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Biomedical subjects

A C Shore

Publications and source records attributed to A C Shore.

At least 55 records · Page 3Linked to original sources
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

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

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

The effect of rapid local cooling on human finger nailfold capillary blood pressure and blood cell velocity.

1. The effect of a rapid local reduction in finger temperature on finger nailfold capillary blood pressure and blood cell velocity was investigated in healthy subjects. 2. Cooling was achieved by placing the finger into an adjustable copper cylindrical finger holder, which incorporated a Peltier element within its base; thus the entire finger from just distal to the nailfold to the interphalangeal joint was cooled. The Peltier element was cooled to 8 degrees C for 5 min. 3. Finger tip temperature was reduced to 76 +/- 12% of its resting value during cooling (28.8 +/- 4.8 degrees C (mean +/- S.D.) baseline versus 22.1 +/- 6.4 degrees C in the fifth minute of cooling, P = 0.012); this was accompanied by a reduction in capillary blood cell velocity similar to that described previously in cooling experiments using cold air (baseline median, 671 microns s-1 (range, 29-4421 microns s-1) versus median during cooling, 221 microns s-1 (range, 6.7-2579 microns s-1), P = 0.012). 4. The magnitude and timing of the capillary pressure response to cooling and recovery varied between individuals. In the group as a whole, there was no significant fall in capillary pressure during cooling (basal before cooling, 16.7 +/- 3.7 mmHg versus minimum during cooling, 15.1 +/- 3.5 mmHg, P = 0.12), whereas capillary pulse pressure amplitude was reduced (basal before cooling, 5.3 +/- 3.1 mmHg versus minimum during cooling, 3.7 +/- 2.6 mmHg, P = 0.028). 5. During the recovery phase, post cooling, both capillary pressure and capillary pulse pressure amplitude were markedly elevated compared to baseline or the cooling phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗
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↗
PubMed1994

The influence of hypertension on microvascular blood flow and resistance to flow in the skin of patients with type 2 (non-insulin-dependent) diabetes.

Maximum microvascular blood flow and resistance to flow were determined in the skin of nine hypertensive and nine normotensive Type 2 (non-insulin-dependent) diabetic patients and nine control subjects to determine the influence of hypertension on these variables. Maximum blood flow was reduced in both the hypertensive (1.05 (0.70-1.42) V) and normotensive (1.04 (0.79-1.63) V) Type 2 diabetic patients when compared with control subjects (1.40 (1.26-2.13) V, p < 0.01 for hypertensive and p < 0.05 for normotensive patients, respectively); however, maximum blood flow was similar in both groups of diabetic patients (p = 0.82). In contrast, resistance to flow was significantly greater in the diabetic patients with hypertension (127.2 (87.5-181.3) mmHg V-1 vs 84.7 (61.9-123.0) mmHg V-1 normotensive diabetic patients, p < 0.02). In addition, R was greater in the normotensive Type 2 diabetic patients than in control subjects (70.7 (44.7-79.9) mmHg V-1, p < 0.05). These results suggest that hypertension is associated with an additional rise in pre-capillary vascular resistance in Type 2 diabetes which, while protecting the microcirculation from the effects of increased arterial pressure, may further diminish protective hyperaemic responses.

Aged↗
PubMed1994

Posturally induced vasoconstriction in diabetes mellitus.

In healthy subjects, standing elicits a reduction in blood flow to the skin of the foot. In adults with insulin dependent diabetes this posturally induced response is deficient, resulting in capillary hypertension when the foot is in the dependent position (that is, below heart level). Such functional abnormalities of the microcirculation in diabetes may precede any evidence of clinically detectable microangiopathy. This study investigates the posturally induced change in blood flow to the skin of the foot in prepubertal and postpubertal patients with insulin dependent diabetes. Laser Doppler fluximetry was used to assess the postural change in blood flow at the pulp of the great toe. Postural vasoconstriction (dependent flux value/supine flux value x 100) was greater after puberty in normal subjects (median (range) 60.4 (7.0-164.9)% prepubertal v 20.5 (5.9-101.0)% postpubertal). Prepubertal children with diabetes did not differ from their healthy peers (69.8 (7.2-192.7)% with diabetes v 60.4 (7.0-164.9)% controls); however postpubertal children with diabetes had a significantly impaired postural vasoconstriction (40.6 (7.9-140.2)% with diabetes v 20.5 (5.9-101.7)% controls). Abnormalities in the normal reduction of blood flow on standing occurred in young postpubertal children with diabetes, most of whom were free of complications.

Adolescent↗
PubMed1994

Capillary pressure in patients with NIDDM.

