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Biomedical subjects

R Simon

Publications and source records attributed to R Simon.

At least 145 records · Page 8Linked to original sources
PubMed1997

Dynamic on-line quantification of biventricular function with acoustic quantification (AQ). Validation, reproducibility and normal values of a new echocardiographic approach.

OBJECTIVES: Acoustic quantification (AQ), a recently developed ultrasonic integrated backscatter imaging system providing on-line measurements of ventricular cavity areas and their functional indexes, was validated in comparison to angiography and Doppler derived systolic dP/dt. Normal AQ-reference values were established. METHODS AND RESULTS: 1. In 45 patients undergoing heart catheterization, AQ derived areas in end-diastole (EDA), end-systole (ESA) and the resulting fractional area change (FAC) in apical 2- and 4-chamber view were compared to the corresponding biplane angiographic data. All correlations yielded significant values (p < 0.0001; EDA: r = 0.90, SEE = 2.6 cm2; ESA: r = 0.91, SEE = 2.2 cm2; FAC: r = 0.90, SEE = 4.1%). However, AQ-areas were underestimated by about 25%. 2. In 36 patients with mitral regurgitation AQ-FAC and AQ derived systolic dA/dt were compared to the Doppler derived systolic dP/dt, yielding significant correlations with r = 0.91 and r = 0.87; p < 0.0001. 3. In 50 healthy subjects, AQ derived EDA, ESA and FAC averaged 25.7 +/- 4.9, 14.7 +/- 3.3 cm2 and 43.2 +/- 4.8% for the left, and 17.1 +/- 3.8, 9.0 +/- 2.9 cm2 and 47.3 +/- 9.2% for the right ventricle. For EDA normalized peak filling (PFR) and ejection rates (PER) yielded 2.7 +/- 0.28 and -2.4 +/- 0.42 EDA/sec for the left and 3.4 +/- 0.74 and -2.9 +/- 0.62 EDA/sec for the right ventricle. The interobserver and day-to-day variability of AQ in healthy subjects and cardiac patients was low for EDA, ESA and FAC (< 12%) and higher for PFR and PER (< 20%). CONCLUSION: In comparison to angiography AQ reliably quantitates on-line left ventricular fractional area change, although AQ-areas are underestimated. AQ offers reproducible values of systolic and diastolic function and a new approach to cardiac patients.

Coronary Angiography↗
PubMed1997

Detection of diastolic dysfunction: acoustic quantification (AQ) in comparison to Doppler echocardiography.

OBJECTIVES: To evaluate the potential of acoustic quantification (AQ) in detection of diastolic dysfunction in comparison to Doppler analysis, we investigated, as a model of restrictive filling pattern, nonrejecting heart transplant recipients early postoperatively. BACKGROUND: AQ, an ultrasonic backscatter imaging system, enables instantaneous calculation of cavity areas and thus provides a new approach to diastolic function. METHODS: Of 27 pts who have undergone heart transplantation, echocardiography has been performed at the day of biopsy. During a time course of 8 weeks echocardiographic data have been analysed at 3 different time points (early, mid and late) in 16 nonrejecting pts. Indexes of the area-change waveform and its 1. derivative (dA/dt) obtained by AQ were opposed to usual Doppler indexes. RESULTS: In comparing data of the early and late time point of investigation, significant changes of early diastolic filling were detectable by AQ as well as by Doppler: End-diastolic areas have increased (p < 0.001), while peak filling rate (p < 0.0001), slope of area change during rapid filling (p < 0.001) and amount of relative area change during rapid filling (p < 0.001) have decreased. Complementary, Doppler derived pressure half-time (p < 0.0001) and isovolumic relaxation time (p < 0.0001) have increased while the peak early filling velocity (p < 0.0001) and its time velocity integral (p < 0.001) have decreased. CONCLUSION: An initial restrictive filling pattern has improved 8 weeks postoperatively. Since multiple indexes, obtained from the area change waveforms, in particular the for end-diastolic area normalized peak filling rate, seem to be highly sensitive in detecting changes of diastolic function, AQ may play an important complementary role in non-invasive evaluation of restrictive filling pattern.

Adult↗
PubMed1997

Evaluation of the resolving power of three different DNA fingerprinting methods to discriminate among isolates of a natural Rhizobium meliloti population.

