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Biomedical subjects

R Harper

Publications and source records attributed to R Harper.

At least 37 records · Page 2Linked to original sources

Accuracy of CT scanning and adrenal vein sampling in the pre-operative localization of aldosterone-secreting adrenal adenomas.

In primary hyperaldosteronism, it is important to distinguish between unilateral and bilateral disease, as management strategies differ. In the period 1983-95, we identified 34 patients with primary hyperaldosteronism. Following further investigations, a diagnosis of aldosterone-secreting adenoma was made in 17 patients, and surgery was performed. Computed tomography clearly localized an apparent adenoma (discrete adenoma=1 cm diameter; normal contralateral gland) in only 10 of these patients (59%); two of these 'adenomas' were subsequently shown to be hyperplastic glands without adenomas. Histological examination showed adrenal adenomas in the remaining 15 patients. An 'adenoma' also appeared to be clearly localized in 3/17 patients later classified as having bilateral adrenal hyperplasia by adrenal vein sampling. CT scanning, therefore clearly localizes adenomas in only 50% of histologically proven cases, and can also produce misleading results. Adrenal vein sampling results altered our management approach in one third of cases. On the basis of our detailed results we would recommend surgery if there is clear evidence of unilateral aldosterone secretion along with CT findings which may not be strictly localizing but are in keeping with the dominant side on adrenal vein sampling. The decision to refer for surgery in primary hyperaldosteronism can be difficult, and we would caution against too heavy a reliance on CT results when recommending adrenalectomy, and suggest that adrenal vein sampling should remain a routine part of the investigation of patients with primary hyperaldosteronism.

Adenoma↗

Generic and condition-specific outcome measures for people with osteoarthritis of the knee.

OBJECTIVES: The aims of this study were to evaluate two condition-specific and two generic health status questionnaires for measuring health-related quality of life in patients with osteoarthritis (OA) of the knee, and to offer guidance to clinicians and researchers in choosing between them. METHODS: Patients were recruited from two settings: 118 from knee surgery waiting lists and 112 from rheumatology clinics. Four self-completion questionnaires [Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Health Assessment Questionnaire (HAQ), Short Form-36 (SF-36) and Euroqol] were sent to subjects on two occasions 6 months apart. Construct validity, convergent validity, internal consistency and responsiveness were examined using primarily non-parametric methods. RESULTS: All instruments proved satisfactory in terms of ease of use, acceptability to patients, internal consistency and reliability. In the surgical group, the OA-specific WOMAC performed better than the HAQ and the generic measures in terms of validity and responsiveness to change, whereas in the rheumatology group the SF-36 was more responsive. CONCLUSION: WOMAC is the instrument of choice for evaluating the outcome of knee replacement surgery in OA. The SF-36 provides a more general insight into patients' health and may be more responsive to change than the WOMAC in a heterogeneous rheumatology clinic population. Researchers wishing to undertake an economic evaluation might consider the EQ-5D for a surgical, but not a rheumatology clinic group.

Aged↗

Factors relating to readmission of term and near-term neonates in the first two weeks of life. Early Discharge Survey Group of the Health Professional Advisory Board of the Greater New York Chapter of the March of Dimes.

AIMS: A multisite study of term and near term infants readmitted in the first two weeks of life to 9 New York City area hospitals in 1995 was conducted to evaluate factors related to readmission, including length of newborn stay. RESULTS: Of the 30,884 infants born at the 9 study hospitals 391 newborns were readmitted. The major admission diagnoses were infection, 40.7%, hyperbilirubinemia, 39.1%, and feeding and/or gastrointestinal problems, 10.5%. In the first week, 65.1% of readmissions were for hyperbilirubinemia and 19.1% were for infection or suspected sepsis. In the second week, 67.8% of readmissions were for infection and 7.6% were for hyperbilirubinemia. Hyperbilirubinemia was the most frequent diagnosis for White and Asian infants, while infection was most frequent for African-American and Hispanic infants. Age at readmission was younger and the interval from discharge was shorter for infants with hyperbilirubinemia. Abnormalities which should have precluded early discharge included feeding difficulties, cyanotic congenital heart defects, hemolytic disease of the newborn, early jaundice or early high bilirubin levels. CONCLUSION: Attention to identification of infants at risk and programs such as lactation counseling and universal screening for bilirubin (with appropriate interpretation) prior to discharge could have reduced the necessity for readmission regardless of the newborn length of stay.

