PubMed Health⌕ Search

Biomedical subjects

P Reed

Publications and source records attributed to P Reed.

At least 19 recordsLinked to original sources
PubMed2003

Novel association suggests multiple independent QTLs within chromosome 5q21-33 region control variation in total humans IgE levels.

Asthma is a common, heterogeneous, complex disease accompanied by raised total and specific immunoglobulin-E (IgE) antibody levels. Despite numerous previous reports of linkage and association of asthma, atopy and serum IgE levels to genes within the 5q21-33 region, definitive, replicable results are still not available. We used the classical twin design to (i) estimate the relative contributions of genes and environment to variation in total IgE levels, (ii) assess genetic linkage, and (iii) examine allelic association of 11 microsatellite markers spanning the 5q21-33 region to total IgE. Variation in total IgE level was shown to be highly heritable (65%). Although evidence for linkage of the 11 microsatellites to IgE was not observed, the omnibus test of association, not confounded by population substructure, showed positive association of D5S393 and D5S673 to IgE. Genes in the vicinity of D5S673 include hepatitis A virus receptor (HAVCR-1) and IL-12B. Recently, the mouse orthologue of HAVCR-1, the T-cell membrane family of proteins, have been shown to be in strong association with expression of airway hyperactivity in a mouse model of human asthma and atopy. IL-12B subserves many proinflammatory functions and also induces B cells proliferation.

Adolescent↗
PubMed2003

Adrenocorticotropic hormone directly stimulates testosterone production by the fetal and neonatal mouse testis.

Adult Leydig cell steroidogenesis is dependent on LH but fetal Leydig cells can function independently of gonadotropin stimulation. To identify factors that may be involved in regulation of fetal Leydig cells expressed sequence tag libraries from fetal and adult testes were compared, and fetal-specific genes identified. The ACTH receptor [melanocortin type 2 receptor (Mc2r)] was identified within this fetal-specific group. Subsequent real-time PCR studies confirmed that Mc2r was expressed in the fetal testis at 100-fold higher levels than in the adult testis. Incubation of fetal or neonatal testes with ACTH in vitro stimulated testosterone production more than 10-fold, although ACTH had no effect on testes from animals aged 20 d or older. The steroidogenic response of fetal and neonatal testes to a maximally stimulating dose of human chorionic gonadotropin was similar to the response shown to ACTH. The ED(50) for ACTH, measured in isolated fetal and neonatal testicular cells, was 5 x 10(-10) M and the lowest dose of ACTH eliciting a response was 2 x 10(-11) M. Circulating ACTH levels in fetal mice were around 8 x 10(-11) M. Neither alpha-MSH nor gamma-MSH had any effect on androgen production in vitro at any age. Fetal testosterone levels were normal in mice that lack circulating ACTH (proopiomelanocortin-null) indicating that ACTH is not essential for fetal Leydig cell function. Results show that both LH and ACTH can regulate testicular steroidogenesis during fetal development in the mouse and suggest that fetal Leydig cells, but not adult Leydig cells, are sensitive to ACTH stimulation.

Adrenocorticotropic Hormone↗
PubMed2002

Linkage and association for bone mineral density and heel ultrasound measurements with a simple tandem repeat polymorphism near the osteocalcin gene in female dizygotic twins.

In this confirmatory candidate gene study, we investigated possible linkage and association for bone density, heel ultrasound and bone turnover with the osteocalcin gene using the nearby (50-180kb) microsatellite marker D1S3737. Non-identical twin sisters aged 18-75 years at first interview were recruited for the study from the St Thomas' UK Adult Twin Registry with 1366 women being genotyped for marker D1S3737. Linkage, allelic association and joint linkage and association tests were carried out using quantitative transmission disequilibrium tests (QTDT), along with post-hoc multivariate tests of linkage and association. Phenotypes tested were bone mineral density (BMD) at the spine, left forearm and left total hip; quantitative ultrasound measurements of the heel including velocity of ultrasound (VOS) and broadband ultrasound attenuation (BUA); and bone turnover markers, urine deoxypyridinoline (DPD), serum osteocalcin, bone specific and total alkaline phosphatase (ALP). BMD and ultrasound variables showed evidence of pleiotropic linkage ( p = 0.05) and association ( p = 0.02) with the marker in postmenopausal women. Bone markers showed little or no evidence of linkage and association for any age group. Evidence for pleiotropic linkage appeared to be strongest for BUA and spine BMD in postmenopausal women. The univariate test statistic for BUA was chi(2)(1)=12.8 ( p = 0.0003), equivalent to a LOD score of 2.8. DPD showed borderline evidence of linkage to the marker for women of all ages. Multivariate model-fitting showed allele 10 to be negatively associated with BMD, VOS and BUA via a common pathway, suggesting the putative functional polymorphism affects both bone content and structure through shared underlying metabolic pathways. It is likely that the alleles are in linkage disequilibrium with functional polymorphism(s) in or nearby the osteocalcin gene, which may contribute to the onset of osteoporosis.

