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Biomedical subjects

R Holder

Publications and source records attributed to R Holder.

At least 19 recordsLinked to original sources
PubMed2006

The effect of the apolipoprotein E gene polymorphisms and haplotypes on behavioural and psychological symptoms in probable Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease and dementia commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in Alzheimer's disease has been demonstrated. Several studies have investigated whether the exon 4 epsilon2/epsilon3/epsilon4 haplotype of the apolipoprotein E (APOE) gene is associated with BPSD, with variable results. OBJECTIVE: We investigated the exon 4 polymorphisms and extended this study to include promoter polymorphisms and the resultant haplotypes across the gene. METHODS: Our large independent cohort of 388 patients with longitudinal measures of BPSD assessed by the Neuropsychiatric Inventory was used to analyse whether any of these variants were associated with the presence of BPSD. RESULTS: We revealed several significant relationships before correction for multiple testing. The exon 4 haplotype was associated with hallucinations and anxiety, A-491T with irritability, T-427C with agitation/aggression and appetite disturbances, and T-219C with depression. Haplotype analyses of all variants did not reveal any statistically significant findings. CONCLUSIONS: Our data and a review of previous studies showed a diversity of relationships, suggesting that these findings might be due to chance and so collectively do not support a role for the APOE gene in BPSD.

Aged↗
PubMed2006

Vaginal vault smears after hysterectomy for reasons other than malignancy: a systematic review of the literature.

BACKGROUND: Vaginal vault smears are used to detect persisting neoplasia of the lower genital tract after hysterectomy. Recent data suggest both widespread use and uncertain evidence of their effectiveness. OBJECTIVES: To identify and synthesise evidence on the use and effectiveness of vaginal vault smears and to assess the quality. SEARCH STRATEGY 'vault smear' OR 'vaginal vault smear' OR 'cervical vault smear' OR ('Hysterectomy') AND ('Follow up' OR 'Smear'). SELECTION CRITERIA Primary research, women who had a hysterectomy and were followed up by vault cytology. DATA COLLECTION AND ANALYSIS: Systematic search (eight electronic databases), supplemented by contact with experts and review of bibliographies. Two independent reviewers determined eligibility/validity and extracted data concerning test performance characteristics. Quality was assessed according to the established criteria. RESULTS: Of 441 unique references, only 19 were suitable. Quality of studies varied considerably and few were of 'high' methodological quality. Studies were geographically diverse, and were published over more than 40 years in 16 journals. From the higher scoring papers, there were 11 659 hysterectomies [6546, benign; 76, cervical intraepithelial neoplasia (CIN) I/CIN II; 5037, CIN III]. Proportions of abnormal vault smears and abnormal biopsies during follow up increased with worsening histology at hysterectomy (P < 0.0001 and P = 0.0001). There was only one report of vaginal cancer subsequent to hysterectomy for CIN and insufficient data to allow for reliable meta-analysis. CONCLUSIONS: Vault smears cause anxiety, consume resources and their value is largely unproven. Inconsistency of study design and limited methodological quality means that the value of vault smears could not be established. High-quality research is required to ensure that the guidelines are evidence based.

Female↗
PubMed2005

Outcome of direct restorations placed within the general dental services in England and Wales (Part 4): influence of time and place.

AIM: It is aim of this paper to investigate the outcome of direct-placement restorations provided within the General Dental Services in England and Wales, in relation to the factors related to time and place of restoration placement. METHODS: A modified version of Kaplan-Meier statistical methodology was used to plot survival curves for restorations placed at different times and places, within the population of patients for whom data were available. RESULTS: The results indicated that overall, restoration survival time to re-intervention has declined over the last decade, but that most of the decline can be accounted for by the change in the relative numbers of amalgam and other direct restorations. Restoration survival to re-intervention is independent of whether the water is fluoridated in the area of the dentist's surgery address. Variation with region is not great, but restorations placed in Wales survived to re-intervention significantly longer than those in England (P<0.0001). CONCLUSIONS: Overall, there was some evidence of a reduction in survival times with time. Restorations placed in Wales survived longer to re-intervention than restorations placed in England. Restoration survival was not dependent on whether the dentist who placed the restoration practised in an area in which the water was fluoridated. Performance of amalgam restorations was not found to have altered significantly with time, but performance of composite and glass ionomer deteriorated with time.

Acrylic Resins↗
PubMed2005

Self management of oral anticoagulation: randomised trial.

