Search PubMed⌕ Search

Biomedical subjects

N D Harris

Publications and source records attributed to N D Harris.

At least 19 recordsLinked to original sources
PubMed2005

Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes.

AIMS/HYPOTHESIS: Hypoglycaemia is associated with heart rate-corrected QT (QTc) interval lengthening on the ECG; this may be important in the pathogenesis of sudden overnight death in young people with diabetes. Since hypoglycaemic QTc lengthening appears to be mediated through the sympathoadrenal response, we tested the hypothesis that beta1-blockade will prevent these changes in type 1 diabetic patients and so provide a potential therapeutic intervention. METHODS: We studied eight type 1 diabetic adults without cardiovascular or renal complications. Similar hypoglycaemic clamp studies were performed on two occasions, at least 4 weeks apart, but immediately before one visit subjects received atenolol 100 mg daily for 7 days. Following a 60-min euglycaemic (5 mmol/l) period, blood glucose was lowered over 30 min to 2.5 mmol/l, and held for 60 min. High-resolution ECG was recorded at baseline and at 0, 30 and 60 min during each glycaemic plateau. QT interval was measured using a semiautomated tangent method and QTc was derived from QT using the Fridericia formula. RESULTS: Mean (SD) baseline QTc was similar at both visits: control 391 (30) ms, post-atenolol 386 (34) ms; (p=0.33). Without atenolol pretreatment, QTc lengthened during hypoglycaemia to a maximum of 448 (34) ms (p<0.001). On atenolol, QTc lengthening was significantly reduced (peak QTc 413 (27) ms; p=0.004 vs control visit). CONCLUSIONS/INTERPRETATION: Hypoglycaemic QTc lengthening is blunted by atenolol in patients with type 1 diabetes. Selective beta1-blockade may help prevent sudden death, if we can identify those at high risk.

Adrenergic beta-Antagonists↗
PubMed2005

Position-sensing technologies for movement analysis in stroke rehabilitation.

Research has focused on improvement of the quality of life of stroke patients. Gait detection, kinematics and kinetics analysis, home-based rehabilitation and telerehabilitation are the areas where there has been increasing research interest. The paper reviews position-sensing technologies and their application for human movement tracking and stroke rehabilitation. The review suggests that it is feasible to build a home-based telerehabilitation system for sensing and tracking the motion of stroke patients.

Biomechanical Phenomena↗
PubMed2004

Prolonged cardiac repolarisation during spontaneous nocturnal hypoglycaemia in children and adolescents with type 1 diabetes.

AIMS/HYPOTHESIS: It has been postulated that hypoglycaemia-related cardiac dysrhythmia and, in particular, prolonged cardiac repolarisation, may contribute to increased mortality rates in children and adolescents with type 1 diabetes. METHODS: We examined the prevalence of prolonged QT interval on ECG during spontaneous hypoglycaemia in 44 type 1 diabetic subjects (aged 7-18 years), and explored the relationships between serial overnight measurements of QT interval corrected for heart rate (QTc) and serum glucose, potassium and epinephrine levels. Each subject underwent two overnight profiles; blood was sampled every 15 min for glucose measurements and hourly for potassium and epinephrine. Serial ECGs recorded half-hourly between 23.00 and 07.00 hours were available on 74 nights: 29 with spontaneous hypoglycaemia (defined as blood glucose <3.5 mmol/l) and 45 without hypoglycaemia. RESULTS: Mean overnight QTc was longer in females than in males (412 vs 400 ms, p=0.02), but was not related to age, diabetes duration or HbA(1)c. Prolonged QTc (>440 ms) occurred on 20 out of 74 (27%) nights, with no significant differences between male and female subjects, and was more prevalent on nights with hypoglycaemia (13/29, 44%) than on nights without (7/45, 15%, p=0.0008). Potassium levels were lower on nights when hypoglycaemia occurred (minimum potassium 3.4 vs 3.7 mmol/l, p=0.0003) and were inversely correlated with maximum QTc (r=-0.40, p=0.03). In contrast, epinephrine levels were not higher on nights with hypoglycaemia and were not related to QTc. CONCLUSIONS/INTERPRETATION: In young type 1 diabetic subjects, prolonged QTc occurred frequently with spontaneous overnight hypoglycaemia and may be related to insulin-induced hypokalaemia.

Adolescent↗
PubMed2004

Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with Type 1 diabetes.

