Subjective sensation during interaction between horizontal vestibular and vertical pursuit stimulation.
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Darkness↗
Biomedical subjects
C Lau
Publications and source records attributed to C Lau.
Reproductive development and functions in the rat after repeated maternal deprivation stress.
The present study examines whether interruptions of maternal-neonatal behaviors may alter the maturation of reproductive organs and functions, thereby potentially confounding the interpretation of toxicity data with stress-induced responses. Sprague-Dawley rat neonates were removed from their dams for 6 hr daily beginning on Day 4 of postnatal age and continuing until Day 21. Vaginal opening and preputial separation were monitored as indices of puberty. Sperm production in the male rats, estrous cycles in the female rats, and reproductive tissues were weighed when the animals reached sexual maturity. In addition, rats were mated for the elevation of pregnancy outcomes. Maternal separation stress in itself did not appear to alter these parameters, although potential interactions of stress responses with a toxicant should still be considered.
Animals↗
Effect of fluorescein on the tear stability of Hong Kong-Chinese.
We used the noninvasive tear break-up time (NITBUT) technique to measure the tear stability of 24 asymptomatic Hong Kong (HK)-Chinese before and after instillation of fluorescein. One eye was used as the test eye while the fellow eye served as control. We compared the NITBUT of the test eyes pre- and postinstillation of fluorescein, and compared the NITBUT of the test eyes measured postinstillation of fluorescein with the NITBUT of the control eyes. After instillation of fluorescein, both longer and shorter NITBUT were recorded in the test eyes; similar results were observed for the control eyes (no fluorescein instilled) between the first and second measurement. The median NITBUT of the test eye pre- and postfluorescein instillation were 13.3 and 13.0 s, respectively. Fluorescein did not cause any significant change in the NITBUT of HK-Chinese and the instillation of fluorescein in one eye does not affect the NITBUT of the fellow eye. Fluorescein did not appear to affect the locations of tear break up (tear defects) observed using the NITBUT test. Tear defects are most frequent near the inferior periphery of the cornea.
Adult↗
Survey of cardiac pacing in Canada (1993).
INTRODUCTION: The status of cardiac pacing in Canada in 1993 was determined from data provided by 33 of 128 physicians surveyed (25% response) and four major manufacturer/distributors. DEMOGRAPHICS: There were 268 new implants per million population, similar to the 1989 data, 279 per million. INDICATIONS: Sinus node disorders accounted for 38.2% of implants, atrial fibrillation with slow ventricular response for 18.1% and atrioventricular node dysfunction for 33.1% of patients. Implants for tachyarrhythmias accounted for only 3.5%. TECHNOLOGY: Single chamber units were implanted in 76% of patients and dual chamber in 23%, with rate modulation used in 35% of primary implants. There was an increase in the use of single chamber rate adaptive units from 1989 (from 15.9% to 25%). The per venous sheath introducer technique was used in 55% of lead insertions. Bipolar leads were used in 78% of atrial and 63% of ventricular leads; passive steroid leads were used in 50% of atrial and 55% of ventricular lead implants; 40% of atrial leads and 7.5% of ventricular leads had active fixation. FOLLOW-UP: Most pulse generators were reprogrammed peri-operatively or within three months (97.4%). Most patients with new implants (92%) required hospital admission for 2.5 days, while 75% of replacements were out-patient procedures. CONCLUSIONS: Comparison with previous surveys and other countries revealed little growth in pacemaker sales or new implant rates per million population; conservative indications and relatively constant use of dual chamber devices; and an increase in single chamber rate responsive units. The authors express concern regarding budget constraints and resource availability as factors limiting growth in pacemaker therapy.
Aged↗
Maintaining physiological pacing in AV block using a new generation single lead VDD pacemaker.
