PubMed HealthSearch

Biomedical subjects

M J Cook

Publications and source records attributed to M J Cook.

At least 19 recordsLinked to original sources

Hippocampal atrophy is not a major determinant of regional hypometabolism in temporal lobe epilepsy.

PURPOSE: The pathophysiologic basis for the [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) temporal lobe hypometabolism in patients with hippocampal sclerosis (HS) is uncertain. We tested the hypothesis that hippocampal atrophy, which is strongly correlated with hippocampal cell loss, is largely responsible for the regional hypometabolism in HS. METHODS: Regions of interest (ROIs) on FDG-PET scanning were determined in the medial, lateral, and posterior temporal lobe, thalamus, and basal ganglia. A right/left asymmetry index for each ROI was calculated. These results were correlated with hippocampal magnetic resonance imaging (MRI) volume ratios. RESULTS: There was no correlation between the magnitudes of the FDG-PET asymmetry index and the MRI volume ratio for the mesial or lateral temporal regions (r = -0.09, r = -0.04). When the right/left asymmetry index was compared with the right/left hippocampal volume ratio, correlations for the mesial temporal ROI (r = 0.79, p < 0.0001) and lateral temporal ROI (r = 0.57, p < 0.0005) were found. These, however, simply indicated that both tests accurately reflect the side of the epileptogenic region. The concordance of the side of relative hypometabolism of the FDG-PET with the side of the hippocampal atrophy was higher for the mesial temporal region (100%) than for the lateral (77.5%). CONCLUSIONS: The lack of correlation between the magnitudes of the ratios argues against hippocampal atrophy and cell loss having a central role in the FDG-PET temporal hypometabolism.

Adult

Reliability of visual inspection for detection of volumetric hippocampal asymmetry.

Volumetric measurement of the hippocampus is of use in localisation of lesions causing focal epilepsy and in lateralisation of epilepsy due to mesial temporal sclerosis. However, it is time consuming and requires specialised equipment. Hence, we compared volumetric measurement with visual detection of hippocampal asymmetry by five trained observers. MRI studies of 19 neurologically normal subjects and of 34 consecutive patients with epilepsy and hippocampal volume ratios below the lowest normal value were employed. Agreement between visual and quantitative diagnoses was 59% for all subjects (kappa = 0.38) and 65% for those with volumetric hippocampal asymmetry. Disagreements in visual and volumetric lateralisation of hippocampal asymmetry were relatively uncommon. Visual estimates of the extent of hippocampal involvement and the observers' confidence in the diagnosis influenced the accuracy of visual inspection. However, discordance in diagnoses occurred even when confidence in the visual diagnosis was high. Reliable visual detection occurred for hippocampal volume ratios below 0.7, suggesting that visual determination of hippocampal asymmetry is of greatest clinical value in the lateralisation of seizure foci in patients already selected for the presence of intractable temporal lobe epilepsy. Volumetric measurements are particularly important if hippocampal asymmetry is used for seizure localisation in groups of patients with temporal or extratemporal epilepsy.

Adolescent

Fetal and maternal endocrine responses to experimental intrauterine infection in rhesus monkeys.

OBJECTIVE: Our purpose was to describe the temporal and quantitative relationships among intrauterine infection, fetal-placental steroid biosynthesis, and preterm labor in a nonhuman primate model. STUDY DESIGN: On approximately day 130 of gestation (term 167 days) chronically instrumented rhesus monkeys (Macaca mulatta) were infected with 10(6) colony-forming units of group B streptococci either by intraamniotic (n = 4) or choriodecidual (n = 2) inoculation. As controls, four additionally chronically instrumented noninfected monkeys were followed up to spontaneous parturition. Amniotic fluid and maternal and fetal arterial blood were serially sampled in all monkeys (both before and after infection) for progesterone, estrone, estradiol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and cortisol by specific radioimmunoassays, and uterine activity was continuously recorded. RESULTS: Spontaneous parturition was preceded by gradual and significant increases in the plasma concentrations of fetal dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione and fetal and maternal levels of estrone, estradiol, and progesterone but not by changes in cortisol. In contrast, infection-associated parturition (either intraamniotic or choriodecidual) was characterized by abrupt increases in fetal dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, progesterone, and cortisol but not by increases in maternal or fetal estrone or estradiol. Infection-associated steroid changes occurred concurrently with or after increases in uterine activity. CONCLUSION: Infection-associated preterm parturition is associated with dramatic increases in fetal adrenal steroid biosynthesis but not by corresponding increases in placental estrogen biosynthesis. This suggests that fetal stress in accompanied by placental dysfunction and that infection-associated parturition is not dependent on the increased estrogen biosynthesis observed in spontaneous parturition.

