Mental health. Eye off the ball?
Explore the source record for details and available documents.
Education, Nursing, Continuing↗
Biomedical subjects
D Richards
Publications and source records attributed to D Richards.
Association between Alzheimer's disease and a functional polymorphism in the Myeloperoxidase gene.
A polymorphism in the Myeloperoxidase gene (MPO) has previously been demonstrated to be associated with gender-specific risk in an Alzheimer's Disease (AD) autopsy sample. We have investigated this polymorphism in our own samples of 226 Caucasian cases and 166 controls and 59 Hispanic cases and 75 controls. In Caucasians we find a significant association between MPO genotype and AD (P = 0.03), although we do not observe any effects of gender or any interaction with the APOE gene. Specifically, the MPO GG genotype contributes a 1.57-fold increased risk for AD. In Hispanics there was no effect of MPO genotype, or of MPO genotype in interaction with age or gender, on diagnosis of AD.
Age Distribution↗
Oral cancer screening.
Explore the source record for details and available documents.
Coloring Agents↗
A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer's disease.
OBJECTIVE: To investigate whether or not a coding polymorphism in the cystatin C gene (CST3) contributes risk for AD. DESIGN: A case-control genetic association study of a Caucasian dataset of 309 clinic- and community-based cases and 134 community-based controls. RESULTS: The authors find a signficant interaction between the GG genotype of CST3 and age/age of onset on risk for AD, such that in the over-80 age group the GG genotype contributes two-fold increased risk for the disease. The authors also see a trend toward interaction between APOE epsilon4-carrying genotype and age/age of onset in this dataset, but in the case of APOE the risk decreases with age. Analysis of only the community-based cases versus controls reveals a significant three-way interaction between APOE, CST3 and age/age of onset. CONCLUSION: The reduced or absent risk for AD conferred by APOE in older populations has been well reported in the literature, prompting the suggestion that additional genetic risk factors confer risk for later-onset AD. In the author's dataset the opposite effects of APOE and CST3 genotype on risk for AD with increasing age suggest that CST3 is one of the risk factors for later-onset AD. Although the functional significance of this coding polymorphism has not yet been reported, several hypotheses can be proposed as to how variation in an amyloidogenic cysteine protease inhibitor may have pathologic consequences for AD.
Aged↗
The genetic association between Cathepsin D and Alzheimer's disease.
The aspartyl protease Cathepsin D has previously been suggested to play a role in the Alzheimer's disease (AD) process because of its ability to cleave the beta-amyloid precursor protein and the possibility that it may be one of the 'secretase' enzymes. A functional C-->T polymorphism in the Cathepsin D gene (CATD) has been reported to be associated with increased risk for AD in Caucasian case-control studies; specifically, the T-carrying genotypes confer increased risk. We have examined this association in our own Caucasian dataset of 210 AD cases and 120 controls, and in an additional Hispanic dataset comprising 79 AD cases and 112 controls. In Hispanics we find a modest interaction between CATD genotype and age of onset on risk for AD, such that the non-T-carrying genotype confers increased risk. In our Caucasian dataset we find no evidence for association between the CATD polymorphism and AD, although we do observe a small tendency towards an increase in the T-carrying genotypes in the case group, consistent with previous studies. We conducted an aggregate analysis of the published Caucasian datasets and found evidence that this CATD polymorphism (or another locus in linkage disequilibrium) does contribute significant, but small (<2%) risk for AD.
Aged↗
DNase I footprinting of the human interleukin-5 gene promoter.
A characteristic feature of allergic asthma is the overexpression of the T helper type 2 (Th2) cytokines interleukin-4 (IL-4), IL-5 and IL-13 by T lymphocytes. Of these cytokines, IL-5 is critical for the growth, survival and recruitment of eosinophils which are thought to be responsible for the tissue damage observed in asthmatic airways. The expression of human IL-5 is primarily regulated at the transcriptional level; however, little is known about the mechanisms that control its transcription. Using nuclear extracts from allergen-specific human T-cell clones we have performed DNase I footprinting of the human IL-5 promoter in order to establish sites occupied by transcription factors. We show footprints covering the conserved lymphokine element 0 ¿(CLE0) -60 to -44 base pairs (bp) and GATA (-73 to -62 bp) elements, which have previously been identified to be important in the regulation of the murine IL-5 promoter. We also describe a footprint covering a considerably extended Octamer binding site (-249 to -217 bp), which encompasses two hitherto unidentified CCAAT/enhancer binding protein consensus binding sites. We have also identified a previously unknown Ets binding site (-274 to -264 bp). These novel data on the regions of the human IL-5 promoter that are bound by transcription factors should allow dissection of the regulatory mechanisms involved in the transcription of IL-5 in the T-helper lymphocytes of asthmatics.
