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Biomedical subjects

J Harris

Publications and source records attributed to J Harris.

At least 109 records · Page 6Linked to original sources

Obstetric risks of pregnancy in women less than 18 years old.

OBJECTIVE: To quantify the age-related risks of adverse outcome during pregnancy in women less than 18 years old. METHODS: We analyzed data from 341,708 completed singleton pregnancies in the North West Thames region between 1988 and 1997. Pregnancy outcomes were compared by age at delivery in women less than 18 years old (n = 5246) and 18-34 years old (n = 336,462); women 35 years old or older (n = 48,658) were excluded. Data are presented as percentages of women less than 18 and 18-34-year-old women, with adjusted odds ratios (OR) and 99% confidence intervals (CI). RESULTS: Pregnancy in women less than 18 years old was associated with increased risk of preterm labor before 32 weeks' gestation (OR 1.41, CI 1.02, 1.90), maternal anemia (OR 1.82, CI 1.63, 2.03), chest infection (OR 2.70, CI 1.21, 6.70), and urinary tract infection (OR 1.60, CI 1.11, 2.31), but less obstetric intervention. Operative vaginal delivery (OR 0. 46, CI 0.41, 0.56), elective cesarean (OR 0.47, CI 0.35, 0.65), or emergency cesarean (OR 0.45, CI 0.38, 0.53) were all less likely in women aged less than 18 years. Women less than 18 years old were no more likely to have stillbirths (OR 0.75, CI 0.42, 1.34) or small-for-gestational-age infants (OR 0.95, CI 0.82, 1.09) than women aged 18-34 years. CONCLUSION: Pregnant women less than 18 years old were more likely to deliver preterm than older women. In most other respects they have less maternal and perinatal morbidity and were more likely to have normal vaginal deliveries.

Adolescent↗

Androsterone sulfate increases dentate gyrus population spike amplitude following tetanic stimulation.

We studied the effects of the androgenic hormone, androsterone sulfate, a 17-ketosteroid, on long term potentiation in the dentate gyrus (DG) of urethane anesthesized rats. Intravenous injection of 10 mg of the hormone dissolved in Nutralipid produced a significant increase of the population spike (PS), but not of the excitatory post-synaptic potentials (EPSP). The results are discussed in terms of the potential enhancement that androsterone sulfate may have on memory as was described for one of its parent compounds, dehydroepiandrosterone (DHEA) and its potential use as an antidepressant.

Androsterone↗

A model of the Parkinsonian visual system: support for the dark adaptation hypothesis.

Considerable evidence suggests that some visual abnormalities in Parkinson's disease are mediated by disruption of dopaminergic processes in the retina. Since dopamine is thought to be involved in the process of dark adaptation, and some of these abnormalities are similar to the changes which accompany dark adaptation in normal subjects, it has been proposed that the parkinsonian retina behaves as though inappropriately dark-adapted. In Parkinson's disease, the apparent contrast of peripherally viewed medium and high spatial frequency gratings is reduced. In our first experiment, normal subjects were dark-adapted, and were required to match the apparent contrast of a peripherally viewed grating to that of a foveally viewed grating. The results showed an interaction between spatial frequency and dark adaptation, reflecting a greater reduction in the apparent contrast of peripheral high spatial frequency gratings. In a second experiment, no effect of dark adaptation was found on the apparent spatial frequency of a peripherally viewed grating required to match that of a foveally viewed grating. The first experiment supports the dark adaptation hypothesis of parkinsonian vision, and the second suggests that the changes in apparent contrast are mediated by different amounts of change in contrast gain in central and peripheral vision, rather than by differential changes in receptive field size.

Adaptation, Ocular↗

Evaluation of the onset and duration of effect of azelastine eye drops (0.05%) versus placebo in patients with allergic conjunctivitis using an allergen challenge model.