The hemodynamic hypothesis suggests that raised capillary pressure may play a role in the pathogenesis of diabetic microangiopathy. Although patients with non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes NIDDM) develop a similar range of microvascular complications, differences in their expression and prevalence suggest that different pathogenic mechanisms may be operational. Capillary pressure is elevated in IDDM; the aim of this study was to assess whether capillary pressure was also elevated in NIDDM. Twenty-one patients with NIDDM (15 men) and 21 healthy control subjects matched for age, sex, and skin temperature were investigated supine with the hand at heart level. Finger nailfold capillary pressure was measured after direct cannulation at the summit of the capillary loops using glass micropipettes. The groups were matched for skin temperature (30.4 [24.2-33.8] degrees C, median [95% confidence interval], NIDDM patients vs. 30.0 [23.4-33.6] degrees C control subjects), age (62.0 [39.4-72.7] years NIDDM patients vs. 62.0 [39.4-72.0] years control subjects), and both systolic (sBP) and diastolic (dBP) blood pressures (133.0 [111.0-167.3]/78.0 [57.0-89.5] mmHg NIDDM patients vs. 133.0 [114.1-158.9]/80.0 [68.2-88.9] mmHg control subjects). Capillary pressure did not differ in the two groups (17.6 [13.1-21.2] mmHg NIDDM patients vs. 19.1 [14.1-23.6] mmHg control subjects [NS]). There was no correlation of capillary pressure with either HbA1c or glucose; however, there was a negative association between capillary pressure and diabetes duration (Rs = -0.50, P = 0.020).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Oedema in patients with Addison's disease on replacement therapy: glucocorticoid excess and mineralocorticoid deficiency?

Steroid hormones influence mechanisms related to oedema formation, including postural vasoconstriction and vascular tone. We studied fifteen patients (7 male, 8 female) with primary adrenal failure on clinically optimal replacement therapy. Five patients, all female, had clinically detectable oedema. Patients with oedema had evidence of mineralocorticoid deficiency, with increased supine and erect plasma renin activity and greater postural fall in blood pressure. Mean morning plasma cortisol levels were significantly higher in the group with oedema, suggesting they were receiving insufficient mineralocorticoid and a possible relative excess of glucocorticoid. There were no significant differences between patients with and without oedema in lower-limb cutaneous blood flow or in postural vasoconstrictor responses measured by laser Doppler flowmetry. The mechanism of oedema formation is unclear, but appears not to be modulated by haemodynamic mechanisms with expansion of intravascular volume or, in contrast to the known effects of sex hormones, by impairment of postural vasoconstriction. Theoretically, excess glucocorticoid replacement may result in oedema formation, by direct action on vascular tone, by altering capillary permeability, or by influencing other factors such as atrial natriuretic peptide. Measurement of plasma renin activity in conjunction with plasma cortisol profiles may be useful in adjusting replacement therapy in patients with Addison's disease and oedema.

Addison Disease↗
PubMed1993

Increased microvascular fluid permeability in young type 1 (insulin-dependent) diabetic patients.

Microvascular fluid permeability was assessed by determination of the capillary filtration coefficient in the forearm of ten young Type 1 (insulin-dependent) diabetic patients with a short duration of diabetes, satisfactory glycaemic control and minimal evidence of microangiopathy, and ten age- and sex-matched control subjects. A strain gauge plethysmographic method with a computer based logging and analysis system was used. This enabled differentiation between the volume filling and fluid filtration components of the response to venous pressure elevation. The median capillary filtration coefficient was found to be significantly higher in the young diabetic patients in comparison with control subjects (9.2 x 10(-3) ml.min-1.100 g tissue-1.mmHg-1 vs 3.8 x 10(-3) ml.min-1.100 g tissue-1.mmHg-1, p < 0.001). There were no significant correlations between capillary filtration coefficient and either plasma glucose concentration, haemoglobin A1c or duration of diabetes. As there is no evidence from other studies to support an increase in capillary surface area in the forearms of young Type 1 diabetic patients, these results may reflect a primary change in microvascular fluid permeability.

Adolescent↗
PubMed1993

Effect of an increase in systemic blood pressure on nailfold capillary pressure in humans.

