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Biomedical subjects

R Taylor

Publications and source records attributed to R Taylor.

At least 109 records · Page 6Linked to original sources
PubMed2001

Estimating risk of breast cancer from population incidence affected by widespread mammographic screening.

OBJECTIVES: To estimate the absolute risk of breast cancer in women, allowing for the effect on incidence of the introduction of widespread mammographic screening. DESIGN: Annual breast cancer incidences were compared with numbers of annual mammograms in the population for 1980-96 to identify periods most likely to be affected by screening. Age specific breast cancer incidences 1972-96 were modelled by Poisson regression with an age, period, and cohort analysis. The 1996 age specific incidence was recalculated with the stable period effect 1972-89, and the age and cohort effects. Age specific incidence was converted to cumulative risk of breast cancer to age 79. SETTING: Population based data from all women in New South Wales (NSW), Australia. PATIENTS OR PARTICIPANTS: Breast cancer incidence in women 1972-96 obtained from the NSW Central Cancer Registry and female populations derived from successive censuses. Mammographic data from private sector mammograms (1985-96), and the mammographic screening service (1988-96) for NSW women. INTERVENTIONS: Introduction of population mammographic screening. MAIN OUTCOME MEASURES: Recorded age specific incidence and absolute risk of breast cancer to age 79 was compared with underlying incidence and cumulative absolute risk, adjusted for recent period effects, most likely due to mammographic screening in the population. RESULTS: The age, period, and cohort model showed an increasing effect for birth cohorts 1910-44 then a plateau, and prominent period effects in 1991 and 1994-6. Increased incidence of breast cancer coincided with an increase in mammographic examinations in the private sector (1991), and prevalent rounds of mammographic screening in the population (1994-6) after introduction of a statewide mammographic screening service. Recorded incidence produced a breast cancer risk to age 79 of 9.9% (1 in 10) for 1996, whereas estimation of underlying incidence yielded a risk of 8.5% (1 in 12). CONCLUSIONS: The introduction of mammographic screening in a population inflates the incidence of breast cancer because of diagnosis of prevalent cases. For the purpose of public and clinical communication, it is more reasonable and responsible to adjust for period effects (due to screening) rather than produce risk estimates based on recorded incidence, which may show an alarming increase in risk of breast cancer over a short period.

Adult↗
PubMed2001

Cavovarus foot treated with combined calcaneus and metatarsal osteotomies.

Twenty-one feet in fifteen patients underwent osteotomies of the calcaneus and one or more metatarsals for symptomatic cavovarus foot deformity. Seven (nine feet) were male, and eight (twelve feet) were female. The etiology included hereditary motor sensory neuropathy (HMSN) (fifteen feet), post-polio syndrome (two feet), sacral cord lipomeningocele (two feet), parietal lobe porencephalic cyst (one foot), and idiopathic peripheral neuropathy (one foot). Presenting complaints were metatarsalgia (fifteen feet), ankle instablility (five), and ulceration beneath the second metatarsal head (one foot). Eleven feet were assessed using the Maryland Foot Rating Score. Maryland Foot Rating Score (University of Maryland, Baltimore, MD) improved from 72.1 (avg.) preoperatively to 89.9 (avg.) post-operatively (follow-up 70.9 months avg.). Eight feet were assessed using the AOFAS (American Orthopaedic Foot and Ankle Society) Ankle-Hindfoot and Midfoot Scores. The AOFAS Ankle-Hindfoot Score improved from 46.3 (avg.) pre-operatively to 89.1 (avg.) post-operatively, and the AOFAS Midfoot Score improved from 40.9 (avg.) pre-operatively to 88.8 (avg.) post-operatively (follow-up 20.8 months avg.). The postoperative AOFAS Ankle-Hindfoot Score for all nineteen feet was 90.8 (avg.) and the post-operative AOFAS Midfoot Score for all nineteen feet was 90.2 (avg.). Two patients were lost to follow-up and were not included in the study. Ankle, hindfoot, and midfoot motion was maintained or improved in sixteen feet. Complications included delayed union in two and nonunion in three of 66 metatarsal osteotomies. While three patients required an AFO (ankle-foot orthosis) for ambulation preoperatively, all patients were brace free postoperatively. All patients expressed willingness to undergo the same procedure again if it were necessary. Weight-bearing radiographs were available for 17 feet. Radiographic analysis revealed a decrease in forefoot adduction (9.6 degrees avg.) and a reduction in both hindfoot (9.1 degrees avg.) and forefoot cavus (10.6 degrees) leading to an overall 13 percent reduction in the height of the longitudinal arch. Lateral sliding elevating calcaneal osteotomy combined with dorsolateral closing wedge osteotomies of one or more metatarsal bases in the severe symptomatic cavovarus foot can provide a pain-free, plantigrade foot with a lowered longitudinal arch and a stable ankle without sacrificing motion.

