Intermediate hypocretin-1 cerebrospinal fluid levels and typical cataplexy: their significance in the diagnosis of narcolepsy type 1

Study ObjectivesThe diagnosis of narcolepsy type 1 (NT1) is based upon the presence of cataplexy and/or a cerebrospinal fluid (CSF) hypocretin-1/orexin-A level ≤ 110 pg/mL. We determined the clinical and diagnostic characteristics of patients with intermediate hypocretin-1 levels (111–200 pg/mL) and the diagnostic value of cataplexy characteristics in individuals with central disorders of hypersomnolence.MethodsRetrospective cross-sectional study of 355 people with known CSF hypocretin-1 levels who visited specialized Sleep-Wake Centers in the Netherlands. For n = 271, we had full data on cataplexy type (“typical” or “atypical” cataplexy).ResultsCompared to those with normal hypocretin-1 levels (>200 pg/mL), a higher percentage of individuals with intermediate hypocretin-1 levels had typical cataplexy (75% or 12/16 vs 9% or 8/88, p < .05), and/or met the diagnostic polysomnographic (PSG) and Multiple Sleep Latency Test (MSLT) criteria for narcolepsy (50 vs 6%, p < .001). Of those with typical cataplexy, 88% had low, 7% intermediate, and 5% normal hypocretin-1 levels (p < .001). Atypical cataplexy was also associated with hypocretin deficiency but to a lesser extent. A hypocretin-1 cutoff of 150 pg/mL best predicted the presence of typical cataplexy and/or positive PSG and MSLT findings.ConclusionIndividuals with intermediate hypocretin-1 levels or typical cataplexy more often have outcomes fitting the PSG and MSLT criteria for narcolepsy than those with normal levels or atypical cataplexy. In addition, typical cataplexy has a much stronger association with hypocretin-1 deficiency than atypical cataplexy. We suggest increasing the NT1 diagnostic hypocretin-1 cutoff and adding the presence of clearly defined typical cataplexy to the diagnostic criteria of NT1. Clinical trial information: This study is not registered in a clinical trial register, as it has a retrospective database design.     

Viral antibodies in cerebrospinal fluid of multiple sclerosis and control patients: comparison between radioimmunoassay and conventional techniques.

Cerebrospinal fluid antibodies to measles, rubella, vaccinia, herpes simplex, and varicella-zoster viruses in four patient study groups (clinically definite multiple sclerosis [MS], early probable MS, optic neuritis, and control patients with other neurological diseases) were assayed by radioimmunoassay, complement fixation, hemagglutination-inhibition, or complement-enhanced plaque reduction methods. Antibodies were more frequently found and at higher dilutions by radioimmunoassay than by other techniques. Measles virus antibody, the most frequently found antibody, was present in the cerebrospinal fluid of 72% of MS patients and 5% of control patients. The differences between the numbers of MS patients and control patients with antibodies to other viruses were not as marked. Thus, 58% of MS patients versus 21% of control patients had antibody to rubella virus, 20 versus 3% had antibody to vaccinia virus, 50 versus 33% had antibody to herpes simplex virus, and 25 versus 8% had antibody to varicella virus. Sixty-seven percent of MS patients and 26% of control patients had antibodies to two or more viruses in their cerebrospinal fluid.     

Tau in cerebrospinal fluid: a sensitive sandwich enzyme-linked immunosorbent assay using tyramide signal amplification

Tau in cerebrospinal fluid (CSF) has been proposed as a diagnostic marker for Alzheimer's disease (AD). This paper presents a new sensitive sandwich ELISA allowing quantitation of tau from 8 microl CSF/well. A human specific monoclonal tau antibody HT7 was used as a capture antibody and a mixture of polyclonal tau antibodies, 92e and R134d was used as reporter antibodies. Tyramide signal amplification (TSA) technology was used in the last step to increase the sensitivity. With this TSA-ELISA, the lowest detection limit for tau was 14.3 pg/ml. Tau levels in CSF were found to be increased in AD patients (807+/-304 pg/ml, p<0.001) compared with controls (252+/-94 pg/ml). Thirty-five of 38 AD cases (92% sensitivity) yielded signals greater than cutoff, while only 1 of 38 control cases (97% specificity) was greater. A highly significant correlation was found between this assay and a commonly used kit, INNOTEST hTAU Antigen.     

