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Biomedical subjects

S M Barlow

Publications and source records attributed to S M Barlow.

At least 19 recordsLinked to original sources
PubMed2006

Developmental toxicity evaluation of triclopyr butoxyethyl ester and triclopyr triethylamine salt in the CD rat.

Triclopyr (3,5,6-trichloro-2-pyridyloxyacetic acid) is an herbicide used extensively in the control of woody plants and broadleaf weeds, and is often formulated as a triethylamine salt (T-TEA) or butoxyethyl ester (T-BEE). This study evaluated the developmental toxicity of T-TEA or T-BEE in time-mated CD rats gavaged on gestation days 6-15 with 0, 30, 100 or 300 mg/kg body weight(bw)/day. The doses of each compound were equimolar and equivalent to 22, 76, 216 mg/kg bw/day of triclopyr, based on prior studies indicating rapid cleavage of the salt or ester and equivalent pharmacokinetics for the active ingredient. T-TEA caused maternal toxicity, evidenced by the death of one high-dose dam, reduced body weight gain, increased relative liver and kidney weights (300 mg/kg bw/day), reduced feed consumption, and increased water consumption (100 and 300 mg/kg bw/day). Developmental effects were limited to slightly decreased fetal body weight and reduced skeletal ossification at the high dose level. T-BEE caused similar, albeit slightly more severe, maternal toxicity, with three maternal deaths at 300 mg/kg bw/day, and slight maternal effects at 30 mg/kg bw/day. Due to an equivocal increase in malformations, which were mainly clustered in litters from three high dose dams with marked maternal toxicity, the T-BEE study was repeated using 30 dams/group, investigator-blind fetal evaluations, and an additional dose group (5 mg/kg bw/day). In the repeat study, the only reproducible fetal effect was an increased incidence of 14th thoracolumbar rib at 300 mg/kg bw/day. Overall analysis of the two T-BEE studies suggested that the fetal malformations unique to the initial study likely reflected a combination of spontaneous events, exacerbated by marked maternal toxicity. The combined weight of evidence from these developmental toxicity studies, coupled with their known pharmacokinetic equivalence, indicates that T-BEE and T-TEA are not selectively toxic to the fetus. The respective maternal toxicity no-observed effect levels (NOEL) for T-BEE and T-TEA were 5 and 30 mg/kg bw/day, while the NOEL for developmental toxicity was 100 mg/kg bw/day for both compounds.

Abnormalities, Drug-Induced↗
PubMed2001

Mechanically evoked perioral reflexes in premature and term human infants.

Neurophysiological assessment of the preterm human neonatal oromotor system has been limited due to their fragile medical state, and methodological limitations. A new, noninvasive technology known as the actifier was developed and used to evoke perioral motor unit activity during non-nutritive suck in preterm infants. A significant ontologic trend for the early component of the perioral reflex (R1) was discovered in the context of spontaneous, centrally-patterned oromotor behavior.

Electromyography↗
PubMed2001

Risk assessment of the use of deltamethrin on bednets for the prevention of malaria.

Risk assessments covering the use of the pyrethroid, deltamethrin, on bednets for the prevention of malaria have been conducted The toxicity of deltamethrin in humans and animals is reviewed following both dermal and oral exposure. The no-adverse-effect level (NOEL) for exposure via the dermal route was 1000 mg/kg body weight/day. From this an acceptable exposure level (AEL) of 10 mg/kg body weight/day has been derived. The NOEL for exposure via the oral route was 1 mg/kg body weight/day, with exposures above this causing neurotoxic effects in animals. This NOEL has been used to derive margins of safety compared with predicted exposures. While direct skin contact does not seem to cause systemic toxicity in humans, it can cause burning, numbness and tingling of the skin, which is a local effect. This too is taken into account in the risk assessments. The risk assessments cover those treating bednets, on an intermittent or regular basis, the washing of treated nets, sleeping under treated nets (infants, children and adults). Worst case scenarios for each of these situations show that dermal exposures are low (one-tenth or less of the AEL) and the margins of safety for systemic exposure derived from oral data are acceptable, ranging from 10 to 3300. The benefits of the use of treated bednets in reducing morbidity and mortality from malaria are considerable and it can be concluded that the risk:benefit ratio is very favourable.