OBJECTIVE: The trial evaluated the effectiveness of the investigational antihistaminic and antiallergic compound Azelastine Eye Drops (AZE) in the treatment of allergic conjunctivitis using an allergen challenge model. DESIGN: Randomized, double-blind, placebo-controlled, paired-eye study. PARTICIPANTS: Adults with a history of allergic conjunctivitis (>/=2 years) who were asymptomatic throughout the trial, had a positive skin test (cat dander, grass, or ragweed pollen within the last year), and had a positive conjunctival reaction (score 2+ or more for itching and redness in both eyes on a 0-4 scale) during two separate conjunctival provocation tests (CPT) before randomization. METHODS: Eighty patients underwent a 2-week screening period (visits 1 and 2) that included a CPT during visit 1 to establish the allergen threshold dose and a second confirmatory CPT performed at visit 2. Eye symptom assessments for itching (evaluated by patient) and conjunctival redness (evaluated by physician) were performed 5 and 10 minutes after CPT using a 5-point scale (from 0 = none to 4+ = severe). Qualified patients were randomized to receive one drop of AZE (0.015 mg of azelastine hydrochloride) in one eye and one drop of placebo in the other eye 20 minutes before CPT at visit 3 (onset) and 8 or 10 hours before CPT at visit 4 (duration). MAIN OUTCOME MEASURES: Individual severity scores for itching (evaluated by patient) and conjunctival redness (evaluated by physician) for each eye at 3, 5, and 10 minutes after CPT at visits 3 and 4 using a 5-point scale (0 = none to 4+ = very severe). RESULTS: Each of the 80 randomized patients completed the trial. Mean itching and conjunctival redness scores at visit 3 (onset) were significantly lower (P: < 0.001) in the AZE-treated eyes than in the placebo-treated eyes. At visit 4 (duration), mean itching and conjunctival redness scores (P: </= 0.003) for the 8-hour group and mean itching scores (P: </= 0.001) for the 10-hour group were significantly lower in the AZE-treated eyes than in the placebo-treated eyes. Significant differences in mean tearing and chemosis severity scores were also seen at visit 3 (onset) and visit 4 (duration) in the AZE-treated eyes when compared with the placebo-treated eyes. Treatment with AZE was well tolerated. CONCLUSIONS: Therapy of experimentally induced allergic conjunctivitis with AZE was highly effective, with an onset of action seen within 3 minutes and a duration of effect of at least 8 to 10 hours.

Adolescent↗

Dehydroepiandrosterone sulfate (DHEAS) counteracts decremental effects of corticosterone on dentate gyrus LTP. Implications for depression.

It is well-established that levels of corticosterone sufficient to occupy Type II glucocorticoid receptors produce a decrement in long-term potentiation (LTP) in the dentate gyrus of the hippocampus in rats. In the present series of experiments we investigate the interaction of corticosterone and the neurosteroid dehydroepiandrosterone sulfate (DHEAS) on LTP in the rat dentate gyrus. In confirmation of previous studies, we found that corticosterone (2 mg/kg) had decremental effects on LTP. However, simultaneous injection of corticosterone and DHEAS (30 mg/kg) elicited excitatory post-synaptic potentials and population spikes that were not significantly different from those observed in control animals. The results are discussed in terms of the interaction of the two hormones, the agonist effects of DHEAS on sigma receptors, and their relation with the antidepressant effects of DHEA.

Action Potentials↗

Is apoptosis present in progression to chronic hypertensive heart failure?

BACKGROUND: Cardiomyocyte apoptosis is believed to occur in hypertension. Isolated myocyte data from spontaneously hypertensive heart failure (SHHF) rats, however, suggest that significant myocyte loss does not occur in this model. To investigate this issue further, heart sections from failing and nonfailing SHHF rats were examined by using in situ terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labeling (TUNEL). Additional hearts were optimally fixed by perfusion with glutaraldehyde and histologically examined for evidence of myocyte damage or loss. METHODS AND RESULTS: Five Sprague-Dawley (SD) rats, 8 failing SHHF rats, and 6 nonfailing SHHF rats were perfusion-fixed with formaldehyde and used for TUNEL assay. Heart sections from each group were also treated with DNase for positive controls. There were no significant differences in the number of TUNEL-positive cells in SD, failing SHHF, and nonfailing SHHF rats. Additionally, extensive screening of 1-microm sections of optimally fixed failing hearts revealed little evidence of myocyte loss or nuclear characteristics suggestive of apoptosis. CONCLUSION: Apoptosis does not appear to be an important component of myocardial remodeling in SHHF rats during hypertrophy or end-stage heart failure. Examination of myocyte nuclear structure by high-resolution microscopy of optimally fixed tissues is recommended as an alternative approach to study apoptosis.

