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D Stewart

Publications and source records attributed to D Stewart.

At least 37 records · Page 2Linked to original sources
PubMed2004

Glucose self-monitoring in primary care: a survey of current practice.

BACKGROUND: The role of long-term glycaemic control in minimizing long-term complications of diabetes mellitus is evidence-based and national guidelines recommend a target glycosylated haemoglobin level of approximately 7%. Although the role of self-monitoring blood and urine glucose is less well defined, this activity consumes vast National Health Service (NHS) resources. AIMS: The aims of this study were to (i) determine the current practice of glucose self-monitoring in primary care, (ii) determine any changes to therapy made as a result and (iii) compare monitoring and frequency of monitoring in those patients using insulin with those patients taking oral hypoglycaemic agents. METHODS: Postal questionnaire to 311 patients using insulin or oral hypoglycaemic agents identified from three general practices. RESULTS: The response rate was 59.8% (186/311), with the majority of responding patients (n = 158, 87.3%) performing self-monitoring. The patients using insulin were more likely to be self-monitoring than those taking oral therapy (chi(2), P < 0.001, d.f. = 1). The majority of patients who self-monitored and were using insulin (n = 45, 61.1%) altered the dose of insulin if a reading was beyond their target range. However, the majority of patients who self-monitored and were taking oral therapy (n = 48, 68.6%) took no action at all. CONCLUSIONS: Blood glucose self-monitoring was common in those treated with insulin or oral hypoglycaemics, although those using insulin were more likely to self-monitor. Notably many patients, particularly those on oral therapy, took no action based on the results of self-monitoring.

Administration, Oral↗
PubMed2004

How can we build resilience in primary school aged children? The importance of social support from adults and peers in family, school and community settings.

This study examines the association between firstly, student resiliency and their perceptions of social support from parents/caregivers, teachers, and peers, and secondly, between student's perception of their general health status and their social support. A cross-sectional research project was designed and conducted in 2003 in an urban and remote area of Queensland, Australia. The study population comprised of 2580 students (Years three, five, and seven) across 20 primary schools. The main outcome measures were self-reported health status and resiliency behaviours. Independent variables included student perceptions of support from parents/caregivers, teachers, school peers, and prosocial groups. Students who perceived parents, teachers, and peers as supportive were more likely to have higher resiliency behaviour in communication and cooperation, self-esteem, empathy, help-seeking, goals and aspirations. Students who considered that their parents, peers at school and prosocial groups were supportive, were more likely to feel healthy. Findings suggest that providing adult and peer support to students at primary school age is a vital strategy in promoting student resiliency and general health for children of primary school age.

Adult↗
PubMed2003

Predominant expression of Kv1.3 voltage-gated K+ channel subunit in rat prostate cancer cell lines: electrophysiological, pharmacological and molecular characterisation.

Voltage-gated K+ currents expressed in two rat prostate cancer ("Dunning") cell lines of markedly different metastatic ability were characterised using electrophysiological, pharmacological and molecular approaches. Whole-cell patch-clamp recordings showed that both strongly metastatic MAT-LyLu and weakly metastatic AT-2 cell lines possessed outward (delayed-rectifier type) K+ currents, which activated at around -40 mV. From the parameters measured, several characteristics of the two cell lines were similar. However, a number of statistically significant differences were noted for MAT-LyLu versus the AT-2 cells as follows: (1) current densities were smaller; (2) the slope factor for channel activation was smaller; (3) the voltage at which current was half-inactivated, and the slope factor for channel inactivation were greater; (4) the time constants for current decay at -20 and 0 mV were smaller; and (5) the residual peak current was larger following 60 s of repetitive voltage pulses for stimulation frequencies in the range 0.05-0.2 Hz. On the other hand, the K+ currents in both cell lines showed similar pharmacological profiles. Thus, the currents were blocked by 4-aminopyridine, tetraethylammonium, verapamil, margatoxin, and charybdotoxin, with highly similar IC(50)s for given blockers. The electrophysiological and pharmacological data taken together suggested expression of voltage-gated K+ channels of the Kv1 family, expression of the Kv1.3 subunit being predominant. Western blot and RT-PCR tests both confirmed that the cells indeed expressed Kv1.3 and to a lesser extent Kv1.4 and Kv1.6 channel alpha-subunits. In view of the similarity of channel expression in the two cell lines, voltage-gated K+ channel activity may not be a primary determinant of metastatic potential in the rat model of prostate cancer, but the possible contribution of K+ channel activity to the metastatic process is discussed.

