Erupción variceliforme de Kaposi y enfermedad de Darier / Kaposi's varicelliform rash and Darier's disease

La erupción variceliforme de Kaposi es una infección cutánea diseminada, causada en la mayor parte de los casos por el virus Herpes simple tipo 1. Se suele presentar en pacientes con alteraciones preexistentes de la barrera cutánea, especialmente en niños con dermatitis atópica. Se comunica el caso de un paciente de 84 años, quien negaba enfermedades cutáneas previas, que consultó por lesiones dolorosas y pruriginosas, en la piel del tórax y el abdomen, de 3 semanas de evolución. Con sospecha de una enfermedad infecciosa viral, bacteriana, ampollar o neutrofílica, se realizó inmunofluorescencia directa para herpes, cultivo y biopsia de piel para estudio histológico. La inmunofluorescencia fue positiva para Herpes simple tipo 1 y el estudio histopatológico mostró cambios compatibles con infección herpética y enfermedad de Darier. La enfermedad de Darier es una genodermatosis infrecuente que se suele manifestar en la adolescencia. Si bien su diagnóstico en la ancianidad es excepcional, este caso ilustra que se debe considerar en todos los pacientes que presenten erupción variceliforme. (AU)

Kaposi's varicelliform rash is a disseminated cutaneous infection, caused by Herpes virus 1. It usually presents in patients with pre-existing skin barrier disorders, especially in children with atopic dermatitis. We report the case of an 84-year-old patient, who reported having no previous skin diseases, who consulted for painful, itchy, 3-week-old skin lesions. As we suspected viral, bacterial, bullous or neutrophilic disease, direct immunofluorescence, culture, and skin biopsy for histological study were performed. Immunofluorescence was positive for Herpes simplex type 1 and the histopathological study showed changes compatible with herpetic infection and Darier's disease. Darier's disease is a rare genodermatosis that usually manifests in adolescence. Although its diagnosis in old age is anecdotal, it should be considered in patients with a varicelliform rash. (AU)

Presentación atípica anogenital de virus herpes simple en un adulto VIH positivo, manejo exitoso con foscarnet: reporte de caso / Atypical anogenital herpes simple virus infection in an hiv patient, successfully treatment with foscarnet: a case report

Las lesiones anogenitales hipertróficas, pseudotumorales y similares a placas, son presentaciones atípicas del virus herpes simple (VHS). Estas lesiones desarrollan resistencia a los tratamientos y se presentan en inmunocomprometidos, especialmente aquellos con infección por el virus de inmunodeficiencia humana (VIH). Presentamos el caso de un paciente masculino de 38 años de edad, VIH/SIDA, con antecedente de carcinoma escamocelular infiltrante de canal anal, con lesiones múltiples hipertróficas anogenitales y exudativas, a quien se le confirma infección por VHS-1, sin respuesta a aciclovir ni valaciclovir a dosis óptimas, el cual resuelve con 21 días de foscarnet intravenoso. Nuestro caso muestra la importancia de considerar el uso de foscarnet en adultos con infección de VIH y del VHS, que no respondan a tratamiento de primera línea, en un país donde no hay esquemas establecidos de manejo para este tipo de presentaciones y donde existe la limitante de no haber disponibilidad en pruebas para resistencia a antivirales.

Pseudotumoral, hypertrophic, plaque-like anogenital ulcers are atypical features of herpes simplex infection. These ulcers develop treatment resistance and they appear in immunocompromised mainly those infected by human immunodeficiency virus. We present a 38 years-old man with AIDS and personal history of infiltrative squamous carcinoma of anal canal with multiple hypertrophic and exudative ulcers secondary to VHS-1 etiology without response to acyclovir neither valacyclovir at optimal doses but complete answer with 21 days of foscarnet treatment. Our case highlights the role of foscarnet in adults with HIV-HSV coinfection that don't respond to frst line treatment in a country that doesn't have clear treatment recommendations in these cases and with the limitations of absence of antiviral resistance test.