Animals↗

The welfare of the child.

The interests or welfare of the child are rightly central to any discussion of the ethics of reproduction. The problematic nature of this legitimate concern is seldom, if ever, noticed or if it is, it is misunderstood. A prominent example of this sort of misunderstanding occurs in the Department of Health's recent and important 'Surrogacy Review' chaired by Margaret Brazier (The Brazier Report) and the same misunderstanding makes nonsense of at least one provision of the Human Fertilization and Embryology Act 1990. (The HFE Act). This paper explores and hopefully resolves this misunderstanding and sets out the ways in which the idea of the interests of the child can legitimately function in bioethics.

Child↗

Epidemiologic characteristics of kidney malformations.

Infants with kidney agenesis or dysgenesis, infants with cystic kidneys, and infants with horseshoe kidneys were studied, based on data from three large and population-based congenital malformation registers: a total of 2666 infants among 5.83 million births. There is a strong variability between programs of the rates of registered unilateral kidney malformations and these are strongly over-represented in dead infants or infants with other malformations. There is a male excess but this varies in strength between different types of kidney malformations and between bilateral and unilateral forms. An increased twinning rate was found. The different types of kidney malformation differed with respect to kind of associated non-urological malformations in multimalformed infants. We conclude that for monitoring purposes one should restrict analysis to bilateral forms but that unilateral forms can be of interest in epidemiological analyses.

Abnormalities, Multiple↗

Total and specific IgE (house dust mite and intestinal helminths) in asthmatics and controls from Gondar, Ethiopia.

BACKGROUND: The role, if any, of parasitosis in the development of asthma remains incompletely understood; both 'protective' and 'predictive' associations have been reported. We report a study which examined immunoglobulin (Ig) E responses to two common helminths in asthmatics living in Ethiopia. OBJECTIVE: To compare the frequencies of specific IgE antibodies to Ascaris and Necator species and to Der p 1 among 84 adult asthmatics and a referent group of nonasthmatics. METHODS: A case-control analysis. RESULTS: Total IgE levels were not different between the two groups. The presence of specific IgE to Der p 1 was strongly associated with asthma (P = 0.001). Raised levels of Ascaris-(P = 0.010) and Necator- (P = 0.001) specific IgE antibodies were more common among referents; there were no associations between specific IgE production to Der p 1 and either of the two parasites. CONCLUSION: These findings confirm the association between Der p 1 sensitization and asthma among urban, adult Ethiopians. While they also indicate a negative relationship with two indicators of helminth infestation it appears that this is not mediated through the immunological response to common aeroallergens.

Adolescent↗

Activation of spinal cannabinoid 1 receptors inhibits C-fibre driven hyperexcitable neuronal responses and increases [35S]GTPgammaS binding in the dorsal horn of the spinal cord of noninflamed and inflamed rats.

The analgesic potential of cannabinoid (CB) receptor agonists is of clinical interest. Improved understanding of the mechanisms of action of cannabinoids at sites involved in the modulation of acute and sustained inflammatory nociceptive transmission, such as the spinal cord, is essential. In vivo electrophysiology was used to compare the effect of the synthetic CB agonist, HU210, on acute transcutaneous electrical-evoked responses of dorsal horn neurons of noninflamed anaesthetized rats and anaesthetized rats with a peripheral carrageenin inflammation. CB receptor G-protein coupling in lumbar spinal cord sections of noninflamed and carrageenin-inflamed rats was studied with in vitro autoradiography of guanylyl 5'-[gamma-[35S]thio]triphosphate ([35S]GTPgammaS) binding. Spinal HU210 significantly inhibited the C-fibre-mediated late (300-800 ms) postdischarge response of dorsal horn neurons of noninflamed and carrageenin-inflamed rats; the CB1 receptor antagonist SR141716A blocked the effect of HU210. HU210 had limited effects on A-fibre-evoked dorsal horn neuronal responses of both groups of rats. HU210 significantly increased [35S]GTPgammaS binding in the dorsal horn of the spinal cord of both groups of rats compared with basal [35S]GTPgammaS binding; SR141716A blocked these effects. The predominant effect of spinal HU210, via CB1 receptor activation, was on the C-fibre driven postdischarge responses, a measure of neuronal hyperexcitability following repetitive C-fibre stimulation. Sustained, but not enhanced, antinociceptive effects of HU210 following carrageenin inflammation are reported; CB receptor G-protein coupling was not altered by inflammation. These results strengthen the body of evidence suggesting CB agonists may be an important novel analgesic approach for the treatment of sustained pain states.

