更昔洛韦治疗婴幼儿手足口病的疗效观察

目的 探讨更昔洛韦对婴幼儿手足口病（HFMD）的临床疗效。方法 将65例婴幼儿HFMD患儿随机分为治疗组和对照组，治疗组加用更昔洛韦，观察临床有效率及不良反应率，并对结果进行统计学分析。结果 临床有效率治疗组为90．91地，对照组56．25％，引起白细胞下降，血小板下降治疗组为33．33％、27．27％，对照组为9．38％、3．13％，差异均有显著性。结论 治疗组疗效优于对照组，但须随访对白细胞和血小板的影响。     

以更昔洛韦为主综合治疗婴幼儿毛细支气管炎

目的 为了探讨以静脉注射更昔洛韦为主综合治疗婴幼儿毛细支气管炎的临床疗效。方法 将78例毛细支气管炎患儿随机分为两组,观察组给予更昔洛韦治疗,对照组给予病毒唑治疗,并均佐以镇静、吸氧、超雾、止咳化痰、激素治疗、预防应用抗茵素等,对照两组方法治疗毛细支气管炎前后症状体征平均持续时间,疗效及观察治疗前后实验室指标如血常规及C-反应蛋白,胸部X线检查,支原体抗体测定及衣原体抗原测定,病毒血清学检测结果。结果 观察组气促缓解时间,肺部罗音、哮鸣音咳嗽消失时间,住院日及疗效与对照组比较均有显著差异性(P<0.01)。结论 更昔洛韦对于抗病毒疗效显著,作用迅速,抗病毒谱广,临床应用的安全性也相对较好,短期应用无明显的骨髓抑制作用。每日更昔洛韦(10 mg/kg)有较好的病毒抑制作用,为今后治疗病毒感染的研究提供了广阔的前景,值得推广应用。     

Clinical Utility of Cytomegalovirus Viral Load Testing for Predicting CMV Disease in D+/R- Solid Organ Transplant Recipients

Despite prophylaxis, cytomegalovirus (CMV) disease is common in donor seropositive (D+)/recipient seronegative (R-) transplant patients after cessation of prophylaxis. Early detection of CMV may allow for pre-emptive therapy to prevent active disease. The clinical utility of quantitative plasma viral load measurements for predicting CMV disease was determined in 364 D+/R- organ transplant patients receiving prophylaxis (100 d of valganciclovir or oral ganciclovir). Measurements were performed every 2 weeks until day 100 and at months 4, 4.5, 5, 6, 8 and 12 post-transplant. CMV disease occurred in 64 (17.6%) patients by 12 months. Using a positive cut-off value of >400 copies/mL, sensitivity was 38%, specificity 60%, positive predictive value 17%, and negative predictive value 82% for prediction of CMV disease. Therefore, routine monitoring would have predicted disease in only 24/64 (38%) patients. The test characteristics were not improved by changing the viral load cut-off point for defining a positive result. Similarly, single time point measures at the end of prophylaxis or month 4 had low sensitivity for disease prediction. Overall, regular CMV plasma viral load measurements were only of modest value in predicting CMV disease.     

Patterns of cytomegalovirus infection in simultaneous kidney–pancreas transplant recipients receiving tacrolimus, mycophenolate mofetil, and prednisone with ganciclovir prophylaxis

Abstract: Background: The impact of tacrolimus (TAC), mycophenolate mofetil (MMF) and steroid immunosuppression on cytomegalovirus (CMV) infection in combination with ganciclovir prophylaxis in simultaneous kidney–pancreas transplantation (SKPT) has not been well studied. Methods: A retrospective analysis was made of 75 SKPTs performed between 1 January 1996 and 7 January 1999. All patients received ganciclovir for 3 months, but CMV donor (D)+/ recipient (R)? patients received ganciclovir for 6 months. Results: 16/74 (22%) were CMV D+/R?, 25 (33%) D+/R+, 16 (22%) D?/R+, and 17 (23%) D?/R? (1 patient with unknown donor serology was excluded). The mean time to CMV infection was 198 days post‐transplant. The incidence of either CMV infection or tissue invasive CMV disease was 16/74 (22%), including 9 (12%) with CMV infection and 7 (10%) CMV disease. The one‐year patient, kidney, and pancreas graft survival rates were 91%, 89%, and 83%, respectively. The mean follow‐up was 29 months (minimum of 12 months). CMV infection was not associated with an increased incidence of graft failure or mortality. The D+/R? group had the highest incidence of CMV infection (44%) compared with the other serologic groups (17%, P=0.02). Concurrent CMV and rejection occurred more frequently in the D+/R? than the other serologic groups (25% vs. 7%, P=0.03). The D?/R? group had the best outcomes, with no CMV infection, improved kidney graft survival at the end of follow‐up (82% vs. 72%, P=0.04) and the highest event‐free survival (no CMV infection, rejection, or graft loss) when compared to the other groups (76% vs. 33%, P<0.01). Conclusions: Compared to previous studies, ganciclovir prophylaxis delayed the onset and reduced the severity of CMV infection in patients receiving TAC, MMF, and steroids. Despite ganciclovir prophylaxis, CMV seronegative patients receiving CMV D+ organs had worse outcomes than seronegative recipients receiving CMV D? organs.     