Moderate autoregulation of capillary pressure occurs during changes in arterial and/or venous pressure in animals. Whether an increase in systemic blood pressure is transmitted to capillaries in humans is unknown. Eight healthy volunteers performed isometric handgrip exercise (30% of maximum) while nailfold capillary pressure (CP) and digital arterial blood pressure (DBP) were measured in the contralateral hand. CP was measured for 40 s before exercise and 40-100 s during exercise. Only experiments with no change in pipette position and no artifactual changes in flow were accepted. Basal DBP was stable [91.5 +/- 12.7 mmHg (-40 to -20 s basal) and 91.3 +/- 11.8 mmHg (-20 to 0 s basal)], and isometric exercise increased DBP [100.4 +/- 13.9 mmHg (0-20 s exercise) and 103.1 +/- 15.3 mmHg (20-40 s exercise); P < 0.05]. CP was unchanged during the first 40 s of exercise [18.9 +/- 4.9 mmHg (-40 to 20 s basal), 18.9 +/- 5.2 mmHg (-20 to 0 s basal), 18.4 +/- 4.7 mmHg (0-20 s exercise), and 18.3 +/- 5.3 mmHg (20-40 s exercise)] and remained unchanged for up to 100 s (n = 5), despite a continued elevation of DBP. These data suggest that protective mechanisms minimize the transmission of increases in systemic blood pressure to the capillary bed in humans.

Adult↗
PubMed1992

Relation of skin capillary pressure in patients with insulin-dependent diabetes mellitus to complications and metabolic control.

BACKGROUND: Microvascular disease is a major problem in patients with diabetes mellitus. It has been suggested that diabetic microangiopathy may result from an increase in capillary blood flow and capillary hypertension, but direct evidence of capillary hypertension in such patients is lacking. METHODS: We measured capillary pressure at the summit of the capillary loop by direct microcannulation of skin nail-fold capillaries and a dynamic method of pressure measurement in 29 patients with insulin-dependent (Type I) diabetes and 29 normal subjects matched for age and sex. Among the diabetic patients, 7 had had diabetes for less than one year, 12 had incipient nephropathy (albumin excretion, 20 to 200 micrograms per minute), and 10 had overt nephropathy (albumin excretion, greater than 200 micrograms per minute). In addition, seven patients with no evidence of nephropathy were studied before and after three months of improved glycemic control. RESULTS: The median capillary pressure in the diabetic patients was 20.4 mm Hg (range, 13.6 to 25.3), as compared with 16.7 mm Hg (range, 12.8 to 22.8; P less than 0.001) in the normal subjects. The values were higher in each subgroup of diabetic patients than in the corresponding group of normal subjects, but the values did not differ among the three subgroups of diabetic patients. In the seven patients who were studied before and after three months of improved glycemic control, the median capillary pressure fell from 20.0 mm Hg (range, 18.5 to 21.7) to 17.8 mm Hg (range, 14.1 to 20.3; P = 0.02). CONCLUSIONS: Nail-fold capillary hypertension may develop early in the course of diabetes, before the emergence of microvascular disease, and may be influenced by changes in metabolic control.

Adolescent↗
PubMed1991

Microvascular hemodynamics in hypertension and diabetes.

Microvascular damage occurs in both diabetes and hypertension and hypertension is a risk factor for diabetic microangiopathy. In both conditions, indirect evidence suggests that capillary pressure might be raised. A servonulling pressure measuring technique has been used in conjunction with direct micropuncture of finger nailfold capillaries to determine capillary pressure dynamically. In patients with essential hypertension, capillary pressure is raised compared to matched normotensive controls. In insulin-dependent diabetic patients, capillary pressure is also raised, to a degree that correlates with recent diabetic control. In a pilot study of hypertensive diabetic patients, elevated capillary pressure has been normalized using an angiotensin-converting enzyme inhibitor. Manipulation of microvascular hemodynamics in diabetes and hypertension may provide a means of protecting against the microvascular complications of these two conditions.

Adult↗
PubMed1988

Endocrine and renal response to water loading and water restriction in normal man.

1. Nine normal subjects (eight male, one female) on a fixed daily intake of 150 mmol of sodium and 80 mmol of potassium, were randomized to receive either 3 days of 1.0 litre total water intake/24 h (food + fluid) or 4 days of 6.8 litres total water intake/24 h, and were then crossed over after a 3 day control period (2.7 litres water/24 h). 2. During water restriction, urine volume fell from 1.94 litres/24 h to less than 1 litre/24 h by the first day and was 0.77 litre/24 h on the final day. Plasma atrial natriuretic peptide levels were unchanged from baseline despite a large increase in plasma vasopressin and plasma and urine osmolality. Urinary sodium was unaltered throughout, while urinary potassium was increased on the final 2 days of water restriction. 3. During water loading, urine volume increased from 1.85 litres/24 h to 5.44 litres/24 h on the first day and remained at approximately 6 litres/24 h for the final 3 days. Plasma atrial natriuretic peptide showed no change. Plasma vasopressin and plasma and urine osmolality were reduced. Urinary sodium and potassium output were unchanged from baseline. 4. These results suggest that changes in plasma atrial natriuretic peptide are unlikely to be involved in the normal homoeostatic response to changes in water balance in man.

Adolescent↗