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Biomedical subjects

J E Tooke

Publications and source records attributed to J E Tooke.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1995

Capillary pressure, pulse pressure amplitude, and pressure waveform in healthy volunteers.

The influence of gender, local temperature, and systemic blood pressure on human capillary pressure is unknown. Finger nail fold capillary pressure was therefore directly measured in 74 healthy supine volunteers (40 female) at midaxillary level. Capillary pressure was lower in women than in men (15.9 +/- 3.0 vs. 18.2 +/- 2.3 mmHg; P = 0.001), particularly in premenopausal women, but was not related to systolic, diastolic, or mean blood pressure. Capillary pulse pressure amplitude was related to skin temperature, an effect more marked in women (P = 0.003). There was a significant association between skin temperature and the time taken for the systolic pressure rise to reach the capillary, in women only (r = -0.69, P < 0.001). Increasing age reduced the high-frequency waves in the pressure waveform [2nd harmonic percentage of fundamental: r = -0.52 and P = 0.002 (women), r = -0.52 and P = 0.004 (men)]. Thus mean capillary pressure and the pressure waveform may be influenced by gender, age, and skin temperature, illustrating the necessity to adequately match control groups during assessments of capillary pressure pathophysiology.

Adult↗
PubMed1995

Quality of life in type II diabetes: evaluation and applications.

Issues of quality of life (QOL) have often been considered for patients with insulin-dependent diabetes mellitus (IDDM, type I diabetes). Daily blood glucose monitoring and need for self-injections pose an obvious threat to the attainment of QOL, as does concern about long term complications. In contrast, non-insulin-dependent diabetes mellitus (NIDDM, type II diabetes) may be considered less severe, and has attracted less research interest. In fact, type II patients may also be aware of their heightened vulnerability to physical complications, as well as being affected by the need for heightened vigilance and attention to diet and exercise regimens. Issues associated with the theory and development of QOL measures are discussed largely in relation to type I diabetes and cancer. Generic measures have advantages in allowing comparisons to be made across different disease groups, and are, therefore, often favoured by health economists. In contrast, disease-specific scales are more sensitive to changes in treatment regimens, and may therefore be the instruments of choice in evaluating new treatments. In general, there has been less attention paid to how the meaning of QOL changes throughout the lifespan, and our review of the literature therefore emphasises a developmental perspective when considering the processes through which diabetes may affect an individual's QOL. Measures which, at the least, take into account changes in meaning of QOL throughout the lifespan need to be developed.

Age Factors↗
PubMed1995

Direct and indirect costs of cardiovascular and cerebrovascular complications of type II diabetes.

Macroangiopathy (atherosclerosis) is a common chronic complication in non-insulin-dependent diabetes mellitus (NIDDM, type II diabetes) with a significant attendant mortality and morbidity. While there are inherent difficulties in estimating the economic burden of large vessel disease in type II diabetes, this has been attempted in several studies by use of insurance claims, hospital inpatient statistics, and extrapolation from standard mortality data. This evidence suggests that the macrovascular complications of type II diabetes (ischaemic heart disease, peripheral vascular disease, and cerebrovascular disease) account for approximately one-third of all healthcare expenditures and one-quarter of disability related to type II diabetes in developed countries. The large and growing economic burden of these complications of diabetes in developing countries is unknown.

Arteriosclerosis↗
PubMed1995

Microvascular function in human diabetes. A physiological perspective.

The late complications of diabetes represent in large part microvascular dysfunction. The development of techniques to measure microvascular function has resulted in a clearer picture of the stages of development of microangiopathy and the key pathophysiological processes involved. Considerable evidence supports the hemodynamic hypothesis of pathogenesis, which argues that early insulin-dependent diabetes is characterized by increased microvascular pressure and flow. Resultant injury to the microvascular endothelium causes adaptive microvascular sclerosis contributing to a loss of vasodilatory reserve and autoregulatory capacity with increasing disease duration. High susceptibility to microangiopathy appears to be characterized by both high capillary pressure and increased permeability, although the interrelationship between these variables needs to be better defined. In normotensive non-insulin-dependent diabetes subjects, a different pattern of microvascular functional abnormalities is apparent; it is hypothesized that these differences represent the impact of a prediabetic insulin-resistant phase on microvascular behavior and may in part explain the differential expression of vascular pathology in the two major types of diabetes. The physiological framework that has been defined reveals those pivotal processes upon which scientific attention should be centered and facilitates the generation of plausible molecular and cellular mechanisms that fit the physiological facts.

