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D Smith

Publications and source records attributed to D Smith.

At least 73 records · Page 4Linked to original sources
PubMed2003

The Strengths and Difficulties Questionnaire: a pilot study of a new computer version of the self-report scale.

A computer-based version of the self-report Strengths and Difficulties Questionnaire (SDQ) was developed with colourful graphics illustrating each question. One hundred and two children referred to child and adolescent mental health services were recruited and randomly allocated to complete either the new computer-based version or the paper original. A further 112 children from local schools were recruited and completed the computer-based version of the scale. All children who took part in the study were aged between 8 and 15 years. The paper version of the SDQ is recommended for use in children aged 11 and over and, in this age group, the computer-based questionnaire was able to discriminate between the clinical and community sample (ROC = 0.761, 95 % CI 0.676-0.846). Comparison of the paper-based SDQ and computer-based SDQ within the clinic sample found trends towards better test-retest reliability, inter-rater reliability and significantly better user satisfaction in the computer version compared to the paper-based version. The computer-based SDQ has the added advantage of results being automatically added to a spreadsheet out of view from the user reducing the chance of operator error in coding and entering the data. These preliminary results suggest that the computer-based version of the SDQ may represent a further improvement on the paper SDQ. All versions of the SDQ, including the computer-based version, can be downloaded from the Strengths and Difficulties website address www.sdqinfo.com.

Adolescent↗
PubMed2003

A long-term follow-up report on allogeneic stem cell transplantation for patients with primary refractory acute myelogenous leukemia: impact of cytogenetic characteristics on transplantation outcome.

The prognosis of patients with primary refractory acute myelogenous leukemia (AML) is poor. Our initial report suggested that some patients could achieve durable remission after allogeneic stem cell transplantation (SCT). Herein, we update our initial experience and report further analysis of this group of patients to determine whether there are pre-SCT prognostic factors predictive of posttransplantation relapse and survival. We reviewed the records of 68 patients who consecutively underwent transplantation at the City of Hope Cancer Center with allogeneic SCT for primary refractory AML between July 1978 and August 2000. Potential factors associated with overall survival and disease-free survival were examined. With a median follow-up of 3 years, the 3-year cumulative probabilities of disease-free survival (DFS), overall survival (OS), and relapse rate for all 68 patients were 31% (95% confidence interval [CI], 20%-42%), 30% (95% CI, 18%-41%), and 51% (95% CI, 38%-65%), respectively. In multivariate analysis, the only variables associated with shortened OS and DFS included the use of an unrelated donor as the stem cell source (relative risk, 2.23 [OS] and 2.05 [DFS]; P =.0005 and.0014, respectively) and unfavorable cytogenetics before SCT (relative risk: 1.68 [OS] and 1.58 [DFS]; P =.0107 and.0038, respectively). Allogeneic SCT can cure approximately one third of patients with primary refractory AML. Cytogenetic characteristics before SCT correlate with transplantation outcome and posttransplantation relapse.

Adolescent↗
PubMed2003

The substance P (NK1) receptor antagonist L-760735 inhibits fear conditioning in gerbils.

The ability of the substance P (NK(1) receptor) antagonist (SPA) L-760735 to inhibit conditioned fear was assessed in gerbils using a four plate apparatus. Animals that had been treated with diazepam (3 mg/kg) or L-760735 (3 mg/kg) 30 min before a 3 min conditioning session in the apparatus exhibited a release of plate crossings during the retest session approximately 3 h later. Plate crossings were also increased when animals received diazepam or L-760735 30 min before the retest session. In contrast, fluoxetine and venlafaxine (30 mg/kg) did not exhibit anxiolytic-like effects. During the retest session, gerbils drummed their hind feet on the floor; this behaviour was not observed spontaneously in gerbils that were naïve to the apparatus. Foot drumming was abolished by pretreatment with L-760735 or diazepam (3 mg/kg) but was markedly increased following administration of fluoxetine or venlafaxine (30 mg/kg). Foot drumming elicited by aversive conditioning alone or in combination with fluoxetine was abolished by administration of L-760735 and by amygdala lesions involving the basolateral and lateral nuclei, indicating that this behaviour is an alarm signal or fear response mediated via release of substance P in brain circuits involving the amygdala. The observations provide further evidence for an anxiolytic-like profile of SPAs in preclinical assays and demonstrate a clear difference between the actions of SPAs and established antidepressant drugs.

