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Biomedical subjects

E D Cooke

Publications and source records attributed to E D Cooke.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

Reflex sympathetic dystrophy (algoneurodystrophy): temperature studies in the upper limb.

The temperature response of the hands to mild cold stress (20 degrees C for one minute) has been measured in 20 normal subjects, 20 patients with reflex sympathetic dystrophy (RSD) and 10 patients with chronic upper limb pain (CULP) of uncertain origin. The results of RSD and CULP groups were significantly (p less than 0.05) different from normal but were indistinguishable. For each patient, 11 variables obtained from the thermal stress test were compared with the normal range. Ten of the RSD group and seven of the CULP group had four or more abnormal variables and were considered to have a thermoregulatory abnormality. The thermal stress test is useful in the objective assessment of RSD. It is non-invasive, patient acceptable and reproducible.

Adult↗

High quality photoplethysmograph signals from a laser Doppler flowmeter: preliminary studies of two simultaneous outputs from the finger.

An improvement in the quality of a photoplethysmography signal derived from a laser Doppler flowmeter probe has been achieved by incorporating an auxiliary fibre in the probe head. This fibre is positioned at an optimum distance from the laser light transmitting fibre and overcomes the problem of high frequency signals which mask the detailed features of the photoplethysmograph pulse when a small fibre separation is used. These two signals may be recorded simultaneously from the same site and a correlation between the Doppler output and the photoplethysmograph amplitude has been demonstrated in the finger. The amplitude is shown to be affected by the relative position of the point of measurement with respect to the heart, a factor which does not appear to influence significantly the Doppler output.

Equipment Design↗

Noninvasive measurement of the human peripheral circulation: relationship between laser Doppler flowmeter and photoplethysmograph signals from the finger.

Under certain conditions laser Doppler flowmeter (LDF) signals obtained from the finger pulp may appear very similar to those obtained by use of a direct current (dc) photoplethysmograph (PPG). A combined LDF/PPG system was used in conjunction with a circumference strain gauge as an index of volume change to identify the conditions in which the correlation between these signals was good. Simultaneous LDF and dc PPG measurements were made on 10 normal volunteers by using arterial occlusion and on 7 normal subjects by using the Valsalva maneuver at different elevations of the forearm and hand with respect to the midsternum. By altering the elevation of the upper limb the influence of venous filling on each of the signals during these maneuvers was observed. Since the dc PPG signal always appeared similar to the volume change indicated by the circumference strain gauge, it is concluded that the dc PPG signal is related to blood volume change if allowance is made for the effects of blood oxygenation. In circumstances of low venous filling, however, blood volume changes correlate well with blood flow changes, producing the correlation between the dc PPG and LDF traces. The dc PPG signal may be used as a means of monitoring changes in blood flow in the finger only when venous filling is low and the return remains unrestricted. Thus, in investigations using this method, the relative position of the limb with respect to the heart should always be indicated. The LDF method appears to be a reliable indicator of blood flow changes in the microcirculation irrespective of the degree of venous filling.

Adult↗

Peripheral vascular effects of beta-adrenoceptor blockade: comparison of two agents.

1. The effects of atenolol (100 mg), a beta 1-adrenoceptor blocker, and bevantolol (200 mg) were compared on heart rate, blood pressure, lung function and on the peripheral circulation in normal volunteers before and after isoprenaline infusion. Recordings were obtained 2 and 24 h following a single dose and 24 h after continuous dosage for 7 days. 2. The effect of atenolol on the blockade of beta-adrenergic stimuli, as measured by the ability to reduce isoprenaline-induced tachycardia, was greater than that of bevantolol. Though both drugs achieved a similar reduction in systolic pressure there was a significantly greater reduction in diastolic pressure with bevantolol. The lung function tests gave similar results to those with other beta-adrenoceptor blockers. 3. Atenolol produced a fall in peripheral blood flow consistent with unopposed peripheral alpha-adrenoceptor stimulation. The effect of bevantolol differs from that of atenolol, an initial fall in peripheral blood flow being followed by a rapid recovery to baseline or greater. This effect may be due to partial alpha-adrenoceptor agonist activity.

Adrenergic beta-Antagonists↗

Prolonged increase in digital blood flow following iloprost infusion in patients with systemic sclerosis.

Thirteen patients with Raynaud's phenomenon secondary to systemic sclerosis received three 8-hour infusions of a synthetic prostacyclin analogue (Iloprost) on consecutive days and were followed-up over a period of 10 weeks during the winter of 1985/86. Six weeks after infusion, digital peripheral vascular resistance had fallen (P less than 0.05) and dicrotic notch proportion of pulse amplitude increased (P less than 0.05). Digital blood flow and pulse amplitude (measured by photoplethymography) were also increased but did not reach statistical significance. The trend of improvement in these blood flow parameters was still evident after 10 weeks. The number of cutaneous lesions (digital ulcers, etc) fell from 26 lesions before infusion to only 7 lesions by the end of the study, confirming the subjective improvement reported by the patients.

Adult↗

Salivary beta-thromboglobulin: a possible marker for deep vein thrombosis following elective hip surgery.