Androstenedione

Tumour-localising and -photosensitising properties of a novel zinc(II) octadecylphthalocyanine.

1,4,8,11,15,18,22,25-Octadecylphthalocyaninato zinc(II), ZnODPc, incorporated into a Cremophor emulsion, was assayed for its pharmacokinetic and phototherapeutic properties in Balb/c mice bearing an intramuscularly transplanted MS-2 fibrosarcoma. The phthalocyanine was injected intravenously (i.v.) in three doses, i.e. 1.46, 0.73 and 0.37 mumol kg-1 body weight. In all cases, the octadecyl-substituted phthalocyanine showed an unusually high affinity for serum low-density lipoproteins (LDLs) and a high efficiency and selectivity of tumour targeting: the maximum accumulation in the tumour occurred at 24 h after injection, whereas no detectable amount of phthalocyanine was recovered from the muscle, i.e. the peritumoral tissue, between 1 h and 1 week after injection. At the same time, low amounts of phthalocyanine were recovered from skin and then only at short times after injection, with skin photosensitivity rapidly disappearing and the phthalocyanine present in the serum only. Tumour photosensitisation studies were carried out at 24 h after administration of 1.46 mumol kg-1 ZnODPc and showed that this phthalocyanine has a very high phototherapeutic efficiency; this is probably a consequence of the multiple mechanisms by which the phthalocyanine induces tumour damage, involving both direct modification of malignant cells and impairment of blood flow, as well as the alteration of a variety of subcellular components, such as mitochondria, the rough endoplasmic reticulum, the perinuclear membrane and, occasionally, cell nuclei. Tumour necrosis appears to be the consequence of both random cell death and apoptosis.

Animals

Temporal lobe epilepsy caused by mesial temporal sclerosis and temporal neocortical lesions. A clinical and electroencephalographic study of 46 pathologically proven cases.

This study aims to determine whether there are important clinico-electrical differences between patients with temporal lobe epilepsy (TLE) secondary to mesial temporal sclerosis (MTS) and those with TLE secondary to a discrete temporal neocortical lesion (NL). The case histories, interictal EEG, seizure semiology, ictal EEG and postoperative outcome of 46 pathologically proven patients (31 MTS and 15 NL) were compared. A history of febrile convulsions (FC) was more common in MTS patients (58% versus 26%, P < 0.05), as was a history of a significant cerebral event at < 4 years of age (22% versus 0%, P < 0.05). There were no statistically significant differences in the incidence or nature of auras. No statistically significant differences between the groups were found in the interictal-EEG. With ictal semiology dystonic posturing occurred more frequently in MTS patients (mean 52% versus 26%, P < 0.05). Facial grimacing/ twitching occurred earlier in the seizures of NL patients (median 19 s versus 35 s, P < 0.05). There was an increased frequency of fast rhythmic sharp waves (> 4 Hz) in the ictal-EEG of MTS patients (mean 81% versus 60%, P = 0.05). The patients with NL developed bilateral ictal EEG changes more often (mean 55% versus 26%, P < 0.05) and more rapidly (mean 23 s versus 74 s, P < 0.005). The onset of ictal EEG seizure activity was bilateral more often in patients with NL (20% versus 4%, P < 0.005). There were no significant differences between the two groups for any of the video-EEG features, in terms of whether or not the feature occurred at least once in an individual patients. There was a tendency for MTS patients to have a higher seizure-free postsurgical outcome (87% versus 60%, P = 0.057). However, all the NL patients who were not free of seizures had had an incomplete lesion resection. We conclude that there are a number of clinico-electrical differences between patients with mesial TLE (MTLE) and patients with neocortical TLE (NCTLE), but that none of these are sufficient to allow a distinction to be made in an individual patient.

Adolescent

Tooth-brushing epilepsy: a report of a case with structural and functional imaging and electrophysiology demonstrating a right frontal focus.

