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Biomedical subjects

L Cooke

Publications and source records attributed to L Cooke.

At least 19 recordsLinked to original sources

Nephrotoxic effects of immunosuppressant therapy in pediatric liver transplant recipients.

Drugs used for immunosuppression have been implicated in causing numerous long-term side effects including nephrotoxicity, glucose intolerance, and hyperlipidemia. In this study, we reviewed our pediatric liver transplant recipients in terms of glomerular filtration rate (GFR) as well as fasting glucose and lipid profiles. To date, 79 pediatric liver transplantations have been performed at our center: 24 transplantations of at least 5 months to a maximum of 7.3 years posttransplant are reviewed herein. The mean time posttransplantation was 2.1 years. Nine boys and 15 girls showed a distribution of 19 mixed race, 3 black, and 2 white patients. The mean age at the time of transplantation was 6.6 years (0.8-13.3 years) with 8 cases under the age of 3 years. All recipients started with Cyclosporine Neoral (CSA) as first line, but, at the time of testing, immunosuppression included 5 children on CSA and 19 on Tacrolimus. Radionuclide 51 Cr-EDTA Glomerular Filtration Rates (GFR) showed a range from 21 to 220 mL/min/1.73 m2 (mean 96.1, median 89.8). Seven cases had a GFR less than 75 mL/min/1.73 m2. Twenty-one children were on antihypertensives agents: 15 children on 1 agent and 6 children on 2 agents. On full fasting lipid profiles, the total cholesterol ranged from 2 to 7.9 mmol/L (mean 4.4). Only 1 child is currently on statin therapy. Fasting glucose ranged from 3.2 to 5.9 mmol/L (mean 4.1) No difference was observed in glucose values between CsA and Tacrolimus. Thus, immunosuppressive therapies, such as the calcineurin inhibitors, are known to cause nephrotoxicity, which is of concern in pediatric liver transplant recipients. Almost all our patients currently require antihypertensive therapy. At present, the renal function is adequate in the majority of the group, but this study needs to be extended to other pediatric liver transplant recipients with particular emphasis on those who are more than 5 years posttransplantation.

Adolescent↗

Liver transplantation for children: Red Cross Children's Hospital experience.

BACKGROUND: The liver transplant program for infants and children at the Red Cross Children's Memorial Hospital is the only established pediatric service in sub-Saharan Africa. Since 1985, 250 infants and children have been assessed and 155 accepted for transplantation. METHODS: Since 1987, 76 children (range 6 months to 14 years) have had 79 liver transplants, with biliary atresia being the most frequent diagnosis. The indications for transplantation include biliary atresia (n = 44), metabolic (n = 7), fulminant hepatic failure (n = 10), redo transplants (n = 3), and other (n = 15). Three combined liver/kidney transplants have been performed. Forty-nine were reduced-size transplants with donor: recipient weight ratios ranging from 2:1 to 11:1, and 29 children weighed < 10 kg. RESULTS: Fifty-six (74%) patients survived 3 months to 12 years posttransplant. Cumulative 1- and 5-year patient survival data are 79% and 70%, respectively. However, with the introduction of prophylactic intravenous gancyclovir and the exclusion of hepatitis B virus (HBV) IgG core Ab-positive donors, the projected 5-year pediatric survival has been >80%. Early (<1 month) post-liver-transplant mortality was low, but included: primary malfunction (n = 1); inferior vena cava thrombosis (n = 1); bleeding esophageal ulcer (n = 1); and sepsis (n = 1). Late morbidity and mortality was mainly due to infections: de novo hepatitis B (5 patients, 2 deaths); Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disease (12 patients, 7 deaths); and cytomegalovirus disease (10 patients, 5 deaths). Tuberculosis (TB) treatment in three patients was complicated by chronic rejection (n = 1) and TB drug-induced subfulminant liver failure (n = 1). CONCLUSIONS: Despite limited resources, a successful pediatric program has been established with good patient and graft survival figures and excellent quality of life. Shortage of donors due to HBV and human immunodeficiency virus (HIV) leads to significant waiting list mortality and infrequent transplantation.