In a comparative study, the PCR-based RAPD and ERIC fingerprint methods were evaluated for their resolving power to discriminate among 21 isolates of a natural Rhizobium meliloti population. PCR fingerprint patterns were analysed by using an automated laser fluorescent (ALF) DNA sequencer, thus allowing the automated on-line storage of data. Results obtained were compared to a classification system using insertion sequence (IS) fingerprinting. Both PCR fingerprint methods were comparable in their ability to resolve differences amongst Rh. meliloti isolates. Grouping of strains on the basis of their RAPD as well as their ERIC fingerprints correlated with grouping of strains according to their IS fingerprints. Moreover, strains displaying identical PCR patterns could be further differentiated according to their IS fingerprints, thus allowing a detailed insight into phylogenetic relationship among strains. The automated evaluation of strain-specific fingerprint patterns has the potential to become a valuable tool for studies of bacterial population genetics. Moreover, the rapid identification of single strains, e.g. pathogens in epidemiological studies seems feasible.

Bacterial Typing Techniques↗
PubMed1997

Repolarization dispersion and sudden cardiac death in patients with impaired left ventricular function.

AIMS: Prolongation of repolarization dispersion measured from the 12-lead surface ECG has been associated with sudden cardiac death and ventricular tachyarrhythmia in a variety of heart disorders. This study tested the hypothesis that increased repolarization dispersion is of prognostic value in identifying chronic heart failure patients at high risk of sudden cardiac death and ventricular tachyarrhythmia. RESULTS: In 163 patients, ischaemic (n = 126) and idiopathic dilated (n = 37) cardiomyopathy with a left ventricular ejection fraction < or = 40% were diagnosed by left ventricular angiography. During follow-up (26 +/- 15 months) 24 patients died suddenly, 10 experienced ventricular tachyarrhythmia, 19 died from pump failure, six died from acute myocardial infarction, and 97 survived. Bazett's formula rate-corrected JT-interval dispersion (JTc-d) was found to be 109 +/- 23 ms in sudden cardiac death/ventricular tachyarrhythmia patients, 57 +/- 20 ms in survivors, and 55 +/- 20 ms in patients who died from pump failure or acute myocardial infarction. Both univariate and multivariate analyses showed JTc-d to be the most important independent predictor of sudden cardiac death/ventricular tachyarrhythmia. A cut-off value of 85 ms for JTc-d had a 74% positive and a 98% negative predictive accuracy in identifying patients at risk for sudden cardiac death/ventricular tachyarrhythmia. CONCLUSION: Analysis of repolarization dispersion from the 12-lead surface ECG seems to be a useful screening method for identifying chronic heart failure patients at high risk for sudden cardiac death/ventricular tachyarrhythmia.

Angiography↗
PubMed1997

Multiple coronary artery-left ventricular fistulae: haemodynamic quantification by intracoronary Doppler ultrasound.

Multiple coronary artery-left ventricular fistulae involving all three major coronary arteries are extremely rare. Clinical findings are heterogeneous but include a history of typical or atypical angina pectoris in most cases. Coronary arteriography in a 65 year old woman who presented with chest pain at rest revealed multiple fine fistulae arising from the left anterior descending, left circumflex, and right coronary arteries. Left-to-left shunt was estimated by measurements of coronary artery flow velocity with intravascular Doppler ultrasound.

Aged↗
PubMed1997

Role of independent data-monitoring committees in randomized clinical trials sponsored by the National Cancer Institute.

PURPOSE: To describe the rationale for independent data monitoring committees (DMCs) for National Cancer Institute (NCI)-sponsored phase III cooperative group clinical trials. DESIGN: We review the necessity for interim monitoring of outcome data during the course of randomized clinical trials and summarize the reasons for establishing DMCs with requisite expertise and with appropriate independence from study investigators. RESULTS: The important components of the policy for cooperative group DMCs are described with a focus on the makeup of these bodies and on the complementary roles of study committee leadership and DMCs in protecting patient safety during the conduct of randomized clinical trials. CONCLUSION: The cooperative group DMCs that are independent of the study committees and that have the requisite expertise to examine accumulating data and to base decisions on monitoring guidelines that are specified in advance by the study committee provide a body able to protect patient safety, to protect the integrity of the clinical experiments on which patients have consented to participate, and to assure the public that conflicts of interest do not compromise either patient safety or trial integrity.

