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Biomedical subjects

P D Hughes

Publications and source records attributed to P D Hughes.

At least 19 recordsLinked to original sources
PubMed2001

Inspiratory muscle relaxation rate slows during exhaustive treadmill walking in patients with chronic heart failure.

Exercise intolerance is a feature of chronic heart failure (CHF). We hypothesized that excessive loading of the respiratory muscle pump might contribute to exertional breathlessness. One marker of excessive muscle-loading is slowing of maximum relaxation rate (MRR) and, therefore, to test our hypothesis, we investigated the effect of exhaustive treadmill walking on inspiratory muscle MRR in patients with CHF. We studied eight stable patients with mild-moderate CHF walking on a treadmill until termination because of severe dyspnea. Inspiratory muscle MRR was determined from esophageal pressure (Pes) change during submaximal sniffs (Sn) before and immediately after exercise to a mean (SD) minute ventilation of 77 () L/min. For comparison, nine healthy subjects performed a similar protocol; exercise was terminated either by severe dyspnea or when minute ventilation reached 100 L/min. There were no significant differences in terms of heart rate, respiratory rate, tidal volume, or inspiratory duty cycle at cessation of exercise. The mean slowing of Sn Pes MRR in the first minute after termination of exercise in the CHF group was 22.4% and in the normal control group it was 2.8% (p < 0.01). Our data show that slowing of inspiratory muscle relaxation rate occurs in patients with CHF walking to severe breathlessness. We conclude that severe loading of the inspiratory muscles is a feature of exertional dyspnea in CHF.

Adult↗
PubMed2000

Anterior magnetic phrenic nerve stimulation: laboratory and clinical evaluation.

OBJECTIVE: Anterior magnetic stimulation (aMS) of the phrenic nerves is a new method for the assessment of diaphragm contractility that might have particular applications for the clinical assessment of critically ill patients who are commonly supine. DESIGN: We compared aMS with existing techniques for measurement of diaphragm weakness and fatigue in 10 normal subjects, 27 ambulant patients with suspected diaphragm weakness and 10 critically ill patients. SETTING: Laboratory and intensive care unit of two university hospitals. RESULTS: Although aMS was not demonstrably supramaximal in normal subjects, the mean value of twitch transdiaphragmatic pressure (Tw Pdi) obtained at 100% of stimulator output, 23.7 cmH2O, did not differ significantly from that obtained with bilateral supramaximal electrical stimulation (ES), 24.9 cmH2O, or bilateral anterior magnetic phrenic nerve stimulation (BAMPS), 27.3 cmH2O. A fatiguing protocol produced a 20 % fall in aMS-Tw Pdi and a 19% fall in BAMPS-Tw Pdi; the fall in aMS-Tw Pdi correlated with the fall in BAMPS-Tw Pdi (r2 = 0.84, p = 0.03) indicating that aMS can detect diaphragm fatigue. In ambulant patients aMS agreed closely with existing measures of diaphragm strength. The maximal sniff Pdi correlated with both the aMS-Tw Pdi (r2 = 0.60, p < 0.0001) and the BAMPS-Tw Pdi (r2 = 0.65, p < 0.0001) and the aMS-Tw Pdi was a mean (SD) 2.2 (4.3) cmH2O less than BAMPS-Tw Pdi. In addition, aMS correctly identified diaphragm dysfunction in patients studied on the ICU. CONCLUSIONS: We conclude that aMS is of clinical value for the investigation of suspected diaphragm weakness.

Action Potentials↗
PubMed2000

Synthesis and characterisation of phosphorylcholine-based polymers useful for coating blood filtration devices.

Copolymers of 2-methacryloyloxyethylphosphorylcholine (MPC) and lauryl methacrylate (LMA) of molar ratios MPC: LMAX where x = 1, 2 or 4, have been synthesised by two different free-radical polymerisation techniques. The solubility characteristics of the resulting materials were investigated in a variety of water: alcohol solvent mixtures and found to be influenced not only by the molar ratio of MPC: LMA, but also the method of synthesis. A window of solubility was observed for certain copolymers and the alcohol used in the solvent mixture was also found to have a profound influence on the solubility profile of the polymers. These materials were soluble in a wider range of aqueous methanol mixtures compared to aqueous mixtures of higher aliphatic alcohols, such as ethanol or isopropyl alcohol, which was rationalised in terms of the affinity of the phosphorylcholine headgroup for the various alcohols relative to water. 1H nuclear magnetic resonance spectroscopy was used to further examine the solution properties of the copolymers in various solvents. The copolymer MPC: LMA2 was coated onto a variety of substrates from both alcohol-only and water: alcohol solvent systems and the surface properties of the films compared by static and dynamic contact angle, atomic force microscopy (AFM) and attenuated internal reflectance Fourier transform infrared spectroscopy (ATR-IR). The coating formed from the water: alcohol solvent was found to be hydrophilic in nature, possessing spontaneous wettability, whereas films formed from alcohol-only solvents were hydrophobic, and only on conditioning with water were more wettable surfaces attained. This phenomenon was applied in the coating of leukocyte filtration material, where the aqueous-based systems demonstrated lower critical wetting surface tension (CWST) and shorter wetting times relative to both uncoated filters and those coated from alcohol-only systems. The haemocompatibility of the coated filters was equivalent for both coating solvent systems. employed, and far superior when compared to the uncoated control.

