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Biomedical subjects

John L Carroll

Publications and source records attributed to John L Carroll.

15 recordsLinked to original sources
PubMed2006

Long-term follow-up of oropharyngeal dysphagia in children without apparent risk factors.

BACKGROUND: The presence of swallowing dysfunction in children without obvious risk factors remains under appreciated. Early identification and prompt initiation of appropriate treatments are critical for reduction of morbidities associated with dysphagia. OBJECTIVE: : To describe the clinical presentations, radiologic characteristics, and long-term outcomes in children with oropharyngeal dysphagia presenting as unexplained respiratory problems. We completed a retrospective chart review of all children without known dysphagic risk factors upon presentation to Speech-Language Pathology (December 1991-April 1995) for feeding/swallowing evaluations because of refractory respiratory problems and dysphagic concerns, and who subsequently were diagnosed with dysphagia on Videofluoroscopic Swallow Study (VFSS). In August 2002, follow-up telephone interviews were conducted with caregivers of 14 children. RESULTS: : We identified 19 children (mean age 1.14 years; range 0.9-5.75) with dysphagia presenting as unexplained respiratory problems. On VFSS, delayed pharyngeal swallow onset was the most common abnormal radiologic finding and always preceded penetration or tracheal aspiration. Eleven (57.9%) children aspirated. Aspiration occurred only with liquids and 100% of aspiration events were silent (i.e., no cough). Dysphagia was not a concern in 11 children at a mean age 3.2 years (range 0.7-10) and persisted in three children who were 9 years or older. CONCLUSIONS: : Oropharyngeal dysphagia should be considered in the differential diagnosis of young children without known risk factors associated with swallowing dysfunction when they present with unexplained respiratory problems. Although the prognosis for resolution of dysphagic concerns is very good, it may take several years.

Adolescent↗
PubMed2006

Ethical issues in mobile psychiatric treatment with homebound elderly patients: the Psychogeriatric Assessment and Treatment in City Housing experience.

Unique and challenging ethical difficulties arise during mobile psychiatric treatment of elderly patients. This article outlines and analyzes five of these challenges that have been encountered during nearly 20 years of experience with the Psychogeriatric Assessment and Treatment in City Housing Program in Baltimore, Maryland. The ethical challenges reviewed are: establishing the treatment contract versus the right to refuse treatment, protecting confidentiality versus patient protection, protecting autonomy versus asserting beneficence, treatment termination versus open-ended treatment, and cost versus benefit of care. Ethical challenges with homebound elderly patients are unique because of patient characteristics as well as features of the treatment environment.

Aged↗
PubMed2005

Postnatal development of carotid body glomus cell O2 sensitivity.

In mammals, the main sensors of arterial oxygen level are the carotid chemoreceptors, which exhibit low sensitivity to hypoxia at birth and become more sensitive over the first few days or weeks of life. This postnatal increase in hypoxia sensitivity of the arterial chemoreceptors, termed "resetting", remains poorly understood. In the carotid body, hypoxia is transduced by glomus cells, which are secretory sensory neurons that respond to hypoxia at higher P(O2) levels than non-chemoreceptor cell types. Maturation or resetting of carotid body O2 sensitivity potentially involves numerous aspects of the O2 transduction cascade at the glomus cell level, including glomus cell neurotransmitter secretion, neuromodulator function, neurotransmitter receptor expression, glomus cell depolarization in response to hypoxia, [Ca2+]i responses to hypoxia, K+ and Ca2+ channel O2 sensitivity and K+ channel expression. However, although progress has been made in the understanding of carotid body development, the precise mechanisms underlying postnatal maturation of these numerous aspects of chemotransduction remain obscure.

Animals↗
PubMed2005

Neurotransmitters in carotid body development.

This review examines the possible role of neurotransmitters present in the carotid body on the functional expression of chemosensory activity during postnatal development. In particular, dopamine, acetylcholine, adenosine and neuropeptides are reviewed. Evidence to date shows involvement of these transmitters in signal transmission from the chemoreceptor cells to chemosensory afferent fibers of the sinus nerve, with clear age- or maturation-dependence of some aspects. However, it remains unresolved whether these neurotransmitters, some of which are expressed in the carotid body before birth, are directly involved in the maturation of the functional properties of the carotid chemoreceptors in sensing oxygen or other stimuli during postnatal development.

Animals↗
PubMed2005

Left ventricular function in children with sleep-disordered breathing.

Severe obstructive sleep apnea in children leads to congestive heart failure. We studied the early changes in left ventricular function across a range of severity of the disorder. A dose-dependent decrease in diastolic function with increased severity of obstructive apnea was demonstrated.

Adolescent↗
PubMed2005

Perinatal hyperoxia for 14 days increases nerve conduction time and the acute unitary response to hypoxia of rat carotid body chemoreceptors.

