bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single‐dose pharmacokinetics and anticonvulsant efficacy of primidone in mice
Authors: Leal K. W. , Rapport R. L. , Wilensky A. J. , Friel P. N. 
Published: January 2005

AbstractThe pharmacokinetics and efficacy of the anticonvulsant primidone (PRM) and its active metabolites, phenobarbital (PB) and phenylethylmalonamide (PEMA), were studied after single‐dose administration in mice. The half‐life of PB is twice that of PRM and PEMA. The plasma/brain ratios provide evidence of poor penetration of PRM into brain. The results support our findings of negligible or absent PRM concentrations in the brains of patients on primidone therapy who were undergoing surgery for intractable epilepsy.The anticonvulsant properties of PRM, PB, and PEMA against maximal electroshock in mice were also studied with the use of the metabolic inhibitor SKF 525A. The half‐life, potency, peak anticonvulsant effect, and effective dose curves of these compounds indicate that the anticonvulsant effect of short‐term oral PRM administration in mice is from derived PB.
Effects of reserpine, propranolol, and aminophylline on seizure activity and CNS cyclic nucleotides
Authors: Gross Robert A. , Ferrendelli James A. 
Published: January 2005

AbstractConvulsant doses of pentylenetetrazol (100 mg/kg) increase levels of both cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) in mouse cerebral cortex and hippocampus. In animals pretreated with reserpine, propranolol, or aminophylline, pentylenetetrazol seizures were more severe, cyclic AMP elevations were attenuated or blocked, and cyclic GMP increases were unaffected or augmented. These data indicate that norepinephrine, adenosine, and perhaps other biogenic amines have a regulatory effect on cyclic AMP, but not cyclic GMP, levels in epileptic brain. An increased levels of cyclic AMP in brain tissue may have an antiepileptic effect leading to seizure attenuation or termination. By contrast, elevated levels of cyclic GMP may have an antiepileptic effect leading to seizure attenuation or termination. By contrast, elevated levels of cyclic GMP may have an epileptogenic effect in initiating or maintaining seizure activity.
Perisulcal infarcts: Lesions caused by hypotension during increased intracranial pressure
Authors: Janzer R. C. , Friede R. L. 
Published: January 2005

AbstractA pattern of cortical necrosis surrounding the cerebral sulci and similar to ulegyria was found in 5 patients. The lesions were widely disseminated in all parts of the hemispheric cortex, affecting mostly the deep cortex of several adjacent sulci. They were hemorrhagic in 3 patients, ischemic in the others. Each patient had suffered a severe brain injury and became comatose thereafter. Increased intracranial pressure was evident from clinical findings, necropsy changes, or both. While in coma, each patient had at least one episode of hypotension. The data suggest that perisulcal infarcts are a manifestation of diminished vascular perfusion during a period of increased intracranial pressure.
Clinical pharmacology of mephenytoin and ethotoin
Authors: Troupin Allan S. , Friel Patrick , Lovely Mary Pat , Wilensky Alan J. 
Published: January 2005

AbstractEffective prescribing of anticonvulsants requires foreknowledge of baseline pharmacokinetic data. Little such information is available about the hydantoins other than phenytoin, although one of them, mephenytoin, is widely used. Useful pharmacokinetic data should be derived from patients already exposed to anticonvulsants to reflect the induction of hepatic oxidative enzymes. Single‐dose studies of mephenytoin (Mesantoin) and ethotoin (Peganone) were performed in adult inpatients on stable regimens of other anticonvulsants. Five patients received mephenytion, 7 mg per kilogram of body weight. Serial blood sampling was performed rigorously. The time to peak concentration (Tmax) for mephenytoin was 1 hour, with a half‐life (T1/2) of 7 hours; the T1/2 of its metabolite, 5‐ethyl‐5‐phenylhydantion, was 96 hours. Ethotoin administration was 25 mg per kilogram in 5 patients. Ethotoin Tmax was 2 hours, with a T1/2 of 5 hours. Saliva accurately represented the unbound fraction for all three agents. Mean salivary levels (as percentage of total levels) were 61% for mephenytoin, 73% for its metabolite, and 54% for ethotoin.The implication for therapy are that following mephenytoin administration, the metabolite 5‐ethyl‐5‐phenylhydantoin will provide anticonvulsant effectiveness, with its long half‐life producing stable blood levels on simple dose schedules. Ethotoin, in contrast, has a short half‐life and would require divided daily doses to achieve a steady state. This, rather than pharmacological ineffectiveness, limits its usefulness.
Alzheimer neurofibrillary tangles: Antiserum and immunohistological staining
Authors: Grundke‐Iqbal Inge , Johnson Anne B. , Terry Robert D. , Wisniewski Henryk M. , Iqbal Khalid 
Published: January 2005

