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Biomedical subjects

David T Burke

Publications and source records attributed to David T Burke.

At least 19 recordsLinked to original sources

Quantitative trait loci for insulin-like growth factor I, leptin, thyroxine, and corticosterone in genetically heterogeneous mice.

Genotype information was collected at 87 loci in a group of 1,108 UM-HET3 mice bred as the progeny of [BALB/cJ x C57BL/6J]F1 mothers and [C3H/HeJ x DBA/2J]F1 fathers, for which thyroxine (T4), insulin-like growth factor I (IGF-I), and leptin levels had been measured at 4 and 15 mo of age. The data provided significant evidence for quantitative trait loci (QTL) modulating IGF-I levels on chromosomes 1, 3, 8, 10, and 17; for loci affecting T4 on chromosomes 4, 15, and 17; and for leptin on chromosome 3. Fecal levels of corticosterone at 17 mo of age were influenced by a QTL on chromosome 1. Nine other gene/hormone associations reached a nominal P < 0.01, providing suggestive but not statistical evidence for additional QTL. QTL with an influence on a given hormone were in nearly all cases additive, with little or no evidence for epistasis. Of the 12 strongest QTL, 5 had effects that were age dependent, having more effect in 15-mo-old than in 4-mo-old mice in all but one case; the other QTL had effects that were apparently age-independent. These results show that the genetic controls over late-life hormone levels are complex and dependent on effects of genes that act both early and late in the life course.

Aging↗

Selective extraction of size-fractioned DNA samples in microfabricated electrophoresis devices.

We have designed and constructed a microfabricated device for separation of double-stranded DNA fragments using a crosslinked sieving medium and spatially selective extraction of the desired fraction. Based on measuring the width and spacing of migrating bands, a narrow side channel is constructed perpendicular to the separation channel to collect the DNA fragments of interest. This selective collection technique was tested using a 100 base pair double-stranded DNA ladder. We successfully demonstrate selective extraction of the desired fragment with minimal interference from the adjacent bands in an electric field of 31 V/cm. We also achieve extraction of multiple DNA fragments using an array of microelectrodes in this side channel. The device uses cross-linked polyacrylamide gel matrix, allowing the separation to be performed in a distance of 1 cm or less and at a low electric field strength. Together with on-chip electrode, this design is amenable to integration with reaction chambers into a single device for portable genetic-based analysis.

DNA↗

A versatile microfabricated platform for electrophoresis of double- and single-stranded DNA.

We demonstrate a versatile microfabricated electrophoresis platform, incorporating arrays of integrated on-chip electrodes, heaters, and temperature sensors. This design allows a range of different sieving gels to be used within the same device to perform separations involving both single- and double-stranded DNA over distances on the order of 1 cm. We use this device to compare linear and cross-linked polyacrylamide, agarose, and thermo-reversible Pluronic-F127 gels on the basis of gel casting ease, reusability, and overall separation performance using a 100 base pair double-stranded DNA ladder as a standard sample. While cross-linked polyacrylamide matrices provide consistently high-quality separations in our system over a wide range of DNA fragment sizes, Pluronic gels also offer compelling advantages in terms of the ability to remove and reload the gel. Agarose gels offer good separation performance, however, additional care must be exercised to ensure consistent gel properties as a consequence of the need for elevated gel loading temperatures. We also demonstrate the use of denaturing cross-linked polyacrylamide gels at concentrations up to 19% to separate single-stranded DNA fragments ranging in size from 18 to 400 bases in length. Primers differing by 4 bases at a read length of 30 bases can be separated with a resolution of 0.9-1.0 in under 20 min. This level of performance is sufficient to conduct a variety of genotyping assays including the rapid detection of single nucleotide polymorphisms (SNPs) in a microfabricated platform. The ability to use a single microelectrophoresis system to satisfy a wide range of separation applications offers molecular biologists an unprecedented level of flexibility in a portable and inexpensive format.

Acrylic Resins↗

A mysterious temporal penetrating head wound without fracture.