Amygdala↗
PubMed2003

Chronic lithium treatment with or without haloperidol fails to affect the morphology of the rat cerebellum.

We used unbiased stereological principles to determine whether long-term administration of lithium at human therapeutic levels, with or without haloperidol, affects the number or sizes of cerebellar Purkinje cells or the volume of histological layers in the rat cerebellum. Twenty-eight rats were randomly divided into three groups, receiving either no treatment, lithium, or lithium combined with haloperidol. The serum lithium levels ranged from 0.50 to 0.77 mmol/l. Haloperidol was given at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the cerebelli were histologically prepared. No statistically significant differences were observed between the groups with respect to the cerebellar measures.

Animals↗
PubMed2003

A critical period for retinoic acid teratogenesis and loss of neurophilic migration of pontine nuclei neurons.

Abnormalities in the pontine nuclei (PN) and inferior olive are hallmarks of human retinoic acid (RA) teratogenesis. This study shows that RA exposure of the mouse at a specific embryonic stage alters morphological structures that derive from the wall of the IVth ventricle to form components of the precerebellar system (the inferior olivary nucleus and the PN). The study employs both normal and a RAREhspLacZ transgenic RA reporter mouse. It is shown that abnormalities in the PN and inferior olive result from exposure at a critical period of embryonic day 9.5 and 10.5. The abnormalities in the PN are due to a failure in their usual neurophilic migration. The compact stream of cells that leads from the anterior rhombic lip to the ventral pons is instead scattered widely over the anterior medulla. Given that the RA exposure occurs after the resolution of rhombomere identity this suggests that teratogenic RA interferes with a regulatory event that overlays this original pattern.

Abnormalities, Drug-Induced↗
PubMed2003

A phase II/III study comparing intravenous ZD9331 with gemcitabine in patients with pancreatic cancer.

ZD9331 is a novel antifolate inhibitor of thymidylate synthase (TS). This multicentre, randomised, phase II/III study compared the efficacy and safety of ZD9331 with gemcitabine in 55 patients with chemonai;ve, locally advanced or metastatic pancreatic cancer. Patients received intravenous (i.v.) ZD9331 (n=30), on days 1 and 8 of a 3-week cycle or i.v. gemcitabine (n=25), once a week for 7 weeks followed by a 1-week rest, then on days 1, 8 and 15 of a 4-week cycle. Objective tumour response and clinical benefit response (CBR) were similar for both groups. More ZD9331 patients were alive at the data cut-off point compared with gemcitabine patients (13 and 8%, respectively). Median survival (152 versus 109 days, respectively) and time to progression (70 versus 58 days, respectively) were longer in the ZD9331 group. Nausea and vomiting (grade 1/2) were the most common toxicities in both groups. These results suggest that, in pancreatic cancer, ZD9331 is equivalent to gemcitabine and may offer a promising alternative to current therapies.

Adult↗
PubMed2003

Reduced-intensity allogeneic stem cell transplantation for patients whose prior autologous stem cell transplantation for hematologic malignancy failed.

