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Biomedical subjects

John Moxham

Publications and source records attributed to John Moxham.

29 records · Page 2Linked to original sources

Diaphragmatic function in infants with surgically corrected anomalies.

Infants with surgically correctable anomalies, abdominal wall defects (AWD) or congenital diaphragmatic hernia (CDH) may have poor postnatal diaphragmatic function, because the low intra-abdominal pressure experienced by such patients in utero could result in impaired diaphragmatic development. Our objective was to compare postoperative diaphragmatic function of infants with CDH or AWD to that of gestational age-matched controls. Diaphragmatic function was assessed by measurement of the transdiaphragmatic pressure and maximum inspiratory pressure at the mouth generated during crying against an occlusion. In addition, the transdiaphragmatic pressure produced by unilateral and/or bilateral magnetic stimulation of the phrenic nerves (TwPdi) was examined. Lung volume was assessed by measurement of functional residual capacity (FRC) using a helium gas dilution technique. Ten infants with CDH, 26 with AWD infants (19 gastroschisis, seven exomphalos), and 36 gestational age-matched controls were studied. Compared with their matched controls, the eight CDH infants with left-sided defects had significantly lower left (p < 0.01) and right (p < 0.05) TwPdi and FRC (p < 0.01), and the gastroschisis infants, but not those with exomphalos, had significantly lower left and right TwPdi (p < 0.05). There were no significant differences in transdiaphragmatic pressure and maximum inspiratory pressure at the mouth between the CDH or AWD infants and the controls. Diaphragmatic function postoperatively is impaired in infants with CDH or gastroschisis.

Abdominal Wall↗

Effect of voluntary facilitation on the diaphragmatic response to transcranial magnetic stimulation.

We assessed recruitment curves of the surface diaphragm motor-evoked potential (MEP) after transcranial magnetic stimulation during relaxation and at three different levels of facilitation (20, 40, and 60% of maximal inspiratory esophageal pressure) in 10 healthy subjects (six young and four elderly). MEP amplitude recruitment curves varied between individuals during relaxation and at each level of facilitation. Amplitude recruitment curves during relaxation were reproducible in individual subjects. Inspiratory maneuvers caused a decrease in motor threshold and latency and an increase in MEP amplitude, positively correlated to the intensity of facilitation. These changes were similar in young and elderly subjects. The best fit for MEP amplitude recruitment curves for each condition was obtained with a Boltzmann model. The performance of repeated submaximal inspiratory maneuvers did not affect the amplitude recruitment curves of the relaxed diaphragm. We conclude that the recruitment curve of the diaphragm with transcranial magnetic stimulation is repeatable and changes consistently with facilitation and will, therefore, be a robust experimental tool for the investigation of supraspinal pathways to the diaphragm.

Adult↗

Influence of maturation on infant diaphragm function assessed by magnetic stimulation of phrenic nerves.

Infant diaphragm function may be adversely affected in a variety of disorders and conditions. Key to establishing an accurate diagnosis are appropriate control data. The aim of this study was to determine the effect of maturation on diaphragm function, using a nonvolitional test. Diaphragm function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated by magnetic stimulation of the phrenic nerves. Ballon catheters were positioned in the lower third of the esophagus and stomach. Esophageal (Pes) and gastric (Pgas) pressure changes were measured using differential pressure transducers. The pressure signals were amplified and displayed in real time on a computer (running Labview trade mark software) and Pdi derived by online subtraction of Pes from Pgas. Twenty-nine infants (14 born preterm), at a median gestational age of 37 (range, 25-42) weeks, were studied at a median postconceptional age (PCA) of 39 (range, 32-44) weeks. At time of measurement, none had respiratory problems or were hyperinflated (functional residual capacity ranged from 23-35 mL/kg). The preterm infants had significantly lower transdiaphragmatic pressures responses following median left (4.0, range 2.5-6.8 cmH(2)O vs. 4.8, range 2.8-7.2 cmH(2)O) and median right phrenic nerve stimulation (3.6, range 2.6-4.8 cmH(2)O vs. 4.3, range 2.7-6.8 cmH(2)O) (P < 0.05) than term infants. Following left and right phrenic nerve stimulation, Pdi correlated significantly with gestational age (r = 0.4, P < 0.05, and r = 0.4, P < 0.05, respectively) and PCA (r = 0.37, P = 0.05, and r = 0.56, P < 0.01, respectively). We conclude that gestational age at birth and postconceptional age at time of measurements must be taken into account when interpreting the results of infant diaphragm function tests.

