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Biomedical subjects

L K Smith

Publications and source records attributed to L K Smith.

At least 19 recordsLinked to original sources
PubMed2000

A quality control program for crossmatching procedures for solid organ transplantation. The participating laboratories of the Australasian and South Asian Tissue Typing Association.

The National Kidney Matching Scheme (NKMS) allows matching and allocation of donor organs throughout Australia. Sera from potential recipients are distributed to each interstate tissue typing laboratory on a monthly basis for crossmatching in the event of a cadaver donor. Therefore, it is essential there is consensus for results between these laboratories in order for donated organs to be allocated appropriately. A quality control program conducted under the auspices of ASEATTA was undertaken for (1) panel reactive antibody characterization; (2) routine T lymphocyte crossmatching; and (3) characterization of antibody isotype by DTT treatment. These aims were achieved by distribution of (1) six sera for the determination of PRA activity; (2) 20 scrambled trays including replicate dilutions of a strongly positive lymphocytotoxic serum, high titer monoclonal antibody and negative sera and; (3) 20 trays containing sera with IgG and/or IgM antibodies. These were then evaluated by each laboratory on a panel of T cells. There was concordance between laboratories for PRA levels and antibody characterization. However, there was considerable variation in crossmatch sensitivity and reproducibility, several laboratories had carryover and others could not detect weak IgM antibodies. These results demonstrate the utility and need for ongoing crossmatch exchange programs, particularly for laboratories participating in organ exchange programs.

Dithiothreitol↗
PubMed1999

The therapy of amblyopia: an analysis comparing the results of amblyopia therapy utilizing two pooled data sets.

CONTEXT: We previously presented the results of an original pooled data set of 961 amblyopic patients who underwent patching therapy for amblyopia from 1965 to 1994 (study group 1). Three types of amblyopia were considered: anisometropic, anisometropic-strabismic, and strabismic. Analysis of this group's success was related to the age at which therapy was initiated, the type of amblyopia, and the depth of visual loss before treatment was begun. The purpose of the current study is to test the validity of these findings on a second group of 961 amblyopes employing the data set used by Woodruff and associates in their publications (study group 2). These 2 data sets, after adjustment to conform to the definitions of age, amblyopia, anisometropia, and similar items utilized in common between the 2 study groups, will be compared for the risk factors predictive of successful occlusion therapy. OUTCOME: As in the previous study, the success of occlusion therapy is defined as a visual acuity of 20/40 or better at the end of treatment. RESULTS: Success by the 20/40 criteria was achieved in 73.7% in study group 1 and in 59.9% in study group 2. By category, the rate of success in study group 1 was 77.2% in strabismic amblyopia, 67.2% in anisometropic-strabismic amblyopia, and 66.0% in anisometropic amblyopia. In study group 2, success was 61.2% in strabismic amblyopia, 51.2% in anisometropic-strabismic amblyopia, and 63.0% in anisometropic amblyopia. Study group 1 univariate analysis related success in each group to the age at which therapy was initiated, the type of amblyopia, and the depth of visual loss before treatment in each group. In study group 2, univariate analysis related success of occlusion therapy to age and the depth of visual loss before treatment. Type of amblyopia was not related to outcome success in this group. When the 2 data sets were pooled, the risk factors for success were age and depth of visual loss at onset of treatment. CONCLUSIONS: Factors that appeared closely related to a successful outcome of patching therapy were patient age and depth of visual loss before treatment. These conclusions further support the value of early detection and screening for amblyopia, its prevention, where possible, and its adequate and vigorous treatment when it is detected and diagnosed.

Amblyopia↗
PubMed1998

Effectiveness of three different doses of carvedilol for exertional angina. Carvedilol-Angina Study Group.

Carvedilol is a nonselective beta-receptor antagonist with vasodilating properties primarily due to selective alpha-1 antagonism. This 4-treatment, 5-period, double-blind, crossover study evaluated the efficacy and safety of 3 doses of carvedilol (12.5, 25, and 50 mg given twice daily) versus placebo in 122 patients with chronic stable angina. Carvedilol in doses of 25 mg twice daily and 50 mg twice daily was statistically superior to placebo with respect to time to angina (placebo: 316 seconds; 25 mg carvedilol: 337 seconds, p = 0.0039; 50 mg: 345 seconds, p <0.0001) and time to 1-mm ST-segment depression (placebo: 301 seconds; 25 mg: 313 seconds; 50 mg: 323 seconds; p <0.0001). The percentage of patients reporting any adverse experience was slightly less in those receiving placebo (placebo: 28.4%; 12.5 mg: 33.1%; 25 mg: 34.5%; 50 mg: 31.9%). Carvedilol is effective and safe in treating patients with chronic stable angina.

Aged↗
PubMed1998

Comparison of the fixed combination of enalapril/diltiazem ER and their monotherapies in stage 1 to 3 essential hypertension.

