Biomedical subjects

P G Wilcox

Publications and source records attributed to P G Wilcox.

At least 19 recordsLinked to original sources

PubMed1997

Noninvasive positive pressure ventilation in acute respiratory failure of chronic obstructive pulmonary disease.

Noninvasive positive pressure ventilation (NPPV) has reemerged as an effective strategy for reducing morbidity and mortality associated with acute exacerbations of chronic obstructive pulmonary disease (COPD). During acute respiratory failure, dynamic hyperinflation, intrinsic PEEP, and increased airway resistance result in a mechanical workload that exceeds inspiratory muscle capacity. NPPV provides augmentation of alveolar ventilation and respiratory muscle rest. Observational, cohort, and more recently, randomized controlled trials have demonstrated the ability of NPPV to increase the need for endotracheal intubation and decrease complications and mortality. NPPV performs better in COPD patients without significant comorbid illness. It should be initiated during COPD exacerbations if arterial pH is less than 7.35 or if the patient is severely distressed. Pressure support ventilation (10-20 cmH2O) via face mask is likely the optimal technique and, when successful, results in rapid clinical improvement.

Acute Disease↗

PubMed1997

Pregnancy and cystic fibrosis: a case-controlled study.

STUDY OBJECTIVES: Changes in cardiorespiratory and pulmonary function that occur with normal pregnancy along with increased maternal and fetal demands related to cystic fibrosis (CF) may augment morbidity for the woman with CF. Status prior to pregnancy is implicated in pregnancy outcome and maternal life expectancy postpartum. The purpose of this study was to investigate the effect of pregnancy on these patients' course during pregnancy and document prepregnancy status and 2-year postpregnancy survival. DESIGN: Patients with documented pregnancies were matched to nonpregnant CF patients of similar age (+/-2 years), severity of airflow obstruction (percent predicted forced expiratory volume in 1 min [+/-15%]), weight (+/-10 kg), height (+/-5 cm), and pancreatic sufficiency status at 1 year preconception. PATIENTS: Using their 1-year preconception data, seven women with CF and with documented pregnancies were matched to nonpregnant control subjects. All patients were pancreatic insufficient. INTERVENTIONS: Weight, forced expiratory volume in 1 min (% FEV1), FVC, Schwachman-Kulczycki (S-K) and Brasfield scores, sputum cultures, pregnancy outcome, and pulmonary exacerbations were followed from 1 year preconception, during pregnancy, and 2 years postpregnancy. MEASUREMENTS AND RESULTS: Mean weight gain during pregnancy was 5.2 kg. There were no differences between the groups in the rate of decline for pulmonary function or S-K scores over time. Greater rate of decline was noted in the pregnancy group, however, for body weight and Brasfield scores in the postpartum interval. One patient in the pregnancy group died 6 months postpartum. CONCLUSIONS: Pregnancy has little adverse effect on patients with stable CF, but poor outcomes can occur in individuals with more advanced disease.

Adult↗

PubMed1996

Effect of the beta-agonist clenbuterol on dexamethasone-induced diaphragm dysfunction in rabbits.

The present study was designed to examine whether clenbuterol (CLEN) could reduce dexamethasone (DEX)-induced diaphragm dysfunction. We studied four groups of New Zealand white (NZW) rabbits, each receiving one of the following daily injections subcutaneously for 2 wk: saline (control), DEX 3 mg/kg, DEX 3 mg/kg + CLEN 2 mg/kg, and CLEN 2 mg/kg. Diaphragm fiber cross-sectional areas (CSA) were measured. Twitch transdiaphragmatic pressure (Pdi) and tetanic Pdi were measured during bilateral phrenic stimulation both before and after 60 min of inspiratory resistive loading (IRL). DEX produced a marked atrophy of type IIa and type IIb diaphragm fibers. This diaphragm atrophy was prevented by CLEN in the DEX plus CLEN group. CLEN alone increased CSAs of all three types of diaphragm fibers. Significant reductions in twitch Pdi and tetanic Pdi at all stimulation frequencies both before and after IRL were observed similarly in the DEX group as well as in the DEX plus CLEN group compared with the control animals. We conclude that DEX produces significant diaphragm atrophy and decreases diaphragmatic contractility. CLEN produces hypertrophy of the diaphragm and minimizes diaphragm atrophy induced by DEX, but it has no demonstrable protective effect on DEX-induced diaphragm dysfunction.

