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Biomedical subjects

P Teale

Publications and source records attributed to P Teale.

At least 19 recordsLinked to original sources
PubMed2005

N-deethylation and N-oxidation of etamiphylline: identification of etamiphylline-N-oxide in greyhound urine by high performance liquid chromatography-mass spectrometry.

Millophyline-V, (etamiphylline camsylate) was administered intramuscularly to two racing greyhounds at a dose of 10 mg kg(-1). Unhydrolysed pre- and post-administration urine samples were extracted using mixed mode solid phase extraction (SPE) cartridges, the basic isolates derivatised as trimethylsilyl ethers and analysed by positive ion electron ionisation gas chromatography-mass spectrometry (GC/EI+/MS). The parent drug and one metabolite, N-desethyletamiphylline, were detected in urine for up to 72 h. For semi-quantification, urine samples were extracted on-line using a Prospekt sample handler. The analytes retained on the C2 SPE cartridge were eluted by the mobile phase directly on to the analytical high performance liquid chromatography column and analysed by positive ion atmospheric pressure chemical ionisation (LC/APCI+) MS in the multiple selective-ion recording mode. A major peak containing both ions (m/z) 280 and (m/z) 252 was observed. Full scan LC/APCI+/MS of the unknown indicated that the ion at (m/z) 280 was formed by the loss of an oxygen atom [MH+ -->(MH+-O)]. Samples were analysed by positive ion electrospray ionisation LC/MS on two different instruments and the unknown compound was identified as an N-oxide of the tert. nitrogen atom of the 2-(diethylamino)ethyl substituent on N7 of the theophylline nucleus. This compound has not been reported previously either as an in vivo or in vitro metabolite of etamiphylline in any species. Thermal decomposition of the N-oxide could lead to an increase the detection period of the parent drug during routine GC/MS screening of post-competition greyhound urine samples.

Animals↗
PubMed2001

Reduced hippocampal volume in association with p50 nonsuppression following traumatic brain injury.

Traumatic brain injury (TBI) may produce persistently impaired auditory gating. This cholinergic-dependent, hippocampally mediated preattentive cognitive function that facilitates filtering of auditory stimuli may be indexed by the P50 evoked waveform to paired auditory stimuli. Abnormal P50 suppression post TBI is believed to result from injury to the hippocampus and/or its afferent cholinergic projections. This hypothesis was tested by comparing hippocampal and total brain volumes on MRI between ten P50-nonsuppressing TBI patients and ten normal control subjects matched for age, gender, and education. TBI subjects had highly significant bilateral hippocampal volume reductions, even when covaried for reductions in total brain volume. Degree of volume loss was not correlated with initial TBI severity. Findings support the hypothesis that hippocampal injury underlies P50 nonsuppression post TBI and suggest that such structural abnormalities may be observed even in "mildly" injured persons.

Adult↗
PubMed2000

Fine structure of the auditory M100 in schizophrenia and schizoaffective disorder.

BACKGROUND: Several studies have demonstrated anomalous asymmetry of the 100-msec latency auditory-evoked field (M100) in schizophrenia. Recent evidence suggests this may be a compound component, however. Our study examines the localization of two M100 subcomponents in patients with schizophrenia and schizoaffective disorder. METHODS: Magnetoencephalographic recordings of auditory-evoked fields were obtained for 14 subjects with schizophrenia, 12 with schizoaffective disorder, and 23 control subjects. Two M100 subcomponents were identified and localized in each hemisphere. RESULTS: Both patient groups exhibited different lateralization compared with control subjects, with the second subcomponent tending to be less lateralized. CONCLUSIONS: The second subcomponent may be the major contributor to previously reported laterality differences. Future studies might benefit by separating M100 subcomponents so that specific functions could be addressed.

Adult↗
PubMed1999

Sex differences in the refractory period of the 100 ms auditory evoked magnetic field.

The 100 ms latency auditory evoked magnetic response (M100) has been implicated in the earliest stage of acoustic memory encoding in the brain. Sex differences in this response have been found in its location within the brain and its functional properties. We recorded the M100 in 25 adults in response to changes in interstimulus interval of an auditory stimulus. Response amplitudes of the M100 were used to compute a measure of the M100 refractory period, which has been proposed to index the decay time constant of echoic memory. This time constant was significantly longer in both hemispheres of the female participants when compared to the male participants. Possible implications of this for behavioral sex differences in human memory performance are discussed.

Acoustic Stimulation↗
PubMed1999

Schizoaffective disorder: evidence for reversed cerebral asymmetry.

