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H S Tan

Publications and source records attributed to H S Tan.

At least 37 records · Page 2Linked to original sources

Three-dimensional organization of optokinetic responses in the rabbit.

1. Three-dimensional rotations of both eyes were measured in alert rabbits during optokinetic stimulation about axes lying in the horizontal plane or about an earth-vertical axis, with either one or both eyes viewing the stimulus. Optokinetic stimulus speed was 2 degrees /s, either continuous or alternating in polarity (triangular stimulus). In addition to the gains of the responses, the orientations of the response axes relative to the stimulus axes were determined. 2. In comparison to the response to constant-speed optokinetic stimulation about the vertical axis, the response to constant-speed optokinetic stimulation about horizontal axes was characterized by the lack of a speed buildup. In many cases, slow phase tracking was good as long as the eye was within the central oculomotor range but deteriorated when eye deviation became more eccentric and fast phases failed to be generated. These features suggest that the optokinetic reflex about horizontal axes functions as a position-control system, rather than as a velocity-control system. 3. Binocular optokinetic stimulation at constant speed (2 degrees/s) about the roll axis (0 degrees azimuth horizontal axis) elicited disconjugate responses. Although the gain of the response was not significantly different in the two eyes (0.38 for downward and 0.44 for upward stimulation), the response axes of the two eyes differed by as much as 51 degrees. 4. Monocular, horizontal axis optokinetic stimulation at constant speed elicited responses that were grossly dissociated between the two eyes. The magnitude of the responses was anisotropic in that it varied with the azimuthal orientation of the stimulus axis; the maximum gain for each eye (0.41 for the seeing and 0.33 for the covered eye) was at 135 degrees azimuth for each eye. The axis orientation and direction (sense of rotation) of the optokinetic stimulus eliciting the maximal response for each eye coincided with the optic flow normally associated with the maximal excitation of the corresponding ipsilateral anterior canal. 5. Binocular, triangular optokinetic stimulation with small excursions (+/- 10 degrees), which avoided the saturation problems of constant-speed stimulation, elicited adequate responses without systematic directional asymmetries. Gain was approximately 0.9 for all stimulus axis orientations in the horizontal plane. 6. During monocular stimulation with triangular stimuli, the response of the seeing eye showed a gain of approximately 0.5 for all orientations of the stimulus axis. In contrast, the covered eye showed anisotropic responses, with a maximum gain of approximately 0.5 during stimulation of the seeing eye about its 45 degree axis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Pharmacokinetics and relative bioavailability of nimodipine capsules and tablets in 8 Chinese healthy men.

A single oral dose of tablets or capsules of 239 mumol nimodipine was given to 8 healthy volunteers of Han nationality in a randomized crossover study. Plasma levels were determined with HPLC method. The plasma concentration-time curve fitted to a first order absorption, 1-compartment open model, and the T1/2K was around 2 h. Although the capsules could reach peak level faster, the bioavailability was not significantly different from that of the tablets.

Adult↗

Adaptation of the vestibulo-ocular reflex with the head in different orientations and positions relative to the axis of body rotation.

We investigated the influence of static head orientation and position, relative to the axis of body rotation, upon vestibular adaptation. With the head centered, displaced anterior to the axis of body rotation, or tilted 40 degrees to 45 degrees in roll or pitch, the gain of the vestibulo-ocular reflex (VOR) was trained (to go either up or down) for one hour using artificial manipulation of the visual surround to produce a visual-vestibular mismatch. Before and after each training session, the VOR was measured in darkness with the head in the training as well as in several non-training positions. We found that transfer of VOR adaptation to non-training positions was almost complete when comparing head eccentric versus head-centered rotations. For tilts, however, transfer of VOR learning was far less complete suggesting that static otolith signals provide a strong contextual cue that gates the expression of an adaptive VOR response. Finally, following training to increase the VOR, gain was greater for centripetally than centrifugally directed slow phases. Centripetally directed postsaccadic drift also developed. These findings imply that the gain increase paradigm also leads to abnormal function of the velocity-to-position neural integrator, which holds eccentric positions of gaze.

Adaptation, Physiological↗

Muscarinic nature of cholinergic receptors in the cerebellar flocculus involved in the enhancement of the rabbit's optokinetic response.