Encefalitis por herpes simple resistente al aciclovir en un niño tratado satisfactoriamente con el agregado de foscarnet: A propósito de un caso / Acyclovir Unresponsive Herpes Simplex Encephalitis in a child successfully treated with the addition of Foscarnet: Case report

La encefalitis por herpes simple (EHS) es la causa más frecuente de encefalitis focal esporádica en todo el mundo. El aciclovir es el tratamiento preferido para la EHS desde la década de 1980. Después del uso generalizado del aciclovir, se redujo la tasa de mortalidad relacionada con la EHS pero surgieron cepas resistentes. Se ha informado que la incidencia de virus del herpes simple (VHS) resistente al aciclovir es del 0,5 % y del 3,5 %-10 % aproximadamente en los pacientes inmunocompetentes e inmunocomprometidos, respectivamente. En este artículo, describimos el caso de un paciente inmunocompetente de 12 años de edad con encefalitis por VHS-1 tratado satisfactoriamente con aciclovir y foscarnet. En el caso de una condición clínica que desmejora con el tratamiento con aciclovir, incluso si no se demuestra un aumento de la carga viral del VHS en el líquido cefalorraquídeo, se podría considerar la posibilidad de EHS resistente al aciclovir y el agregado de foscarnet al tratamiento con aciclovir.

Herpes simplex encephalitis (HSE) is the most common cause of sporadic focal encephalitis worldwide. Acyclovir is the treatment of choice of HSE since the 1980s. After the widespread use of acyclovir, HSE related mortality rate had reduced but resistant strains emerged. Acyclovir resistant HSV incidence was reported as about 0.5 % and 3.5 %-10 % in immunocompetent and immunocompromised patients, respectively. Herein, a 12-year-old immunocompetent patient with HSV-1 encephalitis who was successfully treated with combined acyclovir and foscarnet therapy is described. In the case of deteriorating clinical condition under acyclovir treatment even if the absence of demonstration of increased CSF HSV viral load, the possibility of acyclovir resistant HSE and the addition of foscarnet to the acyclovir treatment might be considered.

Manifestaciones oculares de enfermedad Sistémica: Retinitis por CMV en pacientes no HIV / Ocular Manifestations of Systemic Disease: CMV Retinitis in Non-HIV Patients

La retinitis es la manifestación más común de la infección por CMV en inmunocomprometidos. Es una infección oportunista representando el 90% de las retinitis infecciosas, y la principal causa de ceguera en este grupo de pacientes. La retinitis por Citomegalovirus (CMV) puede desarrollarse en pacientes no HIV con deterioro de la inmunidad secundario a medicación inmunodepresora o enfermedades malignas que originen por ser estados de inmunodepresión. Se presentan dos estudios de casos. A continuación una síntesis de la evidencia que incluye información del diagnóstico, tratamiento tanto con Ganciclovir, como con Foscarnet.

Retinitis is the most common manifestation of CMV infection in immunocompromised patients. It is an opportunistic infection that accounts for 90% of infectious retinitis andthe main cause of blindness in this group of patients. Cytomegalovirus (CMV) retinitis can develop in non-HIV patients with impaired immunity due to immunosuppressive medication or malignant disease resulting from the status of immunosuppression. Two case studies are presented. Below, there is a synthesis of the evidence, including information on the diagnosis and treatment with both Ganciclovir and Foscarnet.

A Case of Progressive Outer Retinal Necrosis Treated by Combined Intravitreal Foscarnet and Ganciclovir

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.

