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Biomedical subjects

M D Flynn

Publications and source records attributed to M D Flynn.

At least 19 recordsLinked to original sources
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

The prevalence of autonomic and peripheral neuropathy in insulin-treated diabetic subjects.

The prevalence of autonomic and peripheral neuropathy was examined in 506 diabetic subjects treated with insulin, mean age 43 years, diabetes duration 15 (range 1-54) years. Autonomic neuropathy was present if two or more (of four) cardiovascular autonomic function tests were abnormal using age-related ranges derived from 310 normal control subjects. Peripheral neuropathy was defined as a vibration threshold > 95th centile for age combined with absent/impaired ankle reflexes. Eighty-four (16.6%) of diabetic subjects had abnormal autonomic function and 119 (23.5%) peripheral neuropathy, concordant in 44/506 (8.7%). Of the diabetic subjects with autonomic neuropathy 40/84 (47.6%) did not have peripheral neuropathy and only 44/119 (37.0%) with peripheral neuropathy had abnormal autonomic function (p < 0.001). The prevalence of both neuropathies increased in relation to diabetes duration (both p < 0.001). Autonomic neuropathy was more common in subjects diagnosed < 20 years of age (18.2%) vs age > 40 years (11.1%) (p < 0.05). In contrast peripheral neuropathy was more common with older age at diagnosis (< 20 years 13.5% vs 36.8% > 40 years, p < 0.001). The age-related prevalence of autonomic neuropathy peaked at age 40-49 years while peripheral neuropathy increased progressively with age (p < 0.001). The prevalence of peripheral exceeded autonomic neuropathy 20 years after diagnosis (40.2% vs 30.7%, p < 0.001).

Adult↗
PubMed1995

Decreased sialidase activity in mononuclear leucocytes of type 1 diabetic subjects: relationship to diabetic complications and glycaemic control.

Leucocyte surface sialic acid content influences surface charge, deformability, and leucocyte-endothelial interaction. Abnormal leucocyte structure and function contributes both to microvascular damage and diabetic complications. The aim of this study was to investigate altered leucocyte SA metabolism in diabetic subjects and measure lysosomal sialidase which regulates leucocyte surface sialylation. We examined 26 Type 1 (insulin-dependent) diabetic subjects with retinopathy, 26 Type 1 diabetic subjects without complications, and 38 matched normal control subjects. Sialidase was assayed in freshly prepared sonicates of pure mononuclear leucocytes (MNLs), using the fluorometric substrate 4-methyl-umbelliferyl-N-acetylneuraminic acid. In the subjects with diabetes there was a significant negative correlation between MNL sialidase activity and both HbA1c (rs = 0.37, p = 0.007) and fructosamine (rs = -0.31, p = 0.026). MNL sialidase activity was significantly decreased in diabetic subjects with clinical evidence of complications compared to control subjects. HbA1c was significantly higher (p = 0.036) in diabetic patients with complications compared to those without. The observed decrease in MNL sialidase activity related to diabetic control may be important in the pathogenesis of vascular damage. Diabetes-associated changes in sialylation of functional cell surface glycoconjugates may have important clinical consequences.

Adolescent↗
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

Splanchnic blood flow in man: evidence for mediation via a beta-adrenergic mechanism.

1. Superior mesenteric artery blood flow was examined by Doppler ultrasound in six male subjects aged 19-23 years during the infusion of saline (control), 10 and 40 ng of adrenaline min-1kg-1 for 30 min, or propranolol and 10 ng of adrenaline min-1kg-1 for 30 min, on four separate occasions. 2. Adrenaline infusion resulted in significant peak mean (SEM) rises in circulating adrenaline concentrations during the infusion period only [control, 0.20 (0.05) nmol/l; 10 ng of adrenaline min-1kg-1, 1.37 (0.29) nmol/l; 40 ng of adrenaline min-1kg-1, 3.73 (0.40) nmol/l; 10 ng of adrenaline min-1kg-1 and propranolol, 1.48 (0.16) nmol/l, P < 0.001 versus control]. These values are within the physiological range. 3. Superior mesenteric artery blood flow rose in a dose-dependent manner during the adrenaline infusions alone, but not during the infusion of adrenaline and propranolol [mean (95% confidence interval) area under the curve: control, -4.2 (-11 to +2.7)%; 10 ng of adrenaline min-1kg-1, +4 (-1 to 11.9)%; 40 ng of adrenaline min-1kg-1, +34 (+6.5 to +61.5)%; 10 ng of adrenaline min-1kg-1 and propranolol, -8.4 (-23 to +6)%]. 4. Superior mesenteric artery resistance fell during the adrenaline infusions alone and rose during the combined adrenaline and propranolol infusion [mean (SEM) area under the curve: control, 6.4 (2.7)%; 10 ng of adrenaline min-1kg-1, -2.9 (2.5)%; 40 ng of adrenaline min-1kg-1, -15 (1.4)%; 10ng of adrenaline min-1kg-1 and propranolol, 16.9 (10)%]. 5. These data suggest that splanchnic vasodilatation is mediated via a beta-adrenergic mechanism.

