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R Corbett

Publications and source records attributed to R Corbett.

At least 19 recordsLinked to original sources
PubMed2000

Comparison of the distribution of magnesium in plasma determined by size exclusion chromatography and 31P NMR spectroscopy.

The distribution of magnesium in plasma, bound to proteins (pMg), complexed to low molecular weight anions (cMg) and ionized (iMg), was compared by size exclusion chromatography and an approach using a combination of atomic absorption spectroscopy, ion selective electrodes and 31P nuclear magnetic resonance spectroscopy. The distribution of pMg:cMg:iMg was 28:13:59 as determined by chromatography and 26:14:60 as determined by the latter methodology. These results are consistent with the hypothesis that plasma proteins and weak complexing anions correspond to high and low affinity magnesium binding ligands in plasma, respectively.

Adult↗
PubMed1999

Maturational changes in cerebral lactate and acid clearance following ischemia measured in vivo using magnetic resonance spectroscopy and microdialysis.

Intraischemic hyperglycemia has different effects on neurologic outcome in mature vs. immature brain, and may reflect differences in the extent or duration of cerebral lactic acidosis. We examined the hypotheses that post-ischemic lactate and acid clearance rates depend on the severity of intraischemic cerebral acidosis, and that rates of clearance change as a function of brain maturation. In vivo 31P and 1H magnetic resonance spectroscopy (MRS) was used to compare intracellular acid and lactate clearance rates in newborn and 1-month old swine following a 14-min episode of transient near-complete global ischemia. In the same animals, in vivo microdialysis was used to determine if extracellular lactate clearance changed as a function of cerebral lactic acidosis or differed between age groups following ischemia. Plasma glucose concentration was altered in individual animals to study a range of intraischemic cerebral lactic acidosis. For both age-groups, maximal brain acidosis and lactosis occurred in the post-ischemia interval, indicating a delay in the re-establishment of oxidative metabolism following ischemia. Clearance half-lives of both cerebral acidosis and lactosis increase as a function of increased intraischemic cerebral acidosis. For either age group, the clearance half-life for acidosis was faster than the half-life for lactate. However, the subgroup of 1-month old swine who experienced severe cerebral acidosis (i.e., pH<6.1) had a longer cerebral lactate clearance half-life as compared to the subgroup of newborn animals with a similar severity of acidosis. In both age groups, there were comparable maximal increases in extracellular lactate concentrations in the post-ischemic period and similar rates of decline from the maximum. These results demonstrate that post-ischemic lactate and acid clearance are altered by the extent of intraischemic acidosis, and the extent of post-ischemic uncoupling between brain acid and lactate clearance increases with advancing age. The transmembrane clearance of lactate was not a prominent mechanism that differentiated lactate clearance rates between newborn and 1-month old swine.

Acidosis, Lactic↗
PubMed1999

Patient cost-benefit analysis of teledermatology measured in a randomized control trial.

A randomized controlled trial of the costs and benefits of teledermatology consultations compared with traditional hospital consultations was carried out. Over a nine-month period, 197 patients were referred from general practice for a dermatological opinion, 98 for a teledermatology consultation and 99 for a hospital consultation. Eighty patients required an additional subsequent hospital appointment. Patients were asked to complete an economic questionnaire after each consultation, and 164 questionnaires were returned: 62% of those randomized to the teledermatology consultation responded compared with 58% of those randomized to the hospital consultation. Patients seen by teledermatology at their own health centre had shorter distances to travel and spent less time overall attending the appointment compared with those seen at the hospital. However, the teledermatology consultations were more time-consuming for the general practitioner and dermatologist. These findings indicate that teledermatology has more benefits for the patient than for the health-care delivery team.

Adolescent↗
PubMed1999

A macrocyclic reporter ligand for Mg2+: analytical implications for clinical magnesium determinations.

