Comparison of caffeine-induced changes in cerebral blood flow and middle cerebral artery blood velocity shows that caffeine reduces middle cerebral artery diameter.

Changes in cerebral blood flow (CBF) can be assessed directly with xenon clearance (XeC) or indirectly by measuring changes in middle cerebral artery blood velocity (Vmca) with transcranial Doppler (TCD). The aim of this study was to compare the changes in CBF and Vmca following caffeine ingestion. Nineteen patients (age 48-86, recovering from an acute stroke) and ten controls (age 52-85) were each studied twice. Bilateral measurements of CBF and Vmca were made before and after ingestion of 250 mg caffeine or matched placebo. The percentage change in CBF and Vmca after caffeine was calculated. Full results (CBF and Vmca) were obtained from 14 patients and 9 controls. There was no significant difference between patients and controls, so results were combined. Caffeine reduced CBF by 22% (95% confidence interval (CI) = 17% to 28%) and reduced Vmca by 13% (95% CI = 10% to 17%). The fall in Vmca was significantly less than that in CBF (p = 0.0016), showing that caffeine reduces mca diameter. Analysis based on Poiseuille flow in the arterioles suggests that caffeine reduced arteriole diameter by 5.9% (95% CI = 4.6% to 7.3%) and mca diameter by 4.3% (95% CI = 2.0% to 6.6%). TCD is being used as an alternative to XeC for assessing the effect of vasoconstrictors and vasodilators on CBF. This study has demonstrated that in mca diameter can be changed by the vasoactive agents, and that changes in Vmca do not necessarily reflect changes in CBF.

Influence of alcohol on cognitive performance during mild hypoglycaemia; implications for Type 1 diabetes.

AIMS: Alcohol and hypoglycaemia independently affect cognitive function. This may be relevant for insulin-treated diabetic patients who drive motor vehicles. The aim of this study was to examine the effect of mild hypoglycaemia (2.8 mmol/l) with modest alcohol intoxication (levels below UK driving limits) on intellectual performance in patients with Type 1 diabetes. METHODS: A hyperinsulinaemic glucose clamp (60 mU/m2) was used to study 17 subjects [age 35 +/- 8 years, HbA1c 8.1 +/- 1.4% (mean +/- sd)] on four occasions: (A) euglycaemia (4.5 mmol/l) with placebo, (B) euglycaemia with alcohol, (C) hypoglycaemia (2.8 mmol/l) with placebo, and (D) hypoglycaemia with alcohol. Cognitive performance was assessed using four-choice reaction time (4CRT, primary outcome), measurements of general intellectual skills [trail making B (TMB) and digit symbol substitution (DSST)], and visual information processing [visual change detection (VCD)]. A test related to driving performance (hazard perception) was also used. RESULTS: In experiments B and D the average blood alcohol level was 43 mg/dl. This was associated with deterioration in 4CRT [+ 35 ms [95% confidence interval (CI) 20, 50]] and TMB, whereas hypoglycaemia without alcohol increased 4CRT only [+ 39 ms (95% CI 5, 73)]. However, when alcohol was combined with hypoglycaemia, there was marked deterioration in all the cognitive function tests [4CRT 74 ms (95% CI 35, 113), TMB, DSST and VCD]. Hazard perception was not affected. The effect of alcohol was no different in euglycaemia than in hypoglycaemia, i.e. there was no interaction. Whereas hypoglycaemia did not reduce the likelihood that the subjects would drive, alcohol did. CONCLUSIONS: The cumulative effect of alcohol and hypoglycaemia on cognitive function together has implications for driving in patients with Type 1 diabetes. Both independently impair cognitive function and together the effects are additive. Patients with Type 1 diabetes should be educated about hypoglycaemia and driving and should avoid alcohol completely if planning to drive.

Ultrasonic power balances--effect of a coupling window on the power measured from physiotherapy ultrasound units.

The output from physiotherapy ultrasound (US) probes is usually measured using a radiation force balance. Some balances are sealed and incorporate a membrane coupling window. The probes are highly resonant, and the output may be affected by changes in acoustic loading caused by the membrane. A model has been developed to examine this effect, and predicts that a polythene membrane 100-microm thick can change the output power by up to 17%.

Transcranial Doppler blood velocity measurement--the effect of changes in velocity profile.