The safety and efficacy of two fixed dose combinations of enalapril and diltiazem extended release formation (ER) (E/D) were compared with their monotherapies and placebo in patients with stage 1 to 3 hypertension. The trial design was a multicenter, randomized, double blind, placebo controlled, parallel group, 12 week treatment phase, followed by a 36 week, open label phase. A total of 891 patients with sitting diastolic blood pressure (SiDBP) between 95 and 115 mm Hg were randomly assigned to enalapril 5 mg, diltiazem ER 120 mg, diltiazem ER 180 mg, enalapril 5 mg/diltiazem ER 120 mg (E5/D120), enalapril 5 mg/ diltiazem ER 180 mg (E5/D180), or placebo. In the open label phase, 562 patients received the fixed combination, titrated as needed to control SiDBP < 90 mm Hg. Efficacy was determined with trough (24 +/- 2 h postdose) sitting blood pressure measurements at week 12 and at the end of the open label part of the study. Safety was evaluated based on patient symptoms, clinical laboratories, and electrocardiograms (ECG). E5/D120 and E5/D180 significantly reduced trough SiDBP (-7.6 and -8.3 mm Hg, respectively; P < .05) versus their monotherapies. E5/D120 and E5/D180 significantly reduced trough sitting systolic blood pressure (-7.9 and -9.0, respectively; P < .05) versus both diltiazem ER monotherapies. All active treatments significantly decreased SiDBP and SiSBP versus placebo. E/D effectively lowered SiDBP and SiSBP during the open label extension. No significant difference was seen among treatment groups for the overall incidence of adverse events. The most common drug related adverse events were headache, edema/swelling, dizziness, asthenia/fatigue, cough, rash, and impotence. The event frequency for the combinations were similar to those seen with the monotherapies. Fixed combinations of E/D were generally well tolerated, with an increased blood pressure lowering effect as compared with the individual components in patients with stage I to III hypertension.

Adult↗
PubMed1998

Emergency admissions of older people to hospital: a link with material deprivation.

BACKGROUND: The aim was to investigate whether variations in emergency admission to hospital amongst older people in Leicestershire vary with the level of material deprivation of the area in which they live. METHODS: Data were extracted from the Trent Patient Information System for patients aged 65 and over, admitted as an emergency medical admission to Leicestershire's acute and community hospitals on at least one occasion during the period October 1993-September 1994. The 1991 Census was used to examine the nature of the areas from which these emergency admissions were drawn and variations in emergency admission rates across Leicestershire. The relationship between emergency medical admissions and age, sex and material deprivation as measured by the Townsend deprivation score was examined. RESULTS: There were 13,305 people aged 65 or over with at least one emergency medical admission out of an estimated population (65 and over) in 1994 of 134,608 (9.9 per cent). Unconditional logistic regression showed that the risk of emergency admission increased with age and was also higher for men than for women. Emergency admissions increased significantly with increasing deprivation for each age group. This was most notable in the 65-74 years age group, yielding an odds ratio of 2.06 [95 per cent confidence interval (1.86, 2.29)], when comparing those from the most deprived areas with those from the least deprived areas. CONCLUSIONS: The increased risk of emergency medical admission to hospital, which is associated with residence in areas characterized as deprived by Census-based indicators, suggests there are enduring inequalities in health or health care amongst older people. Inequalities noted for all ages persist into old age, although in the 'oldest' age groups, the effect is weaker. Material deprivation may also be a proxy for other factors, such as differences in social support and the type of care received.

Aged↗
PubMed1998

Mechanisms underlying the absence of the pubertal shift in the playful defense of female rats.

Due to the action of testicular hormones in the perinatal period, juvenile male rats engage in more play fighting than juvenile females. Also, following puberty, males, but not females, switch to using adultlike defensive tactics more frequently during play. This change in play is also due to the action of testicular hormones perinatally. In this study, two experiments were conducted to determine if the pubertal transition in defense could be induced in females. For Experiment 1, male and female cagemates were tested before and after puberty with familiar and unfamiliar partners. Even when playfully interacting with subadult males, females did not increase the use of the adultlike defensive tactics. For Experiment 2, neonatal females were either injected with testosterone propionate (TP) or ovariectomized (OVX), and again tested before and after puberty. While the TP-treated females had higher frequencies of play fighting, they did not change their pattern of defense following puberty. The OVX females exhibited the lower frequency of play fighting typical of females, but changed their pattern of defense with increased age. Thus, it appears that the pattern of pubertal change in playful defense typical of males is inhibited by ovarian hormones. The mechanisms by which ovarian hormones could exert this effect on developing females are discussed.

Agonistic Behavior↗
PubMed1997

The postpubertal change in the playful defense of male rats depends upon neonatal exposure to gonadal hormones.

