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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
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Spasmodic dysphonia: new diagnosis and treatment opportunities.

The ability to communicate is a basic need. Spasmodic dysphonia, a rare dystonia focal to the larynx, affects the vocal muscles resulting in abnormal sound and speech production. The voice may become hoarse, strained, strangled, tremulous, whispered, or aphonic. Lack of appropriate diagnosis along with the continued use of an abnormal voice often results in frustration, anxiety, and depression. Improved diagnostic ability and unique treatment with botulinum toxin injection (Botox) are now available to patients in several large medical centers across the United States and Canada. A knowledgeable and observant health care provider can alert patients and families to the possibility of treatment for a chronic voice disturbance.

Botulinum Toxins↗
PubMed1994

Imaging in epilepsy.

Neuroimaging in epilepsy now includes magnetic resonance imaging, positron emission tomography (PET), single-photon emission tomography (SPECT), magnetoencephalography, and magnetic resonance spectroscopy. Recent advances in neuroimaging include improved rates of detection of lesions on structural imaging using quantitative methods, identification of metabolic patterns on functional imaging with PET, and recognition of the value of ictal SPECT in seizure localization.

Brain↗
PubMed1994

Mesial temporal sclerosis and volumetric investigations.

Volumetric MRI data acquisition permits reliable and accurate measurement of mesial temporal lobe structures. In normal subjects, these structures are very symmetric. A high degree of pathological specificity is associated with the finding of even minor volume asymmetries. Definition in this manner allows precise estimation of both absolute and relative volume differences, and precise anatomical localisation of volume loss within the hippocampus. There are good EEG and clinical correlates with the distribution of volume loss defined on MRI studies. Volumetric assessment is fast, reliable, non-invasive, and a relatively inexpensive component of the pre-operative work-up. It is the method of choice when imaging patients with clinical temporal lobe epilepsy undergoing pre-surgical evaluation. The finding of significant hippocampal volume asymmetry in a patient with clinical temporal lobe seizures being evaluated for epilepsy surgery may obviate the need for alternative sophisticated, invasive, or expensive investigative procedures. At our centre, such MRI allows "fast track" cases to proceed to surgery without further invasive investigations, and is likely to have a dramatic effect on pre-operative evaluation in most centres practising epilepsy surgery.

Amygdala↗
PubMed1994

Image guided audit of surgery for temporal lobe epilepsy.

Studies on surgery for temporal lobe epilepsy are hampered by lack of information about the actual surgery that has taken place. A method is described for accurately measuring the volumes of resection by MRI after surgery. Ten cases of surgically treated temporal lobe epilepsy (nine non-tailored resections, one selective amygdalohippocampectomy) are presented to show the technique. Indices of extent of resection in both the mesiobasal and lateral temporal lobe compartments have been measured, compared, and evaluated. By comparison with identical preoperative volumetric MRI the hippocampal resections have been correlated with the demonstrated hippocampal volume loss, thought to be of relevance in the aetiology of temporal lobe epilepsy. Detailed postoperative audit in this manner is vital in providing a rational basis for follow up studies of outcome.

Adolescent↗
PubMed1994

Association of hippocampal sclerosis with cortical dysgenesis in patients with epilepsy.

The possible dual occurrence of hippocampal sclerosis (HS) and other structural lesions (especially cortical dysgenesis [CD]) is well established in patients with chronic partial epilepsy. We describe the frequency of additional CD in a series of 100 patients with evidence of HS, using volumetric MRI. Additional, often subtle, CD was present in 15 patients: subependymal heterotopia (six), forme fruste of tuberous sclerosis (two), focal macrogyria (two), focal cortical dysplasia (one), laminar heterotopia (one), bilateral schizencephaly (one), and simplified gyral patterns (two). In contrast, in 46 healthy volunteers, only one had possible CD (p < 0.05). Only 2 of 15 patients had a history of childhood febrile convulsions. HS is a heterogeneous condition; patients being evaluated for temporal lobe surgery should be carefully screened for additional CD using appropriate MR techniques.

