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Biomedical subjects

J E Tooke

Publications and source records attributed to J E Tooke.

124 records · Page 7Linked to original sources
PubMed1981

The influence of a combined oral contraceptive pill and menstrual cycle phase on digital microvascular haemodynamics.

1. Nailfold capillary pressure, digital blood flow and skin temperature have been measured on days 7, 14, 21 and 28 of the menstrual cycle in 10 women on a combined oral contraceptive pill and 10 control subjects with normal menstrual cycles. 2. Capillary pressure and digital blood flow were statistically significantly higher in the group taking an oral contraceptive pill compared with control subjects. 3. Capillary pressure values for women failed to show the same positive correlation with skin temperature previously described in normal men. 4. The results are interpreted as evidence for a powerful modulating influence of sex steroids on digital microvascular haemodynamics.

Adult↗
PubMed1981

The treatment of idiopathic orthostatic hypotension: a combined fludrocortisone and flurbiprofen regime.

We report our experience in the management of idiopathic orthostatic hypotension using the prostaglandin synthetase inhibitor, flurbiprofen. In five subjects with proven autonomic failure the effect on blood pressure of the addition of flurbiprofen (or fludrocortisone) to the previous drug regime was assessed. Both lying and standing blood pressure were seen to rise with fludrocortisone treatment although the change in standing blood pressure was not statistically significant. Flurbiprofen, in contrast, produced no change in lying blood pressure but a significant rise in standing blood pressure. Digital blood flow measurements were made on three subjects before and after flurbiprofen and a dose-related reduction in post-occlusive reactive hyperaemia was demonstrated suggesting an effect of this drug on precapillary smooth muscle tonus. Two patients failed to maintain a long-term response to treatment with flurbiprofen and fludrocortisone but have been helped by the addition of I) ephedrine or II) tyramine an monoamine oxidase inhibitor (phenelzine). We recommend a stepwise approach to treatment in this condition commencing with flurbiprofen and adding fludrocortisone later if necessary. This approach would appear to offer the maximum benefit with a minimum of side effects.

Adolescent↗
PubMed1980

A capillary pressure disturbance in young diabetics.

Finger nailfold capillary pressure (CP) was determined by direct microinjection technique in nine insulin-dependent male diabetic and nine matched control subjects. Mean CP, recorded under resting conditions after acclimatization in a constant temperature room at 24 degree C, was similar in all parts of the capillary loop in the two groups. Control subjects demonstrated a positive correlation between skin temperature and CP (r = + 0.74 and P < 0.01, arterial limb values; r = + 0.61 and P < 0.01, summit and venous limb values). No such relationship was found for diabetics under the initial warm conditions of study (r = - 0.15, arterial limb values; r = - 0.44, summit and venous limb values). Mean arterial limb CP, recorded during postocclusive reactive hyperemia, was significantly higher in control subjects than in diabetics (P < 0.001). The diabetic group exhibited no clinical evidence of neuropathy, and their digital vasoconstrictor capacity appeared to be intact. These findings are interpreted as evidence for an intrinsic microvascular lesion at the precapillary sphincter level in insulin-dependent diabetic patients, which may result in the failure of vasodilatation to respond to physiologic stress.

Adolescent↗
PubMedDate not supplied

Capillary filtration coefficient in type II (non-insulin-dependent) diabetes.

Changes in microvascular permeability may be important in the pathogenesis of diabetic microangiopathy. In order to assess microvascular fluid permeability, the capillary filtration coefficient was determined in the forearm of 24 normotensive type II diabetic patients with minimal evidence of microangiopathy and satisfactory glycemic control, and 24 age- and sex-matched control subjects, using a sensitive strain gauge plethysmographic system. The median capillary filtration coefficient was not significantly different in the type II diabetic patients and control subjects [5.3 (3.2 - 9.1) x 10(-3) mL.min-1.100 g tissue-1.mm Hg-1 versus 5.4 (3.5 - 8.0) x 10(-3) mL.min-1.100 g tissue-1.mm Hg-1, p = 0.98)]. There were no correlations between capillary filtration coefficient and age, blood pressure, body mass index, duration of diabetes, glycemic control, or the presence of microvascular complications. These findings contrast with type I diabetes, where capillary filtration coefficient is elevated at an early stage in the disease, and lend support to the theory that there are differences in early microvascular functional abnormalities between type I and type II diabetes.

Adult↗
PubMedDate not supplied

Possible pathophysiological mechanisms for diabetic angiopathy in type 2 diabetes.

The expression of large and small vessel disease in type 2 diabetes differs from that observed in type 1, with a higher prevalence of atherosclerosis and hypertension, maculopathy rather than proliferative retinopathy, and nephropathy of a more complex nature. Such differences are mirrored by differences in vascular pathophysiology with an early impairment of microvascular vasodilatory reserve being a prominent feature. The defect appears to be endothelium dependent and in conjunction with evidence of endothelium activation suggests that the endothelium plays a crucial role in the pathogenesis of vascular disease in type 2 diabetes and may even be an intrinsic feature or common antecedent of the insulin resistance syndrome. Several cellular mechanisms may be proposed linking insulin resistance and endothelial dysfunction including (i) abnormalities of common signal transduction mechanisms, (ii) alterations in cell membrane fluidity altering the expression and/or presentation of a wide range of receptors, or (iii) changes in oxidative stress. It is intuitively unlikely that the alteration of a single signal transduction mechanism could be a common cause, particularly as aspects of endothelial dysfunction implicate different mechanisms. Accordingly, changes in oxidative stress, either stemming from glucose-mediated increased free-radical generation and/or reduction of antioxidant capacity, are strong contender mechanisms. Not only may increased oxidative stress result in the quenching of nitric oxide, neutralizing its many protective functions, but it may also damage DNA, protein structure, and membrane properties. Elucidating the links between oxidative stress, endothelial function, and insulin resistance has important implications for the prevention of diabetic angiopathy and perhaps for the prevention of diabetes itself.

