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Biomedical subjects

L Shaw

Publications and source records attributed to L Shaw.

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

Safety of a new conjugate meningococcal C vaccine in infants.

BACKGROUND: Group C conjugate meningococcal vaccines (Men C) were introduced into the UK primary immunisation schedule in November 1999. There has been extensive professional and public interest in their efficacy and safety. AIM: To determine the occurrence of at least one uncommon adverse event in infants related to the administration of the Chiron Men C vaccine. METHODS: A total of 2796 infants aged approximately 2 months were recruited into the study from areas in and around Sheffield and from Scotland. They were vaccinated with the Chiron Men C vaccine at 2, 3, and 4 months along with routine immunisations. Data on adverse events occurring one month after each dose were collected actively and prospectively and reviewed for possible relation to the vaccine. RESULTS: There were no deaths. There were no serious adverse events considered definitely or probably caused by the vaccine. Four infants developed serious adverse events (hypotonia, screaming syndrome, maculopapular rash, and agitation, respectively) that were considered possibly related to the vaccine. All recovered completely. Adverse events were seen in 1804 children but were considered possibly related to the vaccine in only 49 (1.8%). On subsequent immunisation there were no recurrences of adverse events considered to be possibly related to the vaccine.

Female↗
PubMed2001

Dens evaginatus on the labial surface of a central incisor: a case report.

A 7-year-old girl in the mixed dentition phase presented with abnormal morphology of the upper right central incisor. The diagnosis was a dens evaginatus, an anomaly of odontogenesis of unknown aetiology. This article describes the management of this anomaly and discusses the importance of maintaining space in the developing dentition. The aetiology and natural history of dens evaginatus are also considered.

Child↗
PubMed2001

Localized scleroderma in a 12-year-old girl presenting as gingival recession. A case report and literature review.

Scleroderma is a connective tissue disorder that displays considerable clinical heterogeneity. This case describes a 12-year-old girl who presented with a localized form of the disease. The consequences were a severe and progressive localized gingival recession affecting two maxillary incisors, a localized lip defect and scarring of the forehead. The case illustrates the difficulties in diagnosis and management of young patients with localized scleroderma.

Child↗
PubMed2000

Clinical characteristics and long-term outcomes of patients with heart failure and preserved systolic function.

Although the syndrome of heart failure with preserved systolic function may occur in up to 40% of all heart failure patients, the clinical, angiographic characteristics, and long-term outcomes of these patients are poorly understood. We prospectively evaluated 2,498 consecutive patients with New York Heart Association class II to IV symptoms and ejection fractions of >40%, who underwent cardiac catheterization between January 1984 and December 1996 at Duke University Medical Center. The median age for the entire cohort was 63 years; 25% of the population was >71 years old. In addition, 55% of the patients were women, 65% had ischemic heart disease, 28% had a history of diabetes, and 62% had a history of hypertension. The median ejection fraction was 58%. One third of the patients had multivessel disease by coronary angiography. The overall 5-year mortality of the total population was 28%. The independent predictors of mortality (p <0.05) using a multivariable Cox proportional hazard model were age, class IV symptoms, ejection fraction, coronary artery disease index, diabetes, peripheral vascular disease, and minority ethnic group. Heart failure with preserved systolic function is characterized by unique clinical and angiographic characteristics associated with a 5-year mortality rate of 28%. Furthermore, several clinical and angiographic characteristics are predictive of long-term survival.

Aged↗
PubMed2000

Development and characterization of human and mouse specific antibodies to CuZn-superoxide dismutase (SOD1).

Mutations in the copper/zinc superoxide dismutase (SOD1) gene are associated with 15-20% of the familial forms of motor neuron disease. Mice where a transgene has been incorporated that encodes for the human SOD1 mutation develop a form of motor neurone disease that closely resembles human forms of this disease. We have produced and characterized species-specific antibodies to epitopes in the SOD1 protein, amino acids 25-37, a region that distinguishes between the human and the mouse species of SOD1. The antisera generated were unable to immunoprecipitate the mouse or the human forms of SOD1 from tissue extracts unless the homodimeric complex of SOD1 was denatured. As SOD1 exists as a homodimeric complex in the cytoplasm of cells, this suggests that amino acids in position, 25-37 are close to the dimeric interface of SOD1.

Animals↗
PubMed2000

RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion.