PCR assay using cerebrospinal fluid for diagnosis of cerebral toxoplasmosis in Brazilian AIDS patients

Highly active antiretroviral therapy has decreased the incidence of opportunistic infections in the central nervous system in AIDS patients. However, neurological abnormalities still remain important causes of mortality and morbidity in developing countries. In Brazil, cerebral toxoplasmosis is the most common cerebral mass lesion in AIDS patients. For these reasons, early, inexpensive, and sensitive diagnostic tests must be evaluated. The aim of this study was to evaluate PCR, using cerebrospinal fluid (CSF) samples to detect Toxoplasma gondii DNA, and to determine if the association of PCR with immunological assays can contribute to a timely diagnosis. We studied two sample groups. First, we analyzed stored CSF samples from 29 newborns and from 39 adults with AIDS without a definitive diagnosis of toxoplasmosis. The goal of this step was to standardize the methodology with a simple and economical procedure to recover the T. gondii DNA. Next, we prospectively evaluated CSF samples from 12 AIDS patients with a first episode of cerebral toxoplasmosis and 18 AIDS patients with other neurological opportunistic diseases and without previous cerebral toxoplasmosis. In all PCR samples, an indirect immunofluorescent assay and an enzyme-linked immunosorbent assay were performed. Samples from all patients with cerebral toxoplasmosis presented positive PCR results (sensitivity, 100%), and a sample from one of the 18 AIDS patients with other neurological diseases also presented positive PCR results (specificity, 94.4%). These findings suggest the clinical utility of PCR in the diagnosis of cerebral toxoplasmosis in developing countries.     

Improved vigilance after sodium oxybate treatment in narcolepsy: a comparison between in‐field and in‐laboratory measurements

This two‐centre observational study of vigilance measurements assessed the feasibility of vigilance measurements on multiple days using the Sustained Attention to Response Task and the Psychomotor Vigilance Test with portable task equipment, and subsequently assessed the effect of sodium oxybate treatment on vigilance in patients with narcolepsy. Twenty‐six patients with narcolepsy and 15 healthy controls were included. The study comprised two in‐laboratory days for the Maintenance of Wakefulness Test and the Oxford Sleep Resistance test, followed by 7‐day portable vigilance battery measurements. This procedure was repeated for patients with narcolepsy after at least 3 months of stable treatment with sodium oxybate. Patients with narcolepsy had a higher Sustained Attention to Response Task error count, lower Psychomotor Vigilance Test reciprocal reaction time, higher Oxford Sleep Resistance test omission error count adjusted for test duration (Oxford Sleep Resistance test_OMIS/MIN), and lower Oxford Sleep Resistance test and Maintenance of Wakefulness Test sleep latency compared with controls (all P < 0.01). Treatment with sodium oxybate was associated with a longer Maintenance of Wakefulness Test sleep latency (P < 0.01), lower Oxford Sleep Resistance test_OMIS/MIN (P = 0.01) and a lower Sustained Attention to Response Task error count (P = 0.01) in patients with narcolepsy, but not with absolute changes in Oxford Sleep Resistance test sleep latency or Psychomotor Vigilance Test reciprocal reaction time. It was concluded that portable measurements of sustained attention as well as in‐laboratory Oxford Sleep Resistance test and Maintenance of Wakefulness Test measurements revealed worse performance for narcoleptic patients compared with controls, and that sodium oxybate was associated with an improvement of sustained attention and a better resistance to sleep.     

