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Biomedical subjects

R H Carpenter

Publications and source records attributed to R H Carpenter.

At least 19 recordsLinked to original sources

Effects of low-dose isoflurane on saccadic eye movement generation.

The effects of 0.15% quasi-steady-state end-tidal isoflurane on two saccadic eye-movement tests were examined in five volunteers using a newly devised computer-based recording system. The tests were saccadic latency and a countermanding task, the latter being an indicator of the highest levels of conscious performance. A moving light-emitting diode target was displayed on a screen and in the saccadic-latency task the latency of eye movement to the target was measured. In all five subjects the latency increased with anaesthetic by an amount which varied from 8 to 45 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In the countermanding task, the subject had to voluntarily inhibit movement to the target. Again anaesthetic increased the latency of response, which varied from 6 to 33 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In these studies it appeared that two tasks, one a simple latency test and the other, the countermanding task, requiring higher cortical processing were equally impaired at subanaesthetic concentrations of isoflurane.

Anesthetics, Inhalation

Movement control. Moving the mental maps.

The brain's maps of the outside world must be shifted when the point of view changes. Recent experiments on cortical neurons imply that this is done by modulating a distributed population code for position.

Animals

Neural computation of log likelihood in control of saccadic eye movements.

The latency between the appearance of a visual target and the start of the saccadic eye movement made to look at it varies from trial to trial to an extent that is inexplicable in terms of ordinary 'physiological' processes such as synaptic delays and conduction velocities. An alternative interpretation is that it represents the time needed to decide whether a target is in fact present: decision processes are necessarily stochastic, because they depend on extracting information from noisy sensory signals. In one such model, the presence of a target causes a signal in a decision unit to rise linearly at a rate r from its initial value s0 until it reaches a fixed threshold theta, when a saccade is initiated. One can regard this decision signal as a neural estimate of the log likelihood of the hypothesis that the target is present, the threshold being the significance criterion or likelihood level at which the target is presumed to be present. Experiments manipulating the prior probability of the target's appearing confirm this notion: the latency distribution then changes in the way expected if s0 simply reflects the prior log likelihood of the stimulus.

Humans

Saccadic eye movements while reading music.

Subjects' eye movements were measured whilst they read and performed lines of music consisting of rhythmic information only, in conventional musical notation. The relationship between the spatial pattern of the notes displayed and of the fixations made in reading them is stochastic, and similar to that in ordinary reading, but with a tendency to fixate salient details of the notation such as notes and barlines rather than the spaces in between. Shorter notes are less likely to be fixated than longer ones, and this is determined by their performance length rather than their visual appearance. Despite the timing constraints imposed by the music, the time of execution of individual saccades appears to be entirely unrelated to the time of the execution of elements of the performance itself. However, as the tempo of performance of a given piece of music is increased, the average time between saccades decreases but their mean amplitude increases. These observations suggest a new model of the oculomotor and perceptual processes involved, in which an central, iconic representation of the fixated image is internally scanned and interpreted to a given criterion of accuracy, the scan ending when this criterion cannot be reached, and this end-point determining the position of the next fixation. It is proposed that the fullness of the buffer between the perceptual and motor processes determines the strictness of the criterion which is adopted, and hence the amplitude and timing of the eye movements.

Fixation, Ocular

"Express" smooth pursuit.

For the majority of human smooth pursuit eye movements made to a horizontal ramp target of unpredictable direction, the reciprocal of the latency appears to have a Gaussian distribution of the same general form as for saccades to step targets, but with smaller median. There are more latencies shorter than some 100 msec than would be expected from such a distribution: they form a distinct population ("express smooth pursuit responses") whose distribution is similar to that of express saccades. They still occur in the absence of a cue, when the target is unpredictable.

Adult

Frontal cortex. Choosing where to look.

Recording from neurons in the frontal cerebral cortex has brought us one stage closer to identifying the neural mechanisms underlying the very highest levels of decision making in the brain.

Animals

Co-variability of smooth and saccadic latencies in oculomotor pursuit.

Latencies of smooth pursuit and saccadic eye movement responses to a horizontal ramp target show considerable random variation from trial to trial, which is uncorrelated between the two types of response. This implies that the functional pathways that are responsible for most of the delay in each case are essentially independent.

Eye Movements

Beyond the Darrow-Yannet diagram: an enhanced plot for body fluid spaces and osmolality.

The C-plot is a new method of plotting the volumes and osmolality of extracellular and intracellular body fluids, which in many circumstances is an improvement on the classical Darrow-Yannet diagram. The C-plot allows natural perturbations to be seen easily, and enables the relation between threats to fluid homoeostasis and the physiological mechanisms that counter those threats to be appreciated. The course of such events can also be shown in a single diagram.

Body Fluid Compartments

Distribution of quick-phase intervals in optokinetic nystagmus.

The distribution of the intervals between quick phases in optokinetic nystagmus shows the same general characteristics as saccadic latency to visual targets and as congenital nystagmus. In each case, for intervals of 150 ms and above, the distribution of reciprocal latency is normal; at shorter intervals, there may be a second component equivalent to 'express' saccades.

Humans

Subchronic oral administration of acemannan in the rat and dog.

Acemannan is the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed O-acetyl groups, with a mannose monomer/acetyl ratio of approximately 1:1. This complex polysaccharide is extracted from Aloe vera (barbadensis Miller); the technical material contains approximately 78% acemannan. Technical grade acemannan was administered po to rats for 14 d at 5% of the diet and for 6 mo at up to 2,000 mg/kg/d, and to beagle dogs for 90 d at up to 1,500 mg/kg/d without significant effect on any parameter measured in either species.

Administration, Oral

Toxicologic evaluation of injectable acemannan in the mouse, rat and dog.

