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Biomedical subjects

V A Spence

Publications and source records attributed to V A Spence.

At least 19 recordsLinked to original sources
PubMed2004

Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome.

The aetiology of chronic fatigue syndrome (CFS) remains controversial and a number of hypotheses have been put forward to explain it. Research into the condition is hindered by the considerable heterogeneity seen across patients but several reports have highlighted disturbances to cholinergic mechanisms in terms of central nervous system activity, neuromuscular function and autoantibodies to muscarinic cholinergic receptors. This paper examines an altogether separate function for acetylcholine and that is its role as an important and generalized vasodilator. Most diseases are accompanied by a blunted response to acetylcholine but the opposite is true for CFS. Such sensitivity is normally associated with physical training so the finding in CFS is anomalous and may well be relevant to vascular symptoms that characterise many patients. There are several mechanisms that might lead to ACh endothelial sensitivity in CFS patients and various experiments have been designed to unravel the enigma. These are reported here.

Acetylcholine↗
PubMed1992

Cutaneous vascular responses and thermoregulation in relation to age.

1. Sympathetic vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge were assessed in fingertip skin in relation to age and were correlated with vasoconstrictor ability during body cooling. The above relationship was also examined in diabetic patients in whom vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge had been shown previously to be markedly impaired. 2. Vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge, measured by laser Doppler flowmetry, were significantly reduced in the elderly group, although individual responses varied from normal to absent, and they also had a considerably greater variability as measured on three separate occasions than seen in young subjects. Discriminant analysis showed that, from each of three occasions, 65% of vasoconstrictor responses were abnormal in the elderly group. 3. Body cooling was performed by reducing the environmental temperature from 40 degrees C to 12 degrees C, and the time taken for blood flow to fall to 75%, 50% and 25% of the pre-cooling level (VC75, VC50, VC25, respectively) was calculated. Vasoconstriction was rapid in young subjects and was consistent with good vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge. In the elderly group, vasoconstriction was slower, but only the VC25 value differed significantly [elderly group, 13.3 (7.9-31.0) min, young group, 5.7 (2.7-15.5) min; median (interquartile range); P less than 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Quantification of sympathetic vascular responses in skin by laser Doppler flowmetry.

An improved physiological test of focal sympathetic nervous function using a laser Doppler flowmeter is presented. The test evaluates rapid reflex changes in skin blood flow at the finger tip where there are abundant arteriovenous anastomoses with dense sympathetic innervation. Indirect body heating was employed in all subjects to induce central vasodilation and to obtain stable comparable finger tip blood flows prior to stimulus. The reflex vasoconstriction which occurs following inspiratory gasp and contralateral hand cold challenge was quantified and its reproducibility investigated on three separate occasions in 20 young subjects. The variability in responses both within and between young subjects was small. The test was applied to 10 diabetic patients with autonomic neuropathy and to 10 age-matched control subjects. Vasoconstrictor reflexes were significantly lower in the diabetic group (p less than 0.005) with responses lower than 2 SD from the mean for age-matched controls. In conclusion, the test provides an assessment of focal autonomic damage which can be applied to other regions of the body rich in arteriovenous anastomoses and may have application in clinical studies investigating autonomic activity.

Adult↗
PubMed1990

The influence of histamine and PGE2-induced hyperaemia and oedema on respiratory metabolism in normal human forearm skin.

Transcutaneous measurements of pO2 and pCO2 were made on the forearm skin after intradermal injection of histamine, PGE2, and saline. The mediators, used at concentrations which induce intense hyperaemia, did not modify the steady state tcpO2/pCO2 levels measured with a sensor head temperature of 44 degrees C when breathing air or hyperbaric (2ATA) oxygen. It was deduced that gas transport is unaffected by mediator-induced conditions in the skin. The rates of fall of tcpO2 and of rise of tcpCO2 after arresting the forearm circulation by cuff occlusion of the arm were significantly less at the histamine site than at the PGE2 and saline sites. The values over the PGE2 and saline injection sites were less than those over undisturbed skin. The dynamic tests of respiratory gas exchange indicate that the skin metabolic rate is reduced at all injection sites and the greatest effect was seen with histamine. Measurement of dermal thickness after saline injection has shown that the excess interstitial fluid persists at the time of maximal hyperaemia: this is further accentuated at the histamine site through active oedema formation. Accumulation of excess interstitial fluid (persistence of aqueous injection or oedema generated by the action of mediator) separates the tissue cells. The reduction in the number of cells per unit volume is sufficient to explain the observed reduction in oxygen consumption per unit volume of skin. It is concluded that the increased diffusional distances in mediator-induced oedema are unimportant for the respiration of otherwise normal tissues, but that oedema by reducing oxygen flux may contribute appreciably to the hypoxia of inflamed tissue infiltrated with metabolically active cells.