Diaphragm↗

The effect of treatment on diaphragm contractility in obstructive sleep apnea syndrome.

In untreated obstructive sleep apnea syndrome (OSAS) inspiratory efforts are made against an occluded airway and diaphragm fatigue might therefore complicate OSAS. To test this hypothesis we measured twitch transdiaphragmatic pressure (Tw Pdi) in response to bilateral cervical magnetic stimulation of the phrenic nerve roots in nine patients with OSAS before and one month after successful therapy with nasal continuous positive airways pressure (nCPAP). The mean Tw Pdi before therapy was 23.2cm H2O and after therapy was 22.8cm H2O (P = 0.59); the mean change after initiation of nCPAP was 0.4cm H2O with 95% confidence intervals of -1.3cm H2O and +2.1 cm H2O. We conclude that low frequency diaphragm fatigue does not complicate untreated OSAS.

Adult↗

Intracortical inhibition and facilitation of the response of the diaphragm to transcranial magnetic stimulation.

Respiratory muscles respond to a subcortical automatic command and to a neocortical voluntary command. In diseases such as stroke or motor neurone disease, an abnormal diaphragmatic response to single transcranial magnetic stimuli can identify a central source for respiratory disorders, but this is not likely to be the case in disorders affecting intracortical inhibitory and facilitatory mechanisms. This study describes the response of the diaphragm to paired transcranial magnetic stimulation. Thirteen normal subjects were studied (age range, 22 to 43 years; 7 men; phrenic conduction, <6.8 msec; latency of diaphragmatic motor evoked potential, <20.5 msec). Motor evoked potentials in response to paired stimulation were obtained in eight subjects only, with the motor threshold in the remaining five subjects too high to absorb the loss of power inherent in the double-stimulation montage. Interstimulus intervals less than 5 msec resulted in a statistically significant inhibition (p < 0.01 for interstimulus intervals of 1 and 3 ms), whereas intervals longer than 6 msec were facilitatory (maximal, 15 msec). The diaphragmatic pattern matched that of the biceps brachii. The authors conclude that it is possible to study intracortical inhibition and facilitation of diaphragmatic control, although not in all subjects. Technical improvement should alleviate current limitations and make paired transcranial magnetic stimulation a tool to study respiratory muscle abnormalities in settings in which intracortical interactions are important, such as movement disorders.

Action Potentials↗

Changes in pulmonary mechanics with increasing disease severity in children and young adults with cystic fibrosis.

As forced expiratory volume in 1 second (FEV(1)) is a major predictor of outcome in patients with cystic fibrosis (CF), we investigated the effect of FEV(1) on pulmonary mechanics in children and young adults with CF. We measured respiratory rate; tidal volume; minute ventilation; arterial blood gases; sniff esophageal pressure; dynamic lung compliance; total pulmonary resistance; intrinsic positive end expiratory pressure; and total, elastic, and resistive work of breathing in 32 patients (FEV(1) range: 12-49% predicted). We observed correlations between FEV(1) and Pa(O(2)) (r = 0.76, p < 0.0001) and Pa(CO(2)) (r = -0.70, p < 0.0001), FEV(1) and respiratory rate/tidal volume (r = -0.41, p = 0.02), FEV(1) and dynamic lung compliance (r = 0.64, p < 0.0001), and FEV(1) and total work of breathing (r = -0.52, p = 0.002) and elastic work of breathing (r = -0.60. p = 0.0003). No correlations were observed between FEV(1) and sniff esophageal pressure (p = 0.5), minute ventilation (p = 0.9), total pulmonary resistance (p = 0.3), intrinsic positive end expiratory pressure (p = 0.3), or resistive work of breathing (p = 0.1). As FEV(1) declines in children and young adults with CF, there is an increase in the elastic load and work of breathing, resulting in a rapid shallow breathing pattern, that is associated with further impairment of gas exchange.