Acemannan, the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed 0-acetyl groups with a mannose monomer/acetyl ratio of approximately 1:1 and extracted from Aloe vera (barbadensis Miller), was administered as a 1.0 mg/ml solution to mice, rats and dogs, either as single dose or repeated at 4-d intervals for 8 doses by iv or ip routes. No significant signs of intoxication and no deaths occurred in animals treated with the single injection of acemannan at dosages of 80 mg/kg iv or 200 mg/kg ip in mice, 15 mg/kg iv or 50 mg/kg ip in rats, and 10 mg/kg iv or 50 mg/kg ip in dogs. On repeated injections systemic toxicity was limited to obvious transient discomfort that appeared dose related. There was accumulation of macrophages and monocytes without subsequent inflammatory reaction in lungs of the iv-treated animals, and in liver and spleen and on peritoneal surfaces of ip-treated animals. The effects were not considered adverse, but were consistent with the known immune stimulating activity of acemannan. A few deaths occurred in mice and rats that were suggestive of resulting from improper injection or sequella of necrosis of the injection site. The NOAELs for acemannan determined from these repeated injection studies were 20 mg/kg iv or ip in the mouse, 4.0 mg/kg iv and 50 mg/kg ip in the rat, and 1.0 mg/kg iv in dogs; 5.0 mg acemannan/kg ip in the dog was considered to be LOAEL, based on the emesis and abdominal discomfort induced.

Animals

In vitro evaluation of the synergistic antiviral effects of acemannan in combination with azidothymidine and acyclovir.

The antiviral effects of selected combinations between acemannan (ACE-M), a long-chained, polydispersed, beta-(1,4)-acetylated mannan, were tested in combination with azidothymidine (AZT) and acyclovir (ACY) in vitro. The rationale for such combinations was based on the antiviral and immunomodulatory properties exhibited by ACE-M. In addition, the observed antiviral effects of ACE-M against human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses appear to be related to modification of the glycosylation of viral glycoproteins. Therefore, the inhibitory effect of ACE-M does not overlap with that of AZT or ACY. The studies presented herein show that ACE-M combined with suboptimal noncytotoxic concentrations of AZT or ACY act synergistically to inhibit the replication of HIV-1 and herpes simplex virus type 1 (HSV-1), respectively. The median effect method was not applicable for analysis because the test compounds show mutually nonexclusive drug effects. For a meaningful evaluation and interpretation of the effects of drug combinations, the biological significance of combinations must be considered, that is, the protective effect of the combination, the noncytotoxicity of the combination, the mechanism(s) of action of the individual compounds comprising the combination, and so forth. With respect to effects on U1 cells latently infected with HIV-1, treatment with combinations of AZT and ACE-M does not potentiate virus replication.

Acyclovir

Inhibition of AIDS virus replication by acemannan in vitro.

Acemannan (ACE-M), a beta-(1,4)-linked acetylated mannan, was evaluated for in vitro activity against human immunodeficiency virus type 1 (HIV-1). Castanospermine (CAS), deoxymannojirimycin (DMN), swainsonine (SWS), azidothymidine (AZT), and dideoxythymidine (DDC) were tested in parallel as control compounds. In vitro antiviral efficacy of ACE-M was evaluated in a variety of cell lines including human peripheral mononuclear, CEM-SS1 and MT-2(2) cells. The virus strain, number of infectious units per cell, and target cell line were important factors in determining the degree of inhibition of viral cytopathic effect in the presence of ACE-M and other control compounds tested. Maximum inhibitory effect was observed in CEM-SS cells infected with the RFII strain of HIV-1. This inhibitory effect was determined to be concentration-dependent. Assay design included primary screening to measure cell viabilities of infected target cells in the presence and absence of test compounds. When tested on HIV-1/RFII-infected CEM-SS cells, the 50% inhibitory effect of CAS (IC50 = 28), an inhibitor of alpha-glucosidase I, was determined to be similar to that observed for ACE-M (IC50 = 45). However, DMN and SWS, inhibitors of mannosidase I and II, tested in parallel to CAS and ACE-M, exhibited no IC50 values. Antiviral potential of ACE-M as an inhibitor of syncytia formation was also explored using CEM-SS cells. Suppression of syncytia formation was observed at an ACE-M concentration of 31.25 micrograms/ml, and complete inhibition was observed at 62.5 micrograms/ml. In addition, HIV-1 RNA levels were studied to establish the antiviral potential of ACE-M in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiviral Agents

The biological activities of mannans and related complex carbohydrates.

Complex polymers containing mannose (mannans) possess significant biological activity when administered to mammals. When given orally, they inhibit cholesterol absorption and induce hypocholesterolemia. If administered by other routes, they bind to mannose-binding proteins and induce macrophage activation and interleukin-1 release, inhibit viral replication, stimulate bone marrow activity, promote wound healing and inhibit tumor growth. This range of activities makes the mannans, potentially important biological-response modifiers and therapeutic agents.

Animals

Automated and manual quantitative assays of choriogonadotropin in serum compared.

We found the analytical performance of a rapid, automated assay of human choriogonadotropin (hCG) in serum, the Stratus hCG Fluorometric Enzyme Immunoassay, superior to a widely used manual assay for hCG (Hybritech Tandem-E hCG). The two assays were comparable in sensitivity; recovery; cross reactivity with lutropin, follitropin, and thyrotropin; and freedom from interference from hemoglobin and bilirubin. Patient-correlation studies indicated good quantitative agreement [Stratus hCG = (1.08 X Tandem hCG) - 4.3 int. units/L]. However, intra- and interassay precision was substantially better with the Stratus hCG assay, and this may allow earlier confirmation of pregnancy.

Antibodies, Monoclonal