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Biomedical subjects

J Moxham

Publications and source records attributed to J Moxham.

At least 127 records · Page 7Linked to original sources

Comparison of cervical magnetic stimulation and bilateral percutaneous electrical stimulation of the phrenic nerves in normal subjects.

Cervical magnetic stimulation is a new technique for stimulating the phrenic nerves, and may offer an alternative to percutaneous electrical stimulation for assessing diaphragmatic strength in normal subjects and patients in whom electrical stimulation is technically difficult or poorly tolerated. We compared cervical magnetic stimulation with conventional supramaximal bilateral percutaneous electrical stimulation in nine normal subjects. We measured oesophageal pressure (Poes), gastric pressure (Pgas) and transdiaphragmatic pressure (Pdi). The maximal relaxation rate (MRR) was also measured. The mean magnetic twitch Pdi was 36.5 cmH2O (range 27-48 cmH2O), significantly larger than electrical twitch Pdi, mean 29.7 cmH2O (range 22-40 cmH2O). The difference in twitch Pdi was explained entirely by twitch Poes, and it is possible that the magnetic technique stimulates some of the nerves to the upper chest wall muscles as well as the phrenic nerves. We compared bilateral, rectified, integrated, diaphragm surface electromyographic (EMG) responses in three subjects and found results within 10% in each subject, indicating similar diaphragmatic activation. The within occasion coefficient of variation, i.e. same subject/same session, was 6.7% both for magnetic and electrical twitch Pdi. The between occasion coefficient of variation, i.e. same subject/different days, was 6.6% for magnetic stimulation and 8.8% for electrical. There was no difference between relaxation rates measured with either technique. We conclude that magnetic stimulation is a reproducible and acceptable technique for stimulating the phrenic nerves, and that it provides a potentially useful alternative to conventional electrical stimulation as a nonvolitional test of diaphragm strength.

Action Potentials↗

Assessment of respiratory muscle strength in the intensive care unit.

The measurement of respiratory muscle strength in the intensive care unit (ICU) is potentially useful for the prediction of weaning outcome. An easy and accurate measure would also allow investigation of respiratory muscle weakness in critically ill patients. At present, there is no satisfactory method of strength measurement in the intensive care unit. Vital capacity is a nonspecific, volitional and relatively insensitive measure of strength. True maximum respiratory pressures are difficult to achieve and, in stable patients, results vary greatly both over time and between observers. For these reasons, there are few good data of respiratory muscle strength in the intensive care unit. Of the new techniques being developed, magnetic stimulation of the phrenic nerves, combined with the measurement of transdiaphragmatic, oesophageal, or endotracheal tube pressure, offers the greatest promise.

Humans↗

Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease.

Acute exacerbations of chronic obstructive airways disease (COAD) are a common cause of admission to hospital, and have a high mortality. Nasal intermittent positive pressure ventilation (NIPPV) has been used successfully in patients with respiratory failure due to neuromuscular and skeletal disorders, but the outcome of treatment in patients with COAD is less well known. We carried out a prospective randomised controlled trial of conventional treatment versus conventional treatment plus NIPPV, in 60 patients with acute ventilatory failure due to exacerbations of COAD. For the NIPPV group there was a rise in pH, compared with a fall in the controls (mean difference of change between the groups 0.046 [95% CI 0.06-0.02, p < 0.001]), and a larger fall in PaCO2 (mean difference in change between the groups 1.2 kPa [95% CI 0.45 to 2.03, p < 0.01]). Median visual analogue scores over the first 3 days of admission showed less breathlessness in the NIPPV group (2.3 cm [range 0.1-5.5]) than in the control group (4.5 cm [range 0.9-8.8]) (p < 0.025). Survival rates at 30 days were compared for intention-to-treat and efficacy populations. In the efficacy mortality comparison, mortality in the NIPPV group was reduced: 1/26 vs 9/30 (relative risk = 0.13, CI = 0.02-0.95, p = 0.014). This effect was less in the intention-to-treat analysis: 3/30 vs 9/30 (relative risk = 0.33, CI = 0.10-1.11, p = 0.106). In patients with acute ventilatory failure due to COAD who received NIPPV there was a significant rise in pH, a reduction in PaCO2 and breathlessness, and reduced mortality.

Adrenal Cortex Hormones↗

Acute effects of inhaled salbutamol on the metabolic rate of normal subjects.

