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Sulfadiazine, acyclovir, indinavir, triamterene, and MTX are known to cause crystal nephropathy. Recently, several medications, including orlistat, ciprofloxacin, and oral sodium phosphate solution, along with underlying risk factors have been described as causing crystal nephropathy.
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We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) in The Cochrane Library (Issue 3, 2006), MEDLINE (1966 to July 2006, week 3), EMBASE (1980 to 2006, week 30), LILACS (up to August 2006), SIGLE (1980 to March 2005), ZETOC (1 August 2006), BIOSIS (up to 2005), JICT-EPlus (up to 2005), Index Medicus (1960 to 1965), Excerpta Medica Ophthalmology (1960 to 1973), reference lists of primary reports and review articles, and conference proceedings pertaining to ocular virology.
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Manifestations of herpes zoster ophthalmicus (HZO) infection are well known in HIV-seropositive White patients in developed countries, but this association has not been previously noted in African AIDS patients. This paper analyzes 8 cases (3 men and 5 women) 24-40 years of age who were treated at the Eye Department of the University of Nigeria Teaching Hospital, Enugu, for HZO in 1994-97. Of the 6 patients who consented to HIV screening, 4 were HIV-seropositive. One of the HIV-infected patients had been treated for pulmonary tuberculosis a year prior to the present illness, but the remaining 7 were in apparent good health. The patients presented with skin eruptions in the area of distribution of the trigeminal nerve on the affected side of the face and head. Visual acuity was impaired in all 8 cases. The most common ocular findings were lid edema, ptosis, conjunctival infection, corneal anesthesia, keratitis, uveal inflammation, and abnormal pupillary reaction. The severity of presentation was similar in HIV-positive and HIV-negative patients and all improved during follow-up; however, clinical improvement was less rapid or pronounced among the HIV-positive patients. These findings suggest that HZO infection in young Africans should be regarded as a possible indicator of HIV infection.
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The transmission of human immunodeficiency virus (HIV) through transplantation of human tissues and organs is rare but not impossible. A 27-year-old Bulgarian woman received a kidney transplant from a cadaveric donor owing to chronic renal failure due to glomerulonephritis of unknown etiology. Five days after the donation, the tissues showed HIV-1 infection, so she was immediately initiated on highly active antiretroviral therapy (HAART) with lopinavir/ritonavir, zidovudine, enfuvirtide, and lamivudine. Subsequently, according to the genotypic test which revealed a complex resistance pattern of the HIV-1, we changed the regimen to darunavir/ritonavir, etravirine, lamivudine, and enfuvirtide. The HIV-1 genome (550 UI/mL), which was detected at 5 days after transplantation, rapidly declined to undetectable levels at 3 weeks after HAART. The CD4+ T-cell nadir was 432 cells/microL (40%) to 1,400 cells/microL after 2 years. The posttransplantation course was complicated by cytomegalovirus pneumonia. At 32 months after transplantation, the patient had experienced hypertension with secondary retinopathy, bilateral cataracts, diabetes, hypothyroidism, osteoporosis with multiple vertebral fractures, a hip prosthesis, and a bone infarction of the femur. Major management problems had been related to steroid and HAART treatment side effects. Therapeutic interactions between the immunosuppressants and the antiretroviral drugs were complex for management, requiring frequent checks of drug levels and dose-adjustments. We finally obtained a stable clinical and viroimmunologic condition. The transmission of multiresistant strains of HIV from unknown patients requires complex multidisciplinary management.
To assess the efficacy of antiviral agents in solid organ transplant recipients in the prevention of cytomegalovirus infection and symptomatic disease and in the reduction of the incidence of acute rejection, graft loss and death.
Uniform acyclovir-resistant or acyclovir-sensitive sequential isolates were identified in 4 and 2 patients, respectively. Notably, the acyclovir susceptibility of sequential isolates changed from acyclovir sensitive to acyclovir resistant (5 patients) or from acyclovir resistant to acyclovir sensitive (3 patients). The acyclovir-resistant phenotype of the isolates correlated with the patient's unresponsiveness to acyclovir therapy. Combined analyses of the TK gene and genotype of sequential isolates showed that acyclovir-sensitive isolates contained multiple acyclovir-resistant variants of the same virus and that an identical acyclovir-resistant HSV-1 strain reappeared in the patient's cornea during RHK episodes.
