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Biomedical subjects

R Harper

Publications and source records attributed to R Harper.

At least 55 records · Page 3Linked to original sources

Treatment of diabetic ketoacidosis using normalization of blood 3-hydroxybutyrate concentration as the endpoint of emergency management. A randomized controlled study.

OBJECTIVE: To compare the efficacy of an extended insulin regimen using correction of hyperketonemia as endpoint with a more conventional regimen in the treatment of diabetic ketoacidosis. RESEARCH DESIGN AND METHODS: A total of 22 patients admitted to a Belfast teaching hospital with clinical and biochemical features of diabetic ketoacidosis (pH < 7.25 and/or bicarbonate < 16 mmol/l) were randomized to either conventional or extended insulin regimens. In the conventional regimen, insulin was administered at 5 U/h until near-normoglycemia (blood glucose < or = 10 mmol/l) and then administered at a reduced rate until clinical recovery. In the extended regimen, administration of insulin at 5 U/h was continued beyond attainment of normoglycemia, until resolution of hyperketonemia (3-hydroxybutyrate < 0.5 mmol/l). Main outcome measures were 3-hydroxybutyrate and bicarbonate levels during the 24 h after attainment of near-normoglycemia. RESULTS: After near-normoglycemia, correction of hyperketonemia was achieved earlier with the extended treatment (5.9 +/- 0.8 vs. 21.8 +/- 3.4 h, P = 0.0004 [mean +/- SD]). The area under the curve of 3-hydroxybutyrate against time for 24 h after near-normoglycemia was reduced with the extended treatment (24.9 +/- 3.8 vs. 55.9 +/- 6.7 mmol.l-1.h-1, P = 0.001). These differences remained statistically significant after adjustment for higher baseline levels of 3-hydroxybutyrate at near-normoglycemia in the extended treatment group. Bicarbonate levels at 6 and 12 h after near-normoglycemia were not significantly different between groups. CONCLUSIONS: The extended insulin regimen, which was easy to implement at ward level, produced a more rapid resolution of ketosis than the conventional regimen.

3-Hydroxybutyric Acid↗

Continuous-processing--related event-related potentials in children with attention deficit hyperactivity disorder.

Visual information processing in children with attention deficit hyperactivity disorder (ADHD) was studied using event-related potentials recorded during two versions of the Continuous Performance Task (CPT). ADHD children made more errors, and had longer reaction times than normal children on both the single- and dual-target CPT. Event-related potential waveforms were normal in the ADHD children with reference to early processing stages, i.e., contingent negative variation, P1-N1 laterality, and processing negativities, suggesting that ADHD children did not differ in their level of preparedness or their ability to mobilize resources for target identification and categorization. With respect to later processing, P3 amplitude was reduced in the ADHD group, whereas P3 latency was longer than normal. ADHD children had a diminished late frontal negative component, suggestive of reduced involvement in postdecisional processing.

Adolescent↗

CD14-independent responses to LPS require a serum factor that is absent from neonates.

Monocytes/macrophages and neutrophils can respond to endotoxin via a high-affinity receptor (CD14), requiring low levels of LPS (< 1 ng/ml) as well as through another pathway(s) that requires high levels of LPS (> 10 ng/ml). Both pathways result in the secretion of high levels of cytokines, such as TNF-alpha, and the up-regulation of various other effector molecules. To further define the activation of cells by LPS via a pathway that does not involve CD14, we have used an experimental model that distinguishes CD14-dependent from CD14-independent responses using saturating amounts of an anti-CD14 Ab to block the CD14-dependent response. Analysis of the ability of various individuals to respond to LPS via via both the CD14-dependent and CD14-independent pathways shows that adults can respond via both pathways; furthermore, in the presence of 100 ng of LPS/ml, the primary response is CD14 independent. In contrast to the response by adults, neonates can only respond via the CD14-dependent pathway. Further analysis has shown that the CD14-independent pathway requires a non-CD14 plasma protein present in adult plasma that is either missing or nonfunctional in neonate (cord) plasma.

Adult↗

A comparison of the effects of low- and conventional-dose thiazide diuretic on insulin action in hypertensive patients with NIDDM.

