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Biomedical subjects

C Grant

Publications and source records attributed to C Grant.

At least 37 records · Page 2Linked to original sources
PubMed2002

Cerebrovascular carbon dioxide reactivity in sheep: effect of propofol or isoflurane anaesthesia.

Propofol and isoflurane are commonly used in neuroanaesthesia. Some published data suggest that the use of these agents is associated with impaired cerebral blood flow/carbon dioxide (CO2) reactivity. Cerebrovascular CO2 reactivity was therefore measured in three cohorts of adult merino sheep: awake (n=6), anaesthetized with steady-state propofol (15 mg/min; n=6) and anaesthetized with 2% isoflurane (n=6). Changes in cerebral blood flow were measured continuously from changes in velocities of blood in the sagittal sinus via a Doppler probe. Alterations in the partial pressure of carbon dioxide in arterial blood (PaCO2) over the range 18-63 mmHg were achieved by altering either the inspired CO2 concentration or the rate of mechanical ventilation. Cerebral blood flow/CO2 relationships were determined by linear regression analysis, with changes in cerebral blood flow expressed as a percentage of the value for a PaCO2 of 35 mmHg. Propofol decreased cerebral blood flow by 55% relative to pre-anaesthesia values (P=0.0001), while isoflurane did not significantly alter cerebral blood flow (88.45% of baseline, P=0.39). Significant linear relationships between cerebral blood flow and CO2 tension were determined in all individual studies (r2 ranged from 0.72 to 0.99). The slopes of the lines were highly variable between individuals for the awake cohort (mean 4.73, 1.42-7.12, 95% CI). The slopes for the propofol (mean 2.67, 2.06-3.28, 95% CI) and isoflurane (mean 2.82, 219-3.45, 95% CI) cohorts were more predictable. However, there was no significant difference between these anaesthetic agents with respect to the CO2 reactivity of cerebral blood flow.

Anesthetics, Inhalation↗
PubMed2002

The cerebrovascular effects of adrenaline, noradrenaline and dopamine infusions under propofol and isoflurane anaesthesia in sheep.

Infusions of catecholamines are frequently administered to patients receiving propofol or isoflurane anaesthesia. Interactions between these drugs may affect regional circulations, such as the brain. The aim of this animal (sheep) study was to determine the effects of ramped infusions of adrenaline, noradrenaline (10, 20, 40 micrograms/min) and dopamine (10, 20, 40 micrograms/kg/min) on cerebral blood flow (CBF), intracranial pressure (ICP), cerebrovascular resistance (CVR) and cerebral metabolic rate for oxygen (CMRO2). These measurements were made under awake physiological conditions, and during continuous propofol (15 mg/min) or 2% isoflurane anaesthesia. All three catecholamines significantly and equivalently increased mean arterial pressure from baseline in a dose-dependent manner in the three cohorts (P < 0.001). In the awake cohort (n = 8), dopamine (P < 0.01) significantly increased CBF from baseline whilst adrenaline and noradrenaline did not (P > 0.05). Under propofol (n = 6) and isoflurane (n = 6), all three catecholamines significantly increased CBF (P < 0.001). Dopamine caused the greatest increase in CBF, and was associated with significant increases in ICP (awake: P < 0.001; propofol P < 0.05; isoflurane P < 0.001) and CVR (isoflurane P < 0.05). No significant changes in CMRO2 were demonstrated. Under propofol and isoflurane anaesthesia, the cerebrovascular effects of catecholamines were significantly different from the awake, physiological state, with dopamine demonstrating the most pronounced effects, particularly under propofol. Dopamine-induced hyperaemia was associated with other cerebrovascular changes. In the presence of an equivalent effect on mean arterial pressure, the exaggerated cerebrovascular effects under anaesthesia appear to be centrally mediated, possibly induced by propofol- or isoflurane-dependent changes in blood-brain barrier permeability, thereby causing a direct influence on the cerebral vasculature.

