brain injury in collegiate athletes.

OBJECTIVES: There is still limited understanding regarding the effect of mild brain injury (MBI) on normal functioning of the human brain with respect to motor control and coordination. To our knowledge, no research exists on how both the accuracy of force production and underlying neurophysiological concomitants are interactively affected by MBI. The aim of this study is to provide empirical evidence that there are at least transient functional changes in the brain associated with motor control and coordination in collegiate athletes suffering from MBI as reflected in alterations of force trajectory patterns and electroencephalogram (EEG) potentials both in time and frequency domains. METHODS: Comparisons of the performance and concomitant EEG waveforms both in time and frequency domains of 6 collegiate athletes with MBI and 6 normal subjects in a series of isometric force production tasks were made. The traditional averaging techniques to obtain the slow-wave movement-related potentials (MRP) and Morlet wavelet transform to obtain EEG time-frequency (TF) profiles associated with task performance were used. Subjects performed isometric force production tasks when the level of nominal force was experimentally manipulated. EEG recordings from the frontal-central areas were analyzed with respect to the accuracy of force production during the ramp phase. RESULTS: Behaviorally, the accuracy of force trajectory performance was considerably impaired in MBI subjects even when the amount of task force was only increased from 25 to 50% maximum voluntary contraction (MVC) within a given subject. Electro-cortically, impaired performance in MBI subjects was associated with alterations in EEG waveforms, amplitude of MRP and TF profiles of EEG. CONCLUSIONS: Both behavioral and electro-cortical data of control subjects generally were comparable with those from subjects with MBI when small amounts of force were regulated. However, differences become apparent as the amount of task force production was increased. Overall our findings identify the presence of transient functional changes in the brain associated with motor control and coordination in subjects suffering from MBI.

Adult↗
PubMed2002

Comparison of microarray designs for class comparison and class discovery.

MOTIVATION: Two-color microarray experiments in which an aliquot derived from a common RNA sample is placed on each array are called reference designs. Traditionally, microarray experiments have used reference designs, but designs without a reference have recently been proposed as alternatives. RESULTS: We develop a statistical model that distinguishes the different levels of variation typically present in cancer data, including biological variation among RNA samples, experimental error and variation attributable to phenotype. Within the context of this model, we examine the reference design and two designs which do not use a reference, the balanced block design and the loop design, focusing particularly on efficiency of estimates and the performance of cluster analysis. We calculate the relative efficiency of designs when there are a fixed number of arrays available, and when there are a fixed number of samples available. Monte Carlo simulation is used to compare the designs when the objective is class discovery based on cluster analysis of the samples. The number of discrepancies between the estimated clusters and the true clusters were significantly smaller for the reference design than for the loop design. The efficiency of the reference design relative to the loop and block designs depends on the relation between inter- and intra-sample variance. These results suggest that if cluster analysis is a major goal of the experiment, then a reference design is preferable. If identification of differentially expressed genes is the main concern, then design selection may involve a consideration of several factors.

Algorithms↗
PubMed2002

[Molecular genetics of urinary bladder cancer progression].

UNLABELLED: Extensive cytogenetic and molecular analyses have recently helped to gain a much better understanding of the biology of urinary bladder cancer. Early studies had suggested two different pathways of bladder cancer development, one characterized by chromosome 9 losses and the other by p53 mutations. Subsequent studies have greatly expanded these data. Overall, there is compelling evidence for two entirely different bladder tumor entities. One entity consists of genetically unstable tumors that have many cytogenetic alterations, including p53 alterations in about 50% of the cases. Other cytogenetic alterations that can be found frequently in these tumors are deletions of 8p, 9p, 11p, 11q, and Y as well as gains of 1q, 8q, 17q, and 20q. More than 20 chromosomal regions can undergo high level DNA amplification including 17q21 (HER-2/neu). Phenotypically, these tumors are characterized by a high degree of cytological atypia. Their growth pattern can be non-invasive flat (carcinoma in situ), non-invasive papillary (pTaG3) or invasive (papillary or solid). The other, "benign" bladder cancer entity is composed of tumors with a low level of genetic instability, a low number of cytogenetic alterations, and absence of p53 mutations. Morphologically, these tumors are papillary non-invasive neoplasms with a low degree of cytological atypia. Progression to invasively growing carcinoma is extremely rare. CONCLUSION: Molecular studies have revealed profound genetic differences between invasive and non-invasive bladder cancers. This argues against the previously used combination of pTa and pT1 tumor stages as "superficial bladder cancer". The high frequency of genetic alterations in invasive carcinomas enables a markedly improved detection of bladder cancer cells in voided urine using fluorescence in situ hybridization (FISH) assays.

