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[Blood and cerebrospinal fluid B and T lymphocytes in mumps-meningitis (author's transl)].

20 children, 12 boys and 8 girls, with mumps-meningitis have been investigated during the acute stage of illness. Immunoglobulin-concentration, B and T cell ratios were determined in venous blood and cerebrospinal fluid. In the blood no correlation between the percentage of B cells and immunoglobulin-levels, or the course of illness could be observed. Total protein level as well as cell count, the concentration of glucose and chloride were determined in the cerebrospinal fluid at the same time. No correlation between the percentage of B cells and immunoglobulin-levels could be observed in cerebrospinal fluid. No difference in the number of B and T cells was observed between blood and cerebrospinal fluid. These results demonstrate, that the lymphocytes in cerebrospinal fluid in meningitis possess the same surface markers and show about the same B to T cell ratio as it is found on the lymphocytes of blood.

B-Lymphocytes↗

Characterization of lipoproteins in cerebrospinal fluid of mares during pregnancy and lactation.

OBJECTIVE: To measure apolipoproteins in cerebrospinal fluid (CSF) from healthy mares and to determine whether CSF concentrations of apolipoproteins change during pregnancy and lactation. ANIMALS: 5 healthy pregnant mares. PROCEDURE: 2 sets of CSF samples were obtained; initial samples were obtained 10 to 30 days before parturition (mean, 18 days; median, 17 days), and second samples were obtained 19 to 26 days after parturition (mean, 23 days; median, 23 days). Cerebrospinal fluid was collected from the lumbosacral subarachnoid space of standing horses by use of routine collection techniques. Cerebrospinal fluid cholesterol concentrations were measured by use of a sensitive enzymatic assay. Ultracentrifugal fractions of CSF lipoproteins were characterized by determining the distribution of apolipoproteins, using polyacrylamide gel electrophoresis. RESULTS: Analyses of isolated ultracentrifugal fractions by polyacrylamide gel electrophoresis revealed 2 apolipoproteins, with the expected molecular weights for apolipoprotein E and apolipoprotein A-I. No significant differences were observed between pre- and postpartum values in mares. The concentration of cholesterol in CSF fluid of mares was comparable to values reported in other mammals. CONCLUSIONS AND CLINICAL RELEVANCE: Apolipoprotein E in CSF of horses is a major apolipoprotein associated with high-density lipoproteins, which is similar to findings in other mammals. Additional characterization of the role of apolipoproteins in mammalian CSF may provide critical insight into various degenerative neurologic disease processes.

Animals↗

Prolactin levels in cerebrospinal fluid of patients with infantile spasms.

Infantile spasms are an age-related epileptic syndrome of infancy and are characterized by the combination of clusters of epileptic spasms and specific electroencephalographic findings. The etiology and the pathogenesis of the disease is still unclear. Prolactin has been thought to be specifically related to epileptic seizures. To investigate the possible mechanism of prolactin secretion in infantile spasms cerebrospinal fluid prolactin levels were examined. Fifteen patients with infantile spasms (10 females and five males), 3-16 months of age, were evaluated and compared with age- and sex-matched control subject. Cerebrospinal fluid samples for prolactin were obtained before and after treatment. The mean prolactin levels in the cerebrospinal fluid of the patients before therapy (3.25 +/- 1.48 ng/mL) was higher than the control group (2.38 +/- 0.89 ng/mL), and the difference between the two groups was statistically significant (P < 0.001). The mean prolactin level in the cerebrospinal fluid of the patients after therapy (4.69 +/- 1.47 ng/mL) was demonstrated to be higher than the mean prolactin level before therapy (3.25 +/- 1.48 ng/mL) and the difference between the two groups was statistically significant (P = 0.037). Elevation of cerebrospinal fluid prolactin levels before and after treatment in patients with infantile spasms provided evidence that the cerebrospinal fluid prolactin level is related with neuronal injury.

Female↗

Cerebrospinal fluid and peripheral blood lymphocyte subpopulations in multiple sclerosis. Evaluation by means of monoclonal antibodies (a preliminary note).