Adolescent↗
PubMed1993

Hippocampal sclerosis in epilepsy and childhood febrile seizures.

The connection between hippocampal sclerosis and childhood febrile seizures (CFS) is a contentious issue in the study of epilepsy. We investigated 107 patients with drug-resistant epilepsy by high-resolution volumetric magnetic resonance imaging (MRI). 20 had a history of CFS, 45 had focal (26) or diffuse (19) hippocampal volume loss (HVL). The frequency of CFS was significantly (p < 0.001) higher in the patients with HVL, especially of the diffuse pattern, compared to other epileptic patients without HVL and to the general population. Furthermore, the severity of HVL was greatest in those with a history of CFS. No other clinical or demographic features were associated with either a history of CFS or HVL. The frequency of CFS in patients with other structural congenital causes of epilepsy did not differ from that in a general population. Although these findings show that hippocampal sclerosis is strongly associated with a history of CFS, they do not indicate whether this is a causal relationship. If CFS do cause some cases of hippocampal sclerosis, this can not be the only mechanism, as 64% of those with HVL gave no history of CFS. As diffuse HVL is more strongly associated with a history of CFS than focal HVL, it is also possible that CFS convert pre-existing congenital focal abnormalities into diffuse hippocampal sclerosis. Given the possibility that CFS may cause hippocampal damage and epilepsy, they require urgent medical intervention.

Adolescent↗
PubMed1993

H(+)-coupled (Na(+)-independent) proline transport in human intestinal (Caco-2) epithelial cell monolayers.

Previously, absorption of L-proline across the apical membrane of the intestinal enterocyte has been attributed to transport via the Na(+)-dependent Imino system. However, net (absorptive) transport of proline across intact Caco-2 cell monolayers was enhanced by acidification of the apical environment, under both Na(+)-containing and Na(+)-free conditions. This Na(+)-independent pH-dependent proline flux was associated with H+ flow across the apical membrane as determined by continuous measurement of intracellular pH. H+/proline symport was associated with an inward Isc in voltage-clamped Caco-2 epithelial layers demonstrating the electrogenic nature of this transport process. In conclusion Caco-2 cells possess an apically-localised, Na(+)-independent, electrogenic H+/imino acid transporter which may play an important role in intestinal proline absorption.

Biological Transport↗
PubMed1993

Ketorolac and indomethacin are equally efficacious for the relief of minor postoperative pain.

Injectable ketorolac is an effective analgesic in ambulatory surgery patients. However, no studies have compared ketorolac with other NSAIDs in this setting. The analgesic efficacy of intramuscular ketorolac, rectal indomethacin and placebo was compared in healthy women undergoing gynaecological or breast surgery as outpatients. Ninety patients received 30 mg im ketorolac, 100 mg pr indomethacin or placebo in a prospective, randomized, double-blind manner. A standardized anaesthetic protocol was followed. Patients graded their pain on a 10 cm visual analogue scale in the recovery room, twice in the surgical day care unit and during the car ride home. The patients' postoperative fentanyl requirements, time to recovery milestones, and side effects were recorded. The placebo group received more fentanyl in the PACU but did not achieve the same pain relief as either of the NSAID-treated group (ketorolac 44 +/- 53 micrograms, indomethacin 39 +/- 55 micrograms, placebo 87 +/- 100 micrograms, P < 0.05). Patients who received an NSAID had less pain at 15 and 90 min (P < 0.05). The PACU stay was longer for the placebo group (ketorolac 50 +/- 13 min, indomethacin 49 +/- 12 min, placebo 62 +/- 35 min, P < 0.05). Time to ambulation was also longer in the placebo group (ketorolac 117 +/- 25 min, indomethacin 121 +/- 49 min, placebo 140 +/- 51 min, P < 0.05). However, no differences were observed between the two NSAIDS. Side effects were similar in all groups. We conclude that im ketorolac and pr indomethacin are equally effective analgesics in this group of patients.

