Efficacy of vacuum erectile devices (VEDs) after radical prostatectomy: the initial Irish experience of a dedicated VED clinic.

Controversy exists regarding optimal penile rehabilitation program following radical prostatectomy (RP). Vacuum erectile devices (VEDs) have become an important component of penile rehabilitation protocols. The aim of this study was to assess the efficacy and patient satisfaction of a dedicated VED clinic. A voluntary telephone questionnaire was performed of all patients who attended a VED clinic to date in two university teaching hospitals. Patient demographics, histopathological characteristics and functional status (International Index of Erectile Function (IIEF) scores) were obtained from a retrospective review of a prospectively maintained database. Sixty-five men attended the dedicated VED clinic in the two university teaching hospitals. Forty-men (76.3%) men purchased a VED following the dedicated clinic. There was significant differences noted between the mean preoperative and the 3-month postoperative IIEF scores (22.08±3.16 vs 11.3±3.08, P=0.0001) and between the 3-month postoperative IIEF score and the post-VED use IIEF score (11.3±3.08 vs 16.74±2.62, P=0.0001). Despite VED use, there was a significant reduction in erectile function from presurgery status (22.08±3.16 vs 16.74±2.62, P=0.0001). All patients reported that the dedicated VED was helpful and would recommend it to other patients. Our study demonstrates that, despite a reduction in erectile function after RP, successful erections are attainable with a VED. There is potential and need for the development of a standard penile rehabilitation program and treatment of ED after RP internationally.

Phenotypic resolution of spontaneous and D1-like agonist-induced orofacial movement topographies in congenic dopamine D1A receptor 'knockout' mice.

A novel system was used to assess the role of D(1)-like dopamine receptors in distinct topographies of orofacial movements in mice with congenic D(1A) receptor knockout. Under spontaneous conditions, vertical jaw movements in wild-types declined with time at a rate that was reduced in D(1A) mutants, while horizontal jaw movements emerged progressively in wild-types but not in D(1A) mutants; tongue protrusions were absent in D(1A) mutants, while incisor chattering was initially reduced in D(1A) mutants but rose subsequently to reach the level of wild-types. D(1A) receptors exert a topographically specific role in regulating individual spontaneous orofacial movements, and these involve interactions with psychomotor processes which 'sculpt' behavioural change over time. The anomalous D(1)-like agonist SK&F 83959, which fails to stimulate, and indeed inhibits the stimulation of adenylyl cyclase induced by dopamine, readily stimulated vertical jaw movements, tongue protrusions and incisor chattering, and these response topographies were absent in D(1A) mutants. These results suggest that D(1A) receptors may exert some form of permissive role over orofacial topographies initiated via a novel, putative D(1)-like site not linked to adenylyl cyclase, or that some D(1A) receptors might be coupled to a transduction system other than adenylyl cyclase.

Treatment of obstructive sleep apnea syndrome in children.

Obstructive sleep apnea (OSA) has been identified and recorded in paediatric patients, the potential mechanisms for OSA include anatomical abnormalities that lead to a narrowed airway space, reduced muscle tone and abnormal central ventilatory control. Several treatments have been developed and are routinely used to treat OSA in infants and children. Nasal mask continuous positive airway pressure (CPAP) is an effective non-invasive treatment that prevents the majority of obstructive events, reverses sleep disturbances, improves daytime performance and is associated with increased growth in patients with failure to thrive. Surgery to correct underlying anatomical abnormalities is frequently used and usually results in an improvement in symptoms and in some cases, it is curative. Other forms of treatment include pharmacological interventions, positioning and nasopharyngeal intubation.

Sleep-disordered breathing and its effects on sleep in infants.

Sleep apnea has been recorded in many infants, but little data exist concerning the amount and range of apnea in infants. We studied 49 infants referred to the sleep disorders unit. Single polysomnographic studies were performed on each infant. We examined the amount of apnea, presence and amount of upper airway obstruction and the sleeping pattern in each infant. Central apnea was common to all infants and varied in amount. Upper airway obstruction, recorded as mixed apnea, was found in 36 infants. Twenty of these infants had only occasional mixed apnea ( < 2 apneas/hour), whereas 16 infants displayed a higher amount of obstruction. All infants were separated into two groups according to amount of apnea and obstruction. Sixteen infants with obstruction plus 3 infants with a high amount of central apnea represented group I. The remaining 30 infants represented group II. Marked differences in the sleeping pattern were found when the groups of infants were separated. Infants from group I had significantly less rapid eye movement (REM) sleep than infants from group II. We conclude that sleep-disordered breathing in infants is associated with disruptions in sleep.

