Biomedical subjects

Derick R Peterson

Publications and source records attributed to Derick R Peterson.

9 recordsLinked to original sources

PubMed2005

The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells.

Recent studies have described malignant stem cells as central to the initiation, growth, and potential relapse of acute and chronic myelogenous leukemia (AML and CML). Because of their important role in pathogenesis, rare and biologically distinct leukemia stem cells (LSCs) represent a critical target for therapeutic intervention. However, to date, very few agents have been shown to directly target the LSC population. The present studies demonstrate that parthenolide (PTL), a naturally occurring small molecule, induces robust apoptosis in primary human AML cells and blast crisis CML (bcCML) cells while sparing normal hematopoietic cells. Furthermore, analysis of progenitor cells using in vitro colony assays, as well as stem cells using the nonobese diabetic/severe combined immunodeficient (NOD/SCID) xenograft model, show that PTL also preferentially targets AML progenitor and stem cell populations. Notably, in comparison to the standard chemotherapy drug cytosine arabinoside (Ara-C), PTL is much more specific to leukemia cells. The molecular mechanism of PTL-mediated apoptosis is strongly associated with inhibition of nuclear factor kappa B (NF-kappaB), proapoptotic activation of p53, and increased reactive oxygen species (ROS). On the basis of these findings, we propose that the activity of PTL triggers LSC-specific apoptosis and as such represents a potentially important new class of drugs for LSC-targeted therapy.

Animals↗

PubMed2004

Risk factors for severe respiratory syncytial virus infection in elderly persons.

Risk factors for severe respiratory syncytial virus (RSV) infection were determined in 3 cohorts of adults during 2 consecutive winters (1999-2000 and 2000-2001) in Rochester, New York. Community-dwelling healthy persons > or =65 years old and persons >21 years old who had underlying symptomatic cardiopulmonary conditions were prospectively evaluated for RSV infection. Evidence of infection was also sought in persons who were > or =65 years old or had underlying cardiopulmonary disease and who were hospitalized with acute respiratory symptoms. Sixty-nine RSV infections were identified by culture, reverse-transcription polymerase chain reaction, or serologic testing in the prospective groups, and 61 were identified in the hospitalized group. The presence of underlying chronic pulmonary disease (odds ratio [OR], 3.97), functional disability (OR, 1.67/integer increase in Instruments of Activities of Daily Living score), and low serum neutralizing antibody titer (OR, 5.89) were each independently associated with increased risk of severe disease, defined as "hospitalization with RSV infection." These data suggest that the induction of neutralizing serum antibody with an RSV vaccine may potentially reduce disease severity in adult populations.

Aged↗

PubMed2004

Variations in risk-adjusted outcomes in a managed acute/long-term care program for frail elderly individuals.

OBJECTIVE: To develop and investigate the properties of three performance measures based on risk-adjusted health outcomes for a frail, elderly, community-dwelling population enrolled in a managed, acute, and long-term care program. DESIGN: Retrospective analyses of an administrative dataset containing individual level records with information about socioeconomics, health, functional and cognitive status, diagnoses, and treatments. We estimated risk-adjustment models predicting mortality, decline in functional status, and decline in self-assessed health. Each model includes individual risk factors and indicator variables for the program site in which the individual enrolled. Sites were ranked based on their performance in each risk-adjusted outcome, and the properties of these performance measures were investigated. SETTING: Twenty-eight sites of the Program of All-Inclusive Care for the Elderly (PACE) that provide primary, acute, and long-term care services under capitated Medicare and Medicaid payment to a nursing home certifiable, and functionally and cognitively frail community-dwelling elderly population. STUDY PARTICIPANTS: Three thousand one hundred and thirty-eight individuals who were newly enrolled between 1 January 1998 and 31 December 1999. The average age of these enrollees was 78 years, 27% were male, 50% were diagnosed with dementia, and they had approximately 4 Activities of Daily Living limitations and 7.4 Instrumental Activities of Daily Living limitations. MAIN OUTCOME MEASURES: Risk-adjustment models, performance ranking for each site, and correlations between performance rankings. RESULTS: We present risk-adjustment models for mortality, change in functional status, and self-assessed health status. We found substantial variation across sites in performance, but no correlation between performance with respect to different outcomes. CONCLUSIONS: The variations in outcomes suggest that sites can improve their performance by learning from the practices of those with the best outcomes. Further research is required to identify processes of care that lead to best outcomes.

