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Biomedical subjects

A J Woods

Publications and source records attributed to A J Woods.

At least 19 recordsLinked to original sources

Perception of motor strength and stimulus magnitude are correlated in stroke patients.

The authors examined whether perception of contralateral limb strength is altered and whether perception of strength correlates with perception of stimulus intensity (magnitude) in a prospective sample of patients with unilateral right (RHL: n = 13) and left (LHL: n = 6) hemisphere lesions due to stroke. Patients with RHL tended to overestimate strength and patients with LHL tended to underestimate strength; both patterns were highly correlated with altered perception of stimulus magnitude.

Adult↗

Disorganized search on cancellation is not a consequence of neglect.

BACKGROUND: Some studies have suggested that in stroke patients, spatial inattention on the cancellation test is closely related to disorganized visual search. However, methods to assess spatial aspects of search organization on cancellation tests have not been well developed. In this study the authors design and evaluate new methods to quantify strategies of spatial exploration on the cancellation test in stroke patients who showed a broad range of spatial attentional abilities, and test whether disorganization and inattention are related. METHODS: Twenty stroke patients were videotaped while they performed a cancellation test. Several variables that reflect spatial aspects of search organization were measured through subsequent video playback. Two patients with severe neglect were excluded from further analysis to avoid constraining the spatial expression of search organization. Spearman correlations were used to assess whether severity of spatial inattention correlated with the individual search organization measures. RESULTS: Of the 18 remaining patients, 10 had mild-moderate spatial neglect (pathologic inattention), while the other 8 omitted at most one target (normal performance). There were no significant correlations between the number of targets omitted and any of the search organization measures. CONCLUSIONS: Spatial inattention on cancellation due to neglect following stroke is not closely related to the organization of visual search. Instead, search disorganization during cancellation may reflect disturbance of an unspecified executive control mechanism.

Aged↗

The development of the emetic reflex in the house musk shrew, Suncus murinus.

The emetic (retching and vomiting) reflex is an important component of the body's defence system against accidentally ingested toxins and emesis is also a common symptom of disease and a side-effect of a number of pharmacological therapies. The development of the reflex has been the subject of few systematic studies. The aim of this study was to characterise the development of the emetic reflex in Suncus murinus (the house musk shrew) using emetic stimuli acting via three different afferent pathways: motion via the vestibular system, pyrogallol via abdominal vagal afferents and resiniferatoxin (a capsaicin analog) via the brainstem. The emetic reflex was not present to any stimulus prior to postnatal day 10 but the onset of the response to motion lagged behind that to the other stimuli in not being present until postnatal day 15. Body weight was not a determinant of the presence of the reflex. It is proposed that the delayed presence of the emetic reflex in Suncus makes it an ideal species in which to investigate factors regulating its development.

Age Factors↗

The effect of the NK1 receptor antagonist CP-99,994 on emesis and c-fos protein induction by loperamide in the ferret.

The site of the anti-emetic action of the neurokinin1 receptor antagonist CP-99,994 was studied in the ferret using the centrally acting opiate receptor agonist loperamide at a dose (0.5 mg/kg s.c.) which induced emesis in all animals tested. CP-99,994 (1 mg/kg, s.c.x2) abolished the emetic response (retching and vomiting) and the behaviours (licking, wet dog shakes, mouth scratching and gagging) induced by loperamide over a 2-h observation period. The enantiomer of this compound CP-100,263 (1 mg/kg, s.c.x2) did not have any significant effect on emesis or related behaviours. Loperamide (0.5 mg/kg s.c.) administration (but not its vehicle) resulted in dense fos-like immunoreactivity (FLI) mainly throughout the rostro-caudal extent of the nucleus tractus solitarius but not the area postrema. Although CP-99,994 (1 mg/kgx2) abolished the loperamide-induced emesis, it did not have any statistically significant effect on FLI in the brainstem. In loperamide and CP-100,263 (1 mg/kg, s.c.x2) treated animals FLI was comparable to that in animals treated with loperamide and CP-99,994. The results from this study taken together with those from previous studies indicate that loperamide exerts its emetic effect via nucleus tractus solitarius dendrites projecting into the area postrema. The lack of significant effect of CP-99,994 on the FLI induced by loperamide in this nucleus suggests that it is acting at a site "deep" in the nucleus tractus solitarius or elsewhere. The marked reduction in behaviours associated with loperamide administration by CP-99,994 provides a preliminary indication that NK1 receptor antagonist (as represented by CP-99,994) may in the clinic have effects on behaviours induced by emetic agents in addition to their previously described effects on retching and vomiting.

Animals↗

The emetic and anti-emetic effects of the capsaicin analogue resiniferatoxin in Suncus murinus, the house musk shrew.

