Tissue oxygen tension in normal and ischaemic human skin.

Tissue oxygen tension has been measured in the skin of the lower limbs in ten normal subjects and in six patients with peripheral vascular disease. Measurements of oxygen tension breathing air, PO2(air) and breathing oxygen for 4 min, PO2(O2:4) were assessed in the thigh, below knee and foot levels of all subjects. In normal subjects PO2(air) and PO2(O2:4) values were (+/- SD) 4.9 +/- 0.8 kPa (37.2 +/- 6.1 mmHg) and 14.8 +/- 2.2 kPa (111 +/- 16.3 mmHg) respectively with no significant difference at any level. In ischaemic subjects PO2 (air) values were significantly reduced at the foot level but PO2(O2:4) values were significantly reduced at both below knee and foot levels. Our results suggest that the rise in oxygen tension following a change from air to oxygen breathing may be a better indicator of local blood flow conditions than a measure of the tissue oxygen tension by itself.

Measurement of skin swelling in the tuberculin test by ultrasonography.

A new method is described for non-invasive measurement of the thickness of the skin at the site of a skin test from the echo pattern of a pulsed ultrasonic (15 MHz) A-mode scanner. In tuberculin tests on normal volunteers, the skin thickness increased rapidly during days 1 and 2 and was usually greatest at day 4. The echogram measurements can be used to calculate the increase in skin volume and this is disproportionately greater than would be expected from measurements of the diameters of erythema and induration.

Increased neutrophil apoptosis in chronic fatigue syndrome.

BACKGROUND/AIMS: Many patients with chronic fatigue syndrome (CFS) have symptoms that are consistent with an underlying viral or toxic illness. Because increased neutrophil apoptosis occurs in patients with infection, this study examined whether this phenomenon also occurs in patients with CFS. METHODS: Apoptosis was assessed in patients with CFS in conjunction with concentrations of the anti-inflammatory cytokine, transforming growth factor beta1 (TGFbeta1). RESULTS: The 47 patients with CFS had higher numbers of apoptotic neutrophils, lower numbers of viable neutrophils, increased annexin V binding, and increased expression of the death receptor, tumour necrosis factor receptor-I, on their neutrophils than did the 34 healthy controls. Patients with CFS also had raised concentrations of active TGFbeta1 (p < 0.005). CONCLUSIONS: These findings provide new evidence that patients with CFS have an underlying detectable abnormality in their immune cells.

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.

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.

Serum thiocyanate levels in subjects who halve their cigarette consumption.

The serum thiocyanate levels were measured in sixteen volunteers who smoked their own brands of cigarettes normally. When their cigarette consumption was reduced by half, the serum thiocyanate levels remained unaltered. The most likely explanation of this finding is that the volunteers changed their inhalation behaviour.

Amputation of the ischemic limb: selection of the optimum site by thermography.

This report describes the value of infrared thermography in assessing the optimum level of amputation of an ischemic limb. Interpretation of thermograms and the factors that can significantly alter the thermal image of the lower limbs are detailed. Results from 104 patients demonstrate that the thermographic method is a reliable indicator of the level of a major limb amputation. A rationale for the inadequacy of the method when attempting to determine the outcome of a partial foot amputation is considered.

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.

Assessment of tissue viability in relation to the selection of amputation level.

Assessment of the optimum level of amputation of an ischaemic limb can be exceptionally difficult. For this reason there has been an intensive effort, particularly in the past 20 years, to find suitable non-invasive ancillary methods to aid in the amputation level selection. This paper reviews three separate research and development areas which have evolved simultaneously in our laboratory: skin partial oxygen pressure, skin blood flow, and infrared thermography. The physiological basis for each of these measurements is discussed along with the merits and demerits of each.

A rationale for skew flaps in below-knee amputation surgery.

The use of thermography in the assessment of amputation levels has demonstrated a medial to lateral thermal gradient in many cases. In order to see whether this reflected a true medial to lateral skin blood flow gradient, a prospective study was set up to measure blood flow medially and laterally below the knee. Twenty-one patients, presenting for amputation assessment with end-stage peripheral vascular disease, were studied. Skin blood flows were measured using an intradermal radioisotope clearance technique. Results showed a highly significant difference between medial and lateral skin blood flows (t = 4.79; p less than 0.001). In view of the significantly higher blood flow in the medial skin of the lower leg, it is suggested that a more medially based posterior below-knee amputation skin flap may be of more value in some patients.

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.

The relationship between temperature isotherms and skin blood flow in the ischemic limb.

This study was conducted in order to establish a relationship between thermographically defined levels of viability in the ischemic limb and a measurement of skin blood flow. Color thermograms (10 colors, 0.6 degree C apart) defined the temperature gradient and skin blood flow was measured, using the radioactive clearance method in three discrete isotherms set 1.8 degrees C apart. The differences in skin blood flow measured in the three separate isotherms were significant (P less than 0.001). The results of this study support previously unqualified assertions that thermographic temperature gradients along an ischemic limb are indicative of local microcirculatory status. The potential of the thermographic method for demarcating viable and nonviable skin flaps at the chosen site of amputation is confirmed.

Patterns of blood flow in the microcirculation of the skin during the course of the tuberculin reaction in normal human subjects.

Digital thermographic imaging and laser-Doppler velocimetry techniques were used to study the sequence of microcirculatory changes in typical Type IV (DHS-type) skin reactions to intradermal injection of PPD into seven healthy tuberculin-positive subjects. Thermography has shown that there is very little change in thermal status at 6 hr, that there is an area of raised temperature roughly corresponding to that of erythema around the site of antigen injection at 24 hr, and that the area of 'hot' skin starts to exceed that of the clinically observed reaction at 48 hr and remains extensive even at 96 hr. The area of the increased RBC flux detected by the laser-Doppler technique corresponded generally to that of erythema for the first 48 hr, but thereafter became smaller than the clinically observable reaction. Cuff occlusion experiments showed that the phenomenon of reactive hyperaemia is abolished at 24 and 48 hr in conditions of maximal hyperaemia, but that this response is recovering by 96 hr. Vasomotion was significantly exaggerated between 48 hr and 96 hr. These studies indicate that there is maximal arteriolar vasodilatation during the first 2 days of the reaction with rapid blood flow in the congested capillaries of the dermal papillae, and that engorgement of deeper venous plexus of the dermis is the predominant vascular change in the resolving response at 72-96 hr.

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.

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.