Adrenergic beta-Agonists↗

PubMed1995

Ventilatory muscle strength and endurance in myasthenia gravis.

Patients with generalized myasthenia gravis (MG) often have associated ventilatory muscle involvement. It is not known whether patients with isolated ocular muscle involvement have identifiable involvement of their ventilatory muscles. Most studies have assessed muscle involvement by measuring muscle strength; however, we hypothesized that measures of ventilatory muscle endurance may be more sensitive tests of ventilatory muscle involvement in myasthenia gravis. We studied 17 patients with myasthenia gravis (four with ocular involvement alone and 13 with varying degrees of generalized myasthenia gravis). Spirometry, ventilatory muscle strength (maximum inspiratory and expiratory pressures (MIP and MEP)) and endurance (2 min incremental threshold loading test) were measured before and 20 min after i.m. neostigmine. We compared the results with those of 10 normal controls. We found no difference between patients with isolated ocular involvement and controls. Ocular myasthenia gravis patients did not improve after neostigmine. The patients with generalized myasthenia gravis had reduced baseline ventilatory muscle strength (MIP 67 cmH2O (70% of predicted), MEP 86 cmH2O (50% of pred) and endurance (mean maximal load achieved = 246 g, mean pressure at highest load (P) = 19.4 cmH2O) compared with controls. After neostigmine, there was a significant increase in MIP in patients with generalized myasthenia gravis and a trend towards an increased MEP. As a group, the patients with generalized myasthenia gravis did not demonstrate a change in their ventilatory muscle endurance after neostigmine; however, there was considerable interpatient variability in response. We conclude that patients with isolated ocular MG have normal ventilatory muscle strength when tested conventionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Decrease in left ventricular contractility after tumor necrosis factor-alpha infusion in dogs.

Whether systolic contractility or diastolic compliance changes soon after tumor necrosis factor-alpha (TNF-alpha) exposure is not known. Accordingly, we measured hemodynamics, left ventricular contractility using the slope of the end-systolic pressure-volume relationship, and diastolic pressure-volume relationships in six control dogs and in six dogs receiving 60 micrograms.kg-1.h-1 i.v. of TNF-alpha. Mean aortic pressure decreased by 22% 1 h after TNF-alpha infusion and remained decreased (P < 0.05). Cardiac output increased by 19% 1 h after TNF-alpha infusion and remained significantly greater than control values (P < 0.05). Left ventricular contractility decreased by 23% (P < 0.05) 1 h after TNF-alpha infusion and decreased by 52% (P < 0.01) 5 h after TNF-alpha infusion. The diastolic pressure-volume relationship did not change in the TNF-alpha group or the control group. Ejection fraction did not change after TNF-alpha infusion despite the decrease in contractility because afterload decreased. We conclude that TNF-alpha is important in causing the hypotensive, hyperdynamic circulation of sepsis. The new finding that left ventricular contractility is decreased shortly after TNF-alpha infusion suggests that TNF-alpha, or another mediator released very soon after TNF-alpha, is an important myocardial depressant factor.

Animals↗

PubMed1994

Tumor necrosis factor alpha decreases in vivo diaphragm contractility in dogs.