4-Aminopyridine↗
PubMed2003

Phase II study of troxacitabine (BCH-4556) in patients with advanced and/or metastatic renal cell carcinoma: a trial of the National Cancer Institute of Canada-Clinical Trials Group.

PURPOSE: A multi-institution phase II study was undertaken by National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of intravenous troxacitabine (Troxatyl; Shire Pharmaceuticals Plc, Laval, Quebec, Canada), in patients with renal cell carcinoma. PATIENTS AND METHODS: Between June 1999 and March 2000, 35 patients (24 male) with a mean age of 60 years who had advanced and/or metastatic disease were treated with troxacitabine given as an intravenous infusion over 30 minutes at a dose of 10 mg/m2 intravenously, once every 3 weeks. RESULTS: Of the 33 of 35 patients evaluable for response, there were two confirmed partial responses, 21 patients had stable disease (median duration, 4.4 months), and 10 patients had progressive disease. Eight patients remained stable for more than 6 months, of whom six remain free of progression. The most common drug-related nonhematologic toxicities observed were skin rash (77.1%), hand-foot syndrome (68.6%), alopecia (51.4%), fatigue (51.4%), and nausea (57.1%). Out of a total of 145 cycles of treatment, 98 were given without steroid premedication, whereas 47 cycles were given with steroid premedication. Without premedication, skin rash occurred in 37% of cycles compared with 26% when steroids were given prophylactically. CONCLUSION: Troxacitabine given at a dose of 10 mg/m2 once every 3 weeks was well tolerated in patients with metastatic renal cell cancer, with common toxicities being a moderate to severe granulocytopenia and skin rash. Steroid premedication may reduce the frequency and severity of the skin rash. Our current study suggests that the nucleoside analog troxacitabine may have modest activity against renal cell carcinoma; however, larger studies are required to confirm this.

Aged↗
PubMed2003

Fluoxetine improves functional work capacity in women with premenstrual dysphoric disorder.

Interference with social and occupational functioning is a key criterion for premenstrual dysphoric disorder (PMDD) and distinguishes it from the less severe premenstrual syndrome (PMS). We conducted a post hoc analysis of the results of a previously reported study evaluating the efficacy of fluoxetine in the management of PMDD, to determine the extent to which women with PMDD perceived impairment in their functional work capacity during the luteal phase of their menstrual cycle. The effects of two doses of fluoxetine vs placebo in alleviating PMDD symptoms and restoring normal work capacity during this period were assessed. We measured baseline follicular vs luteal phase presence of 8 patient-rated functional work capacity-related symptoms on the Premenstrual Tension Scale-Self Rated in 320 women who met diagnostic criteria for late luteal phase dysphoric disorder, now known as PMDD. Women were then randomized to double-blind treatment with either fluoxetine 20 mg/d, fluoxetine 60 mg/d, or placebo daily for 6 menstrual cycles. All 8 work capacity-related symptoms were more likely to be present in the baseline luteal phase than in the baseline follicular phase. A statistically significant improvement from baseline to the average treatment score for the work capacity subscale was detected for both fluoxetine groups compared to the placebo group. This beneficial response to fluoxetine was evident by the first cycle of treatment. Our results demonstrate that fluoxetine at a relatively low dose of 20 mg/d quickly reduced symptoms that negatively affect work capacity and was well tolerated.

Adolescent↗
PubMed2003

Micrometastases in apheresis products predict shorter progression-free and overall survival in patients with breast cancer undergoing high-dose chemotherapy (HDCT) and autologous blood stem cell transplantation (ABSCT).