Administration, Oral↗
PubMed2001

Review of risk factors for sudden infant death syndrome.

Sudden infant death syndrome (SIDS) accounts for the largest number of deaths during the first year of life in developed countries. The possible causes of SIDS are numerous and, to date, there is no adequate unifying pathological explanation for SIDS. Epidemiological studies have played a key role in identifying risk factors, knowledge of which has underpinned successful preventive programmes. This review critically assesses information on the main risk factors and causal hypotheses put forward for SIDS, focusing on research published since 1994. The overall picture that emerges from this review is that affected infants are not completely normal in development, but possess some inherent weakness, which may only become obvious when the infant is subjected to stress. Initially there may be some minor impairment or delay in development of respiratory, cardiovascular or neuromuscular function. None of these is likely to be sufficient, in isolation, to cause death and, provided the infant survives the first year of life, may no longer be of any significance. However, when a compromised infant is confronted with one or more stressful situations, several of which are now clearly identified as risk factors, and from which the majority of infants would normally escape, the combination may prove fatal.

Adult↗
PubMed1999

Dilemmas facing regulatory and advisory bodies dealing with conflicting results.

Regulatory and advisory bodies have to take into account the possibility that conventional toxicological screening and testing methods may be failing to pick up relevant effects, with the implication that testing may need to go down to much lower exposure levels and use specifically designed studies. In the paper, attention is focused on the problems of understanding endocrine disrupting activity. The shape of the dose-response curve for endocrine disrupters may differ from that normally associated with toxic chemicals (the monotonic sigmoid curve). Thus, prediction of both the nature of the effects of potential endocrine disrupters and the intensity of those effects at different doses may be equally difficult. Endocrine effects are not currently amenable to analysis by a single apical assay. While existing toxicological tests can pick up many end-organ and functional effects that are relevant to endocrine disturbances, they are generally poor at exploring apparently subtle effects such as disturbances of brain endocrine homeostatic mechanisms which may be critical for normal development.

Animals↗
PubMed1999

Dietary vitamin A and teratogenic risk: European Teratology Society discussion paper.

This review discusses the predictive value of animal models in assessment of possible risk from excess vitamin A consumption during pregnancy and the human evidence concerning risk of congenital malformations from excess vitamin A in the diet, consumed either as a constituent of normal foods or in the form of dietary vitamin supplements. Other sources of exposure to vitamin A include medicines (dermal and oral preparations) and cosmetics, but these are not further considered here. Conservative estimates of the likely safe intake of vitamin A during pregnancy are available, based on results from scientific research to date. However, current uncertainties are such that further research is needed to more clearly define intakes which may be on the borderline between those which are beneficial and those which may pose a risk to the developing embryo and fetus.

Abnormalities, Drug-Induced↗
PubMed1998

Intrinsic dynamics and mechanosensory modulation of non-nutritive sucking in human infants.

The human infant is endowed with a complex mechanism for the ingestion of nutrients that becomes functional in late fetal life. The sucking motor pattern is generally accepted to be under the control of pattern generating circuitry located in the brainstem reticular formation. Systems under the control of a central pattern generator (CPG) may use afferent feedback to allow for changing environmental conditions. Although it is clear that afferent pathways serving the orofacial region become responsive to mechanical stimulation early in fetal life, little is known about the integration of afferent information into the suck CPG. The actifier, a device for the mechanical stimulation of intraoral and perioral tissues, was designed and used to investigate the response properties of the human infant suck CPG to patterned mechanical stimulation. Sinusoid and square waveform stimuli elicited responses including modulation of jaw kinematics and synchronization [entrainment] of non-nutritive suck motor patterns to the mechanical stimulus. These data provide evidence that the suck CPG is responsive to mechanical stimulation of perioral and intraoral soft tissues.

Afferent Pathways↗
PubMed1996

Comparison of perioral reflex modulation in the upper and lower lip.