Administration, Rectal↗
PubMed1993

Anaesthesia for adenotonsillectomy: a comparison between tracheal intubation and the armoured laryngeal mask airway.

A prototype armoured laryngeal mask airway (LMA) was compared with tracheal intubation (ETT) for anaesthesia for adenotonsillectomy. Fifty-five children were randomised into the LMA group and 54 into the ETT group. During insertion of the LMA, peripheral oxyhaemoglobin desaturation (SpO2) < 94% occurred in ten patients (18.2%) and in seven patients (13%) during tracheal intubation (NS). After opening the Boyle-Davis gag, airway obstruction occurred in ten patients (18.2%) in the LMA group and in three patients (6%) in the ETT group (P = 0.07). In five patients (9%) the LMA was abandoned in favour of tracheal intubation. In all others (91%), when the need for adequate depth of anaesthesia was realized, a satisfactory airway was achieved more rapidly than with tracheal intubation (P < 0.001), and maintained throughout surgery. Manually assisted ventilation was required in all patients in the ETT group, mean duration 373 +/- 385 sec, and in 26 patients (52%) in the LMA group, mean duration 134 +/- 110 sec, P < 0.001. Mean end-tidal CO2 (PetCO2) was 45.5 +/- 6.21 mmHg in the ETT group and 46.6 +/- 6.09 in the LMA group (NS). The LMA did not limit surgical access. Heart rate, MAP and blood loss in the LMA group were 110 +/- 21, 74 +/- 9 mmHg and 1.92 +/- 1.22 ml.kg-1 respectively, compared with 143 +/- 13 (P < 0.001), 85 +/- 12 mmHg (P < 0.001) and 2.62 +/- 1.36 ml.kg-1 (P < 0.05) with tracheal intubation. Fibreoptic laryngoscopy at the end of surgery in 19 patients in the LMA group revealed no blood in the larynx.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoidectomy↗
PubMed1993

Plasma oxytocin and nocturnal uterine activity: maternal but not fetal concentrations increase progressively during late pregnancy and delivery in rhesus monkeys.

OBJECTIVE: The purpose of the study was to determine whether rising maternal or fetal plasma oxytocin concentrations could be responsible for the increasing levels of nocturnal uterine activity on the nights preceding delivery. STUDY DESIGN: Chronically catheterized pregnant rhesus monkeys were exposed to a 16-hour light, 8-hour dark photoperiod (dark 11 PM to 7 AM). Uterine activity and maternal arterial plasma oxytocin concentrations were measured concurrently at weekly intervals in late gestation, on the night preceding term delivery (158 to 167 days, n = 4), and during delivery (149 to 170 days, n = 6). Fetal carotid arterial plasma oxytocin levels were measured during episodes of nocturnal uterine activity in six animals. The effect of oxytocin infusions into the fetus (30 to 480 ng/kg/hr) on uterine activity and on maternal and fetal plasma oxytocin levels was also determined (n = 3). RESULTS: Maximal nocturnal oxytocin concentrations in the maternal plasma rose progressively during late gestation from 9.9 +/- 3.5 pg/ml at 130 to 139 days to 28.7 +/- 9.8 pg/ml on the night preceding term delivery (p < 0.005); a significant increase in nocturnal uterine activity accompanied this rise (p < 0.001). Maternal oxytocin concentrations were elevated during labor and increased further at delivery (62.5 +/- 5.5 pg/ml, p < 0.05). There was no increase in fetal plasma oxytocin during nocturnal uterine activity (3.1 +/- 0.2 pg/ml) or during labor. Fetal oxytocin infusions raised fetal plasma oxytocin concentrations sixtyfold but had no effect on maternal plasma oxytocin concentrations or on uterine activity. CONCLUSIONS: Elevated maternal plasma oxytocin concentrations are responsible, at least in part, for the increasing magnitude of nocturnal uterine activity episodes as term approaches and for the elevated uterine activity before delivery at night. Fetal plasma oxytocin does not contribute to nocturnal uterine activity or to maternal plasma oxytocin concentrations.

