Warfarin-induced skin necrosis in HIV-1-infected patients with tuberculosis and venous thrombosis

Background. At the turn of the century, only 300 cases of warfarin-induced skin necrosis (WISN) had been reported. WISN is a rare but potentially fatal complication of warfarin therapy. There are no published reports of WISN occurring in patients with HIV-1 infection or tuberculosis (TB).Methods. We retrospectively reviewed cases of WISN presenting from April 2005 to July 2008 at a referral hospital in Cape Town, South Africa.Results. Six cases of WISN occurred in 973 patients receiving warfarin therapy for venous thrombosis (0.62%, 95% CI 0.25 - 1.37%). All 6 cases occurred in HIV-1-infected women (median age 30 years, range 27 - 42) with microbiologically confirmed TB and venous thrombosis. All were profoundly immunosuppressed (median CD4+ count at TB diagnosis49 cells/μl, interquartile range 23 - 170). Of the 3 patients receiving combination antiretroviral therapy, 2 had TB-IRIS (immune reconstitution inflammatory syndrome). The median interval from initiation of antituberculosis treatment to venous thrombosis was 37 days (range 0 - 150). The median duration of parallel heparin and warfarin therapy was 2days (range 1 - 6). WISN manifested 6 days (range 4 - 8) after initiation of warfarin therapy. The international normalised ratio (INR) at WISN onset was supra-therapeutic, median 5.6 (range 3.8 - 6.6). Sites of WISN included breasts, buttocks and thighs. Four of 6 WISN sites were secondarily infected with drug-resistant nosocomial bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter, extendedspectrumβ-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae) 17 - 37 days after WISN onset. In 4 patients, the median interval from WISN onset to death was 43 days (range 25 - 45). One of the 2 patients who survived underwent bilateral mastectomies and extensive skin graftingat a specialist centre. Conclusion. This is one of the largest case series of WISN. We report a novel clinical entity: WISN in HIV-1 infected patients with TB and venous thrombosis. The occurrence of 6 WISN cases in a 40-month period may be attributed to (i) hypercoagulability, secondary to HIV-1 and TB; (ii) shortconcurrent heparin and warfarin therapy; and (iii) high loading doses of warfarin. Active prevention and appropriate management of WISN are likely to improve the dire morbidity and mortality of this unusual condition.S Afr Med J 2010; 100: 372-377

The Mystery of the Missing Boundary Layer

The question of the nature of the ultraviolet and X-ray radiation field of cataclysmic binaries is addressed. The spectrum and luminosity of this radiation are important in determining the mass transfer rate and energy budget of the system and in studies of the ejecta surrounding novae. In many systems, the soft X-ray luminosity is ~ 102-104 times weaker than predicted by simple accretion models. We discuss several possible solutions to this discrepancy. The most likely are either that the optical luminosity of a typical old nova is produced partly by reprocessed ultraviolet light from the white dwarf, or that the boundary layer, where accreted matter settles onto the white dwarf is both larger and more complicated than predicted by existing accretion disk models. The solution to this problem is of fundamental importance to accretion disk theory and will have implications for the study of most aspects of these systems, including models of the nova outburst itself

Nuclear spin coherence in a quantum wire

We have observed millisecond-long coherent evolution of nuclear spins in a quantum wire at 1.2 K. Local, all-electrical manipulation of nuclear spins is achieved by dynamic nuclear polarization in the breakdown regime of the Integer Quantum Hall Effect combined with pulsed Nuclear Magnetic Resonance. The excitation thresholds for the breakdown are significantly smaller than what would be expected for our sample and the direction of the nuclear polarization can be controlled by the voltage bias. As a four-level spin system, the device is equivalent to two qubits.Comment: 5 pages, 5 figure

Warfarin-induced skin necrosis in HIV-infected patients with tuberculosis and venous thrombosis