OBJECTIVE: To determine the clinical effectiveness of self management compared with routine care in patients on long term oral anticoagulants. DESIGN: Multicentre open randomised controlled trial. SETTING: Midlands region of the UK. PARTICIPANTS: 617 patients aged over 18 and receiving warfarin randomised to intervention (n = 337) and routine care (n = from 2470 invited; 193/337 (57%) completed the 12 month intervention. INTERVENTION: Intervention patients used a point of care device to measure international normalised ratio twice a week and a simple dosing chart to interpret their dose of warfarin. MAIN OUTCOME MEASURE: Percentage of time spent within the therapeutic range of international normalised ratio. RESULTS: No significant differences were found in percentage of time in the therapeutic range between self management and routine care (70% v 68%). Self managed patients with poor control before the study showed an improvement in control that was not seen in the routine care group. Nine patients (2.8/100 patient years) had serious adverse events in the self managed group, compared with seven (2.7/100 patient years) in the routine care arm (chi2(df = 1) = 0.02, P = 0.89). CONCLUSION: With appropriate training, self management is safe and reliable for a sizeable proportion of patients receiving oral anticoagulation treatment. It may improve the time spent the therapeutic range for patients with initially poor control. Trial registration ISRCTN 19313375.

Administration, Oral↗
PubMed2004

Effect of fasting on the VO2-fh relationship in king penguins, Aptenodytes patagonicus.

King penguins (Aptenodytes patagonicus) may fast for up to 30 days during their breeding period. As such extended fasting may affect the relationship between the rate of O(2) consumption (Vo(2)) and heart rate (f(H)), five male king penguins were exercised at various speeds on repeated occasions during a fasting period of 24-31 days. In addition, Vo(2) and f(H) were measured in the same animals during rest in cold air and water (4 degrees C). Vo(2) and f(H) at rest and Vo(2) during exercise decreased with fasting. There was a significant relation between Vo(2) and f(H) (r(2) = 0.56) that was improved by including speed, body mass (M(b)), number of days fasting (t), and a cross term between f(H) and t (r(2) = 0.92). It was concluded that there was a significant change in the Vo(2)-f(H) relationship with fasting during exercise. As t is measurable in the field and was shown to be significant and, therefore, a practical covariate, a regression equation for use when birds are ashore was obtained by removing speed and M(b). When this equation was used, predicted Vo(2) was in good agreement with the observed data, with an overall error of 3.0%. There was no change in the Vo(2)-f(H) relationship in penguins at rest in water.

Algorithms↗
PubMed2001

An audit of management of differentiated thyroid cancer in specialist and non-specialist clinic settings.

OBJECTIVE: Thyroid cancer is the most common endocrine malignancy but is none the less rare. Some aspects of its management remain controversial. Previous audits of patient management in the United Kingdom have revealed deficiencies, especially in communication between specialists. We have audited patient management in a large university-associated teaching hospital, assessing points of good practice identified from published guidelines and reviews, and have compared findings in groups of patients managed jointly by specialists with an interest in thyroid cancer (including surgeon, endocrinologist and oncologist) with a group managed by other clinicians outside that setting. DESIGN AND PATIENTS: Retrospective case-note review of 205 patients with differentiated (papillary or follicular) cancer including group A (n = 134; managed in a specialist multi-disciplinary clinic setting) and group B (n = 71; managed in other clinic settings). Points of good practice investigated were adequacy of surgery, surgical complications, prescription and adequacy of T4 treatment, adequacy of monitoring by measurement of serum thyroglobulin and action taken and appropriate administration of ablative radioiodine. RESULTS: Deficiencies in management of the cohort as a whole were identified, including inadequate surgery and inadequate TSH suppression in approximately one-fifth of the cases. Monitoring with thyroglobulin measurements and action when serum thyroglobulin was high were also inadequate in some cases and ablative radioiodine was not given, despite being indicated in 11.7% of the cohort. Inadequate surgery and failure to administer radioiodine were less common in those managed in a specialist clinic setting than in those managed in other clinic settings. CONCLUSIONS: The findings highlight the need for locally agreed protocols in managing relatively rare endocrine disorders such as thyroid cancer and argue in favour of centralization of expertise and patient management in multi-disciplinary specialist clinic settings.

Adolescent↗
PubMed2001

Weight gain following treatment of hyperthyroidism.

