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Biomedical subjects

R Holder

Publications and source records attributed to R Holder.

At least 37 records · Page 2Linked to original sources

Magnitude and time course of impaired primary haemostasis after stopping chronic low and medium dose aspirin in healthy volunteers.

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.

Adult↗

Is the international normalised ratio (INR) reliable? A trial of comparative measurements in hospital laboratory and primary care settings.

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.

Anticoagulants↗

Serum and tissue antioxidant capacity in cervical intraepithelial neoplasia investigated using an enhanced chemiluminescent reaction.

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.

Adult↗

Blood lancing systems for skin puncture.

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.

Blood Specimen Collection↗

Selecting blood glucose monitoring systems.

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.

Bias↗

T lymphocyte responses to anti-neutrophil cytoplasmic autoantibody (ANCA) antigens are present in patients with ANCA-associated systemic vasculitis and persist during disease remission.

ANCA with specificity for myeloperoxidase (MPO) and proteinase 3 (PR3) are present in patients with systemic vasculitis. The aim of this work was to determine whether such patients have T cell responses to these antigens and whether these responses are related to disease activity. Peripheral blood lymphocytes from 45 patients and 19 controls were cultured with ANCA antigens and proliferation measured. The antigens used were heat-inactivated (HI) MPO, HI PR3, native (non-HI) PR3, HI whole alpha-granules, and 25 overlapping peptides covering the entire PR3 sequence. Significant responses to both whole PR3 preparations were seen from patient and control groups, and to the alpha-granules from the patient group. Patients responded at all stages of disease: active, remitting, treated or untreated. Only two patients responded significantly to MPO. Responses were significantly higher with the patient group than the control group to all four whole ANCA antigens. Responses to those PR3 peptides containing epitopes known to be recognized by ANCA were detected from one patient. Thus, these studies demonstrate that T cells from vasculitis patients can proliferate to PR3 and occasionally to associated ANCA antigens. Further, responses may persist even after disease remission has been achieved.

Amino Acid Sequence↗

Reducing the dose of gonadotrophin-releasing hormone agonist on starting ovarian stimulation: effect on ovarian response and in-vitro fertilization outcome.

The aim of this study was to examine if lowering the dose of gonadotrophin-releasing hormone agonist (GnRHa) on starting ovarian stimulation could be beneficial in in-vitro fertilization (IVF) programmes. A total of 64 normally ovulating patients entering an IVF programme were randomized to receive GnRHa (nafarelin acetate/Synarel) as an intranasal spray commencing in the midluteal phase, either at a dosage of 200 microg three times daily until the day of human chorionic gonadotrophin (HCG) administration, or to be reduced to 200 microg twice daily as ovarian stimulation was initiated. Patients in both groups were below 35 years with a body mass index below 30. All patients received three ampoules of Metrodin HP per day. Blood samples were taken on the day of HCG administration to measure luteinizing hormone (LH), oestradiol, and progesterone. LH and oestradiol were found to be significantly higher in the lower Synarel dose group. Our results show that reducing the GnRHa dose during ovarian stimulation in IVF might be beneficial in terms of significantly more oocytes recovered, and significantly greater number of embryos available for transfer and freezing, with no incidence of premature luteinization.

Adult↗

Measurement of serum TSH in the investigation of patients presenting with thyroid enlargement.

In otherwise euthyroid patients presenting with thyroid enlargement, reduction in serum thyrotrophin (TSH) concentrations measured in a sensitive assay may be a marker of thyroid autonomy and may therefore indicate a benign underlying pathology. We investigated prospectively a cohort of 467 subjects presenting consecutively to our thyroid clinic with nodular or diffuse enlargement of the thyroid. Subjects were divided into those with normal (0.4-5.5 mU/l), low but detectable (0.1-0.39 mU/l) or undetectable (< 0.1 mU/l) serum TSH concentrations. The final pathological diagnosis was defined by fine-needle aspiration cytology and clinical follow-up of at least 2 years or by fine-needle aspiration cytology and histology following surgical treatment. Serum TSH concentrations below normal were found in 75 patients (16.1%), those with low serum TSH results having higher mean free T4 concentrations, were older and were more likely to be female. In those with undetectable serum TSH, no patient had a diagnosis of thyroid neoplasia and in those with low but detectable TSH, thyroid neoplasms were diagnosed in two patients (3.4%). In those with normal serum TSH, 12.0% had a final diagnosis of thyroid neoplasm (p = 0.013). Overall, thyroid malignancy was found in one patient (1.3%) of those with a serum TSH measurement below the normal range and 6.9% of those with normal serum TSH (p < 0.06). Reduction in serum TSH at presentation may identify a group which requires less intensive investigation and follow-up than those without biochemical evidence of thyroid autonomy.

Biomarkers↗

Blood glucose measuring systems.

Glucose monitoring and lancing systems have proved useful in a range of patient testing applications in hospitals, general practice and for use by patients at home. Products are becoming easier to use and less technique dependent. It is important to be aware of their specific characteristics and to adhere to manufacturers' and local hospital laboratory guidelines.

Blood Glucose Self-Monitoring↗

Alternative treatments for a traumatic bone cyst: a longitudinal case report.