Interferon treatment with or without oral ganciclovir in HBeAg-negative chronic hepatitis B: a randomized study

The treatment of HBeAg-negative chronic hepatitis B with alpha interferon alone is unsatisfactory. We evaluated the efficacy of combined administration of interferon-a2a (IFN) with oral ganciclovir, a nucleoside analogue. Forty patients with hepatitis B virus (HBV)-DNA-positive/HBeAg-negative chronic hepatitis B, were randomized to receive 4.5 MU IFN thrice weekly, subcutaneously, alone or in combination with 3 g ganciclovir per os daily for 26 weeks and followed for 12 months after treatment. Mean serum HBV-DNA levels decreased by 4.0 log10 in the combination group (from 5 x 106 to 4.8 x 102 copies/ml) and by 2.2 log10 in the interferon group (from 8 x 106 to 4.8 x 104 copies/ml) by quantitative polymerase chain reaction (PCR). HBV-DNA became undetectable in 11 of 20 (55%) and in three of 20 (15%) patients in the two groups, respectively (P=0.02). The alanine aminotransferase levels became normal in all patients receiving combination therapy, compared to 75% of those in the interferon group. After cessation of therapy, HBV-DNA increased or reappeared in all patients with 85% also relapsing biochemically. One year after treatment, three patients in each group (15%) remained in sustained biochemical remission with very low serum HBV-DNA levels (median 15 700 copies/ml). We conclude that, in HBeAg-negative chronic hepatitis B, 6-month combination therapy with oral ganciclovir and IFN is associated with complete biochemical remission in all treated patients and a 4 log10 decrease in serum HBV-DNA levels. The end of treatment efficacy of this combination scheme is far super- ior to that of IFN monotherapy but sustained responses are few. Further studies are warranted to evaluate the efficacy of prolonged combination schemes with nucleoside analogues and IFN, compared to IFN monotherapy.     

The role of antiviral and immunoglobulin therapy in the prevention of Epstein–Barr virus infection and post-transplant lymphoproliferative disease following solid organ transplantation

Abstract: The recognition of the importance of Epstein–Barr virus (EBV) infection, including EBV-associated post-transplant lymphoproliferative disease (PTLD), has led to a new focus on the prevention of this problem. This paper reviews the scientific rationale behind, and clinical experience with, the use of chemoprophylaxis (using acyclovir or ganciclovir) and immunoprophylaxis (using intravenous immunoglobulin) in the prevention of EBV/PTLD. While some centers have already introduced the use of one or both of these agents as standard prophylaxis against the development of this complication, published data in support of these protocols are currently lacking. Well designed clinical trials are necessary to evaluate the potential role of both antiviral and immunoglobulin agents in the prevention of EBV/PTLD in organ transplant recipients.     

Changing results of HLA-identical sibling bone marrow transplantation in patients with haematological malignancy during the period 1981–1990

:During the years 1981-90 inclusive 227 patients with haematological malignancy received an HLA-identical sibling first transplant at St Vincent's Hospital, Sydney. Recipients with acute leukaemia in first remission or chronic myeloid leukaemia in first chronic phase were analysed as good risk, and those beyond these stages, as poor risk patients. Good risk patients transplanted in the years 1986-90 ( n = 52) showed improved actuarial survival (74%) compared to those ( n = 58) transplanted during 1981-85 (37%, p = 0.01). There was a suggestion that leukaemia-free survival was also improved in those transplanted during the later time period (62% versus 36%, p = 0.07). In contrast, poor risk patients transplanted during 1986-90 ( n =55) appeared to have worse leukaemia-free survival (15%) compared to those transplanted during 1981-85 ( n = 62) (22%, p = 0.09). The incidence of acute graft-versus-host disease (GVHD) grades I-IV in all patients was 94% in those transplanted during 1981-85 ( n =120) and 86% in those transplanted during 1986-90 ( n =107) ( p = 0.002). The incidence of acute GVHD grades II-IV was 37% during 1981-83, 20% during 1984-86, and 28% during 1987-90 ( p = 0.1). The decrease in incidence and severity of acute GVHD correlated with the introduction of the cyclosporin/short methotrexate regimen in our practice. The incidence of cytomegalovirus (CMV) pneumonitis was 18% in 1981-85, and 11% in 1986-90 ( p = 0.09). In 1989 and 1990 no cases of CMV pneumonitis occurred. The decrease in incidence of CMV pneumonitis correlated with the introduction of prophylactic ganciclovir. The reduction of the transplant-related complications acute GVHD and CMV pneumonitis has resulted in improved survival for good risk patients, but not for bad risk patients. (Aust NZ J Med 1993; 23: 181–186.)     

Successful outcome of ganciclovir-resistant cytomegalovirus infection in organ transplant recipients after conversion to mTOR inhibitors

Ganciclovir-resistant (GanR) cytomegalovirus (CMV) infection after organ transplantation is emerging as a significant therapeutic challenge. We report two cases of GanR CMV infection successfully managed by switching immunosuppression from calcineurin inhibitors to an mTOR inhibitor-based regimen. This salvage therapy should be considered when other options are not available.     

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.