Search PubMed⌕ Search

Biomedical subjects

D A Scott

Publications and source records attributed to D A Scott.

At least 19 recordsLinked to original sources
PubMed2006

Increased local matrix metalloproteinase-8 expression in the periodontal connective tissues of smokers with periodontal disease.

Matrix metalloproteinase (MMP)-8 has been associated with the progression of periodontitis, a common inflammatory disease of the supporting structures of the teeth, and with other degradative diseases. Tobacco smokers are at high risk of developing periodontitis that may progress more rapidly and respond poorly to treatment. Therefore, MMP-8 expression was determined by immunofluorescence staining in 60 random, computer-selected fields in the excised periodontal tissues of smokers and non-smokers, balanced for age, gender, and periodontal status. Immunofluorescence intensity, representing MMP-8 expression, in the periodontal tissues of smokers (30 fields from 6 subjects, mean 1154+/-124 units) was significantly higher than that in the periodontal tissues of non-smokers (30 fields from 6 subjects, mean 817+/-60 units; p < 0.05). Serum MMP-8 concentrations were measured by ELISA and compared in a larger group of smokers (n = 20) and age- and gender-balanced non-smokers (n = 20). Systemic MMP-8 concentrations in smokers and non-smokers were not significantly different (p > 0.05). A local tobacco-related increase in MMP-8 burden may contribute to periodontal disease progression in tobacco smokers. This finding may also have relevance to other tobacco-induced inflammatory diseases, such as vascular and pulmonary diseases.

Adult↗
PubMed2006

Congenital diaphragmatic hernia associated with duplication of 11q23-qter.

Congenital diaphragmatic hernia (CDH) is a relatively common birth defect with a high mortality. Although little is known about its etiology, there is increasing evidence for a strong genetic contribution. Both numerical and structural chromosomal abnormalities have been described in patients with CDH. Partial trisomy 11q and partial trisomy 22 associated with the common t(11;22) has been reported in several cases of CDH. It has been assumed that the diaphragmatic defect seen in these individuals was primarily due to duplication of material from chromosome 22q11. However, in this report we describe a family with a t(11;12) in which one of two brothers with partial trisomy 11q has a left sided posterolateral CDH. This is the second case of CDH in partial trisomy 11q due to an unbalanced translocation other than t(11;22). Using array-based comparative genomic hybridization and fluorescent in situ hybridization, we mapped the breakpoints in both brothers and their mother who is a balanced translocation carrier. Our results suggest that duplication of one or more genes on a approximately 19 Mb region of 11q23.3-qter predisposes to the development of CDH. These effects may be the primary cause of CDH in individuals t(11;22) or may be additive to effects from the duplication of chromosome 22 material. We also conclude that the partial trisomy 11q syndrome has a variable phenotype and that CDH should be added to the spectrum of anomalies that can be present in this syndrome.

Adult↗
PubMed2006

WAGR(O?) syndrome and congenital ptosis caused by an unbalanced t(11;15)(p13;p11.2)dn demonstrating a 7 megabase deletion by FISH.

Aniridia usually occurs in isolation, but may also occur as part of the WAGR contiguous gene deletion syndrome, which includes Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation. The aniridia and predisposition for Wilms tumor seen in WAGR are caused by haploinsufficiency for PAX 6 and WT1, respectively. We present a female infant with aniridia, bilateral ptosis, bilateral posterior capsular cataracts, nystagmus, left-sided glaucoma, microcephaly, mild unilateral hydronephrosis, poor linear growth, and gross motor delay consistent with a clinical diagnosis of WAGR syndrome. In addition, weight-for-height ratio at 12 months is at the 94th centile, raising the possibility of a diagnosis of WAGRO (WAGR + Obesity). Chromosome analysis revealed a translocation (11;15)(p13;p11.2) which has not been previously associated with a diagnosis of WAGR. Subsequent clinical WAGR fluorescent in situ hybridization (FISH) analysis demonstrated a deletion of 11p13 including PAX6 and WT1. A complete FISH-mapping of the breakpoints on chromosome 11 revealed a 7 Mb deletion within 11p13-11p14. The patient is examined in light of other reported patients with deletions and/or translocations involving the regions between 11p12 --> 11p14 including patients with WAGR + obesity (WAGRO) as well as with other reported patients with aniridia and congenital ptosis.