AbstractA 50,000‐dalton polypeptide has been purified from fractions enriched with neurofibrillary tangles of paired helical filaments from human autopsy specimens of Alzheimer disease and senile dementia of the Alzheimer type. An antiserum to this polypeptide was raised in a rabbit. This antiserum formed an immunoprecipition line with the purified antigen and with human neurotubules in Ouchterlong double‐diffusion plates. The reactivity of the anti‐paired helical filament protein serum with neurofibrillary tangles was studied by immunof uorescence on cryostat sections of hippocampus from Alzheimer autopsy tissue and by the peroxidase‐antiperoxidase technique on paraffin sections of an Alzheimer brain biopsy. The tangles were stained with the antiserum in both systems. Preimmune rabbit serum and unrelated hyperimmune sera, used as controls, did not stain the tangles. These results show that the 50,000‐dalton polypeptide purified form the neurofibrillary tangle‐enriched fractions is a constituent of Alzheimer neurofibrillary tangles and, perhaps, of the paired helical filaments of which the tangles are composed.
Central cholinergic activity in aluminum‐induced neurofibrillary degeneration
Authors: Hetnarski Bogumil , Wisniewski Henryk M. , Iqbal Khalid , Dziedzic John D. , Lajtha Abel 
Published: January 2005

AbstractCholine acetyltransferase (CAT) and acetylcholinesterase (AChE) activities were measured in spinal cord homogenates from rabbits with aluminum‐induced neurofibrillary degeneration and a group of salinetreated, age‐matched controls. All Aluminum ‐treated animals showed neurofibrillary changes in the spinal cord, but CAT and AChE activities were not significantly different from levels in control animals. These results are at variance with the greatly reduced activity of these enzymes observed in Alzheimer disease and senile dementia of the Alzheimer type.
Treatment of myoclonus with l‐5‐hydroxytryptophan and carbidopa: Clinical, electrophusiological, and biochemical observations
Authors: Thal Leon J. , Sharpless Nansie S. , Wolfson Leslie , Katzman Robert 
Published: January 2005

AbstractSix patients with myoclonus of varying cause were treated with L‐5‐hydroxytryptophan (L‐5‐HTP) and carbidopa. While spontaneous myoclonus decreased in three of the patients and action myoclonus in four, only two patients had marked functional improvement. Side effects included gastrointestinal and affective disturbances. L‐5‐HTP therapy caused a diminished frequency of paroxysmal discharges in the electroencephalograms of three patients which did not always correlate with clinical improvement. Lumbar cerebrospinal fluid 5‐hydroxyindoleacetic acid (5‐HIAA) concentration after probenecid was decreased in all patients prior to therapy, but this reduction did not predict treatment response. Urinary excretion patterns for 5‐HTP, serotonin, and 5‐HIAA during treatment were similar in responders and nonresponders. It is concluded that while some patients with myoclonus do benefit from L‐5‐HTP therapy, biochemical and electrophysilogical tests are not useful predictors of treatment response, and the high incidence of side effects limits the usefulness of this therapy.
Barrier mechanisms for neurotransmitter monoamines and their precursors at the blood‐brain interface
Authors: Hardebo Jan Erik , Owman Christer 
Published: January 2005