Adolescent↗
PubMed2001

Antioxidants and protein carbonyls in bronchoalveolar lavage fluid of children: normal data.

Antioxidant-oxidant imbalances in bronchoalveolar lavage fluid (BAL) are thought to contribute to oxidative stress in respiratory disease. However, normal reference ranges for BAL antioxidants and oxidized proteins in children are not available. In this study, we recruited 124 children attending for elective surgery for a noninflammatory condition; 83 were nonasthmatic, nonatopic (N) and 41 were nonasthmatic, atopic (NA). A nonbronchoscopic lavage was performed and ascorbate, uric acid, alpha-tocopherol, and protein carbonyl (as a measure of oxidative damage) concentrations were determined in BAL fluid. The 95% reference range was 0.112-1.897 micromol/L for ascorbate, 0.149-2.163 micromol/L for urate, 0.0029-0.066 micromol/L for alpha-tocopherol, and 0.280-4.529 nmol/mg for protein carbonyls in BAL fluid. Age, gender, and exposure to environmental tobacco smoke did not affect the concentration of ascorbate, urate, alpha-tocopherol, or protein carbonyls. However, in multiple linear regression analyses, the type of home heating (glass-fronted fires or oil-fired central heating) was found to influence ascorbate and urate concentrations in the BAL fluid (ss-coefficient for ascorbate: 0.445, p = 0.031; for urate: 0.114, p = 0.001). There was no significant difference between the N and NA group in BAL fluid concentrations of ascorbate, urate, or protein carbonyls. The alpha-tocopherol concentration was significantly increased in the NA group (p = 0.037). Uric acid and alpha-tocopherol concentrations in BAL fluid and serum were not correlated. Intriguingly, serum and BAL ascorbate concentrations were significantly correlated (r = 0.297, p = 0.018, n = 63), which may offer an explanation for why supplementing the diet with vitamin C can improve asthma symptoms. Further studies will investigate the role of BAL antioxidant concentrations in children with inflammatory respiratory diseases.

Antioxidants↗
PubMed2001

Using health outcomes data to inform decision-making: government agency perspective.

In the developed world, the demand for healthcare is rising faster than supply, so that governments are faced with the need to allocate limited resources for maximum benefit. Many governments are responding to these pressures by developing health technology assessment agencies, which evaluate the cost effectiveness of new pharmaceutical and medical products relative to existing interventions. In England and Wales, the agency concerned with health technology assessment is the National Institute for Clinical Excellence (NICE). NICE brings together evidence of clinical and cost effectiveness to judge the value of the treatment relative to alternative uses of National Health Service (NHS) resources and makes recommendations on use of the treatment by the NHS in England and Wales. NICE evaluates technologies where they may result in significant impact on NHS resources or key healthcare policy. The health technology assessment includes a review of the clinical effectiveness, cost effectiveness and service impact of the technology under consideration. This health technology assessment report, together with submissions from the technology manufacturer, and patient and healthcare professionals groups, is then considered by an appraisal committee that formulates guidance to the NHS and is ultimately published by NICE. A number of countries have formal guidelines on the use of outcome measures and economic evaluations in the submissions required for health technology assessment prior to market access. These guidelines vary in both the detail and level of mandatory requirement to be followed by technology manufacturers. NICE has recently updated its guidance to technology manufacturers on their submissions. These guidelines, developed in consultation with the healthcare industry, provide detailed specification of the requirements of NICE for health outcomes data and economic evaluation. These details are described in more detail in this paper.