Abnormalities, Multiple↗
PubMed2006

The sensitivity and specificity of three common statistical rules for the classification of post-operative cognitive dysfunction following coronary artery bypass graft surgery.

BACKGROUND: The application of statistical rules to determine post-operative cognitive dysfunction (POCD) has varied, and partially explains the wide range of reported incidences of POCD in the literature. The current study assessed the sensitivity and specificity of three commonly used statistical rules in a sample of coronary artery bypass graft (CABG) patients and healthy non-surgical controls. METHODS: Two hundred and four CABG patients [mean age, 68.8 years; standard deviation (SD), 7.0 years] completed neuropsychological assessment pre-operatively (baseline) and 1 week and 3 months post-operatively. Ninety age- and gender-matched non-surgical controls (mean age, 67.8 years; SD, 7.9 years) completed the same tasks at the same time points. POCD was determined in each group using three rules: the 1SD decline on two or more tasks; the 20% decline on 20% of tasks rule; and a modified reliable change index. RESULTS: The modified reliable change index demonstrated the greatest combination of sensitivity and specificity. The 20% decline on 20% of tasks rule detected the largest incidence of impairment in the CABG group, but showed large incidences of false positive classifications in the control group. The 1SD rule detected the lowest incidence of POCD in the CABG group, but detected a larger incidence of impairment in the control group. CONCLUSIONS: The use of the modified reliable change index is recommended, given the sensitivity to change it displayed and the low rates of false positive classification in the control sample. The use of control groups in future research is also recommended.

Aged↗
PubMed2005

Congenital diaphragmatic hernia in WAGR syndrome.

Wilms tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome is a contiguous gene deletion syndrome involving the Wilms tumor 1 gene (WT1), the paired box gene 6 (PAX6), and possibly other genes on chromosome 11p13. WT1 is required for normal formation of the genitourinary system and the high incidence of Wilms tumor and genitourinary anomalies found in patients with WAGR are attributed to haploinsufficiency of this gene. It has been hypothesized that WT1 also plays an important role in the development of the diaphragm. During mammalian embryonic development, WT1 is expressed in the pleural and abdominal mesothelium that forms part of the diaphragm. Furthermore, mice that are homozygous for a deletion in the mouse homolog of WT1 have diaphragmatic hernias. Case reports describing congenital diaphragmatic hernias in infants with Denys-Drash and Frasier syndromes, both of which can be caused by mutations in WT1, provide additional support for this hypothesis. We report an infant with aniridia, bilateral cryptorchidism, vesicoureteral reflux, and a right-sided Morgagni-type diaphragmatic hernia. G-banded chromosome analysis revealed a deletion of 11p12-p15.1. Breakpoint regions were refined by fluorescence in situ hybridization (FISH) and deletion of the WAGR critical region, including WT1, was confirmed. A review of the medical literature identified a second patient with a deletion of 11p13, a left-sided Bochdalek-type diaphragmatic hernia, and anomalies that suggest a diagnosis of WAGR including bilateral microphthalmia, a small penis, bilateral cryptorchidism, and a hypoplastic scrotum. These cases demonstrate that congenital diaphragmatic hernia can be associated with WAGR syndrome and suggest that deletions of WT1 may predispose individuals to develop congenital diaphragmatic hernia.

Abnormalities, Multiple↗
PubMed2005

The influence of vitamin C on systemic markers of endothelial and inflammatory cell activation in smokers and non-smokers.