AbstractThe integrity of the endothelial cell lining of the cerebrovascular bed constitutes a morphological blood‐brain barrier mechanism to neurotransmitter monoamines. Circulating monoamines are prevented from entering the brain primarily at the luminal membrane of the endothelial lining. The small percentage of amines that may pass this membrane is deaminated within the endothelial cells and pericytes of brain microvessels (capillaries, venules, and small veins) and, in the case of large parenchymal and pial vessels, in the smooth muscle layers, where Omethylation also takes place. In the choroid plexus a corresponding deamination and O‐methylation takes place in the epithelial cells. The presence of these enzymes constitutes a further, enzymatic, blood‐brain barrier in the brain vessels for these monoamines. The monoamine precursors L‐3,4‐dihydroxyphenylalanine (L‐dopa) and L‐5‐hydroxytryptophan readily pass from the luminal endothelial cell membrane but are trapped by another enzymatic barrier mechanism. Within the endothelial cells and pericytes of the microvasculature, these compounds are decarboxylated to their corresponding amines and then immediately deaminated. One clinical implication of these enzymatic barrier mechanisms is the use of decarboxylase and monoamine oxidase inhibitors as adjuncts to L‐dopa treatment of Parkinson disease; these substances facilitate the entry of L‐dopa into brain and thus increase the amount of dopamine available at receptor sites. A brief hypertensive or hypertonic stimulus can transiently open the blood‐brain barrier through an effect on endothelial cell linings. High circulating concentrations of monoamines can also open the morphological barrier, but probably only indirectly by inducing an acute rise in systemic blood pressure. Once the barrier is open, systemically administered monoamines enter the brain parenchyma, where they can induce pronounced changes in cerebral blood flow and metabolism.
Sodium valproate and bone marrow suppression
Authors: Smith F. R. , Boots M. 
Published: January 2005

AbstractBone marrow suppression developed in a patient while she was on a regimen of sodium valproate. In addition, she had high titers of platelet autoantibodies and a coagulopathy, both recognized complications of valproate therapy. It is postulated that this drug was also responsible for the marrow suppression.
Long‐term cerebral effects of small doses of X‐irradiation in childhood as manifested in adult visual evoked responses
Authors: Yaar I. , Ron E. , Modan M. , Peretz H. , Modan B. 
Published: January 2005

AbstractIn Israel between the years 1949 and 1960, approximately 20,000 children ranging from 1 to 15 years of age were irradiated for eradication of tinea capitis. Radiation to the cerebral hemispheres ranged up to 140 rads. Of those treated, now adults, 44 subjects were elected by stratified sampling for recording and analysis of visual evoked responses (VERs). A control group of 57 subjects similar in age and ethnic origin was chosen. Two occipital leads, a right and a left, were recorded by the international 10–20 system. Fifty responses to diffuse white‐flash stimulation were averaged in each case. The first 256 msec (data points) of each VER were reduced to 77 variables by repeated averaging over three adjacent data points; these variables were then analyzed by several statistical methods.The analyses detected significant differences between the VER averages in study subjects compared with controls. These differences may reflect delayed, probably permanent functional damage to the central nervous system caused by small doses of x‐radiation (XR) to immature normal human brain. The left hemispheres appeared to be more involved, consistent with the fact that these children received, on the average, more XR to the left side of the brain, as was shown in simulated phantom models. This disparity is reflected in a greater degree of difference between the left VERs of the irradiated versus control group. The major differences between the VERs occurred in the first part of the secondary response and suggest possible subcortical involvement. The results strengthen previous evidence of potential hazards of XR in children.
Long‐term neurological implications of somnolence syndrome in children with acute lymphocytic leukemia
Authors: Ch'ien Lawrence T. , Aur Rhomes J. A. , Stagner Shirley , Cavallo Katie , Wood Adynel , Goff John , Pitner Samuel , Omar Hustu H. , Seifert M. J. , Simone Joseph V. 
Published: January 2005

AbstractA longitudinal study of 49 children with acute lymphocytic leukemia (ALL) assessed the long‐term effects of central nervous system (CNS) prophylaxis on brain function. From 10 to 12 electroencephalograms (EEGs) were done before and at intervals during and after 30 months of treatment that included 2,400 rads of CNS irradiation plus intrathecal methotrexate therapy. None of the children had CNS leukemia, and all remained in first complete remissions. All 49 had abnormally slow EEG background frequencies during the four‐year study, and 29 (60%) developed somnolence syndrome six to eight weeks after CNS prophylaxis. During this syndrome, EEG background frequencies decreased more than 3 standard deviations below the expected mean values for normal children. Thereafter, 7 of the 29 began to show signs of learning disabilities and 7 developed recurrent seizures. Of the 20 children who did not have the syndrome, none showed later evidence of CNS dysfunction. Somnolence may be an early indicator of long‐term neurological sequelae after cranial irradiation.
The dissociation of cerebral blood flow, metabolism, and function in the early stages of developing cerebral infarction
Authors: Kogure K. , Busto R. , Schwartzman R. J. , Scheinberg P. 
Published: January 2005

