Prolactin levels in cerebrospinal fluid of patients with chronic schizophrenia

Baseline concentrations of prolactin (PRL) was determined in the CSF of 28 lobotomized and 28 non-lobotomized patients with chronic schizophrenia. The mean PRL level of the female patients was significantly higher than that of the male patients (p < 0.001). In addition, non-lobotomized patients had significantly higher concentrations of CSF PRL than patients of the lobotomized group (p < 0.05). On the other hand, patients belonging to the latter group exhibited significantly more central as well as cortical brain atrophy than the patients on whom no psychosurgery had been performed (0.05 > p < 0.001). The significance of cerebrospinal PRL as an index of central dopamine metabolism is discussed.     

Hyaluronan in human cerebrospinal fluid

We studied the concentration of hyaluronan in cerebrospinal fluid (CSF) in various diseases and attempted to define its reference interval. A radioassay utilizing cartilage proteins with affinity for hyaluronan was used in determining the concentration of 200 lumbar and 27 ventricular CSF specimens and 11 brain cyst fluids. Molecular weight distributions were determined by gel chromatography and localization in brain tissue by histochemistry. The hyaluronan level of lumbar CSF showed an increase with age; comparatively healthy children had (mean +/- SD) 50 +/- 41 micrograms/L (n = 40) and adults 166 +/- 77 micrograms/L (n = 9); i.e. significantly different values. The highest level was recorded in a patient with meningitis (> 8000 micrograms/L). More than 4000 micrograms/ L was noted in a patient with tumour metastasis in the cerebellum. Significantly elevated levels were especially found with spinal stenosis, head injury and cerebral infarction, but also in inflammatory medical disorders, hydrocephalus and encephalitis. We found no significant increase in multiple sclerosis and some other neurological diseases. Ventricular CSF of adults contained significantly less hyaluronan (53 +/- 73 micrograms/L; n = 16) than lumbar CSF. Hyaluronan in cyst fluids varied from 31 to 25,000 micrograms/L. Weight average molecular weight of hyaluronan in CSF was 2.9-3.0 x 10(5) and in brain tumour cyst fluid 2.4 x 10(6). In search for the origin of hyaluronan in CSF it was found that its concentration in the choroid plexus and leptomeninges was low, but that hyaluronan was accumulated in the superficial layer of the cerebral cortex. Continued screening for hyaluronan in CSF may be valuable in cases of inflammatory diseases, tumours and obstruction to CSF flow.     

Mannan-binding lectin in human serum, cerebrospinal fluid and brain tissue and its role in Alzheimer's disease

Mannan-Binding lectin (MBL) is a serum lectin which can activate the classical complement pathway. Complement proteins of the classical pathway have been found in the brains of patients with Alzheimer's disease (AD) in association with AD brain pathology. To investigate the role for MBL in AD we have looked for its presence in the brain by immunohistochemistry and determined the levels of MBL in paired samples of cerebrospinal fluid and serum from AD patients and controls. MBL was detected in association with blood vessels in the brain tissue of both AD patients and control subjects. There was no apparent difference in the distribution of MBL in the brain tissue between the two groups. The mean concentration of MBL in the CSF was 44% lower in AD patients than in controls (AD 154 +/- 35 pg/ml, n = 19; non-AD 276 +/- 50 pg/ml, n = 15, p < 0.05). The levels of MBL in serum were not significantly different in the two groups. Thus, this study shows that MBL is associated with blood vessels in the brains of both AD and control subjects. Moreover, CSF levels of MBL appear to be lower in AD patients than in control subjects which may indicate a higher degree of MBL consumption connected with complement activation in the AD patients.     

Changes in serum and cerebrospinal fluid enzyme activity after head injury

We studied simultaneously in serum (S) and CSF (L) the enzyme activities of GOT, GPT, LDH, ICDH, MDH, ALD, and CPK in 28 patients with head injuries divided into three groups according to the severity of the trauma. We found a correlation between severity of brain lesion and enzyme activity. The best correlation was found for SGOT, SCPK, LGOT, LLDH, LMDH and LCPK. We do not believe that enzyme activity is of prognostic value. We think that further studies should be made of the specific isoenzymes of the Central Nervous System.     