Humans↗
PubMed1997

Preparing the next generation of clinicians to manage information.

Curriculum development in informatics must be underpinned by knowledge of the information environment new recruits encounter after qualification. A pilot study was carried out to identify the type of information handling tasks newly qualified healthcare professionals are expected to undertake. This data was related to the skills junior staff possess at the point of entry to hospital posts. Data was collected on the opportunities these recently qualified individuals had to acquire IT skills and generic competence in information handling in their prequalification courses. Self-report data was supplemented by direct observation of junior staff on the wards. In addition to investigating the perspective of the junior staff, the study also explored the attitudes and expectations of senior clinicians, educationalists and NHS trust staff. The purpose of the study was to provide guidance to those involved in developing informatics curricula for clinical students at the prequalification stage. This paper reports some of our preliminary findings.

Adult↗
PubMed1997

Exaggerated lithotomy position-related rhabdomyolysis.

A case report and review of the exaggerated lithotomy position, in particular, and other position-related rhabdomyolysis is presented. The objective is to emphasize that the exaggerated lithotomy position, although providing good exposure for urethral and prostatic surgery, is associated with a low but definite risk of rhabdomyolysis and acute renal failure. Certain risk factors for the complication have been outlined. Close perioperative monitoring, including the use of pulmonary artery pressure and lower-extremity compartment pressure measurements in high-risk cases, is suggested for the prevention and the early detection of these cases. Prompt volume replacement and diuresis is the cornerstone of therapy in preventing acute renal failure in patients who develop rhabdomyolysis and myoglobinuria.

Acute Kidney Injury↗
PubMed1997

Bayesian design and analysis of two x two factorial clinical trials.

The 2 x 2 factorial design has been advocated for improving the efficiency of clinical trials. Most such trials are designed on the assumption that there is no interaction between the levels of the factors and outcome. This assumption is often problematic, however, because interactions are usually possible in clinical trials and the sample sizes often used provide little power in testing for interactions. We consider the use of Bayesian methods for the design and analysis of 2 x 2 factorial clinical trials. This approach avoids the need to dichotomize one's assumptions that interactions either do or do not exist and provides a flexible approach to the design and analysis of such clinical trials. Exact results are developed for balanced factorial designs with normal response. Approximations are then presented for factorial designs based on the logistic model for binary response or the proportional hazards model for time-to-event data. The resulting approximate posterior distributions are normal and hence no extensive computations are required. Suggestions for specification of prior distributions are presented.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Assessing whether to perform a confirmatory randomized clinical trial.

BACKGROUND: A confirmatory randomized clinical trial is a trial that is aimed at assessing whether a treatment effect observed in a previous randomized trial (or trials) is real and important. There is often considerable disagreement about the need for such confirmatory trials. PURPOSE: Our aim is to provide a general statistical framework for evaluating whether a confirmatory trial is warranted in a particular situation. METHODS AND RESULTS: The results of two clinical trials are considered: 1) a Cancer and Leukemia Group B trial comparing induction chemotherapy plus radiotherapy with radiotherapy alone in the treatment of patients with locally advanced non-small-cell lung cancer and 2) a North Central Cancer Treatment Group trial comparing surgery plus adjuvant chemotherapy with surgery alone in the treatment of patients with advanced colon cancer. In our analysis, we argue that differences in the interpretation of results from a randomized trial are based on differences in prior beliefs about the efficacy of the treatment(s) under study. We believe that a major factor in the decision to perform a confirmatory trial is prior skepticism about the clinical worth of the treatment in question. Both the level of prior skepticism and the minimum treatment effect deemed clinically worthwhile require subjective judgment. We develop a Bayesian framework to allow differences in interpretation to be examined systematically and the need for a confirmatory trial to be assessed. Our model allows the addition of prior belief (specified in the form of a prior distribution of treatment effect) to the results of a trial to yield a posterior distribution. The interpretation of trial results is based on the posterior distribution and will vary as the prior distribution (i.e., the prior belief) varies. To aid in the interpretation of trial results, we also advocate the specification of a minimum clinically worthwhile treatment effect at the start of a trial. CONCLUSIONS AND IMPLICATIONS: Our approach acknowledges that a number of different prior beliefs are possible, giving rise to a range of interpretations of results from a clinical trial. This approach provides a formal and systematic basis for considering both the range of likely opinions and the subsequent decision to be made with regard to the need for a confirmatory trial. We recommend that this approach be considered in the discussion of future confirmatory randomized clinical trials.

