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Biomedical subjects

S Clark

Publications and source records attributed to S Clark.

At least 55 records · Page 3Linked to original sources
PubMed2001

Risk factors for lack of asthma self-management knowledge among ED patients not on inhaled steroids.

The study objective was to estimate the level of asthma knowledge and self-management skills among asthmatic patients who are not on inhaled corticosteroids and who present with acute asthma to the emergency department (ED). The design was to interview of patients by telephone at 90 to 100 days after enrollment in the Fourth Multicenter Airways Research Collaboration (MARC-4), a randomized trial comparing inhaled fluticasone versus placebo in addition to standard post-ED therapy. The setting was a multicenter trial involving 41 US urban EDs. Persons aged 12 to 54, not on inhaled steroids, who presented to the ED with acute asthma were studied. Of the 617 patients enrolled on MARC-4 405 (66%) were contacted. Mean (+/-SD) age was 30 (+/-11); 54% were women; acute asthma severity was 44% moderate and 56% severe; and 9% had prior intubation. Twenty percent (95% CI 16%-24%) responded that asthma could not be monitored and 40% (95% CI 35%-44%) scored low on a hypothetical acute asthma attack scenario. Predictors for lack of asthma knowledge and self-management skills were: less than a high school education; current smoking; lower median household income; and no history of steroid use. These data suggest that many ED patients with asthma have poor knowledge of asthma monitoring and poor self-management skills and that a "high risk" group is also identifiable. Efforts to design and implement an ED-based educational program should be tailored to better meet the needs of this high risk group.

Acute Disease↗
PubMed2001

Evaluation of dynamic balance among community-dwelling older adult fallers: a generalizability study of the limits of stability test.

OBJECTIVE: To establish reliability estimates of the 75% Limits of Stability Test (75% LOS test) when administered to community-dwelling older adults with a history of falls. DESIGN: Generalizability theory was used to estimate both the relative contribution of identified error sources to the total measurement error and generalizability coefficients. A random effects repeated-measures analysis of variance (ANOVA) was used to assess consistency of LOS test movement variables across both days and targets. SETTING: A motor control research laboratory in a university setting. PARTICIPANTS: Fifty community-dwelling older adults with 2 or more falls in the previous year. MAIN OUTCOME MEASURES: Spatial and temporal measures of dynamic balance derived from the 75% LOS test included average movement velocity, maximum center of gravity (COG) excursion, end-point COG excursion, and directional control. RESULTS: Estimated generalizability coefficients for 2 testing days ranged from.58 to.87. Total variance in LOS test measures attributable to inconsistencies in day-to-day test performance (Day and Subject x Day facets) ranged from 2.5% to 8.4%. The ANOVA results indicated that no significant differences were observed in the LOS test variables across the 2 testing days. CONCLUSIONS: The 75% LOS test administered to older adult fallers on 2 consecutive days provides consistent and reliable measures of dynamic balance.

Accidental Falls↗
PubMed2001

Differences between men and women in reporting of symptoms during an asthma exacerbation.

STUDY OBJECTIVE: Compared with men, women presenting to the emergency department with acute asthma are more likely to be admitted and to have a longer hospital stay. This study compares peak expiratory flow rate (PEFR) with reported symptom severity between men and women with acute asthma. The null hypothesis was that men and women report similar severity symptoms for similar levels of airway obstruction. METHODS: This study combined data from 4 prospective cohort studies performed from 1996 to 1998 as part of the Multicenter Airway Research Collaboration. Using a standardized protocol, investigators at 64 EDs in 21 US states and 4 Canadian provinces provided 24-hour per day coverage for a median of 2 weeks. RESULTS: Of the 1,291 patients with moderate to severe exacerbations (initial percentage of predicted PEFR <80%), 62% were women. Women were more likely than men to report "severe" complaints in terms of symptom frequency, symptom intensity, and resulting activity limitations (all P <.05). Women with moderate exacerbations were especially likely to describe their exacerbation as causing "severe" activity limitations (sex-PEFR interaction, P =.05). CONCLUSION: Men are less likely than women to report severe asthma symptoms and activity limitations in the presence of airway obstruction. This finding supports use of objective measures of airway obstruction when managing patients with asthma so that those whose symptoms do not reflect the severity of their obstruction can be recognized and properly treated. It also reconfirms the need for increased research on differences between men and women in acute asthma.

Adult↗
PubMed2001

Mapping grief: an active approach to grief resolution.