Adolescent↗

Effect of severe isolated unilateral and bilateral diaphragm weakness on exercise performance.

Patients with isolated diaphragm paralysis depend on recruitment of extradiaphragmatic respiratory muscles to increase ventilation, but little is known about exercise performance or the response of the inspiratory muscles to loaded breathing. By convention, unilateral diaphragm paralysis is regarded as a trivial condition whereas bilateral paralysis is considered to be potentially life-threatening. In fact, no data exist concerning exercise performance under these conditions. We studied incremental treadmill exercise performed by eight patients with bilateral diaphragm paralysis, eight patients with unilateral diaphragm paralysis, and eight age-matched control subjects. Respiratory muscle endurance (RME) was also measured by an inspiratory threshold loading method. Exercise time, compared with control subjects (671 seconds), was moderately reduced in unilateral diaphragm paralysis (512 seconds, p = 0.07) and further reduced in bilateral diaphragm paralysis (456 seconds, p = 0.02). Similarly, peak minute ventilation was lower in patients with unilateral diaphragm paralysis (84 L x min(-1), p = 0.01) and in patients with bilateral diaphragm paralysis (69 L x min(-1), p = 0.001) compared with control subjects (114 L x min(-1)). However, patients with unilateral diaphragm paralysis and patients with bilateral diaphragm paralysis had increased ratios of peak oxygen consumption to peak minute ventilation compared with control subjects (p = 0.0007 and p < 0.0001, respectively). Nine patients had normal RME; exercise time was moderately increased in these patients (502 seconds) compared with seven patients with reduced RME (461 seconds). In conclusion, although exercise performance is impaired in bilateral diaphragm paralysis, these patients can sustain a reasonable exercise load, particularly if RME is preserved and compensatory mechanisms have developed. In addition, exercise tolerance is diminished in patients with unilateral diaphragm paralysis.

Adult↗

Does undernutrition contribute to diaphragm weakness in patients with severe COPD?

BACKGROUND AND AIMS: The assumption that undernourishment contributes to diaphragm weakness in chronic obstructive pulmonary disease (COPD) remains unproven. METHODS: We, therefore, studied diaphragm strength, measured as transdiaphragmatic pressure during a maximal voluntary sniff (Sn P(di)) and cervical magnetic stimulation (Tw P(di)), in two groups of 10 patients with severe COPD. The groups had equally severe COPD as judged by FEV(1) and thoracic gas volume (V(tg)). The malnourished group had a mean body mass index (BMI) of 17.3 kg/m(2) compared with 27 kg/m(2) for the normally nourished group (mean difference -9.7 kg/m(2); 95% confidence intervals -6.8 to -12.6 kg/m(2),P <0.0001). RESULTS: There was no significant difference between Tw P(di) (mean difference 2.1 cm H(2)O; 95% CI-3 to + 7.4 cm H(2)O, P=0.39) or Sn P(di) (mean difference -2.4 cm H(2)O; 95% CI-21 cm H(2)O to +16 cm H(2)O,P =0.8). CONCLUSION: We conclude that undernourishment of the severity studied does not contribute to diaphragm weakness in severe COPD.

Adult↗

Depression of diaphragm contractility by nitrous oxide in humans.