We are investigating peripheral blood and cerebrospinal fluid lymphocyte subpopulations in multiple sclerosis patients by monoclonal antibodies directed at T-helper, T-suppressor and total mature T-cell subsets. Patients affected by other neurological diseases are also being studied as a control population. Antibodies' selectivity together with careful cell handling, allowed us a detailed study even of small lymphocyte numbers usually recovered from multiple sclerosis cerebrospinal fluid. First results point to a marked increase in T-helper population, with a helper/suppressor imbalance in MS patients' cerebrospinal fluid, but not in peripheral blood. No difference could be detected between cerebrospinal fluid and peripheral blood lymphocyte subpopulations in control patients. Further work is now needed to achieve more complete and significative results.

Adult↗

Inhibition of methotrexate transport from cerebrospinal fluid by probenecid.

In rabbit, the efflux of intraventricularly injected methotrexate from the cerebrospinal fluid was retarded by pretreatment with 200 mg/kg of ip probenecid. In vitro, the ability of the isolated choroid plexus to concentrate methotrexate was depressed by the inclusion of probenecid in the incubation medium. These experimental results are consistent with the hypothesis that probenecid depresses the clearance of methotrexate from the cerebrospinal fluid by blocking the transport of methotrexate from cerebrospinal fluid to blood via the choroid plexus.

Animals↗

Liquid-chromatographic measurement of taurine in cerebrospinal fluid of normal individuals and patients with meningitis.

Taurine was measured in cerebrospinal fluid by reacting it with fluorescamine to form a fluorescent derivative, followed by separation on a reversed-phase column and fluorometric detection and evaluation. The assay is rapid (17 min) and sensitive to as little as 1 mumol/L. The mean value for 27 cerebrospinal fluid samples collected from patients free from meningitis and aneurysm was 5.7 +/- 1.8 mumol/L. Twenty-two patients with bacterial meningitis showed a 0- to 20-fold increase in cerebrospinal fluid taurine, with a return to normal values after antibiotic treatment.

Chromatography, High Pressure Liquid↗

Progression of hearing loss in experimental pneumococcal meningitis: correlation with cerebrospinal fluid cytochemistry.

The development of hearing loss and concomitant cerebrospinal fluid (CSF) cytochemical changes in a model of pneumococcal meningitis were examined. Rabbits were injected intracisternally with 10(5) pneumococci. Auditory evoked potentials to clicks and to 10- and 1-kHz tone bursts were recorded hourly; CSF was analyzed every 4 h. Sensorineural hearing loss developed in all animals beginning 12 h after infection and progressed to severe deafness. The onset of hearing loss was preceded by a CSF leukocytosis of > 2000 cells/microL and elevation of CSF protein and lactate concentrations to > or = 1 mg/mL. Temporal bone histopathology showed pneumococci and leukocytes extending from the CSF to the perilymph via the cochlear aqueduct. Hearing loss can develop early in the course of meningitis and is preceded by the abrupt onset of inflammatory changes in CSF. Progression of hearing loss is rapid and proceeds from cochlear base to apex in parallel with the degree of inflammation.

Animals↗

Comparison of cerebrospinal fluid transport in fetal and adult sheep.

We quantified cerebrospinal fluid (CSF) transport (conductance) and CSF outflow resistance in late-gestation fetal and adult sheep using two methods, a constant pressure infusion method and a bolus injection technique into the lateral ventricles. No significant differences in CSF conductance (fetus 0.013 +/- 0.002, adult 0.014 +/- 0.003 ml x min(-1) x cm H(2)O(-1)) or CSF outflow resistance (fetus 83.7 +/- 9.8, adult 84.7 +/- 19.7 cm H(2)O x ml(-1) x min) were observed. To confirm CSF transport to plasma in fetal animals, (125)I- or (131)I-labeled human serum albumin (HSA) was injected into the lateral ventricles. The tracer entered fetal plasma with an average mass transport rate of 1.91 +/- 0.47% injected/h (n = 9). In two fetuses, we monitored the tracer appearance in plasma and cervical and thoracic duct lymph after injection of radioactive HSA into the ventricular CSF. As was the case in adult animals, fetal tracer concentrations increased in all three compartments over time, with the highest concentrations measured in lymph collected from the cervical lymphatics. These results 1) indicate that global CSF transport parameters in the late-gestation fetus and adult sheep are similar and 2) suggest an important role for extracranial lymphatic vessels in CSF transport before birth.

Animals↗

Post-cranioplasty cerebrospinal fluid hydrodynamic changes: magnetic resonance imaging quantitative analysis.