BACKGROUND: This study was designed to investigate the contribution of inhaled salbutamol to the increase in resting metabolic rate found in patients with chronic airflow limitation who were receiving bronchodilator therapy. METHODS: The resting metabolic rate of 10 normal subjects (age 20-47 years, weight 42-105 kg, seven men) was studied after inhalations of salbutamol or placebo. An open canopy method of indirect calorimetry was used to measure resting oxygen consumption (VO2) and resting carbon dioxide production (VCO2). Subjects inhaled two, four, eight, or 12 puffs (100 micrograms/puff) of salbutamol or placebo in a double blind manner. Recordings of VO2 and VCO2 were made after inhalation of the four doses of salbutamol or placebo, integrated over one hour, and compared. RESULTS: VO2 and VCO2 increased in a dose dependent manner after inhaled salbutamol with a maximum effect at five minutes after inhalation. After four puffs, VO2 was 203 and 188 ml/kg/h for salbutamol and placebo respectively. After eight puffs, VO2 was 207 and 185 and VCO2 was 167 and 155 ml/kg/h. After 12 puffs, VO2 was 220 and 190 with a VCO2 of 181 and 168 ml/kg/h. Twelve puffs of salbutamol increased the mean (SE) respiratory quotient from 0.85 (0.01) to 0.93 (0.04) at five minutes indicating an increase in ventilation in excess of metabolic demand. Mean heart rate increased in parallel with VO2. CONCLUSION: Inhaled salbutamol significantly increases resting metabolic rate in a dose dependent manner.

Administration, Inhalation↗

Modification of the thermogenic effect of acutely inhaled salbutamol by chronic inhalation in normal subjects.

BACKGROUND: Acute inhalation of clinical doses of salbutamol in normal volunteers increases resting metabolic rate by up to 20% above control values. This study was designed to see if chronic treatment with salbutamol causes a sustained increase in metabolic rate and whether it modifies the acute thermogenic response to the drug. METHODS: The effects of chronic inhaled salbutamol on resting oxygen consumption (VO2) and carbon dioxide output (VCO2) were studied in seven normal subjects (age 20-47 years, weight 52-105 kg, five men). An open canopy method of indirect calorimetry was used to measure VO2, VCO2, and respiratory quotient (RQ). Subjects inhaled two puffs of salbutamol or placebo four times a day in a double blind manner. Measurements of resting VO2 and VCO2 after 10 days of salbutamol were compared with the values after 10 days of placebo and with those taken at the start of the study. At the end of each treatment period subjects inhaled eight puffs (800 micrograms) of salbutamol and the acute effects on VO2, VCO2 and RQ were monitored for one hour. RESULTS: Resting VO2, VCO2, and RQ were not significantly different at the end of the salbutamol and placebo periods but the acute response to eight puffs of salbutamol was abolished by regular inhalation. The mean VO2 integrated over one hour after 800 micrograms salbutamol given acutely was different (241.3 and 210.7 ml/kg/h in the placebo and salbutamol groups respectively). Differences were not significant between placebo and salbutamol groups for changes in VCO2, heart rate, blood pressure, and RQ after acute inhalation. CONCLUSION: Regular treatment with inhaled salbutamol (800 micrograms/day) does not cause a sustained increase in resting metabolic rate but prevents the increase in VO2 that occurs after acute inhalations in normal subjects.

Administration, Inhalation↗

Diaphragmatic dysfunction in neuralgic amyotrophy: an electrophysiologic evaluation of 16 patients presenting with dyspnea.

We report 16 adult men (age, 41 to 75 yr) with neuralgic amyotrophy (NA) who presented with dyspnea due to involvement of the diaphragm. All patients developed breathlessness after a prodrome of acute severe neck and shoulder pain. Bilateral diaphragm paralysis (BDP) was confirmed in 12 patients and unilateral diaphragm paralysis (UDP) in four by the absence of electrical and mechanical responses to percutaneous phrenic nerve stimulation. Global expiratory muscle strength was well preserved in all patients, but inspiratory muscle strength was reduced in proportion to the extent of diaphragmatic involvement. Lung function showed low lung volumes with preservation of carbon monoxide transfer coefficient in all patients. Two BDP patients were hypoxic (PaO2 = 67 and 54 mm Hg, respectively) on daytime arterial blood gas analysis; the latter patient with pre-existing chronic obstructive pulmonary disease and marked obesity also had borderline hypercapnia (PaO2 = 49 mm Hg). Overnight sleep studies in three BDP and two UDP patients showed frequent intermittent arterial oxygen desaturations apparently caused by obstructive sleep apneas, but there was no evidence of alveolar hypoventilation. Follow-up muscle studies in five BDP and four UDP patients between 2 and 4 yr after initial referral showed complete recovery of diaphragmatic function in only two UDP patients, one of whom relapsed a year later. We postulate that NA may be an important but underrecognized cause of diaphragmatic paralysis in otherwise normal patients. Diaphragmatic strength returns very slowly, if at all.

