Cytomegalovirus (CMV) remains an important pathogen in organ transplant recipients, and ganciclovir has been the antiviral agent of choice both for prevention and treatment of CMV disease. Recently ganciclovir-resistant cytomegalovirus has been reported with increasing frequency in organ transplant recipient and is an emerging clinical problem in transplant recipients. Ganciclovir-resistant CMV infection has been associated with clinical progression of CMV disease and high mortality even with foscarnet therapy. We report here a case of disseminated ganciclovir-resistant CMV disease in a 34-year-old renal transplant recipient, who died of multiorgan failure despite treatment with both ganciclovir and foscarnet.
Adult ; Cytomegalovirus Infections* ; Cytomegalovirus* ; Foscarnet ; Ganciclovir ; Humans ; Kidney Transplantation* ; Mortality ; Transplantation ; Transplants

Direct exposure of renal tubular brush-border membranes (BBM) to free cadmium (Cd) causes a reduction in phosphate (Pi) transport capacity. Biochemical mechanism of this reduction was investigated in the present study. Renal proximal tubular brush-border membrane vesicles (BBMV) were isolated from rabbit kidney outer cortex by Mg precipitation method. Vesicles were exposed to 50~200 muM CdCl2 for 30 min, then the phosphate transporter activity was determined. The range of Cd concentration employed in this study was comparable to that of the unbound Cd documented in renal cortical tissues of Cd-exposed animals at the time of onset of renal dysfunction. The rate of sodium-dependent phosphate transport (Na+-Pi cotransport) by BBMV was determined by 32P-labeled inorganic phosphate uptake, and the number of Na+/-Pi cotransporters in the BBM was assessed by Pi-protectable 14C-labeled phosphonoformic acid ((14C)PFA) binding. The exposure of BBMV to Cd decreased the Na+-Pi cotransport activity in proportion to the Cd concentration in the preincubation medium, but it showed no apparent effect on the Pi-protectable PFA binding. These results indicate that an interaction of renal BBM with free Cd induces a reduction in Na+-Pi cotransport activity without altering the carrier density in the membrane. This, in turn, suggest that the suppression of phosphate transport capacity (Vmax) observed in Cd-treated renal BBM is due to a reduction in Na+-Pi translocation by existing carriers, possibly by Cd-induced fall in membrane fluidity.
Animals ; Cadmium ; Cadmium Chloride ; Foscarnet* ; Kidney ; Membrane Fluidity ; Membranes* ; Phosphate Transport Proteins*

Serious cytomegalovirus (CMV) infection occurs frequently in immunocompromised patients and is a common cause of death. Although primary infection in immunocompetent hosts is normally subclinical, mononucleosis-like syndrome that is characterized by malaise, protracted fever, mild liver function abnormalities, and lymphocytosis with atypical lymphocytes occurs in -10% of patients. Rarely fulminant infection may develop. In both the United States and the United Kingdom, ganciclovir and foscarnet are recommended for the treatment of serious CMV infections in immunocompromised patients. In contrast, there are no recommendations for treatment of severe CMV disease in immunocompetent patients. We describe a case of 45-year-old woman with CMV pneumonia with a fatal outcome for whom there was no evidence of prior immunodeficiency.
Cause of Death ; Cytomegalovirus* ; Fatal Outcome ; Female ; Fever ; Foscarnet ; Ganciclovir ; Great Britain ; Humans ; Immunocompromised Host ; Liver ; Lymphocytes ; Lymphocytosis ; Middle Aged ; Pneumonia* ; United States

OBJECTIVETo investigate the effectiveness of foscarnet sodium in the treatment of severe chronic hepatitis B.

METHODSTwo hundred and eight patients were enrolled in a multicenter, double-blind, controlled study. The patients received foscarnet sodium (foscarnet group) or saline (control group) injections for 4 weeks, and were then followed for 24 weeks.