A new approach is presented for measuring Mg in plasma using the macrocyclic reporter ligand, NOTMP (1, 4, 7-triazacyclononane- 1, 4, 7-tris (methylene methylphosphinate)) and 31P nuclear magnetic resonance spectroscopy (NMR). By virtue of its intermediate binding constant for Mg (Kd = 0.35 mM), measurements of Mg using NOTMP allows one to discriminate between Mg bound to the high and low affinity ligands present in plasma, when combined with more conventional measurements of Mg. We used this approach in conjunction with measurements of total Mg using atomic absorption spectroscopy (AAS) and ionized Mg using an ion selective electrode (ISE) to characterize the distribution of Mg in the plasma of 16 normal adults. The percentage of Mg distributed among high and low affinity ligands and in an ionized fraction was 31, 14 and 55 per cent respectively. Similar measurements on plasma following equilibrium dialysis suggest that the high and low affinity ligands in plasma correspond to high and low molecular weight compounds, respectively. Measurement of Mg by NOTMP, AAS and ISE were not affected by the storage of blood samples for up to 48 h at 4 degrees C. The addition of MgSO4 to plasma and its subsequent analysis by these three methods suggests that the added Mg is primarily distributed among the high affinity ligands (mostly likely proteins) and ionized fractions. The approach presented here may offer novel insights into assessing the distribution of Mg in clinical samples.

Adult↗
PubMed1998

Alteration of dopamine metabolites in CSF and behavioral impairments induced by neonatal hippocampal lesions.

Alterations of monoamine metabolites in CSF and behavioral abnormalities were studied in rats with neonatal hippocampal lesions and controls. Lesions of the ventral hippocampus were produced bilaterally by ibotenic acid on postnatal day 7. Lesion-induced neurochemical alterations and behavioral impairments were examined concurrently when rats were 12 weeks old. CSF from the cisterna magna was sampled repeatedly from freely moving rats. The levels of free 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in CSF were determined. An exposure to a novel environment induced hyperexploratory behavior and elevated the level of free DOPAC in CSF in lesioned rats. Although a swim stress increased the levels of free DOPAC and 5-HIAA in CSF in both control and lesioned groups, rats with hippocampal lesions had a further elevation of free DOPAC in CSF and greater spontaneous activity relative to controls shortly after stress. Amphetamine (1.5 mg/kg, i.p.) induced hyperlocomotion in lesioned rats compared to controls. For the control group, the levels of the three monoamine metabolites in CSF were not significantly influenced by amphetamine. However, for the lesioned group, the level of DOPAC significantly decreased compared to preinjection of amphetamine. The results indicate that neonatal hippocampal lesion-induced impairments can be manifested by behavioral and neurochemical abnormalities. Alterations of monoamine metabolites in CSF may be determined quantitatively and used as indices for monitoring lesion-impaired monoaminergic function in the central nervous system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

DARPP-32: regulator of the efficacy of dopaminergic neurotransmission.

Dopaminergic neurons exert a major modulatory effect on the forebrain. Dopamine and adenosine 3',5'-monophosphate-regulated phosphoprotein (32 kilodaltons) (DARPP-32), which is enriched in all neurons that receive a dopaminergic input, is converted in response to dopamine into a potent protein phosphatase inhibitor. Mice generated to contain a targeted disruption of the DARPP-32 gene showed profound deficits in their molecular, electrophysiological, and behavioral responses to dopamine, drugs of abuse, and antipsychotic medication. The results show that DARPP-32 plays a central role in regulating the efficacy of dopaminergic neurotransmission.

Amphetamines↗
PubMed1998

Age-related differences in the effect of dichloroacetate on postischemic lactate and acid clearance measured in vivo using magnetic resonance spectroscopy and microdialysis.

