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Background: 11C-flumazenil (FMZ) positron emission tomography (PET) is a new entrant into the armamentarium for pre-surgical evaluation of patients with intractable temporal lobe epilepsy (TLE)., Aims: To analyze the clinical utility of FMZ PET to detect lesional and remote cortical areas of abnormal benzodiazepine receptor binding in relation to magnetic resonance imaging (MRI), 2-Deoxy-2 [18F] fluoro-D-glucose, (18F FDG) PET, electrophysiological findings and semiology of epilepsy in patients with intractable TLE., Materials and Methods: Patients underwent a high resolution MRI, prolonged Video-EEG monitoring before 18F FDG and 11C FMZ PET studies. Regional cortical FMZ PET abnormalities were defined on co-registered PET images using an objective method based on definition of areas of abnormal asymmetry (asymmetry index {AI}>10%)., Settings and Design: Prospective., Statistical Analysis: Student's "t" test., Results: Twenty patients (Mean age: 35.2 years [20-51]; M:F=12:8) completed the study. Mean age at seizure onset was 10.3 years (birth-38 years); mean duration, 23.9 years (6-50 years). Concordance with the MRI lesion was seen in 10 patients (nine with hippocampal sclerosis and one with tuberous sclerosis). In the other 10, with either normal or ambiguous MRI findings, FMZ and FDG uptake were abnormal in all, concordant with the electrophysiological localization of the epileptic foci. Remote FMZ PET abnormalities (n=18) were associated with early age of seizure onset (P=0.005) and long duration of epilepsy (P=0.01)., Conclusions: FMZ-binding asymmetry is a sensitive method to detect regions of epileptic foci in patients with intractable TLE.

Numerous functional neuroimaging techniques have progressively been added to the presurgical evaluation of refractory partial epilepsies. These investigations can help confirm the origin of seizure onset previously suggested by MR imaging and electro-clinical data, provide independent prognostic information, and provide critical diagnostic value when MR imaging results are strictly normal or show multifocal abnormalities. Of the various functional neuroimaging modalities, [11C]methionine positron emission tomography for methionine uptake into seizure foci is still in the preliminary stages of investigation. A single case of medically intractable epilepsy with focal cortical dysplasia documented by [11C]methionine positron emission tomography and possible hypotheses to explain the methionine uptake into the seizure focus are described below.

Glucose 6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy of human beings and is the most common cause of jaundice and acute hemolytic anemia in South East Asia. The deficiency causes acute hemolytic anemia following ingestion of 6-amino quinoline antimalarials, phenacetin, and other substances. The rapid identification of infants or patients with this deficiency would help to prevent their exposure to these substances and subsequent risk to health. The assay is relatively simple. A 3mm punch from a dried blood spot sample is placed in a well of a black fluorescent microtiter plate containing calibrators and controls in duplicate. 100 microl of reagent is added and the sample is allowed to react for 30 minutes at ambient temperature after which 200 microl of stop reagent is added. The plate may be read immediately or up to one hour in a fluorescent reader (ex 355 nm: em 460 nm). Glutathione. ascorbate and bilirubin do not affect the assay. hemoglobin does quench the fluorescence by about 1.1 fluorescence units/g/dHb. This would not cause any false negatives and deficients would not be missed. G6PD activity in whole blood normal samples was examined at -20, 6 and 37 degrees C over 14 days. The samples lost about 20% activity after 48 hours and 31% by the end of 14 days. The samples stored at -20 degrees C and 6 degrees C remained relatively stable over this period. In a preliminary study eight diagnosed G6PD deficient samples had a mean value of 2.0 U/gHb (range 0.8 to 4.4) and fell within 3 SD units of the mean. Forty one normal samples had a mean of 6.6 micromol/min/gHb. Only one sample with a low hemoglobin level fell outside of 3 SD units of the mean. The Wallac assay was compared to the Sigma G6PD assay and although the values appeared lower at normal levels, the deficient samples compared well.

