27 results on '"Nolan, Philip"'
Search Results
2. Pericardial Tuberculosis in a Non-endemic Region Presenting as a Persistent Upper Respiratory Tract Infection With Negative Serology, Bronchial Washings, and Pleural Aspirate.
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Nolan P, Samad S, and Kiernan T
- Abstract
This paper reports on the unlikely case of a 68-year-old man presenting with a non-resolving, mild lower respiratory tract infection, subsequently diagnosed with pericardial tuberculosis (TB) in the absence of TB risk factors and with negative TB serology. Pericardial and pleural effusions were found incidentally on CT pulmonary angiogram, with a small pericardial effusion without tamponade seen on the echocardiogram. During his three-month inpatient stay, the patient was rarely very unwell, though no treatment led to clinical and biochemical resolution of symptoms. Later deterioration prompted another echocardiogram, which found a moderate-sized pericardial effusion, septal bounce, and new regional wall motion abnormalities. To avert the impending cardiac tamponade, the patient underwent pericardiectomy, which provided a tissue diagnosis of TB. Pericardial TB is extremely uncommon, especially outside of TB endemic regions, though it is well described. This case is especially noteworthy, as serology, bronchial washings, and pleural aspirate had been negative for TB though a Quantiferon test was positive. The diagnosis was only confirmed after pericardiectomy. The patient was subsequently treated with anti-TB therapy, with a good clinical response. This case highlights diagnostic challenges and strategies for investigating and managing similar complex scenarios, particularly in non-endemic settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Nolan et al.)
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- 2024
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3. Salt restriction for treatment of hypertension - current state and future directions.
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Nolan P and McEvoy JW
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- Adult, Humans, Sodium Chloride, Dietary adverse effects, Antihypertensive Agents therapeutic use, Blood Pressure physiology, Sodium pharmacology, Randomized Controlled Trials as Topic, Hypertension drug therapy, Sodium, Dietary adverse effects, Cardiovascular Diseases drug therapy
- Abstract
Purpose of Review: Given the adverse effects of excess dietary sodium chloride (also known as table salt) on blood pressure (BP) and cardiovascular disease (CVD), restriction of dietary sodium is recommended by numerous guidelines. The strictest of these recommend no more than 1.5 g/day of dietary sodium among hypertensive persons. However, average dietary sodium intake in the population is closer to 5 g/day and there is debate about whether too much sodium restriction may be associated with increased CVD risk. Herein, we aim to provide a balanced update on this topic., Recent Findings: In 2021, the Salt Substitute and Stroke Study (SSaSS) demonstrated a significant reduction in BP, CVD, and death among Chinese adults randomized to a low sodium salt-substitute supplemented with potassium. This trial largely puts to rest any remaining debate about the benefits of dietary sodium restriction among persons with excess baseline intake (dietary sodium intake fell from approximately 5 down to 4 g/day in the active arm of SSaSS). However, whether achieving and maintaining a dietary sodium of less than1.5 g/day is feasible in real-world settings and whether this low an intake is harmful remain open questions., Summary: Aiming for sodium intakes of 2--3 g/day in the general population and as low as 2 g/day in persons with hypertension or CVD seems most reasonable, but there is some uncertainty around lower targets., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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4. Predictors of Conduction Disturbances Requiring New Permanent Pacemaker Implantation following Transcatheter Aortic Valve Implantation Using the Evolut Series.
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Abdelshafy M, Elkoumy A, Elzomor H, Abdelghani M, Campbell R, Kennedy C, Kenny Gibson W, Fezzi S, Nolan P, Wagener M, Arsang-Jang S, Mohamed SK, Mostafa M, Shawky I, MacNeill B, McInerney A, Mylotte D, and Soliman O
- Abstract
(1) Background: Conduction disturbance requiring a new permanent pacemaker (PPM) after transcatheter aortic valve implantation (TAVI) has traditionally been a common complication. New implantation techniques with self-expanding platforms have reportedly reduced the incidence of PPM. We sought to investigate the predictors of PPM at 30 days after TAVI using Evolut R/PRO/PRO+; (2) Methods: Consecutive patients who underwent TAVI with the Evolut platform between October 2019 and August 2022 at University Hospital Galway, Ireland, were included. Patients who had a prior PPM ( n = 10), valve-in-valve procedures ( n = 8) or received >1 valve during the index procedure ( n = 3) were excluded. Baseline clinical, electrocardiographic (ECG), echocardiographic and multislice computed tomography (MSCT) parameters were analyzed. Pre-TAVI MSCT analysis included membranous septum (MS) length, a semi-quantitative calcification analysis of the aortic valve leaflets, left ventricular outflow tract, and mitral annulus. Furthermore, the implantation depth (ID) was measured from the final aortography. Multivariate binary logistic analysis and receiver operating characteristic (ROC) curve analysis were used to identify independent predictors and the optimal MS and ID cutoff values to predict new PPM requirements, respectively; (3) Results: A total of 129 TAVI patients were included (age = 81.3 ± 5.3 years; 36% female; median EuroSCORE II 3.2 [2.0, 5.4]). Fifteen patients (11.6%) required PPM after 30 days. The patients requiring new PPM at 30 days were more likely to have a lower European System for Cardiac Operative Risk Evaluation II, increased prevalence of right bundle branch block (RBBB) at baseline ECG, have a higher mitral annular calcification severity and have a shorter MS on preprocedural MSCT analysis, and have a ID, as shown on the final aortogram. From the multivariate analysis, pre-TAVI RBBB, MS length, and ID were shown to be predictors of new PPM. An MS length of <2.85 mm (AUC = 0.85, 95%CI: (0.77, 0.93)) and ID of >3.99 mm (area under the curve (AUC) = 0.79, (95% confidence interval (CI): (0.68, 0.90)) were found to be the optimal cut-offs for predicting new PPM requirements; (4) Conclusions: Membranous septum length and implantation depth were found to be independent predictors of new PPM post-TAVI with the Evolut platform. Patient-specific implantation depth could be used to mitigate the requirement for new PPM.
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- 2023
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5. Numbers of close contacts of individuals infected with SARS-CoV-2 and their association with government intervention strategies.
