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Biomedical subjects

J E Tooke

Publications and source records attributed to J E Tooke.

At least 19 recordsLinked to original sources
PubMed1997

Relationship of insulin resistance to microvascular dysfunction in subjects with fasting hyperglycaemia.

Microvascular hyperaemia is decreased in subjects at risk of developing non-insulin-dependent diabetes mellitus (NIDDM) who have fasting hyperglycaemia. Such microvascular abnormalities may be involved in the pathogenesis of diabetic microangiopathy. To investigate the relationship of reduced microvascular hyperaemia to metabolic and blood pressure abnormalities associated with the prediabetic state, we studied 24 subjects with fasting hyperglycaemia and 24 age- and sex-matched control subjects. The microvascular hyperaemic response to local heating of the skin on the dorsum of the foot measured by laser Doppler fluximetry was reduced in the subjects with fasting hyperglycaemia (1.18 [0.87-1.83] volts vs 1.51 [1.30-2.14] volts normal subjects; p = 0.0002) and was negatively correlated with fasting plasma insulin concentration (Rs = 0.70; p = 0.001) and positively related to insulin sensitivity determined by continuous infusion of glucose with model assessment (CIGMA) (Rs = 0.52; p = 0.01), but showed no association with fasting plasma glucose, beta-cell function 24 h ambulatory blood pressure profiles or serum lipid concentrations. These results suggests that hyperinsulinaemia, as a result of insulin resistance, may have a detrimental effect on microvascular function in the prediabetic state.

Adult↗
PubMed1997

Capillary filtration coefficient and urinary albumin leak at altitude.

Rapid ascent to altitude risks the development of acute mountain sickness. This study demonstrates changes in peripheral capillary filtration coefficient and renal protein loss in subjects suffering from various degrees of mountain sickness after passive ascent to 4559 m. Capillary filtration coefficient of the calf capillary bed, measured by computer-based multistep strain gauge plethysmography, increased significantly after 23.5 h at altitude when symptoms were most severe: 4.45 (2.76-6.03) to 6.31 (3.86-11.07) ml min(-1) per 100 g of tissue mmHg(-1), median (range) (P < 0.02). Urinary albumin excretion was increased after one night at altitude from 1.1 (0.6-1.5) to 2.45 (1.0-6-8) mg of albumin per mmol of creatinine (P < 0.05). These results demonstrate simultaneous leakage of a peripheral capillary bed to fluid measured by strain gauge plethysmography, and renal albumin leak, and suggest a systemic process of increased capillary leakage for different-sized molecules caused by rapid exposure to hypobaric hypoxia.

Adult↗
PubMed1996

Skin capillary density in subjects with impaired glucose tolerance and patients with type 2 diabetes.

In view of recent interest in the role of impaired early development and the pathogenesis of cardiovascular disease and carbohydrate intolerance in adults, this study examines whether reduced skin capillary density contributes to the limited microvascular hyperaemic responses observed in patients with Type 2 diabetes and subjects with impaired glucose tolerance (IGT). Fifteen patients with Type 2 diabetes, 15 subjects with IGT and 15 matched non-diabetic control subjects were studied. Capillary videomicroscopy was used to record images of the skin capillaries on the dorsum of the middle phalanx of the left middle finger before and after 10 min venous occlusion at 35 mmHg. There were no significant differences between the three groups in either basal capillary density (112 (71-144) caps mm-2 Type 2 patients (median and range) vs 107 (76-140) caps mm-2 IGT subjects vs 112 (76-138) caps mm-2 control subjects; p = 0.9, Kruskal Wallis), or following venous occlusion (122 (87-157) caps mm-2 vs 121 (90-143) caps mm-2 vs 123 (81-147) caps mm-1; p = 0.9). In addition there were no differences in blood pressure, BMI or skin temperature. These results do not support the concept of impaired early development of the skin microcirculation in patients with Type 2 diabetes or IGT and suggest that mechanisms other than reduced capillary density are involved in limiting microvascular vasodilation.

Adult↗
PubMed1996

Magnetic resonance imaging reveals micro-haemorrhage in the feet of diabetic patients with a history of ulceration.

