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Biomedical subjects

S Evans

Publications and source records attributed to S Evans.

At least 145 records · Page 8Linked to original sources

Automated detection of hereditary syndromes using data mining.

Computer-based data mining methodology applied to family history clinical data can algorithmically create highly accurate, clinically oriented hereditary disease pattern recognizers. For the example of hereditary colon cancer, the data mining's selection of relevant factors to assess for hereditary colon cancer was statistically significant (P < 0.05). All final recognizer-formulated patterns of hereditary colon cancer were independently confirmed by a clinical expert. Applied to previously analyzed family histories, the recognizer identified the definitive hereditary histories, correctly responded negatively to the putative hereditary histories, and correctly responded negatively to empirically elevated colon cancer risk situations. This capability facilitates patient selection for DNA studies in search of gene mutations. When genetic mutations are included as parameters in a patient database for a genetic disease, the process yields an expert system which characterizes variations in clinical disease presentations in terms of genetic mutations. Such information can greatly improve the efficiency of gene testing.

Adult↗

A scoring system for the prediction of successful delivery in low-risk birthing units.

OBJECTIVE: To establish and test the effectiveness of a low-risk scoring system to predict obstetric outcome for the selection of women suitable for confinement in low-intervention units. METHODS: Retrospective analyses were performed on data from 2900 women enrolled in the Western Australian Pregnancy Cohort Study and 1353 women managed at a midwifery-based birth center. A combination of the principal predictors of obstetric outcome, incorporating a previously published scoring system and various clinical features, was used to exclude high-risk cases at 18 weeks' and 36 weeks' gestation. Stepwise multivariate logistic regression analyses of the remaining pregnancies then produced a low-risk scoring system. RESULTS: This system predicted a 55% chance of an uncomplicated delivery in a midwifery-based setting after allocating 54% of women to the low-risk category. It predicted an 82% chance of an uncomplicated delivery in a primary medical care setting with the allocation of 84% of women as low risk. CONCLUSION: The results of this study suggest that adding induction and augmentation of labor, together with low pelvic instrumental delivery, to the treatment options in a low-intervention unit would raise the rate of successful confinement within the unit from 55% to 82%. Our scoring system now requires prospective evaluation to further assess its clinical value.

Adult↗

Oral terbinafine in the treatment of toenail onychomycosis: North American multicenter trial.

BACKGROUND: Onychomycosis is an increasing problem with limited therapeutic options. OBJECTIVE: We evaluated the safety and efficacy, of oral terbinafine, a new fungicidal antimycotic, in patients with toenail onychomycosis. METHODS: A North American multicenter, double-blind, placebo-controlled study evaluated the mycologic and clinical efficacy of oral terbinafine 250 mg/day for 12 or 24 weeks in 358 patients with toenail onychomycosis. RESULTS: A total of 74% of patients treated with 12 or 24 weeks of terbinafine achieved a successful clinical outcome. Approximately 11% of terbinafine responders showed evidence of relapse 18 of 21 months after cessation of treatment. Terbinafine was well tolerated; most adverse events were transient and mild to moderate in severity. CONCLUSION: The results of this study confirm that oral terbinafine is a safe and effective therapy for the treatment of onychomycosis.

Abdominal Pain↗

Cyclosporine as maintenance therapy in patients with severe psoriasis.

BACKGROUND: Low-dose cyclosporine therapy for severe plaque psoriasis is effective. Most side effects can be controlled by patient monitoring, with appropriate dose adjustment or pharmacologic intervention, or both, if indicated. Prevention or reversibility of laboratory and chemical abnormalities may be achieved by discontinuation of therapy after the induction of clearing. However, relapse occurs rapidly on discontinuation. Maintenance therapy with cyclosporine after induction has not been fully evaluated. OBJECTIVE: Our purpose was to compare a regimen of 3.0 mg/kg per day of oral cyclosporine with placebo in maintaining remission or improvement in patients with psoriasis. METHODS: After a 16-week unblinded induction phase in which 181 patients received cyclosporine, 5.0 mg/kg per day (an increase up to 6.0 mg/kg per day and a decrease to 3.0 mg/kg per day were allowed, if required, to achieve efficacy or tolerability, respectively), those patients showing a 70% decrease or more in involved body surface area (BSA) entered the 24-week maintenance phase and were randomly assigned to either placebo, cyclosporine, 1.5 mg/kg per day, or cyclosporine, 3.0 mg/kg per day. Patients were considered to have had a relapse when BSA returned to 50% or more of the prestudy baseline value. Clinical efficacy, adverse effects, and laboratory values were monitored regularly throughout both study phases. RESULTS: During induction, cyclosporine at approximately 5.0 mg/kg per day produced a reduction in BSA of 70% or more in 86% of the patients. During maintenance, the median time to relapse was 6 weeks in both the placebo and cyclosporine 1.5 mg/kg per day groups, but was longer than the 24-week maintenance period in the 3.0 mg/kg per day group (p < 0.001 vs placebo). By the end of the maintenance period, 42% of the patients in the 3.0 mg/kg per day cyclosporine group had a relapse compared with 84% in the placebo group. Changes in laboratory values associated with the higher induction dosage generally exhibited partial or complete return toward mean prestudy baseline values during the maintenance phase, with the greatest degree of normalization in the placebo group. CONCLUSION: Cyclosporine, 3.0 mg/kg per day, adequately and safely maintained 58% of patients with psoriasis for a 6-month period after clearing of their psoriasis with doses of approximately 5.0 mg/kg per day.

