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Biomedical subjects

A Watkins

Publications and source records attributed to A Watkins.

At least 19 recordsLinked to original sources
PubMed2005

Validity of sleep nasendoscopy in the investigation of sleep related breathing disorders.

OBJECTIVE: To validate the technique of sleep nasendoscopy using target controlled infusion in symptomatic patients and a control group of asymptomatic individuals. DESIGN: Prospective cohort study. SETTING: Department of otolaryngology-head and neck surgery and anesthesia in a teaching hospital. PARTICIPANTS: Two groups of patients were compared and matched for their body mass index. The first group consisted of 53 patients with a history suggestive of obstructive sleep apnea. The second group consisted of 54 patients with partner-confirmed history of no snoring. These patients were undergoing anesthesia for other reasons. Both groups of patients were free of associated otorhinolaryngologic symptoms. MAIN OUTCOME MEASURE: Assessment of production of snoring or obstruction in patients with no documented history of snoring when sedation was administered as part of general anesthesia using target controlled infusion with propofol. RESULTS AND CONCLUSIONS: None of the patients in the asymptomatic group snored or obstructed at any level of propofol, and this was clearly significant on comparison with the symptomatic group (P < .001). All of the symptomatic patients were induced to become symptomatic (snoring/obstruction).

Body Mass Index↗
PubMed2005

Coagulation and inflammatory markers in Alzheimer's and vascular dementia.

Alzheimer's disease is classified as a degenerative dementia while vascular dementia is known to be associated with atherothrombosis and classical vascular risk factors. However, over the last decade, there is increasing evidence of the role of haemostatic factors and inflammatory mechanisms in the pathogenesis of Alzheimer's disease. Serum markers of hypercoagulability and markers of inflammation could lead to thrombosis, accelerated atherogenesis and resulting dementia of both Alzheimer's and vascular dementia. In this case control study, we studied these serum markers of coagulation and inflammation in patients suffering from dementia.

Alzheimer Disease↗
PubMed2004

A randomised comparison of resuscitation with an anaesthetic rebreathing circuit or an infant ventilator in very preterm infants.

Twenty four preterm infants (< 27 weeks gestation) were randomised to resuscitation with an anaesthetic rebreathing circuit or a ventilator with volume guarantee. There was no difference in weight or gestation between the groups. End expiratory pressures were higher and less variable with the ventilator. This pilot study shows that very preterm infants can be safely and effectively resuscitated using a ventilator.

Anesthesiology↗
PubMed2002

Current understanding of cellular and molecular events in intervertebral disc degeneration: implications for therapy.

Until recently, material removed from the intervertebral disc (IVD) at surgery consisted either of 'loose bodies' from the centre of the IVD or discal tissue displaced (prolapsed) into the intervertebral root or spinal canals. This material is best regarded as a by-product of disc degeneration and therefore not representative of the disease process itself. Recent advances in surgical techniques, particularly anterior fusion, in which large segments of the anterior part of the IVD are excised with the anatomical relationships between different components intact, have generated material that can be investigated with modern molecular and cell biological techniques. This is an important area of study because degeneration of the lumbar IVDs is associated, perhaps causally, with low back pain, one of the most common and debilitating conditions in the West. 'Degeneration' carries implications of inevitable progression of wear-and-tear associated conditions. Modern research on human IVD tissue has shown that this is far from the case and that disruption of the micro-anatomy described as degeneration is an active process, regulated by locally produced molecules. The exciting consequence of this observation is the possibility of being able to inhibit or even reverse the processes of degeneration using targeted therapy.

Cytokines↗
PubMed2002

Nerve growth factor expression and innervation of the painful intervertebral disc.

Following a previous description of nociceptive nerve fibre growth into usually aneural inner parts of painful intervertebral disc (IVD), this study has investigated whether nociceptive nerve ingrowth into painful IVD is stimulated by local production of neurotrophins. Immunohistochemistry and in situ hybridization have been used to investigate expression of the candidate neurotrophin, nerve growth factor (NGF), and its high- and low-affinity receptors trk-A and p75, respectively, in painful IVD excised for the management of low back pain. IVD from patients with back pain were of two types: those that when examined by discography reproduced the patient symptoms (pain level IVD) and those that did not (non-pain level IVD). Microvascular blood vessels accompanied nerve fibres growing into pain level IVD and these expressed NGF. The adjacent nerves expressed the high-affinity NGF receptor trk-A. These vessels entered the normally avascular IVD through the discal end plates. NGF expression was not identified in non-pain level or control IVD. Some non-pain level IVD had vessels within them, which entered through the annulus fibrosus. These did not express NGF nor did nerves accompany them. These findings show that nociceptive nerve ingrowth into painful IVD is causally linked with NGF production by blood vessels growing into the IVD, from adjacent vertebral bodies.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Expression of chondrocyte markers by cells of normal and degenerate intervertebral discs.