OBJECTIVE: A prospective evaluation of patients with AV block using a single pass lead, VDD pacing system. DESIGN: Fifteen patients with AV block, eight males, seven females, average age 68.1 years (range 22.3 to 86.5) were implanted with the THERA VDD 8948 pacemaker and 5032 single pass steroid eluting lead (Medtronic, Inc). P wave sensing and ventricular thresholds were done predischarge and at one, three, and six months and subsequent six-month periods postimplant. P wave sensing was evaluated with exercise testing and other provocative tests. Twenty-four hour Holter monitoring was done before discharge. Patients were given a quality of life questionnaire pre- and postimplant. SETTING: Tertiary care hospital. RESULTS: Average follow-up was 6.4 months (1.5 to 18). Ventricular thresholds remained stable. P wave amplitude at implant (average 2.2 mV; 1.6 to 3.6) showed a significant decrease at the initial visit (average 1.1 mV, 0.5 to 2.4), however, it remained stable at subsequent visits. This initial decrease had no clinical significance as the maximum atrial sensitivity of the device is 0.18 mV. The 24 hr Holter monitoring confirmed reliable AV synchronous pacing in 14 of 15 patient pacemakers programmed in the VDD mode. The sleep function maintained AV synchrony during nocturnal bradycardia; atrial rate histograms available at follow-up imply appropriate intrinsic rate variation and provocative sensing tests and exercise protocol demonstrated reliable atrial sensing. There was a significant improvement in overall patient well-being score using a quality of life questionnaire. CONCLUSIONS: During the follow-up period, this new generation VDD pacemaker, using a single pass lead, provided reliable AV synchronous pacing for patients diagnosed with AV block and normal sinus node function, as well as improved patient well-being.
Adult↗
Oral motor function in the neonate.
The information in this article illustrates the importance of evaluating oral motor function of the infant, not only as function of his or her own ability but also of external and maternal assistance. The proper development of maternal behavior as a contribution toward the development of sucking behavior may not be readily evident; however, awareness is growing that a close mother-infant interaction can positively affect the infant's ability to feed, as well as his or her psychosomatic development. As a consequence, it becomes essential that the integrity of the nursing dyad be protected. More often than not, caretakers have seen the latter break down when mother or infant becomes too involved. Studies focusing on maternal and neonatal non-nutritional attributes stress the importance of acquiring a better appreciation of the psychosomatic benefits that can be generated by the nursing dyad. With such understanding, interventions may be developed to enhance the expression of these factors to help safeguard mother-infant relationship during difficult times.
Bottle Feeding↗
Managing and understanding variances in clinical path methodology: a case study.
Clinical path is a tool to improve efficiency. The increasing use of this methodology is evidenced by the proliferation of literature documenting its usage. A search of Cumulative Index to Nursing & Allied Health Literature (CINAHL) alone yielded over 38 articles related to clinical path. This trend of using clinical path to manage patient care is also evident from the recent literature in Australia. However, the literature has been silent on the documentation, interpretation and management of the variances. The purpose of this paper is to describe our three years' experience with clinical path management. Some examples of the variances we have experienced in the cardiac unit will be discussed.
Australia↗
Comparison of preferred frequency gain settings obtained with category rating and modified simplex procedure.
We examined the relations between the preferred frequency gain settings obtained from the modified simplex procedure and those that were rated highest during category rating at three speech and noise levels (speech and noise levels at 60/65, 63/63, 65/60, all in dBA). During category rating, subjects rated short discourse passages on a 7-point scale using clarity and noise interference as criteria. Clarity was used as criterion in the modified simplex procedure. Results indicated that most subjects gave the same high rating to two or more frequency gain settings during category rating. Such settings varied across subjects and test conditions. The preferred frequency gain settings selected with the modified simplex procedure matched closely those rated highest in clarify and lowest in noise interference. This suggests that the modified simplex procedure may be used to determine preferred frequency gain setting on a hearing aid.
Adult↗
Biological modeling of 5-fluorouracil developmental toxicity.
