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Biomedical subjects

P D Andrew

Publications and source records attributed to P D Andrew.

18 recordsLinked to original sources
PubMed2005

Characterization of the metabolites of alosetron in experimental animals and human.

The metabolism of radiolabelled alosetron was studied in rat, dog, rabbit, mouse and human. The metabolism in rat and dog was studied at a low and an elevated dose designed to generate sufficient quantities of metabolite for definitive identification. A strategy for the characterization of metabolites in cases of extensive metabolism was developed and demonstrated for alosetron. Semi-preparative high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR) and liquid chromatography-nuclear magnetic resonance (HPLC-NMR) enabled the isolation and characterization of 28 metabolites of alosetron. The characterization of the metabolites in animal excreta facilitated the identification of human systemic metabolites.

Animals↗
PubMed2000

Effect of simulating leg length inequality on pelvic torsion and trunk mobility.

Although techniques such as roentgenograms and magnetic resonance imaging can provide definitive information about leg length inequality, they are not easily implemented for screening purposes. Using relative heights of palpated iliac crests as criteria for determining degree of lateral pelvic tilt, we examined the immediate effect of simulating leg length inequality on pelvic torsion and trunk flexion. In seven healthy men and 22 healthy women, 18-28 years of age, a lift of at least 15 mm was placed under either foot to laterally tilt the pelvis 1.2 degrees or more. In eight subjects with pre-existing lateral pelvic tilts of 1.8 degrees or more, a lift was also used to eliminate the tilt. We examined how this tilting affected torsion between the innominates and mobility of the trunk. The innominate contralateral to the lift became more anteriorly rotated than the ipsilateral innominate and lateral flexion of the trunk increased toward the side of the lift. Both of these effects can be associated with clinical leg length inequality, so a lateral pelvic tilt on the order of 1.2 degrees, if encountered in the clinic, should signal the suitability of more extensive examination for possible lower limb asymmetry.

Adolescent↗
PubMed1998

Short-term effect of correcting leg length discrepancy on performance of a forceful body extension task in young adults.

In this study we assessed the short-term effect of correcting leg length discrepancy on a vigorously performed task of resisted full body extension in 10 men, 18 to 35 years old, who had estimated leg length discrepancies of 10-15 mm. Using a cable ergometer we examined work performed, initial peak tension exerted on the ergometer, second peak tension, time to first peak tension, and mean velocity of the whole task. Each subject performed the task both with and without a heel lift, introduced to equalize leg length. The interval between testing under these two conditions was 48 hr. In the task of pulling the cable upward, each subject began from floor level with knees and trunk flexed, progressing to full body extension with the arms pulling the cable overhead with maximal effort. For each trial the task was repeated 15 times, with intervals of 90 seconds between the repetitions. Use of the lift failed to have a statistically significant effect on any of the variables, although it clearly enabled three of the subjects to exert greater strength with the arms and trunk during the second peak tension. This suggests that 1) overall body extension is influenced by too many factors to be affected in a consistently predictable way by a heel lift to correct leg length discrepancy, and 2) the heel lift may aid certain subjects with leg length discrepancy specifically during extension of the trunk in this task.

Adaptation, Physiological↗
PubMed1996

The effect of nontraumatic immobilization on ankle dorsiflexion stiffness in rats.

Experimental evidence supports the general conclusion that 6 or more weeks of immobilization will cause joint contractures due to changes in the capsules of animals whose limbs have been traumatized. There is controversy whether contractures will form in 6 weeks in limbs which are free of trauma. The purpose of this study was to determine if range of motion would be lost in ankle joints of rats following nontraumatic immobilization of the hindlimb for 2 or 6 weeks. The right hindlimb of each animal was immobilized in a plaster cast for 2 or 6 weeks with the left hindlimb serving as a matched control (N = 8). Nonimmobilized rats served as additional controls (N = 4). Following 2 or 6 weeks of immobilization, each rat was sacrificed and the lower leg removed at the knee. An electrogoniometer measured the change in dorsiflexion as torque was applied in increasing increments to the ankle. Load-deformation tests were performed to determine: 1) torque to end range of dorsiflexion, 2) joint excursion with application of 3.57 mNm torque for 2.5 seconds, and 3) joint excursion with prolonged application of 3.57 mNm torque. Only the group casted for 6 weeks demonstrated a significant (p < 0.05) decrease in both degrees of dorsiflexion and joint compliance. The group casted for 6 weeks required five times more torque to achieve end range than the other groups and had a 70% decrease in ankle dorsiflexion when a fixed torque of 3.57 mNm was applied. No significant differences were noted among the remaining groups. These findings suggest that in nontraumatically immobilized joints of rats, dense connective tissue remodels in such a way that mobility is unaffected after 2 weeks, but becomes quite limited by 6 weeks.

Animals↗
PubMed1994

Radioimmunoassay for the determination of alosetron in human urine and saliva.