1. In SUNCUS: murinus the ultrapotent capsaicin analogue resiniferatoxin (RTX) induced an emetic response in the dose range 1 - 1000 microg kg(-1), s.c. The latency was inversely related to dose and ranged from 41.2+/-4.4 min. (1 microg kg(-1), s.c.) to 2.7+/-0.6 min. (1000 microg kg(-1), s.c.). 2. The emetic response to RTX (10 or 100 microg kg(-1), s.c.) was blocked or markedly reduced by pre-treatment with RTX (100 microg kg(-1), s.c.), 8-OH-DPAT (100 microg kg(-1), s.c.), morphine (2 mg kg(-1), s.c.), neonatal capsaicin (100 mg kg(-1), s.c.) and the NK(1) receptor antagonist CP-99,994 (10 - 20 mg kg(-1), s.c.) but not by the 5-HT(3) receptor antagonist tropisetron (200 microg kg(-1), s.c.). 3. RTX (100 microg kg(-1), s.c.) induced c-fos-like immunoreactivity in the area postrema and parts of the nucleus tractus solitarius. This pattern is consistent with the proposal that the emetic effect is mediated via one or both of these structures and an involvement of substance P is discussed. 4. RTX (10 and 100 microg kg(-1), s.c.) had broad-spectrum antiemetic effects in Suncus as indicated by its ability to block or markedly reduce the emetic response to motion (1 Hz, 4 cm lateral, 10 min.), cisplatin (20 mg kg(-1), i.p.), intragastric copper sulphate (40 mg kg(-1), p.o.), nicotine (10 mg kg(-1), s.c.) and RTX (100 microg kg(-1), s.c.) itself. 5. It is proposed that the site of the anti-emetic effect is in the nucleus tractus solitarius and mechanisms involving the modulation of substance P release are discussed. 6. The general utility of SUNCUS: for investigations of vanilloid receptors is reviewed in the light of the exquisite sensitivity of the emetic reflex in this species to resiniferatoxin.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Inhibition of brown fat activity during hypothalamic stimulation in the rat.

Previous work has shown that low-level electrical stimulation of the ventromedial hypothalamus (VMH) in anesthetized rats produces a sustained decrease (phase 1) in interscapular brown adipose tissue (IBAT) temperature followed by a rise (phase 2) after the stimulus has stopped [Woods, A. J., and M. J. Stock. Am. J. Physiol. 266 (Regulatory, Integrative Comp. Physiol. 35): R328-R337, 1994]. In this study, rat oxygen consumption was found to decrease (24%) and then increase (74%) during phase 1 and 2, respectively. The effect of norepinephrine, alpha-adrenoceptor antagonists, substance P, and neuropeptide Y, with and/or without VMH stimulation, suggested that vasoconstriction was unlikely to account for the phase 1 decreases in thermogenesis and temperature. However, measurement with radio-labeled microspheres showed that IBAT capillary blood flow was reduced by 70% during phase 1, and this, plus a 50% decrease in blood oxygen extraction, indicated that phase 1 could be due to vasodilatation of arteriovenous anastomoses. It was postulated that phase 1 resulted from release of neuropeptides, such as substance P, causing diversion of arterial blood away from IBAT capillaries, thereby increasing convective heat loss and inhibiting heat production during phase 1.

Adipose Tissue, Brown↗

Cisplatin acutely reduces 5-hydroxytryptamine-induced vagal depolarization in the rat: protective action of dexamethasone.

The effect of the anti-cancer cytotoxic drug cisplatin on KCl and 5-hydroxytryptamine (5-HT)-induced depolarization in the rat isolated cervical vagus nerve was investigated using the 'grease gap' extracellular recording technique. KCl (10 mM) perfused onto the isolated nerve previously incubated for 2 h in 10 microM cisplatin initiated a d.c. potential of 1.06 +/- 0.09 mV compared to a potential of 1.29 +/- 0.13 mV in control nerves. Perfusion with 5 microM 5-HT produced a markedly reduced depolarization (0.23 +/- 0.02 mV) in cisplatin-treated nerves compared with control nerves (0.42 +/- 0.04 mV, P = 0.005). This effect was enhanced when 5-HT was reapplied 30 min later (0.19 +/- 0.02 mV in cisplatin-treated compared with 0.42 +/- 0.03 mV in controls, P < 0.0001). The inhibitory effect of cisplatin on 5-HT-induced depolarization was found to be significantly (P = 0.004) reduced by the addition of dexamethasone (10 microM) to the incubation buffer (0.34 +/- 0.04 mV). These results are discussed in the light of the emetic and neurotoxic effects of cisplatin and the protective effects of dexamethasone.

Animals↗

An electrophysiological investigation of the effects of cisplatin and the protective actions of dexamethasone on cultured dorsal root ganglion neurones from neonatal rats.

