Search PubMed⌕ Search

Biomedical subjects

N Thomas

Publications and source records attributed to N Thomas.

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

In vivo inhibition of cyclooxygenase-2 by a selective phosphorothioated oligonucleotide.

Inhibition of cyclooxygenase-2 (cox-2) is considered to be anti-inflammatory, whereas inhibition of the constitutive isozyme cox-1 causes renal and gastrointestinal toxicity. Therefore, to achieve an optimal anti-inflammatory effect, an inhibitor should be cox-2 selective without inhibiting cox-1. For this purpose, 10 different cox-2-selective phosphorothioated oligonucleotides (S-oligos) were tested to inhibit the cox-2 enzyme selectively in vivo. An aqueous solution of these S-oligos (3 mg/kg body weight) was injected intraperitoneally (i.p.) into male Sprague-Dawley rats with colitis induced by trinitrobenzene sulfonic acid (TNBS). The colonic levels of cox-2 protein, mRNA, myeloperoxidase (MPO), and prostaglandin E2 (PGE2) were increased significantly on day 1 and remained significantly elevated until day 7 post-TNBS administration, whereas cox-1 remained unaltered. Two S-oligos were found to be effective in reducing the level of cox-2 protein selectively without any effect on the cox-1. The effective S-oligo, but not the mismatched control oligo, reduced the tissue levels of PGE2 and MPO activity significantly. The effective S-oligo reduced the level of cox-2 but not the cox-1 mRNA significantly, whereas a mismatched or a sense control oligo did not affect the levels of these isoforms. M-fold analysis demonstrated extensive secondary structure formation in the cox-2 mRNA. These findings demonstrate that only a few selected sites in the cox-2 target mRNA are accessible in vivo, probably because of the presence of secondary structures. Suppression of cox-2 protein, PGE2, and MPO activity by the S-oligo might prove to be an anti-inflammatory property.

Animals↗
PubMed2001

Correlates of recent suicide attempts in a triethnic group of adolescents.

PURPOSE: To describe recent self-reported suicide attempts in a triethnic group of adolescents, to analyze differences in the correlates of attempts by ethnicity and gender, and to explore theoretical correlates of recent suicide attempts using a resilience framework. METHODS: Quantitative data were collected from 10,059 students in 7th, 9th, and 11th grades in Connecticut in 1996. Secondary analysis was done to compare respondents of African American, Hispanic Latino, and Caucasian ethnicities. Data were analyzed using bivariate and multivariate procedures. Logistic regression was used to identify the best set of explanatory variables for recent suicide attempts. RESULTS: The percentage of suicide attempts was significantly higher among Hispanic Latina girls (19.3%) than in any other ethnic-gender group. Significant relationships were found between recent suicide attempts and (a) family history of suicide attempt, (b) friend's history of suicide attempt, (c) history of sexual abuse, (d) history of physical abuse, and (e) environmental stress. The significant set of explanatory variables for recent suicide attempts for the three ethnic groups combined were stress, internalizing and externalizing behaviors, physical and sexual abuse, family and friend attempted suicide, social connectedness, and religious influence. CONCLUSIONS: Findings support use of a resilience model for suicide attempts among three ethnic groups. The finding of a significantly higher percentage of recent suicide attempts by Hispanic girls compared to girls in other ethnic-gender groups warrants further investigation along with development and testing of culturally sensitive preventive interventions.

Adolescent↗
PubMed2001

Pediatric simple open heart surgery critical pathway.

In 1997, administrators discovered that DRG 108 (other major cardiothoracic procedures), which includes many of the surgical repairs for congenital heart disease, was one of the biggest money losers for Vanderbilt Children's Hospital, resulting in a loss of approximately $1 million dollars per year. Time for action.

Child↗
PubMed2000

Smokers eligible for a clinical trial. Correlates of not returning for randomization.

PURPOSE: Recruitment and retention of minority participants is often the rate-limiting step towards successful completion of clinical trials. Participants who are eligible, and express interest in, enrolling into a trial will sometimes not return for their randomization visit. Factors associated with failure to return for randomization are largely unknown.METHODS: We compared 287 eligible African American (AA) smokers who enrolled, but did not return for randomization (NR), to 500 AA smokers who returned and were randomized (R) to participate in a study comparing culturally sensitive educational materials to usual care materials for smoking cessation in AAs. An analysis was conducted on variables potentially associated with not returning for randomization.RESULTS:Table 1CONCLUSIONS: Potential NR participants differed in a number of ways from those who returned for randomization. Better understanding of these factors may allow researchers to target recruitment efforts, potentially resulting in enhanced accrual and retention, and therefore, generalizability.