Soft tissue haemorrhage in the foot is a possible precursor of ulceration in patients with diabetic peripheral neuropathy. High resolution 'targetted' magnetic resonance imaging was used to scan the forefoot. Neuropathic patients with and without previous ulceration were matched for degree of neuropathy, mean vibration perception threshold 33.5 +/- 4.2 V (previous ulcer) vs 31.0 +/- 6.9 V (no ulcer), age, sex, and duration of diabetes against non-neuropathic controls. There were nine patients in each category. Paramagnetic materials, e.g. iron compounds, cause a signal void ('drop-out') on gradient-echo images which disappear on spin-echo images. Evidence of haemorrhage was seen in 6 patients with previous ulceration, and none in the other groups (p = 0.009, chi square test). Autologous injection of 20 microliters of blood into the foot of a healthy volunteer produced similar images, a 'drop-out' 1 cm across being visible on magnetic resonance scanning 3 days later. Peak vertical forefoot pressures were not significantly different in the neuropathic groups 0.67 +/- 0.20 vs 0.60 +/- 0.13 Pa but were lower in the non-neuropathic group, 0.43 +/- 0.11 Pa (p = 0.0004, Mann-Whitney), and do not explain the appearance of these haemorrhages. Magnetic resonance imaging provides a sensitive way of detecting micro-haemorrhage and its presence may predict an increased risk of foot ulceration.

Blood Pressure↗
PubMed1996

Microvascular functional abnormalities in diabetes: the role of the endothelium.

The development of techniques for measuring microvascular pressure, flow and permeability in man has allowed the construct of a pathophysiological framework for the development of diabetic microangiopathy. In insulin dependent disease the abnormalities observed conform to the haemodynamic hypothesis with early elevation of capillary pressure playing a primary role. In non insulin dependent diabetes differences are apparent, supporting the concept that changes in microvascular vasodilatory mechanisms may antedate the emergence of diabetes. Given the crucial role played by the endothelium in the regulation of local microvascular haemodynamics it is not surprising that disturbance of this tissue has been implicated in the pathogenetic process, an assertion supported by mounting experimental evidence suggesting that the nitric oxide pathway is crucially involved.

Diabetes Mellitus, Type 1↗
PubMed1996

Peripheral microvascular disease in diabetes.

In recent years a variety of techniques have been developed for studying peripheral microvascular function in man, which have provided important information regarding the functional breakdown of the microcirculation in diabetes mellitus. In insulin dependent diabetes a sequence of physiological changes have been described which support the so-called haemodynamic hypothesis: control-dependent increases in capillary pressure result in microvascular sclerosis leading to limitation of hyperaemia and loss of autoregulation. Furthermore, capillary pressure appears to be especially raised in patients with incipient nephropathy who are at particular risk of microangiopathy. The limitation of maximum hyperaemia is duration related, may be observed in early childhood, and is correlated with the degree of basement membrane thickening. In contrast in normotensive non-insulin dependent patients a different array of functional disturbances are described: Capillary pressure and capillary filtration coefficient are normal whereas maximum hyperaemia is profoundly depressed even at diagnosis. This differential pattern of abnormalities arguably reflects the impact of a prediabetic insulin resistant phase on the subsequent expression of microangiopathy. An understanding of the physiological breakdown of the microcirculation in diabetes permits the generation of plausible candidate cellular and molecular mechanisms, knowledge of which will accelerate the development of protective therapy.

Blood Pressure↗
PubMed1996

Differences in microvascular fluid permeability between long-duration type I (insulin-dependent) diabetic patients with and without significant microangiopathy.

