Biomedical subjects

D Stewart

Publications and source records attributed to D Stewart.

At least 109 records · Page 6Linked to original sources

PubMed2000

Current status of high dose chemotherapy in breast cancer.

To date, no definite answers are available to the initial question, whether or not HDCT and ASCT can improve quantity or quality of life. Completing the available prospective, randomized phase III studies; using HDCT earlier in the course of treatment; applying drugs that are active breast cancer; comparing the experimental treatment to standard therapy; and using appropriate sample size to detect clinically meaningful and statistically significant differences are all paramount requirements to answer the question successfully. Within the next few years, a number of European [13] and two Canadian Studies [6, 14] that are currently accruing patients, will contribute versus important information regarding the role of HDCT and ABMT for breast cancer.

Breast Neoplasms↗

PubMed1999

Treatment retention and 1 year outcomes for residential programmes in England.

This paper reports changes in substance use behaviours at 1-year follow-up, and investigates the relationship between time in treatment and observed outcomes. A total of 408 clients were interviewed at intake to 23 residential treatment programmes, and 286 (70%) of these were interviewed at 1 year. Substantial improvements were found in terms of abstinence from opiates, psychostimulants and benzodiazepines. At 1 year, half of the clients were abstinent from heroin. Reductions in injecting, sharing injecting equipment, heavy drinking and criminal behaviour were found. Critical treatment thresholds were identified using multiple logistic regression analyses. Longer stays in treatment were predictive of better 1 year outcomes.

Adolescent↗

PubMed1999

Baseline characteristics of the study population in the Diabetes Atherosclerosis Intervention Study (DAIS). World Health Organization Collaborating Centre for the Study of Atherosclerosis in Diabetes.

The Diabetes Atherosclerosis Intervention Study (DAIS) is the first study designed a priori to determine whether correcting dyslipoproteinemia in type II diabetes will alter coronary atherosclerosis. It is a multinational randomized double-blind, placebo-controlled trial using micronized fenofibrate. Its primary end point is a change in the average mean segment diameter determined on coronary angiograms taken at the beginning and end of the treatment period. This study describes the population baseline characteristics. Four hundred eighteen individuals (305 men and 113 women) were randomized; 168 patients were from Canadian clinics and 250 from those in Europe. Because the patients in both regions were very similar, it was possible to pool their data. All had > or = 1 minimally visible lesion on coronary angiography. Their average (+/-SD) lipid levels were: triglycerides 2.42 +/- 1.00 mmol/L, total cholesterol 5.57 +/- 0.70 mmol/L, low-density lipoprotein cholesterol 3.43 +/- 0.70 mmol/L, and high-density lipoprotein cholesterol 1.03 +/- 0.20 mmol/L. They were in very good glycemic control (hemoglobin A1c [HbA1c] 7.51 +/- 1.20%). The remainder of the coronary risk factors and demographic characteristics are described in the following. The characteristics of the DAIS population should determine whether correcting the dyslipoproteinemia seen in type II diabetes alters the progression and/or regression of angiographically determined coronary disease, to ascertain whether there is a difference between those with previous coronary intervention and those without, and to determine whether there is a gender effect.

Adult↗

PubMed1999

Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene.

Stress response elements, which mediate induction of the mouse heme oxygenase-1 (HO-1) gene by several agents, resemble the binding site for the activator protein-1 (Jun/Fos), Maf, and Cap'n'Collar/basic leucine zipper (CNC-bZIP) families of proteins. In L929 fibroblasts, significant activation of an HO-1 enhancer-reporter fusion gene was observed only with the CNC-bZIP class of proteins with Nrf2 exhibiting the highest level of trans-activation, between 25- and 30-fold. To further examine the role of this factor in HO-1 gene regulation, a dominant-negative mutant, Nrf2M, was generated and conditionally expressed in L929 cells. The mutant protein was detected in cytoplasmic and nuclear fractions but did not affect cell growth. Under conditions of Nrf2M overexpression, HO-1 mRNA accumulation in response to heme, cadmium, zinc, arsenite, and tert-butylhydroquinone was inhibited by 85-95%. In contrast, overexpression of a dominant-negative mutant of c-Jun decreased L929 cell growth but did not inhibit HO-1 gene activation. Nrf2 does not homodimerize, but CNC-bZIP.small Maf protein heterodimers and Nrf2. Jun protein complexes are proposed to function as trans-activators. Co-expression of Jun proteins or p18, however, had no significant affect or inhibited Nrf2-mediated trans-activation. Taken together, these results implicate Nrf2 in the induction of the HO-1 gene but suggest that the Nrf2 partner in this function is a factor other than p18 or Jun proteins.