The presence of cancer cells in autografts of breast cancer patients has been described to have prognostic value or directly lead to relapse. Previously, we demonstrated that apheresis products (APs) collected after induction chemotherapy have a significantly lower likelihood of tumor cell contamination. Here, we examine the prognostic value of micrometastases in autografts. Data from 83 patients with breast cancer treated with autologous blood stem cell transplantation were analyzed. Pan-cytokeratin-FITC conjugated antibodies were used to detect contaminating breast cancer cells in the APs. Progression and survival data analyzed on the basis of three or fewer cancer cells showed no significant differences in outcomes. Of the 83 patients, 11 had more than three cancer cells detectable in their APs. In total, 72 patients were shown to have less than three cells detectable. When patients with more than three cells were compared to patients with 0-3, we found statistically significant differences in progression-free survival. We also found a significant difference in overall survival (OS) between the two groups. No difference was observed in OS since the time of diagnosis. We conclude that patients with more than three contaminating cells in their APs have micrometastases and represent a poor prognosis group.

Adult↗
PubMed2003

Safety of plasmin in the setting of concomitant aspirin and heparin administration in an animal model of bleeding.

Plasmin is a direct thrombolytic which has been shown to have a strikingly favorable benefit to risk profile in comparison with plasminogen activators, notably tissue plasminogen activator (t-PA). As heparin is known to increase the risk of hemorrhage when co-administered with a plasminogen activator, we asked whether adjunct antithrombotic agents such as aspirin and heparin would affect the safety of plasmin. Three groups of rabbits were administered plasmin at a dose (4 mg kg-1) designed to induce significant decreases in antiplasmin, fibrinogen and factor (F)VIII, to about 25, 40 and 40%, respectively, of baseline values, but not cause prolongation of the ear puncture bleeding time. In a blinded and randomized trial, the results show that an intravenous aspirin bolus plus heparin administered as a bolus followed by a maintenance continuous infusion did not significantly prolong the bleeding time during plasmin infusion. These data indicate that in the rabbit, concomitant use of aspirin plus heparin does not affect the safety of a therapeutic dose of plasmin.

Animals↗
PubMed2003

Drug utilization review of celecoxib in Ontario.

Cyclooxygenase (COX)-2-specific inhibitors were developed to circumvent the gastrointestinal toxicity of non-specific non-steroidal anti-inflammatory drugs while maintaining efficacy. However, the higher acquisition cost of COX-2-specific inhibitors has resulted in the implementation of a programme for cost containment in the Ontario public drug program. This programme consists of limited use (LU) criteria that need to be met for drug reimbursement of patients with osteoarthritis (OA) or rheumatoid arthritis (RA). Determining the proportion of patients eligible for reimbursement for celecoxib according to the LU criteria (based on prior treatment failure and the presence or history of serious ulcer-related gastrointestinal complications) can provide an indication of the extent of adherence to suggested guidelines. Using a patient-based survey and an analysis of the Ontario Drug Benefit Program database, the proportion of patients prescribed celecoxib who met rigorous or pragmatic definitions of the LU criteria was determined. The extent of coprescription of gastroprotective agents among patients taking celecoxib was also determined. Using the pragmatic definition, the majority of patients in the patient-based survey (53% for OA and 81% for RA) met the LU criteria. Similarly, in the database analysis, the majority of patients (76% for OA and 78% for RA) met the LU criteria. These data suggest that physician prescribing of celecoxib is consistent with the LU criteria. Concomitant prescription of gastroprotective agents in patients taking celecoxib was approximately 40%. It is recommended that further investigations be performed to determine the long-term impact of LU criteria on clinical and economic outcomes, since these criteria may also serve to restrict use in patients who may benefit from taking COX-2-specific inhibitors.

Aged↗
PubMed2003

Association of CCR5Delta32 with reduced risk of childhood but not adult asthma.