Focal adhesions and actin cytoskeleton are involved in cell growth, shape and movement and in tumor invasion. Mitogen-induced changes in actin cytoskeleton are accompanied by changes in the tyrosine phosphorylation of several focal adhesion proteins. In this study, we have investigated the role of RAFTK, a cytoplasmic tyrosine kinase related to focal adhesion kinase (FAK), in heregulin-mediated signal transduction in breast cancer cells. Stimulation of T47D cells with heregulin (HRG) induced the tyrosine phosphorylation of RAFTK and the formation of a multiprotein complex. Analyses of the members of the HRG-stimulated complex revealed that RAFTK is associated with p190 RhoGAP (p190), RasGAP and ErbB-2, and plays an essential role in mediating the tyrosine phosphorylation of p190 by Src. Mutation of the Src binding site within RAFTK (402) abolished the phosphorylation of p190. In addition, upon HRG stimulation of T47D cells, association of ErbB-2 with RAFTK was observed and found to be indirect and mediated by Src. Expression of wild-type RAFTK (WT) significantly increased MDA-MB-435 and MCF-7 breast cancer cell invasion, while expression of the kinase-mutated RAFTK-R457 (KM) or the Src binding site mutant RAFTK (402) did not affect this cell invasion. Furthermore, HRG leads to the activation of MAP kinase which is mediated by RAFTK. These findings indicate that RAFTK serves as a mediator and an integration point between the GAP proteins and HRG-mediated signaling in breast cancer cells, and implicate RAFTK involvement in the MAP kinase pathway and in breast cancer cell invasion.

Breast Neoplasms↗
PubMed2000

Development and evaluation of a stand-alone web-based CAL program. A case study.

The use of web browser technology allows the construction of computer-aided learning programs which will have a familiar interface to dentists. This paper reports on the evaluation of a web-based CAL program which covered the topic of tooth wear with an emphasis on the rôle of erosion in its aetiology. Evaluation of the software was made by 50 dentists contacted by an electronic mailing list. They completed a questionnaire which evaluated aspects of the functionality of the program educational objectives. The average age of the dentists was 39 years (range 24-70) and 82% were male. The average time of use was 1 h 10 min (range 15 min to 3 h). A significant change in their knowledge of tooth wear before and after using the program was recorded. Both the use of patient cases and leaflets scored highly with other aspects such as treatment planning and patient advice receiving high marks. All dentists commented that they had gained greater knowledge with particular reference to treatment and advice of tooth wear problems. 34 dentists (68%) found the web interface easy to use. Negative comments were mainly attributed to the quality of the pictures (4/50) which were corrected in the final release version. Respondents were asked to compare the program to other educational media on the same subject. 80% rated this CAL program as better than video, and 14% claimed it was as good as video. 84% rated it better than books, and 14% said it was as good as books. 98% preferred it to audio tapes and 86% preferred it to journals. The average amount that they would pay for a CAL package such as "tooth wear" would be 42 ECU. It is concluded that web browser software is a suitable medium for the use of a CAL program and this is reflected in its ease of use by dentists.

Adult↗
PubMed2000

Mechanisms of 17 beta-oestradiol induced vasodilatation in isolated pressurized rat small arteries.

1. The influence of 17 beta-oestradiol on pressurized isolated rat mesenteric and coronary small arteries was investigated. 2. 17 beta-oestradiol caused rapid (t1.0 < 5 mins) concentration-dependent relaxations of pre-contracted pressurized (50 mmHg) isolated rat mesenteric and coronary arteries. Similar responses were observed in both vessel types. Significant relaxations were only observed at concentrations exceeding 3 microM. 3. The vasodilatory responses in both types of artery were unaffected by 10 microM L-nitro arginine (L-NNA) alone or in the presence of 10 microM indomethacin, inhibitors of nitric oxide and prostaglandin synthesis respectively. They were also unaffected by the pre-contracting agent used i.e. high K+ or U46619 (a thromboxane analogue). 4. Neither the oestrogen receptor antagonist ICI 182,780 (10 microM) nor the protein synthesis inhibitor cycloheximide (100 microM) had any effect on the responses of mesenteric arteries to 17 beta-oestradiol. 5. 17 alpha-oestradiol had only a minor effect on mesenteric arterial diameter over a concentration range similar to the effective vasodilatory range for 17 beta-oestradiol. 6. Membrane impermeant 17 beta-oestradiol conjugated to bovine serum albumin (beta-oestradiol-17-hemisuccinate-BSA) (E-H-BSA) resulted in a vasodilatation of pressurized arteries. 7. Wortmannin, an inhibitor of myosin light chain kinase, near maximally relaxed pressurized mesenteric arteries although the time course for the response was significantly slower than that for 17 beta-oestradiol. 8. These results taken together suggest that the acute effects of 17 beta-oestradiol on isolated pressurized arterial tone may be due to effects directly on the vascular smooth muscle via non-genomic mechanisms that involve a stereospecific interaction at the plasma membrane.

