Cerebrospinal fluid methylmalonic acid concentrations in neurological patients with low and normal serum cobalamin concentrations

OBJECTIVE: To determine whether cerebrospinal fluid (CSF) methylmalonic acid (MMA) is increased in neurological patients with low serum cobalamin (Cbl, vitamin B12) concentrations as opposed to neurological patients with normal serum Cbl concentrations. MATERIAL AND METHODS: We measured MMA concentrations in serum and CSF of neurological patients with low serum cobalamin concentrations, but without overt cobalamin related manifestations such as anemia or combined disease of the cord, and neurological patients with normal serum cobalamin concentrations (controls). RESULTS: Serum and CSF MMA concentrations were significantly higher in patients than in controls. Serum MMA was elevated in 4 patients of whom 3 had clearly elevated CSF MMA concentrations. CONCLUSION: Strong indications for cobalamin deficiency can be found not only in serum but also in CSF of patients with seemingly asymptomatic low serum cobalamin concentrations.     

Cerebrospinal fluid ceftazidime kinetics in patients with external ventriculostomies

Ceftazidime has proven to be effective for the treatment of bacterial meningitis caused by multiresistant gram-negative bacteria. Since nosocomial central nervous system infections are often accompanied by only a minor dysfunction of the blood-cerebrospinal fluid (CSF) barrier, patients with noninflammatory occlusive hydrocephalus who had undergone external ventriculostomy were studied (n = 8). Serum and CSF were drawn repeatedly after the administration of the first dose of ceftazidime (3 g over 30 min intravenously), and concentrations were determined by high-performance liquid chromatography by using UV detection. The concentrations of ceftazidime in CSF were maximal at 1 to 13 h (median, 5.5 h) after the end of the infusion and ranged from 0.73 to 2.80 mg/liter (median, 1.56 mg/liter). The elimination half-lives were 3.13 to 18.1 h (median, 10.7 h) in CSF compared with 2.02 to 5.24 h (median, 3.74 h) in serum. The ratios of the areas under the concentration-time curves in CSF and serum (AUCCSF/AUCS) ranged from 0.027 to 0.123 (median, 0.054). After the administration of a single dose of 3 g, the maximum concentrations of ceftazidime in CSF were approximately four times higher than those after the administration of 2-g intravenous doses of cefotaxime (median, 0.44 mg/liter) and ceftriaxone (median, 0.43 mg/liter) (R. Nau, H. W. Prange, P. Muth, G. Mahr, S. Menck, H. Kolenda, and F. S?rgel, Antimicrob. Agents Chemother. 37:1518-1524, 1993). The median AUCCSF/AUCS ratio of ceftazidime was slightly below that of cefotaxime (0.12), but it was 1 order of magnitude above the median AUCCSF/AUCS of ceftriaxone (0.007) (Nau et al., Antimicrob. Agents Chemother. 37:1518-1524, 1993). The concentrations of ceftazidime observed in CSF were above the MICs for most Pseudomonas aeruginosa strains. However, they are probably not high enough to be rapidly bactericidal. For this reason, the daily dose should be increased to 12 g in cases of P. aeruginosa infections of the central nervous system when the blood-CSF barrier is minimally impaired.     

Cerebrospinal fluid selenium and chromium levels in patients with Parkinson's disease

We compared CSF and serum levels of selenium and chromium, measured by atomic absorption spectrophotometry, in 28 patients with Parkinson's disease (PD) and 43 matched controls. The CSF and serum levels of these trace metals did not differ significantly between PD patients and controls. CSF selenium and chromium levels were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group. Although antiparkinsonian therapy did not influence significantly the CSF levels of selenium, PD patients not treated with levodopa had significantly higher CSF selenium levels than controls (p < 0.01). It is possible that increased CSF selenium levels could indicate an attempt of protection against oxidative stress. The normality of CSF and serum chromium levels suggest that these values are not related with the risk for PD.     

Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results

To investigate the contribution of dietary carbohydrate to glutamate and acetyl CoA synthesis, two groups of adult mice were fed a high- (HCD) or a low-carbohydrate diet (LCD) in which 5% of the carbohydrate was [U-13C]-glucose. Four animals from each dietary group were killed after 1, 2 and 5 d. The tracer:tracee ratios of [13C3] and [13C6]blood glucose and of the [13C2] and [13C3] isotopomers of blood, mucosal, hepatic and muscle alanine and glutamate were used to calculate the fractional contribution of glucose to the 3-carbon, acetyl CoA and oxaloacetate pools of each tissue. In the HCD mice, glucose contributed 66, 33 and 31% of the acetyl CoA pool of muscle, liver and mucosa, respectively. The contribution of glucose to acetyl CoA was lowered by 33% (P < 0.05) and 55% (P < 0.01) in the liver and muscle of the LCD group, respectively, but was unaltered in the mucosa. Glucose made a minor contribution to glutamate synthesis via oxaloacetate in the liver (23%) and muscle (10%) of the HCD group. The fraction of hepatic and muscle glutamate synthesis derived from glucose was not affected by the diet. We conclude that glucose oxidation in liver and muscle parallels the contribution of carbohydrate to dietary energy and that glucose is not a major carbon precursor for muscle glutamate synthesis. Net glutamate synthesis in extraintestinal tissues is preserved when dietary carbohydrate is restricted.     

Cerebrospinal fluid lysozyme activity in patients with central nervous system tumours

The presence of lysozyme in the CSF is considered with regard to its value in the early diagnosis of primary or secondary CNS Tumours. Since the appearance of this enzyme in the CSF is secondary to the increase of protein in the fluid, the search for lysozyme in the CSF is of no practical help in the diagnosis of CNS tumours.     

Cerebrospinal fluid levels of transition metals in patients with Parkinson's disease

We compared CSF and serum levels of iron, copper, manganese, and zinc, measured by atomic absorption spectrophotometry, in 37 patients with Parkinson's disease (PD) and 37 matched controls. The CSF levels of zinc were significantly decreased in PD patients as compared with controls (p < 0.05). The serum levels of zinc, and the CSF and serum levels of iron, copper, and manganese, did not differ significantly between PD-patient and control groups. There was no influence of antiparkinsonian therapy on CSF levels of none of these transition metals. These values were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group, with the exception of CSF copper levels with the duration of the disease (r = 0.38, p < 0.05). These results suggest that low CSF zinc concentrations might be related with the risk for PD, although they could be related with oxidative stress processes.     

Immunological findings in serum and synovial fluid in patients with rheumatoid arthritis (author's transl)

Sera and synovial fluid were investigated in 45 patients with rheumatoid Arthritis and 50 patients with osteoarthritis in inflammatory exacerbation (control group). The following tests were performed: IgG, IgM, IgA determinations, complement components C3, C3, C4, C3-proactivator, ceruloplasmin, electrophoresis, LDH and total acid phosphatase. 1. Serum levels of the ceruloplasmin, alpha 1, alpha 2 and gamma fractions of electrophoresis are significantly higher in patients with rheumatoid arthritis than in patients with osteoarthritis. 2. Synovial fluid: a) There is a significantly higher concentration of IgG, IgM, IgA, C3-proactivator and total acid phosphatase in the synovial fluid of patients with rheumatoid arthritis. b) C4 is significantly lower in patients with rheumatoid arthritis. c) Both groups were also compared with the help of a point system. Every patient received a plus point when the following criteria were seen: IgM greater than 150 mg/100 ml, C3 greater than 50 mg/100 ml, ceruloplasmin greater than 35 mg/100 ml, alpha 1 greater than 0.21 g%, alpha 2 greater than 0.44 g%, beta greater than 0.60 g% and gamma fraction on electrophoresis greater than 0.90 g%. Another point was added if the criteria ceruloplasmin greater than 22 mg/100 ml and C4 less than 17 mg/100 ml were simultaneously seen. With the help of this points system 48 out of the 50 osteoarthritis patients (96%) received zero points, one received 1 point and one 2 points, as opposed to the patients with rheumatoid arthritis where 35 out of 45 (78%) received one or more points. d) The differentation is not improved through additional testing of the rheumatic factors.     

Cerebrospinal fluid passage of intravenous magnesium sulfate in neurosurgical patients

The presence of immune molecules induced by microorganisms in the haemolymph of Lutzomyia longipalpis sandflies has been investigated. Injections of Escherichia coli and Micrococcus luteus into female sandflies induced anti-bacterial activity in the haemolymph. Inhibition zone assays showed that haemolymph from E. coli and M.luteus injected sandflies differentially inhibited M.luteus growth. This differential effect was specific to M.luteus infection since anti-E.coli activity was similar in haemolymph from both E.coli or M.luteus injected sandflies. Haemolymph following injection of either bacteria showed the induction of a 4 kDa peptide. Haemolymph from M.luteus injected sandflies also contained a 33 kDa polypeptide which was absent in haemolymph from E.coli and control uninfected insects. Sandflies, in common with other insects, were shown to possess general and specific humoral immune responses to the presence of microorganisms.     