Adult↗
PubMed1992

Increases in plasma lysosomal enzymes in type 1 (insulin-dependent) diabetes mellitus: relationship to diabetic complications and glycaemic control.

Lysosomal enzymes degrade membrane glycoconjugates, and increased circulating enzyme activity may be an important mechanism in the pathogenesis of diabetic microangiopathy. We have assayed a profile of seven lysosomal enzyme activities (nmol.h-1.ml-1) in platelet-free plasma from 54 Type 1 (insulin-dependent) diabetic subjects (median age 31 years) and 42 matched normal control subjects. A significant increase in median (interquartile range) enzyme activity was measured in diabetic compared to control subjects for beta-D-glucuronidase, 121 (97.7-171) vs 88.8 (62.8-113), p less than 0.001; beta-D-Nacetylglucosaminidase, 693 (568-799) vs 568 (462-686), p less than 0.001; alpha-D-mannosidase, 23.8 (16.7-28.9) vs 14.5 (10.1-20.0), p less than 0.001; and beta-D-galactosidase, 6.94 (6.11-9.99) vs 6.66 (4.78-8.33), p less than 0.04. In contrast, alpha-L-fucosidase, alpha-D-galactosidase and beta-D-mannosidase activities were similar in diabetic and control subjects. None of the enzyme activities differed significantly (p less than 0.05) between 24 diabetic patients with clinical complications and 30 complication-free diabetic patients with similar glycaemic control which does not support the hypothesis that enzyme increases in diabetes arise simply by leakage from damaged tissues. In the diabetic subjects HbA1, median (interquartile range) 9.10 (7.40-10.60), was significantly related to beta-D-glucuronidase (rs = 0.56, p less than 0.001) and beta-D-Nacetylglucosaminidase (rs = 0.55, p less than 0.001). We have therefore demonstrated in diabetic subjects an increase in certain lysosomal glycosidases, that correlates with glycaemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1992

Adrenal suppression with intranasal betamethasone drops.

Intranasal betamethasone sodium phosphate drops (Betnesol) are frequently used to relieve nasal congestion due to polyposis. We report a case of significant hypothalamic-pituitary-adrenal suppression secondary to the long-term use of intranasal betamethasone drops. This case emphasizes that the topical application of potent corticosteroids may produce systemic effects.

Administration, Intranasal↗
PubMed1992

Aetiology of diabetic foot ulceration: a role for the microcirculation?

Neuropathy, mechanical stress, and macrovascular disease are involved in the pathogenesis of diabetic foot ulceration. Implicit in the development of gangrene and ulceration is the recognition that these factors interact with the microcirculation, resulting in the failure of skin capillary flow to meet nutritive requirements. There is little evidence to associate structural microangiopathy with foot microcirculatory failure. Significant functional abnormalities of the microcirculation have been defined. In accord with the haemodynamic hypothesis early hyperaemia and capillary hypertension promote more sinister late functional abnormalities with increasing duration of diabetes. These late functional abnormalities include loss of autoregulation and reduced hyperaemic responses which interact with loss of neurogenic flow regulation, disturbed endothelial function, and abnormal rheology to produce the familiar clinical picture of the diabetic foot. Ischaemia secondary to multi-segment arterial disease induces additional abnormalities of microcirculatory function which are superimposed on the pre-existing diabetic microvascular structural and functional microangiopathy.

Diabetic Angiopathies↗
PubMed1989

Effect of postural change and thermoregulatory stress on the capillary microcirculation of the human toe.