Administration, Oral↗

Defining radiographic osteoarthritis for the whole knee.

OBJECTIVE: To determine in the knee which individual radiographic feature or combination of features in the patellofemoral and tibiofemoral joints correlate best with a nonradiographic definition of clinical osteoarthritis in order to recommend a definition of radiographic osteoarthritis for use in studies. METHODS: Using data from the Framingham Osteoarthritis Study, we tested the correlation of clinical OA, defined as frequent knee pain plus crepitus, with a variety of definitions of radiographic OA including those based on individual radiographic features, e.g. > or = grade 2 osteophyte 0-3 scale, and new definitions that included alternative combinations of features, [e.g. either > or = grade 2 osteophyte or joint space narrowing > or = grade 2 (0-3 scale) with a bone feature (such as cyst, sclerosis, or grade 1 osteophyte)]. We performed analyses looking at participants who had obtained both weight-bearing anteroposterior (AP) and lateral radiographs of both knees. RESULTS: In 519 participants, we found that the definitions of radiographic osteoarthritis best correlated with clinical OA were definite osteophyte > or = grade 2' (efficiency 62.4-67.1%) and an 'alternate definition' of either osteophytes > or = grade 2 or joint space narrowing > or = grade 2 with a bony feature of OA (efficiency 62.8-68.1%). A recursive partitioning analysis selected the 'alternate definition' as best. Also, we found that adding lateral views to the AP view improved the diagnostic test performance of the best performing radiographic definitions. CONCLUSION: We suggest that a knee should be characterized as having radiographic OA if there is either an osteophyte of grade 2 or greater severity (0-3 scale) present or the presence of moderate to severe joint space narrowing (> or = 2 on a 0.3 scale) with co-occurrence of a bony feature in the compartment affected.

Aged↗

The prediction of pregnancy outcome by haemoglobin measurement before 20 weeks' gestation.

Maternal haemoglobin levels were measured before 21 weeks' gestation in a prospective study of 1276 singleton pregnancies. Reference ranges were constructed and then applied to a further cohort of 1227 singleton pregnancies to determine the ability of haemoglobin level before 21 weeks' gestation to predict pregnancy outcome. Haemoglobin level decreased significantly with advancing gestational age from 6 to 21 weeks (P < 0.05). Low haemoglobin level was associated with a decreased risk of pregnancy-induced hypertension (adjusted odds ratio 0.51, 95% CI 0.35-0.74). High haemoglobin level was positively correlated with subsequent pregnancy-induced hypertension (P = 0.002) with values > 95th percentile for gestational age having positive and negative predictive values of 33% and 94% respectively. Haemoglobin values (either high or low) were not predictive of proteinuric pre-eclampsia, preterm prelabour rupture of the membranes, preterm birth, low birth weight or the need for neonatal resuscitation of admission to the special care baby unit. The finding of a high maternal haemoglobin before 21 weeks' gestation is not sufficiently predictive of pregnancyinduced hypertension to be of clinical use, but the ability of a low level to predict favourable outcome may be of use in a scoring system designed to identify women suitable for midwifery-based care.

Journal Article↗

Non-specialist management of tropical talipes.

Talipes equinovarus (clubfoot) is a complex deformity which in the West is usually treated by trained orthopaedic surgeons. In developing countries, however, most clubfeet will need to be treated by medical officers lacking specialist training. We report one author's experience in treating clubfeet in a small, rural East African hospital and review the literature in order to assist other non-specialists in managing this difficult condition in the face of poverty and poor parental compliance.

Casts, Surgical↗

Neonatal screening for cystic fibrosis in the Trent region (UK): two-stage immunoreactive trypsin screening compared with a three-stage protocol with DNA analysis as an intermediate step.

