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Showing papers by "St Thomas' Hospital published in 2000"


Journal ArticleDOI
TL;DR: There is no evidence in these twin data that the overall genetic contribution to RA differs by sex, age, age at disease onset, and disease severity.
Abstract: Objective Twin concordance data for rheumatoid arthritis (RA) on their own provide only limited insight into the relative genetic and environmental contribution to the disease. We applied quantitative genetic methods to assess the heritability of RA and to examine for evidence of differences in the genetic contribution according to sex, age, and clinical disease characteristics. Methods Data were analyzed from 2 previously published nationwide studies of twins with RA conducted in Finland and the United Kingdom. Heritability was assessed by variance components analysis. Differences in the genetic contribution by sex, age, age at disease onset, and clinical characteristics were examined by stratification. The power of the twin study design to detect these differences was examined through simulation. Results The heritability of RA was 65% (95% confidence interval [95% CI] 50–77) in the Finnish data and 53% (95% CI 40–65) in the UK data. There was no significant difference in the strength of the genetic contribution according to sex, age, age at onset, or disease severity subgroup. Both study designs had power to detect a contribution of at least 40% from the common family environment, and a difference in the genetic contribution of at least 50% between subgroups. Conclusion Genetic factors have a substantial contribution to RA in the population, accounting for ∼60% of the variation in liability to disease. Although tempered by power considerations, there is no evidence in these twin data that the overall genetic contribution to RA differs by sex, age, age at disease onset, and disease severity.

1,130 citations


Journal ArticleDOI
01 Apr 2000-Pain
TL;DR: Patients’ use of VASs and NRSs is examined, with particular attention to rating of multiple pains, of different dimensions of pain, and of interpretation and use of lower and upper endpoints and increments on the scales, which have implications for the approximation of the scales to psychometric requirements.
Abstract: Assumptions of reliability and consistency of self-report of pain by patients using visual analogue scales (VAS) and numerical rating scales (NRS) are based on narrow considerations of possible sources of error. This study examined patients' use of VASs and NRSs, by their own description, with particular attention to rating of multiple pains, of different dimensions of pain, and of interpretation and use of lower and upper endpoints and increments on the scales. These have implications for the approximation of the scales to psychometric requirements. An interview developed from a small pilot project was given to 78 volunteer chronic pain patients embarking on a pain management course, and consisted of both forced choice questions and free response. Data are described with reference to lack of concordance between patients and of consistency within patients; responses suggested that ratings incorporate multiple partially differentiated dimensions of pain, with particular importance placed on function or mobility. Labels assigned to scale endpoints by researchers, whether lexical or numerical, appeared to affect their use; however, covert relabelling of scale points was revealed in free response. The action of arriving at a rating is better conceptualised as an attempt to construct meaning, influenced by and with reference to a range of internal and external factors and private meanings, rather than as a task of matching a distance or number to a discrete internal stimulus.

391 citations


Journal ArticleDOI
TL;DR: It is suggested that aPL recognition of both anionic PL and adhered beta2GPI on trophoblast cell structures might represent a potential pathogenetic mechanism for defective placentation in women with the antiphospholipid syndrome.
Abstract: Antiphospholipid antibodies (aPL) are associated with poor obstetric outcome, such as recurrent abortions, fetal death, growth retardation, and early preeclampsia (1). Passive transfer of whole immunoglobulin fractions from aPL-positive sera has been found to induce fetal loss and growth retardation in pregnant naive mice, suggesting a direct pathogenetic role (2–4). Although it has been assumed that aPL are directed against anionic PL, current advances in the field suggest that antibodies to PL-binding plasma proteins, such as β2-glycoprotein I (β2GPI), can be detected in standard aPL assays (5). Antibodies specific for β2GPI have been identified and found to be associated with the clinical manifestations of the antiphospholipid syndrome (APS) (6–22). The in vivo immunohistologic demonstration of β2GPI on trophoblast surfaces (23,24) and the induction of fetal loss by anti-β2GPI antibodies in experimental animal models (25,26) suggested a role of anti-β2GPI antibodies in fetal loss. Moreover, even murine and human aPL monoclonal antibodies (mAb) specifically reacting with anionic PL in the absence of any plasma cofactor have been shown to produce fetal loss, growth retardation, placental deposition, and necrosis in experimental animal models (3,27,28). Although experimental models have emphasized the role of thrombotic phenomena in placental tissue (4,27), studies in humans have shown that thrombotic events cannot account for all of the histopathologic findings in placentae from women with the APS (29,30). The possibility of direct villous and extravillous trophoblastic damage by aPL through the recognition of phosphatidylserine (PS) exposed during syncytium formation has been suggested (31). Reported direct effects of aPL on trophoblasts have included inhibition of the intercytotrophoblast fusion process (31), of human chorionic gonadotropin (hCG) or placental lactogen secretion (31,32), and/or of trophoblast invasiveness (31). Furthermore, whole IgG fractions from APS patient sera or xenogenic murine anti-PS mAb have been shown to displace annexin V from trophoblasts (and endothelial cell surfaces in the case of human IgG), thus creating conditions favorable to procoagulant state in vitro (31,33). The purpose of the present study was to investigate the in vitro ability of IgG from sera containing high levels of aPL to bind human trophoblast cells and to affect hCG secretion and invasiveness. Furthermore, to identify whether specific effects were related to individual antibody subpopulations, human mAb reacting with β2GPI or with anionic PL in the absence of any plasma cofactor were investigated for their ability to reproduce the binding to trophoblast cell membranes and the modulation of hormone secretion as well as invasiveness. From our results, it appears that trophoblast cells might represent one target for circulating aPL reacting with β2GPI and/or with “pure” anionic PL (whose binding is independent of any plasma cofactor) and that such antibodies affect trophoblast differentiation–related activities.

