No abstract

Over the past decade there has been great interest in the therapeutic potential of brain cooling for epilepsy, stroke, asphyxia and other neurological diseases. However, there is still no consensus regarding the neurophysiological effect(s) of brain cooling. We employed standard physiological techniques and 2-photon microscopy to directly examine the effect of temperature on evoked neurotransmitter release in rat hippocampal slices. We observed a monotonic decline in extracellular synaptic potentials and their initial slope over the temperature range 33-20• C, when the slices were cooled to a new set point in less than 5 s. Imaging the fluorescent synaptic marker FM1-43 with 2-photon microscopy showed that the same cooling protocol dramatically reduced transmitter release between 33 and 20• C. Cooling also reduced the terminal FM1-43 destaining that was induced by direct depolarization with elevated K + , indicating that axonal conduction block cannot account for our observations. The temperature dependence of FM1-43 destaining correlated well with the effect of temperature on field potential slope, compatible with a presynaptic explanation for our electrophysiological observations. Optical measurement of FM1-43 dissociation from cell membranes was not affected by temperature, and rapid cooling of slices loaded with FM1-43 did not increase their fluorescence. Our experiments provide visible evidence that a major neurophysiological effect of cooling in the mammalian brain is a reduction in the efficacy of neurotransmitter release. This presynaptic effect may account for some of the therapeutic benefits of cooling in epilepsy and possibly stroke.

We have investigated the effects of alcuronium (0.15 mg/kg body weight) on heart rate, stroke volume, cardiac output, mean arterial blood pressure and total peripheral resistance in 22 artificially ventilated patients anaesthetized with 60 per cent nitrous oxide in oxygen, plus either tubocurarine (25-35 mg, according to body weight) and 0.2 per cent methoxyflurane-series I-or phenoperidine (1 mg/15 kg body weight)-series II. End-tidal Pco 3 was maintained constant. The most striking effect was a significant increase of heart rate in the series II patients, accompanied by a significant fall of cardiac output and of stroke volume. There was no significant change of mean arterial pressure in either series of patients; therefore the fall of cardiac output was accompanied by a compensatory increase of total peripheral resistance.

Carcinoma of Bronchus-Beicher and Anderson MEDICAL URANeither the operative mortality nor the survival rate had changed significantly during the 15 years. The survival rate was not affected by the proportion of lobectomies among the resections, although this had risen considerably during the 15 years.There was some correlation between the five-year survival rate and the resection rate. REFERENCES Barrett, R. J., Day, J. C., O'Rourke, P. V., Chapman, P. T., Sadeghi Adams, 1944) that the intravascular injection of a local anaesthetic agent was associated with analgesia in the area supplied by that vessel, this knowledge was not put to practical use until Bier (1908) published his account of venous anaesthesia for limb surgery. His method achieved considerable popularity in the next few years, and its use was widely reported.Bier's technique, though effective, was cumbersome, and although an improvement in the form of a single-tourniquet method was described by Morrison (1931) few were then employing venous anaesthesia in this country. The subject was well reviewed by Adams (1944), but the credit for the reintroduction of the "technique" undoubtedly goes to Holmes. His series consisted chiefly of relatively short operative procedures of a type suitable for the casualty department. Our aims in the present trial were twofold: (1) to assess the suitability of the method for more extensive limb surgery, and (2) to investigate the incidence and nature of lignocaine toxicity phenomena occurring after release of the tourniquet. Materials and MethodThe technique described by Holmes was used. An indwelling needle was inserted in a vein before application of an Esmarch bandage and tourniquet. After exsanguination of the limb lignocaine was injected.Patients due for peripheral limb surgery were interviewed, and, after explanation of the method, were asked whether they would agree to have their operation performed under analgesia of this type. Premedication, usually with an appropriate dose of papaveretum and hyoscine, was given in over three-quarters of the cases. Plate electrodes were attached to each limb in the anaesthetic room and connected to a direct-writing E.C.G. machine. A von Recklinghausen oscillotonometer cuff was put on the arm not scheduled for surgery and the systolic bloodpressure recorded. Difficulty was occasionally experienced through Gordh needles becoming dislodged from veins during application of the Esmarch bandage; polyvinyl chloride catheters inserted through a Macgregor (1960) introducing needle or fine-gauge Intracaths were occasionally used. After injection of the lignocaine and positioning the patient standard lead E.C.G. tracings were obtained. During surgery the bloodpressure was recorded by the oscillotonometer on at least four occasions.After completion of surgery the tourniquet was deflated and an E.C.G. tracing begun: this ran for two and a half minutes. or longer if any irregularity was noticed. The blood-pressure was recorded at half-minute intervals during this period, and the appearanc...

Intracellular free calcium concentrations ([Ca2+]i) are assessed by measuring indicator fluorescence in entire cells or subcellular regions using fluorescence microscopy. [Ca2+]i is calculated using equations which link fluorescence intensities (or intensity ratios) to calcium concentrations [G. Grynkiewicz, M. Poenie, R.Y. Tsien, A new generation of Ca2+ indicators with greatly improved fluorescence properties, J. Biol. Chem. 260 (1985) 3440-3450]. However, if calcium ions are heterogeneously distributed within a region of interest, then the observed average fluorescence intensity may not reflect average [Ca2+]i. We assessed potential calcium determination errors in mathematical and experimental models consisting of 'low' and 'high' calcium compartments, using indicators with different affinity for calcium. [Ca2+] calculated using average fluorescence intensity was lower than the actual mean concentrations. Low affinity indicators reported higher (more accurate) values than their high affinity counterparts. To estimate compartment dimensions and respective [Ca2+], we extended the standard approach by using different indicator responses to the same [Ca2+]. While two indicators were sufficient to provide a partial characterization of two-compartment model systems, the use of three or more indicators offered full description of the model provided compartmental [Ca2+] were within the indicator sensitivity ranges. These results show that uneven calcium distribution causes underestimation of actual [Ca2+], and offers novel approaches to estimating calcium heterogeneity.