Geographical variation in coronary revascularisation rates.
Explore the source record for details and available documents.
Angioplasty, Balloon, Coronary↗
Biomedical subjects
L K Smith
Publications and source records attributed to L K Smith.
Wortmannin and LY294002 inhibit the insulin-induced down-regulation of IRS-1 in 3T3-L1 adipocytes.
The insulin receptor substrate-1 (IRS-1) is expressed in 3T3-L1 adipocytes and is involved in at least some insulin responses, notably mitogenesis. Chronic exposure to insulin down regulates IRS-1 in these cells by stimulating its degradation (Rice, K.M., Turnbow, M.A. and Garner, C.W. (1993) Biochem. Biophys. Res. Commun. 190, 961-967). This insulin response was completely inhibited by wortmannin and LY294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one), two inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase). Neither wortmannin nor LY294002 had any effect on the calcium-dependent degradation of IRS-1 in vitro nor did they inhibit the phosphorylation of IRS-1 in vitro. In addition, neomycin, a cationic aminoglycoside antibiotic that binds to phosphoinositides, inhibited the insulin-induced down-regulation of IRS-1 in 3T3-L1 adipocytes and, also, the C8-PIP3-stimulated degradation of IRS-1 in vitro. These results suggest that PI 3-kinase and its 3-phosphoinositide products mediate the insulin-induced down-regulation of IRS-1 in 3T3-L1 adipocytes.
3T3 Cells↗
Parents' views of health surveillance.
The aim of the study was to discover the views of parents about the 1991 Leicestershire child health surveillance programme, its organisation, and content. The study design was a postal questionnaire survey to parents of a sample of children eligible for the new surveillance programme. One thousand parents received questionnaires, of which 66% (660) were returned. Poor access for prams and wheelchairs (595 responses) and inadequate general cleanliness (249 responses) caused most criticism of clinic premises. The experiences of parents from ethnic minorities were significantly worse for some professional consultation factors, but they received significantly more health advice than other parents. Parents lacked sufficient information about the surveillance programme and their most frequent reasons for non-attendance were time related factors. Minimum standards for child health surveillance premises are required. At present, many fail to reach adequate standards of privacy and accessibility. Schemes to ensure an equal partnership in child health surveillance between parents and professionals are essential.
Asia↗
Children's vision screening: impact on inequalities in central England.
STUDY OBJECTIVE: To investigate the relationship between age at presentation of amblyopia and social deprivation before and after the introduction of changes to a vision screening service. DESIGN: Two cohorts of children treated for amblyopia in 1983 and 1992. SETTING: THe orthoptic department of Leicester Royal Infirmary. PARTICIPANTS: The 209 patients treated for amblyopia who first attended the orthoptic department in 1983, and 203 who first attended in 1992. MEASUREMENTS: Age at presentation to the orthoptic department was the main outcome measure. Social deprivation was measured by Townsend deprivation score for the electoral ward in which the child lived, using 1981 and 1991 census data. MAIN RESULTS: After the introduction of changes in the screening programme, the mean at presentation of amblyopia associated with microtropia or no strabismus was reduced from 6.6 years to 5.0 years. In 1983 there was a significant relationship between deprivation and age at presentation (p = 0.0001), with those from more deprived areas presenting later. No similar association was found in children referred in 1992 (p = 0.17). There was no change in mean age of presentation of amblyopia associated with a large angle of strabismus (3.3 years in 1983 and 1992) and no relationship between deprivation and age at presentation 1983 or 1992 (p = 0.24 and p = 0.39 respectively). CONCLUSION: Since the introduction of changes to vision screening, the relationship between social deprivation and the age of presentation of asymptomatic amblyopia seems to have disappeared. Children are now referred earlier and those from deprived areas are not being overlooked.
Age Factors↗
The oxazolidinedione CP-92,768-2 partially protects insulin receptor substrate-1 from dexamethasone down-regulation in 3T3-L1 adipocytes.
