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Biomedical subjects

J Thornton

Publications and source records attributed to J Thornton.

At least 19 recordsLinked to original sources

Attitudes and behaviour of ophthalmologists to smoking cessation.

AIMS: Growing evidence suggests a causal association between smoking and eye disease. This study explores the current beliefs and practice among UK consultant ophthalmologists towards delivering smoking cessation advice to eye clinic attenders. METHODS: A cross-sectional survey using a postal questionnaire of all UK NHS hospital based consultant ophthalmologists was conducted. The questionnaire explored whether: ophthalmologists identify the smoking status of their patients, advise about the increased risk of eye diseases among smokers, and deliver smoking cessation advice. The availability of departmental smoking cessation resources was also ascertained. RESULTS: The response rate was 55% (485/886). Of the responders 79% were males. Only 35% of responders asked about smoking status every time or most times for new patients and 5% for follow-up patients. In all, 40% claimed to always or usually advise patients to quit smoking and 61% claimed to always or usually mention eye disease as a reason to quit. Only 14% assessed motivation to quit and 22% provided advice and assistance about how to stop smoking to smokers who wished to quit. Female ophthalmologists were more likely to undertake most aspects of smoking assessment and intervention. Only 18% of responders stated that their departments provide information about smoking for patients and 6% stated that support is available for patients wanting to quit smoking. CONCLUSION: The assessment of smoking status and provision of targeted support for smokers to quit could be substantially improved in UK ophthalmology departments. There is a need to introduce smoking cessation support into routine ophthalmic practice and provide the resources to support this.

Attitude of Health Personnel↗

Cigarette smoking and thyroid eye disease: a systematic review.

PURPOSE: To evaluate the epidemiological evidence for a causal association between tobacco smoking and thyroid eye disease (TED). METHODS: Systematic review, including quality assessment, of published epidemiological studies and evaluation of the evidence using established causality criteria. RESULTS: Fourteen papers describing 15 studies were included. There was a positive association between smoking and TED in four case-control studies when compared with control patients with Graves' disease but no ophthalmopathy (odds ratio (OR) 1.94-10.1) and in seven case-control studies in which control subjects did not have thyroid disease (OR 1.22-20.2). Two cohort studies examined the occurrence of new cases of TED; one study found an increased incidence of TED with smoking. Four cohort studies investigated progression or outcome of treatment in patients with established TED, three finding an association between smoking and poorer outcome. The quality of the studies was variable, but the association with smoking was strong in the most methodologically rigorous studies. Other evidence supporting a causal link was a consistent association across studies, a dose-response effect, a reduced risk of TED in ex-smokers, and a temporal relationship. CONCLUSION: This systematic review provided strong evidence for a causal association between smoking and development of TED. Current-smokers were also more likely to experience disease progression or poorer outcome of treatment. Patients with Graves' disease and the general public should be educated about the risk of smoking and TED. These findings suggest that patients with Graves' disease or TED who are smokers should be given effective support to stop smoking.

Disease Progression↗

Systematic review of effectiveness of bisphosphonates in treatment of low bone mineral density and fragility fractures in juvenile idiopathic arthritis.

AIMS: To evaluate the currently available evidence for the effectiveness of bisphosphonates in children with low bone mineral density (BMD) and fragility fractures associated with juvenile idiopathic arthritis (JIA), and the safety of bisphosphonates in JIA and other conditions. METHODS: Literature databases were searched using a structured search strategy. The effectiveness review included any studies of children with JIA treated with bisphosphonates. The safety review also included studies of osteogenesis imperfecta. Quantitative data analysis was not undertaken because of the heterogeneity of the studies; findings were summarised using tables and narrative synthesis. RESULTS: Ninety four studies were identified. Sixteen studies (78 JIA children) were included in the effectiveness review: one randomised controlled trial, three controlled cohort studies, 11 case series, and one case report. At baseline, children had low BMD below the expected values for age and sex matched children. In all studies, treatment with bisphosphonates increased BMD compared with baseline: the mean percentage increase in spine BMD ranged from 4.5% to 19.1%. Overall, studies were heterogeneous and of variable quality. A total of 59 papers were included in the safety review; treatment durations were up to three years. The most common side effect was a flu-like reaction with intravenous treatment. This occurred during the first infusion and was transient; the symptoms were managed with paracetamol and did not occur during subsequent cycles. CONCLUSIONS: Bisphosphonates are a promising treatment for low BMD and fragility fractures in children with JIA. However, the quality of the current evidence is variable and better studies are needed to more clearly assess their role.

