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Biomedical subjects

T M Young

Publications and source records attributed to T M Young.

At least 19 recordsLinked to original sources

Skin vasomotor reflex responses in two contrasting groups of autonomic failure: multiple system atrophy and pure autonomic failure.

BACKGROUND & AIM: A variety of stimuli such as deep inspiration, isometric exercise and mental arithmetic, result in a transient vasoconstriction,mediated by sympathetic efferent nerves, in the skin of the fingers and toes of healthy controls (Skin Vasomotor Reflex: SkVR). Multiple system atrophy (MSA) and pure autonomic failure (PAF) provide contrasting models of autonomic failure. In MSA the lesion is central and preganglionic, whilst in PAF the lesion site is peripheral and postganglionic. We evaluated the SkVR in response to various stimuli in MSA and PAF, to determine differences in skin vasomotor involvement between these two patient groups. METHODS: 25 subjects (10 MSA, 7 PAF, 8 healthy controls) were studied. Baseline recordings of skin blood flow were obtained with a laser Doppler probe on the left index finger pulp and forearm. The subject then underwent a variety of stimuli with rest periods in between to reestablish baseline SkBF. These stimuli were: single deep inspiration (inspiratory gasp); mental arithmetic; bilateral leg elevation and cutaneous cold. RESULTS: Healthy control subjects demonstrated marked SkVRs on the finger pulp to each of the stimuli of a magnitude similar to those seen in previous studies, but no SkVRs on the forearm. In MSA SkVRs to inspiratory gasp on the finger pulp were reduced relative to controls. In PAF SkVRs were reduced relative to controls or MSA. The magnitude of SkVR response to gasp and cutaneous cold in PAF was significantly less than in healthy controls. In addition, the magnitude of the response in PAF was significantly less than in MSA for inspiratory gasp. CONCLUSIONS: PAF showed a decreased SkVR response to all 4 stimuli, the response being significantly less than controls (for inspiratory gasp and cutaneous cold) or MSA (cutaneous cold inspiratory gasp). The decreased responses in PAF may reflect the extensive postganglionic sympathetic denervation seen in this group. The measurement of SkVR may therefore provide a non-invasive aid to the differentiation of MSA and PAF.

Age Factors↗

Heat-provoked skin vasodilatation in innervated and denervated trunk dermatomes in human spinal cord injury.

STUDY DESIGN: Cross-sectional, observational, controlled study. OBJECTIVE: High spinal cord injury (SCI) results in disruption of sympathetic vasomotor control. Vasodilatation as a response to local heating is a biphasic mechanism: the first phase (neurogenic) is mediated by the axon-reflex and is modulated by activity of sympathetic nerves. Our objective was to determine whether the response to heat provocation in trunk dermatomes may provide a measure of vasomotor sympathetic function in SCI. SETTING: National Spinal Injuries Centre, Stoke Mandeville Hospital, Buckinghamshire, UK; Autonomic Unit, The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Neurovascular Medicine Unit, Imperial College London at St Mary's Hospital, UK. SUBJECTS: A total of 30 subjects were studied; 18 had chronic complete SCI (level C6-T11) and 12 were healthy controls. METHODS: Recordings of skin blood flow (SkBF) were obtained with thermostatic laser Doppler probes placed in the upper trunk (at C4) and lower trunk (T10 or T12) dermatomes. RESULTS: SkBF at baseline (SkBF(bas)) and SkBF at the first peak of vasodilatation (SkBF(max)) showed no significant differences between SCI and controls either in upper or lower trunk dermatomes. However, the ratio of SkBF(max)/SkBF(bas) was significantly different in lower trunk dermatomes in SCI at C6-T5 level (7.5+/-3.5 PU) compared to SCI at T6-T11 level (3.5+/-1.5 PU) (P < 0.01). CONCLUSION: Measurement of SkBF in response to local heating may provide a safe, noninvasive method to assess integrity of sympathetic spinal pathways to the local vasculature. This may aid the classification of the SCI lesions, as the autonomic component currently is not included in the accepted American Spinal Injury Association scoring.

Adult↗

On-line monitoring of the buffer capacity of particleboard furnish by near-infrared spectroscopy.