Alcohols↗
PubMed1999

Ureteric reflux in adults and children treated exclusively by endoscopic Teflon injection: a 10-year experience.

BACKGROUND: Since 1988 the author has used only endoscopic injection of Teflon (polytetrafluoroethylene) paste in the correction of ureteric reflux, in adults and children. METHODS: The present paper reports a series of 32 patients, 18 children and 14 adults, with 45 refluxing ureters so treated. Intra-operative cystogram was carried out and a second Teflon paste injection was given under the same anaesthetic where persistent reflux was demonstrated after the initial Teflon injection, to reduce the number of anaesthetics given. RESULTS: In those patients who consented to a delayed cystogram after the first injection of Teflon, there was a cure rate of 83.3% in children and 70% in adults from that first injection. CONCLUSION: Endoscopic retro-ureteric injection of Teflon paste is done as a day case under general anaesthesia and causes the patient no pain postoperatively. It gives a high cure rate and is an option that should be offered to every patient where a decision has been made to correct ureteric reflux.

Adult↗
PubMed1999

Diaphragm strength in chronic heart failure.

Reduced respiratory muscle strength has been reported in chronic heart failure (CHF) in several studies. The data supporting this conclusion come almost exclusively from static inspiratory and expiratory mouth pressure maneuvers (MIP, MEP), which many subjects find difficult to perform. We therefore performed a study using measurements that are less dependent on patient aptitude and also provide specific data on diaphragm strength. In 20 male patients and 15 control subjects we measured MIP and MEP as well as esophageal and transdiaphragmatic pressure during maximal sniffs (Sn Pes, Sn Pdi) and cervical magnetic phrenic nerve stimulation (Tw Pdi). In a subgroup the response to paired phrenic nerve stimulation (pTw Pdi) at interpulse intervals from 10 to 200 ms (5 to 100 Hz) was also determined. As expected, MIP was significantly reduced in the CHF group (CHF, 69.5 cm H(2)O; control, 96.7 cm H(2)O; p = 0.01), but differences were much less marked for Sn Pes (CHF, 95.2 cm H(2)O; control, 104.8 cm H(2)O; p = 0.20) and MEP (CHF, 109.1 cm H(2)O; control, 135.7 cm H(2)O; p = 0.09). Diaphragm strength was significantly reduced (Sn Pdi: CHF, 123.8 cm H(2)O; control 143.5 cm H(2)O; p = 0.04. Tw Pdi: CHF, 21.4 cm H(2)O; control, 28.5 cm H(2)O; p = 0.0005). Paired phrenic nerve stimulation suggested a trend to increased twitch summation at 5 to 20 Hz in CHF, although this did not reach significance. We conclude that mild reduction in diaphragm strength occurs in CHF, possibly because of an increased proportion of slow fibers, but overall strength of the respiratory muscles remains well preserved.

Adult↗
PubMed1999

Long-term recovery of diaphragm strength in neuralgic amyotrophy.

Diaphragm paralysis is a recognized complication of neuralgic amyotrophy that causes severe dyspnoea. Although recovery of strength in the arm muscles, when affected, is common, there are little data on recovery of diaphragm function. This study, therefore, re-assessed diaphragm strength in cases of bilateral diaphragm paralysis due to neuralgic amyotrophy that had previously been diagnosed at the authors institutions. Fourteen patients were recalled between 2 and 11 yrs after the original diagnosis. Respiratory muscle and diaphragm strength were measured by volitional manoeuvres as maximal inspiratory pressure and sniff transdiaphragmatic pressure. Cervical magnetic phrenic nerve stimulation was used to give a nonvolitional measure of diaphragm strength: twitch transdiaphragmatic pressure. Only two patients remained severely breathless. Ten of the 14 patients had evidence of some recovery of diaphragm strength, in seven cases to within 50% of the lower limit of normal. The rate of recovery was variable: one patient had some recovery after 2 yrs, and the rest took 3 yrs or more. In conclusion, in most patients with diaphragm paralysis due to neuralgic amyotrophy, some recovery of the diaphragm strength occurs, but the rate of recovery may be slow.