OBJECTIVE AND DESIGN: To determine the influence of vitamin C supplementation (500 mg, bd, 14 days) on the circulating concentrations of soluble ICAM-1 (a marker of endothelial activation), neopterin (a marker of monocyte activation), and neutrophil elastase (a marker of neutrophil activation) in smokers and non-smokers in a randomised, double-blind, placebo-controlled trial in a hospital setting. SUBJECTS: Twenty smokers (serum cotinine > or = 20 ng ml(-1)) and 20 age- and gender-matched non-smokers (serum cotinine < or = 13.7 ng ml(-1)). RESULTS: At baseline, there was a significant elevation in the concentration of sICAM-1 in smokers (median 247, IQR 199 to 357 ng ml(-1)) compared to non-smokers (median 207, IQR 189 to 227 ng ml(-1); p = 0.014). Vitamin C supplementation did not influence the circulating concentrations of ICAM-1 or neopterin, or leukocyte elastase activity, in smokers, non-smokers, or in the total population. CONCLUSIONS: Markers of monocyte and neutrophil activation were not influenced by smoking status in this study population. However, sICAM-1 concentrations were significantly elevated in tobacco smokers, reflecting tobacco-induced vascular activation that is unaffected by Vitamin C supplementation.

Adult↗
PubMed2005

The clinical and cost-effectiveness of left ventricular assist devices for end-stage heart failure: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical and cost-effectiveness of left ventricular assist devices (LVADs) as a bridge to heart transplantation (BTT), as a bridge to myocardial recovery (BTR) or as a long-term chronic support (LTCS) for people with end-stage heart failure (ESHF). DATA SOURCES: For the systematic review, electronic databases and bibliographies of related publications plus experts and manufacturers. For the economic evaluations, data originated from the systematic review of clinical and cost-effectiveness, UK hospitals, device manufacturers and expert opinion. REVIEW METHODS: For the systematic review, studies were selected and assessed against a set of rigorous criteria; data were then synthesised using a narrative approach through subgroup analysis based on the indication for treatment, type of LVAD and quality of studies. The economic evaluation developed two models to evaluate the use of LVADs, first as a BTT and second as LTCS for patients suffering from ESHF. RESULTS: Sixteen studies assessed the clinical effectiveness of LVADs as a BTT. Despite the poor methodological quality of the evidence, LVADs appeared beneficial compared to other treatment options (i.e. inotropic agents or usual care) or to no care (i.e. the natural history of ESHF) improving the survival of people with ESHF during the period of support and following heart transplantation. Patients supported by an LVAD appeared to have an improved functional status compared with those on usual care and experienced an improvement in their quality of life from before device implantation to the period during support. Serious adverse events are a risk for patients with an LVAD. With a scarcity of evidence directly comparing different devices, it is difficult to identify specific devices as the most clinically effective. The HeartMate LVAD is the only device that has evidence comparing it with the different alternatives, appearing to be more clinically effective than inotropic agents and usual care and as clinically effective as the Novacor device. Second generation devices, such as Jarvik 2000 and MicroMed Debakey LVADs, are early in their development but show considerable promise that should be assessed through long-term studies. Evidence of the clinical effectiveness of LVADs as a BTR was limited to seven non-comparative observational studies that appeared to show that the LVADs were beneficial in providing support until myocardial recovery. It was not possible to assess whether the LVADs are more effective than other alternatives or specific devices. No evidence was found on the quality of life or functional status of patients and limited information on adverse events was reported. Six studies assessed the clinical effectiveness of LVADs as an LTCS and from these it was evident that LVADs provided benefits in terms of improved survival, functional status and quality of life. Nineteen studies assessed the costs and cost-effectiveness of LVADS for people with ESHF, with the majority being simple costing studies and very few studies of the cost-effectiveness of LVADs. With no relevant cost-effectiveness studies available, an economic evaluation for BTT and LTCS was developed. The economic evaluation has shown that neither LVAD indication considered, that is, BTT and LTCS, is a cost-effective use. For the HeartMate LVAD used as a BTT the cost per QALY was pound 65,242. In the less restrictive indication, LTCS, where LVADs are not just given to patients awaiting transplantation, the analysis has shown that LTCS is not cost-effective. The baseline cost per QALY of the first-generation HeartMate LVAD was pound 170,616. One- and multi-way sensitivity analysis had limited effect on the cost per QALY. A hypothetical scenario based on the cost of a second-generation MicroMed DeBakey device illustrated that a 60% improvement in survival over first-generation devices was necessary before the incremental cost-effectiveness approached pound 40,000 per QALY. CONCLUSIONS: Although the review showed that LVADs are clinically effective as a BTT with ESHF, the economic evaluation indicated that they are not cost-effective. With the limited and declining availability of donor hearts for transplantation, it appears that the future of the technology is in its use as an LTCS. Further research is needed to examine the clinical effectiveness of LVADs for people with ESHF, assessing patient survival, functional ability, quality of life and adverse events. Evaluations of the clinical effectiveness of LVADs should include economic evaluations, as well as data on quality of life, utilities, resources and costs. A systematic review of the epidemiology of ESHF should be undertaken to assess its potential impact.