Anesthesia↗
PubMed2001

The genome of the natural genetic engineer Agrobacterium tumefaciens C58.

The 5.67-megabase genome of the plant pathogen Agrobacterium tumefaciens C58 consists of a circular chromosome, a linear chromosome, and two plasmids. Extensive orthology and nucleotide colinearity between the genomes of A. tumefaciens and the plant symbiont Sinorhizobium meliloti suggest a recent evolutionary divergence. Their similarities include metabolic, transport, and regulatory systems that promote survival in the highly competitive rhizosphere; differences are apparent in their genome structure and virulence gene complement. Availability of the A. tumefaciens sequence will facilitate investigations into the molecular basis of pathogenesis and the evolutionary divergence of pathogenic and symbiotic lifestyles.

Agrobacterium tumefaciens↗
PubMed2001

Epinephrine, norepinephrine and dopamine infusions decrease propofol concentrations during continuous propofol infusion in an ovine model.

OBJECTIVE: To determine the effects of exogenous ramped infusions of epinephrine, norepinephrine and dopamine on arterial and effluent brain blood concentrations of propofol under steady state intravenous anesthesia. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Five adult female merino sheep. INTERVENTIONS: Induction (5 mg/kg) and continuous infusion of propofol (15 mg/min) with controlled mechanical ventilation to maintain PaCO2 40 mmHg. After 1 h of continuous anesthesia, each animal randomly received ramped infusions of epinephrine, norepinephrine (10, 20, 40 microg/min) and dopamine (10, 20, 40 microg x kg x min) in 3 x 5 min intervals followed by a 30-min washout period. MEASUREMENTS: Arterial and sagittal sinus whole blood for determination of propofol concentrations using high-pressure liquid chromatography. Cardiac output using a thermodilution method. Level of consciousness using an observational scale. MAIN RESULTS: All three drugs significantly and transiently increased cardiac output in a dose-dependent fashion to a maximum of 146-169% of baseline. Baseline arterial and sagittal sinus propofol concentrations were not statistically different prior to catecholamine infusions. All three drugs significantly reduced mean arterial propofol concentrations (95 % CI, p < 0.05): epinephrine to 41.8% of baseline (11.4-72), norepinephrine to 63 % (27-99) and dopamine to 52.9 % (18.5-87.3). There were parallel reductions of concentrations in sagittal sinus blood leaving the brain. The lowest blood concentrations were associated with emergence from anesthesia. Arterial concentrations were inversely related to the simultaneously determined cardiac output (r2 = 0.74, p < 0.0001). Comparison of the data with the predictions of a previously developed recirculatory model of propofol disposition in sheep showed the data were consistent with a mechanism based on increased first pass dilution and clearance of propofol secondary to the increased cardiac output. CONCLUSIONS: Catecholamines produced circulatory changes that reversed propofol anesthesia. These observations have potential clinical implications for the use of propofol in hyperdynamic circulatory conditions, either induced by exogenous catecholamine infusions or pathological states.

Anesthetics, Intravenous↗
PubMed2001

In vivo cerebral pharmacokinetics and pharmacodynamics of diazepam and midazolam after short intravenous infusion administration in sheep.

The cerebral pharmacokinetics and pharmacodynamics of midazolam and diazepam were examined in chronically instrumented sheep via measurements of their arterio-venous concentration difference across the brain during and after 2-min i.v. infusions. Diazepam (30 mg) or midazolam (10 mg) were administered on 5 separate occasions to 4 sheep. For both drugs, rapid cerebral uptake occurred during the infusion, which quickly turned to elution in the postinfusion period. However, this process was more rapid for midazolam than diazepam. The cerebral pharmacokinetics of both was better described by a kinetic model with slight membrane limitation rather than flow limitation. For diazepam, the estimated brain:plasma partition coefficient was 2.67, and the first and second compartments filled with half-lives of 2.2 and 0.5 min, respectively. For midazolam, these values were 0.27, 0.26 and 1.34 min, respectively. In a subset of sheep, pulmonary arterial-arterial gradients were too small to measure suggesting limited metabolism and small distribution volumes for both drugs in the lungs. Simultaneous dynamic measurements of cerebral blood flow and algesimetry lagged behind both the arterial and sagittal sinus blood concentrations. The changes in cerebral blood flow were best described by a previously published a dynamic model that incorporated long half-lives for drug dissociation from the benzodiazepine receptor (13.3 and 5.5 min for midazolam and diazepam, respectively). Effect compartment modeling of the cerebral blood flow data showed apparent effect compartment half-lives (t1/2,keo) that were longer than the half-lives of cerebral equilibration.