Hyperoxia in the immediate perinatal period, but not in adult life, is associated with a life-long impairment of the ventilatory response to acute hypoxia. This effect is attributed to a functional impairment of peripheral chemoreceptors, including a reduction in the number of chemoreceptor afferent fibers and a reduction in "whole nerve" afferent activity. The purpose of the present study was to assess the activity levels of single chemoreceptor units in the immediate posthyperoxic period to determine whether functional impairment extended to single chemoreceptor units and whether the impairment was only induced by hyperoxia exposure in the immediate postnatal period. Two groups of rat pups were exposed to 60% inspired O2 fraction for 2 wk at ages 0-14 days and 14-28 days, at which time single-unit activities were isolated and recorded in vitro. Compared with control pups, hyperoxia-treated pups had a 10-fold reduction in baseline (normoxia) spiking activity. Peak unit responses to 12, 5, and 0% O2 were reduced and nerve conduction time was significantly slower in both hyperoxia-treated groups compared with control groups. We conclude that 1) hyperoxia greatly reduces single-unit chemoreceptor activities during normoxia and acute hypoxia, 2) the treatment effect is not limited to the immediate newborn period, and 3) at least part of the impairment may be due to changes in the afferent axonal excitability.

Action Potentials↗
PubMed2005

Mitochondrial function and carotid body transduction.

Carotid body chemoreceptors respond to a decrease in arterial oxygen tension by increasing spiking activity on the sinus nerve. Our understanding of the oxygen-transducing ability of the organ arose from studies in the 1930s intended to understand how metabolic poisons stimulated breathing. Since that time, an intimate link between energy state and hypoxia sensing has been assumed and forms the basis of the metabolic hypothesis of oxygen sensing. This hypothesis is supported by studies demonstrating a loss of mitochondrial potential in carotid body cells at oxygen tensions that cause no change in cells from other tissues. Although the nature of the coupling between mitochondrial function and nerve excitation remains unresolved, experimental evidence supports roles for (1) release of mitochondrial calcium stores, (2) modulation of membrane channels that are linked to mitochondrial complexes I and IV, and (3) generation of signaling intermediates, such as reactive oxygen species (ROS) from complex I and III of the electron transport chain. If the mitochondrion is the oxygen-sensing site for peripheral chemoreceptors, then there exists the potential ability to manipulate, perhaps pharmacologically, the sensing function by alterations in expression of uncoupler proteins or chemicals that can alter the affinity of cytochrome oxidase for oxygen. Such manipulation may be useful for the treatment of hypoventilation syndromes or high altitude accommodation.

Acclimatization↗
PubMed2004

Postnatal development of E-4031-sensitive potassium current in rat carotid chemoreceptor cells.

The O2 sensitivity of dissociated type I cells from rat carotid body increases with age until approximately 14-16 days. Hypoxia-induced depolarization appears to be mediated by an O2-sensitive K+ current, but other K+ currents may modulate depolarization. We hypothesized that membrane potential may be stabilized in newborn type I cells by human ether-a-go-go-related gene (HERG)-like K+ currents that inhibit hypoxia-induced depolarization and that a decrease in this current with age could underlie, in part, the developmental increase in type I cell depolarization response to hypoxia. In dissociated type I cells from 0- to 1- and 11- to 16-day-old rats, using perforated patch-clamp and 70 mM K+ extracellular solution, we measured repolarization-induced inward K+ tail currents in the absence and presence of E-4031, a specific HERG channel blocker. This allowed isolation of the E-4031-sensitive HERG-like current. E-4031-sensitive peak currents in type I cells from 0- to- 1-day-old rats were 2.5-fold larger than in cells from 11- to 16-day-old rats. E-4031-sensitive current density in newborn type I cells was twofold greater than in cells from 11- to 16-day-old rats. Under current clamp conditions, E-4031 enhanced hypoxia-induced depolarization in type I cells from 0- to- 1-day-old but not 11- to 16-day-old rats. With use of fura 2 to measure intracellular Ca2+, E-4031 increased the cytosolic Ca2+ concentration response to anoxia in cells from 0- to- 1-day-old but not cells from 11- to 16-day-old rats. E-4031-sensitive K+ currents are present in newborn carotid body type I cells and decline with age. These findings are consistent with a role for E-4031-sensitive K+ current, and possibly HERG-like K+ currents, in the type I cell hypoxia response maturation.

Aging↗
PubMed2004

Twenty-four-hour ambulatory blood pressure in children with sleep-disordered breathing.