Numerous studies using adult animal models suggest that dichloroacetate (DCA) may have neuroprotective properties by virtue of its ability to increase rates of metabolism and, therefore, clearance of brain lactic acidosis, which may accumulate during cerebral ischemia. We tested the hypothesis that postischemic DCA administration affects lactate and acid clearance to different extents in immature versus mature brain. 31P and 1H magnetic resonance spectroscopy were used to measure intracellular acid and lactate clearance rates in vivo in newborn and 1-month-old swine after a 14-min episode of transient near-complete global ischemia. Simultaneous monitoring of extracellular lactate efflux and clearance was measured in the same animals by in vivo microdialysis. Plasma glucose concentrations were elevated in order to study animals with severe cerebral lactic acidosis. Maximal levels of brain lactosis (16-20 micromol/g) and acidosis (PHintracellular 5.8-6.0) were reached during the first 10 min of recovery and were the same in age groups and in subgroups either acting as controls or treated with DCA (200 mg/kg) given from the last minute of ischemia to 5-7 min after ischemia. For newborns, DCA administration improved the postischemic clearance rate of cerebral acidosis and cerebral phosphocreatine, with similar trends for the clearance of lactosis and increased rates of recovery of nucleotide triphosphates, compared with controls. In contrast, DCA administration in 1-month-olds resulted in a modest trend for improvement of cerebral lactate clearance, but did not affect acid clearance or the recovery rate of phosphocreatine or nucleotide triphosphates. Extracellular brain lactate concentrations had similar relative increases and rates of decline for subgroups of either age treated with DCA versus controls. The results of this study indicate that postischemic DCA administration helps to resolve cerebral acidosis to a greater degree in immature than more mature brain, suggesting that DCA may have cerebroprotective properties for neonatal hypoxic-ischemic encephalopathy.

Acids↗
PubMed1998

Patient satisfaction with realtime teledermatology in Northern Ireland.

Teledermatology consultations were organized between two health centers and two hospitals in Northern Ireland using low-cost videoconferencing equipment. A prospective study of patient satisfaction was carried out. Following each teleconsultation, patients were asked to complete a questionnaire assessing their satisfaction with the service. Over 22 months, 334 patients were seen by a dermatologist over the video-link, and 292 patients (87%) completed the 16-item questionnaire. Patients reported universal satisfaction with the technical aspects of teledermatology. The quality of both the audio and the display was highly acceptable to patients. Personal experiences of the teledermatology consultation were also favourable: 85% felt comfortable using the video-link. The benefits of teledermatology were generally recognized: 88% of patients thought that a teleconsultation could save time. Patients found the teledermatology consultation to be as acceptable as the conventional dermatology consultation. These findings suggest overall patient satisfaction with realtime teledermatology.

Adolescent↗
PubMed1998

Preliminary results from the Northern Ireland arms of the UK Multicentre Teledermatology Trial: is clinical management by realtime teledermatology possible?

Results from phase 1 of the UK Multicentre Teledermatology Trial demonstrated the diagnostic accuracy of realtime teledermatology using low-cost equipment. Phase 2 of the trial aimed to assess its effectiveness as a management tool for dermatological disease. Teledermatology consultations were organized between two health centres and two hospitals in Northern Ireland using low-cost videoconferencing equipment. For 205 patients seen by a dermatologist over the video-link a diagnosis and management plan were recorded. A subsequent face-to-face consultation was arranged on the same day to confirm the diagnosis and treatment regime. A comparison of these management plans revealed that the same plan was recommended in 64% of cases; the teledermatologist was unable to advocate a suitable management plan in 19% of cases; a suboptimal treatment plan was suggested by the teledermatologist in 6% of cases; and in 11% of cases, the teledermatologist suggested an inappropriate treatment plan. These findings indicate that appropriate clinical management was possible in approximately two-thirds of dermatology consultations via the video-link.

Adolescent↗
PubMed1998

Diagnostic accuracy and clinical management by realtime teledermatology. Results from the Northern Ireland arms of the UK Multicentre Teledermatology Trial.

