Biomedical subjects

David Allison

Publications and source records attributed to David Allison.

5 recordsLinked to original sources

PubMed2006

Increased expression of thymidylate synthetase (TS), ubiquitin specific protease 10 (USP10) and survivin is associated with poor survival in glioblastoma multiforme (GBM).

BACKGROUND: The limited success of empirically designed treatment paradigms for patients diagnosed with glioblastoma multiforme (GBM) emphasizes the need for rationally designed treatment strategies based on the molecular profile of tumor samples and their correlation to clinical parameters. METHODS: In the current study, we utilize a novel real-time quantitative low density array (RTQ-LDA) to identify differentially expressed genes in de novo GBM tissues obtained from patients with distinctly different clinical outcomes. Total RNA was isolated from a cohort of 21 GBM specimens obtained from patients with either good (long-term survival (LTS) >36 months post surgery, n = 8) or poor (died of the disease (DOD) <24 months post surgery, n = 13) prognosis. Non-neoplastic brain tissue (n = 5) was obtained from patients who underwent surgery for refractory epilepsy. Demographic data was assessed for correlation with survival using Cox proportional hazards models. Sufficient RNA was available to use RTQ-LDA to quantify the expression of 93 independent genes in 5 LTS, 4 DOD, and 5 non-neoplastic brain samples. The eight differentially expressed genes identified by RTQ-LDA in LTS versus DOD (P <or= 0.050) were subsequently quantified in all 21 GBM samples by real-time quantitative PCR (RTQ). RESULTS: A correlation between younger patients and good prognosis was demonstrated (P <or= 0.05). The combination of RTQ-LDA and RTQ identified thymidylate synthetase (TS), ubiquitin specific protease 10 (USP10), and survivin as significantly over-expressed (P <or= 0.050) in DOD compared to LTS patients. Ribonucleotide reductase subunit M2 (RRM2) was identified as tumor-specific, but not associated with survival. CONCLUSIONS: Taken collectively, TS, USP10, survivin and RRM2 may be useful as prognostic indicators and/or in the development of rationally designed treatment protocols.

Adolescent↗

PubMed2006

Rationale for fixed dosing of pertuzumab in cancer patients based on population pharmacokinetic analysis.

OBJECTIVE: Our objectives were to develop the population pharmacokinetic (PK) for pertuzumab and examine the variability of steady-state trough serum concentrations (C(SS,trough)) and exposure after fixed, body-weight-based, or body-surface area (BSA)-based dosing methods in cancer patients. METHODS: Pertuzumab was administered by i.v. infusion (every 3 weeks) either as a weight-based dose (0.5-15 mg/kg) or a fixed dose (420 or 1050 mg). Data from three clinical studies, comprising 153 patients and 1458 concentration-time points, were pooled for this analysis using NONMEM. RESULTS: A linear two-compartment model best described the data. Body weight and BSA were significant covariates affecting clearance (CL) and distribution volume (Vc), respectively. However, weight and BSA only explained small percentage of interpatient variability for CL and Vc, respectively. Simulation results indicated that PK profiles were very similar after the three dosing methods. Compared to fixed dosing, weight- and BSA-based dosing only reduced the population variability of C(SS,trough) moderately. CONCLUSION: A population PK model was developed for pertuzumab, the first monoclonal IgG1 antibody in a new class of agents known as HER dimerization inhibitors. In addition, our analyses demonstrate the feasibility of administering pertuzumab using a fixed dose in women with ovarian and breast cancers.

Adult↗

PubMed2006

A review of pediatric nonrespiratory sleep disorders.

Sleep problems are extremely common during childhood, from infancy to adolescence. Despite the prevalence of sleep problems, childhood sleep disorders are often underrecognized and undiagnosed, despite being either preventable or treatable. Sleep impacts almost all aspects of a child's functioning, and thus the increased recognition and treatment of sleep disorders will positively affect a child's well-being. Children experience the same broad range of sleep disturbances encountered in adults, including sleep apnea, insomnia, parasomnia, delayed sleep phase, narcolepsy, and restless legs, but their clinical presentation, evaluation, and management may differ. Although snoring and sleep apnea may be the most common indication for an overnight sleep study in a child, one quarter of children presenting to a sleep clinic for evaluation will have a second sleep diagnosis, which is often nonrespiratory in nature. Especially in children, ruling out sleep apnea is rarely the end point of the sleep evaluation. Clinicians involved in sleep medicine must be prepared to recognize, evaluate, and manage plans for sleep disorders across the lifespan of the patient. This article will provide an updated review of nonrespiratory pediatric sleep disorders within a developmental framework.

Adolescent↗

PubMed2005

Empirical bayes method for incorporating data from multiple genome scans.

Individual genome scans tend to have low power and can produce markedly biased estimates of QTL effects. Further, the confidence interval for their location is often prohibitively large for subsequent fine mapping and positional cloning. Given that a large number of genome scans have been conducted, not to mention the large number of variables and subsets tested, it is difficult to confidently rule out type 1 error as an explanation for significant effects even when there is apparent replication in a separate data set. We adapted Empirical Bayes (EB) methods [1] to analyze data from multiple genome scans simultaneously and alleviate each of these problems while still allowing for different QTL population effects across studies. We investigated the effects of using the EB method to include data from background studies to update the results of a single study of interest via simulation and demonstrated that it has a stable confidence level over a wide range of parameters defining the background studies and increased the power to detect linkage, even when some of the background studies were null or had QTL effect at other markers. This EB method for incorporating data from multiple studies into genome scan analyses seems promising.

Alzheimer Disease↗

PubMed2002

Quantitative prediction of body diameter in severely obese individuals.

The prevalence of obesity and severe obesity continues to increase in the developed world. Apart from obesity's strong association with a variety of health conditions, severely obese individuals (i.e. > or = 300 lb [136 kg]) sometimes have difficulty with ambulation, and often cannot use regular sized clothes, furniture, and assistive devices such as walkers and wheelchairs. The purpose of this study was to assess the relationship between linear body measurements (anthropometry) and weight in severely obese people in order to generate equations to predict such measurements from weight alone. Various body size measurements were obtained from three independent data sets (74 severely obese individuals evaluated at the New York Obesity Research Center, 103 severely obese individuals who participated in the National Center for Health Statistics' National Health and Nutrition Examination Survey III, and a further 90 severely obese individuals evaluated at the New York Obesity Research Center). Linear regression analyses revealed that for each increase of 10 kg (22.04 lb) above 136 kg (300 lb), body diameter measurements increase by 0.9-1.1 cm. These analyses provide body size-to-weight estimates that may help manufacturers develop products and services that are more appropriate for increasing numbers of severely obese individuals.

Adolescent↗