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Biomedical subjects

A L Miller

Publications and source records attributed to A L Miller.

At least 37 records · Page 2Linked to original sources
PubMed2000

Differential protective effects of neurotrophins in the attenuation of noise-induced hair cell loss.

The protective efficacy of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) at 1 or 10 microg/ml was assessed in guinea pigs exposed to 4 kHz octave band noise at 115 dB SPL for 5 h. BDNF, NT-3 or artificial perilymph was delivered to the scala tympani via a mini-osmotic pump, beginning 4 days prior to noise exposure and continuing for 1 week post-exposure. Protection was assessed physiologically by the change in auditory brainstem response (ABR) threshold, and histologically by outer hair cell (OHC) survival. There was a statistically significant increase in OHC survival and a decrease in ABR threshold shift in animals receiving NT-3 at a concentration of 10 microg/ml. In animals receiving 1 microg/ml NT-3, there was a significant increase in OHC survival in the first row of OHC, but no significant change in ABR threshold, relative to control animals. In animals treated with BDNF, no significant functional or histological protection was observed. The protection afforded by NT-3 (10 microg/ml) treatment was similar in magnitude to that reported previously with glial cell line-derived neurotrophic factor and suggests that several factors may be involved in the protective response.

Animals↗
PubMed2000

Emotional expressiveness during peer conflicts: a predictor of social maladjustment among high-risk preschoolers.

Preschool boys' emotional displays during conflicts with mixed-sex peers were related to individual differences in peer sociometric status and teacher ratings of disruptive behavior. Participants were 60 4- to 5-year old boys from low-income families who were videotaped with a small group of classmates in a Head Start preschool classroom. Conflicts were identified and emotional displays were coded from videotape. Results indicated that conflicts were more negative in emotional tone at the end than at the beginning of the year. Furthermore, children tended to mirror each others' emotional displays at the end but not the beginning of the preschool year. In addition, gleeful taunting, a form of emotional aggression, more strongly predicted negative peer nominations and teacher ratings than anger, suggesting that anger may be a more socially accepted form of emotional expression during conflicts among preschool-age children. Implications and directions for future research and interventions are discussed.

Aggression↗
PubMed2000

Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity.

Gentamicin administration often results in cochlear and/or vestibular hair cell loss and hearing and balance impairment. It has been demonstrated that adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor (GDNF) can protect cochlear hair cells against ototoxic injury. In this study, we evaluated the protective effects of adenovirus-mediated overexpression of GDNF against gentamicin ototoxicity. An adenovirus vector expressing the human GDNF gene (Ad.GDNF) was administered into the scala vestibuli as a rescue agent at the same time as gentamicin, or as a protective agent, 7 days before gentamicin administration. Animals in the Rescue group displayed hearing thresholds that were significantly better than those measured in the Gentamicin or Ad.LacZ/Gentamicin groups. In the Protection group, Ad.GDNF afforded significant preservation of utricular hair cells. The data demonstrated protection of the inner ear structure, and rescue of the inner ear structure and function against ototoxic insults. These experiments suggest that inner ear gene therapy may be developed as a clinical tool for protecting the ear against environmentally induced insults.

Adenoviridae↗
PubMed2000

On the mechanism of ooplasmic segregation in single-cell zebrafish embryos.

It has been previously shown that localized elevations of free cytosolic calcium are associated with a morphological contraction in the forming blastodisc and animal hemisphere cortex during ooplasmic segregation in zebrafish zygotes. It was subsequently proposed, in a hypothetical model, that these calcium transients might be linked to the contraction of a cortically located actin microfilament network as a potential driving force for segregation. Here, by labeling single-cell embryos during the major phase of segregation with rhodamine-phalloidin, direct evidence is presented to indicate that the surface contraction was generated by an actin-based cortical network. Furthermore, while zygotes incubated with colchicine underwent normal ooplasmic segregation, those incubated with cytochalasin B did not generate a constriction band or segregate to form a blastodisc. During segregation at the single-cell stage, ooplasm simultaneously moved in two directions: toward the blastodisc within the so-called axial streamers, and toward the vegetal pole in the peripheral ooplasm. The velocities of both axial and peripheral streaming movements are reported. By injection of a fluorescein isothiocyanate (FITC)-labeled 2000 kDa dextran into the peripheral ooplasm it was demonstrated that a portion of it feeds into the bases of the extending streamers, which helps to explain the lack of accumulation of ooplasm at the vegetal pole. These new data were incorporated into the original model to link the bipolar ooplasmic movements with the calcium-modulated, actin-mediated contraction of the animal hemisphere cortex as a means of establishing and driving ooplasmic segregation in zebrafish.

