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Biomedical subjects

C Fox

Publications and source records attributed to C Fox.

At least 19 recordsLinked to original sources
PubMed2007

Malignancy and mortality in a population-based cohort of patients with coeliac disease or "gluten sensitivity".

AIM: To determine the risk of malignancy and mortality in patients with a positive endomysial or anti-gliadin antibody test in Northern Ireland. METHODS: A population-based retrospective cohort study design was used. Laboratory test results used in the diagnosis of coeliac disease were obtained from the Regional Immunology Laboratory, cancer statistics from the Northern Ireland Cancer Registry and mortality statistics from the General Registrar Office, Northern Ireland. Age standardized incidence ratios of malignant neoplasms and standardized mortality ratios of all-cause and cause-specific mortality were calculated. RESULTS: A total of 13 338 people had an endomysial antibody and/or an anti-gliadin antibody test in Northern Ireland between 1993 and 1996. There were 490 patients who tested positive for endomysial antibodies and they were assumed to have coeliac disease. There were 1133 patients who tested positive for anti-gliadin antibodies and they were defined as gluten sensitive. Malignant neoplasms were not significantly associated with coeliac disease; however, all-cause mortality was significantly increased following diagnosis. The standardized incidence and mortality ratios for non-Hodgkin's lymphoma were increased in coeliac disease patients but did not reach statistical significance. Lung and breast cancer incidence were significantly lower and all-cause mortality, mortality from malignant neoplasms, non-Hodgkin's lymphoma and digestive system disorders were significantly higher in gluten sensitive patients compared to the Northern Ireland population. CONCLUSION: Patients with coeliac disease or gluten sensitivity had higher mortality rates than the Northern Ireland population. This association persists more than one year after diagnosis in patients testing positive for anti-gliadin antibodies. Breast cancer is significantly reduced in the cohort of patients with gluten sensitivity.

Adolescent↗
PubMed2006

Cholinesterase inhibitors for Parkinson's disease dementia.

BACKGROUND: The loss of cholinergic, dopaminergic and noradrenergic innervations seen in Parkinson's Disease Dementia (PDD) suggest a potential role for cholinesterase inhibitors. Concerns have been expressed about a theoretical worsening of Parkinson's disease related symptoms particularly movement symptoms. OBJECTIVES: To assess the efficacy, safety, tolerability and health economic data relating to the use of cholinesterase inhibitors in PDD. SEARCH STRATEGY: The trials were identified from the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 19 April 2005 using the search term parkinson*This register contains records from major health care databases and many ongoing trial databases and is updated regularly.Comprehensive searches of abstracts from major scientific meetings were performed. Pharmaceutical companies were approached for information regarding additional and ongoing studies. SELECTION CRITERIA: Randomized, double-blind, placebo-controlled studies assessing the effectiveness of cholinesterase inhibitors in PDD. Inclusion and exclusion criteria were stated to limit bias. DATA COLLECTION AND ANALYSIS: Two reviewers (IM, CF) independently reviewed the quality of the studies utilising criteria from the Cochrane Collaboration Handbook. Medications were examined separately and as a group. The outcome measures assessed were in the following domains: neuropsychiatric features, cognition, global impression, daily living activities, quality of life, burden on caregiver, Parkinsonian related symptoms, treatment acceptability as determined by withdrawal from trials, safety as determined by the frequency of adverse events, institutionalisation, death and health economic factors. MAIN RESULTS: A detailed and systematic search of relevant databases identified one published randomized, double-blind, placebo-controlled study (Emre 2004) involving 541 patients that compared rivastigmine with placebo. Rivastigmine produced statistically significant improvements in several outcome measures. On the primary cognitive measure, the ADAS-Cog, rivastigmine was associated with a 2.80 point ADAS-Cog improvement [WMD -2.80, 95% Cl -4.26 to -1.34, P = 0.0002] and a 2.50 point ADCS-ADL improvement [95% Cl 0.43 to 4.57, P = 0.02] relative to placebo. Clinically meaningful (moderate or marked) improvement occurred in 5.3% more patients on rivastigmine, and meaningful worsening occurred in 10.1% more patients on placebo. Tolerability appeared to be a significant issue. Significantly more patients on rivastigmine dropped out of the study due to adverse events [62/362 versus 14/179, OR 2.44, 95% Cl 1.32 to 4.48, P = 0.004]. Nausea [20/179 versus 105/362, OR 3.25, 95% Cl 1.94 to 5.45, P < 0.00001], tremor [7/179 versus 37/362, OR 2.80, 95% Cl 1.22 to 6.41, P = 0.01] and in particular vomiting [3/179 versus 60/362, OR 11.66, 95% Cl 3.60 to 37.72, P < 0.0001] were significantly more common with rivastigmine. However, significantly fewer patients died on rivastigmine than placebo [4/362 versus 7/179, OR 0.27, 95% CI 0.08 to 0.95, P = 0.04] AUTHORS' CONCLUSIONS: Rivastigmine appears to improve cognition and activities of daily living in patients with PDD. This results in clinically meaningful benefit in about 15% of cases. There is a need for more studies utilising pragmatic measures such as time to residential care facility and both patient and carer quality of life assessments. Future trials should involve other cholinesterase inhibitors, utilise tools to analyse the data that limit any bias and measure health economic factors. It is unlikely that relying solely on the last observation carried forward (LOCF) is sufficient. Publication of the observed case data in the largest trial would assist (Emre 2004). Adverse events were associated with the cholinergic activity of rivastigmine, but may limit patient acceptability as evidenced by the high drop out rate in the active arm.