Biomedical Technology↗
PubMed2001

Endstage renal disease owing to diabetic nephropathy in Mississippi: an examination of factors influencing renal survival in a population prone to late referral.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of endstage renal disease (ESRD) in the United States. We reviewed our experience with DN as a cause of ESRD in a predominantly poor, African American (AA) population. METHODS: Charts of patients who entered the ESRD program through the University of Mississippi Medical Center with a primary diagnosis of DN from 1993 through 1998 were reviewed for factors that may affect renal survival. Time from initial clinic visit to entry into the ESRD program, or time to ESRD (TTE), was the primary end point. RESULTS: Five hundred sixty-two patients entered the ESRD program (85% AA), and 210 of them had DN as their primary ESRD diagnosis. DN accounted for 50.5% of ESRD cases among AA females, but for less than 20% among AA males. In contrast, hypertension was the ESRD diagnosis in 48% of AA males. Patients observed in our nephrology clinic were analyzed further (n=171). At presentation, patients had advanced disease (serum creatinine [Cr]=5.92 mg/dL), were hypertensive, obese, and not likely to be on an angiotensin-converting enzyme (ACE) inhibitor. Determinants of TTE in univariate analysis were race (AA did better), initial blood urea nitrogen and plasma serum Cr levels, starting an ACE inhibitor at the University of Mississippi Medical Center, and the level of mean arterial pressure (MAP) during the course of follow-up. On multivariate analysis only initial Cr and race remained significant The 142 AA diabetics (111 female) were analyzed separately. The only significant sex difference was body mass index (female, 33.6 vs male, 28.4 kg/m2; P=0.0069), but females tended to have relatively shorter TTE and higher blood pressure (BP). Univariate and multivariate analyses revealed the same factors as above as determinants of TTE; however, among AAs, presenting on a calcium channel blocker was negatively correlated with TTE in univariate analysis. Among the entire cohort and the AAs, patients who had MAP between 100 and 110 mm Hg during the course of follow-up did better in terms of renal survival than those who fell outside of that range. CONCLUSIONS: We conclude that AA females in Mississippi are significantly more predisposed to DN as a cause of ESRD than are AA males. Patients with DN in our population had poor BP control, presented to nephrologists with advanced disease, and often were not on an ACE inhibitor. The optimal level of BP control and which BP agents are best for this population need to be determined.

Black People↗
PubMed2001

Effects of tumor necrosis factor-alpha on insulin action in cultured human muscle cells.

Reported discrepancies in the effects of tumor necrosis factor (TNF)-alpha in modulating insulin sensitivity of cultured cells may relate both to cell types studied and to the time course of exposure to the cytokine. Additionally, the relationship of effects on glucose metabolism to changes in the insulin signaling pathway cannot be assumed. For in vitro study, the cell type most relevant to insulin resistance in humans is the cultured human muscle cell. In the present study, TNF brought about no change in the rate of glycogen synthesis in cultured human muscle cells unless present during differentiation. The presence of TNF (5 ng/ml) during the process of differentiation of myoblasts into mature myotubes diminished the response of glycogen synthesis to acute insulin stimulation. This finding was associated with an impairment of differentiation-dependent increases in total cellular glycogen synthase (GS) activity. Under the same conditions of TNF exposure, there was no effect on the response to acute insulin stimulation of the fractional activity of GS. Similarly, there was no effect on the insulin stimulation of protein kinase B (PKB) and inhibition of glycogen synthase kinase 3 (GSK-3). Acute insulin stimulation brought about a 4.08 +/- 0.44-fold stimulation of activity of PKB in the absence of TNF, with 4.81 +/- 0.70-fold stimulation in cells exposed to TNF. GSK-3 activity decreased to 74.0 +/- 5.8% of basal after insulin stimulation without TNF and 78.3 +/- 5.0% after TNF exposure. However, differentiation of myocytes, as defined by an increase in the acetylcholine receptor, myogenin, and mature creatine kinase isoform expression, was impaired in TNF-treated cells. These studies demonstrate that TNF, if present during differentiation, decreases insulin-stimulated rates of storage of glucose as glycogen and total GS activity but does not downregulate the insulin-signaling system to GS. More generally, TNF also inhibits differentiation of human muscle cells in culture.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed2001

Losartan, an angiotensin type I receptor antagonist, improves conduit vessel endothelial function in Type II diabetes.

We have demonstrated previously that inhibition of angiotensin-converting enzyme (ACE) with enalapril and angiotensin II blockade with losartan improve acetylcholine-dependent endothelial function in resistance vessels of patients with Type II diabetes. It was therefore of interest to examine the effect of losartan on conduit vessel function in this group. The influence of losartan (50 mg daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 12 subjects with Type II diabetes using a randomized, double-blind, placebo-controlled crossover protocol. Conduit vessel endothelial function was assessed using high-resolution ultrasound and the brachial artery response to reactive hyperaemia (flow-mediated dilation; FMD); glyceryl trinitrate (GTN) was used as a non-endothelium-dependent dilator. Losartan administration significantly increased the FMD response from 5.2+/-0.7% (mean+/-S.E.M.) to 7.4+/-0.6% of vessel diameter (P<0.05; paired t-test). There was no effect of losartan on the endothelium-independent responses to GTN (17.8+/-1.8% to 17.6+/-1.2%). Consistent with our previous findings in resistance vessels, administration of 50 mg of losartan daily improves NO-mediated dilation in the conduit vessels of subjects with Type II diabetes. Together with the findings that both ACE inhibition and angiotensin II blockade improve resistance vessel function in this group, it is likely that at least some of the beneficial effect is mediated through the angiotensin II/type I receptor pathway. A type I receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain conduit vessel endothelial function in Type II diabetic subjects.