Autologous hematopoietic stem cell transplantation (autoSCT) is an effective treatment for patients with various hematologic malignancies. Despite the significant improvement in the overall outcome, disease progression after transplantation remains the major cause of treatment failure. With longer follow-up, therapy-related myelodysplasia/acute myelogenous leukemia is becoming an important cause of treatment failure. The prognosis for these 2 groups of patients is very poor. Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potential curative treatment for these patients. However, the outcome with conventional myeloablative alloSCT after failed autoSCT is typically poor because of high transplant-related mortality. In an attempt to reduce the treatment-related toxicity, we studied a reduced-intensity conditioning regimen followed by alloSCT for patients with progressive disease or therapy-related myelodysplasia/acute myelogenous leukemia after autoSCT. This report describes the outcomes of 28 patients with hematologic malignancies who received a reduced-intensity alloSCT after having treatment failure with a conventional autoSCT. Fourteen patients received a hematopoietic stem cell transplant from a related donor and 14 from an unrelated donor. The conditioning regimen consisted of low-dose (2 Gy) total body irradiation with or without fludarabine in 4 patients and the combination of melphalan (140 mg/m(2)) and fludarabine in 24. Cyclosporine and mycophenolate mofetil were used for posttransplantation immunosuppressive therapy, as well as graft-versus-host disease (GVHD) prophylaxis, in all patients. All patients engrafted and had >90% donor chimerism on day 100 after SCT. Currently, 13 patients (46%) are alive and disease free, 7 patients (25%) developed disease progression after alloSCT, and 8 (32%) died of nonrelapse causes. Day 100 mortality and nonrelapse mortality were 25% and 21%, respectively. With a median follow-up of 24 months for surviving patients, the 2-year probabilities of overall survival, event-free survival, and relapse rates were 56.5%, 41%, and 41.9%, respectively. Six patients (21%) developed grade III to IV acute GVHD. Among 21 evaluable patients, 15 (67%) developed chronic GVHD. We conclude that (1) reduced-intensity alloSCT is feasible and has an acceptable toxicity profile in patients who have previously received autoSCT and that (2) although follow-up was short, a durable remission may be achieved in some patients who would otherwise be expected to have a poor outcome.

Adult↗
PubMed2003

The heart failure revascularisation trial (HEART): rationale, design and methodology.

BACKGROUND: Most patients with heart failure due to left ventricular systolic dysfunction (LVSD) secondary to coronary artery disease (CAD) have evidence of myocardium in jeopardy (reversible ischaemia and/or stunning hibernation). It is not known whether revascularisation in such cases is safe or beneficial. AIMS: To determine whether revascularisation will improve the survival of patients with LVSD and heart failure secondary to CAD and myocardium in jeopardy. METHODS: This is a randomised controlled trial comparing revascularisation or not, in addition to optimal medical therapy with ACE inhibitors, beta-blockers, aldosterone antagonists and an anti-thrombotic agent. Patients must have heart failure requiring treatment with diuretics, a left ventricular ejection fraction <35% and evidence of coronary disease. Myocardial viability and ischaemia are assessed by a broad range of techniques including stress echocardiography and nuclear imaging. All imaging tests are reviewed in core laboratories to ensure uniform reporting. Any conventional revascularisation technique is permitted. The primary outcome measure is all cause mortality. Symptoms, quality of life and health economic issues will also be explored. Assuming an annual mortality of 10% in the control group and allowing for substantial cross-over rates, a study of 800 patients followed for 5 years has 80% power with an alpha of 0.05 (two-sided) to show a 25% reduction in mortality with revascularisation. RESULTS: At the time of writing 180 patients have been screened for inclusion, 111 have consented to participate and 70 have been randomised. The results of viability testing are awaited in 22 patients. Twenty-six patients had been investigated for myocardial viability and/or by angiography prior to consent, as part of the routine practice in that cardiology department. Of 68 patients who have completed assessment only after consent, 47 (69%) were included. The principal reason for drop-out between consent and randomisation was lack of evidence of myocardial ischaemia or hibernation. CONCLUSION: The HEART trial will help to determine whether investigation of myocardial ischaemia and/or viability with a view to revascularisation should become part of the routine care of patients with heart failure due to LVSD and CAD.