Animals↗
PubMed1993

The cue for contour-curvature discrimination.

Seven potential geometric cues for contour-curvature discrimination were tested: curvature, turning-angle, arc-length, arc-length-divided-by-chord-length, maximum-deviation (sag), mean-deviation and area. Three experiments were performed, each requiring the discrimination of two simultaneously presented, 1-sec-duration, curved-line stimuli, whose chord-lengths ranged from 12 to 48 arcmin visual angle and whose curvatures ranged from 0 to 0.13 arcmin-1. Experiments 1 and 2 determined for each cue the smallest detectable increment (the increment threshold) as a function of cue value, for a set of spatial transformations of the stimulus (one- and two-dimensional scalings) equivalent to changes in viewing distance and direction. In accordance with statistical estimation theory, the "best" cue was defined as the most efficient one, that is, the one which best accounted for the variance in the data. As a control, Expt 3 compared increment-threshold functions for circular and elliptical arcs of constant chord-length and circular arcs of constant arc-length. Over all three experiments, only sag and its linear approximation, mean-deviation, accounted well for the variance in the data; sag provided the best predictor, and its increment-threshold function satisfied Weber's law over almost all of the stimulus range. Additionally, sag has a special theoretical property (shared only with mean-deviation and area): the relationship it defines (in proportional terms) between curved contours in an image of an object or a scene is constant and independent of viewing distance and direction.

Adult↗
PubMed1993

Identification of an orally active, nonpeptidyl oxytocin antagonist.

L-366,509, a member of a novel class of nonpeptidyl compounds, has been characterized as an orally active oxytocin (OT) antagonist. L-366,509 exhibits a moderate binding affinity (K(i) values, 370-780 nM) for the rat, rhesus and human uterine OT receptor. L-366,509 also binds to vasopressin receptor subtypes (arginine vasopressin-V1 and V2) with measurable affinity in rat (K(i) values, 25-30 microM) and primate (K(i) values, 2-6 microM) tissues. In rat uterine slices, L-366,509 inhibits (IC50 = 1.6 microM) the stimulation of phosphatidylinositol turnover induced by OT but not bradykinin. In the rat isolated uterus, L-366,509 is a competitive and reversible OT antagonist (pA2 = 7.32). In vivo, L-366,509 given i.v. (10 mg/kg) or intraduodenally (10-50 mg/kg) to rats causes a marked and long-lasting inhibition of OT-stimulated uterine activity. OT antagonist activity in a pregnant rhesus macaque (approximately day 135 gestation) is also observed with L-366,509 after i.v. or p.o. dosing. L-366,509 represents a prototype for a new chemical class of OT antagonists with significant p.o. bioavailability.

Administration, Oral↗
PubMed1992

Hippocampal volumetric and morphometric studies in frontal and temporal lobe epilepsy.

The most common temporal lobe pathology is Ammons Horn sclerosis (AHS), and several different imaging techniques have been utilized to detect this with varying success. We describe the clinical application of magnetic resonance imaging (MRI) using a three-dimensional volume technique which allows total hippocampal volume to be measured and symmetry evaluated. Hippocampal surface area was calculated in sequential 1.5 mm thick contiguous images, using a GE IC workstation. Total volumes and surface areas were calculated. The cross-sectional surface area at 1.5 mm intervals was displayed graphically, permitting morphometric analysis of the hippocampus throughout its length. Focal atrophy within any part of the hippocampal formation (HF) and its extent could thus be assessed. Patients with well-lateralized temporal lobe epilepsy (TLE) (n = 20) and well-defined frontal lobe epilepsy (FLE) (n = 20) were studied, and volumes compared with normal values derived from 10 neurologically normal controls. Asymmetric hippocampal volume loss was demonstrated in all 20 patients with clinically typed TLE, but not in normal controls or patients with FLE. Volume loss distribution was anterior in 12 patients, posterior in one patient and widespread in seven patients. Secondarily generalized seizures were strongly associated with widespread loss. This method of surface area and volumetric analysis of the hippocampus in TLE can demonstrate asymmetry and focal involvement, and help distinguish between hippocampal and frontal pathologies.