A biologically-based dose-response (BBDR) model is a mathematical description of the biological events leading to expression of a toxic response. As an alternative to current approaches in non-cancer risk assessment, such models will reduce uncertainty in that they will provide a more comprehensive description of toxicity. We are involved in construction of a BBDR model for the developmental toxicity of 5-fluorouracil (5-FU) in the rat using multiple approaches. First, to identify critical events in the pathogenesis of 5-FU developmental toxicity, thymidylate synthetase (TS) inhibition and alterations in cell kinetics and growth were examined in embryos following maternal administration of 5-FU on day 14 of gestation. A dose-related decline in TS activity was observed within 1 h; however, maximal inhibition and recovery were similar at 10, 20 and 40 mg/kg. Dose-dependent cell cycle alterations were observed within 4 h after exposure and were maximal at 8 h. Hindlimb growth reduction was observed 24 h after exposure to 40 mg/kg, but not at lower doses. At term hindlimb defects were observed at doses above 30 mg/kg. An integrated dose-response model for hindlimb defects was derived from empirical relationships among these events. The resultant dose-response somewhat over-predicted the developmental toxicity of 5-FU, although results of a Monte Carlo simulation indicated that these data were not incompatible with model predictions. Overall, the results suggest that TS inhibition is a key component of the mechanism of 5-FU developmental toxicology, but the model does not capture all of the critical events in the induction of hindlimb defects. A preliminary mechanistic model for the inhibition of embryonic TS, DNA synthesis and cell cycle following maternal exposure to 5-FU, independently derived from literature data to further examine the potential role of this pathway in its developmental toxicity, predicted a dose-response for TS inhibition and DNA synthesis that closely reflected the observed patterns. These results further suggest that TS inhibition, resultant deficits in DNA synthesis and cell cycle perturbations represent a critical mechanistic pathway in the developmental toxicity of 5-FU.
Animals↗
A role for CNS alpha-2 adrenergic receptors in opiate-induced muscle rigidity in the rat.
A number of potential neurochemical mediators of opiate-induced muscle rigidity have been proposed based on the results of systemic drug studies and on knowledge of the brain sites implicated in opiate rigidity. The effects of i.c.v. pretreatment with selected opioidergic, alpha adrenergic and serotonergic drugs on muscle rigidity induced with systemic injection of the potent opiate agonist alfentanil (ALF) were investigated in spontaneously ventilating rats. The opiate antagonist methylnaloxonium (MN; 0.2-14 nmol), alpha-2 adrenergic agonists dexmedetomidine (DEX; 0.4-42 nmol) or 2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride (ST91; 4-400 nmol), alpha-1 adrenergic antagonist prazosin (PRZ; 7-70 nmol) or serotonergic antagonist ketanserin (KET; 18-550 nmol) were injected i.c.v. (10 microliters) and ALF (500 micrograms/kg s.c.) was administered 10 min later. S.c. electrodes were used to record gastrocnemius electromyographic activity. Both MN and DEX dose-dependently and potently antagonized ALF-induced rigidity. ST91 produced shorter-lived, less profound, antagonism of ALF rigidity. PRZ, at the highest dose tested, produced a delayed and modest reduction in ALF rigidity. A large, non-selective, dose of KET incompletely attenuated ALF rigidity. These results lend support to the hypothesis that central opioid and alpha-2 adrenergic receptors mediate opiate-induced muscle rigidity in the rat.
Adrenergic alpha-Agonists↗
Developmental exposure to polychlorinated biphenyls (Aroclor 1254) reduces circulating thyroid hormone concentrations and causes hearing deficits in rats.