288 citations


Journal ArticleDOI
TL;DR: The combination of HA with chitosan may afford additional advantages in combining the mucoadhesive potential ofHA with the penetration enhancing effect of chitan, and thereby improve the resultant pharmacokinetic profile.

283 citations


Journal ArticleDOI
TL;DR: An insight is given into the many factors which must be taken into consideration when first establishing these preparations, the range of indices that can be measured and the potential pitfalls which, with a little care, can be readily avoided.

272 citations


Journal ArticleDOI
TL;DR: In this paper, the authors compared OCT with fundus fluorescein angiography (FFA) for the detection of cystoid macular edema (CME) in patients with uveitis.

272 citations


Journal ArticleDOI
TL;DR: Investigation of the role of new, inherited thrombophilic disorders in the pathogenesis of PVT in cirrhotic patients found that this high‐risk group may have implications in patients who are candidates for major surgery or liver transplantation, and may influence the duration of oral anticoagulation.

254 citations


Journal ArticleDOI
TL;DR: FDG-PET is an accurate method of assessing remission and estimating prognosis following treatment of aggressive NHL, with positive and negative predictive accuracies of 100% and 82% respectively.
Abstract: Less than 50%, of newly diagnosed patients with aggressive histology Non-Hodgkin's Lymphoma (NHL) are cured with standard treatment. The ability to accurately monitor response to treatment is cruci...

249 citations


Journal ArticleDOI
TL;DR: The early clinical experience of percutaneous ultrasound-guided fetal balloon valvuloplasty in human fetuses with severe aortic valve obstruction has been poor due to selection of severe cases, technical problems during the procedure, and high postnatal operative mortality in fetuses who survived gestation.
Abstract: Prenatal alleviation of severe fetal aortic valve obstructions by percutaneous ultrasound-guided balloon valvuloplasty has been performed to improve the fate of affected fetuses. The purpose of this study was to analyze the current world experience of these procedures in human fetuses. Data from 12 human fetuses were available for analysis. The mean gestational age at intervention was 29.2 weeks (range 27 to 33). The mean time period between initial presentation and intervention was 3.3 weeks (range 3 days to 9 weeks). Technically successful balloon valvuloplasties were achieved in 7 fetuses, none of whom had an atretic valve. Only 1 of these fetuses remains alive today. Of the 5 remaining technical failures, 1 patient with severe aortic stenosis underwent successful postnatal intervention and remains alive. Six patients who survived prenatal intervention died from cardiac dysfunction or at surgery in the first days or weeks after delivery. Four fetuses died early within 24 hours after the procedure, 1 from a bleeding complication, 2 from persistent bradycardias, and 1 at valvotomy after emergency delivery. Thus, the early clinical experience of percutaneous ultrasound-guided fetal balloon valvuloplasty in human fetuses with severe aortic valve obstruction has been poor due to selection of severe cases, technical problems during the procedure, and high postnatal operative mortality in fetuses who survived gestation. Improved patient selection and technical modifications in interventional methods may hold promise to improve outcome in future cases.