Patients with reflex epilepsies may provide insights into cerebral pathophysiology. We report a patient with an unusual form of reflex epilepsy in whom seizures are induced by tooth brushing. Magnetic resonance imaging (MRI) demonstrated a right posterior frontal low-grade tumor predominantly involving the precentral gyrus. Video-telemetry demonstrated right-sided epileptiform activity during a typical induced complex partial seizure. An ictal single photon emission computed tomography (SPECT) scan showed an area of hyperfusion that corresponded to the MRI lesion on coregistration with a surface-matching technique. A subsequent coregistered interictal SPECT scan demonstrated hypoperfusion in the same region. Ours is the first report to demonstrate a structural focus in this unusual form of reflex epilepsy. Possible mechanisms to explain the induction of the seizures are discussed.

Adult

Epilepsy in the nevoid basal-cell carcinoma syndrome (Gorlin syndrome): report of a case due to a focal neuronal heterotopia.

We present a case of uncontrolled temporal lobe epilepsy due to a focal left temporal neuronal heterotopia associated with the nevoid-basal-cell carcinoma syndrome. This is the first pathologically described lesion associated with temporal lobe epilepsy in this syndrome. Because the patient's seizures resolved after a modified left anterior temporal lobectomy, this case illustrates that epilepsy in patients with the nevoid basal-cell carcinoma syndrome is potentially curable and should be investigated appropriately.

Adolescent

Neuroticism and sense of coherence.

The relationship of scores on sense of coherence with measures of personality traits was assessed using the 29-item Orientation to Life Questionnaire and the Eysenck Personality Inventory. In one group of 95 mixed-sex students scores on Neuroticism bore a highly negative relationship with scores on sense of coherence. Findings support the current literature that health questionnaires may indirectly measure Neuroticism and that personality variables play an important role in general health.

Autonomic Nervous System

Octa-alkyl zinc phthalocyanines: potential photosensitizers for use in the photodynamic therapy of cancer.

The synthesis, characterization and electronic spectra of a series of nine 1,4,8,11,15,18,22,25-octa-alkyl zinc phthalocyanines (ZnPc), potential photosensitizers for the photodynamic therapy of cancer, are described. The substituents on the phthalocyanine (Pc) macrocycle "red-shift" the absorbance maximum, in cyclohexane, of all nine members of this series to a value of 703 +/- 2 nm, with a corrected fluorescence emission maximum for the octadecyl derivative of 715 nm. The solubilities and degree of aggregation of six examples in cyclohexane have been measured. The highest homologue, the octadecyl derivative, remains essentially unaggregated to a concentration of 1.5 x 10(-4) mol dm-3. the photostability of this Pc has been examined and the compound shown to be sensitive to photooxidation processes which lead to its decomposition to 3,6-bis-decylphthalimide. Known singlet oxygen quenchers inhibit the photodecomposition. In a comparative study, the octadecyl ZnPc underwent a more rapid photodecomposition than the corresponding metal-free derivative.

Indoles

Fractal description of cerebral cortical patterns in frontal lobe epilepsy.

The convoluted pattern of normal cerebral cortex resists description by Euclidean geometry. However, subtle abnormalities often unrecognised in vivo may underlie a wide range of neurological disorders. Abnormalities of cortical morphology frequently characterise these lesions, and we applied fractal geometry in an attempt to quantify these abnormalities. We have demonstrated typical fractal scaling properties for the cortical-white matter interface on axial and coronal MR images, with a fractal dimension (Df) of 1.45 +0.06 (mean +1 standard deviation) in normal subjects. We have also applied this to 16 patients with frontal lobe epilepsy, a condition associated with subtle disruptions of the cortical ribbon, all of whom had no obvious abnormality on visual inspection of the images. Nine of these 16 had a Df < 1.27 (mean -3 standard deviations). A control group of 10 patients with temporal lobe epilepsy with a focal foreign tissue lesion (vascular or tumoural) all had Df in the normal range. Analysis of shape using this method identifies subtle abnormalities of the cortical ribbon, and has potential application to images of the human brain in a wide range of clinical and pathophysiological settings.

Adolescent

Frequency and characteristics of dual pathology in patients with lesional epilepsy.

