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Biomedical subjects

N Thomas

Publications and source records attributed to N Thomas.

At least 19 recordsLinked to original sources
PubMed2003

Triage score for severity of illness.

OBJECTIVE: To evolve a triage scoring system for severity of illness based on clinical variables related to systemic inflammatory response syndrome (SIRS). DESIGN: Prospective study in a tertiary-care hospital. METHODS: Consecutive pediatric patients admitted to the ward or pediatric intensive care unit (PICU) were studied. The respiratory rate, heart rate, capillary refill time, oxygen saturation (SpO2), systolic blood pressure and temperature were noted, Sensorium level was assessed on AVPU score. Variables were based on SIRS criteria and criteria mentioned in Advanced Pediatric Life Support (APLS). Each study variable was scored as 0 or 1 (normal or abnormal) and total score for each child obtained. The survival at discharge was correlated with the study variables and the total score. Another score based on the magnitudes of the coefficients in multiple logistic regression analysis was computed and the correlation between this score and mortality was also studied. ROC curve analysis was performed to see the overall predictive ability of the score as well as a cut off at which maximum discrimination occurred. RESULTS: Of 1099 children studied, 44 died. Of the seven variables, only five variables were abnormal in the study subjects. Except heart rate and respiratory rate, all other variables and age showed significant association with survival status (P < 0.01). The mortality increased with increase in the number of abnormal variables: 0.4% 2.2% 6.1% 15.3% 19.4% and 29.4%for scores of 0,1,2,3,4 and 5 respectively and the linear trend was significant (P < 0.01). Mortality also increased with a decrease in age (P < 0.01). Children with a score of 2 or more (2 or more abnormal clinical variables) had significantly higher mortality as compared to those with no abnormal clinical variables (score = 0). Based on the regression coefficients, the maximum possible score was 9.8. Regression based score was found to predict survival status well. The area under the ROC curve was 0.887, indicating that overall 88.7% of the subjects could be predicted correctly. Maximum discrimination was observed at a score of 2.5 (sensitivity 84.1% specificity 82.2%). CONCLUSION: For triage scoring, any child with 2 or more abnormal clinical variables should be taken as serious that might lead to death. With a more detailed scoring, score of 2.5 can be taken as cut-off to select children who possibly need admission and closer observation.

Child↗
PubMed2003

The dental caries experience of 5-year-old children in England and Wales. Surveys co-ordinated by the British Association for the Study of Community Dentistry in 2001/2002.

OBJECTIVE: This paper reports the results of standardised clinical caries examinations of 170,731 5-year-old children from across England and Wales. These 2001/2002 co-ordinated surveys are the latest in a series which seek to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating health authorities and boards and caries was diagnosed at the caries into dentine threshold using a visual method without radiography or fibre-optic transillumination. RESULTS: The results again demonstrated a wide variation in prevalence across Britain, with mean values for d3mft for the current English Strategic Health Authorities (SHA) (of the National Health Service), Wales and British 'territories' ranging from 0.75 in Jersey and 0.84 in Kent & Medway to 2.73 in Gwent and 2.47 in Greater Manchester. Mean d3mft across England and Wales was 1.52 (d.t = 1.11, mt = 0.20, ft = 0.20). Overall, 40% of children had evidence of caries experience (d3mft > 0); the percentages ranged between 23% (Jersey) or 29% (Essex) and 61% (Gwent) or 54% (Greater Manchester). The distribution of caries was highly skewed. Thus the mean caries experience for those with disease in England and Wales was 3.83, as opposed to the overall mean of 1.52. Trends over time demonstrate slight increase of 3% in overall d3mft for England and Wales since 1999/2000, compared to the 4% improvement seen for the two previous years. Of the three components of dmft, d3t and mt have increased while ft has fallen. The care index has also fallen (13.2% in 2001/2002, compared to 14.3% in 1999/2000); SHA/country percentages for 2001/2002 ranged from 8-29%. This indicator has not, however, regained the levels seen in the past. CONCLUSION: There has been no improvement in the dental health of 5-year-old children. Overall, the provision of operative care for those with dentinal decay has decreased slightly; significant groups remain within the population of 5-year-old children who have dental disease and who are in need of dental care.