248 citations


Journal ArticleDOI
TL;DR: Insecure attachment is common in eating disordered populations, with implications for therapy and further work with refined instruments may clarify whether or not there is a specific association between attachment style and eating disorder subgroup.
Abstract: Aim. In a recent review, disturbances in attachment have been linked with eating disorder symptomatology. However, because of the limitations of study design, few inferences could be drawn about these processes in the aetiology and maintenance of eating disorder. Since that review, there has been further development in the instruments used and the publication of several further studies of attachment processes in eating disorders. We reviewed the field, expecting that greater clarity may have emerged in the 3 years since the previous review. Method. A review of the literature was carried out, using the computer search PsychLIT, Medline, Embase and The Cochrane Library. Results. There have been more studies published in this area in the last 3 years than in the entire period up until then. These can broadly be divided into those carried out in clinical and non-clinical populations, with greater weight ascribed to the former. The vast majority of studies found that attachment processes, by whatever method measured, are abnormal in eating disordered populations. Attachment style (dismissing versus preoccupied) may be linked with eating disorder diagnostic subgroup. Conclusions. Insecure attachment is common in eating disordered populations, with implications for therapy. Further work with refined instruments may clarify whether or not there is a specific association between attachment style and eating disorder subgroup. However, such an association is likely to be complicated and it may be more fruitful to study specific aspects of attachment, rather than global attachment style, in relation to eating disorder behaviour. The transgenerational transmission of attachment is a fruitful area for further investigation in eating disordered populations.

242 citations


Journal ArticleDOI
TL;DR: A rapid (<4 h) detection and identification system that uses universal PCR primers to amplify a variable region of bacterial 23S ribosomal DNA, followed by reverse hybridization of the products to a panel of oligonucleotides was successful in discriminating a range of bacteria in pure cultures.
Abstract: The rapid identification of bacteria in blood cultures and other clinical specimens is important for patient management and antimicrobial therapy. We describe a rapid (<4 h) detection and identification system that uses universal PCR primers to amplify a variable region of bacterial 23S ribosomal DNA, followed by reverse hybridization of the products to a panel of oligonucleotides. This procedure was successful in discriminating a range of bacteria in pure cultures. When this procedure was applied directly to 158 unselected positive blood culture broths on the day when growth was detected, 125 (79.7%) were correctly identified, including 4 with mixed cultures. Nine (7.2%) yielded bacteria for which no oligonucleotide targets were present in the oligonucleotide panel, and 16 culture-positive broths (10.3%) produced no PCR product. In seven of the remaining eight broths, streptococci were identified but not subsequently grown, and one isolate of Staphylococcus aureus was misidentified as a coagulase-negative staphylococcus. The accuracy, range, and discriminatory power of the assay can be continually extended by adding further oligonucleotides to the panel without significantly increasing complexity or cost.

Journal ArticleDOI
TL;DR: Fatigue is an important but under-recognised side-effect of hormone therapy and on multivariate analysis psychological distress explained 28% of the variance in fatigue scores.

Journal ArticleDOI
TL;DR: Individual differences in morning salivary cortisol levels may represent an independent risk factor for subsequent major depressive disorder (MDD).
Abstract: Background Whether individual differences in cortisol contribute to subsequent major depressive disorder (MDD) is unknown Aims To determine whether premorbid levels of salivary cortisol and dehydroepiandrosterone (DHEA) were associated with subsequent MDD and how these related to psychosocial factors known to increase the risk for MDD Method Adult women ( n =116) were recruited from general practices None was currently depressed; 83 were ‘psychosocially vulnerable’ to MDD, 33 were not Salivary steroids (cortisol and DHEA at 0800 h and 2000 h), recent life events, current mood and social support were assessed at entry Onset of MDD was recorded during 13 months9 follow-up Results There were no associations between salivary cortisol or DHEA and recent life events or vulnerability Twentyeight onsets of MDD occurred during the follow-up period This was associated with: severe adverse life events and difficulties during the follow-up period; mean morning cortisol levels at entry; and the presence of any of three vulnerability factors Conclusions Individual differences in morning salivary cortisol levels may represent an independent risk factor for subsequent MDD The origin of these differences in cortisol is not yet understood