The concentration of the platelet specific protein B-thromboglobulin, (BTG) was measured in salivary samples obtained pre and postoperatively from 30 patients without evidence of renal disease and having total hip replacement arthroplasty. When postoperative deep-vein thrombosis (DVT) was detected using percutaneous ascending phlebography there was total correlation with elevated salivary BTG levels taking 0.33 micrograms/1 or greater on 2 consecutive occasions or more as indicating a deep venous thrombus. Eight of nine patients with a positive diagnosis of DVT on urokinase scanning would have been diagnosed using the same criterion. However BTG was elevated in a further 5 patients in whom labelled urokinase failed to demonstrate a DVT. These may have been localised in the calf and thus missed by, or lysed prior to, the scanning technique.

Aged↗

Cold sensitivity in essential hypertension: the effect of beta- and combined alpha- and beta-blockade.

The presence of cold sensitivity was investigated in three groups of patients; untreated hypertensives and hypertensives treated by a beta-adrenoceptor blocker (propranolol) or by a combined alpha- and beta-adrenoceptor blocker (labetalol) at two ambient temperatures. At a comfortable ambient (24 degrees C) one-third of the untreated and those treated with beta-blockade only showed cold sensitivity as compared with 16% of patients on the combined therapy. Under conditions of mild cold stress (20 degrees C) cold sensitivity increased in frequency in all three groups, more than half of the untreated and beta-blocked patients were affected and greater than one-third of those with alpha- and beta-blockade. These findings indicate that in the general population of hypertensives treatment with beta-adrenoceptor blockade alone may have little effect on the peripheral vasculature and that a useful degree of protection may be provided by therapy which blocks both receptors.

Adrenergic alpha-Antagonists↗

Transcutaneous oxygen tension as an index of maturity in hypertrophic scars treated by compression.

Sixteen patients undergoing compression treatment for scar hypertrophy were included in a study to evaluate physical indices of scar maturity. The results show that while thermographic measurements of scar temperature were not clinically valuable, rising levels of transcutaneous oxygen tension in treated scars correlated well with a reduction in scar thickness assessed both clinically and by ultrasound. It is postulated that low levels of tcpO2 in immature scars result from low oxygen diffusibility through scar tissue rather than from rapid metabolic consumption of oxygen by scar tissue.

Adolescent↗

Photoplethysmography of the distal pulp in the assessment of the vasospastic hand.

A procedure for assessing the peripheral vasculature and a new technique for determining the characteristics of the a.c. (arterial) photoplethysmographic (PPG) waveform are described. Comparing 12 normal female volunteers and 12 female patients with Raynaud's phenomenon, PPG amplitude is as good as the results of a standard thermographic test in distinguishing between the groups. The limb arterial flow measured by strain gauge plethysmography (SPG) and the timing of features in the PPG waveform showed differences between the groups, which did not reach statistical significance. The rise time of the PPG waveform, however, was found to be correlated with age independently of vasospasticity.

Adult↗

CL115,347, an analogue of prostaglandin E2. Peripheral circulatory effects of single ascending doses administered transdermally in normal subjects and in patients with Raynaud's phenomenon.

The beneficial effects of intra-arterial or intravenous infusion of the prostanoid products of anachridonic acid, PGE and prostacyclin (PGI2) are well documented. More recently an analogue of PGE2, (CL 115,347, American Cynamid Co.) has become available. This substance is absorbed transdermally from a patch placed on the skin. In a placebo-controlled trial the vasodilatory effect of single incremental dosage, 500 mcg, 1000 mcg and 1500 mcg, was measured in a temperature-/humidity controlled laboratory in normal subjects and in patients with primary and secondary Raynaud's phenomenon. The optimal dosage proved to be 1000 mcg; the effect may last for 84 hours; higher dosage may be associated with a "steal" phenomenon.

Administration, Topical↗

The role of endogenous opioids in the chlorpropamide alcohol flush.

The response of plasma immunoreactive met-enkephalin (IR-met-enkephalin) to ethanol (8 g by mouth) after chlorpropamide (250 mg daily for 14 d) was studied in three groups of non-insulin dependent diabetics (a) six diabetics who showed chlorpropamide alcohol flush (CPAF) and in whom the reaction could be blocked by indomethacin, (b) five diabetics who showed CPAF but in whom the flush could not be blocked by indomethacin and (c) five diabetics who did not show CPAF. A rise in plasma IR-met-enkephalin was observed in all three groups. When the two groups of flushers were re-tested with the addition of an infusion of naloxone a rise in plasma IR-met-enkephalin was still demonstrated in both groups regardless of whether the flush was blocked by naloxone. Naloxone blocked the flush only in those six subjects whose flush could be blocked by indomethacin. In five subjects, all flushers, CPAF was tested using intravenous and oral ethanol in doses producing similar plasma ethanol levels. A facial flush was induced by both intravenous and oral ethanol. In three flushers, plasma IR-met-enkephalin levels were measured during CPAF testing with both intravenous and oral ethanol. None showed a rise in plasma IR-met-enkephalin after intravenous ethanol, despite the appearance of a facial flush, whereas all showed a rise after oral ethanol. We therefore conclude that CPAF is unlikely to be caused by a rise in plasma IR-met-enkephalin.

Administration, Oral↗