In this study, we hypothesized that tumor necrosis factor alpha (TNF alpha) is an important mediator of sepsis-related impairment in diaphragm contractility (1-2). In 12 anesthetized, ventilated dogs, bipolar stimulating electrodes were placed on the phrenic nerves and diaphragm electromyographic activity (EMG) and shortening were recorded with needle electrodes and piezoelectric crystals, respectively. Transdiaphragmatic pressure (Pdi) was also recorded using esophageal (Pes) and abdominal balloon catheters (Pdi = Pab-Pes). Dogs were randomized to receive saline injection (n = 6), or TNF alpha 60 micrograms/kg (n = 6). All parameters were recorded hourly for 6 h. Mean arterial blood pressure decreased 1 h after infusion in TNF alpha animals (p < 0.05) with no significant change thereafter. Cardiac output increased early after TNF alpha infusion (p < 0.05) and remained at greater than baseline values at study termination. Diaphragm pressure generation and costal shortening decreased progressively from 3 to 6 h post TNF alpha infusion (p < 0.05) with no significant change in control animals. Compound diaphragm action potential in response to supramaximal phrenic stimulation decreased in TNF alpha animals (p < 0.01) with no significant change in control animals 3 and 6 h postinfusion. We conclude that TNF alpha infusion was associated with significant declines in isotonic and quasi-isometric diaphragm contraction and that this could be explained, at least in part, by impaired neuromuscular transmission.

Action Potentials↗

PubMed1994

Respiratory dysrhythmias in patients with tardive dyskinesia.

Tardive dyskinesia (TD) is a disorder characterized by abnormal involuntary movements and associated with neuroleptic therapy. To determine whether the respiratory muscles are involved in this condition, we compared the breathing pattern of ten patients with TD with ten patients with chronic schizophrenia receiving neuroleptic therapy without evidence of TD, and ten age-matched normal control subjects during resting tidal breathing, forearm pronation-supination (a maneuver designed to elicit the abnormal movements of TD), and breathing to a set frequency. Breathing patterns were also assessed in seven patients with TD during a progressive incremental exercise test and an overnight polysomnogram. Patients with TD had an irregular tidal breathing pattern, with a greater variability in both tidal volume and time of the total respiratory cycle (TTOT). Both groups of patients receiving neuroleptic therapy had a rapid shallow breathing pattern when performing forearm pronation-supination compared with control subjects. There were no differences between any of the subject groups when breathing to a set frequency. The patients with TD had a normal response to progressive exercise and inspiratory time and TTOT values were less variable during non-rapid eye movement sleep compared with wakefulness. We conclude that patients with TD have irregular rapid shallow breathing which is less variable during sleep and does not limit their exercise performance.

Adult↗

PubMed1991

Normal values and ranges for ventilation and breathing pattern at maximal exercise.

Assessment of the breathing pattern at maximal exercise in patients is limited because the range of ventilatory responses (minute ventilation; tidal volume; respiratory rate) at maximal exercise in normal humans is unknown. We studied 231 normal subjects (120 women; 111 men) equally distributed according to age from 20 to 80 years. Each subject performed a progressive incremental cycle ergometer exercise test to their symptom-limited maximum. Mean ventilation at the end of exercise (Vemax) was significantly higher in men (mean +/- SD, 97 +/- 25 L/min) than in women (69 +/- 22 L/min) (p less than 0.001). Minute ventilation at the end of exercise as a fraction of predicted maximal voluntary ventilation (Vemax/MVV) for all subjects was 0.61 +/- 0.14 (range, 0.28 to 1.02). There was no difference in Vemax/MVV between men (0.62 +/- 0.14) and women (0.59 +/- 0.14). Tidal volume at the end of exercise (Vtmax) was higher in men (2.70 +/- 0.48 L) than in women (1.92 +/- 0.41 L) (p less than 0.001). Any differences in Vtmax between men and women disappeared when Vtmax was corrected for baseline FVC. Respiratory rate at the end of exercise (RRmax) was 36.1 +/- 9.2 breaths per minute for all subjects. There was no difference in RRmax between men and women. The Vemax correlated best with carbon dioxide output at the end of exercise (r = 0.91; p less than 0.001) and with maximal oxygen uptake (r = 0.90; p less than 0.001) for all subjects. This study of a large group of subjects has demonstrated the wide range of possible breathing patterns which are adopted during exercise and has provided a wide range of "normal" responses which must be taken into consideration when maximal ventilatory data from exercise tests are analyzed.

Adult↗

PubMed1990

Respiratory muscle weakness and dyspnea in thyrotoxic patients.