Distribution and characterization of enterostatin-like immunoreactivity in human cerebrospinal fluid

The effects of two highly fermentable dietary fibers (guar gum and pectin) on the type and concentrations of cecal polyamines as affected by the intestinal microflora were studied in groups of germ-free (n = 10/group) and conventional rats (n = 6/group). Both germ-free and conventional rats were randomly assigned to one of three treatments as follows: 1) fiber-free control diet, 2) control diet + 10% guar gum and 3) control diet + 10% pectin. In germ-free rats, guar gum and pectin had no effect on cecal polyamine concentrations. Putrescine was confirmed to be the major endogenous polyamine within the gut lumen. In cecal contents of conventional rats, both guar gum and pectin led to the appearance of cadaverine and to elevated putrescine concentrations in comparison with the fiber-free control diet (1.35 +/- 0.15 and 2.27 +/- 0.32, respectively, vs. 0.20 +/- 0.03 micromol/g dry weight, P < 0.05). The cecal cadaverine concentration was higher in pectin- than in guar-fed rats (8.20 +/- 0.89 vs. 1.92 +/- 0.27 micromol/g dry weight, P < 0.05). Counts of total bacteria, bacteroides, fusobacteria and enterobacteria were higher (P < 0.05) in rats fed guar gum and pectin. Bifidobacteria were found exclusively in guar-fed rats. In vitro studies on selected species representing the numerically dominant population groups of the human gut flora (bacteroides, fusobacteria, anaerobic cocci and bifidobacteria) were examined for their ability to synthesize intracellular polyamines. These experiments demonstrated the ability of bacteroides, fusobacteria and anaerobic cocci to synthesize high amounts of putrescine and spermidine. Calculations based on these results suggest that the intestinal microflora are a major source of polyamines in the contents of the large intestine.     

Albumin and immunoglobulin levels in cerebrospinal fluid and serum in tick borne meningoencephalitis

The levels of albumin and immunoglobulins G, A, M were determined by using nephelometry technique in the cerebrospinal fluid and serum in 14 adults with tick borne meningoencephalitis at the beginning and after four weeks of disease. Intra blood-brain synthesis of IgG, IgA, IgM was evaluated by indexes of synthesis (Tibbling formula). The blood-brain integrity was estimated by CSF/serum albumin ratio. Increased albumin and immunoglobulins G, A, M levels were demonstrated in first examination and only elevated levels of albumin and immunoglobulin M lasted after four weeks. Albumin level in cerebrospinal fluid and albumin ratio were elevated in both examinations. The serum levels of albumin and immunoglobulins were similar in first and second examination. On the basis these results we conclude that in tested patients blood-brain integrity was disturbed still after four weeks of disease.     

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.     

Anticardiolipin antibodies in serum and cerebrospinal fluid from patients with systemic lupus erythematosus

Anticardiolipin antibodies were studied in serum and cerebrospinal fluid from 32 consecutive patients with systemic lupus erythematosus, admitted for the assessment of neuropsychiatric disease. Ten of the 16 patients with active neuropsychiatric complaints showed positive anticardiolipin antibodies in cerebrospinal fluid, including eight with the simultaneous presence of antibodies in their sera. By contrast, only 2 of the 16 patients with headaches, lacking further data of neurological disease, revealed anticardiolipin antibodies in their cerebrospinal fluid. The assessment of Q-albumin index showed abnormal values in a subset of patients with active neuropsychiatric changes who showed positive cerebrospinal anticardiolipin antibodies, suggesting that an impairment of the blood brain barrier function may lead to a leakage of intrathecal antiphospholipid antibodies from systemic circulation. Additionally, few patients revealed normal Q-albumin values with high IgG-cerebrospinal fluid index suggesting increased intrathecal synthesis of autoantibodies. The study of anticardiolipin antibodies in cerebrospinal fluid was useful to detect active neuropsychiatric disease in systemic lupus erythematosus.     