RESULTSHBV DNA negative rate was 12.8% in the foscarnet group and 7.1% in the control group at the end of treatment; and it was 5.5% and 3.0% at the end of the follow-up period respectively (P > 0.05). The rate of HBV DNA decrease of more than 2 log copies/ml was 53.2% in the foscarnet group and 16.2% in the control group at the end of treatment, and 23.9% and 8.1% (P < 0.01) respectively at the end of the follow-up period. The rate of HBV DNA < 10(5) copies/ml was 64.2% and 30.3% at week 4 in the two groups respectively, and 40.4% and 22.2% (P < 0.01) at the end of the follow-up period. HBeAg negative rate was 17.3% and 5.8% at the end of the treatment, and 22% and 5.4% at the end of the follow-up period (P < 0.01). The rate of HBeAg seroconversion was 12.7% and 3.7% at week 4, and 16.7% and 1.5% at the end of the follow-up period. Response rate was 60.6% and 21.2% at the end of week 4 (P < 0.05).

CONCLUSIONFoscarnet sodium injection has a good effect on severe chronic hepatitis B patients and it is safe to use on them.

Adolescent ; Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Foscarnet ; adverse effects ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Middle Aged ; Young Adult

Cisplatin treatment increases the excretion of inorganic phosphate in vivo. However, the mechanism by which cisplatin reduces phosphate uptake through renal proximal tubular cells has not yet been elucidated. We examined the effect of cisplatin on Na+-dependent phosphate uptake in opossum kidney (OK) cells, an established proximal tubular cell line. Cells were exposed to cisplatin for an appropriate time period and phosphate uptake was measured using [32P]-phosphate. Changes in the number of phosphate transporter in membranes were evaluated by kinetic analysis, [14C]phosphonoformic acid binding, and Western blot analysis. Cisplatin inhibited phosphate uptake in a time- and dose-dependent manner, and also the Na+-dependent uptake without altering Na+-independent uptake. The cisplatin inhibition was not affected by the hydrogen peroxide scavenger catalase, but completely prevented by the hydroxyl radical scavenger dimethylthiourea. Antioxidants were ineffective in preventing the cisplatin-induced inhibition of phosphate uptake. Kinetic analysis indicated that cisplatin decreased Vmax of Na+-dependent phosphate uptake without any change in the Km value. Na+-dependent phosphonoformic acid binding was decreased by cisplatin treatment. Western blot analysis showed that cisplatin caused degradation of Na+-dependent phosphate transporter protein. Taken together, these data suggest that cisplatin inhibits phosphate transport in renal proximal tubular cells through the reduction in the number of functional phosphate transport units. Such effects of cisplatin are mediated by production of hydroxyl radicals.
Antioxidants ; Blotting, Western ; Catalase ; Cell Line ; Cisplatin ; Epithelial Cells* ; Foscarnet ; Hydrogen Peroxide ; Hydroxyl Radical ; Kidney ; Kinetics ; Membranes ; Opossums ; Phosphate Transport Proteins

PURPOSE: To report a case of progressive outer retinal necrosis treated by combined intravitreal foscarnet and ganciclovir. CASE SUMMARY: A 11-year-old male with a history of chemotherapy and cord blood transplantation due to precursor T-cell leukemia developed Herpes zoster lesion on his forehead and rapidly progressing peripheral retinal necrosis without vasculitis in the right eye. Varicella-Zoster virus was confirmed in his cerebrospinal fluid using polymerase chain reaction (PCR); and the patient was diagnosed with progressive outer retinal necrosis. Despite combined treatment with intravenous acyclovir and foscarnet and intravitreal foscarnet, retinal necrosis progressed to retinal detachment and total retinal necrosis. During follow-up, new retinal necrosis was observed in his left eye. The patient was started on combined intravenous and intravitreal foscarnet and ganciclovir; retinal necrosis in the left eye regressed and posterior pole was spared. With subsequent oral valganciclovir and intravitreal foscarnet and ganciclovir, the remaining retina was preserved with maintained vision.
Acyclovir ; Cerebrospinal Fluid ; Child ; Drug Therapy ; Fetal Blood ; Follow-Up Studies ; Forehead ; Foscarnet* ; Ganciclovir* ; Herpes Zoster ; Herpesvirus 3, Human ; Humans ; Leukemia, T-Cell ; Male ; Necrosis* ; Polymerase Chain Reaction ; Retina ; Retinal Detachment ; Retinaldehyde* ; Vasculitis