Adult↗
PubMed1990

Assessment of the respiratory metabolism in the skin from transcutaneous measurements of pO2 and pCO2: potential for non-invasive monitoring of response to tuberculin skin testing.

A method is described for non-invasive transcutaneous (tc) measurement of tissue respiratory gas tensions in the skin on the forearm for study of delayed hypersensitivity reactions in man. Steady state values for tcpO2 and tcpCO2 were measured, and the skin respiratory rate (oxygen consumption) and the tissue pH were estimated from the changes in tcpO2 and tcpCO2 observed after interruption of the arterial circulation by cuff occlusion for 4 minutes. The extent of within-experiment and between subject variation in the steady-state measurements was not great (coefficient of variation 10%): tcpCO2.ss (steady state) was higher in men and tcpO2.ss was higher in women, but the extent of these sex differences was also small. Reference ranges have been established for tc measurements and calculated indices of tissue respiration in the undisturbed forearm skin of normal volunteers, against which the changes induced by tuberculin testing can be assessed. Severe changes, indicative of profound hypoxia and acidosis, are seen in intense delayed hypersensitivity reactions. Similar, but less severe changes were seen at the site of skin tests on BCG-vaccinated subjects who were 'negative' by conventional criteria of measurement of dermal induration and they became greatly exaggerated after successful re-vaccination. Intradermal injection of saline did not induce hypoxia or local acidosis. These new methods are very sensitive indicators of the tissue response in the DHS reaction.

BCG Vaccine↗
PubMed1989

Histometric studies on biopsies of tuberculin skin tests showing evidence of ischaemia and necrosis.

In a study of tuberculin skin tests in 216 consecutive untreated pulmonary tuberculosis patients, one showed central necrosis at 48 h: there was no effective blood flow at the centre of this lesion, but the periphery was markedly hyperaemic. Many dermal capillaries and venules contained deposits of fibrin, but none was occluded completely: the surviving cells in the dermal infiltrate were almost all macrophages. Five patients with strongly positive reactions at 48 h showed slower blood flow at the centre of the reaction than at the periphery (central relative slowing, CRS), possibly indicating central ischaemia short of necrosis: no fibrin deposits were seen in the dermal vessels of these skin test sites. The cellular infiltrate in the dermis was similar in distribution, but more abundant than that seen in uncomplicated positive reactions of comparable clinical size and with blood flow velocity maximal at the centre. At 48 h, lymphocytes were more numerous than macrophages in both groups, CD8 lymphocytes were more abundant in CRS reactions, but CD4 and CD25 (activated) T-lymphocytes and macrophages had a similar density in both groups. Epidermal CD1 cells were less frequent in CRS reactions than in uncomplicated positive reactions. Although CRS reactions showed more intense inflammation than the uncomplicated controls, none of the histometric measurements correlated with the extent of CRS. Follow-up studies showed that CRS reactions reverted to a normal hyperaemic blood flow pattern 5 days after antigen injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Effect of topically applied local anaesthesia on histamine flare in man measured by laser Doppler velocimetry.

