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Biomedical subjects

W Young

Publications and source records attributed to W Young.

At least 19 recordsLinked to original sources
PubMed2006

The effects of changing temperature correction factors on measures of acidity calculated from gastric and oesophageal pH recordings.

BACKGROUND: Recently, Medtronic notified customers that new correction factors should be used for their Slimline and Zinetics24 single-use, internal-standard pH catheters. AIM AND METHODS: We selected 24-h recordings of oesophageal and gastric pH with the Zinetics24 from our archives for five healthy subjects and for five gastro-oesophageal reflux disease subjects who were studied at baseline and again after 8 days of treatment with a proton-pump inhibitor. All pH values obtained with the old correction factors were rescaled using the new correction factors. Values for median pH, integrated acidity and time pH < or = 4 were then calculated from pH values with old and new correction factors. RESULTS: The new correction factors changed values for median pH, integrated acidity and time pH < or = 4. Values for median pH and integrated acidity changed in a predictable, proportionate way, whereas values for time pH < or = 4 did not. CONCLUSIONS: The new correction factors will not change the interpretation of previously published results with median pH or integrated acidity. In contrast, values for time < or =4 cannot be converted in an obvious way with the new correction factors. Instead, the raw pH data will need to be rescaled and values for time pH < or = 4 recalculated using the rescaled pH data.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

Effects of static stretching volume and intensity on plantar flexor explosive force production and range of motion.

AIM: The aim of the study was to determine the effects of volume and intensity of static stretching in a warm-up on explosive force production and range of motion (ROM) of the plantar flexors. METHODS: Twenty subjects performed 5 warm-ups on different days. The warm-ups contained a 5 min treadmill run and various protocols of 30 s static stretches (SS) of the plantar flexors. Stretching involved dorsi flexion just before the pain threshold, which was considered 100% intensity. The treatments that immediately followed the run were: (i) no other treatment (control); (ii) 1 min SS; (iii) 2 min SS; (iv) 4 min SS; (v) 2 min SS at 90% intensity. Ankle ROM was assessed before and after each warm-up and a concentric calf raise and drop jump (DJ) test was conducted after each warm-up. RESULTS: There were no significant differences (P > 0.05) in peak force or rate of force production in the explosive calf raise between any of the warm-ups. However the run plus 2 min stretch and the run plus 4 min stretch protocols produced significantly lower (P < 0.05) DJ performance (jump height/ground contact time) than the run. The run plus 4 min stretch warm-up also produced a significantly lower DJ score than the run plus 1 min stretch warm-up. There were no significant differences between any of the warm-ups in ankle ROM. CONCLUSIONS: The addition of 2-4 min of SS at 100% intensity to a run caused an impairment to fast stretch shortening cycle muscle performance. The greater impairment from the 4 min stretching condition supported a volume-effect. Two minutes of stretching at 90% intensity had no significant influence on muscle function. The addition of up to 4 min of SS to a run had no appreciable effect on ankle ROM, possibly because of the prior influence of the run.

Adolescent↗
PubMed2005

The fractal nature of human gastro-oesophageal reflux.

BACKGROUND: We are unaware of the analyses of time series data resulting from 24 h recordings of human gastric or oesophageal pH. As a result, we have no understanding of the quantitative changes in gastric or oesophageal acidity over time, the patterns that might characterize these changes, or the physiological significance of gastro-oesophageal reflux. AIM: To examine the time series for gastric and oesophageal pH. METHODS: Detrended fluctuation analysis and lag analysis were used to analyse data from 24 h recordings of oesophageal and gastric pH in five normal subjects and five subjects with gastro-oesophageal reflux disease. RESULTS: Analyses of the patterns of gastric and oesophageal pH over time in normal subjects and subjects with gastro-oesophageal reflux disease indicate that the fluctuations in pH are self-similar across different time scales and are consistent with an underlying fractal process. Furthermore, there is a significant statistical association between sequential pH values separated by as much as 2.2 h. CONCLUSIONS: We hypothesize that the self-similar, fractal pattern encodes information about gastric acidity and that the oesophagus decodes this information and, when appropriate, may signal the stomach to reduce gastric acidity. Subjects with gastro-oesophageal reflux disease might have an impaired oesophageal-gastric feedback mechanism that results in increased gastric acid, which reflux from the stomach into the oesophagus.