Habituation of the infant arousal response.

STUDY OBJECTIVES: Arousal is considered to be an important protective response in a sleeping infant and its depression could leave an infant vulnerable to a life threatening stimulus. We found previously that arousal to a non-respiratory (tactile) stimulus occurs in a sequence of events that begins with spinal, followed by brainstem responses, and then a cortical electroencephalographic (EEG) arousal response. We hypothesized that repeated stimuli would depress the arousal responses by habituation and that spinal and brainstem responses would be more resistant to habituation than cortical responses. PARTICIPANTS: We studied 22 normal infants. INTERVENTIONS: The infants underwent polysomnographic monitoring during a daytime nap. Tactile stimuli was applied to the infants foot at 5-second intervals. MEASUREMENTS AND RESULTS: We found that spinal, brainstem, and cortical responses occurred on the first trial of each test. Repeated trials during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep resulted in a decrease in the incidence of each individual response and eventually elimination of the arousal responses. Cortical responses were eliminated first, followed by brainstem responses and finally spinal responses. The elimination of each of the responses occurred more rapidly during REM sleep that during NREM sleep. CONCLUSIONS: Habituation of the infant arousal sequence occurs with repeated tactile stimulation. There is a serial habituation of responses from the cortical to the spinal level, which occurs more rapidly during REM sleep. Rapid habituation to innocuous stimuli is probably beneficial in avoiding detrimental sleep disruptions. However, in situations requiring the protective functions of arousal, such habituation could be detrimental to an infant.

Obstructive sleep apnea in infants and its management with nasal continuous positive airway pressure.

STUDY OBJECTIVES: Nasal continuous positive airway pressure (nCPAP) is the most common treatment for obstructive sleep apnea (OSA) in adults, and it has been effective in the treatment of OSA in children. We wanted to determine the effectiveness of long-term nCPAP therapy for OSA in infants. PATIENTS: Twenty-four infants who had OSA were treated with nCPAP via nose mask. These infants had clinical histories that included a family history of sudden infant death syndrome, an apparent life-threatening event, or facial and upper airway anatomic abnormalities. INTERVENTIONS: Overnight polysomnographic studies were performed to assess the severity of OSA in each infant and to determine the appropriate level of continuous positive airway pressure (CPAP). Studies were repeated to determine the progress of OSA and the continuing need for CPAP in each infant. RESULTS: nCPAP pressures between 4 and 6 cm H2O prevented obstruction and reversed sleep disturbances that were associated with OSA. Eighteen of the infants continued treatment at home from 1 month to > 4 years. CPAP therapy was discontinued in 13 infants after their OSA resolved. Five infants who have upper airway anatomic abnormalities remain on CPAP, and the pressure level required to prevent obstructive events during sleep has needed to be increased to as high as 10 cm H2O. CONCLUSIONS: nCPAP is an effective therapy for the management of OSA in infants, and it can be used effectively in the home environment. Regular follow-up is necessary, because the requirements for CPAP and pressure levels change with the infant's growth and development.

Effects of nasal CPAP therapy on respiratory and spontaneous arousals in infants with OSA.

Obstructive sleep apnea (OSA) in infants has been shown to resolve frequently without a cortical arousal. It is unknown whether infants do not require arousal to terminate apneas or whether this is a consequence of the OSA. We studied the apnea and arousal patterns of eight infants with OSA before and after treatment with nasal continuous positive airway pressure (CPAP). These infants were age matched to eight untreated infants with OSA and eight normal infants. Polysomnographic studies were performed on each infant. We found that the majority of central and obstructive apneas were terminated without arousal in all OSA infants. After several weeks of nasal CPAP treatment, the proportion of apneas terminating with an arousal during rapid-eye-movement sleep increased in treated infants compared with untreated infants. Spontaneous arousals during rapid-eye-movement sleep were reduced in all OSA infants; however, during CPAP treatment, the spontaneous arousals increased to the normal control level. We conclude that OSA in infants possibly depresses the arousal response and treatment of these infants with nasal CPAP partially reverses this depression.