Animals↗

PubMed1999

A novel tumor-specific replication-restricted adenoviral vector for gene therapy of hepatocellular carcinoma.

Transducing and distributing a vector throughout a tumor mass are presently insufficient for effective cancer gene therapy. To overcome these difficulties an adenoviral vector was designed that would replicate specifically in tumor cells. This tumor-specific replication-restricted adenoviral (TSRRA) vector was constructed by requiring that the essential E1A gene be expressed from a tumor-specific promoter, namely, the alpha-fetoprotein (AFP) gene promoter. This promoter was chosen since the AFP gene is highly expressed in 70-80% of patients with hepatocellular carcinoma (HCC) but not in normal adults. HCC is one of the major worldwide causes of cancer death. A vector was constructed (AvE1a04i) and demonstrated to replicate in human AFP-producing HCC cell lines. However, little replication was observed in seven other, non-AFP-producing human cell lines, as well as primary cultures of normal human lung epithelial and endothelial cells. In addition, AvE1a04i was shown to prevent tumor growth of an ex vivo-transduced AFP-expressing HCC cell line but not a non-AFP-expressing cell line. Finally, in situ administration of AvE1a04i into preestablished tumors resulted in a greater than 50% long-term survival rate. This novel TSRRA vector for HCC demonstrated both specificity and efficacy in vitro and in vivo.

Adenoviruses, Human↗

PubMed1999

Continued heroin use during methadone treatment: relationships between frequency of use and reasons reported for heroin use.

Seventy-seven (71%) of a group of 109 attenders at an out-patient drug treatment service reported that they had used heroin in the 90 days before interview, of whom 24 (31%) had used every day. Daily users were more likely to explain their use in terms of needing to curb withdrawals than were occasional heroin users. The latter group were more likely to report availability as a reason for use. From a clinical perspective, it is likely that those who use opportunistically are less likely to change their use as a function of clinical responses (e.g. higher methadone dose) than are those whose use is motivated by the attempt to curb withdrawal symptoms.

Adult↗

PubMed1999

Characterization and biosynthesis of non-degradable polymers in plant cuticles.

The structure and monomeric composition of the highly aliphatic and non-saponifiable fraction of cutans isolated from the leaf cuticles of Agave americana L. and Clivia miniata Reg. have been elucidated. Spectroscopic Fourier transform infrared and 13C-nuclear magnetic resonance, calorimetric and X-ray diffraction studies, together with biopolymer analysis after exhaustive ozonolysis, showed that the cutan fraction consists of an amorphous three-dimensional network linked by ether bonds containing double bonds and free carboxylic acid functions. Data obtained from fatty acid sorption indicated that the new biopolymer investigated here has a highly hydrophobic character constituting an additional barrier biopolymer in those cuticles where it is present. Labelled [14C]linoleic acid was preferentially incorporated into the non-ester part of C. miniata leaf disks in comparison with the cutin fraction of the cuticular membrane. This indicates that the cis-pentadiene system of polyunsaturated fatty acids is involved in the formation of intramolecular linkages, mainly ether bonds, of the aliphatic biopolymer.

Biological Transport↗

PubMed1999

The measurement of premenstrual mood symptoms.

INTRODUCTION: To aid in the diagnosis and management of premenstrual syndromes, dozens of symptom measurement instruments have been created and several methods for classifying clinically important change in symptoms have been defined. While the diagnosis of premenstrual dysphoric disorder (PMDD) has become standardized through the application of research criteria, consensus amongst investigators as to the instruments best able to confirm the diagnosis and measure treatment effects has yet to be reached. OBJECTIVE: To determine the performance and inter-correlations of three prospective symptom rating scales used to establish severity of premenstrual mood symptoms and measure efficacy during a treatment trial for premenstrual dysphoria. METHODS: Single item visual analogue scales (VASs) for irritability, tension, depression and mood swings were used in combination with the Premenstrual Tension Syndrome Observer (PMTS-O) and Self-Rating (PMTS-SR) scales to measure the severity of premenstrual mood symptoms at baseline and during treatment. RESULTS: Premenstrual mood symptoms as measured by VASs significantly correlated with PMTS-0 and PMTS-SR scale scores (range 0.70 to 0.82, P < 0.001). All scales were sensitive to premenstrual symptom worsening (which is a required characteristic of this disorder) and revealed differences in effects of treatment on premenstrual mood symptoms (P < 0.001). CONCLUSIONS: VASs in combination with the PMTS-O are low in burden to the client, reliable, valid and sensitive to change. In light of the current debates regarding instruments most appropriate for the classification and measurement of treatment effects in women diagnosed with premenstrual dysphoria, further refinement of these scales is warranted.