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McAloon CG, Wall P, Butler F, Codd M, Gormley E, Walsh C, Duggan J, Murphy TB, Nolan P, Smyth B, O'Brien K, Teljeur C, Green MJ, O'Grady L, Culhane K, Buckley C, Carroll C, Doyle S, Martin J, and More SJ
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- Contact Tracing, Government, Humans, Ireland, COVID-19, SARS-CoV-2
- Abstract
Background: Contact tracing is conducted with the primary purpose of interrupting transmission from individuals who are likely to be infectious to others. Secondary analyses of data on the numbers of close contacts of confirmed cases could also: provide an early signal of increases in contact patterns that might precede larger than expected case numbers; evaluate the impact of government interventions on the number of contacts of confirmed cases; or provide data information on contact rates between age cohorts for the purpose of epidemiological modelling. We analysed data from 140,204 close contacts of 39,861 cases in Ireland from 1st May to 1st December 2020., Results: Negative binomial regression models highlighted greater numbers of contacts within specific population demographics, after correcting for temporal associations. Separate segmented regression models of the number of cases over time and the average number of contacts per case indicated that a breakpoint indicating a rapid decrease in the number of contacts per case in October 2020 preceded a breakpoint indicating a reduction in the number of cases by 11 days., Conclusions: We found that the number of contacts per infected case was overdispersed, the mean varied considerable over time and was temporally associated with government interventions. Analysis of the reported number of contacts per individual in contact tracing data may be a useful early indicator of changes in behaviour in response to, or indeed despite, government restrictions. This study provides useful information for triangulating assumptions regarding the contact mixing rates between different age cohorts for epidemiological modelling., (© 2021. The Author(s).)
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- 2021
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6. Estimation of the serial interval and proportion of pre-symptomatic transmission events of COVID- 19 in Ireland using contact tracing data.
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McAloon CG, Wall P, Griffin J, Casey M, Barber A, Codd M, Gormley E, Butler F, McV Messam LL, Walsh C, Teljeur C, Smyth B, Nolan P, Green MJ, O'Grady L, Culhane K, Buckley C, Carroll C, Doyle S, Martin J, and More SJ
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- Aged, Humans, Ireland epidemiology, SARS-CoV-2, Time Factors, COVID-19, Contact Tracing
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Background: The serial interval is the period of time between the onset of symptoms in an infector and an infectee and is an important parameter which can impact on the estimation of the reproduction number. Whilst several parameters influencing infection transmission are expected to be consistent across populations, the serial interval can vary across and within populations over time. Therefore, local estimates are preferable for use in epidemiological models developed at a regional level. We used data collected as part of the national contact tracing process in Ireland to estimate the serial interval of SARS-CoV-2 infection in the Irish population, and to estimate the proportion of transmission events that occurred prior to the onset of symptoms., Results: After data cleaning, the final dataset consisted of 471 infected close contacts from 471 primary cases. The median serial interval was 4 days, mean serial interval was 4.0 (95% confidence intervals 3.7, 4.3) days, whilst the 25th and 75th percentiles were 2 and 6 days respectively. We found that intervals were lower when the primary or secondary case were in the older age cohort (greater than 64 years). Simulating from an incubation period distribution from international literature, we estimated that 67% of transmission events had greater than 50% probability of occurring prior to the onset of symptoms in the infector., Conclusions: Whilst our analysis was based on a large sample size, data were collected for the primary purpose of interrupting transmission chains. Similar to other studies estimating the serial interval, our analysis is restricted to transmission pairs where the infector is known with some degree of certainty. Such pairs may represent more intense contacts with infected individuals than might occur in the overall population. It is therefore possible that our analysis is biased towards shorter serial intervals than the overall population.
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- 2021
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7. Treatment-resistant priapism associated with long-term low-molecular-weight heparin.
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Bouchier-Hayes D, Nolan P, and Pate G
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- Heparin, Low-Molecular-Weight adverse effects, Humans, Male, Middle Aged, Penis, Phenylephrine, Tinzaparin, Penile Prosthesis, Priapism chemically induced
- Abstract
This case report summarises the case of a 56-year-old man with low-flow, ischaemic priapism requiring urgent insertion of a penile prosthesis following prophylactic anticoagulation with tinzaparin. Low-molecular-weight heparin (LMWH) has been proposed as a cause of ischaemic priapism, although reported cases of this are rare. This particular side effect of tinzaparin has been reported once in a case report in 2018, and there are scant other reports of LMWH-induced priapism. This case was refractory to the full treatment algorithm, including multiple aspirations, phenylephrine injection, cavernosal shunt and required transfer for implantation of a penile prosthesis. Only one other case of such a severe case of priapism has been documented, involving LMWH and warfarin. Documented evidence of possible causes of priapism are vital, given the rarity of this condition, the frequency of LMWH and the potentially devastating complications., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2021
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8. Changes in the harmonic components of the flicker electroretinogram during light adaptation.
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McAnany JJ and Nolan PR
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- Adult, Electroretinography, Female, Fourier Analysis, Humans, Male, Middle Aged, Young Adult, Adaptation, Ocular physiology, Light, Retina physiology
- Abstract
Purpose: To evaluate the nature and extent of changes in the fundamental and harmonic components of the 31-Hz flicker electroretinogram (ERG) during light adaptation., Methods: Full-field ERGs were recorded from five visually normal subjects (ages 21-60 years). Following 30 min of dark adaptation, the subjects were exposed to a uniform adapting field of 50 cd/m(2). The field, which was presented for approximately 15 min, was intermittently modulated sinusoidally at 31.25 Hz. The ERG was recorded during the sinusoidal modulation, and Fourier analysis was used to obtain the amplitude and phase of the fundamental (F), second (2F), and third (3F) harmonic response components., Results: F amplitude increased by almost a factor of two over approximately 6 min (time constant, τ, of 3.0 min). The 2F amplitude increased by a smaller amount, a factor of 1.4, and the time-course was approximately eight times faster than that of F (τ = 0.4 min). The 3F amplitude increased by a factor of 4.6, an increase that was larger than F or 2F, with a time-course that was between that of F and 2F (τ = 1.4 min). F phase was unaffected by light adaptation, whereas the 2F and 3F phases both increased by approximately 45° over similar time-courses (τ = 2.0 min)., Conclusions: Light adaptation had different effects on the fundamental, second, and third harmonic components of the 31-Hz flicker ERG, which resulted in a change in waveform shape during light adaptation. The previously reported flicker ERG amplitude growth is driven primarily, but not entirely, by changes in the fundamental.
