Biomedical subjects

David T Burke

Publications and source records attributed to David T Burke.

At least 19 recordsLinked to original sources

PubMed2004

Phase change microvalve for integrated devices.

An active microvalve that uses a meltable piston in place of a conventional solid material to obstruct fluid flow in a microfluidic channel has been developed. This phase change valve is simple to operate and requires no additional fabrication steps. The valve is inherently latched, reusable, and leak-proof (to at least 250 psi) and can be electronically addressed using resistive heaters. The valve has been characterized for a range of operational parameters that will serve as a design guide. For the designs tested, piston displacements of 5 mm or more in 1 s have been achieved. Valves 1.4 mm in length in a 50 microm x 200 microm channel have been integrated on a biochemical reaction device, and successful DNA amplification using PCR has been achieved. The phase change valve can be easily implemented in an array format that can be used to realize complex microfluidic circuits.

Glass↗

PubMed2004

Quantitative trait loci that modulate femoral mechanical properties in a genetically heterogeneous mouse population.

UNLABELLED: The goal of this study was to investigate genetic effects on mechanical properties of the mouse femur. We found evidence for QTL on eight chromosomes that affect mechanical traits. Some of these QTL may have primary effects on body weight or femoral geometry, and others seem to affect bone quality directly. INTRODUCTION: Previous studies have shown a dependence of fragility-related fracture risk on genetic background. Although many of these studies investigated the effect of genetics on BMD, basic measures of bone geometry and mechanical integrity may provide a more comprehensive characterization of the genetic effects on bone fragility. The purpose of this study was to identify quantitative trait loci (QTL) that affect mechanical and material properties of cortical bone in a genetically heterogeneous mouse population. MATERIALS AND METHODS: A total of 486 female UM-HET3 mice was used for this study. UM-HET3 mice are produced as the offspring of (BALB/cJ x C57BL/6J) F(1) females and (C3H/HeJ x DBA/2J) F(1) males. Femurs from 18-month-old mice were tested to failure in four-point bending to assess mechanical properties of cortical bone; these properties were compared with genotype data from 185 biallelic loci. A permutation-based test was used to detect significant associations between genetic markers and mechanical traits. This test generates p values that account for the effect of testing multiple hypotheses. Throughout the experiment, p < or = 0.05 was considered statistically significant. Analysis of covariance was used to examine possible effects of body weight and femoral geometry. RESULTS: We found evidence for genes on maternal chromosomes 11 and 13 and paternal chromosomes 2, 4, 7, 10, 11, and 17 that affect mechanical and material properties of femoral bone. The total variance explained by genetic effects on each mechanical trait ranges from 2.9% to 15.4%. Most of the identified polymorphisms influence mechanical traits even after adjustment for body weight. Adjustment for femoral geometry reduces the effects of some of the QTL, but those on chromosomes 2 and 10 do not seem to be influenced by femoral geometry. CONCLUSIONS: Many genes and chromosomes are involved in the genetic control over mechanical integrity of cortical bone. QTL on paternal chromosomes 4 and 11 may mediate mechanical properties, at least in part, by modulation of femoral geometry. Other QTL identified here may directly affect bone tissue quality.

Animals↗

PubMed2004

Body weight, hormones and T cell subsets as predictors of life span in genetically heterogeneous mice.

Previous studies have shown that T cell subset levels, early life body weight, and levels of leptin and thyroid hormones can each serve, independently, as predictors of life span in populations of genetically heterogeneous mice. New data now confirm, in a replicate cohort, that T cell subset patterns predict longevity, and show that they can do so when measured in mice as young as 8 months of age. Individual T cell subsets, as well as composite indices that combine data from two or more T cell measures at 8 or 18 months, can be combined with 3- and 9-month body weight data to provide better prediction of life span than either immune or weight measures alone. Mice whose immune and weight measures are both in the lowest quartile have mean and maximal life spans that are 18% and 16-25% higher, respectively, than mice in the opposite quartiles for both traits. Thyroxine levels measured at 4 months lead to further improvement over models that combine weight and immune data only. A genome scan provided evidence for loci on chromosomes 2, 12, 13, and 17 that modulate age-sensitive T cell subset patterns at both 8 and 18 months of age. These data show that late-life mortality risks are influenced to a measurable degree by factors that modulate growth trajectory and hormone and immune status in the first third of the life span, and provide clues as to which early life systems deserve further scrutiny as potential mediators of late life disease risk.

Aging↗

PubMed2004

Acquired brain injury, visual attention, and the useful field of view test: A pilot study.

OBJECTIVE: To compare the findings of the Useful Field of View (UFOV) test with those of conventional neuropsychologic tests to determine the utility of the UFOV test as a measure of attention in a population with brain injury. DESIGN: Cohort study. SETTING: Freestanding rehabilitation hospital. PARTICIPANTS: Fifteen inpatients with severe brain injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: UFOV test, FIM\T instrument, length of stay (LOS), and standard neuropsychologic testing. RESULTS: The UFOV subtest UF2 correlated strongly with the other 2 subtests, UF1 and UF3. The UF2 subtest correlated most strongly with paper and pencil tests of visual attention. The UF2 predicted 52% of the FIM change and 60% of the LOS variance, second only to admission FIM score, which predicted 75% and 80% of FIM change and LOS variance, respectively. CONCLUSIONS: Among the patients in our study, the UFOV test can be used to determine the visual divided attention of patients with acquired brain injury. The results also showed that the UFOV test correlated with LOS and FIM change in patients with acquired brain injury recovering in a rehabilitation facility. Because the UFOV test is much more quickly administered and scored than other measures of attention and divided attention, these results suggest that the UFOV test may provide an easy means to measure a critical variable in the population with head injury.