Intrafloccular micro-injection of the aselective cholinergic agonist carbachol enhances the optokinetic reflex (OKR)17. Histochemical and physiological studies have identified cholinergic receptors of the muscarinic as well as nicotinic type in the cerebellar cortex, and both have been implicated in cholinergic transmission. The present study was undertaken to elucidate the receptor type involved in the control of OKR. For that purpose, effects of injections of the nicotinic N1 agonist DMPP on the OKR and vestibulo-ocular reflex (VOR) were compared with injections of the muscarinic agonist betanechol and the aselective cholinergic agonist carbachol. Injection of betanechol mimicked the enhancement of the OKR by carbachol, while DMPP had no effect. We conclude that muscarinic receptors are involved in the positive modulatory action of the cholinergic system in the cerebellar flocculus.

Animals↗

Cholinergic and noradrenergic stimulation in the rabbit flocculus have synergistic facilitatory effects on optokinetic responses.

A recent study (Exp. Brain Res., 85 (1991) 475-481) showed that injection of the cholinergic agonist carbachol into the cerebellar flocculi had a pronounced facilitatory effect on the gains of the optokinetic (OKR) and vestibulo-ocular (VOR) reflexes, suggesting a positive modulatory role of the cholinergic system in the flocculus. Because many behavioral and electrophysiological studies throughout the brain have revealed a functional relationship between acetylcholine (ACh) and noradrenaline (NA), the present study was undertaken to compare the effects of floccular injection of the ACh agonist carbachol, the beta-adrenergic agonist isoproterenol and the conjoint injection of both of these substances on the basic gain of the VOR and the OKR. Carbachol and isoproterenol both significantly raised the gain of the OKR, by 0.14 and 0.11 respectively. Neither of the two substances significantly affected the gain of the VOR in light or darkness. Conjoint injection of the same amounts of carbachol and isoproterenol resulted in an increase in the gain of the OKR by 0.29 without significant changes in the gains of the VOR in the light or in darkness. These results suggest a synergistic and positive modulatory role of ACh and NA in the flocculus.

Animals↗

Enhancement of optokinetic and vestibuloocular responses in the rabbit by cholinergic stimulation of the flocculus.

Bilateral microinjections into the cerebellar flocculus of the rabbit of carbachol, a general cholinergic agonist, profoundly affect vestibuloocular (VOR) and optokinetic (OKR) reflexes. For sinusoidal stimuli (0.15 Hz, 5 deg peak to peak), the gain of the OKR was strongly increased, while the gain of the VOR was moderately increased. These effects were partially mimicked by floccular injection of the acetylcholinesterase inhibitor eserine. Floccular injection of the muscarinic blocker atropine significantly lowered the gain of the OKR. The effects of the nicotinic blocker mecamylamine were not significant. Optokinetic nystagmus (OKN) in response to constant stimulus velocities (1-30 deg/second) showed a markedly accelerated buildup and a shortened optokinetic after-nystagmus (OKAN) after floccular injections of carbachol. The steady-state gain of OKN remained unaffected. None of the described effects occurred after floccular injection of the solvent, saline. It is postulated that cholinergic cerebellar afferents, one probable source of which are the vestibular nuclei, enhance the optokinetic and vestibular modulation of floccular Purkinje cells.

Animals↗

Optokinetic nystagmus in the rabbit and its modulation by bilateral microinjection of carbachol in the cerebellar flocculus.