The development of a radioimmunoassay (RIA) for the sub-ng ml-1 determination of alosetron, a potent and selective 5HT3 receptor antagonist, in human urine and saliva is described. The antiserum was raised in Soay sheep following primary and booster immunizations with an immunogen prepared by conjugating alosetron-p-azobenzoic acid to bovine serum albumin (BSA). The radioligand consisted of alosetron specifically 125-iodinated on the 2-position of the imidazole group. The mean (+/- standard deviation) theoretical sensitivity (minimum detectable dose corresponding to the imprecision of the zero standard) of the RIA is 3.2 +/- 2.6 pg ml-1 (n = 12) of alosetron in assay diluent (0.1% m/v gelatine-0.05% m/v sodium azide in 0.1 mol l-1 phosphate buffer solution, pH 7.4). The working calibration range using 0.1 ml samples of saliva and 20-fold diluted urine is 0.10-6.40 ng ml-1 of alosetron. Urine samples were diluted prior to assay to overcome adverse matrix effects; consequently, the lower limit of quantification for undiluted urine is 2.0 ng ml-1 of alosetron. Inter- and intra-assay bias and imprecision over the working calibration range were generally < +/- 12% and < 13%, respectively, except at the 0.10 ng ml-1 alosetron level, where the corresponding values were < +/- 17.3% and < 20.2%. The antiserum was free from adverse cross-reactivity with either a synthetic precursor of alosetron or with four major metabolites of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbolines↗
PubMed1994

Effects of three different posting methods on controlling abnormal subtalar pronation.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the effects of different orthotic posting methods on controlling abnormal foot pronation during ambulation. SUBJECTS: Twenty-two individuals with forefoot varus deformities of at least 8 degrees (13 women, aged 21-40 years, and 9 men, aged 20-50 years) participated in the study. The female subjects had an average height and weight of 162.6 cm (64 in) and 55.3 kg (122 lb), and the male subjects had an average height and weight of 175.3 cm (69 in) and 80.7 kg (178 lb). METHODS: The subjects were examined with a computerized video motion analysis system. A control trial consisted of walking at 4.0 km/h in running shoes. Experimental trials included walking at 4.0 km/h in running shoes with unposted orthotic shells and with orthotic shells posted in the forefoot, the rear foot, and both forefoot and rear foot. RESULTS: Maximal calf-to-calcaneus and calcaneus-to-vertical angles were decreased more by orthoses posted in both the forefoot and the rear foot than by orthoses posted only in the forefoot. No difference in maximal calf-to-calcaneus and calcaneus-to-vertical angles were found with combined forefoot and rear-foot posting compared with posting in the rear foot alone. The maximal calf-to-calcaneus angle was decreased by orthoses posted in any of the three methods and by the orthotic shell alone when compared with shoes alone. The maximal calcaneus-to-vertical angle was decreased by orthoses posted in any of the three methods, but not by the orthotic shell alone when compared with shoes alone. CONCLUSION AND DISCUSSION: Clinicians should consider combined posting or rear-foot posting alone when maximal control of rear-foot frontal-plane pronation is desired, though forefoot posting alone and the orthotic shell also provide control of rear-foot frontal-plane pronation.

Adult↗
PubMed1993

Determination of sumatriptan succinate in plasma and urine by high-performance liquid chromatography with electrochemical detection.

Methods are described for the determination of sumatriptan succinate (1) in plasma and urine. Prior to chromatography, plasma is subjected to liquid/liquid extraction and urine is diluted in pH 7 buffer without further pretreatment. Both procedures use reversed-phase high-performance liquid chromatography with electrochemical detection. The analytical range for the plasma assay is 1-30 ng/mL and that for the urine assay is 0.2-12 micrograms/mL. The assays are linear over the analytical ranges and specific with respect to endogenous interference and the major metabolite (2) of sumatriptan. For the plasma assay, intra-assay data (n = 6) indicate a maximum coefficient of variation (CV) and bias across the calibration range of 6.0 and 3.0%, respectively. The interassay CV (n = 4) is approximately 15% at the bottom of the calibration range, falling to 4% or less at 8 ng/mL and above. Bias is approximately 12% at the bottom, reducing to < 2% at 8 ng/mL and above. The urine intra-assay data indicate a maximum CV and bias of 8.9 and 8.3%, respectively. The interassay is CV 15% for the lowest calibrant, reducing steadily across the calibration range to < 2% for the top calibration value, and bias is < 7% across the range.

Chromatography, High Pressure Liquid↗
PubMed1991

Lateral distribution of hypothalamic signals controlling thermoregulatory vasomotor activity and shivering in rats.

The present study explored the laterality of central nervous thermoregulatory control in anesthetized rats by measuring paw skin vasomotor activity and cold-induced shivering in hind leg muscles during unilateral preoptic area and anterior hypothalamus (POAH) warming and electrical stimulation or during unilateral thermal stimulation of abdominal skin. Unilateral POAH warming produced vasodilation on both sides of the body, but vasodilation on the ipsilateral side always either occurred at a lower threshold hypothalamic temperature or was stronger than on the contralateral side. In a cold environment (5 degrees C), shivering was suppressed simultaneously in both hind legs when one side of the POAH was warmed, and shivering reappeared simultaneously on both sides when POAH warming stopped. These results suggest that different thermoregulatory effectors are regulated in a different way by each side of the POAH. Unilateral thermal stimulation of the abdominal skin, on the other hand, affected vasomotor activity and shivering equally on both sides of the body, as previously reported for its influence on salivary secretion. Skin thermal signals from both sides of the body therefore seem to converge before they act on different thermoregulatory effector systems.