Animals↗
PubMed2001

A comparison of effects measured with isotonic and isometric recording: I. Concentration-effect curves for agonists.

Concentration-effect curves were obtained with carbachol tested on isolated preparations of guinea-pig ileum taken from adjacent sites in the same animal, one recorded isotonically, the other isometrically: similar experiments were made with histamine as agonist and with carbachol on rat uterus (in oestrus). The position and steepness of the curves was expressed as the values of [EC(50)] and the exponent, P: with carbachol or histamine on guinea-pig ileum the curves were significantly steeper with isotonic recording (P<0.02, sign test) and displaced towards lower concentrations (P<0.005) but there were significant correlations (P<0.05) between values obtained with tissues from the same animal. The curves for carbachol on the rat uterus were very steep: with isotonic recording the exponent (often eight or more) was consistently higher than with isometric (P<0.001): there was no significant displacement but there was a significant correlation (P<0.05) between values of [EC(50)] obtained with tissues from the same animal. Although the results obtained by the two methods are different, they are correlated. These effects are to be expected because with isotonic recording there can be no change in length until the tension exceeds the load and the tissue bulk sets an upper limit to shortening: the range within which an effect can be measured (the "operational window") is smaller. The observed effects on [EC(50)] and P have been reproduced with theoretical data.

Animals↗
PubMed2001

A comparison of effects measured with isotonic and isometric recording: II. Concentration-effect curves for physiological antagonists.

If one drug, B, antagonizes another, A, by producing the opposite physiological effect, the antagonist concentration-effect curves should be affected by the recording system, which limits the range of agonist responses. With pieces of isolated guinea-pig ileum taken from adjacent parts of the same animal, one recorded isotonically, the other isometrically with the same load, the isotonic IC(50) values for (-)isoprenaline opposing carbachol or histamine were lower than the isometric values (P<0.01) but there was a significant correlation between them (P<0.01): the isotonic curves were steeper (P<0.01) and there were wider shifts in IC(50) before increasing the agonist reduced the maximum relaxation. In similar experiments with pieces of rat uterus in oestrus from the same animal, the concentration-effect curves for carbachol opposed by increasing concentrations of (-)isoprenaline or (-)adrenaline had slightly lower EC(50) values with isometric recording but there was a significant correlation (P<0.01) with isotonic values. The antagonist effect (ratio of the EC(50) relative to that for the control) was higher with isotonic recording (P<0.01 for (-)isoprenaline, P<0.025 for (-)adrenaline) and all (27) curves were steeper than the corresponding isometric curve (P<0.001). The influence of the method of recording on the results is expected from the narrower operational window and smaller upper limit to relaxation with isotonic recording. A way of obtaining measurements of IC(50) against a standard agonist effect is suggested in an Appendix.

Animals↗
PubMed2001

The anti-nociceptive efficacy of low dose intramuscular xylazine in lambs.

The anti-nociceptive effects of 50 microg kg(-1)of intramuscular xylazine were examined in seven lambs of 4-6 weeks of age using an electrical nociceptive testing method. Lamb anti-nociception increased from an average baseline of 5.88+/-0.72 mA to an average peak value of 13.66+/-1.49 mA at 21 minutes (mean+/-SEM) after the dose, and remained above baseline for the duration of the experimental period (60 minutes). All values were significantly above baseline from 5 minutes post-xylazine administration onwards. These data were also compared with previously published data from adult sheep undergoing the same treatment. There were no differences in the analgesic response between the adult or lamb groups suggesting xylazine dose requirements scale with bodyweight and are unaffected by age over this range. These findings support the use of xylazine as an effective analgesic in sheep with comparable effects and consistent dosing requirements per unit body weight between adult sheep and lambs.