Actins↗
PubMed2000

Do specific neurocognitive deficits predict specific domains of community function in schizophrenia?

We examined whether specific neurocognitive deficits predicted specific domains of community outcome in 40 schizophrenic patients. Neuropsychological assessments were conducted before hospital discharge, and measures of functional outcome were obtained 1 to 3.5 years later. A priori hypotheses were generated based upon a recent review by Green (Green MF [1996] What are the functional consequences of neurocognitive deficits in schizophrenia? American Journal of Psychiatry, 153(3):321-330). As hypothesized, verbal memory predicted all measures of community outcome, vigilance predicted social outcomes, and executive functioning predicted work and activities of daily living (ADLs). However, in addition to the predicted relationships, many other associations were found between neuropsychological test scores and adaptive function. Furthermore, both cognitive and functional measures were intercorrelated. If deficits in adaptive functioning are neurocognitively multi-determined, utilizing compensatory strategies to bypass multiple areas of cognitive impairment may be more efficient than cognitive remediation in improving community outcomes.

Activities of Daily Living↗
PubMed2000

Randomized controlled trial of the use of compensatory strategies to enhance adaptive functioning in outpatients with schizophrenia.

OBJECTIVE: Cognitive adaptation training is a novel psychosocial treatment approach designed to improve adaptive functioning by using compensatory strategies in the home or work environment to bypass the cognitive deficits associated with schizophrenia. The authors tested the effect of cognitive adaptation training on level of adaptive functioning in outpatients with schizophrenia. METHOD: Forty-five patients with DSM-IV schizophrenia or schizoaffective disorder were randomly assigned for 9 months to one of three treatment conditions: 1) standard medication follow-up, 2) standard medication follow-up plus cognitive adaptation training, and 3) standard medication follow-up plus a condition designed to control for therapist time and provide environmental changes unrelated to cognitive deficits. Comprehensive assessments were conducted every 3 months by raters who were blind to treatment condition. RESULTS: Significant differences were found between the three treatment groups in levels of psychotic symptoms, motivation, and global functioning at the end of the 9-month study period. Patients in the cognitive adaptation training group overall had higher levels of improvement, compared with those in the remaining treatment conditions. In addition, the three groups had significantly different relapse rates over the 9-month study: 13% for the cognitive adaptation training group, 69% for the group in which therapist time and environmental changes were controlled, and 33% for the group who received standard follow-up only. CONCLUSIONS: Compensatory strategies may improve outcomes for patients with schizophrenia.

Adult↗
PubMed2000

Imaging patterns of calcium transients during neural induction in Xenopus laevis embryos.

Through the injection of f-aequorin (a calcium-sensitive bioluminescent reporter) into the dorsal micromeres of 8-cell stage Xenopus laevis embryos, and the use of a Photon Imaging Microscope, distinct patterns of calcium signalling were visualised during the gastrulation period. We present results to show that localised domains of elevated calcium were observed exclusively in the anterior dorsal part of the ectoderm, and that these transients increased in number and amplitude between stages 9 to 11, just prior to the onset of neural induction. During this time, however, no increase in cytosolic free calcium was observed in the ventral ectoderm, mesoderm or endoderm. The origin and role of these dorsal calcium-signalling patterns were also investigated. Calcium transients require the presence of functional L-type voltage-sensitive calcium channels. Inhibition of channel activation from stages 8 to 14 with the specific antagonist R(+)BayK 8644 led to a complete inhibition of the calcium transients during gastrulation and resulted in severe defects in the subsequent formation of the anterior nervous system. BayK treatment also led to a reduction in the expression of Zic3 and geminin in whole embryos, and of NCAM in noggin-treated animal caps. The possible role of calcium transients in regulating developmental gene expression is discussed.

Aequorin↗
PubMed1999

A wave of free cytosolic calcium traverses zebrafish eggs on activation.