Adolescent↗

The Escherichia coli AmtB protein as a model system for understanding ammonium transport by Amt and Rh proteins.

The Escherichia coli ammonium transport protein (AmtB) has become the model system of choice for analysis of the process of ammonium uptake by the ubiquitous Amt family of inner membrane proteins. Over the past 6 years we have developed a range of genetic and biochemical tools in this system. These have allowed structure/function analysis to develop rapidly, offering insight initially into the membrane topology of the protein and most recently leading to the solution of high-resolution 3D structures. Genetic analysis has revealed a novel regulatory mechanism that is apparently conserved in prokaryotic Amt proteins and genetic approaches are also now being used to dissect structure/function relationships in Amt proteins. The now well-recognised homology between the Amt proteins, found in archaea, eubacteria, fungi and plants, and the Rhesus proteins, found characteristically in animals, also means that studies on E. coli AmtB can potentially shed light on structure/function relationships in the clinically important Rh proteins.

Ammonia↗

Assessing medical student knowledge, attitudes, and behaviors regarding organ donation.

PURPOSE: To measure medical students' knowledge of the central issues in organ donation and transplantation and to understand their perception of the extent of training they received prior to and during medical school. METHODS: A previously validated, 41-question instrument assessing organ donation, allocation, and transplantation knowledge was directly administered to 537 first- and second-year medical students attending one of three Ohio schools from January through April 2005. Students were also asked about their support for organ donation and the donation training they had received. RESULTS: Two hundred sixty four first-year and 236 second-year students responded (response rate = 93%). Few students to date received donation and transplantation training before (11%) or during (22%) medical school. Second-year students were more likely than first-year students to have received training during medical school (40% vs 6%, P < .001) and to have read articles regarding donation (24% vs 15%, P = .017). However, both first- and second-year medical students answered the majority of the knowledge questions incorrectly (43% vs 48%, P < .002). Knowledge regarding brain death was lower among medical students compared to a random sample of Ohio adults (P < .001). Donation coursework prior to or during medical school was significantly associated with an increased knowledge regarding donation (odds ratio [OR] = 2.01, P = .001) and knowing where to find answers to patients' questions regarding donation (OR = 2.76, P < .001). CONCLUSION: Medical students have significant gaps in knowledge regarding the organ donation and transplantation system. Donation and transplantation education is associated with improved knowledge in the area and comfort in knowing how to address patient questions.

Adult↗

Amniocentesis results: investigation of anxiety. The ARIA trial.