Developmental hypothyroidism causes growth deficits, motor dysfunction, and hearing disorders in humans and animals. Therefore, environmental toxicants, such as polychlorinated biphenyls (PCBs), may secondarily affect these endpoints via thyrotoxicity. In this study, Long-Evans rats were given Aroclor 1254 (po), at 0, 1, 4, or 8 mg/kg from Gestation Day 6 through Postnatal Day (PND) 21. We evaluated the offspring at various age intervals for circulating thyroid hormone concentrations [thyroid-stimulating hormone, and free and total triiodothyronine (T3) and thyroxin (T4)], body weight, eye opening, survival, motor activity development, auditory startle response, and auditory thresholds. Circulating T4 concentrations were sharply reduced in a dose-dependent fashion in PCB-exposed groups at PND 1, 7, 14, 21, and 30 but recovered to control levels by PND 45. Moderate reductions in T3 concentrations were apparent in the 4 and 8 mg/kg groups on PND 21 and 30. Deficits in body weight gain and early eye opening were apparent in the treated pups; by weaning, pup mortality was 20% in the 4 mg/kg group and 50% at the highest dose. Motor activity was also transiently reduced in 15 day old offspring from the 8 mg/kg group. At this dose, animals showed reduced auditory startle amplitudes at PND 24, but not when tested as adults. Importantly, Aroclor 1254 caused permanent auditory deficits (20-30 dB threshold shift) at the lowest frequency tested (1 kHz) in both the 4 and 8 mg/kg groups, whereas auditory thresholds were not significantly affected at higher frequencies (4, 16, 32, or 40 kHz). These data indicate that while some effects of Aroclor 1254 exposure are dissimilar to drug-induced hypothyroidism (e.g., age of eye opening), effects on hormone levels and body weight are comparable. Detection of auditory deficits in PCB-treated animals is a novel finding and may reflect the effects of thyroid hormone disruption on the development of the cochlea.
Acoustic Stimulation↗
Retroviral gene transfer into the intestinal epithelium.
The epithelial cells of the gastrointestinal tract may be attractive targets for somatic gene therapy. In these studies, we have used rats and mice to explore the feasibility of gene transfer into the small intestinal epithelium using retroviral vectors. The first series of experiments was conducted in mature Sprague-Dawley rats using an ecotropic retroviral vector that has bacterial beta-galactosidase (beta-Gal) as the reporter gene. The vector was introduced into the lumen of ligated segments of terminal ileum. After a 4-hr exposure period, the ligatures were removed. Sham-operated animals were subjected to the same ligation procedure but received only tissue culture medium in the ligated segment. All animals were sacrificed 6 days later, and tissue from both the experimental segment and an upstream control segment was assessed for cytoplasmic beta-Gal activity using X-Gal histochemistry. Expression of the reporter gene was observed in the crypt epithelium of tissue exposed to the vector. In the villus epithelium, high background staining precluded accurate assessment of reporter gene expression. To obviate the latter problem, we sought an alternative reporter gene for which there would be no background staining in control animals. We repeated the experiments with beta-glucuronidase as the reporter gene in MPS VII mutant mice, which are devoid of this enzyme. In these studies, ileal segments exposed to the vector demonstrated expression of the reporter gene in both the crypt and villus epithelium 4 days after exposure. These results indicate that genes can be transferred into the intestinal epithelium using retroviral vectors introduced luminally.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effect of initial setting on convergence to optimal hearing aid setting using a simplex method.
We examined the final preferred frequency gain response (i.e. final setting) selected using different starting points (i.e. initial settings) with a modified simplex procedure. These starting points included a frequency response close to the one recommended by NAL-R (Byrne and Dillon, 1986), a frequency response with the high and low frequency gain set to the maximum (max), a frequency response with the high and low frequency gain set to the minimum (min), and one in-between these values (mid). The time taken to converge to the final setting was also recorded. Subjects judged the clarity of short discourse passages presented at 63 dB(A) in the presence of babble noise (S/N = 0). The results indicated that the majority of subjects selected the same preferred frequency response regardless of initial settings. Variations in initial settings mainly affected the convergence time to the final choice. The frequency response recommended by NAL-R required the least time to converge, while those of the extremes (min and max) required the longest convergence time. Clinical implications are discussed.
