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Biomedical subjects

A Clarke

Publications and source records attributed to A Clarke.

At least 55 records · Page 3Linked to original sources
PubMed2004

Breast cancer stage at time of detection in women with systemic lupus erythematosus.

Mounting evidence suggests an increased cancer risk in several autoimmune diseases, including systemic lupus erythematosus (SLE). However, greater scrutiny for cancer in subjects with chronic disease (compared to the general population) might explain this apparent association. If so, one would expect cancers in SLE to be diagnosed at earlier stages than in the general population. This might be particularly evident in cancers where screening is available, such as breast cancer. We linked the University of Pittsburgh lupus cohort with the Pennsylvania Cancer Registry to determine the frequency distribution for stage at diagnosis of invasive breast cancers in the SLE subjects. Data on staging of cancers occurring in the general population of Pennsylvania were obtained from The US Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. A lower percentage of women with SLE presented with localized breast cancer (nine of the 16, 56.2%) compared to the general population of women (63.5%). Although not definitive, this evidence suggests that cancers in SLE are not necessarily diagnosed at earlier stages than in the general population.

Adult↗
PubMed2004

Proposed modifications to 1982 ACR classification criteria for systemic lupus erythematosus: serositis criterion.

The SLICC group believed that the definition of pleuritis should be expanded to include new pleural thickening and pericarditis to include characteristic history. Furthermore, SLICC suggested the addition of abdominal serositis to the current serositis criterion, manifested as either diffuse abdominal pain, with rebound or guarding, and/or ascites or bowel wall edema in the absence of other causes. Abdominal serositis can be secondary to either acute or chronic lupus peritonitis, with the former usually presenting as acute, generalized pain, and the latter as painless ascites.

Humans↗
PubMed2004

Two brothers with trichiasis, entropion and corneal scarring, sensorineural hearing loss, progressive thinning of scalp hair, mild learning difficulties and distinct facial features. A new syndrome?

Two brothers with very similar phenotypes involving trichiasis (misdirected lashes), entropion with corneal abrasions, strabismus, progressive thinning of the scalp hair, sensorineural hearing impairment, mild learning difficulties, and inguinal hernias are described. They have similar, distinctive facial features with deep-set eyes, a high nasal bridge and a short philtrum. Both brothers are carriers of a maternally inherited apparently balanced translocation of chromosomes 11 and 18: 46,XY, t(11;18)(p13;q21)mat. However, this is thought to be coincidental, since their younger brother also carries this translocation and is phenotypically normal. Although they have many features that are found in the ectodermal dysplasia syndromes, their combination of features is distinct and has to our knowledge not been previously reported.

Adolescent↗
PubMed2004

Glenothoracic fusion. An adjunct to radical scapulectomy.

We describe a surgical procedure used to achieve glenothoracic fusion after one-stage radical, near total scapulectomy for primary or secondary malignant lesions in six patients. The aim was complete excision of the lesion and preservation of the glenoid to provide a fulcrum for movement of the arm. Post-operative assessment involved determination of the range of movement and the application of the Musculoskeletal Tumour Society score and the Constant score to evaluate function. The results showed that a functional range of movement was attainable despite such radical surgery, although there was a considerable reduction in power and ability to lift.

Adult↗
PubMed2003

A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition.