Action Potentials↗

The effects of beta 2-agonists and caffeine on respiratory and limb muscle performance.

The possibility that respiratory muscle function may be improved by drug therapy is of clinical importance, but remains controversial. A series of studies concerning the effects of maximally tolerated dosages of terbutaline, tulobuterol (a new beta 2-agonist) and caffeine on respiratory muscle strength and limb muscle strength and endurance were undertaken in normal subjects. Drugs were administered orally, 2 h before study. Caffeine produced a small but statistically significant increase in the stimulated contraction force at 20 Hz, and a small beneficial effect on recovery from a fatiguing protocol; maximum voluntary contraction force of the quadriceps was increased by 3.8%. Terbutaline and tulobuterol had no beneficial effects on either respiratory or limb muscle function. We conclude that conventional dosages of these bronchodilator drugs do not greatly affect skeletal muscle performance.

Adrenergic beta-Agonists↗

An evaluation of P0.1 measured in mouth and oesophagus, during carbon dioxide rebreathing in COPD.

The pressure generated 100 ms after the onset of an occluded inspiratory effort (P0.1) is advocated and used as a measure of respiratory centre drive. We have re-examined P0.1, measured simultaneously in the mouth (Pmo0.1) and the oesophagus (Poes0.1), during carbon dioxide rebreathing, in eight patients with severe chronic obstructive pulmonary disease, to see whether either indicates central respiratory drive. Pmo0.1 was identical to Poes0.1 in 4 out of 61, greater than Poes0.1 in 18 out of 61, and less than Poes0.1 in 39 out of 61 measurements (overall Poes0.1-Pmo0.1, median +0.075, range -0.175 to +1.01 kPa). Within a rebreathing run in an individual patient, there was considerable variability in the relationship Pmo0.1/Poes0.1 (0.89 +/- 0.24), coefficient of variation (CoV%) 14.4 +/- 3.7%), in the end-expiratory oesophageal pressure (0.7 +/- 0.54 kPa, CoV% 105 +/- 106%), and in the time delay between the onset of a fall in oesophageal pressure (Poes) from the end-expiratory level to the beginning of inspiration, defined as starting when mouth pressure (Pmo) fell below atmospheric pressure (129 +/- 25 ms, CoV% 22.5 +/- 5.3%). We conclude that the problem of determining the true onset of inspiratory muscle activity from pressure data, and the likelihood that breaths are taken from different lung volumes, make it unlikely that Poes0.1 accurately represents central respiratory drive during rebreathing in chronic obstructive pulmonary disease. Furthermore, Pmo0.1 differed from Poes0.1 during rebreathing, and their relationship was not constant, so that Pmo0.1 is even less likely to be a useful reflection of central nervous system output or respiratory centre drive in such patients.

Esophagus↗

Lack of effect of acute hypoxia and hypercapnia on muscle relaxation rate in man.

The effect of acute hypoxia and hypercapnia on skeletal muscle relaxation rate was investigated in man. The contractile force of limb muscles (quadriceps femoris and adductor pollicis) was studied in normal subjects using electrical stimulation. The twitch transdiaphragmatic pressure was used to investigate the diaphragm. The maximum relaxation rate was measured from contractions of the non-fatigued quadriceps femoris, adductor pollicis and diaphragm. Severe hypoxia (mean transcutaneous oxygen tension 40 mmHg) did not alter the maximum relaxation rate from 20 Hz stimulated contractions of the non-fatigued quadriceps. Acute hypercapnia (mean end-tidal CO2 tension 65.1 mmHg) did not significantly change the maximum relaxation rate from 20 and 100 Hz tetanic contractions of non-fatigued quadriceps. The maximum relaxation rate from 1 Hz twitch tension and 20 Hz tetanic tension of adductor pollicis was also not altered by acute hypercapnia (mean end-tidal carbon dioxide tension 63 and 60 mmHg, respectively). The maximum relaxation rate from twitch transdiaphragmatic pressure was not altered by acute hypercapnia (mean end-tidal carbon dioxide tension 69.7 mmHg).

Acidosis, Respiratory↗

Inspiratory muscle effort during nasal intermittent positive pressure ventilation in patients with chronic obstructive airways disease.

