Simultaneous approach for nonculture PCR-based identification and serogroup prediction of Neisseria meningitidis.
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A nonculture PCR-based method to characterize Neisseria meningitidis was used to test 225 clinical specimens. PCR correctly identified and predicted the serogroups of N. meningitidis of culture-proven meningococcal diseases and confirmed this diagnosis in 35% of suspected samples. This approach could be useful when culture fails to isolate N. meningitidis. (+info)
Leukocyte counts in cerebrospinal fluid with the automated hematology analyzer CellDyn 3500 and the urine flow cytometer UF-100.
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BACKGROUND: The counting of leukocytes and erythrocytes in cerebrospinal fluid (CSF) is still performed microscopically, e.g., using a chamber in most laboratories. This requires sufficient practical experience, is time-consuming, and may constitute a problem in emergency diagnostics. Specific automated systems for CSF cell counting are not available at present. METHODS: We tested the hematology analyzer CellDyn 3500 (CD) and the urine flow cytometer UF-100 (UF), which are not designed for CSF analysis. We studied >104 samples with both analyzers, and the counts obtained were compared with the reference method (Fuchs-Rosenthal chamber). RESULTS: Good linearity in the medically relevant range of 15 x 10(6) to 1000 x 10(6) leukocytes/L and a high degree of within-run accuracy were seen for both analyzers. Cell counting on the UF was excellent, especially when low cell counts were encountered (CV, 4. 9% compared with 28% observed for the CD). Method comparison showed that identical results could be detected for a majority of the count pairs. For a few samples, there was a discrepancy between the results from the analyzers and the counting chamber. In most cases, these were CSF samples containing a high proportion of lymphocytes. For these samples, the CD result led to a false-positive high leukocyte count, and on the UF these cells were not allocated to the leukocyte population, thus leading to false-negative counts. CONCLUSIONS: Both analyzers should not be used for CSF cell counting in all cases at present. However, once the technical and software problems have been solved, routine use of the two analyzers for CSF analysis should be seriously contemplated. (+info)
Visualization of intravenously administered contrast material in the CSF on fluid-attenuated inversion-recovery MR images: an in vitro and animal-model investigation.
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BACKGROUND AND PURPOSE: The FLAIR (fluid-attenuated inversion-recovery) pulse sequence has been shown to be sensitive to abnormalities of the subarachnoid space. Our clinical experience led us to investigate whether intravenously injected contrast material can affect the appearance of the subarachnoid space on FLAIR MR images. METHODS: After noting unexplained high signal in the subarachnoid space on FLAIR images in a patient, we studied two dogs with sequential FLAIR MR imaging after i.v. administration of contrast material. A third dog was studied with a 6-hour delayed FLAIR sequence after triple-dose (0.3 mmol/kg) i.v. contrast administration. CSF was obtained from two animals for measurement of gadolinium concentration. A phantom was developed to determine the lowest concentration at which the effects of gadolinium were evident on FLAIR images in vitro. RESULTS: In all three animals, the appearance of the CSF in the ventricles or subarachnoid space was modified after administration of i.v. contrast. This was most evident on delayed images. The CSF samples showed a gadolinium concentration of 0.007 mmol/L in the dog who received the 0.1 mmol/kg dose and 0.02 mmol/L in the dog who received a triple dose. In our in vitro phantom experiments, gadolinium effects were evident on FLAIR images at a concentration four times lower than those on T1-weighted images. CONCLUSION: I.v. contrast material can cross into the CSF in sufficient concentration to alter the appearance of the subarachnoid space on FLAIR images in normal dogs. Although we encountered two patients with CNS disease in whom enhancement of the CSF was seen on postcontrast FLAIR images, additional investigation is needed in humans to determine whether enhancement may occur at triple dose in healthy subjects. (+info)
Phase-contrast MR imaging of the cervical CSF and spinal cord: volumetric motion analysis in patients with Chiari I malformation.
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BACKGROUND AND PURPOSE: Most previous MR studies of the dynamics of Chiari I malformation have been confined to sagittal images and operator-dependent measurement points in the midline. To obtain a deeper insight into the pathophysiology of the Chiari I malformation, we performed a prospective study using axial slices at the level of C2 to analyze volumetric motion data of the spinal cord and CSF over the whole cross-sectional area. METHODS: Eighteen patients with Chiari I malformation and 18 healthy control subjects underwent cardiac-gated phase-contrast imaging. Cross-sectional area measurements and volumetric flow/motion data calculations were made for the following compartments: the entire intradural space, the spinal cord, and the anterior and posterior subarachnoid space. RESULTS: The most striking feature was an increased early systolic caudal and diastolic cranial motion of the spinal cord in the patients. CSF pulsations in the anterior subarachnoid space were unchanged at systole but showed an impaired diastolic upward flow. In the posterior compartment, the CSF systole was slightly shortened, with an impairment of diastolic upward flow. Fourteen of the 18 patients had associated syringeal cavities. This subgroup showed an increased systolic downward displacement of the cord as compared with patients without a syrinx. CONCLUSION: Obstruction of the foramen magnum in patients with Chiari I malformation causes an abrupt systolic downward displacement of the spinal cord and impairs the recoil of CSF during diastole. (+info)
Antiretroviral resistance mutations in human immunodeficiency virus type 1 reverse transcriptase and protease from paired cerebrospinal fluid and plasma samples.