Obstructive sleep apnea causes intermittent elevation of systemic blood pressure (BP) during sleep. To determine whether obstructive apnea in children has a tonic effect on diurnal BP, 24-hour ambulatory blood pressure was obtained from 60 children with mean age of 10.8 +/- 3.5 years. Thirty-nine children had obstructive apnea and 21 had primary snoring. Children with obstructive apnea had significantly greater mean BP variability during wakefulness and sleep, a higher night-to-day systolic BP, and a smaller nocturnal dipping of mean BP. Variability of mean arterial pressure during wakefulness was predicted by the desaturation, body mass, and arousal indices, whereas variability during sleep was predicted by apnea-hypopnea and body mass indices. Nocturnal BP dipping was predicted by the desaturation index. There were no significant differences in systolic, diastolic, or mean arterial BP during sleep between the groups. Diastolic BP during wakefulness was significantly different between the groups and correlated negatively with apnea-hypopnea index. We conclude that obstructive apnea in children is associated with 24-hour BP dysregulation and that, independent of obesity, the frequency of obstructive apnea, oxygen desaturation, and arousal contributes to abnormal BP control.

Adolescent↗
PubMed2003

Obstructive sleep-disordered breathing in children: new controversies, new directions.

Although it may seem that confusion and uncertainty reign in the field of pediatric sleep medicine, the recent realizations that the scope of childhood SDB is wider, the symptomatology is broader, and the prevalence is higher than previously believed are major advances. Likewise, recent acknowledgment of the lack of true "gold standards" for diagnosing UARS and OSAS in children is also a major advancement in this field. Critical assessment of the current "state of the art" by the 2002 AAP Technical Report on the Diagnosis and Management of Childhood Obstructive Sleep Apnea Syndrome [37] is another major advance that sets the stage for the next steps. The field needs an evidence-based definitions conference, standardization of definitions across all research studies, and much more research on clinical features, pathophysiology, diagnosis, and treatment of the "new" obstructive SDB, including the full range of morbidity caused by increased upper airway resistance. This should include further inquiry into the origins of adult morbidity that resulted from childhood SDB and how it can be prevented.

Child↗
PubMed2003

Developmental plasticity in respiratory control.

Development of the mammalian respiratory control system begins early in gestation and does not achieve mature form until weeks or months after birth. A relatively long gestation and period of postnatal maturation allows for prolonged pre- and postnatal interactions with the environment, including experiences such as episodic or chronic hypoxia, hyperoxia, and drug or toxin exposures. Developmental plasticity occurs when such experiences, during critical periods of maturation, result in long-term alterations in the structure or function of the respiratory control neural network. A critical period is a time window during development devoted to structural and/or functional shaping of the neural systems subserving respiratory control. Experience during the critical period can disrupt and alter developmental trajectory, whereas the same experience before or after has little or no effect. One of the clearest examples to date is blunting of the adult ventilatory response to acute hypoxia challenge by early postnatal hyperoxia exposure in the newborn. Developmental plasticity in neural respiratory control development can occur at multiple sites during formation of brain stem neuronal networks and chemoafferent pathways, at multiple times during development, by multiple mechanisms. Past concepts of respiratory control system maturation as rigidly predetermined by a genetic blueprint have now yielded to a different view in which extremely complex interactions between genes, transcriptional factors, growth factors, and other gene products shape the respiratory control system, and experience plays a key role in guiding normal respiratory control development. Early-life experiences may also lead to maladaptive changes in respiratory control. Pathological conditions as well as normal phenotypic diversity in mature respiratory control may have their roots, at least in part, in developmental plasticity.

Aging↗
PubMed2003

Differential changes in dopamine D2- and D1-receptor mRNA levels induced by hypoxia in the arterial chemoreflex pathway organs in one-day-old and adult rabbits.

This study determined: (1) whether dopamine (DA) D2-receptor (R) and D1-R mRNA levels in the carotid body (CB), petrosal ganglion (PG) and superior cervical ganglion (SCG) are modulated by hypoxia; (2) the role of hypoxia intensity and exposure duration, and (3) whether the pattern of modulation differs between newborn (1-day-old) and adult rabbits. Rabbits were exposed to five FiO2 conditions: 21% (control); 15%/6 h; 15%/24 h; 8%/6 h and 8%/24 h. D2- and D1-R mRNA expression levels were calculated for each hypoxia condition relative to control using RT-PCR analysis. In the CB of 1-day-old rabbits, D2- and D1-R transcript levels increased and decreased after exposure to 15 and 8% O2, respectively. In the adult CB, D2- and D1-R transcript levels decreased independently of hypoxia intensities. Only changes in D1-R mRNA levels were dependent on exposure time. In the PG, both hypoxia intensities decreased the D2-R transcript levels in 1-day-old and adult rabbits; but for the D1-R mRNA levels, hypoxia decreased its level in 1-day-old rabbits and increased it in adults regardless of exposure duration. In the SCG, hypoxia had no determinant effect on the D2-R mRNA levels either in newborn or adult rabbits while it induced a decrease of D1-R transcript levels in 1-day-old rabbits and an increase in adult rabbits. It is concluded that hypoxia affects DA D2- or D1-R mRNA levels in the chemoreflex pathway in an age-dependent and site-specific manner.

Aging↗