Double-Blind Method↗

PubMed1999

What's happening? Current status of high dose chemotherapy in breast cancer.

To date, no definite answers are available to the initial question, as to whether or not HDCT and ASCT can improve the quantity or quality of life. Completing the available prospective, randomized phase III studies; using HDCT earlier in the course of treatment, applying drugs that are active against breast cancer, comparing the experimental treatment to standard therapy, and using appropriate sample size to detect clinically meaningful and statistically significant differences are all paramount requirements to answer the question successfully. Within the next few years, a number of European [13] and two Canadian studies [6,14] that are currently accruing patients, will contribute important information regarding the role of HDCT and ABMT for breast cancer.

Antineoplastic Agents↗

PubMed1999

Behavioral rehabilitation and the reduction of aggressive and self-injurious behaviors with cognitively impaired, chronic psychiatric inpatients.

Aggressive behavior has been identified as a significant concern and occupational hazard in psychiatric inpatient settings. Several factors, including lax or unclear ward structure, have been identified as contributing to the exhibition of aggressive behavior. Token economies are effective in increasing ward structure and reducing aggressive behavior. This study evaluated the effects of rehabilitation programming, based on Gordon Paul's social learning approach (SLA), on rates of aggressive and self-injurious behaviors in a group of cognitively impaired, chronic psychiatric inpatients, compared to three long-term wards of similar patients. While no differences were found between the two groups prior to implementing SLA procedures, lower rates of aggression and self-injurious behavior were observed at one and two years on the Paul-derived ward. These results support the use of Paul's approach with multiply-impaired psychiatric inpatients in reducing patient aggression.

Adult↗

PubMed1999

Expression of C-erbB-2/HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous blood stem cell support.

C-erbB-2/HER-2 (designated HER-2) is overexpressed in both primary and metastatic breast cancer and predicts poor prognosis. We investigated the expression of HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) with autologous blood stem cell (ABSC) support and correlated the presence (positive) or absence (negative) of HER-2 overexpression in these patients with response to treatment, progression-free survival (PFS) and overall survival (OS). The level of HER-2 expression was analyzed in 57 patients with metastatic breast cancer undergoing HDCT with ABSC support. Plasma from peripheral blood was taken at three different time points during the course of treatment and was analyzed using an enzyme immunoassay (EIA) to detect circulating levels of the extracellular portion of HER-2. HER-2 levels were elevated (>0.2 U/mg protein) in 27/57 (47.4%) patients at one or more time points during treatment. The level of HER-2 varied during the course of treatment. Following induction chemotherapy (ICT), five patients who were negative initially, showed overexpression of HER-2. Three patients overexpressed HER-2 only after HDCT/ABSC. Response to treatment was similar in patients independent of plasma HER-2 levels. Overexpression of HER-2 was associated with a significantly shorter PFS (P = 0.004, log rank) and OS (P = 0.003, log rank) after HDCT/ABSC. HER-2 overexpression, patient age, estrogen receptor status, progesterone receptor status, and previous hormone treatment were assessed by univariate and multivariate analysis. Univariate analysis determined that only HER-2 overexpression correlated significantly with decreases in progression free survival (P = 0.005, Cox regression). Decreased overall survival correlated significantly with HER-2 overexpression (P = 0.004) and decreased expression of both estrogen receptor (P = 0.032) and progesterone receptor (P = 0.039). In multivariate analysis of these variables, only HER-2 expression levels proved to be of independent statistical significance in predicting outcome for both PFS (P = 0.007) and OS (P = 0.002). These results suggest that overexpression of HER-2, measured by EIA in plasma may predict a shorter PFS and OS in patients with metastatic breast cancer treated with HDCT and ABSC support.

Adult↗

PubMed1999

Allogeneic blood stem cell and bone marrow transplantation for acute myelogenous leukemia and myelodysplasia: influence of stem cell source on outcome.

