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Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) during primary infection and persists in this compartment by unknown mechanisms over the course of infection. In this study, we examined viral population dynamics in four asymptomatic subjects commencing antiretroviral therapy to characterize cellular sources of HIV-1 in the CNS. The inability to monitor viruses directly in the brain poses a major challenge in studying HIV-1 dynamics in the CNS. Studies of HIV-1 in cerebrospinal fluid (CSF) provide a useful surrogate for the sampling of virus in the CNS, but they are complicated by the fact that infected cells in local CNS tissues and in the periphery contribute to the population pool of HIV-1 in CSF. We utilized heteroduplex tracking assays to differentiate CSF HIV-1 variants that were shared with peripheral blood plasma from those that were compartmentalized in CSF and therefore presumably derived from local CNS tissues. We then tracked the relative decline of individual viral variants during the initial days of antiretroviral therapy. We found that HIV-1 variants compartmentalized in CSF declined rapidly during therapy, with maximum half-lives of approximately 1 to 3 days. These kinetics emulate the decline in HIV-1 produced from short-lived CD4+ T cells in the periphery, suggesting that a similarly short-lived, HIV-infected cell population exists within the CNS. We propose that short-lived CD4+ T cells trafficking between the CNS and the periphery play an important role in amplifying and maintaining HIV-1 populations in the CNS during the asymptomatic phase of infection.
Mammalian reoviruses are non-enveloped viruses that contain a segmented, double-stranded RNA genome. Reoviruses infect most mammalian species, although infection with these viruses in humans is usually asymptomatic. We report the isolation of a novel reovirus strain from a 6.5-week-old child with meningitis. Hemagglutination and neutralization assays indicated that the isolate is a serotype 3 strain, leading to the designation T3/Human/Colorado/1996 (T3C/96). Sequence analysis of the T3C/96 S1 gene segment, which encodes the viral attachment protein, sigma 1, confirmed the serotype assignment for this strain and indicated that T3C/96 is a novel reovirus isolate. T3C/96 is capable of systemic spread in newborn mice after peroral inoculation and produces lethal encephalitis. These results suggest that serotype 3 reoviruses can cause meningitis in humans.
Lipid peroxidation is one of the major outcomes of free radical-mediated injury that directly damages membranes and generates a number of secondary products, both from fission and endocyclization of oxygenated fatty acids that possess neurotoxic activity. Numerous studies have demonstrated increased lipid peroxidation in brain of patients with Alzheimer's disease (AD) compared with age-matched controls. These data include quantification of fission and endocyclized products such as 4-hydroxy-2-nonenal, acrolein, isoprostanes, and neuroprostanes. Immunohistochemical and biochemical studies have localized the majority of lipid peroxidation products to neurons. A few studies have consistently demonstrated increased cerebrospinal fluid (CSF) levels of isoprostanes in AD patients early in the course of their dementia, and one study has suggested that CSF isoprostanes may improve the laboratory diagnostic accuracy for AD. Similar analyses of control individuals over a wide range of ages indicate that brain lipid peroxidation is not a significant feature of usual aging. Quantification of isoprostanes in plasma and urine of AD patients has yielded inconsistent results. These results indicate that brain lipid peroxidation is a potential therapeutic target in probable AD patients, and that CSF isoprostanes may aid in the assessment of antioxidant experimental therapeutics and the laboratory diagnosis of AD.
OBJECTIVE - To establish the appropriate length of antibiotic therapy for negative late-onset sepsis evaluations in the neonatal intensive care unit (NICU), based on time to detection of positive bacterial cultures.
STUDY DESIGN - Culture results from late-onset sepsis evaluations between January 1, 1994 and June 30, 1998 from outborn neonates at the Arkansas Children's Hospital NICU were retrospectively reviewed. The time period from specimen collection to notification of NICU personnel was calculated for positive cultures.
RESULTS - There were 2,783 blood, 724 urine, and 294 cerebrospinal fluid cultures obtained, of which 10.2%, 6.6%, and 5.4%, respectively, were positive for bacterial isolates. Of positive cultures, 98% had a time to detection < or = 48 hours. Of cultures that became positive > 48 hours, 7 of 8 grew coagulase-negative staphylococci; 4 were contaminants.
CONCLUSION - Discontinuing antibiotic therapy for neonates with possible late-onset sepsis and negative cultures at 48 hours is appropriate and is now standard care in our NICU.
Image-guided neurosurgery relies on accurate registration of the patient, the preoperative image series, and the surgical instruments in the same coordinate space. Recent clinical reports have documented the magnitude of gravity-induced brain deformation in the operating room and suggest these levels of tissue motion may compromise the integrity of such systems. We are investigating a model-based strategy which exploits the wealth of readily-available preoperative information in conjunction with intraoperatively acquired data to construct and drive a three dimensional (3-D) computational model which estimates volumetric displacements in order to update the neuronavigational image set. Using model calculations, the preoperative image database can be deformed to generate a more accurate representation of the surgical focus during an operation. In this paper, we present a preliminary study of four patients that experienced substantial brain deformation from gravity and correlate cortical shift measurements with model predictions. Additionally, we illustrate our image deforming algorithm and demonstrate that preoperative image resolution is maintained. Results over the four cases show that the brain shifted, on average, 5.7 mm in the direction of gravity and that model predictions could reduce this misregistration error to an average of 1.2 mm.
Meningitis is an unusual manifestation of infection caused by Blastomyces dermatitidis. We describe a patient who presented with fulminant blastomycotic meningitis. Examination of the lumbar CSF demonstrated > 5,000 polymorphonuclear leukocytes/mm3. The diagnosis of B. dermatitidis meningitis was initially suggested by cytologic examination of CSF and confirmed by culture. Pleocytosis of this magnitude had not been previously described in association with blastomycosis, although review of the published literature revealed that neutrophilic pleocytosis is a common manifestation of blastomycotic meningitis and should suggest the diagnosis. This report broadens the clinical spectrum of blastomycotic meningitis and suggests that cytologic examination of CSF is a useful way to establish this diagnosis.
We analyzed data from the records of 422 patients with acute bacterial or viral meningitis. A cerebrospinal fluid (CSF) glucose level less than 1.9 mmol/L, a CSF-blood glucose ratio less than 0.23, a CSF protein level greater than 2.2 g/L, more than 2000 x 10(6)/L CSF leukocytes, or more than 1180 x 10(6)/L CSF polymorphonuclear leukocytes were individual predictors of bacterial infection with 99% certainty or better. Although any one of these tests could rule in bacterial meningitis with high probability, none could rule it out. To better predict whether a patient has bacterial vs viral infection, we developed a logistic multiple regression model using CSF-blood glucose ratio, total polymorphonuclear leukocyte count in CSF, age, and month of onset. This proved highly reliable when validated in an independent test sample, with an area under receiver operating characteristic curve of 0.97. The model should allow physicians to differentiate between acute viral and acute bacterial meningitis with greater accuracy.