The determination of the complement components C1q, C4 and C3 in serum and cerebrospinal fluid by radioimmunoassay

Non-competitive 2-site radioimmunoassays (RIA) for the determination of the complement proteins C1q, C4 and C3 in cerebrospinal fluid (CSF) are described. The quantitative results of the RIAs were the same as those obtained by other assay methods: radial immunodiffusion and turbidimetry and, in the case of C4, the haemolytic assay. The concentrations of the complement proteins in paired CSF and serum samples from a group of 60 patients were measured, as well as those of albumin and IgG. The ratios (concentration in CSF)/(concentration in serum) of the complement proteins correlated poorly with that of albumin. In contrast, the ratio of IgG was significantly correlated with that of albumin. The ratios of the complement proteins were higher than might be expected on the basis of their molecular masses. This suggests that these proteins may be synthesized within the normal central nervous system.     

Relationship between the occurrence of virus in plasma and cerebrospinal fluid of HIV-1 infected individuals

Attempts to isolate human immunodeficiency virus type 1 (HIV-1) were carried out on cerebrospinal fluid (CSF) and blood plasma samples from 111 HIV-1 infected subjects in various stages of infection. HIV-1 was recovered at a low rate from CSF of persons with normal immunological parameters but frequently from patients with abnormal values, in all stages of immune system involvement. Isolation from plasma was positive in the majority of the patients, in all stages of infection, with a frequency that was related to the degree of immunodeficiency. HIV-1 could be recovered from the CSF of most patients (74%) with viremia when 85 paired specimens of 58 patients were analyzed. By contrast, HIV-1 was isolated from CSF, but not from plasma, in one case only. HIV-1 p24 antigen measured by an enzyme-linked immunosorbent assay (ELISA) was detectable in only four CSF samples compared with 15 serum samples in paired specimens. These findings indicate that most patients with HIV-1 infection have circulating cell-free infectious virus in the blood and simultaneously demonstrable HIV-1 in the CSF. Replication of HIV-1 exclusively in the central nervous system (CNS) appears to be a rare event.     

Impact of uncertainty in longitudinal T1 measurements on quantification of dynamic contrast‐enhanced MRI

The objective of this study was to assess the uncertainty in T₁ measurement, by estimating the repeatability coefficient (RC) from two repeated scans, in normal appearing brain tissues employing two different T₁ mapping methods. All brain MRI scans were performed on a 3 T MR scanner in 10 patients who had low grade/benign tumors and partial brain radiation therapy (RT) without chemotherapy, at pre‐RT, 3 weeks into RT, end RT (6 weeks) and 11, 33, and 85 weeks after RT. T₁‐weighted images were acquired using (1) a spoiled gradient echo sequence with two flip angles (2FA: 5° and 15°) and (2) a progressive saturation recovery sequence (pSR) with five different TR values (100–2000 ms). Manually drawn volumes of interest (VOIs) included left and right normal putamen and thalamus in gray matter, and frontal and parietal white matter, which were distant from tumors and received a total of accumulated radiation doses less than 5 Gy at 3 weeks. No significant changes or even trends in mean T₁ from pre‐RT to 3 weeks into RT in these VOIs (p ≥ 0.11, Wilcoxon sign test) allowed us to calculate the repeatability statistics of between‐subject means of squares, within‐subject means of squares, F‐score, and RC. The 2FA method produced RCs in the range of (9.7–11.7)% in gray matter and (12.2–14.5)% in white matter; while the pSR method led to RCs ranging from 10.9 to 17.9% in gray matter and 7.5 to 10.3% in white matter. The overall mean (±SD) RCs produced by the two methods, 12.0 (±1.6)% for 2FA and 12.0 (±3.8)% for pSR, were not significantly different (p = 0.97). A similar repeatability in T₁ measurement produced by the time efficient 2FA method compared with the time consuming pSR method demonstrates that the 2FA method is desirable to integrate into dynamic contrast‐enhanced MRI for rapid acquisition. Copyright © 2016 John Wiley & Sons, Ltd.     