Thrombopoietin serum concentration in patients with reactive and myeloproliferative thrombocytosis

We wished to test whether thrombopoietin (TPO) is entirely regulated by receptor binding or if other factors may play a role in the mechanism of TPO regulation. Therefore, we analyzed the TPO serum levels in 43 patients with reactive (secondary) thrombocytosis and in 37 with myeloproliferative thrombocytosis. Thrombocytosis was defined as a platelet level greater than 440 x 10(9)/l. Forty-two patients (98%) with reactive thrombocytosis had high concentrations of IL-6 correlating with elevated C-reactive protein levels. Twenty-three patients (53%) in this group had TPO serum concentrations of more than 300 pg/ml (normal: below 300 pg/ml). Only nine patients (24%) with myeloproliferative thrombocytosis had TPO serum levels above normal range, whereas 28 patients (76%) had normal levels of TPO. No correlation between the TPO serum levels and the concentrations of IL-6 or EPO was established. The other investigated thrombopoietic cytokines (IL-3, IL-11, GM-CSF) were unmeasurable; therefore, a correlation could not be assessed. We conclude that TPO concentrations are not strictly inversely related to platelet count. TPO serum levels are elevated especially in a considerable percentage of patients with reactive thrombocytosis, arguing for the existence of additional mechanisms of TPO regulation.     

Cerebrospinal fluid monoamine metabolites in fluoxetine-treated patients with major depression and in healthy volunteers

Cerebrospinal fluid (CSF) levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) were measured in three groups: 46 healthy volunteers; 9 medication-free patients with DSM III-R major depressive disorder, recurrent; and these same 9 patients following at least 4 weeks of fluoxetine treatment at 20 mg/day. CSF monoamine metabolite levels in medication-free patients did not differ from healthy volunteers; however, CSF 5-HIAA and MHPG decreased significantly from 95.9 +/- 24.6 (all values +/- SD) to 64.2 +/- 26.1 pmol/ml and from 46.7 +/- 14.2 to 42.6 +/- 11.6 pmol/ml, respectively, following fluoxetine treatment. Fluoxetine also significantly decreased mean Hamilton Depression Rating Scale scores from 23.2 +/- 6.5 to 17.4 +/- 5.0 and significantly increased the CSF HVA/5-HIAA ratio.     

Cerebrospinal fluid corticotropin-releasing factor concentrations in patients with anxiety disorders and normal comparison subjects

A simple immunosensor based on a conductivity method was developed for determination of methamphetamine (MA, a stimulant drug) in urine. Anti-MA antibody was immobilized onto the surface of a pair of platinum electrodes. The reaction of MA with the antibody causes a decrease in the conductivity of the anti-MA immobilized layer between the electrodes. A linear relationship was obtained between the conductivity and MA concentration in the range of 1-10 micrograms/ml. The method requires the sample to be rinsed with water on the electrodes after the immunoreaction. This detection system was applied to the determination of MA in urine and proved to be a useful and a simple detection technique of MA in forensic science in comparison with a gas chromatography-mass spectrometry method.     

Histological findings of gallbladder mucosa in 95 control subjects and 80 patients with asymptomatic gallstones