OBJECTIVES: To assess neonatal screening for cystic fibrosis using immunoreactive trypsin, either alone or in conjunction with DNA analysis for the delta F508 mutation. A novel three-stage screening protocol was compared with the previously introduced two-stage immunoreactive trypsin-DNA protocol. DESIGN: (a) Collection of data from a 4 1/2 year period (phase 1) of two-stage immunoreactive trypsin screening. The initial dried blood samples were obtained at 6 days of age and repeat samples at 27 days of age from babies with results above the 99.5th centile. Babies with persistent hypertrypsinaemia were referred for a diagnostic sweat test. (b) Retrospective DNA analysis: patients with cystic fibrosis diagnosed in phase 1 were genotyped and most samples from babies with increased initial immunoreactive trypsin but normal results in the second sample were analysed for the delta F508 mutation. (c) Phase 2, a prospective study of a three-stage neonatal screening protocol, in which only babies heterozygous for the delta F508 cystic fibrosis mutation progressed to the second immunoreactive trypsin test. SETTING: The Trent neonatal screening programme. SUBJECTS: 437 859 babies born between August 1989 and March 1996. MAIN OUTCOME MEASURES: Proportions of unaffected babies requiring a second blood sample or a sweat test. Overall sensitivity for the detection of cystic fibrosis. RESULTS: The two-stage screen failed to identify six out of 94 cases of cystic fibrosis (without meconium ileus). The introduction of the DNA analysis step would have resulted in one additional case being missed. With the three-stage screen there was a 92% reduction in babies requiring a second blood sample and an 80% reduction in negative sweat tests, results close to the predictions of the retrospective study. CONCLUSIONS: The three-stage screening protocol is a marked improvement on the two-stage immunoreactive trypsin strategy and on the two-stage immunoreactive trypsin-DNA strategy recently introduced in some other screening programmes.

Cystic Fibrosis↗

Effects of psychotherapy in moderately severe COPD: a pilot study.

Anxiety is common in the "pink puffer" syndrome associated with chronic obstructive pulmonary disease (COPD). The degree of anxiety correlates well with perceived dyspnoea. This pilot study examines the effect of group psychotherapy on anxiety, exercise tolerance, dyspnoea and quality of life. Ten patients with moderately severe, stable COPD (mean forced expiratory volume in one second (FEV1)-1.15 L) had six 90 min sessions of cognitive and behavioural psychotherapy at weekly intervals. Patients completed the Hospital Anxiety and Depression Scale (HADS), Medical Research Council Questionnaire (MRCQ) and St George's Respiratory Questionnaires (SGRQ), 1 week before and after therapy. FEV1, forced vital capacity (FVC), slow vital capacity (SVC), blood gas tensions and 6 min walking distance (6MWD) were measured. Eight control patients attended weekly for lung function and 6MWD for 6 weeks, but had no psychotherapy. Mean baseline HADS score was significantly higher in the psychotherapy group (12) than in controls (7), but otherwise there were no differences in lung function, blood gas tensions, 6MWD, or the other questionnaire scores between groups. After treatment, the physiological and psychological parameters where unchanged in both groups with the exception of the mean 6MWD, which had improved in the psychotherapy group only, from 351 to 423 m (p<0.001), an increase of 24%. Three months after treatment, the 6MWD was still 16% above the baseline value (p=0.02). In conclusion, six sessions of cognitive and behavioural psychotherapy produced a sustained improvement in exercise tolerance in a group of 10 anxious patients with severe chronic obstructive pulmonary disease, without any change in anxiety scores on the Hospital Anxiety and Depression Scale. Further studies of more prolonged, intensive psychotherapy would establish whether better symptom and quality of life scores accompany more dramatic increases in exercise tolerance in "pink puffers".

Aged↗

CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2-5 homeobox gene pathway.