BACKGROUND: A number of potential candidate genes have been implicated in the pathogenesis of asthma. A 32 base pair deletion in the CCR5 gene renders this chemokine receptor non-functioning and has been shown to be associated with a reduced prevalence of asthma in childhood. The mechanism may be related to impairment of pathogen entry into cells and modified host inflammatory response. We sought to determine the influence of the CCR5Delta32 mutation on asthma and allergy in the transition from childhood to adulthood. METHODS: 627 individuals first studied as part of a whole population schoolchildren cohort in 1989 when aged 8-12 years were followed up 10 years later for respiratory and allergy symptoms and laboratory markers of atopy. CCR5Delta32 status was also characterised and the association with childhood and adulthood symptoms determined. RESULTS: The follow up sample was representative of the original cohort except for a slightly greater prevalence of symptomatic individuals. As children, none who were homozygous for the CCR5Delta32 mutation had a current physician's diagnosis of asthma. In multivariate analysis and controlling for known confounders, the protective effect of carrying the allele in childhood was highly significant (OR 0.31, 95% CI 0.14 to 0.72, p=0.006). There was no protective association with "current asthma" as classified in adulthood within the same population. Subjective or laboratory markers of atopy in childhood or adulthood were not associated with the CCR5Delta32 mutation. Methacholine bronchial hyperresponsiveness in adulthood was also unrelated to gene carrier status. CONCLUSIONS: In a population with a high allelic frequency for the CCR5Delta32 mutation, a significant protection against childhood asthma is evident which is independent of atopy. This protection is lost in the transition between childhood and early adulthood. The contribution of different genetic candidates to the expression of asthma may change with advancing maturity and confound the interpretation of association and linkage studies unless age is taken into account.

Adult↗
PubMed2003

Effect of temperature on the growth response of Salmonella enteritidis inoculated onto the vitelline membranes of fresh eggs.

The growth response of Salmonella Enteritidis (SE) on the vitelline membrane in vitro was studied with the use of a special tube devised specifically for the inoculation of SE onto the vitelline membrane and for the sampling of the yolk near the inoculation site. This latter ability allowed the detection of the movement of SE into the yolk. The growth of SE on the membrane was compared with that of SE inoculated into yolk and albumen in vitro and in ovo in fresh in-shell eggs. The incubation time was 2 days, and the incubation temperatures were 4, 8, 15, 27, and 37 degrees C. Comparison of the results obtained for in vitro growth showed that at 4, 8, and 15 degrees C, SE behaved as if it were in the albumen, with its numbers decreasing over time. At 27 and 37 degrees C, SE grew as if it were in yolk, with a maximum increase of 4.5 log CFU after 2 days at 37 degrees C. In no experiments involving growth on the vitelline membrane did SE appear in the yolk. Comparisons between in vitro and in ovo growth responses of SE in yolk and albumen indicate that SE growth on the membrane parallels that in the in-shell egg.

Animals↗
PubMed2002

Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis.

Fifty-seven patients receiving unrelated donor (UD) BMT were matched for disease and stage with 57 recipients of genotypically matched related donor (MRD) BMT. All UD recipients were matched serologically for A and B and by high resolution for DR and DQ antigens. All patients received CsA and 'short course' methotrexate with folinic acid. Unrelated donor BMT patients also received thymoglobulin 4.5 mg/kg (6 mg/kg if <30 kg) in divided doses over 3 days pretransplant. For UD and RD BMT, respectively, incidence of acute GVHD grade II-IV was 19 +/- 6% vs 36 +/- 8%, grade III-IV 10 +/- 6% vs 18 +/- 7%, chronic GVHD 44 +/- 8% vs 51 +/- 8%, non-relapse mortality 15 +/- 5% vs 8 +/- 4% at 100 days, 28 +/- 8% vs 36 +/- 7% at 3 years. At 3 years, relapse was 45 +/- 7% vs 42 +/- 7%, and disease-free survival 39 +/- 7% vs 37 +/- 7%. None of these differences are significant. Three-year overall survival was identical at 42 +/- 7%. For 29 patients with low/intermediate risk leukemia, disease-free survival was 68 +/- 10% after UD BMT vs 59 +/- 9% for RD BMT recipients (P = NS). Corresponding figures for high risk patients were 14 +/- 7% and 21 +/- 8%, respectively. We conclude that UD BMT recipients matched as above and given pretransplant ATG have similar outcomes to recipients of MRD BMT using conventional drug prophylaxis. Unrelated donor BMT should be considered in any circumstance where MRD BMT is routine.

Antilymphocyte Serum↗
PubMed2002

Optimising parameters for peripheral blood leukapheresis after r-metHuG-CSF (filgrastim) and r-metHuSCF (ancestim) in patients with multiple myeloma: a temporal analysis of CD34(+) absolute counts and subsets.