Cholinesterase Inhibitors↗
PubMed2006

Peripheral skin necrosis in the recipient of monochorionic twins complicated by twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) complicates approximately 15% of monochorionic, diamniotic twin pregnancies and if untreated carries a high perinatal loss rate of between 80% and 100%, depending on the stage. The underlying pathology in TTTS appears to be an imbalanced intertwin perfusion difference, secondary to functional unidirectional arteriovenous anastomoses within a monochorionic placenta. We report two cases of monochorionic twin pregnancy complicated by TTTS, in which the pregnancies were treated by serial aggressive amnioreduction. However, the recipient twin in each pregnancy developed 'ischemic damage' to a lower limb.

Adult↗
PubMed2006

Biphasic insulin aspart given thrice daily is as efficacious as a basal-bolus insulin regimen with four daily injections: a randomised open-label parallel group four months comparison in patients with type 2 diabetes.

AIMS: To show that a thrice daily meal-time biphasic insulin aspart (BIAsp) treatment regimen is as efficacious as a 4 times daily basal-bolus regimen with human isophane insulin (NPH) and insulin aspart (IAsp). METHODS: A multinational, randomised, open-label parallel-group trial in 394 patients with type 2 diabetes on a once or twice daily insulin regimen. Patients were randomised 1:1 to BIAsp or IAsp+NPH for 16 weeks. The BIAsp group was treated according to individual needs using BMI as a surrogate index of insulin resistance. Subjects administered BIAsp 70 (BMI< or =30 kg/m (2)) or BIAsp 50 (BMI>30 kg/m (2)) with breakfast and lunch and BIAsp 30 with dinner. The IAsp+NPH group injected IAsp at meals and NPH at bedtime as basal insulin. HbAlc levels after 16 weeks were compared between treatments using a predefined non-inferiority criterion of 0.4%. The incidence of hypoglycaemic episodes and adverse events was evaluated. RESULTS: Mean HbAlc (+/-SD) decreased from 9.1+/-0.7% to 7.8+/-1.0% with both treatments. Glycaemic control provided by BIAsp was non-inferior to that obtained by the IAsp+NPH (intention to treat ITT) population: diff, HbAlc -0.05%; 95% CI (-0.24; 0.14); per protocol (PP) population: diff, HbAlc -0.03%; 95% CI (-0.23; 0.16). Similar improvements in glycaemic control in both groups were confirmed by self-measured 8-point plasma glucose (PG) profiles, average and fasting PG concentrations, and average prandial PG increments. The incidence of adverse events and hypoglycaemic episodes was similar in the two treatment groups. CONCLUSIONS: A thrice daily meal-time BIAsp regimen is a suitable alternative to an intensified insulin regimen in people with inadequately controlled type 2 diabetes mellitus, and requires fewer daily injections than a basal-bolus therapy without compromising efficacy and safety.