Adjuvants, Immunologic↗
PubMed1996

Activation of floral meristem identity genes in Arabidopsis.

The Arabidopsis floral meristem-identity genes APETALA1 (AP1) and LEAFY (LFY) confer floral identity on developing floral primordia, whereas TERMINAL FLOWER (TFL) is required to repress their expression within shoot and inflorescence meristems. LFY and AP1 are expressed in floral primordia in response to environmental conditions, such as day length, which regulate the onset of flowering, and presumably also in response to the action of genes that influence flowering time. However, the relationship between these flowering-time genes and the floral meristem-identity genes has been difficult to assess because flowering time is determined by several interacting genetic pathways. Here we describe a method to regulate expression of the flowering-time gene CONSTANS (CO) and demonstrate that CO expression is sufficient to trigger flowering, irrespective of day length. In response to CO expression, transcription of LFY and TFL is initiated rapidly, whereas transcription of AP1 occurs much later. We propose that CO acts within a genetic pathway that is sufficient to activate LFY and TFL transcription, but that rapid activation of AP1 requires an additional pathway.

Arabidopsis↗
PubMed1996

A simulation study of cross-validation for selecting an optimal cutpoint in univariate survival analysis.

Continuous measurements are often dichotomized for classification of subjects. This paper evaluates two procedures for determining a best cutpoint for a continuous prognostic factor with right censored outcome data. One procedure selects the cutpoint that minimizes the significance level of a logrank test with comparison of the two groups defined by the cutpoint. This procedure adjusts the significance level for maximal selection. The other procedure uses a cross-validation approach. The latter easily extends to accommodate multiple other prognostic factors. We compare the methods in terms of statistical power and bias in estimation of the true relative risk associated with the prognostic factor. Both procedures produce approximately the correct type I error rate. Use of a maximally selected cutpoint without adjustment of the significance level, however, results in a substantially elevated type I error rate. The cross-validation procedure unbiasedly estimated the relative risk under the null hypothesis while the procedure based on the maximally selected test resulted in an upward bias. When the relative risk for the two groups defined by the covariate and true changepoint was small, the cross-validation procedure provided greater power than the maximally selected test. The cross-validation based estimate of relative risk was unbiased while the procedure based on the maximally selected test produced a biased estimate. As the true relative risk increased, the power of the maximally selected test was about 10 per cent greater than the power obtained using cross-validation. The maximally selected test overestimated the relative risk by about 10 per cent. The cross-validation procedure produced at most 5 per cent underestimation of the true relative risk. Finally, we report the effect of dichotomizing a continuous non-linear relationship between covariate and risk. We compare using a linear proportional hazard model to using models based on optimally selected cutpoints. Our simulation study indicates that we can have a substantial loss of statistical power when we use cutpoint models in cases where there is a continuous relationship between covariate and risk.

Humans↗
PubMed1996

Cytoplasmic polyadenylation of activin receptor mRNA and the control of pattern formation in Xenopus development.

The activin receptor, a transmembrane serine-threonine kinase, is a key component necessary for pattern formation in early Xenopus development. This protein interacts with members of the transforming growth factor beta family and stimulates cells of the marginal zone to differentiate along the mesodermal pathway. In large part, this function of the activin receptor has been inferred from observations of phenotypes induced by injected mRNA encoding wild-type or mutant forms of the protein. Naturally occurring activin receptor mRNA is maternally inherited and contains within its 3' untranslated region an embryonic-type cytoplasmic polyadenylation element (CPE), an oligouridylic acid sequence that promotes cytoplasmic polyadenylation and resultant translational activation. Based on the presence of this element, we predicted in a previous report that activin receptor mRNA expression in embryos might be regulated by cytoplasmic polyadenylation (Simon and Richter, Mol. Cell. Biol. 14, 7867-7875, 1994). In this study, we have tested this hypothesis and show that not only do endogenous and injected activin receptor mRNAs undergo cytoplasmic polyadenylation during embryogenesis, but also that this process is necessary for stimulating translation and inducing the morphological defects observed by mRNA overexpression. The activin receptor CPE is bound by a Mr 36 x 10(3) protein in vitro, and competition for this factor between mRNAs in vivo inhibits activin receptor mRNA polyadenylation. This competition may be responsible for the lack of mesoderm formation observed in such injected embryos. These data suggest that cytoplasmic polyadenylation controls differentiation and pattern formation in early Xenopus development.

