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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 361 records · Page 20Linked to original sources

Effects of septal lesions on fear-potentiated startle, and on the anxiolytic effects of buspirone and diazepam.

The present study evaluated the effect of septal lesions on baseline startle amplitude, potentiated startle (a measure of conditioned fear), and the ability of either buspirone or diazepam to block potentiated startle. Baseline responding to an acoustic stimulus was obtained for all rats, followed by potentiated startle training (ten light-shock pairings on each of two days). Rats were then given bilateral electrolytic lesions of the septum or sham surgery. Four and seven days following surgery all rats were tested again for baseline startle amplitude. Ten days postsurgery, rats were injected with either 5.0 mg/kg buspirone or vehicle and tested for potentiated startle (increased acoustic startle in the presence of a light previously paired with shock). Five days later septal-lesioned animals were injected with either 5.0 mg/kg of diazepam or vehicle and again tested for potentiated startle. Septal lesions increased baseline startle amplitude significantly, but did not alter the magnitude of potentiated startle or impair the ability of buspirone or diazepam to block potentiated startle. In Experiment 2 rats were trained using the above procedures, and were subsequently given discrete bilateral lesions of the lateral septum or sham surgery. Lateral septal lesions again had no effect on the magnitude of potentiated startle. These findings do not support an involvement of the septum in the inhibition of fear, or in the mediation of the anxiolytic effects of buspirone or diazepam.

Animals↗

Topical mechlorethamine in the treatment of mycosis fungoides. Uniformity of application and potential for environmental contamination.

Topical mechlorethamine hydrochloride is commonly used in the treatment of mycosis fungoides and has been formulated in both aqueous and ointment vehicles. Two concerns regarding the topical application of mechlorethamine hydrochloride relate to the adequacy of skin coverage that can be attained by the patient and the extent to which others in the patient's household might be exposed to the drug. In this study six patients applied either aqueous or ointment vehicles containing a fluorescent dye. Subsequent examination of the skin under a Wood's lamp revealed a significant percentage of body surface area to be missed during application; several areas were noted to be missed most commonly. These observations have led to specific alterations in instructions given to patients regarding drug application. Examination of the surrounding environment showed minimal evidence of contamination.

Administration, Cutaneous↗

Efferent pathway of the amygdala involved in conditioned fear as measured with the fear-potentiated startle paradigm.

Fear-potentiated startle in the rat is a measure of conditioned fear that is blocked by lesions of the central nucleus of the amygdala. In a companion study, Rosen, Hitchcock, Sananes, Miserendino, and Davis (1991) demonstrated a direct anatomical projection from the central nucleus to the brainstem startle reflex circuit. In the present study, fear-potentiated startle was blocked by lesions that interrupted this pathway at 3 different levels or by a crossed lesion that interrupted the pathway at its source on one side and at a more caudal level on the other side. Although synaptic relays have not been ruled out entirely, the data suggest that the direct projection from the central nucleus of the amygdala to the startle circuit mediates the expression of fear-potentiated startle. These findings are consistent with the literature indicating that efferent projections from the central nucleus to various brainstem structures are involved in the expression of several conditioned fear responses.

Amygdala↗

A direct projection from the central nucleus of the amygdala to the acoustic startle pathway: anterograde and retrograde tracing studies.

Previous work has shown that lesions of the central nucleus of the amygdala block fear-potentiated acoustic startle and that electrical simulation of the central nucleus enhances acoustic startle in rats. In the present study, the anterograde tracer Phaseolus vulgaris-leucoagglutinin was used to identify and delineate the course of a direct projection from the central nucleus of the amygdala to the nucleus reticularis pontis caudalis, a nucleus in the acoustic startle circuit. Experiments using the retrograde tracer Fluoro-Gold confirmed this and indicated that the rostral part of the medial subdivision of the central nucleus of the amygdala contains the cells that project to the startle circuit. With this information, lesion studies (see companion article Hitchcock & Davis, 1991) may be used to determine whether this projection plays a role in fear-potentiated startle.

Amygdala↗

Immunogenetic heterogeneity in rheumatoid disease as illustrated by different MHC associations (DQ, Dw and C4) in articular and extra-articular subsets.

Genetic variants at DRB1 (Dw subtypes), DQB, and C4 loci were compared in rheumatoid disease subjects with or without the extra-articular feature of Felty's syndrome or major vasculitis. DR4 positive subjects with rheumatoid arthritis alone showed no preferential associations with DQB or Dw variants or with C4 null alleles. Felty's subjects showed associations with the DQB encoded DQw7 allele and with the C4B null allele but no preferential associations with any Dw subtype of DR4. By contrast DR4 +ve rheumatoid-vasculitic subjects showed associations with the Dw14 as well as with DQw7 and the C4A null allele. These different MHC associations in different clinical disease subsets show that rheumatoid disease is immunogenetically heterogeneous and suggest that MHC genes outside the DRB1 locus may also influence susceptibility or modify expression of the rheumatoid disease process.