Adolescent↗
PubMed2005

The development of a test of reactive agility for netball: a new methodology.

The purpose of this study was to present a new methodology for the measurement of agility for netball that is considered more ecologically valid than previous agility tests. Specifically, the agility performance of highly-skilled (n = 12), moderately-skilled (n = 12) and lesser-skilled players (n = 8) when responding to a life-size, interactive video display of a netball player initiating a pass was compared to a traditional, pre-planned agility movement where no external stimulus was present. The total movement times and decision times of the players were the primary dependent measures of interest. A second purpose of the research was to determine the test-retest reliability of the testing approach. Results revealed significant differences existed between the 2 test conditions demonstrating that they were measuring different types of agility. The highly-skilled group was significantly faster in both the reactive and planned test conditions relative to the lesser-skilled group, while the moderately-skilled group was significantly faster than the lesser-skilled group in the reactive test condition. The decision time component within the reactive test condition revealed that the highly-skilled players made significantly faster decisions than the lesser-skilled players. It is reasoned that it is this decision-making component of reactive agility that contributes to the significant differences between the two test conditions. The testing approach was shown to have good test-retest reliability with an intra-class correlation of r = .83.

Adolescent↗
PubMed2004

Acute effects of static stretching on hip flexor and quadriceps flexibility, range of motion and foot speed in kicking a football.

The purpose of this research was to determine the effect of static stretching in a warm-up on hip flexor and quadriceps flexibility as measured by a modified Thomas test and on range of motion (ROM) of the leg and foot speed at impact in kicking a football with maximum effort. Sixteen Australian Rules (AR) footballers performed two different warm-ups on different days. One warm-up involved five minutes of sub-maximum running followed by seven practice kicks, while the other also included 4.5 minutes static stretching of the hip flexors and quadriceps after the running. A modified Thomas test was conduced before and after each warm-up. Players performed maximum effort drop punt kicks into a net while being videotaped to determine the ROM of the kicking leg and foot speed at impact with the ball. There were no significant changes in flexibility (p > 0.05) as a result of either warm-up and there were no significant differences between the warm-ups in the kicking variables (p > 0.05). It was concluded that the Thomas test may not have been sensitive to possible acute changes in flexibility from the warm-ups, and that stretching had no influence on kicking ROM or foot speed, possibly because of the complexity of the kicking skill.

Adolescent↗
PubMed2004

Registered nurses' experiences with an evidence-based home care pathway for myocardial infarction clients.

OBJECTIVES: To obtain home health nurses' comments on an evidence-based care pathway for post myocardial infarction. DESIGN: A qualitative design was used. SETTING: Culturally diverse, lower income area of a large city. PARTICIPANTS: All home health nurses from one nursing agency who participated in a comparative study on the impact of the evidence-based care pathway. RESULTS: The largest number of comments made by the nurses were related to the beneficial impact of the pathway on the provision of quality nursing care and on increased job satisfaction. The home health nurses reported that the pathway increased clients' knowledge of medications and diet. In addition, they commented that they were able to use the pathway effectively because of the training they received from the inpatient cardiac nurses. CONCLUSIONS: This qualitative study demonstrates the benefits of investing in the implementation of best practice guidelines by home health nurses. However, nursing associations, such as the Canadian Community Health Nurses Initiatives Group, will need to continue to champion for additional funds to support the additional expenses incurred.

Aged↗
PubMed2002

DNA microarray analysis of the contused spinal cord: effect of NMDA receptor inhibition.