Adult↗
PubMed1991

Comparison of plasma oxytocin and catecholamine concentrations with uterine activity in pregnant rhesus monkeys.

Pregnant rhesus monkeys exhibit diurnal changes in uterine activity (UA), with episodes of increased UA during the early hours of darkness. The estrogenic environment during late pregnancy serves a permissive role in the maintenance of nocturnal UA episodes and may involve myometrial interactions with oxytocin (OT) and/or alpha-adrenergic stimuli. In the present study we have used chronically catheterized pregnant rhesus monkeys to measure diurnal changes in maternal plasma OT, epinephrine, norepinephrine, and dopamine. We also determined the effects of infusing an OT antagonist (ORF 22164) and the alpha-adrenergic antagonist phentolamine on nocturnal UA episodes. Animals were exposed to a 16-h light, 8-h dark photo-period, with the hours of darkness between 2300-0700 h. Maternal plasma samples were collected at 3-h intervals for 36 h and analyzed by RIA for OT and by high performance liquid chromatography for catecholamines. Plasma OT was correlated with UA in animals that displayed nocturnal UA episodes (r = 0.76; P less than 0.01). Maximal OT concentrations occurred at 2400 h in these animals; plasma OT was higher during the hours of darkness compared to levels during the light phase (10.4 +/- 1.9 and 3.0 +/- 0.3 pmol/L, respectively; n = 4). Some animals did not display nocturnal episodes of increased UA and showed no increase in OT concentrations during the hours of darkness. Maternal plasma catecholamine concentrations were not correlated with nocturnal UA and were maximal during the light phase. Nocturnal UA was abolished within 30 min of infusion of the OT antagonist, but phentolamine infusions had no effect on nocturnal UA. We conclude that 1) changes in maternal plasma catecholamine concentrations are not involved in the generation of nocturnal UA; 2) the presence of episodes of increased UA at night results from increased maternal plasma OT concentrations; and 3) the absence of nocturnal UA in some animals can be explained by a reduced level of OT secretion.

Animals↗
PubMed1991

Antagonism of oxytocin in rats and pregnant rhesus monkeys by the novel cyclic hexapeptides, L-366,682 and L-366,948.

Two cyclic hexapeptides unrelated in chemical structure to oxytocin (OT) were shown in vivo to be antagonists of the contractile action of OT on the uterus. In anesthetized rats challenged with OT (1 micrograms/kg) administered as an i.v. bolus, L-366,682 [cyclo-(L-Pro-D-Trp-L-Ile-D-pipecolic acid-L-pipecolic acid-D-His)] and L-366,948 (D-2-naphthyl-alanine in place of D-Trp) were equipotent with AD50 values of about 100 micrograms/kg i.v. At doses of L-366,682 or L-366,948 causing approximately 90 to 95% block (approximately the AD95 dose) of OT, the duration of action of the antagonists exceeded 145 min. Both compounds exhibited selectivity in the rat, as a dose of either at 300 micrograms/kg i.v. shifted the dose-response for OT-induced uterine contraction to the right by approximately 5-fold but did not affect the dose-response to prostaglandin F2 alpha. Furthermore, neither compound, at a dose of 3 mg/kg i.v., antagonized the action of arginine vasopressin acting at V-1 (pressor effect in pithed rats) or V-2 (antidiuretic) receptors. In conscious, freely moving, pregnant rhesus monkeys, L-366,948 or L-366,682 given i.v. or s.c. were effective antagonists of uterine contractions elicited by an infusion of OT. OT- or arginine vasopressin-like agonist activity was not observed in any of the in vivo models. It is concluded that L-366,682 and L-366,948 act in vivo as reasonably potent, long-acting and selective antagonists at OT receptors in the rat and rhesus uterus.

Animals↗