Effective intermittent positive pressure ventilation can be achieved noninvasively using a nasal mask, but patient comfort may be compromised and respiratory effort increased unless the trigger threshold is low and the response time of the ventilator short. The effect of nasal ventilation upon inspiratory muscle effort and the functional characteristics of the trigger of a purpose-built ventilator were evaluated in five patients with chronic obstructive airways disease. A measure of inspiratory muscle effort, the average pressure time integral per minute, decreased by at least 80% in four patients and by 50% in one. Only two patients had significant numbers of triggered breaths (17% and 47% of total) during 1 h of ventilation with settings as used at home. Therefore trigger function was evaluated when the patients were made to trigger the ventilator by slowing the control rate. A high resting end-expiratory intrathoracic pressure decreased the effective trigger sensitivity so that a mean (SD) change in oesophageal pressure of 14.8 cmH2O was required to lower mask pressure by 2.4 (0.3) cmH2O and activate the trigger. Even under these conditions of lowest trigger sensitivity inspiratory muscle effort was not increased compared to spontaneous ventilation.

Carbon Dioxide↗

A clinically relevant modification to existing inhaler therapy.

A modified formulation of inhaled salbutamol and a new inhaler device were studied in a group of 11 moderate-to-severe asthmatic patients. Changes in airway calibre (FEV1, Vmax30) were measured before and after inhalation of the new formulation, and compared with changes following inhalation of conventional salbutamol. A standard Rotahaler was used as a reference for the new inhaler. The study was conducted as a two-part randomized, double-blind cross-over trial. We found a significantly greater bronchodilatation of the larger airways using the modified drug in the Rotahaler. The new inhaler did not show any superiority over the Rotahaler, contrary to expectations from in vitro work. A slightly shorter model may better reflect the in vitro results. The study has implications for inhalation therapy in general.

Adult↗

Detection of HIV in haemopoietic progenitors.

Peripheral blood cytopenias present a major problem in the management of patients with HIV infection. Their pathophysiology is likely to be multifactorial, although there is controversy as to whether haemopoietic progenitors are a target for HIV. In order to investigate the haemopoietic defect in HIV infection, we looked at bone marrow culture characteristics of marrow from eight HIV+ patients compared to normal controls. We performed long-term liquid culture (LTC) and colony forming assays for granulocyte-macrophage (CFU-GM) and granulocyte, erythroid, megakaryocyte, macrophage (CFU-GEMM). In LTC we found normal stromal appearance and haemopoietic focus formation. There was no difference in colony assays of CFU-GM and CFU-GEMM between HIV+ and normal controls. Colonies taken from CFU-GM and CFU-GEMM were analysed for HIV DNA sequences, and we were able to detect HIV DNA in colonies from all HIV+ patients. Our results indicate that despite infection of haemopoietic progenitor cells by HIV, bone marrow function is preserved. This suggests that HIV-related cytopenias may be due to alternative mechanisms not present in our in vitro system.

Adult↗

Short term effect of oxygen on renal haemodynamics in patients with hypoxaemic chronic obstructive airways disease.

BACKGROUND: Oxygen therapy is effective in the prevention and treatment of oedematous exacerbations of cor pulmonale. As renal blood flow is reduced in cor pulmonale a study was designed to investigate whether one of the beneficial effects of oxygen was to increase renal blood flow. The effect of oxygen therapy on renal haemodynamics measured noninvasively was examined in patients with chronic obstructive airways disease and previous episodes of oedema. METHODS: Renal blood flow waveforms were recorded in a single vessel by colour flow Doppler ultrasound in nine hypoxaemic patients (PaO2) (arterial oxygen tension < 8 kPa while they were breathing air) with chronic obstructive airways disease and previous oedema and eight age matched normoxaemic volunteers (arterial oxygen saturation (SaO2) 97% or more when breathing air) while they were breathing air and oxygen. SaO2 and transcutaneous PaO2 (TcPO2) and PaCO2 (TcPCO2) were monitored. Five renal velocity profile recordings were made from the same segmental vessel with the patient breathing room air for one hour followed by oxygen titrated to achieve an oxygen saturation of 95% or more without a rise in TcPCO2 for 15 minutes. Control subjects breathed 35% oxygen. RESULTS: No significant change in the pulsatility index (a measure of distal vascular resistance) or mean height of the waveform (Tamx, a measure of renal blood flow) occurred in the control subjects while they were breathing air or oxygen. The pulsatility index of the patients with chronic obstructive airways disease was significantly greater than that in the control subjects breathing air (1.44 (SD 0.28) v 1.03 (0.14). Breathing oxygen was associated with an increase in TcPO2 in the patients (from 6.9 (1.9) to 11.5 (0.7) kPa), a fall in pulsatility index (from 1.44 (0.28) to 1.26 (0.14) and an increase in Tamx (from 0.187 (0.055) to 0.234 (0.087) m/s). CONCLUSIONS: The results suggest that renal vascular resistance is increased in patients with chronic obstructive airways disease and hypoxaemia and that short term oxygen therapy reduces renal vascular resistance and increases blood flow. Some of the benefits of oxygen therapy in cor pulmonale may be due to improvements in renal haemodynamics.

Aged↗