Comparison of vibration perception thresholds in individuals with diffuse upper limb pain and carpal tunnel syndrome.

The study objective was to compare vibration perception and patterns of blood flow in outpatients with diffuse upper limb pain disorder (ULPD), carpal tunnel syndrome (CTS) and age and sex matched healthy controls. Vibration perception and discrimination thresholds were compared in subjects with ULPD (n=27), CTS (n=27) and healthy matched controls (n=54). Vibration measurements were taken bilaterally at three sites: (a) over the dorsum of the second and (b) fifth metacarpals and (c) the palmar aspect of the first and second metacarpals, corresponding to the innervation territories of the radial, ulnar and median nerves, respectively. Non-invasive assessments of peripheral blood flow were also performed in both limbs. When compared to healthy controls, subjects with ULPD had widespread elevation of vibration thresholds both ipsilateral and contralateral to the symptomatic limb. Subjects with CTS had similarly elevated vibration thresholds at sites both adjacent to and distant from the site of peripheral nerve injury. The responses to cold pressor testing of the upper limbs were physiologically normal in both the CTS and ULPD patient groups. Furthermore, there were no significant differences in the haemodynamic responses between the patient groups. The global elevation of vibration thresholds in subjects with both ULPD and CTS is consistent with altered central nervous system mechanisms, common to both conditions, which may be either adaptive to or maintaining the perception of pain.

Effect of nitric-oxide-generating system on microcirculatory blood flow in skin of patients with severe Raynaud's syndrome: a randomised trial.

BACKGROUND: Patients with Raynaud's syndrome have abnormal digital vasoconstriction, which may be secondary to impaired synthesis of, or impaired sensitivity to, nitric oxide. We studied the effect on microcirculation of a nitric-oxide-generating system applied topically to the finger and forearm of healthy volunteers and patients with primary Raynaud's syndrome. METHODS: We did a single-blind, randomised, placebo controlled, cross-over study of the microcirculatory response to topical application of a nitric-oxidegenerating gel in 20 patients with severe Raynaud's syndrome, and ten healthy volunteers. We prepared the nitric-oxide-generating system by mixing a solution of KY jelly and sodium nitrite (5% weight/volume), with a solution of KY jelly and ascorbic acid (5% weight/volume). About 0.5 mL of each solution was separately applied to the skin of the forearm (3 cm2), and then mixed with a sterile cotton bud. A similar procedure was done simultaneously on the other arm with KY jelly only (placebo). The procedure was then repeated on the finger pulps. Changes in skin microcirculatory volume and flux were measured bilaterally by infrared photoplethysmography and laser doppler fluxmetry, respectively. FINDINGS: In the forearm, blood flow increased significantly after application of the active gel both in patients with Raynaud's syndrome (microcirculatory volume from mean area under the curve 98 [SE 14] to 1024 [130]; microcirculatory flux from 5060 [462] to 74,800 [3940]) and in healthy controls (volume from 85 [19] to 1020 [60]; flux from 4420 [435] to 84,500 [7000]). In the fingers, although baseline blood flow was lower in patients than in controls, both groups showed increases with application of active gel (volume from 1100 [194] to 3280 [672] and 2380 [441] to 6160 [1160], respectively; flux from 33,400 [4200] to 108,000 [13,600] and 52,000 [8950] to 185,000 [19,500]). Increases in blood flow with placebo gel were not significant. No adverse effects were reported. INTERPRETATION: In primary Raynaud's syndrome, topical application of a nitric-oxide-generating system can stimulate an increase in both microcirculatory volume and flux.

Measurements of calf muscle pump efficiency during simulated ambulation.

OBJECTIVE: To determine the acceptability and reproducibility of a novel method of measuring calf muscle pump efficiency (CMPE). If confirmed, to examine if the results had implications for the use of elastic compression stockings. EXPERIMENTAL DESIGN: A system devised to measure pressure/volume relationships in the calf during simulated ambulation and from which may be derived a value for CMPE. SETTING: A temperature/humidity controlled vascular laboratory. PARTICIPANTS: The study groups were normal subjects and patients with leg pain of more than three months duration with and without chronic venous insufficiency (CVI) identified using infra-red photoplethysmography. RESULTS: The system described is widely acceptable and reproducible (r = 0.923). Group analysis showed a significant reduction of CMPE in patients with CVI. However, CMPE varies widely in these patients. Some patients with insufficiency of the deep veins have a normal CMPE. CONCLUSIONS: These findings have implications for the use of elastic compression stockings and the degree of compression applied.