In conventional doses, thiazide diuretics impair glucose tolerance and decrease insulin sensitivity, making them an unpopular choice for treating diabetic patients with hypertension. However, use of low-dose thiazide diuretics may avoid the adverse metabolic effects seen with conventional doses. In a double-blind, randomised crossover study we assessed peripheral and hepatic insulin action in 13 hypertensive non-insulin-dependent diabetic patients after a 6-week placebo run-in and following two 12-week treatment periods with either low (1.25 mg) or conventional (5.0mg) dose bendrofluazide. There were no differences between doses in their effects on systolic and diastolic blood pressure. Bendrofluazide 1.25 mg had significantly less effect on serum potassium, uric acid, fasting glucose and HbA1C concentrations than the 5.00 mg dose. Exogenous glucose infusion rates required to maintain euglycaemia were significantly different between doses (p < 0.05) with conventional-dose bendrofluazide worsening peripheral insulin resistance compared to baseline (23.8 +/- 2.9 vs 27.3 +/- 3.5 mumol.kg-1.min-1, p < 0.05) and low-dose bendrofluazide producing no change compared to baseline (26.8 +/- 3.6 vs 27.3 +/- 3.5 mumol.kg-1.min-1, p = NS). Postabsorptive endogenous glucose production was higher on treatment with bendrofluazide 5.0 mg compared to 1.25 mg (11.7 +/- 0.5 vs 10.2 +/- 0.3 mumol.kg-1.min-1, p < 0.05) and suppressed to a lesser extent following insulin (4.0 +/- 0.7 vs 2.0 +/- 0.4 mumol.kg-1.min-1, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

World Wide Web resources for the biologist.

The World Wide Web is currently the major networking resource for biologists. It has passed Gopher and simple electronic mail (email) servers in popularity. In the 1990s, the advent of client-server software will be the main driving force in bioinformatics. During the past few years, biologists have used the Internet increasingly to distribute data, and the methods of doing this have become more and more sophisticated as the speed with which network links can be made has increased.

Biology↗

A quantitative physiologic model of blood oxygenation for functional magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Variations in venous deoxyhemoglobin levels in response to neuronal activation represent a complex interplay between focal changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and regional metabolism. The authors present a mathematic model that characterizes the response of venous oxygenation to changes in these variables. METHODS: Using a mass balance approach, the equations for a simple input-output model are derived and solved using Matlab. Changes in blood oxygenation are related to available results from functional magnetic resonance imaging experiments. RESULTS: Increases in CBF produce declines in oxygen extraction fraction and venous deoxyhemoglobin according to Fick's law, and are quantitatively in agreement with available magnetic resonance and positron-emission tomography data. A flow-volume envelope defines the changes in CBF relative to CBV. CONCLUSIONS: It is possible to obtain a quantitative understanding of changes in blood oxygenation and to relate these changes to the observed dynamics of magnetic resonance signal change in the setting of functional stimulation.

Algorithms↗

Failure of complete suppression of endogenous glucose production by euglycaemic hyperinsulinaemia in normal humans.

In normal subjects, endogenous glucose production (EGP) is usually assumed to be completely suppressed during euglycaemic clamp studies performed at high insulin levels (> 100 mU L-1). However, this assumption is based on non-steady-state tracer measurements of EGP which are prone to negative errors. We have used purified [6-(3)H]glucose in an optimal tracer infusion protocol to assess the suppression of EGP during 4 h euglycaemic clamps in eight normal men. An insulin infusion rate of 5 mU kg-1 min-1 was chosen to achieve supraphysiological (> 500 mU L-1) plasma insulin concentrations. Using a labelled exogenous glucose infusion, plasma glucose (mean +/- SEM 5.3 +/- 0.1 mmol L-1) and glucose specific activities (mean 100 +/- 3% of basal) were maintained constant from 80 to 240 min. During hyperinsulinaemia, isotopically determined glucose appearance rates (Ra) were greater than glucose infusion rates (GIR) throughout the euglycaemic clamp period (P < 0.001) and EGP (Ra-GIR) was always greater than zero. In seven of the eight subjects studied EGP was partly suppressed but showed a wide variation (EGP 5 to 91% of basal at 80-120 min and 12 to 87% of basal at 200-240 min) while in one subject EGP rose above basal (by 72% at 80-120 min and 49% at 200-240 min). We conclude that EGP is not completely suppressed during euglycaemic clamps at high insulin levels.

Adult↗

Can we prevent accidental injury to adolescents? A systematic review of the evidence.

OBJECTIVES: As part of the Department of Health strategy The Health of the Nation, a systematic review of published and unpublished literature relating to the effectiveness of interventions in reducing accidental injury in the population aged 15-24 years was carried out. METHODS: The literature was reviewed under the standard setting headings of road, work, home, and sports and leisure, and graded for quality of evidence and strength of recommendation using a scale published in the UK national epidemiologically based needs assessment programme. RESULTS: The most effective measures appear to be legislative and regulatory controls in road, sport, and workplace settings. Environmental engineering measures on the road and in sports have relatively low implementation costs and result in fewer injuries at all ages. There is little evidence that purely educational measures reduced injuries in the short term. Community based approaches may be effective in all age groups, and incentives to encourage safer behaviour hold promise but require further evaluation. The potential of multifactorial approaches seems greater than narrowly based linear approaches. CONCLUSIONS: Few interventions to reduce injury in adolescents have been rigorously evaluated using good quality randomised controlled trials, and where such evidence is available, fewer have been shown to be definitely worthwhile. Many studies relied on surrogate measures rather than actual injury rates, and substantial issues relating to the efficacy or implementation of preventive measures in adolescent and young adult populations remain unresolved.