Unwitnessed head injuries are often diagnostic and management dilemmas. Low-velocity penetrating head wounds are rare. This paper describes a case of an accidental low-velocity penetrating head wound through the soft tissue of the temporal region. This lesion resulted in a deep intra-cerebral haemorrhage, after the initial assessment revealed no evidence of skull fracture, missile or missile track. The diagnostic evaluation and medical course of this case are presented. This is the first case in the medical literature of a brain injury by an object that penetrated the calvarium at low velocity but which did not produce a fracture of the skull. The evolving diagnostic dilemma is outlined to its conclusion, through 3 years of follow-up observation.

Adult↗

Effects of methylphenidate on heart rate and blood pressure among inpatients with acquired brain injury.

OBJECTIVE: The purpose of this study was to evaluate the effects of methylphenidate on heart rate and blood pressure in patients with acquired brain injury. DESIGN: The records of 60 consecutive hospitalized patients with acquired brain injury were reviewed for treatment with methylphenidate. Seventeen patients met the inclusion criteria. Systolic blood pressure, diastolic blood pressure, and heart rate recordings were compared before and after the introduction of methylphenidate. RESULTS: There was no significant difference in mean systolic blood pressure, diastolic blood pressure, and heart rate when patients received (118 mm Hg, 74 mm Hg, and 88 bpm) and did not receive (118 mm Hg, 73 mm Hg, and 86 bpm) methylphenidate. It was unclear whether there was a true trend toward medication effect on heart rate and blood pressure during the peak dose period. CONCLUSIONS: This retrospective study points to safe sympathetic effects of methylphenidate, yet future prospective studies are warranted to clarify the effects of methylphenidate on heart rate and blood pressure in the acquired brain injury population.

Adult↗

Upper-extremity deep vein thrombosis.

Upper-extremity deep vein thrombosis (UEDVT) was an understudied disease until recently. Previously thought of as benign, UEDVT has been shown in recent studies to pose a significant risk for pulmonary embolus and death. This article reviews the epidemiology, risk factors, clinical features, diagnostic tests, treatment options, complications, and prevention strategies for patients with UEDVT.

Anticoagulants↗

Quantitative trait loci for femoral size and shape in a genetically heterogeneous mouse population.

UNLABELLED: The aim of this study was to examine the genetic effects on cortical bone geometry. Genotypes from 487 mice were compared with geometric traits obtained from microCT. We found 14 genetic markers that associate with geometric traits, showing the complexity of genetic control over bone geometry. INTRODUCTION: Previous studies have shown that genetic background affects bone characteristics, particularly bone mineral density, in both mouse and human populations. Much less is known, however, about the effects of polymorphic genes on bone size, shape, and mechanical integrity. In this study, we investigated the genetic determinants of geometric properties of cortical bone in mice. MATERIALS AND METHODS: This study used a genetically heterogeneous mouse population, which is denoted UM-HET3 stock and is derived as the progeny of (BALB/cJ X C57BL/6J) F1 females and (C3H/HeJ X DBA/2J) F1 males. The experimental group consisted of 487 female UM-HET3 mice. Genotypic data from 99 polymorphic genetic loci was obtained from the mice at 4 weeks of age. At 18 months of age, the mice were humanely killed, and the right femurs were scanned with microcomputed tomography to assess geometric properties of cortical bone. A permutation-based test was used to detect significant associations between genetic markers and geometric traits. This test generates experiment-wise p values, which account for the effect of testing multiple hypotheses. An experiment-wise p < or = 0.05 was considered statistically significant. RESULTS: Fourteen genetic markers were found to significantly associate with one or more geometric traits. Two markers (D3Mit62 and D4Mit155) were associated with traits describing bone size; 2 (D12Mit167 and D14Mit170) were linked with traits describing bone shape; and 10 (D1Nds2, D5Mit95, D6Mit216, D7Mit91, D8Mit51, D9Mit110, D11Mit83, D15Mit100, D15Mit171, and D17Mit46) were associated with both size and shape. CONCLUSIONS: Our results indicate that the genetic control of cortical bone geometry is complex and that femoral size and shape may be influenced by different, although overlapping, groups of polymorphic loci.

Animals↗

Eye-movements and ongoing task processing.