Essential fatty acids in the serum and cerebrospinal fluid of multiple sclerosis patients

Statistical evaluation of essential fatty acids (determined by gas chromatography) in the serum and cerebrospinal fluid of patients with definite MS and acute CCT showed marked differences as compared to healthy subjects. It was also evident that the decrease of essential fatty acids in MS patients differed from that of CCT patients. Whereas the fatty acid levels in the serum of MS patients revealed only minor differences as compared to the controls and CCT patients, MS patients did show a clear decrease, especially of linoleic and arachidonic acids, in the CSF. This difference was most pronounced in cholesterol esters in the CSF. One absorption study with safflower oil demonstrated normal enteral absorption of essential fatty acids and the ability to cross the blood-CSF barrier.     

Immunofixation electrophoretic techniques applied to identification of proteins in serum and cerebrospinal fluid

We describe the application of immunofixation staining of agarose-gel electrophoretograms in areas where its use in the clinical laboratory is appropriate. Immunofixation electrophoresis consists of an electrophoretic phase followed by a fixation phase in which antiserum is used to precipitate the protein. As long as the antibody is in slight excess or near equivalency, the antigen/antibody complex remains insoluble. The reaction can be detected by visual inspection in indirect light, by protein staining, or by use of antibodies labeled with fluorescein, enzyme, or isotope. In the method described here we primarily have used protein staining (Coomassie Blue) to accentuate the proteins fixed by antisera. All unreacted proteins are removed by pressing with filter paper and saline washing. In the clinical laboratory, this method expedites immunochemical evaluation of samples and may also supplement immunoelectrophoresis. It has been applied successfully in identifying small obscure monoclonal proteins in the serum and cerebrospinal fluid of patients with multiple sclerosis, subacute sclerosing panencephalitis, biclonal gammopathies, serum monoclonal light chains, and mobility shifts of certain proteins, particularly of the complement series. Immunofixation demonstrates that the protein bands present in spinal fluid from multiple sclerosis and subacute sclerosing panencephalitis patients are of the IgG class of immunoglobulins; and non-IgG protein, such as beta and gamma trace proteins, are not detected. We also comment on reverse immunofixation with labeled antigen as a branch of the procedure that allows detection of function of the immunoglobulins separated by electrophoresis.     

Insulin-like growth factor system in serum and cerebrospinal fluid in patients with multiple sclerosis

Perforation during attempted gas-enema reduction of intussusception is more common than during a barium enema. In a review of 650 consecutive attempted gas enemas, perforation occurred in 7 infants (1.1%). Gross abdominal distension from the pneumoperitoneum may be rapid and cause splinting of the diaphragm, which leads to acute respiratory distress. This complication is readily recognised at the time of the gas enema, and may require immediate intervention by paracentesis using a 14-gauge needle. A review of 7 children with intussusception in whom perforation occurred revealed that all had radiologic evidence of bowel obstruction (air-fluid levels) prior to the enema, and the patients had had a relatively long history since the onset of symptoms. No perforation occurred during a delayed repeat enema reduction. Perforation during gas enema produces minimal peritoneal contamination. No pathological lesion at the lead point of the intussusception was identified in any of the children in whom perforation occurred.     

Apolipoprotein E allelic influence on human cerebrospinal fluid apolipoproteins

A full length cDNA copy of the genomic RNA of lettuce mosaic virus (LMV) was constructed under the control of an enhanced CaMV 35S promoter and of the NOS terminator. This construct was found infectious when inoculated to lettuce plants. The intron II of the bean nitrite reductase gene was engineered into the LMV FL cDNA in order to relieve possible deleterious effects of viral sequences to Escherichia coli cells and to evaluate the effects of the presence of the intron on the FL cDNA infectivity. The intron-less FL cDNA was found to be as stable as its intron-containing counterpart in E. coli. Sequence analysis of progeny RNA derived from plants inoculated with the intron-containing FL cDNA demonstrated that the inserted intron was perfectly spliced out. The symptoms induced in lettuce by either the intron-less or the intro-containing constructs were identical to those caused by the wild-type virus. However a slight delay in the establishment of infection in lettuce and a more obvious lag in Nicotiana benthamiana were observed with the intron-containing FL cDNA.     