Seven randomised comparative studies were conducted in healthy volunteers to compare the pharmacokinetic and pharmacodynamic profiles of selegiline hydrochloride in a new formulation designed for buccal absorption "Zydis Selegiline" (1.25-10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg). A total of 156 healthy volunteers participated in these studies. Plasma concentrations of selegiline and its primary metabolites, N-desmethylselegiline (DMS), l-amphetamine (AMT), and l-methamphetamine (MET) were measured using Gas Chromatography Mass Spectrometry (GCMS) and gas liquid chromatography (GLC) assays. Inhibition of monoamine-oxidase type B (MAO-B) and monoamine oxidase type A (MAO-A) activity was determined by measurement of as beta-phenylethylamine (PEA) by GCMS and 5-hydroxyindoleacetic acid (5-HIAA) by High Performance Liquid Chromatography (HPLC) assays. Almost a third (2.96 mg) of a 10 mg selegiline dose in Zydis Selegiline was absorbed pre-gastrically (predominantly buccally) within 1 minute. Mean [SD] area-under-the curve (AUC(0- infinity)) values following Zydis Selegiline 10 mg (5.85 [7.31] ng.h/mL) were approximately five times higher than those following conventional selegiline tablets 10 mg (1.16 [1.05] ng.h/mL). In contrast, plasma concentrations of metabolites were significantly ( p<0.001) lower following Zydis Selegiline 10 mg than following conventional selegiline tablets 10 mg. Plasma concentrations of selegiline and its metabolites increased in a dose-dependent manner over the dose-range Zydis Selegiline 1.25-5 mg. Bioavailability was determined using AUC and peak plasma concentrations (C(max)). The C(max) of selegiline was similar following administration of Zydis Selegiline 1.25 mg (1.52 ng/mL) or conventional selegiline tablets 10 mg (1.14 mg/mL). The range of values for AUC(0- infinity) and C(max) following Zydis Selegiline 1.25 mg were entirely contained within the range following conventional selegiline tablets 10 mg, with a much higher variability of plasma selegiline concentrations occurring after conventional selegiline tablets than after Zydis Selegiline. As expected, peak plasma concentrations for DMS, AMT and MET were consistently lower after Zydis Selegiline 1.25 mg (1.19, 0.34, 0.93 ng/ml, respectively) than after conventional selegiline tablets 10 mg (18.37, 3.60, 12.92 ng/ml, respectively). A significant (r=0.0001) correlation between daily PEA excretion (a measure of brain MAO-B inhibition) and the log-transformed AUC((0-t)) for selegiline was demonstrated. Mean daily PEA excretion was similar following Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg (13.0 microg versus 17.6 microg). In contrast, there was no correlation between PEA excretion and selegiline metabolites, indicating that selegiline metabolites do not significantly inhibit MAO-B. Urinary excretion of 5-HIAA (used as a marker for MAO-A inhibition) was unrelated to plasma concentrations of selegiline or DMS following single or repeat dosing of Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg. However, comparison of treatment groups revealed a significantly lower excretion of 5-HIAA in the conventional selegiline tablets 10 mg group than in the Zydis Selegiline 1.25 mg group after repeated administration over 13 days. In summary, by reducing the opportunity for first-pass metabolism, the absorption of selegiline from Zydis Selegiline was more efficient and less variable than from conventional selegiline tablets. Compared with conventional selegiline tablets 10 mg, Zydis Selegiline 1.25 mg yielded similar plasma concentrations of selegiline and degree of MAO-B inhibition, but markedly reduced concentrations of the principal metabolites. Thus, the lower but equally MAO-B inhibitory dose of selegiline in Zydis Selegiline 1.25 mg, which is associated with lower concentrations of potentially harmful metabolites, could offer a safer and more predictable treatment in the management of patients with Parkinson's disease.

Administration, Oral↗
PubMed2003

A new low-dose formulation of selegiline: clinical efficacy, patient preference and selectivity for MAO-B inhibition.

