OBJECTIVE Ultrasound can be precisely focused through the intact human skull to target deep regions of the brain for stereotactic ablations. Acoustic energy at much lower intensities is capable of both exciting and inhibiting neural tissues without causing tissue heating or damage. The objective of this study was to demonstrate the effects of low-intensity focused ultrasound (LIFU) for neuromodulation and selective mapping in the thalamus of a large-brain animal. METHODS Ten Yorkshire swine ( Sus scrofa domesticus) were used in this study. In the first neuromodulation experiment, the lemniscal sensory thalamus was stereotactically targeted with LIFU, and somatosensory evoked potentials (SSEPs) were monitored. In a second mapping experiment, the ventromedial and ventroposterolateral sensory thalamic nuclei were alternately targeted with LIFU, while both trigeminal and tibial evoked SSEPs were recorded. Temperature at the acoustic focus was assessed using MR thermography. At the end of the experiments, all tissues were assessed histologically for damage. RESULTS LIFU targeted to the ventroposterolateral thalamic nucleus suppressed SSEP amplitude to 71.6% ± 11.4% (mean ± SD) compared with baseline recordings. Second, we found a similar degree of inhibition with a high spatial resolution (∼ 2 mm) since adjacent thalamic nuclei could be selectively inhibited. The ventromedial thalamic nucleus could be inhibited without affecting the ventrolateral nucleus. During MR thermography imaging, there was no observed tissue heating during LIFU sonications and no histological evidence of tissue damage. CONCLUSIONS These results suggest that LIFU can be safely used to modulate neuronal circuits in the central nervous system and that noninvasive brain mapping with focused ultrasound may be feasible in humans.

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We have studied the effects of clinically useful anthraquinones on the cardiac sarcoplasmic reticulum calcium-release channel. (Circulaion Research 1990;67:272-283) Anthraquinones are highly effective chemotherapeutic agents with a wide spectrum of antitumor activity. Their clinical use is limited principally by a dose-dependent cardiotoxicity, which is produced both by anthracyclines' (e.g., doxorubicin, epirubicin, and idarubicin) and by anthracenediones2 (e.g., mitoxantrone), although the histological features produced by each group are reported to show significant differences.3 Among the anthracyclines, epirubicin and idarubicin are less cardiotoxic than doxorubicin.4 The subcellular effects of doxorubicin in the heart have been extensively investigated,5 but the mechanism of cardiotoxicity remains unclear.Doxorubicin can undergo a reduction reaction to a semiquinone species that is a potential generator of oxygen-derived free radicals.6 It has been proposed that this might initiate generalized membrane system disruption through lipid peroxidation,7 leading to intracellular calcium overload. Abnormalities of the sarcoplasmic reticulum (SR) are characteristic early

The properties of calcium-release channels of sheep cardiac muscle junctional sarcoplasmic reticulum (SR), have been investigated under voltage-clamp conditions following the fusion of isolated membrane vesicles with planar phospholipid bilayers. In the presence of activating calcium on the cytosolic side of the membrane, additions of the benzimidazole derivative sulmazole (AR-L 115BS) increased the open probability (Po) of the channel reaching saturating values of 1.0 at 3 mM sulmazole. The drug did not affect single-channel conductance and activation was readily reversible. Analysis of channel open and closed lifetimes suggested that low concentrations of sulmazole (0.1 mM) may sensitize the channel to activating calcium, while at higher concentrations (1 mM and above), calcium and sulmazole act synergistically to produce a unique gating scheme for the channel. Millimolar concentrations of sulmazole also stimulate a degree of channel opening at subactivating (60 pM) calcium concentrations. Openings occurring under these conditions show very different kinetics to those of the calcium-activated channel but have an identical single-channel conductance and are modified by ATP, magnesium, ruthenium red and ryanodine in a similar manner to the calcium-activated channel. The release of calcium from the SR following the activation of the calcium-release channel by sulmazole may contribute to the positive inotropic action of this drug on mammalian cardiac muscle.

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The transport of methionine into unfertilized and fertilized mouse eggs appears to involve active transport mechanisms with similar Vmax, Km, substrate specificity and independence from Na+. An exchange diffusion system with a similar amino acid specificity to the uptake system has also been found in both types of egg. An estimate of 6.5 fmol has been made for the size of the total internal pool of exchangeable amino acids.

Native membrane vesicles of human cardiac sarcoplasmic reticulum have been fused with artificial lipid bilayers to obtain recordings of single chloride and calcium release channels. Tissue was obtained from the explanted hearts of patients with end-stage cardiac failure undergoing heart transplantation. Although previous studies of calcium uptake and release have shown that the function of the sarcoplasmic reticulum is abnormal in end-stage cardiac failure, the basic properties of the channels are similar to those reported for equivalent channels from normal animal tissue.

Background-The value of angioplasty in occluded coronary arteries is limited by a restenosis/reocclusion rate of 50-70%. In patients with subtotal occlusion, stent implantation has been shown to reduce clinical and angiographic restenosis. Retrospective observational studies have suggested that stenting could reduce restenosis in total occlusions. The value of sustained coronary patency on global and regional left ventricular function in this clinical setting has not been defined clearly. Objectives-To assess the medium term eVect of elective intracoronary stent deployment after successful percutaneous transluminal coronary angioplasty (PTCA) of an occluded coronary artery. Methods-Sixty patients with a total coronary occlusion successfully treated by PTCA were randomised to receive an intracoronary stent or no stent. Patients underwent clinical and angiographic follow up at six months. Results-Thirty patients received a stent (group A) and 30 were treated by angioplasty alone (group B), all with initial success. One patient in group B required repeat angioplasty with stenting at 24 hours and one patient died after 10 days. Angiographic follow up was available for 57 patients. This showed a significantly reduced reocclusion rate in group A compared with group B (7% v 29%, p < 0.01) and a tendency to a reduced restenosis rate (22% v 40%, p = 0.105) in patients with no reocclusion. Left ventricular function, both global and regional, improved in group A. Only the regional left ventricular function in the area supplied by the target coronary artery improved in group B. Recurrence of symptoms and clinical events such as repeat angioplasty, coronary artery bypass grafting, death or myocardial infarction tended to be reduced in group A (4 (13%) v 9 (30%)). Conclusions-Intracoronary stent insertion is eVective in reducing the rate of reocclusion and shows a trend towards reduced restenosis after opening of a total coronary occlusion by balloon angioplasty. Sustained patency of the target coronary artery is associated with improvement in global and regional left ventricular function.(Heart 1998;79:18-23) Keywords: intracoronary stenting; total coronary occlusion; left ventricular function Percutaneous transluminal coronary angioplasty (PTCA) in patients with chronic total occlusion (defined as total interruption of the vessel with thrombolysis in myocardial infarction (TIMI) grade 0 or 1 1 flow for at least three days 2 ), has been associated with an initial primary success rate of 50-75% and a high restenosis rate of the order of 50-70%. 3Restenosis/reocclusion rates may be more favourable for TIMI 1 type lesions than TIMI 0. Initial success rates may be higher for more recent occlusions but the reocclusion/ restenosis rates remain high. 4 Because of this, operators have lacked enthusiasm for this technique and have favoured coronary artery bypass grafting for the treatment of totally occluded coronary arteries.More recently, a retrospective analysis of intracoronary stent implantation after balloon angioplasty...