A Technique Utilizing a Steerable Hydrophilic Guidewire for Permanent Pacemaker Implantation

We report the use of a steerable hydrophilic guidewire for permanent pacemaker implantation. This wire, previously used for peripheral vascular and cardiac angiography, is able to be steered and passed in many situations when a standard guidewire cannot be used. We report three cases where the standard J-tipped guidewire could not be passed by either the cephalic or subclavian route and the hydrophilic guidewire allowed for successful atraumatic placement of a sheath and pacemaker lead.     

The effect of pertussis toxin on α1-adrenoceptor-mediated vasoconstriction by the full agonist, cirazoline, and the partial agonist, (-)-dobutamine, in pithed rats

The role of pertussis toxin-sensitive guanine nucleotide regulatory proteins (G-proteins) in the signal transduction process(es) involved in postjunctional vascular alpha 1-adrenoceptor-mediated vasoconstriction produced by the full agonist, cirazoline, and the partial agonist, (-)-dobutamine, have been investigated in the cardiovascular system of the pithed rat. Pertussis toxin pretreatment (50 micrograms/kg, iv, 3 days prior to experimentation) only slightly inhibited the pressor response of cirazoline, and the degree of inhibition produced by pertussis toxin was roughly equivalent to the inhibition produced by the calcium channel antagonist, nifedipine (1 mg/kg, ia). In contrast, pertussis toxin pretreatment produced marked inhibition of the alpha 1-adrenoceptor-mediated pressor response to the partial agonist, (-)-dobutamine, and this large degree of inhibition was qualitatively and quantitatively similar to the degree of inhibition produced by nifedipine. The differential pattern of inhibition of full and partial alpha 1-adrenoceptor agonists by pertussis toxin suggests that the vasoconstrictor response of an alpha 1-adrenoceptor partial agonist, which is more dependent upon the translocation of extracellular calcium than a full agonist, as evidenced by its sensitivity to inhibition by nifedipine, involves a pertussis toxin-sensitive G-protein that couples the alpha 1-adrenoceptor to the calcium channel. Furthermore, for alpha 1-adrenoceptor-mediated vasoconstriction by full agonists with high intrinsic efficacy, which involves both intracellular and extracellular pools of calcium, and particularly the former, pertussis toxin only inhibits that component of the alpha 1-adrenoceptor response which is dependent upon the translocation of extracellular calcium, accounting for the limited degree of inhibition of the response to cirazoline by pertussis toxin and by nifedipine. By inference, the other component of the alpha 1-adrenoceptor-mediated pressor response to a full agonist, which is dependent upon the mobilization of intracellular stores of calcium through a process believed to involve the activation of phospholipase C, likely utilizes a pertussis toxin insensitive G-protein that is distinct from that which we propose couples the alpha 1-adrenoceptor to the calcium channel. We conclude, therefore, that the alpha 1-adrenoceptor in the vasculature of the pithed rat may be coupled to 2 distinct G-proteins, only one of which is sensitive to inhibition by pertussis toxin and links the alpha 1-adrenoceptor to the membrane calcium channel, and which may be utilized by both full agonists and partial agonists.     

Neural dynamics in a model of the thalamocortical system. I. Layers, loops and the emergence of fast synchronous rhythms

A large-scale computer model was constructed to gain insight into the structural basis for the generation of fast synchronous rhythms (20-60 Hz) in the thalamocortical system. The model consisted of 65,000 spiking neurons organized topographically to represent sectors of a primary and secondary area of mammalian visual cortex, and two associated regions of the dorsal thalamus and the thalamic reticular nucleus. Cortical neurons, both excitatory and inhibitory, were organized in supragranular layers, infraganular layers and layer IV. Reciprocal intra- and interlaminar, interareal, thalamocortical, corticothalamic and thalamoreticular connections were set up based on known anatomical constraints. Simulations of neuronal responses to visual input revealed sporadic epochs of synchronous oscillations involving all levels of the model, similar to the fast rhythms recorded in vivo. By systematically modifying physiological and structural parameters in the model, specific network properties were found to play a major role in the generation of this rhythmic activity. For example, fast synchronous rhythms could be sustained autonomously by lateral and interlaminar interactions within and among local cortical circuits. In addition, these oscillations were propagated to the thalamus and amplified by corticothalamocortical loops, including the thalamic reticular complex. Finally, synchronous oscillations were differentially affected by lesioning forward and backward interareal connections.      

Therapy of severe aplastic anemia with anti-human thymocyte globulin and androgens: the effect of HLA-haploidentical marrow infusion

Fifty-four patients with severe aplastic anemia were treated with horse anti-human thymocyte globulin (ATG) and androgens. Thirty of these patients also received an infusion of HLA-haploidentical marrow cells. Only those patients having evidence of hematologic recovery within 3 mo after ATG therapy were considered responders to the immunosuppressive regimen. Of 53 patients evaluable for response, 21 had complete or partial responses and 7 had minimal improvement by defined criteria. The remaining patients did not respond or died. Factors correlated with response to therapy included a short duration of aplasia and a high admission granulocyte count. Thirty-six patients (66.7%) are surviving between 18 and 43 mo, and 18 have died. Deaths were due to hemorrhage and/or infection. Short duration of aplasia and high granulocyte counts also correlated with survival, as did younger age. Four patients with complete or partial responses had a recurrence of severe aplasia 6-17 mo after their first course of ATG. Three of these patients were retreated with ATG (and oxymetholone in two cases). All three had second responses to therapy, but two of the three have had second relapses. The fourth patient responded to oxymetholone alone, but died after a second relapse. Mismatched marrow infusion had no effect on the incidence of response or survival.     

Epstein-Barr virus genomes are restricted to secondary neoplastic cells following bone marrow transplantation

DNA from mononuclear blood and tumor cells from 33 patients undergoing bone marrow transplantation for leukemia was examined for the presence of Epstein-Barr virus (EBV) genomes by blot hybridization. Four groups of patients were studied soon after engraftment, during long-term remission, after relapse of the original leukemia, and after development of secondary B cell neoplasms. Only the cells of patients with secondary neoplasms demonstrated EBV genomes, where all five adequately studied samples were positive. Samples from all other patient categories were negative for EBV genomes. We conclude that EBV genomes do not frequently persist in normal engrafted lymphocytes or in mononuclear cells of patients suffering recurrent leukemia. These results are consistent with EBV playing a role in the genesis of secondary B cell neoplasms following bone marrow transplantation.