Fetuses with homozygous alpha-thalassemia 1, in which the deletion of all four alpha-globin genes results in the absence of any alpha-globin chains, are severely anemic with clinical features of hydrops fetalis. Definitive diagnosis of alpha-thalassemia 1 carriers is difficult since there are few red cell abnormalities. Recently Chui et al. found that minute amounts of embryonic zeta-globin chains are present in adult hemoglobin of the Southeast Asian type of alpha-thalassemia 1 carriers. In this study, we screened 521 cord bloods for alpha-thalassemia 1. Hemoglobin analysis, including quantitation of Hb Bart's, was performed using the automated HPLC, alpha-thalassemia short program (VARIANT, Bio-Rad, Hercules, CA). Of these, 200 cord blood samples in which Hb Bart's was demonstrated were tested for the presence of zeta-globin chains by ELISA using labeled anti-zeta monoclonal antibody. Zeta-globin ranged between 0.21 and 0.83% in 19 specimens carrying alpha-thalassemia 1 gene. In the remaining 90 out of 109 specimens in which Hb Bart's was greater than 1.2%, zeta-globin was less than 0.17%. DNA analysis revealed the presence of normal alpha-genotype and other types of alpha-thalassemia including alpha-thalassemia 2 and Hb Constant Spring. One false positive was found in which the zeta-globin was 0.25% by ELISA but in which PCR indicated an alpha-thalassemia 2 heterozygote. Ninety-one samples with Hb Bart's of less than 1.2% by HPLC are most likely normal with a zeta-globin range between 0 and 0.14%. This study also showed that the frequency of alpha-thalassemia 1 in Bangkok is 3.65%.

Monoclonal antibodies (MAB) to subsite A (25C9) and subsite D (44C11) of the S protein of transmissible gastroenteritis virus (TGEV) were used in a blocking ELISA on fixed TGEV-infected swine testis cells to differentiate sera from pigs experimentally inoculated with either TGEV or porcine respiratory coronavirus (PRCV). Serum samples were obtained from pigs at various intervals from postinoculation day (PID) 0 through at least PID 22 to 40. Eleven-day-old pigs, seronegative for TGEV-neutralizing antibodies at the time of inoculation, were inoculated orally and nasally with either the virulent Miller (M5C) strain or the attenuated Purdue (P115) strain of TGEV, or with the ISU-1 strain of PRCV. Gastroenteritis was observed in 100% of the M5C-TGEV-inoculated pigs; but clinical signs of disease were not observed in either the P115-TGEV- or PRCV-inoculated pigs. Virus-neutralization (VN) antibody titer in sera was determined by use of a plaque-reduction assay. Blocking ELISA antibody titer for subsites A and D was determined from the serum dilution that produced 50% reduction in the absorbance values when it competed with biotinylated MAB 25C9 and 44C11, respectively. In sera from the inoculated pigs, the VN antibody titer began to increase by PID 7 and reached maximum by PID 15 to 16. For pigs inoculated with TGEV M5C, subsite A and subsite D blocking antibody titers in the serum paralleled the VN antibody titer, began to increase after PID 7, and reached maximum by PID 15 to 16.(ABSTRACT TRUNCATED AT 250 WORDS)

Five monoclonal antibodies (MAbs) to porcine group (gp) C rotaviruses (Cowden and Ah strains) reactive with both gp A and C rotaviruses in cell culture immunofluorescence (CCIF) tests were produced and characterized. These MAbs reacted with three strains of gp A and two strains of gp C rotaviruses in a CCIF test and were classified into two groups based on their CCIF titers. The MAbs also reacted to various degrees with cell-culture-propagated porcine gp C rotavirus (Cowden) and bovine gp A rotavirus (NCDV) in an enzyme-linked immunosorbent assay by using the MAbs as capture antibodies. Fecal samples containing human, bovine, and porcine strains of gp A and C rotaviruses were positive when tested using one of the MAbs in this assay. The MAbs recognized VP6 of gp A rotavirus and the VP6 counterpart (41-kDa protein) of gp C rotavirus in a Western blot assay. Results of competitive binding assays on four MAbs indicated that gp A and gp C rotaviruses share three overlapping epitopes within a single antigenic domain. These results suggest that gp A and C rotaviruses share a common antigen located on the VP6 protein, which is recognized by certain MAbs in various serologic assays.

