The determination of the phase shift and the light shift in our optically pumped Cs beam is reported here. We show that an error on the phase difference value determined by our fit method, without beam reversal, can be induced if the light shift is not taken into account. If the experimental data are corrected for the light shift, the results of the fit method are in very good agreement with the beam reversal results. This allows us to reduce the related uncertainty in the accuracy budget of our standard. The resulting overall accuracy of the standard is now estimated to be 6.3x10(-15).
Twenty-five patients with haematological diseases were treated orally with the highly potent and selective anti-herpes agent, bromovinyldeoxyuridine (BVDU), in a dosage of 7.5 mg/kg/day (divided over three or four doses a day) for 5 days for an intercurrent mucocutaneous herpesvirus infection. Of these 25 patients, 8 were severely granulocytopenic at the time of the viral infection, and 12 recently had undergone bone-marrow transplantation; 5 were under cytotoxic therapy for a lymphoproliferative disorder; 13 had herpes simplex virus type 1 (HSV-1); 1 had herpes simplex virus type 2 (HSV-2); and 11 had varicella-zoster virus (VZV) infection. In all but two patients, BVDU arrested progression of the HSV or VZV infection within 1-2 days after treatment was started. One of the two patients who failed to respond to BVDU had an HSV-2 infection. The other had an HSV-1 infection, which was highly sensitive to BVDU in vitro; BVDU may have failed in this patient because of incomplete drug intake or profuse diarrhoea, or both. The results of this preliminary uncontrolled clinical trial suggest that BVDU may be an effective and safe drug for the oral treatment of HSV-1 and VZV infections in severely immunosuppressed patients.
Until 1963, only viruses were known to stimulate interferon production in cells. The nucleic acid of the virus was generally regarded as the essential stimulus for interferon production.<sup>1</sup>Rotem et al and Isaacs et al<sup>2,3</sup>demonstrated in 1963 that nonviral nucleic acids, provided they were foreign to the cells (heterologous or chemically modified homologous RNA), could also initiate the production of interferon. Although their "foreign nucleic acid" hypothesis was received with some scepticism and retracted later,<sup>4</sup>it offered a reasonable explanation for the nucleic acid-induced resistance to viral infection, which had been described<sup>5</sup>as early as 1953. Moreover, it raised a possible explanation for the antiviral action of agents such as bacteria or apparently nonviral agents as the mold products statolon (culture filtrate of<i>Penicillium stoloniferum</i>) and helenine (mycelium extract of<i>Penicillium funiculosum</i>) which had been found active in a number of experimental viral infections.<sup>6-13</sup>
Mycophenolate mofetil (MMF) has been approved as an immunosuppressive agent in kidney transplant recipients and may thus be used concomitantly with antiherpetic agents, which are used for the treatment of intercurrent herpesvirus infections. We have recently demonstrated that MMF and its parent compound mycophenolic acid (MPA), which is a potent inhibitor of IMP dehydrogenase, potentiate the antiherpesvirus activity of acyclovir, ganciclovir, and penciclovir. We have now evaluated the antiviral efficacy of the combination of MPA and the novel antiherpesvirus agent H2G [(R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine]. When combined with H2G, MPA (at concentrations ranging from 0.25 to 10 microgram/ml, which are readily attainable in human plasma) markedly potentiated the antiviral efficacy of H2G against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), as reflected by a 10- to 150-fold decrease in the 50% effective concentration. Moreover, the activity of H2G against a thymidine kinase-deficient strain of HSV-1 (TK- HSV-1) was increased more than 2,500-fold when combined with MPA. MPA by itself had little or no effect on the replication of these viruses. Similar observations were made for varicella-zoster virus. Also, ribavirin (another inhibitor of IMP dehydrogenase) caused a marked enhancement of the activity of H2G against HSV-1 (10-fold), HSV-2 (10-fold), and TK- HSV-1 (>185-fold). Exogenously added guanosine reversed the potentiating effects of MPA on the antiviral activity of H2G, indicating that this potentiating effect resulted from a depletion of the endogenous dGTP pools, thus favoring the inhibitory action of the H2G triphosphate on the viral DNA polymerase.
No abstract is provided for this article.
