Tubulointerstitial nephritis caused by the antiviral agent foscarnet

The antiviral agent foscarnet has long been used in our unit to treat cytomegalovirus (CMV) infections in renal transplant patients. The clinical effect has been convincing and, apart from changes in serum calcium levels, very few side effects have been noted. We have, however, observed a nephrotoxic reaction in a series of patients with initially good renal function who therefore received high doses of foscarnet. Transplant biopsies performed in five of those patients revealed degenerative changes in the tubular epithelial cells as well as tubular calcium deposits and an infiltration of the interstitium by mixed mononuclear and polymorphonuclear leucocytes. Renal insufficiency was accompanied by high fever. After withdrawal of the drug, the temperature rapidly normalized, whereas serum creatinine continued to rise for about 3 days and then fell back towards previous levels. We conclude that transplant biopsies are of great value in distinguishing between a foscarnet nephrotoxic effect and CMV nephritis, various forms of rejection, and other causes of impaired renal function.     

膦甲酸钠治疗慢性乙型肝炎的近期疗效观察

目的 探讨膦甲酸钠(可耐)治疗慢性乙型肝炎的近期疗效及毒副作用。方法 选择慢性乙型肝炎46例,随机分为2组,对照组13例仅给予常规护肝药物,治疗组33例在对照组治疗基础上加用膦甲酸钠,疗程28 d。治疗前后检测肝功能、乙肝病毒标志物和乙肝病毒DNA,同时观察患者症状、体征的改变及药物的不良反应。结果 治疗组HBV-DNA平均值由(5.95±4.45)×10 copies·mL-1下降至(3.05±4.14)×105copies·mL-1(P<0.05),对照组HBV-DNA平均值由(7.66±7.21)×105 copies·mL-1下降为(6.40±7.54)×105 copies·mL-1(P>0.05);治疗组、对照组HBeAg阴转率分别为6/20(30％)、2/10(20％) (P>0.05);治疗组的ALT、 SB、TBA在治疗前后有显著性差异(P<0.05),对照组仅ALT治疗前后有显著性差异(P<0.05)。在治疗过程中未发生严重不良反应。结论 短期静脉注射膦甲酸钠具有较好的抑制乙型肝炎病毒复制的效果,同时有助于改善肝功能,远期疗效有待追踪观察。     

膦甲酸钠治疗肾移植患者巨细胞病毒抗原血症及护理

目的 了解膦甲酸钠(PFA)治疗肾移植患者巨细胞病毒(CMV)抗原血症的临床疗效和不良反应,为临床用药提供依据.方法 60例CMV-PP65抗原阳性肾移植患者随机分为治疗组和对照组,治疗组用PFA 60 mg/(kg·d)静脉滴注,治疗2～4周,对照组不使用抗病毒药物.结果 治疗组用药后显效24例(80%),有效3例(10%),无效3例(10%), 显效、有效病例随访6月CMV-PP65抗原无转阳, 对照组随访6月无1例CMV-PP65抗原转阴.PFA的不良反应为胃肠不适、低钙、低钾及一过性血肌酐升高.结论 PFA可以有效清除肾移植患者CMV-PP65抗原,不良反应轻微,一般不必停药,值得临床参考应用.     

高效液相色谱法测定膦甲酸钠氯化钠注射液中膦甲酸钠的含量

目的建立HPLC法测定膦甲酸钠氯化钠注射液中膦甲酸钠含量的方法.方法采用阴离子交换柱(Waters IC Pak A柱,50 mm× 4.6 mm,5 μm);以0.05 mol·L-1邻苯二甲酸氢钾溶液(取邻苯二甲酸氢钾0.204 g,加水适量,振摇使溶解,加1mol·L-1硝酸溶液5 mL,加水稀释至2 000 mL,摇匀即得)为流动相;流速1.4 mL·min-1,检测波长290nm.结果本方法在0.98～4.90g·L-1浓度范围呈良好线性关系(r=0.999 4),进样重现性RSD为0.71%(n=5),平均回收率为98.93%.结论本法简便、快速、结果准确可靠,可用于膦甲酸钠氯化钠注射液中膦甲酸钠的含量测定.     

Selective inhibition of herpesvirus DAN synthesis by foscarnet

The inhibition of cellular and herpesvirus DNA synthesis by phosphonoformate (INN; foscarnet sodium) has been determined after isopycnic separation of cellular and viral DNA in CsCl gradients. The DNA synthesis was determined as the incorporation of ortho[³²P]phosphate and [³H]thymidine into DNA. A 50% inhibition of herpes simplex virus DNA synthesis was observed at 50 μM phosphonoformate. At this concentration cellular DNA synthesis was not inhibited. At 500 μM phosphonoformate more than 95% of the viral DNA synthesis was inhibited, while the cellular DNA synthesis in infected and uninfected cells were inhibited to about 10%. The same results were obtained in both Vero and GMK cells and using either ortho[³²P]phosphate or [³H]thymidine to label the newly synthesized DNA. The 50% inhibitory concentration of phosphonoformate was similar for inhibition of herpes DNA synthesis and plaque reduction.     