The First Case of Ganciclovir-Resistant Cytomegalovirus Colitis with a 597-600 Deletion in UL97 Gene after Stem Cell Transplantation in Korea / 대한임상미생물학회지

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.

comparison study on the clinical effects of foscarnet sodium injection and interferon on human immunodeficiency virus-infected patients complicated with herpes zoster

To compare the clinical effects of foscarnet sodium injection and interferon on human immunodeficiency virus [HIV]-infected patients complicated with herpes zoster. Ninety HIV-infected patients complicated with herpes zoster were divided into a treatment group and a control group that were both treated routinely first. Then the control group and treatment group were administered with interferon and foscarnet sodium injection respectively for four consecutive weeks. After four weeks, the effective rates of the treatment and control groups were 95.6% and 80.0% respectively, which were significantly different [P < 0.05]. The pain scores of the two groups were similar before treatment, but the scores of the treatment group were significantly lower than those of the control group two and four weeks after treatment [P < 0.05] as well as were significantly lower than those before treatment [P < 0.05]. The numbers of CD4+ cells and the contents of IL-2 of both groups two and four weeks after treatment significantly exceeded those before treatment [P < 0.05], with significant inter-group differences also [P < 0.05]. Two and four weeks after treatment, the treatment group scored significantly higher in physical activity, energy, sleep, social life and emotional reaction than the control group did [P < 0.05]. HIV-infected patients are prone to being complicated with herpes zoster. Compared with interferon, foscarnet sodium injection better improves the clinical outcomes by effectively relieving pain and by regulating immune mediated inflammatory diseases, thus boosting the prognostic quality of life

The Use of Orphan Drugs for Infectious Disease: Current Status and Unmet Needs / 대한내과학회지

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.

Herpes simplex virus: isolation, cytopathological characterization and antiviral sensitivity

BACKGROUND: Herpes simplex virus (HSV) infection is an endemic disease and it is estimated that 6095% of the adult population are infected with symptoms that are usually self-limiting, though they can be serious, extensive and prolonged in immunocompromised individuals, highlighted by the emergence of drug-resistant strains. The study of the wild-type HSV strains based on the cytopathogenic features and its antiviral sensitivity are important in the establishment of an antivirogram for controlling the infection. OBJECTIVE: This study sought to isolate and examine the cytopathological characteristics of circulating strains of the Herpes simplex virus, from clinical specimens and their sensitivity to commercially available antiherpesvirus drugs, acyclovir, phosphonophormic acid and trifluridine. METHODS: Herpes simplex virus isolation, cytopathological features and antiviral sensitivity assays were performed in cell culture by tissue culture infectious dose or plaque forming unit assay. RESULTS: From twenty-two clinical specimens, we isolated and adapted nine strains. Overall, the cytopathic effect was detected 24 h post-infection (p.i.) and the presence of syncytia was remarkable 48 h p.i., observed after cell staining. Out of eight isolates, four developed plaques of varying sizes. All the isolates were sensitive to acyclovir, phosphonophormic and trifluridine, with the percentage of virus inhibition (%VI) ranging from 49.7-100%. CONCLUSIONS: The methodology for HSV isolation and characterization is a straightforward approach, but the drug sensitivity test, regarded as being of great practical importance, needs to be better understood. .

Clinical analysis of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

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.

Successful Treatment of Pneumonia caused by Aspergillus terrerus and Cytomegalovirus after Chemotherapy for Acute Myelogenous Leukemia / 감염과화학요법

We report a case of pneumonia caused by Aspergillus terreus and cytomegalovirus (CMV) in a patient with acute myleogenous leukemia (AML) after remission induction chemotherapy. A 19-year-old woman underwent chemotherapy for AML. Twenty-three days after completing chemotherapy, she experienced a neutropenic fever with a rapidly-progressive pulmonary infiltration. In those days, her serum galactomannan immunoassay was 4.7 and she was treated with intravenous voriconazole (6 mg/kg q12h for 2 doses, followed by 4 mg/kg q12h) because of persistent fever and radiological worsening, despite the administration of amphotericin B deoxycholate (1 mg/kg q24h) for 7 days. A chest CT showed wedge-shaped consolidation with a central hypodense lesion and an air-crescent sign in the right middle lobe. With maintenance therapy of oral voriconazole for 10 weeks, a partial response was shown and neutrophil count was still less than 100/mm3. A lobectomy of the right middle lobe was performed. A. terreus was discovered from the lung tissue. At the same time, giant cells with intranuclear inclusions were found and immunohistochemical staining for CMV was positive. Ganciclovir (5 mg/kg q12h) was added to voriconazole therapy for 3 weeks after surgery, and then cord blood hematopoietic stem cell transplantation (HSCT) was performed. During HSCT, foscarnet (60 mg/kg q12h) was substituted for ganciclovir, and both antiviral agents were used alternatively due to CMV DNAemia. After 83 days from HSCT, the patient achieved successful engraftment and discharged without worsening the pneumonia.