Alleles↗

Hepatotoxicity of antidepressants.

Detection of abnormal liver function tests in a patient receiving an antidepressant or other psychopharmacological agent presents a major problem to the clinician, who must decide whether or not to withdraw a drug which may be of central importance in the patient's management. Experimental studies have clearly demonstrated a hepatotoxic potential for many of these compounds, but in the clinical situation the picture is far less clear cut because there are remarkably little published data on the incidence of liver damage from these agents in man. Furthermore, interpretation of abnormal liver function tests and ascribing them to a drug rather than to an alternative cause is not always straightforward. Hepatic drug reactions fall into two categories; those which are predictable and dose-related (e.g. acute hepatic necrosis following suicidal overdose with the analgesic paracetamol), and those which are unpredictable and dose-independent, complicating treatment with a drug at therapeutic dosage (Davis and Williams, 1985). Most hepatic drug reactions, including those caused by antidepressants, fall into the second category. The spectrum of severity may vary widely, from minor abnormalities in biochemical liver function tests with no constitutional disturbance, to severe hepatitis and/or cholestasis which can sometimes be fatal. Chronic liver disease has also been described.

Antidepressive Agents, Tricyclic↗

Neuroscience patients: under attack by fungi.

An intact skin with its acid mantle is the patient's first line of defense. Neuroscience nurses are the patient's second line of defense since they are responsible for assessment and treatment of the skin. Several risk factors make neuroscience patients susceptible to candidiasis. Skin properties, risk factors, assessment, complications and selected nursing and medical treatment of candidiasis are discussed in this article.

Candidiasis, Cutaneous↗

Fear-potentiated startle in humans: effects of anticipatory anxiety on the acoustic blink reflex.

The effects of fear/anticipatory anxiety on the acoustic startle reflex were investigated in humans using a paradigm involving anticipation of electric shocks. The eyeblink component of the startle reflex, elicited by an abrupt auditory stimulus, was measured in 9 normal volunteers during either the anticipation of electric shocks (anticipatory anxiety) or periods in which no shocks were anticipated (safe period). The eyeblink was consistently higher in amplitude, and shorter in latency, during periods when the subjects anticipated shocks, compared to the safe periods. This effect could not be attributed solely to a reduction in habituation and was statistically significant before the subjects actually received any shock (a single 30 mA stimulation on the median nerve). These results indicate that anticipatory anxiety can be measured objectively in humans using the fear-potentiated startle reflex in a paradigm not actually requiring any shock. Because a great deal is known about the neuroanatomical and pharmacological mechanisms of fear-potentiated startle in laboratory animals, this test procedure may be especially useful in humans to investigate the neurobiological substrates of anxiety disorders and their pharmacological treatments.

Acoustic Stimulation↗

Sampling issues in nursing home research.

It has been suggested that two common methods of sampling nursing home populations, cross-sectional sampling and discharge sampling, result in samples with different characteristics and lengths of stay. Comparison of these samples to a sample of nursing home admissions has not been studied. This study compares characteristics and lengths of stay among cross-sectional, discharge, and admission samples. All current residents of three nursing homes in February 1987 made up the cross-sectional sample, all admissions in the following year made up the admission sample, and all discharges in the same year made up the discharge sample. The results of comparing these three sampling techniques show that the most striking differences occur between the cross-sectional sample and the admission sample. Persons in the cross-sectional sample tended to have longer nursing home stays as well as less social support and more behavioral and functional problems than persons in the admission sample, who tended to have shorter stays and more acute medical problems. The discharge sample was more similar to the admission sample than it was to the cross-sectional sample; however, some differences were found between the discharge and admission samples. Based on the differences found among the three samples, appropriate uses for each sample are discussed.

Aged↗

Chain breaking antioxidant status in rheumatoid arthritis: clinical and laboratory correlates.

The ability of fresh sera to resist attack by peroxyl radicals (TRAP) was found to be significantly lower in 20 patients with rheumatoid arthritis (RA) than in 20 healthy controls, consistent with the existence of a redox stress in RA imposed by inflammation. TRAP values in RA varied inversely with a combination of visual analogue pain scale, duration of early morning stiffness, grip strength, and articular index (reflecting inflammatory activity) using multiple linear regression analysis. The concentration of the antioxidant vitamin ascorbic acid was lower in RA plasma and the oxidation-reduction equilibrium of ascorbic acid was disturbed, giving further support to the existence of a redox stress. The major determinant of TRAP in vitro was found to be serum uric acid in RA and serum vitamin E in controls. Serum urate concentration in RA correlated inversely with oxidative changes in serum albumin and IgG. It is suggested that serum urate might have an antioxidant role under certain conditions by limiting free radical induced oxidative changes to protein during inflammation.

Arthritis, Rheumatoid↗

The pitted duodenal bulb.