Adolescent↗

Compliance with methodological standards when evaluating ophthalmic diagnostic tests.

PURPOSE: To draw attention to the importance of methodological standards when carrying out evaluations of ophthalmic diagnostic tests by reviewing the extent of compliance with these standards in reports of evaluations published within the ophthalmic literature. METHODS: Twenty published evaluations of ophthalmic screening/diagnostic tests or technologies were independently assessed by two reviewers for compliance with the following methodological standards: specification of the spectrum composition for populations used in the evaluation, analysis of pertinent subgroups, avoidance of work-up (verification) bias, avoidance of review bias, presentation of precision of results for test accuracy, presentation of indeterminate test results, and presentation of test reproducibility. RESULTS: Compliance ranged from just 10% (95%CI, 1%-32%) for presentation of test reproducibility data and avoidance of review bias to 70% (95%CI, 46%-88%) for avoidance of work-up bias and presentation of indeterminate test results. Only 5 of the 20 evaluations complied with four or more of the methodological standards and none with more than five of the standards. CONCLUSIONS: The evaluations of ophthalmic diagnostic tests discussed in this article show limited compliance with accepted methodological standards but are no worse than previously described for evaluations published in general medical journals. Adherence to these standards by researchers can improve the study design and reporting of evaluations of new diagnostic techniques. Limited compliance, combined with a lack of awareness of the standards among users of research evidence, may lead to the inappropriate adoption of new diagnostic technologies, with a consequent waste of health care resources.

Bias↗

Introduction of the Multilink stent into routine angioplasty practice: early angiographic and clinical outcome.

To assess the early outcome of implantation of the Multilink stent in everyday angioplasty practice, we prospectively collected procedural and 1-mo follow-up data on the first 126 patients (93 male, mean age 61+/-9 yr) in 3 centers. One hundred and seventy-four stents were implanted for 134 lesions: left anterior descending artery in 46%, circumflex in 20%, right coronary artery in 31%, and protected left main in 3%. The indication was elective in 56%, a suboptimal result in 43%, and bailout in 1%. Stents were deployed at 10.8+/-1.9 atmospheres and postdilated to 15.7+/-2.4 atmospheres. There were 115 patients who received ticlopidine and aspirin, 10 received aspirin alone, and 1 received warfarin and aspirin following the procedure. The reference diameter increased from 3.02+/-0.44 mm pre- to 3.13+/-0.43 mm postprocedure, with the minimal luminal diameter increasing from 0.82+/-0.47 to 2.86+/-0.45 mm (diameter stenosis 73% pre- and 9% postprocedure). The procedural success rate was 93.7%. There were no deaths, 1 (0.8%) Q- and 5 (4.0%) non-Q-wave myocardial infarctions, 3 (2.4%) emergency bypass operations, and 1 (0.8%) repeat angioplasty during the hospital admission (median stay, 1 day). There were 2 (1.6%) cases of subacute stent thrombosis. At 1-mo follow-up there were no additional events, with 88% of patients remaining free of angina. Implantation of the Multilink stent is safe and effective in everyday angioplasty practice, with a complication rate comparable to those of published trials of carefully selected patients.

Adult↗

Deriving a preference-based single index from the UK SF-36 Health Survey.