BACKGROUND: Schizoaffective disorder is one of the most severe of the affective psychoses, but its pathophysiology is poorly understood. Because cerebral lateralization may be disturbed in psychotic disorders generally, studies examining cerebral asymmetry may improve understanding of the neurobiology specific to schizoaffective disorder. This study examines cerebral lateralization in this patient population using magnetic source localization. METHODS: We studied 16 subjects with schizoaffective disorder and 16 controls. Magnetic source localization was used to identify the location of the 20 msec latency somatosensory evoked field component (M20). RESULTS: In control subjects, the source location was further anterior in the right hemisphere. The subjects with schizoaffective disorder were reverse lateralized. CONCLUSIONS: The findings of a reversed asymmetry of the M20 in patients with schizoaffective disorder suggest an anatomical shift in the placement of the post central gyrus in this disorder, compatible with a disorder of cerebral lateralization. Whether this finding converges or diverges with measurement of the M20 in other psychotic disorders will require further investigation.

Adult↗
PubMed1999

Magnetoencephalography: applications in psychiatry.

Magnetoencephalography (MEG) measures the extracranial magnetic fields produced by intraneuronal ionic current flow within appropriately oriented cortical pyramidal cells. Based upon superconducting quantum interference device technology operating at liquid helium temperatures (4 K), MEG offers excellent temporal and spatial resolution for selected sources, and complements information obtained from electroencephalograms and other functional imaging strategies. Current instrumentation permits recording up to several hundred channels simultaneously with head-shaped dewars, although the cost of such systems is high. The fact that magnetic fields fall off with the square of the distance from the source is both a benefit (when separating activity in the two hemispheres) and a limitation (when attempting to record deep sources). The lack of skin contact facilitates using MEG to record direct current and very high frequency (> 600 Hz) brain activity. The clinical utility of MEG includes presurgical mapping of sensory cortical areas and localization of epileptiform abnormalities, and localization of areas of brain hypoperfusion in stroke patients. MEG studies in psychiatric disorders have contributed materially to improved understanding of anomalous brain lateralization in the psychoses, have suggested that P50 abnormalities may reflect altered gamma band activity, and have provided evidence of hemisphere-specific abnormalities of short-term auditory memory function.

Auditory Perception↗
PubMed1999

The thalamus and the schizophrenia phenotype: failure to replicate reduced volume.

BACKGROUND: Thalamic abnormalities resulting in impaired attention and information processing may form a foundation for cognitive and perceptual disturbances in schizophrenia. Measurements of the thalamus in patients with schizophrenia have shown reductions relative to normal comparison subjects. METHODS: In the current project, magnetic resonance images of the brain were obtained in 10 male and 11 female subjects with paranoid-type schizophrenia, and 15 male and 12 female normal comparison subjects. Total brain and bilateral thalamic volumes were calculated. RESULTS: There were no significant diagnosis, hemisphere, or gender differences in thalamic volumes. CONCLUSIONS: Structural thalamic abnormalities are not likely to universally and parsimoniously explain the schizophrenia phenotype. Abnormal thalamic size in patients with schizophrenia should be understood as reflecting one of several possible structural abnormalities contributing to production of the schizophrenia phenotype, but must be regarded with caution unless paired with functional studies.

Adult↗
PubMed1999

In vitro percutaneous absorption of fusidic acid and betamethasone 17-valerate across canine skin.

The penetration of betamethasone 17-valerate and fusidic acid through dog skin was measured in vitro. In order to detect the small amounts of diffused compounds, a liquid chromatography-mass spectrometric method was developed with sensitivity limits for both compounds of 5 ng/ml. After application to the skin surface of a topical gel preparation containing these compounds at the anticipated therapeutic dose rate, about 10 per cent of the betamethasone 17-valerate penetrated the skin over a 24-hour period, with no significant metabolism of the ester. About 1.3 per cent of the applied dose of fusidic acid was similarly recovered. The results demonstrated rapid penetration of both compounds through the epidermis.

Administration, Cutaneous↗
PubMed1999

Bipolar disorder: anomalous brain asymmetry associated with psychosis.