The activation process in a variety of deuterostome and protostome eggs is accompanied by cytosolic calcium transients that usually take the form of either a single or multiple propagating waves. Here we report that the eggs of zebrafish (Danio rerio) are no exception in that they generate a single activation wave that traverses the egg at a velocity of around 9 microm/s. There appears, however, to be no difference between the calcium-mediated activation response of eggs with regard to the presence or absence of sperm in the spawning medium. This leads us to suggest that these eggs are normally activated when they come in contact with their spawning medium and are then subsequently fertilized. The aspermic wave is initiated at the animal pole in the region of the micropyle, appears to propagate mainly through the yolk-free egg cortex, and then terminates at the vegetal pole. As neither sperm nor external calcium is required for the initiation (or propagation) of the activation wave, this suggests that an alternative wave trigger must be involved.

Animals↗
PubMed1999

Predicting quality of life from symptomatology in schizophrenia at exacerbation and stabilization.

There has been little research investigating how symptoms of schizophrenia and changes in symptomatology across the course of the illness relate to measures of quality of life in patients. We examined this issue in 45 patients assessed at hospital admission for illness exacerbation, at stabilization (prior to discharge) and at follow-up (5-9 months post-discharge). Symptom ratings at each time period consisted of the Brief Psychiatric Rating Scale (BPRS) and the Negative Symptom Assessment (NSA). The Heinrichs-Carpenter Quality of Life Scale (QLS) was administered upon admission to the hospital (assessing the 3 months prior to admission) and again at follow-up. Correlational analyses revealed relationships of both positive and negative symptoms with quality of life. These relationships are particularly strong at stabilization. Stepwise regression analyses revealed changes in the NSA motivation component to be most important in predicting quality of life for the patients at follow-up. BPRS psychosis and paranoia components are important predictors of quality of life at stabilization (but not during acute exacerbation). These results are important in terms of understanding the impact of changes in symptomatology on the quality of life for patients with schizophrenia as well as in targeting specific symptom clusters for treatment to maximize quality of life post-hospitalization.

Acute Disease↗
PubMed1999

Imaging of multicellular large-scale rhythmic calcium waves during zebrafish gastrulation.

Oscillations of cytosolic free calcium levels have been shown to influence gene regulation and cell differentiation in a variety of model systems. Intercellular calcium waves thus present a plausible mechanism for coordinating cellular processes during embryogenesis. Herein we report use of aequorin and a photon imaging microscope to directly observe a rhythmic series of intercellular calcium waves that circumnavigate zebrafish embryos over a 10-h period during gastrulation and axial segmentation. These waves first appeared at about 65% epiboly and continued to arise every 5-10 min up to at least the 16-somite stage. The waves originated from loci of high calcium activity bordering the blastoderm margin. Several initiating loci were active early in the wave series, whereas later a dorsal marginal midline locus predominated. On completion of epiboly, the dorsal locus was incorporated into the developing tail bud and continued to generate calcium waves. The locations and timing at which calcium dynamics are most active appear to correspond closely to embryonic cellular and syncytial sites of known morphogenetic importance. The observations suggest that a panembryonic calcium signaling system operating in a clock-like fashion might play a role during vertebrate axial patterning.

Aequorin↗
PubMed1999

Across-species comparisons of psychophysical detection thresholds for electrical stimulation of the cochlea: I. Sinusoidal stimuli.

Several species have been, and continue to be, used as subjects in studies of electrical stimulation of the cochlea. Few attempts, however, have been made to determine if data obtained from different species are quantitatively or qualitatively similar. The present work compares psychophysical absolute detection threshold vs. frequency functions for sinusoidal stimuli obtained from humans, nonhuman primates, cats, and guinea pigs. Threshold data for monopolar and bipolar electrode configurations from both previously published and unpublished studies are compared. In general, within all four species, significant intersubject variation in detection threshold level was found, but slopes of threshold vs. frequency functions were relatively well conserved within a species, under the conditions studied. With one exception (cat bipolar stimulation), threshold functions reached a minimum at or near 100 Hz across species and electrode configurations. In all cases, thresholds were significantly lower for monopolar, as compared with bipolar, configurations. Statistically, there were no significant differences in absolute threshold level across species. Threshold levels increased with frequency above 100 Hz at a rate of 3.0-7.9 dB/octave, depending on both electrode configuration and species. Slopes were steeper for monopolar than for bipolar configurations. When slopes were averaged between 200 and 2000 Hz, no statistically significant differences in overall slopes were found, nor was there a significant interaction between electrode configuration and species. There were, however, consistent species differences within more restricted regions of the function. Human functions for both monopolar and bipolar stimulation were steeper than all animal functions in the range of 100-300 Hz. Within this range, the differences between slopes for human and nonhuman subjects were statistically significant. In addition, differences were noted in the frequency at which slope decreased, with slopes for nonhuman subjects showing the decrease at higher frequencies than did those for human subjects. These differences may be true species differences, or may reflect the influence of confounding variables associated with each experimental-subject model.