Angiotensin I↗
PubMed2001

Reconstructing hierarchical tetrahedral mesh density models of bony anatomy.

We proposed an efficient and automatic method to reconstruct hierarchical tetrahedral meshes and build density models for bony anatomy from CT data sets. The mesh is reconstructed from contours extracted in CT images corresponding to the outer bone surfaces and the boundaries between compact bone, spongy bone and medullary cavity. Key problems, such as tiling problem, branching problem, correspondence problem, and constraint problem, have been solved. We then approximated bone density variations by means of continuous density functions in each tetrahedron. The density functions are written as smooth Bernstein polynomial spline expressed in terms of barycentric coordinates associated with each tetrahedron. We further performed the tetrahedral mesh simplification by edge collapsing and built hierarchical structure of multiple resolution meshes. We applied our density model to efficiently generate Digitally Reconstructed Radiographs. This research is part of our effort to build a bone density atlas.

Algorithms↗
PubMed2001

Platelet-activating factor antagonism and streptokinase-induced hypotension in clinical acute myocardial infarction.

Continuing efforts are being made to improve thrombolytic therapy for acute myocardial infarction (AMI). The rate of streptokinase (SK) infusion is commonly limited by the hypotension that is induced. If this could be avoided, an accelerated regimen of SK could be given, analagous to that used for other thrombolytic agents such as alteplase. The mechanism of the SK-induced hypotension is unknown, but there is some evidence that platelet-activating factor (PAF) plays a role. The potent PAF receptor antagonist lexipafant (10 mg) (n=35), or matching placebo (n=36), was administered intravenously over 5 min, in a randomized double-blinded protocol, to consecutive patients about to receive SK for AMI; all but three had inferior MI, because of the preference for strategies other than SK therapy in patients with anterior MI. The rate of infusion of SK was set to give 1.5x10(6) units over 30 min, anticipating significant hypotension. Blood pressure fell sharply over the first 10 min of SK administration. The maximum fall in systolic blood pressure occurred between 8 and 12 min, and averaged 43+/-28 mmHg (mean+/-S.D.) and 40+/-26 mmHg in patients given placebo and lexipafant respectively. Systolic pressure having fallen to <90 mmHg, according to protocol the SK administration rate was reduced in 21 of 36 (58%) of patients given placebo and in 19 of 35 (54%) of patients given lexipafant. The total SK dose was given to all subjects over 40.3+/-17.5 and 40.2+/-13.4 min for the placebo and lexipafant groups respectively. Peak and time integrals of creatine kinase were not different in the two groups. There were no adverse effects attributable to lexipafant. It is concluded that the PAF receptor antagonist lexipafant has no significant effect on SK-induced hypotension and does not facilitate an accelerated regimen of administration.

Aged↗
PubMed2001

Challenges of the Blackwood Basin, Western Australia.

Growing concern about the declining state of the catchment and river led to the formation of the Blackwood Basin Group in 1992. Funded primarily by the Natural Heritage Trust and using the river as the focus, the group aims to provide leadership and support to achieve sustainable management of natural resources in the catchment. Through an Integrated Catchment Management approach, the Blackwood Basin Group has managed a range of projects to improve the community's understanding and management of the Blackwood River and its catchment. A number of research, education, demonstration and on-ground action activities relating to river management have been undertaken in partnership with community and local, state and federal government organisations. Activities include demonstrations and evaluations of riparian restoration, funding riparian restoration activities, protection of high conservation value remnant vegetation, a flood risk study, zone action planning and monitoring the condition of the river and its tributaries.

Community-Institutional Relations↗
PubMed2001

Quantification of galactosylsphingosine in the twitcher mouse using electrospray ionization-tandem mass spectrometry.

Globoid cell leukodystrophy (Krabbe disease) is an autosomal recessive inherited neurodegenerative disorder caused by the deficiency of the lysosomal enzyme beta-galactosylceramidase. The pathogenesis of the disorder has been proposed to arise from the accumulation of the cytotoxic metabolite galactosylsphingosine (psychosine). The twitcher mouse is a naturally occurring murine model of globoid cell leukodystrophy. We have developed a rapid, sensitive, and specific mass spectrometric method for determining the galactosylsphingosine concentration in the tissues of twitcher mice. Galactosylsphingosine is extracted from the tissues in methanol, isolated using strong cation-exchange and C18 solid-phase extraction chromatography, and then directly analyzed using electrospray ionization-tandem mass spectrometry. A lactosylsphingosine internal standard has been employed for quantification. The assay demonstrated significant accumulation of galactosylsphingosine in the brain, spinal cord, and kidney of twitcher mice. It is anticipated that this method may be of use in the monitoring of experimental therapies for globoid cell leukodystrophy.