Patients (n = 69) with multiple myeloma undergoing peripheral blood stem cell collection (PBSC) were treated with cyclophosphamide and a combination of recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) and recombinant methionyl human stem cell factor (r-metHuSCF, ancestim). The objectives of this study were to determine: (1) The proportion of patients reaching a target yield of >or=5 x 10(6) CD34(+) cells/kg in one or two successive large-volume (20 liter) leukapheresis procedures; (2) the optimal collection time for leukapheresis; (3) mobilization kinetics of CD34(+) subsets in response to G-CSF/SCF. All patients were mobilized with cyclophosphamide (2.5 g/m(2)) on day 0 followed by filgrastim (10 microg/kg ) plus ancestim (20 microg/kg) commencing day 1 and continuing to day 11 or 12. Of the 65 evaluable patients, 57 were considered not heavily pretreated and 96.5% obtained a target of >or=5 x 10(6)/kg in one collection. The median CD34(+) cells/kg was 39.5 x 10(6) (range: 5.2-221.2 x 10(6)). Subset analysis demonstrated the number of CD38(-), CD33(-), and CD133(+) peaked at day 11; and CD34(+), CD90(+) cells peaked at day 10. The optimum day for leukapheresis was determined to be day 11. The median absolute peripheral blood CD34(+) cell numbers on day 11 was 665 x 10(6)/l (range: 76-1481 x 10(6)/l). Eight of the 10 heavily pretreated patients were evaluable: three achieved the target dose in one leukapheresis (37.5%) and three (37.5%) achieved the target dose with two leukaphereses. Use of this mobilization strategy allowed the collection of high numbers of CD34(+) cells and early progenitors and the ability to predictably schedule leukapheresis.

Adult↗
PubMed2002

Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes.

The availability of an i.v. form of busulfan (Bu) has prompted investigation of administration schedules other than the 4-times-daily dosage commonly used with oral Bu. We have studied an allogeneic stem cell transplantation (SCT) preparative regimen comprising fludarabine (FLU) 50 mg/m2 on days -6 to -2 plus i.v. Bu 3.2 mg/kg daily in a 3-hour infusion on days -5 to -2. The regimen was given to 70 patients aged 15 to 64 years (median, 41 years) with hematologic malignancy. Thirty-six patients (51%) had high-risk malignancy, 28 (40%) had unrelated or genotypically mismatched related donors (alternate donors [AD]) and 29 (41%) received bone marrow rather than blood as stem cell source. Acute GVHD prevention comprised antithymocyte globulin 4.5 mg/kg over 3 days pretransplantation, cyclosporin A, and short-course methotrexate with folinic acid. Hepatic toxicity was transient and there was no clinically diagnosed veno-occlusive disease. Grade II stomatitis occurred in 49 patients (70%) and hemorrhagic cystitis in 9 patients (13%). One patient with subtherapeutic phenytoin levels had a convulsion 8 hours after the third i.v. Bu dose, but no other neurotoxicity was apparent. Incidence of acute GVHD grades II to IV was 8% and incidence of grade III-IV was 3%, with no deaths from this cause. Actuarial incidence of chronic GVHD at 2 years is 38%. There were 2 cases of graft failure in unrelated donor BMT recipients, 1 of which was reversed by asecond transplantation. With a median follow-up of 16 months (range, 6-27 months), transplantation-related mortality at 100 days and 2 years was 2% and 5% for matched related donor (MRD) SCT and 8% and 19% for AD SCT, respectively (P = not significant). Relapse rates were 21% for 34 patients with acute myeloid leukemia (AML) in complete remission or chronic myeloid leukemia in chronic phase (low-risk), 66% for 19 patients with high-risk AML, and 18% for 17 patients with other active malignancy. Projected disease-free and overall survival rates at 2 years were 74% and 88% for low-risk disease, 26% and 37% for advanced AML, and 65% and 71% for other high-risk disease, respectively. Pharmacokinetic studies were done using 11 samples with the first and fourth doses of Bu. Kinetics were linear, and for the first and fourth doses, the half-lives were 2.60 +/- 0.44 and 2.57 +/- 0.36 hours, respectively. Clearances were 106.77 +/- 16.68 and 106.86 +/- 21.57 mL/min per m2, peak concentrations (Cmax) were 3.92 +/- 0.31 and 3.96 +/- 0.28 mcg/mL, and Bu areas under the plasma concentration versus time curve (AUC) were 4866.51 +/- 771.42 and 4980 +/- 882.80 microM x min, respectively. Bu was completely cleared within 24 hours and the day 4 pharmacokinetic values were very similar to those on day 1 for every patient. The cumulative AUC was comparable to the target range established for p.o. Bu. This regimen incorporating once-daily i.v. Bu is convenient to give, is relatively well tolerated, gives predictable blood levels, and deserves further study in circumstances in which cytoreduction as well as immune suppression is needed.