Treatment of severe Raynaud's syndrome by injection of autologous blood pretreated by heating, ozonation and exposure to ultraviolet light (H-O-U) therapy.

OBJECTIVE: To determine the effect of re-injection of small samples of autologous blood, pretreated with heat, ozone and ultraviolet light (H-O-U therapy) in patients with severe Raynaud's syndrome. EXPERIMENTAL DESIGN: Open trial in 4 patients. SETTING: Temperature/humidity controlled vascular laboratory. PATIENTS: Severe Raynaud's syndrome of more than 5 years duration and defined as more than 5 attacks daily or 10 attacks in one week, at least half of which were painful and lasting for more than 30 minutes. Three patients were refractory to infusions of Iloprost. INTERVENTIONS: Patients were treated daily or on alternate days for a two to three weeks period by re-injection of citrated autologous blood pre-treated with heat, ozone and ultraviolet light (H-O-U therapy). MEASURES: Clinical observations; mean equilibrated hand temperature (infrared thermography); distributive and microcirculatory blood-flow (venous occlusion strain-gauge plethysmography, infrared photoplethysmography, laser Doppler flowmetry) iontophoresis of acetylcholine and sodium nitroprusside; estimations: serum levels of 6-keto-PGF1alpha and serum levels of anti-hsp65 antibody. RESULTS: Reduction or abolition of Raynaud's attacks for at least three months after treatment. Mean equilibrated hand temperature increased but did not normalise. Blood flow parameters improved but did not reach statistical significance. Iontophoresis of acetylcholine showed an increase in laser Doppler flowmetry which was statistically significant. Serum levels of 6-keto-PGF1alpha, fell significantly in three patients. Serum levels of anti-hsp65 antibody fell in the one patient which was followed sequentially. CONCLUSIONS: H-O-U therapy may prove useful in patients with severe Raynaud's syndrome.

Correlation of pain with temperature and blood-flow changes in the lower limb following chemical lumbar sympathectomy in reflex sympathetic dystrophy. A case report.

Temperature and microcirculatory blood flow studies have been measured before and after chemical sympathectomy in a patient with reflex sympathetic dystrophy of the left leg present for at least three years following surgery for glomus tumour. Normalisation of temperature and blood flow was associated with the relief of pain, present initially when the limb was hypothermic and vasoconstricted and recurring when the limb was hyperthermic and vasodilated. It is possible that such objective measurement may be used to determine the optimal management of RSD.

Oral iloprost as a treatment for Raynaud's syndrome: a double blind multicentre placebo controlled study.

OBJECTIVE: To compare the efficacy, tolerance and safety of 50-150 micrograms orally administered iloprost given twice a day versus placebo in patients with Raynaud's syndrome. METHODS: The study was multicentre (n = 3), double blind and placebo controlled. Sixty three patients who had eight or more vasospastic attacks per week were enrolled. After a one week run-in period, all patients received either iloprost or placebo treatment to a maximum tolerated dose of 150 micrograms twice a day for 10 days. Diary cards assessed the duration and severity of the vasospastic attacks. Side effects were monitored by direct questioning. A global assessment of treatment efficacy was made by the patient at the end of treatment and two weeks later. RESULTS: Patient opinion tended to favour iloprost at the end of the 10 day treatment phase (p = 0.09) and this was significant at day 24 (the follow up visit) (p = 0.011). Although the duration and severity of attacks tended to decrease in the iloprost treated group, these results tended not to reach statistical significance (for severity p = 0.06 at end of treatment, p = 0.09 on day 24). CONCLUSION: Iloprost administered intravenously has been shown to be of benefit in the treatment of the Raynaud's syndrome associated with systemic sclerosis, but this route of administration is inconvenient. This study evaluated the use of iloprost administered orally to patients with Raynaud's syndrome. Patient documented improvement was significantly improved by iloprost. Diary card analysis showed a trend in favour of iloprost, but these results did not reach statistical significance.

A comparison of the functioning of arteriovenous anastomoses in secondary Raynaud's phenomenon and control subjects in response to local hand warming.