Adult↗
Biologically based dose-response modeling in developmental toxicology: biochemical and cellular sequelae of 5-fluorouracil exposure in the developing rat.
Mechanistically based dose-response models for developmental toxicity require elucidation of critical biological events that intervene between maternal exposure and adverse developmental outcome. We have examined some of the major events in the rat embryo/fetus following a subcutaneous injection of 5-fluorouracil (5-FU; 0-40 mg/kg) to the dam on Day 14 of gestation. This treatment resulted in reduced fetal weight that was significant at doses of 20 mg/kg and higher, generalized reduced ossification at doses above 25 mg/kg, and wavy ribs at doses of 30 mg/kg and higher. Numerous malformations including cleft palate and hindlimb defects were substantially increased at doses of 35 and 40 mg/kg. 5-FU inhibits thymidylate synthetase (TS), resulting in inhibited growth of rapidly proliferating tissues. To identify early events in the pathogenesis of hindlimb defects, we examined the effects of 5-FU on TS activity, cell cycle, growth, and morphology in the developing hindlimb as a function of dose and time. The rate of decline of TS activity following 5-FU exposure was dose related, although maximal inhibition and recovery were similar at doses within (20 and 40 mg/kg) and below (10 mg/kg) the range of detectable developmental toxicity. Flow cytometric analysis of nuclei from embryonic hindlimbs revealed a transient increase in the percentage of cells in S phase and decrease in G0/G1 phase 8 hr after maternal injection of 20-40 mg 5-FU/kg, but not at lower doses. Reduction in growth and morphometric changes of hindlimbs were observed only after maternal exposure to 40 mg/kg. The tissue specificity of these effects was examined by comparing the hindlimb with other embryonic tissues. There was also a dose-related decline of TS activity in the embryonic liver. However, the pattern of recovery of TS activity and cell cycle alterations were different in the liver than in the hindlimb, probably reflecting the higher cell proliferative rate in the liver at this stage. We have derived a quantitative, empirical model for induction of hindlimb defects based on TS inhibition and subsequent cellular events following 5-FU exposure. The model predicted a dose response similar to that of the observed data although the predicted curve was shifted toward lower doses. These results suggest that while this model may not capture all of the critical events involved in the induction of hindlimb defects following maternal exposure to 5-FU, it does reflect a central mechanism of its developmental toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Glucocorticoids enhance intracellular signaling via adenylate cyclase at three distinct loci in the fetus: a mechanism for heterologous teratogenic sensitization?
Although high doses of glucocorticoids are teratogenic, endogenous hormones are necessary for development. Because of the central role of cAMP to control cell differentiation, we examined the dose dependence, tissue selectivity, and critical periods involved in glucocorticoid regulation of fetal intracellular signaling mediated by adenylate cyclase. Pregnant rats were given dexamethasone at doses spanning the threshold for therapeutic effects (0.05, 0.2, and 0.8 mg/kg) on either Gestational Days 11, 12, and 13 or Days 17, 18, and 19. Development of adenylate cyclase was evaluated in cell membrane preparations using basal activity in the absence or presence of GTP, maximal G-protein activation by fluoride, and maximal catalytic subunit stimulation by forskolin-Mn2+. Even at the lowest dose, dexamethasone on gestational days 11 through 13 enhanced fetal adenylate cyclase activity by accelerating development of both the G-protein component and the catalytic subunit. As a result, supersensitivity of the response to beta-adrenergic receptor stimulation by isoproterenol was also produced, even though development of beta-adrenergic receptors was unaffected. Treatment with dexamethasone later in gestation similarly fostered development of both G-protein and catalytic subunit components, with selectivity for liver and heart as opposed to brain. Again, heterologous sensitization to isoproterenol stimulation was demonstrable; in addition, late gestational treatment elevated yet a third signal transduction locus, the beta-adrenergic receptor binding site. These effects are likely contributors to glucocorticoid teratogenesis (high doses) or to more subtle disruption of cell development (low doses); because adenylate cyclase is at the convergence of multiple neuronal, hormonal, and environmental inputs, glucocorticoids may sensitize the cell to heterologous stimuli, lowering the threshold for teratogenesis by other agents.