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- 2014
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9. Long-term facilitation of upper airway muscle activity induced by episodic upper airway negative pressure and hypoxia in spontaneously breathing anaesthetized rats.
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Ryan S and Nolan P
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- Animals, Diaphragm physiopathology, Electromyography, Homeostasis, Humans, Male, Muscle Contraction physiology, Pressure, Rats, Rats, Wistar, Sleep Apnea, Obstructive physiopathology, Time Factors, Tongue physiopathology, Hypoxia physiopathology, Respiratory Mechanics physiology, Respiratory Muscles physiopathology
- Abstract
Obstruction of the upper airway (UA) is associated with episodes of hypoxia and upper airway negative pressure (UANP). In the companion paper it is shown that episodic hypoxia elicits long-term facilitation (LTF) of tongue protrudor, retractor and respiratory pump muscle activity. However, whether repeated exposure to UANP also induces LTF is unknown. We hypothesized that repetitive exposure to UANP would induce LTF of UA and respiratory pump muscle activity and when coupled with hypoxia, as occurs when the UA obstructs, would lead to an even greater facilitation of muscle activity and the response to UANP. Experiments were performed in 24 anaesthetized, spontaneously breathing rats with intact vagi. To induce LTF, UANP stimuli (-10 cmH(2)O) of 5 s duration were delivered every 30 s for 3 min (+/- hypoxia). This was repeated eight times over 1 h, each 3 min episode separated by 5 min of normoxia. Genioglossus (GG), hyoglossus (HG) and diaphragm (Dia) muscle activity was recorded before, during and for 1 h following the last exposure to episodic UANP alone (n = 8), UANP and hypoxia together (n = 8) or normoxia alone (n = 8). During the final hour, single pulses of UANP were applied at 1 min and every 10 min thereafter to determine whether LTF of the response to UANP had been induced. Our results show that LTF of GG muscle activity and its response to UANP was induced following exposure to episodic UANP stimuli alone and UANP applied during hypoxia. However, there was no significant difference between these responses. Episodic UANP alone also induced LTF of HG muscle activity but this effect did not manifest until 40 min following the last episode of repeated UANP stimulation. In the presence of hypoxia, no LTF of HG muscle response to UANP was found. In conclusion, episodic UANP stimulation induces LTF of UA dilator and retractor tongue muscles, but no further facilitation occurs when coupled with hypoxia. This response may serve as an important protective mechanism of respiratory homeostasis during sleep, particularly in patients who suffer from obstructive sleep apnoea.
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- 2009
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10. Episodic hypoxia induces long-term facilitation of upper airway muscle activity in spontaneously breathing anaesthetized rats.
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Ryan S and Nolan P
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- Animals, Diaphragm physiopathology, Electromyography, Male, Muscle Contraction physiology, Rats, Rats, Wistar, Respiratory Mechanics physiology, Time Factors, Vagus Nerve physiopathology, Hypoxia physiopathology, Respiratory Muscles physiopathology
- Abstract
We performed these experiments to determine if repeated exposure to episodic hypoxia induces long term facilitation (LTF) in anaesthetized spontaneously breathing rats. A previous study in spontaneously breathing rats was unable to demonstrate evidence of LTF with repeated hypoxia, but this may have been due to the low number of hypoxic episodes used. We hypothesized that with sufficient exposure, episodic hypoxia LTF of genioglossus (GG), hyoglossus (HG) and diaphragm (Dia) activities would be elicited. Experiments were performed in 24 anaesthetized spontaneously breathing rats with intact vagi. Peak and tonic GG, HG and Dia EMG activities were recorded before, during and for 1 h following exposure to eight (n = 8) or three (n = 8) episodes of isocapnic hypoxia ( = 0.1) each of 3 min duration. A third time control series was also performed with exposure to normoxia alone ( = 0.28, n = 8). Short-term potentiation of GG and HG muscle activity developed during the early period after repeated exposure to eight and three hypoxic episodes. LTF, however, occurred only after eight hypoxic episodes. This manifested as an increase in peak GG and Dia inspiratory muscle activity and tonic HG activity. LTF of respiratory breathing frequency was also induced, reflected by a reduction in inspiratory and expiratory time. These findings support our initial hypothesis that LTF in the anaesthetized, spontaneously breathing rat is dependent on the number of exposures to hypoxia and show that the responses to repetitive hypoxia are composed of both short and long-term facilitatory changes.
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- 2009
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11. Electrocardiogram recording as a screening tool for sleep disordered breathing.
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Heneghan C, de Chazal P, Ryan S, Chua CP, Doherty L, Boyle P, Nolan P, and McNicholas WT
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- Adult, Algorithms, Electrocardiography, Ambulatory, Female, Humans, Male, Middle Aged, Polysomnography, Severity of Illness Index, Sleep Apnea, Obstructive diagnosis, Sleep Apnea, Obstructive epidemiology, Electrocardiography, Mass Screening methods, Sleep Apnea Syndromes diagnosis, Sleep Apnea Syndromes epidemiology
- Abstract
Study Objectives: Transient changes in heart rate associated with obstructive apneas have been suggested for screening of sleep disordered breathing (SDB). This study prospectively compares the outcomes of an automated ECG-based SDB screening tool with simultaneous polysomnography., Methods: The previously-developed automated algorithm was applied to a single channel ECG obtained during standard overnight polysomnography (92 subjects) to obtain an apnea-hypopnea index (AHI) estimate. Using AHI thresholds of < 5 and > or =15 to define absence and presence of SDB, respectively, we determined the likelihood ratios of the proposed technique., Results: The automated algorithm achieved positive and negative likelihood ratios of 2.16 and 0.08. Estimated and reference AHI were highly correlated (r = 0.88). Pathologically insignificant arrhythmia in some subjects had no discernible impact on the algorithm., Conclusions: ECG-based assessment provides a simple but limited means of recognizing subjects with obstructive sleep apnea.