Cost-Benefit Analysis↗
PubMed2004

Detection of cognitive decline after coronary surgery: a comparison of computerized and conventional tests.

BACKGROUND: Postoperative cognitive decline is a common complication after coronary artery bypass graft (CABG) surgery. Postoperative cognitive decline is defined on the basis of change in cognitive function detected with repeated assessments using neuropsychological tests. Therefore improvement in neuropsychological testing instruments may increase our understanding of postoperative cognitive decline. METHODS: Fifty patients undergoing CABG surgery completed both a conventional and a computerized battery of tests before and 6 days after CABG surgery. Fifty age- and education-matched controls completed the same test batteries 6 days apart. The reliability and the sensitivity to postoperative cognitive decline were computed for each battery. RESULTS: Both test batteries detected postoperative cognitive decline 6 days after CABG surgery. For the computerized battery, the reliability of the reaction times (intraclass correlation 0.89-0.92) was greater than for any test from the conventional battery (intraclass correlation 0.56-0.71), although accuracy measures were less reliable (intraclass correlation 0.61-0.89). The computerized battery detected all the cases of POCD identified by the conventional test battery and also five cases that were classified as normal by the conventional tests. CONCLUSION: Computerized tests are suitable for measuring cognitive change after CABG surgery and may detect change in a greater proportion of patients 6 days after CABG surgery than conventional neuropsychological tests.

Aged↗
PubMed2004

Suppression of overt gingival inflammation in tobacco smokers - clinical and mechanistic considerations.

Gingivitis is a reversible inflammatory disease of the periodontal tissues. Periodontitis, in addition, involves destruction of the supporting structures of teeth. Diagnoses of gingivitis and periodontitis are predominantly dependent on clinical measurements of key inflammatory indices. Smokers are more susceptible to developing periodontal diseases, yet smoking masks overt signs of inflammation, presenting dental professionals with a clinical conundrum. We review the evidence that tobacco smoke may (i) cause acute periodontal vasoconstriction, (ii) inhibit periodontal angiogenesis in response to inflammatory stimuli, and/or (iii) suppress the production of pro-inflammatory mediators. It is clear that the mechanisms by which cigarette smoking dampens the periodontal inflammatory response are not yet fully understood. Further research into inflammatory suppression is warranted and should point to improved methods of diagnosis, not only in smokers, but also in non-smokers.

Disease Susceptibility↗
PubMed2003

Tobacco-induced alterations to the Fourier-transform infrared spectrum of serum.

Infrared (IR) spectroscopy can distinguish differences in the characteristics of diverse molecules by using infrared radiation to probe chemical bonds. Consequently, alterations to the molecular characteristics of tissues and body fluids that help define specific pathological processes and conditions can be identified by IR spectroscopy. This study analyzed the molecular spectrum of cotinine by IR spectroscopy and determined tobacco-induced alterations to the IR profile of serum to establish whether these alterations can differentiate smokers and nonsmokers. The IR spectra of serum samples obtained from 20 smokers and 25 nonsmokers were captured using a FTS-40 IR spectrometer. Linear discriminant analysis method was used to partition the samples into smoker and nonsmoker groups according to the discriminatory patterns in the data and into a validation set to test the accuracy of the trained algorithm in distinguishing smokers and nonsmokers. Cotinine molecules were shown to exhibit a characteristic IR absorption spectrum. Several differences in the sera spectra of the two groups were observed, including an overall shift in the secondary structure of serum proteins favoring increased beta-sheet content in smokers. The overall accuracy of the training and validation sets was 96.7%, and 82.8%, respectively. The identification of specific absorption peaks for tobacco-induced alterations to the IR molecular profile of serum permits the development of an IR spectroscopy technique that can be used to differentiate smokers from nonsmokers. This further extends the utility of IR spectroscopy as a rapidly emerging tool in the field of molecular biodiagnostics.