Animals↗
PubMed2000

Conformationally constrained anesthetic steroids that modulate GABA(A) receptors.

Various cyclic ether and other 3 alpha-hydroxyandrostane derivatives bearing a conformationally constrained hydrogen-bonding moiety were prepared. Their anesthetic potency and their binding affinity for GABA(A) receptors, measured by intravenous administration to mice and inhibition of [(35)S]TBPS binding to rat whole brain membranes, were compared with that of known anesthetic 3 alpha-hydroxypregnan-20-ones. Synthetic steroids with similar in vitro and in vivo activities to the endogenous 3 alpha-hydroxypregnan-20-ones all had an ether oxygen on the beta-face of the steroid D-ring. These results suggest that for optimal GABA(A) receptor modulation, the hydrogen bond-accepting substituent should be near perpendicular to the plane of the D-ring on the beta-face of the steroid.

Androstanols↗
PubMed2000

Losartan, an angiotensin type 1 receptor antagonist, improves endothelial function in non-insulin-dependent diabetes.

OBJECTIVES: The present study examined the effect on forearm endothelial function of an angiotensin II type 1 receptor antagonist, losartan, in subjects with non-insulin-dependent diabetes mellitus (NIDDM). BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition with enalapril improves acetylcholine (ACh)-dependent endothelial function in patients with NIDDM. This could be mediated through angiotensin II and the type 1 receptor or could be due to inhibition of kininase II and a bradykinin preserving effect. It is therefore relevant to determine whether a type 1 receptor antagonist improves endothelial function. METHODS: The influence of losartan (50 mg daily for four weeks) on endothelium-dependent and independent vasodilator function was determined in 9 NIDDM subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gauge plethysmography. RESULTS: Losartan significantly decreased infused arm vascular resistance in response to three incremental doses of intrabrachial acetylcholine (p < 0.05, ANOVA). The forearm blood flow ratio (flow in infused to noninfused arm) was also increased (p < 0.01). Responses to sodium nitroprusside and monomethyl arginine were not significantly changed. CONCLUSIONS: Losartan administration at 50 mg per day improved endothelium-dependent dilation of resistance vessels in patients with NIDDM. That is, blockade of the angiotensin II type 1 receptors improves endothelial function in NIDDM. At least some of the similarly beneficial effect of ACE inhibition is probably mediated also through the angiotensin II-type 1 receptor pathway. The use of a type 1 receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain endothelial function in NIDDM subjects.

Angiotensin Receptor Antagonists↗
PubMed2000

Treating electrical storm : sympathetic blockade versus advanced cardiac life support-guided therapy.

BACKGROUND: Electrical storm (ES), defined as recurrent multiple ventricular fibrillation (VF) episodes, often occurs in patients with recent myocardial infarction. Because treating ES according to the Advanced Cardiac Life Support (ACLS) guidelines yields a poor outcome, we evaluated the efficacy of sympathetic blockade in treating ES patients and compared their outcome with that of patients treated according to the ACLS guidelines. METHODS AND RESULTS: Forty-nine patients (36 men, 13 women, mean age 57+/-10 years) who had ES associated with a recent myocardial infarction were separated into 2 groups. Patients in group 1 (n=27) received sympathetic blockade treatment: 6 left stellate ganglionic blockade, 7 esmolol, and 14 propranolol. Patients in group 2 (n=22) received antiarrhythmic medication as recommended by the ACLS guidelines. Patient characteristics were similar in the 2 groups. The 1-week mortality rate was higher in group 2: 18 (82%) of the 22 patients died, all of refractory VF; 6 (22%) of the 27 group 1 patients died, 3 of refractory VF (P<0.0001). Patients who survived the initial ES event did well over the 1-year follow-up period: Overall survival in group 1 was 67%, compared with 5% in group 2 (P<0.0001). CONCLUSIONS: Sympathetic blockade is superior to the antiarrhythmic therapy recommended by the ACLS guidelines in treating ES patients. Our study emphasizes the role of increased sympathetic activity in the genesis of ES. Sympathetic blockade-not class 1 antiarrhythmic drugs-should be the treatment of choice for ES.

Adrenergic beta-Antagonists↗