Journal ArticleDOI
01 Jan 2000-Analyst
TL;DR: Titanium dioxide is a common food additive of increasing interest in dietary intake studies and dietary exclusion studies and a method was developed for its rapid determination in foods using acid digestion and inductively coupled plasma optical emission spectrometry (ICPOES).
Abstract: Titanium dioxide is a common food additive of increasing interest in dietary intake studies and dietary exclusion studies. Food labelling for titanium dioxide is imprecise so a method was developed for its rapid determination in foods using acid digestion and inductively coupled plasma optical emission spectrometry (ICPOES). Twenty-five foods thought to contain titanium dioxide were obtained. Based on preliminary digestion studies, samples (500 mg) were digested in 18 mol l-1 H2SO4 at 250 degrees C for 1 h and then diluted to 5.9 mol l-1 H2SO4 before determination of titanium by ICPOES at 336.121 nm. Emission intensity was suppressed by H2SO4 so standards were matched for acid concentration. Titanium dioxide embedded in gelatine was used to assess accuracy. A standard reference material of known titanium concentration and six foods of known titanium dioxide content were used as external reference materials. Limits of detection were 2-7.5 ppb, depending on spectral integration times, and the signal was linear up to 5 ppm. Results for all control samples were in good agreement with the expected values. Twelve of the foods contained detectable titanium, ranging from 0.001 to 0.782% by weight, but only eight indicated this on their labels, four being exempt under food labelling regulations. Based on food portion sizes, an individual's daily intake of titanium dioxide could exceed 200 mg from just one of these products. This method may facilitate future studies on titanium dioxide intake, given the present limitations of food labelling.

Journal ArticleDOI
Robert Carr1
TL;DR: Clinical evidence of the preterm neonate's immune incompetence is the pattern of bacterial infections which closely parallels that seen in patients with profound neutropenia and the frequent development of neutropania in response to bacterial sepsis.
Abstract: Bacterial infection is a major cause of death and long-term morbidity in preterm neonates. Infection rates among neonates undergoing intensive care range from 25% to 50% (Stoll et al, 1996; Cooke et al, 1997; Fanaroff et al, 1998) and, in spite of effective antibiotic therapy, sepsisrelated mortality has remained constant at 15±20% for nearly two decades (Gladstone et al, 1990). The reason for such high sepsis rates and attendant mortality are largely due to the immaturity of bactericidal mechanisms. Clinical evidence of the preterm neonate's immune incompetence is the pattern of bacterial infections which closely parallels that seen in patients with profound neutropenia (Stoll et al, 1996) and the frequent development of neutropenia in response to bacterial sepsis (Engle et al, 1984; Gessler et al, 1995). These two phenomena can be directly related to immaturity of neutrophil function and production.

Journal ArticleDOI
TL;DR: A quantitative MR perfusion method showed reduced whitematter CBF in patients with ischaemic leukoaraiosis, but normal grey matter CBF, consistent with hypoperfusion playing a part in the pathogenesis of ischaemia leukoARaiosis.
Abstract: OBJECTIVE: White matter hypoperfusion may play a part in the pathogenesis of ischaemic leukoaraiosis, but demonstration of this requires a high resolution quantitative method of cerebral blood flow (CBF) measurement. Initial exogenous contrast based MRI methods only allowed measurement of relative cerebral blood volume (CBV) values, but more recently a mathematical approach has been developed which enables absolute regional CBF and CBV to be determined. This technique was applied to patients with ischaemic leukoaraiosis to determine whether reduced white matter CBF in this patient group could be demonstrated. METHODS: Eight patients with ischaemic leukoaraiosis (radiological leukoaraiosis and clinical lacunar stroke), and nine age matched controls were studied. A spin echo echoplanar image sequence was used on a 1.5 Tesla MR system. An arterial input function was obtained from voxels placed over the middle cerebral arteries. Cerebral blood flow, CBV, and mean transit (MTT) maps were derived. Regions of interest were placed at standard positions in the white and grey matter and mean values of CBF, CBV, and MTT were compared between the two groups. RESULTS: Mean (SD) white matter CBF was significantly reduced in patients by 38% (13.40 (4.87) v 21.74 (3.53) ml/min/ 100 g, p=0.002). Significant reductions in CBF were seen in all white matter regions. By contrast there was no reduction in CBF in any grey matter region. There was no significant difference in white matter CBV between cases and controls; mean values were lower in all white matter regions for patients but this did not reach significance for any region. By contrast mean grey matter CBV was significantly higher in patients than in controls. Mean MTT values were higher in all regions of grey and white matter in the patient group, but this only achieved significance for the superior white matter. CONCLUSION: A quantitative MR perfusion method showed reduced white matter CBF in patients with ischaemic leukoaraiosis, but normal grey matter CBF. This is consistent with hypoperfusion playing a part in the pathogenesis of ischaemic leukoaraiosis. The absolute values of white matter and grey matter CBF obtained in the patient groups were very similar to those in previous PET studies, providing further evidence for the validity of the regional CBF measurements obtained using this quantitative MR perfusion technique. The high spatial resolution and lack of radioactive administration makes such techniques ideal for longitudinal studies in this condition.