The direct and indirect effects of histamine on the cutaneous microvasculature were measured by laser Doppler velocimetry. Histamine (6.51 x 10(-4) M) was injected intradermally into the forearms of eight healthy subjects following treatment with a topically applied local anaesthetic cream (EMLA) or equivalent placebo. The blood flow at the injection site (0 cm) and at 1 and 2 cm proximally was measured by laser Doppler velocimetry over 80 minutes. Analysis of the changes in magnitude of the hyperaemic responses with time showed no difference at the 0 and 1 cm sites, but a marked reduction was found at the 2 cm site following EMLA treatment (p less than 0.05). At all three sites the decay of the histamine-induced hyperaemia was faster following EMLA treatment than with placebo (p less than 0.04). The experiments showed that the indirect effect of histamine on the cutaneous microvasculature in the peripheral flare around the injection site was greatly diminished by prior application of EMLA cream and this supports the neurogenic hypothesis: pre-treatment with EMLA cream did not affect the development of hyperaemia and oedema at the site of histamine injection where the mediator acts directly on the cutaneous microvasculature.

Administration, Cutaneous↗
PubMed1989

Dynamic thermographic imaging method for quantifying dermal perfusion: potential and limitations.

A new method of quantifying dermal perfusion on a regional basis using a dynamic thermographic technique is investigated. The technique is based on the relationship between dermal perfusion and the rate of skin surface reheating following the application of a transient cold challenge predicted by a theoretical model. Measurements were made using images from a Philips thermographic camera under rigorously controlled conditions. Experimentation on undisturbed volar forearm skin of normal subjects showed that measurements could be repeated with good accuracy but that differences in normalised reheat temperatures between subjects were highly dependent on subcutaneous fat thickness. Comparisons between normal and occluded forearms indicated that reheat temperatures were not sensitive to changes in low levels of dermal perfusion. Conversely, stimulation of dermal blood flow with prostaglandin E2 did produce significant differences from control conditions, but quantifying the extent of this hyperaemia was limited by the effects of intersubject variations in fat thickness. Quantifying skin blood flow from skin temperature reheat rates is shown to be limited by a lack of sensitivity and a dependence on subcutaneous fat thickness, although dynamic thermography is able to provide useful information on regional variations in skin perfusion which could not be reliably obtained from static temperature measurements alone.

Adult↗
PubMed1989

The relation between cutaneous blood flow and cell content in the tuberculin reaction.

The relationship of velocity of blood flow to density and microanatomical distribution of inflammatory cells in the dermis was studied in 20 human tuberculin tests. Most positive reactions showed maximal blood flow velocities (measured as red blood cell (RBC) flux) at the centre of the reaction, but the two most intense responses showed 'central relative slowing' (CRS) with higher RBC flux at the periphery. Two of the four clinically negative reactions showed a considerable acceleration of blood flow, but the other two showed no such acceleration. The packing density of lymphocytes/monocytes in the perivascular zone was greater in the stronger positives than in the weaker reactions. The density of cells in the intervening dermis was markedly lower than in the foci: the lesions with CRS had the highest density of cells in the diffuse infiltrate of the reticular dermis. At the centre of the reaction, blood flow velocity was generally related to density of cellular infiltrate, except in those with CRS, which had a disproportionately lower blood flow velocity. The finding that the circulatory adaptation to a delayed hypersensitivity reaction can be inadequate may explain the dermal acidosis previously observed in intense skin test reactions, and may be the underlying mechanism of necrosis in hypersensitivity reactions.

Blood Flow Velocity↗
PubMed1989

Arterial stiffening and reduced cutaneous hyperaemic response in patients with end-stage renal failure.

Superficial dermal vasodilatory capacity and indirect segmental systolic arterial pressure were measured in 10 patients with end-stage renal failure and 13 controls. Laser-Doppler flowmetry was used to measure skin blood flow on the dorsum of the feet prior to and during local skin heating to 40 degrees C. Basal skin blood flow was not significantly different between the two groups (mean 0.8 +/- (SD) 0.3 vs. 0.7 +/- 0.2 U). Peak stimulated flow at 40 degrees C was significantly greater in the controls than in the azotaemic patients (10.0 +/- 3.5 vs. 3.5 +/- 1.6 U, p less than 0.01). Stiffening of the major limb arteries was detected in the majority of the azotaemic patients (10.0 +/- 3.5 vs. 3.5 +/- 1.6 U, p less than 0.01). Stiffening of the major limb arteries was detected in the majority of the azotaemic patients and may have contributed to the reduction in vasodilatory capacity.

Arteries↗
PubMed1988

Amputation for peripheral vascular disease: the case for level selection.

