Biomedical subjects

Jason P Fine

Publications and source records attributed to Jason P Fine.

9 recordsLinked to original sources

PubMed2004

Large-volume radiofrequency ablation of ex vivo bovine liver with multiple cooled cluster electrodes.

Three methods of creating large thermal lesions with cool-tip cluster electrodes were compared. Three cluster electrodes were arranged 4 cm apart in a triangular array. Eight lesions were created ex vivo in fresh bovine liver (from a butcher) with each method: sequential ablation (three electrodes, 12 minutes each); simultaneous activation of electrodes (12 minutes); and rapid switching of power between electrodes (12 minutes), for which an electronic computer-controlled switch was developed. For sequential, rapid switching, and simultaneous methods, lesion volumes were 137.5 cm(3)+/- 22.2, 116.4 cm(3)+/- 15.2, and 22.3 cm(3)+/- 6.4 (P < .05), respectively, and final temperatures at lesion center were 80 degrees C +/- 5, 97 degrees C +/- 8, and 41 degrees C +/- 3 (P < .001), respectively. Because of electrical interference between electrodes, simultaneous method led to little heating at the center between the electrodes and created small discontinuous lesions. Rapid switching created large round lesions by employing multiple electrodes concurrently, which substantially reduced treatment time and resulted in more effective heating between electrodes.

Animals↗

PubMed2004

Nonparametric estimation of the effects of quantitative trait loci.

Interval mapping of quantitative trait loci from breeding experiments plays an important role in understanding the mechanisms of disease, both in humans and other organisms. Standard approaches to estimation involve parametric assumptions for the component distributions and may be sensitive to model misspecification. Some nonparametric tests have been studied. However, nonparametric estimation of the phenotypic distributions has not been considered in the genetics literature, even though such methods might provide essential nonparametric summaries for comparing different loci. We develop a sufficient condition for identifiability of the phenotypic distributions. Simple nonparametric estimators for the distributions are proposed for uncensored and right censored data. They have a closed form and their small and large sample properties are readily established. Their practical utility as numerical summaries which complement nonparametric tests is demonstrated on two recent genetics examples.

Animals↗

PubMed2004

Microwave ablation with loop antenna: in vivo porcine liver model.

PURPOSE: To determine the effectiveness of tissue ablation with a loop microwave antenna in various configurations in porcine liver tissue. MATERIALS AND METHODS: Microwave energy was applied for 7 minutes at 60 W in six porcine livers (mean weight, 68.2 kg) by using single (n = 7) or dual 2.7-cm loop microwave probes in parallel (n = 9) or orthogonal (n = 9) configurations. Volume, diameter, shape, and temperature of the zone of necrosis and the presence of viable tissue inside the loop were determined and compared by means of factorial analysis of variance. RESULTS: Mean lesion volume and maximum diameter, respectively, were 32.2 cm(3) +/- 14.4 (SD) and 4.6 cm +/- 1.4 for lesions ablated with parallel probes (parallel lesions), 29.5 cm(3) +/- 8.1 and 4.3 cm +/- 0.6 for lesions ablated with orthogonal probes (orthogonal lesions), and 6.4 cm(3) +/- 1.9 and 3.4 cm +/- 0.62 for lesions ablated with single probes (single lesions) (P <.05, single vs parallel and orthogonal lesions). Mean minimum diameter was greatest for orthogonal lesions (3.5 cm +/- 0.53; P =.017, parallel vs orthogonal lesions). Orthogonal lesions had the highest mean internal temperature (97.2 degrees C) versus parallel (91.9 degrees C) and single (60.0 degrees C) lesions. All orthogonal lesions heated to 60 degrees C in comparison to eight of nine parallel and four of seven single lesions. The mean time to reach 60 degrees C was shortest for orthogonal lesions (93.3 seconds) versus parallel (123.8 seconds) and single (263.0 seconds) lesions. Orthogonal lesions were the most spherical. Viable tissue was present in the center of five of seven single, six of nine parallel, and zero of nine orthogonal lesions. CONCLUSION: Loop microwave antennas allow precise control and effective ablation of targeted tissue, particularly in the orthogonal configuration.