Dyspnea on exertion is a frequently reported symptom of thyrotoxicosis. In the majority of cases, there is no obvious cause of dyspnea, but as skeletal myopathy is also common in thyrotoxic patients, it has been postulated that increased dyspnea could be secondary to respiratory muscle weakness. We sought to determine whether thyrotoxic patients were in fact more dyspneic on exertion than age- and sex-matched controls, and if so, whether the increased dyspnea was secondary to respiratory muscle weakness. The study group consisted of 12 thyrotoxic patients and 12 control subjects matched for age and gender. We measured lung volumes, compliance, elastic recoil, respiratory muscle strength, maximal exercise performance, and the intensity of breathlessness (modified Borg scale) at various levels of exercise in all subjects. The respiratory muscles were weaker in patients than controls. This weakness improved in treated patients (p less than 0.05) with concomitant increases in VC, IC, and TLC (all p less than 0.05). Despite this, we found no differences in breathlessness intensity scores between patients and controls or in patients before and after successful antithyroid therapy.

Adult↗

PubMed1990

Respiratory muscle function during obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. Inspiratory muscles may be subjected to potentially fatiguing loads during an obstructive apnea and this may be related to the termination of obstructive apnea. We have measured transdiaphragmatic pressure (Pdi) and breathing patterns in six male patients with OSA during sleep to characterize respiratory muscle function in OSA and determine whether apnea termination is consistently related to a pressure time index of the diaphragm (PTI) associated with respiratory muscle fatigue. There was a large intersubject variability in Pdi generation during apnea. No consistent level of PTI was associated with apnea termination. During prolonged apneas, the respiratory duty cycle plateaued, which is suggestive of an inhibitory reflex possibly mediated by chest wall afferents. There were intersubject differences in both inspiratory and expiratory muscle recruitment during apnea. In the majority of patients, the diaphragm appeared to be the primary inspiratory muscle during apnea, but in some it appeared to be the intercostal/accessory muscles. The majority of patients demonstrated an increase in gastric pressure and inward abdominal movement during the expiratory phases of an apnea, consistent with abdominal muscle recruitment stimulated by increased ventilatory drive.

Diaphragm↗

PubMed1990

Recovery of the ventilatory and upper airway muscles and exercise performance after type A botulism.

We studied six patients with type A botulism to determine the degree of initial respiratory compromise and to quantitate the time course and extent of recovery of the ventilatory and upper airway muscles and exercise performance. The VM weakness was identified in all patients early after botulism. Upper airway muscle weakness was also common, requiring intubation for airway protection in one patient. Recovery of VM and upper airway muscle strength occurred in all patients, predominantly over the first 12 weeks but continued up to one year in several. A similar time course of improvement was noted for exercise performance. Ventilatory limitation was an unusual cause for exercise limitation. By 12 months, lung function, VM and upper airway muscle strength and exercise performance had returned to normal in all but one patient. We conclude that VM and upper airway muscle weakness occurs in most patients with clinically significant type A botulism.

Adult↗

PubMed1990

Recovery after unilateral phrenic injury associated with coronary artery revascularization.

Hemidiaphragmatic paralysis occurs in some patients following CAB surgery, possibly related to an intraoperative stretch or cold-induced phrenic injury. To determine the time and extent of recovery of phrenic nerve function, we studied five patients with left phrenic paresis or paralysis after CAB. The FVC, FEV1, Pmax and PEmax pressures, latency of conduction and amplitude of CDAP with phrenic nerve stimulation, and diaphragmatic excursion during fluoroscopy were measured for 12 months after CAB. Left phrenic paralysis was substantiated in four of five patients, and paresis was present in the other patient. Recovery of the left phrenic nerve occurred in all patients, complete in one and partial in four, but was delayed and continued for up to 12 months. We conclude that phrenic nerve recovery is delayed after CAB-associated injury and may be incomplete up to 14 months later, in keeping with rates of regeneration of other peripheral nerves.

Action Potentials↗

PubMed1989

Diaphragmatic weakness and paralysis.