We have compared the outcomes of 87 patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS) receiving matched sibling transplants with stem cells from peripheral blood (blood cell transplant, BCT) or bone marrow (BMT). In good risk patients (AML in CR1) granulocytes recovered to 0.5 x 10(9)/l a median of 14 days after BCT compared with 19 days after BMT (P < 0.0001). For patients with poor risk disease (AML beyond CR1 and MDS) corresponding figures were 16 vs 26 days (P < 0.0001). Platelet recovery to 20 x 10(9)/l was also faster after BCT (good risk 12 vs 20 days, P < 0.0001; poor risk 17 vs 22 days, P = 0.04). Red cell transfusions were unaffected by cell source, but BCT recipients required less platelet transfusions (good risk 1 vs 5, P = 0.002; poor risk 5 vs 11, P = 0.004). Blood cell transplants resulted in more chronic GVHD (86% vs 48%, P = 0.005) and a significantly higher proportion of recipients with KPS of 80% or less (48% vs 5%, P = 0.004). Disease-free survival at 4 years was 23% for both groups of poor risk patients but outcome in good risk patients was better after BCT (93% vs 62%, P = 0.047) related mainly to less relapse. While disease-free survival may be better after BCT than BMT for AML in CR1, quality of life may be relatively impaired.

Adolescent↗

PubMed1999

Withdrawal of peripheral vasodilators in primary care.

AIMS: To investigate the use of peripheral vasodilators in selected practices in primary care and to observe the effect of withdrawing therapy in a sample of patients. METHODS: Patients receiving repeat prescriptions for peripheral vasodilators, identified from two practices in Grampian, were interviewed prior to and following withdrawal of therapy. RESULTS: Of the 35 patients, review of the continued need for therapy was documented in the medical notes of only one patient. Treatment was successfully withdrawn from 17 patients, generating considerable savings. CONCLUSIONS: Review of peripheral vasodilators merits further attention in larger numbers of patients.

Adult↗

PubMed1999

The attitudes and attributions of student nurses: do they alter according to a person's diagnosis or sexuality and what is the effect of nurse training?

The threat of an AIDS (acquired immune deficiency syndrome) epidemic in the early 1980s saw the emergence of strong negative attitudes from both the public and health care professionals alike. Certain 'high risk' groups in society, who were considered as susceptible to the disease, homosexuals and intravenous drug users in particular, became the victims of prejudice and discrimination. More recent research has indicated a possible shift to a more positive orientation, although the findings are far from conclusive. In this current study, the Prejudicial Evaluation and Social Interaction Scale (PESIS) was administered to four separate cohorts of student nurses approximately a year apart in training (n = 192). Each cohort was divided into four groups, each one completing the PESIS after reading a version of a vignette that described either a person with AIDS or leukaemia, and who was either homosexual or heterosexual. The design therefore allowed for within-group and between-group comparisons. Overall the results showed that the student nurses held positive attitudes although they reported a significantly greater prejudice towards AIDS. No significant differences were found for sexual orientation. Additionally significantly greater levels of blame and responsibility were associated with the person with AIDS, but again there was no effect for sexual orientation. The findings suggest that a slightly more negative attitude continues to be associated with a diagnosis of AIDS but no longer with homosexuality. No effect across cohorts was noted either, student nurses being as positive at the beginning of training as at the end. Some of the limitations of PESIS and the difficulties of attitude assessment in general are discussed and future areas of research are identified.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Biochemical characterization, molecular cloning and expression of laccases - a divergent gene family - in poplar.

The nature of the enzyme(s) involved in the dehydrogenative polymerization of lignin monomers is still a matter of debate. Potential candidates include laccases which have recently received attention due to their capacity to oxidize lignin monomers and close spatial and temporal correlation with lignin deposition. We have characterized two H2O2-independent phenoloxidases with approximate molecular masses of 90 kDa and 110 kDa from cell walls of Populus euramericana xylem that are capable of oxidizing coniferyl alcohol. The 90-kDa protein was purified to apparent homogeneity and extensively characterized at the biochemical and structural levels. To our knowledge, this is the first report of a plant laccase purified to homogeneity from a lignifying tissue of an angiosperm. The cDNA clones corresponding to the 90-kDa and 110-kDa proteins, lac90 and lac110, were obtained by a PCR-based approach using specific oligonucleotides derived from peptide sequences. Sequence analysis indicated that lac90 and lac110 encoded two distinct laccases. In addition, heterologous screening using an Acer pseudoplatanus laccase cDNA enabled us to obtain three additional cDNAs (lac1, lac2, lac3) that did not correspond to lac90 and lac110. The five laccase cDNAs correspond to a highly divergent multigene family but Northern analysis with gene-specific probes indicated that all of the genes are exclusively and abundantly expressed in stems. These results highlight the polymorphism of plant laccases by an integrated biochemical and molecular approach, and provide the tools that will enable us to clearly determine the function of these enzymes in plants by molecular and genetic approaches.