Asthma↗
Cellular immune profile of patients with advanced cancer before and after taxane treatment.
The purpose of this study is to determine immune recovery and function after treatment with docetaxel or paclitaxel. Peripheral blood mononuclear cells were harvested before chemotherapy and at weekly times afterwards for cycle 1. Leukocyte subsets ICD45hiCD14lo polymorphonuclear neutrophils, CD45hiCD14hi monocytes, CD45hiCD14- lymphocytes, CD3+CD4/CD8+ T cells, CD3-CD19+ B cells, CD3-CD16/CD56+ natural killer (NK) cells], and circulating cytokine levels [tumor necrosis factor-alpha, gamma-interferon (gamma-IFN), and interleukins (IL-2, IL-10, IL-12)] were followed. In addition, T-cell mitogenic function, NK function, and lymphokine activated killer (LAK) function was assessed. Ten patients were entered in the trial. T-cell frequency, B-cell frequency, and CD4/CD8 ratio did not change. IL-10 serum levels significantly decreased in paclitaxel-treated patients (4.4+/-1.3 pg/ml at week 4 versus 7.8+/-2.1 pg/ml at baseline; p < 0.05). IL-2, IL-12, and gamma-IFN levels were not detectable. NK cytotoxic activity decreased in docetaxel-treated patients. LAK cell activity was not altered. Four patients achieved a partial or complete response. They demonstrated higher than normal CD4:CD8 T-cell ratios and an improved phytohemagglutinin stimulation index (SI = 2.5). In conclusion, our findings suggest that immune function was affected more significantly after docetaxel treatment. Investigational approaches, which enhance cellular immunity, may be of greater relevance after treatment with docetaxel. Additional studies monitoring NK function after chemotherapy are recommended.
Aged↗
Cloning of the Arabidopsis RSF1 gene by using a mapping strategy based on high-density DNA arrays and denaturing high-performance liquid chromatography.
Mapping genes by chromosome walking is a widely used technique applicable to cloning virtually any gene that is identifiable by mutagenesis. We isolated the gene responsible for the recessive mutation rsf1 (for reduced sensitivity to far-red light) in the Arabidopsis Columbia accession by using classical genetic analysis and two recently developed technologies: genotyping high-density oligonucleotide DNA array and denaturing high-performance liquid chromatography (DHPLC). The Arabidopsis AT412 genotyping array and 32 F(2) plants were used to map the rsf1 mutation close to the top of chromosome 1 to an interval of approximately 500 kb. Using DHPLC, we found and genotyped additional markers for fine mapping, shortening the interval to approximately 50 kb. The mutant gene was directly identified by DHPLC by comparing amplicons generated separately from the rsf1 mutant and the parent strain Columbia. DHPLC analysis yielded polymorphic profiles in two overlapping polymorphic amplicons attributable to a 13-bp deletion in the third of five exons of a gene encoding a 292-amino acid protein with a basic helix-loop-helix (bHLH) domain. The mutation in rsf1 results in a truncated protein consisting of the first 129 amino acids but lacking the bHLH domain. Cloning the RSF1 gene strongly suggests that numerous phytochrome A-mediated responses require a bHLH class transcription factor.
Alleles↗
Symptom severity, personal and social variables after armed robbery.
OBJECTIVES: To investigate the relative importance of personal and social variables on post-trauma symptom recovery. DESIGN: Prospective survey of armed robbery victims. METHODS: Fifty-one consecutive armed robbery victims were assessed immediately and at 1 month post-raid for post-traumatic stress. One month post-raid, crisis support, causal attribution and coping were also measured. Thirty-one of the sample were assessed for symptoms 6 months after the raid. RESULTS: Both the main and follow-up samples had high levels of post-traumatic stress symptoms immediately after the raid which reduced significantly 1 month later and, for the follow-up subsample, further still 6 months later. Higher levels of symptoms at 1 month and poor crisis support were associated with higher levels of symptoms at follow-up. CONCLUSIONS: Purposeful coping, symptom severity and social support effect post-trauma recovery.
Adaptation, Psychological↗
Community networking as a means for identifying people with diabetes in a rural, predominantly bicultural community in New Zealand.
AIMS: To assess the use of community networking to estimate the prevalence of diabetes in a predominantly New Zealand Maori and European community. METHODS: A cross-sectional survey of people with known diabetes identified either through general practice or community networks (others with diabetes, public notices or public meetings) was undertaken. Ascertainment was compared using capture-recapture methods for two independent samples. RESULTS: Overall ascertainment by community networking was greater for Maori than Europeans (40 +/- 3% vs 15 +/- 2%, p < 0.001). Ascertainment using general practice registers was comparable in the two ethnic groups (48 +/- 4% vs 55 +/- 5%, respectively). Women were more likely than men to be contacted through community networking (odds ratio 1.47, 1.05-2.06). CONCLUSION: In closely knit communities, community networking provides an independent source for estimating the prevalence of diabetes.