1. In the alert, pigmented rabbit, eye movements were recorded during optokinetic nystagmus (OKN) and during optokinetic after nystagmus (OKAN). These responses were elicited by steps in surround-velocity ranging from 5-110 degrees/s during binocular as well as monocular viewing. 2. In the baseline condition, OKN showed an approximately linear build-up of eye velocity to a steady-state, followed by a linear decay of eye velocity during OKAN after the lights were turned off. Build-up during binocular viewing was characterized by a constant, maximum eye-acceleration (about 1 degree/s2) for stimulus velocities up to 60 degrees/s. OKAN, instead, was characterized by a fixed duration (about 10 s) for stimulus velocities up to 20 degrees/s. Steady-state eye velocity saturated at about 50 degrees/s. 3. Monocular stimulation in the preferred (nasal) direction elicited a build-up that was on average twice as slow as during binocular stimulation. Steady-state velocity during monocular stimulation saturated at about 20 degrees/s. OKAN was of equal duration as during binocular stimulation. In the non-preferred direction, a very irregular nystagmus was elicited without velocity build-up. The stronger response to binocular stimulation, compared to the responses under monocular viewing condition in either nasal and temporal direction suggests potentiation of the signals of either eye during binocular viewing. 4. OKN and OKAN were re-assessed after intra-floccular micro-injection of the nonselective cholinergic agonist carbachol. In the binocular viewing condition, eye-acceleration during build-up was strongly enhanced from 1 degree/s2 before to 2.5 degrees/s2 after injection. The saturation level of steady-state eye velocity was also increased, from 50 degrees/s before to more than 60 degrees/s after carbachol. The duration of OKAN, however, was shortened from 10 s before to 6 s after injection. The response to monocular stimulation in the preferred direction revealed similar changes. 5. The flocculus appears to be involved in the control of the dynamics of OKN in the rabbit. Cholinergic mechanisms affect the floccular control of the rate at which slow-phase velocity can be built up and the rate of decay of eye velocity during OKAN. Cholinergic stimulation of the flocculus enhances the dynamics of OKN, while velocity storage is shortened.

Animals↗

Context-specific adaptation of the gain of the vestibulo-ocular reflex in humans.

Previous experiments show that altered visual feedback can change VOR gain. Such changes also presumably occur when eyeglasses are donned and doffed, or when bifocals are worn. In these cases, a nonvisual cue accompanies the required gain adjustment (frames on/off for eyeglasses, looking up/down for bifocals). We set out to show that a subject can establish two VOR gains, and to determine if one of the associated nonvisual cues alone is sufficient to subsequently determine which gain to employ. Each of three subjects sat in a rotating chair inside an OKN drum during 2 hours of sinusoidal rotation at 0.2 Hz, 30 degrees/s peak. For 10 minutes the chair and drum counterrotated , driving VOR gain toward 1.7, while subjects looked up 20 degrees. Chair and drum were then coupled for 10 minutes, driving gain toward zero, during which subjects looked down 20 degrees. This sequence was repeated for 2 hours. Immediately thereafter, VOR gains were measured while subjects looked alternately up and down, using 20 degrees to 40 degrees step rotations. A fixation target, presented before and after each step, provided accurate gain determination by measuring the size of the re-fixation saccade. Results show a consistent reduced VOR gain looking downward (average 6%) and increased gain looking upward (average 6%) and increased gain looking upward (average 8%). We conclude that humans can adjust their VOR gain dependent on a situational context; we speculate that this context can take many forms.

Adaptation, Ocular↗

Elective total hip replacement: incidence, emergency readmission rate, and postoperative mortality.

OBJECTIVES: To report the incidence of elective total hip replacement and postoperative mortality, emergency readmission rates, and the demographic factors associated with these rates in a large defined population. DESIGN: Analysis of linked, routine abstracts of hospital inpatient records and death certificates. SETTING: 10 hospitals in six districts in Oxford Regional Health Authority covered by the Oxford record linkage study. SUBJECTS: Records for 11,607 total hip replacements performed electively in 1976-85. MAIN OUTCOME MEASURES: Incidence of operation, postoperative mortality, relative mortality ratios, and incidence of emergency readmission. RESULTS: NHS operation rates increased over time from 43 to 58 operations/100,000 population. Variation in operation rates between districts reduced over time. Operation rates were on average 25% higher in women than men. There were 93 deaths (11/1000 operations) within 90 days of the operation and 208 emergency readmissions (28/1000 operations) within 28 days of discharge. Postoperative mortality and emergency readmission rates increased with age. No significant trend with time was found. Mortality in the 90 days after the operation was 2.5-fold higher (1.9 to 3.0) than in the rest of the first postoperative year. This represented an estimated excess of 6.5 (4.2 to 8.8) early postoperative deaths/1000 operations. Most deaths were ascribed to cardiovascular events. Thromboembolic disease was the commonest reason for emergency readmission. CONCLUSIONS: The pronounced increase in operations in districts with initially low rates suggests a trend towards greater equity in the local provision of NHS hip arthroplasty. The early postoperative clusters of deaths attributed to cardiovascular disease and of readmissions for thromboembolic disease suggest that there is scope for investigating ways of reducing the incidence of major adverse postoperative events.