Adult↗
PubMed2003

Gingival bleeding on probing increases after quitting smoking.

BACKGROUND: Gingival inflammation associated with plaque accumulation is delayed or impaired in smokers. Anecdotal evidence suggests that smokers who quit experience an increase in gingival bleeding. METHOD: A group of 27 subjects on a Quit-smoking programme were examined for changes in gingival health over a 4-6-week period. RESULTS: The bleeding on probing with a constant force probe increased from 16% of sites to 32% of sites, despite improvements in the subjects oral hygiene. CONCLUSION: This provides further evidence that tobacco smoking affects the inflammatory response and that these changes are reversible on quitting.

Adult↗
PubMed2002

Analysis of two common alpha 1-antitrypsin deficiency alleles (PI*Z and PI*S) in subjects with periodontitis.

BACKGROUND: pi alpha 1-Antitrypsin deficiency is a genetically determined condition resulting in predisposition to certain inflammatory diseases due to a protease: antiprotease imbalance that is exacerbated by tobacco smoking. Limited evidence suggests that there may be a significant enrichment of mild alpha 1-antitrypsin deficiency phenotypes in subjects with chronic inflammatory periodontal disease. OBJECTIVE: To examine the prevalence of two common alpha1-antitrypsin deficiency alleles (PI*Z and PI*S) in a UK population of subjects with periodontitis. SUBJECTS AND METHODS: The prevalence of PI*M, PI*S and PI*Z allele combinations was determined in 31 subjects with periodontitis and compared with 31 healthy control subjects matched for smoking status, ethnicity, age and gender. alpha 1-Antitrypsin genotyping was performed by multiplex real-time fluorescence polymerase chain reaction (PCR) using DNA extracted from whole blood. RESULTS: There was no difference in the proportion of any alpha 1-antitrypsin genotype found in the diseased and control populations. CONCLUSIONS: We did not find evidence to support an association between mutant PI* alleles and periodontitis in a small, controlled study. Larger studies will be required to clarify the relationship between alpha1-antitrypsin genotype and susceptibility to inflammatory periodontal disease.

Adult↗
PubMed2002

Expression of ICAM-1 and E-selectin in gingival tissues of smokers and non-smokers with periodontitis.

BACKGROUND: Tobacco smoking affects systemic concentrations of soluble intercellular adhesion molecule (ICAM)-1, but its effect on local expression of adhesion molecules in gingival tissue has not been studied previously. METHODS: E-selectin and ICAM-1 expression on small blood vessel endothelia in gingival biopsies obtained from smokers (n=17) and non-smokers (n=17) with periodontitis was examined with immunohistochemistry. Blood vessels were identified with monoclonal antibody for von Willebrand's factor. RESULTS: A significantly larger number of vessels were observed in inflamed tissues of non-smokers than smokers (P<0.05). The number and proportion of vessels expressing both ICAM-1 and E-selectin was greater in sites with inflammation compared to non-inflamed sites in both smokers and non-smokers (P<0.05). The proportion of the total number of vessels expressing ICAM-1 in non-inflamed sites was greater in non-smokers compared with smokers (P<0.05). CONCLUSIONS: These results suggest that the inflammatory response in smokers with periodontitis may not be accompanied by an equivalent increase in vascularity. Reduced ICAM-1 expression in non-inflamed areas of smokers could reflect a systemic effect of tobacco smoking on ICAM-1 independent of inflammation.

Adult↗
PubMed2002

Effect of nicotine replacement and quitting smoking on circulating adhesion molecule profiles (sICAM-1, sCD44v5, sCD44v6).