A patient presented with a large, multilocular, refractory traumatic bone cyst. The radiolucency had increased in dimension since her last recall. Over 11 years, therapy had included needle aspiration biopsies followed by simple curettage and closure, the most common therapy for traumatic bone cysts. However, all treatment had proved unsuccessful for this patient. It was decided to treat the patient with a slightly unique method. After curettage of the lesion, the traumatic bone cyst was packed with a mixture of autogenous blood, harvested autogenous bone chips, and hydroxyapatite.

Blood↗

The acute phase and function in early rheumatoid arthritis. C-reactive protein levels correlate with functional outcome.

OBJECTIVE: To discover whether normalization of C-reactive protein (CRP) in patients with rheumatoid arthritis (RA) results in stabilization of their functional state, and whether a measure of disease activity can be used as a predictor of functional outcome. To examine the relationship between change of CRP and Health Assessment Questionnaire (HAQ) over a 24 mo period to define the sensitivity of HAQ to change. METHODS: A prospective study of 109 consecutive patients who fulfilled the American College of Rheumatology criteria for RA and had elevated CRP before steroid or 2nd line therapy. A full clinical assessment including HAQ was performed at presentation and at 3, 6, 12, and 24 mo. On the basis of the change in CRP at 6 mo, patients were divided into 3 groups: (1) CRP suppression to normal, (2) 50% reduction in CRP, and (3) less than 50% CRP change. RESULTS: The 3 groups were clinically and immunologically similar at onset. At 6 mo the median HAQ fell to 5 (lower to upper quartiles 7.5 to 19) in Group 1 (CRP normalized, n = 34), 6 (3.75 to 10) in Group 2 (CRP reduced by 50%, n = 30), and 12 (6 to 18) in Group 3 (less than 50% CRP change, n = 44), p < 0.005 for Groups 1 and 2 versus Group 3. At 12 and 24 mo HAQ remained significantly lower in Groups 1 and 2 compared with Group 3. In Group 1, patients either maintained a normal CRP (n = 28) or their CRP became elevated (n = 6). Only in those patients in whom a re-elevation of the CRP occurred was deterioration in HAQ subsequently seen. CONCLUSION: Suppression of elevated CRP in patients with active RA is associated with improvement in functional score, whereas persistent elevation of CRP is associated with functional deterioration. Once abnormal CRP is suppressed, no functional deterioration is likely to occur without re-elevation in CRP. Therefore, elevated CRP provides a convenient short term correlation with functional outcome and can be used as a guide for therapy. A HAQ score is a sensitive indicator of change in early disease.

Analysis of Variance↗

A simple near-patient test for nicotine and its metabolites in urine to assess smoking habit.

We describe a disposable, near-patient urine test to monitor cigarette smoking. A plastic device contains the sealed dried reagents to measure nicotine and its metabolites, by a colorimetric assay. The device can be used to give a qualitative assessment of tobacco consumption, simply by observing a colour change. Alternatively, the test can be quantified by measuring the light absorbance with a simple colorimeter, and a concentration of nicotinic metabolites obtained with reference to a cotinine standard. A correction factor for the concentration of the urine sample, based on light absorbance, allows the result to be expressed as a ratio to urine concentration. This method correlates with reported daily cigarette consumption (r = 0.69, p < 0.0001) and compares favourably with cotinine, as measured by gas chromatography (r = 0.89, p < 0.0001). The method provides a simple-to-use, inexpensive way to monitoring tobacco consumption in extralaboratory situations.

Chromatography, Gas↗

Clinical associations of dual-energy X-ray absorptiometry measurement of hand bone mass in rheumatoid arthritis.

Hand bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) has potential as a marker of progression in early rheumatoid arthritis (RA). We examined a DXA methodology and studied in a cross-sectional manner 202 patients with RA. Hand BMD correlated inversely with age and was higher in males. Hand BMD correlated with lumbar and femoral sites. In females, BMD of the hand correlated positively with grip strength and negatively with disability. Those with higher C-reactive protein (CRP) had significantly lower hand BMD than those with normal CRP. In patients with a normal CRP, the hand BMD:lumbar BMD ratios were significantly higher in patients with longer disease duration. Hand BMD correlates with measures of disease activity, functional capacity and also with lumbar and femoral BMD. Hand bone loss occurs in early disease, in the absence of detectable systemic disease, and before lumbar BMD loss. It has the potential to be an outcome measure in early disease.

Absorptiometry, Photon↗

Evaluation of computerized decision support for oral anticoagulation management based in primary care.

BACKGROUND: Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. AIM: To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as within the appropriate therapeutic range of International Normalised Ratio (INR). METHOD: All patients receiving warfarin from two Birmingham inner city general practices were invited to attend a practice-based anticoagulation clinic. In practice A all patients were managed using DSS. In practice B patients were randomized to receive dosing advice either through DSS or through the local hospital laboratory. Clinical outcomes, adverse events and patient acceptability were recorded. RESULTS: Forty-nine patients were seen in total. There were significant improvements in INR control from 23% to 86% (P > 0.001) in the practice where all patients received dosing through DSS. In the practice where patients were randomized to either DSS or hospital dosing, logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients (P < 0.001). Mean recall times were significantly extended in patients who were dosed by the practice DSS through the full 12 months (24 days to 36 days) (P = 0.033). Adverse events were comparable between hospital and practice-dosed patients, although a number of esoteric events occurred. Patient satisfaction with the practice clinics was high. CONCLUSION: Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control, frequency of review and general acceptability.

Administration, Oral↗