Adult↗

Effects of alpha-noradrenergic substances on the optokinetic and vestibulo-ocular responses in the rabbit: a study with systemic and intrafloccular injections.

The effects of microinjection of alpha-noradrenergic agonists and antagonists in the flocculus on the basic gain and adaptibility of vestibulo-ocular and optokinetic responses were investigated. A complementary, previous investigation had shown that the adaptation, but not the basic performance, of compensatory oculomotor responses were markedly influenced by beta-noradrenergic mechanisms in the flocculus. In contrast, the present experiments with bilateral, intrafloccular injections of phenylephrine, prazosin, clonidine and idazoxan failed to reveal any effect of alpha 1- or alpha 2-noradrenergic mechanisms on either basic performance or adaptation of compensatory eye movements. Intravenous administration of clonidine, however, reduced the gain of the optokinetic and vestibulo-ocular responses by about 70 and 50%, respectively, at dosages of 0.07 mg/kg. Recovery from this effect took about 1.5 h. A higher dosage of clonidine (0.7 mg/kg) had a similar, but longer lasting effect, and also markedly increased the frequency of spontaneous saccades. Intravenous administration of phenylephrine did not affect the oculomotor responses. It is concluded that the control of oculomotor responses is not susceptible to alpha-noradrenergic influences at the level of the flocculus, but that alpha 2-agonistic action inhibits these responses through an extra-floccular structure.

Adaptation, Physiological↗

Determination of benzyl alcohol and its metabolite in plasma by reversed-phase high-performance liquid chromatography.

A study undertaken following recent reports of deaths in neonatal children associated with the use of benzyl alcohol resulted in the development of a stability-indicating high-performance liquid chromatographic assay of benzyl alcohol in plasma using benzocaine as internal standard. Thawed plasma samples were diluted and subjected to solid-phase extraction using Extrelut and eluted with ethyl acetate. The evaporated eluate was reconstituted with mobile phase and chromatographed on a C18 column with water-acetonitrile-glacial acetic acid as mobile phase and detection at 254 nm. Baseline separation was achieved within 12 min for benzyl alcohol, benzaldehyde, benzoic acid, hippuric acid and benzocaine. Peak-height ratios were linear over 80-640 ng of benzyl alcohol injected (r = 0.998) and over 10-80 ng of benzoic acid injected (r = 0.999). Benzaldehyde and hippuric acid were not quantitated because these compounds were not detectable in actual dog plasma. Validation studies by spiking dog plasma with benzyl alcohol and benzoic acid gave overall percent recoveries (+/- relative standard deviation, n = 4) of 98.3 +/- 3.0 and 101.4 +/- 7.6%, respectively. The method was applied to the assay of actual plasma samples. Since benzyl alcohol is very susceptible to oxidation to benzaldehyde and benzoic acid, its purity in bulk liquid samples can be determined by this method.

Animals↗

Cholinergic modulation of optokinetic and vestibulo-ocular responses: a study with microinjections in the flocculus of the rabbit.

In spite of a large body of histochemical evidence for a cholinergic system in the cerebellum, particularly in lobules IX and X, the physiological role of such a system has remained obscure. In view of the important role of these same lobules in the control of the vestibulo-ocular (VOR) and optokinetic (OKR) responses, we tested the effect of microinjections of cholinergic (ant)agonists in the flocculus of the rabbit on these reflexes. Very marked effects were found. Bilateral floccular injection of the aspecific cholinergic agonist carbachol raised the gain of the OKR by about 0.46 above the baseline values, while the gain of the VOR in darkness was raised by about 0.14. These effects were statistically significant and persisted for several hours. Similar, but smaller effects were obtained after injection of eserine, an inhibitor of acetylcholinesterase. Thus, the effects could be produced by increasing the naturally present amount of acetylcholine. Microinjections of the nicotinic blocker mecamylamine reduced the gain of the VOR and OKR, although these effects did not reach statistical significance. The muscarinic blocker atropine significantly reduced the gain of the OKR, but not of the VOR. The present results argue strongly for an important physiological role of the cholinergic system in the cerebellum. Specifically, acetylcholine appears to be involved in the modulation of oculomotor reflexes through the flocculus.