In this study we have investigated the acute and chronic effects of cisplatin on whole cell currents in cultured dorsal root ganglion neurones. Consistent with effects on action potentials measured under current clamp, acute (5 min) application of cisplatin (5 microM) attenuated voltage-activated potassium, and mixed cation currents by approximately 50% in both cases. Chronic treatment (5-7 days) of cultured neurones with 5 microM cisplatin also resulted in greatly reduced voltage-activated potassium currents (by 50%) and calcium currents (by 60%) compared to events recorded from neurones not treated with cisplatin. In contrast, the amplitude of inward cation current activated by hyperpolarization was doubled by 5-12 days treatment with cisplatin. Studies on action potential after-depolarizations and calcium-activated chloride currents suggest that cisplatin disturbs calcium homeostatic mechanisms. These observations may account for anode break spike excitation and the low efficiency with which cells buffer intracellular calcium following cisplatin treatment. Dexamethasone has been found to enhance the anti-emetic effects of 5-HT3 receptor antagonists in patients treated with cisplatin. For this reason the actions of dexamethasone were studied in combination with cisplatin treatment. Although acute application of dexamethasone (1-10 microM) produced transient depolarizations and bursts of action potentials, after 5 minutes application it had no effect on membrane potential, input resistance, or the properties of action potentials evoked by depolarizing current commands.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tracheal epithelial damage alters tracer fluxes and effects of tracheal osmolaity in sheep in vivo.

Tracheal osmolaity affects blood flow and the flux of a tracer, technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA), from tracheal lumen to venous blood in anesthetized sheep. Hyperosmolar liquids increase blood flow and slightly decrease 99mTc-DTPA flux, whereas hyposmolar liquids have no effect on blood flow and greatly increase 99mTc-DTPA flux. We have now investigated whether epithelial damage induced by exposure of the tracheal lumen to a detergent (0.2% Triton X-100) alters these effects. A tracheal artery was perfused, and tracheal venous blood was collected. The initial tracheal volume was 12.8 +/- 0.7 ml. Triton X-100 greatly increased the permeability coefficient for 99mTc-DTPA from -2.1 x 10(-7) to -240 x 10(-7) cm/s. Hyperosmolar Krebs-Henseleit solution (KH; 739 +/- 6 mosmol/kg) increased arterial (+14.3%) and venous (+21.5%) flows and decreased 99mTc-DTPA output by 51.7%. Water flux into the lumen (+0.3 +/- 0.1 ml) was not significant, and the osmolality decreased by 99 +/- 9 mosmol/kg. Hyposmolar KH (124 +/- 2 mosmol/kg) had no effect on arterial and venous flows (-1.3% for both), and the increase in 99mTc-DTPA output (+8.3%) was small and not significant. The volume decreased by 0.4 +/- 0.1 ml, and the osmolaity increased by 36 +/- 4 mosmol/kg. Thus epithelial damage greatly increases the baseline permeability of the tracheal wall to 99mTc-DTPA. It does not alter the qualitative effects of hypersomolar KH on blood flow and 99mTc-DTPA output but does reduce the effect of hyposmolar KH on 99mTc-DTPA output. The latter effect may be a consequence of the reduced net water movement in response to non-isosmolar solutions after epithelial damage.

Animals↗

Thermoregulatory effects of resiniferatoxin in the rat.

When administered acutely, the vanilloid (capsaicin) receptor agonist resiniferatoxin induces marked hypothermia in the ferret, rat and mouse. The aim of this study was to further characterise the thermoregulatory effects of resiniferatoxin in the rat in an attempt to understand the mechanism by which resiniferatoxin induces this hypothermic effect. Three doses of resiniferatoxin were administered (50, 100, 200 micrograms/kg s.c.) in separate animals at an ambient temperature (Ta) of 20 degrees C but there was no apparent dose-related effect on the decrease in colonic temperature over this range. Resiniferatoxin (50 micrograms/kg s.c.) decreased whole body oxygen consumption when measured below thermoneutrality (Ta = 20 degrees C) but not at thermoneutrality (Ta = 29 degrees C); likewise there was no hypothermic response to resiniferatoxin when measured at a Ta of 29 degrees C. Operant responding for radiant heat in a cold environment (-8 degrees C) was also measured in resiniferatoxin-treated (50 micrograms/kg s.c.) rats. These experiments showed that resiniferatoxin-treated rats attempted to defend body temperature by lever pressing for more radiant heat. However, this was not sufficient to reverse the hypothermia. Two repeat doses, 1 week apart, had little or no effect on colonic temperature, oxygen consumption or operant responding in the cold. Resiniferatoxin (50 micrograms/kg s.c.) also produced hypothermia (Ta = 20 degrees C) in neonatally capsaicinized adult rats. The exact site and mode of action is still under investigation, but it is postulated that resiniferatoxin activates, and then destroys or desensitizes warm thermoreceptors.