Community Health Planning↗
The effect of decreasing digital image resolution on teledermatology diagnosis.
OBJECTIVE: To determine the effect of degraded digital image resolution (as viewed on a monitor) on the accuracy and confidence of dermatologic interpretation. MATERIALS AND METHODS: Eight dermatologists interpreted 180 clinical cases divided into three Logical Competitor Sets (LCS) (pigmented lesions, non-pigmented lesions, and inflammatory dermatoses). Each case was digitized at three different resolutions. The images were randomized and divided into (9) 60-image sessions. The physicians were completely blinded concerning the image resolution. After 60 seconds per image, the viewer recorded a diagnosis and level of confidence. The resultant ROC curves compared the effect of LCS, level of clinical difficulty, and resolution of the digital image. One-way analysis of variance (ANOVA) compared the curves. RESULTS: The areas beneath the ROC curves did not demonstrate any consistently significant difference between the digital image resolutions for all LCS and levels of difficulty. The only significant effect observed was amongst pigmented lesions (LCS-A) where the ROC curve area was significantly smaller in the easy images at high resolution compared to low and medium resolutions. For all other ROC curve comparisons within LCS-A, at all other levels of difficulty, as well as within the other LCS at all levels of difficulty, none of the differences was significant. CONCLUSION: A 720 x 500 pixel image can be considered equivalent to a 1490 x 1000 pixel image for most store-and-forward teledermatology consultations.
Analysis of Variance↗
Phase I evaluation of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C-alpha, in patients with advanced cancer.
PURPOSE: To determine the maximum-tolerated dose (MTD) and pharmacologic behavior of ISIS 3521 (ISI 641A), an antisense phosphorothioate oligonucleotide to protein kinase C-alpha. PATIENTS AND METHODS: Thirty-six patients with advanced cancer received 99 cycles of ISIS 3521 (0.15 to 6.0 mg/kg/d) as a 2-hour intravenous infusion administered three times per week for 3 consecutive weeks and repeated every 4 weeks. Plasma and urine sampling was performed during the first week of treatment and subjected to capillary gel electrophoresis to determine full-length antisense oligonucleotide in addition to chain-shortened metabolites. RESULTS: Drug-related toxicities included mild to moderate nausea, vomiting, fever, chills, and fatigue. Hematologic toxicity was limited to thrombocytopenia (grade 1, four patients; grade 2, one patient; grade 3, one patient). There was no relationship between dose, maximum concentration of the drug (C(max)), or area under the plasma concentration versus time curve (AUC) and coagulation times or complement levels. Dose escalation was discontinued because of the attainment of peak plasma concentrations, which approached that associated with complement activation in primates. Two patients with non-Hodgkin's lymphoma who completed 17 and nine cycles of therapy achieved complete responses. The pharmacokinetic profile of ISIS 3521 revealed a short elimination half-life (18 to 92 minutes), as well as a dose-dependent decrease in clearance and dose-dependent increases in C(max), AUC, and elimination half-life. CONCLUSION: No dose-limiting toxicity of ISIS 3521 was identified, and clinical activity was observed. A short elimination half-life was identified, which suggests that alternate schedules with prolonged administration may be necessary for further clinical development.
Adult↗
Corticosteroid-resistant bronchial asthma is associated with increased c-fos expression in monocytes and T lymphocytes.
Unstimulated peripheral blood mononuclear cells (PBMCs) from corticosteroid-resistant (CR) but not corticosteroid-sensitive (CS) asthmatics demonstrate increased activating peptide-1 (AP-1)- and decreased glucocorticoid receptor (GR)-DNA binding. We test whether these abnormalities are associated with excessive generation of c-fos, the inducible component of AP-1. The c-fos transcription rate, mRNA and protein levels, and GR-DNA binding were quantitated in PBMCs, T cells, and monocytes from CS, CR, and nonasthmatic subjects. There was a 1.7-, 4.2-, and 2.3-fold greater increase in the baseline c-fos transcription rate, mRNA expression, and protein levels, respectively, in PBMCs derived from CR compared with CS patients. At optimal stimulation with PMA, there was a 5.7-, 3.4-, and 2-fold greater increase in the c-fos transcription rate, mRNA accumulation, and protein levels, respectively, in CR compared with CS PBMCs. These abnormalities were detected in both the T cell and monocyte subpopulations. PMA stimulation converted PBMCs from a CS to a CR phenotype and was associated with direct interaction between c-Fos and the GR. Pretreatment of PBMCs from CR patients with c-fos antisense oligonucleotides enhanced GR-DNA binding activity in CR PBMCs stimulated with dexamethasone. We suggest that increased c-fos synthesis provides a major mechanism for the increased AP-1- and decreased GR- DNA binding seen in CR asthma.