Catchment Area, Health↗
PubMed2002

Observations of comet 19P/Borrelly by the miniature integrated camera and spectrometer aboard Deep Space 1.

The nucleus of the Jupiter-family comet 19P/Borrelly was closely observed by the Miniature Integrated Camera and Spectrometer aboard the Deep Space 1 spacecraft on 22 September 2001. The 8-kilometer-long body is highly variegated on a scale of 200 meters, exhibiting large albedo variations (0.01 to 0.03) and complex geologic relationships. Short-wavelength infrared spectra (1.3 to 2.6 micrometers) show a slope toward the red and a hot, dry surface (</=345 kelvin, with no trace of water ice or hydrated minerals), consistent with approximately 10% or less of the surface actively sublimating. Borrelly's coma exhibits two types of dust features: fans and highly collimated jets. At encounter, the near-nucleus coma was dominated by a prominent dust jet that resolved into at least three smaller jets emanating from a broad basin in the middle of the nucleus. Because the major dust jet remained fixed in orientation, it is evidently aligned near the rotation axis of the nucleus.

Carbon↗
PubMed2002

Correlation of intra-operative duplex findings during carotid endarterectomy with neurological events and recurrent stenosis at one year.

OBJECTIVES: Carotid endarterectomy has been used to treat both asymptomatic and symptomatic disease and this has meant that recurrent stenosis and its effect on late stroke risk have become increasingly important. In this study we compared anatomical defects and residual stenosis identified intra-operatively with recurrent stenosis and new symptoms developing in the first year after surgery. DESIGN, MATERIALS & METHODS: Two hundred and forty-four consecutive patients undergoing carotid endarterectomy were studied prospectively. Residual anatomical defects were noted; residual stenosis was defined by intra-operative duplex ultrasound as >50%. New stenoses and clinical events during the one-year surveillance period were documented. RESULTS: There was an increased incidence of recurrent stenosis at one year in vessels with residual stenoses (p<0.001) and in vessels containing a residual anatomical defect (p=0.037). There was no significant difference in recurrent stenosis rate with respect to closure (primary or patch) or seniority of surgeon but recurrent stenosis was increased in females (p=0.026). The majority (70%) of restenotic lesions were localised to the origin of the internal carotid artery. The late stroke rate was 0.9% and was not related to recurrent stenosis or symptoms. CONCLUSIONS: Residual stenosis and intra-luminal defects at completion increase the recurrent stenosis rate at one year. The aetiology of recurrent stenosis is multi-factorial and further studies are required to determine whether it is justified to modify the criteria for re-exploration with a view to reducing recurrent stenosis.

Adult↗
PubMed2002

Cyclooxygenase-2 inhibition and experimental colitis: beneficial effects of phosphorothioated antisense oligonucleotide and meloxicam.

BACKGROUND: The effects of cyclooxygenase-2 (cox-2) inhibition by a cox-2 selective antisense phosphorothioated oligonucleotide (AS) and meloxicam were examined in experimental colitis. METHODS: Colitis was induced by trinitrobenzenesulphonic acid (TNBS) and acetic acid (Hac) separately in male Sprague-Dawley rats. Both groups of animals were treated daily intraperitoneally with AS and a mismatched control oligo (CO) (3 mg/kg), and orally with meloxicam (7.5 mg/kg) 1 h before induction of colitis. The animals were killed on day 4 (Hac) and on day 5 (TNBS). Tissue samples from colon, ileum, liver, kidney and spleen were collected for mRNA, myeloperoxidase activity (MPO), prostaglandin E2 (PGE2) estimation and for histology, and blood samples for PGE2, thromboxane B2 (TxB2) and TNF-alpha. RESULTS: Both TNBS and Hac increased colonic MPO activity, PGE2 concentrations and infiltration of colonic wall by inflammatory cells. Serum levels of TNF-alpha were increased in both models, whereas PGE2 was increased only in TNBS colitis. Only meloxicam suppressed the level of PGE2 significantly below the basal level. The animals in both models also showed splenomegaly. The colitis-induced changes were significantly suppressed by the treatment of the test compounds but not by the CO. Cox-2 mRNA but not cox-1 was decreased by the AS, but not by meloxicam or in CO-treated colitic animals. CONCLUSION: The findings demonstrate comparable beneficial effects of the cox-2 selective antisense oligonucleotide and meloxicam, which seem to be mediated by a combined inhibition of both PGE2 and TNF-alpha in the present models of colitis.