Animals↗

PubMed2004

The effects of estradiol and progesterone on plantarflexor muscle fatigue in ovariectomized mice.

The aim of this study was to examine specific and interactional effects of estradiol and progesterone on the time-to-fatigue of eccentrically contracted plantarflexor muscles and on the percent of plantarflexor isometric torque remaining immediately after an eccentric contraction (EC) protocol. Ovariectomized 6- to 8-week-old C57BL/6 mice were implanted with 21-day 0.05 mg-placebo, 0.05 mg-17-beta estradiol (OE), 15 mg-progesterone (OP), or estradiol and progesterone pellets (OEP). On the 16th day of hormone treatment, the isometric torque of the left plantarflexor muscles was measured. The left plantarflexor muscles then underwent 1 set of 150 ECs followed by 2 immediate post-EC isometric torque measurements. A group of ovarian-intact female mice of a similar age underwent the same isometric torque measurements and EC protocol. Plantarflexor muscle fatigue during ECs took 30%-41% longer to occur in the OP group (n = 9) than it did in the intact (n = 8, P = 0.02), OC (n = 11, P = 0.003), and OEP (n = 9, P = 0.007) groups. Peak active isometric torque had decreased immediately after ECs at 2 time points (M1 and M2). The OP group exhibited the greatest percent of isometric torque remaining immediately after ECs (M1, P = 0.03; M2, P = 0.04). These findings suggest that progesterone reduces muscle fatigue in response to ECs and that this progesterone effect is blunted when estradiol also is present. Therefore, ovarian hormone status may need to be considered when evaluating a response to physical activities, especially those activities involving ECs.

Analysis of Variance↗

PubMed2004

An efficient resampling method for assessing genome-wide statistical significance in mapping quantitative trait Loci.

Assessing genome-wide statistical significance is an important and difficult problem in multipoint linkage analysis. Due to multiple tests on the same genome, the usual pointwise significance level based on the chi-square approximation is inappropriate. Permutation is widely used to determine genome-wide significance. Theoretical approximations are available for simple experimental crosses. In this article, we propose a resampling procedure to assess the significance of genome-wide QTL mapping for experimental crosses. The proposed method is computationally much less intensive than the permutation procedure (in the order of 10(2) or higher) and is applicable to complex breeding designs and sophisticated genetic models that cannot be handled by the permutation and theoretical methods. The usefulness of the proposed method is demonstrated through simulation studies and an application to a Drosophila backcross.

Animals↗

PubMed2003

Estimating the distribution of nonterminal event time in the presence of mortality or informative dropout.

We consider estimating the distribution of nonterminal event time that may be censored by a terminal event but not vice versa. This problem may arise in two scenarios: (1) clinical trials involving both terminal and nonterminal events, or (2) when the primary outcome of the trial is nonterminal but there exists informative dropout. Inference is complicated by the dependent censoring from mortality or informative dropout. In this paper, we show that the joint distribution of the events can be formulated such that only the association is parameterized, with the marginal distributions unspecified. A closed form estimator for the association parameter is obtained from a novel adaptation of Oakes' concordance estimating equation. Tests for independence and goodness-of-fit of the model are also developed. A computationally simple, consistent and asymptotically normal estimator for the marginal distribution of the nonterminal event is given. Simulations demonstrate that the methods work well with practical sample sizes. The proposals are illustrated with data from an AIDS clinical trial.

Anti-HIV Agents↗

PubMed2003

Rank-based statistical methodologies for quantitative trait locus mapping.

This article addresses the identification of genetic loci (QTL and elsewhere) that influence nonnormal quantitative traits with focus on experimental crosses. QTL mapping is typically based on the assumption that the traits follow normal distributions, which may not be true in practice. Model-free tests have been proposed. However, nonparametric estimation of genetic effects has not been studied. We propose an estimation procedure based on the linear rank test statistics. The properties of the new procedure are compared with those of traditional likelihood-based interval mapping and regression interval mapping via simulations and a real data example. The results indicate that the nonparametric method is a competitive alternative to the existing parametric methodologies.