Arousal pattern following central and obstructive breathing abnormalities in infants and children.

We analyzed the polysomnographic records of 15 children and 20 infants with obstructive sleep apnea (OSA) to examine the interaction between central and obstructive breathing abnormalities and arousal from sleep. Each patient was matched for age with an infant or child who had no OSA. We found that the majority of respiratory events in infants and children was not terminated with arousal. In children, arousals terminated 39.3 +/- 7.2% of respiratory events during quiet sleep and 37.8 +/- 7.2% of events during active (rapid-eye-movement) sleep. In infants, arousals terminated 7.9 +/- 1.0% of events during quiet sleep and 7.9 +/- 1.2% of events during active sleep. In both infants and children, however, respiratory-related arousals occurred more frequently after obstructive apneas and hypopneas than after central events. Spontaneous arousals occurred in all patients with OSA during quiet and active sleep. The frequency of spontaneous arousals was not different between children with OSA and their matched controls. During active sleep, however, infants with OSA had significantly fewer spontaneous arousals than did control infants. We conclude that arousals is not an important mechanism in the termination of respiratory events in infants and children and that electroencephalographic criteria are not essential to determine the clinical severity of OSA in the pediatric population.

Characteristics of the infant arousal response.

Arousal is considered to be an important response to a life-threatening stimulus. Recently, it has been shown that the infant arousal response to an elevated inspired CO2 level occurs as a sequence of events involving presumptive brain stem responses before awakening (A. Lijowska, N. Reed, B. Chiodini, and B. T. Thach. Am. J. Respir. Crit. Care Med. 151: A151, 1995; A. S. Lijowska, N. W. Reed, B. A. Mertins Chiodini, and B. T. Thach. J. Appl. Physiol. 83: 219-228, 1997). We wanted to further evaluate the relationship of subcortical reflexes to cortical arousal in infants. We used a nonrespiratory (tactile) stimulus to elicit arousal in infants during non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. We found that a tactile stimulus elicited an arousal sequence that commenced with a spinal withdrawal reflex, was followed by brain stem responses (respiratory and startle responses), and ended in a cortical arousal. The entire pathway or part of it in the order of spinal to cortical responses could be elicited. REM and NREM responses were similar except for significant differences in the latencies of spinal and subcortical reflexes. These observations suggest that the infant arousal response to a tactile stimulus involves a progression of central nervous system activation from the spinal to cortical levels. The different components of the arousal pathway may be important for an infant to respond appropriately to stimuli during sleep without necessarily disturbing sleep.

Effects of upper airway pressure on abdominal muscle activity in conscious dogs.

We have examined arousal and abdominal muscle electromyogram (EMGabd) responses to upper airway pressure stimuli during physiological sleep in four dogs with permanent side-hole tracheal stomata. The dogs were trained to sleep with a tightly fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep stage was determined by behavioral and electroencephalographic criteria. EMGabd activity was measured using bipolar fine-wire electrodes inserted into the abdominal muscle layers. Static increases or decreases in upper airway pressure (+/- 6 cmH2O), when applied at the snout mask or larynx (upper trachea), caused an immediate decrease in EMGabd on the first two to three breaths; EMGabd usually returned to control levels within the 1-min test interval. In contrast, oscillatory pressure waves at 30 Hz and +/- 3 cmH2O amplitude (or -2 to -8 cmH2O amplitude) produced an immediate and sustained reduction in IMGabd in all sleep states. Inhibition of EMGabd could be maintained over many minutes when the oscillatory pressure stimulus was pulsed by using a cycle of 0.5 s on and 0.5 s off. Oscillatory upper airway pressures were also found to be powerful arousal-promoting stimuli, producing arousal in 94% of tests in drowsiness and 66% of tests in slowwave sleep. The results demonstrate the presence of breath-by-breath upper airway control of abdominal muscle activity.

Topographical assessment and pharmacological characterization of orofacial movements in mice: dopamine D(1)-like vs. D(2)-like receptor regulation.