Adult↗

PubMed2004

Functional outcomes following anoxic brain injury: a comparison with traumatic brain injury.

PRIMARY OBJECTIVE: To compare the functional outcomes of patients with anoxic brain injury (ABI) and patients with traumatic brain injury (TBI) following inpatient rehabilitation. RESEARCH DESIGN: Retrospective chart review. METHODS AND PROCEDURES: Data on 68 patients with brain injury (34 with ABI and 34 with TBI) were collected. MAIN OUTCOMES AND RESULTS: The ABI and TBI groups were demographically similar, except that patients with ABI were more likely to be married. Both groups significantly improved their function and were similar upon discharge. For the ABI group, there were trends toward a shorter length of stay, increased total FIM efficiency and decreased cost of stay when compared with the TBI group. The patients with ABI tended to be discharged to a sub-acute rehabilitation facility more than those in the TBI group. CONCLUSIONS: This study is important because it shows that patients with ABI benefit from inpatient rehabilitation and made significant functional gains comparable to the gains of patients with TBI.

Activities of Daily Living↗

PubMed2004

Reading habits of physical medicine and rehabilitation resident physicians.

OBJECTIVE: To investigate the focus and extent of the resident physician reading habits, to compare how these change over the years of their training, and to compare these habits with those of physiatrists in practice. DESIGN: A total of 1,076 surveys were sent to 80 physical medicine and rehabilitation residency programs accredited by the Accreditation Council for Graduate Medical Education. The questionnaire contained a list of 36 journals pertinent to the field of Physical Medicine and Rehabilitation. Resident physicians were asked to indicate which journals they read during the past year and how extensively they read them. Respondents were also asked whether they participated in a journal club and if they read as much as they would like. RESULTS: A total of 324 surveys (30.1%) were completed correctly. At least half of the surveyed resident physicians scanned or read six journals:Archives of Physical Medicine and Rehabilitation (85.2%), American Journal of Physical Medicine and Rehabilitation (80.6%), Journal of the American Medical Association (68.8%), New England Journal of Medicine (60.5%), American Journal of Sports Medicine (50.9%), and Rehab in Review (49.7%). Most resident physicians (93.9%) responded that they do not read as much as they would like, and 90.1% of resident physicians participate in some form of journal club. CONCLUSION: Most resident physicians in the field of physical medicine and rehabilitation tend to scan for important articles within one of six journals, with most of these physicians noting that they do not read as much as they would like. As the resident physicians advance in postgraduate-year level, the number of journals that they scan increases. The reading habits of the resident physicians were quite similar to those noted in our previous study of the reading habits of practicing physiatrists.

Adult↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

Light-induced molecular cutting: localized reaction on a single DNA molecule.

A short focused pulse of light was used to selectively cut lambda-phage DNA molecules at specific restriction sites. Lambda DNA (48.5 kbp) was stretched and placed in a solution containing a restriction enzyme (Sma 1), caged magnesium ions (using a DM-Nitrophen complex), and a chelating agent (EDTA). When a pulse of UV light was directed at a particular location on the stretched DNA molecule, magnesium ions were released into solution. A series of binding reactions then occur in which the enzyme and the chelating agent compete for free Mg2+ ions. Since Sma 1 functions only in the presence of Mg2+, as is true of most endonucleases, the site(s) in the vicinity of the pulse (typically approximately 6 microm) were cut while other sites (three total for this DNA/enzyme pair) were not. The ratio of the concentration of the chelating agent to that of the magnesium ions was used to control the radius of this reaction zone with higher ratios leading to smaller, localized reaction areas. This optically based reaction mechanism could be useful to understand single molecule enzymatic kinetics, and when coupled with other DNA analysis techniques, this could be used to construct complex genotyping and sequencing devices that would analyze parts of single DNA molecules.

Bacteriophage lambda↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

Age-associated activation of epigenetically repressed genes in the mouse.

Epigenetic control of gene expression is a consistent feature of differentiated mammalian cell types. Epigenetic expression patterns are mitotically heritable and are stably maintained in adult cells. However, unlike somatic DNA mutation, little is known about the occurrence of epigenetic change, or epimutation, during normal adult life. We have monitored the age-associated maintenance of two epigenetic systems--X inactivation and genomic imprinting--using the genes Atp7a and Igf2, respectively. Quantitative measurements of RNA transcripts from the inactive and active alleles were performed in mice from 2 to 24 months of age. For both genes, older animal cohorts showed reproducible increases in transcripts expressed from the silenced alleles. Loss of X chromosome silencing showed cohort mean increases of up to 2.2%, while imprinted-gene activation increased up to 6.7%. The results support the hypothesis that epigenetic loss of gene repression occurs in normal tissues and may be a contributing factor in progressive physiological dysfunction seen during mammalian aging. Quantitatively, the loss of epigenetic control may be one to two orders of magnitude greater than previously determined somatic DNA mutation.

Adenosine Triphosphatases↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2002

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↗

PubMed2002

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↗