Adult↗
PubMed2001

Interference with judgements of control and learning as a result of prior exposure to controllable and uncontrollable feedback during concept-learning tasks.

Two experiments examined whether exposure to an uncontrollable relationship between an action and its outcome during a nonaversive pretreatment phase would attenuate subsequent ratings of control given to actions emitted by subjects. In Experiment 1, such an interference effect was demonstrated relative to a group that received prior training with a controllable action-outcome relationship, and relative to a group not exposed to any prior relationship. In Experiment 2, these effects were replicated, and interference was also found to occur when learning a maze task. Thus, the effects of helplessness were shown to be quite general, to be produced by a nonaversive induction procedure, and to occur most readily when the current contingency between action and outcome was weakest.

Adolescent↗
PubMed2001

Treatment of newly-diagnosed acute promyelocytic leukemia with liposomal all-trans retinoic acid.

It has been postulated that recurrence of disease in some patients with newly-diagnosed APL induced into CR, and subsequently maintained, with single agent oral ATRA results from the decline in ATRA levels that occurs with repeated dosing. Administration of liposomal ATRA (lipoATRA) circumvents, for perhaps several months, the decrease in ATRA levels and produces CRs in patients with relapsed APL. These findings led us to administer lipoATRA "monotherapy" to patients with newly-diagnosed APL. Patients received lipoATRA (90 mg/m2) for induction and continued to receive the drug, by itself, for 9 months unless 2 PCR tests done within 2-4 weeks of each other at a sensitivity level of 10(-4) were positive at 3 or 6 months from CR date, in which case idarubicin was added to lipoATRA. If the PCR test was negative 9 months from CR date, treatment stopped. 34 patients were enrolled, of whom 79% entered CR. The PCR test at time of CR was positive in 23/24 patients, but was negative in 24/26 (92%) 3 months later. Of most interest 11 of the 26 evaluable responding patients have remained PCR negative (tested Q 3 months) with a median follow-up of 18 months (range up to 34 months). It is generally believed that this type of result would be unlikely with oral ATRA monotherapy. Recurrence of morphologic APL has occurred in 4 patients, at 5, 6, 12, and 12 months, with a median follow-up time of 18 months in the patients remaining alive in CR. Comparison of this lipoATRA +/- idarubicin trial with oral ATRA + idarubicin induction and idarubicin + POMP maintenance, our previous trial, indicates similar survival, CR, and DFS in CR rates, with a suggestion that lipoATRA may produce lower CR rates and hence shorter survival in patients with high-risk disease (wbc count > 10,000/microliter. Nonetheless, the rates and duration of PCR negativity produced by lipoATRA monotherapy suggest that lipoATRA is a superior anti-APL agent than oral ATRA.

Administration, Oral↗
PubMed2001

Development and validation of the pharmaceutical care satisfaction questionnaire.

The development and validation of a survey instrument to assess consumer satisfaction with pharmacy services is discussed. The Pharmaceutical Care Satisfaction Questionnaire (PCSQ) is a 30-item instrument administered by someone other than the pharmacist that uses a Likert scale to score respondents' answers. The PCSQ is written approximately at a seventh grade reading level. Following initial development, the PCSQ was administered to 360 consumers in ambulatory pharmacies and to 311 patients in a multicenter hyperlipidemia outcomes study. The Cronbach coefficient alpha was .94 for the consumer data, with a 64.8% variance accounted for by the 4-factor solution. A coefficient alpha of .84 was found on all 30 items in the hyperlipidemia study, with a variance of 63.78% in control patients and 60.16% in treatment patients. The PCSQ is easy to administer and score, with minimal cost. Unlike other satisfaction surveys, the PCSQ contains patient evaluations regarding outcomes of care. A primary limitation of the PCSQ is that it is a newly developed instrument that needs to be used in more studies to strengthen its validity.