AIMS: To investigate the phenotype of cells in normal and degenerate intervertebral discs by studying the expression of molecules characteristic of chondrocytes in situ. METHODS: Human intervertebral discs taken at surgery were graded histologically, and classified on this basis as normal or degenerate. Eighteen of each type were selected, and in situ hybridisation was performed for the chondrocytic markers Sox9 and collagen II using (35)S labelled cDNA probes. Aggrecan was located by immunohistochemistry, using the monoclonal antibody HAG7E1, and visualised with an avidin-biotin peroxidase system. RESULTS: In the normal discs, strong signals for Sox9 and collagen II mRNA, and strong staining for the aggrecan protein were seen for the cells of the nucleus pulposus (NP), but reactions were weak or absent over the cells of the annulus fibrosus (AF). In degenerate discs, the Sox9 and collagen II mRNA signals remained visible over the cells of the NP and were again absent in the AF. Aggrecan staining was not visible in the NP cells, and was again absent in the AF. CONCLUSIONS: Cells of the normal NP showed expression of all three markers, clearly indicating a chondrocytic phenotype. In degeneration, there was evidence of a loss of aggrecan synthesis, which may contribute to the pathogenesis of disc degeneration. AF cells showed no evidence of a chondrocytic phenotype in either normal or degenerate discs.

Adult↗
PubMed2001

Anions modulate the potency of geranylgeranyl-protein transferase I inhibitors.

We have identified and characterized potent and specific inhibitors of geranylgeranyl-protein transferase type I (GGPTase I), as well as dual inhibitors of GGPTase I and farnesyl-protein transferase. Many of these inhibitors require the presence of phosphate anions for maximum activity against GGPTase I in vitro. Inhibitors with a strong anion dependence were competitive with geranylgeranyl pyrophosphate (GGPP), rather than with the peptide substrate, which had served as the original template for inhibitor design. One of the most effective anions was ATP, which at low millimolar concentrations increased the potency of GGPTase I inhibitors up to several hundred-fold. In the case of clinical candidate l-778,123, this increase in potency was shown to result from two major interactions: competitive binding of inhibitor and GGPP, and competitive binding of ATP and GGPP. At 5 mm, ATP caused an increase in the apparent K(d) for the GGPP-GGPTase I interaction from 20 pm to 4 nm, resulting in correspondingly tighter inhibitor binding. A subset of very potent GGPP-competitive inhibitors displayed slow tight binding to GGPTase I with apparent on and off rates on the order of 10(6) m(-)1 s(-)1 and 10(-)3 s(-)1, respectively. Slow binding and the anion requirement suggest that these inhibitors may act as transition state analogs. After accounting for anion requirement, slow binding, and mechanism of competition, the structure-activity relationship determined in vitro correlated well with the inhibition of processing of GGPTase I substrate Rap1a in vivo.

Adenosine Triphosphate↗
PubMed2001

The effects of temperature and time on thermal bond strength in tendons.

Flexor tendon injuries are a common problem requiring sutured repair followed by early postoperative mobilisation. Results are better if active rather than passive flexion is allowed, however active movement increases the incidence of dehiscence. This has prompted examination of thermal bonding as a strategy for strengthening tendon repairs. Three experiments are described, using method and experimental design similar to those previously described. The strength of thermal bonds created between sections of bovine Achilles tendon at a range of temperatures and times was measured. Bonds were created by heating compressed sections in a water bath. Bond strength was measured on a tensiometer as load (N) and stress (N/mm2 and N m kg-1) then calculated using measured cross-sectional area, weight and length. Results were in broad agreement with those previously described, showing peak bond strength in samples heated to 62 degrees C for 8 min (median 17.11 N/cm2, SD 2.13). The effects of cooling to 0 degree C for 10 min immediately after bonding was to increase median bond strength when compared with non-cooled samples bonded under similar conditions (non-cooled, 9.11 N/cm2, SD 3.11; cooled, 11.96 N/cm2, SD 2.93). Statistical analysis using a quadratic regression model showed a close correlation between experimental data and curves modelled to best fit the data. Peak values for thermal bonds created using the methods described approached and in some cases exceeded that reported for the epitendinous element of modified Kessler tendon repairs in human digital flexor tendons. If such bonds could be created in vivo, thermal bonding may have a role in augmenting the strength of tendon repairs. The methods described are impractical for a non-laboratory environment. A laser would seem the most attractive alternative source of heat energy.