Background. At the turn of the century, only 300 cases of warfarin-induced skin necrosis (WISN) had been reported. WISN is a rare but potentially fatal complication of warfarin therapy. There are no published reports of WISN occurring in patients with HIV-1 infection or tuberculosis (TB). Methods. We retrospectively reviewed cases of WISN presenting from April 2005 to July 2008 at a referral hospital in Cape Town, South Africa. Results. Six cases of WISN occurred in 973 patients receiving warfarin therapy for venous thrombosis (0.62%, 95% CI 0.25 - 1.37%). All 6 cases occurred in HIV-1-infected women (median age 30 years, range 27 - 42) with microbiologically confirmed TB and venous thrombosis. All were profoundly immunosuppressed (median CD4+ count at TB diagnosis 49 cells/µl, interquartile range 23 - 170). Of the 3 patients receiving combination antiretroviral therapy, 2 had TB-IRIS (immune reconstitution inflammatory syndrome). The median interval from initiation of antituberculosis treatment to venous thrombosis was 37 days (range 0 - 150). The median duration of parallel heparin and warfarin therapy was 2 days (range 1 - 6). WISN manifested 6 days (range 4 - 8) after initiation of warfarin therapy. The international normalised ratio (INR) at WISN onset was supra-therapeutic, median 5.6 (range 3.8 - 6.6). Sites of WISN included breasts, buttocks and thighs. Four of 6 WISN sites were secondarily infected with drug-resistant nosocomial bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter, extendedspectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae) 17 - 37 days after WISN onset. In 4 patients, the median interval from WISN onset to death was 43 days (range 25 - 45). One of the 2 patients who survived underwent bilateral mastectomies and extensive skin grafting at a specialist centre. Conclusion. This is one of the largest case series of WISN. We report a novel clinical entity: WISN in HIV-1 infected patients with TB and venous thrombosis. The occurrence of 6 WISN cases in a 40-month period may be attributed to (i) hypercoagulability, secondary to HIV-1 and TB; (ii) short concurrent heparin and warfarin therapy; and (iii) high loading doses of warfarin. Active prevention and appropriate management of WISN are likely to improve the dire morbidity and mortality of this unusual condition

Brain health: time matters in multiple sclerosis

publisher: Elsevier articletitle: Brain health: time matters in multiple sclerosis journaltitle: Multiple Sclerosis and Related Disorders articlelink: http://dx.doi.org/10.1016/j.msard.2016.07.003 content_type: article copyright: © 2016 Oxford PharmaGenesis Ltd. Published by Elsevier B.V

Radiative Kaon Decays K±→π±π0γK^\pm\to\pi^\pm\pi^0\gamma and Direct CP Violation

It is stressed that a measurement of the electric dipole amplitude for direct photon emission in \kpm decays through its interference with inner bremsstrahlung is important for differentiating among various models. Effects of amplitude CP violation in the radiative decays of the charged kaon are analyzed in the Standard Model in conjunction with the large $N_c$ approach. We point out that gluon and electromagnetic penguin contributions to the CP-violating asymmetry between the Dalitz plots of \kpm are of equal weight. The magnitude of CP asymmetry ranges from $2\times 10^{-6}$ to $1\times 10^{-5}$ when the photon energy in the kaon rest frame varies from 50 MeV to 170 MeV.Comment: Latex, 11 pages, ITP-SB-93-36, IP-ASTP-22-9

Metal-insulator transition at B=0 in a dilute two dimensional GaAs-AlGaAs hole gas

We report the observation of a metal insulator transition at B=0 in a high mobility two dimensional hole gas in a GaAs-AlGaAs heterostructure. A clear critical point separates the insulating phase from the metallic phase, demonstrating the existence of a well defined minimum metallic conductivity sigma(min)=2e/h. The sigma(T) data either side of the transition can be `scaled' on to one curve with a single parameter (To). The application of a parallel magnetic field increases sigma(min) and broadens the transition. We argue that strong electron-electron interactions (rs = 10) destroy phase coherence, removing quantum intereference corrections to the conductivity.Comment: 4 pages RevTex + 4 figures. Submitted to PRL. Originally posted 22 September 1997. Revised 12 October 1997 - minor changes to referencing, figure cations and figure