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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
PubMed2006

Socioeconomic inequalities in very preterm birth rates.

AIMS: To investigate the extent of socioeconomic inequalities in the incidence of very preterm birth over the past decade. METHODS: Ecological study of all 549 618 births in the former Trent health region, UK, from 1 January 1994 to 31 December 2003. All singleton births of 22(+0) to 32(+6) weeks gestation (7 185 births) were identified from population surveys of neonatal services and stillbirths. Poisson regression was used to calculate incidence of very preterm birth (22-32 weeks) and extremely preterm birth (22-28 weeks) by year of birth and decile of deprivation (child poverty section of the Index of Multiple Deprivation). RESULTS: Incidence of very preterm singleton birth rose from 11.9 per 1000 births in 1994 to 13.7 per 1000 births in 2003. Those from the most deprived decile were at nearly twice the risk of very preterm birth compared with those from the least deprived decile, with 16.4 per 1000 births in the most deprived decile compared with 8.5 per 1000 births in the least deprived decile (incidence rate ratio 1.94; 95% CI (1.73 to 2.17)). This deprivation gap remained unchanged throughout the 10-year period. The magnitude of socio-economic inequalities was the same for extremely preterm births (22-28 weeks incidence rate ratio 1.94; 95% CI (1.62 to 2.32)). CONCLUSIONS: This large, unique dataset of very preterm births shows wide socio-economic inequalities that persist over time. These findings are likely to have consequences on the burden of long-term morbidity. Our research can assist future healthcare planning, the monitoring of socio-economic inequalities and the targeting of interventions in order to reduce this persistent deprivation gap.

England↗
PubMed2003

Latest trends in cancer incidence among UK South Asians in Leicester.

Using cancer registry data, we show that although South Asians have lower rates of cancer than the rest of the population, this is changing with age and time. Younger South Asians, particularly children, are at increased risk. While generally cancer rates have fallen over the last decade, they are increasing among South Asians.

Adolescent↗
PubMed2003

Up-to-date estimates of long-term cancer survival in England and Wales.

Cancer survival in England and Wales has improved over the last 30 years. However, cohort survival estimates delay recognition of these improvements. Here we show that period survival estimates, based on survival in a recent time period, suggest a more optimistic pattern for England and Wales than cohort-based measures for most cancers.British Journal of Cancer (2003) 89, 74-76. doi:10.1038/sj.bjc.6600976 www.bjcancer.com

Adolescent↗
PubMed2002

A study of heredity as a risk factor in strabismus.

AIMS: Inheritance is recognised to have a part in the aetiology of strabismus but previous studies have not adequately distinguished between different types of strabismus leading to wide variations in reported findings. The aim of this study was to investigate the importance of heredity in different types of strabismus. METHODS: The parents of children attending for treatment of strabismus over a one-month period were interviewed to identify relatives with a history of strabismus. A complete three-generation pedigree was established for 96 index cases who were classified into four groups: infantile esotropia (26 cases), accommodative esotropia (49 cases), anisometropic esotropia (15 cases), and exotropia (six cases). RESULTS: Forty-three of a total of 165 (26.1%) first degree relatives of patients with hypermetropic accommodative esotropia were affected. In contrast, 15 of a total of 101 (14.9%) first degree relatives of patients with infantile esotropia, eight of a total of 66 (12.1%) first degree relatives of patients with anisometropic esotropia, and one of a total of 25 (4%) first degree relatives of patients with exotropia were affected. Analysing the data using logistic regression with a random term for family showed a significantly higher proportion of affected first degree relatives in the accommodative group than in any of the other three diagnostic groups. CONCLUSION: A history of strabismus appears to be more common in hypermetropic accommodative esotropia than in infantile esotropia, anisometropic esotropia or exotropia. More detailed investigation of the role of heredity in the aetiology of accommodative esotropia is needed.

Child↗
PubMed2001

Relation of coronary artery calcium identified by electron beam tomography to serum lipoprotein levels and implications for treatment.

This study was designed to determine whether the National Cholesterol Education Program (NCEP) lipid guidelines accurately identify subclinical atherosclerosis and whether low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels are related to the extent and prematurity of coronary artery disease (CAD) as determined by electron beam tomography (EBT). Out of personal concern for CAD risk, 930 consecutive asymptomatic subjects, without clinical CAD and on no lipid-lowering agents, underwent EBT. Calcium score and percentile were correlated with total cholesterol (TC), LDL-C, HDL-C, triglycerides, and demographic parameters. A calcium score of > 0 (EBT+) was found in 55% of patients; 45% of patients had a 0 score (EBT-). Mean age (58.0 +/- 10.5 vs 49.3 +/- 9.7 years, p = 0.0001), TC (218 +/- 39 vs 211 +/- 41 mg/dl, p = 0.006), LDL-C (136 +/- 36 vs 127 +/- 27 mg/dl, p = 0.005), and TC/HDL-C (4.6 +/- 1.4 vs 4.2 +/- 1.5, p = 0.0001) were significantly higher and HDL-C (52.2 +/- 17.6 vs 55.4 +/- 19.3 mg/dl, p = 0.008) lower in the EBT+ compared with EBT- group. In the EBT+ group, 75.1% of subjects had LDL-C < 160 mg/dl and would not be advised to use lipid-lowering medications according to NCEP guidelines. In subjects with LDL-C < 160 mg/dl, 51.8% of subjects were EBT+, as were 46.1% of those with LDL-C < 100 mg/dl. There were no significant differences in the calcium scores throughout the entire range of all lipid parameters; calcium percentiles were virtually identical within lipid value subgroups. We conclude that asymptomatic patients with EBT-defined subclinical atherosclerosis are not reliably identified by NCEP guidelines, and TC, LDL-C, HDL-C, TC/HDL-C, and triglyceride levels do not correlate with either the extent or prematurity of calcified plaque burden.

Analysis of Variance↗
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↗