Journal ArticleDOI
TL;DR: Cognitive-behavioral therapy for psychosis draws on the cognitive models and therapy approach of Beck and colleagues, combined with an application of stress-vulnerability models of schizophrenia and cognitive models of psychotic symptoms, and there is encouraging evidence for the efficacy.
Abstract: Cognitive-behavioral therapy for psychosis is described. It draws on the cognitive models and therapy approach of Beck and colleagues, combined with an application of stress-vulnerability models of schizophrenia and cognitive models of psychotic symptoms. There is encouraging evidence for the efficacy of this approach. Four controlled trials have found that cognitive-behavioral therapy reduces symptoms of psychosis, and there is some evidence that it may contribute to relapse reduction. Studies that have examined factors that predict treatment response are reviewed. There is preliminary evidence that a good outcome is partially predicted by a measure of cognitive flexibility or a "chink of insight." People who present with only negative symptoms may show poorer outcome. However, there is no evidence that intelligence or symptom severity is associated with outcome. Implications for selecting patients and for optimal duration of treatment are discussed. Finally, the importance of taking account of the heterogeneity of people with psychosis, so that individual treatment goals are identified, is discussed.


Journal ArticleDOI
01 Sep 2000-Stroke
TL;DR: Raised plasma osmolality on admission is associated with stroke mortality, after correcting for case mix and trials are required to determine whether correcting dehydration after stroke improves outcome.
Abstract: Background and Purpose —Abnormal physiological parameters after acute stroke may induce early neurological deterioration. Studies of the effect of dehydration on stroke outcome are limited. We examined the association of raised plasma osmolality on stroke outcome at 3 months and the change of plasma osmolality with hydration during the first week after stroke. Methods —Acute stroke patients had their plasma osmolality measured at admission and at days 1, 3, and 7. Maximum plasma osmolality and the area under curve (AUC) were also calculated during the first week. Patients were stratified according to how they were hydrated: orally, intravenously, or both. Outcome included survival at 3 months after stroke. Logistic regression was performed to examine the association between raised plasma osmolality (>296 mOsm/kg) and survival, adjusting for stroke severity. Linear regression was performed to examine the pattern of plasma osmolality across hydration groups. Results —One hundred sixty-seven patients were included. Mean admission (300 mOsm/kg, SD 11.4), maximum (308.1 mOsm/kg, SD 17.1), and AUC (298.3 mOsm/kg, SD 11.7) plasma osmolality were significantly higher in those who died compared with survivors (293.1 mOsm/kg [SD 8.2], 297.7 mOsm/kg [SD 8.7], and 291.7 mOsm/kg [SD 8.1], respectively; P 296 mOsm/kg was significantly associated with mortality (OR 2.4, 95% CI 1.0 to 5.9). In patients hydrated intravenously, there was no significant fall in plasma osmolality compared with patients hydrated orally ( P =0.68). Conclusions —Raised plasma osmolality on admission is associated with stroke mortality, after correcting for case mix. Correction of dehydration after stroke requires a more systematic approach. Trials are required to determine whether correcting dehydration after stroke improves outcome.

Journal ArticleDOI
TL;DR: A case of endocarditis in a human infected with Bartonella vinsonii subsp.
Abstract: We report a case of endocarditis in a human infected with Bartonella vinsonii subsp. berkhoffii, which causes bacteremia and endocarditis in dogs. Bacterial identification was established by PCR amplification and sequencing of an intergenic spacer region (ITS1), 16S ribosomal DNA, and a gene encoding citrate synthase (gltA). Bartonella antibodies were detected by immunofluorescence.