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- 2008
12. The human genioglossus response to negative airway pressure: stimulus timing and route of delivery.
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Doherty LS, Cullen JP, Nolan P, and McNicholas WT
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- Adult, Air Pressure, Electric Stimulation, Electrodes, Electromyography, Female, Humans, Male, Respiratory Mechanics physiology, Supine Position physiology, Respiratory Muscles physiology
- Abstract
The genioglossus reflex response to sudden onset pulses of negative airway pressure (NAP) in humans is reported to occur more commonly at end rather than onset of expiration when delivered via a mouthpiece. We examined whether this response was modulated by the route of stimulus delivery throughout the respiratory cycle. The genioglossus surface EMG (GGsEMG) response to NAP delivered randomly throughout the respiratory cycle was measured in a set of experiments: (i) 40 stimuli of NAP at -5, -7.5 and -10 cmH2O applied to eight healthy, awake, supine males via nose-mask; and (ii) 60 stimuli of -7.5 cmH2O NAP applied to 15 subjects via both nose-mask and mouthpiece in random order. Despite similar pressure changes being detected in the epiglottis during both routes of stimulus delivery, far lower pressure changes were measured at the nasal choanae during mouthpiece compared with nose-mask delivery. There were no significant differences between the responses during any phase of respiration, nor when NAP was delivered via nose-mask or mouthpiece. We conclude that the sensitivity of the GGsEMG response to NAP in humans does not vary significantly with phase of respiration or route of breathing.
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- 2008
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13. Improved surface EMG electrode for measuring genioglossus muscle activity.
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O'Connor CM, Lowery MM, Doherty LS, McHugh M, O'Muircheartaigh C, Cullen J, Nolan P, McNicholas WT, and O'Malley MJ
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- Adult, Electric Impedance, Equipment Design, Humans, Male, Muscle Contraction physiology, Silver, Silver Compounds, Sleep Apnea, Obstructive diagnosis, Sleep Apnea, Obstructive physiopathology, Electrodes, Electromyography instrumentation, Muscle, Skeletal physiology, Tongue physiology
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Activation of the genioglossus (GG) muscles is necessary to maintain the patency of the upper airway. In the condition of obstructive sleep apnea (OSA) this mechanism fails and the possible role of fatigue in its pathogenesis is still not fully understood. In this paper, a new electrode design for recording the genioglossus surface electromyogram (sEMG) is presented. The new design differs from a widely used GG surface electrode in both electrode configuration (unilateral rather than bilateral) and electrode material (Ag-AgCl rather than stainless steel (SS)). The separate effects of these factors were evaluated during force-varying and fatiguing contractions on normal human subjects and using GG sEMG model simulations. Unilateral sEMG was found to have lower amplitude, lower frequency content and a different rate of change of median frequency during fatiguing contractions. It was shown to overcome several disadvantages posed by the bilateral configuration and be more selective. Ag-AgCl has more favorable impedance characteristics and resulted in greater signal amplitudes. It was concluded that the new design is more suitable for detecting GG sEMG and allows more reliable interpretation of changes in sEMG due to physiological mechanisms, thus providing a new methodology for studying GG function and the role of fatigue in OSA.
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- 2007
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14. Design of surface electrode array for measuring conduction velocity in the human genioglossus muscle.
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O'Connor CM, van der Merwe L, Langran S, O'Sullivan M, Nolan P, Vaughan CL, and O'Malley MJ
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- Adult, Electromyography methods, Equipment Design, Equipment Failure Analysis, Humans, Male, Electrodes, Electromyography instrumentation, Muscle, Skeletal innervation, Muscle, Skeletal physiology, Neural Conduction physiology, Tongue innervation, Tongue physiology
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A new appliance, incorporating linear arrays of pin electrodes for genioglossus (GG) surface electromyography measurement, is presented. This design enables the estimation of GG muscle fiber conduction velocity, which decreases with fatigue. The performance of the device was evaluated for ten healthy human subjects during fatiguing and force varying contractions.
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- 2007
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15. Superior laryngeal and hypoglossal afferents tonically influence upper airway motor excitability in anesthetized rats.
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Ryan S and Nolan P
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- Animals, Male, Pharynx innervation, Rats, Rats, Wistar, Afferent Pathways physiology, Hypoglossal Nerve physiology, Laryngeal Nerves physiology, Larynx physiology, Muscle Contraction physiology, Muscle, Skeletal innervation, Muscle, Skeletal physiology, Pharynx physiology
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Upper airway (UA) muscle activity is stimulated by changes in UA transmural pressure and by asphyxia. These responses are reduced by muscle relaxation. We hypothesized that this is due to a change in afferent feedback in the ansa hypoglossi and/or superior laryngeal nerve (SLN). We examined 1) the glossopharyngeal motor responses to UA transmural pressure and asphyxia and 2) how these responses were changed by muscle relaxation in animals where one or both of these afferent pathways had been sectioned bilaterally. Experiments were performed in 24 anesthetized, thoracotomized, artificially ventilated rats. Baseline glossopharyngeal activity and its response to UA transmural pressure and asphyxia were moderately reduced after bilateral section of the ansa hypoglossi (P < 0.05). Conversely, bilateral SLN section increased baseline glossopharyngeal activity, augmented the response to asphyxia, and abolished the response to UA transmural pressure. Muscle relaxation reduced resting glossopharyngeal activity and the response to asphyxia (P < 0.001). This occurred whether or not the ansa hypoglossi, the SLN, or both afferent pathways had been interrupted. We conclude that ansa hypoglossi afferents tonically excite and SLN afferents tonically inhibit UA motor activity. Muscle relaxation depressed UA motor activity after section of the ansa hypoglossi and SLN. This suggests that some or all of the response to muscle relaxation is mediated by alterations in the activity of afferent fibers other than those in the ansa hypoglossi or SLN.
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- 2005
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16. Effects of topical anesthesia on upper airway resistance during wake-sleep transitions.