Arteriosclerosis↗
PubMed1995

Disturbance of peripheral microvascular function in congestive heart failure secondary to idiopathic dilated cardiomyopathy.

OBJECTIVES: Previous studies of peripheral microvascular function in human heart failure have concentrated on changes in flow, and there is little information concerning the impact of heart failure on the principal determinants of transcapillary fluid exchange. This study investigated whether alterations in capillary pressure and microvascular fluid permeability can be detected in subjects with idiopathic dilated cardiomyopathy. METHODS: Finger nailfold capillary pressure and calf capillary filtration coefficient (CFC) were measured in parallel studies of two overlapping groups of 12 non-oedematous subjects with idiopathic dilated cardiomyopathy and mild to moderate heart failure and in age- and sex-matched healthy controls. Capillary pressure was measured by direct cannulation using an electronic resistance feedback servonulling technique, and CFC by mercury-in-silastic strain gauge plethysmography using a modification of the technique which avoids assumptions concerning isovolumetric venous pressure. RESULTS: Following correction for differences in skin temperature, capillary pressure was lower in the subjects with heart failure (P = 0.02). Both CFC and isovolumetric venous pressure were greater in the subjects with heart failure than in controls (3.4 +/- 0.9 vs. 2.6 +/- 0.7 ml.min-1.mmHg-1.100 ml-1, P = 0.03; 27.1 +/- 8.4 vs. 17.2 +/- 7.2 mmHg, P = 0.01). CONCLUSIONS: These data suggest that factors other than changes in arterial inflow and venous outflow pressures are likely to play an important role in the disruption of microvascular homeostasis which occurs in heart failure. Changes in capillary hydraulic conductance may contribute to the pathogenesis of oedema.

Adult↗
PubMed1994

Reduced microvascular hyperaemia in subjects at risk of developing type 2 (non-insulin-dependent) diabetes mellitus.

Abnormalities of microvascular function may be important in the pathogenesis of diabetic microangiopathy. As such changes are already present at diagnosis in patients with Type 2 (non-insulin-dependent) diabetes mellitus, subjects at risk of developing the disease, who had elevated fasting plasma glucose concentrations below the diabetic range, were studied. The maximal microvascular hyperaemic response to local heating was determined in the feet of 11 subjects with fasting hyperglycaemia and 11 age- and sex-matched control subjects. There was reduced maximal hyperaemia in the subjects with fasting hyperglycaemia (1.01 [0.71-1.57]V, median and range), when compared to control subjects (1.41 [1.32-2.13]V, p < 0.001). It is unlikely that this limited vasodilation is a result of the mild degree of hyperglycaemia observed in the subjects included in this study. Further studies are therefore required to address the possible mechanisms of limited microvascular reactivity in subjects at risk of developing Type 2 diabetes.

Adult↗
PubMed1994

The peripheral microcirculation in atrial fibrillation: preservation of capillary pressure and filtration coefficient.

OBJECTIVE: The aim was to assess whether atrial fibrillation results in disturbances of capillary pressure and capillary filtration coefficient in man. METHODS: Finger nailfold capillary pressure and calf capillary filtration coefficient were measured in subjects in atrial fibrillation and in matched healthy controls in sinus rhythm. Capillary pressure was measured by direct cannulation using an electronic resistance feedback servonulling technique, and capillary filtration coefficient by mercury-in-Silastic strain gauge plethysmography using a technique believed not to invoke the venoarteriolar response. RESULTS: Mean capillary pressure did not differ significantly between subjects in atrial fibrillation and those in sinus rhythm [18.4(SD 5.1) mm Hg in atrial fibrillation v 18.0(2.9) mm Hg in sinus rhythm]. In a subgroup of patients restored to sinus rhythm (n = 7) by dc cardioversion there was no significant alteration in capillary pressure [15.3(4.2) mm Hg v 16.6(2.8) mm Hg]. Capillary filtration coefficient was also similar in subjects in atrial fibrillation to that in healthy controls in sinus rhythm [2.81(0.65) kfu in atrial fibrillation v 2.87(0.69) kfu in sinus rhythm]. CONCLUSIONS: These data would suggest that under resting conditions autoregulatory mechanisms are able to preserve microvascular homeostasis despite the central changes associated with atrial fibrillation.

Atrial Fibrillation↗