We studied 167 patients who had identifiable lesions and temporal or extratemporal partial epilepsy. Pathology included neuronal migration disorders (NMDs) (48), low-grade tumors (52), vascular malformations (34), porencephalic cysts (16), and gliotic lesions as a result of cerebral insults early in life (17). MRI volumetric studies using thin (1.5- or 3-mm) coronal images were performed in all patients and in 44 age-matched normal controls. An atrophic hippocampal formation (HF), indicating dual pathology, was present in 25 patients (15%). Abnormal HF volumes were present in those with lesions involving temporal (17%) but also extratemporal (14%) areas. Age at onset and duration of epilepsy did not influence the presence of HF atrophy. However, febrile seizures in early childhood were more frequently, although not exclusively, found in patients with hippocampal atrophy. The frequency of hippocampal atrophy in our patients with low-grade tumors (2%) and vascular lesions (9%) was low. Dual pathology was far more common in patients with NMDs (25%), porencephalic cysts (31%), and reactive gliosis (23.5%). Some structural lesions, such as NMDs, are more likely to be associated with hippocampal atrophy, independent of the distance of the lesion from the HF. In other types of lesions, such as vascular malformations, dual pathology was found when the lesion was close to the HF. A common pathogenic mechanism during pre- or perinatal development may explain the occurrence of concomitant mesial temporal sclerosis and other structural lesions because of either (1) associated developmental abnormalities or (2) predisposition to prolonged febrile convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Methods for normalization of hippocampal volumes measured with MR.

PURPOSE: To investigate the use of six cerebral measures as correlates for hippocampal volumes and, therefore, to enable normalized absolute hippocampal volumes to be calculated via two correction processes. METHODS: Hippocampal volumes and six cerebral measures were estimated from MR data in 20 control subjects. Three of these measures (the cranial volume, the cerebral volume, and the midsagittal cranial area) were then applied to a group of 32 control subjects, and regression analysis was performed to investigate the linear relationship between hippocampal volume and each measure. Division of hippocampal volume by cerebral measure and correction via a covariance calculation enabled corrected absolute hippocampal volumes to be determined for 32 control subjects and 23 patients with temporal lobe epilepsy. RESULTS: Correction processes reduced the variance in absolute hippocampal volumes in control subjects and enabled abnormally small absolute volumes to be defined. Of 11 patients with unilateral volume ratio abnormalities, 8 had unilateral abnormally small absolute hippocampal volumes. Of 12 patients with normal volume ratios, 4 had bilateral abnormally small absolute hippocampal volumes. CONCLUSION: Correction processes can define absolute hippocampal volumes for correlation studies and may enable identification of unsuspected bilateral hippocampal volume loss.

Adult

Estimation of resection volumes in lesional epilepsy surgery.

An MR-based method for measuring resection volumes in lesional epilepsy surgery is described. The volume of the preoperative lesion, the resection cavity and, as a result, the volume of the brain surrounding the lesion resected during surgery have been calculated in 13 patients.

Adolescent

An experimental model for intraamniotic infection and preterm labor in rhesus monkeys.

OBJECTIVE: Our purpose was to describe the temporal and quantitative relationship between intraamniotic infection and preterm labor in a nonhuman primate model. STUDY DESIGN: On day 130 of gestation (term 167 days) four chronically instrumented rhesus monkeys (Macaca mulatta) were infected with an intraamniotic inoculation of 10(6) colony-forming units of group B streptococci. Four additional noninfected monkeys were followed up to spontaneous parturition as controls. Amniotic fluid was serially sampled in all monkeys both before and after inoculation for bacterial growth, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, prostaglandin E2, and prostaglandin F2 alpha, and uterine activity was continuously recorded. RESULTS: Increases in uterine contractility occurred 28 hours (range 14 to 40 hours) after inoculation and were preceded by increases in amniotic fluid cytokines and prostaglandins. Intraamniotic concentrations of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta all rose dramatically 9, 15, and 18 hours after infection and 10 to 20 hours before increases in uterine contractility. In spontaneous parturition only interleukin-6 concentrations rose moderately (from 0.1 to 1.2 ng/ml). Increases in prostaglandin E2 and prostaglandin F2 alpha paralleled those of the cytokines. Peak prostaglandin concentrations in intraamniotic infection exceeded by severalfold concentrations seen in spontaneous parturition (16,046 pg/ml vs 2765 pg/ml for prostaglandin E2, p < 0.05; and 5547 pg/ml vs 708 pg/ml for prostaglandin F2 alpha, p < 0.05). In spite of intraamniotic none of the monkeys were febrile or had peripheral leukocytosis at the onset of labor. CONCLUSION: In the rhesus monkey, after intraamniotic infection, there is a predictable and sequential increase in amniotic fluid tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, followed by increases in prostaglandin E2 and prostaglandin F2 alpha. These increases all occur before an increase in uterine contractility and before clinical signs of infection. Our data provide evidence for a cause-and-effect relationship between intraamniotic infection and preterm labor and support the utility of measuring interleukin-6 or other cytokines in the diagnosis of intraamniotic infection.