Animals↗
PubMed1999

Across-species comparisons of psychophysical detection thresholds for electrical stimulation of the cochlea: II. Strength-duration functions for single, biphasic pulses.

This paper compares psychophysical detection threshold data (new and previously published) for pulsatile electrical stimulation of the deafened inner ear, obtained from different human and nonhuman subjects. Subjects were grouped according to species. Other variables, however, such as the electrode array type and method of deafening, varied within and across species. Detection threshold levels and slopes of threshold versus phase duration functions for presentations of single, biphasic pulsatile stimuli (strength-duration functions) were compared for humans, macaques, cats, and guinea pigs. For bipolar stimulation, statistically significant differences in threshold level were observed between human subjects and all other species. The species difference did not depend on the phase duration tested. For monopolar stimulation, only nonhuman species were tested. Effects of electrode configuration on both the level and slope of psychophysical strength-duration functions were statistically significant across nonhuman species, but there was not a statistically significant interaction between species and electrode configuration. The similarity in function shape and relative paucity of significant differences in psychophysical functions across species support the continued use of multiple species for cochlear implant research.

Animals↗
PubMed1999

The Texas Medication Algorithm Project: development and implementation of the schizophrenia algorithm.

The Texas Medication Algorithm Project is a program designed to improve the quality of care of persons with serious mental disorders across sites in the Texas public mental health system and to create a uniform clinical environment from which cost estimates can be made. This paper describes the process of developing a pharmacological treatment algorithm for schizophrenia that addresses use of antipsychotics as well as other medications for side effects and co-existing symptoms. Input from clinicians, consultants, and consumers informed development of the algorithm, which was based on existing expert consensus guidelines. Information about the project can be found on the Internet at www.mhmr.state.tx.us/meds/tmap.htm. The authors present and describe the original and current versions of the algorithm, outline the feedback process by which it will be refined, and discuss how new medications will be incorporated as they enter the market.

Algorithms↗
PubMed1999

Medication treatment for the severely and persistently mentally ill: the Texas Medication Algorithm Project.

This article provides an overview of the issues involved in developing, using, and evaluating specific medication guidelines for patients with psychiatric disorders. The potential advantages and disadvantages, as well as the essential elements in the structure of algorithms, are illustrated by experience to date with the Texas Medication Algorithm Project, a public-academic collaboration. Phase 1 entailed assembling research findings on the efficacy of medications for schizophrenic, bipolar, and major depressive disorders. This knowledge was evaluated for its quality and relevance, integrated with expert clinical judgment as well as input by practicing clinicians, family advocates, and patients. Phase 1 (the design and development of the algorithms) was followed by a feasibility test (Phase 2). Phase 3 is an ongoing evaluation comparing the clinical and economic effects of using specific medication guidelines (algorithms) versus treatment as usual in public sector patients with severe and persistent mental illnesses.

Algorithms↗
PubMed1999

The Texas Medication Algorithm Project (TMAP) schizophrenia algorithms.

BACKGROUND: In the Texas Medication Algorithm Project (TMAP), detailed guidelines for medication management of schizophrenia and related disorders, bipolar disorders, and major depressive disorders have been developed and implemented. DISCUSSION: This article describes the algorithms developed for medication treatment of schizophrenia and related disorders. The guidelines recommend a sequence of medications and discuss dosing, duration, and switch-over tactics. They also specify response criteria at each stage of the algorithm for both positive and negative symptoms. The rationale and evidence for each aspect of the algorithms are presented.

Algorithms↗
PubMed1999

Mental health care from the public perspective: the Texas Medication Algorithm Project.

Medication treatment algorithms have been suggested as a strategy to provide uniform care at predictable costs. The Texas Medication Algorithm Project is a 3-phase study designed to provide solid data on the usefulness of medication algorithms. In phase 1, medication algorithms for the treatment of schizophrenia, major depressive disorder, and bipolar disorder were developed. Phase 2 was a feasibility study of these algorithms, and phase 3, now underway, compares the costs and outcome in 3 groups, one using a combination of an algorithm and patient/family education, a second using treatment as usual in a clinic that uses an algorithm for a different disorder, and a third using treatment as usual in a nonalgorithm clinic.

Algorithms↗