OBJECTIVE: Patients frequently express concern that treating hyperthyroidism will lead to excessive weight gain. This study aimed to determine the extent of, and risk factors for, weight gain in an unselected group of hyperthyroid patients. DESIGN AND SUBJECTS: We investigated 162 consecutive hyperthyroid patients followed for at least 6 months. Height, weight, clinical features, biochemistry and management were recorded at each clinic visit. RESULTS: Documented weight gain was 5.42 +/- 0.46 kg (mean +/- SE) and increase in BMI was 8.49 +/- 0.71%, over a mean 24.2 +/- 1.6 months. Pre-existing obesity, Graves' disease causing hyperthyroidism, weight loss before presentation and length of follow-up each independently predicted weight gain. Patients treated with thionamides or radioiodine gained a similar amount of weight (thionamides, n = 87, 5.16 +/- 0.63 kg vs. radioiodine, n = 62, 4.75 +/- 0.57 kg, P = 0.645), but patients who underwent thyroidectomy (n = 13) gained more weight (10.27 +/- 2.56 kg vs. others, P = 0.007). Development of hypothyroidism (even transiently) was associated with weight gain (never hypothyroid, n = 102, 4.57 +/- 0.52 kg, transiently hypothyroid, n = 29, 5.37 +/- 0.85 kg, on T4, n = 31, 8.06 +/- 1.42 kg, P = 0.014). This difference remained after correcting for length of follow-up. In the whole cohort, weight increased by 3.95 +/- 0.40 kg at 1 year (n = 144) to 9.91 +/- 1.62 kg after 4 years (n = 27) (P = 0.008), representing a mean weight gain of 3.66 +/- 0.44 kg/year. CONCLUSION: We have demonstrated marked weight gain after treatment of hyperthyroidism. Pre-existing obesity, a diagnosis of Graves' disease and prior weight loss independently predicted weight gain and weight continued to rise with time. Patients who became hypothyroid, despite T4 replacement, gained most weight.

Adolescent↗
PubMed2001

The anxieties of male and female medical students on commencing clinical studies: the role of gender.

CONTEXT: Many medical students experience considerable anxiety when starting hospital experiences. OBJECTIVES: To investigate the role of gender in this transitional experience. METHOD: A questionnaire study was conducted in 1992 and 1995 to compare female and male anxieties about clinical situations they anticipated encountering. The 31-item questionnaire listed potential anxiety-provoking situations and requested the respondents' ratings of their reactions (from 1=not anxious to 4=very anxious). RESULTS: Differences in rankings between males and females were consistent between 1992 and 1995. More detailed analysis of 1995 data showed females had significantly higher totals; for 16/31 situations the difference was statistically significantly higher. For 4/31 situations male score was statistically significantly higher. Males ranked clinical situations involving intimate contact with patients significantly higher. Females scored situations involving interactions with consultants significantly higher than other situations and higher than did males. Females compared to males ranked 6/31 situations over five places different. CONCLUSIONS: Customisation of clinical introductory courses should be introduced. Earlier community-based clinical experience may help reduce non-productive anxiety.

Journal Article↗
PubMed2001

Measurement of nicotine intake in pregnant women--associations to changes in blood cell count.

Self-reported information about smoking is imprecise and subject to bias, with accuracy varying according to circumstances. Biochemical assessment gives much clearer indications of the effects of tobacco intake on physiological parameters. As part of a randomized controlled trial, a new point-of-care test for smoking was used as a tool to reduce smoking in pregnancy. Measurements of nicotine metabolites in urine were related to a physiological effect of smoking, notably changes to blood parameters, assessed as a routine part of antenatal care. One hundred and eighty-seven pregnant women attending outpatient antenatal care were initially questioned by a midwife about smoking habits and later questioned by the investigators, during which the test was performed and the results relayed back to the patient. Self-reported smoking habit and cigarette consumption, either reported to midwives or the investigators, were shown to be poor indicators of the effects of smoking on blood parameters. The biochemical assessment of nicotine intake was significantly related to white blood count, haemoglobin concentration, haematocrit, mean cell volume, and mean cell haemoglobin. Red cell count, mean cell haemoglobin concentration, and platelet count were unrelated to nicotine metabolite measurements. We concluded that the new test was a reliable measure of nicotine intake in pregnancy and the results correlated with smoking-related changes to haematological parameters.

Adult↗
PubMed2001

Myxoid angiomyoma of the hard palate: a case report.

Angiomyomas are found with some frequency in the female genital tract. They can also appear in both sexes in the gastrointestinal tract and in the skin. The oral cavity is an unusual site for an angiomyoma. In this article, we describe the case of a 74-year-old woman who came to us with a nodule at the palatal midline. Following surgical excision of the growth and stent placement over the wound site, a biopsy analysis was performed. Histology of the removed tissue revealed an unusual variant of an angiomyoma: a myxoid angiomyoma.

Aged↗
PubMed2000

Outcome after prenatal diagnosis of hypoplastic left-heart syndrome: a case series.