This paper reports on a study of on-line monitoring of the buffer capacity of particleboard furnish using near-infrared (NIR) spectroscopy and multivariate analysis models (chemometrics). The buffer capacity of wood furnish is known to affect the quality of polymerization and the curing rates of urea-formaldehyde (UF) resins, which may affect the mechanical properties of manufactured panel. The first phase of the study consisted of building multivariate calibration and validation models from NIR spectroscopy data to predict the buffer capacity of particleboard furnish in a laboratory environment. During this phase, a spectrometer (Ocean Optics USB2000) operating in the 550-1100 nm spectral range was evaluated. The second phase of the study took place at a North American particleboard plant over several weeks. Several multivariate calibration models were constructed and tested on-line during a four-day test period. The on-line root mean square error of prediction (RMSEP) and the coefficient of variation (CV) for buffer capacity predictions ranged from 3.45 to 0.92 and 22.4% to 5.8%, respectively.

Journal Article↗

Geochemistry and bioavailability of metals in sediments from northern San Francisco Bay.

In this study, metals (Be, Cr, Mn, Fe, Ni, Cu, Zn, Ag, Cd, Pb and Hg) in the fine-grained fraction (<63 microm) from 12 sites at different locations in northern San Francisco Bay over a year period from March 2000 to March 2001 were analyzed after acid extraction. The results showed that metal concentrations in the sediments varied from site to site, whereas some of them were found elevated with respect to the sediment of Tomales Bay, CA, which has little contamination history, indicating an enrichment of the metals in the sediment samples analyzed. Sediment toxicity and bioaccumulation evaluation by a clam species, Macoma nasuta, exposed to the sediment samples collected from the six sampling sites was carried out. The results showed that the sediment samples tested significantly reduced clam survival. Toxicity of the sediments to the clam was, in part, related to elevated metal concentrations in the sediments. In order to examine geochemistry of the metals and to understand potential correlations between metal concentrations and geochemical matrix elements of the sediments, bioavailability and toxicity of the metals, detailed analysis of metal concentrations associated with total organic carbon and the Fe-oxy-hydroxides in the sediment samples was performed. The analysis showed that sediment geochemistry appeared to influence metal bioavailability and may have important impacts on the toxicity of these metals to the clam.

Animals↗

Water drinking in the management of orthostatic intolerance due to orthostatic hypotension, vasovagal syncope and the postural tachycardia syndrome.

Water drinking recently has been shown to raise blood pressure in normal subjects and in patients with autonomic failure who have orthostatic hypotension. However, in normal young subjects, ingestion of approximately 500 ml has no pressor effect; but in older subjects there is an increase in blood pressure. An even greater rise in blood pressure occurs in cases with autonomic failure. The possible mechanisms responsible for the pressor response to water include neural and humoral factors; fluid redistribution also needs to be considered. This review will concentrate on the water pressor response in normal subjects and different groups of patients with autonomic diseases who have orthostatic intolerance, on the mechanisms that could be involved, and on whether this pressor response may be used in the management of orthostatic hypotension, vasovagal syncope and the postural tachycardia syndrome.

Autonomic Nervous System↗

The effects of water ingestion on orthostatic hypotension in two groups of chronic autonomic failure: multiple system atrophy and pure autonomic failure.

BACKGROUND: Oral ingestion of water increases seated blood pressure in patients with chronic autonomic failure by mechanisms that remain unclear. As orthostatic hypotension is common in chronic autonomic failure, and is not always adequately controlled by medication, the potential benefits of water ingestion on standing blood pressure were studied in two types of autonomic failure: multiple system atrophy (MSA), in which the lesion is central and pre-ganglionic, and pure autonomic failure (PAF), in which the lesion is post-ganglionic. METHODS: In 14 patients with autonomic failure (seven PAF and seven MSA) standing blood pressure and heart rate were measured before, and 15 and 35 minutes after ingestion of 480 ml distilled water. Patients remained seated for 15 minutes after water ingestion, with beat to beat cardiovascular indices measured with the Portapres II device with subsequent Modelflow analysis. RESULTS: Standing prior to water ingestion caused a significant fall in blood pressure in all patients. After water ingestion there was a rise in seated blood pressure. Seated and standing blood pressure at 15 and 35 minutes after water ingestion was significantly higher than before water, with an improvement in orthostatic symptoms. The time to first significant rise in seated blood pressure occurred at 5 minutes post water ingestion in PAF and at 13 minutes in MSA. These increases were accompanied by increases in total peripheral resistance, reaching significance by 5 minutes in PAF and 13 minutes in MSA. There were no significant changes in cardiac output, stroke volume, or ejection fraction. CONCLUSIONS: Water is thus beneficial in improving standing BP in AF, acting within 15 minutes in both MSA and PAF. The earlier onset of the pressor effect in PAF may reflect the differing lesion site and underlying pathophysiology between these conditions.