This article presents the results of a study to derive a preference-based single index from the SF-36. The study was an attempt to reconcile a profile health status measure, the SF-36, with the "quality adjusted life years" approach. The study undertook a parsimonious restructuring of the SF-36 using explicit criteria to form the SF-6D health state classification. A sample of multidimensional health states defined by this classification were valued by a convenience sample of health professionals, managers, and patients, who responded to a set of visual analogue scale ratings and standard gamble questions, with highly complete and consistent answers. Statistical models were estimated to predict single index scores for all 9000 health states defined by the new classification. The resultant algorithms can be applied to existing SF-36 data sets and used in the assessment of the cost-effectiveness of health technologies. This preliminary work forms the basis of a larger study currently being undertaken in the UK.

Algorithms↗

Effects of combination therapy with an angiotensin converting enzyme inhibitor and thiazide diuretic on insulin action in essential hypertension.

OBJECTIVE: To determine whether combination of an angiotensin converting enzyme inhibitor with a high dose of thiazide diuretic avoids adverse metabolic consequences of thiazide diuretics. DESIGN: Double-blind randomized crossover study of two 12-week treatment periods with captopril (up to 100 mg/day) either alone or in combination with 5 mg bendrofluazide given after a 6-week placebo run-in period. Treatment periods were separated by a 6-week placebo washout period. SETTING: Outpatient clinics in greater Belfast. PATIENTS: Fifteen white non-diabetic essential hypertensives (seven male) aged < 65 years recruited from general practices in greater Belfast. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures and peripheral and hepatic insulin action. RESULTS: Two patients failed to complete the study. Blood pressure was lowered (139/89+/-18/7 mmHg combination versus 160/97+/-21/7 mmHg captopril; P < 0.001). Fasting insulin level was raised (7.9+/-3.6 mU/l combination versus 6.2+/-3.2 mU/l baseline; P < 0.001). There were no differences between treatments for glucose, urate, cholesterol and triglyceride levels. Serum potassium level was lowered (3.8+/-0.4 mmol/l combination versus 4.2+/-0.4 mmol/l captopril, P < 0.05). Postabsorptive endogenous glucose production was raised (10.8+/-1.7 micromol/kg per min combination versus 10.0+/-1.5 micromol/kg per min captopril; P < 0.01) and was greater than baseline (9.7+/-2.1 micromol/kg per min, P < 0.05). Suppression of glucose production by insulin was similar with both treatments. Exogenous glucose infusion rates required to maintain euglycaemia did not differ (32.4+/-7.6 micromol/kg per min captopril, 32.7+/-6.2 micromol/kg per min combination, 31.5+/-7.2 micromol/kg per min baseline). CONCLUSIONS: Combination therapy increased glucose production (compared with captopril alone), indicating hepatic insulin resistance. It cannot be assumed that combined preparations with angiotensin converting enzyme inhibitors will ameliorate adverse effects of high doses of thiazide diuretics on insulin action.

Angiotensin-Converting Enzyme Inhibitors↗

Event-related potential correlates of linguistic information processing in schizophrenics.

Event-related potentials (ERPs) were recorded from adult schizophrenics and age- and education-matched normal controls during performance of an idiom recognition task involving judgments of the meaningfulness of idiomatic, literal, and nonsense phrases. Schizophrenics produced more errors and had prolonged reaction times while attempting to correctly differentiate meaningful from meaningless phrases. An ERP correlate of that deficit was a larger than normal N400 to idioms and literals, with no difference in N400 amplitude to nonsense phrases. This result was interpreted as evidence that the influence of the linguistic context provided by the first word of two-word idiomatic and literal phrases is reduced in schizophrenia. Schizophrenics also showed reduced amplitude P300.

Adult↗

Immunophenotyping of T lymphocytes by three-color flow cytometry in healthy newborns, children, and adults.