Activities of Daily Living↗

PubMed2004

The life and death of oligodendrocytes in vanishing white matter disease.

Vanishing white matter disease (VWM) is a progressive cavitating disease of central white matter due to a deficiency of the translation initiation factor eIF2B. Oligodendrocytes appear to be numerically increased in some white matter areas, while decreased in others. We compared oligodendrocytes of cerebral, cerebellar, and pontine white matter from 5 VWM patients with those of age-matched controls by light microscopy and immunohistochemistry using antibodies to activated caspase-3, bak, bax, bcl-2, survivin, and Ki-67, as well as by the TUNEL technique. Oligodendrocytes were identified morphologically and quantified using an ocular grid. We observed statistically significant increases in their densities at all sites; Ki-67-labeled oligodendrocytes were identified in 2 of 5 patients. Apoptotic oligodendrocytes were documented in 3 of 5 patients, while bcl-2 and survivin labeling was observed in 2 of 5 and 2 of 2 patients, respectively. There was a trend toward an increase in apoptotic labeling of oligodendrocytes that was strongest in the cerebrum, the major locus of VWM, in the youngest and most severely affected patients. These data conclusively demonstrate increased oligodendrocytic densities in VWM; the increase is not an artifact of white matter contraction. Our data also document that oligodendrocytes undergo apoptosis, perhaps in conjunction with major neurologic crises, and that a subset of oligodendrocytes are able to persist and proliferate. Conflicting proliferative, cell-death, and survival signals impact the oligodendrocytes of VWM.

Adolescent↗

PubMed2004

Social support and risk-adjusted mortality in a frail older population.

OBJECTIVE: The objective of this study was to test the hypothesis that social support is an important predictor of mortality in a frail older population receiving formal long-term care services. RESEARCH DESIGN AND METHODS: The analysis is based on 3138 individuals enrolled in 28 Programs of All-Inclusive Care for the Elderly (PACE). Information about the enrollees is obtained from dataPACE. Semiparametric Cox proportional hazards models are estimated to assess the importance of individual risk factors, program effect, and social support. RESULTS: The introduction of the social support variables into the mortality model containing the sociodemographic, health needs, and the PACE-site indicator variables results in a significant improvement of the overall model fit. Several social support variables are statistically significant predictors of mortality. Controlling for all participant and caregiver characteristics, participants whose caregiver is a spouse have a significantly lower risk of mortality (hazard ratio = 0.63) compared with those whose caregiver is not a spouse. Furthermore, caregivers' assistance with meals confers a significantly lower risk of morality (hazard ratio = 0.66) compared with no assistance with meals. CONCLUSIONS: This study shows that certain aspects of informal caregiving are important factors enhancing survival in a population of frail, nursing home-certifiable individuals enrolled in a health program that already provides extensive services, including personal care, chores, and meals. Further research to better differentiate between the affective versus the instrumental dimensions of social support is needed to guide programs on how to balance the use of resources to provide both the necessary formal services and the support for the informal caregivers.

Activities of Daily Living↗

PubMed2004

Physical activity intervention for older adults with intellectual disability: report on a pilot project.

A 12-week pilot project on physical activity was introduced in a day habilitation setting to a group of 12 older adults with intellectual disability and a variety of physical and behavioral conditions. Our purpose was to determine whether (a) this intervention would positively impact physical function in this population, (b) consumers would choose to participate in physical activity sessions, and (c) day habilitation staff could sustain this program beyond the intervention period. Findings indicate that 92% of participants experienced improvement in at least one domain of physical function, physical activity sessions remained a popular activity choice for consumers, and many participants sustained functional gains 1 year after habilitation staff assumed responsibility for sessions.