A novel procedure for the assessment of orofacial movement topographies in mice was used to study, for the first time, the individual and interactive involvement of dopamine D(1)-like vs. D(2)-like receptors in their regulation. The dopamine D(1)-like receptor agonists A 68930 ([1R,3S]-1-aminomethyl-5,6-dihydroxy-3-phenyl-isochroman) and SK&F 83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine) each induced vertical jaw movements with tongue protrusions and incisor chattering. The dopamine D(1)-like receptor antagonists SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) and BW 737C ([S]-6-chloro-1-[2,5-dimethoxy-4-propylbenzyl]-7-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) antagonised these responses, while the dopamine D(2)-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide) attenuated those to SK&F 83959 and released horizontal jaw movements. These findings suggest some role for a dopamine D(1)-like receptor that is coupled to a transduction system other than/additional to adenylyl cyclase, and for dopamine D(1)-like:D(2)-like receptor interactions, in the regulation of individual orofacial movement topographies in the mouse. This methodology will allow the use of knockout mice to clarify the roles of individual dopamine receptor subtypes in their regulation.

The psychopharmacology-molecular biology interface: exploring the behavioural roles of dopamine receptor subtypes using targeted gene deletion ('knockout').

In the absence of selective agonists and antagonists able to discriminate between individual members of the D1-like and D2-like families of dopamine receptor subtypes, functional parcellation has remained problematic. 'Knockout' of these subtypes by targeted gene deletion offers a new approach to evaluating their roles in the regulation of behaviour. Like any new technique, 'knockout' has associated with it a number of methodological limitations that are now being addressed in a systematic manner. Studies on the phenotype of D1(A/1), D(1B/5), D2, D3 and D4 'knockouts' at the level of spontaneous and agonist/antagonist-induced behaviour are reviewed, in terms of methodological issues, neuronal implications and potential clinical relevance. Dopamine receptor subtype 'knockout' is a nascent technology that is now beginning to fulfil its potential. It is being complemented by more systematic phenotypic characterisation at the level of behaviour and additional, molecular biologically-based approaches.

Mice lacking the alpha4 nicotinic receptor subunit fail to modulate dopaminergic neuronal arbors and possess impaired dopamine transporter function.

Neuronal nicotinic acetylcholine receptors (nAChRs) at presynaptic sites can modulate dopaminergic synaptic transmission by regulating dopamine (DA) release and uptake. Dopaminergic transmission in nigrostriatal and mesolimbic pathways is vital for the coordination of movement and is associated with learning and behavioral reinforcement. We reported recently that the D2 DA receptor plays a central role in regulating the arbor size of substantia nigra dopaminergic neurons. Given the known effects of nAChRs on dopaminergic neurotransmission, we assessed the ability of the alpha4 nAChR subunit to regulate arbor size of dopaminergic neurons by comparing responses of wild-type and alpha4 nAChR subunit knockout [alpha4(-/-)] mice to long-term exposure to cocaine, amphetamine, nicotine, and haloperidol, and after substantia nigra neurotoxic lesioning. We found that dopaminergic neurons in adult drug-naive alpha4(-/-) mice had significantly larger terminal arbors, and despite normal short-term behavioral responses to drugs acting on pre- and postsynaptic D2 DA receptors, they were unable to modulate their terminal arbor in response to pharmacological manipulation or after lesioning. In addition, although synaptosome DA uptake studies showed that the interaction of the D2 DA receptor and the dopamine transporter (DAT) was preserved in alpha4(-/-) mice, DAT function was found to be impaired. These findings suggest that the alpha4 subunit of the nAChR is an independent regulator of terminal arbor size of nigrostriatal dopaminergic neurons and that reduced functionality of presynaptic DAT may contribute to this effect by impairing DA uptake.

Evolution of sleep-disordered breathing and sleep in infants.

OBJECTIVE: The evolution of sleep-disordered breathing and sleeping patterns in a group of high-risk infants was studied throughout the first year of life. METHODOLOGY: Eleven infants with documented sleep apnoea underwent overnight polysomnographic studies at monthly intervals to 6 months, then at 9 and 12 months of age. RESULTS: All infants had central apnoea and obstructive events recorded on their initial sleep studies. The sleep-disordered breathing in these infants was associated with disturbed sleeping patterns. The amount of rapid eye movement (REM) sleep recorded in each study was inversely proportional to the amount of apnoea. The amount of apnoea and sleep disturbances were highest at 2 months of age and then progressively improved and obstructive events resolved by 1 year of age. CONCLUSIONS: The respiratory abnormalities and sleep disturbances peaked in severity at the age reported to have the highest incidence of sudden infant death syndrome (SIDS) and may have implications for its aetiology.

