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Biomedical subjects

J E Black

Publications and source records attributed to J E Black.

At least 19 recordsLinked to original sources
PubMed2006

Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome.

OBJECTIVE: Armodafinil is the R-enantiomer of racemic modafinil and has a significantly longer half-life than the S-enantiomer. This study evaluated armodafinil 150 mg/day as an adjunct treatment for residual excessive sleepiness in patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) who were otherwise well controlled with nasal continuous positive airway pressure (nCPAP). We assessed the ability of armodafinil to improve wakefulness and cognition and reduce fatigue in this population. METHODS: In this 12-week, randomized, double-blind study, patients (n=259) received armodafinil (150 mg) or placebo once daily. Efficacy assessments at baseline and weeks 4, 8, and 12 included the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Change (CGI-C), Cognitive Drug Research battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory. RESULTS: At final visit, mean (SD) MWT sleep latency increased from baseline by 2.3 (7.8) min with armodafinil and decreased by 1.3 (7.1) min in the placebo group (P=0.0003). Armodafinil improved clinical condition (CGI-C, 71% vs. 53% for armodafinil and placebo, respectively; P=0.0069). Armodafinil significantly improved episodic secondary memory (P=0.0102) and patient-estimated wakefulness (P<0.01) and reduced fatigue (P<0.05) compared with placebo. Armodafinil did not adversely affect nCPAP use. The most common adverse event associated with armodafinil was headache. Sleep macroarchitecture was not altered by armodafinil. CONCLUSION: Adjunct treatment with armodafinil significantly improved alertness, overall clinical condition, and long-term memory. Armodafinil also reduced fatigue and the impact of sleepiness on daily activities in patients with OSA/HS who have residual excessive sleepiness notwithstanding regular use of nCPAP. Armodafinil was well tolerated.

Adjuvants, Pharmaceutic↗
PubMed2001

Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea.

Patients with obstructive sleep apnea/hypopnea syndrome can experience residual daytime sleepiness despite regular use of nasal continuous positive airway pressure therapy. This randomized, double-blind, placebo-controlled, parallel group study assessed the efficacy and safety of modafinil for the treatment of residual daytime sleepiness in such patients. Patients received modafinil (n = 77) (200 mg/d, Week 1; 400 mg/d, Weeks 2 to 4) or matching placebo (n = 80) once daily for 4 wk. Modafinil significantly improved daytime sleepiness, with significantly greater mean changes from baseline in Epworth Sleepiness Scale scores at Weeks 1 and 4 (p < 0.001) and in multiple sleep latency times (MSLT) at Week 4 (p < 0.05). The percentage of patients with normalized daytime sleepiness (Epworth score < 10) was significantly higher with modafinil (51%) than with placebo (27%) (p < 0.01), but not for MSLT (> 10 min; 29% versus 25%). Headache (modafinil, 23%; placebo, 11%; p = 0.044) and nervousness (modafinil, 12%; placebo, 3%; p = 0.024) were the most common adverse events. During modafinil or placebo treatment, the mean duration of nCPAP use was 6.2 h/night, with no significant change from baseline observed between groups. Modafinil may be a useful adjunct treatment for the management of residual daytime sleepiness in patients with obstructive sleep apnea/hypopnea syndrome who are regular users of nasal continuous positive airway pressure therapy.

Adult↗
PubMed2001

Parent-child interaction during foster care visits.

The case-based research discussed in this article describes the variety of strategies mothers and young children spontaneously used to negotiate the complexities of foster care visiting. Nine mothers and their 24- to 48-month-old children were videotaped during their foster care visits. After each visit, the mother participated in an in-depth, audiotaped interview. Mothers and children displayed a wide variety of responses to visits. Mothers spontaneously discussed the challenges of visits, particularly separating at the end of visits. Implications for enhancing the quality of visits and strengthening services are discussed.

Adolescent↗
PubMed2000

Upper airway resistance syndrome. Central electroencephalographic power and changes in breathing effort.