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Doherty LS, Nolan P, and McNicholas WT
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- Administration, Topical, Adult, Anesthetics, Local administration & dosage, Female, Humans, Male, Sleep drug effects, Wakefulness drug effects, Airway Resistance drug effects, Airway Resistance physiology, Lidocaine administration & dosage, Pharynx drug effects, Pharynx physiology, Sleep physiology, Wakefulness physiology
- Abstract
Deformation of the upper airway (UA) by negative transmural pressure alters the activity of UA mechanoreceptors, causing a reflex increase in UA muscle activity. Topical anesthesia of the UA mucosa, which greatly reduces this reflex response, causes an increase in UA resistance during stage 2 sleep. We hypothesized that topical anesthesia of the UA mucosa would predispose to UA instability at sleep onset and, therefore, examined the effect of UA anesthesia on pharyngeal resistance (Rph) in stage 1 sleep. Eleven normal, healthy volunteers were instrumented to record standard polysomnographic variables, respiratory airflow, and UA pressure at the nasal choanae and the epiglottis. Subjects were permitted to sleep until stable stage 2 sleep was reached and were then awoken. This procedure was repeated three times to obtain reproducible wake-sleep transitions. The UA mucosa was then anesthetized with 10% lidocaine to the oropharynx and laryngopharynx, and the pharyngeal mechanics were studied during the subsequent wake-sleep transition. Three subjects were excluded because of failure to resume sleep postanesthesia. Rph was significantly higher after anesthesia during stage 1 sleep [2.88 +/- 0.77 cmH(2)O.l(-1).s (mean +/- SE)] compared with control (0.95 +/- 0.35 cmH(2)O.l(-1).s; P < 0.05), but there was no difference during wakefulness. Furthermore, there was a significant rise in Rph at wake-to-sleep transitions and a significant fall in Rph at sleep-to-wake transitions after anesthesia (P < 0.05) but not in the control condition. We conclude that sensory receptors in the UA mucosa contribute to the maintenance of UA patency at wake-sleep transition in normal humans.
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- 2005
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17. Simultaneous recording of breathing and respiratory related neuronal activity in the brainstem of conscious rats.
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Martial FP, Dunleavy M, Nolan P, McNicholas WT, O'Regan RG, and Bradford A
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- Action Potentials physiology, Animals, Brain Stem physiology, Electrodes, Plethysmography methods, Rats, Brain Stem cytology, Consciousness physiology, Neurons physiology, Respiration
- Abstract
One aim of integrative neurophysiology is to understand the relationship between neuronal activity and normal evolution of other physiological parameters. In this respect, anaesthetics or paralyzing agents, that have been shown to have a significant effect on several vital physiological processes, can be seen as a real problem for the interpretation of observations. Eletrophysiological recording in awake animals avoids this problem. Recordings in forebrain areas are now used routinely but a number of specific difficulties have limited their application to the medullary areas. In this paper, we describe a preparation that allows us to simultaneously record neuronal activity in the dorsal brainstem and respiratory activity in awake rats, while applying different types of respiratory challenges.
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- 2005
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18. 5-HT at hypoglossal motor nucleus and respiratory control of genioglossus muscle in anesthetized rats.
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Sood S, Liu X, Liu H, Nolan P, and Horner RL
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- Analysis of Variance, Animals, Blood Pressure, Carbon Dioxide pharmacology, Diaphragm drug effects, Diaphragm physiology, Dose-Response Relationship, Drug, Electroencephalography, Electromyography, Hypercapnia parasitology, Hypoglossal Nerve physiology, Male, Medulla Oblongata anatomy & histology, Medulla Oblongata physiology, Mianserin pharmacology, Microdialysis methods, Motor Neurons physiology, Muscle Contraction drug effects, Rats, Rats, Wistar, Serotonin Antagonists pharmacology, Tracheostomy methods, Vagotomy methods, Hypoglossal Nerve drug effects, Medulla Oblongata drug effects, Motor Neurons drug effects, Respiration drug effects, Serotonin pharmacology
- Abstract
Serotonin (5-HT) from medullary raphe neurons excites hypoglossal motoneurons innervating genioglossus (GG) muscle. Since some raphe neurons also show increased activity in hypercapnia, we tested the hypothesis that serotonergic mechanisms at the hypoglossal motor nucleus (HMN) modulate GG activity and responses to CO2. Seventeen urethane-anesthetized, tracheotomized and vagotomized rats were studied. Microdialysis probes were used to deliver mianserin (5-HT receptor antagonist, 0 and 0.1 mM) or 5-HT (eight doses, 0-50 mM) to the HMN during room air or CO2-stimulated breathing. Mianserin decreased respiratory-related GG activity during room air and CO2-stimulated breathing (P<0.001), and also suppressed GG responses to CO2 (P=0.05). In contrast, GG activity was increased by 5-HT at the HMN, and was further increased in hypercapnia (P<0.02). However, 5-HT increased respiratory-related GG activity at levels lower (1 mM) than those eliciting tonic GG activity (10-30 mM 5-HT). The results show that 5-HT at the HMN contributes to the respiratory control of GG muscle.
- Published
- 2003
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19. Role of inhibitory amino acids in control of hypoglossal motor outflow to genioglossus muscle in naturally sleeping rats.