Spinal cord injury (SCI)-induced neurodegeneration leads to irreversible and devastating motor and sensory dysfunction. Post-traumatic outcomes are determined by events occurring during the first 24 hours after SCI. An increase in extracellular glutamate concentration to neurotoxic levels is one of the earliest events after SCI. We used Affymetrix DNA oligonucleotide microarrays (with 1,322 DNA probes) analysis to measure gene expression in order to test the hypothesis that SCI-induced N-methyl-D-aspartate (NMDA) receptor activation triggers significant postinjury transcriptional changes. Here we report that SCI, 1 hour after trauma, induced change in mRNA levels of 165 genes and expression sequence tags (ESTs). SCI affected mRNA levels of those genes that regulate predominantly transcription factors, inflammation, cell survival, and membrane excitability. We also report that NMDA receptor inhibition (with -(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate [MK-801]) reversed the effect of SCI on about 50% of the SCI-affected mRNAs. Especially interesting is the finding that NMDA receptor activation participates in the up-regulation of inflammatory factors. Therefore, SCI-induced NMDA receptor activation is one of the dominant, early signals after trauma that leads to changes in mRNA levels of a number of genes relevant to recovery processes. The majority of MK-801 effects on the SCI-induced mRNA changes reported here are novel. Additionally, we found that the MK-801 treatment also changed the mRNA levels of 168 genes and ESTs that had not been affected by SCI alone, and that some of their gene products could have harmful effects on SCI outcome.

Animals↗
PubMed2001

Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss.

We have completed the first large-scale gene expression study of acute spinal cord injury (SCI) in rat. Oligonucleotide microarrays containing 1,200 gene-specific probes were used to quantify mRNA levels, relative to uninjured controls, in spinal cords injured using a standard contusion model. Our results revealed a marked loss of neuron-specific mRNAs at the injury site. The surviving cells showed a characteristic inflammatory response that started at the injury site and spread to the distal cord. Changes in several mRNA levels were associated with putative regenerative responses in the spinal cord. Notably, phosphodiesterase 4, nestin, glia-derived neurite promoting factor, and GAP-43 mRNAs increased significantly. Other mRNAs clustered temporally and spatially with these regeneration-associated genes. Thus we have described global patterns of gene expression following acute SCI, and we have identified targets for future study and possible therapeutic intervention.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

A novel serine protease inhibition motif involving a multi-centered short hydrogen bonding network at the active site.

We describe a new serine protease inhibition motif in which binding is mediated by a cluster of very short hydrogen bonds (<2.3 A) at the active site. This protease-inhibitor binding paradigm is observed at high resolution in a large set of crystal structures of trypsin, thrombin, and urokinase-type plasminogen activator (uPA) bound with a series of small molecule inhibitors (2-(2-phenol)indoles and 2-(2-phenol)benzimidazoles). In each complex there are eight enzyme-inhibitor or enzyme-water-inhibitor hydrogen bonds at the active site, three of which are very short. These short hydrogen bonds connect a triangle of oxygen atoms comprising O(gamma)(Ser195), a water molecule co-bound in the oxyanion hole (H(2)O(oxy)), and the phenolate oxygen atom of the inhibitor (O6'). Two of the other hydrogen bonds between the inhibitor and active site of the trypsin and uPA complexes become short in the thrombin counterparts, extending the three-centered short hydrogen-bonding array into a tetrahedral array of atoms (three oxygen and one nitrogen) involved in short hydrogen bonds. In the uPA complexes, the extensive hydrogen-bonding interactions at the active site prevent the inhibitor S1 amidine from forming direct hydrogen bonds with Asp189 because the S1 site is deeper in uPA than in trypsin or thrombin. Ionization equilibria at the active site associated with inhibitor binding are probed through determination and comparison of structures over a wide range of pH (3.5 to 11.4) of thrombin complexes and of trypsin complexes in three different crystal forms. The high-pH trypsin-inhibitor structures suggest that His57 is protonated at pH values as high as 9.5. The pH-dependent inhibition of trypsin, thrombin, uPA and factor Xa by 2-(2-phenol)benzimidazole analogs in which the pK(a) of the phenol group is modulated is shown to be consistent with a binding process involving ionization of both the inhibitor and the enzyme. These data further suggest that the pK(a) of His57 of each protease in the unbound state in solution is about the same, approximately 6.8. By comparing inhibition constants (K(i) values), inhibitor solubilities, inhibitor conformational energies and corresponding structures of short and normal hydrogen bond-mediated complexes, we have estimated the contribution of the short hydrogen bond networks to inhibitor affinity ( approximately 1.7 kcal/mol). The structures and K(i) values associated with the short hydrogen-bonding motif are compared with those corresponding to an alternate, Zn(2+)-mediated inhibition motif at the active site. Structural differences among apo-enzymes, enzyme-inhibitor and enzyme-inhibitor-Zn(2+) complexes are discussed in the context of affinity determinants, selectivity development, and structure-based inhibitor design.