OBJECTIVES: The Amniocentesis Results: Investigation of Anxiety (ARIA) trial tested two hypotheses: first, that giving amniocentesis results out on a fixed date alters maternal anxiety during the waiting period, compared with a policy of telling parents that the result will be issued 'when available' (i.e. a variable date), and secondly, that issuing early results from a rapid molecular test alters maternal anxiety during the waiting period, compared with not receiving any results prior to the karyotype. The effects of the two interventions on anxiety 1 month after receiving karyotype results were also examined. DESIGN: A multi-centre, randomised, controlled, open fixed sample, 2 x 2 factorial design trial, with equal randomisation. SETTING: Twelve hospitals in England offering amniocentesis as a diagnostic test for Down's syndrome. PARTICIPANTS: A total of 226 women who had had an amniocentesis were randomised between June 2002 and July 2004. Eight women with abnormal results or test failure were excluded post-randomisation. INTERVENTIONS: Issuing karyotype results on a prespecified fixed date, rather than issuing them as soon as they became available and issuing karyotype results alone, or subsequent to issuing results from a rapid molecular test for the most common chromosomal abnormalities. MAIN OUTCOME MEASURES: Average anxiety during the waiting period, calculated using daily scores from the short version of the Spielberger State-Trait Anxiety Inventory (STAI). Recalled anxiety, measured 1 month after receiving karyotype results, using a rating scale. Anxiety at the 1-month follow-up, measured using the short-form STAI. RESULTS: There was no evidence that giving out karyotype results on a fixed or on a variable date altered maternal anxiety during the waiting period. However, the analysis only had sufficient power to detect a moderate to large effect. Issuing early results from a partial, but rapid, test reduced maternal anxiety during the waiting period, compared with receiving only the full karyotype results. This was a moderate to large effect. In addition, group differences in recalled anxiety reflected fairly closely the differences in anxiety women had experienced while waiting for results. One month after receiving normal karyotype results, anxiety was low in all groups, but women who had been given rapid test results were more anxious than those who had not. This was a small to moderate effect. CONCLUSIONS: Since there are no clear advantages in anxiety terms of issuing karyotype results as soon as they become available, or on a fixed date, women could be given a choice between them. Rapid testing was a beneficial addition to karyotyping, at least in the short term. This does not necessarily imply that early results would be preferred to comprehensive ones if women had to choose between them. There should be further research, including more qualitative studies, into the causes, characteristics and consequences of anxiety associated with prenatal testing. The effects of different testing regimes on short- and long-term anxiety, on the preferences of women and on the relationship between anxiety and preference should be investigated. More research is needed on the ways in which information might be used to minimise anxiety in different testing regimes. Further research is also required into the policy implications of incorporating individual preferences for different testing regimes into prenatal testing programmes.

Adult↗

Clinical and economic choices in the treatment of respiratory infections in cystic fibrosis: comparing hospital and home care.

BACKGROUND: A cost-effectiveness evaluation comparing home-based and hospital-based treatment with intravenous antibiotics for respiratory exacerbations in adults with cystic fibrosis (CF) has not been previously undertaken. METHODS: The study was conducted in a UK adult CF centre from a health service perspective. Clinical outcome and resource use data were obtained from a retrospective one-year study and combined with unit cost data in an incremental economic analysis. The primary outcome measure was percentage change in FEV(1); "effectiveness" was defined as maintenance of baseline average FEV(1) over the one-year study period. RESULTS: 116 patients received 454 courses of intravenous antibiotics. At the end of 1 year, there had been a mean percentage decline in FEV(1) compared with baseline average for home-treated patients but an improvement for hospital-treated patients (Tukey's HSD mean difference 10.1%, 95% CI 2.9 to 17.2, p = 0.003). Treatment was deemed "effective" in more hospital (58.8%) than home (42.6%) patients. The cost of hospital treatment was higher than home treatment (mean difference 9,005 pounds, 95% CI 3,507 to 14,700, p<0.001). The mean ICER was 46,098 pounds (2.5th and 97.5th percentiles -374,044 and 362,472). CONCLUSIONS: Hospital treatment was more effective but more expensive than home treatment. Potential methods to improve outcome at home should be considered but these may have resource implications.

Analysis of Variance↗

Perceptions of blindness related to smoking: a hospital-based cross-sectional study.

AIMS: Smoking is associated with several serious eye diseases. Awareness of smoking and blindness, and its potential to act, as a stimulus to assist stopping smoking has not been investigated. METHODS: A cross-sectional survey using a structured interview of adult patients attending district general hospital ophthalmology, general surgery, and orthopaedic clinics. The interview investigated the awareness and fear of blindness for three established smoking-related diseases, and a distractor condition (deafness), and the likelihood that smokers would quit on developing early signs of each condition. RESULTS: Response was 89.1% (358/402). In all, 183 (51.1%) of responders were male and 175 (48.9%) female. Only 9.5% of patients believed that smoking was definitely or probably a cause of blindness, compared with 92.2% for lung cancer, 87.6% for heart disease, and 70.6% for stroke. Patients ranked their fear of each of the five conditions, scoring five for the most feared and one for the least feared. Patients were significantly (P<0.01) less fearful of blindness (mean score 2.80) than lung cancer (3.89), heart disease (3.58), and stroke (3.35). About one-half of smokers stated that they would definitely or probably quit smoking if they developed early signs of blindness or the three established smoking-related conditions, with no significant differences in proportions for these four conditions. CONCLUSION: The findings suggest that awareness of the risk of blindness from smoking is low, but that the fear of blindness is as compelling a motivation to quit as fear of lung cancer, heart disease, and stroke. The link between smoking and eye disease should be publicised to help reduce smoking prevalence.