Obstructive sleep apnea in infants: relation to family history of sudden infant death syndrome, apparent life-threatening events, and obstructive sleep apnea.

OBJECTIVES: Familial aggregation of obstructive sleep apnea (OSA) has been shown to be associated with sudden infant death syndrome (SIDS) and apparent life-threatening events (ALTE) in infants. We wanted to determine the incidence of OSA in infants with siblings with ALTE and SIDS referred to our sleep clinic and to ascertain whether OSA was more common in infants who have family histories of SIDS, ALTE, and OSA. STUDY DESIGN: We studied 125 infants (mean age, 11.5 +/- 0.6 weeks) who were separated into 2 groups on the basis of their family history; polysomnographic studies were performed on each infant. RESULTS: Twenty infants had a multiple family history of SIDS, ALTE, or OSA (group 1), whereas the other 105 infants (group 2) had only one case of SIDS or ALTE within the family and no known history of OSA. We found that 19 of 20 infants in group 1 had OSA, whereas only 31 of 105 infants in group 2 had OSA (chi-squared analysis, P <.05). The OSA recorded was more frequent in infants of group 1 than in those of group 2. Follow-up studies in some infants with OSA demonstrated a progressive decrease in OSA, which resolved between 6 and 12 months of age. CONCLUSION: We conclude that infants of families with multiple histories of SIDS, ALTE, and OSA are more likely to have OSA than infants of families with only one case of SIDS or ALTE.

Effects of nasal continuous positive airway pressure on apnoea index and sleep in infants.

OBJECTIVE: We examined the effectiveness of nasal continuous positive airway pressure (CPAP) for treatment of sleep apnoea in infants. METHODOLOGY: We studied five infants who all had significant central and mixed apnoea and severe sleep fragmentation. Polysomnographic recordings were performed on 2 consecutive nights in these infants. One night was used as a control study and during the second night nasal CPAP was applied throughout the night. RESULTS: Nasal CPAP significantly reduced apnoea in each infant, with the apnoea index (apnoeas/h) decreasing from 65.6 +/- 14.6 during the control study to 10.5 +/- 14.6 during CPAP in non-rapid eye movement (non-REM) sleep, and from 106 +/- 13.9 during the control study to 26.6 +/- 13.9 during CPAP in REM sleep. Nasal CPAP also improved the sleep fragmentation markedly; REM sleep increased from 14.2 +/- 1.2% of sleep during the control study to 27.1 +/- 1.2% of sleep during CPAP. CONCLUSIONS: We conclude that nasal CPAP is an effective treatment for infantile apnoea. Sleep apnoea in these infants is associated with profound sleep fragmentation, which is reversed by nasal CPAP.

Suppression of sigma spindle electroencephalographic activity as a measure of transient arousal after spontaneous and occlusion-evoked sighs and startles.

Defective arousal mechanisms are viewed as contributory to sleep hypopnea disorders and sudden infant death syndrome. Sighs (i.e. augmented breaths) as well as startles have not traditionally been viewed as arousal-related phenomena in infants. We hypothesized that, if sighs and startles are the initial event in a sequential arousal process, then they might be associated with specific EEG activity changes, because activation of the arousal-related ascending reticular activating system can suppress thalamus-generated sigma spindle oscillations. We studied spontaneous sighs and startles and those elicited by briefly occluding the infants face mask airway in 12 normal infants (age 10-19 wk) during non-rapid eye movement sleep. We recorded EEG (C3-P3), ECG, O2 saturation, diaphragmatic electromyography, limb electromyography, and video of the infant. The startle intensity was scored on a scale of 0 to 3 based on video recorded movements. Sleep spindle periodicity was analyzed by using a threshold over a compressed spectral band array. Spontaneous sighs and sleep startles were immediately followed by an interspindle interval prolongation from (mean +/- SEM) 8.0 +/- 0.16 s (control period) to 17.9 +/- 1.45 s after spontaneous sighs, to 23.8 +/- 1.26 s after spontaneous sighs accompanied by startles and to 26.5 +/- 1.45 s after occlusion-related sighs and startles. Furthermore, the intensity of occlusion-evoked startles was positively correlated with the interspindle interval prolongation (p < 0.01). We conclude that spontaneous as well as evoked sighs and startles are immediately followed by a transient sleep spindle suppression. This phenomenon indicates a close linkage between sighs, startles, and reticular formation-related arousal mechanisms.