This study tests the relation between eye-movements and thought processing. Subjects were given specific modality tasks (visual, gustatory, kinesthetic) and assessed on whether they responded with distinct eye-movements. Some subjects' eye-movements reflected ongoing thought processing. Instead of a universal pattern, as suggested by the neurolinguistic programming hypothesis, this study yielded subject-specific idiosyncratic eye-movements across all modalities. Included is a discussion of the neurolinguistic programming hypothesis regarding eye-movements and its implications for the eye-movement desensitization and reprocessing theory.

Choice Behavior↗

Electrostretching DNA molecules using polymer-enhanced media within microfabricated devices.

In this paper, we demonstrate immobilization and stretching of single lambda-phage DNA molecules within microfluidic systems using ac fields. We present a novel "thiol-on-gold"-based immobilization technique for fixing one specific end (3' end) of a DNA molecule onto a gold electrode. A polymer-enhanced medium (approximately 3.75 wt % linear polyacrylamide in Tris-HCl) is used to obtain fully stretched configurations (21 microm) of fluorescently stained lambda-DNA molecules. We also present an optimized microelectrode design with pointed electrodes and an electrode spacing of 20 microm for stretching DNA molecules with an ac field (1 MHz, 3 x 10(5) V/m). Finally, using these techniques, we immobilize a single DNA molecule at one electrode edge, stretch the molecule, and fix the other end at an adjacent electrode edge, forming a bridge between two electrodes within a microfabricated device.

Acrylic Resins↗

Cross-linked polyacrylamide gel electrophoresis of single-stranded DNA for microfabricated genomic analysis systems.

Microfabricated devices are poised to offer inexpensive self-contained alternatives to conventional benchtop-scale laboratory equipment for performing a variety of important DNA analysis assays. In order to realize the dramatic cost savings possible through photolithographic fabrication techniques, these devices must occupy an extremely compact footprint on the silicon wafer. This requirement implies that electrophoretic separations must be performed over ultrashort distances. Employing cross-linked polyacrylamide gels in place of conventional uncross-linked sieving media offers a convenient strategy to achieve this goal. In this paper, we show how the increased resolving power offered by cross-linked polyacrylamide gels, along with improved sample injection techniques, can be exploited to enhance separation performance in microscale systems. We use these techniques to perform high-resolution gel electrophoresis of single-stranded DNA fragments in microfabricated devices over separation distances of 1.5 cm or less. The results presented here are in agreement with theoretical predictions and suggest that it is possible to perform DNA sequencing on compact microchips. More importantly, the separation performance demonstrated in this work is already more than adequate to perform a number of important genomic assays imposing less stringent resolution requirements than sequencing. Successfully adapting even a few of these assays to the microdevice format has the potential to provide a new generation of inexpensive and portable devices suitable for direct end-user applications.

Acrylic Resins↗

Microdevice-based measurements of diffusion and dispersion in cross-linked and linear polyacrylamide DNA sequencing gels.

We use microfabricated gel electrophoresis devices incorporating integrated on-chip electrodes, heaters, and temperature sensors to measure diffusion and dispersion of single-stranded DNA fragments in cross-linked and uncross-linked polyacrylamide gels. The microdevice format allows a complete set of diffusion and dispersion data to be collected in approximately one hour. These results are compared with corresponding data obtained in a macroscale DNA sequencer, and the effects of gel composition and initiation chemistry are explored. Although the diffusion and dispersion data exhibit similar qualitative trends both on chip and on the macroscale, the magnitudes of the coefficients measured in the microdevice are somewhat higher. This discrepancy is likely due to altered polymerization kinetics arising as a consequence of using a UV-initiated polymerization chemistry to cast the on-chip gels as opposed to the standard chemical polymerization employed on the macroscale. We also find that reductions in the magnitudes of diffusion and dispersion coefficients are achieved at higher polymer concentrations and at operating temperatures in the vicinity of 50 degrees C. Finally, we find that cross-linked polyacrylamide gels yield significantly lower diffusion and dispersion coefficients than linear polyacrylamide. These findings can be used to identify rational strategies to improve separation performance in both micro- and macroscale gel electrophoresis systems.

Cross-Linking Reagents↗

Deliberate self-poisoning in Oman.