Crosses, Genetic↗

PubMed2003

Stratification by risk factors predicts survival on the active treatment arm in a randomized phase II study of interferon-gamma plus/minus interferon-alpha in advanced renal cell carcinoma (E6890).

INTRODUCTION: Standard therapy for recurrent or metastatic renal carcinoma includes the biologic response modifiers interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). The response rate for both agents is modest and toxicity is significant. New agents are needed. Interferon-gamma (IFN-gamma) is a type II interferon that demonstrated promising activity in renal carcinoma in early clinical trials. In vitro data suggested synergistic activity when IFN-gamma was combined with IFN-alpha. The Eastern Cooperative Oncology Group conducted a randomized phase II trial to confirm the efficacy of IFN-gamma as a single agent and to evaluate the efficacy and toxicity of IFN-gamma in combination with IFN-alpha in the treatment of patients with metastatic or recurrent renal carcinomas. MATERIALS AND METHODS: Ninety-five patients with recurrent or metastatic renal carcinoma were entered on trial. Patients were stratified based on risk assessment using the Elson method. Patients were randomly assigned to receive either IFN-gamma 0.1 mg/m2 weekly (arm A) or IFN-gamma 0.3 mg/m2 iv daily x 5 every 3 wk plus IFN-alpha 10 MU/m2 daily (arm B). Treatment efficacy was evaluated every 6 weeks. RESULTS: Toxicity in the arm A was minimal. Significant toxicity was noted in arm B, with four cases of grade 4 neurotoxicity. No responses were seen with IFN-gamma alone. Five responses (two CR and three PR) were noted in the combination arm for an overall response rate of 10%. Four of five responders were classified as "good risk." Median survival for arm A was 7.0 mo vs 10.4 mo for arm B. Risk stratification was significant in arm B. CONCLUSION: IFN-gamma at this dose and schedule failed to demonstrate activity in metastatic/recurrent renal carcinoma. The combination of IFN-gamma and IFN-alpha demonstrated a response rate similar to IFN-alpha alone. There was no evidence of synergy between IFN-gamma and IFN-alpha.

Adult↗

PubMed2002

Cystic fibrosis: a worldwide analysis of CFTR mutations--correlation with incidence data and application to screening.

Although there have been numerous reports from around the world of mutations in the gene of chromosome 7 known as CFTR (cystic fibrosis transmembrane conductance regulator), little attention has been given to integrating these mutant alleles into a global understanding of the population molecular genetics associated with cystic fibrosis (CF). We determined the distribution of CFTR mutations in as many regions throughout the world as possible in an effort designed to: 1) increase our understanding of ancestry-genotype relationships, 2) compare mutational arrays with disease incidence, and 3) gain insight for decisions regarding screening program enhancement through CFTR multi-mutational analyses. Information on all mutations that have been published since the identification and cloning of the CFTR gene's most common allele, DeltaF508 (or F508del), was reviewed and integrated into a centralized database. The data were then sorted and regional CFTR arrays were determined using mutations that appeared in a given region with a frequency of 0.5% or greater. Final analyses were based on 72,431 CF chromosomes, using data compiled from over 100 original papers, and over 80 regions from around the world, including all nations where CF has been studied using analytical molecular genetics. Initial results confirmed wide mutational heterogeneity throughout the world; however, characterization of the most common mutations across most populations was possible. We also examined CF incidence, DeltaF508 frequency, and regional mutational heterogeneity in a subset of populations. Data for these analyses were filtered for reliability and methodological strength before being incorporated into the final analysis. Statistical assessment of these variables revealed that there is a significant positive correlation between DeltaF508 frequency and the CF incidence levels of regional populations. Regional analyses were also performed to search for trends in the distribution of CFTR mutations across migrant and related populations; this led to clarification of ancestry-genotype patterns that can be used to design CFTR multi-mutation panels for CF screening programs. From comprehensive assessment of these data, we offer recommendations that multiple CFTR alleles should eventually be included to increase the sensitivity of newborn screening programs employing two-tier testing with trypsinogen and DNA analysis.

Cystic Fibrosis↗