Animals↗

Water content, lens hardness and cataract appearance.

Hardening of a cataractous lens is associated with the clinical appearance of brunescence and advancing age. Alterations in the nature and concentration of proteins, lens fibre compaction and other biochemical changes may all be contributing factors towards increased hardness. As the nucleus confers most of the rigidity to the lens and water content decreases towards the centre of the nucleus, the hardness might be thought to be related to total water content. To study the relationship between water content, hardness and the clinical appearance of cataract, 135 lenses were obtained from eyes undergoing extracapsular cataract surgery. The cataracts were assessed and classified pre-operatively. Lens hardness was determined by a specially designed guillotine and water content was measured by weighing the lens before and after desiccation. A regression analysis was carried out to look at the variation of lens water content with hardness, degree of nuclear sclerosis, extent of cortical and posterior subcapsular cataract, vacuolation and age. Multivariate analysis of data demonstrated a relationship between lens hardness and lens water content, degree of nuclear sclerosis and age (R2 = 0.59). An association could not be detected between lens water content and age, degree of nuclear sclerosis, extent of cortical and posterior subcapsular cataract and vacuoles. This study suggests that hardening of the lens is reflected by a respective decrease in water content. Increased hardness is associated with coloration and advancing age.

Adult↗

Biphasic brown fat temperature responses to hypothalamic stimulation in rats.

Low-level electrical stimulation (monophasic square-wave pulses: 15 Hz, 7.0 microA, 0.5 ms) of the ventromedial hypothalamus (VMH) in anesthetized rats produced a decrease (phase 1) in interscapular brown adipose tissue (IBAT) temperature that was sustained for as long as the stimulus was applied (2-45 min). A rise in IBAT temperature (phase 2) occurred only after the stimulation had stopped. VMH stimulations ipsilateral and contralateral to a lateral hypothalamic (LH) lesion indicated that the phase 1 response required an intact LH, and denervation of IBAT showed that both phases required an intact sympathetic innervation. Central intracerebroventricular injections of amphetamine and dopamine produced decreases in IBAT temperature similar in magnitude to the phase 1 response to electrical stimulation of the VMH. This, as well as the observation that pimozide blocked phase 1, suggested that dopaminergic pathways were responsible for mediating the phase 1 decrease in IBAT temperature. The peripheral mechanisms responsible for phase 1 are unknown, but a vascular component might explain the unexpected decrease in IBAT temperature seen during sustained VMH stimulation.

Adipose Tissue, Brown↗

Liveweight estimation of cattle by scale and by tape, a method comparison study.

The repeatability of weight estimation of cattle by scale and by tape and the agreement of weight estimates obtained by the 2 methods were evaluated. The within-subject standard deviation of replicates was used as a measure of repeatability while the agreement of the 2 methods was evaluated by analysis of the differences in weight estimates. In young cattle, the measurement error of the tape was about twice that of the scale while in adult cattle it was more than 4 times as great. Although weight estimates by the 2 methods were highly correlated, considerable differences occurred in individual cattle. The same was true for estimates of weight gain. It does not appear advisable to use the tape in trials where weight is an independent variable whereas the use of the tape can be justified in experiments where weight is the dependent variable.

Animal Husbandry↗

Effects of central injection of glucose on thermogenesis in normal, VMH-lesioned and genetically obese rats.

Intra-cerebroventricular (i.c.v.) injection of glucose (0.1-1.0 mumol) caused dose-dependent increases in resting oxygen consumption (Vo2) of conscious rats (maximum increase of 15.4 +/- 2% at 0.5 mumol). These effects were significantly attenuated by peripheral (i.p.) pretreatment with the beta-adrenoceptor propranolol, indicating the importance of the sympathetic nervous system (SNS) in the response. Plasma glucose concentrations were elevated (11%) 30 min after central injection of glucose, but intravenous glucose (0.5 mumol) did not affect resting Vo2. Animals which had been fasted for 12 h prior to Vo2 measurement exhibited reduced basal Vo2 values, but the nutritional state of the animal did not affect the metabolic response to central injections of glucose (0.5 mumol). Rats exhibiting genetic (fa/fa Zucker rats) and hypothalamic (VMH-lesioned) obesity showed similar thermogenic responses to centrally administered glucose, to their lean counterparts. These data suggest a dual action of central glucose in the regulation of energy balance, involving stimulation of energy expenditure in addition to its reported inhibition of energy intake. The defective diet-induced thermogenesis associated with VMH and genetic obesities does not appear to result from an inability to respond to changes in intracerebroventricular glucose concentrations.

Animals↗

Towards an advisor for MRI.

This paper discusses the role of a computer advisor in MR image acquisition, interpretation and the diagnosis of cerebral disease. The development of an image and statistical database for use in providing advice is described.

Brain Diseases↗