Adult↗
PubMed1998

Measurement of sniff nasal and diaphragm twitch mouth pressure in patients.

BACKGROUND: Inspiratory muscle weakness is a recognised cause of unexplained dyspnoea. It may be suggested by the finding of a low static inspiratory mouth pressure (MIP), but MIP is a difficult test to perform, with a wide normal range; a low MIP may also occur if the patient has not properly performed the manoeuvre. Further investigation conventionally requires balloon catheters to obtain oesophageal (Poes) and transdiaphragmatic pressure (Pdi) during sniffs or phrenic nerve stimulation. Two non-invasive tests of inspiratory muscle strength have recently been described--nasal pressure during a maximal sniff (Sn Pnas) and mouth pressure during magnetic stimulation of the phrenic nerves (Tw Pmo). The use of these two tests in combination might identify patients without inspiratory muscle weakness who are unable to produce a satisfactory MIP< therefore avoiding the need for investigation with balloon catheters. METHODS: Thirty consecutive patients with clinically suspected inspiratory muscle weakness and a low MIP underwent both conventional (Sn Poes and Tw Pdi) and non-invasive testing (Sn Pnas and Tw Pmo). Weakness was considered to be excluded by a Sn Poes of > or = 80 cm H20 or a Tw Pdi of > or = 20 cm H20. The limit values used to test the hypothesis were Sn Pnas > or = 70 cm H20 or Tw Pmo > or = 12 cm H20. RESULTS: Inspiratory muscle weakness was excluded in 17 of the 30 patients. Fifteen of these would have been identified using Sn Pnas and Tw Pmo, with better results when the two tests were combined. The cut off values selected for Sn Pnas and Tw Pmo were shown by ROC plots to indicate normal strength conservatively, avoiding failure to detect mild degrees of weakness. No patient with global weakness was considered normal by Sn Pnas or Tw Pmo. CONCLUSIONS: In most patients with normal inspiratory strength and a low MIP, Tw Pmo and Sn Pnas used in combination can reliably exclude global inspiratory muscle weakness, reducing the number of patients who need testing with balloon catheters.

Adult↗
PubMed1998

Influence of acute lung volume change on contractile properties of human diaphragm.

The effect of stimulus frequency on the in vivo pressure generating capacity of the human diaphragm is unknown at lung volumes other than functional residual capacity. The transdiaphragmatic pressure (Pdi) produced by a pair of phrenic nerve stimuli may be viewed as the sum of the Pdi elicited by the first (T1 Pdi) and second (T2 Pdi) stimuli. We used bilateral anterior supramaximal magnetic phrenic nerve stimulation and a digital subtraction technique to obtain the T2 Pdi at interstimulus intervals of 999, 100, 50, 33, and 10 ms in eight normal subjects at lung volumes between residual volume and total lung capacity. The reduction in T2 Pdi that we observed as lung volume increased was greatest at long interstimulus intervals, whereas the T2 Pdi obtained with short interstimulus intervals remained relatively stable over the 50% of vital capacity around functional residual capacity. For all interstimulus intervals, the total pressure produced by the pair decreased as a function of increasing lung volume. These data demonstrate that, in the human diaphragm, hyperinflation has a disproportionately severe effect on the summation of pressure responses elicited by low-frequency stimulations; this effect is distinct from and additional to the known length-tension relationship.

Adult↗
PubMed1998

Effect of prenatal ethanol exposure on the developmental profile of the NMDA receptor subunits in rat forebrain and hippocampus.

The effects of prenatal ethanol exposure on the NMDAR1 protein expression (postnatal days 1 and 7) and on the developmental profile of the NMDAR2A and NMDAR2B subunits in rat forebrain and hippocampus were investigated. Forebrain and hippocampal membrane proteins were isolated from pups of various ages (postnatal days 1 to 21) from prenatally ethanol exposed, pair-fed and ad libitum control groups. A semiquantitative immunoblot procedure was used with antibodies raised against the NMDAR1, NMDAR2A, and the NMDAR2B subunits to assess the NMDA subunit protein expression in the samples. NMDAR1 protein expression was unaffected by prenatal ethanol exposure at postnatal day 1 or 7 in both the forebrain and hippocampus. NMDAR2A protein expression levels rose rapidly in both forebrain and hippocampus during the time frame of study. Prenatal ethanol exposure caused a significant reduction in protein expression levels of the NMDAR2A in forebrain through postnatal day 14. NMDAR2B protein expression levels were high throughout the study in both forebrain and hippocampus. Prenatal ethanol exposure significantly reduced protein expression of the NMDAR2B in the forebrain (through postnatal day 14) and hippocampus (up to day 7). The results suggest that there may be a link between the depressed expression of the NMDAR2 subunits and the neurodevelopmental disorders associated with fetal ethanol exposure.