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Twenty-four adults infected with human immunodeficiency virus type 1 (HIV-1) with central nervous system symptoms were studied for antiretroviral resistance mutations in HIV-1 RNA obtained from paired cerebrospinal fluid (CSF) and plasma samples. Paired sequences were obtained from 21 and 13 patients for reverse transcriptase (RT) and for protease, respectively. Mutations conferring resistance to the RT inhibitors zidovudine, lamivudine, or nevirapine were detected in 14 patients, including 11 pretreated and 3 drug-naive subjects. The mutation patterns in the 2 compartments were different in most patients. Genotypic resistance to protease inhibitors was detected in both plasma and CSF from 1 patient treated with multiple protease inhibitors. However, accessory protease inhibitor resistance mutations at polymorphic sites were different in plasma and CSF in several patients. Partially independent evolution of viral quasispecies occurs in plasma and CSF, raising the possibility that compartmentalization of drug resistance may affect response to antiretroviral treatment. (+info)
Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier.
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Multidrug resistance protein 1 (MRP1) is a transporter protein that helps to protect normal cells and tumor cells against the influx of certain xenobiotics. We previously showed that Mrp1 protects against cytotoxic drugs at the testis-blood barrier, the oral epithelium, and the kidney urinary collecting duct tubules. Here, we generated Mrp1/Mdr1a/Mdr1b triple-knockout (TKO) mice, and used them together with Mdr1a/Mdr1b double-knockout (DKO) mice to study the contribution of Mrp1 to the tissue distribution and pharmacokinetics of etoposide. We observed increased toxicity in the TKO mice, which accumulated etoposide in brown adipose tissue, colon, salivary gland, heart, and the female urogenital system. Immunohistochemical staining revealed the presence of Mrp1 in the oviduct, uterus, salivary gland, and choroid plexus (CP) epithelium. To explore the transport function of Mrp1 in the CP epithelium, we used TKO and DKO mice cannulated for cerebrospinal fluid (CSF). We show here that the lack of Mrp1 protein causes etoposide levels to increase about 10-fold in the CSF after intravenous administration of the drug. Our results indicate that Mrp1 helps to limit tissue distribution of certain drugs and contributes to the blood-CSF drug-permeability barrier. (+info)
Gemifloxacin is effective in experimental pneumococcal meningitis.
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In a rabbit model of Streptococcus pneumoniae meningitis, 5 mg of gemifloxacin mesylate (SB-265805) per kg/h reduced the bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as 10 mg of ceftriaxone per kg/h (Deltalog CFU/ml/h +/- standard deviation [SD], -0.25 +/- 0.09 versus -0.38 +/- 0.11; serum and CSF concentrations of gemifloxacin were 2.1 +/- 1.4 mg/liter and 0.59 +/- 0.38 mg/liter, respectively, at 24 h). Coadministration of 1 mg of dexamethasone per kg did not affect gemifloxacin serum and CSF levels (2.7 +/- 1.4 mg/liter and 0.75 +/- 0.34 mg/liter, respectively, at 24 h) or activity (Deltalog CFU/ml/h +/- SD, -0.26 +/- 0.11). (+info)
Transduction of the contralateral ear after adenovirus-mediated cochlear gene transfer.
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Cochlear gene transfer is a promising new approach for inner ear therapy. Previous studies have demonstrated hair cell protection with cochlear gene transfer not only in the inoculated, but also in the uninoculated ear. To characterize the kinetics of viral spread, we investigated the extent of transgene expression in the contralateral (uninoculated) cochlea after unilateral adenoviral cochlear gene transfer. We used a lacZ reporter gene vector, and demonstrated spread of the adenovirus into the cerebrospinal fluid (CSF) after cochlear inoculation of 25 microl viral vector. Direct virus application into the CSF resulted in transduction of both cochleae, whereas virus inoculation into the bloodstream did not. The cochlear aqueduct was identified as the most likely route of virus spread to the contralateral cochlea. These data enhance our understanding of the kinetics of virus-mediated transgene expression in the inner ear, and assist in the development of clinical applications for inner ear gene therapy. Our results showed a functional communication between the CSF and the perilymphatic space of the inner ear, that is not only of importance for otological gene transfer, but also for CNS gene transfer. Gene Therapy (2000) 7, 377-383. (+info)