Little information is available on the functioning of the arteriovenous anastomoses (AVA's) and their involvement in the pathophysiology of cold sensitivity and abnormal thermoregulation in scleroderma. Twenty-four patients with scleroderma and twenty two control subjects were included in an investigation to test the hypothesis of abnormal functioning of AVA's. Cutaneous microcirculatory flow was measured using non-invasive instrumentation (infrared photoplethysmography, laser Doppler flowmetry and thermography) which allowed microcirculatory flow to be characterized at different levels, before and after warming of the hand at 40 degrees C for 5 minutes. The sclerodermics showed significantly reduced microcirculatory flow and hand temperatures throughout the investigation indicating the presence of organic vascular structural changes. However, the most striking finding was the reduction in microcirculatory volume in the control hand in contrast to the increase in the sclerodermic hand, on warming. We propose that the decrease in microcirculatory volume in the controls is due to a form of "steal" phenomenon where dilatation of the AVA's allow the shunting of blood away from the capillaries directly into the deeper cutaneous veins. The absence of this response in the sclerodermic group suggests the failure of the AVA's to open on warming. It is likely that the morphological vascular changes may be only partly responsible for the abnormal functioning of the AVA's and that dysfunction of the peripheral nervous system, as a consequence of microangiopathy, may also be a contributory factor.

Elements of a consensus on the therapeutic approach to thromboembolic disease.

A committee of twenty-nine international experts met at Windsor, England, during November 1991. Their purpose was to make recommendations on the current practice of prophylaxis against venous thromboembolic disease. This article is intended to provide a synopsis of some of the problems addressed at the meeting and the solutions proposed. It does not in any way replace the final consensus statement recently published.

Reflex sympathetic dystrophy and repetitive strain injury: temperature and microcirculatory changes following mild cold stress.

Temperature and blood flow studies were performed in the upper limbs of six patients with reflex sympathetic dystrophy (RSD), nine patients with repetitive strain injury (RSI) and 12 control subjects using thermography, laser Doppler flowmetry, infrared photoplethysmography and venous occlusion strain gauge plethysmography. The contralateral responses of the symptomatic and asymptomatic limbs were examined after being subjected, separately, to mild cold stress (20 degrees C for 1 min). Altered thermoregulation and haemodynamics were evident in RSD. Though the pattern of response to contralateral cold challenge is similar to normal in RSI, vasodilatation and reduced vasomotion appears to be characteristic in this condition. Such changes may assist in distinguishing between RSD and RSI from other causes of chronic upper limb pain.

Design and evaluation of a device for measurement of interface pressure.

An electropneumatic device has been designed to measure the interface pressure profile under compression bandages. The device uses commercially available pneumatic sensors (Talley Group Ltd, SJ235/3) and measures interface pressure at up to eight sites simultaneously along the lower limb, with an accuracy of +/- 3 mmHg. Measurements can be made in one of two modes: continuously at a rate of up to three samples per second with the results output to a suitable display device, or single measurements of interface pressure can be made and displayed on a digital display incorporated in the device. This enables the monitoring and recording of interface pressure under compression bandages during either ambulation or passive recumbency. The electropneumatic system is described together with its following characteristics: the hysteresis of the Talley pneumatic sensors, the accuracy of pressure measurement and the maximum achievable sample rate. Dynamic measurements in a single normal volunteer are shown.

A comparison of the effects of captopril and enalapril on skin responses to intradermal bradykinin and skin blood flow in the human forearm.

1. The effects of captopril and enalapril on skin responses to intradermal injections of bradykinin and skin blood flow in the forearm were investigated in this randomised, double-blind, placebo-controlled, cross-over study. 2. Intradermal injections of 0, 1, 2.5 and 5 micrograms of bradykinin in 0.9% sodium chloride were made into the forearm of twelve healthy volunteers before and at 2, 6 and 24 h after single oral doses of 25 mg captopril, 10 mg enalapril or placebo. Forearm skin blood flow was measured by the technique of laser Doppler flowmetry (LDF) before the injections were made and the skin responses evaluated at 15 min after injections of bradykinin by measurement of cutaneous blood flow outside the induced weal, erythema area and weal volume. 3. The bradykinin-induced cutaneous responses measured by LDF, erythema area and weal volume increased with incremental bradykinin dose. Compared with placebo, captopril significantly augmented the cutaneous vasodilator effects of bradykinin, measured by LDF and erythema area, at 2 h and the weal responses at 2 and 6 h. Enalapril enhanced the vasodilator responses to bradykinin at 2 and 6 h and the weal responses at 2, 6 and 24 h. Neither captopril nor enalapril significantly affected forearm skin blood flow. 4. This study showed that captopril and enalapril potentiated the effects of intradermal bradykinin both with respect to blood flow changes and weal formation in keeping with effective kininase II inhibition and the time course of these changes are consistent with enalapril being a longer acting drug than captopril. Captopril and enalapril exerted no influence on forearm skin blood flow measured by LDF.