Diagnostic accuracy and management recommendations of realtime teledermatology consultations using low-cost telemedicine equipment were evaluated. Patients were seen by a dermatologist over a video-link and a diagnosis and treatment plan were recorded. This was followed by a face-to-face consultation on the same day to confirm the earlier diagnosis and management plan. A total of 351 patients with 427 diagnoses participated. Sixty-seven per cent of the diagnoses made over the video-link agreed with the face-to-face diagnosis. Clinical management plans were recorded for 214 patients with 252 diagnoses. For this cohort, 44% of the patients were seen by the same dermatologist at both consultations, while 56% were seen by a different dermatologist. In 64% of cases the same management plan was recommended at both consultations; a sub-optimum treatment plan was recommended in 8% of cases; and in 9% of cases the video-link management plans were judged to be inappropriate. In 20% of cases the dermatologist was unable to recommend a suitable management plan by video-link. There were significant differences in the ability to recommend an optimum management plan by video-link when a different dermatologist made the reference management plan. The results indicate that a high proportion of dermatological conditions can be successfully managed by realtime teledermatology.

Adolescent↗
PubMed1997

Lung involvement in neuroblastoma: incidence and characteristics.

The presence of lung metastases in neuroblastoma often leads to doubt about the diagnosis due to rarity of disease at this site. To determine more precisely the incidence and nature of pulmonary disease in neuroblastoma the data base of the European Neuroblastoma Study Group (ENSG) was examined. Information was obtained about 35/746 stage IV patients (and 1 patient who was registered as having stage II disease) documented to have pulmonary disease at presentation. Of these 5 were registered with pleural effusions, 18 pleural infiltrations, and 13 intrapulmonary lesions. Review of these cases, however, suggested that only 9 patients (1.2%; 95% exact confidence interval 0.42-1.99%, binomial distribution) had disease consistent with secondary neuroblastoma in lung or pleura. There was no correlation with clinical features, age, sex, or other disease sites, and outcome was uniformly poor.

Adolescent↗
PubMed1997

Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors.

This review examines the possible receptor basis of the atypical action of those atypical antipsychotic drugs that elicit low levels of Parkinsonism. Such an examination requires consistent and accurate dissociation constants for the antipsychotic drugs at the relevant dopamine and serotonin receptors. It has long been known, however, that the dissociation constant of a given antipsychotic drug at the dopamine D2 receptor varies between laboratories. Although such variation depends on several factors, it has recently been recognized that the radioligand used to measure the competition between the antipsychotic drug and the radioligand is an important variable. The present review summarizes information on this radioligand dependence. In general, a radioligand of low solubility in the membrane (i.e., low tissue:buffer partition) results in a low value for the antipsychotic dissociation constant when the drug competes with the radioligand. Hence, by first obtaining the antipsychotic dissociation constants using different radioligands of different solubility in the membrane, one can then extrapolate the data to low or "zero" ligand solubility. The extrapolated value represents the radioligand-independent dissociation constant of the antipsychotic. These values are here given for dopamine D2 and D4 receptors, as well as for serotonin 5-HT2A receptors. These values, moreover, agree with the dissociation constant directly obtained with the radioactive antipsychotic itself. For example, clozapine revealed a radioligand-independent value of 1.6 nM at the dopamine D4 receptor, agreeing with the value directly measured with [3H]-clozapine at D4. However, because clozapine competes with endogenous dopamine, the in vivo concentration of clozapine (to occupy dopamine D4 receptors) can be derived to be about 13 nM, agreeing with the value of 12 to 20 nM in the plasma water or spinal fluid observed in treated patients. The atypical neuroleptics remoxipride, clozapine, perlapine, seroquel, and melperone had low affinity for the dopamine D2 receptor (radioligand-independent dissociation constants of 30 to 90 nM). Such low affinity makes these latter five drugs readily displaceable by high levels of endogenous dopamine in the caudate or putamen. Most typical neuroleptics have radioligand-independent values of 0.3 to 5 nM at dopamine D2 receptors, making them more resistant to displacement by endogenous dopamine. Finally, a relation was found between the neuroleptic doses for rat catalepsy and the D2:D4 ratio of the radioligand-independent K values for these two receptors. Thus, the atypical neuroleptics appear to fall into two groups, those that have a low affinity for dopamine D2 receptors and those that are selective for dopamine D4 receptors.

Animals↗
PubMed1997

Enhancement of postsynaptic sensitivity to dopaminergic agonists induced by neonatal hippocampal lesions.