Animals↗

Effect of timing of prostaglandin PGF 2 alpha injection subsequent to embryo collection on the resumption of normal follicular development following superovulatory treatment in cattle.

Nonlactating Holstein and Jersey cows (n = 24) were superovulated and ovarian follicular development was monitored by transrectal ultrasound during the period after embryo recovery. Luteolysis was induced by two injections of prostaglandin F(2)alpha (PGF; 25 mg Lutalyse; 12-h interval) at specific times after superovulatory induced estrus (Treatment 1, Day 9; Treatment 2, Day 12; Treatment 3, Day 17; Treatment 4, Day 25; superovulatory estrus = Day 0 of Cycle 1). Follicular development was monitored during Cycle 1 before and after PGF injection and continued through the ensuing estrous cycle (Cycle 2). Superovulation led to more than one embryo collected in 14 cows (mean = 8.71 embryos: positive superovulatory response [PSR] cows), while 10 cows were not successfully superovulated (mean = 0.1 embryo; negative superovulatory response [NSR] cows). These cows differed in terms of number of unovulated follicles detected at embryo collection (4.21 vs 17.2, PSR vs NSR) and plasma progesterone during the superovulatory estrous cycle (32.3 ng/ml PSR vs 8.6 ng/ml NSR). Follicular development during Cycle 1 started sooner in NSR than in PSR cows (day by class by response P<0.03) and was initiated on Days 11 to 12 in NSR cows and on Days 19 to 20 in PSR cows. Interval to estrus after PGF averaged 6.3 d. Cows having short intervals to estrus had follicles at the time of PGF injection. Treatment influenced the length of Cycle 1, but it did not affect the interval to estrus after PGF, the length of Cycle 2, or follicular development during Cycle 2. The results indicate that 1) the timing of PGF injection after embryo collection does not influence subsequent follicular populations, 2) elongated estrous cycles and intervals to estrus after PGF in superovulated cattle are a function of decreased follicular activity, and 3) the presence of numerous corpora lutea and not the superovulatory treatment, per se, seem to attenuate follicular growth.

Journal Article↗

Reciprocal changes in atrial natriuretic peptide levels and plasma renin activity during treatment of pulmonary embolism.

We followed atrial natriuretic peptide (ANP) levels in 12 patients during anticoagulant treatment of pulmonary embolism. In each patient with this disorder ANP decreased during treatment. Concomitantly, plasma renin activity (PRA) markedly rose. The decrease in ANP was significantly related to the rise in PRA. No consistent changes in ANP or in PRA were observed in five patients with peripheral venous thrombosis receiving the same anticoagulant treatment. Plasma aldosterone levels did not change in either group.

Adult↗

Development of resistance to a long-acting somatostatin analogue during treatment of two patients with metastatic endocrine pancreatic tumours.

UNLABELLED: Two patients with metastatic endocrine pancreatic tumours initially responded well to therapy with the long-acting somatostatin analogue SMS 201-995. In the first patient with an insulinoma both the number of hypoglycemic attacks and the increased insulin levels decreased initially, but returned to pretreatment intensity and concentrations within 9 days after the start of therapy with 200-300 micrograms SMS 201-995 daily. After a short interruption, no effect was observed of re-institution of therapy at a dose of 400 micrograms SMS 201-995 daily. In the other patient with a metastatic vipoma both diarrhea, hypokalemia and plasma VIP levels reacted initially well to SMS 201-995 treatment with 300 micrograms per day, but resistance to therapy developed after 2 weeks. An increase in the dose of the analogue to maximally 600 micrograms/day was followed by a transient improvement, but finally both the volume of diarrhea and the levels of vasoactive intestinal polypeptide were higher than those before the start of therapy. CONCLUSIONS: Development of resistance to SMS 201-995 both with regard to the clinical effect and to the inhibitory effect on tumour hormone secretion can be expected in some patients with metastatic endocrine pancreatic tumours. On the basis of our clinical observations down-regulation of somatostatin receptors is suggested to be one of the mechanisms of this development.

Adenoma, Islet Cell↗