Aged↗

Clonogenic analysis reveals reserve stem cells in postnatal mammals: I. Pluripotent mesenchymal stem cells.

Clonal populations of lineage-uncommitted pluripotent mesenchymal stem cells have been identified in prenatal avians and rodents. These cells reside in the connective tissue matrices of many organs and tissues. They demonstrate extended capabilities for self-renewal and the ability to differentiate into multiple separate tissues within the mesodermal germ line. This study was designed to determine whether such cells are present in the connective tissues of postnatal mammals. This report describes a cell clone derived by isolation from postnatal rat connective tissues, cryopreservation, extended propagation, and serial dilution clonogenic analysis. In the undifferentiated state, this clone demonstrates a high nuclear-to-cytoplasmic ratio and extended capacity for self-renewal. Subsequent morphological, histochemical, and immunochemical analysis after the induction of differentiation revealed phenotypic markers characteristic of multiple cell types of mesodermal origin, such as skeletal muscle, smooth muscle, fat cells, cartilage, and bone. These results indicate that this clone consists of pluripotent mesenchymal stem cells. This report demonstrates that clonal populations of reserve stem cells are present in mammals after birth. Potential roles for such cells in the maintenance, repair, and regeneration of mesodermal tissues are discussed.

Animals↗

Contaminant interactions with geosorbent organic matter: insights drawn from polymer sciences.

This is a state-of-science review of interrelationships between the sorption/desorption behaviors and chemical structures of natural organic matter (NOM) matrices associated with soils, sediments and aquifer materials. It identifies similarities between these behavior-property interrelationships for natural geosorbents and those for synthetic organic polymers. It then invokes, with appropriate restrictions and modifications, several structure-function relationships that have been developed for synthetic polymers to explain the behavior of NOM matrices with respect to the sorption and desorption of hydrophobic organic contaminants (HOCs). Previous research regarding HOC sorption and desorption by different types of NOM and by synthetic polymers is summarized, and research requirements for further refinement of the NOM-polymer analogy are examined. The discussion focuses on structural and compositional heterogeneities that exist at the particle and aggregate scale, a scale at which homogeneity is commonly, and often improperly, assumed in the development of contaminant fate and transport models.

Adsorption↗

The effect of lower-extremity position on cerebrospinal fluid pressures.

OBJECTIVE: To determine the effects of lower-extremity positioning on cerebrospinal fluid opening pressure (CSFp). The authors believed that during lumbar puncture (LP), CSFp does not meaningfully decrease when the lower extremities are extended from flexion, as is often suggested. METHODS: In a convenience sample of adult patients who clinically required LP in an urban emergency department, three sequential CSFp measurements were obtained in either sequence A (knee, hip, and neck flexion [90 degrees ], then extension, then flexion) or sequence B (extension, flexion, then extension) prior to CSF withdrawal. The neck was flexed at 30 degrees when the lower extremities were flexed, while the thoracolumbar spine was kept in the neutral position for all measurements. RESULTS: Nineteen patients were studied in each sequence. Although variable, overall within-patient changes between positions were not clinically meaningful. Mean and 95% confidence intervals (95% CIs) for the decrease in CSFp from position 1 to position 3 (same position) were 0.2 cm H(2)O (1.7%) and 0.9 to -0.6 cm H(2)O (6% to -2.7%), respectively. Changing from flexion to extension decreased pressure measurements by a mean of 0.9 cm H(2)O (2.5%) [95% CI = 2.1 to -0.1 cm H(2)O (7.6% to -2.4%)]. Changing from extension to flexion increased CSFp by a mean of 1.1 cm H(2)O (6.1%) [95% CI = 0.2 to 2.0 cm H(2)O (1.3% to 11.5%)], a statistically but not clinically meaningful change. CONCLUSIONS: Changing lower-extremity position did not meaningfully change mean CSFp. These data do not support the common suggestion that extending the lower extremities during LP meaningfully decreases CSF opening pressures.