Accident Prevention↗

Effects of low dose versus conventional dose thiazide diuretic on insulin action in essential hypertension.

OBJECTIVE: To see whether low dose thiazide diuretics given to patients with essential hypertension might avoid the adverse metabolic consequences seen with conventional doses. DESIGN: Double blind randomised crossover study of two 12 week treatment periods with either low dose (1.25 mg) or conventional dose (5.0 mg) bendrofluazide given after a six week placebo run in period. SETTING: Outpatient clinics serving the greater Belfast area. SUBJECTS: 16 white non-diabetic patients (9 male) under 65 with essential hypertension recruited from general practices within the greater Belfast area. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure and peripheral and hepatic insulin action. RESULTS: One man failed to complete the study. There were no differences between doses in their effects on systolic and diastolic blood pressure. Bendrofluazide 1.25 mg had substantially less effect on serum potassium concentration than the 5.0 mg dose. There were no intertreatment differences in fasting glucose, insulin, cholesterol, and triglyceride concentrations. Bendrofluazide 5.0 mg significantly increased postabsorptive endogenous glucose production compared with baseline (mean 10.9 (SD 1.2) v 10.0 (0.8) mumol/kg/min), whereas bendrofluazide 1.25 mg did not. Postabsorptive endogenous glucose production was significantly higher with bendrofluazide 5.0 mg compared with 1.25 mg (10.9 (1.2) v 9.9 (0.8) mumol/kg/min) but was suppressed to a similar extent after insulin (bendrofluazide 5.0 mg 2.8 (1.5) mumol/kg/min v bendrofluazide 1.25 mg 2.2 (1.5) mumol/kg/min). Exogenous glucose infusion rates required to maintain euglycaemia were not significantly different between doses and were similar to baseline. CONCLUSIONS: Bendrofluazide 1.25 mg is as effective as conventional doses but has less adverse metabolic effect. In contrast with conventional doses, low dose bendrofluazide has no effect on hepatic insulin action. There is no difference between low and conventional doses of bendrofluazide in their effect on peripheral insulin sensitivity.

Bendroflumethiazide↗

Prenatal evaluation and in utero platelet transfusion for thrombocytopenia absent radii syndrome.

A fetus with absent radii in both forearms was discovered on routine ultrasound examination performed at 18 weeks of pregnancy. No other significant abnormalities were found, and no signs of haemorrhage were detected. Serial ultrasound examinations revealed no evidence of fetal internal bleeding. At 37 weeks of pregnancy, a CBC obtained by cordocentesis under ultrasound guidance confirmed the diagnosis of thrombocytopenia absent radii (TAR) syndrome. Apheresis platelets were transfused into the umbilical vein to correct the thrombocytopenia and was followed by an uncomplicated delivery. No bleeding was encountered during the remainder of the baby's neonatal course. We conclude that TAR syndrome can be readily identified prenatally on sonogram, and if severe thrombocytopenia is confirmed by cordocentesis, platelets should be transfused to diminish the risk of serious internal bleeding during and immediately after delivery.

Adult↗

Access to DNA and protein databases on the Internet.

During the past year, the number of biological databases that can be queried via Internet has dramatically increased. This increase has resulted from the introduction of networking tools, such as Gopher and WAIS, that make it easy for research workers to index databases and make them available for on-line browsing. Biocomputing in the nineties will see the advent of more client/server options for the solution of problems in bioinformatics.

Amino Acid Sequence↗

Detection of psychiatric disorders in elderly medical inpatients.

In a psychiatric census of a 196-bed acute inpatient Medicine for the Elderly unit, 76.1% of patients resident during 1 week were screened and interviewed in a two-stage diagnostic procedure. Of 153 patients studied, 11.1% were delirious, 26.8% were demented, and 9.2% were depressed. Overall, 56.9% of the cases were identified by ward nurses, and 55.5% by the ward doctors; taken together, ward staff identified 75.0% of the cases (kappa = 0.46), indicating that detection of psychiatric disorder in this population might be improved if doctors and nurses pooled their observations on this aspect of patient assessment.

Aged↗