Adult↗

PubMed2003

Modulating effects of age and gender on the clinical course of long QT syndrome by genotype.

OBJECTIVES: We aimed to determine whether long QT syndrome (LQTS) genotype has a differential effect on clinical course of disease in male and female children and adults after adjustment for QTc duration. BACKGROUND: Genotype influences clinical course of the LQTS; however, data on the effect of age and gender on this association are limited. METHODS: The LQTS genotype, QTc duration, and follow-up were determined in 243 cases of LQTS caused by the KCNQ1 potassium channel gene mutations (LQT1), 209 cases of LQTS caused by the HERG potassium channel gene mutations (LQT2), and 81 cases of LQTS caused by the SCN5A sodium channel gene mutation (LQT3) gene carriers. The probability of cardiac events (syncope, aborted cardiac arrest, or sudden death) was analyzed by genotype, gender, and age (children < or = 15 years and adults 16 to 40 years). In addition, the risk of sudden death and lethality of cardiac events were evaluated in 1,075 LQT1, 976 LQT2, and 324 LQT3 family members from families with known genotype. RESULTS: During childhood, the risk of cardiac events was significantly higher in LQT1 males than in LQT1 females (hazard ratio [HR] = 1.72), whereas there was no significant gender-related difference in the risk of cardiac events among LQT2 and LQT3 carriers. During adulthood, LQT2 females (HR = 3.71) and LQT1 females (HR = 3.35) had a significantly higher risk of cardiac events than respective males. The lethality of cardiac events was highest in LQT3 males and females (19% and 18%), and higher in LQT1 and LQT2 males (5% and 6%) than in LQT1 and LQT2 females (2% for both). CONCLUSIONS; Age and gender have different, genotype-specific modulating effects on the probability of cardiac events and electrocardiographic presentation in LQT1 and LQT2 patients.

Adolescent↗

PubMed2003

Using local correlation in kernel-based smoothers for dependent data.

We consider the general problem of smoothing correlated data to estimate the nonparametric mean function when a random, but bounded, number of measurements is available for each independent subject. We propose a simple extension to the local polynomial regression smoother that retains the asymptotic properties of the working independence estimator, while typically reducing both the conditional bias and variance for practical sample sizes, as demonstrated by exact calculations for some particular models. We illustrate our method by smoothing longitudinal functional decline data for 100 patients with Huntington's disease. The class of local polynomial kernel-based estimating equations previously considered in the literature is shown to use the global correlation structure in an apparently detrimental way, which explains why some previous attempts to incorporate correlation were found to be asymptotically inferior to the working independence estimator.

Biometry↗

PubMed2002

Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel.

BACKGROUND: The hereditary long-QT syndrome is characterized by prolonged ventricular repolarization and a variable clinical course with arrhythmia-related syncope and sudden death. Mutations involving the human ether-a-go-go-related gene (HERG) channel are responsible for the LQT2 form of long-QT syndrome, and in cellular expression studies these mutations are associated with reduction in the rapid component of the delayed rectifier repolarizing current (I(Kr)). We investigated the clinical features and prognostic implications of mutations involving pore and nonpore regions of the HERG channel in the LQT2 form of this disorder. METHODS AND RESULTS: A total of 44 different HERG mutations were identified in 201 subjects, with 14 mutations located in the pore region (amino acid residues 550 through 650). Thirty-five subjects had mutations in the pore region and 166 in nonpore regions. Follow-up extended through age 40 years. Subjects with pore mutations had more severe clinical manifestations of the genetic disorder and experienced a higher frequency (74% versus 35%; P<0.001) of arrhythmia-related cardiac events occurring at earlier age than did subjects with nonpore mutations. Multivariate Cox proportional hazard regression analysis revealed that pore mutations dominated the risk, with hazard ratios in the range of 11 (P<0.0001) for QTc at 500 ms, with a 16% increase in the pore hazard ratio for each 10-ms increase in QTc. CONCLUSION: Patients with mutations in the pore region of the HERG gene are at markedly increased risk for arrhythmia-related cardiac events compared with patients with nonpore mutations.

Adolescent↗