1. We have applied the technique of television capillary microscopy to make direct measurements of nutritional capillary flow in the toe nailfold (i) at heart level and (ii) in a near standing position, with the foot 96 cm below heart level. By indirect heating we have examined the relationship between posture-related changes and thermoregulation in the capillary circulation of the toe. 2. Capillary blood flow in 14 male subjects with their feet at heart level showed a positive correlation with increasing skin temperature. 3. On quiet standing, capillary blood flow decreased to 11.3% of supine values, achieved both by a reduction in capillary blood velocity and the duration of flow. 4. Indirect heating of the trunk led to a partial release of sympathetic tone and induced a significant increase in capillary blood flow in both the supine and dependent positions. However during heating, the percentage fall in capillary blood flow associated with dependency remained unchanged. 5. In conclusion, it appears that in the dependent foot, compensatory mechanisms exist to limit nutritional capillary blood flow by regulating both erythrocyte velocity and the duration of flow. These mechanisms fulfil a physiological requirement to limit the rate of oedema formation. The preservation of this response during the partial sympathetic release induced by indirect heating suggests a mechanism independent of that controlling flow through arteriovenous shunts. Our results are compatible with the hypothesis that a local vasoconstrictor mechanism is operative in the vascular resistance elements in closest relation with the capillary bed, and distal to that regulating arteriovenous shunt flow.

Adult↗
PubMed1989

Glycated fibrinogen: a new index of short-term diabetic control.

Fibrinogen is a plasma protein with a short half-life of four days and, therefore, glycated fibrinogen may be valuable as an index of short-term diabetic control. We have developed a simple, rapid method for determining glycated fibrinogen using affinity chromatography. The differences in the percentage of glycated fibrinogen between normal subjects, well-controlled diabetics and poorly-controlled diabetics were highly significant. There was a significant correlation between glycated fibrinogen and glycated haemoglobin for all these subjects. However, in selected subjects with rapidly improving diabetic control the difference between the fall over three days in glycated fibrinogen and glycated haemoglobin was highly significant. In subjects with deteriorating control over an average of four weeks there was a significant difference between the increase in glycated fibrinogen and glycated haemoglobin. We suggest that glycated fibrinogen may be a valuable adjunct to glucose measurements in the assessment of short-term diabetic control due to its rapid change following alterations in control.

Adult↗
PubMed1988

Direct measurement of capillary blood flow in the diabetic neuropathic foot.

The two major components of the microcirculation in the diabetic neuropathic foot have been examined in detail. Nutritive capillary blood flow was measured directly using the non-invasive technique of television microscopy, applied to the toe nailfold. Arteriovenous shunt flow was assessed using the technique of laser Doppler flowmetry, applied to the toe pulp. Fourteen diabetic patients with peripheral and autonomic neuropathy, 11 with no clinical evidence of neuropathy and 14 normal subjects were studied. Laser Doppler flowmetry (predominantly arteriovenous shunt flow) was increased more than three-fold (p less than 0.01) in the diabetic patients with neuropathy compared to control subjects, (median 3.57, interquartile range 2.00-5.32 volts vs median 0.93, interquartile range 0.47-2.36 volts, respectively). There was no evidence of skin capillary closure. The calculated capillary blood flow (erythrocyte flux) was significantly increased in the diabetic neuropathic patients compared to control subjects (median 76.4, interquartile range 34.4-109.8 picolitres/s vs median 23.2, range 8.0-44.8 picolitres/s, p less than 0.01). This study demonstrates that foot skin capillary blood flow is increased in diabetic patients with neuropathy. There is, therefore, no evidence to support the supposition that capillary ischaemia, either secondary to a "capillary steal phenomenon" or "advanced microangiopathy", is a feature of diabetic neuropathy under resting conditions.

Adult↗
PubMed1988

Antepartum pituitary necrosis in diabetes mellitus.

Pituitary infarction occurred during pregnancy in two insulin-dependent diabetic patients aged 32 and 33 years. The diagnosis was delayed in each case before being confirmed biochemically and radiologically. A decreasing insulin requirement and recurrent hypoglycaemia made it possible to determine the exact time that pituitary infarction occurred during pregnancy. The clinical features of these cases should alert physicians to the possibility of pituitary infarction in diabetic pregnancy and minimize the delay in diagnosis.

Adult↗
PubMed1984

The elderly and their ankle jerks.

The ankle jerks of 200 consecutive patients admitted to a geriatric department were assessed on the second or third hospital days by two independent observers. The test consisted of a "plantar" rather than Achilles tendon strike with a standard patellar hammer. 188 patients had ankle jerks. This finding is at variance with most previous reports on the subject. This difference may be due to, amongst other factors, the timing and method of testing.

Achilles Tendon↗