Oxazolidinediones are a class of oral antidiabetic agents that are closely related structurally and pharmacologically to thiazolidinediones. The thiazolidinediones have been shown to partially reverse the loss in insulin-responsive glucose uptake caused by chronic treatment with dexamethasone. This study was conducted to determine certain aspects of the mechanism of thiazolidinedione and oxazolidinedione action. We selected the oxazolidinedione CP-92,768-2 (5-[2-[(5-methyl2-phenyl-4-oxazolyl)methyl]5-benzofuranyl methyl]2,4- oxazolidinedione) to determine whether these agents could reverse the dexamethasone-induced down-regulation of IRS-1, the insulin receptor substrate-1. In 3T3-L1 adipocytes, dexamethasone treatment resulted in down-regulation of IRS-1 to 60% of control values. Simultaneous treatment with CP-92,768-2 significantly increased IRS-1 to 78% of the control value (EC50, < 10 nM), although it did not completely reverse the dexamethasone effect at any concentration tested. CP-92,768-2 alone did not have any effect on IRS-1. CP-92,768-2 did not affect the stability of IRS-1 protein in the presence or absence of dexamethasone, as measured by [35S]methionine pulse-chase labeling. Dexamethasone decreased messenger RNA (mRNA) for IRS-1 after 24 h of treatment to 40% of the control value. CP-92,768-2 partially reversed this decrease in IRS-1 mRNA to 65% of the control value after 24 h of treatment, but had no effect on IRS-1 mRNA in the absence of dexamethasone. Dexamethasone down-regulated the insulin stimulation of [3H]thymidine incorporation to 68% of the control value. Dexamethasone in the presence of CP-92,768-2 down-regulated insulin stimulation of thymidine incorporation by only 9%. Dexamethasone also down-regulated the expression of phosphoenolpyruvate carboxykinase (PEPCK) protein by 50%. CP-92,768-2 partially protected PEPCK from the dexamethasone down-regulation. Conversely, the up-regulation of expression of PEPCK and IRS-1 produced by dexamethasone in KRC-7 hepatoma cells was not affected by CP-92,768-2. One contribution of oxazolidinediones to an increase in insulin responsiveness in the presence of glucocorticoids may be the up-regulation of IRS-1 in adipose cells.
3T3 Cells↗
Matching for MHC haplotypes results in improved survival following unrelated bone marrow transplantation.
Unrelated bone marrow donor-recipient pairs were assessed retrospectively for matching of the HLA-B, -C region (beta-block) and HLA-DR, DQ region (delta block) of the major histocompatibility complex (MHC) using a new DNA-based method referred to as MHC-block typing. The method utilises non-HLA DNA polymorphisms in the MHC as markers of blocks of ancestral haplotypes. Kaplan-Meier analysis of recipients who were matched at both the beta- and delta-blocks revealed a 6 months survival of 54%. Survival was better than for patients who were matched only by conventional criteria, including SSO-typing for class II.
Adult↗
Cardiac rehabilitation as secondary prevention. Agency for Health Care Policy and Research and National Heart, Lung, and Blood Institute.
This Quick Reference Guide for Clinicians highlights the conclusions and recommendations from Cardiac Rehabilitation, Clinical Practice Guideline No. 17, which was formulated by a panel representing the major health care disciplines involved in cardiac rehabilitation. The conclusions and recommendations were derived from an extensive and critical review of the scientific literature pertaining to cardiac rehabilitation, as well as from the expert opinion of the panel. This guide addresses the role of cardiac rehabilitation and the potential benefits to be derived in the comprehensive care of the 13.5 million patients with heart disease in the United States, as well as the 4.7 million patients with heart failure and the several thousand patients undergoing heart transplantation. This Quick Reference Guide for Clinicians highlights the major effects of multifactorial cardiac rehabilitation services: medical evaluation; prescribed exercise; cardiac risk factor modification; and education, counseling, and behavioral interventions. The outcomes of and recommendations for cardiac rehabilitation services are categorized as to their effects on exercise tolerance, strength training, exercise habits, symptoms, smoking, lipids, body weight, blood pressure, psychological well-being, social adjustment and functioning, return to work, morbidity and safety issues, mortality and safety issues, and pathophysiologic measures. Patients with heart failure and after cardiac transplantation, as well as elderly patients, are specifically addressed. Alternate approaches to the delivery of cardiac rehabilitation services are presented.
Aged↗
Safety and compatibility of betaxolol hydrochloride combined with diltiazem or nifedipine therapy in stable angina pectoris.
