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Biomedical subjects

M J Cook

Publications and source records attributed to M J Cook.

At least 37 records · Page 2Linked to original sources
PubMed1997

Inhibition and augmentation of progesterone production during pregnancy: effects on parturition in rhesus monkeys.

OBJECTIVES: Uterine quiescence during mammalian pregnancy is attributed to progesterone. However. systemic progesterone levels remain elevated in primates before parturition. Epostane, a selective 3beta-hydroxysteroid dehydrogenase inhibitor, and progesterone (with or without epostane) were administered to late pregnant rhesus monkeys to clarify the role of progesterone in primate parturition. STUDY DESIGN: On days 122 to 132 of gestation (term 167 days), 11 rhesus monkeys (Macaca mulatta) with timed pregnancies were divided into three treatment groups: (1) epostane alone (10 mg/kg subcutaneously), (2) epostane with progesterone subcutaneously in Silastic silicone rubber capsules, and (3) progesterone implants only with no surgical instrumentation. Maternal and fetal blood and amniotic fluid were sampled for progesterone, estrone, estradiol, cortisol, testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and amniotic fluid was sampled for prostaglandins E2 and F2alpha. Uterine activity was monitored continuously by electromyography and intraamniotic pressure. Cervical status was assessed by a modified Bishop's score. Production of prostaglandins E2 and F2alpha by amnion was determined by tissue superfusion. The group of three noninstrumented monkeys, which received only progesterone Silastic silicone rubber implants subcutaneously at 146 to 148 days, were observed until spontaneous vaginal delivery. RESULTS: Epostane reduced maternal and fetal progesterone levels by 75% and 50%, respectively, followed by increased uterine activity and cervical ripening within 24 hours and vaginal delivery within 48 hours. Amniotic fluid progesterone decreased to undetectable levels. Progesterone implants prevented the epostane-induced decrease in maternal and fetal progesterone levels and the associated myometrial and cervical changes until the implants were removed. Alterations in other steroid hormones were consistent with inhibition of 3beta-hydroxysteroid dehydrogenase. Amniotic prostaglandin E2 production was increased sixfold by epostane (p < 0.05) but did not reach the high levels normally seen at spontaneous parturition. Animals that received progesterone implants alone had markedly elevated circulating progesterone concentrations yet were delivered spontaneously at term (range 163 to 167 days). CONCLUSIONS: Progesterone withdrawal induces preterm labor and delivery (which can be blocked by progesterone substitution) but exogenous progesterone, even in substantial quantities, does not prevent parturition at term.

Amniotic Fluid↗
PubMed1997

Tumour-localizing and tumour-photosensitizing properties of zinc(II)-octapentyl-phthalocyanine.

Zn(II)-octapentyl-phthalocyanine (ZnOPPc), incorporated into a Cremophor oil emulsion, was found to be a highly selective tumour-targeting agent (50-fold larger concentration in the tumour than in the peritumoral tissue) when injected at a dose of 1.46 mumol (kg body weight)-1 in Balb/c mice bearing an intramuscularly transplanted MS-2 fibrosarcoma. The pharmacokinetic properties of this phthalocyanine were closely similar to those found for the analogous octadecyl derivative, whereas the unsubstituted Zn(II)-phthalocyanine showed a lower efficiency and selectivity of tumour targeting than the octaalkyl-substituted phthalocyanines. Irradiation of the ZnOPPc-loaded tumour with 620-700 nm light 24 h after injection caused a significant delay of tumour growth with a gradual shrinkage of the neoplastic mass; the damage involved important contributions from both random necrosis and apoptosis of malignant cells.

Animals↗
PubMed1997

Quantitative MRI in outpatient childhood epilepsy.