Animals↗
PubMed2002

Cadasil: presenting as a mood disorder.

CADASIL is an autosomal dominant non-atherosclerotic vasculopathy that frequently presents as recurrent subcortical strokes, or vascular dementia in middle age. Some patients may have prominent mental symptoms or migraine. Widespread white matter demyelination and subcortical lacunar infarcts are demonstrated by magnetic resonance imaging. Demonstration of granular osmophilic material in arteries in skin biopsies is a useful diagnostic tool. CADASIL has been linked to mutation in the Notch 3 gene locus on chromosome 19. Genetic testing is available for clinical diagnosis.

Dementia, Multi-Infarct↗
PubMed2001

Molecular motors: thermodynamics and the random walk.

The biochemical cycle of a molecular motor provides the essential link between its thermodynamics and kinetics. The thermodynamics of the cycle determine the motor's ability to perform mechanical work, whilst the kinetics of the cycle govern its stochastic behaviour. We concentrate here on tightly coupled, processive molecular motors, such as kinesin and myosin V, which hydrolyse one molecule of ATP per forward step. Thermodynamics require that, when such a motor pulls against a constant load f, the ratio of the forward and backward products of the rate constants for its cycle is exp [-(DeltaG + u(0)f)/kT], where -DeltaG is the free energy available from ATP hydrolysis and u(0) is the motor's step size. A hypothetical one-state motor can therefore act as a chemically driven ratchet executing a biased random walk. Treating this random walk as a diffusion problem, we calculate the forward velocity v and the diffusion coefficient D and we find that its randomness parameter r is determined solely by thermodynamics. However, real molecular motors pass through several states at each attachment site. They satisfy a modified diffusion equation that follows directly from the rate equations for the biochemical cycle and their effective diffusion coefficient is reduced to D-v(2)tau, where tau is the time-constant for the motor to reach the steady state. Hence, the randomness of multistate motors is reduced compared with the one-state case and can be used for determining tau. Our analysis therefore demonstrates the intimate relationship between the biochemical cycle, the force-velocity relation and the random motion of molecular motors.

Adenosine Triphosphate↗
PubMed2001

Loss of heterozygosity at 7q22 and mutation analysis of the CDP gene in human epithelial ovarian tumors.

Many tumor types including that of the ovary show loss of heterozygosity (LOH) on chromosome arm 7q, which suggests the existence of at least one tumor suppressor gene (TSG) on this chromosome arm. We have studied the region surrounding the putative tumor suppressor gene CUTL1 at 7q22 in 127 epithelial ovarian tumors. LOH was found across 7q22 in 31% of malignant and 14% of benign ovarian tumors. In 16% of the tumors the LOH appeared to be centered on the CUTL1 gene. This gene has been implicated previously as a TSG in both uterine leiomyomas and breast carcinoma. However, mutation analysis of the CUTL1 gene in 47 tumors with 7q22 LOH failed to identify any somatic alterations in the coding regions. This finding suggests that CUTL1 may not be the target of the 7q22 LOH in ovarian cancers.

Adenocarcinoma, Mucinous↗
PubMed2001

FLAIR imaging in the follow-up of low-grade gliomas: time to dispense with the dual-echo?