Amino Acid Motifs↗
PubMed2001

Regulation of Trk receptors following contusion of the rat spinal cord.

Neurotrophins function through high-affinity tyrosine kinase (Trk) receptors to promote growth and survival of cells in the injured nervous system. To investigate the role of Trk receptors in the adult nervous system, we examined TrkA, TrkB, and TrkC mRNA expression in spinal cord and brain after spinal contusion. At 1 day postinjury, all Trk receptor transcripts were down regulated at and around the site of injury, a situation that persisted through the first week. By 42 days, Trk expression was absent only within the cavity. In addition, truncated TrkB expression was substantially increased in ependymal cells and astrocytes surrounding the lesion cavity of chronically injured spinal cords. Rostral and caudal to the injury site, TrkA, TrkB, and TrkC mRNA expression did not differ from that of uninjured control spinal cords. Furthermore, no changes were observed in TrkB or TrkC expression in the axotomized corticospinal and rubrospinal neurons. These studies suggest that loss of Trk receptors at the injury site may contribute to the early progressive cellular loss in injured spinal cords, while increased presence of truncated TrkB receptors in the chronic injured spinal cord may sequester and restrict BDNF availability to support axonal regeneration and neuronal survival. The persistence of Trk receptors on supraspinal neurons suggests that neurotrophin application can support growth and survival in the acute and chronic injury states.

Animals↗
PubMed2001

In vitro intestinal permeability of factor Xa inhibitors: influence of chemical structure on passive transport and susceptibility to efflux.

PURPOSE: To study the in vitro intestinal permeability of a number of newly synthesised factor Xa inhibitors to better understand the poor oral absorption of these compounds. METHODS: The bidirectional transport of the fXa inhibitors was studied in the Caco-2 cell model and isolated rat ileal tissue. An attempt was made to characterize efflux mechanisms with the help of commonly used substrates and inhibitors of various transport proteins. In addition, the transport of the fXa inhibitors was studied in MDCK cells transfected with the human MDR1 gene and expressing large amounts of P-glycoprotein (Pgp). RESULTS: The in vitro absorptive permeability was low for all but one of the fXa inhibitors. For compounds with non-substituted amidine, a charge (due to ionisation at neutral pH) may have resulted in poor membrane partitioning. Neutral compounds with substituted amidines were effluxed from the epithelial cells. The significance of the secretion process was illustrated by the results obtained for a neutral analogue showing high absorptive Caco-2 cell permeability that was not obviated by efflux. Transport inhibition studies in Caco-2 and permeability studies in the MDR1-transfected MDCK cells consistently showed that Pgp is not involved in the secretion of fXa inhibitors. Besides efflux, metabolic liability limited the permeation of the neutral lipophilic analogues with a carbamate ester. CONCLUSIONS: Poor intestinal permeability may be an important factor in the incomplete oral absorption of the bisbenzimidazole-type fXa inhibitors. Poor permeability may be related to poor membrane partitioning for hydrophilic analogues, whereas susceptibility to efflux transports and gastro-intestinal enzymatic degradation may limit the permeability of some of the neutral less hydrophilic derivatives.

Animals↗
PubMed2001

Syndromes with salivary dysfunction predispose to tooth wear: Case reports of congenital dysfunction of major salivary glands, Prader-Willi, congenital rubella, and Sjögren's syndromes.