UNLABELLED: Nitrous oxide is widely used in anesthesia and critical care medicine. The effect of nitrous oxide on diaphragm contractility in humans is unknown. We evaluated the effect of a 50% nitrous oxide-50% oxygen mixture on diaphragm contractility in healthy adult volunteers. The sniff transdiaphragmatic pressure (Sn Pdi) and the twitch transdiaphragmatic pressure (Tw Pdi) elicited by bilateral supramaximal phrenic nerve stimulation were measured before during and after inhalation of a mixture of 50% nitrous oxide and 50% oxygen. Sn Pdi decreased by 15.4% during nitrous oxide inhalation, with a value of 136 +/- 21 cm H(2)O before nitrous oxide and a value of 115 +/- 27 cm H(2)O during nitrous oxide inhalation (P = 0.03). Similarly, Tw Pdi decreased from 21.2 +/- 1.8 cm H(2)O before nitrous oxide inhalation to 16.9 +/- 4.1 cm H(2)O during nitrous oxide inhalation (P = 0.03). The effect of nitrous oxide was totally abolished 20 min after its discontinuation. Nitrous oxide has a short-acting suppressant effect on the pressure generating capacity of the diaphragm in healthy humans. IMPLICATIONS: We investigated whether nitrous oxide (a common component of gas anesthesia) reduces diaphragm strength in humans. Diaphragm strength is reduced by nitrous oxide but the effect wears off within 20 min of administration. Caution is advised when using nitrous oxide without anesthesiologist supervision in patients at risk of ventilatory failure

Administration, Inhalation↗

Magnetic phrenic nerve stimulation to assess diaphragm function in children following liver transplantation.

BACKGROUND: An accurate and practical test of diaphragm function in children in the intensive care unit is desirable. Diaphragm dysfunction can occur after liver transplantation and may be a contributory factor in the respiratory complications after the procedure. OBJECTIVE: Our aim was to assess if magnetic stimulation (MS) of the phrenic nerves could be used to assess diaphragm strength in children receiving intensive care. SETTING: Pediatric intensive care unit. PATIENTS: Eight supine, ventilated, sedated children (mean age, 7.3; range, 0.6-15 yrs) were studied within 12 hrs of liver transplantation. INTERVENTIONS: MS was performed using either 90-mm double circular coils or 43-mm figure of eight coils placed over the phrenic nerves on the anterior aspect of the neck. Measurements: The produced diaphragm force was assessed by measuring the transdiaphragmatic pressure (Pdi) with balloons in the mid-esophagus and stomach. During MS, the endotracheal tube was briefly occluded by using a pneumatic valve. MAIN RESULTS: Supramaximal diaphragm force responses were obtained in all subjects; mean Pdi, 7.8 (sd, 3.1) cmH(2)O for left, 5.2 (sd, 3.4) cmH(2)O for right, and 14.8 (sd, 9.2) cmH(2)O for bilateral stimulation. Bland and Altman analysis indicated close agreement between esophageal and airway pressure during MS (mean difference, -0.76 [sd, 0.99] cmH(2)O for left stimulation, 0.81 [sd, 1.25] cmH(2)O for right stimulation, and -0.63 [sd, 1.55] cmH(2)O for bilateral stimulation). In three children, there was a >50% difference between the Pdi generated after left and right unilateral MS and the results of MS indicated complete right hemidiaphragm paralysis in one child. CONCLUSION: MS of the phrenic nerves provides a practical technique for assessing diaphragm function in children receiving intensive care. Measurement of airway pressure during MS may provide a noninvasive technique for assessing diaphragm strength when the use of balloon catheters is contraindicated.

Journal Article↗

Attacking the disease spiral in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the commonest respiratory cause of mortality and morbidity in adults in the UK. Although the condition is initially a pulmonary one, data exist to support the concept that factors associated with COPD, including immobility, gives rise to secondary effects, including a quadriceps myopathy, which in turn cause anaerobic metabolism at low work rates. This, through bicarbonate buffering, leads to CO2 retention which, because of constraints imposed by pulmonary mechanics, cause acidosis and dyspnoea. Various therapeutic strategies to reverse this spiral may be employed including pulmonary rehabilitation, quadriceps strength training and surgical or bronchoscopic lung volume reduction.

Carbon Dioxide↗