Prolactin and human reproduction

Prolactin was isolated and identified as a separate pituitary hormone distinct from human growth hormone. Since that time a rapidly expanding literature has accumulated on the physiology of pituitary prolactin secretion in normal and pathologic conditions. Currently the physiology and pathophysiology of pituitary prolactin secretion are under intensive investigation. Development of sensitive, specific radioimmunoassay for prolactin and improved roentgenographic techniques have increased the diagnostic acumen for incipient pituitary microadenomas. Dynamic function tests of prolactin secretion have not helped to distinguish whether a patient has a microadenoma or not. The basal prolactin level is probably the most useful single investigation for diagnosis a pituitary tumour. If women with pituitary tumours have ovulation induced with bromocriptine therapy, then there is a considerable risk of rapid enlargement of the tumour with the development of serious visual field defects often during the last trimester. The precise level of the risk is not clear, but is probably not great. The introduction of bromocriptine has heralded a major change in the menagement of the hyperprolactinaemia-hypogonadism syndromes and resulted in safer and easier treatment of many cases of infertility, menstrual disorders and, to a lesser extent of impotence. At present, bromocriptine therapy is the treatment of choice for hyperprolactinaemia.     

Prostaglandin D synthase concentration in cerebrospinal fluid and serum of patients with neurological disorders

Prostaglandin D synthase (PGD synthase) or beta-trace protein is a major constituent of human cerebrospinal fluid (CSF) representing-3% of the total CSF protein. We have recently developed a highly specific immunofluorometric assay for PGD synthase, which enabled us to quantify the presence of PGD synthase in fluids and tissues not associated with the CNS. In this report we provide quantitative data of the presence of PGD synthase in CSF and serum from 302 subjects with various neurological diseases and symptoms. PGD synthase levels in CSF are approximately 35-fold higher than those of serum, with a median concentration of 11,299 micrograms/L. A statistically significant association of PGD synthase concentration in CSF was observed with both patient age and gender. There was no correlation between PGD synthase concentration in serum and patient age or gender. To evaluate the clinical utility of PGD synthase in diagnosing neurological diseases, the distribution pattern of PGD synthase in CSF and serum was examined for each neuropathology of 268 patients whose diagnosis was known. No statistical difference was observed between PGD synthase concentration in the CSF (129 cases) or the serum (94 cases) of multiple sclerosis afflicted subjects in comparison to all other patients studied. The distribution pattern was also not different for PGD synthase levels in CSF of patients with HIV/AIDS related neuropathies, viral meningitis and fibromyalgia. We conclude that PGD synthase measurement presents no clinical utility in diagnosing neurological disorders in adulthood. PGD synthase may have a physiological and/or pathological role in the developing brain and in neurodegenerative diseases.     

Lumbar cerebrospinal fluid drainage for prevention of cerebrospinal fluid fistulas

Leakage of cerebrospinal fluid may complicate surgical procedures of the temporal bone and skull base. This presentation details experience utilizing 7 days lumbar drainage in an attempt to prevent the occurrence of a postoperative CSF fistula. Thirty-nine patients underwent surgery for various intracranial pathologies and were felt to be at high risk for the development of postoperative CSF fistulae. None of the patients was given prophylactic antibiotics. Ten patients developed clinical and laboratory findings consistent with early meningitis and were treated with appropriate antibiotics. Three patients eventually developed a CSF fistula, with two resolving spontaneously and the third requiring a second surgical procedure to repair the dura (again using lumbar drainage postoperatively). Our conclusions suggest that prophylactic placement of a lumbar catheter in high risk patients increases the likelihood of successful dural closure with an acceptable morbidity. Is these patients routine antibiotic coverage is not indicated.