Comparative detection of enterovirus RNA in cerebrospinal fluid: GeneXpert system vs. real-time RT-PCR assay

Enteroviruses (EVs) constitute the most common cause of aseptic meningitis in both children and adults. Molecular techniques have now been recognized as the reference standard for the diagnosis of EV infections, and the rapidity of the molecular diagnosis of EV meningitis has been shown to be a determining factor in the management of patients. The rapid documentation of EV RNA in cerebrospinal fluid (CSF) is key to adapting patient management and the therapeutic regimen. To shorten the time needed for virological documentation, we implemented EV RNA detection in two point-of-care (POC) laboratories. Here, we present the results of the POC detection of EV RNA with the Xpert EV kit on the GeneXpert integrated system, and a comparison with the real-time RT-PCR (rtRT-PCR) assay routinely used in the core virology laboratory. From January to September 2009, a total of 310 CSF samples were tested. The rtRT-PCR gave 81 positive, 225 negative and four ‘indeterminate’ results. POC results were concordant in 81.6% (253/310). Most of the discrepancies consisted of ‘indeterminate’ results at the POC level (16%). Calculated performances (excluding the indeterminate results) of the Xpert EV kit on the GeneXpert system in POC settings were 100%, 98.9%, 97.6% and 100% for Sensibility, Specificity, positive predictive value and negative predictive value, respectively. Taken together, these results indicate that the implementation of POC detection of EV RNA can provide robust results in <4 h, and may have a significant impact on patient management, therapeutic attitude, and hospitalization costs.     

Performance of the GeneXpert enterovirus assay for detection of enteroviral RNA in cerebrospinal fluid

BACKGROUND: The GeneXpert((R)) Dx System allows for automated extraction, processing, amplification and real-time detection of target nucleic acids. OBJECTIVES: To evaluate the performance of the Cepheid Xperttrade mark enterovirus (EV) assay for detection of EV RNA compared to a nucleic acid sequence based amplification (NASBA((R))) assay and a user-developed TaqMan((R)) RT-PCR assay. STUDY DESIGN: Assays were evaluated using a 12-member proficiency panel and up to 138 CSF specimens. Samples in which EV RNA was detected by two or more assays were considered true positives. RESULTS: The GeneXpert, NASBA, and TaqMan assays correctly identified 10, 8, and 7 of 12 proficiency panel members, respectively. For detection of EV RNA in CSF, the sensitivities of the GeneXpert, NASBA, and TaqMan were 100%, 87.5%, and 96%, respectively. There were no false positives. Two samples tested by GeneXpert and NASBA yielded indeterminate or invalid results and could not be resolved. CONCLUSIONS: The Xpert EV assay is a sensitive and specific method for detection of EV RNA in CSF specimens. The ease of use, random access capability, and minimal hands-on time with the automated GeneXpert system affords laboratories with little molecular diagnostics expertise an opportunity to complete a clinically useful testing within 2.5h.     

Detection and quantification of HIV-1 RNA with a fully automated transcription-mediated-amplification assay

BackgroundNucleic acid testing is the major method used to monitor HIV viral load. Commercial systems based on real-time PCR assays are available for high-volume centralized laboratory testing, but they are not fully automated.Objectives and study designWe have compared the diagnostic performance of the Hologic Aptima HIV-1 Quant Dx assay (Aptima) (based on real-time TMA) on the Panther instrument, a fully-automated random access platform, to that of, the Roche Cobas Ampliprep Cobas TaqMan (CAP/CTM) HIV-1 version 2.0 (based on real-time PCR).ResultsProbit analysis of replicate dilutions of NIBSC WHO International HIV-1 Standard, gave LODs of 8.6 c/ml for Aptima and 15.2 c/ml for CAP/CTM. The agreement between the assays was excellent when measuring HIV RNA in a calibrated reference (κ = 0.90, p < 0.001) and good when measuring clinical samples (κ = 0.62, p < 0.001). The correlation among the samples quantified by the two methods was very good (r = 0.95, p< 0.001) and the mean difference between the values obtained with the two assays was 0.02 log c/ml for B and non-B subtypes. The vast majority of results showed <0.5 log variance between the two assays (89%); only one sample showed results that differed by over 1.0 log c/ml.ConclusionThe performance of the new fully automated Aptima assay is adequate for clinical monitoring of HIV-1 RNA during infections and treatment. The Aptima assay is well suited for routine laboratory use.     