Reagents are now available which allow simultaneous assessment of three different fluorescence wave-lengths on most commercially available flow cytometers. Such three-color analyses provide more information than single- or dual-color analyses. The present study was undertaken in order to establish age-related differences in lymphocyte subpopulations by simultaneously measuring three surface antigens in newborns, children, and adults. A whole blood method was used to label cells with antibodies conjugated to FITC, PE, and perCP. We found that the percentage of lymphocytes expressing HLA-DR/CD28/CD8, HLA-DR/ CD38/CD8, CD95/CD45RO/CD8, CD95/CD45RO/CD4, CD95/CD4, and CD95/CD8 showed relative increases with age. The percentage of lymphocytes expressing CD28/CD8, CD38/CD8, and CD38/CD4 showed relative decreases with age, while the subset HLA-DR/CD38/ CD4 did not change. Three-color flow cytometry is a powerful tool to more precisely define lymphocyte subsets than the current two-color methods. We present values using a three-color panel in healthy newborns, children, and adults.

Adolescent↗

Insulin action and hepatic glucose cycling in Cushing's syndrome.

OBJECTIVE: Although it is well established that hypercortisolism causes insulin resistance, the mechanisms responsible for impaired insulin action in Cushing's syndrome are unclear. This study investigated the contribution of the glucose/glucose-6-phosphate substrate cycle (G/G6P). PATIENTS: Eight patients with Cushing's syndrome and seven control subjects were studied. All had normal fasting plasma glucose. DESIGN: Insulin action was assessed using the euglycaemic glucose clamp at insulin infusion rates of 0.4 and 2.0 mU/kg/min combined with a simultaneous infusion of [2(3)H]- and [6(3)-H]-glucose. Glucose/ glucose-6-phosphate cycle activity was calculated as the difference in glucose turnover rates determined separately for [2(3)H]- and [6(3)H]-glucose by selective enzymatic detritiation. MEASUREMENTS AND RESULTS: Exogenous glucose infusion rates required to maintain euglycaemia were significantly lower in Cushing's patients compared to controls, during the 0.4 mU/kg/min (7.8 +/- 1.2 vs 15.7 +/- 0.5 mumol/kg/min, P < 0.001) and the 2.0 mU/ kg/min insulin infusions (26.2 +/- 2.8 vs 51.5 +/- 3.5 mumol/ kg/min, P < 0.001). Endogenous glucose production was similar in both groups in the postabsorptive state (10.2 +/- 0.3 vs 10.8 +/- 0.4 mumol/kg/min, P = 0.50) and suppressed to a similar degree during hyperinsulinaemia. G/G6P cycle activity was markedly increased in the Cushing's group in the postabsorptive state (5.4 +/- 1.1 vs 2.0 +/- 0.5 mumol/kg/min, P = 0.028) and during the 0.4 mU/kg/min (3.2 +/- 0.6 vs 1.2 +/- 0.4 mumol/kg/min, P = 0.014) and 2.0 mU/kg/min insulin infusions (3.3 +/- 0.8 vs 1.1 +/- 0.5 mumol/kg/min, P = 0.049). CONCLUSIONS: Patients with Cushing's syndrome show marked peripheral insulin resistance and enhanced hepatic G/G6P cycle activity. In the fasting state increased glucose/glucose-6-phosphate cycle activity may be a protective mechanism limiting hyperglycaemia. During hyperinsulinaemia G/G6P cycle activity was increased but insulin resistance was predominantly due to reduced peripheral glucose uptake.

3-Hydroxybutyric Acid↗

Skeletal muscle blood flow is not a determinant of insulin resistance in essential hypertension.

OBJECTIVE: To investigate the haemodynamic effects of insulin and their relationship to insulin resistance in essential hypertension. DESIGN: Group comparison between patients with essential hypertension and normal controls. SETTING: Outpatient clinics serving the greater Belfast area. PATIENTS: Eleven patients with essential hypertension and eight age-, sex- and weight-matched control subjects were recruited. Administration of all antihypertensive agents to the hypertensive patients was stopped 6 weeks prior to the study. METHODS: Leg blood flow was measured using venous occlusion plethysmography. Insulin action was assessed using the hyperinsulinaemic euglycaemic clamp technique. RESULTS: The hypertensive subjects were insulin-resistant compared with the normal controls. Insulin infusion resulted in similar increases in calf blood flow in the two groups. There was no correlation between calf blood flow and measurements of insulin sensitivity in either group. CONCLUSIONS: Differences in whole-body glucose uptake in hypertensive and control subjects are not likely to be related to differences in insulin-induced stimulation of muscle blood flow.