Abdomen↗
PubMed1986

Neuronal activities in ventrobasal complex of thalamus and in trigeminal main sensory nucleus during EEG desynchronization in anesthetized rats.

Activities of somatosensory relay neurons responding to orofacial mechanical stimulation were examined in the ventrobasal complex of the thalamus (VB) and in the trigeminal main sensory nucleus (MSN) during EEG desynchronization in urethane-anesthetized rats. EEG desynchronization was induced by scrotal warming in a temperature range of 35-40 degrees C. Responses of most VB neurons to receptive-field stimulation were augmented during EEG desynchronization, when compared to responses during synchronization. Spontaneous activity of VB neurons also increased with EEG desynchronization. Responses of MSN neurons to receptive-field stimulation did not change appreciably when the EEG pattern was altered. If a VB neuron was induced by iontophoretic application of glutamate to fire at the same rate as seen during EEG desynchronization, a similar increased response to receptive-field stimuli was also observed. The augmented response of the VB neuron during desynchronization may thus have resulted from increased excitability of the neuron itself.

Animals↗
PubMed1985

Motor unit activity under low tensions as muscle changes length.

Twenty men between 24 and 38 years of age performed tracking tasks involving abduction, adduction, and holding the position of the little finger against constant adductive torques of 5, 10, and 15 percent of maximal abductive effort. Abduction and adduction were performed at 12 degrees per second between 0 and 30 degrees of abduction. Isometric tasks were performed at 10, 15, and 20 degrees. Myoelectric activity from the abductor digiti minimi muscle, recorded through fine wires, occurring between 10 and 20 degrees of abduction was analyzed in terms of global content (by rectifying and averaging the electromyograms) and in terms of identifiable action potentials of individual motor units. For the rectified electromyograms, averaged amplitude at a given load was greatest when the muscle was shortening (abduction), next greatest when the muscle was lengthening (adduction), and least when the muscle was isometric. Change in rectified electromyographic amplitude between 10 and 20 degrees of abduction was greater when the muscle was shortening than when it was lengthening or isometric. Mean firing rate for identified motor units was higher when the muscle was shortening than when lengthening or remaining isometric. The results of this study suggest that maintaining muscle activity against a small load is most easily done if the muscle is isometric, and least easily done if the muscle is shortening.

Adult↗
PubMedDate not supplied

Electromyographic study of newborn stepping in neonates and young infants.

The purpose of this study was to examine the developmental changes in the functional mechanisms of leg muscles in newborn stepping over the first four months in ten normal neonates. Neonatal stepping in the first month showed excessive coactivation, that is, co-contraction patterns of mutual antagonists appeared especially during stance phase. The discharge patterns of co-contraction in neonatal stepping began to change to reciprocal patterns in young infant stepping (after the first month), but excessive muscular activities associated with a slightly squatted posture and forward lean still remained. Strong muscle activities of leg extensors due to a parachute reaction of the legs before floor contact, not seen in the neonatal period, began to appear in the young infant period from one month of age to three months. We suggest that these gradual changes of leg muscular activity in newborn stepping are evoked by development of balance, postural control, and strength, thereby modulating the neonatal stepping reflex.

Child Development↗
PubMedDate not supplied

Disposition of sumatriptan in laboratory animals and humans.

Sumatriptan is a new 5HT1-like agonist that has proved a novel and effective treatment for migraine. The disposition of the 14C-radiolabeled drug in laboratory animals and humans after oral and parenteral administration is described. Oral absorption of sumatriptan is essentially complete in dogs and rabbits, but only approximately 50% in rat. In humans, at least 57% of an oral dose is absorbed. Bioavailabilities are species dependent (14, 23, 37, and 58% in humans, rabbits, rats, and dogs) reflecting differing degrees of first-pass metabolism. These data correlate well with hepatic extraction ratios, which are highest in rabbits and humans and lowest in dogs. Renal clearance is significant in all species and exceeds the glomerular filtration rate in rats, rabbits, and humans, but not in dogs. The compound is a weak base that shows widespread tissue distribution, including passage across the placental barrier and into milk, but low CNS penetration. Protein binding of sumatriptan is low in all species. Elimination half-lives of sumatriptan are approximately 1 hr in rats and rabbits, and approximately 2 hr in dogs and humans. In all species the majority of the absorbed dose is renally excreted, predominantly as the indole acetic acid metabolite and unchanged drug. Interesting species differences are evident in the metabolism of sumatriptan. Thus, in humans, the indole acetic acid metabolite is excreted partly as a glucuronide, whereas in animals conjugation of this metabolite is not apparent. In addition, demethylation of the sulfonamide side chain of the drug is evident in rodent and lagomorph species only.

Administration, Oral↗