Compared with placebo, adding betaxolol 20 mg every day to nifedipine (up to 60 mg/day in divided doses) or diltiazem (up to 360 mg/day in divided doses) for a 3-week treatment period in 135 patients with stable angina pectoris significantly (p < 0.05) lengthened the time to onset of moderate angina during exercise tolerance tests at all treatment time points. The median increases in the time to onset of moderate angina at the final exercise tolerance test (end point) compared with baseline were 1.08 and 0.53 minutes for betaxolol and placebo groups, respectively (p = 0.002, betaxolol and placebo groups, respectively (p = 0.002, betaxolol vs placebo). The time to onset of 1 mm ST-segment depression increased significantly (p < 0.05) with betaxolol compared with placebo at all but 1 treatment time point (median increase [p = 0.001] 1.77 and 0.37 minutes, respectively, at end point). Duration of exercise also was increased significantly (p < 0.05) after the third week of treatment and at end point (median 0.62 and 0.50 minutes, respectively; p = 0.03). Generally comparable results were found within the diltiazem (n = 128) and nifedipine (n = 25) subgroups, although the nifedipine group was too small to detect statistically significant differences between betaxolol and placebo treatment. Resting systolic blood pressure, heart rate and the rate-pressure product, measured both when angina occurred and at the end of exercise, also were influenced significantly (p < 0.05) by the betaxolol addition. The only serious adverse effect associated with betaxolol treatment was syncope, seen in 2 patients.
Adult↗
The presentation of children with amblyopia.
This study reports the presentation of 961 children who underwent amblyopia treatment at seven orthoptic centres in the United Kingdom. We confirmed previous authors' findings of a small but significant increased incidence of left-sided compared with right-sided amblyopia overall. For pure anisometropic amblyopia this difference was very marked and a possible pathophysiological mechanism is proposed. The mean age of presentation for anismetropic, strabismic and mixed amblyopia was 5.6, 3.3 and 4.4 years, respectively. Neither sex nor race affected the age of presentation. Despite their older age, children with pure anisometropic amblyopia had the best initial visual acuity, with 25% of anisometropes having an initial visual acuity of less than 6/18 compared with 39% of strabismics and 50% of mixed amblyopes. The ages and initial acuities of the strabismic patients in this series are at least as favourable as those of patients reported from outside the UK. There were variations in the age and proportion of patients presenting with anisometropic amblyopia at the different centres, suggesting a failure in the referral of anisometropic amblyopia of importance in interpreting epidemiological studies.
Age Factors↗
Factors affecting the outcome of children treated for amblyopia.
The outcome of treatment for amblyopia and the factors that affect this are not well understood. A major reason for this has been the exclusion from previous large studies of a sometimes unknown number of patients because of failure to comply with treatment. This paper analyses the outcome of amblyopia treatment in a retrospective review of the orthoptic records of a cohort of 961 children treated for amblyopia at seven centres who first attended in 1983. The final visual acuity was recorded by Snellen or matching methods in 894 children (93%). Of these, 48% achieved 6/9 or better, 35% less than 6/9 but better than or equal to 6/18, and 17% achieved less than 6/18. The outcome was best for pure anisometropic amblyopia, intermediate for pure strabismic amblyopia and least good for mixed strabismic and anisometropic amblyopia with a final visual acuity of 6/10.2, 6/12.8 and 6/14.8 respectively. While the age at start of treatment did not correlate with final visual acuity both poor initial visual acuity and poor compliance were associated with poor outcome. The main factor affecting the outcome of amblyopia treatment is the initial visual acuity. Comparison with the literature suggests that the results of treatment in this country may be falling far short of what would be possible in ideal circumstances with unlimited resources.
Age Factors↗
Social deprivation and age at presentation in amblyopia.
BACKGROUND: Amblyopia is the most common visual disability in children. Early treatment is thought to be more effective, and therefore factors affecting the age at presentation are important. A relationship between social deprivation and access to health care and screening services is well known. We hypothesized that social deprivation might be associated with later presentation of amblyopia, particularly of anisometropic amblyopia which depends on vision screening for referral. METHODS: Data from a historical cohort of 897 children with amblyopia, from seven UK orthoptic clinics, were used to test this hypothesis. Social deprivation was measured by the Townsend score of the ward in which the child lived. RESULTS: A relationship between social deprivation and age at presentation was found in children with anisometropic amblyopia even after adjusting for differences between clinics (p = 0.01) but no similar association was evident in children with amblyopia associated with strabismus. There was a difference of 22 months in the average age at presentation between children with anisometropic amblyopia in the most deprived and least deprived areas of the study. CONCLUSIONS: If screening for anisometropic amblyopia is to be undertaken, priority should be given to screening children from areas of social deprivation.