Aged↗
PubMed2006

Concurrent end-phase boost high-dose radiation therapy for non-small-cell lung cancer with or without cisplatin chemotherapy.

The aim of this study was to audit the results of a high-dose, combined-modality prospective protocol for non-small-cell lung cancer in terms of survival, disease-specific survival and toxicity. One hundred and twenty-one patients with non-small-cell lung cancer were treated with a concurrent, end-phase, boost, high-dose radiotherapy protocol with 65 Gy in 35 fractions for more than 5 weeks. Sixty-six patients received radiotherapy alone (group 1), 29 received concurrent chemoradiation (group 2) and 26 received neoadjuvant and concurrent chemotherapy (group 3). Thirty-four patients had stage I disease, six had stage II and 81 had stage III. Overall median survival was 23 months: 75% at 1 year and 23% at 5 years. Median survivals for patients with stage I and stages II and III disease were 43 and 19 months, respectively. For stages II and III patients by groups 1-3, median survivals were 18, 25 and 18 months, respectively, and 2-year survivals were 36, 52 and 38%, respectively. Toxicity was acceptable. Overall, 9% had symptomatic pneumonitis and 7% had grades 3 and 4 oesophagitis. For those who had the mediastinum included in the volume, grade > or = 3 oesophagitis occurred in 0, 11 and 22% (n = 110, P = 0.001), respectively, for treatment groups 1-3. Overall treatment-related mortality was 3%, consisting of two septic deaths, one pneumonitis and possibly one late cardiac event, all occurring in patients who had chemotherapy (7% of 55 patients). Treatment-related mortality declined over the study period. Accelerated radiotherapy was well tolerated, with only moderate increased acute toxicity when combined with concurrent platinum chemotherapy. Toxicity was enhanced by induction chemotherapy. Overall survival outcomes were excellent for this condition. Continued use of this radiotherapy schedule is recommended as the platform for assessment of other chemotherapy schedules.

Adult↗
PubMed2006

A controlled trial of the impact of exposure to positive images of dentistry on anticipatory dental fear in children.

OBJECTIVES: Dental anxiety is common in children. This study sought to determine the impact of viewing positive images of dentistry prior to a dental appointment on the anticipatory dental anxiety levels of children attending for dental treatment. METHODS: Controlled trial. Assessment of anxiety and analysis of data were conducted blind to experimental condition. Assessment of anxiety was carried out in the waiting room postintervention but before the patient entered the dental surgery for treatment. PARTICIPANTS: Thirty-eight children and young adults attending a dental clinic in South West England. INTERVENTION: Participants were randomly assigned to one of two conditions. In both conditions the participant was asked to look at photographs for 2 min in the waiting area prior to their appointment. The intervention consisted of viewing positive images of dentistry and dental treatment, the control condition consisted of dentally neutral images. Positive and neutral images were validated independently by four paediatric dentists. The assessment of anticipatory dental anxiety was made blind to experimental condition and statistical analysis was conducted blind to group membership. OUTCOME MEASURE: Anticipatory anxiety assessed by the Venham Picture Test. FINDINGS: A significant difference in anticipatory dental anxiety was found between the two groups (median-positive images = 0, median-neutral images = 3; P < 0.001). Anticipatory anxiety was not correlated to age (rho = 0.04 P > 0.05), there was no difference between male and female participants in their level of anticipatory anxiety (median-males = 0.5, median-females = 1 P > 0.05). CONCLUSIONS: Viewing positive images of dentistry and dentists results in short-term reductions in anticipatory anxiety in children.