BACKGROUND: Traditionally, after prenatal diagnosis of hypoplastic left-heart syndrome (HLHS) couples have been offered termination of pregnancy or comfort care. Success of postnatal surgical options such as the Norwood procedure have been associated with survival of up to 60%. Whether survival is affected by the congenital anomaly being identified prenatally or postnatally remains uncertain. METHODS: We reviewed all cases of prenatally diagnosed HLHS referred to the Fetal Medicine Unit at Birmingham Women's Hospital over 6 years between 1994 and 1999. FINDINGS: 87 cases of HLHS were referred at a median gestational age (95% CI) of 23 (19-37) weeks. Of these, 53 (61%) chose prenatal karyotyping. The overall frequency of abnormal karyotype was found in seven of 59 cases (12%) and associated structural anomalies in 18 of 87 (21%). After counselling, 38 of 87 couples (44%) chose termination of pregnancy. Of the remaining 49 fetuses, 11 (23%) were not considered for postnatal surgery because of parental choice and they died after compassionate care. Of the 36 babies who had surgery postnatally, 12 survived (33%). We recorded a survival rate of 38% for the stage-1 Norwood procedure in the prenatally diagnosed HLHS in our centre. These data suggest that at the point of prenatal detection, the overall survival rate for fetuses with HLHS is 25% (if terminated pregnancies are excluded). INTERPRETATION: Fetal echocardiography allows early diagnosis of HLHS and gives clinicians the opportunity to triage this group dependent on prenatal findings, including karyotyping and the exclusion of other structural anomalies. These prospective data provide up-to-date information on the basis of which parents can make decisions.

Abortion, Induced↗
PubMed2000

Near-patient test for nicotine and its metabolites in saliva to assess smoking habit.

Smoking is a major risk factor for periodontal disease, causing bone and tooth loss. Effective management of many oral conditions requires accurate information about smoking. We describe a disposable, 10-min, near-patient saliva test to monitor cigarette smoking. A plastic device contains the dried reagents to measure nicotine and its metabolites by a colorimetric assay. The device can be used to give a semi-quantitative assessment of tobacco consumption by observing a colour change and comparing it to a reference chart. Alternatively, the test can be quantified by measuring the light absorbance with a colorimeter and determining the concentration of nicotine metabolites by reference to a cotinine standard. This method correlates with reported daily cigarette consumption (r=0.62, P<0.0001) and nicotine yield of cigarettes smoked (r=0.35, P<0.01) and compares favourably with cotinine, as measured independently by radioimmunoassay (r=0.57, P<0.005). The method provides a simple-to-use, inexpensive way of monitoring tobacco consumption in dental surgeries.

Adult↗
PubMed2000

Pregnancy outcome in women with type 2 diabetes mellitus needs to be addressed.

Maternal diabetes mellitus (types 1 and 2) is the most chronic prevalent medical condition affecting the pregnant population and is associated with a less satisfactory pregnancy outcome for both mother and infant when compared with the non-diabetic population. Most reports have focused on women with type 1 disease, type 2 disease being perceived as a less serious condition. However, type 2 disease is far more common (and is increasing) in some areas of the UK, especially where there is a high proportion of women from the Indian subcontinent. This paper shows that pregnancy complicated by type 2 diabetes mellitus is a high-risk state, with miscarriage and congenital malformations almost twice that seen in type 1 disease. These adverse outcomes are contributed to by poor attendance for pre-pregnancy care, later booking for antenatal clinic and poor glycaemic control at booking. Offspring of pregnancies complicated by type 2 diabetes are more likely to be delivered before 37 weeks gestation and be large in size for gestational age. We must dispel the myth, in women of childbearing age and in their healthcare providers, that diabetes treated with diet and/or tablets (type 2) is a less serious problem than type 1 disease.

Abortion, Spontaneous↗
PubMed1999

Gender, clinical findings, and serum thyrotropin measurements in the prediction of thyroid neoplasia in 1005 patients presenting with thyroid enlargement and investigated by fine-needle aspiration cytology.

One thousand five euthyroid patients (870 females and 135 males, mean age 47 years), who presented with thyroid enlargement were evaluated by fine-needle aspiration cytology (FNAC) of the thyroid as the first-line investigation. The final cytological or histological diagnosis was determined after surgery (n = 312) or clinical follow-up for a minimum period of 2 years (range 2-14 years, mean 6.7 years). Goiter type was assessed clinically and was classified as diffuse in 147, multinodular in 247, or solitary nodule in 611. The overall sensitivity and specificity of the procedure in the detection of thyroid neoplasia was 88% and 89%, respectively. Males who presented with thyroid enlargement had significantly higher rates of malignancy (p = 0.007) and neoplasia (benign + malignant) (p = 0.002) than females, as did subjects with solitary nodule compared with diffuse or multinodular goiters (malignancy p = 0.001, neoplasia p < 0.001). Subjects with normal thyrotropin (TSH) (>0.4 mU/L) at presentation had a nonsignificantly increased risk of thyroid neoplasia (p = 0.07) and malignancy, in contrast to those with low TSH (<0.4 mU/L). We confirmed FNAC of the thyroid to be an accurate test in the detection of thyroid neoplasia. Gender and goiter type at presentation both contribute significantly to the prediction of the diagnosis of thyroid neoplasia.

Adolescent↗