The radiologic, endoscopic, and histologic findings in two patients with flaskshaped or collar-button collections of barium in the duodenum are presented. These abnormal mucosal depressions, which may be related to inflammation, were seen endoscopically and identified radiographically and have not been reported previously.

Aged↗

Blockade of the spinal excitatory effect of cAMP on the startle reflex by intrathecal administration of the isoquinoline sulfonamide H-8: comparison to the protein kinase C inhibitor H-7.

Drugs thought to inhibit the actions of protein kinase C (PKC) and cAMP dependent protein kinase (A-kinase) were infused intrathecally into the subarachnoid space of the lumbar region of the spinal cord, and the effects on acoustic startle were measured. Previous work has shown that intrathecal infusion of drugs thought to increase cAMP increase the startle response. The present experiment evaluated whether inhibition of A-kinase would prevent this effect. Rats were infused with the isoquinoline sulfonamide, H-8 (360 nmol) or vehicle (50% dimethyl sulfoxide), 30 min prior to infusion of 100 nmol of dibutyryl cAMP. By itself, H-8 had little effect on startle, but completely blocked the normal excitatory effect of dibutyryl cAMP on startle. In contrast, the isoquinoline sulfonamide, H-7, which is less active in blocking A-kinase, but more active in blocking PKC, did not block dibutyryl cAMP. Moreover, H-8 did not block the excitatory effect of intrathecal infusion of the 5-HT1A receptor agonist, 8-OH-dipropylaminotetraline (8-OH-DPAT). Thus, the blockade of dibutyryl cAMP by H-8 appears somewhat specific and suggests an involvement of A-kinase in the excitatory effects of dibutyryl cAMP on the acoustic startle response. In a second experiment, it was found that administration of the isoquinoline sulfonamide H-7 caused a marked, dose-dependent (150-800 nmol) facilitation of the startle reflex in comparison with its vehicle. Tris buffer (0.1 M). Like H-7, another PKC inhibitor, GT1b (20 nmol) produced a marked increase in the startle reflex versus its vehicle, 0.01 M phosphate buffer.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala.

Receptors for N-methyl-D-aspartate (NMDA) seem to have a critical role in synaptic plasticity. NMDA antagonists (such as AP5) prevent induction of long-term potentiation, an activity-dependent enhancement of synaptic efficacy mediated by neural mechanisms that might also underlie learning and memory. They also attenuate memory formation in several behavioural tasks; there are few data, however, implicating an NMDA-sensitive measure of conditioning based on local infusion of antagonists into a brain area tightly coupled to the behavioural response used to assess conditioning. We now show that NMDA antagonists infused into the amygdala block the acquisition, but not the expression, of fear conditioning measured with a behavioural assay mediated by a defined neural circuit (fear-potentiation of the acoustic startle reflex). This effect showed anatomical and pharmacological specificity, and was not attributable to reduced salience of the stimuli of light or shock used in training. The data indicate that an NMDA-dependent process in the amygdala subserves associative fear conditioning.

2-Amino-5-phosphonovalerate↗

Differential blockade of early and late components of acoustic startle following intrathecal infusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or D,L-2-amino-5-phosphonovaleric acid (AP-5).

The present study investigated the individual contributions of spinal cord N-methyl-D-aspartate (NMDA) and non-NMDA receptors to the acoustic startle reflex in rats. The first experiment measured whole body acoustic startle before and after intrathecal infusion of various doses of either the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (AP-5), or the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Both compounds depressed startle in a dose-dependent fashion with similar potencies. A second experiment measured startle electromyographically (EMG) in the quadriceps femoris muscle complex in the hindlimbs during auditory stimulation to characterized the effects of these two compounds on the early (approximately 8 ms) or late (approximately 15 ms) EMG components of the startle response. CNQX preferentially blocked the early EMG component of startle, whereas AP-5 preferentially blocked the late component. These results suggest that the acoustic startle reflex involves an early EMG component mediated by spinal non-NMDA receptors, and a late EMG component mediated by spinal NMDA receptors.

2-Amino-5-phosphonovalerate↗

Nonverbal behavior and client state changes during psychotherapy.

In an intensive videotape analysis of 10 psychotherapy sessions, the body positions and gesticulation patterns of the client were examined in relation to changes in her verbal behavior. Verbal ratings were obtained on the Experiencing Scale (Klein, Mathieu, Gendlin, & Kiesler, 1970), and nonverbal ratings were obtained on the Davis Nonverbal States Scales (Davis, 1986). Results revealed that the position "accessibility" ratings were related significantly to levels of self-disclosure and involvement as determined by the verbal ratings. The client's gesticulation ratings were not related significantly to the Experiencing Scale ratings, but clinically interesting relationships between gesticulation patterns and verbal content were noted. While body movement long has been recognized as an important source of clinical information, replicable coding of complex patterns of position and gesture has been very difficult to develop. This study presents data that support a promising, replicable method for coding nonverbal behavior in psychotherapy process research.

Adult↗