Diabetes Mellitus, Type 2↗
PubMedDate not supplied

Impaired microvascular hyperaemic response in children with diabetes mellitus.

Clinically detectable microvascular complications of diabetes are uncommon in children with diabetes especially in the prepubertal group. It is unclear whether subtle functional abnormalities of the microcirculation occur in children without evidence of clinical microangiopathy and in particular whether abnormalities can be demonstrated in children before puberty. The maximum hyperaemic response to direct local heating (44 degrees C) of the foot skin was measured by laser Doppler fluximetry in 50 diabetic and 50 non-diabetic children. An impaired hyperaemic response occurred in the diabetic children compared with control children (diabetic 1.25 (95% CI 1.13-1.37) V; control 1.74 (1.60-1.88) V; p less than 0.001) and was significantly related to duration of diabetes but not to long-term blood glucose control. The impaired response was also present in prepubertal diabetic children (diabetic 1.37 (1.16-1.58) V; control 1.89 (1.67-2.12) V; p less than 0.001). Systolic and diastolic blood pressure were significantly raised in the prepubertal diabetic children. These data suggest that a functional abnormality of the microcirculation occurs in children with diabetes in the absence of clinically detectable microangiopathy, and even before puberty.

Adolescent↗
PubMedDate not supplied

The effect of insulin infusion on capillary blood flow in the diabetic neuropathic foot.

The effect of a short-term improvement in glycaemic control induced by insulin infusion on foot skin capillary blood flow was previously unknown. In seven Type 2 (non-insulin-dependent) diabetic subjects with neuropathy capillary blood flow was measured in the great toe nailfold by television microscopy. An estimate of arteriovenous shunt flow was obtained simultaneously in the pulp of the great toe by laser Doppler flowmetry. After omission of oral hypoglycaemic therapy for 24 h mean blood glucose was 15.7 +/- 0.7 (SEM) mmol l-1. A priming infusion of 0.1 U kg-1 of insulin was given intravenously over 15 min, followed by a variable rate insulin infusion adjusted to steadily reduce blood glucose avoiding hypoglycaemia. At the end of the study blood glucose was reduced to 6.9 +/- 0.7 mmol l-1 (p less than 0.001). During the insulin infusion, capillary blood velocity increased by 28.8% (p less than 0.05), and the diameter of the capillary erythrocyte column increased from 7.6 +/- 0.2 to 9.2 +/- 0.3 micron (p less than 0.01). Thus during the insulin infusion, the calculated capillary flow increased to 226 +/- 36% above basal values (p less than 0.01). Laser Doppler flow did not change significantly, suggesting that during insulin infusion skin blood flow is redistributed with an increase in capillary flow relative to arteriovenous shunt flow.

Blood Flow Velocity↗
PubMedDate not supplied

Capillary pulse waveform in aortic stenosis.

The importance of the dynamic nature of perfusion pressure within the peripheral microcirculation is increasingly recognised. Capillary pressure is determined not only by arterial inflow pressure, but is also subject to a variety of local and systemic influences which have been shown to affect both mean pressure and the capillary pulse waveform. To what extent changes in central pulse waveform influence capillary pressure has yet to be determined. By using a dynamic technique of capillary pressure measurement in human subjects with aortic stenosis, we have been able to show that the characteristics of the pulse waveform typically associated with large vessels in this condition are also readily detectable at a capillary level despite local influences. However, changes in the rate of pulse wave transmission described in large arteries were not apparent at a microvascular level. Unlike mean capillary pressure and capillary pulse pressure, pulse waveform in the capillary mimics central haemodynamics.

Aged↗
PubMedDate not supplied

Postural vasoconstrictor response in human heart failure.

In order to study whether posturally induced vasoconstriction is impaired in subjects with heart failure, laser Doppler fluximetry was used to measure blood flow in the cutaneous microvascular bed of the foot at rest and during passive lowering of the extremity below heart level, in subjects with idiopathic dilated cardiomyopathy and in healthy controls. Two sites were studied: the toe pulp where arteriovenous anastomoses are numerous and the dorsum of the foot where such anastomoses are absent. Despite demonstrating a marked reduction in cutaneous blood flow at rest at each site [dorsum 3.0 AU (1.8-4.5) [median (range)] in heart failure patients vs 4.5 AU (1.8-31.6) in controls; toe 8.7 AU (3.1-33.5) in heart failure vs. 44.7 AU (5.2-280.0) in controls, p < 0.01], the results suggest that in non-oedematous subjects with severe left ventricular dysfunction there is no major disturbance of the postural vasoconstrictor response, either at a site rich in highly innervated anastomoses [43.6% (14.5-89.4) vs. 43.7% (15.6-91.1)] or in a site with few such anastomoses [79.7% (39.6-92.3) vs 69.6% (10.1-94.9)].

Adult↗
PubMedDate not supplied

Clinical television microscopy.

The technique of television microscopy is the only available technique for the direct quantitative measurement of skin capillary blood flow. Television microscopy has applications in both research and clinical practice, and has attracted considerable interest from clinical groups attempting to study capillary blood flow. The critical requirements for a functioning system are difficult to ascertain from the published literature. The aim of this article is therefore to describe the individual components of a television microscope system, outline the current methods of analysis and briefly describe some of the clinical applications of television microscopy.

Blood Flow Velocity↗