The pattern of playful defense used during play fighting by male rats (Rattus norvegicus) castrated at birth was compared to that of sham-operated and untreated controls during the juvenile phase and after puberty. The neonatal castrates failed to exhibit the age-related changes in playful defense present in intact male rats of the same age. Following puberty, control rats, but not neonatal castrates, switched from juvenile to more adult-typical defensive tactics. That the neonatal castrations were effective was independently shown by the animals' failure to exhibit the asymmetries in weight and play behavior indicative of dominance-subordinance relationships present in normal adult males. A previous study found that castration following weaning did not prevent the pubertal change in playful defense, but did block the formation of dominance-subordinance relationships. Therefore, it appears that the age-related shift in playful defense is a feature of the development of play fighting in males that is likely preprogrammed by gonadal hormone exposure in the perinatal period.

Aggression↗
PubMed1997

Multiple differences in the play fighting of male and female rats. Implications for the causes and functions of play.

Play fighting is the most commonly occurring form of social play in juvenile mammals. Typically, males engage in more play fighting than females, and this difference has been shown to depend on the action of androgens perinatally. It is generally believed that the differences in play fighting between the sexes are quantitative and do not involve qualitative differences in the behavior performed. We show that this is an incorrect characterization of sex difference in play fighting. For example, in laboratory rats, there are at least five different mechanisms that contribute to the observed sex differences in play fighting. These mechanisms involve (I) the motivation to initiate play, (II) the sensory capacity to detect and respond to a play partner, (III) the organization of the motor patterns used to interact with a partner, (IV) age-related changes at puberty in initiating play and in responding to playful contact, and (V) dominance-related changes in adulthood in the pattern of playful interaction. Sex differences in the play fighting of rats are due to an interaction of all of these mechanisms, some of which are sex-typical not play-typical, and involve both quantitative and qualitative differences. This is clearly different from the prevailing view that play fighting is a unitary behavior which is masculinized perinatally. Indeed, even though all five mechanisms are androgenized perinatally, the sensorimotor differences also involve defeminization (i.e. reduction of female-typical qualities). This expanded view of the mechanisms contributing to the sex differences in play fighting has implications for both the analysis of the neural systems involved, and for the functional significance of this activity in childhood and adulthood.

Animals↗
PubMed1996

The insulin-induced down-regulation of IRS-1 in 3T3-L1 adipocytes is mediated by a calcium-dependent thiol protease.

Insulin receptor substrate-1 (IRS-1) is a protein expressed in 3T3-L1 adipocytes that is involved in most, if not all of the biological responses to insulin. Chronic exposure of these cells to insulin down-regulates IRS-1 by stimulating its degradation (Rice, K.M., Turnbow, M.A. and Garner, C.W. (1993) Biochem. Biophys. Res. Commun. 190, 961-967). This insulin-induced down-regulation of IRS-1 was totally abolished by BAPTA-AM (cell-permeable calcium chelator), E-64d (cell-permeable thiol protease inhibitor), Cbz-Leu-Nleu-H and Cbz-Leu-Leu-Tyr-CHN2 (selective cell-permeable calpain inhibitor peptides). Calpastatin (specific calpain inhibitor protein) also inhibited the insulin-induced down-regulation of IRS-1 in transiently permeabilized cells. In addition, 3T3-L1 adipocytes express endogenous calpain which can degrade IRS-1 in cell-free extracts. These results suggest that the insulin-induced down-regulation of IRS-1 in 3T3-L1 adipocytes is mediated by a calcium-dependent thiol protease which is sensitive to inhibition by calpain inhibitors.

Adipocytes↗
PubMed1996

Cost and time savings following introduction of rejection criteria for clinical specimens.

We have evaluated the yield of several tests and have instituted specimen rejection criteria to reduce costs and save time. For a 12-month period, we recorded the reduction of these tests and calculated the resultant cost and time savings. Seven changes were analyzed: not performing fungal or mycobacterial (acid-fast bacillus) cultures on cerebrospinal fluid (CSF) specimens from patients without known immunosuppression when chemistry and cell count are normal; not performing routine stool culture or ovum and parasite examination on specimens from patients in the hospital for > 3 days; not culturing endotracheal suction aspirates when no organisms or > 10 squamous epithelial cells are present; discontinuing broth cultures on all specimens except for tissue, continuous ambulatory peritoneal dialysis fluid, and CSF from patients with shunts; and eliminating bacterial antigen tests. For each test, the number not performed (n), reagent savings, and technologist time saved, respectively, were as follows: CSF fungal culture, 267, $999, and 67 h; CSF acid-fast bacillus culture, 275, $1,662, and 124 h; stool cultures, 320, $2,991, and 98 h; ovum and parasite examinations, 216, $525, and 108 h; endotracheal suction aspirate cultures, 1,505, $4,447, and 306 h; broth cultures, 5,218, $4,931, and 80 h; and bacterial antigen tests, 2,598, $2,293, and 299 h. Overall, 5,181 tests were rejected and 5,218 broth cultures were omitted. Achievable savings were $28,000 in reagent costs and 1,082 h of technologist time. In conclusion, rejecting specimens of proven low yield saves reagent costs and, more importantly, saves technologist time. This time can be spent on specimens having greater diagnostic utility.

Antigens, Bacterial↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