Activin Receptors↗
PubMed1996

Herbage density of third-stage larvae of goat strongyles during the dry season in Guadeloupe.

The objective of this study was to determine the main sources of variation in herbage densities of infective third stage larvae of goat strongyles during the marked dry season of 1994 in Guadeloupe (FWI). Herbage samples were collected for L3 density (LD) determination by an accurate method, 4 times at 4-week intervals in 58 paddocks of 21 farms spread out in five regions of the archipel of Guadeloupe. At the same time, FEC of each grazing animal and fecal culture for parasite genus determination according to sex and age were carried out. Stocking rate, dry matter content of soil, and daily climatic data were also recorded. An index of egg development in larvae (IEDL) was calculated as the ratio of LD to the eggs deposed during the 4th, 3rd, and 2nd weeks before sampling. Medians of LD in herbage were 3397, 1853, 1410, and 324 L3/kg DM for all parasites, Haemonchus, Trichostrongylus, and Oesophagostomum, respectively. Date of sampling, region, and irrigation practice in the northern windward region were the main sources of variation in LD and in frequency of each parasite. LD decreased as the dryness lasted, but it remained important (500 L3/kg DM) despite the drought. LD in windward regions were higher than in other regions. The region, the farm, and the paddock were the main sources of variation of IEDL. LD of each parasites were inversely correlated to global radiation recorded 1 to 3 weeks before herbage sampling, but no relation was found with rainfall data. Trichostrongylus frequency in L3 population increased as the dryness lasted. A dryness axis was extracted from environmental variables (climatic data, dry matter of soil, duration of dryness) by a multiple factorial procedure. LD and Haemonchus frequency in L3 population were inversely correlated to dryness axis (p < 0.01). In contrast, Trichostrongylus frequency was positively correlated to the dryness component.

Animal Feed↗
PubMed1996

Microbiological contamination of drinking water in a commercial household water filter system.

The microbiological quality of filtered water in a commercial water filter system (Brita) was tested in households and in two laboratories. In 24 of 34 filters used in households, bacterial counts increased in the filtered water up to 6,000 cfu/ml. In 4 of 6 filters tested in the laboratory, bacterial counts in the fresh filtrate were higher than in tap water after approximately one week of use both at room temperature and at 4 degrees C, suggesting growth or biofilm formation in the filter material. In some cases colony counts in the filtered water were 10,000 times those in tap water. The filter material of 5 of 13 new commercial filters was contaminated with bacteria or moulds. National or international regulatory agencies should ensure that water filters marketed for domestic use do not allow deterioration in the microbiological quality of drinking water.

Bacteria↗
PubMed1996

[Comparative genomic hybridization in pathology. A new molecular cytogenetic method].

Comparative genomic hybridisation (CGH) is a new cytogenetic method, which is based on a combination of fluorescence microscopy and digital image analysis. The molecular genetic basis is the hybridization of a mixture of fluorescein labeled test-DNA and reference-DNA on normal metaphase chromosomes. Comparative analysis allows the identification of all unbalanced chromosomal aberrations of the test-DNA in a single experimental step. The resulting DNA gains or DNA losses on the chromosomal or subchromosomal level mirror possible amplifications of oncogenes or losses of suppress orgenes. As CGH can be performed with genomic DNA of formalin-fixed and fresh-frozen tissue or cells, this new method is a very effective tool for pathologists and cytologists in the extended genomic screening of tumors and genetically altered tissues. Despite CGH analysis at present is restricted to research applications; its widespread dissemination as a routine method in diagnostic pathology can be expected in the near future.

Animals↗