Neurologic cytomegalovirus complications in patients with AIDS: retrospective review of 13 cases and review of the literature / Complicações neurológicas causadas pelo citomegalovírus em pacientes com AIDS: estudo retrospectivo de 13 casos e revisão da literatura

Neurological disorders caused by Cytomegalovirus (CMV) in patients with Acquired Immunodeficiency Syndrome (AIDS) are rarely reported in the Highly Active Antiretroviral Therapy (HAART) period. The objective of this study was to describe the main clinical and laboratory features of patients with CMV-related neurological complications in HIV-infected patients admitted to a referral center in São Paulo, Brazil. CMV disease requires the identification of the virus in the cerebrospinal fluid (CSF) using Polymerase Chain Reaction (PCR). Thirteen cases were identified between January, 2004 and December, 2008. The median age of patients was 38 years and nine (69 percent) were men. At admission all patients were aware of their HIV status and only four (31 percent) patients were on HAART. Patients who were not on antiretroviral therapy before admission received HAART while inpatients. CMV disease was the first AIDS-defining illness in eight (62 percent) patients. The neurologic syndromes identified were diffuse encephalitis (n = 7; 62 percent), polyradiculopathy (n = 7; 54 percent), focal encephalitis (rhombencephalitis) (n = 1; 8 percent), and ventriculo-encephalitis (n = 1; 8 percent). Seven (54 percent) patients presented extra-neural CMV disease and four (31 percent) had retinitis. The median of CD4+ T-cell count was 13 cells/µL (range: 1-124 cells/µL). Overall in-hospital mortality was 38 percent. Eight patients used ganciclovir or foscarnet (in-hospital mortality: 50 percent) and five patients used ganciclovir and foscarnet (in-hospital mortality: 20 percent). None of the patients fulfilled the diagnosis criteria of immune reconstitution inflammatory syndrome. Four patients were lost to follow-up, and three patients presented immune recovery and discontinued secondary prophylaxis. Although infrequent, distinct neurological syndromes caused by CMV continue to cause high mortality among AIDS patients. Survival depends upon the use of effective antiviral therapy against CMV and the early introduction of HAART.

As complicações neurológicas causadas pelo Citomegalovírus (CMV) em pacientes com aids são raramente relatadas na era HAART. O objetivo deste estudo foi descrever as principais características clínicas e laboratoriais de pacientes com complicações neurológicas associadas ao CMV em pacientes com aids admitidos em centro de referência em Sao Paulo, Brasil. A doença citomegálica precisou da identificação do vírus no líquor mediante a reação em cadeia da polimerase (PCR). Treze casos foram identificados entre janeiro de 2004 e dezembro de 2008. A mediana da idade foi 38 anos e nove (69 por cento) eram homens. Na admissão, todos os pacientes sabiam do seu status sorológico para o HIV e apenas quatro (31 por cento) pacientes usavam HAART. A doença citomegálica foi a primeira doença definidora de aids em oito (62 por cento) pacientes. As síndromes neurológicas identificadas foram: encefalite difusa (n = 7; 62 por cento), polirradiculopatia (n = 7; 54 por cento), encefalite focal (romboencefalite) (n = 1; 8 por cento), e ventrículo-encefalite (n = 1; 8 por cento). Sete (54 por cento) pacientes apresentaram doença citomegálica fora do sistema nervoso e quatro (31 por cento) tiveram retinite. A mediana da contagem de células CD4+ foi 13 células/µL. A mortalidade global durante a internação foi 38 por cento. Oito pacientes usaram ganciclovir ou foscarnet (mortalidade: 50 por cento) e cinco pacientes usaram ganciclovir e foscarnet (mortalidade: 20 por cento). Nenhum paciente apresentou critérios diagnósticos da síndrome inflamatória de reconstituição imunológica. Quatro pacientes foram perdidos do acompanhamento ambulatorial e três pacientes apresentaram reconstituição imunológica e descontinuaram as profilaxias secundárias. Embora raras, as particulares síndromes neurológicas causadas pelo CMV continuam causando elevada mortalidade em pacientes com aids. A sobrevida depende do uso de terapia antiviral efetiva contra o CMV e a introdução oportuna do HAART.