1. To further investigate the role of microvascular functional changes in the pathogenesis of diabetic microangiopathy in type 1 diabetes, microvascular fluid permeability was measured in nine patients with a long disease duration and no or minimal (background retinopathy alone) microangiopathy, nine age-, sex- and duration-matched patients with microalbuminuria and nine control subjects. Microvascular fluid permeability was assessed by determination of the forearm capillary filtration coefficient using a sensitive strain-gauge plethysmographic technique. 2. Microvascular fluid permeability was significantly higher in the patients with microalbuminuria [8.5 (6.8-15.2) x 10(-3)ml min-1 100g-1 of tissue mmHg-1; median (range)] than in the patients with no or minimal complications [5.2 (3.6-7.0) x 10(-3) ml min-1 100g-1 of tissue mmHg-1, P < 0.001]. There was, however, no significant difference in microvascular fluid permeability between the patients with no or minimal complications and control subjects [4.5 (3.2-5.7) x 10(-3) ml min-1 100g-1 of tissue mmHg-1, P = 0.31]. Blood pressure and glycaemic control were similar in the two groups of diabetic patients. 3. These results provide further evidence that changes in microvascular permeability are found in other vascular beds in patients with incipient nephropathy, whereas no such changes are found in patients with a long disease duration and little evidence of microangiopathy.

Adult↗
PubMed1996

Disturbance of peripheral microvascular fluid permeability by the onset of atrioventricular asynchrony in patients with programmable pacemakers.

BACKGROUND: In vitro and in vivo evidence suggests that atrial natriuretic peptide can enhance fluid flux from intravascular to extravascular compartments. The relevance of this to human pathophysiology remains unclear. OBJECTIVES: To determine whether a central haemodynamic change associated with increased plasma concentrations of atrial natriuretic peptide produces detectable change in the capillary filtration coefficient in a peripheral microvascular bed. PATIENTS: 12 patients with programmable dual chamber permanent pacemakers. METHODS: Calf capillary filtration coefficient (using a modified plethysmographic technique) and plasma atrial natriuretic peptide concentrations were measured during atrioventricular synchronous and ventricular pacing. RESULTS: Atrioventricular asynchrony was associated with higher mean (SD) concentrations of atrial natriuretic peptide (231.9 (123.1) v 53.5 (38.8) pg/ml) and an increased mean (SD) calf capillary filtration coefficient (4.2 (1.1) v 3.6 (1.1) ml/min.mm Hg.100 ml x 10(-3)), but there was no correlation between the magnitude of the change in these variables in individual patients. CONCLUSIONS: The peripheral capillary filtration coefficient may change in response to altered central haemodynamics. Atrial natriuretic peptide remains one potential candidate mechanism, but other factors are also likely to be involved.

Adult↗
PubMed1995

Capillary pressure during and after incremental venous pressure elevation in man.

1. The relationship between capillary pressure and venous pressure was investigated during incremental venous pressure elevation in seven healthy volunteers. Pressure was measured simultaneously at the apex of finger nailfold capillaries and in the dorsal vein of the ipsilateral hand. Elevation of venous pressure was accomplished by inflation of a sphygmomanometer cuff around the upper arm. 2. As venous pressure rose, apical capillary pressure (Pc) approached venous pressure (Pv). For changes in Pv greater than 20 mmHg, the increment in Pc was invariably less than the increment in Pv. 3. Above a cuff pressure of 20 mmHg, capillary pulse pressure amplitude (CPPA) tended to decline. At 50 mmHg cuff pressure, CPPA was lower than at baseline for all subjects. At baseline, CPPA was 4.2 +/- 2.0 mmHg (mean +/- S.D.) and at 50 mmHg it was 2.3 +/- 1.1 mmHg (P = 0.02). 4. In the period between 1 and 6 min following cuff release, both Pc and CPPA were lower than at baseline. (At baseline, Pc was 16.1 +/- 2.3 mmHg and following cuff release it was 11.2 +/- 1.5 mmHg (P = 0.02). At baseline, CPPA was 4.2 +/- 2.0 mmHg and following cuff release it was 1.8 +/- 1.1 mmHg (P = 0.03).) 5. Estimated changes in the ratio of pre- to postcapillary resistance (Ra/Rv), using arterial blood pressure (Pa) measured in the contralateral arm, and taking (Pa-Pc)/(Pc-Pv) to approximate to Ra/Rv, closely mirrored changes in CPPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Responses of the skin microcirculation to acetylcholine and sodium nitroprusside in patients with NIDDM.