To identify the molecular pathways that guide cardiac ventricular chamber specification, maturation and morphogenesis, we have sought to characterize factors that regulate the expression of the ventricular myosin light chain-2 gene, one of the earliest markers of ventricular regionalization during mammalian cardiogenesis. Previously, our laboratory identified a 28 bp HF-la/MEF-2 element in the MLC-2v promoter region, which confers cardiac ventricular chamber-specific gene expression during murine cardiogenesis, and showed that the ubiquitous transcription factor YB-1 binds to the HF-la site in conjunction with a co-factor. In a search for interacting co-factors, a nuclear ankyrin-like repeat protein CARP (cardiac ankyrin repeat protein) was isolated from a rat neonatal heart cDNA library by yeast two-hybrid screening, using YB-1 as the bait. Co-immunoprecipitation and GST-CARP pulldown studies reveal that CARP forms a physical complex with YB-1 in cardiac myocytes and immunostaining shows that endogenous CARP is localized in the cardiac myocyte nucleus. Co-transfection assays indicate that CARP can negatively regulate an HF-1-TK minimal promoter in an HF-1 sequence-dependent manner in cardiac myocytes, and CARP displays a transcriptional inhibitory activity when fused to a GAL4 DNA-binding domain in both cardiac and noncardiac cell context. Northern analysis revealed that carp mRNA is highly enriched in the adult heart, with only trace levels in skeletal muscle. During murine embryogenesis, endogenous carp expression was first clearly detected as early as E8.5 specifically in heart and is regulated temporally and spatially in the myocardium. Nkx2-5, the murine homologue of Drosophila gene tinman was previously shown to be required for heart tube looping morphogenesis and ventricular chamber-specific myosin light chain-2 expression during mammalian heart development. In Nkx2-5(-/-)embryos, carp expression was found to be significantly and selectively reduced as assessed by both whole-mount in situ hybridizations and RNase protection assays, suggesting that carp is downstream of the homeobox gene Nkx2-5 in the cardiac regulatory network. Co-transfection assays using a dominant negative mutant Nkx2-5 construct with CARP promoter-luciferase reporter constructs in cardiac myocytes confirms that Nkx2-5 either directly or indirectly regulates carp at the transcriptional level. Finally, a carp promoter-lacZ transgene, which displays cardiac-specific expression in wild-type and Nkx2-5(+/-) background, was also significantly reduced in Nkx2-5(-/-) embryos, indicating that Nkx2-5 either directly or indirectly regulates carp promoter activity during in vivo cardiogenesis as well as in cultured cardiac myocytes. Thus, CARP is a YB-1 associated factor and represents the first identified cardiac-restricted downstream regulatory gene in the homeobox gene Nkx2-5 pathway and may serve as a negative regulator of HF-1-dependent pathways for ventricular muscle gene expression.

Amino Acid Sequence↗

British agencies for adoption and fostering in Scotland--Scottish Medical Advisers' survey.

Children in local authority care (The survey was conducted before the term 'in care' was replaced by 'looked after' on The Children (Scotland) Act coming into force in October 1996) come from backgrounds of high incidence of mental illness, substance abuse and learning difficulties and have often suffered from neglect and/or abuse. They have a high incidence of medical problems affecting both physical and mental health. The Committee of the Scottish Section of the Medical Group of British Agencies for Adoption and Fostering (BAAF) were concerned about the provision and co-ordination of medical services for children in local authority care. The aim of the survey was to identify the current and evolving practice among medical advisers across Scotland. Questionnaires were returned from 40 Medical Advisers representing each of the local authorities in Scotland. The responses highlighted a variation in the implementation of practice in clinical services provided to children in care and by whom. It confirmed that difficulties in follow-up did exist and revealed widespread confusion surrounding co-ordination of medical services, absence of procedures and ignorance of legal requirements. The study confirms that involved medical practitioners need to have a pro-active role in co-operating closely with social work colleagues to provide a well co-ordinated service of medical supervision providing a comprehensive assessment of health care needs as part of the overall child care plan.

Adolescent↗

Using data mining to characterize DNA mutations by patient clinical features.

In most hereditary cancer syndromes, finding a correspondence between various genetic mutations within a gene (genotype) and a patient's clinical cancer history (phenotype) is challenging; to date there are few clinically meaningful correlations between specific DNA intragenic mutations and corresponding cancer types. To define possible genotype and phenotype correlations, we evaluated the application of data mining methodology whereby the clinical cancer histories of gene-mutation-positive patients were used to define valid or "true" patterns for a specific DNA intragenic mutation. The clinical histories of patients with their corresponding detailed attributes without the same oncologic intragenic mutation were labeled incorrect or "false" patterns. The results of data mining technology yielded characterizing rules for the true cases that constituted clinical features which predicted the intragenic mutation. Some of the initial results derived correlations already independently known in the literature, adding to the confidence of using this methodological approach.

Age of Onset↗

Angiotensin II stimulates sperm motility.

The physiological factors which induce and maintain mammalian sperm maturation and motility generally remain unclear, although several agents are known to be involved. We recently described the application of immunocytochemical and immunoblotting methods to identify the angiotensin II type 1 (AT1) receptor in the tails of ejaculated rat and human sperm, and gave evidence to show that angiotensin II may promote sperm motility. These data are extended here by the application of a computerised sperm tracking system (the Hobson Sperm Tracker) to demonstrate that AII has actions on specific motility parameters, including curvilinear velocity, straight line velocity, and amplitude of lateral head movement. Since local tissue renin-angiotensin systems are present in both male and female tracts, the data suggest that angiotensin II has a role in the maintenance of sperm function and fertility.

Angiotensin I↗