Long-term potentiation at excitatory amino acid synapses on midbrain dopamine neurons

Evidence suggests that a process analogous to long-term potentiation (LTP) may underlie the enhanced behavioural responses attending chronic administration of amphetamine and cocaine in animals (behavioural sensitization). Augmented excitatory amino acid (EAA)-mediated transmission at the level of midbrain dopamine neurons has been implicated as a change critical to the development of sensitization. Here we provide an initial demonstration that EAA synapses on dopamine neurons can undergo plasticity. Tetanic stimulation of the subthalamic nucleus induced a long-lasting increase (39.2 +/- 10.4%) in the amplitude of excitatory postsynaptic potentials recorded in dopamine neurons of the substantia nigra. This LTP, which did not occur in the presence of NMDA antagonists, may constitute the mechanism that lies at the heart of sensitization.     

Infrapopliteal prosthetic graft patency by use of the distal adjunctive arteriovenous fistula

From November 1979 through December 1989, 210 distal arteriovenous fistulas were constructed as adjuncts to tibial and peroneal vascular reconstructive procedures in 203 patients threatened with limb loss. Two-year cumulative patency rates were calculated by grouping patients on the basis of changing indications in sequential time periods: group 1 (n = 61): 1979 to 1983, 18%; group 2 (n = 80): 1983 to 1986, 33%; group 3 (n = 69): 1986 to 1989, 44%. Although the therapeutic results observed in these groups are not statistically comparable, they show a perceptible trend. Postoperative arteriography showed that flow is prograde in the distal vessels beyond the distal arteriovenous fistula. Graft surveillance by duplex ultrasonography also confirmed that flow in the distal arteries is prograde and that "steal" does not occur. Peak systolic velocity (174 +/- 38 cm/sec) and mean velocity (92 +/- 23) flow rates are increased in grafts with patent distal arteriovenous fistulas compared to those bypasses with closed distal arteriovenous fistulas (p less than 0.01). There were no differences in the flow measurements for the arteries beyond the distal anastomoses and distal arteriovenous fistulas, confirming the prograde nature of the distal flow. In 22 patients analysis of graft and fistula patency by duplex sonography showed that one fourth of all grafts were patent without fistulas at 1 and 2 years after operation. Alternatively, 68% of patent grafts at 1 year had patent fistulas and 58% had patent fistulas at 2 years. We conclude that the distal arteriovenous fistula will increase graft flow and simultaneously prevent distal arterial overload without causing "steal." This technique should be considered whenever a prosthetic graft is necessary for crural reconstruction and only in selected instances of revascularization with autologous veins.     

Preliminary clinical results from U.S. fast neutron teletherapy studies.

Over 700 patients with cancer have been treated with fast neutron beams since 1972 in three U.S. programs at the M.D. Anderson-TAMVEC (Houston and College Station, Texas), University of Washington (Seattle, Washington), and MANTA (Naval Research Laboratory, Washington, D.C.). Clinical applications are about to start at the Fermilab (Batavia, Illinois) and Cleveland Clinic-NASA (Cleveland, Ohio). To date, studies have included: 1) effects of different treatment patterns and doses; 2) responses of several tumor types at many anatomic sites; and 3) acute and long-term normal tissue tolerances. Responses of several cancers, such as extensive epidermoid carcinoma of the cervix and "fixed" metastatic cervical adenopathy, have been encouraging. In patients with glioblastoma multiforme, good tumor responses have not lengthened survival compared with the following conventional radiation therapy. Both local tumor control and "cure" have been compromised by the inclusion of patients with very extensive cancers. In general, treatment has been well tolerated. These preliminary studies provide the basis for planned clinical trials.