Journal Article↗
PubMed2000

Low mini-mental status predicts mortality in asymptomatic carotid arterial stenosis. Asymptomatic Carotid Atherosclerosis Study investigators.

OBJECTIVE: To determine whether carotid endarterectomy is superior to best medical therapy in preserving cognition, and whether low Mini-Mental State Examination (MMSE) scores predict TIA, stroke, myocardial infarction, or death. METHODS: Subjects participating in the Asymptomatic Carotid Atherosclerosis Study were administered the MMSE at periodic intervals. Group means were calculated at randomization, 1 and 3 months later, and every 6 months thereafter. The group means were compared by treatment and over time. A proportional hazard regression model incorporating postrandomization MMSE score as a predictor variable was used to estimate risk of death, stroke, or other outcome events. RESULTS: There was no intergroup difference in mean MMSE score during 5 years of observation. For individual patients, the relationship between a low postrandomization score on the MMSE and increased risk of death was significant (p </= 0.0001). Patients who experienced stroke after randomization also had a significant and persistent reduction in MMSE score (p </= 0.0001). CONCLUSIONS: Carotid endarterectomy had no impact on MMSE score in this study. Patients with low postrandomization MMSE scores had a greater likelihood of death. Stroke reduced MMSE scores and may portend cognitive impairment. The authors recommend the routine inclusion of cognitive testing in future clinical trials designed to evaluate prophylaxis or acute therapy of stroke.

Carotid Stenosis↗
PubMed2000

Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location.

Mutations in the methyl-CpG-binding protein gene MECP2 at Xq28 cause Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder characterized by a period of stagnation followed by regression in the development of young girls. Mutations were sought in MECP2 in 48 females with classical sporadic RTT, seven families with possible familial RTT and five sporadic females with features suggestive, but not diagnostic of RTT. Long distance PCR coupled with long-read direct sequencing was employed to sequence the entire MECP2 gene coding region in all cases. Mutations were identified in 44/55 (80%) unrelated classical sporadic and familial RTT patients, but only 1/5 (20%) sporadic cases with suggestive but non-diagnostic features of RTT. Twenty-one different mutations were identified (12 missense, four nonsense and five frame-shift mutations); 14 of these were novel. All missense mutations were located either in the methyl-CpG-binding domain or in the transcription repression domain. Nine recurrent mutations were characterized in a total of 33 unrelated cases (73% of all cases with MECP2 mutations). Significantly milder disease was noted in patients carrying missense mutations as compared with those with truncating mutations ( P = 0. 0023), and milder disease was associated with late as compared with early truncating mutations ( P = 0.0190).

Amino Acid Sequence↗
PubMed2000

Human gene mutation database-a biomedical information and research resource.

Although 20 years have elapsed since the first single basepair substitution underlying an inherited disease in humans was characterised at the DNA level, the initiative has only recently been taken to establish central database resources for pathological genetic variants. Disease-associated gene lesions are currently collected and publicised by the Human Gene Mutation Database (HGMD) in Cardiff, locus-specific mutation databases, and to some extent also by the Genome Database (GDB) and Online Mendelian Inheritance in Man (OMIM). To date, HGMD represents the only comprehensive and publicly available database of gene lesions underlying human inherited disease. By July 1999, HGMD contained over 18,000 different mutations from some 900 human genes, the majority being single basepair substitutions. In addition to its potential as an information resource for clinicians and genetic counsellors, HGMD has allowed molecular geneticists to address a variety of biological questions through meta-analysis of the collated data. HGMD also promises to assist research workers in optimising mutation search strategies for a given gene. A questionnaire sent out to, and answered by, the editors of 20 key journals revealed that human genetics journals are increasingly reluctant to publish mutation reports. Electronic data submission and publication facilities are therefore urgently required. The World Wide Web (WWW) provides an excellent medium within which to combine the centralised management of basic mutation data, including rigorous quality control, with the possibility of publishing additional mutation-related information. In response to these needs, HGMD has both instituted a collaboration with Springer-Verlag GmbH, Heidelberg, to potentiate free online submission and electronic publication of human gene mutation data and developed links with the curators of locus-specific mutation databases.