Age Factors↗
The insulin receptor substrate (IRS-1) is a PEST protein that is susceptible to calpain degradation in vitro.
The insulin receptor substrate 1 (IRS-1) contains at least 11 sequence motifs that are rich in proline (P), glutamic acid (E), serine (S), and threonine (T), i.e., PEST regions. Proteins with PEST regions turn over rapidly. IRS-1 is degraded rapidly in vivo upon exposure of 3T3-L1 adipocytes to insulin. The intracellular, calcium-dependent, neutral proteases known as calpains are one possible mechanism by which IRS-1 may be degraded. To begin to investigate this possibility, purified exogenous calpain was shown to degrade IRS-1 in cell-free extracts from basal and insulin-treated cells and rat recombinant IRS-1 in vitro. Only two proteolytic fragments could be detected. One had a mol wt of approximately 79 kDa, arising from the C-terminus end, and the second had a mol wt of approximately 90 kDa arising from near the N-terminus, possibly a product of the same cleavage event, since the mol wt of IRS-1 from insulin-treated cells was approximately 170 kDa. These results suggest that IRS-1 may serve as a substrate for calpain in vivo, accounting for its rapid degradation.
3T3 Cells↗
Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study.
BACKGROUND: Although digoxin is effective in the treatment of patients with chronic heart failure who are receiving diuretic agents, it is not clear whether the drug has a role when patients are receiving angiotensin-converting-enzyme inhibitors, as is often the case in current practice. METHODS: We studied 178 patients with New York Heart Association class II or III heart failure and left ventricular ejection fractions of 35 percent or less in normal sinus rhythm who were clinically stable while receiving digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor (captopril or enalapril). The patients were randomly assigned in a double-blind fashion either to continue receiving digoxin (85 patients) or to be switched to placebo (93 patients) for 12 weeks. Otherwise, their medical therapy for heart failure was not changed. RESULTS: Worsening heart failure necessitating withdrawal from the study developed in 23 patients switched to placebo, but in only 4 patients who continued to receive digoxin (P < 0.001). The relative risk of worsening heart failure in the placebo group as compared with the digoxin group was 5.9 (95 percent confidence interval, 2.1 to 17.2). All measures of functional capacity deteriorated in the patients receiving placebo as compared with those continuing to receive digoxin (P = 0.033 for maximal exercise tolerance, P = 0.01 for submaximal exercise endurance, and P = 0.019 for New York Heart Association class). In addition, the patients switched from digoxin to placebo had lower quality-of-life scores (P = 0.04), decreased ejection fractions (P = 0.001), and increases in heart rate (P = 0.001) and body weight (P < 0.001). CONCLUSIONS: These findings indicate that the withdrawal of digoxin carries considerable risks for patients with chronic heart failure and impaired systolic function who have remained clinically stable while receiving digoxin and angiotensin-converting-enzyme inhibitors.
Captopril↗
Membrane-bound choline-O-acetyltransferase in rat hippocampal tissue is anchored by glycosyl-phosphatidylinositol.
In an earlier study, we presented evidence to suggest that some of the particulate choline-O-acetyltransferase (ChAT) in rat hippocampal tissue might be linked to membranes by a glycosyl-phosphatidylinositol (GPI) anchor. In the present report, we attempted to determine if any of this GPI-anchored ChAT might be intracellular. Internalization of phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus thuringiensis into rat hippocampal synaptosomes by the DMSO (dimethyl sulfoxide) freeze/thawing procedure caused an increase in cytosolic and a decrease in membrane-bound ChAT. Incubation of a plasma membrane enriched subcellular fraction at 16 degrees C relative to 4 degrees C led to a conversion of the membrane-bound, amphiphilic ChAT into hydrophilic ChAT. This conversion was blocked by zinc, an inhibitor of GPI-PLC. The cytosolic fraction of ChAT immunoreacted on western blots with an antibody directed against the cross-reacting determinant (CRD) of the GPI anchor. We suggest that some of the membrane-bound ChAT in rat hippocampal tissue is GPI-anchored intracellularly; also, that an endogenous GPI-PLC-like enzyme acts to release it into the cytosol.
Animals↗
Histocompatibility matching for bone marrow transplantation. Donor-recipient pairs in the 4AOHW cell panel.