BACKGROUND AND PURPOSE: Decisions on invasive arteriovenous malformation (AVM) treatment are currently based on natural-course risk estimates of AVM bleeding and assumptions on morbidity from cerebral hemorrhage in general. However, morbidity of AVM hemorrhage has rarely been reported. We sought to assess the morbidity of intracranial hemorrhage in patients with cerebral AVMs. METHODS: From a prospective AVM database, 119 patients were analyzed: 115 had a hemorrhage as the diagnostic event, and 27 of them suffered a second hemorrhage during follow-up; an additional 4 patients had other diagnostic symptoms but bled during follow-up. The type (parenchymal, subarachnoid, intraventricular) and location of AVM hemorrhage were determined by CT/MR brain imaging. Disability and neurological impairment were assessed with the Barthel Index, the Rankin Scale, and the National Institutes of Health Stroke Scale, with a mean follow-up time of 16.2 months. RESULTS: Of the 115 incident hemorrhages, 34 (30%) were subarachnoid, 27 (23%) parenchymal, 18 (16%) intraventricular, and 36 (31%) in combined locations. In 54 patients (47%; 95% confidence interval [CI], 38% to 56%) the incident hemorrhage resulted in no neurological deficit, and an additional 43 patients (37%; 95% CI, 28% to 46%) were independent in their daily activities (Rankin 1). Fifteen patients (13%; 95% CI, 7% to 19%) were moderately disabled (Rankin 2 or 3), and 3 (3%; 95% CI, 0% to 6%) were severely disabled (Rankin > or =4). Parenchymal hemorrhages were most likely to result in a neurological deficit (52%). Type and morbidity of hemorrhage during follow-up were similar to incident events. Twenty (74%) of 27 patients with both incident and follow-up hemorrhages were normal or independent (Rankin 0 or 1). None of the patients with a hemorrhage during follow-up died during the observation period. CONCLUSIONS: Hemorrhage from cerebral AVMs appears to have a lower morbidity than currently assumed. This finding encourages a reevaluation of the risks and benefits of invasive AVM treatment.     

Titer and subclass distribution of serum IgG antibody reactive with Actinobacillus actinomycetemcomitans in localized juvenile periodontitis

Most patients with localized juvenile periodontitis (LJP) manifest serum IgG antibodies specifically reactive with antigens of Actinobacillus actinomycetemcomitans serotype b (Aa-b). Whether these antibodies are protective, destructive, or irrelevant to the progress of the disease remains unclear. We report results of studies aimed at assessing the subclass IgG responses in 35 LJP patients and 35 periodontally normal control subjects using well-characterized monoclonal antibody subclass reagents in an enzyme-linked immunosorbent assay. Our data show that the mean value for total IgG reactive with antigens of Aa-b was more than sevenfold higher for patients than for normal control sera (2349.6 micrograms/ml for patients vs 332.2 micrograms/ml for controls). Individual patients and control subjects were classified as high- or low-titer, using twice the median value for total anti-Aa-b IgG in control sera as the cutoff. Of 35 patients, 26 (74%) were high-titer, and 9 (26%) were low-titer. This compares to 5 normal control subjects (14%) high-titer and 30 (86%) low-titer. IgG2 accounted for the major quantitative response in both patients and control subjects. Indeed, the mean IgG2 values for both concentration and percentage of total specific IgG were greater than the combined values for specific anti-Aa-b IgG1, IgG3, and IgG4. Of the 26 high-titer sera, IgG2 predominated in 24, with IgG1 and IgG3 predominating in 1 each; IgG2 predominated in only 2 of the low-titer sera.     

Cerebrospinal fluid glutamate inversely correlates with positive symptom severity in unmedicated male schizophrenic/schizoaffective patients

OBJECTIVE: To determine the efficacy of polymyxin B-dextran 70 (PBD) for treatment of endotoxemic horses. ANIMALS: 15 horses during study 1 and 6 horses during study 2. PROCEDURES: 3 groups were used in study 1. Horses in groups 1 and 2 were given 30 ng of lipopolysaccharide (LPS)/kg of body weight, IV, over 60 minutes. Horses in group 3 were given saline (0.9% NaCl) solution. Beginning 15 minutes before LPS infusion and continuing for 75 minutes, horses in groups 1 and 3 were given PBD, IV. Horses in group 2 were given dextran 70. Blood samples were obtained for hemograms and determination of cytokine, lactate, and prostanoid concentrations. In study 2, horses were given ketoprofen (2.2 mg/kg) or saline solution 15 minutes before infusion of PBD. Fourteen days later, treatments were reversed, using a crossover design. Blood samples were obtained for measurement of thromboxane B2 (TXB2) concentration. RESULTS: For study 1, prior treatment with PBD completely blocked endotoxin-induced changes for heart and respiratory rates, rectal temperature, WBC count, and plasma tumor necrosis factor, interleukin 6, TXB2, and prostaglandin F1 concentrations. There was transient tachypnea, sweating, and increased plasma TXB2 concentration in horses given PBD (with or without LPS). Prior treatment with ketoprofen eliminated all PBD-induced signs and prevented the increase in plasma TXB2 concentration. CONCLUSIONS: Signs of endotoxemia were prevented in horses by treatment with PBD, although its use was associated with mild adverse effects. CLINICAL RELEVANCE: When used in combination with a cyclooxygenase-inhibiting drug, PBD has potential for treatment of horses with endotoxemia.     