Adult↗

Smoking and age-related macular degeneration: a review of association.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss in the Western world. As there is no effective treatment for all types of AMD, identifying modifiable risk factors is of great importance. This review evaluates the epidemiological evidence associating smoking with AMD. METHODS: Systematic review of published epidemiological studies evaluated against established criteria for evidence of a causal relationship. RESULTS: In total, 17 studies (cross-sectional studies, prospective cohort studies, and case-control studies) were included in the review. A total of 13 studies found a statistically significant association between smoking and AMD with increased risk of AMD of two- to three-fold in current-smokers compared with never-smokers. Five studies found no association between smoking and AMD. There was also evidence of dose-response, a temporal relationship and reversibility of effect. CONCLUSION: The literature review confirmed a strong association between current smoking and AMD, which fulfilled established causality criteria. Cigarette smoking is likely to have toxic effects on the retina. In spite of the strength of this evidence, there appears to be a lack of awareness about the risks of developing eye disease from smoking among both healthcare professionals and the general public.

Aged↗

July 2004: 40-year-old man with headaches and dyspnea.

A 40-year-old man had a 6-week history of severe frontal headaches and dry cough. Chest x-ray showed hilar adenopathy with bilateral parenchymal infiltrates. A diagnosis of atypical pneumonia was made. Four weeks later he was admitted with persistent headache. Infectious screen was negative. Brain MR post contrast, revealed cerebellar enhancement and swelling with moderate tonsillar herniation; findings which precluded the performance of a lumbar puncture. High resolution CT thorax confirmed hilar abnormalities; shown by microscopy to represent non caseating granulomata. A presumptive diagnosis of sarcoidosis was reached. Despite an initial symptomatic improvement his headache persisted. Repeat MRI, eleven days after admission, showed reduced cerebellar enhancement and swelling with no change in the degree of tonsillar herniation. He deteriorated acutely and died two weeks after admission. Autopsy revealed cerebral oedema with tonsillar herniation secondary to cryptococcal meningitis variety neoformans. There was no evidence of neurosarcoid. Active and inactive sarcoid was identified in the lungs and hilar nodes with no evidence of systemic sarcoid. Focal evidence of cryptococcal pneumonitis was present in the lung as a necrotic focus. A strong index of clinical suspicion is necessary to diagnose the rare association of cryptococcus complicating sarcoidosis.

Adult↗

The effect of diverticular disease on the colonic J pouch.

OBJECTIVE: The aim of this study was to assess the impact of the diverticular disease (DD) on function and on postoperative complications of the colonic J-pouch (CJP) with pouch-anal anastomosis. METHODS: Patients who underwent a CJP between December 1990 and August 2001, were retrospectively reviewed. The presence of DD in the CJP was assessed on pouchogram prior to ileostomy closure. A questionnaire designed to evaluate the degree of continence (total incontinence score (IS): 0 = worst, 20 = best) and pouch evacuation (total evacuation score (ES): 0 = worst, 28 = best) was used for comparison between patients with DD and those without DD (NDD). RESULTS: Sixty-six patients (47 males; 19 females) with a median age of 68 years (range 28-87 years) were included. The median follow-up period was 22 months (range 2-106 months). Twenty-four patients comprised the DD group and 42 were in the NDD group. The two groups were comparable for age, gender and time from ileostomy closure; all patients with postoperative chemoradiation therapy were in the NDD group. The total ES and IS total did not significantly differ between the two groups with a P-value of 0.11 and 0.09 respectively. Furthermore, there was no significant difference in the total incidence of pouch complications between the two groups (3 strictures, 1 leak, 1 fistula in the NDD group vs. 1 pelvic sepsis in the DD group; P = 0.4). CONCLUSIONS: The presence of DD in a CJP does not seem to impact pouch function or the postoperative complication rate.