Upper airway resistance syndrome (UARS) is defined by excessive daytime sleepiness and tiredness, and is associated with increased breathing effort. Its polygraphic features involve progressive increases in esophageal pressure (Pes), terminated by arousal (AR) as defined by the American Sleep Disorders Association (ASDA). With the arousal there is an abrupt decrease in Pes, called Pes reversal. However, Pes reversal can be seen without the presence of an AR. We performed spectral analysis on electroencephalographic data from a central lead for both AR and nonarousal (N-AR) events obtained from 15 UARS patients (eight men and seven women). Delta band activity was increased before and surrounding Pes reversal regardless of the presence or absence of AR. In the period after Pes reversal, alpha, sigma, and beta activity showed a greater increase in AR events than in N-AR events. The Pes measures were identical leading up to the point of reversal, but showed a longer-lasting and significantly greater decrease in respiratory effort after an AR. The data indicate that substantial electroencephalographic changes can be identified in association with Pes events, even when ARs cannot be detected according to standard criteria; however, visually identifiable electroencephalographic arousals clearly have a greater impact on ongoing inspiratory effort.

Adult↗
PubMed1995

Serotonergic mechanisms of cocaine effects in humans.

The objective of this study was to investigate the role of serotonin (5-HT) in mediating the effects of cocaine in humans. To accomplish this, 12 subjects each participated in two randomized, double-blind test sessions separated by 1 week. In one session, subjects underwent acute depletion of the 5-HT amino acid precursor tryptophan (TRP), followed by a test dose of intranasal cocaine. In the other session, the cocaine test dose was preceded by sham depletion. Subject ratings of cocaine "high" were significantly lower following active TRP depletion than after the sham procedure. Subjects also showed an earlier but less sustained rise in self-rated nervousness during active TRP depletion. These findings are consistent with the hypothesis that 5-HT may be involved in mediating the euphorigenic and modulating the anxiogenic effects of cocaine in humans, either directly or through actions on other (e.g., dopaminergic) systems.

Adult↗
PubMed1994

Noradrenergic dysregulation during discontinuation of cocaine use in addicts.

BACKGROUND: The primary objective of the study was to prospectively determine possible noradrenergic dysregulation in cocaine addicts by assessing biochemical, behavioral, and cardiovascular responses to intravenous yohimbine hydrochloride during early and late discontinuation of cocaine use. METHODS: Twelve male and two female hospitalized cocaine-dependent subjects (mean +/- SD age, 30.9 +/- 7.3 years) who were not seeking primary treatment for addiction participated voluntarily for monetary remuneration. Following an initial test dose of intranasal cocaine, 2 mg/kg, cocaine addicts received single-blind, monitored cocaine insufflation, 2 mg/kg three times each day, for 3 consecutive days. One to two days (early discontinuation) and 15 to 16 days (late discontinuation) after the last dose of cocaine, subjects received double-blind, randomized intravenous infusions of yohimbine hydrochloride, 0.4 mg/kg, or placebo. Plasma 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and plasma cortisol levels, anxiety-related symptoms on clinician- and subject-rated scales, blood pressure, and heart rate were measured throughout each test day. Ten of 14 subjects completed the entire study. RESULTS: Subjects had a significantly greater placebo-corrected MHPG response to yohimbine during early compared with late discontinuation. Subjects rated themselves significantly more nervous following yohimbine administration during early compared with late discontinuation. Seventy-one percent of subjects experienced a yohimbine-induced panic attack during early discontinuation compared with none during late discontinuation. CONCLUSIONS: The results of this study provide evidence of an underlying dysregulation in noradrenergic function and a vulnerability to panic anxiety during early discontinuation of cocaine use in addicts. Additional investigations of noradrenergic function appear warranted to further clarify derangements associated with cocaine addiction.

Administration, Intranasal↗
PubMed1994

Glial hypertrophy is associated with synaptogenesis following motor-skill learning, but not with angiogenesis following exercise.

Rats reared from weaning in a complex environment have an increase in 1) glial surface area, 2) capillary volume, and 3) the number of synapses, per neuron. In that paradigm it has not been possible to determine whether the glial increase more closely correlates with the increase in synaptic numbers or with angiogenesis. More recently we have found that rats that exercised had an increase in the density of capillaries without an increase in the synaptic numbers, whereas rats that learned new motor skills had a greater number of synapses per neuron without an increase in the density of capillaries. Those findings provided the opportunity to investigate whether changes in glial volume in the cerebellum correspond to changes in the number of synapses or in capillary volume. Glial area fraction estimates were obtained using point counts on electron micrographs from the previous studies. The skill learning group had a greater volume of molecular layer per Purkinje cell, and also a greater volume of glia per Purkinje cell, than rats in either an inactive group or rats in two exercise groups. No significant differences were found in glial volume per synapse and glial volume per capillary across groups, although there was a tendency for glial volume per capillary to be lower in the exercise groups. The data indicate that glial volume correlates with synaptic numbers and not with capillary density.