Human cytomegalovirus (CMV) infection has been a major concern in hematopoietic stem cell transplant recipients. Ganciclovir (GCV) resistance results mostly from mutations within the protein kinase UL97 gene. The three hot spots for GCV resistance (codons 460, 520, and 590-607) were well known. We describe a case of GCV-resistant CMV colitis caused by a 597-600 deletion in UL97 after haplo-identical peripheral blood stem cell transplantation (h-PBSCT) in a 46 year-old man with myelodysplastic syndrome. On post-PBSCT day 28, CMV antigenemia turned positive. Treatment of GCV was started and continued for 12 weeks but CMV antigenemia did not respond to the treatment and CMV colitis was worsened. The UL97 showed the in-frame deletion between codons 597 and 600 by direct sequencing. The treatment was switched to foscarnet and the antigenemia test was consecutively negative twice, and clinical symptoms improved. Despite the recovery of the patient from CMV colitis, the patient expired post-PBSCT day 146 from acute liver failure, hepatorenal syndrome and septic shock. This case is a first report of a deletion 597-600 in CMV UL97 in Korea. A 597-600 deletion in UL97 was responsible for the GCV resistance while preserving susceptibility to foscarnet.
Codon ; Colitis* ; Cytomegalovirus* ; Drug Resistance ; Foscarnet ; Ganciclovir ; Hematopoietic Stem Cells ; Hepatorenal Syndrome ; Humans ; Korea ; Liver Failure, Acute ; Myelodysplastic Syndromes ; Peripheral Blood Stem Cell Transplantation ; Protein Kinases ; Shock, Septic ; Stem Cell Transplantation* ; Transplantation

BACKGROUND/AIMS: The aim of this study was to investigate the inconveniences and potential improvements in the use of orphan drugs for the treatment of infectious diseases, as determined by a survey of medical professionals. METHODS: An email was sent twice to the members of the Korean Society for Chemotherapy, and an online survey was conducted. The data collected were analyzed in terms of the frequency of drug use and associated difficulties as well as the scope for improvement. RESULTS: A total of 77 medical professionals participated in this survey. Rabies vaccine (n = 52), rabies immunoglobulin (n = 47), and foscarnet injection (n = 43) were supplied mainly through the Korea Orphan Drug Center (KODC), while artesunate (n = 29), quinine sulfate capsule (n = 24), quinine dihydrochloride injection (n = 23), and quinidine gluconate injection (n = 21) were supplied mainly through the National Medical Center (NMC). Difficulties in obtaining orphan drugs through the KODC were related to the KODC drug retrieval system (n = 67, 95.7% of respondents), lack of supplies on holidays (n = 66, 94.3%), complicated application procedures and documents (n = 61, 87.1%), and shipping inconveniences (n = 61, 87.1%). With regard to the use of orphan drugs supplied through the NMC, 52 participants (98.1%) responded that a staff visit should be mandatory for obtaining the drugs. CONCLUSIONS: Antivirals and antimalarial drugs are major orphan drugs used for the treatment of rare infections. It is necessary to establish a more efficient system to ensure a stable supply of orphan drugs, including on holidays, to enhance the smart drug searching system, and to simplify related administrative procedures.
Antimalarials ; Antiviral Agents ; Child ; Child, Orphaned* ; Communicable Diseases* ; Drug Therapy ; Electronic Mail ; Equipment and Supplies ; Foscarnet ; Holidays ; Humans ; Immunoglobulins ; Infectious Disease Medicine ; Korea ; Orphan Drug Production* ; Quinidine ; Quinine ; Rabies ; Rabies Vaccines ; Rare Diseases ; Ships