Animals↗
PubMed1997

Diaphragm performance during maximal voluntary ventilation in chronic obstructive pulmonary disease.

In normal subjects 2 min of maximal voluntary hyperventilation results in failure of tension generation and low-frequency fatigue of the diaphragm. Patients with severe chronic obstructive pulmonary disease (COPD) do not develop diaphragm fatigue during exhaustive treadmill exercise despite excessive inspiratory muscle loading and we hypothesized that they might be relatively resistant to the development of diaphragm fatigue during maximal ventilation. In six patients with severe COPD (mean FEV1 0.671) we therefore loaded the diaphragm using 2 min of maximal isocapnic ventilation (MIV). Initial mean ventilation was 28.6 L/min and diaphragm pressure-time product (PTPdi) 602 cm H2O x s/min; these values were sustained throughout MIV without significant decline. Mean twitch transdiaphragmatic pressure (Tw Pdi) was 19.7 cm H2O 25 min after a control run and 20.5 cm H2O at the same time after MIV [corrected]. Compared with normal subjects previously studied in our laboratory (Hamnegard, C.-H., et al. Eur. Respir. J. 1996;9:241-247) the reduction in PTPdi was disproportionately greater than the reduction in Tw Pdi. We conclude that, unlike normal subjects, 2 min of MIV causes neither failure of diaphragm performance nor low-frequency diaphragm fatigue in patients with severe COPD. It is likely that the diaphragm makes a relatively limited contribution to the generation of maximal levels of ventilation in severe COPD.

Aged↗
PubMed1997

The contractile properties of the elderly human diaphragm.

It has previously been reported that aging is associated with a substantial decrease in diaphragm strength. To test this hypothesis we studied 15 (10 male, 5 female) subjects with a mean age of 29 (range 21 to 40) and 15 elderly (10 male, 5 female) subjects, mean age 73 (range 67 to 81). We measured transdiaphragmatic pressure (Pdi) during a maximal sniff (Sniff Pdi) and during bilateral cervical magnetic stimulation (CMS) of the phrenic nerve roots (Tw Pdi). Additionally in 17 subjects (9 elderly and 8 young) the Pdi elicited by paired CMS (pTw Pdi) was obtained at interstimulus intervals ranging from 10 to 999 ms (1 to 100 Hz). There was considerable overlap between groups. Mean Sniff Pdi in the elderly was 119 cm H2O compared with 136 cm H2O for the young subjects; this represented a median reduction of 18 cm H2O or 13% (p = 0.05, 95% Cl of difference 0 to 33 cm H2O). Mean Twitch Pdi in the elderly was 26.8 cm H2O compared with 35.2 cm H2O, a median reduction of 8 cm H2O or 23% (p = 0.004, 95% Cl 3 to 13 cm H2O). At 10 Hz the elderly tended to generate a higher fraction of the Pdi obtained at 100 Hz than the young, but this trend did not achieve statistical significance (p = 0.11). We conclude that aging is associated with a reduction in diaphragm strength. However the magnitude of the reduction is small and may be offset by a leftward shift of the force-frequency relationship.

Adult↗
PubMed1997

Simulation of cough in man by magnetic stimulation of the thoracic nerve roots.

Normal cough requires abdominal muscle contraction. We have previously reported contraction of the abdominal muscles elicited by a single percutaneous magnetic stimulation of the thoracic nerve roots. We hypothesized that paired magnetic twitches could generate sufficient tension in the abdominal muscles to simulate cough. Therefore, six normal subjects were stimulated at the T10 intervertebral level in the seated position. We measured the gastric pressure elicited by paired magnetic stimuli (pTw Pga) with interstimulus intervals in the range of 10 ms (100 Hz) to 999 ms (1 Hz). In the second part of the study we evaluated paired stimuli (at the frequency found to produce the greatest response) using a valve to simulate the function of the glottis; the valve was arranged such that it opened once mouth pressure exceeded a predetermined threshold. Mean pTw Pga during stimulation for the 6 subjects was 74 cm H2O (range, 30-109), and mean peak flow was 209 L/min (range, 128-345 L/min). These values were increased if the subject took a prior inspiration or had previously made a vigorous expiratory effort. Comparable values for a maximal natural cough were 212 cm H2O and 649 L/min. We conclude that paired magnetic thoracic nerve root stimulation produces gastric pressure and expiratory flow of an order of magnitude comparable to a natural cough.

Abdominal Muscles↗