Journal ArticleDOI
TL;DR: It is demonstrated that αvβ3 is a pivotal integrin for the growth of human melanomas and strong evidence of the therapeutic potential of αv‐integrin antagonists for the treatment of such tumors is provided.
Abstract: Integrin alphavbeta3 (vitronectin receptor) has been implicated in human malignant melanoma progression and angiogenesis as a receptor that provides survival signals. However, little is known about the therapeutic potential of antagonists of alphavbeta3. In this report, we characterize the activities of 2 antagonists of alphavbeta3 integrins: a human specific monoclonal antibody (MAb), 17E6, and a cyclic RGD peptide that blocked cell adhesion and induced detachment of previously substrate-attached cells in vitro. In vivo, alphavbeta3 antagonists behaved as anti-tumor drugs in a dose- and time-dependent manner. Moreover, different therapeutic treatments proved to be effective even in the therapy of established macroscopic tumor masses, thus supporting the use of these antagonists in clinical therapy. Using a panel of 6 human melanomas and 5 carcinomas, MAb 17E6 efficiently blocked the in vivo tumor growth of melanomas expressing alphavbeta3 as xenografts but did not affect the alphavbeta3-negative (although alphav integrin-positive) tumors. This demonstrated that alphavbeta3 is a pivotal integrin for the growth of human melanomas. Furthermore, since MAb 17E6 does not recognize murine alphavbeta3, the effect is due only to the direct anti-tumor activity and not to the well-known anti-angiogenic activity of alphav-integrin antagonists. Taken together, our results confirm the essential role of alphavbeta3 integrin in the growth of human malignant melanoma in vivo and provide strong evidence of the therapeutic potential of alphav-integrin antagonists for the treatment of such tumors.

Journal ArticleDOI
Joanne May1, C H Chan, Anna King, L Williams, Gary French 
TL;DR: This study determined the kill rate of tea tree oil against several multidrug-resistant organisms, including MRSA, glycopeptide-resistant enterococci, aminoglycoside- resistant klebsiellae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia, and also against sensitive microorganisms.
Abstract: Tea tree oil has recently emerged as an effective topical antimicrobial agent active against a wide range of organisms. Tea tree oil may have a clinical application in both the hospital and community, especially for clearance of methicillin-resistant Staphylococcus aureus (MRSA) carriage or as a hand disinfectant to prevent cross-infection with Gram-positive and Gramnegative epidemic organisms. Our study, based on the time-kill approach, determined the kill rate of tea tree oil against several multidrug-resistant organisms, including MRSA, glycopeptide-resistant enterococci, aminoglycoside-resistant klebsiellae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia, and also against sensitive microorganisms. The study was performed with two chemically different tea tree oils. One was a standard oil and the other was Clone 88 extracted from a specially bred tree, which has been selected and bred for increased activity and decreased skin irritation. Our results confirm that the cloned oil had increased antimicrobial activity when compared with the standard oil. Most results indicated that the susceptibility pattern and Gram reaction of the organism did not influence the kill rate. A rapid killing time (less than 60 min) was achieved with both tea tree oils with most isolates, but MRSA was killed more slowly than other organisms.

Journal ArticleDOI
TL;DR: Genetic factors have a significant contribution to OA at the hip in women and account for approximately 60% of the variation in population liability to the disease.
Abstract: Objective To assess the genetic contribution to radiographic hip osteoarthritis (OA) by measuring the distribution of disease features in monozygotic (MZ) and dizygotic (DZ) twins Methods A population-based, cross-sectional study was conducted of 135 MZ and 277 DZ healthy female twin pairs, 50 years of age and older, who were recruited into the St Thomas' UK Adult Twin Registry Pelvic radiographs were read by a single observer who was blinded to the pairing and zygosity of the twins The films were assessed for overall OA grade using a modification of the Kellgren and Lawrence scheme, and assessed for individual radiographic features Results There was evidence of significant familial clustering for grade I and grade II OA changes, with an excess concordance in MZ twins compared with DZ twins, suggesting a genetic effect The MZ versus DZ excess was also apparent for those classified as having more severe disease, although the number of pairs with these disease features was small Familial clustering attributable to genetic factors was evident for joint space narrowing of <25 mm Familial, but not genetic, clustering was seen for subchondral sclerosis The number of pairs concordant for definite osteophytes in the sample was too low to assess this feature alone These results translate into a significant heritability of 58% for OA overall and 64% for joint space narrowing The heritability estimates decreased a little when the potential confounding influences of age, body mass index, and hip bone density were taken into account Conclusion Genetic factors have a significant contribution to OA at the hip in women and account for ∼60% of the variation in population liability to the disease