Pancreas transplantation is an effective treatment option for patients with complicated diabetes mellitus. Pancreas allograft recipients are followed with laboratory markers such as serum amylase, lipase and glucose levels. Hyperglycemia may indicate severe acute rejection and has recently been associated with antibody-mediated (humoral) rejection. In this report, we describe a unique case of a pancreas-after-kidney (PAK) transplant recipient with the rare presentation of pancreatic panniculitis, biopsy-proven severe acute cellular and antibody-mediated pancreas allograft rejection and surprisingly well-preserved endocrine function despite treatment with high dose steroids. We discuss the clinicopathologic features of antibody-mediated pancreas rejection, including the importance of correlating pancreas allograft biopsy, C4d staining and donor specific antibodies, to diagnose antibody-mediated rejection and initiate the correct treatment.
In the setting of CMV preemptive therapy, a differentiated varicella zoster virus-specific prophylaxis might be necessary for patients with HZ risk factors.
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Several recent studies have indicated that conventional multiround infectivity assays are inferior to single cycle assays at both low and high levels of inhibition. Multiround infectivity assays can fail to detect subtle but clinically significant anti-HIV activity. The discoveries of the anti-HIV activity of the hepatitis B drug entecavir and the herpes simplex drug acyclovir were facilitated by single-round infectivity assays. Recent studies using a single-round infectivity assay have shown that a previously neglected parameter, the dose-response curve slope, is an extremely important determinant of antiviral activity. Some antiretroviral drugs have steep slopes that result in extraordinary levels of antiviral activity. The instantaneous inhibitory potential, the log reduction in infectivity in a single-round assay at clinical drug concentrations, has been proposed as a novel index for comparing antiviral activity.
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The authors report the case of a patient aged 60-year-old who survived ulcerative colitis complicated by toxic megacolon and disseminated intravascular coagulation. This patient was not known for this ulcerative colitis and was first hospitalised for a suspicion of diverticulitis. The admission symptoms were fever, abdominal pain and bloody diarrhoea. The evolution was defavorable under antibiotics and sulfasalazine. The patient was readmitted 5 days after he left hospital, and the diagnosis of UC was based on colon biopsy made during the first hospitalisation. A treatment with methylprednisolone was started and the patient worsened day by day with apparition of toxic megacolon and disseminated intravascular coagulation. Subtotal colectomy was performed for degradation of general status and coagulation factors. Pathological findings confirmed ulcerative colitis with toxic megacolon. Cytomegalovirus inclusions were demonstrated on the colonic specimen and confirmed by PCR. In this report the authors discuss the etiology of toxic megacolon and disseminated intravascular coagulation in ulcerative colitis surinfected by cytomegalovirus. Mortality of these pathologies is high necessitating rapid diagnosis of cytomegalovirus infection by sigmoid biopsy. Management requires immunosupression interruption and ganciclovir therapy, or surgery in unsuccessful medical treatment.
Presumed herpetic anterior uveitis with or without keratitis has characteristic clinical findings that enable the diagnosis. Long-term prophylactic antiviral therapy should be considered especially in patients <50 years old.
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The validated method is useful for both therapeutic drug monitoring and pharmacokinetic studies. It could be applied to the daily clinical laboratory practice to measure the concentration of ganciclovir in human plasma.
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A 45-year-old white man with long-standing, multidrug-resistant human immunodeficiency virus (HIV) infection and severe immunodeficiency despite multiple antiretroviral drug regimens, presented to the eye clinic reporting decreased vision and spider web patterns in his left eye for the past week. Best-corrected visual acuity was 20/20 in the right (O.D.) and 20/25 in the left eye (O.S.). Dilated funduscopic examination of the left eye found vasculitis of the midperipheral inferonasal arcade in the midperiphery, with surrounding intraretinal hemorrhage and granular retinal necrosis. Diagnosis of cytomegalovirus retinitis was made, and the patient began induction therapy with oral valganciclovir 900 mg twice a day for 3 weeks. Maintenance therapy after retinitis stabilization was 900 mg every day until any observed recurrence of infection. Three months after complete resolution of the active retinitis, the patient returned to the clinic reporting new floaters of recent onset. A reactivation of the CMV retinitis warranted a reinduction with valganciclovir 900 mg orally twice a day for 3 weeks.