Four cases-of congenital dysfunction of the major salivary glands as well as of Prader-Willi, congenital rubella, and Sjögren's syndromes-were identified in a series of 500 patients referred for excessive tooth wear. Although there was evidence of consumption of highly acidic drinks, some occlusal parafunction, and unacceptable toothbrushing habits, salivary dysfunction was the salient factor predisposing a patient to tooth wear in these syndromal cases. The 500 subjects have been characterized either as having medical conditions and medications that predispose them to xerostomia or lifestyles in which workplace- and sports-related dehydration lead to reduced salivary flow. Normal salivation, by buffering capacity, clearance by swallowing, pellicle formation, and capacity for remineralization of demineralized enamel, protects the teeth from extrinsic and intrinsic acids that initiate dental erosion. Thus, the syndromes, unrelated in many respects, underline the importance of normal salivation in the protection of teeth against tooth wear by erosion, attrition, and abrasion.

Adult↗
PubMed2000

Cyclooxygenase-2 is required for tumor necrosis factor-alpha- and angiotensin II-mediated proliferation of vascular smooth muscle cells.

Tumor necrosis factor-alpha (TNF-alpha) and angiotensin II (Ang II) induced a transient increase in vascular smooth muscle cell (VSMC) cyclooxygenase-2 (COX-2) mRNA accumulation, without affecting COX-1 mRNA levels. The kinetics of COX-2 mRNA accumulation were similar in VSMCs challenged with either TNF-alpha or Ang II; mRNA accumulation peaked at 2 hours and decreased to control levels by approximately 6 hours. Accumulation of COX-2 mRNA was associated with a time-dependent increase of COX-2 protein expression that displayed similar kinetics in response to either TNF-alpha or Ang II. Both the increase in COX-2 mRNA accumulation and protein expression in response to either TNF-alpha or Ang II were inhibited by the mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD098059. In addition, the AT(1)-selective receptor antagonist losartan attenuated the Ang II-mediated increase in COX-2 mRNA accumulation; the AT(2)-selective antagonist PD123319 had no effect. Prostacyclin I(2) synthesis was tightly coupled to expression of COX-2, whereas prostaglandin E(2) and thromboxane A(2) (TXA(2)) synthesis may be associated with differential usage of COX-1 and COX-2. The COX-2-selective inhibitors NS-398 and nimesulide and the TXA(2) receptor antagonist BMS 180,291 inhibited TNF-alpha- and Ang II-mediated increases in DNA content and cell number by approximately 95%. These findings suggest that a prostanoid derived from COX-2, possibly TXA(2), may contribute to VSMC hyperplasia in vessel injury or pathophysiological conditions associated with elevated levels of either TNF-alpha or Ang II.

Angiotensin II↗
PubMed2000

Costs and outcomes associated with alternative discharge strategies following joint replacement surgery: analysis of an observational study using a propensity score.

We estimated the impact of alternative discharge strategies, following joint replacement (JR) surgery, on acute care readmission rates and the total cost of a continuum of care. Following surgery, patients were discharged to one of four destinations. Propensity scores were used to adjust costs and outcomes for potential bias in the assignment of discharge destinations. We demonstrated that the use of rehabilitation hospitals may lower readmission rates, but at a prohibitive incremental cost of each saved readmission, that patients discharged with home care had longer acute care stays than other patients, that the provision of home care services increased health system costs, and that acute care readmission rates were greatest among patients discharged with home care. Our study should be seen as one important stepping stone towards a full economic evaluation of the continuum of care for patients.

Aftercare↗
PubMed2000

Comparison of transformation zone sampling rates--a potentially useful indicator of smear taker performance.

Retrospective analysis of 18555 routinely collected smears from women in the age range 20-50 years reveals that there is a statistically significant relationship between the overall transformation zone sampling rate achieved in general practice and the detection rates for cervical abnormality. Similar analysis comparing unsatisfactory smear rates with rates for the detection of abnormality demonstrates a negative correlation which fails to achieve statistical significance. Comparison of transformation zone sampling rates achieved by smear takers sending samples to the same laboratory is proposed as a potentially useful performance indicator for smear takers.

Adult↗