Achilles Tendon↗
PubMed2001

Exploration of xenon as a potential cardiostable sedative: a comparison with propofol after cardiac surgery.

Xenon anaesthesia is thought to have minimal haemodynamic side-effects. It is, however, expensive and requires special delivery systems for economic use. In this randomised cross-over study, we: (i) investigated the haemodynamic profile and recovery characteristics of xenon compared with propofol sedation in postoperative cardiac surgery patients, and (ii) evaluated a fully closed breathing system to minimise xenon consumption. We demonstrated a significantly faster recovery from xenon (3 min 11 s) than propofol sedation (25 min 23 s). Relative to propofol, xenon sedation produced no change in heart rate or mean arterial pressure and there were significantly higher mean values for central venous pressure (10.6 vs. 8.9 mmHg), pulmonary artery occlusion pressure (11.2 vs. 9.5 mmHg), mean pulmonary artery pressure (20.1 vs. 18.3 mmHg) and systemic vascular resistance index (2170 vs. 1896 dyn.s.cm-5.m-2). The haemodynamic profile seen with propofol reflected its known vasodilator effects. This was supported by the almost identical left ventricular stroke work indexes seen with both methods of sedation.

Aged↗
PubMed2001

Respiratory distress syndrome and birth order in premature twins.

OBJECTIVE: To determine the effect of birth order on respiratory distress syndrome (RDS) in the outcome of twins in a large premature population managed in a modern neonatal intensive care unit. METHODS: An historical cohort study design was used to analyse the neonatal outcomes of 301 premature liveborn twin sibling pairs of between 23 and 31 weeks gestation from the Australia and New Zealand Neonatal Network 1995 database. RESULTS: Among the 56 twin sibling pairs who were discordant for RDS, the second twin was affected in 41 cases (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.5 to 5.3). The excess risk of RDS in the second twin increased with gestation and was statistically significant for twins above 29 weeks gestation (OR 4.4, 95% CI 1.6 to 15). CONCLUSIONS: There is a significant increased risk of RDS associated with being the second born of premature twins, which appears to depend on gestation.

Birth Order↗
PubMed2000

Loss of CD4+ T cell proliferative ability but not loss of human immunodeficiency virus type 1 specificity equates with progression to disease.

In this study, we compared human immunodeficiency virus (HIV) type 1-specific proliferative responses with HIV-1-induced intracellular cytokine production in a cohort of clinically nonprogressing patients and individuals with progressive HIV-1 infection. We found strong HIV-1-specific proliferative responses in the clinical nonprogressor cohort that correlated with significant numbers of circulating HIV-1-specific CD4(+) T cells. In contrast, HIV-1-specific proliferative responses were absent in most individuals with progressive HIV-1 infection, even though interferon-gamma-producing HIV-1-specific CD4(+) T cells were detectable by flow cytometry. The implication of these data is that the important dysfunction seen in most HIV-positive patients from very early in disease may be an inability of HIV-1-specific CD4(+) memory T cells to proliferate in response to HIV antigens rather than an absolute loss of circulating virus-specific CD4(+) T cells.

Antigens, Viral↗
PubMed2000

Neural cell recognition molecule L1: relating biological complexity to human disease mutations.

Human single gene disorders that affect the nervous system provide a host of natural mutations that can be deployed in the quest to understand its development and function. A paradigm for this approach is the study of disorders caused by mutations in the gene for the neural cell recognition molecule L1. L1 is the founder member of a subfamily of cell adhesion molecules that are primarily expressed in the nervous system, and to date it is the only one to be associated with a hereditary disease. In this review we will summarize how the analysis of pathological mutations in L1 is complementing the study of mouse models and in vitro analysis of L1 function.