Cutaneous blood flow changes and weal induced by intradermal bradykinin following pretreatment with indomethacin and captopril.

The effects of indomethacin and captopril on local cutaneous blood flow changes and weal induced by intradermal injections of bradykinin were assessed in two randomised, double-blind, placebo-controlled studies in healthy volunteers. Alterations in cutaneous blood flow were estimated by laser Doppler flowmetry (LDF) and erythema area. LDF output, erythema area and weal volume increased with incremental bradykinin dose. Single doses of indomethacin 25 mg and 75 mg did not affect these cutaneous responses compared with placebo. Captopril 25 mg significantly potentiated the increase in local cutaneous blood flow measured by LDF, but not erythema area, and weal volume induced by bradykinin. The effects of the combined treatment of indomethacin 75 mg and captopril 25 mg were not significantly different from those due to captopril alone. The enhanced cutaneous effects of bradykinin following administration of captopril are in keeping with effective kininase II inhibition in the tissues. Cyclo-oxygenase products release does not appear to contribute to the cutaneous actions of bradykinin nor the potentiation of these responses by captopril.

Effects of selective histamine receptor antagonists on skin responses to intradermal bradykinin in healthy volunteers.

The effects of chlorpheniramine and cimetidine on the cutaneous responses to intradermal injections of bradykinin were investigated in a randomized, double-blind, placebo-controlled, cross-over study. Chlorpheniramine significantly attenuated the increase in cutaneous blood flow and erythema induced by bradykinin but not the weal response. Cimetidine was without influence on these parameters and the effects of the combined therapy of chlorpheniramine and cimetidine were not significantly different from those due to chlorpheniramine alone. These results suggest that the cutaneous vasodilator effect of bradykinin is in part due to histamine release acting on histamine H1-receptors.

Absence of potentiation of the skin response to intradermal bradykinin by a long-acting angiotensin converting enzyme inhibitor, trandolapril, at conventional antihypertensive dosage in human volunteers: a double-blind, randomized, cross-over, placebo-controlled trial.

A double-blind, randomized, cross-over, placebo-controlled study was carried out to determine the extent and duration of potentiation of the action of bradykinin introduced intradermally by a long-acting novel angiotensin converting enzyme (ACE) inhibitor, trandolapril. The investigations were performed in a temperature and humidity-controlled laboratory. Intradermal injections of 1 microgram, 2.5 micrograms and 5 micrograms of bradykinin and normal saline (as control) were made into the forearm skin of eight healthy normotensive male volunteers aged 21-33 years (mean 28 years) at baseline, 2, 4, 8, 24, 48, 72 and 96 hours after either 2 mg trandolapril or placebo given orally. Skin blood flow outside the induced weal was monitored by laser Doppler flowmetry (mean of recordings at four sites adjacent to the weal within the flare area). Flare area and weal volume were also measured. Trandolapril reduced the mean arterial pressure. However, there was no evidence that this activity was associated with a potentiation of the cutaneous action of bradykinin. In conclusion, it would appear that potentiation of the action of bradykinin may not be an important contributing factor to the fall in total peripheral vascular resistance associated with ACE inhibition in humans in the control of hypertension.

Skin blood flow changes following intradermal bradykinin injections measured by laser Doppler flowmetry: comparison with weal and flare.

Intradermal injections of normal saline and different concentrations of bradykinin were made into the forearms of healthy volunteers. Cutaneous blood flow was recorded just outside and over the centre of the weals by laser Doppler flowmetry (LDF), and flare area and weal volume were measured. There were concentration-related changes in the mean LDF output adjacent to the weal, flare area and weal volume. LDF recordings performed over the centre of the weals, however, failed to show any dose-response relationship. When similar concentrations of bradykinin were injected intradermally and the skin response measured by the above parameters, there was less variation in the mean LDF output adjacent to the weal than flare or weal measurements. The non-invasive technique of LDF is a useful, objective and sensitive technique of quantifying the skin blood flow changes induced by intradermal bradykinin and provides an alternative method of quantifying skin response to intradermal bradykinin to measurement of flare or weal sizes.