Adrenal Cortex Hormones↗
Biochemical basis for the impaired immune response in chronic renal failure?
Explore the source record for details and available documents.
Adenine Nucleotides↗
Methadone in rural general practice: addiction or rehabilitation.
This article presents the reflections of a rural general practitioner who has been involved in the Victorian methadone program for some years. Its object is to highlight some perceived strengths and weaknesses in the Methadone Program, particularly as it operates in rural areas, and to suggest some ways in which it could be modified to provide better for the needs of opiate-dependent persons who live outside the major cities.
Counseling↗
Portable satellite telemedicine in practice.
The US army's first portable telemedicine unit was built in 1993 and comprised a 'ruggedized' videoconferencing unit. The unit was initially used in the United Nations' operations in Macedonia in February 1994 and subsequently in support of the Mobile Army Surgical Hospitals in Haiti, but its dimensions made it suitable only for locations where a move at short notice was unlikely. The second portable telemedicine unit comprised a PC linked to an Inmarsat B earth station through a modern. The unit allowed videoconferencing at 64 kbit/s. Three and a half years of clinical experience with both units has shown this to be quite adequate for the majority of clinical telemedicine. Portable telemedicine units have been a major benefit to medical commanders in the field.
Bosnia and Herzegovina↗
Maternal cigarette smoking and child psychiatric morbidity: a longitudinal study.
OBJECTIVE: Previous studies have linked maternal smoking during pregnancy with behavioral disturbance in children. However, additional evidence is needed to address the causality of the relationship. The present study analyses result from an Australian cohort of 5342 5-year-old children whose mothers were recruited early in pregnancy. METHODS: Smoking history was gathered for prepregnancy, first clinic visit (FCV), late pregnancy, and when the child was 6 months and 5 years of age. Behavior problems at the age of 5 were assessed using a modified Child Behavior Check List (CBCL) shown to have high agreement with the complete CBCL. This resulted in the formation of three scales: internalizing; social, attentional and thought; and externalizing behavior problems, which were then dichotimized at the 90th percentile in each case. Logistic regression was used to model these outcomes as a function of maternal smoking at five time points during which it was assessed. A series of models explored the effect of additional adjustment for confounding. The predictors of attrition (29.5%) throughout the cohort were also identified by multivariate modeling. RESULTS: The final analysis was carried out on a cohort of mother-child pairs for whom data and child behavior outcomes were complete. The mean age of children was 5 years, 6 months with a range from 4 to 6 years. The mean age of mothers at the time of birth of the child was 25 years, with a range from 13 to 47 years. Mothers lost to follow-up were more likely to be younger, single, and less well-educated than those who continued participation, although maternal smoking was not an independent determinant. Unadjusted analyses showed strong associations between externalizing child behavior and maternal smoking during pregnancy and at the 5-year follow-up, with relative risks (RRs) up to 2.6 for children of women smoking at least 20 cigarettes per day at the first antenatal clinic visit. A clear dose-response relationship existed in most relationships with higher levels of smoking being associated with higher rates of externalizing behavior problems. Weaker relationships occurred for internalizing behavior and social, attentional and thought behavior problems. Multivariate analysis of the timing in more detail that the association between maternal smoking and child behavior problems persisted, although the evidence for dose-response diminished. Moreover, it was primarily associated with smoking as determined by questions asked at the FCV (RR = 1.52, 2.03, 2.16) for 1 to 9, 10 to 19, and >/=20 cigarettes per day, respectively, compared with nonsmoking and secondarily by smoking determined at the 5-year follow-up (RR = 1.52, 1.87, 1.29) for 1 to 9, 10 to 19, and >/=20 cigarettes per day respectively, compared with nonsmoking. This association appeared to be independent of a wide range of possible confounders such as maternal age, education, social class, marital status and mental health, gestation at FCV, complications during pregnancy, the child's sex, gestational age at birth, and age at last follow-up. Adjustments were also made for the mother's employment since birth, family structure, and maternal mental health at the time of the CBCL assessment. Associations between externalizing behavior problems and maternal smoking at other times, and those between other behavioral problems examined and maternal smoking were not significant. CONCLUSION: Although previous studies have found evidence for an association between maternal smoking and child behavior problems, the strength of this study lies in its size, its detailed and consistent measurement of maternal smoking, and its ability to control for many social and biological factors linked to maternal smoking and child behavior. (ABSTRACT TRUNCATED)
Adolescent↗
Putting CQI to work.
Explore the source record for details and available documents.
Attitude of Health Personnel↗