Health Care Surveys↗
PubMed2001

Schedules of reinforcement as determinants of human causality judgments and response rates.

Experiments examined the effect of relationships between a response and an outcome on human judgments of causal effectiveness. In Experiment 1, the time between outcomes obtained on a variable ratio (VR) schedule became the intervals for a yoked variable interval (VI) schedule. Response rates were higher on the VR than on the VI schedule. In Experiment 2, the number of responses required per outcome on a VR schedule were matched to that on a master VI 20-s schedule. Both ratings of causal effectiveness and response rates were higher in the VR schedule. In Experiment 3, tandem VI fixed-ratio (FR) schedules produced higher rates and judgments than equivalent conjunctive VI FR schedule. In Experiment 4, a VI schedule with a reinforcement requirement for a short interresponse time (IRT) produced higher rates and judgments than a simple VI schedule. These results corroborate the view that schedules are a determinant of both response rates and causal judgments. Few current theories of causal judgment predict this pattern of results.

Adolescent↗
PubMed2000

Free-operant performance on variable interval schedules with a linear feedback loop: no evidence for molar sensitivities in rats.

Four experiments examined rats' sensitivity to molar and molecular factors on instrumental schedules of reinforcement. Rats were exposed to a variable interval schedule with a positive feedback loop (VI+), such that faster responding led to a shorter interreinforcement interval. In Experiments 1 and 2, rats responded faster on a variable response (VR) schedule than on either a VI schedule matched for reinforcement rate or a VI+ schedule matched for the feedback function. In Experiment 3, rats responded no differently on a VI schedule than they did on a VI+ schedule with equated rates of reinforcement. In Experiment 4, rats responded faster on a VI+ schedule with an interresponse time requirement yoked to that experienced on a VR schedule, than on a VI+ schedule with the same feedback function as the VR schedule. Taken together these results suggest that rats are more sensitive to the molecular than the molar properties of the schedules.

Animals↗
PubMed2000

Serial position effects in recognition memory for odors.

Five experiments examined recognition memory for sequentially presented odors. Participants were presented with a sequence of odors and then had to identify an odor from the list in a test probe containing 2 odors. All experiments demonstrated enhanced recognition of odors presented at the start and end of a series, compared with those presented in the middle of the series when a 3-s retention interval between list termination and test was used. In Experiments 2 and 3, when a 30-s or 60-s retention interval was used, participants performed at slightly lower levels, although the serial position function was similar to that obtained with the 3-s retention interval. These results were noted with a 5-item (Experiments 1 and 4), 7-item (Experiment 2), 6-item (Experiment 3), and 4-item (Experiment 5) list of odors. As the number of test trials increased, recognition performance decreased, indicating a strong role for olfactory fatigue or interference in these procedures. A verbal suppression task, used in Experiments 4 and 5, had little influence on serial-position-based performance.

Adult↗
PubMed2000

Effect of cricoid pressure on insertion of and ventilation through the cuffed oropharyngeal airway.

We have assessed the effect of cricoid pressure on insertion of and ventilation through the cuffed oropharyngeal airway (COPA) in 53 patients, in a double-blind, randomized study. Two anaesthetists assessed adequacy of ventilation in anaesthetized and paralysed patients at the same time but using different methods. The first assessed ventilation clinically, by observing synchronized chest expansion with gentle manual ventilation and the second noted measurements of tidal volume (VT) and peak inspiratory pressure (PIP). Five mask ventilated breaths ('baseline') were assessed as above. Patients were then allocated randomly to receive cricoid pressure (group A, n = 28) or no cricoid pressure (group B, n = 25). Five further mask ventilated breaths ('after manoeuvre') were again assessed. A COPA was then inserted and five further breaths ('after COPA') were assessed. A COPA was inserted at the first attempt in all patients except for one in group A who required two attempts. COPA placement was difficult in one patient in group B who had a small distance between the incisor teeth. Ventilation was clinically 'adequate' in all patients except for one in the cricoid pressure group. There were no significant differences in measured VT or PIP between 'baseline' and 'after manoeuvre' breaths. Significant differences in VT and PIP were found after COPA insertion in the group that received cricoid pressure, with a mean decrease in VT of 108 ml (P = 0.0049) and a mean increase in PIP of 5.2 cm H2O (P = 0.0111).