Adolescent↗

Internal poverty and teen pregnancy.

The subjects for the present study were drawn from the female students who participated in the National Education Longitudinal Study (NELS) initial eighth-grade data collection. Adolescent females who later became pregnant were matched on race, birth month, and birth year with adolescent females who did not report a pregnancy. The study examined selected predictor variables from the baseline 1988 wave of data in relation to the outcome variable of pregnancy status. Results indicated a statistically significant difference in locus of control between those females who later became pregnant and those who later did not experience a pregnancy during adolescence. Those who later became pregnant were much more likely to have an external locus of control (p = .0001). Females who later became pregnant were also more likely to have a poorer sense of personal efficacy (p = .0001). Finally, females who later experienced a teen pregnancy had more traditional occupational expectations (p = .006) and lower educational expectations (p = .001) than did those who did not later report a teen pregnancy.

Adolescent↗

Sympathetic activity and baroreflex sensitivity in young women taking oral contraceptives.

BACKGROUND: We tested sympathetic and cardiovagal baroreflex sensitivity during the placebo or "low-hormone" phase (LH) and 2 to 3 weeks later during the "high-hormone" phase (HH) of oral contraceptive (OC) use in 9 women. METHODS AND RESULTS: Sympathetic baroreflex sensitivity was assessed by intravenous doses of sodium nitroprusside and phenylephrine and defined as the slope relating muscle sympathetic nerve activity (by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. No difference was observed for resting muscle sympathetic nerve activity or plasma norepinephrine levels. However, sympathetic baroreflex sensitivity was greater and mean arterial pressure was higher during the LH than in the HH phase. Similarly, cardiovagal baroreflex sensitivity was greater in the LH than in the HH phase. CONCLUSIONS: Sympathetic and cardiovagal baroreflex sensitivities change during the 28-day course of OC use. Furthermore, changes in baroreflex sensitivity with OC differ from changes in baroreflex sensitivity during the normal menstrual cycle.

Adult↗

Influence of the menstrual cycle on sympathetic activity, baroreflex sensitivity, and vascular transduction in young women.

BACKGROUND: Our goal was to test sympathetic and cardiovagal baroreflex sensitivity and the transduction of sympathetic traffic into vascular resistance during the early follicular (EF) and midluteal (ML) phases of the menstrual cycle. METHODS AND RESULTS: Sympathetic baroreflex sensitivity was assessed by lowering and raising blood pressure with intravenous bolus doses of sodium nitroprusside and phenylephrine. It was defined as the slope relating muscle sympathetic nerve activity (MSNA; determined by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. Vascular transduction was evaluated during ischemic handgrip exercise and postexercise ischemia, and it was defined as the slope relating MSNA and calf vascular resistance (determined by plethysmography). Resting MSNA (EF, 1170+/-151 U/min; ML, 2252+/-251 U/min; P<0.001) and plasma norepinephrine levels (EF, 240+/-21 pg/mL; ML, 294+/-25 pg/mL; P=0. 025) were significantly higher in the ML than in the EF phase. Furthermore, sympathetic baroreflex sensitivity was greater during the ML than the EF phase in every subject (MSNA/diastolic blood pressure slopes: EF, -4.15; FL, -5.42; P=0.005). No significant differences in cardiovagal baroreflex sensitivity or vascular transduction were observed. CONCLUSIONS: The present study suggests that the hormonal fluctuations that occur during the normal menstrual cycle may alter sympathetic outflow but not the transduction of sympathetic activity into vascular resistance.

Adult↗

Supercritical fluid extraction of 2,4,6-trichloroanisole from cork stoppers.