The syndrome of the trephined has been described in many patients with cranial defects as an indication for cranioplasty. Cerebral blood flow changes, the effect of the atmospheric pressure on the brain, as well as cerebrospinal fluid hydrodynamic changes have been postulated as the possible reasons for this syndrome. Using dynamic phase-contrast magnetic resonance imaging we measured arterial, venous, and cerebrospinal fluid flow into and out of the skull, before and after cranioplasty in one patient whose bone flap was removed because of osteomyelitis. We report significant changes in the oscillatory CSF flow after cranioplasty. A moderate increase in venous outflow as well as a two-fold increase in craniocaudal cerebrospinal fluid systolic flow velocity was measured after the skull closure. The changes in the cerebrospinal fluid oscillatory flow at the level of the craniovertebral junction could reflect changes in the compliance of the craniospinal system produced by closure of the cranial defect.

Adult↗

Enhanced penetration of indinavir in cerebrospinal fluid and semen after the addition of low-dose ritonavir.

OBJECTIVE: Penetration of antiretroviral drugs into anatomical HIV-1 reservoirs such as the male genital tract and the central nervous system is important. Data on indinavir (IDV) concentrations in seminal plasma are lacking and IDV concentrations in cerebrospinal fluid are at best borderline. DESIGN: Thirteen patients were treated with zidovudine (or stavudine), lamivudine, abacavir, nevirapine and IDV (1000 mg three times daily). When nevirapine led to low IDV concentrations, IDV was changed into the combination IDV/ritonavir (RTV) 800/100 mg twice daily to improve the pharmacokinetic profile of IDV. METHODS: A serum pharmacokinetic profile, a semen sample and a cerebrospinal fluid sample were collected at weeks 8, 24, 48 and 72. RESULTS: Addition of RTV increased the median IDV trough concentration in serum from 65 to 336 ng/ml (P = 0.005). Median IDV concentration in seminal plasma increased from 141 to 1634 ng/ml (P = 0.002) (n = 9) and in cerebrospinal fluid from 39 (n = 12) to 104 (n = 7) ng/ml (P < 0.001). In six patients with samples collected both before and after the addition of RTV, the IDV concentration in seminal plasma increased 8.2 times [95% confidence interval (CI) 5.2-11.6], and in cerebrospinal fluid 2.4 times (95% CI 1.8-3.9). CONCLUSIONS: IDV penetrates well into the male genital tract. The addition of low-dose RTV not only increases IDV concentrations in serum but also in seminal plasma and cerebrospinal fluid, thereby probably improving the potency of the regimen in these anatomical HIV reservoirs. Higher serum trough levels alone can not sufficiently explain the observed increases in seminal plasma and cerebrospinal fluid concentrations. Inhibition of P-glycoprotein-mediated transport by RTV might be an additional mechanism.

Adult↗

Serum cortisol and cerebrospinal fluid beta-endorphins in status epilepticus. Their possible relation to prognosis.

OBJECTIVE: To determine if blood cortisol and cerebrospinal fluid beta-endorphin levels correlate with prognosis following status epilepticus. DESIGN: Twenty-seven adult patients with status epilepticus had blood cortisol and cerebrospinal fluid beta-endorphin levels measured within 12 hours after the cessation of clinical seizures. SETTING: Patients with status epilepticus as well as patients with non-status epilepticus seizures came from the Comprehensive Epilepsy Program at the Medical College of Virginia, Richmond. PATIENTS: Twenty-seven patients with status epilepticus. Control patients for the cortisol study were patients who had acute seizures who did not meet the criteria for status epilepticus. The cerebrospinal fluid control subjects were patients without neurologic symptoms undergoing spinal anesthesia. OUTCOME MEASURES: The clinical status of the patients 1 week after status epilepticus as well as the Glascow Outcome Score and the Glascow Coma Score 1 week after status epilepticus. RESULTS: The difference in blood cortisol levels in patients with status epilepticus with poor prognosis was significantly different from both patients with non-status epilepticus seizures (P < .001) and patients with status epilepticus with good prognosis (P < .01). Cerebrospinal fluid beta-endorphin levels were elevated in patients with status epilepticus patients vs control subjects (P < .05), but no significant difference was noted between the patients with status epilepticus with good and poor prognosis. CONCLUSIONS: Serum cortisol levels may provide a useful predictive indicator of prognosis in status epilepticus and cortisol level elevation may play a role in the pathophysiologic condition of status epilepticus.

