Continuous infusion of porcine factor VIII in the management of patients with factor VIII inhibitors

Increased detection thresholds for pure tones were observed in a large cohort of children exposed to lead environmentally while smaller studies in lead-exposed workers have reported conflicting results on assessments of auditory function. Pure tone detection thresholds were determined in a group of monkeys (Macaca fascicularis) dosed with 2 mg/kg/day of lead from birth through testing at 13 years of age. Blood lead concentrations were stable at about 30 micrograms/dl until monkeys were 10-11 years of age at which time they increased to between 50 and 70 micrograms/dl. Five age- and rearing-matched monkeys served as controls. Detection thresholds were determined at six frequencies between 0.125 and 31.5 kHz. Ear phones were fit over both ears, and thresholds were determined for each ear separately. The monkey signaled detection of the tone by breaking contact with a stainless steel bar. Three lead-exposed monkeys exhibited normal pure tone detection functions. Three monkeys had thresholds outside of the control range at some frequencies; there was a tendency for higher frequencies to be differentially more affected. These findings are consistent with reports of elevated pure tone thresholds in humans exposed to lead developmentally, although the effect is smaller than might have been predicted given the concurrent blood lead concentrations of these monkeys.     

Calibration of a pyroelectric detector at 10.6 microm with the National Institute of Standards and Technology high-accuracy cryogenic radiometer

The National Institute of Standards and Technology (NIST) is establishing an infrared detector calibration facility to improve radiometric standards at infrared wavelengths. The absolute response of the cryogenic bolometer that serves as the transfer standard for this facility is being linked to the NIST high- accuracy cryogenic radiometer (HACR) at a few laser wavelengths. At the 10.6-microm CO(2) laser line, this link is being established through a pyroelectric detector that has been calibrated against the HACR. We describe the apparatus, methods, and uncertainties for the calibration of this pyroelectric detector.     

High-frequency heterojunction bipolar transistor device design andtechnology

This paper identifies and reviews those aspects of new materials and device technological advances that have pushed HBT circuits towards a 100 GHz operating frequency. The operating principles of the HBT are initially discussed in relation to their differences from homojunction bipolar transistors. The advantages and disadvantages of the various materials systems available to HBTs, how the particular material properties relate to the device performance and a brief outline of growth technologies are then presented. Those device parameters contributing to the frequency performance figures-of-merit are identified and the resulting design approaches discussed. Current device fabrication technology is then reviewed, with the latest results and the most important design aspects for high-frequency operation identified. This is then followed by examples of achievements in both digital and analogue circuit applications. Finally, an attempt is made to identify those device and materials aspects that are likely to contribute to a further improvement in the frequency performance of HBTs     

Assembly and analysis of conical models for the HIV-1 core

The genome of the human immunodeficiency virus (HIV) is packaged within an unusual conical core particle located at the center of the infectious virion. The core is composed of a complex of the NC (nucleocapsid) protein and genomic RNA, surrounded by a shell of the CA (capsid) protein. A method was developed for assembling cones in vitro using pure recombinant HIV-1 CA-NC fusion proteins and RNA templates. These synthetic cores are capped at both ends and appear similar in size and morphology to authentic viral cores. It is proposed that both viral and synthetic cores are organized on conical hexagonal lattices, which by Euler's theorem requires quantization of their cone angles. Electron microscopic analyses revealed that the cone angles of synthetic cores were indeed quantized into the five allowed angles. The viral core and most synthetic cones exhibited cone angles of approximately 19 degrees (the narrowest of the allowed angles). These observations suggest that the core of HIV is organized on the principles of a fullerene cone, in analogy to structures recently observed for elemental carbon.     

Evidence that mechanisms dependent and independent of nitric oxide mediate endothelium-dependent relaxation to bradykinin in human small resistance-like coronary arteries

1. The effects of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (L-NOARG), the NO scavenger, oxyhaemoglobin (HbO) and high extracellular K+ upon endothelium-dependent relaxation to bradykinin were investigated in human isolated small coronary arteries. 2. Endothelium-dependent relaxations to bradykinin were compared in vessels contracted to approximately 50% of their maximum contraction to 124 mM KCl Krebs solution, regardless of treatments, with the thromboxane A2 mimetic, U46619 and acetylcholine. All relaxations were expressed as percentage reversal of the initial level of active force. 3. L-NOARG (100 microM) caused a small but significant, 12% (P < 0.01), decrease in the maximum relaxation (Rmax: 91.5 +/- 5.4%) to bradykinin but did not significantly affect the sensitivity (pEC50: 8.08 +/- 0.17). Increasing the concentration of L-NOARG to 300 microM had no further effect on the pEC50 or Rmax to bradykinin. HbO (20 microM) and a combination of HbO (20 microM) and L-NOARG (100 microM) reduced Rmax to bradykinin by 58% (P < 0.05) and 54% (P < 0.05), respectively. HbO (20 microM) and L-NOARG (100 microM, combined but not HbO (20 microM) alone, caused a significant 11 fold (P < 0.05) decrease in sensitivity to bradykinin. HbO (20 microM) decreased the sensitivity to the endothelium-independent NO donor, S-nitroso-N-acetylpenicillamine (SNAP), approximately 17 fold (P < 0.05). 4. Raising the extracellular concentration of K+ isotonically to 30 mM, reduced the Rmax to bradykinin from 96.6 +/- 3.1% to 43.9 +/- 10.1% (P < 0.01) with no significant change in sensitivity. A combination of HbO, L-NOARG and high K+ (30 mM) abolished the response to bradykinin. High K+ did not change either the sensitivity or maximum relaxation to SNAP. 5. In conclusion, L-NOARG does not completely inhibit endothelial cell NO synthesis in human isolated small coronary arteries. By comparison, HbO appeared to block all the effects of NO in this tissue and revealed that most of the relaxation to bradykinin was due to NO. The non-NO -dependent relaxation to bradykinin in the human isolated small coronary arteries appeared to be mediated by a K(+)-sensitive vasodilator mechanism, possibly endothelium-derived hyperpolarizing factor (EDHF).     

Diffuse leptomeningeal gliomatosis associated with multifocal CNS infarcts

BACKGROUND: Widespread dissemination of astrocytoma throughout the cerebrospinal fluid is unusual, especially as the initial presentation in a patient, and association with cerebral infarcts is rare. CASE DESCRIPTION A 47-year-old man subacutely developed progressive headache and backache, vomiting, altered consciousness, and numbness in both arms. Brain computerized axial tomography showed calcification in the fourth ventricle and magnetic resonance imaging demonstrated diffuse meningeal enhancement, a lesion in the canal of Magendie, and T2-weighted hyperintense lesions in several locations. Angiography showed vasospasm/vasculopathy involving multiple cerebral vessels. Biopsy of the fourth ventricular mass revealed a subependymoma with an overlying leptomeningeal anaplastic astrocytoma with numerous Rosenthal fibers. The patient was treated with three doses of intrathecal methotrexate via lumbar puncture but suddenly became unresponsive and died 6 days later, 8 weeks after initial symptoms. Autopsy demonstrated the subependymoma and a widespread leptomeningeal anaplastic astrocytoma, which showed no clear-cut origin from the subependymoma, but microscopically infiltrated the left medial temporal lobe. Multiple subacute and acute infarcts of the brain, brain stem, and upper spinal cord were seen only in areas with leptomeningeal tumor. CONCLUSION Glioma cells surrounding and focally permeating central nervous system vessels without lumenal occlusion can lead to vasospasm and widespread infarcts.