One hundred major lower limb amputations were performed for end stage peripheral vascular disease over a 15-month period. Selection of amputation level was made on the basis of laboratory criteria using skin blood flow and infrared thermography data. Eighty-one amputations were performed at the below-knee level with six failures. This resulted in a final below-knee: above-knee amputation ratio of 3:1. It is clear that there are still many centres in the UK where above-knee amputation is the accepted operation, despite the inherent drawbacks to this procedure. We recommend that more attention is given to achieving higher below-knee amputation rates to improve the chances of amputee mobility and therefore quality of life.

Amputation, Surgical↗
PubMed1988

Transcutaneous measurement of PO2 and PCO2 in the dermis at the site of the tuberculin reaction in healthy human subjects.

The respiration of the skin at the site of a delayed hypersensitivity reaction in tuberculin skin tests was studied by transcutaneous measurement of dermal oxygen and carbon dioxide tensions in normal individuals who had been immunized with BCG: six reactions were strong positives, four were weak positives, and four without induration were regarded as negative. The tcPO2 fell over the first 2 days of the reaction and remained low for the next 2 days: the severity of the changes was greater in the 'strong' reactions than in the 'weak' reactions. The tcPCO2 showed a reciprocal rise over the first 2 days and, although still high, tended to recover over the fourth day. These results indicate that local hypoxia and hypercapnia are prominent features of the positive tuberculin test, probably as a consequence of the respiration of the infiltrating lymphocytes and monocytes. It is likely that similar respiratory changes occur in those chronic inflammatory diseases where delayed hypersensitivity reactions make a contribution to the pathogenesis of the lesion.

Adult↗
PubMed1988

Effect of histamine and prostaglandin E2 on the microcirculation in the skin.

The response of the cutaneous microvasculature to two vasoactive mediators, histamine and prostaglandin E2, was measured by laser Doppler velocimetry. Four concentrations of histamine (1.01 to 65.1 X 10(-5) M, in fourfold dilutions) were injected intradermally into the forearms of six healthy subjects: Prostaglandin E2 (1.77 to 114.0 X 10(-8) M, also in fourfold dilutions) was injected several weeks later. The blood flow at the injection site was measured by laser Doppler velocimetry at five minute intervals until the response resolved. Both mediators produced hyperaemia with markedly accelerated cutaneous blood flow. Analysis of the dose response data showed that, for a given mediator, the differences in responses between subjects were not substantial and, in particular, that the kinetics of the decay of hyperaemia did not vary significantly between subjects. The response to histamine differed from that to Prostaglandin E2 in terms of time to maximum response, duration of maximum response and coefficient of decay.

Adult↗
PubMed1988

Further experience in the healing rate of lower limb amputations.

Results of lower limb amputation in the Tayside Region in the years 1981-1985 have been analysed. Three-hundred and twenty-four amputations were performed on three-hundred and eight patients. Two-hundred and thirty-six amputations were attempted at the below-knee level. Only 19 required proximal revision. Prior to amputation, all patients should have a detailed vascular assessment, and the operation should be performed by experienced amputation surgeons using meticulous technique.

Adult↗
PubMed1988

A tissue heat transfer model for relating dynamic skin temperature changes to physiological parameters.

A physical and mathematical model of the superficial tissues of the body is presented which takes into account tissue physiology, structure and blood supply. The model relates transient temperature changes at the skin surface to underlying physiological parameters. The analysis is based on a one-dimensional finite difference version of the bioheat equation applied to a multi-layered model of the superficial 10 mm of body tissue. Application of the model to the volar forearm predicts that under steady-state conditions skin surface temperature is maintained primarily by heat transfer from tissues below 10 mm, to a lesser extent by perfusion and to a small extent by superficial tissue metabolism. Model predictions of the reheat curve following a 15 s cold challenge to the skin agree closely with preliminary experimental data provided by thermography. The model also provides a physical explanation for the shape of the skin temperature reheat curve. Calculations further suggest that transient skin surface temperature measurements can provide a better indication of dermal perfusion than static temperature measurements as the effects of variations in environmental conditions, deep tissue temperature and tissue metabolism can be reduced.

Hot Temperature↗