Three studies were performed using a fast dissolving formulation of selegiline hydrochloride designed for buccal absorption "Zydis Selegiline". The aim of the first study was to compare the therapeutic efficacy of Zydis Selegiline (1.25 mg or 10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg) in patients with Parkinson's disease (PD) who were previously treated with conventional selegiline tablets as an adjunct to levodopa/dopamine agonist therapy. Patients were observed for 4 weeks to ensure that they were stable. Stable patients (n=197) were then randomised to continue with conventional selegiline tablets 10 mg (n=68), or to treatment with Zydis Selegiline 1.25 mg (n=64) or Zydis Selegiline 10 mg (n=62) for 12 weeks in this randomised, parallel group study. A further aim was to establish the acceptability of Zydis Selegiline compared with conventional selegiline tablets. Patient preference for Zydis Selegiline was also evaluated in a second study, a single-dose, randomised, two-way crossover study conducted in patients with PD (n=148). Patients were stratified by the presence or absence of swallowing and salivation problems and were randomised to either Zydis Selegiline 5 mg or a placebo fast-dissolving formulation. In a third study, the degree of potentiation of the tyramine pressor effect following Zydis Selegiline was compared with that following conventional selegiline tablets in healthy volunteers. A total of 24 healthy volunteers were randomised to receive Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg for 14-16 days in an open-label, randomised parallel group study. Both Zydis Selegiline (1.25 mg and 10 mg) treatments were shown to be therapeutically equivalent to conventional selegiline tablets 10 mg based on comparison of mean total Unified Parkinson's Disease Rating Scale (UPDRS) scores. Therapeutic equivalence was defined a priori as the 90% confidence interval (CI) for the difference in total UPDRS scores between groups to lie entirely within the range +/-5. The difference (90% CI) in mean adjusted total UPDRS between Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg was -2.50 (-4.84, -0.17), and for Zydis Selegiline 10 mg and conventional selegiline tablets 10 mg, 0.04 (-2.30, 2.38). For the motor subscores of the UPDRS, differences between adjusted means (90% CI) compared with the conventional selegiline tablets group were: Zydis Selegiline 1.25 mg, -2.14 (-3.94, -0.33) and Zydis Selegiline 10 mg, -0.90 (-2.70, +0.91). Patients who switched from conventional selegiline tablets to Zydis Selegiline 1.25 mg showed a slight improvement in UPDRS scores following 12 weeks of treatment (standard error of difference 1.039; p=0.01). In the single-dose crossover study, most (61%) patients liked Zydis Selegiline 5 mg; a significantly greater proportion than the null hypothesis of 50% (p<0.002). However, only 62 patients (46%) indicated that they liked the taste of Zydis Selegiline. Nevertheless, the proportion of patients who preferred Zydis Selegiline (65%) to their usual medication was significantly greater than the null hypothesis of 50% (p<0.001). Similar findings were demonstrated in the 12-week study where a higher proportion of patients who received up to 3 months of treatment indicated a preference for either Zydis Selegiline 1.25 mg (90%) or Zydis Selegiline 10 mg (86%) over conventional selegiline tablets 10 mg. More than 90% of patients found Zydis Selegiline easy to take, with 61% rating it as extremely easy. Most (81%) patients taking Zydis Selegiline 1.25 mg liked the taste compared with 45% taking Zydis Selegiline 5 mg (in the previous study). Zydis Selegiline did not potentiate the tyramine effect: a pressor effect was elicited after 400 mg tyramine both before and after 14 days of treatment with Zydis Selegiline 1.25 mg. In contrast, after 14 days treatment with conventional selegiline tablets 10 mg, the threshold dose required to elicit the tyramine pressor response was significantly (p<0.0001) reduced from 400 mg to 200 mg. In summary, Zydis Selegiline at doses of 1.25 mg and 10 mg was therapeutically equivalent to conventional selegiline tablets 10 mg. The Zydis Selegiline formulation was well-liked by all patients, with most preferring Zydis Selegiline 1.25 mg to their usual selegiline tablet. Furthermore, Zydis Selegiline was well tolerated and, unlike conventional selegiline tablets, appeared to retain specificity for inhibition of monoamine oxidase type B (MAO-B), since it did not potentiate the pressor response to tyramine.

Administration, Oral↗
PubMed2003

Psychosocial distress associated with disfiguring eye conditions.

PURPOSE OF STUDY: Visible disfigurement is associated with a range of psychosocial difficulties; however, the problems encountered by patients with eye conditions are under-researched. This study aimed to establish the extent and type of psychosocial distress in this patient population, and to explore the extent to which patients' needs are currently met. METHOD: Standardised measures (anxiety, depression, appearance-related distress, and quality of life) and a semistructured interview (exploring individual experiences and satisfaction with care) were administered to 153 consecutive attenders at outpatient eye clinics in three different hospitals. Responses were analysed using descriptive statistics, multiple regression, and cluster analyses. RESULTS: Between 10 and 49% of the patient sample scored unfavourably on standardised measures in comparison with normative values. Cluster analyses revealed that more distressed patients typically exhibited higher levels of anxiety, depression, social anxiety, self-consciousness, and social avoidance. Quality of life scores were also less favourable. Distressed patients felt less well informed, less involved in their treatment, and less well supported in the clinic setting. Variability within the sample was high; however, the effects of the cause and duration of the condition were not significantly related to distress. Clinic staff identified a variety of constraints to meeting patients' need, including patient numbers, the lack of appropriate training, and the lack of referral possibilities. CONCLUSIONS: A considerable proportion of patients with disfiguring eye conditions experience high levels of psychosocial distress. Several options exist for ways in which patients' needs might more effectively be met within the constraints currently facing care providers.