PURPOSE: In adult studies, MRI volumetrics is a proven technique in presurgical assessment of epilepsy. Hippocampal volume loss is maximal in the syndrome of mesial temporal lobe epilepsy. We aimed (a) to validate this methodology in a pediatric outpatient epilepsy population (b) to determine the relationship of hippocampal asymmetry (HA) to epileptic syndromes and risk factors. METHODS: Two neurologists classified the epileptic syndrome in 79 pediatric outpatients, according to the International Classification of Epilepsies and Epileptic Syndromes (ILAE). Hippocampal volumetrics were performed in all patients. HA was defined according to adult control values. RESULTS: Inter-rater variability on measurement of HA was very small (Correlation of test retest of 0.97 on 17 children <3 years old). The rate of HA was 44/79 (57%). In 21 patients, (27%) potentially epileptogenic lesions (other than HA) were identified (cerebral dysgenesis n = 11). HA was present in 9/15 (60%) of temporal lobe epilepsy and in 15/28 (54%) extratemporal onset epilepsy and 5/11 (46%) of generalized symptomatic epilepsy. Analysis confined to <13 years also showed HA was not specific for epileptic syndrome. There was no significant association of febrile convulsions (13%) with HA or temporal lobe epilepsy. CONCLUSIONS: There is a high incidence of HA in childhood epilepsy. HA was not confined to clinically defined temporal lobe epilepsy. The poor correlation of epileptic syndrome to quantitative MRI findings may be due to the inadequacies of epilepsy classification in the younger child, with the clinical semiology providing misleading localizing information. Normative childhood data for hippocampal volumes and symmetry is needed.

Adolescent↗
PubMed1997

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↗
PubMed1997

Perfusion patterns in postictal 99mTc-HMPAO SPECT after coregistration with MRI in patients with mesial temporal lobe epilepsy.

OBJECTIVES: To assess patterns of postictal cerebral blood flow in the mesial temporal lobe by coregistration of postictal 99mTc-HMPAO SPECT with MRI in patients with confirmed mesial temporal lobe epilepsy. METHODS: Ten postictal and interictal 99mTc-HMPAO SPECT scans were coregistered with MRI in 10 patients with confirmed mesial temporal lobe epilepsy. Volumetric tracings of the hippocampus and amygdala from the MRI were superimposed on the postictal and interictal SPECT. Asymmetries in hippocampal and amygdala SPECT signal were then calculated using the equation: % Asymmetry =100 x (right - left) / (right + left)/2. RESULTS: In the postictal studies, quantitative measurements of amygdala SPECT intensities were greatest on the side of seizure onset in all cases, with an average % asymmetry of 11.1, range 5.2-21.9. Hippocampal intensities were greatest on the side of seizure onset in six studies, with an average % asymmetry of 9.6, range 4.7-12.0. In four scans the hippocampal intensities were less on the side of seizure onset, with an average % asymmetry of 10.2, range 5.7-15.5. There was no localising quantitative pattern in interictal studies. CONCLUSIONS: Postictal SPECT shows distinctive perfusion patterns when coregistered with MRI, which assist in lateralisation of temporal lobe seizures. Hyperperfusion in the region of the amygdala is more consistently lateralising than hyperperfusion in the region of the hippocampus in postictal studies.

Amygdala↗
PubMed1997

Surgical treatment of patients with single and dual pathology: relevance of lesion and of hippocampal atrophy to seizure outcome.

Modern neuroimaging can disclose epileptogenic lesions in many patients with partial epilepsy and, at times, display the coexistence of hippocampal atrophy in addition to an extrahippocampal lesion (dual pathology). We studied the postoperative seizure outcome of 64 patients with lesional epilepsy (median follow-up, 30 months) and considered separately the surgical results in the 51 patients with a single lesion and in the 13 who had dual pathology. In patients with a single lesion, 85% were seizure free or significantly improved (Engel's class I-II) when the lesion was totally removed compared with only 40% when there was incomplete resection (p < 0.007). All three patients with dual pathology who had both the lesion and the atrophic hippocampus removed became seizure free. In contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed at the lesion or at the hippocampus alone became seizure free (p < 0.05), although 4 of them showed significant improvement (Engel's class II). We conclude that the outcome in patients with single epileptogenic lesions is usually dependent upon the completeness of lesion resection. In patients with dual pathology, surgery should, if possible, include resection of both the lesion and the atrophic hippocampus.

Adolescent↗
PubMed1997

Do health questionnaires which do not consider sex differences miss important information?

The influence of gender on subsets of scores of Sense of Coherence, Hardiness, and personality traits was assessed in relation to psychological well-being using the Sense of Coherence Questionnaire, the Dispositional Resilience Scale, the Eysenck Personality Inventory, and the 12-item General Health Questionnaire. In a sample of Open University students (67 men aged 21 to 71 years and 239 women aged 19 to 66 years) sex differences were found in subsets of scores of Sense of Coherence, Hardiness, personality, and psychological well-being.

Adaptation, Psychological↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