Cerebrospinal fluid amino acid levels in newborn infants with intracranial hemorrhage

Cerebrospinal fluid (CSF) amino acid levels including excitatory amino acids (i.e. glutamate and aspartate) in 25 preterm and 18 full-term newborn infants with no serious disease except intracranial hemorrhage (ICH) were measured. ICH was detected in 13 preterm and six full-term infants on the basis of the clinical, lumbar puncture (LP) and cranial ultrasonography (CraUSG) findings. Twelve preterm and 12 full-term infants who were neurologically healthy comprised the control group. The mean concentration of CSF amino acids did not differ between preterm and full-term infants. The CSF concentrations of taurine, threonine, glycine, alanine, valine, isoleucine, leucine, tyrosine and phenylalanine in preterm infants, and threonine, aspartic acid and alanine in full-term infants were significantly elevated in infants with ICH. These abnormalities, especially in preterm infants, are probably related to cerebral hypoxia in CSF amino acid concentrations in newborn infants with ICH.     

Differences between intraocular and serum antibody responses in patients with ocular toxoplasmosis

The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is present in many regions of the adult and developing brain as are receptors for PACAP. PACAP stimulates different signalling cascades in neurons, involving cAMP, MAP kinase, and calcium. These characteristics suggest that PACAP may influence neuronal development. Here we have studied the effects of PACAP on mesencephalic dopaminergic neurons using primary cultures from embryonic rats. PACAP increased the number of tyrosine hydroxylase (TH)-immunoreactive neurons, elevated TH protein, and enhanced tritiated dopamine uptake in these cultures. Moreover, PACAP counteracted the effects of 6-hydroxydopamine treatments, which induce cell death of dopaminergic neurons. In situ hybridisation showed that both PACAP and PACAP receptor type 1 are present in developing and adult rat mesencephalon. These results show that PACAP has a neurotrophic action on dopaminergic neurons and partially protects them against 6-OHDA induced neurotoxicity.     

Cerebrospinal fluid rhinorrhea in achondroplasia with hydrocephalus (author''s transl)

Intradermal (ID) administration of 0.1 ml of a bivalent influenza vaccine containing 40 CCA units each of influenza A/New Jersey (Hswine 1N1) and A/Victoria (H3N2) virus antigens and of a monovalent vaccine containing 100 CCA units of influenza B/Hong Kong virus to 70 adult volunteers produced no serious reactions and only 7% bothersome side effects. Excluding persons with high (1:64 or greater) initial antibody titers, then 90% and 85% of persons had fourfold or greater rises in HAI antibodies to A/New Jersey and B/Hong Kong antigens, whereas 53% had rises to A/Victoria. The authors feel the ID route deserves further consideration for giving killed influenza vaccines to adults. However, an influenza virus type that was prevalent for many years may fail to give sufficient rise in HAI to consider the patient protected.     

Neurotrophic factors in cerebrospinal fluid and serum of patients with Rett syndrome

Rett syndrome is now considered to be a neurodevelopmental disease. Its cause is unknown, but it has been suggested that neuronal growth factors and neurotransmitters play important roles. We measured levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in cerebrospinal fluid, and nerve growth factor and brain-derived neurotrophic factor in serum in child and adolescent patients with Rett syndrome. Levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in cerebrospinal fluid were below the limit of sensitivity of the methods used. Serum levels of nerve growth factor and brain-derived neurotrophic factor did not differ from control values. In Rett syndrome, the normal serum levels of nerve growth factor together and previously reported low levels of the factor in cerebrospinal fluid indicate that the latter may reflect low levels of nerve growth factor in the central nervous system.     

Cerebrospinal fluid pleocytosis in children with pneumonia but lacking evidence of meningitis

Headache, nuchal rigidity, positive Kernig's sign, and even convulsions may be observed during severe bacterial infections such as pneumonia, pyelonephritis, typhoid fever, and bacillary dysentery. In such cases, meningitis can be excluded only by documentation of normal cerebrospinal fluid (CSF). The authors describe four children with lobar pneumonia in whom the clinical signs of meningeal irritation were associated with a mild increase in the white blood cell count in the CSF (pleocytosis) although there was no other evidence of meningeal infection.