Adenylyl Cyclases↗
Beta-adrenergic receptor overexpression in the fetal rat: distribution, receptor subtypes, and coupling to adenylate cyclase activity via G-proteins.
Biogenic amines are hypothesized to play a role in the control of cell differentiation. We assessed the development of beta-adrenergic receptors and their linkage to adenylate cyclase activity in order to determine whether catecholaminergic cell signaling can take place early in development. On Gestational Day 12, beta-receptors were present in rat embryo in concentrations comparable to those in mature adrenergic target tissues; the concentrations climbed fivefold by Gestational Day 18. beta-Receptor expression was higher in liver than in heart and brain, as identified both by binding to isolated membrane preparations and by receptor autoradiography; nevertheless, receptor distribution was quite widespread, with labeling visible throughout the fetus. Receptor subtype selectivities (beta 2 in liver, beta 1 in heart, predominantly beta 2 in whole fetus) were already in place in early development, but receptor coupling to adenylate cyclase via G-proteins showed substantial developmental changes. Agonist-induced displacement of radioligand binding showed little or no GTP sensitivity on Gestational Day 12, suggesting relatively poor receptor linkage to Gs. In contrast, by Day 18, GTP produced a large shift in the agonist displacement curve. Receptor stimulation of adenylate cyclase by isoproterenol also showed a developmental spike by Gestational Day 18; the pattern for isoproterenol stimulation was distinct from the ontogeny of adenylate cyclase itself and from stimulation by forskolin-Mn2+ (which bypasses the need for receptors or G-proteins) or by fluoride (which activates G-proteins nonselectively). Thus, beta-receptors are highly expressed during fetal development and the receptors are readily capable of modulating intracellular cAMP production. Fetal catecholamines, which are produced and released by the adrenal medulla, extraadrenal chromaffin tissue, and cells that transiently express adrenergic phenotype, can thus have a direct impact on the differentiation of a wide variety of cells.
Adenylyl Cyclases↗
Improving access to intestinal stem cells as a step toward intestinal gene transfer.
In previous studies exploring the intestinal epithelium as a potential site for somatic gene therapy, we concluded that the mucus lining the intestine constitutes a significant barrier to any attempts at gene transfer via the lumenal route. The mucus problem is aggravated by the fact that the epithelial stem cells, which are the logical target for gene transfer, are located deep in the intestinal crypts. The goals of the current study were to develop procedures that would improve accessibility to the intestinal stem cells and which would effect in vivo mucus removal without damaging the underlying epithelium. Initial experiments involved evaluation of the use of distension to improve accessibility to the intestinal crypts and the use of the mucolytic agents dithiothreitol (DTT) and N-acetyl-cysteine (NAC) versus a control solution of phosphate-buffered saline (PBS) for mucus removal. Catheters were inserted in each end of 3-cm terminal ileal segments in anesthetized rats. Two milliliters of agent was instilled into the clamped segment for 2 min, removed, and repeated. Lumenal distension resulted in shortened villi with wider intervillus spacing, thereby improving crypt access. Both NAC and DTT washes removed significant mucus between the villi but failed to reach the crypt lumen. To enhance mucus release from the crypt lumen, pilocarpine was selected due to its cholinergic properties and preferential binding to muscarinic receptors on crypt goblet cells. Pilocarpine given intraperitoneally 30 min prior to the mucolytic or PBS wash resulted in significant eradication of mucus down into the crypt lumen. This effect was still evident 3-4 hr later provided the intestine remained undisturbed.
Acetylcysteine↗
A human retinoic acid receptor gamma isoform is homologous to the murine retinoic acid receptor gamma 7.
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Animals↗