Efeitos do Foscarnet sobre a infecção pelos herpesvírus bovino tipos 1 e 5 em coelhos / Effects of Foscarnet on the infection by bovine herpesviruses 1 and 5 in rabbits

O efeito antiviral do Foscarnet (PFA) foi demonstrado anteriormente em células de cultivo infectadas com três herpesvírus bovino (BoHV). No presente estudo, investigaram-se os seus efeitos sobre a infecção e doença causadas pelo BoHV-1 e BoHV-5 em coelhos infectados experimentalmente. Coelhos inoculados com o BoHV-5 pela via intraconjuntival (IC) e tratados com o PFA (100mg/kg/dia) a partir do dia 1 pós-inoculação (pi) apresentaram uma redução nos títulos de vírus excretados entre os dias 2 e 6 pi em comparação com o grupo não-tratado; essa diferença foi significativa no dia 3 pi [F(9,108) = 2,23; P<0,03)]. Os coelhos inoculados com o BoHV-5 e tratados com o PFA apresentaram uma redução significativa nos índices de morbidade e mortalidade (95,4 por cento [21/22] nos controles; 50 por cento [11/22] nos tratados; [P<0,0008]). Em coelhos inoculados com o BoHV-1 pela via IC, o tratamento com o PFA resultou em redução nos títulos de vírus excretados, entre os dias 1 e 4, e 6 e 7 pi. Esses animais apresentaram um período de incubação mais curto e um curso clínico mais longo comparando-se com o grupo controle não tratado (P<0,005 e P<0,04, respectivamente). O PFA também reduziu a freqüência e severidade da doença ocular nos coelhos inoculados com o BoHV-1. Esses resultados demonstram que o PFA possui atividade frente ao BoHV-1 e BoHV-5 in vivo e são promissores para o uso desse fármaco em terapias experimentais das infecções herpéticas dos animais domésticos.

The activity of Foscarnet (PFA) against three bovine herpesviruses (BoHVs) was previously demonstrated in cell culture. Herein we evaluated the effects of PFA on the infection and disease by BoHV-1 and BoHV-5 in a rabbit model. Rabbits inoculated with BoHV-5 in the conjunctival sac (IC) and treated with PFA (100 mg/kg/day) from day 1 to 17 post-inoculation (pi) shed less virus between days 2 and 6 pi comparing to untreated controls; this difference was significant at day 3 pi [F(9,108) = 2,23; P<0.03]. The morbidity and mortality rates of rabbits inoculated with BoHV-5 IC or intranasally (IN) were also significantly reduced in PFA-treated rabbits (50 percent; 11/22) comparing to untreated controls (95.4 percent; 21/22) (P<0.0008). In rabbits inoculated IC with BoHV-1, a reduction in virus shedding was observed in PFA-treated animals between days 1 and 4 pi; 6 and 7 pi. In addition, PFA-treated rabbits presented a longer incubation period and a shorter clinical course comparing to untreated controls (P<0.005 and P<0.04, respectively). The frequency and severity of ocular signs were also reduced in the PFA-treated group. These results demonstrate that PFA is effective against BoHV-1 and BoHV-5 in vivo and open the way towards its use in experimental therapy of herpetic infections in domestic animals.

Cisplatin-induced Alterations of Na+-dependent Phosphate Uptake in Renal Epithelial Cells

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.