Animals↗
PubMed1999

Operational and resource management of an RCT: some of the pitfalls and lessons learned.

Nurses frequently fulfil important functions within a research team involved in clinical trials. This paper describes the challenges inherent in developing and managing a large clinical trial involving the evaluation of homoeopathy and asthma. Teamwork, a clear and comprehensive understanding of the research protocol, marketing the project, and the ability to manage human resources within both a primary and secondary care environment are all essential aspects of clinical research. Our experience in establishing and managing this project has suggested to us that a high standard of clinical research demands an open approach to problem-solving as well as the realization that efficient research is as much about the management of people as it is about scientific rigour.

Adolescent↗
PubMed1999

Correlations of family medicine clerkship evaluations and Objective Structured Clinical Examination scores and residency directors' ratings.

BACKGROUND AND OBJECTIVES: This study validated the evaluation methods used in a family medicine clerkship by comparing students' scores to how students are rated in their first year of residency by residency directors. The clerkship evaluations consisted of three components: problem solving in small groups, clinical evaluations, and a final examination. These components were combined to form a composite clerkship score. Residency director ratings consisted of 20 individual scores and an overall average. METHODS: Scores received by students in the clerkship were correlated with ratings by residency directors given toward the end of the first year of residency. The correlations between Objective Structured Clinical Examination (OSCE) scores and residency directors' ratings were used as comparison. RESULTS: The composite clerkship score correlated with the director's rating, overall average, at r = .278. The highest individual component correlation was achieved by the clerkship final exam (r = .269). The total OSCE score correlated with the director's rating overall average at r = .304. CONCLUSIONS: This study provides evidence that, while not perfect, the family medicine clerkship evaluations perform nearly as well as the OSCE as a predictor of how students will be rated by their residency directors in their first year of residency.

Arizona↗
PubMed1997

A knee simulating machine for performance evaluation of total knee replacements.

A knee simulating machine is required for the design and evaluation of total knee replacements, the kinematics and the long-term wear being aspects of particular importance. There are no generally agreed design criteria, such that existing designs of simulator have a wide variety of input and constraint conditions. In this study, it was postulated that in order to reproduce physiological wear patterns, the correct kinematics is required, on the basis that the wear will be a direct function of the sliding, rolling and tractive rolling conditions at the joint surfaces. In turn, the correct kinematics would only be achieved by the input of physiological forces, by the appropriate constraints on the fixtures holding the components, and by simulating the soft tissue restraints. A knee simulating machine based on these principles was constructed, and used to test the kinematics of a range of contemporary condylar replacement knees. The displacements and rotations varied over a range of almost two times, even with the soft tissue restraints. Without the restraints, the low constraint designs would have dislocated or moved unrealistically. It was concluded that a simulating machine should be based on the input of forces and moments, rather than on displacements and rotations, in order to provide data of kinematics and wear.

Biomechanical Phenomena↗
PubMed1997

Differential gender response produced by meal and ad lib feedings of a high-fat diet in Osborne-Mendel rats.

We investigated if there were gender differences in metabolic consequences produced by meal feeding of a high-fat (HF) diet in male and female Osborne-Mendel rats. An HF diet was fed either ad lib (AL) or in 1 meal (MF) during the last 3 h of the dark cycle for 4 weeks (lights off from 2400 h to 1200 h). All rats were sacrificed at 1 of 3 time-points: prior to MF rats receiving their food at 0900 h, after food was taken from MF groups at 1200 h or 1500 h. Food intake, body weight, body fat weight, retroperitoneal adipose tissue lipoprotein lipase activity, plasma cholesterol, or HDL-cholesterol levels did not differ between MF- and AL-fed groups, but were higher in male than in female rats. There were no differences between the male and female groups in plasma levels of insulin and glucose or systolic blood pressures. Plasma triglyceride levels at 1200 h were significantly different between MF and AL Groups within either gender, but this was not observed at 0900 h or 1500 h. Body weights were correlated with internal fat weights and plasma cholesterol levels in both males (r = 0.57, p < 0.05) and females (r = 0.59, p < 0.05). Hence, it is the amount of HF diet ingested, rather than the pattern of meal feeding, that was the most significant factor related to gender differences in weight gain, increases in fat mass, and metabolic differences.

Animals↗