Chromosome Aberrations↗
PubMed2002

[HER-2 and TOP 2A gene amplifications in urinary bladder carcinoma].

The HER-2/neu gene is frequently amplified in bladder cancer. Topoisomerase 2 Alpha (TOP2A) which is located nearby the HER-2/neu gene is an important molecular target for several anti cancer drugs. The frequency of TOP2A amplification in urinary bladder cancer is unknown. It was the aim of this study to determine the frequency of HER-2 and TOP2A amplification in urinary bladder cancer and to evaluate the association of these amplifications with tumor phenotype. For this purpose a tissue microarray containing 768 pTa, 425 pT1 and 571 pT2-4 carcinomas was analyzed by fluorescence in situ hybridization (FISH). Amplifications of both genes were significantly associated with advanced tumor stage and high grade. HER-2 amplification was found in 1.6% of pTa, 7.2% of pT1 and 13.8% of pT2-4 carcinomas (p < 0.0001). HER-2 amplification was present in only 1.1% of grade 1 and 0.8% of grade 2 tumors but in 14.2% of grade 3 tumors (p < 0.0001). TOP2A amplification was present in 0.7% pTa, 1.8% pT1 and 3.4% pT2-4 carcinomas (p < 0.0001). TOP2A was found in none of the grade 1, in 0.2% of grade 2 and 3.8% of grade 3 tumors (p < 0.0001). 1% of all analyzed tumors had simultaneously high level amplification of TOP2A and HER-2. Amplification of both genes were significantly associated with tumor specific survival if all tumors were analyzed together. Given the high frequency of HER-2 amplification in urinary bladder cancer, some of these tumors may respond favorable to Herceptin therapy. The TOP2A amplification status may influence response to anthracyclin treatment.

Antigens, Neoplasm↗
PubMed2001

Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia.

The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression "signature," irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease.

Gene Expression↗
PubMed2001

The World Trade Center attack. Lessons for disaster management.

As the largest, and one of the most eclectic, urban center in the United States, New York City felt the need to develop an Office of Emergency Management to coordinate communications and direct resources in the event of a mass disaster. Practice drills were then carried out to assess and improve disaster preparedness. The day of 11 September 2001 began with the unimaginable. As events unfolded, previous plans based on drills were found not to address the unique issues faced and new plans rapidly evolved out of necessity. Heroic actions were commonplace. Much can be learned from the events of 11 September 2001. Natural and unnatural disasters will happen again, so it is critical that these lessons be learned. Proper preparation will undoubtedly save lives and resources.

Aircraft↗
PubMed2001

Anthrax nation.

Explore the source record for details and available documents.

Anthrax↗
PubMed2001

Graph models of oncogenesis with an application to melanoma.

We describe several analytical techniques for use in developing genetic models of oncogenesis including: methods for the selection of important genetic events, construction of graph models (including distance-based trees, branching trees, contingency trees and directed acyclic graph models) from these events and methods for interpretation of the resulting models. The models can be used to make predictions about: which genetic events tend to occur early, which events tend to occur together and the likely order of events. Unlike simple path models of oncogenesis, our models allow dependencies to exist between specific genetic changes and allow for multiple, divergent paths in tumor progression. A variety of genetic events can be used with the graph models including chromosome breaks, losses or gains of large DNA regions, small mutations and changes in methylation. As an application of the techniques, we use a recently published cytogenetic analysis of 206 melanoma cases [Nelson et al. (2000), Cancer Genet. Cytogenet.122, 101-109] to derive graph models for chromosome breaks in melanoma. Among our predictions are: (1) breaks in 6q1 and 1q1 are early events, with 6q1 preferentially occurring first and increasing the probability of a break in 1q1 and (2) breaks in the two sets [1p1, 1p2, 9q1] and [1q1, 7p2, 9p2] tend to occur together. This study illustrates that the application of graph models to genetic data from tumor sets provide new information on the interrelationships among genetic changes during tumor progression.

Chromosome Breakage↗