Foscarnet sodium for treatment in patients with severe chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effectiveness of foscarnet sodium in the treatment of severe chronic hepatitis B.</p><p><b>METHODS</b>Two 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.</p><p><b>RESULTS</b>HBV 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).</p><p><b>CONCLUSION</b>Foscarnet sodium injection has a good effect on severe chronic hepatitis B patients and it is safe to use on them.</p>

Clinical Features and Treatment of Cytomegalovirus Retinitis in Korea / 감염과화학요법

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.

Clinical Features and Treatment of Cytomegalovirus Retinitis in Korea / 감염과화학요법

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.

Foscarnet Effects on the Rat Pregnancy Outcome / Efectos del Foscarnet Sobre la Rata Preñada

There are few long-term data on which to base decisions of drug management of HIV infection in pregnancy. The determination of safe medications must take into consideration the need for certain drugs and the possibility of inadvertent fetal exposure because of unplanned pregnancies. The aim of this study was to evaluate the effects of foscarnet on the entire period of rat pregnancy. Female pregnant rats were randomly assigned to four treatment groups (n = 10): one control (C) ­ treated with the drug vehicle (bidestilled water) and three experimental groups (E1, E2 and E3) ­ treated with 180, 360 or 720 mg/Kg of foscarnet, respectively. Rats were treated by gavage once daily. The treatment period extended from the first until the 20th day of pregnancy. Body weights were recorded weekly along this period. At term, the rats were sacrificed, the implantation sites and the number of fetuses and resorptions were recorded. The fetuses were evaluated for externally visible abnormalities under a stereomicroscope. No differences in body weights among the groups were observed; however, foscarnet-treated rats showed reduced fetal and placental weights. The incidence 137of resorptions and major malformations (shortening of limbs) in the E3 group was significantly raised. Foscarnet treatment during the entire period of rat pregnancy can produce definite toxic effects, mainly on the placental and fetal compartments.

Foscarnet es un inhibidor de la transcriptasis reversa del HIV que actúa en la síntesis del DNA. En este trabajo evaluamos los efectos crónicos del foscarnet durante la preñez de la rata albina. Ratas preñadas fueron distribuidas aleatoriamente en cuatro grupos (n = 10 para cada grupo): uno control (C), tratadas con agua bidestilada, y tres experimentales (E1, E2 y E3), tratadas con 180, 360 o 720 mg/Kg al día de foscarnet. El fármaco y el vehículo (siempre 1 ml) fueron administrados una vez al día desde el día 0 hasta el día 20 de la gestación. Las ratas fueron pesadas semanalmente y sacrificadas al término de la preñez. No se observaron alteraciones significativas en cuanto al incremento de peso corporal entre los grupos. Sin embargo, las ratas tratadas con foscarnet (especialmente las de los grupos E2 y E3) presentaron reducciones del peso promedio de los fetos y de las respectivas placentas. La incidencia de reabsorciones y malformaciones (acortamiento de miembros) fue significativa en el grupo E3. Se concluye que la administración de foscarnet durante toda la preñez de la rata puede producir efectos tóxicos definidos, especialmente en los compartimientos placentario y fetal.

Intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS.

To determine the visual outcome, progression, and complications of patients with acquired immuno-deficiency syndrome-related cytomegalovirus (CMV) retinitis treated with intravitrealfoscarnet (2.4 mg in 0.1 ml per injection), a retrospective study was carried out in 193 patients. Induction therapy consisted of two injections a week until the lesions were inactive. Maintenance therapy consisted of one injection a week until relapse, then re-induction was instituted. In 301 treated eyes, visual acuity remained stable in 184 (61%), improved in 16 (5%), and decreased in 101 (34%). Of these, 15 retinal detachments, 13 intravitreal hemorrhages, 3 endophthalmitis, and 2 cataract occurred. Median time of first progression was 15 weeks. Involvement of the fellow eye occurred in 35% of the patients during treatment of the first eye. Intravitreal foscarnet appeared to be a useful alternative treatment for patients intolerant or unaffordable to intravenous anti-CMV drugs, but the complications of this treatment should also be considered.