The mechanisms involved in the pathogenesis of microangiopathy occurring in non-insulin-dependent diabetes mellitus (NIDDM) are unclear. In the present study, blood flow responses to the vasodilators acetylcholine (which acts via the endothelium) and sodium nitroprusside (a smooth muscle relaxant) were evaluated in this patient group. In 14 male patients with NIDDM, treated with either diet alone (n = 6) or diet plus insulin, (mean age 59 years) and 14 age-pair-matched control subjects, forearm skin perfusion following multiple doses of iontophoretically applied 1% acetylcholine and 0.01% sodium nitroprusside was recorded by laser Doppler perfusion imaging. Basal skin blood flow was not significantly different in the diabetic group compared with the control group. The following results are expressed as drug-minus-vehicle response. Acetylcholine significantly increased forearm skin perfusion (p < 0.001, analysis of variance) in all subjects, but the vasodilatation was attenuated in the patient group compared with control subjects (0.86 +/- 0.09 vs 1.36 +/- 0.14 arbitrary units of volts (V) respectively, at the fifth measurement point, mean +/- SEM, p < 0.01). Skin perfusion significantly increased following sodium nitroprusside (p < 0.001) but was lower in patients than control subjects (0.12 +/- 0.05 vs 0.45 +/- 0.11 V, respectively, at the fifth measurement point, p < 0.01). These data suggest that endothelial and/or smooth muscle function may be impaired in the skin microcirculation of patients with NIDDM.

Acetylcholine↗
PubMed1995

Microvascular function in type 2 (non-insulin-dependent) diabetes: improved vasodilation after one year of good glycaemic control.

Abnormalities of microvascular function may be important in the development of diabetic microangiopathy. The major functional abnormality identified in patients with Type 2 diabetes has been a marked limitation of microvascular vasodilation, which is present from the time of diagnosis. The effects of sustained improvements in glycaemic control on vasodilator capacity in Type 2 diabetes are unknown. Twelve Type 2 diabetic patients were studied prospectively for 1 year after diagnosis. The reduced maximum hyperaemic response to local heating of the foot skin present at the time of diagnosis remained unchanged after 3 months of improved glycaemic control (1.12 +/- 0.56 V at diagnosis vs 1.21 +/- 0.69 V at 3 months, mean +/- SD; p = 0.25), but was improved after 1 year (1.42 +/- 0.91 V; p = 0.04 vs 3 months). The percentage increase in maximum hyperaemia correlated with the percentage decrease in HbA1c (rs = 0.53, p = 0.04). These results suggest that the early microvascular abnormalities demonstrated in Type 2 diabetes are potentially reversible and provide a further reason for striving for optimal glycaemic control in this patient group.

Adult↗
PubMed1995

Diabetic neuropathy and the microcirculation.

There is a close relationship between the abnormal microcirculation in diabetic subjects and diabetic neuropathy. Neurogenic factors play a prominent role in the regulation of the microcirculation. In diabetic neuropathy, damage to these mechanisms results in a profound haemodynamic disturbance with increased arteriovenous shunting, abnormal postural regulation of blood flow, and abnormal inflammatory responses to tissue injury. Abnormal neurogenic regulation of microvascular haemodynamics may contribute to the development of microangiopathy manifest as increased basement thickening and both are undoubtedly implicated in the pathogenesis of diabetic foot ulceration. In turn it is now recognized that microvascular abnormalities may contribute to the ischaemic aetiology of diabetic neuropathy.

Autonomic Nervous System↗
PubMed1995

A report on the use of technician ophthalmoscopy combined with the use of the Canon non-mydriatic camera in screening for diabetic retinopathy in the community.

This paper describes a general practice based diabetic retinopathy screening service employing a technician trained in direct and indirect ophthalmoscopy and taking photographs with a Canon CR3 45 NM non-mydriatic polaroid camera analysed by a consultant ophthalmologist to provide a comparison with the screener's opinion. Prospective data is presented from the first 1050 patients screened for diabetic retinopathy in the Exeter Health Authority area. Analysis of data collected showed a prevalence of diabetic retinopathy in the screened population of 27%, 14% previously undetected with a 0.5% prevalence of sight-threatening retinopathy. There was almost complete agreement between ophthalmoscopy findings and the consultant analysis of photographs. Screening costs were calculated at 10.38 pounds per patient screened. A specially trained non-medically qualified technician can provide a good quality cost-effective screening service for diabetic retinopathy within a primary care setting.

Adolescent↗