Adolescent↗

Prospective evaluation of the value of direct referral hearing aid clinic in management of young patients with bilateral hearing loss.

The purpose of this study was to evaluate the value and effectiveness of a direct referral hearing aid clinic (DRHAC) in providing appropriate hearing aids to young patients aged 18-60 years while at the same time identifying patients with significant ear disease who need an otologist's opinion. The patients were referred to a tertiary referral hearing assessment clinic. A total of 137 patients (18-60 years) met the criteria to be included in the study to be assessed in the clinic by both an audiometrician and an otologist. The main outcome measures were hearing evaluation and audiometrician's management. Of them, 114 patients attended the research clinic (83%), 23 patients (17%) did not attend the clinic and 57 patients (51%) did not need any treatment or further investigation as their hearing was normal or near normal. Thirty patients (27%) were given hearing aids. Twenty-five patients (22%) failed the audiometrician assessment and were referred to the otologist. Only 13 (18%) of the 25 patients referred for an otological opinion actually required further investigations, medical or surgical treatment. DRHAC is as viable a system in the younger as in the elderly population.

Acoustic Impedance Tests↗

Indomethacin for asymptomatic patent ductus arteriosus in preterm infants.

BACKGROUND: Patent Ductus Arteriosus (PDA remains a significant cause of mortality and morbidity in premature infants. Indomethacin is an effective treatment to close a PDA, and has been used for many years with several treatment regimes, including prophylactic use in all at risk premature infants. There are however concerns regarding adverse side effects of indomethacin. By targeting a group of infants with an asymptomatic PDA, rather than treating all VLBW infants prophylactically, indomethacin use would be restricted, limiting the possibility of significant side effects to those with greater chance of benefit. OBJECTIVES: To assess whether in premature neonates with asymptomatic PDA, treatment with indomethacin improves short and long term outcomes; in particular: incidence of symptomatic PDA, mortality, chronic neonatal lung disease (CLD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), neurodevelopmental outcome, length of ventilation. SEARCH STRATEGY: Standard strategies of the Cochrane Neonatal Review Group were used. Searches were made of the Oxford Database of Perinatal Trials, MEDLINE and EMBASE from 1966 to September 2002, CINAHL from 1982 to September 2002, and the Cochrane Controlled Trials Register (CENTRAL/CCTR) in The Cochrane Library, Issue 3, 2002. Searches were also made of previous reviews including cross-referencing, abstracts, and conference and symposia proceedings published in Pediatric Research. SELECTION CRITERIA: All randomised controlled trials of indomethacin compared with placebo or no intervention for the treatment of asymptomatic PDA in premature infants were eligible. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Neonatal Review Group were used. Trials identified by the search strategy were independently reviewed by each author and assessed for eligibility and trial quality. Data were then extracted independently by each author and compared, with any differences resolved following discussion. Any additional information required was requested from trial authors. Only published data was available for review. Results are expressed as typical relative risk and typical risk difference for dichotomous outcomes, and weighted mean difference for continuous variables. MAIN RESULTS: Three small trials involving a total of 97 infants were included. Meta analysis of combined data was possible for seven outcomes. Treatment of an asymptomatic PDA with indomethacin significantly reduced the incidence of symptomatic PDA (RR 0.36, 95% CI 0.19, 0.68) and duration of supplemental oxygen (WMD -12.5, 95% CI -23.8, -1.26). There was no evidence of effect on mortality (RR 1.32, 95% CI 0.45, 3.86), CLD (RR 0.91, 95% CI 0.62, 1.35), IVH (RR 1.21, 95% CI 0.62, 2.37), ROP (RR 0.68, 95% CI 0.26, 1.78), or length of ventilation (WMD -7.00 days, 95%CI -17.33, 3.34). Long term neurodevelopmental outcomes were not reported. One trial reported a significant reduction in the duration of supplemental oxygen following treatment with indomethacin in the subgroup of infants with birth weight less than 1000g. REVIEWER'S CONCLUSIONS: This review demonstrates a significant decrease in the incidence of symptomatic PDA following treatment of an asymptomatic PDA with indomethacin. There is also a small but statistically significant decrease in the duration of requirement for supplemental oxygen. There are no reported long term outcomes in the included trials, and so it is not possible to comment on possible long term effects. Further studies are required to determine the long term benefits or harms of closing a PDA prior to the onset of symptoms.