Coronary Artery Disease↗
PubMed2003

Prospective randomised double-blind comparative study of rocuronium and pancuronium in adult patients scheduled for elective 'fast-track' cardiac surgery involving hypothermic cardiopulmonary bypass.

The majority of cardiac anaesthetists in the UK use pancuronium for fast-track cardiac surgery. We compared the duration of action of pancuronium and rocuronium in patients undergoing fast-track hypothermic cardiopulmonary bypass and cardiac surgery. We determined whether patients would have had residual neuromuscular blockade at extubation. Twenty patients were randomly allocated to receive either pancuronium 0.1 mg x kg(-1) or rocuronium 1 mg x kg(-1). Neuromuscular function was assessed by acceleromyography; spontaneous recovery was evaluated by the train-of-four ratio measured at the adductor pollicis longus muscle. Median times to recover train-of-four ratio of 0.9 were 3 h 38 min for rocuronium and 7 h 52 min for pancuronium. The median difference in recovery times was 4 h 15 min (95% CI 2 h 30 min to 6 h 20 min; p = 0.0003 by Mann-Whitney test). None of the patients in the rocuronium group and seven of 10 patients in the pancuronium group had their extubations delayed because of residual neuromuscular blockade. Unless fast-track patients have neuromuscular function assessed before extubation, pancuronium should not be used.

Aged↗
PubMed2003

HIV lipodystrophy: prevalence, severity and correlates of risk in Australia.

OBJECTIVE: To establish the prevalence, severity and factors associated with the HIV lipodystrophy syndrome. METHODS: Cross-sectional study of lipodystrophy conducted in high HIV caseload primary care sites and HIV outpatient clinics. A subset of patients was examined using dual energy X-ray absorptiometry (DEXA) and single cut abdominal computerized tomography (CT) at the L4 vertebral level to quantify regional and total body fat. Factors associated with lipodystrophy, lipoatrophy and lipohypertrophy were assessed using multiple logistic regression based on assignment of cases and non-cases. RESULTS: One thousand, three hundred and forty-eight patients (95% male) were surveyed, 20% had AIDS, the mean CD4 lymphocyte count was 486 cells/microL, and 55% had <500 HIV-1 RNA copies/mL. Most participants (87%) had previously received or were currently receiving combination antiretroviral therapy, 73% with at least one protease inhibitor (PI) and 14% a non-PI-containing regimen. Lipodystrophy prevalence was 53% and of these, 55% reported both peripheral lipoatrophy and central lipohypertrophy, 31% experienced peripheral lipoatrophy only and 14% had central lipohypertrophy only. The prevalence of any body habitus change was 62% in PI-experienced patients, 33% in PI-naive patients and 21% in antiretroviral-naive patients. Lipodystrophy severity was less in antiretroviral-naive patients and most severe in PI-experienced patients. Increasing severity of lipodystrophy was both positively and significantly correlated with elevated liver enzymes, decreased testosterone levels, decreased skin-fold thickness, lower levels of total and peripheral fat (DEXA) and higher levels of visceral fat (CT). Lipodystrophy was also significantly associated with increasing age, symptomatic HIV disease, effective viral suppression, and increasing duration of therapy with both nucleoside reverse transcriptase inhibitors and PIs. CONCLUSIONS: The prevalence and severity of lipodystrophy reflects both length and type of treatment with antiretroviral therapy and is associated with decreased testosterone, increases in liver enzymes and greater suppression of HIV RNA. The reports of lipodystrophy in a small percentage of antiretroviral-naive patients suggests that factors other than antiretroviral therapy may be involved in the aetiology of this syndrome or that some conditions, such as wasting or age-associated obesity, may mimic lipoatrophy and lipohypertrophy, respectively.

Absorptiometry, Photon↗
PubMed2003

Practical system to detect and assess consequences of radioactivity in a wound.