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Morrison JL, Sood S, Liu H, Park E, Liu X, Nolan P, and Horner RL
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- Animals, Carbon Dioxide pharmacology, Electromyography, GABA Antagonists pharmacology, GABA-A Receptor Antagonists, Glycine pharmacology, Glycine Agents pharmacology, Male, Median Eminence drug effects, Median Eminence physiology, Rats, Rats, Wistar, Receptors, Glycine physiology, Serotonin pharmacology, Sleep Stages physiology, Sleep, REM physiology, Strychnine pharmacology, Tongue drug effects, Amino Acids physiology, Hypoglossal Nerve physiology, Motor Neurons physiology, Neural Inhibition physiology, Sleep physiology, Tongue innervation, Tongue physiology
- Abstract
The hypoglossal motor nucleus innervates the genioglossus (GG) muscle of the tongue, a muscle that helps maintain an open airway for effective breathing. Rapid-eye-movement (REM) sleep, however, recruits powerful neural mechanisms that can abolish GG activity even during strong reflex stimulation such as by hypercapnia, effects that can predispose to sleep-related breathing problems in humans. We have developed an animal model to chronically manipulate neurotransmission at the hypoglossal motor nucleus using in vivo microdialysis in freely behaving rats. This study tests the hypothesis that glycine receptor antagonism at the hypoglossal motor nucleus, either alone or in combination with GABAA receptor antagonism, will prevent suppression of GG activity in natural REM sleep during room air and CO2-stimulated breathing. Rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and GG and diaphragm electrodes for respiratory muscle recording. Microdialysis probes were implanted into the hypoglossal motor nucleus for perfusion of artificial cerebrospinal fluid (ACSF) and strychnine (glycine receptor antagonist, 0.1 mM) either alone or combined with bicuculline (GABAA antagonist, 0.1 mM) during room air and CO2-stimulated breathing. Compared to ACSF controls, glycine receptor antagonism at the hypoglossal motor nucleus increased respiratory-related GG activity in room air (P = 0.010) but not hypercapnia (P = 0.221). This stimulating effect of strychnine in room air did not depend on the prevailing sleep-wake state (P = 0.625) indicating removal of a non-specific background inhibitory glycinergic tone. Nevertheless, GG activity remained minimal in those REM sleep periods without phasic twitches in GG muscle, with GG suppression from non-REM (NREM) sleep being > 85 % whether ACSF or strychnine was at the hypoglossal motor nucleus or the inspired gas was room air or 7 % CO2. While GG activity was minimal in these REM sleep periods, there was a small but measurable increase in GG activity after strychnine (P < 0.05). GG activity was also minimal, and effectively abolished, in the REM sleep periods without GG twitches with combined glycine and GABAA receptor antagonism at the hypoglossal motor nucleus. We conclude that these data in freely behaving rats confirm that inhibitory glycine and GABAA receptor mechanisms are present at the hypoglossal motor nucleus and are tonically active, but that such inhibitory mechanisms make only a small contribution to the marked suppression of GG activity and reflex responses observed in periods of natural REM sleep.
- Published
- 2003
- Full Text
- View/download PDF
20. Automated processing of the single-lead electrocardiogram for the detection of obstructive sleep apnoea.
- Author
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de Chazal P, Heneghan C, Sheridan E, Reilly R, Nolan P, and O'Malley M
- Subjects
- Adult, Algorithms, Female, Humans, Male, Middle Aged, Pattern Recognition, Automated, Reference Values, Reproducibility of Results, Sensitivity and Specificity, Signal Processing, Computer-Assisted, Sleep Apnea, Obstructive classification, Diagnosis, Computer-Assisted methods, Electrocardiography methods, Heart Rate, Respiratory Mechanics, Sleep Apnea, Obstructive diagnosis
- Abstract
A method for the automatic processing of the electrocardiogram (ECG) for the detection of obstructive apnoea is presented. The method screens nighttime single-lead ECG recordings for the presence of major sleep apnoea and provides a minute-by-minute analysis of disordered breathing. A large independently validated database of 70 ECG recordings acquired from normal subjects and subjects with obstructive and mixed sleep apnoea, each of approximately eight hours in duration, was used throughout the study. Thirty-five of these recordings were used for training and 35 retained for independent testing. A wide variety of features based on heartbeat intervals and an ECG-derived respiratory signal were considered. Classifiers based on linear and quadratic discriminants were compared. Feature selection and regularization of classifier parameters were used to optimize classifier performance. Results show that the normal recordings could be separated from the apnoea recordings with a 100% success rate and a minute-by-minute classification accuracy of over 90% is achievable.
- Published
- 2003
- Full Text
- View/download PDF
21. Intralaryngeal neuroanatomy of the recurrent laryngeal nerve of the rabbit.
- Author
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Ryan S, McNicholas WT, O'Regan RG, and Nolan P
- Subjects
- Animals, Coloring Agents, Laryngeal Muscles innervation, Rabbits anatomy & histology, Recurrent Laryngeal Nerve anatomy & histology
- Abstract
We undertook this study to determine the detailed neuroanatomy of the terminal branches of the recurrent laryngeal nerve (RLN) in the rabbit to facilitate future neurophysiological recordings from identified branches of this nerve. The whole larynx was isolated post mortem in 17 adult New Zealand White rabbits and prepared using a modified Sihler's technique, which stains axons and renders other tissues transparent so that nerve branches can be seen in whole mount preparations. Of the 34 hemi-laryngeal preparations processed, 28 stained well and these were dissected and used to characterize the neuroanatomy of the RLN. In most cases (23/28) the posterior cricoarytenoid muscle (PCA) was supplied by a single branch arising from the RLN, though in five PCA specimens there were two or three separate branches to the PCA. The interarytenoid muscle (IA) was supplied by two parallel filaments arising from the main trunk of the RLN rostral to the branch(es) to the PCA. The lateral cricoarytenoid muscle (LCA) commonly received innervation from two fine twigs branching from the RLN main trunk and travelling laterally towards the LCA. The remaining fibres of the RLN innervated the thyroarytenoid muscle (TA) and comprised two distinct branches, one supplying the pars vocalis and the other branching extensively to supply the remainder of the TA. No communicating anastomosis between the RLN and superior laryngeal nerve within the larynx was found. Our results suggest it is feasible to make electrophysiological recordings from identified terminal branches of the RLN supplying laryngeal adductor muscles separate from the branch or branches to the PCA. However, the very small size of the motor nerves to the IA and LCA suggests that it would be very difficult to record selectively from the nerve supply to individual laryngeal adductor muscles.
- Published
- 2003
- Full Text
- View/download PDF
22. GABAA receptor antagonism at the hypoglossal motor nucleus increases genioglossus muscle activity in NREM but not REM sleep.