Adult↗

Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections.

The kinetics and distribution of methotrexate in intraventricular and intrathecal cerebrospinal-fluid spaces were studied in patients with meningeal leukemia and meningeal carcinomatosis after drug administration by intravenous infusion, indwelling intraventricular subcutaneous reservoir (Ommaya), or standard lumbar puncture. Negligible ventricular concentrations followed a single intravenous dose. During an intravenous infusion (500 mg per square meter for 24 hours) the ventricular cerebrospinal-fluid concentration rose to 6 times 10-minus 7 M. Methotrexate administered by Ommaya reservoir, at a dose of 6.25 mg per square meter, rapidly distributed in the subarachnoid space; the peak ventricular concentration of 2 times 10-minus 4 M declined exponentially over 48 hours. Lumbar cerebrospinal-fluid concentration reached a maximum of 5 times 10-minus 5 M four hours after injection and then fell exponentially. Administration by lumbar puncture occasionally produced epidural and subdural leakage; even with successful lumbar puncture, ventricular methotrexate concentration varied considerably from patient to patient despite similar doses. Administration by Ommaya reservoir more reliably produced adequate cerebrospinal fluid distribution than administration by lumbar puncture.

Adolescent↗

Penetration of aztreonam into cerebrospinal fluid of patients with bacterial meningitis.

The penetration of aztreonam into the cerebrospinal fluid was determined in 16 patients with bacterial meningitis undergoing treatment with other antibiotics. Three aztreonam doses of 30 mg/kg were infused intravenously over 30 to 45 min at 8-h intervals, first between days 2 and 4 and again between days 11 and 20 after onset of the disease. Concentrations of aztreonam in serum and cerebrospinal fluid samples obtained at 60, 90, 120, and 240 min after the third aztreonam dose were measured by high-pressure liquid chromatography. The concentrations of aztreonam in cerebrospinal fluid ranged from 3.5 to 62 micrograms/ml, depending on the sampling time and the time elapsed since the onset of the disease. These concentrations were equal to or higher than the MICs for most of the gram-negative bacilli (including Pseudomonas aeruginosa).

Adult↗

Cerebrospinal fluid plasminogen activator inhibitor-1: a prognostic factor in posthaemorrhagic hydrocephalus.

Intraventricular fibrinolytic enhancement with plasminogen activators is an experimental treatment for posthaemorrhagic hydrocephalus, but some infants do not respond. The objectives of this study were to investigate whether plasminogen activator inhibitor-1 is detectable in normal or posthaemorrhagic neonatal cerebrospinal fluid and whether higher neonatal cerebrospinal fluid concentrations of plasminogen activator inhibitor-1 are associated with failure of fibrinolytic therapy. Cerebrospinal fluid samples from 7 controls and 16 infants with posthaemorrhagic hydrocephalus (15 treated with exogenous fibrinolytic agents) were analysed for plasminogen activator inhibitor-1. Plasminogen activator inhibitor-1 was not detectable in any of the control samples but was detectable in all but one of the posthaemorrhagic samples, and at significantly higher levels in the treatment failures (median 94 ng ml(-1)) than in the treatment successes (median 25 ng ml(-1)). High levels of plasminogen activator inhibitor-1 in the cerebrospinal fluid are predictive of, and provide a plausible biological explanation for, failure of intraventricular fibrinolytic therapy.

Brain Damage, Chronic↗

Mining the human cerebrospinal fluid proteome by immunodepletion and shotgun mass spectrometry.

We have analyzed the proteome of human cerebrospinal fluid with the help of shotgun mass spectrometry. In order to identify low-abundant proteins in these fluids, we have found it necessary to remove the abundant protein components from the mixture. Immunodepletion of the abundant proteins has allowed us to identify more than 100 proteins in cerebrospinal fluids from a patient suffering from normal pressure hydrocephalus. The identified proteins belong to a variety of different classes ranging from serum proteins to intracellular mediators that are involved in signal transduction and transcription. This work establishes a platform for future studies aimed at the comparative proteome analysis of cerebrospinal fluids from different groups of patients suffering from various psychiatric and neurological disorders.

Blood Proteins↗