The objective of this study was to explore the incidence and therapeutic efficacy of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 140 patients undergoing allo-HSCT in our department of hematology from 2010-01 to 2012-01 were retrospectively analyzed. The results showed that the incidence of CMV infection was 4.3% (48/140), the time for the first detection of positive CMV-DNA was at day 45 (33 to 68) after allo-HSCT, and the CMV quantitative range was 1.25×10(3) - 5.5×10(6). There were 2 cases of CMV-related interstitial pneumonia and 5 cases of hemorrhagic bladder inflammation. A total of 65 patients suffered from graft versus host disease (GVHD), in which 32 cases (49.2%) were accompanied with CMV infection, CMV-DNA negative in patients treated with ganciclovir, foscarnet sodium anti-CMV was at day 45 (33 to 68) with the effective rate of 100%. 12 patients with CMV infection were accompanied with transient neutropenia and thrombocytopenia. It is concluded that after allo-HSCT the CMV infection occurs frequently. The patients with GVHD have a higher incidence of CMV infection. Ganciclovir and foscarnet sodium are reliable to be used for treatment of CMV infection with fewer adverse reactions.
Adolescent ; Adult ; Child ; Child, Preschool ; Cytomegalovirus Infections ; drug therapy ; etiology ; Female ; Foscarnet ; therapeutic use ; Ganciclovir ; therapeutic use ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Transplantation, Homologous ; Young Adult

BACKGROUND: Cytomegalovirus (CMV) infection is an important cause of opportunistic diseases in HIV infected patients and also, "non-HIVs". This study was focused on the clinical features and efficacies of treatment of patients with CMV retinitis. MATERIALS AND METHODS: The medical records of patients diagnosed as CMV retinitis at the Severance hospital, Yonsei University Medical College from January 1992 to February 2006 were reviewed retrospectively. RESULTS: There were 16 HIV patients and 9 non-HIV patients; total 25 cases. The ratio of male and female was 6.3:1. 5 cases were infected with HIV by homosexual contacts, 6 cases were by heterosexual contacts, and 2 cases were by the infection which was pertinent to transfusion and blood products. Infection routes of 3 cases were unable to be determined. At the time of the diagnosis of HIV infection, the average age of patients was 38.2+/-6.6 years, and afterwards, the interval to the development of CMV retinitis was average 2.2+/-3.4 years. The number of CD4+ lymphocytes at the time of the diagnosis of HIV infection, and the diagnosis of CMV retinitis was 122.9/mm3 and 68.9/ mm3, respectively. One of non-HIV patients had undergone kidney-transplantation, and two had malignant lymphoma and four had aplastic anemia as their underlying diseases. The other one had systemic lupus. Their symptoms included visual disturbance, floater and visual field defects, but three of them felt no visual discomfort. In 5 AIDS patients, while administering the induction therapy of ganciclovir, it was terminated due to leukopenia caused by bone marrow suppression. One patient already lost the eyesight at the time of the diagnosis, and thus antiviral drugs were not administered. The other 19 cases were treated by intravenous ganciclovir or foscarnet, and their symptoms were improved. Among 16 HIV patients, 12 patients died an average of 8.0 months after the diagnosis of CMV retinitis. There was no mortality among non-HIV patients within 2 years. CONCLUSION: These results suggested that HIV patients with CD4 T lymphocytes lower than 100/mm3 were susceptible to CMV retinitis. There were clinical improvements in 68.8% prescribed with ganciclovir. In the fatalities' point of view, the awareness and recognition of CMV retinitis on AIDS patients has become increasingly important. In the immunocompromised hosts, it is important to perform aggressive treatment of CMV retinitis to prevent their complications.
Anemia, Aplastic ; Antiviral Agents ; Bone Marrow ; Cytomegalovirus Retinitis* ; Cytomegalovirus* ; Diagnosis ; Female ; Foscarnet ; Ganciclovir ; Heterosexuality ; HIV ; HIV Infections ; Homosexuality ; Humans ; Immunocompromised Host ; Korea* ; Leukopenia ; Lymphocytes ; Lymphoma ; Male ; Medical Records ; Mortality ; Retinitis ; Retrospective Studies ; T-Lymphocytes ; Visual Fields