Five nonneutralizing monoclonal antibodies (MAb) generated to the virulent Miller strain of transmissible gastroenteritis virus (TGEV) and specific for the S protein were characterized. Competition assays between purified and biotinylated MAb indicated that MAb 75B10 and 8G11 mapped near a new subsite, designated V and 2 MAb, 44C11 and 45A8, mapped to a previously designated subsite D. A fifth MAb mapped between subsites V and E. These MAb were tested with 3 previously characterized MAb to subsites A, E, and F in fixed-cell ELISA and cell culture immunofluorescent assays against 5 reference and 9 field strains of TGEV and 2 US strains (ISU-1 and ISU-3) of porcine respiratory coronavirus (PRCV). Subsites A, E, and F were conserved on all TGEV and PRCV strains examined. The 2 MAb to subsite V, 8G11 and 75B10, reacted only with the Miller TGEV strains (M5C, M6, and M60), except that 75B10 also recognized field strain U328. The MAb 11H8 did not react with 4 field strains or the Purdue strains of TGEV. The 2 MAb to subsite D reacted with all TGEV strains examined, but not with 2 US PRCV strains, 2 European PRCV strains, 1 feline infectious peritonitis virus strain, and 1 canine coronavirus strain. Because of this specificity for TGEV, but not PRCV, these latter 2 subsite D MAb may be useful for the development of competition ELISA to differentiate serologically between TGEV and PRCV infections in swine, similar to the currently used European subsite D MAb.

Magnetic fields were measured with SQUID magnetometry outside the skull of anaesthetised rabbits during initiation and propagation of spreading depression (SD) in the cortex. Slowly changing fields (up to 1.4 pT) were observed during the propagation phase, from 4-8.5 min after initiation of SD with KCl application, with maxima at about 6 min. The peak amplitude of the equivalent net dipole generators in the brain was ca. 28 microA.mm, substantially less than previously observed with SD in vitro, but large enough that similar signals might be detectable in man.

Neuromagnetic signals consistent with spreading cortical depression have been observed in 9 of 12 migraine patients studied, but not in normal controls (out of 8 studied) or in patients with non-migrainous headache (4 studied). These signals consist of large amplitude, usually biphasic waveforms presumably arising from the onset or offset of spreading cortical depression in a sulcus, and prolonged attenuation of magnetic amplitudes, associated with suppressed neuronal activity. Techniques are described which recognize various kinds of artefacts and which distinguish changes in state of arousal of the patient from the presumed spreading cortical depression signals.

We report for the first time the detection by magnetoencephalography (MEG) of signals observable in migraine patients during headache, but not in controls. These signals consisted of three features: suppression of spontaneous cortical activity, long duration field changes, and large amplitude waves (LAW) of several seconds duration. LAW were also seen during the interictal period. We discuss the possible relationship of these signals to spreading depression (SD), and why the LAW have not been observed in previous studies of SD.

The epidemiological, clinical and basic science evidence for a role of estrogen in migraine is reviewed. The hypothesis is put forward that estrogen exerts its influence by modulating sympathetic control of the cerebral vasculature.

Twenty-four neurologically normal subjects, 12 in their twenties and 12 in their sixties, were included in a protocol that studied the relationship of resting cerebral blood flow and cerebral blood flow activation by neuropsychological testing to age and stroke risk factors. Both age and a stroke risk index were predictive of a reduced resting cerebral blood flow. Despite this, cerebral blood flow activation relative to resting flow was preserved. Subclinical lesions of deep white matter are proposed to explain the apparently paradoxical result that resting cerebral blood flow is decreased by factors that damage cerebral vessels, while cerebral vascular reactivity is unimpaired.