Transcranial Doppler (TCD) units measure blood velocity in the middle cerebral artery (MCA) and are used to examine the effects of pharmacological agents. The units actually measure the average of the maximum blood velocity envelope (aveV(max)) and it is assumed that changes in aveV(max) follow changes in the true mean velocity (aveV(mean)). This may not be true if there are changes in velocity profile. Results from previous TCD studies using acetazolamide (ACZ) and caffeine were examined for evidence for changes in velocity profile. ACZ increased aveV(max) by 21% (95% CI 13 to 29%) and aveV(mean) by 14% (95% CI 9 to 19%). Caffeine decreased aveV(max) by 8% (95% CI 4 to 12%) and aveV(mean) by 5% (95% CI 4% increase to 13% decrease). In both cases, the true change, measured using aveV(mean) was lower, indicating possible changes in velocity profile. We conclude that the possibility of changes in velocity profile must be considered when using TCD to quantify changes in blood velocity.

Reversal of caffeine withdrawal by ingestion of a soft beverage.

Followlng regular use, acute cessation of caffeine is associated with a characteristic withdrawal syndrome. Despite this, caffeine remains popular with its consumers. The aim of this study was to examine the physiologic and psychologic effects of small caffeine doses, administered in the form of a market-leading soft drink, on healthy women who were acutely withdrawn from caffeine. After 48-h abstinence and overnight fast, 11 healthy (22 to 40 years) female volunteers, all regular caffeine users (daily consumption 143 to 773 mg) consumed using a double-blind. randomized, controlled cross-over design either 2 tins of regular or caffeine-free Diet Coke. On both visits a Mars bar was eaten to prevent hypoglycaemia. Thus, the caffeine load was 76 or 10 mg respectively. Following ingestion of regular Diet Coke, there was a l0% fall in middle cerebral artery velocity (95% CI [6%-l4%], p < 0.005 versus caffeine free) and improvement in feelings of pleasure (p < 0.046) and energy (p < 0.037). Intellectual function (4-choice reaction time) was unaffected by caffeine status. On both visits, ingestion of Diet Coke induced a pressor response (maximum rise in systolic pressure +15+/- 2 mm Hg with caffeine and +l2 +/- 2 mm Hg with caffeine-free beverage, both p < 0.001 compared with baseline). In conclusion, in women acutely withdrawn from caffeine, ingestion of a popular soft beverage containing modest amounts of caffeine is associated with demonstrable physiologic and psychologic effects.

Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes.

OBJECTIVE: To examine the influence of caffeine on the frequency and perception of hypoglycemia in "free-living" patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 34 patients with type 1 diabetes were recruited for a prospective randomized placebo-controlled double-blind study. After a lead-in phase and while adhering to a low-caffeine diet, subjects were randomized to capsules containing either 200 mg caffeine or matched placebo with crossover at 3 months. Hypoglycemic episodes were monitored throughout with capillary blood glucose readings and a symptom questionnaire. During the study, measurements of blood pressure, middle cerebral artery blood velocity (a surrogate measure of cerebral blood flow), cognitive function (via a four-choice reaction time test), HbAlc levels, and lipid profiles were taken at the beginning and end of each phase. RESULTS: Throughout the study, no changes were evident regarding glycemic control or lipid profile. The number of symptomatic episodes was greater with caffeine (1.3 vs. 0.9 episodes/week; P < 0.03) and was associated with more intense warning symptoms (29 vs. 26 total symptom score; P < 0.05). For women, caffeine ingestion caused a modest pressor response (115 vs. 110 mmHg; P < 0.01). Four-choice reaction time improved slightly with caffeine supplementation (P < 0.05). CONCLUSIONS: Ingestion of modest amounts of caffeine enhances the intensity of hypoglycemia warning symptoms in patients with type 1 diabetes without altering the prevailing standard of glycemic control or increasing the incidence of severe hypoglycemic episodes.

Review of duplex and colour Doppler imaging of lower-limb arteries and veins.

Ultrasonic imaging provides a non-invasive assessment of the arterial and venous circulation in the lower limb and is accepted as a valuable diagnostic technique. Grey-scale images identify plaque and thrombus, duplex assessment provides a measurement of blood velocity through a vessel, and colour Doppler imaging enables the rapid localization of arterial stenoses and occlusions and the identification of incompetent veins. This article outlines the principles of the different techniques and presents normal images. Procedures for investigating arterial stenoses, superficial venous incompetence and deep venous thrombosis are described, abnormal images presented and the limitations discussed. It is hoped to provide an insight into the strengths and limitations of ultrasonic vascular investigations for those involved in tissue viability and ulcer management.

Surface heating of diagnostic ultrasound transducers.