Diaphragmatic weakness implies a decrease in the strength of the diaphragm. Diaphragmatic paralysis is an extreme form of diaphragmatic weakness. Diaphragmatic paralysis is an uncommon clinical problem while diaphragmatic weakness, although uncommon, is probably frequently unrecognized because appropriate tests to detect its presence are not performed. Weakness of the diaphragm can result from abnormalities at any site along its neuromuscular axis, although it most frequently arises from diseases in the phrenic nerves or from myopathies affecting the diaphragm itself. Presence of diaphragmatic weakness may be suspected from the complaint of dyspnea (particularly on exertion) or orthopnea; the presence of rapid, shallow breathing or, more importantly, paradoxical inward motion of the abdomen during inspiration on physical examination; a restrictive pattern on lung function testing; an elevated hemidiaphragm on chest radiograph; paradoxical upward movement of 1 hemidiaphragm during fluoroscopic imaging; or reductions in maximal static inspiratory pressure. The diagnosis of diaphragmatic weakness is confirmed, however, by a reduction in maximal static transdiaphragmatic pressure (Pdimax). The diagnosis of diaphragmatic paralysis is confirmed by the absence of a compound diaphragm action potential on phrenic nerve stimulation. There are many causes of diaphragmatic weakness and paralysis. In this review we outline an approach we have found useful in attempting to determine a specific cause. Most frequently the cause is either a phrenic neuropathy or diaphragmatic myopathy. Often the neuropathy or myopathy affects other nerves or muscles that can be more easily investigated to determine the specific pathologic basis, and, by association, it is presumed that the diaphragmatic weakness or paralysis is secondary to the same disease process.

Diaphragm↗

PubMed1989

Maximal static respiratory pressures in the normal elderly.

To determine if a relationship exists between maximal static respiratory pressures measured at the mouth and age greater than 55 yr, and if so, whether regression equations can be derived that accurately reflect this, we measured maximal inspiratory (Plmax) and expiratory (PEmax) pressures in 64 normal women and 40 normal men older than 55 yr of age. We found no relationship between PImax and PEmax and age greater than 55 yr (all r squared values less than 0.14). We tested the reproducibility of our measurements of PImax and PEmax in 13 and 12 subjects, respectively, on three separate occasions. Repeated measures analysis showed no significant differences in these measurements. Using the measurements obtained in this large study, we calculated 95% confidence limits for PImax and PEmax values in men and women older than 55 yr of age. The 95% confidence limits for PImax in men were 55 to 161 cm H2O, and 26 to 124 cm H2O in women. The 95% confidence limits for PEmax in men were 90 to 256 cm H2O, and 46 to 184 cm H2O in women. We conclude that given the large interindividual variation, a cross-sectional study such as this or other previous studies may not be able to reveal age-dependent changes unless very large numbers are used, and even then potential for bias exists. However, with the small intraindividual coefficients of variation in repeated measurements of PImax and PEmax, a longitudinal study may provide more pertinent information.

Aged↗

PubMed1989

Prediction of maximal oxygen uptake and power during cycle ergometry in subjects older than 55 years of age.

One hundred twenty-eight healthy volunteers (81 women, 47 men) older than 55 yr of age were studied with an incremental progressive cycle ergometer test to a symptom-limited, maximal tolerable work load. Mean (+/- SD) age was 66 +/- 6 yr in women and 66 +/- 5 years in men. Subjects with a history of ischemic heart disease, diabetes, pulmonary disease, or neuromuscular disease were excluded. Smokers were included, but all subjects had normal FEV1 and FVC. The objective of the study was to compare measured values of VO2max and Wmax in this older population with previously published predicted values based on subjects of all ages. We found that Wmax observed exceeded Wmax predicted by 9.5 +/- 22% (mean +/- SD) and that VO2max observed exceeded VO2max predicted by 17.5 +/- 22%. Because of this systematic underestimate of VO2max and Wmax by the previous prediction equations, we constructed new prediction equations for use in subjects older than 55 yr of age using height, weight, age, and sex as variables. We conclude that these new prediction equations more accurately predict Wmax and VO2max in subjects older than 55 yr of age because they are based solely on subjects in this age group.

Age Factors↗

PubMed1989

Pathologic changes and contractile properties of the diaphragm in corticosteroid myopathy in hamsters: comparison to peripheral muscle.