Animals↗

Increasing pneumococcal vaccination rates among residents of long-term--care facilities: provider-based improvement strategies implemented by peer-review organizations in four western states.

OBJECTIVE: To evaluate collaborative efforts and intervention strategies by peer-review organizations (PROs) and long-term-care facilities (LTCFs) for improving pneumococcal vaccination rates among residents of LTCFs. DESIGN: Prospective, before-after quality improvement project. SETTING: 133 LTCFs in Alaska, Idaho, Montana, and Wyoming. PATIENTS: All residents of participating LTCFs. METHODS: Baseline pneumococcal vaccination rates were determined by medical-record review, self-reporting by patient or family members, and review of Medicare claims information. Remeasurement of vaccination rates was accomplished from documentation of vaccination of eligible residents by each LTCF. RESULTS: 133 LTCFs with 7,623 residents from Alaska, Idaho, Montana, and Wyoming participated in this quality-improvement project. This accounted for 41% (133/321) of the potential nursing homes and resident population in the participating states. Baseline overall vaccination rates were 40% (3,050/7,589). The overall vaccination rate improved to 75% (5,720/7,623, P<.001). The number of facilities meeting the Healthy People 2000 vaccination goal of 80% improved from 18% (24/133) to 62% (83/133, P<.001). Initial use of chart stickers and implementation of standing orders led to similar increases in vaccination rates, but the standing-order strategy required commitment of fewer PRO resources at a statewide level. Remeasurement of vaccination rates in a subset of participating Idaho LTCFs 1 year after initial vaccination efforts demonstrated a sustained vaccination rate of 70% in facilities enforcing a standing-order policy. CONCLUSIONS: Simple and straightforward vaccination strategies implemented in LTCFs over a short period of time can have a significant impact on vaccination rates. Collaborative efforts between state PROs and LTCFs enhance implementation of these strategies and can result in the achievement of national vaccination objectives. Standing orders appear to be one intervention effective in sustaining successful vaccination efforts. Regardless of the specific interventions employed, PROs played a significant role in facilitating vaccination program development and intervention implementation.

Aged↗

The risks associated with pregnancy in women aged 35 years or older.

The obstetric risks of adverse outcome during pregnancy in women aged > or =35 years were quantified using a retrospective analysis of data from 385 120 singleton pregnancies in the North West Thames Region, UK, between 1988 and 1997. A comparison of pregnancy outcome was made on the basis of maternal age at delivery: 18-34 years (n = 336 462), 35-40 years (n = 41 327) and women aged > 40 years (n = 7331). Women aged <18 years (n = 5246) were excluded from the study. Data are presented as percentages of 18-34 year old women, 35-40 year old and > 40 year old women, with adjusted odds ratios (OR) according to age group. Pregnant women aged 35-40 years were at increased risk of: gestational diabetes, OR = 2.63 [99% confidence interval (CI) 2.40-2.89]; placenta praevia = 1.93 (1.58-2.35); breech presentation = 1.37 (1.28-1.47); operative vaginal delivery = 1.5 (1.43-1.57); elective Caesarean section = 1.77 (1.68-1.87); emergency Caesarean section = 1.59 (1.52-1.67); postpartum haemorrhage = 1.14 (1.09-1.19); delivery before 32 weeks gestation = 1.41 (1.24-1.61); birthweight below the 5th centile = 1.28 (1.20-1. 36); and stillbirth = 1.41 (1.17-1.70). Women aged >40 years had higher OR for the same risks. Pregnant women aged >/=35 years are at increased risk of complications in pregnancy compared with younger women.

Adult↗

Asthma and wheezing among Norwegian elite athletes.