Surface temperatures of a variety of transducers used with common commercial ultrasonic diagnostic equipment have been measured. Transducers operating in imaging mode, in both continuous and pulsed Doppler modes, and in mixed modes were investigated. A total of 30 transducers and scan-heads used with equipment from 10 manufacturers were examined, including a range of array types, mechanical sectors and continuous-wave Doppler transducers. Measurements were made using an infrared radiometer, or a thermocouple probe, with the transducers operating in air. Surface temperatures of 13 transducers operating in imaging mode were found to be in the range 0.0-13.1 degrees C above ambient after 5 min operation. Some transducers operating in pulsed Doppler mode reached considerably higher temperatures. The most extreme example increased the surface temperature by 36.5 degrees C after 1 min and reached a steady-state temperature of almost 80 degrees C. Transducers operating at these temperatures cannot be retained on the skin of a conscious subject without pain, and will cause skin burns within a brief period of time. A linear relationship has been demonstrated between temperature increase and spatial-average acoustic intensity. The rate of increase in air was found to be about 10 times greater for pulsed arrays than for continuous-wave Doppler transducers.

Continuous 24 hour ambulatory monitoring of intragastric pH in man.

A system has been developed which permits continuous 24 hour ambulatory recording of intragastric pH under near-physiological conditions. The system utilises a Cecar combination pH electrode connected through a pre-amplifier to an Oxford Medical Systems Medilog 4-24 cassette recorder, and the pH recorded continuously on to tape. The data is replayed at high speed, digitised and then analysed. Sources of error included system drift, system noise and the effect of changes in electrode environment due to saliva, food, loss of fluid contact, temperature variations and electrode time constant. These were found to be small. In contrast, the major changes in pH detected reflect real changes at the electrode tip. These changes can be recorded by the system. Developments in electronics and improvements in both the size and quality of pH electrodes, over the past few decades, has enabled intragastric pH recordings to be made with greater ease. However, a large number of investigators still assess gastric acidity by infrequent, intermittent sampling of gastric secretion through a naso-gastric tube. This new ambulatory system is a significant improvement and its versatility allows studies in acid secretion physiology, pharmacology and pathophysiology.

The effects of pulsed magnetic fields of the type used in the stimulation of bone fracture healing.

The main impression received by us whilst writing this review is the scarcity of technical data in the clinical studies and the total absence of controlled trials. The spatial patterns of the stimulus have not been measured, and no experiments have proved that there is an effect from the magnetic field itself. Control experiments using dummy stimulators must be done, since the orthopaedic management of the stimulated patients is different from conventional management and this may have significant and beneficial clinical effects. There is no clinical study at present which shows a direct therapeutic benefit due solely to the application of the magnetic field component of the overall treatment regime. The in vivo animal experiments suggest that there may be effects due to the magnetic fields used but results are very scarce compared with the accumulated data from direct current stimulation. In vitro studies are far removed from the clinical situation, but could nonetheless prove useful if the opportunity of controlling the stimulus can be taken. In the majority of experiments, approximately spatially uniform magnetic fields have been applied, but temporal changes in the magnetic field and both spatial and temporal variation in electric field lead to non-uniform stimulation. Little attempt has been made to assess or control the induced fields by defining the system geometry. Hence it is still unknown whether effects are due to the magnetic field, the induced extracellular electric field or to fields induced at cellular level by regions of different conductivity. In conclusion, we believe that, unlike steady current work, the pulsed magnetic field treatment of fractures has not been sufficiently well investigated and, although some of the animal experiments suggest significant effects, the benefit of using magnetic fields in the clinical management of non-union and delayed union has still to be proven. Double blind trials are essential and, if these do prove that there is a definite effect of the fields, the mechanisms must then be studied using a combination of theoretical, in vivo and in vitro techniques.

The optimum frequency and angle of insonation for a Doppler ultrasonic flow velocity meter.

A simple model is used to indicate the optimum ultrasonic frequency and angle of insonation for Doppler studies on vessels at different depths in the body. The criterion taken in determining this optimum frequency is the minimum error in a mean or root mean square frequency meter. The analysis shows that theoretically there is an optimum angle and frequency that depends on the depth of the vessel being examined, and that the optimum frequency is much lower than that normally used.

A simple radiation balance for measuring ultrasonic power.

The design and construction of a beam balance for measuring the power outputs of therapeutic and diagnostic ultrasonic instruments is described. Power outputs down to 4 mW have been measured using a low magnification microscope.