Journal ArticleDOI
TL;DR: The Astra Tech Implants ST were highly successful in single tooth replacement and bone levels during 5 years of function were stable.
Abstract: Aim— To evaluate the AstraTech Implant ST (Molndal, Sweden) for single tooth replacement clinically and radiographically after 5 years in function. Subjects and method— Fifteen patients (age range 16 to 48) with missing maxillary anterior teeth (6 central incisors, 8 laterals, 1 bicuspid) had four 13 mm and eleven 15 mm single tooth implants provided. All patients were seen at 4- to 6-monthly intervals for oral hygiene maintenance. Periapical radiographs using Rinn holders and a long cone technique were taken at the crown insertion and after 1 year, 3 and 5 years. Results— No implant losses were observed in 14 of the 15 patients available for evaluation. No abutment screw loosening or soft tissue problems were observed. At crown insertion the mean bone level was 0.46±0.55 to 0.48 ±0.56 mm apical to the top of the implant neck and there were no statistically significant changes in the radiographic bone level over the 5 years of the study (0.36±0.37 to 0.43±0.46 mm at year 5). One crown was recemented after 18 months in function and 1 crown was replaced because of a fracture to the porcelain incisal edge. Conclusion— The Astra Tech Implants ST were highly successful in single tooth replacement and bone levels during 5 years of function were stable. Resume Le but de cette etude a ete d'evaluer cliniquement et radiologiquement le systeme Astra Tech Implant ST pour le remplacement d'une dent, apres cinq annees en fonction. Quinze patients de seize a 48 ans avec une dent anterosuperieure manquante (six incisives centrales, huit laterales et une premolaire) ont ete implantes avec quatre implants de 13 mm et onze de 15 mm. Tous les patients ont ete revus a des intervalles de quatre a six mois pour l'entretien de l'hygiene buccale. Des radiographies periapicales utilisant la methode de Rinn avec long cone ont ete prises lors de l'insertion de la couronne et apres une, trois et cinq annees. Aucune perte implantaire n'a ete observee pour quatorze parmi les quinze patients. Aucune vis de l'implant ne s'est devissee et aucun probleme de tissus mous n'a ete observe. Lors du placement de la couronne, le niveau osseux moyen etait de 0.46±0.55 a 0.48 ±0.56 mm apicalement par rapport au sommet du col de l'implant. Il n'y avait aucune variation statistiquement significative pour les niveaux osseux radiographiques durant les cinq ans a la fin desquels ces mesures etaient respectivement de 0.36±0.37 a 0.43 ±0.46 mm. Une couronne a ete rescellee apres 18 mois. Une autre a ete remplacee suite a une fracture du bord incisif en porcelaine. Le systeme implantaire Astra Tech ST s'est revele excellent pour le remplacement unitaire, les niveaux osseux durant les cinq annees de fonction sont restes stables. Zusammenfassung Ziel: Das Astra Tech Implantat ST (Molndal Sweden) uber einen Zeitraum von 5 Jahren in Funktion klinisch und radiologisch zu untersuchen. Material und Methode. 15 Patienten (Alter zwischen 16 und 48) mit fehlenden Zahnen in der Oberkieferfront (6 zentrale Inzisiven, 8 laterale Inzisiven, 1 Pramolar) wurden vier 13 mm und elf 15 mm lange Einzelimplantate eingesetzt. Alle Patienten wurden alle 4 bis 6 Monate nachkontrolliert und die Mundhygiene uberwacht. Nach dem Einsetzen der Kronen und 1 Jahr, 3 und 5 Jahre nach dem Einsetzen der Kronen wurden periapikale Rontgenaufnahmen mit dem Filmhaltern des Rinnsystems und der Langtubustecknik aufgenommen. Resultate: Bei den 14 von insgesamt 15 Patienten, welche nachuntersucht werden konnten, war kein Implantatverlust zu verzeichnen. Es konnten keine lockeren Schrauben bei den Prothetikaufbauten und keine Probleme an den Weichgeweben beobachtet werden. Beim Einsetzen der Kronen lag das Knochenniveau 0.46±0.55 bis 0.48±0.56 mm apikal vom Oberteil des Implantathalses und es fanden wahrend der 5 Jahre dauernden Beobachtungszeit keine statistisch signifikanten Veranderungen im radiologischen Knochenniveau statt (0.36±0.37 bis 0.43±0.46 mm nach 5 Jahren). Eine Krone musste nach 18 Monaten in Funktion rezementiert und eine Krone wegen einer Porzellanfraktur der Inzisalkante ersetzt werden. Schlussfolgerung: Die Astra Tech Implantate ST waren fur den Einzelzahnersatz sehr erfolgreich und die Knochenniveaus waren wahrend der Beobachtungszeit von 5 Jahren in Funktion stabil. Resumen Intencion— Evaluar clinica y radiograficamente el implante Astra Tech ST (Molndal Suecia) para sustitucion de diente unico tras 5 anos en function. Sujetos y metodo− 15 pacientes (rango de edad de 16 a 48) con ausencia de dientes maxilares anteriores (6 incisivos centrales, 8 laterales, 1 bicuspide) recibieron cuatro implantes unitarios de 13 mm y once de 15 mm. Todos los pacientes fueron vistos con intervalos de 4 a 6 meses para mantenimiento de higiene oral. Se tomaron radiografias periapicales usando soportes Rinn y tecnica de cono largo en el momento de insercion de la corona y al ano, 3 y 5 anos. Resultados— No se observaron perdidas de implantes en 14 de los 15 pacientes disponibles para la evaluacion. No se observaron movilidades en los pilares o problemas de los tejidos blandos. En el momento de insertion de la corona el nivel medio de hueso fue de 0.46±0.55 a 0.48±0.56 mm apical de la parte alta del cuello del implante y no hubo cambios estadisticamente significativos en el nivel radiografico de hueso a lo largo de los 5 anos del estudio (0.36±0.37 a 0.43±0.46 mm en el quinto ano). Una corona se recemento despues de 18 meses en funcion y una corona se sustituyo por fractura de la porcelana en el borde incisai. Conclusion— Los implantes Astra Tech ST fueron altamente exitosos en la sustitucion de dientes unitarios y los niveles de hueso a los 5 anos se mantuvieron estables.