Androstadienes↗
PubMed2000

Prediction of myocardial perfusion abnormalities by quantitative regional function using a radionuclide angiography database: a comparison with wall motion analysis.

PURPOSE: Myocardial perfusion and functional information during the same study is now feasible. A new assessment of regional ejection fraction at rest and peak exercise by first-pass radionuclide angiography using a "normal" database file has been developed. OBJECTIVE: This study was performed to assess the relation between this new method of quantitative regional ejection fraction and myocardial perfusion abnormalities and to compare this new technique with visual analysis of regional wall motion. METHODS: Consecutive patients (n = 126) with simultaneous first-pass radionuclide angiography and perfusion SPECT imaging were studied at rest and peak exercise using a same-day protocol. The area under the receiver-operator characteristic curve (C index) was used to assess the concordance probability between perfusion and functional measurements, and logistic regression models were used to examine the ability of functional variables to predict perfusion results. RESULTS: A high concordance was found between the visual analysis of wall motion and perfusion abnormalities (C index = 0.796), and also between regional ejection fraction and perfusion defects (C index = 0.784). The maximal predictive power of functional variables was obtained by combining wall motion analysis and regional ejection fraction (C index = 0.859). Regional ejection fraction contributed, with 20% more information than provided by wall motion analysis alone (chi2 = 9.2, P = 0.0025). CONCLUSIONS: Quantitative regional ejection fraction using a normal database file has a strong relation to perfusion abnormalities and provides incremental information to regional wall motion analysis for predicting perfusion abnormalities. This new technique should be regarded as a potential adjunct to functional studies to evaluate patients with ischemic heart disease.

Cardiac Catheterization↗
PubMed2000

Predictive performance study of two digoxin assays in subjects with various degrees of renal function.

This prospective study was conducted to compare the predictive performance of fluorescence polarization immunoassay (FPIA, Abbott TDx Digoxin II) and radioimmunoassay (RIA, Kallestad Labs) with combined low-pressure liquid chromatography/RIA (LPLC/RIA) digoxin assay in measuring 15-17 serum digoxin concentrations (SDC) obtained after a single 10 microg/kg intravenous digoxin dose in patients with various degrees of renal function and at different SDC ranges. Eighteen men and women were stratified into 3 age- and gender-matched groups based upon renal function [N = 6 in each, group I (Cl(cr) < 10 mL/min), group II (Cl(cr) = 10-50 mL/min), and group III (Cl(cr) > 50 mL/min)]. Serum digoxin concentrations were measured at time zero; at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, and 12 hours; and at 2, 3, 4, and 5-7 days after the digoxin dose, using the three different digoxin assays. TDx Digoxin II was unbiased [mean error -0.09 (95% CI -0.19, 0.01)] and RIA biased [mean error -0.29 (95% CI -0.36, -0.21)] to over-predict SDC by 14.2%. In group I patients, the analysis revealed a bias to over-predict SDC by 6.0% for TDx Digoxin II [mean error -0.16 (95% CI -0.29, -0.07)] and an unbiased performance by RIA. In groups II and III, both TDx Digoxin II and RIA showed biased performance, the mean magnitude of bias was low (< 20%). For intermediate SDC range (> 0.5 ng/mL and < or = 3.0 ng/mL), TDx Digoxin II was unbiased in predicting SDC, whereas RIA was biased to under-predict SDC [mean error 0.13 (95% CI 0.10, 0.16)] by 9.9%. The magnitude of bias observed in all cases was less than 20%. Both assays, TDx Digoxin II and RIA, imprecisely measured SDC for all samples combined, different groups and SDC ranges. In all time-paired samples, TDx Digoxin II (FPIA) performed better than the RIA. In conclusion, the magnitude of bias observed with either assay at different groups and SDC ranges was not likely to be clinically relevant. Therefore, either assay may be used to measure SDC in clinical practice.