The spatiotemporal organization and specificity of the mechanically evoked, short latency perioral response (R1) was sampled from a group of normal adult humans. Perioral reflex activity was sampled during passive and active static force conditions in the presence of servo-controlled mechanical inputs to lip vermilion. Results confirmed that the sensorimotor apparatus of the lower face is very responsive to low level mechanical inputs and highly dependent on several factors including input site (upper vs. lower lip), amount of glabrous tissue stimulated (contactor array size), and task dynamics (passive vs. active subject-generated lip force). Arguments are presented to support the idea that several features of the peripheral sensory environment encoded by primary trigeminal afferents, including afferent gain, specificity, locus, and spatial summation, collectively provide inputs vital to higher order sensory relays in the development of a central representation and dynamic conformational map of perioral space. These sensorimotor features encoded by trigeminal afferents are presumed important for motor learning and maintenance of oromotor control during speech, suck, mastication and swallow, and gesture.

Adolescent↗
PubMed1996

Mechanosensory modulation of perioral neuronal groups during active force dynamics.

The spatiotemporal organization of the mechanically evoked perioral sensorimotor response was sampled from five normal females using a custom-designed linear motor operating under force feedback. Electromyographic activity was sampled from the superior and inferior segments of the orbicularis oris muscle during the production of a visually guided ramp-and-hold lip-rounding task. Brief mechanical inputs of approximately 0.45 N delivered to the left upper lip during the ramp-and-hold task produced a composite myogenic response characterized by phases of excitation and suppression. Modulation of the primary excitatory component (R1) of the mechanically evoked perioral response was found to be highly dependent upon the rate of force recruitment (1 N/s vs. 4 N/s) and the phase of force recruitment (20% vs. 50% vs. 80% of 1 N end-point force). Modulation of later occurring inhibitory (S1) and excitatory (R2) potentials were also found to be dependent upon differences in the rate and phase of force recruitment. The organization of the perioral sensorimotor response is considered in relation to speech motor control and the dynamic organization of neuronal groups subserving perioral sensorimotor activity.

Adolescent↗
PubMed1996

The actifier: a device for neurophysiological studies of orofacial control in human infants.

A new device for the stimulation of intraoral tissues in human neonates is described. This instrument, known as an actifier, features a wide frequency range for mechanical stimulation, integrated multichannel electomyographic electrode pairs, and the capacity for transducing law compression during non-nutritive sucking behavior. The stimulus/recording interface consists of a modified pacifier. The actifier has been used to investigate the responsiveness of the sucking central pattern generator in human infants to mechanical perturbation.

Electromyography↗
PubMed1995

Case of recurrent, reversible, sudden sensorineural hearing loss in a child.

This paper describes audiologic, electrophysiologic, and medical test results for a now 10-year-old girl who has had 45 episodes of reversible, sudden sensorineural hearing loss over the last 8 years. Episodes have lasted from 6 to 72 hours and often have been accompanied by a mild illness. Acoustic immittance measures have been consistent with normal middle-ear function with the exception of absent ipsilateral and contralateral acoustic reflexes. Mechanically evoked perioral reflex activity was markedly asymmetric following lower lip stimulation. The asymmetry of R1 activation between right and left side lower lip inputs raises questions about the integrity of central connections within the brain stem, including internuncial pathways coursing between trigeminal sensory relay nuclei and the facial motor nucleus. An electrocochleographic evaluation revealed cochlear microphonic but absent or markedly abnormal whole nerve action potentials. Auditory brainstem responses (ABR) have been either absent or poorly formed and significantly delayed, regardless of hearing sensitivity. Middle and late auditory evoked potentials were essentially normal. Both transient-evoked and distortion-product otoacoustic emissions were present regardless of peripheral auditory sensitivity. All medical tests have been essentially normal. Although no definitive diagnosis has been reached, beta blockers have been used with some success. Taken together, these data document a very unusual case of fluctuating hearing loss. The electrocochleographic and otoacoustic emission data suggest that the outer hair cells are functioning normally and that the loss is not cochlear in origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Audiometry, Evoked Response↗
PubMed1994

Modulation of the mechanically evoked perioral reflex during active force dynamics in young adults.