Databases, Factual↗
PubMed2000

Dietary restraint and self-reported meal sizes: diary studies with differentially informed consent.

Psychometric methods were used to explore the reliability and criterion validity of self-reported food intake in studies of dietary restraint. In Study 1 the reliabilities over days of daily aggregate intakes and of intakes at meals at particular times of day were assessed in 7 day food diaries by 27 low-BMI females. The sizes of particular meals correlated poorly with each other and with the total of all other meals; daily aggregate intakes also had poor reliability (Cronbach's alpha). Individuals meal sizes were consistent from day to day, with high inter-correlations between meal sizes, high correlations between meals at particular times and the sum of the remainder and high reliabilities. Aggregate intake had moderate criterion validity. Of individual meals, only breakfast achieved criterion validity, but there was a significant cubic component in its relationship with restraint. In Study 2, young male and female participants with various BMIs, completed a food diary on a single day. Again, aggregate daily intake had low reliability. Total intake and breakfast both had criterion validity, dietary restraint correlating negatively with total intake and breakfast size in the whole sample and in females, but there were significant quadratic components in the relationships. In contrast, restraint correlated positively with lunch size in the whole sample and in males. The combination of low reliability of individual meals as estimates of total intake, and the low criterion validity of all meals except breakfast, suggests that it may be inappropriate to study dietary restraint using aggregate self-reported intake measures.

Adult↗
PubMed2000

Renal medullary carcinoma: sonographic, computed tomography, magnetic resonance and angiographic findings.

Renal medullary carcinoma is a recently described, highly aggressive tumour, occurring predominantly in young patients of African descent with sickle cell trait (SCT). All have been metastatic at surgery. Surgery, radiotherapy and chemotherapy do not appear to alter the course of the disease. The survival time is very short. Presentation is usually with haematuria, abdominal pain and weight loss. Forty-nine patients have been reported from the USA, of these 47 were African/Americans. The reports have mostly appeared in pathology journals. On review of the imaging findings reported in the radiological journals, it becomes apparent that it is possible for a radiologist to suggest a specific diagnosis in the appropriate demographic and clinical setting. Here the first British patient of Afro-Caribbean decent in whom a pre-operative diagnosis was suggested on the imaging findings of a centrally located renal pelvic tumour, encasing the pelvis on a background of SCT in a 28-year-old is described. It is expected that a high index of suspicion in the appropriate clinical setting may lead to earlier diagnosis, treatment and survival of patients. The patient is alive and reasonably well 9 months after surgery. The full range of imaging findings in renal medullary carcinoma are described.

Adult↗
PubMed2000

Associations of fat distribution and obesity with hypertension in a bi-ethnic population: the ARIC study. Atherosclerosis Risk in Communities Study.

OBJECTIVE: To examine associations of hypertension with obesity and fat distribution among African American and white men and women. RESEARCH METHODS AND PROCEDURES: The analysis sample included 15,063 African American and white men and women between the ages of 45 and 64 years who were participants in the 1987 through 1989 examination of the Atherosclerosis Risk in Communities Study (ARIC). Odds ratios and adjusted prevalences of hypertension were calculated across sex-specific quintiles of body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, and waist-to-height ratio (waist/ height) and adjusted for age, research center, smoking, education, physical activity, alcohol consumption, hormone replacement therapy, and menopausal status. RESULTS: The prevalence of hypertension was higher among African Americans than whites. In the lowest quintile of BMI, 41% of African American women and 43% of African American men had hypertension compared with 14% of white women and 19% of white men. Elevated BMI, WHR, waist circumference, and waist/height were associated with increased odds of hypertension in African American and white men and women. In women, but not in men, there were significant interactions between ethnicity and the anthropometric variables studied here. The direction of the interaction indicated larger odds ratios for hypertension with increasing levels of anthropometric indices in white compared with African American women. DISCUSSION: Obesity and abdominal fat preponderance were associated with increased prevalence of hypertension in African American and white men and women. Associations were similar among African American and white men, but obesity and fat patterning were less strongly associated with hypertension in African American than in white women.

Adipose Tissue↗
PubMed2000

Fourier transform infrared spectroscopy of follicular fluids from large and small antral follicles.