OBJECTIVE: Anomalous cerebral asymmetry in schizophreniform disorders has been described, but its presence in psychotic mood disorders has not been established. Measures of cerebral asymmetry may distinguish patients with psychotic mood disorders from those with nonpsychotic mood disorders and from comparison subjects. To test this hypothesis, the authors examined functional cerebral asymmetry by using a metric based on magnetic source imaging. METHOD: A total of 33 subjects participated. Nine were patients with bipolar I disorder and a negative history of psychotic symptoms during mood disorder episodes, 12 were patients with bipolar I disorder and a positive history of psychotic symptoms during mood disorder episodes, and 12 were nonpsychiatric comparison subjects. Equivalent current dipole generators in both hemispheres were estimated for the 20-msec-latency somatosensory evoked field (M20) component produced by stimulation of the contralateral median nerve. RESULTS: The comparison subjects demonstrated asymmetry in anterior-posterior equivalent current dipole locations of the M20 (right anterior to left), and the bipolar subjects with no history of psychosis were similarly asymmetric. The bipolar subjects with a history of psychosis during mood episodes, however, demonstrated a reversal of cerebral asymmetry of the M20 (left anterior to right). CONCLUSIONS: Cerebral lateralization of the M20 distinguished bipolar subjects with psychosis from those without psychosis and comparison subjects. The M20 is generated in area 3b of the postcentral gyrus. These findings suggest anatomical displacement of the postcentral gyrus in psychotic disorders and support the hypothesis that anomalous cerebral asymmetry is a feature of psychotic disorders generally, including psychotic mood disorders.

Bipolar Disorder↗
PubMed1999

Hippocampal to pituitary volume ratio: a specific measure of reciprocal neuroendocrine alterations in alcohol dependence.

OBJECTIVE: Studies to date provide conflicting views of the relationship between corticosteroids and decreased hippocampal volume in alcoholism. If this were mediated through the hypothalamic-pituitary-adrenal (HPA) axis, enlarged pituitary volumes relative to hippocampal volumes might be expected and be measurable using the hippocampus to pituitary volume (H:P) ratio. METHOD: Using magnetic resonance imaging (MRI), we performed volumetric analysis of the pituitary and hippocampus on 10 subjects with alcohol dependence (AD) and on 10 normal control subjects. RESULTS: Compared to normal controls, AD subjects demonstrated a trend towards decreased hippocampal volume (p < .06) and increased pituitary volume (p < .07). More importantly, H:P ratios were significantly smaller in AD subjects (p < .01). This observation persisted even when covaried for age. CONCLUSIONS: Reduced H:P ratio fits the hypothesis that ethanol stimulates pituitary corticotrophs resulting in elevated corticosteroid levels and possible injury to the hippocampus. If replicated, reduced H:P ratio may serve as a clinical measure of reciprocal neuroendocrine changes in chronic heavy ethanol use.

Adrenal Cortex Hormones↗
PubMed1998

Sequential source of the M100 exhibits inter-hemispheric asymmetry.

The most prominent auditory evoked field component occurs at about 100 ms latency and is termed the M100. We recorded M100 data from 20 subjects, in both hemispheres. We modeled the generators with a single equivalent current dipole in a 10 ms sliding window from 0 to 245 ms post-stimulus. A residual error curve was plotted, and a search for local minima identified two latencies at about 75 and 100 ms. In the left hemisphere, the early generator was about 6 mm above the later source; in the right hemisphere the early source was about 3 mm above the later, and 11 mm posterior. The M100 is a compound source, and the model may provide additional information in cases with reported laterality differences.

Acoustic Stimulation↗
PubMed1997

Magnetic source imaging evidence of sex differences in cerebral lateralization in schizophrenia.

BACKGROUND: It has been postulated that schizophrenia represents a disorder of anomalous cerebral lateralization. This study is a replication of earlier preliminary findings using a multichannel neuromagnetometer, suggesting altered lateralization in schizophrenia in male subjects, with an extension of the findings to female subjects. METHODS: We used magnetoencephalography-based magnetic source imaging to estimate the intracranial location of the 100-millisecond latency auditory-evoked field component (M100) in both left and right hemispheres of 20 patients with paranoid schizophrenia and 20 controls without schizophrenia. Neuroanatomical data were obtained by means of magnetic resonance imaging, from which we segmented and computed volumes of both total brain and left and right superior temporal gyri. RESULTS: Locations of M100 source were compatible with neuronal generators located in the transverse gyri of Heschl on the superior temporal gyri in both study groups; M100 sources were asymmetric in all the control subjects. The male patient subgroup exhibited significantly less asymmetry than the control group, while the female patient subgroup actually showed significantly more asymmetry. The male patient subgroup generally had smaller superior temporal gyri than the control group. No evidence of total brain volume differences was observed. CONCLUSIONS: Our findings support previous magnetoencephalography-based studies suggesting anomalous cerebral lateralization in schizophrenia. Further, in extending our studies to female patients, our data suggest that the nature of this anomaly is sex specific, a finding that, to our knowledge, has not previously been reported.