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We enrolled 326 centrally confirmed cases of AIS and 115 stroke-free controls with trauma (29 days to 18 years of age) with acute blood samples (≤3 weeks after stroke/trauma); cases had convalescent samples (7-28 days later) when feasible. Samples were tested by commercial enzyme-linked immunosorbent assay kits for immunoglobulin M/immunoglobulin G antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, and varicella zoster virus. An algorithm developed a priori classified serological evidence of past and acute herpesvirus infection as dichotomous variables. The median (quartiles) age was 7.7 (3.1-14.3) years for cases and 10.7 (6.9-13.2) years for controls (P=0.03). Serological evidence of past infection did not differ between cases and controls. However, serological evidence of acute herpesvirus infection doubled the odds of childhood AIS, even after adjusting for age, race, and socioeconomic status (odds ratio, 2.2; 95% confidence interval, 1.2-4.0; P=0.007). Among 187 cases with acute and convalescent blood samples, 85 (45%) showed evidence of acute herpesvirus infection; herpes simplex virus 1 was found most often. Most infections were asymptomatic.
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Nauclea latifolia Smith, a shrub belonging to the family Rubiaceae is a very popular medicinal plant in Cameroon and neighboring countries where it is used to treat jaundice, yellow fever, rheumatism, abdominal pains, hepatitis, diarrhea, dysentery, hypertension, as well as diabetes. The ethno-medicinal use against yellow fever, jaundice and diarrhea prompted us to investigate on the antiviral activity of the root bark of N. latifolia. In this study, HSV-2 was chosen as a viral model because of its strong impact on HIV transmission and acquisition.
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Cytomegalovirus (CMV) infection is a common cause of morbidity and mortality among patients receiving chronic maintenance immunosuppression and is often considered the most important infection in renal transplantation. CMV gastritis has been reported in transplant patients. We present a case of CMV gastritis with epigastric pain that decreased in supine position, increased while sitting, and further increased when standing or walking. To our knowledge this is the second article presented to the literature so far.
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Rapid quantifiable diagnostic techniques for the diagnosis of cytomegalovirus (CMV) infection may predict patients at risk of CMV pneumonitis and allow preemptive antiviral treatment.
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Two patients with lysinuric protein intolerance (LPI) had near-fatal generalized varicella infection with severe interstitial pneumonitis, hepatitis, decreased platelet count, bleeding and hypoalbuminaemia. Active haemolysis resulted in anaemia and massive haemoglobinuria. Serum lactate dehydrogenase activity and ferritin concentration, which in patients with LPI in normal circumstances exceed the upper reference values 3-folds to 10-fold, increased to > 10,000 U/L and > 10,000 micrograms/L, respectively. The patients were treated with fresh frozen plasma, red-cell transfusions and intravenous acyclovir for 14 days, and recovered clinically in a month. Retrospectively, 3 of the 32 other known Finnish patients with LPI had had varicella infection that had been more severe than that in the other children in the family or in subjects in the neighbourhood and had led to hospital admission. Varicella antibodies were measured in 24 patients; 5 had no antibodies and 5 had very low antibody titres. Primary vaccination of three patients with living varicella vaccine increased antibody titres measurably in one patient. We suggest that patients with LPI who have no varicella zoster antibodies should be treated with acyclovir if exposed to varicella and should be (re)vaccinated against chickenpox.
The dipeptide monoester GCV prodrugs, owning to higher lipophilicity and OPT-mediated translocation across RPE, appear to be promising candidates in the treatment of ocular cytomegalovirus infections following an episcleral administration.
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Symptoms and visual acuity improved within 2 weeks to 1 month in 3 of 4 patients (75%) treated with oral antiviral medication. One patient required surgical treatment for asymptomatic retinal detachment after 3 weeks of treatment; retinal detachment in the fellow eye was repaired 2 months later. Duration of antiviral therapy ranged from 5 weeks to 3 months.
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Mexican oregano (Lippia graveolens) is a plant found in Mexico and Central America that is traditionally used as a medicinal herb. In the present study, we investigated the antiviral activity of the essential oil of Mexican oregano and its major component, carvacrol, against different human and animal viruses. The MTT test (3-4,5-dimethythiazol-2yl)-2,5-diphenyl tetrazolium bromide) was conducted to determine the selectivity index (SI) of the essential oil, which was equal to 13.1, 7.4, 10.8, 9.7, and 7.2 for acyclovir-resistant herpes simplex virus type 1 (ACVR-HHV-1), acyclovir-sensitive HHV-1, human respiratory syncytial virus (HRSV), bovine herpesvirus type 2 (BoHV-2), and bovine viral diarrhoea virus (BVDV), respectively. The human rotavirus (RV) and BoHV-1 and 5 were not inhibited by the essential oil. Carvacrol alone exhibited high antiviral activity against RV with a SI of 33, but it was less efficient than the oil for the other viruses. Thus, Mexican oregano oil and its main component, carvacrol, are able to inhibit different human and animal viruses in vitro. Specifically, the antiviral effects of Mexican oregano oil on ACVR-HHV-1 and HRSV and of carvacrol on RV justify more detailed studies.