Fluid-attenuated inversion-recovery (FLAIR) imaging has established its utility in neuroimaging. We propose this imaging sequence as a replacement for proton density (PD) and T2-weighted spin-echo sequences in the follow-up of low-grade glioma. 26 MRI examinations of 18 patients with such tumours were reviewed by three neuroradiologists and a neurosurgeon. FLAIR was found to be superior for appreciation of the lesion (91% of studies) and for demonstration of its margin (92%). FLAIR was also better at showing different tumour components, particularly in regions difficult to demonstrate in some planes, such as the vertex in axial imaging. The sequence also defines the postoperative cavity, shows the least amount of susceptibility effect associated with surgical clips, and demonstrates local spread (to white matter tracts, subependymal and capsular) more distinctly. We conclude that FLAIR can replace PD and T2-weighted spin-echo imaging in radiological follow-up of low-grade glioma.

Adult↗
PubMed2001

Expression and sub cellular localization of the sodium hydrogen exchanger isoform-1 in rat tissues: a possible functional relevance.

In an attempt to understand the mechanism underlying the tissue-dependent function, the expression of NHE-1 protein and its sub cellular localization was examined in the rat GI-tract and other tissues. Rat NHE-1 polyclonal antibodies were raised in rabbits using a NHE-1 fusion protein antigen. The antibodies recognized a 110 kD protein in rats and mice, but not in human or rabbit RBCs. Colon, stomach, brain, spleen and kidney expressed NHE-1 protein abundantly, whereas the skeletal muscle the least abundant. Ouabain-sensitive-K+-stimulated p-nitrophenylphosphatase (PNPPase), the partial activity of the sodium pump and alkaline phosphatase (Apase) were used as the markers of the basolateral and apical membranes. NHE-1 was detected predominantly in the PNPPase enriched membrane fractions, but was also detected in the apical membrane enriched fractions in the kidney cortex, jejunum and colon at a lower level. NHE-1 was detected in the plasma membrane enriched fractions from the skeletal muscle and ventricle. Immunofluorescence data showed a similar localization pattern of NHE-1 in the colon and kidney sections. These findings suggest that NHE-1 is localized both on the apical and basolateral membrane. In view of its similar sub cellular localization in the GI-tract and kidney, but a different level of expression, might suggest that the level of protein, but not the sub cellular distribution is important to regulate its tissue-dependent function.

4-Nitrophenylphosphatase↗
PubMed2001

Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection.

Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log(10) reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P <.05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients.

Administration, Oral↗
PubMed2001

Outcome of varicella pneumonitis in immunocompetent adults requiring treatment in a high dependency unit.

OBJECTIVES: The incidence of varicella infection is increasing in adults, where primary pneumonitis is the main complication. Little information exists concerning treatment of those patients who require admission to a high dependency unit (HDU) facility. A study was performed to examine the risk factors for developing varicella pneumonitis (VP), to document disease progression and assess prognosis for patients with VP requiring HDU admission. METHODS: A 10-year retrospective casenote review of patients admitted to the Regional Infectious Diseases Unit HDU. Varicella pneumonitis (VP) was defined as diffuse nodular shadowing on a chest X-ray (CXR) of a patient with a classical chickenpox rash. Severe pneumonitis was defined as an hypoxaemia index (pO2 in mmHG/FiO2) of less than 150 at any time during hospital stay. All patients were treated with intravenous acyclovir at a dose of 10 mg/kg. RESULTS: A total of 33 patients were admitted to the HDU with VP over the study period, 30 were included in the study. Annual admission rates remained constant. Most patients (76.7%) had at least one recognised risk factor for severe VP: smoking 18/30, pregnancy 9/30, chronic lung disease 7/30. Twelve (40%) patients had severe VP, eight (26.7%) required assisted ventilation. The presence of greater than one risk factor (p < 0.02) was associated with progression to severe VP. There was one death: a 63-year-old man with a long history of chronic airflow limitation whose treatment had included domicillary long-term oxygen therapy. Nine (30%) patients developed secondary bacterial pneumonia; all recovered with appropriate antibiotic treatment. The period of stay in HDU for the majority of patients was short (mean 4.5 days). CONCLUSIONS: The prognosis for severe adult VP with current available treatment is good. The only predictor on admission for severe VP is the presence of more than one recognised risk factor for developing VP.

Acyclovir↗
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↗