Adolescent↗
PubMed2005

Direct measurement of the 14N(p,gamma)15O S factor.

The 14N(p,gamma)15O reaction regulates the rate of energy generation in the stellar CN cycle. Because discrepancies have been found in the analysis and interpretation of previous capture data, we have measured the 14N(p,gamma)15O excitation function for energies in the range E(lab)(p)=155-524 keV. Fits of these data using R-matrix theory yield a value for the S factor at zero energy of 1.68+/-0.09(stat)+/-0.16(syst) keV b, which is significantly smaller than the previous result. The corresponding reduction in the stellar reaction rate for 14N(p,gamma)15O has a number of interesting consequences, including an impact on estimates for the age of the Galaxy derived from globular clusters.

Journal Article↗
PubMed2005

A review of studies describing the use of acetyl cholinesterase inhibitors in Parkinson's disease dementia.

OBJECTIVE: To review the literature relating to the use of acetyl cholinesterase inhibitors in Parkinson's disease dementia (PDD). METHOD: MEDLINE (1966--December 2004), PsychINFO (1972--December 2004), EMBASE (1980--December 2004), CINHAL (1982--December 2004), and the Cochrane Collaboration were searched in December 2004. RESULTS: Three controlled trials and seven open studies were identified. Efficacy was assessed in three key domains: cognitive, neuropsychiatric and parkinsonian symptoms. CONCLUSION: Cholinesterase inhibitors have a moderate effect against cognitive symptoms. There is no clear evidence of a noticeable clinical effect against neuropsychiatric symptoms. Tolerability including exacerbation of motor symptoms--in particular tremor--may limit the utility of cholinesterase inhibitors.

Aged↗
PubMed2004

Explosive hydrogen burning of 17O in classical novae.

We report on the observation of a new resonance at E(lab)(R)=190 keV in the 17O(p,gamma)18F reaction. The measured resonance strength amounts to omegagamma(pgamma)=(1.2+/-0.2)x10(-6) eV. With this new value, the uncertainties in the 17O(p,gamma)18F and 17O(p,alpha)14N thermonuclear reaction rates are reduced by orders of magnitude at nova temperatures. Our significantly improved reaction rates have major implications for the galactic synthesis of 17O, the stellar production of the radioisotope 18F, and the predicted oxygen isotopic ratios in nova ejecta.

Journal Article↗
PubMed2004

Actin-dependent motility of melanosomes from fish retinal pigment epithelial (RPE) cells investigated using in vitro motility assays.

Melanosomes (pigment granules) within retinal pigment epithelial (RPE) cells of fish and amphibians undergo massive migrations in response to light conditions to control light flux to the retina. Previous research has shown that melanosome motility within apical projections of dissociated fish RPE cells requires an intact actin cytoskeleton, but the mechanisms and motors involved in melanosome transport in RPE have not been identified. Two in vitro motility assays, the Nitella assay and the sliding filament assay, were used to characterize actin-dependent motor activity of RPE melanosomes. Melanosomes applied to dissected filets of the Characean alga, Nitella, moved along actin cables at a mean rate of 2 microm/min, similar to the rate of melanosome motility in dissociated, cultured RPE cells. Path lengths of motile melanosomes ranged from 9 to 37 microm. Melanosome motility in the sliding filament assay was much more variable, ranging from 0.4-33 microm/min; 70% of velocities ranged from 1-15 microm/min. Latex beads coated with skeletal muscle myosin II and added to Nitella filets moved in the same direction as RPE melanosomes, indicating that the motility is barbed-end directed. Immunoblotting using antibodies against myosin VIIa and rab27a revealed that both proteins are enriched on melanosome membranes, suggesting that they could play a role in melanosome transport within apical projections of fish RPE.