Cyclooxygenase Inhibitors↗

Modifying children's food preferences: the effects of exposure and reward on acceptance of an unfamiliar vegetable.

OBJECTIVE: The aim of this study was to evaluate two interventions (one reward-based and one exposure-based) for increasing children's acceptance of an unfamiliar vegetable compared with a no-treatment control. It was predicted that the exposure condition would increase liking for, and consumption of, the vegetable relative to either the reward or control group. DESIGN: Using a randomized controlled design, participants were assigned to one of two intervention groups (exposure or reward) or to a no-treatment control condition, for a 2 week period. Liking for, and consumption of, red pepper was assessed before and after the treatment period. SETTING: The study was conducted in three primary schools in London. SUBJECTS: Parental consent was obtained for 49 out of a possible 72 children. INTERVENTIONS: Interventions comprised eight daily sessions during which participants in the exposure group were offered a taste of sweet red pepper and told that they could eat as much as they liked. Participants in the reward group were shown a sheet of cartoon stickers and told that they could choose one of them on condition that they ate at least one piece of the pepper. RESULTS: The exposure-based intervention significantly increased both liking (P=0.006) and consumption (P=0.03) compared with the control group. The outcome of the reward intervention was intermediate and did not differ significantly from the exposure or control conditions. CONCLUSIONS: Repeated exposure to the taste of unfamiliar foods is a promising strategy for promoting liking of previously rejected foods in children.

Child↗

Doctors' professional values: results from a cohort study of United Kingdom medical graduates.

OBJECTIVES: To examine young doctors' views on a number of professional issues including professional regulation, multidisciplinary teamwork, priority setting, clinical autonomy and private practice. METHOD: Postal survey of 545 doctors who graduated from United Kingdom medical schools in 1995. RESULTS: Questionnaires were returned by 95% of the cohort (515/545). On issues of professional regulation, teamwork and clinical autonomy, the majority of doctors held views consistent with current General Medical Council guidance. The majority supported the right of doctors working in the NHS to engage in private practice. Most respondents thought that public expectations of doctors, medicine and the NHS were too high, and that some form of rationing was inevitable. On many issues there was considerable variation in attitudes on the basis of sex and intended branch of medicine. CONCLUSIONS: The results highlight the heterogeneity of the profession and the influence of specialty and gender on professional values. Doctors' attitudes had also been shaped by broader social changes, especially debates surrounding regulation of the profession, rising public expectations and the need for rationing of NHS care.

Adult↗

Searching for one versus two identical targets: when visual search has a memory.

A recent study has suggested that observers' visual explorations of the external world can proceed unimpaired when the visual environment precludes the operation of memory processes (as, for instance, when the display elements change locations every 100 ms). One theoretical limitation of this study was that distractors were the only elements that had the potential to be tagged during visual search. The present study sought to clarify the amnesic-search hypothesis by investigating whether memory processes can guide search in other contexts in which targets also have the potential to be tagged. Accordingly, the experimental conditions of the previous study were repeated using a different search task in which observers had to decide whether one target or two were present among a variable number of similar distractors. Under these search conditions, the present findings provided strong evidence that memory processes can guide visual search.

Adult↗

Education and training in the senior house officer grade: results from a cohort study of United Kingdom medical graduates.