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TL;DR: Significantly more sites of disease were identified by PET than CT resulting in stage changes and a modification of therapy in 25% of patients, which has important implications not only for current patient management but also for the design of future clinical trials.

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TL;DR: The unique matching of identical twins provides researchers with ways to isolate the function of individual genes involved in disease together with approaches to understanding how genes and the environment interact.

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TL;DR: It is demonstrated that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo.
Abstract: Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P < 0.001), and a moderate sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer.

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TL;DR: Within the scope of this present study, it has not been possible to address issues such as inter-sample variability, losses during storage or the bioavailability from different foods and further work on these aspects is needed.
Abstract: This paper reports the compilation of a food composition database for phylloquinone (vitamin K1) derived from the direct analysis of foods, recipe calculation and the assignment of values based on food similarities. All the basic and other food items used in these calculations had been analysed by HPLC and about 170 of the items had been obtained and assayed in the UK. Recipe calculations took account of the cooking method and changes in water and fat content. Currently, approximately 1501 food items with Royal Society of Chemistry/Ministry of Agriculture, Fisheries and Food food codes have been allocated a vitamin K1 value, and a further 282 new recipe codes are included in the database. Representative values from each food group are reported together with an indication of the potential variation. Detailed examples of some recipe calculations are included, and also the impact of changing the type of fat in recipes. Vitamin K1 is associated with, and most abundant in, photosynthetic tissues of plants. Accordingly, the highest concentrations (3000-6000 micrograms/kg) are found in dark-green leafy vegetables and herbs, such as kale, parsley, spinach and green cabbage. Intermediate concentrations (1000-2000 micrograms/kg) are found in plants with paler leaves such as white cabbage and lettuce or in green, non-leafy vegetables such as broccoli and brussel sprouts. Fats and oils contain variable amounts of vitamin K1 with the highest concentrations (300-1300 micrograms/kg) in soyabean, rapeseed and olive oils and the margarines based on them. Other foods such as dairy products, meat dishes and cereal-based foods (bread, biscuits, cakes, desserts etc.), although not in themselves particularly rich in vitamin K1 (< 200 micrograms/kg), may contribute significantly to intakes when consumption of green vegetables is poor. Within the scope of this present study, it has not been possible to address issues such as inter-sample variability, losses during storage or the bioavailability from different foods and further work on these aspects is needed.

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01 Jan 2000-Medicine
TL;DR: A careful medical history, a previous history of thrombosis and/or fetal loss, an abnormal localization of the lesions in MRI, and the response to anticoagulant therapy might be helpful in the differential diagnosis.