This article describes a clinical tool, the Grief Map, that is designed to assist those who are grieving death and non-death losses. The map provides a constructive multidimensional framework for dealing with the phenomena of the grieving process and for rebuilding life following major loss. The method of developing the map and its various uses as an assessment, educational, and therapeutic tool are detailed with illustrative case examples. The underlying precepts on which the map is based and its correlates with current theory and research are discussed. The limitations of the map and issues for further research are discussed.

Grief↗
PubMed2001

Tsl and LP-BM5: a comparison of two murine retrovirus models for HIV.

The ts1 murine leukemia virus produces an immunodeficiency state in mice that parallels human immunodeficiency virus (HIV) infection in humans. Other murine leukemia viruses, such as LP-BM5 used in the murine acquired immune deficiency virus (MAIDS) model, have been studied extensively as a small animal model for HIV research, but lack many key similarities to HIV. Mice infected with ts1, however, utilize CD4 target cells for infection, undergo neuronal loss and demyelination, and develop clinical immunodeficiency. These features make this retrovirus in many ways an ideal candidate for a small animal model for HIV research. In this review article, the early development, the molecular and clinical pathogenesis of both the ts1 mutant of the Moloney murine leukemia virus and LP-BM5 are examined. Based on an extensive evaluation of the literature on LP-BM5 and ts1, it is concluded that the ts1 virus may serve as a better animal model to human retrovirus infection.

Amino Acid Sequence↗
PubMed2001

A tropomyosin-2 mutation suppresses a troponin I myopathy in Drosophila.

A suppressor mutation, D53, of the held-up(2) allele of the Drosophila melanogaster Troponin I (wupA) gene is described. D53, a missense mutation, S185F, of the tropomyosin-2, Tm2, gene fully suppresses all the phenotypic effects of held-up(2), including the destructive hypercontraction of the indirect flight muscles (IFMs), a lack of jumping, the progressive myopathy of the walking muscles, and reductions in larval crawling and feeding behavior. The suppressor restores normal function of the IFMs, but flight ability decreases with age and correlates with an unusual, progressive structural collapse of the myofibrillar lattice starting at the center. The S185F substitution in Tm2 is close to a troponin T binding site on tropomyosin. Models to explain suppression by D53, derived from current knowledge of the vertebrate troponin-tropomyosin complex structure and functions, are discussed. The effects of S185F are compared with those of two mutations in residues 175 and 180 of human alpha-tropomyosin 1 which cause familial hypertrophic cardiomyopathy (HCM).

Amino Acid Sequence↗
PubMed2001

Stroke genomics: approaches to identify, validate, and understand ischemic stroke gene expression.

Sequencing of the human genome is nearing completion and biologists, molecular biologists, and bioinformatics specialists have teamed up to develop global genomic technologies to help decipher the complex nature of pathophysiologic gene function. This review will focus on differential gene expression in ischemic stroke. It will discuss inheritance in the broader stroke population, how experimental models of spontaneous stroke might be applied to humans to identify chromosomal loci of increased risk and ischemic sensitivity, and also how the gene expression induced by stroke is related to the poststroke processes of brain injury, repair, and recovery. In addition, we discuss and summarise the literature of experimental stroke genomics and compare several approaches of differential gene expression analyzes. These include a comparison of representational difference analysis we have provided using an experimental stroke model that is representative of stroke evolution observed most often in man, and a summary of available data on stroke differential gene expression. Issues regarding validation of potential genes as stroke targets, the verification of message translation to protein products, the relevance of the expression of neuroprotective and neurodestructive genes and their specific timings, and the emerging problems of handling novel genes that may be discovered during differential gene expression analyses will also be addressed.

Animals↗
PubMed2001

Youth suicide issues in general practice.

OBJECTIVE: To identify the factors that predispose to suicidal thinking and behaviours in young Australians who visit a general practitioner. METHOD: A clinical audit program that required a pre-entry survey of 50 young people attending a GP. RESULTS: Suicidal thinking and behaviours in young people have been increasing over the past decades. In this survey of over 6000 young Australians, evidence suggests that there are fundamental mental health factors that all GPs should explore with young people to assess the risk of self harm. These include feelings of hopelessness and powerlessness, the pattern and type of drug use, a history of sexual abuse, concerns about sexuality and sexual identity. DISCUSSION: General practitioners should not rely on their previous knowledge of a young person but continue to explore issues of suicide where any combinations of the above factors are present.