Adult↗
PubMed2000

The impact of angiotensin-converting enzyme inhibitors on managed care: economic, clinical, and humanistic outcomes.

This article examines evidence of the improved clinical, economic, and humanistic outcomes associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) in clinical practice, in particular in the areas of hypertension, diabetic nephropathies, post-myocardial infarction, and congestive heart failure. Pharmacodynamic and pharmacokinetic differences may exist among this class, however, these may not be clinically relevant when the drugs are given in equivalent doses. Although additional studies are necessary before a class effect can be assumed for each of these outcomes, it is important for clinicians to consider all of these outcomes when using ACEIs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

A comparison of clinical response to electroconvulsive therapy in puerperal and non-puerperal psychoses.

BACKGROUND: There is a widespread belief that puerperal psychosis is particularly responsive to electroconvulsive therapy (ECT), but research evidence for this is lacking. METHOD: We have conducted a retrospective case-note study of clinical improvement following ECT in puerperal and non-puerperal psychosis. The main outcome measure was improvement in mental state at the end of a course of ECT, rated by a blind rater on a simple four-point scale. Additional indicators of responsiveness to ECT were improvement in mental state 4 weeks after stopping ECT, duration of in-patient stay following ECT and number of ECT received. RESULTS: Women with puerperal psychosis showed greater clinical improvement than women with non-puerperal psychosis. The results were not explained by the greater preponderance of depressive illness in the puerperal group, as the same results were also found when the analysis was confined to women with a clinical diagnosis of depressive illness. CONCLUSION: These findings are the first evidence of a particular sensitivity of ECT in puerperal psychosis. However, they are preliminary and a number of explanations are possible, including good responsiveness to treatment in general. A prospective study using standardised clinical ratings and definitions of key variables is now required. CLINICAL IMPLICATIONS: Clinicians treating severe postpartum illness should continue to regard ECT as a treatment option. LIMITATIONS OF THE STUDY: The study is limited by its reliance on retrospective examination of information recorded in case notes. Ratings of clinical improvement were not standardised.

Adult↗
PubMed1999

Treatment of newly diagnosed AML, RAEB-t or RAEB with lisofylline or placebo in addition to chemotherapy.

To determine whether the addition of lisofylline (LSF) to idarubicin (12 mg/m2 daily x 3) + ara-C (1.5 g/m2 daily x 4) affects the rates of infection, serious infection, CR or mortality during remission induction of newly diagnosed AML, RAEB-t or RAEB, we randomized 70 patients to 3 mg/kg lisofylline or placebo every 6 h i.v., to begin 6 h before the first dose of idarubicin and to continue until recovery of neutrophil and platelet counts or for 28 days, whichever came first. Eligibility required that patients be below age 71 years, have no history of abnormal counts, or chemotherapy for a prior malignancy, and have a creatinine <1.6 mg/dl and bilirubin <3.0 mg/dl. The study was double-blinded and infections were tabulated separately and independently at MD Anderson and by a three-member outside panel of experts. Logistic regression was used to assess the relative effects of treatment arm (LSF or placebo), age, performance status, treatment site (laminar air flow room or not), and cytogenetics on rates of infection and serious infection following the first course of chemotherapy, and on CR rate. There were 84% and 87% concordance between the expert panel and MD Anderson enumerations of infection and serious infections, respectively. Both analyses found no significant (P < 0.05) differences between the rates of infection, or serious infection, in the placebo and LSF groups. CR, 60-day, and overall mortality rates were similar in the two groups, as were time to neutrophil and blood count recovery and outcome once in CR. Logistic regression analyses supported the above conclusions. Severe nausea/vomiting and mucositis were more frequent in the LSF group. Our results suggest that larger studies of LSF in newly diagnosed AML, RAEB-t, or RAEB are not warranted.

Acute Disease↗