Corticosteroids have been shown to produce a myopathy of peripheral skeletal muscle, characterized predominantly by Type II fiber atrophy. To determine if similar histologic and histochemical changes occur in the diaphragm and whether the in vitro contractile properties of this muscle are adversely affected by steroids, we studied two groups of hamsters. The experimental group received triamcinolone while a control group received saline, both given daily for 3 wk as i.m. injections. Soleus (Sol) and extensor digitorum longus (EDL) muscles and costal diaphragm muscle sections were stained for histologic (hematoxylin and eosin, modified Gomori trichrome) and histochemical (myosin ATPase, succinate dehydrogenase [SDH]) analysis. Muscle fiber proportions and cross-sectional areas (CSA) were measured from myosin ATPase sections. In vitro studies of isometric contractions were carried out on small strips of costal diaphragm, measuring maximal isometric twitch (Pt) and tetanus (Po) tensions, time to peak tension (TTP), half relaxation time (1/2 RT), force-frequency relationship, and fatigue characteristics (60 Hz tetani; duty cycle, 0.5). Triamcinolone treatment resulted in no change in muscle fiber proportions. There was no effect on Type I fiber CSA; however, there was Type IIa (Sol, EDL) and Type IIb (diaphragm, EDL) fiber atrophy in triamcinolone-treated animals. Pt and Po (normalized for weight) of diaphragm strips were not different. There was a prolongation in TTP and 1/2 RT, a left shift in the force-frequency curve, and a reduced fatiguability of triamcinolone-treated diaphragm (P less than 0.05). We conclude that a steroid myopathy could be explained by a loss of muscle mass (Type IIb fiber atrophy) rather than an intrinsic impairment in contractile function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Comparison of two-minute incremental threshold loading and maximal loading as measures of respiratory muscle endurance.

We performed a two-minute incremental threshold loading test (incremental test) in ten normal subjects on three occasions, and having ascertained the maximum load (max load) against which they could inspire for two minutes, measured how long this load could be tolerated by these same subjects on three further occasions (tlim test). We compared the reproducibility of the two tests. There were no significant differences found in the mean max loads in the three incremental tests, or in the endurance times in the three tlim tests. However, the intraindividual coefficients of variation of max load in the incremental test (0 to 14 percent) were much smaller than the intraindividual coefficients of variation of endurance time in the tlim test (20 to 65 percent). We found that the large variability in endurance time in our tlim tests was most likely accounted for by variability in breathing pattern, inspiratory flow rate and breath-by-breath mouth pressure generation. Differences in these parameters did not, however, explain why in the tlim test a given subject could tolerate for 19 minutes a load only 100 g less than that which he was unable to tolerate for two minutes in the incremental test. These findings emphasize the differences between these two tests of respiratory muscle endurance. Since there was less intraindividual variability in the two-minute incremental threshold loading test, we suggest that this test may be more useful than the tlim test.

Adult↗

PubMed1989

Cardiac output at rest and in exercise in elderly subjects.

We measured cardiac output (Q), at rest and during graded exercise, in 68 women and 41 men over the age of 55 yr, using a CO2 rebreathing method. Mean (+/- SD) age was 66 +/- 5 yr in women and 66 +/- 6 yr in men. Only subjects with no history or physical examination findings of pulmonary, cardiac, neuromuscular, or endocrine disease and normal electrocardiography and spirometry were studied. We found a linear relationship between Q and oxygen uptake (VO2) in males and females. The regression equation expressing this relationship in males was Q = 2.9 + 5 VO2 1.min-1 (SEE 2.8) and, in females, Q = 2.9 + 4.6 VO2 1.min-1 (SEE 2.8). This is similar to the relationship previously estimated for elderly males using the direct Fick method and concurs with other reports in the literature which show that, while the Q-VO2 relationship in the elderly has a slope similar to that in younger groups, the Q-VO2 intercept is lower. This means that the absolute level of cardiac output for a given level of work is lower in the elderly than in younger populations. This may reflect an age-related decrease in active metabolic tissue in the elderly and/or altered metabolic regulation with increased oxygen extraction from blood.

Aged↗