Fourier transform infrared spectroscopy (FTIR) was used to obtain 'biochemical fingerprints' for the constitution of follicular fluids from large and small antral luteinized follicles (n = 54 pairs). All samples gave reproducible characteristic biological infrared absorption spectra, with recognizable amide I protein vibrations and acyl vibrations from fatty acids. Discriminant function analysis of the first derivative FTIR spectra, together with hierarchical cluster analysis used to construct a dendrogram, showed fluid from large follicles formed a homogeneous closely related cluster, whilst that from small follicles was distinct from the large, and heterogeneous in nature. The large follicle fluids showed closer biochemical similarity to each other than to the corresponding fluid taken from small matched follicles. An artificial neural network was trained and following validation with an independent test set, successfully distinguished follicular fluids from large and small follicles. The sex steroid concentrations in the fluids from large and small follicles were significantly different. These results show that fluid from large follicles is distinct in biochemical nature from that from small follicles, but the degree of homogeneity implies size-specific changes take place. These may have consequences for the developmental potential of the oocyte.

Discriminant Analysis↗
PubMed2000

Reverse and intermediate segregation of large beads in dry granular media

Mixtures of two types of glass beads have been sheared in a chute flow, in a half-filled rotating drum, and placed in a funnel to form a pile. In the three experimental devices, for small size ratios, there is a segregation of the large beads at the surface of the flowing phase (usual case), but for high size ratios (above about 5) the large beads segregate inside (reverse segregation). Precise measurements show that the segregation drives the large beads to an intermediate level inside the bed. In all devices, there is a continuous evolution of the location of the segregated beads from the surface to deep inside, when increasing the size ratio between the beads. The location of the segregated beads at intermediate levels is well defined both for high size ratios (above 5) and for very small size ratios (about 2), the level being very close to the surface in that case. The reverse and intermediate segregations are masked when using high fractions of large beads in the experiments. Their interpretation involves the high mass of the large particles balancing geometrical effects at a particular intermediate level inside the flowing layer.

Journal Article↗
PubMed1999

Sex and race differences in short-term prognosis after acute coronary heart disease events: the Atherosclerosis Risk In Communities (ARIC) study.

BACKGROUND: Case fatality after myocardial infarction (MI) among patients admitted to the hospital may differ between men and women and blacks and whites. Furthermore, a different pattern of sex and race differences in case fatality may occur when coronary deaths outside the hospital are included in the analysis. The ARIC study provides community-based data to examine 28-day case fatality rates after coronary heart disease (CHD) events. METHOD AND RESULTS: Surveillance of out-of-hospital CHD deaths and hospitalized MI was conducted in 4 U.S. communities from 1987 to 1993. Hospital discharges and death certificates were sampled, medical records abstracted, and interviews conducted with witnesses of out-of-hospital deaths. MI and out-of-hospital death classifications followed a standard algorithm. Linkage of hospitalized MIs to fatality within 28 days ensured complete ascertainment of case fatality rate. Comorbidities and complications during hospital stay were compared to assess possible explanatory factors for differences in case fatality. Overall, age-adjusted 28-day case fatality (MI plus CHD) was higher in black men compared with white men (odds ratio 1.78, 95% confidence interval 1.4-2.2) and in black women compared with white women (odds ratio 1.5, 95% confidence interval 1. 2-2.0). Although men had higher overall case fatality rates than did women, this difference was not statistically significant. After a hospitalized MI, 28-day case fatality rate was not statistically significantly different between men compared with women or blacks compared with whites. CONCLUSION: Race and sex differences in case fatality after hospitalized MI were not evident in these data, although when out-of-hospital deaths were included, men and blacks were more likely than women and whites to die within 28 days of an acute cardiac event. A majority of deaths occurred before hospital admission, and additional study of possible reasons for these differences should be a priority.

Adult↗
PubMed1999

Beagle 2: a proposed exobiology lander for ESA's 2003 Mars Express mission.

The aim of the proposed Beagle 2 small lander for ESA's 2003 Mars Express mission is to search for organic material on and below the surface of Mars and to study the inorganic chemistry and mineralogy of the landing site. The lander will have a total mass of 60kg including entry, descent, and landing system. Experiments will be deployed on the surface using a robotic arm. It will use a mechanical mole and grinder to obtain samples from below the surface, under rocks, and inside rocks. Sample analysis by a mass spectrometer will include isotopic analysis. An optical microscope, an X-ray spectrometer and a Mossbauer spectrometer will conduct in-situ rock studies.

Equipment Design↗