Actins↗
PubMed2004

Stroke in Devon: knowledge was good, but action was poor.

BACKGROUND AND AIM: Effective implementation of early treatment strategies for stroke requires prompt admission to hospital. There are several reasons for delayed admission. Good awareness should facilitate early admission. We identified local targets for education. METHODS: Four groups, each of 40 people, completed questionnaires to determine their knowledge of stroke symptoms and risk factors, and the action they took or would take in the event of a stroke. The groups were: patients with a diagnosis of stroke or TIA (within 48 hrs of admission); patients at risk of stroke; the general population; and nurses. RESULTS: Forty per cent of stroke patients identified their stroke. Median time from onset of symptoms to seeking medical help was 30 minutes. Medical help was sought by the patient themselves in only 15% of cases. In 80% of cases the GP was called rather than an ambulance. Of the at risk group, 93% were able to list at least one symptom of acute stroke, as were 88% of the general population. An ambulance would be called by 73% of the at risk group in the event of a stroke. Patients with self reported risk factors for stroke were largely unaware of their increased risk. Only 7.5% of at risk patients acquired their stroke information from the medical profession. CONCLUSIONS: Public knowledge about stroke is good. However, stroke patients access acute services poorly. At risk patients have limited awareness of their increased risk. A campaign should target people at risk, reinforcing the diagnosis of stroke and access to medical services.

Aged↗
PubMed2003

Why a breast boost should remain a controversial aspect of routine breast conservation management in Australia and New Zealand in 2002.

Two randomized trials have recently shown a statistically significant improvement in local control when a boost is employed in the conservative treatment of early breast cancer. However, unresolved issues of cost effectiveness, potentially increased toxicity and the inability to automatically generalize these results to Australian and New Zealand practice remain. In view of these unresolved controversies, the St George and Wollongong hospitals breast boost trial (SGW trial) will continue to recruit.

Aged↗
PubMed2002

The ELF -97 phosphatase substrate provides a sensitive, photostable method for labelling cytological targets.

We compared fluorescent signals obtained with fluorescein conjugates and the ELF-97 (enzyme-labelled fluorescence) phosphatase substrate [2-(5'-chloro-2-phosphoryloxyphenyl)-6-chloro-4(3H)-quinazolinone] in labelling cytological structures requiring high spatial resolution. Enzymatic cleavage of the ELF-97 phosphatase substrate yields an extremely fine precipitate that remains well localized to the site of enzymatic activity. This precipitate fluoresces bright yellow-green, with maximal excitation at approximately 360 nm and maximal emission at approximately approximately 530 nm. The ELF substrate was used with streptavidin-alkaline phosphatase, to fluorescently label site-specific probes bound to their targets, including cell-surface sites, cytoplasmic organelles, nuclear antigens and cytoskeletal networks. All targets were labelled successfully with both the ELF substrate and fluoresceinated probes or protein conjugates. However, the ELF method was frequently more sensitive, with lower background fluorescence, allowing detection of more lysosomes, actin filaments, microtubules and nuclear targets than were visible with corresponding fluoresceinated probes. The ELF substrate was also used with antifluorescein-alkaline phosphatase to amplify fluorescein signals. We found that the ELF signal was in all cases brighter and more photostable than fluorescein signals, permitting shorter film exposures and allowing more time for examining samples. Surprisingly, relative brightness and photostability depended on the target, rather than being a general phenomenon related to the choice of dye alone.

3T3 Cells↗
PubMed2002

Molecular pathogenesis of iron overload.

Our current understanding of iron absorption under normal conditions is presented, together with an overview of the clinical disorders of iron overload and the molecular processes that contribute to increased iron deposition in iron overload. Recently, a number of new genes involved in iron metabolism have been identified which is allowing the molecular mechanisms of iron absorption to be elucidated.

Enterocytes↗