Adult↗
PubMed1997

Cortisol concentrations in post competition horse urine: a French and British survey.

The purpose of the present report was to estimate the population parameters of cortisol concentrations in urine, an endogenous hormone used as a 'doping' agent and for which an international threshold (1.0 micrograms/ml) has been proposed. Two data bases (French and UK) corresponding to 112 and 142 samples, respectively were considered. Urine was collected under specific post competition conditions. Cortisol concentrations were obtained by validated methods (HPLC for the French samples, and GC-MS for UK samples). No difference was observed between the 2 data sets and statistical analyses were carried out on the two merged files. The overall geometric mean cortisol concentration was 48 ng/ml. Distribution was not Gaussian. A log-normal distribution was not rejected (for P > 0.05). Using the log-normal distribution, it was calculated that the probability of exceeding a cortisol concentration in urine of 1.0 micrograms/ml was 1.1 x 10(-4). It was concluded that the actual international threshold is specific i.e. robust with regard to the risk of erroneously declaring an unmedicated horse as positive.

Animals↗
PubMed1997

Sex-specific expression of Heschl's gyrus functional and structural abnormalities in paranoid schizophrenia.

OBJECTIVE: Evidence supports abnormal temporal lobe structure and function in schizophrenia. Some abnormalities, particularly involving the auditory cortex, appear to be sex specific. These findings were extended to anatomical and physiological descriptors. METHOD: The authors quantified the volume, surface area, and three-dimensional location of Heschl's gyri on magnetic resonance imaging (MRI) images of 21 patients with paranoid schizophrenia and 24 healthy comparison subjects. Neuromagnetic localizations of the 100-msec latency auditory evoked field (M100) were compared with MRI-determined locations of Heschl's gyri, computed as the geometric center of mass of the volume. RESULTS: Volumetric measures revealed small Heschl's gyri only in male patients. Asymmetry was found in the location of the Heschl's gyrus centroid (more anterior on the right) across all groups. Male comparison subjects had M100 locations posterior to the Heschl's gyrus centroid in the left hemisphere and close to the Heschl's gyrus centroid on the right, while male patients had M100 sources anterior to the Heschl's gyrus centroid on the left. All women had M100 locations posterior to the Heschl's gyrus centroid on the left and anterior to it on the right. CONCLUSIONS: These results demonstrate that some temporal lobe abnormalities in schizophrenia are sex specific. They also suggest that the anomalous lateralization of the auditory evoked field cannot be explained by a shift in the underlying anatomy, since the anatomical substrate is lateralized in both comparison subjects and patients of both sexes. These findings may indicate a sex-specific functional reorganization in the auditory cortex in schizophrenia.

Adult↗
PubMed1996

Reproducibility of MEG auditory evoked field source localizations in normal human subjects using a seven-channel gradiometer.

Magnetoencephalographic (MEG) auditory evoked fields (EF) were recorded from 12 normal adult subjects over both hemispheres on two separate occasions at least one week apart using a seven-channel second-order gradiometer. Stimuli were computer-generated at 25-msec duration, 1 kHz tone pips. Responses to 100 stimuli were averaged, and source estimates with confidence intervals were computed, for the 100-msec latency auditory EF component, termed M100. Root-mean-squared (rms) differences in x, y, and z locations were approximately 0.7 cm on the two occasions; strength and orientation differences were 18 nA-m and 11 degrees, respectively. This spatial accuracy using a seven-channel instrument, compares favorably with other currently available technologies for localization of brain function.

Adult↗
PubMed1995

Cerebral laterality in homosexual males: preliminary communication using magnetoencephalography.

MEG-based auditory M100 source location in the left and right hemispheres of 8 strictly homosexual and 9 strictly heterosexual males were compared to determine if this measure of interhemispheric laterality varies as a function of sexual orientation. MEG fields evoked by auditory tone pips were recorded from left and right hemispheres in response to contralateral ear stimulation. The source of the 100-msec latency component, generated in the superior temporal gyrus, was estimated using a least squares inverse solution algorithm. Auditory sources in heterosexual men were significantly further anterior in the right hemisphere compared to the left hemisphere. Source locations in the homosexual men did not exhibit significant interhemispheric asymmetry, being similarly located in both hemispheres. Findings suggest an anatomic and/or functional difference in the superior temporal gyrus of at least some homosexual men.

Adult↗