Adrenergic alpha-Agonists↗
PubMed2001

Cardiovascular and haemodynamic effects of intramuscular doses of xylazine in conscious sheep.

OBJECTIVE: To determine if a commonly used analgesic dose of xylazine has detrimental cardiovascular or haemodynamic effects in sheep. DESIGN: A physiological study following intramuscular administration of xylazine. PROCEDURE: Xylazine (50 micrograms/kg) was injected intramuscularly into six healthy Merino ewes. For 60 min heart rate, mean arterial blood pressure and cardiac output were recorded; arterial blood samples for the measurement of blood gas tensions were also collected. RESULTS: There were no significant changes in heart rate, mean arterial blood pressure, cardiac output or arterial carbon dioxide tension. A slight degree of arterial hypoxaemia was noted with a 10% reduction in arterial oxygen tension values at 30 min. CONCLUSION: The minimal changes to cardiovascular and respiratory values in this study verify the safety of previously suggested analgesic dosing regimens for sheep. Previously reported hypoxaemic effects in sheep as a result of intravenous xylazine administration appear to be reduced as a result of intramuscular administration.

Adrenergic alpha-Agonists↗
PubMed2001

The cerebral and systemic kinetics of thiopentone and propofol in halothane anaesthetized sheep.

The cerebral and systemic kinetics of intravenous thiopentone (250 mg over 2 minutes, n=5) and propofol (100 mg over 2 minutes, n=6) were determined in sheep anaesthetized with halothane (2.0%) and mechanically ventilated to an end-expired carbon dioxide tension of 40 mmHg. The sheep were previously instrumented with arterial and sagittal sinus (effluent from the brain) blood sampling catheters. Systemic kinetics were inferred from the time-course of the arterial blood concentrations, and cerebral kinetics from the time-course of the arterio-sagittal sinus concentration difference across the brain. Under halothane anaesthesia, the peak arterial concentrations of each drug occurred at the end of the two-minute infusion, and was 42.3 mg/l and 12.3 mg/l for thiopentone and propofol, respectively. Propofol had a significantly larger systemic clearance (3.19 l/min) than thiopentone (0.99 l/min). The brain concentrations of propofol equilibrated more slowly with the arterial concentrations than those of thiopentone. The extraction ratio across the brain near the end of the infusions (1.5 min) were 0.85 and 0.46 respectively. These data were also compared to analogous previously published data for initially conscious sheep. The systemic kinetics of thiopentone were little affected by halothane anaesthesia. For propofol, halothane anaesthesia was associated with a statistically significant reduction in clearance (50% of awake), a slower initial half-life (247% of awake), and the emergence of a second slower half-life in some sheep. The cerebral kinetics of both drugs were subtly altered by halothane anaesthesia.

Anesthesia, Inhalation↗
PubMed2001

Social functioning in first- and multiepisode schizophrenia.

OBJECTIVE: To compare the social functioning of individuals experiencing their first episodes of schizophrenia with those who have experienced multiple episodes and with nonpsychiatrically ill control subjects. METHOD: Subjects included 40 patients with first-episode (FE) schizophrenia, 40 patients with multiepisode (ME) schizophrenia, and a control group of 40 nonpsychiatrically ill individuals. Three social-functioning measures were used: the Social Functioning Scale (SFS), the Quality of Life Scale (QOL), and the Assessment of Interpersonal Problem-Solving Skills (AIPSS). RESULTS: Control subjects significantly outperformed FE and ME participants on all social-functioning measures. FE and ME samples did not differ in their performance on the SFS and the AIPSS. On the QLS, ME participants outperformed FE participants. CONCLUSIONS: This study demonstrated that deficits in social functioning are present near the onset of schizophrenia.