Mechanically evoked reflex activity in the superior and inferior segments of the orbicularis oris muscle was sampled from three normal females using a specially designed linear motor operating under force feedback. Mechanical inputs delivered to the left upper lip during a ramp-and-hold task produced a composite reflex response characterized by phases of excitation and suppression at the homonymous muscle recording site. The modulation of the evoked composite perioral reflex was found to be dependent upon the rate and phase of force recruitment. The organization of the composite perioral reflex response is discussed in relation to speech motor control and load compensatory mechanisms.

Adult↗
PubMed1993

Transitional properties of the mechanically evoked perioral reflex from infancy through adulthood.

The organization of motor responses in the orbicularis oris muscle following the delivery of punctate mechanical inputs to vermilion skin of the lips was studied in a group of young infants, school-age children, and adults during periods of voluntary lip muscle activation. A specially designed multi-point array skin contactor, coupled to a position-servo controlled linear motor, was highly effective in driving the early component of the perioral reflex (R1). Overall, the evoked R1 response obtained from the infant was of variable amplitude relative to the children and adults, lacked response specificity, and occurred at a longer latency. This brainstem mediated sensorimotor action appears to take on several characteristics of the adult form by the age of 12. The emergence and maturation of mechanically evoked perioral reflexes is discussed in relation to the acquisition of motor skills, including speech and smiling.

Adolescent↗
PubMed1992

Mechanically evoked perioral reflexes in infants.

Mechanically evoked activity in the superior and inferior segments of the orbicularis oris muscle was sampled in several young infants using a specially designed position-servo linear motor and a pacifier instrumented with eight miniature EMG electrodes. Unilateral stimulation of lip vermilion resulted in short latency, bilateral activation of the upper and lower lip recording sites. The ontogenesis of facial reflex sensitivity to mechanical inputs is discussed in relation to the acquisition of motor skills, including speech and smiling.

Adult↗
PubMed1992

Vocalizations in the cat: behavioral methodology and spectrographic analysis.

Attempts to understand the neural mechanisms underlying mammalian vocal behaviors, including speech, require study of the neural activity and anatomy of vocalization-controlling brain structures. Such studies necessitate the application of invasive neurobiological techniques in animal models. In the current study, cats are used in the development of an animal model of vocal tract control. The animals are instrumentally conditioned to vocalize for food reward. Acquisition of this task can occur within a few minutes, although additional training generally is required to solidly establish the behavior and to train subjects to produce consistently high rates of vocalization for prolonged periods of time. Following training, animals can generally sustain a rate of two calls per minute for a period of over two hours. Optimal task performance is partly dependent on motivation level. Although there is considerable variation between animals, the vocalizations produced have an average duration of 600 ms and a fundamental frequency of around 500 Hz. In addition, during a typical vocalization, there are dynamic variations of about 150 Hz for fundamental frequency and 17 dB for sound intensity. These variations provide opportunities for relating neural and muscular activity to different aspects of the vocal behavior they control. Based on a number of considerations, the model and techniques discussed here probably are most applicable to studying the neurobiology of sub-cortical nuclei subserving vocal control. Similar mechanisms might well be present in other species, including humans. Thus, data obtained from study of this model may be applicable to understanding the processes underlying vocal tract control during human speech.

Animals↗
PubMed1992

Factors influencing neural activity in parabrachial regions during cat vocalizations.

The parabrachial nucleus in mammals is intimately connected with other vocalization controlling brainstem structures. It, along with ventromedially adjacent structures, also has been identified as the pneumotaxic center, and as such shows strong respiratory related activity in the anesthetized cat. The current study examines the neuronal activity in cat parabrachial regions during production of instrumentally conditioned vocalizations. Most of the units in our sample show considerable activity during periods between vocalizations. For many units, firing rate fluctuates during the respiratory cycle, although apparently not as strongly as reported in the decerebrate cat. Also, there is often strong phasic activity during periods where animals are licking to ingest their food rewards. During the peri-vocalization period, various neural activity patterns can be recorded. Most common is an activity increase during the vocalization itself. Moreover, in some units, this activity increase has an auditory component. A smaller number of units show other activity patterns, including a suppression of activity during vocalization and activity increases preceding the vocalization. Overall, our results suggest that the parabrachial region's involvement in vocal control is quite complex, involving convergence of respiratory, acoustic, vocalization-related, and perhaps somatosensory influences.

Acoustic Stimulation↗