Adolescent↗
PubMed2002

Reduced injection risk and sexual risk behaviours after drug misuse treatment: results from the National Treatment Outcome Research Study.

This paper investigates injecting, shared use of needles/syringes and sexual risk behaviours at intake to treatment and at one-year follow-up among 753 drug users recruited to the National Treatment Outcome Research Study (NTORS). Injecting, sharing and having unprotected sex were substantially reduced among clients admitted to methadone programmes and among those admitted to residential treatments. The overall levels of risk fell after treatment, and the majority of those who were engaged in high risk behaviours at intake had stopped at follow-up. The results also show the variability of individual outcomes. A minority persisted with their risk behaviour, and others who were not at risk at intake who had started to engage in risky behaviours at follow-up. The behaviour of these clients creates a focal point for risk as well as being a threat to public health. Several social and psychological factors were predictive of health risk behaviours. These included frequency and duration of heroin use, polydrug use, alcohol use, gender, ethnicity, having a drug-using partner, anxiety and depression. The results indicate the important role that can be played by treatment services in helping to reduce the risk of blood-borne infections. We suggest that risk reduction interventions are an important and effective component of treatment programmes.

Adult↗
PubMed2002

Storage of blood for in vitro generation of dendritic cells.

BACKGROUND: Since the development of techniques to cultivate DC from peripheral blood, there has been a great deal of interest in the use of these cells in immunotherapeutic strategies. In a clinical setting, delays often occur between when blood is drawn and when it is processed. We therefore investigated the effect of overnight storage on the yield, morphology and phenotype of DC cultured from the peripheral blood of healthy volunteers. METHOD: Blood was processed either immediately, or after storage for 24 h in the fridge (4 degrees C) or at room temperature (RT, 20 degrees C). Samples were compared for starting cell number, DC yield and characteristics (morphology and phenotype). RESULTS: The number of PBMC that could be obtained was significantly lower from the refrigerated samples compared with both the freshly processed sample and that stored at RT. Samples processed after overnight storage at RT yielded cells morphologically identical to DC cultured from freshly processed samples. Only when samples were both stored and processed cold did the cultured cells not have typical DC morphology. DC cultured from the refrigerated samples showed a significant reduction in MHC II expression compared with samples processed fresh or stored at RT. This expression increased slightly when the sample was first warmed. Total DC yield and the percentage yield of cultured DC was not significantly different for any of the groups. DISCUSSION: We conclude that, if immediate processing of blood for in vitro generation of DC is not possible, samples should be stored at room temperature (approximately 20 degrees C).

Adult↗
PubMed2001

Drugs and the dance music scene: a survey of current drug use patterns among a sample of dance music enthusiasts in the UK.

This study explores the utility of a self-completion survey method to quickly and cheaply generate information on patterns and trends among regular "recreational" drug consumers. Data is reported here from 1151 subjects accessed through a dance music publication. In keeping with previous studies of drug use within the dance scene polysubstance use was the norm. Many of those reporting use of "ecstasy" were regularly using multiple tablets often consumed in combination with other substances thus exposing themselves to serious health risks, in particular the risk of dose related neurotoxic effects. Seventy percent were drinking alcohol at hazardous levels. Subjects' patterns of drug purchasing also put them at risk of severe criminal sanction. Data supported evidence that cocaine use had become increasing popular in the UK, but contrasted with some commentators' views that ecstasy use was in decline. The utility of this method and how the results should be interpreted is discussed, as are the data's implications for harm and risk reduction activities.

Adult↗