Long term safety and efficacy of donepezil in the treatment of dementia in Alzheimer's disease in adults with Down syndrome: open label study.
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Biomedical subjects
Publications and source records attributed to R Holder.
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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.
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.
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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.
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.
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.
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.
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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.
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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.
Aspirin ingestion within the previous 7-10 days is often considered a relative contraindication to performing invasive procedures. However, aspirin is an important component of many patients' treatment and withholding therapy for this time may be dangerous. To measure both the magnitude of the impairment in primary haemostasis induced by aspirin and how much recovery of platelet function occurs within 48 h of stopping aspirin, we studied serial changes in bleeding time (BT) in a randomized, double-blind, placebo-controlled study. Fifty-two healthy volunteers had BT performed before and at 2, 9, 24 and 48 h after a 7-day course of either aspirin 75 mg, 300 mg or placebo. The main outcome recorded was BT at each time. Nearly 25% of subjects had extended BT to more than 10 min, but no BT were greater than 10 min, 48 h after stopping aspirin. There was a small but statistically significant (P < 0.01) difference between the 48-h and baseline BT in both aspirin groups (49 and 64 s in the 75 mg and 300 mg groups, respectively). There was no difference in the magnitude or time course of effect between low and medium dose aspirin (P = 0.392 and P = 0.797, respectively). We conclude that despite considerable inter-individual variability in the magnitude of aspirin effect on primary haemostasis, the time course of effect was consistent. In healthy volunteers, the defect in primary haemostasis had largely disappeared 48 h after the last dose.
AIM: To determine the reliability of international normalised ratio (INR) measurement in primary care by practice nurses using near patient testing (NPT), in comparison with results obtained within hospital laboratories by varied methods. METHODS: As part of an MRC funded study into primary care oral anticoagulation management, INR measurements obtained in general practice were validated against values on the same samples obtained in hospital laboratories. A prospective comparative trial was undertaken between three hospital laboratories and nine general practices. All patients attending general practice based anticoagulant clinics had parallel INR estimations performed in general practice and in a hospital laboratory. RESULTS: 405 tests were performed. Comparison between results obtained in the practices and those in the reference hospital laboratory (gold standard), which used the same method of testing for INR, showed a correlation coefficient of 0.96. Correlation coefficients comparing the results with the various standard laboratory techniques ranged from 0.86 to 0.92. It was estimated that up to 53% of tests would have resulted in clinically significant differences (change in warfarin dose) depending upon the site and method of testing. The practice derived results showed a positive bias ranging from 0.28 to 1.55, depending upon the site and method of testing. CONCLUSIONS: No technical problems associated with INR testing within primary care were uncovered. Discrepant INR results are as problematic in hospital settings as they are in primary care. These data highlight the failings of the INR to standardise when different techniques and reagents are used, an issue which needs to be resolved. For primary care to become more involved in therapeutic oral anticoagulation monitoring, close links are needed between hospital laboratories and practices, particularly with regard to training and quality assurance.
Depleted antioxidant defence has been implicated in the pathogenesis of cervical neoplasia. We determined the systemic and local antioxidant status of women with this condition. Thirty-four women with varying grades of cervical intraepithelial neoplasia, 25 patients who had been treated successfully with diathermy loop excision, and 56 women who had no evidence of cervical abnormality acted as controls. Total antioxidant capacity of serum and protein-free serum, and of neat and protein-free homogenized cervical punch biopsies were determined using enhanced chemiluminescence. Mean serum antioxidant capacity of patients with current neoplasia and treated patients was not significantly different from that of controls. However, mean antioxidant capacity of homogenized cervical tissue from women with neoplasia was significantly lower than control means (P < 0.005), while results for treated patients were intermediate between those from diseased and normal samples (P < 0.05). The enhanced chemiluminescence technique has potential as a suitable method for measuring total antioxidant capacity of cervical tissue, and warrants further investigations using other tissue types. Significant antioxidant depletion in cervical intra-epithelial neoplasia appears to be confined to the local cervical mucosa.
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Blood tests increasingly require only a few microlitres of blood. Lancing systems used for the collection of blood have the potential to transmit infection if used improperly. These systems vary in the amount of blood and pain produced.
A wide range of blood glucose monitoring systems is available for use in different applications. The systems have varying characteristics which should be taken into consideration during selection. Operator technique can influence the quality of the results.