Effect of aphidicolin on DNA synthesis in HSV-1 infected and uninfected Vero cells

The effect of aphidicolin on DNA synthesis in herpes simplex virus type 1 (HSV-1) infected and uninfected Vero cells was determined by isodensity banding of [³²P]-labelled DNA. A 50% inhibition of HSV-1 DNA synthesis was observed at 0.07 μM aphidicolin while 2.1 and 1.3 μM were required to inhibit the cellular DNA synthesis to 50% in infected and uninfected Vero cells, respectively. When the viral DNA synthesis was totally inhibited by 10 μM aphidicolin, the cellular DNA synthesis was inhibited to about 90% in both infected and uninfected cells. Aphidicolin inhibited the cellular DNA synthesis in HSV-1 infected and uninfected Vero cells remaining in the presence of 250 μM foscarnet to the same extent as the DNA synthesis in the absence of foscarnet.     

A review of antiviral therapies in the treatment of cytomegalovirus

ABSTRACT: Cytomegalovirus (CMV) is a member of the herpesvirus family that is very prevalent world wide based on serologic testing. In immunocompromised persons CMV produces high rates of morbidity and mortality. Congenital CMV is the leading infectious cause of fetal abnormalities in the United States. Infection of human immunodeficiency virus (HIV) seropositive persons or transplant patients with CMV can produce retinitis, encephalitis, pneumonitis, hepatitis, gastrointestinal ulcerations, and cutaneous lesions. Three intravenous therapies are available for CMV infections: ganciclovir; foscarnet and cidofovir. Most recently a fourth antiviral agent was approved for intravitreal injection. This drug, fomivirsen, is the first antisense oligonucleotide available for therapeutic use. A number of other antiviral drugs and vaccines are currently under study.     

膦甲酸钠抗乙型肝炎病毒近期疗效观察

为观察磷甲酸钠抗乙型肝炎病毒（HBV）的近期疗效，将67例慢性乙型肝炎患者随机分为2组：治疗组47例，在常规保什治疗的基础上加用膦用甲酸钠；对照组20例，仅用常规保肝药物治疗。治疗前后观察患者功能、血清HBVDNA含量、乙肝病毒免疫学标志等的变化。结果显示，治疗2周后，治疗组肝功能均有恢复；47例患者中42例HBVDNA水平下降，以第1周明显，第2周时10例反跳；13例HBVDNA转阴，其中5例在用药1周后即转阴。30例HBeAg阳性患者中，2例出现血清转换，1例转为弱阳性。提示磷甲酸钠具有明显和快速的抑制乙肝病毒复制、降低病毒量的作用，可作为抗病毒序贯疗法的首程用药或联合用药的选择之一。     

Foscarnet in the management of cytomegalovirus infections in hematopoietic stem cell transplant patients

Despite significant advances in the day-to-day management of patients receiving hematopoietic stem cell transplantations, including the introduction of new antiviral drugs, cytomegalovirus (CMV) infection continues to be a major cause of morbidity and mortality. The aim of this article is to undertake a literature-based review of foscarnet in this therapeutic setting and to align current best-published evidence with recent recommendations presented at the European Conference on Infections in Leukaemia. Ganciclovir remains the mainstay of CMV infection/disease antiviral management protocols. However, approximately a third of patients develop severe neutropenia and others become resistant to ganciclovir, and thus, a reasonably large proportion of patients are not able to receive and/or continue with this medication. Foscarnet is a suitable option as both pre-emptive therapy or for the treatment of active disease in these patients. Randomized trials have demonstrated that foscarnet is equally effective when compared with ganciclovir for pre-emptive treatment of CMV infections: the outcome was comparable with ganciclovir in terms of control of antigenemia and survival rates. There is a paucity of information for its use in the prophylaxis of CMV, although preliminary data show that it was effective in some patients at high risk of CMV reactivation. The main adverse events associated with foscarnet are renal impairment, serum electrolyte and hemoglobin disturbances, seizures and local genital irritation/ulceration. Foscarnet is a well-established antiviral option in immunocompromised patients, and it is usually administered as a second-line option to ganciclovir. In patients receiving hematopoietic stem cell transplantation, it has proven efficacy when used pre-emptively to treat CMV reactivation, as an alternative to and also in combination with ganciclovir.