Aged↗

Long term clinical outcome of home and hospital intravenous antibiotic treatment in adults with cystic fibrosis.

BACKGROUND: Several studies have suggested that clinical outcomes in adults with cystic fibrosis (CF) are equivalent after home and hospital treatment with intravenous antibiotics, but these studies were small and selective and only considered one course of treatment. METHODS: A retrospective longitudinal study was performed to compare the clinical outcome over a period of 1 year of all patients attending the Manchester Adult CF Unit who received intravenous antibiotics at home or in hospital. The primary outcome measure was percentage change in forced expiratory volume in 1 second (FEV(1)) at the end of the 1 year period. Baseline "best" and "average" FEV(1) values were established for each patient for the year before the study. The secondary outcome measures were percentage changes in forced vital capacity (FVC) and body weight. RESULTS: A total of 116 patients received 454 courses of intravenous antibiotics. At the end of 1 year there had been a mean percentage decline in FEV(1) compared with the baseline "average" for patients treated mostly at home but an improvement in patients treated mostly in hospital (Tukey's HSD mean difference 10.1%, 95% CI 2.9 to 17.2, p = 0.003). For all patients there was a mean percentage decline in FEV(1) from the baseline "best" value. For each course of treatment the mean percentage improvements in FEV(1) at the end of the course from the start of the course were significantly higher for patients treated in hospital than for those treated at home. CONCLUSIONS: Clinical outcome, as defined by spirometric parameters and body weight, was better after a course of treatment in hospital than after home treatment, and this benefit was maintained over 1 year of treatment. The results suggest that patients treated at home need closer supervision.

Adolescent↗

The CATH database: an extended protein family resource for structural and functional genomics.

The CATH database of protein domain structures (http://www.biochem.ucl.ac.uk/bsm/cath_new) currently contains 34 287 domain structures classified into 1383 superfamilies and 3285 sequence families. Each structural family is expanded with domain sequence relatives recruited from GenBank using a variety of efficient sequence search protocols and reliable thresholds. This extended resource, known as the CATH-protein family database (CATH-PFDB) contains a total of 310 000 domain sequences classified into 26 812 sequence families. New sequence search protocols have been designed, based on these intermediate sequence libraries, to allow more regular updating of the classification. Further developments include the adaptation of a recently developed method for rapid structure comparison, based on secondary structure matching, for domain boundary assignment. The philosophy behind CATHEDRAL is the recognition of recurrent folds already classified in CATH. Benchmarking of CATHEDRAL, using manually validated domain assignments, demonstrated that 43% of domains boundaries could be completely automatically assigned. This is an improvement on a previous consensus approach for which only 10-20% of domains could be reliably processed in a completely automated fashion. Since domain boundary assignment is a significant bottleneck in the classification of new structures, CATHEDRAL will also help to increase the frequency of CATH updates.

Animals↗

Rapid stereological quantitation of temporal neocortex in TLE.