Acrolein↗

PubMed1999

Body composition assessment in American Indian children.

Although the high prevalence of obesity in American Indian children was documented in several surveys that used body mass index (BMI, in kg/m2) as the measure, there is limited information on more direct measurements of body adiposity in this population. The present study evaluated body composition in 81 boys (aged 11.2+/-0.6 y) and 75 girls (aged 11.0+/-0.4 y) attending public schools in 6 American Indian communities: White Mountain Apache, Pima, and Tohono O'Odham in Arizona; Oglala Lakota and Sicangu Lakota in South Dakota; and Navajo in New Mexico and Arizona. These communities were participating in the feasibility phase of Pathways, a multicenter intervention for the primary prevention of obesity. Body composition was estimated by using a combination of skinfold thickness and bioelectrical impedance measurements, with a prediction equation validated previously in this same population. The mean BMI was 20.4+/-4.2 for boys and 21.1+/-5.0 for girls. The sum of the triceps plus subscapular skinfold thicknesses averaged 28.6+/-7.0 mm in boys and 34.0+/-8.0 mm in girls. Mean percentage body fat was 35.6+/-6.9 in boys and 38.8+/-8.5 in girls. The results from this study confirmed the high prevalence of excess body fatness in school-age American Indian children and permitted the development of procedures, training, and quality control for measurement of the main outcome variable in the full-scale Pathways study.

Adipose Tissue↗

PubMed1999

Physical activity assessment in American Indian schoolchildren in the Pathways study.

The objective of the Pathways physical activity feasibility study was to develop methods for comparing type and amount of activity between intervention and control schools participating in a school-based obesity prevention program. Two methods proved feasible: 1) a specially designed 24-h physical activity recall questionnaire for assessing the frequency and type of activities and 2) use of a triaxial accelerometer for assessing amount of activity. Results from pilot studies supporting the use of these methods are described. Analyses of activity during different segments of the day showed that children were most active after school. The activities reported most frequently (e.g., basketball and mixed walking and running) were also the ones found to be most popular in the study population on the basis of formative assessment surveys. Both the physical activity recall questionnaire and the triaxial accelerometer methods will be used to assess the effects of the full-scale intervention on physical activity.

Asian People↗

PubMed1999

Endocrine biomarkers of early fetal loss in cynomolgus macaques (Macaca fascicularis) following exposure to dioxin.

This study examines the endocrine alterations associated with early fetal loss (EFL) induced by an environmental toxin, TCDD (2,3,7, 8-tetrachlorodibenzo-p-dioxin), in the cynomolgus macaque, a well-documented reproductive/developmental model for humans. Females were administered single doses of 1, 2, and 4 microgram/kg TCDD (n = 4 per dose group) on gestational day (GD) 12. Urinary estrogen metabolites (estrone conjugates) were monitored to establish the day of ovulation, and serum hormones (estradiol, progesterone, chorionic gonadotropin, relaxin) were measured to assess ovarian and placental endocrine status before and after treatment. EFL occurred between GDs 22 and 32 in 10 of the 12 animals treated with TCDD. The primary endocrine alterations associated with TCDD treatment were significant decreases in serum estradiol and bioactive chorionic gonadotropin concentrations (p < 0.02). Less pronounced decreases in serum progesterone (p = 0.10) and relaxin (p < 0.08) also followed TCDD treatment. In contrast, immunoreactive chorionic gonadotropin concentrations were not reduced by TCDD exposure at any level, indicating that TCDD targets specific components of the chorionic gonadotropin synthesis machinery within the trophoblast to alter the functional capacity of the hormone. These data demonstrate the value of endocrine biomarkers in identifying a toxic exposure to primate pregnancy many days before direct signs of reproductive toxicity were apparent. The increased EFL that occurred after exposure to TCDD might reflect a toxic response initially mediated via endocrine imbalance, leading to placental insufficiency, compromised embryonic circulation, and subsequent EFL.

Abortion, Spontaneous↗