Blood Flow Velocity↗

Nitric oxide production in burns: plasma nitrate levels are not increased in patients with minor thermal injuries.

BACKGROUND: Recent studies have suggested that adults who sustain burns of less than 15% total body surface area display elevated plasma nitrate levels, indicating increased production of nitric oxide. The present study was initiated to confirm whether plasma nitrate is elevated in minor burn injury and, if so, whether it heralds the onset of a systemic inflammatory response to that injury. METHODS: Plasma samples were taken from 98 control and 10 burns patients. RESULTS: The mean plasma nitrate level for nine burns patients with a mean total body surface area burnt of 7.65% (range, 4-15%) was 42.83 micromol/L on day 1. This was not significantly different from that of a control population of 98 preoperative plastic surgery patients: 36.91 micromol/L (p = 0.162). Eight of 10 burns patients showed a decrease in plasma nitrate to 27.47 micromol/L by day 3 (p = 0.046). Elevated nitrate levels were seen in 2 of 10 burns patients. One had concurrent smoke-inhalation injury preceding multiple organ dysfunction, and one was treated with a cream containing cerium nitrate (Flammacerium, Duphar Laboratories, Southhampton, United Kingdom). CONCLUSIONS: For patients who sustain minor burns, plasma levels of nitrate decrease from those of mean normal controls with time unless there is multiple organ dysfunction or the patient receives extraneous nitrate.

Adult↗

Comparison of outcome measures for patients with chronic obstructive pulmonary disease (COPD) in an outpatient setting.

BACKGROUND: To assist clinicians and researchers in choosing outcome measures for patients with chronic obstructive pulmonary disease attending routine outpatient clinics, a comparative assessment was undertaken of four questionnaires designed to reflect the patients' perception of their physical and emotional health in terms of their feasibility, validity, reliability, and responsiveness to health change. METHODS: Two condition specific questionnaires, the St George's Respiratory Questionnaire (SGRQ) and Guyatt's Chronic Respiratory Questionnaire (CRQ), and two generic questionnaires, the Short Form-36 Health Survey (SF-36) and Euroqol (EQ), were compared for their discriminative and evaluative properties. Spirometric tests and a walking test were also performed. One hundred and fifty six adults who were clinically judged to have COPD and who attended an outpatient chest clinic were assessed at recruitment and six and 12 months later. Patients were also asked whether their health had changed since their last assessment. RESULTS: Completion rates and consistency between items for dimensions of the SGRQ were lower than for dimensions of the other questionnaires. The distributions of responses were skewed for certain dimensions in all questionnaires except the CRQ. Validity was supported for all instruments insofar as patients' scores were associated with differences in disease severity. The generic questionnaires better reflected other health problems. All instruments were reliable over time. The condition specific questionnaires were more responsive between baseline and first follow up visit but this difference did not persist. While certain dimensions of the SF-36 were responsive to patient perceived changes, this did not apply to the derived single index of the EQ. The rating scale of the EQ, however, provided a quick and easy indicator of change. CONCLUSIONS: Evidence from this study supports the CRQ and the SF-36 as comprehensive outcome measures for patients with longstanding COPD.

Aged↗

Experimental simulation of the thrust phases of fast-start swimming of fish

Measurements of the thrust and forward impulse of a simulated fish tail and mathematical modeling indicate that the propulsive forces of fast-start swimming can be optimized by three different effects: (i) exactly inverting the tail tip vortex that is generated with the initial stroke, (ii) using a moderately flexible tail, and (iii) introducing a specific delay between the initial stroke and the return stroke. Experiments were performed with a new computer-controlled fish-tail simulation apparatus, and the results confirm the theoretical predictions of a previous study.

Journal Article↗