OBJECTIVE: To describe the demographics, precipitating factors, substances and methods used for deliberate self-harm in Oman. METHODS: Data were extracted from the Accident and Emergency (A & E) records of patients treated at the A & E units in Muscat from 1993 to 1998. Data were obtained form the history, and clinical findings resulting form deliberate self-harm. RESULTS: During the 5-year study period, 123 persons presented to various hospitals in the Muscat area with injuries that resulted form deliberate self-harm. Most of these cases were women, students and unemployed. There was a high incidence of family, marital and psychiatric or social problems. The methods of self-harm were most often analgesics (such as paracetamol) and non-pharmaceutical chemicals. CONCLUSIONS: The rate of self-injurious behaviour is low in Oman, compared with other countries, including other Islamic countries. The data illustrate a rising rate and a tendency to ingest toxic doses of analgesics or non-pharmaceutical chemicals.

Acculturation↗

Big mice die young: early life body weight predicts longevity in genetically heterogeneous mice.

Small body size has been associated with long life span in four stocks of mutant dwarf mice, and in two varieties of dietary restriction in rodents. In this study, small body size at ages 2-24 months was shown to be a significant predictor of life span in a genetically heterogeneous mouse population derived from four common inbred mouse strains. The association was strongest for weights measured early in adult life, and somewhat weaker, though still statistically significant, at later ages. The effect was seen both in males and females, and was replicated in an independent population of the same genetic background. Body size at ages 2-4 months was correlated with levels of serum leptin in both males and females, and with levels of IGF-I and thyroid hormone in females only. A genome scan showed the presence of polymorphic alleles on chromosomes 2, 6, 7 and 15 with significant effects on body weight at 2-4 months, at 10-12 months, or at both age ranges, showing that weight gain trajectory in this stock is under complex genetic control. Because it provides the earliest known predictor of life span, body weight may be usefully included in screens for induced mutations that alter aging. The evidence that weight in 2-month-old mice is a significant predictor of life span suggests that at least some of the lethal diseases of old age can be timed by factors that influence growth rate in juvenile rodents.

Animals↗

Cutoff score on the apathy evaluation scale in subjects with traumatic brain injury.

This cross-sectional study was designed to determine a cutoff score on the Apathy Evaluation Scale (AES) that predicts a clinician's designation of a subject with TBI as apathetic or not. Forty-five outpatients with TBI completed the AES-S, and 37 family members, friends, or significant others filled out the AES-I. Three clinicians prospectively gave their impressions of the presence or absence of apathy and retrospectively chose the degree of apathy on a 7-point subjective rating scale. The data was analysed by logistic regression and Receiver Operating Characteristic (ROC) curve. Sensitivity and specificity were calculated. No cutoff score on the AES-S or AES-I was found to have reasonable sensitivity and specificity with respect to the ability to predict the clinician's designation of a subject as apathetic. The AES requires further study if it is to be used to measure apathy following TBI.

Adolescent↗

Coordinated genetic control of neoplastic and nonneoplastic diseases in mice.

Some models of aging imply that late-life diseases, though roughly synchronous, are the result of distinct pathophysiological processes, each in turn influenced by polymorphisms at multiple loci. Other models suggest that the dramatic increase in later life of multiple forms of illness might reflect the outcome of a unitary process, of so-far unknown biochemical nature, that proceeds at a species-specific rate to increase the risk of many forms of disease and disability in parallel. We have previously reported the results of genetic linkage analyses documenting the ability of alleles at D9Mit110, D10Mit15, and D12Mit167, and an allele pair at D2Mit58 and D16Mit182 to predict longevity in mice bred as the progeny of (BALB/cJ x C57BL/6J)F1 mothers and (C3H/HeJ x DBA/2J)F1 fathers (the UM-HET3 stock). Here we report the results of post hoc analyses to test the hypothesis that the genes that extend the life span of mice dying of neoplastic diseases also extend the life span of mice that die of nonneoplastic causes. In all four cases we find that the genotype associated with increased survival in mice dying of cancer is also associated for a similar degree of life span extension in mice dying of other causes. For D9Mit110 and the combination of D2Mit58 and D16Mit182, the difference is statistically significant in both the neoplastic and nonneoplastic mouse groups. The data support the hypothesis that many forms of late-life disease may be influenced by shared pathophysiologic mechanisms that are under coordinated genetic control.