Animals↗
PubMed1993

Concurrent cocaine-ethanol ingestion in humans: pharmacology, physiology, behavior, and the role of cocaethylene.

Simultaneous abuse of cocaine and ethanol is a common occurrence. Cocaethylene, the ethyl ester of benzoylecgonine, has been detected in the urine of patients reporting concurrent use of cocaine and ethanol, and high levels have been found in the blood of victims of fatal drug overdose. This placebo-controlled, double-blind study examined the pharmacokinetic, physiologic, and behavioral effects of dual cocaine and ethanol administration in humans (n = 6). Cocaethylene was found in the plasma only after administration of both cocaine and ethanol, and appeared to be eliminated more slowly than cocaine. Plasma cocaine concentrations were significantly higher during cocaine/ethanol administration. Euphorigenic effects were both enhanced and prolonged, and heart rate was significantly increased, following cocaine/ethanol administration as compared to administration of cocaine or ethanol alone.

Adult↗
PubMed1992

Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning.

This study compared the morphology of cerebellar cortex in adult female rats exposed for 1 month to repetitive exercise, motor learning, or an inactive condition. In the exercise conditions, rats that were run on a treadmill or housed with access to a running wheel had a shorter diffusion distance from blood vessels in the molecular layer of the paramedian lobule when compared to rats housed individually or rats that participated in a motor skill learning task. Rats taught complex motor skills substantially increased the volume of the molecular layer per Purkinje neuron and increased blood vessel number sufficiently to maintain the diffusion distance. These results dissociate angiogenesis associated with increased neuropil volume (as seen in the motor learning group) from angiogenesis associated with increased metabolic demands (as seen in the exercise groups). While the volume fraction of mitochondria did not differ among groups, the mitochondrial volume fraction per Purkinje cell was significantly increased in the motor skill rats. This appears to parallel the previously reported increase in synapses and associated neuropil volume change.

Animals↗
PubMed1991

Capillary and mitochondrial support of neural plasticity in adult rat visual cortex.

Young adult rats (60 days old) were placed in complex environments (EC) or kept in individual cages (IC) for 10, 30, or 60 days. Previously reported findings in these same animals of synaptogenesis, decreased neuronal density, and increased cortical thickness in the EC animals demonstrated that cortical volume substantially expanded after 30 days. Such expansion would have spread apart existing capillaries and mitochondria, thereby diluting metabolic support. However, capillary spacing and mitochondrial volume fraction were maintained in these EC animals after 30 days, suggesting that new capillaries and mitochondria had infiltrated the tissue. Furthermore, many small vessels appeared after 10 days of complex experience, followed by expansion in vessel size until vessels from rats in EC for 60 days were larger than those from rats in IC for 60 days. The findings of constant vessel spacing in the face of expanding tissue volume, along with a set of small vessels that subsequently increased in size, suggest that small-sized new vessels were introduced in EC cortex by 10 days but had not matured in size until after 30 days. The results indicate that young adult rats can generate new capillaries and mitochondria in response to increased metabolic demands, but in a less vigorous fashion than in previously described weanling animals.

Animals↗
PubMed1991

Astrocyte hypertrophy in the dentate gyrus of young male rats reflects variation of individual stress rather than group environmental complexity manipulations.

Glial hypertrophy is associated with synaptogenesis in visual cortex and with stress-induced damage in the hippocampus. This study examined astrocytes in the dentate gyrus of male weanling rats exposed to complex or standard laboratory environments. No group differences in astrocytic surface density were observed, as expected in this brain region where group differences in synaptogenesis in male rats are reportedly minimal. Similarly, no group differences in adrenal weight were observed. Across all treatment groups, however, a significant positive correlation (r = 0.57) between adrenal weight and surface density of astrocytic processes was found. Considerable variation in responses of individual rats to their environments occurs in both the complex and the laboratory cage environments, and animals responding poorly may have had heavier adrenals and greater astrocyte reactivity in the dentate gyrus. Thus astrocyte hypertrophy in the dentate gyrus reflects the stress history of the individual rat and not any differential effects of rearing in a complex or a laboratory cage environment.

Adrenal Glands↗
PubMed1990

Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats.