Any wound received within the controlled areas of Dounreay could potentially be contaminated with plutonium and/or uranium isotopes. Wounding bypasses the body's natural barriers to foreign objects, such as the skin and the lining of the alimentary canal. Therefore a relatively low intake can potentially result in a high committed effective dose. The likelihood of contamination of a wound with either plutonium or uranium is low. The decision-making process for dealing with wounds has been continually reviewed and updated by the approved dosimetry service (ADS) at Dounreay. Each wound is considered on an individual basis by the ADS in order to decide what follow-up actions, if any, are necessary. The aim of the process is to maximise the probability that a significant intake is detected, while targeting resources in an appropriate manner.

Decontamination↗
PubMed2003

Comparative studies of high performance swimming in sharks II. Metabolic biochemistry of locomotor and myocardial muscle in endothermic and ectothermic sharks.

Metabolic enzyme activities in red (RM) and white (WM) myotomal muscle and in the heart ventricle (HV) were compared in two lamnid sharks (shortfin mako and salmon shark), the common thresher shark and several other actively swimming shark species. The metabolic enzymes measured were citrate synthase (CS), an index of aerobic capacity, and lactate dehydrogenase (LDH), an index of anaerobic capacity. WM creatine phosphokinase (CPK) activity, an index of rapid ATP production during burst swimming, was also quantified. Enzyme activities in RM, WM and HV were similar in the two lamnid species. Interspecific comparisons of enzyme activities at a common reference temperature (20 degrees C) show no significant differences in RM CS activity but higher CS activity in the WM and HV of the lamnid sharks compared with the other species. For the other enzymes, activities in lamnids overlapped with those of other shark species. Comparison of the HV spongy and compact myocardial layers in mako, salmon and thresher sharks reveals a significantly greater spongy CS activity in all three species but no differences in LDH activity. Adjustment of enzyme activities to in vivo RM and WM temperatures in the endothermic lamnids elevates CS and LDH in both tissues relative to the ectothermic sharks. Thus, through its enhancement of both RM and WM enzyme activity, endothermy may be an important determinant of energy supply for sustained and burst swimming in the lamnids. Although lamnid WM is differentially warmed as a result of RM endothermy, regional differences in WM CS and LDH activities and thermal sensitivities (Q(10) values) were not found. The general pattern of the endothermic myotomal and ectothermic HV muscle metabolic enzyme activities in the endothermic lamnids relative to other active, ectothermic sharks parallels the general pattern demonstrated for the endothermic tunas relative to their ectothermic sister species. However, the activities of all enzymes measured are lower in lamnids than in tunas. Relative to lamnids, the presence of lower WM enzyme activities in the thresher shark (which is in the same order as the lamnids, has an RM morphology similar to that of the mako and salmon sharks and may be endothermic) suggests that other factors, such as behavior and swimming pattern, also affect shark myotomal organization and metabolic function.

Adaptation, Biological↗
PubMed2003

Estimation of linkage disequilibrium in a sample of the United Kingdom dairy cattle population using unphased genotypes.

The association between genetic marker alleles was estimated for two regions of the bovine genome from a random sample of 50 young dairy bulls born in the United Kingdom between 1988 and 1995. Microsatellite marker genotypes were obtained for six markers on chromosome 2 and seven markers on chromosome 6, spanning 38 and 20 cM, respectively. Two different methods, which do not require family information, were used to estimate population haplotype frequencies. Haplotype frequencies were estimated for pairs of loci using the expectation-maximization algorithm and for all linked loci using a Bayesian approach via a Markov chain-Monte Carlo algorithm. Significant (P = 0.0007) linkage disequilibrium was detected between pairs of loci in syntenic groups (that is, loci in the same linkage group), extending to about 10 cM. No significant linkage disequilibrium was detected between markers in nonsyntenic regions. Given the observed level of linkage disequilibrium, mapping methods based on population-wide association might provide a better resolution than traditional quantitative trait loci mapping methods in the U.K. dairy cattle population and may reduce the required sample sizes of the experiments.

Algorithms↗