AIMS/HYPOTHESIS: Experimental hypoglycaemia leads to abnormal cardiac repolarization manifest by a lengthened QT interval and caused by adrenergic stimulation. However it is less clear whether spontaneous clinical episodes lead to similar changes. We have therefore measured cardiac ventricular repolarization and counterregulatory responses in patients with Type 1 diabetes during hypoglycaemic and euglycaemic nights. METHODS: We studied 22 patients with Type 1 diabetes (mean age 40.4+/-17.2 years, duration of diabetes 17.2+/-9.3 years, HbA1c 8.2+/-1.2% overnight). Measurements were taken hourly of blood glucose, plasma potassium, catecholamines and high resolution electrocardiograms. RESULTS: Hypoglycaemia (blood glucose level <2.5 mmol/l) occurred on 7 of the 22 nights. During overnight hypoglycaemia, QTc interval increased by 27 ms (+/-15) above baseline, compared with 9 ms (+/-19) during nights with no nocturnal hypoglycaemia (p=0.034, 95%CI 2, 35). Adrenaline increased by 0.33 nmol/l (+/-0.21) above baseline during hypoglycaemia, compared with -0.05 nmol/l (+/-0.08) during euglycaemia (p=0.001, 95%CI 0.19, 0.56 nmol/l). There was no significant difference between potassium, and noradrenaline concentrations between the two groups. CONCLUSION/INTERPRETATION: QTc interval lengthens significantly during spontaneous nocturnal hypoglycaemia. Increases are generally less than those observed during experimental hypoglycaemia and could reflect attenuated sympathoadrenal responses during clinical episodes. The clinical relevance of these changes is uncertain but is consistent with the hypothesis that clinical hypoglycaemia can cause abnormal cardiac repolarization and an attendant risk of cardiac arrhythmia.

Adult↗
PubMed2003

Increased sural nerve epineurial blood flow in human subjects with painful diabetic neuropathy.

AIMS/HYPOTHESIS: The pathogenesis of painful diabetic neuropathy remains unknown. As a consequence we still do not have any effective, rational treatments and a greater understanding of the mechanisms is urgently required. Previous studies have shown no consistent morphological differences in the nerves of patients with and without painful neuropathy. The aim of this study was to compare epineurial haemodynamics in patients with chronic painful and painless neuropathy. METHODS: The techniques of microlightguide spectrophotometry and fluorescein angiography were used to measure epineurial intravascular oxygen saturation and blood flow respectively. Eleven patients with painful and eight with painless neuropathy were studied, with the groups matched carefully in terms of severity of neuropathy and diabetes control. RESULTS: Intravascular oxygen saturation was higher in the painful neuropathy group compared to those without pain (median 73.8% vs 67.7%, respectively; p=0.021). Fluorescein rise time was also faster in those with painful symptoms (median 18.3 s vs 53.6 s; p=0.046) indicating higher epineurial blood flow in these subjects. CONCLUSION/INTERPRETATION: These results indicate that there are distinct differences in haemodynamics within the epineurium of the sural nerve in subjects with painful and painless neuropathy. Haemodynamic factors could therefore have an important role in the pathogenesis of neuropathic pain and might offer further insight into potential treatments for this distressing condition.

Blood Flow Velocity↗
PubMed2003

Effects of adrenaline and potassium on QTc interval and QT dispersion in man.

BACKGROUND: Hypoglycaemia alters cardiac repolarization acutely, with increases in rate-corrected QT (QTc) interval and QT dispersion (QTd) on the electrocardiogram (ECG); such changes are related to the counterregulatory sympatho-adrenal response. Adrenaline produces both QTc lengthening and a fall in plasma potassium (K+) when infused into healthy volunteers. Hypokalaemia prolongs cardiac repolarization independently however, and therefore our aim was to determine whether adrenaline-induced repolarization changes are mediated directly or through lowered plasma K+. MATERIALS AND METHODS: Ten healthy males were studied on two occasions. At both visits they received similar l-adrenaline infusions but on one occasion potassium was also administered; infusion rates were adjusted to maintain circulating K+ at baseline. The QTc interval, QTd, peripheral physiological responses and plasma adrenaline and potassium concentrations were measured during both visits. RESULTS: The QTc interval and QTd increased both with and without potassium clamping. Without K+ replacement, mean (SE) QTc lengthened from 378 (5) ms to a final maximum value of 433 (10) ms, and QTd increased from 36 (5) ms to 69 (8) ms (both P < 0.001). During K+ replacement, QTc duration at baseline and study end was 385 (7) ms and 423 (11) ms, respectively (P < 0.001), and QTd 38 was (4) ms and 63 (5) ms (P = 0.001). CONCLUSIONS: These data suggest that disturbed cardiac repolarization as a result of increases in circulating adrenaline occurs independently of extracellular potassium. A direct effect of adrenaline upon the myocardium appears the most likely mechanism.

Adult↗
PubMed2001

Spinal-cord involvement in diabetic peripheral neuropathy.