While the results of unrelated bone marrow transplantation are continually improving, a number of important issues remain: what are the histocompatibility requirements, what genes are involved, what mismatches are acceptable, and what are the best methods for determining donor-recipient match? In this study of material provided through the 4AOHW and the US NMDP, the match between 53 donor-recipient pairs was determined using several different markers within the MHC. The data showed that many apparently well-matched pairs have many mismatches, including mismatches for non-HLA genes (i.e., non-class-I or non-class-II) within the MHC. New methods matching for blocks of DNA around HLA-B and around HLA-DR/DQ are available that are sensitive and identify additional mismatches that are not apparent using conventional typing methods. The 4AOHW cells provide a valuable resource for the comparison and assessment of new matching techniques.
Australia↗
Comparison of treadmill walking and stair climbing over a range of exercise intensities in peripheral vascular occlusive disease.
Although claudication pain and hemodynamic responses to exercise are related to the degree of arterial narrowing in the lower extremities, the nature of these responses to different exercise tasks and intensities is less clear. Thus, the purpose of this study was to compare claudication and hemodynamic responses to graded walking, level walking, and stair climbing over a range of exercise intensities. Ten patients with peripheral vascular occlusive disease performed five tests within each of the three exercise tasks. Similar values of oxygen consumption were obtained among exercise tasks at each intensity (p = ns). Time to onset of claudication pain and to maximal pain were similar among exercise tasks (p = ns), and both demonstrated a curvilinear decrease as intensity increased (p < 0.05). Foot transcutaneous oxygen tension, ankle systolic blood pressure, and ankle/brachial systolic pressure index were also similar among the three exercise tasks (p = ns); however, each decreased linearly as exercise intensity increased (p < 0.05). Thus, in peripheral vascular occlusive disease, the imbalance between oxygen delivery to the exercising lower extremity musculature and the local metabolic demand is similar during different weight-bearing activities. Second, even though the peripheral circulation is progressively impaired with increased exercise intensity, anaerobic metabolism in the ischemic lower extremity musculature may prevent a continual decline in claudication times. The clinical implication is that a more thorough assessment of the functional limitations imposed by claudication pain is not obtained by using different types of weight-bearing exercise tests as opposed to using on ly one type.
Aged↗
Medical treatment after myocardial infarction. Results of studies using various methods.
Patients who have had myocardial infarction and are at risk for continued problems may benefit from several treatment methods (table 1). Beta-adrenergic blockers reduce subsequent cardiovascular morbidity and mortality through their effect on the myocardial supply-demand balance. Administration of angiotensin-converting enzyme inhibitors reduces morbidity and mortality rates in myocardial infarction survivors who have diminished left ventricular ejection fraction. Aspirin and other anticoagulants are beneficial through their antiplatelet effects. Cardiac rehabilitation methods and aggressive management of lipids levels are also useful.
Adrenergic beta-Antagonists↗
Comparison of three progressive exercise protocols in peripheral vascular occlusive disease.
Although claudication pain and hemodynamic responses to exercise are usually clinically assessed via graded treadmill walking, measuring these responses to other commonly performed tasks may yield a more nearly complete evaluation of peripheral vascular occlusive disease. Thus, the purpose of this study was twofold: (1) to determine the reliability of claudication and hemodynamic responses to level walking and stairclimbing and (2) to compare these responses with those obtained with graded walking at similar oxygen consumption. Ten patients with stable claudication symptoms performed graded walking, level walking, and stairclimbing progressive protocols with respective increases in grade, walking speed, and stepping rate on a modified stairclimbing device every two minutes. Similar peak oxygen consumption (13.60 to 14.18 mL/kg/min) was attained with the three protocols (P = NS). Reliability coefficients for the times to onset and to maximal claudication pain during level walking (R = 0.95 and 0.95, respectively) and during stairclimbing (R = 0.92 and 0.82, respectively) were similar to those previously obtained during graded walking. Reliability coefficients for foot transcutaneous oxygen tension during and following level walking (R = 0.78 to 0.96) and stairclimbing (R = 0.65 to 0.98) and for ankle systolic blood pressure following level walking (R = 0.95 to 0.97) and stairclimbing (R = 0.90 to 0.98) were also similar to those previously found with graded walking. Additionally, claudication and hemodynamic measurements were similar among the three exercise protocols. Thus, because graded walking, level walking, and stairclimbing progressive exercise protocols yield reliable and similar information about the hemodynamic severity of peripheral vascular occlusive disease, only one is needed for evaluation.
Aged↗