BACKGROUND: Soluble ICAM-1 (sICAM-1; sCD54), sCD44v5 and sCD44v6 are circulating adhesion molecules, with immunomodulatory potential, that have been frequently attributed diagnostic, prognostic and aetiological significance in a number of inflammatory and malignant diseases. We have previously shown that systemic concentrations of these molecules are increased significantly in tobacco smokers, but reduce to within normal levels at 12 months following successful quitting. MATERIALS AND METHODS: We have been able to extend these observations by measuring levels before and 4, 8, 22 and 52 weeks after smoking cessation in subjects receiving high-dose nicotine replacement therapy (25 mg of nicotine; n = 34) or placebo patches (n = 34) for 26 weeks. Smoking cessation was confirmed by regular measurement of expired-air CO levels and by plasma cotinine analysis. RESULTS: Plasma sICAM-1, sCD44v5 and sCD44v6 concentrations all declined rapidly within 4 weeks of smoking cessation (P < 0.001 for all declines). Additionally, no differences were observed between those using nicotine replacement and those who were not for sICAM-1, sCD44v5, or sCD44v6. CONCLUSIONS: The recovery in smoking-associated adhesion molecule profiles represents an almost immediate beneficial effect of smoking cessation. Nicotine replacement therapy is an effective aid to quitting and does not affect these recoveries. The elevated levels of these important risk factors in smokers (sICAM-1, sCD44v5 and sCD44v6) are linked to noxious element(s) in tobacco smoke other than nicotine or nicotine metabolites.

Administration, Cutaneous↗
PubMed2002

Clinical and cost effectiveness of paclitaxel, docetaxel, gemcitabine, and vinorelbine in non-small cell lung cancer: a systematic review.

BACKGROUND: Lung cancer remains a devastating disease with few effective treatment options. Recent developments in chemotherapy have led to cautious optimism. This paper reviews the evidence on the clinical and cost effectiveness of four of the new generation drugs for patients with lung cancer. METHODS: A systematic review of randomised controlled trials (RCTs) identified from 11 electronic databases (including Medline, Cochrane library and Embase), reference lists and contact with experts and industry was performed to assess clinical effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine. Clinical effectiveness was assessed using the outcomes of patient survival, quality of life, and adverse effects. Cost effectiveness was assessed by development of a costing model and presented as incremental cost per life year saved (LYS) compared with best supportive care (BSC). RESULTS: Of the 33 RCTs included, five were judged to be of good quality, 10 of adequate quality, and 18 of poor quality. Gemcitabine, paclitaxel, and vinorelbine as first line treatment and docetaxel as second line treatment appear to be more beneficial for non-small cell lung cancer than BSC and older chemotherapy agents, increasing patient survival by 2-4 months against BSC and some comparator regimes. These gains in survival do not appear to be at the expense of quality of life. Survival gains were delivered at reasonable levels of incremental cost effectiveness for vinorelbine, vinorelbine with cisplatin, gemcitabine, gemcitabine with cisplatin, and paclitaxel with cisplatin regimens compared with BSC. CONCLUSION: Although the clinical benefits of the new drugs appear relatively small, their benefit to patients with lung cancer appears to be worthwhile and cost effective.

Antimetabolites, Antineoplastic↗
PubMed2002

Anaesthesia for endoluminal repair of abdominal aortic aneurysms.

An audit of 100 patients undergoing elective abdominal aortic surgery either by open aortic repair (OAR group 50 patients) or endovascular aortic repair (EAR group 50 patients) was undertaken to document changes in anaesthetic technique and perioperative outcome. The data for the OAR group was collected retrospectively and thatfor the EAR group prospectively. Combined general anaesthesia and thoracic epidural anaesthesia was used in 44 of the OAR group whereas lumbar central neural blockade alone was used in 47 of the EAR group. The major differences between the two groups were that intraoperative blood loss was significantly less in the EAR group (OAR 1,674 +/- 1,008 ml, EAR 459 +/- 350 ml, P<0.001) and that no patient in the EAR group required admission to the Intensive Care Unit (ICU), whereas ICU time for the OAR patients was 29 +/- 22 hours. Hospital stay was also significantly different between the two groups (OAR 13 +/- 6 days, EAR 5 +/- 3 days, P<0.001). Major complications occurred in 20patients in the OAR group but only 4patients in the EAR group (P<0.001). EAR reduces blood loss, the requirement for ICU admission, and hospital stay. Central neural blockade is a satisfactory anaesthetic technique for EAR.

Aged↗