Amnion

Dysembryoplastic neuroepithelial tumor. Features in 16 patients.

Dysembryoplastic neuroepithelial tumour (DNT) is a newly recognized brain mass lesion with distinctive pathological features and a favourable prognosis. We reviewed the clinical, electroencephalographic, neuroimaging and pathological features of 16 patients with DNT who underwent surgery; only one patient did not have epilepsy. Mean age at seizure onset was 9.5 years (range: 1 week to 30 years) and surgery 17 years (range: 7 months to 37 years). The mean verbal IQ was 94.6 (range: 79-110) and performance IQ 105 (range: 79-130) (n = 10). The EEG was abnormal in all cases reviewed (n = 13): localized slow activity was seen in 12 and interictal spiking in 10 patients, being less extensive than or concordant with the lesion in three and more extensive than or distant to the lesion in seven. X-ray CT was normal in three out of 11 patients. Magnetic resonance imaging provided detailed anatomical information: the lesion was predominantly intracortical, although in six patients, there was also white matter involvement. The lesion involved the temporal lobe in all but one patient where it was in the cingulate gyrus. Of the temporal lobe cases, MRI showed that the lesion involved, or was in close proximity to, mesial temporal structures in 11 out of 14 patients. Other magnetic resonance features included: circumscribed hyperintensity on long TE/TR images (10 patients), hypointensity on short TR images (12 patients), and cyst formation (five patients). Calcification was seen on CT in four patients. Post surgical follow-up ranged from 8 to 30 months (mean 16.2 months): 12 patients are seizure free and two have a > 80% reduction in seizure frequency (n = 14). Histopathological characteristics included a heterogeneous composition in all cases, calcification (13 cases), dysplastic features (12 cases) and isolated foci of subpial spread (five cases). The presence of occasional mitoses in 12 cases and immunoreactivity to the proliferating cell nuclear antigen in six cases indicate that these lesions have cellular proliferative activity and that there may be a need to follow these patients postoperatively.

Adolescent

Prostaglandin production during spontaneous labor and after treatment with RU486 in pregnant rhesus macaques.

The production of prostaglandins from amnion, chorion, decidua, and myometrium was studied in a superfusion system to determine the level of prostaglandin production during late pregnancy, during spontaneous labor, and after in vivo treatment with RU486. Tissues were divided into three groups: those from pregnant control animals, those from animals receiving RU486 (20 mg/kg/day for 3 days) in vivo, and those from animals in spontaneous term labor. Tissues were collected at cesarean section and placed in the superfusion system. After a 30-min equilibration period, fractions of media were collected after passing through the tissue chambers and were assayed for prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2). The results showed a significant increase in PGF2 alpha from decidua of animals treated with RU486 compared to pregnant controls (pregnant: 3.01 +/- 0.45 ng/g/min; RU486: 4.45 +/- 0.28 ng/g/min; p < 0.05). There was a dramatic increase in PGE2 production by amnion from animals in spontaneous labor but not after RU486 treatment (pregnant: 0.21 +/- 0.06 ng/g/min; RU486: 0.56 +/- 0.09 ng/g/min; spontaneous labor: 5.83 +/- 0.43 ng/g/min; p < 0.01). We conclude that while progesterone is important for maintaining uterine quiescence during pregnancy, progesterone receptor blockade by RU486 does not lead to an increase in PGE2 production by amnion as is shown during normal spontaneous labor.

Amnion