Adult↗
PubMed2001

A xylazine infusion regimen to provide analgesia in sheep.

The efficacy of continuous low-dose xylazine infusion following an initial loading dose in providing analgesia in sheep was examined using an algesimetry method based on a leg lifting response to an electrical stimulus. Sheep received a 5 mg intramuscular injection of xylazine followed by continuous infusion of intravenous xylazine (2mg/h) for 90 min. This treatment resulted in significant increases in the level of current required to elicit a leg lifting response (287% of baseline) and steady state analgesia was maintained from 10 min after the start of the infusion until the end of the experimental period. This protocol appears to be a simple and effective regimen for providing steady state analgesia in sheep.

Adrenergic alpha-Agonists↗
PubMed2000

Prevalence of iron deficiency in Auckland high school students.

AIMS: To determine the frequency of iron deficiency and anaemia in high school students. METHOD: The survey was carried out at eight Auckland high schools with a high proportion (> or =15%) of Pacific Islands students. All students in Forms 5-7 at these schools were invited to participate, and 1644 students (Pacific Island 765, Asian 350, European 295, Maori 234) had iron assessments (response rate 61%). Iron deficiency was defined as any two (or more) of the following, three: serum ferritin <12 microg/L, iron saturation <14%, or red cell distribution width >14.5%. Anaemia was defined as haemoglobin <120 g/L for females and <130 g/L for males. RESULTS: Iron deficiency and anaemia were each ten times more common in girls (18.3% and 11.5%, respectively) than boys (1.5% and 1.4%). In females, iron deficiency was two to three times more common in Maori (25.6%), Pacific Islanders (20.9%) and Asians (15.4%) compared with Europeans (8.3 %), while anaemia was three to four times more common in Asians (15.9%), Pacific Islanders (12.1%) and Maori (11.2%) compared with Europeans (4.2%). Iron deficiency and anaemia prevalences were inversely associated with aerobic fitness, but not with age or years since menarche. CONCLUSION: Prevalences of iron deficiency and anaemia are high in non-European female adolescents in Auckland, for reasons currently unknown.

Adolescent↗
PubMed2000

A randomised controlled trial and economic evaluation of a referrals facilitator between primary care and the voluntary sector.

OBJECTIVES: To compare outcome and resource utilisation among patients referred to the Amalthea Project, a liaison organisation that facilitates contact between voluntary organisations and patients in primary care, with patients receiving routine general practitioner care. DESIGN: Randomised controlled trial with follow up at one and four months. SETTING: 26 general practices in Avon. PARTICIPANTS: 161 patients identified by their general practitioner as having psychosocial problems. MAIN OUTCOME MEASURES: Primary outcomes were psychological wellbeing (assessed with the hospital anxiety and depression scale) and social support (assessed using the Duke-UNC functional social support questionnaire). Secondary outcomes were quality of life measures (the Dartmouth COOP/WONCA functional health assessment charts and the delighted-terrible faces scale), cost of contacts with the primary healthcare team and Amalthea Project, cost of prescribing in primary care, and cost of referrals to other agencies, over four months. RESULTS: The Amalthea group showed significantly greater improvements in anxiety (average difference between groups after adjustment for baseline -1.9, 95% confidence interval -3.0 to -0.7), other emotional feelings (average adjusted difference -0.5, -0.8 to -0.2), ability to carry out everyday activities (-0.5, -0.8 to -0.2), feelings about general health (-0.4, -0.7 to -0.1), and quality of life (-0.5, -0.9 to -0.1). No difference was detected in depression or perceived social support. The mean cost was significantly greater in the Amalthea arm than the general practitioner care arm ( pound153 v pound133, P=0. 025). CONCLUSION: Referral to the Amalthea Project and subsequent contact with the voluntary sector results in clinically important benefits compared with usual general practitioner care in managing psychosocial problems, but at a higher cost.

Adolescent↗