- Author
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Morrison JL, Sood S, Liu H, Park E, Nolan P, and Horner RL
- Subjects
- Animals, Bicuculline pharmacology, Carbon Dioxide pharmacology, Electrodes, Electroencephalography, Electromyography, Fluoresceins, Fluorescent Dyes, Male, Microdialysis, Rats, Rats, Wistar, Serotonin pharmacology, Stereotaxic Techniques, Stimulation, Chemical, GABA Antagonists pharmacology, GABA-A Receptor Antagonists, Hypoglossal Nerve drug effects, Pharyngeal Muscles drug effects, Sleep physiology, Sleep, REM physiology
- Abstract
The pharyngeal muscles, such as the genioglossus (GG) muscle of the tongue, are important for effective lung ventilation since they maintain an open airspace. Rapid-eye-movement (REM) sleep, however, recruits powerful neural mechanisms that can abolish GG activity, even during strong reflex respiratory stimulation by elevated CO2. In vitro studies have demonstrated the presence of GABAA receptors on hypoglossal motoneurons, and these and other data have led to the speculation that GABAA mechanisms may contribute to the suppression of hypoglossal motor outflow to the GG muscle in REM sleep. We have developed an animal model that allows us to chronically manipulate neurotransmission at the hypoglossal motor nucleus using microdialysis across natural sleep-wake states in rats. The present study tests the hypothesis that microdialysis perfusion of the GABAA receptor antagonist bicuculline into the hypoglossal motor nucleus will prevent the suppression of GG muscle activity in REM sleep during both room-air and CO2-stimulated breathing. Ten rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and GG and diaphragm electrodes for respiratory muscle recording. Microdialysis probes were implanted into the hypoglossal motor nucleus for perfusion of artificial cerebrospinal fluid (ACSF) or 100 microM bicuculline during room-air and CO2-stimulated breathing (7 % inspired CO2). GABAA receptor antagonism at the hypoglossal motor nucleus increased respiratory-related GG activity during both room-air (P = 0.01) and CO2-stimulated breathing (P = 0.007), indicating a background inhibitory GABA tone. However, the effects of bicuculline on GG activity depended on the prevailing sleep-wake state (P < 0.005), with bicuculline increasing GG activity in non-REM (NREM) sleep and wakefulness both in room air and hypercapnia (P < 0.01), but GG activity was effectively abolished in those REM periods without phasic twitches in the GG muscle. This abolition of GG activity in REM sleep occurred regardless of ACSF or bicuculline at the hypoglossal motor nucleus, or room-air or CO2-stimulated breathing (P > 0.63). We conclude that these data in freely behaving rats confirm previous in vitro studies that GABAA receptor mechanisms are present at the hypoglossal motor nucleus and are tonically active, but the data also show that GABAA receptor antagonism at the hypoglossal motor nucleus does not increase GG muscle activity in natural REM sleep.
- Published
- 2003
- Full Text
- View/download PDF
23. Upper airway muscle paralysis reduces reflex upper airway motor response to negative transmural pressure in rat.
- Author
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Ryan S, McNicholas WT, O'Regan RG, and Nolan P
- Subjects
- Animals, Asphyxia physiopathology, Electrophysiology, Glossopharyngeal Nerve physiopathology, Hypoglossal Nerve physiopathology, Laryngeal Nerves physiopathology, Male, Neuromuscular Blockade, Pressure, Rats, Rats, Sprague-Dawley, Time Factors, Paralysis physiopathology, Reflex, Respiratory Muscles
- Abstract
The reflex upper airway (UA) motor response to UA negative pressure (UANP) is attenuated by neuromuscular blockade. We hypothesized that this is due to a reduction in the sensitivity of laryngeal mechanoreceptors to changes in UA pressure. We examined the effect of neuromuscular blockade on hypoglossal motor responses to UANP and to asphyxia in 15 anesthetized, thoracotomized, artificially ventilated rats. The activity of laryngeal mechanoreceptors is influenced by contractions of laryngeal and tongue muscles, so we studied the effect of selective denervation of these muscle groups on the UA motor response to UANP and to asphyxia, recording from the pharyngeal branch of the glossopharyngeal nerve (n = 11). We also examined the effect of tongue and laryngeal muscle denervation on superior laryngeal nerve (SLN) afferent activity at different airway transmural pressures (n = 6). Neuromuscular blockade and denervation of laryngeal and tongue muscles significantly reduced baseline UA motor nerve activity (P < 0.05), caused a small but significant attenuation of the motor response to asphyxia, and markedly attenuated the response to UANP. Motor denervation of tongue and laryngeal muscles significantly decreased SLN afferent activity and altered the response to UANP. We conclude that skeletal muscle relaxation reduces the reflex UA motor response to UANP, and this may be due to a reduction in the excitability of UA motor systems as well as a decrease of the response of SLN afferents to UANP.
- Published
- 2003
- Full Text
- View/download PDF
24. Glycine at hypoglossal motor nucleus: genioglossus activity, CO(2) responses, and the additive effects of GABA.
- Author
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Morrison JL, Sood S, Liu X, Liu H, Park E, Nolan P, and Horner RL
- Subjects
- Animals, Carbon Dioxide pharmacology, Drug Synergism, Electromyography, Glycine antagonists & inhibitors, Glycine Agents pharmacology, Male, Muscles drug effects, Muscles physiology, Rats, Rats, Wistar, Receptors, GABA-A metabolism, Strychnine pharmacology, Tongue drug effects, gamma-Aminobutyric Acid pharmacology, Glycine metabolism, Hypoglossal Nerve physiology, Medulla Oblongata physiology, Tongue physiology
- Abstract
There is evidence for glycine and GABA(A)-receptor-mediated inhibition of hypoglossal motoneurons in vitro. However, comparable studies have not been performed in vivo, and the interactions of such mechanisms with integrative reflex respiratory control have also not been determined. This study tests the hypotheses that glycine at the hypoglossal motor nucleus (HMN) will suppress genioglossus (GG) muscle activity, even in the presence of hypercapnic respiratory stimulation, and the effects of glycine will be blocked by strychnine. We also determined whether coapplication of glycine and muscimol (GABA(A)- receptor agonist) to the HMN is additive in suppressing GG activity. Twenty-four urethane-anesthetized, tracheotomized, and vagotomized rats were studied. Diaphragm and GG activities, the electroencephalogram, and blood pressure were recorded. Microdialysis probes were implanted into the HMN for delivery of artificial cerebrospinal fluid (control), glycine (0.0001-10 mM), or muscimol (0.1 microM). Increasing glycine at the HMN produced graded suppression of GG activity (P < 0.001), although the GG still responded to stimulation with 7% inspired CO(2) (P = 0.002). Strychnine (0.1 mM) reversed the glycine-mediated suppression of GG activity, whereas combined glycine and muscimol were additive in GG muscle suppression. It remains to be determined whether the recruitment of such glycine and GABA mechanisms explains the periods of major GG suppression in behaviors such as rapid eye movement sleep.