Adaptation, Psychological↗
PubMed2003

Exploring the psychosocial concerns of outpatients with disfiguring conditions.

OBJECTIVE: This study was undertaken to establish the extent and type of psychosocial need in outpatients attending for treatment for a variety of disfiguring conditions. METHOD: A total of 220 outpatients receiving treatment for burns, skin conditions or head and neck cancer, together with those seeking plastic surgery for other appearance concerns, completed standardised measures of anxiety, depression, social anxiety and quality of life. Participants also completed a semi-structured interview exploring individual concerns and satisfaction with care. RESULTS: A considerable proportion of the outpatients with disfiguring conditions experienced psychosocial difficulties, displaying raised levels of anxiety, depression, social anxiety and social avoidance and reduced quality of life. Levels of psychosocial distress were not well predicted by the severity of disfigurement. CONCLUSION: The psychosocial needs of these patients are not well met in the outpatient setting. Recommendations are made on how patients' concerns might be more effectively addressed.

Adult↗
PubMed2003

A case control study of the prevalence of perinatal complications associated with fetal macrosomia in Antigua and Barbuda.

The prevalence of obstetric, perinatal and neonatal complications associated with fetal macrosomia at Holberton Hospital in Antigua and Barbuda was assessed by a retrospective, case-control study. All babies of birthweight (BW) greater than 4.5 kg born between July 1991 and January 1997 and all babies with BW greater than 4.0 kg born between July 1991 and January 1995, were included. Control babies, were selected from those born on the same day as the index case. Babies of BW > 4.0 kg and babies of BW > 4.5 kg were 5.7% and 1% of births respectively Records were complete for 157 large babies (40 with BW > 4.5 kg) and 157 control babies < 4.0 kg. Mothers of large babies were significantly older, more parous, more likely to have diabetes mellitus, hypertension, and deliver after 40 weeks gestation. At delivery, mothers of large babies were more likely to bleed. Large babies had lower one minute and five minute Apgar score, were more likely to be meconium stained, have respiratory distress, have birth trauma or dystocia and to be admitted to Special Care Nursery. There was no difference in Caesarean section rate, hospital days, neonatal jaundice or mortality. Babies with BW > 4.5 kg had mortality of 7.5% versus 1.8% for those < 4.5 kg. Fetal macrosomia remains a difficult obstetrical problem associated with significant maternal, perinatal and neonatal consequences. Morbidity and mortality are still significant in developed and developing countries alike.

Antigua and Barbuda↗
PubMed2002

A prospective study of the prevalence of undiagnosed coeliac disease in laboratory defined iron and folate deficiency.

AIMS: To determine the prevalence of coeliac disease in a group of patients in the community who have been shown in the laboratory to have iron and/or folate deficiency. To assess the cost efficiency of this laboratory based case finding strategy. METHODS: The study was undertaken in a large general hospital in the UK serving a population of 300 000. Three hundred and thirty three eligible patients with iron and/or folate deficiency were identified and contacted over an 18 month period. Case finding was by testing for coeliac disease using serological methods and subsequent histological confirmation. RESULTS: Of the 333 eligible and contactable patients with iron and/or folate deficiency, 258 (77%) consented to coeliac disease antibody testing. Twenty eight patients (10.9%) were positive for coeliac disease antibodies. Of these, 24 patients proceeded to endoscopy and biopsy, resulting in 12 cases of histologically confirmed coeliac disease (4.7% (95% confidence interval, 2.1% to 6.8%) of patients tested for coeliac disease antibodies). CONCLUSIONS: This laboratory based methodology detected a considerable number of new coeliac disease cases in the community. Many of these patients did not present with clinical findings suggestive of malabsorption and might not otherwise have been diagnosed. Laboratory based methodologies should be considered in conjunction with other strategies for the early identification and treatment of coeliac disease.

Adolescent↗
PubMed2002

Development and preliminary evaluation of a clinical guidance programme for the decision about prophylactic oophorectomy in women undergoing a hysterectomy.