AbstractTemporal and site correlation of local cerebral blood flow (l‐CBF), tissue redox state, energy metabolism, tissue pH, and cerebral electrophysiological activity in induced cerebral ischemia was performed in rats in an effort to obtain helpful clues for the management of occlusive cerebrovascular disease. CBF decreased acutely in both the embolized and nonembolized hemispheres but returned toward normal in 5 minutes. However, total cerebral oxidative metabolism remained depressed throughout the 30‐minute observation period despite improved perfusion. The change in CBF correlated with the development and resolution of tissue acidosis, which was maximal 3 minutes after embolization but became alkaline after 30 minutes, possibly due to accumulation of sodium lactate. Oxidized form of nicotinamide‐adenine dinucleotide and cytochrome a,a3 quickly became reduced in the ischemic core, but a tardy, spontaneous postischemic tissue perfusion resulted in their hyperoxidation. The CBF‐metabolism uncoupling as well as postischemic hyperoxidation of the electron transport system, which is associated with accumulation of pyruvate and lactate, probably resulted from stagnation of electron flow at the entrance to the mitochondrial respiratory processes. Seizures could not account for these results, as paroxysmal changes in the EEG usually appeared only in the nonembolized hemisphere and were not dependent upon lack of energy.These studies confirm that metabolic failure may persist in ischemic tissue despite adequate reperfusion, which may, in fact, contribute to tissue damage through hyperoxidation.
Cerebral asymmetry and verbal intellectual deficits
Authors: Rosenberger Peter B. , Hier Daniel B. 
Published: January 2005

AbstractIn a group of 53 children and young adults with learning disability, reversed cerebral asymmetry as measured by CT scan correlated highly with the prevalence, and to some extent with the degree, of verbal intellectual deficit as measured by age‐appropriate Wechsler Intelligence Scales. A history of delayed speech also correlated with reversed asymmetry but was not associated with a greater degree of verbal intellectual deficit among the reversedasymmetry cases.
Membrane studies in Huntington's disease: Steady‐state fluorescence studies of intact erythrocytes
Authors: Pettegrew Jay W. , Nichols John S. , Malcolm Stewart R. 
Published: January 2005

AbstractRecent evidence suggests that a membrane abnormality may be present in Huntington's disease (HD), including peripheral tissues such as erythrocytes. Steady‐state fluorescence spectroscopy was performed on intact erythrocytes from patients with HD and from normal age‐ and sex‐matched controls. Fluorescent probes with known specificity for certain membrane areas were used to survey membrane dynamics; these probes included fluorescamine, which binds to primary amines on the cell surface, and both 12(9)‐anthroyl stearate, 12(9)AS, and 2(9)‐anthroyl stearate, 2(9)AS, which insert at different depths in the hydrocarbon core of membranes.In the intact HD erythrocyte, fluorescamine revealed decreased polarization, 12(9)AS showed increased polarization, and 2(9)AS showed no difference as compared to normal erythrocytes. These studies suggest that fluorescamine, attached to primary amines of the cell surface in intact HD erythrocytes, has increased rotational mobility whereas the anthroyl moiety of 12(9)AS in the hydrocarbon interior has decreased rotational mobility. These studies thus support the concept of a membrane abnormality in HD.
Occipital horn asymmetry in children
Authors: Strauss Esther , Fitz Charles 
Published: January 2005

AbstractIn 75 young neurological patients ranging in age from 5 months to nearly 18 years, the left occipital horn was longer than the right in 29 instances whereas the right was longer than the left in only 13 cases (p < 0.025). Elongations of the right occipital horn as well as symmetrical horns were associated with cerebral damage incurred prior to the end of the first year of life (p = 0.06).
Sydenham's chorea: A possible presynaptic dopaminergic dysfunction initially
Authors: Naidu Sakkubai , Narasimhachari N. 
Published: January 2005

AbstractA 10‐year‐old white girl showed chorea with elevated antibody titers indicative of an earlier group A streptococcal infection. Prior to treatment, cerebrospinal fluid homovanillic acid levels were markedly elevated. Haloperidol caused minimal improvement. She was then treated with reserpine alone, which resulted in remarkable improvement within one week. A repeat lumbar puncture one month after reserpine was started showed moderate reduction of homovanillic acid levels. When reserpine was discontinued, symptoms recurred. The data suggest presynaptic dopaminergic overactivity.
Meningeal gliomatosis: A review of 12 cases
Authors: Yung Wai‐Kwan A. , Horten Bruce C. , Shapiro William R. 
Published: January 2005