2,4,6-Trichloroanisole (TCA) is the compound most often associated with cork taint in wines and has been shown to have a very low sensory threshold ( approximately 5 ng/L in wine). A supercritical fluid extraction (SFE) method for TCA in bark cork stoppers was developed with quantification via gas chromatography-mass spectrometry with selected ion monitoring. Supercritical carbon dioxide functioned as the extracting solvent, and temperature and pressure were optimized for the extraction. The method was validated using the stable isotope (2)H(5)-TCA as the internal standard. Recovery of TCA from spiked corks was found to be within 1-4% of the theoretical concentration with a coefficient of variation ranging from 2.6 to 9.7%. TCA levels in corks pulled from wines described as tainted by experienced judges ranged from 0.13 to 2.11 microg/g of cork. The SFE procedure offers a rapid, quantitative, nearly solvent-free, and automated method for the extraction of TCA from complex solid matrices such as cork.

Anisoles↗

Human and rodent transcription elongation factor P-TEFb: interactions with human immunodeficiency virus type 1 tat and carboxy-terminal domain substrate.

The human immunodeficiency virus type 1 transcriptional regulator Tat increases the efficiency of elongation, and complexes containing the cellular kinase CDK9 have been implicated in this process. CDK9 is part of the Tat-associated kinase TAK and of the elongation factor P-TEFb (positive transcription elongation factor-b), which consists minimally of CDK9 and cyclin T. TAK and P-TEFb are both able to phosphorylate the carboxy-terminal domain (CTD) of RNA polymerase II, but their relationships to one another and to the stimulation of elongation by Tat are not well characterized. Here we demonstrate that human cyclin T1 (but not cyclin T2) interacts with the activation domain of Tat and is a component of TAK as well as of P-TEFb. Rodent (mouse and Chinese hamster) cyclin T1 is defective in Tat binding and transactivation, but hamster CDK9 interacts with human cyclin T1 to give active TAK in hybrid cells containing human chromosome 12. Although TAK is phosphorylated on both serine and threonine residues, it specifically phosphorylates serine 5 in the CTD heptamer. TAK is found in the nuclear and cytoplasmic fractions of human cells as a large complex (approximately 950 kDa). Magnesium or zinc ions are required for the association of Tat with the kinase. We suggest a model in which Tat first interacts with P-TEFb to form the TAK complex that engages with TAR RNA and the elongating transcription complex, resulting in hyperphosphorylation of the CTD on serine 5 residues.

Amino Acid Sequence↗

Testing and evaluation of wheelchair caster assemblies subjected to dynamic crash loading.

Wheelchair designs based upon loads applied quasi-statically during normal mobility use are apt to be inadequate to handle the increased level of dynamic crash forces that may be encountered when using the wheelchair as a motor vehicle seat. The purpose of this study was to characterize the integrity of wheelchair caster assemblies under simulated crash conditions. This study utilized dynamic drop (DD) testing, with loading levels and rates adjusted to match those found previously in sled impact testing and computer crash simulations. The results verify that current caster assembly designs may not be able to withstand forces associated with a crash. Five of seven evaluated caster assemblies failed when loaded to 8,007 N, or less, at loading rates seen in sled testing. DD testing used in this study is a valuable tool that can be used in the design of transport wheelchair components.

Accidents↗

Potential interaction involving warfarin and ritonavir.

OBJECTIVE: To report an unexpected decrease in warfarin effect following the addition of ritonavir to the medication regimen. CASE SUMMARY: A 27-year-old patient with advanced HIV taking warfarin for an inferior vena cava thrombus was started on ritonavir, clarithromycin, and zidovudine. The international normalized ratio (INR) decreased over a period of weeks after the addition of ritonavir, clarithromycin, and zidovudine to the drug therapy regimen. The warfarin dosage was almost doubled in order to maintain a therapeutic INR. Months later, when ritonavir alone was discontinued, the INR rose rapidly and the warfarin dose requirements decreased significantly. DISCUSSION: Potential interactions between warfarin and the protease inhibitors are described in the literature. Ritonavir has been shown to be a potent inhibitor of CYP3A4, an enzyme responsible for warfarin metabolism. Potentiation of warfarin effect and subsequent decrease in the warfarin dosage requirement was anticipated following ritonavir administration; however, the opposite occurred. The mechanism of the potential interaction between warfarin and ritonavir is not known, and may represent a complex, multidrug interaction. The paradoxical decrease in the INR is particularly intriguing. CONCLUSIONS: Frequent, careful monitoring of warfarin is recommended when ritonavir therapy is initiated or discontinued in a patient taking warfarin. The potential for either an increase or decrease in the INR should be anticipated.

Adult↗