OBJECTIVES: To develop a decision analysis based and computerised clinical guidance programme (CGP) that provides patient specific guidance on the decision whether or not to undergo a prophylactic oophorectomy to reduce the risk of subsequent ovarian cancer and to undertake a preliminary pilot and evaluation. SUBJECTS: Women who had already agreed to have a hysterectomy who otherwise had no ovarian pathology. SETTING: Oophorectomy decision consultation at the outpatient or pre-admission clinic. METHODS: A CGP was developed with advice from gynaecologists and patient groups, incorporating a set of Markov models within a decision analytical framework to evaluate the benefits of undergoing a prophylactic oophorectomy or not on the basis of quality adjusted life expectancy, life expectancy, and for varying durations of hormone replacement therapy. Sensitivity analysis and preliminary testing of the CGP were undertaken to compare its overall performance with established guidelines and practice. A small convenience sample of women invited to use the CGP were interviewed, the interviews were taped and transcribed, and a thematic analysis was undertaken. RESULTS: The run time of the programme was 20 minutes, depending on the use of opt outs to default values. The CGP functioned well in preliminary testing. Women were able to use the programme and expressed overall satisfaction with it. Some had reservations about the computerised formal and some were surprised at the specificity of the guidance given. CONCLUSIONS: A CGP can be developed for a complex healthcare decision. It can give evidence-based health guidance which can be adjusted to account for individual risk factors and reflects a patient's own values and preferences concerning health outcomes. Future decision aids and support systems need to be developed and evaluated in a way which takes account of the variation in patients' preferences for inclusion in the decision making process.

Adult↗
PubMed2002

Lupus and malignancy.

Explore the source record for details and available documents.

Clinical Trials as Topic↗
PubMed2001

The relative influence of temperature and food on the metabolism of a marine invertebrate.

Many benthic marine invertebrates exhibit a seasonal cycle in activities such as feeding, growth and reproduction. In temperate regions, this seasonality is typically correlated with coincident cycles in photoperiod, temperature and food availability and it can be difficult to determine which of these environmental factors is the key driver. Polar regions are characterised by greatly reduced seasonal variation in temperature, and an enhanced seasonality of food availability; they therefore form a natural laboratory for distinguishing the ecological effects of food from those of temperature. Here, we report a study of the common shallow water urchin Sterechinus neumayeri from Rothera Point, Antarctica. This species exhibits a marked seasonal variation in metabolic rate and feeding activity (which ceases completely in winter). In this study the metabolic rate of urchins collected in late winter and held in the laboratory without food was compared with that of wild urchins undertaking the transition to summer feeding and growth. Starved urchins showed a small rise in metabolic rate in summer which could be explained entirely by the small increase in temperature (Q(10)=2.5). At the same time, the wild population showed a much larger increase in metabolic rate related largely to the costs of feeding and growth. Rates of nitrogen excretion were also much larger in wild urchins, and the O:N atomic ratio indicated that starved urchins were depending to a greater extent on lipid and carbohydrate. Gut mass and test organic content showed no change in starved urchins, indicating that metabolic substrate was being provided by the gonad. The data suggest that in wild S. neumayeri only 15-20% of the summer increase in metabolism is caused directly by the temperature rise whereas 80-85% is caused by increased physiological activity associated with feeding, growth and spawning.

Journal Article↗
PubMed2001

The influence of formulation variables on the properties of pellets containing a self-emulsifying mixture.

A method of converting self-emulsifying drug delivery systems to a pellet form has been studied. Formulations with varied relative quantities of an oil/surfactant mixture, water, microcrystalline cellulose (MCC), and lactose were chosen in a statistical design after preliminary ranging experiments. Pellets were produced by extrusion/spheronization. The characteristics of the pellets were studied by sieving, disintegration testing, diametral compression, image analysis, non-contact laser profilometry, and scanning electron microscopy. The effects of the formulation variables on pellet properties were evaluated by analysis of variance. It was possible to relate the formulation variables to all the quantified pellet properties except the shape. The relative quantities of oil/surfactant and water had an effect on the amount of liquid and oil/surfactant that could be incorporated into the powder, extrusion force, median diameter, size spread, disintegration time, tensile strength, and surface roughness. The relative quantities of lactose and MCC had an effect on the amount of liquid and oil/surfactant that could be incorporated into the powder, tensile strength, and roughness only. Water was an essential element of the formulations. The maximum quantity of the specific oil/surfactant combination studied that can be incorporated was 42% of the dry pellet weight.

Drug Delivery Systems↗