Purified preparations of the inhibitory glycine receptor (GlyR) contain alpha and beta subunits, which share homologous primary structures and a common transmembrane topology with other members of the ligand‐gated ion channel superfamily. Here, a beta subunit‐specific antiserum was shown to precipitate the [3H]strychnine binding sites localized on alpha subunits from membrane extracts of both rat spinal cord and mammalian cells co‐transfected with alpha and beta cDNAs. Further, inhibition of alpha homo‐oligomeric GlyRs by picrotoxinin, a non‐competitive blocker of ion flow, was reduced 50‐ to 200‐fold for alpha/beta hetero‐oligomeric receptors generated by cotransfection. Site‐directed mutagenesis identified residues within the second predicted transmembrane segment (M2) of the beta subunit as major determinants of picrotoxinin resistance. These data implicate the M2 segment in blocker binding to and lining of the GlyR chloride channel.

Sferics are low frequency, low intensity electromagnetic pulses radiating from distant meteorological events and other yet unknown sources. It has been hypothesized that sferics are part of the purported sensitivity to weather changes reported by headache sufferers. We tested this proposal. Patients (migraine and/or tension headache) enrolled in a randomized clinical trial gave daily headache data (intensity, frequency, duration of headache) for at least 18 weeks. Concurrently, a sferics measurement station in the vicinity of the patients recorded frequency and intensity of sferics. Usable headache data from 21 patients and the corresponding sferics series were subjected to time series analysis applying ARIMA models and then cross-correlated. We found significant and consistent cross-correlations of moderate size at lag 0 in one patient between ARIMA-filtered headache intensity and frequency (r = 0.18) and amplitude of sferics (r = 0.20). We conclude that in an unselected sample of headache patients some may indeed be susceptible to the low intensity type of electromagnetic radiation exemplified by sferics pulses. This phenomenon warrants further scrutiny.

We have investigated 6,972 patients with directional continuous-wave Doppler sonography within the last three and a half years, and have derived criteria for the sonographic diagnosis of basilar artery occlusion or tight stenosis in conjunction with 1,071 retrograde brachial angiograms. By sonographic patterns, we have suspected obstruction of the basilar artery or of both distal vertebral arteries in nine cases. Either bilateral sonographic silence or the absence of a diastolic flow component of the vertebral arteries served as criteria in the sonographic evaluation. Angiography of the vertebro-basilar system, performed in eight cases, showed near or complete occlusion in the distal vertebrals or in the proximal basilar artery. Degrees of stenosis less than an 80 percent reduction in lumen diameter could not be detected sonographically. Two further basilar artery occlusions were detected by means of angiography despite negative Doppler sonography: one of these patients showed an extensive collateral circulation between the posterior inferior and the superior cerebellar arteries, and one patient had an occlusion only of the middle and rostral thirds of the basilar artery, the proximal third and the anterior inferior cerebellar arteries being widely patent. Thus, we believe that directional CW Doppler sonography is very useful in the diagnosis of near or complete occlusion of both distal vertebral arteries or of the proximal basilar artery.

We have investigated 6,587 patients with directional continuous-wave (c-w) Doppler sonography of the carotid arteries during the last 33 months, and have developed criteria for the diagnosis of a significant increase in peripheral resistance of the internal carotid artery in conjunction with 1,671 retrograde brachial and direct carotid angiograms. We distinguished stenoses proximal (15 cases) and distal (4) to the origin of the ophthalmic artery, supraclinoid internal carotid artery occlusions (8), stenoses (2) and acute occlusions (10) of the middle cerebral artery. Stenoses in the carotid siphon (proximal or distal to the origin of the ophthalmic artery) of at least 60% reduction in lumen diameter showed a reduction of the relative end-diastolic flow velocity (modified Pourcelot's index) of more than 40%; additionally, stenoses proximal to the origin of the ophthalmic artery exhibited a variable alternating flow, or flow reversal, in the supratrochlear artery. Stenoses distal to the origin of the ophthalmic artery rarely revealed the theoretically expected increase in orthograde flow velocity in the supratrochlear artery. Stenoses of the middle cerebral artery consisting of more than atherosclerotic irregularities proved to be an exception. Supraclinoid occlusions of the internal carotid artery were reliably demonstrated by Doppler sonography. However, the majority of acute occlusions of the middle cerebral artery could not be detected by this means, probably due to anastomoses between the anterior and the middle cerebral arteries, which were detected by angiography. Thus, we believe that c-w Doppler sonography is a reliable tool to detect stenoses of the carotid siphon of more than 60% reduction in lumen diameter and and supraclinoid carotid artery occlusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Using directional continuous-wave Doppler sonography of the vertebral arteries, we have investigated 1,540 patients during the past 5 years. On the basis of unilateral and bilateral retrograde brachial angiograms in the same patients (a total of 1,989 angiograms) we have developed sonographic criteria for demonstrating a significant increase in the peripheral resistance of both distal vertebral arteries and/or the basilar artery. All 11 cases of basilar artery stenosis of at least 60% reduction in lumen diameter (as shown by angiography) exhibited an approximately 40% or higher reduction in the sum of the modified Pourcelot indices of both vertebral arteries with respect to age-matched controls. All 3 stenoses of less than 60% reduction in lumen diameter were not detected by sonography. Even a good collateral circulation through rete mirabile anastomoses did not normalize the modified Pourcelot indices. One case of a persistent primitive trigeminal artery with thin-calibered vertebral arteries was also detected by sonography. The high percent of patients with one hypoplastic vertebral artery in the group with basilar artery stenoses indicates an increased risk for atherosclerosis of the basilar and/or distal vertebral artery in these patients. All 14 angiographically verified occlusions of the basilar artery were detected by sonographic criteria independent of the occlusion localization. Thus, we believe that directional continuous-wave Doppler sonography is a reliable technique for detecting basilar artery stenoses of at least 60% reduction in lumen diameter and basilar artery occlusions. Severe intracranial stenosis of the internal carotid artery can also be diagnosed with this technique. 1 " 5 Previously, we reported the possibility of detecting a substantial increase in peripheral resistance of both distal vertebral and/or the proximal basilar arteries with Doppler pulse curves. 6 In the present study, the use of relative end-diastolic flow velocities of the vertebral arteries as circulatory resistance indices allowed, in comparison with age-matched controls, the sonographic detection of stenotic lesions of at least 60% reduction in lumen diameter in the vertebro-basilar system distal to the point of insonation. Subjects and MethodsThe present article refers to 1,540 patients exhibiting typical symptoms of atherosclerotic cerebrovascular disease, but also includes cases prior to an angiographic investigation for a suspected mass lesion or a vascular malformation. Their routine work-up included die investigation of the carotid and vertebral arteries by directional c-w Doppler sonography. All of these patients underwent at least unilateral retrograde brachial angiography. Of these, we report 29 cases with stenoses or occlusions of both distal vertebral and/or the basilar arteries. All of these 29 patients were examined with c-w Doppler sonography and bilateral retroFrom the Neurologische Klinik der Universitat Heidelberg, Heidelberg, Federal Republic of Germany.Address for reprints: Dr. Stefan Biedert, Zentral...