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Acyclovir has been conjugated to the acyclic isoprenoid chain of squalene to form the squalenoyl-acyclovir prodrug. Its interaction with biomembrane models constituted by dimyristoylphosphatidylcholine (DMPC) monolayers has been studied by employing the Langmuir-Blodgett technique. The aim of the work was to gain information on the interaction of these compounds with phospholipid membranes. DMPC/acyclovir or squalenoyl-acyclovir prodrug mixed monolayers have been prepared at increasing molar fractions of the compound and the isotherm mean molecular area/surface pressure has been registered at 10 and 37 degrees C. Results reveal that the squalenoyl moiety enhances the affinity of acyclovir for the biomembrane model.
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The log P values of n-octanol/water for some guanine derivatives, acyclovir, deoxyaciclovir and their acetyl congeners, were calculated by some commercially available computer programs for log P calculation. These values were compared with those obtained by the conventional shake-flask method. It was established that the calculations of log P values for examined guanine derivatives by these computation programs do not give reliable results.
This approach should be useful for examining the role of the tenascin-negative astroglial subset in the development and regeneration of the central nervous system.
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The dissolution and subsequent oral bioavailability of acyclovir (ACY) is limited by its poor aqueous solubility. An attempt has been made in this work to provide mechanistic insights into the solubility enhancement and dissolution of ACY by using the water-soluble carrier polyethylene glycol 6000 (PEG6000). Solid dispersions with varying ratios of the drug (ACY) and carrier (PEG6000) were prepared and evaluated by phase solubility, in vitro release studies, kinetic analysis, in situ perfusion, and in vitro permeation studies. Solid state characterization was done by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis, and surface morphology was assessed by polarizing microscopic image analysis, scanning electron microscopy, atomic force microscopy, and nuclear magnetic resonance analysis. Thermodynamic parameters indicated the solubilization effect of the carrier. The aqueous solubility and dissolution of ACY was found to be higher in all samples. The findings of XRD, DSC, FTIR and NMR analysis confirmed the formation of solid solution, crystallinity reduction, and the absence of interaction between the drug and carrier. SEM and AFM analysis reports ratified the particle size reduction and change in the surface morphology in samples. The permeation coefficient and amount of ACY diffused were higher in samples in comparison to pure ACY. Stability was found to be higher in dispersions. The results suggest that the study findings provided clear mechanical insights into the solubility and dissolution enhancement of ACY in PEG6000, and such findings could lay the platform for resolving the poor aqueous solubility issues in formulation development.
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The study aimed to investigate the clinical characteristics of acute renal failure (ARF) caused by oral acyclovir.
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This study evaluated the synergistic effect of Allium sativum (AS) with suicide gene therapy for transitional cell carcinoma (TCC) of the bladder. Subcutaneous TCCs were established in syngeneic C3H/He mice with 1 x 10(5) MBT-2 cells. AS liquid extract was injected at the site of tumor transplantation on Day 1 for three weeks (Experiment I) and into the established tumors weekly for five weeks (Experiment II) in combination with or without gene therapy using a replication-defective adenoviral vector containing a herpes simplex virus thymidine kinase (HSV-TK) gene under the transcriptional control of Rous sarcoma virus (RSV) promoter (Ad-RSV-TK, 5 x 10(8) plaque-forming units) plus ganciclovir (20 mg/kg/day i.p.). AS demonstrated a statistically significant reduction in incidence of TCC (cumulative dose 25 mg of AS). Combination AS-suicide gene therapy significantly inhibited the tumor growth compared with the controls, which was evidenced by apoptosis on histomorphological and immunohistochemical studies. These results suggest that AS had a definite antitumor effect in inhibiting tumorigenesis and growth of TCC in a murine model. AS treatment combined with suicide gene therapy had significant additive antitumor effects on TCC and may provide a novel and effective treatment modality for TCC of the bladder.