To determine the extent of neocortical atrophy in the temporal lobe using rapid stereological analysis of magnetic resonance slices in patients with temporal lobe epilepsy and to compare the findings to those obtained by visual analysis of high-resolution magnetic resonance images. 25 patients with temporal lobe epilepsy, along with 25 age-matched controls were scanned using a 1.5 Tesla magnetic resonance imaging machine (GE signa systems Paris). Visual analysis was performed on standard high-resolution images. Volumetric analysis of hippocampus and temporal neocortex was performed using computer-aided stereology (MEASURE program, Patrick Barta, Johns Hopkins, Baltimore, USA). Stereological volumetric analysis demonstrated isolated hippocampal atrophy in only nine (36%) cases including three (12%) with bilateral disease. However, eight (32%) cases had combined hippocampal and neocortical atrophy and three (12%) had isolated neocortical atrophy. All volumetric measurements took less than 10 min. On the other hand, visual analysis suggested that 17 (68%) had hippocampal atrophy alone with only two (8%) having combined neocortical atrophy and a further two (8%) having isolated neocortical atrophy. Nearly half of the patients had temporal neocortical atrophy with or without hippocampal atrophy. This rapid, accurate and non-biased quantitative technique has wide clinical utility and is significantly more valuable in detecting neocortical atrophy than visual analysis alone. The results support the notion that abnormalities may be overlooked by current standards of routine magnetic resonance imaging.

Adult↗

Recombinant vaccines against infectious hematopoietic necrosis virus: production by the Caulobacter crescentus S-layer protein secretion system and evaluation in laboratory trials.

We report the development of an IHNV vaccine produced by a new protein production system based on the bacterium Caulobacter crescentus. The subunit vaccines that were tested contain a 184 amino acid segment of the IHNV glycoprotein in different fusion arrangements with the C. crescentus S-layer protein. Relative percent survival of 26 to 34% was demonstrated in rainbow trout fry for a vaccine that contained the 184 amino acid segment of the IHNV glycoprotein fused to the C-terminal one-quarter of the S-layer protein. Inclusion of the universal mammalian T-cell epitopes developed from the measles fusion protein or the tetanus toxin protein did not increase the effectiveness of the IHNV-G/S-layer recombinant protein.

Adjuvants, Immunologic↗

Guglielmi detachable coiling for intracranial aneurysms: the story so far.

Spontaneous rupture of cerebral aneurysms typically results in subarachnoid hemorrhage. The primary goal of treatment of cerebral aneurysms is to prevent future rupture. Surgical clipping had been the mainstay of treatment of both ruptured and unruptured cerebral aneurysms. In 1991, Guglielmi detachable coil (GDC) embolization was introduced as an alternative method for treating selected patients with aneurysm. The goal of the treatment is prevent the flow of blood into the aneurysm sack by filling the aneurysm with coils and thrombus. Theoretically, there are several advantages of GDC over surgery. These procedures are performed under general anesthesia with the standard transfemoral approaches used in diagnostic angiography. Since its inception, GDC embolization has evolved as a result of both clinical experience and the introduction of technological improvements. We are now better at selecting aneurysms appropriate for coiling, which also have wide necks. Advances in GDC technology have also improved this method of treatment. Over the last several years, the number of coil sizes has been increased, multidimensional coils allowing safer initial coil placement have become available, and, more recently, softer coils have been introduced. Our current approach is to have both surgical and endovascular options for patients.

Cerebral Hemorrhage↗

Spontaneous regression of a large lumbar disc herniation: report of an illustrative case.

A case of spontaneous regression of a large herniated disc at the lumbar level is presented. The disc regression correlated with clinical improvement and was documented on serial MRI studies. Although the phenomenon of spontaneous disappearance of decrease in size of herniated disc fragments is well known, the exact mechanism underlying this process remains unclear. This report discusses three possible explanations for disc regression: retraction into the intervertebral space, dehydration/shrinkage, and resorption due to inflammatory reaction.

Adult↗

A computer system to perform structure comparison using TOPS representations of protein structure.

We describe the design and implementation of a fast topology-based method for protein structure comparison. The approach uses the TOPS topological representation of protein structure, aligning two structures using a common discovered pattern and generating measure of distance derived from an insert score. Heavy use is made of a constraint-based pattern-matching algorithm for TOPS diagrams that we have designed and described elsewhere (Bioinformatics 15(4) (1999) 317). The comparison system is maintained at the European Bioinformatics Institute and is available over the Web at tops.ebi.ac.uk/tops. Users submit a structure description in Protein Data Bank (PDB) format and can compare it with structures in the entire PDB or a representative subset of protein domains, receiving the results by email.

Algorithms↗