PURPOSE: The objectives were to estimate the prevalence of self-reports of asthma and wheezing among Norwegian elite athletes compared with the general population and to estimate the associations between asthma and types of sports, exercise and team level. METHODS: The study population included all Norwegian elite athletes on the national junior and senior teams in 1997 (N = 1620) and a random sample from the general population (N = 1680). The surveys included items for asthma, respiratory symptoms, the history of participation in sports, sports events, and exercise and team level. The associations between the exposure variables and the outcomes adjusting for potential confounding factors were estimated using logistic regression. Crude (c) and adjusted odds ratio (aOR) with 95% confidence interval (CI) are presented. RESULTS: The prevalence of asthma was greater among athletes (10.0%) compared with that in the general population (6.9%) and remained so after controlling for confounders, aOR = 1.5 (95%CI 1.1-2.1). The risk of asthma was highest in sports requiring strength and endurance. This was the case for comparisons between athletes and the general population, aOR = 3.5 (1.6-7.6) for strength and aOR = 2.2 (1.4-3.5) for endurance sports. Comparisons within the sample of athletes using technical sports as the reference category revealed similar results, aOR = 3.0 (1.1-8.0) and aOR = 2.0 (1.0-4.3), respectively. Furthermore, asthma was more common among female than male athletes (aOR 1.7 (1.1-2.7)). Training more than 20 h x wk(-1) was associated with asthma when compared with levels of training less than 10 h x wk(-1) (aOR 1.9 (1.0-4.1)). CONCLUSION: These results indicate that asthma is more common among athletes compared with the general population. Asthma among athletes may define a subgroup of asthma cases for whom etiology is related to extensive exercise.

Adult↗

Human Slug is a repressor that localizes to sites of active transcription.

Snail/Slug family proteins have been identified in diverse species of both vertebrates and invertebrates. The proteins contain four to six zinc fingers and function as DNA-binding transcriptional regulators. Various members of the family have been demonstrated to regulate cell movement, neural cell fate, left-right asymmetry, cell cycle, and apoptosis. However, the molecular mechanisms of how these regulators function and the target genes involved are largely unknown. In this report, we demonstrate that human Slug (hSlug) is a repressor and modulates both activator-dependent and basal transcription. The repression depends on the C-terminal DNA-binding zinc fingers and on a separable repression domain located in the N terminus. This domain may recruit histone deacetylases to modify the chromatin and effect repression. Protein localization study demonstrates that hSlug is present in discrete foci in the nucleus. This subnuclear pattern does not colocalize with the PML foci or the coiled bodies. Instead, the hSlug foci overlap extensively with areas of the SC-35 staining, some of which have been suggested to be sites of active splicing or transcription. These results lead us to postulate that hSlug localizes to target promoters, where activation occurs, to repress basal and activator-mediated transcription.

Base Sequence↗

Necropsy diagnosis of myocarditis: a retrospective study using CD45RO immunohistochemistry.

AIM: To use CD45RO immunohistochemistry to investigate the numbers of T lymphocytes found in sections of myocardium from a routine necropsy series, and to determine the incidence of myocarditis in this series. METHODS: Myocardial sections from 163 routine hospital necropsies were stained with CD45RO and the numbers of positive lymphocytes/mm2 were counted. The results were correlated with the H/E opinion and the clinical context of the necropsy. RESULTS: Most (143) cases showed low numbers (0-3) of CD45RO positive lymphocytes/mm2. Fifteen cases showed 7-13 positive lymphocytes/mm2, comprising a wide variety of clinical conditions, generally with no specific cardiac pathology. Five cases showed 14 or more positive lymphocytes/mm2, comprising one case of active myocarditis, three cases of cardiac transplant rejection, and one post-transplant lymphoproliferative disorder, all conditions in which large numbers of lymphocytes would be expected. CONCLUSIONS: The incidence of myocarditis in our series was 0.6%. In most cases the normal myocardium has a low T lymphocyte count (0-3/mm2). In some cases immunohistochemistry shows more positive cells than would have been expected on light microscopy. Immunohistochemistry is a useful and reliable means of confirming a diagnosis of myocarditis. The results support the conclusion of the 1997 ISFC task force that 14 or more lymphocytes or macrophages/mm2 of myocardium in the appropriate clinical context is a reliable threshold for the diagnosis of chronic myocarditis.

Adolescent↗