The role of the cerebellar cortex in motor learning was investigated by comparing the paramedian lobule of adult rats given difficult acrobatic training to that of rats that had been given extensive physical exercise or had been inactive. The paramedian lobule is activated during limb movements used in both acrobatic training and physical exercise. Acrobatic animals had greater numbers of synapses per Purkinje cell than animals from the exercise or inactive groups. No significant difference in synapse number or size between the exercised and inactive groups was found. This indicates that motor learning required of the acrobatic animals, and not repetitive use of synapses during physical exercise, generates new synapses in cerebellar cortex. In contrast, exercise animals had a greater density of blood vessels in the molecular layer than did either the acrobatic or inactive animals, suggesting that increased synaptic activity elicited compensatory angiogenesis.

Animals↗
PubMed1989

Effects of complex experience on somatic growth and organ development in rats.

Rats kept in complex environments (EC) show an array of brain changes relative to animals housed individually (IC). These effects have been explained as due to (a) information storage, (b) chronic stress that causes brain damage, or (c) neuroendocrine effects on brain maturation. Complex experience also affects somatic growth and organ development, and these may be related to the EC/IC brain differences. We have compared somatic growth and internal organs of 315 weanling and adult rats with various histories. (a) Young EC rats showed slower skeletal and visceral growth, while many brain components expand. (b) Although thymus and spleen were lighter in young ECs, immunocompetence was nonsignificantly (p less than .07) higher than in ICs. (c) Somatic growth of adult rats was slow and not very responsive to experience, whereas studies have shown EC/IC brain effects similar to those in young rats. (d) Males had slightly greater EC/IC somatic and visceral differences. (e) The stress index, adrenal weight, varied across age and experience, so chronic stress can not explain EC/IC brain differences. Training paradigms show brain changes similar to those from complex experience, occurring specifically with learning and in brain regions using the information. Learning and memory, therefore remain the best explanation of the EC brain effects.

Adrenal Glands↗
PubMed1988

Direct evidence that complex experience increases capillary branching and surface area in visual cortex of young rats.

Rats housed in complex environments with toys and other rats generate new synapses, and the expanding neuropil tends to spread apart existing blood vessels. Previous work demonstrated that weanling rats kept in complex environments had more closely packed capillaries, suggesting that new capillaries had sprouted into the newly added neuropil. The present study directly investigates the issue of new branching by using india ink perfusions of weanling rats kept for 30 days in a complex environment (EC), paired in standard caging (SC), or individual cages (IC) to examine the density of capillary branch points and the capillary surface area per unit tissue volume. EC rats had a greater density of branch points than the SC and IC littermates, a finding consistent with increased capillary sprouting. Capillary surface area per unit tissue volume and the number of branch points per unit of capillary surface area were also higher for EC rats. This suggests that blood vessels of EC rats branch off more often than those of animals kept in more standard conditions, and provides further evidence that complex experience can increase angiogenesis in cerebral cortex of postweanling rats.

Animals↗
PubMed1987

Complex experience promotes capillary formation in young rat visual cortex.

The metabolic support of neural plasticity was examined by comparing cerebral vasculature of weanling rats reared in complex environments (EC) to littermates reared individually (IC) or socially in pairs (SC). EC rats have a thicker occipital cortex, more synaptic contacts per neuron and larger dendritic arbors compared to SC or IC rats, potentially increasing local metabolic demands on microvasculature. Capillaries of EC rats were closer together than those of SC or IC rats and potentially filled a greater fraction of cortex with blood. The closer capillary spacing in young EC rats suggests compensatory angiogenesis in response to increased metabolic demand.

Animals↗
PubMed1987

Experience and brain development.

This article considers how experience can influence the developing and mature brain and proposes a new categorization scheme based upon the type of information stored and the brain mechanisms that appear to be involved in storing it. In this scheme, experience-expectant information storage refers to incorporation of environmental information that is ubiquitous in the environment and common to all species members, such as the basic elements of pattern perception. Experience-expectant processes appear to have evolved as a neural preparation for incorporating specific information: in many sensory systems, synaptic connections between nerve cells are overproduced, and a subsequent selection process occurs in which aspects of sensory experience determine the pattern of connections that remains. Experience-dependent information storage refers to incorporation of environmental information that is idiosyncratic, or unique to the individual, such as learning about one's specific physical environment or vocabulary. The neural basis of experience-dependent processes appears to involve active formation of new synaptic connections in response to the events providing the information to be stored. Although these processes probably do not occur entirely independently of one another in development, the categories offer a new view more in accord with neural mechanisms than were terms like "critical" or "sensitive period."

Brain↗