The pathogenesis of diabetic distal symmetrical polyneuropathy (DSP) is poorly understood but there is some evidence that the disease process might extend beyond peripheral nerves. We used magnetic-resonance imaging to measure spinal-cord cross-sectional area in diabetic patients with and without DSP and in healthy controls. There were significant differences in cord area between the groups at C4/5 and T3/4 (p=0.004 and p=0.033, respectively), with a smaller cord area in those with DSP compared with controls (p=0.001 and p=0.016 for C4/5 and T3/4, respectively). These results indicate that DSP is not simply a disease of the peripheral nerve and that there is substantial involvement of the spinal cord.

Adult↗
PubMed2000

Diuretic induced change in lung water assessed by electrical impedance tomography.

Monitoring patients with left ventricular failure can be difficult. Electrical impedance tomography (EIT) produces cross-sectional images of changes in the impedance of the thorax. We measured changes in the electrical impedance of the lung in nine volunteers following a diuretic challenge. The hypothesis was that lung impedance would increase with diuretic induced fluid loss. Heart rate, blood pressure and urine output were also recorded. After diuretic the mean urine output was 1220 ml compared with 187 ml after placebo. Following diuretic administration, mean thoracic impedance increased by 13.6% (p < 0.01) and lung impedance increased by 7.8% (p < 0.05). Taken as a group there was a correlation between overall impedance change and total urine output. However, for each individual, the time course of change in impedance and urine output did not correlate significantly. Our findings show that EIT may offer a better guide to the response of the lung to diuretic treatment than simply measuring urine output. The urine output is neither specific nor sensitive in the assessment of lung water. Mean lung impedance, however, is largely determined by lung water. The study showed that lung impedance can be recorded at supra-normal values. EIT may help in the management of patients with excess lung water.

Adolescent↗
PubMed2000

Measurement of high resolution ECG QT interval during controlled euglycaemia and hypoglycaemia.

During hypoglycaemia, typically there is a change in the surface ECG characterized by a flattened and prolonged T wave, often accompanied by a fused U wave. The QT interval is a useful parameter for quantifying the ECG morphology. However, reliable measurement of QT is not straightforward, particularly for hypoglycaemic ECG morphology. The objective of this study was to compare the ability of two methods of QT measurement to distinguish between ECGs recorded during euglycaemia and hypoglycaemia. The first method involves manually setting the intersection of the isoelectric line and the T wave or, where this is not possible, the nadir between the T and U wave. The second method is semi-automatic and fits a tangent to the point of maximum gradient on the downward slope of the T wave. Two independent observers used both methods to measure the QT for high resolution ECG data recorded during a study of 17 non-diabetic subjects undergoing controlled euglycaemia and hypoglycaemia. Using the mean results of the two observers, the mean +/- SD increase in heart rate corrected QT, QTc, for ECGs recorded during euglycaemia and hypoglycaemia was 32 +/- 25 ms for the non-tangent method and 60 +/- 24 ms for the tangent method. Therefore, the tangent method provides greater distinction between ECGs recorded during euglycaemia and hypoglycaemia than the non-tangent method. A potential clinical application could be the non-invasive detection of impending hypoglycaemia at night, which would be of significant benefit to adults and young children with diabetes.

Adult↗
PubMed2000

The Black Sea Tele-Diab System: development-implementation-clinical evaluation.

This paper describes the application of the GEHR (Good European Health Record) architecture to develop a system to enable the storage and exchange of EHCRs (Electronic Health Care Record) of patients with diabetes, in the Black Sea area. The objectives of the Black Sea Tele Diab System (BSTD) were to develop and evaluate the use of a fully-computerised healthcare record system in a clinical setting, to promote the use of electronic data exchange of healthcare information and to provide a framework for the epidemiological study and monitoring of diabetes care.

Diabetes Mellitus↗
PubMed1999

The potential effect on hip fracture incidence of mass screening for osteoporosis.

With ageing of the Australian population, treatment of osteoporosis-related hip fractures will impose an increasing burden on the healthcare system. Based on current age-adjusted hip fracture incidence and population projections for New South Wales, we estimated a 90% increase in hip fractures by the year 2021. Contributing significantly to this increase will be the number of men reaching the high risk age group for osteoporotic hip fractures. A suggested solution--screening and appropriate therapy for individuals at high risk of osteoporosis--may have only a modest impact. Our calculations show that, even with optimistic screening and therapy compliance rates, hip fractures could still increase by over 50%. Other approaches need to be further explored.

Aged↗
PubMed1999

A new minimally invasive technique to show nerve ischaemia in diabetic neuropathy.