Quantitation of C-reactive protein in cerebrospinal fluid and serum by zone immunoelectrophoresis assay (ZIA)

The zone immunoelectrophoresis assay (ZIA) for C-reactive protein (CRP) determinations is easy to perform and requires only small amount of antiserum, e.g., 25–100 and 0.5–1.0 μ1 anti-CRP antibody/20 serum and CSF samples, respectively. For quantitating CSF-CRP the immunoprecipitates formed were stained using lakaline phosphatase-conjugated secondary antibodies and the lowest standard concentration used was 30 μg/1. The immunoprecipitates formed when measuring CRP in serum were stained by Coomasie brilliant blue R250 with a detection limit of about 300 μg/l.

CRP was determined in cerebrospinal fluid in 27 patients with bacterial meningitis (range <0.03–0.23 mg/l) and in 25 patients with viral meningitis (range <0.03–0.23 mg/l).

CRP was quantitated in 52 sera by both the CRP ZIA method (y) and by electroimmunoassay (x). The correlation coefficient was r = 0.992 with the regression line y = 1.024 x + 0.855.     

Correlation between HIV-1 viral load quantification in plasma,dried blood spots,and dried plasma spots using the Roche COBAS Taqman assay

BackgroundThe use of simplified methods for viral load determination could greatly increase access to treatment monitoring of HIV patients in resource-limited countries.ObjectiveThe aim of the present study was to optimize and evaluate the performance of the Roche COBAS Taqman assay in HIV-RNA quantification from dried blood spots (DBS) and dried plasma spots (DPS).Study designEDTA blood samples from 108 HIV-infected women were used to prepare 129 DBS and 76 DPS on Whatman 903 card. DBS and DPS were stored at ?20 °C. HIV-1 RNA was extracted from DBS/DPS using the MiniMAG system (bioMerieux). Amplification and detection were performed using the Roche COBAS TaqMan assay. Plasma viral load results were used as standard.ResultsThere was a high correlation between measures of viral load in plasma and in DBS/DPS (r = 0.96 and 0.85 respectively, P < 0.001). Overall, viral load values in DBS and DPS tended to be lower than in plasma with mean (SD) differences of 0.32 log (0.22) for DBS and of 0.35 (0.33) for DPS. Detection rates were 96.4% for DBS and 96.1% for DPS in samples with corresponding plasma values >3.0 log copies/ml. Samples with HIV-RNA below 50 copies/ml were correctly identified in 18/19 DBS and in 7/7 DPS.ConclusionsBoth DBS and DPS provided results highly correlated to the plasma values. High detection rate was obtained with both DBS and DPS when HIV-RNA was >3.0 log copies/ml. Our results support the use of DBS/DPS to detect virologic failure in resource-limited settings.     

Levels of nonphosphorylated and phosphorylated tau in cerebrospinal fluid of Alzheimer's disease patients : an ultrasensitive bienzyme-substrate-recycle enzyme-linked immunosorbent assay

We have developed an ultrasensitive bienzyme-substrate-recycle enzyme-linked immunosorbent assay for the measurement of Alzheimer's disease (AD) abnormally hyperphosphorylated tau in cerebrospinal fluid (CSF). The assay, which recognizes attomolar amounts of tau, is approximately 400 and approximately 1300 times more sensitive than conventional enzyme-linked immunosorbent assay in determining the hyperphosphorylated tau and total tau, respectively. With this method, we measured both total tau and tau phosphorylated at Ser-396/Ser-404 in lumbar CSFs from AD and control patients. We found that the total tau was 215 +/- 77 pg/ml in cognitively normal control (n = 56), 234 +/- 92 pg/ml in non-AD neurological (n = 37), 304 +/- 126 pg/ml in vascular dementia (n = 46), and 486 +/- 168 pg/ml (n = 52) in AD patients, respectively. However, a remarkably elevated level in phosphorylated tau was only found in AD (187 +/- 84 pg/ml), as compared with normal controls (54 +/- 33 pg/ml), non-AD (63 +/- 34 pg/ml), and vascular dementia (72 +/- 33 pg/ml) groups. If we used the ratio of hyperphosphorylated tau to total tau of > or =0.33 as cutoff for AD diagnosis, we could confirm the diagnosis in 96% of the clinically diagnosed patients with a specificity of 95%, 86%, 100%, and 94% against nonneurological, non-AD neurological, vascular dementia, and all of the three control groups combined, respectively. It is suggested that the CSF level of tau phosphorylated at Ser-396/Ser-404 is a promising diagnostic marker of AD.     

