What radiation dose for DLA-identical canine marrow grafts? [published erratum appears in Blood 1989 Feb;73(2):624]

In view of reported attempts at marrow grafting after nuclear accidents with a broad range of radiation exposures, the present study explored the total-body irradiation (TBI) conditions needed for engraftment in a canine model by using marrow from DLA-identical littermates. Previous studies have shown that such grafts are consistently successful when recipients are exposed to 920 cGy of TBI delivered at a rate of 7 cGy/min from opposing dual cobalt sources. The present TBI doses were all in the lethal range. Five dogs were administered 450 cGy; seven dogs, 600 cGy; five dogs, 700 cGy; and five dogs, 800 cGy of TBI administered at 7 cGy/min. They received a median of 3.3 x 10(8) marrow cells/kg intravenously after completion of radiation. Results showed transient allogeneic marrow engraftment in all dogs administered the lowest dose of TBI studied (450 cGy). Importantly, transient grafts permitted four of five dogs to live long enough for autologous marrow recovery to occur. At increasing radiation doses, 600, 700, and 800 cGy, the risk of graft failure lessened, with 3 of 7, 2 of 5, and 1 of 5 dogs, respectively, showing graft rejection. Fewer dogs survived with autologous marrow recovery, and more showed sustained allogeneic engraftment (4 of 7, 3 of 5, and 4 of 5 dogs, respectively). We conclude that DLA-identical littermate marrow grafts are beneficial in the setting of otherwise lethal radiation exposures, with most dogs either experiencing sustained allogeneic engraftment or surviving with autologous marrow recovery due to the extended support provided by a transient allogeneic graft.     

EPIDEMIOLOGY OF CARDIOVASCULAR RISK FACTORS IN HONG KONG

1. To facilitate the development of appropriate population-wide coronary heart disease prevention strategies and to monitor their long-term impact, a comprehensive baseline Hong Kong Cardiovascular Risk Factor Prevalence Study was conducted in 1995–96. 2. The data obtained from 2875 men and women aged 25–74 years showed a high prevalence of diabetes mellitus and impaired glucose tolerance, particularly in those aged 65 years and over. Other risk factors, such as hypercholesterolemia and hypertension as well as being overweight, were particularly prominent in older women.     

Atheromatous extracranial carotid arteries: CT evaluation correlated with arteriography and pathologic examination

Dynamic, rapid sequence, axial computed tomography (CT) was employed to evaluate the extracranial common and internal carotid arteries in 17 patients with clinical histories suggesting recent or remote ischemia in the territory supplied by the internal carotid artery. The CT findings were correlated with arteriographic observations and with gross and histologic evaluations of endarterectomy specimens. Areas of arterial wall thickening were evaluated on CT scans with regard to both degree of thickening and radiographic density (attenuation). The degree of vessel wall thickening secondary to atheromatous plaque demonstrated on CT scans corresponded closely to the severity of luminal compromise seen on arteriograms. Isodense or mildly hypodense focal mural thickening noted on CT scans of seven endarterectomy specimens proved to be primarily fibrotic (simple) atheromatous plaque on gross and histologic examination. Areas of markedly lucent focal mural thickening on CT scans of 11 specimens all demonstrated varying amounts of subintimal hemorrhage within loosely arranged and rather acellular (complex) atheromatous plaques on pathologic examination. While arteriography provides information regarding the status of the arterial lumen, CT offers the potential of accurate characterization of pathologic changes in the wall of the extracranial carotid arteries in patients with symptoms of cerebral ischemia.     

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.     

Central integrative role of oestrogen in the regulation of placental steroidogenic maturation and the development of the fetal pituitary-adrenocortical axis in the baboon

The purpose of this review is to summarize the experimentaldata establishing the baboon as a non-human primate model forthe study of the endocrinology of human pregnancy, and to outlinethe results of in-vivo experiments in the baboon which showthat oestrogen plays a central integrative role in the regulationof placental steroidogenic maturation as well as the functionand maturation of the fetal adrenal gland. Thus, oestrogen regulatesthe receptor-mediated uptake of low-density lipoprotein-cholesteroland the P450 cholesterol side chain cleavage system within sycytiotrophoblaststo promote the production of progesterone. Oestrogen concomitantlyacts on the fetal adrenal gland to modulate the production ofandrogen precursors which ensures maintenance of physiologiclevels of oestrogen during the course of gestation. In addition,oestrogen regulates the 11ß-hydroxysteroid dehydrogenaseenzymes controlling placental cortisol-cortisone metabolismand their secretion into the fetal circulation and thus indirectlyregulates the fetal hypothalamic-pituitary-adrenocortical axis.Collectively, these oestrogen-regulated processes ensure themaintenance of pregnancy and the maturation of the fetus includingthe development in utero of adrenocortical self-sufficiencyessential for neonatal survival.     

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.