AbstractDiffuse or multifocal invasion of the leptomeninges by malignant glioma (meningeal gliomatosis) is believed to be rare. From 1971 through 1977, 11 of 52 patients with intracranial malignant gliomas examined at autopsy were found to have meningeal gliomatosis, and 1 additional patient was diagnosed clinically without autopsy (12 cases total). Eight of the 12 patients were diagnosed antemortem with positive cerebrospinal fluid (CSF) cytology, while the other 4 patients were diagnosed at autopsy only. All 11 autopsied patients had multifocal or diffuse meningeal tumor distant from the primary site; 8 patients had spinal subarachnoid seeding with tumor encroachment of cauda equina and spinal nerve roots, and 9 patients had tumor invasion into the lateral ventricles. Three patients had symptomatic spinal cord compression at the thoracic or lumbar level, and 10 patients had hydrocephalus.These 12 patients with meningeal gliomatosis were compared with the other 41 autopsied malignant glioma patients without the complication (controls); the patients with meningeal gliomatosis were significantly younger (mean age, 40 versus 57 years; p < 0.005). Patients with meningeal gliomatosis lived somewhat longer (median, 49 weeks) compared to controls (35 weeks), but the difference was not statistically significant. With the advance of chemotherapy, patients with malignant glioma are living longer and the incidence of meningeal gliomatosis may rise. The diagnosis of meningeal gliomatosis can be suspected, especially if hydrocephalus is present, and can often be confirmed by CSF cytology.
Analysis of leukocyte adherence to measles‐infected cells in multiple sclerosis
Authors: Barna B. P. , Goren H. , Jacobs B. , Conomy J. , Deodhar S. D. 
Published: January 2005

AbstractAn assay for leukocyte adherence to measles‐infected cells (MIC) was evaluated in 56 patients with multiple sclerosis (MS), 37 normal subjects, 29 patients with nonneurological diseases, and 57 patients with other neurological diseases. In the assay, rosettes were formed consisting of three or more leukocytes adherent to one MIC. Two aspects of the rosetting phenomenon were analyzed: (1) quantity of rosettes and (2) quantity of leukocytes contained in the rosettes. By both criteria significant differences (p < 0.05) were observed between MS patients and subjects in other groups, but data sets overlapped extensively. Results in MS patients were variable; some MIC lines produced more leukocyte adherence than did others, even though all lines had surface measles antigen present. A low ENgree of leukocyte adherence to uninfected cell lines was also observed frequently in MS. Exposure of MS leukocytes to extracts of MIC or oligodendrolioma tissue prior to the rosette assay significantly (p < 0.05) ENcreased rosette formation. These data suggest that leukocyte adherence to target cells in MS is partially dependendent on target cell expression of ENterminants, which may resemble glial antigens.
Essential tremor treated with propranolol: Lack of correlation between clinical effect and plasma propranolol levels
Authors: Sørensen Per Soelberg , Paulson Olaf B. , Steiness Eva , Jansen Erik C. 
Published: January 2005

AbstractFive patients with essential tremor were treated with increasing daily doses of propranolol. Tremor intensity was assessed after each propranolol dose had been given daily for a period of at least seven days. The evaluation was made 12 to 15 hours after the last propranolol ingestion. It include a semiquantitative clinical tremor evaluation and quantitative registration with an accelerometer. Electronic integration of the accelerometer curves gave an arbitrary measure of tremor intensity. Plasma propranolol concentration was determined at each tremor measurement.The reduction in tremor correlated with increasing propranolol doses, whereas plasma propranolol concentrations varied among individuals and could not be correlated with tremor reduction. Most of the patients had considerable diminution in tremor at low propranolol doses, often with an unmeasurable plasma propranolol concentration.Determination of plasma concentrations has little value in long‐term treatment of essential tremor with propranolol. The dosage can be sufficiently guided by clinical evaluation of effect.
Parkinsonism provoked by alcoholism
Authors: Carlen P. L. , Lee M. A. , Jacob M. , Livshits O. 
Published: January 2005

AbstractSeven chronic alcoholics, aged 53 to 70, ENmonstrated transient signs of parkinsonism provoked by alcohol withdrawal or chronic severe intoxication. All showed improvement or recovery when they abstained or ENcreased their alcohol intake for several days to weeks. Animal studies have ENmonstrated impaired striatal dopaminergic function during severe ethanol intoxication or withdrawal. Chronic alcoholism apparently can exacerbate or uncover latent central dopaminergic ENficiency.