Adolescent↗
PubMed2001

Reduction of pain episodes and prothrombotic activity in sickle cell disease by dietary n-3 fatty acids.

The effects of dietary n-3 fatty acids (n-3FAs) on the frequency of pain episodes and ex vivo blood tests of thrombosis have been evaluated in patients with sickle cell disease (SCD) utilizing a double-blind, olive oil-controlled clinical trial. Dietary n-3FA therapy (0.1 g/kg/d) was provided as menhaden fish oil (0.25 g/kg/d) containing 12% eicosapentaenoic acid (EPA), and 18% docosahexaenoic acid (DHA). Within 1 month dietary n-3FAs exchanged with n-6FAs in plasma and erythrocyte membrane phospholipids (p <0.01 in all cases). Treatment with dietary n-3FAs for 1 year reduced the frequency of pain episodes requiring presentation to the hospital from 7.8 events during the preceding year to 3.8 events/year (p <0.01; n = 5). By contrast, subjects receiving control dietary olive oil (n = 5) experienced 7.1 pain events/year, compared to 7.6 during the previous year (p >0.4). The reduction in episodes in n-3FA-treated subjects was also significant when compared to control subjects (p <0.01). Dietary n-3FA therapy was not associated with hemorrhagic, gastrointestinal or other adverse effects. Compared to 10 asymptomatic African-American controls, sickle cell subjects demonstrated significantly increased pretreatment: 1) flow cytometric expression of platelet membrane P-selectin (CD62p; p <0.01) and annexin V binding sites (p = 0.02); 2) plasma levels of platelet-specific secretory proteins platelet factor 4 (PF4) and beta-thromboglobulin (betaTG) (p <0.01 in both cases); 3) plasma products of thrombin generation, prothrombin fragment 1.2 (F1.2) and thrombin:antithrombin (TAT) complex (p <0.01 in both cases); and 4) plasma levels of thrombolytic products, D-dimer and plasmin:antiplasmin (PAP) complex (p <0.01 in both cases). Treatment with dietary n-3FAs concurrently decreased plasma levels of F1.2, D-dimer, and PAP (p <0.05, compared to olive oil controls), implying that the reduction in pain events was related to n-3FA-dependent inhibition of thrombosis. We conclude that dietary n-3FAs reduce the frequency of pain episodes perhaps by reducing prothrombotic activity in sickle cell disease.

Adult↗
PubMed2000

Methylation of a CpG island within the promoter region of the KAI1 metastasis suppressor gene is not responsible for down-regulation of KAI1 expression in invasive cancers or cancer cell lines.

The molecular basis for downregulation of the KAI1 metastasis suppressor gene in invasive and metastatic human cancers is unknown. We have used bisulphite methylation analysis of DNA from paraffin-embedded invasive bladder tumour samples and from bladder cancer cell lines to determine if hypermethylation of a CpG island within the KAI1 promoter is responsible for this effect. Representative invasive tumour cell lines were also exposed to 5-aza-2-deoxycytidine. We found no evidence for hypermethylation of the CpG island and suggest that mechanisms other than promoter hypermethylation are responsible for reduced KAI1 expression in invasive bladder tumours and tumour cell lines.

Antigens, CD↗
PubMed2000

A randomized trial of improved weight loss with a prepared meal plan in overweight and obese patients: impact on cardiovascular risk reduction.

OBJECTIVE: To assess the long-term effects of a prepackaged, nutritionally complete, prepared meal plan compared with a usual-care diet (UCD) on weight loss and cardiovascular risk factors in overweight and obese persons. DESIGN: In this randomized multicenter study, 302 persons with hypertension and dyslipidemia (n = 183) or with type 2 diabetes mellitus (n = 119) were randomized to the nutrient-fortified prepared meal plan (approximately 22% energy from fat, 58% from carbohydrate, and 20% from protein) or to a macronutrient-equivalent UCD. MAIN OUTCOME MEASURES: The primary outcome measure was weight change. Secondary measures were changes in blood pressure or plasma lipid, lipoprotein, glucose, or glycosylated hemoglobin levels; quality of life; nutrient intake; and dietary compliance. RESULTS: After 1 year, weight change in the hypertension/dyslipidemia group was -5.8+/-6.8 kg with the prepared meal plan vs -1.7+/-6.5 kg with the UCD plan (P<.001); for the type 2 diabetes mellitus group, the change was -3.0+/-5.4 kg with the prepared meal plan vs -1.0+/-3.8 kg with the UCD plan (P<.001) (data given as mean +/- SD). In both groups, both interventions improved blood pressure, total and low-density lipoprotein cholesterol levels, glycosylated hemoglobin level, and quality of life (P<.02); in the diabetic group, the glucose level was reduced (P<.001). Compared with those in the UCD group, participants with hypertension/dyslipidemia in the prepared meal plan group showed greater improvements in total (P<.01) and high-density lipoprotein (P<.03) cholesterol levels, systolic blood pressure (P<.03), and glucose level (P<.03); in participants with type 2 diabetes mellitus, there were greater improvements in glucose (P =.046) and glycosylated hemoglobin (P<.02) levels. The prepared meal plan group also showed greater improvements in quality of life (P<.05) and compliance (P<.001) than the UCD group. CONCLUSIONS: Long-term dietary interventions induced significant weight loss and improved cardiovascular risk in high-risk patients. The prepared meal plan simultaneously provided the simplicity and nutrient composition necessary to maintain long-term compliance and to reduce cardiovascular risk.