- Published
- 2002
- Full Text
- View/download PDF
25. Effects of sleep-wake state on the genioglossus vs.diaphragm muscle response to CO(2) in rats.
- Author
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Horner RL, Liu X, Gill H, Nolan P, Liu H, and Sood S
- Subjects
- Animals, Electroencephalography, Male, Neck Muscles physiology, Rats, Rats, Wistar, Respiration, Sleep, REM drug effects, Vagus Nerve physiology, Carbon Dioxide pharmacology, Diaphragm drug effects, Respiratory Muscles drug effects, Sleep physiology, Tongue drug effects, Wakefulness physiology
- Abstract
The effects of sleep on the ventilatory responses to hypercapnia have been well described in animals and in humans. In contrast, there is little information for genioglossus (GG) responses to a range of CO(2) stimuli across all sleep-wake states. Given the notion that sleep, especially rapid eye movement (REM) sleep, may cause greater suppression of muscles with both respiratory and nonrespiratory functions, this study tests the hypothesis that GG activity will be differentially affected by sleep-wake states with major suppression in REM sleep despite excitation by CO(2). Seven rats were chronically implanted with electroencephalogram, neck, GG, and diaphragm electrodes, and responses to 0, 1, 3, 5, 7, and 9% CO(2) were recorded. Diaphragm activity and respiratory rate increased with CO(2) (P < 0.001) across sleep-wake states with significant increases at 3-5% CO(2) compared with 0% CO(2) controls (P < 0.05). Phasic GG activity also increased in hypercapnia but required higher CO(2) (7-9%) for significant activation (P < 0.05). Further studies in 15 urethane-anesthetized rats with the vagi intact (n = 6) and cut (n = 9) showed that intact vagi delayed GG recruitment with hypercapnia but did not affect diaphragm responses. In the naturally sleeping rats, we also showed that GG activity was significantly reduced in non-REM and REM sleep (P < 0.04) and was almost abolished in REM even with stimulation by 9% CO(2) (decrease = 80.4% vs. wakefulness). Such major suppression of GG activity in REM, even with significant respiratory stimulation, may explain why obstructive apneas are more common in REM sleep.
- Published
- 2002
- Full Text
- View/download PDF
26. The effectiveness of personal education plans in continuing professional development: an evaluation.
- Author
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Evans A, Ali S, Singleton C, Nolan P, and Bahrami J
- Subjects
- Adult, Education, Medical, Continuing standards, England, Female, Goals, Humans, Interviews as Topic, Male, Middle Aged, Physicians, Family education, Planning Techniques, Surveys and Questionnaires, Attitude of Health Personnel, Education, Medical, Continuing methods, Needs Assessment, Physicians, Family psychology, Program Evaluation
- Abstract
The aim of this study was to evaluate the use of personal education plans (PEPs) as a method of continuing professional development (CPD), by means of a questionnaire, analysis of completed PEP reports, and in-depth interviews. The setting was the Yorkshire Deanery, and the participants were general practitioners (GPs) who had completed a PEP. The main outcome measures were reported identification of learning needs, educational methods used, and support received. GPs' views were received on their experiences of undertaking PEPs, personal and professional development, and changes in patient care that resulted from their PEPs. Personal impression was the most frequently used method of deciding on learning needs. A variety of educational methods were used, the most frequent being personal reading, practical sessions, and taught courses. The majority of respondents felt that they were well supported by their GP tutors, and that the PEP had helped them to enhance their personal knowledge and skills, as well as to improve service to patients. There were gains in terms of increased confidence and self-awareness. Most were keen to use PEPs in future, and hoped to involve other members of the practice. Our results suggest that PEPs are an effective method of CPD in that they frequently lead to reported changes in patient care, and personal and professional development of the learner.
- Published
- 2002
- Full Text
- View/download PDF
27. Effect of upper airway negative pressure and lung inflation on laryngeal motor unit activity in rabbit.
- Author
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Ryan S, McNicholas WT, O'Regan RG, and Nolan P
- Subjects
- Action Potentials physiology, Animals, Blood Gas Analysis, Hydrogen-Ion Concentration, Laryngeal Muscles cytology, Laryngeal Muscles innervation, Laryngeal Nerves cytology, Neurons, Afferent physiology, Phrenic Nerve physiology, Rabbits, Reflex physiology, Stereotaxic Techniques, Laryngeal Muscles physiology, Laryngeal Nerves physiology, Larynx physiology, Lung physiology, Motor Neurons physiology, Muscle Fibers, Skeletal physiology, Respiratory Mechanics physiology, Ventilators, Negative-Pressure
- Abstract
Distortion of the upper airway by negative transmural pressure (UANP) causes reflex vagal bradycardia. This requires activation of cardiac vagal preganglionic neurons, which exhibit postinspiratory (PI) discharge. We hypothesized that UANP would also stimulate cranial respiratory motoneurons with PI activity. We recorded 32 respiratory modulated motor units from the recurrent laryngeal nerve of seven decerebrate paralyzed rabbits and recorded their responses to UANP and to withholding lung inflation using a phrenic-triggered ventilator. The phasic inspiratory (n = 17) and PI (n = 5) neurons detected were stimulated by -10 cmH(2)O UANP and by withdrawal of lung inflation (P < 0.05, Friedman's ANOVA). Expiratory-inspiratory units (n = 10) were tonically active but transiently inhibited in postinspiration; this inhibition was more pronounced and prolonged during UANP stimuli and during no-inflation tests (P < 0.05). We conclude that, in addition to increasing inspiratory activity in the recurrent laryngeal nerve, UANP also stimulates units with PI activity.
- Published
- 2002
- Full Text
- View/download PDF
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