The effects of neonatal hippocampal lesions on behavioral responsiveness to dopaminergic agonists and antagonists were examined. The ventral hippocampus was damaged bilaterally using ibotenic acid on postnatal day 7, and locomotor responses to dopaminergic agonists and antagonists were evaluated on postnatal day 35 (PD35), 56 (PD56), and 70 (PD70). Qunipirole (0.06, 0.125, 0.25, and 0.5 mg/kg SC), but not SKF38393 (5 and 10 mg/kg SC), increased locomotion in a dose-dependent manner in control and lesioned groups on PD35 and PD56. However, lesioned rats displayed a greater behavioral response to quinpirole than controls at the doses of 0.25 and 0.5 mg/kg on both PD35 and PD56. Amphetamine (1.5 mg/kg IP) increased locomotor activity in both groups on PD70, but this effect was greater in lesioned rats than in controls. Raclopride (0.25 and 0.5 mg/kg SC) and SCH23390 (0.01 and 0.02 mg/kg SC) blocked the amphetamine-induced hyperlocomotion in the lesioned and control groups. These results suggest that neonatal hippocampal lesion-induced behavioral hyperresponsiveness to amphetamine is likely related to an increased postsynaptic sensitivity of the D2 subtype of receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Noninvasive measurements of human brain temperature using volume-localized proton magnetic resonance spectroscopy.

Elucidation of the role of cerebral hyperthermia as a secondary factor that worsens outcome after brain injury, and the therapeutic application of modest brain hypothermia would benefit from noninvasive measurements of absolute brain temperature. The present study was performed to evaluate the feasibility of using 1H magnetic resonance (MR) spectroscopy to measure absolute brain temperature in human subjects on a clinical imaging spectroscopy system operating at a field strength of 1.5 T. In vivo calibration results were obtained from swine brain during whole-body heating and cooling, with concurrent measurements of brain temperature via implanted probes. Plots of the frequency differences between the in vivo MR peaks of water and N-acetyl-aspartate and related compounds (NAX), or water and choline and other trimethylamines versus brain temperature were linear over the temperature range studied (28-40 degrees C). These relationships were used to estimate brain temperature from 1H MR spectra obtained from 10 adult human volunteers from 4 cm3-volumes selected from the frontal lobe and thalamus. Oral and forehead temperatures were monitored concurrently with MR data collection to verify normothermia in all the subjects studied. Temperatures determined using N-acetyl-aspartate or choline as the chemical shift reference did not differ significantly, and therefore results from these estimates were averaged. The brain temperature (mean +/- SD) measured from the frontal lobe (37.2 +/- 0.6 degrees C) and thalamus (37.7 +/- 0.6 degrees C) were significantly different from each other (paired t-test, p = 0.035). We conclude that 1H MR spectroscopy provides a viable noninvasive means of measuring regional brain temperatures in normal subjects and is a promising approach for measuring temperatures in brain-injured subjects.

Adult↗
PubMed1997

Preliminary results from the Northern Ireland arms of the UK Multicentre Teledermatology Trial: effect of camera performance on diagnostic accuracy.

The diagnostic accuracy of realtime teledermatology was measured using two different video cameras. One camera was a relatively low-cost, single-chip device (camera 1), while the other was a more expensive three-chip camera (camera 2). The diagnosis obtained via the videolink was compared with the diagnosis made in person. Sixty-five new patients referred to a dermatology clinic were examined using camera 1 followed by a standard face-to-face consultation. A further 65 patients were examined using camera 2 and the same procedure applied. Seventy-six per cent of conditions were correctly diagnosed by telemedicine using camera 2 compared with 59% using camera 1. A working differential diagnosis was obtained in 12% of cases using camera 2 compared with 17% using camera 1. The percentage of 'no diagnosis', wrong and missed diagnoses was halved using camera 2 compared with camera 1. These results suggest that the performance of camera 2 was superior to that of camera 1 for realtime teledermatology.

Adolescent↗