Clinical study on treatment of infantile cytomegalovirus hepatitis with integrated Chinese and Western medicine.

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) in treating infantile cytomegalovirus hepatitis (ICH). METHODS: A total of 100 infant ICH patients were randomly assigned to two groups, 60 in the treatment group and 40 in the control group. Ganciclovir was administered to all patients via intravenous dripping at dose of 5 mg/kg every 12 h for 2 weeks, followed by 5 mg/kg once a day for 5 days every week; the whole treatment course lasted 8 weeks. Besides, the patients in the treatment group were treated with CM of Qinggan Lidan Decoction (, QLD) during icteric stage, and Yigan Jiangmei Decoction (, YJD) in non-icteric hyper-aminotransferase stage by oral medication, while for those in the control group, glucurolactone 50 mg was given three times per day. The efficacy of treatment was evaluated at the ends of 2nd, 4th and 8th weeks, respectively. And a follow-up study was carried out for 6-24 months. RESULTS: The total effective rate was 95.0% (57/60) in the treatment group and 77.5% (31/40) in the control group; the overall curative effect in the former was superior to that in the later, showing a significant difference (P=0.021). Cholestasis and liver function were improved in both groups, and the effect of reducing serum bilirubin level in the treatment group was more rapid and extensive than that in the control group, which could reduce the post-hepatitis cirrhotic risk caused by long-term cholestasis and liver cell damage. CONCLUSION: The therapeutic efficacy of integrated CM and Western medical drug therapy, by using QLD during icteric stage and YJD in nonicteric hyper-aminotransferase stage, was significantly higher than that of routine Western medical treatment alone; it was an ideal project for the treatment of infantile cytomegalovirus hepatitis.

Human cytomegalovirus resistance to antiviral drugs: diagnosis, monitoring and clinical impact.

The incidence of human cytomegalovirus (HCMV) disease in AIDS patients decreased dramatically after the introduction, a few years ago, of highly active antiretroviral combination therapy. As a consequence, the emergence of drug-resistant HCMV strains is no longer a major problem in HIV-infected individuals. However, HCMV resistance to antiviral drugs is presently recognized as an emerging problem in transplantation settings. The mechanisms of HCMV drug resistance will be analysed along with the clinical features relevant to the emergence of drug-resistant HCMV strains during antiviral treatment of patients receiving either solid organ or haematopoietic stem cell transplantation.

Cytomegalovirus infection in infants: an example of a chronopharmacological approach.

A case of a male infant at the age of 3 months with cytomegalovirus (CMV) infection, diagnosed 40 days after the first symptoms, was discussed. While the right dosage and schedule during the initial treatment with ganciclovir (Cymevene) were agreed on, the right time of further application of anti-CMV IgG (Cytotest) and ganciclovir was unclear. Daily mean temperature was taken as an overall measure based on 7 single readings (6:00, 9:00, 12:00, 15:00, 18:00, 21:00 and 24:00 h +/- 10 min). Dynamics of daily mean temperature was studied by descriptive statistics, regression analysis, autocorrelation and periodogram regression analysis (software package "6-D Statistics" PC ver.4.5-98 by B. P. Komitov) with the purpose of identifying the time periods of viral DNA replications and CMV population growth inclinations. A five-step procedure was applied: (1) description of a tendency in the daily mean temperature; (2) studying variations in time series of the daily mean temperature; (3) decomposition of cyclic variations; (4) reconstruction of time series; (5) best model determination and forecasting. Three main cycles in variations of daily mean temperature were revealed (period T approximately 2.25-3.25, 5.5 and 12.25 days, p < 0.05) until the 37th day of therapy, when a strongly decreasing trend of daily mean temperature emerged. The cycle of 2.25-3.25 days disappeared and the daily mean temperature continued to decrease significantly on the background of improvement of the clinical status. It was concluded that (1) cyclic patterns in daily mean temperature (periods T = 2.25-3.25 and 12.25 days) during the etiologic medication stages could be due to the life-cycle of 2-4 days of the cytomegalovirus and a cycle in the viral population growth, respectively. The above findings confirmed previous results on the period of viral DNA replication from in vitro studies. It was possible to forecast the right moment of replication and viral load to adjust the treatment schemes and improve the outcome; (2) the complex time-series approach has shown to be very useful and effective in analyzing and forecasting the temporal dynamics of daily mean temperature in order to optimize the clinical management in this particular case of an infant with CMV infection.

Pathophysiology and treatment of clinically resistant cytomegalovirus retinitis.

PURPOSE: To determine the incidence, pathophysiology, clinical outcome, and survival in patients with clinically resistant retinitis. METHODS: Cytomegalovirus (CMV) retinitis was prospectively studied in 100 patients with acquired immune deficiency syndrome (AIDS). In 11 of these patients, clinically resistant retinitis developed, defined as new activity or progression, despite at least 8 consecutive weeks of induction doses of either foscarnet or ganciclovir. Fundus photography, pharmacokinetics, CMV cultures and sensitivities, and survival analyses were studied. The therapeutic interventions attempted after clinically resistant retinitis was identified included continuing a high dose (induction level) of the same antiviral drug, changing the antiviral drug, and combining antiviral therapy with foscarnet and ganciclovir. RESULTS: Clinically resistant retinitis occurred in 11 (11%) of 100 patients with CMV retinitis and appeared to be a manifestation of acquired CMV antiviral drug resistance. Drug metabolism and pharmacokinetics in these patients were normal. The use of combination therapy with foscarnet and ganciclovir was effective in halting the progression of retinitis in three (75%) of four patients (6 of 7 eyes able to be evaluated) receiving combination therapy. CONCLUSION: Clinically resistant retinitis is a manifestation of infection by CMV that has acquired drug resistance. In these patients, combination antiviral drug treatment should be considered. It is likely that clinically resistant retinitis will become more frequent as patients with CMV retinitis and AIDS survive longer.