The choroid plexuses: a dynamic interface between the blood and the cerebrospinal fluid

The choroid plexuses form one of the interfaces that control the brain microenvironment by regulating the exchanges between the blood and the central nervous system. They appear early during brain development. Originating from four different areas of the neural tube, they protrude into the ventricular system of the brain. The choroidal mechanisms involved in the control of brain homeostasis include the structural properties of the epithelial cells that restrict diffusional processes, as well as specific exchange and secretion mechanisms. In addition to the anatomical and histological organization of the choroidal tissue, this review describes the mechanism of cerebrospinal fluid secretion which is the most studied function of the choroid plexus. Experimental evidence for an implication of the choroid plexuses in neuroprotective mechanisms and in the supply of biologically active polypeptides to the brain are also reviewed.     

Standardization of Alternaria alternata: extraction and quantification of alt a 1 by using an mAb-based 2-site binding assay.

BACKGROUND: Alternaria alternata is recognized as an important cause of allergic disease. As with other molds, the extracts of A alternata used for diagnosis and therapy are highly heterogeneous, and there is a need for improved standardization. The major allergen Alt a 1 is well characterized and has been produced as a recombinant protein, but very few data are available on the Alt a 1 content in extracts. OBJECTIVE: An assay for the quantification of Alt a 1 was developed and used for monitoring batch-to-batch consistency of A alternata extracts, and the correlation between skin prick test responses and Alt a 1 concentrations was studied. METHODS: A 2-site binding assay based on an Alt a 1-specific mAb was developed and used for the quantification of Alt a 1 in allergen extracts. Quantitative skin prick tests were performed on 16 A alternata-sensitive patients and correlated with the Alt a 1 concentration. RESULTS: The Alt a 1-specific mAb was found to be suitable for affinity purification, as well as for a 2-site binding quantification assay. In allergen extracts the Alt a 1 content was estimated as 2% to 4.7% of total protein. Quantitative skin prick tests showed an Alt a 1 concentration-dependent response. CONCLUSION: Quantification of Alt a 1 in A alternata extracts reflects their batch-to-batch consistency. Skin prick test responses to a standardized A alternata extract correlate with the Alt a 1 contents. An extract containing 3.7 microgram/mL Alt a 1 caused a response equal to that of a 1% histamine dihydrochloride solution.     

Levels of parathyroid hormone-related protein in hypercalcemia of malignancy: comparison of midregional radioimmunoassay and two-site immunoradiometric assay

Summary Overproduction of parathyroid hormone-related protein (PTHrP) is a major cause of hypercalcemia of malignancy in patients with solid tumors. We measured plasma levels of the protein by a radioimmunoassay (RIA) against PTHrP(5384) and by an immunoradiometric assay (IRMA) against PTHrP(1–86). Of 16 affected patients 7 had elevated PTHrP levels in both assays and 4 had elevated levels in the RIA only. Median levels were about tenfold higher in these patients when measured by RIA (median of 34 versus 2.2 pmol/1). Measurements from both assays were, however, highly correlated with each other in this patient group (P<0.01). PTHrP was not elevated in 10 normocalcemic patients with lung carcinoma. During long-term follow-up of a patient with a mesothelioma of the pleura, PTHrP levels measured with both assays decreased during chemotherapy in parallel with a normalization of serum calcium. In another hypercalcemic patient suffering from renal carcinoma, PTHrP measured by IRMA decreased by 40% within 12 h after nephrectomy, whereas PTHrP measured by RIA did not show a significant decline. Direct comparison of the assay results thus pointed to the existence of heterogeneity of circulating forms of PTHrP in plasma. In conclusion, both immunoassays detected elevated levels of PTHrP in a fraction of patients with hypercalcemia of malignancy and thus may be a tumor marker during treatment of malignancies.Abbreviations PTHrP parathyroid hormone-related protein - PTH parathyroid hormone - RIA radioimmunoassay - IRMA immunoradiometric assay     