AIMS/HYPOTHESIS: Experimental studies have shown that abnormalities of nerve microcirculation are important factors in the pathogenesis of diabetic neuropathy but there have been few clinical studies. We have applied microlightguide spectrophotometry to measure intravascular oxygen saturation (HbO2%) and blood flow in human sural nerve. METHODS: We studied ten patients with mild-moderate sensory motor diabetic neuropathy, nine patients without neuropathy and nine control subjects. We took 300 measurements of oxygen saturation under direct visual control through a 1.9 mm rigid endoscope over three regions of the nerve. Spectrophotometric measurements of nerve fluorescence were taken after an intravenous injection of sodium fluorescein and the rate of increase in nerve fluorescence (rise time) was used as an indicator of nerve blood flow. RESULTS: Nerve oxygen saturation was reduced in patients with neuropathy compared with control subjects (67.1 +/- 2.2% vs 76.7 +/- 2.1%, p = 0.006). Fluorescein rise time was prolonged in patients with neuropathy compared with the control group (48.5 +/- 7.0 s vs 14.0 +/- 3.1 s, p = 0.001) suggesting impaired nerve blood flow. There was a correlation between rise time, nerve oxygen saturation, glycaemic control and sural nerve sensory conduction velocity (p < 0.01). CONCLUSION/INTERPRETATION: The combination of microlight-guide spectrophotometry and micro-endoscopy provides a valuable minimally invasive technique for clinical investigation of nerve microcirculation. We have shown reduced nerve oxygenation and impaired blood flow in diabetic neuropathy and these findings strongly support a central role of microvascular disease in the pathogenesis of diabetic neuropathy.

Diabetic Neuropathies↗
PubMed1999

Monitoring patients with left ventricular failure by electrical impedance tomography.

Acute left ventricular failure (LVF) is a common medical emergency but detection and monitoring of pulmonary oedema remains problematic. Fluid is an important determinant of tissue impedance. Electrical impedance tomography (EIT) is a non-invasive technique allowing localisation of impedance changes within tissue. We have investigated the relationship between LVF and the electrical impedance of lung tissue. Twenty patients with a clinical diagnosis of acute left ventricular failure were compared with 30 normal subjects. Patients were monitored using serial chest radiographs and electrical impedance tomography measurements of lung impedance during hospital admission. Radiographs were graded according to the severity of pulmonary oedema by two independent radiologists. Lung impedance was significantly (P<0.0001) lower than normal in patients with left ventricular failure. Values returned towards the normal range as LVF resolved. There was a similar improvement in the score of the chest radiographs. The electrical impedance of the lung is low in left ventricular failure and increases following treatment.

Acute Disease↗
PubMed1999

Digital imaging: an accurate and easy method of measuring foot ulcers.

AIMS: A progressive reduction in the area of foot ulcer on serial measurement is traditionally done by tracing the margin of the ulcer on a transparent film and counting the number of squares on a graph paper underneath. We set out to use and validate the measurement of foot ulcers using a digital imaging technique and compare this with the traditional method. METHODS: Thirty diabetic foot ulcers (18 patients) were studied over 10 weeks. Each ulcer was traced by three independent observers with a pen over a flexigrid Opsite film and digital photographs were taken. Each observer calculated the area of an ulcer first using a 1-mm2 graph paper and then with the computer software. For each ulcer we calculated the mean area using measurements from all the observers. We then calculated the deviation from this mean for each observer. RESULTS: There was significantly less interobserver variation using the digital image than the traditional method with mean coefficient of variation (CV) 16% vs. 27%; P = 0.05. CONCLUSIONS: The digital imaging method was faster and easier to use and the patients preferred it, as it was a noncontact method. In addition it also provides a photographic record for comparison.

Diabetic Foot↗
PubMed1999

Combined microlightguide spectrophotometry and microendoscopy for measurement of oxygen saturation in peripheral nerves.

Microlightguide measurements of the spectral composition of backscattered light may be used to determine local tissue oxygen saturation and monitor tissue perfusion using intravenous injection of fluorescein dye as a contrast agent. We have used a combination of microlightguide spectrophotometry and microendoscopy to measure intravascular oxygen saturation (HbSaO2%) and monitor blood flow in the sciatic nerve of 12 healthy male Sprague-Dawley rats. The microlightguide and endoscope combination is a relatively new measurement technique. The aims of this study were to determine whether microlightguide spectrophotometry and microendoscopy could be used to measure HbO2 and blood flow in peripheral nerves and to compare the measurements made using the flexible lightguide with the endoscope-lightguide combination. We found no significant difference between the two types of measurement over similar regions of the nerve. mean SaO2% values 77.1% (95% CI = 75.4-78.8) and 78.8% (95% CI = 77.5-80.1) respectively. During a period of hypoxia there was a similar fall in both arterial and nerve oxygen saturation. Following injection of fluorescein, the rate of increase in nerve fluorescence was used as a measure of perfusion. The combination of microlightguide spectrophotometry and microendoscopy allows the exact site of measurement to be directly visualized. The minimally invasive nature of this technique may allow its application to the study of peripheral nerves in human subjects in conditions such as diabetic neuropathy where vascular factors are thought to have an important role in aetiology.

Animals↗