Alleles↗

Mouse loci associated with life span exhibit sex-specific and epistatic effects.

We have looked for genetic predictors of life span in a sibship of mice created as a four-way cross among inbred grandparental strains BALB/cJ, C57BL/6J, C3H/HeJ, and DBA/2J. To minimize the potential confounding effects of loci that influence early-life illnesses only, we conducted two analyses: one involving all the mice, and the other using a data set from which the first 20% of the deaths were excluded. The two strongest associations reach experimentwise significance levels (p <.01) when tested on the 80% of the mice with the longest life spans. Surprisingly, three of the four strongest associations showed sex-specific effects, with an influence on life span of either male or female mice, but not both. Epistatic interactions among the loci were also identified. The life-span effect of a locus on chromosome 10 (D10Mit15) exhibited epistatic interactions with loci on chromosomes 9 and 16 (D9Mit10 and D16Mit182). In a second example, a locus on chromosome 12 (D12Mit167) depended on the specific combination of alleles inherited from both male and female parents. Our results show that the common laboratory mouse strains are polymorphic at loci that produce substantial differences in life span and that these effects can be sex specific and conditional on alleles inherited at other loci.

Animals↗

Reading habits of practicing physiatrists.

OBJECTIVE: Over the past 30 yr, the number of ACGME accredited specialties has quadrupled, and the number of journals cataloged on MEDLINE has doubled. Given this increase of information, this study sought to determine the amount and extent that pertinent journals are read by specialists in the field of physical medicine and rehabilitation. DESIGN: From a randomly selected list of board-eligible physiatrists and diplomates of the American Board of Physical Medicine and Rehabilitation, 1204 resident physicians, fellows, and attending physicians were sent questionnaires concerning their reading habits. The questionnaire contained a list of 36 journals adapted from a list of journals previously published as being pertinent to physical medicine and rehabilitation. Physicians were asked to specify which journals they read over the past year and how extensively these were read. Respondents were also asked to note whether they participated in an academic or private practice and if they read as much as they would like. RESULTS: The results revealed that very few journals were always read thoroughly, with the modal response among the more popular journals being that of "always scanned the table of contents and read the most important articles." Academic physiatrists were noted to read more than their private practice counterparts. Of the subspecialists who replied, 67% read a journal pertinent to their subspecialty. Eighty-three percent of all respondents reported that they did not read as much as they would like. CONCLUSION: Physiatrists are rarely able to completely read the most relevant journals in their field. When reading journals, most physiatrists only scan the table of contents and read the most important abstracts.

Attitude of Health Personnel↗

Presence and severity of anorexia and bulimia among male and female Omani and non-Omani adolescents.

OBJECTIVE: The population of Oman is a heterogeneous mix of nationalities providing a natural setting for studying the cross-cultural differences in the presence and severity of eating disorders as well as an opportunity for evaluating the performance of measurement instruments for these disorders. METHOD: Disordered eating screening instruments (the Eating Attitude Test and the Bulimic Investigatory Test) were administered to Omani teenagers, non-Omani teenagers, and Omani adults. RESULTS: On the Eating Attitude Test, 33% of Omani teenagers (29.4% females and 36.4% males) and 9% of non-Omani teenagers (7.5% of males and 10.6% females) showed a propensity for anorexic-like behavior. On the Bulimic Investigatory Test, 12.3% of Omani teenagers showed a propensity for binge eating or bulimia (13.7% females and 10.9% males). Among the non-Omani teenagers, 18.4% showed a tendency toward bulimia, with females showing a slightly greater tendency than males. In contrast, barely 2% of Omani adults showed either a presence of or a severity of disorderly behavior with food. CONCLUSION: Omani teenagers scored significantly higher than other ethnic groups and Omani adults. This finding is discussed in the light of emerging evidence from many parts of the world suggesting that cultural transition, compounded by demographic constraints, plays a significant role in abnormal eating attitudes.

Adolescent↗