INTRODUCTION: This paper shows the findings from a survey of 439 senior house officers undertaken as part of the British Medical Association cohort study of 1995 medical graduates. The aim of the study was to assess the quality of senior house officer training in the United Kingdom. METHOD: In July 1997 a postal questionnaire was sent to a sample of 545 doctors who graduated from medical school in 1995. Responses were received from 515 (95%). Only those doctors who had worked as a senior house officer in the previous 12 months were included in the analysis (n = 439). RESULTS: Encouraging results are that 69% of the senior house officers surveyed had discussed their progress directly with their consultant, and 24% rated their supervision by their consultant as 'excellent'. Of concern are the findings that 47% of respondents did not receive protected teaching time and 16% were unable to take study leave. DISCUSSION: The study revealed wide variability in the quality of training received by senior house officers in the United Kingdom. Whilst some respondents - notably those in general practice, accident and emergency, paediatrics and psychiatry - had enjoyed a high standard of education and training, it was clear that a minority of posts continue to offer little if any educational value to the post holder. The results point to a need for a more systematic approach to maintaining standards in senior house officer training with greater incentives for under-performing trusts.

Attitude↗

Papillon-Lefèvre syndrome: a case report.

This case report discusses a very rare condition; Papillon-Lefèvre Syndrome. This is an autosomal recessive condition in which the main features are hyperkeratosis of the palms and the soles and severe periodontal destruction.

Child, Preschool↗

Is erythrocyte alkaline phosphatase activity a marker of zinc status in humans?

The identification of an enzyme activity that responds to changes in Zn intake may serve as a useful biomarker for Zn status. Alkaline phosphatase (ALP) is a dimeric protein with each subunit containing two Zn atoms. The activity of ALP in erythrocytes (E) decreases as a result of a low Zn diet, which suggests that this enzyme may be a marker of Zn status. To investigate this further, we determined the response of E-ALP in six healthy subjects following supplementation with 50 mg Zn (4.2 x RDI) daily for 4 wk. A small but significant increase in plasma Zn was observed with supplementation (p < 0.05), whereas there was no significant change in E-Zn over the same period. Plasma and E-Cu showed no change. Conversely, the activity of E-ALP increased in all subjects from 1.7 +/- 0.5 to 5.9 +/- 0.7 U/g protein (mean +/- SE) (p < 0.0001). The small change observed in plasma Zn is not biologically significant in view of the many documented factors that influence its concentration. Our data support the hypothesis that E-ALP is a marker of Zn status in humans.

Adult↗

Differences in beta adrenergic receptor agonist affinity between cardiac myocytes and coronary arterioles in canine heart.

Beta adrenergic receptors (beta AR) are localized in several tissue compartments of the heart, including cardiac myocytes, coronary arteries and coronary arterioles, but it is unclear whether there are differences between tissues in beta AR coupling to G protein. The goal of these studies was to use receptor autoradiography to analyze beta receptor agonist binding characteristics in different tissue compartments of dog heart, including ventricular myocytes (predominantly beta-1) and coronary arterioles (predominantly beta-2). Frozen sections were incubated in [125I]-pindolol with the beta agonist isoproterenol in the absence and presence of 0.1 mM sodium 5'-guanylylimidodiphosphate (GppNHp, a nonhydrolyzable GTP analog) and analyzed by gamma counting or autoradiography. Nonlinear curve-fitting analyses of ventricular section radioactivity indicated that in the absence of GppNHp, the data were consistent with a two-site fit, with 88% of the receptors in the high-affinity state. In autoradiographic analyses, GppNHp displaced the agonist binding curve to a greater extent in arterioles (approximately 100-fold) than in myocytes (approximately 10-fold). This suggests that beta receptors on arterioles are more tightly coupled to G protein than are beta receptors on myocytes. Thus these studies suggest that 1) beta AR on arterioles are coupled more tightly to G protein than are beta AR on myocytes, possibly because of differences in beta receptor subtype, and 2) more beta AR are in the high-affinity state than has been reported previously in more traditional analyses on membrane preparations.

Adrenergic beta-Agonists↗