Adult↗
PubMed2000

Localization of a recessive gene for North American Indian childhood cirrhosis to chromosome region 16q22-and identification of a shared haplotype.

North American Indian childhood cirrhosis (NAIC, or CIRH1A) is an isolated nonsyndromic form of familial cholestasis reported in Ojibway-Cree children and young adults in northwestern Quebec. The pattern of transmission is consistent with an autosomal recessive mode of inheritance. To map the NAIC locus, we performed a genomewide scan on three DNA pools of samples from 13 patients, 16 unaffected siblings, and 22 parents from five families. Analysis of 333 highly polymorphic markers revealed 3 markers with apparent excess allele sharing among affected individuals. Additional mapping identified a chromosome 16q segment shared by all affected individuals. When the program FASTLINK/LINKAGE was used and a completely penetrant autosomal recessive mode of inheritance was assumed, a maximum LOD score of 4.44 was observed for a recombination fraction of 0, with marker D16S3067. A five-marker haplotype (D16S3067, D16S752, D16S2624, D16S3025, and D16S3106) spanning 4.9 cM was shared by all patients. These results provide significant evidence of linkage for a candidate gene on chromosome 16q22.

Adult↗
PubMed2000

Large-scale test of hypothesised associations between the angiotensin-converting-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls. International Studies of Infarct Survival (ISIS) Collaborators.

BACKGROUND: The original report of a possible association between myocardial infarction and the insertion/deletion (I/D) polymorphism of the gene for the angiotensin-1-converting enzyme (ACE) indicated a risk ratio for myocardial infarction with the DD genotype of 1.34 (95% CI 1.05-1.70), and the association was claimed to be particularly strong in a retrospectively defined low-risk subgroup (3.2 [95% CI 1.7-5.9). Subsequent investigations reached varying conclusions, but all were small, and much larger studies were needed. METHODS: 4629 myocardial infarction cases and 5934 controls were compared. Cases were UK men aged 30-54 years and women aged 30-64 years recruited on presentation to hospital with confirmed myocardial infarction. Controls were aged 30-64 years with no history of cardiovascular disease, but were siblings or children of myocardial infarction survivors, or spouses of such relatives. All risk-ratio calculations allow for this relatedness of some of the controls. An updated meta-analysis of previous studies was also conducted. FINDINGS: The ACE DD genotype was found in 1359 (29.4%) of the myocardial infarction cases and in 1637 (27.6%) of the controls (risk ratio 1.10 [95% CI 1.00-1.21]). The association between myocardial infarction and the DD genotype did not seem to be stronger in the subgroup defined as low risk by previously used criteria (234 [28%] of 836 cases and 911 [28%] of 3253 controls: risk ratio 1.04 [95% CI 0.87-1.24]), or in any other subgroup. Nor was the ACE I/D genotype predictive of subsequent survival. INTERPRETATION: This study involved many more cases than any previously reported study of this question, but did not confirm the existence of any substantial association. In an updated meta-analysis of these results with those of previously published studies, the risk ratio for myocardial infarction with the DD genotype seems to lie in the range 1.0 to about 1.1. Although an increase in risk of up to about 10-15% cannot be ruled out, substantially more extreme risks can be. Moreover, there are not especially strong associations in the subgroups previously selected for emphasis. These findings illustrate the need for some studies of candidate genes to involve much larger populations than is customary, without undue emphasis on retrospectively defined subgroups.

Adult↗