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Biomedical subjects

E D Cooke

Publications and source records attributed to E D Cooke.

At least 19 recordsLinked to original sources
PubMed1997

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.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

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.

Administration, Oral↗
PubMed1995

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.

Arteriovenous Anastomosis↗
PubMed1995

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.

Aged↗
PubMed1994

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.

Adult↗
PubMed1993

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.

Bradykinin↗
PubMed1993

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.

Bandages↗
PubMed1993

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.

Adult↗
PubMed1993

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.

Adult↗
PubMed1992

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.

Adult↗
PubMed1992

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.

Administration, Oral↗
PubMed1990

Raynaud's syndrome.

Explore the source record for details and available documents.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study.

OBJECTIVE: To compare the long term effects of short term intravenous infusions of iloprost with those of oral nifedipine in patients with Raynaud's phenomenon associated with systemic sclerosis. DESIGN: Double blind, placebo controlled, randomised group comparison. SETTING: Dermatology outpatient clinic. PATIENTS: Twenty three patients with Raynaud's phenomenon associated with well documented systemic sclerosis (American Rheumatism Association criteria) and with typical abnormalities in fingernail folds on capillaroscopy. INTERVENTIONS: Twelve patients were randomised to receive intravenous infusions of iloprost starting at 0.5 ng/kg/min and increased by 0.5 ng/kg/min every 15 minutes to a maximum of 2.0 ng/kg/min for eight hours on three consecutive days with a further single infusion at week 8. Placebo capsules were given concurrently. Eleven patients were randomised to receive nifedipine, starting at 30 mg daily and increased to 60 mg daily after four weeks for another 12 weeks. Infusions of placebo were given in the same manner as the infusions of iloprost. One patient from each group withdrew because of social reasons and three patients receiving nifedipine withdrew because of side effects. END POINT: Reduction in number, duration, and severity of attacks of Raynaud's phenomenon, reduction in number of digital lesions, increase in digital blood flow. MEASUREMENTS AND MAIN RESULTS: Measurements were taken at 0, 4, 8, 12, and 16 weeks. Both regimens produced a reduction in the number, duration, and severity of attacks of Raynaud's phenomenon. The mean (SE) number of digital lesions was reduced with iloprost (from 3.5 (1.6) to 0.6 (0.3] and with nifedipine (from 4.3 (0.8) to 1.4 (0.5] after 16 weeks. Hand temperature and digital and microcirculatory blood flow were increased with iloprost but not with nifedipine. CONCLUSION: Both iloprost and nifedipine are beneficial in the treatment of Raynaud's phenomenon. With nifedipine, however, side effects are common. Short term infusions of iloprost provide longlasting relief of symptoms, and side effects occur only during the infusions and are dose dependent.

Administration, Oral↗
PubMed1989

Effect of captopril on skin blood flow following intradermal bradykinin measured by laser Doppler flowmetry.

The effect of captopril on skin response to intradermal injection of bradykinin was investigated by laser Doppler flowmetry (LDF) and weal and flare measurements in this randomised, double-blind, placebo-controlled, cross-over balanced study. Intradermal injections of 1 and 2.5 micrograms of bradykinin and normal saline were made into the forearm skin of six healthy volunteers between 1 and 2 h (t1) and between 3 and 4 h (t2) after either 25 mg captopril or placebo. Skin blood flow outside the induced weal was monitored continuously by LDF for 15 min and the mean LDF values over the last 15 s were used for analysis. Weal and flare sizes were measured at 15 min. On the placebo days, the mean LDF output, weal volume and flare area increased with incremental bradykinin dose. Pre-treatment with captopril significantly increased LDF output following intradermal bradykinin at t1 but not at t2. At both t1 and t2, captopril significantly increased weal volume. There was no significant difference between treatments in flare areas. Skin response following intradermal normal saline, measured by the above parameters, was not affected by captopril. This study showed that captopril potentiated the effects of intradermal bradykinin both with respect to blood flow changes and weal formation. The non-invasive technique of LDF can be used to detect the skin blood flow changes induced by intradermal bradykinin and the potentiation of this effect by captopril. It appears to be a useful and more objective method of quantifying local cutaneous blood flow changes than measurement of flare area.

Adult↗
PubMed1989

Observations on the photoplethysmograph pulse derived from a laser Doppler flowmeter.

A photoplethysmograph signal has been derived from a laser Doppler flowmeter which uses optical fibres separated by 1 mm. When compared with a conventional photoplethysmograph, the trace contains a higher proportion of random signal superimposed on the pulse. The bandlimited laser photoplethysmograph (0.5-16 Hz) was recorded from the finger in six subjects. At low blood flows or during arterial occlusion the random component was more evident, producing a significant signal power increase in the range 8-16 Hz. It is proposed that this noise associated with laser photoplethysmographs is partly intrinsic signal due to low frequency Doppler shifts, which predominate at low blood flows, or intensity fluctuations as slow moving blood cells traverse the laser speckle pattern. Increasing the fibre separation above 2-3 mm reduces the relative amplitude of the random component producing a much improved photoplethysmograph signal. Multiple scattering at this separation tends to reduce the proportion of low frequency Doppler shifts. Signal averaging may be used to smooth the photoplethysmograph from the 1 mm fibre separation to give a pulse essentially identical to the improved signal obtained at higher separations. Photoplethysmograph amplitude demonstrated a non-linear relationship with the laser Doppler value from the same site during finger re-warming following cold stress.

Arterial Occlusive Diseases↗