Relationship between prolactin in the serum and cerebrospinal fluid of ovariectomized female rhesus monkeys

The entry of prolactin into the cerebrospinal fluid from the blood, and the relation between levels in the two compartments were studied under a variety of conditions in ovariectomized rhesus monkeys. Prolonged treatment with either domperidone or sulpiride, both dopamine-receptor blockers, elevated prolactin levels in serum and cerebrospinal fluid proportionately equally, so that the cerebrospinal fluid/serum ratio was unchanged from controls (circa 12–20%). Gel filtration showed that only ‘little’ (monomeric) prolactin entered the cerebrospinal fluid in such monkeys. Following acute elevations of blood prolactin after a single injection of either sulpiride or ovine prolactin, cerebrospinal fluid levels increased linearly over a 90 min sampling period, despite falling serum levels. The rate of entry of prolactin into the cerebrospinal fluid was similar after either procedure, and was independent of absolute serum or cerebrospinal fluid levels, suggesting a rate-limiting mechanism. Furthermore, retrograde portal blood flow from the pituitary is not necessary to account for these results. Clearance of prolactin from the third ventricle was studied following intraventricular injection of prolactin. Prolactin was removed from the cerebrospinal fluid by a mechanism whose efficiency compares with that in serum, so that the half-life of prolactin in either compartment is about the same.Measurement of sodium, potassium and calcium in the cerebrospinal fluid during prolonged hyperprolactinaemia showed no change, indicating that the central effects of prolactin are not due to alteration of these electrolytes.These results show that cerebrospinal fluid levels of prolactin, and hence, those surrounding the brain, can be inferred accurately from those in the blood, and suggest that there may be a selective mechanism regulating the entry of prolactin into the cerebral compartment.     

Comparative study of 2 commercial tests for the detection of HIV-1 antigens in blood and cerebrospinal fluid using immunoenzymology

The authors have carried out, on 150 sera of patients seropositive for the human immunodeficiency virus type I (HIV I) and 11 cerebrospinal fluid of which 5 were patient infected by the HIV I, a comparative study of two commercial tests for the detection of HIV I antigen (Diagnostic Pasteur and Abbott laboratories). A much greater sensitivity was obtained with the specificity being practically identical for the sera with the two tests (100% with Abbott laboratories test, 96.11% with the diagnostic Pasteur test). 4 sera appeared "false negatives" with the Abbott Laboratories test; their optical density was situated between 80 and 100 p. cent of the cut-off level value, whereas that of the "real" negatives was situated between 30 and 60 p. cent of the cut-off level value. 10 of the 11 cerebrospinal fluids appeared false positive with the Diagnostic Pasteur. This seems to be connected with an insufficiency of saturation of protein receptors in the wells. The Diagnostic Pasteur test is not adapted for the detection of HIV I antigen in the body fluids with a weak protein concentration. Contrary to the results obtained with the Encavor test (Abbott laboratories) the analysis in western-blot does not show an inverse prevalence of anti p24 GAG antibodies with regard to antigen HIV I in seropositive patients. On the other hand, the statistical analysis of the positive HIV I sera which are at the same time antigen HIV I positive and antibodies HIV I positive suggests an earlier disappearance of anti p17 GAG antibodies than of anti p24 GAG antibodies.