Anti-Arrhythmia Agents↗
PubMed2000

Modern thoughts on fissure sealants.

It has long been known that fissure sealants are an important part of the prevention and control of dental caries in pits and fissures. However, their usage is still sporadic and generally not related to evidence-based guidelines. Caries prevalence has changed since sealants were introduced and this has significant implications for the criteria on which to select patients who would most benefit from their usage. The clinical technique for successful fissure sealant application is very moisture and operator sensitive. However, there is accumulating evidence that use of fissure sealants can be extended, given suitable investigation, to the early carious lesion as a 'preventive resin restoration'.

Adolescent↗
PubMed1999

Can cardiovascular clinical characteristics be identified and outcome models be developed from an in-patient claims database?

The objective of this study was to assess whether administrative (claims) databases can be used to assess clinical variables and predict outcome. Although administrative databases are useful for assessing resource utilization, their utility for assessing clinical information is less certain. Prospectively gathered clinical databases, however, are expensive and not widely available. The UB92 formulation of the hospital bill was used as an administrative source of data and compared with the clinical cardiovascular database at Emory University. The claims database was compared with the clinical database for 11 variables. Outcome models were developed with multivariate methods. A total of 11,883 patients who underwent catheterization (5,255 underwent percutaneous transluminal coronary angioplasty [PTCA] and 3,794 underwent coronary artery bypass surgery [CABG]) between 1991 and 1995 were included. For some variables, the claims database correlated well (diabetes, sensitivity 87%, specificity 99%), whereas for others the claims database was less accurate (peripheral vascular disease, sensitivity 20%, specificity 99%). Uncertain coding in the claims database, which can result in the same code being used for co-morbid states and severity of disease, as well as complications, limited the ability of claims to predict outcome. Clinical databases may also be limited by lack of objectivity and missing data. The utility of claims databases to assess severity of disease and co-morbid states is limited, and outcome modeling and risk assessment from claims databases may be inappropriate and spurious. Developing better data standards and less expensive methods for acquisition of clinical data is necessary for improved outcome assessment.

Cardiovascular Diseases↗
PubMed1999

Dental erosion--the problem and some practical solutions.

There has been a clinical impression among dental practitioners, particularly those working with children, that the problem of dental erosion is increasing. Is this really the case or are we more aware of the problem? What is causing this increase, if it really exists? Perhaps more importantly, what can we do about it? This article looks at the prevalence, and aetiology of dental erosion, particularly in children, and makes some practical suggestions for possible control.

Adolescent↗
PubMed1999

Effect of exogenous FSH on ovulation rate in homozygous carriers or noncarriers of the Booroola FecB gene after hypothalamic-pituitary disconnection or after treatment with a GnRH agonist.

We have tested the hypothesis "that the ovulation rate in homozygous carriers (BB) and noncarriers (+2) of the Booroola FecB gene would not be different if the plasma concentrations of follicle-stimulating hormone (FSH) in the two genotypes were similar." For this purpose we used two experimental animal models: 1) the hypothalamic-pituitary disconnected (HPD) ovary-intact ewe; and 2) and GnRH agonist (i.e., Deslorelin)-treated ewe. Following HPD or Deslorelin treatment, the animals had low plasma concentrations of gonadotropins and were anovulatory. In both animal models, BB and +2 ewes were treated with exogenous pregnant mares serum gonadotropin (PMSG) and varying doses of FSH to induce preovulatory follicular growth, and human chorionic gonadotropin (hCG) to induce ovulation. HPD or Deslorelin-treated animals administered with pregnant mares serum gonadotropin without FSH followed by human chorionic gonadotropin failed to ovulate. However for both animal models, the proportion of BB and +2 ewes ovulating to various doses of FSH differed such that significantly greater proportions of +2 animals ovulated relative to the BB genotype (P < 0.05). When HPD or Deslorelin-treated BB and +2 ewes were administered identical doses of FSH, the mean ovulation rate and plasma concentrations of FSH in those animals which ovulated was the same in both genotypes. These findings confirm, at least in part, the aforementioned hypothesis. The results also demonstrated that higher ovulation rates were obtained in both genotypes as the FSH dose was increased. Collectively, these findings infer that the higher mean ovulation rate in normal intact BB ewes compared to the +2 genotype is attributable to effects of the FecB gene at the level of ovarian follicular development as well as at the level of pituitary FSH release.

Animals↗