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Biomedical subjects

B Wuyam

Publications and source records attributed to B Wuyam.

34 records · Page 2Linked to original sources

[Skeletal muscle abnormalities in chronic obstructive lung disease with respiratory insufficiency. Value of P31 magnetic resonance spectroscopy].

31P magnetic resonance spectroscopy (31P MRS) is a non-invasive method to evaluate high energy compounds [adenosine triphosphate (ATP), phosphocreatin (PCr), inorganic phosphates (Pi)] and intracellular pH (pHi) of skeletal muscle during exercise and recovery. It is a clinically applicable method of investigation for severe COPD patients with respiratory failure since exercise is limited to a single group of muscle (calf). Pronounced alterations of muscular metabolism have been shown in these patients: (1) reduced aerobic capacity (as reflected by the ratio of Pi/PCr as a function of power and changes in recovery kinetics of PCr after exercise and (2) increased anaerobic metabolism (reflected by a decrease in intracellular pH). Four different studies reveal similar abnormalities. Acute oxygen administration partially improves these parameters, suggesting that other factors in addition to hypoxaemia may contribute to the metabolic impairment. The effect of increased physical activity on these abnormalities deserve further investigations.

Adenosine Triphosphate↗

Management of simple snoring, upper airway resistance syndrome, and moderate sleep apnea syndrome.

The spectrum of respiratory sleep disorders has been extended in the last years to include conditions that are less well defined than severe obstructive sleep apnea (OSA). Moderate OSA, snoring, and upper airway resistance syndrome (UARS) represent three conditions in which there are still unresolved pathophysiological, epidemiological, and clinical questions. Therefore, the therapeutic approach remains unclear. We have tried to define these entities and to review the respective indications and efficacy of pharmacological treatment, weight loss, sleep posture, oral appliances, upper airway surgery, and finally, continuous positive airway pressure (CPAP). From these data, we also aim to define strategies of treatment for moderate OSA, snoring, and UARS. However, these conditions are likely to be particularly appropriate for randomized trials comparing different modalities of treatment that may be the only way to validate these treatment strategies.

Airway Obstruction↗

Critical analysis of the results of surgery in the treatment of snoring, upper airway resistance syndrome (UARS), and obstructive sleep apnea (OSA).

Surgery is widely considered to be the first-line therapy for "simple" snoring and moderate sleep apnea syndrome. Surgical treatment of severe obstructive sleep apnea (OSA) is currently generally considered to be second-line therapy after continuous positive airway pressure (CPAP) treatment. Many patients, however, find difficulty in complying with the continued long-term demands of CPAP treatment and seek a more definitive one-off solution to their sleep-related problem. Surgical therapy has been found useful for snoring, at least on subjective grounds; this has incited patient demand and led surgeons to expand its use for upper airway resistance syndrome (UARS) and possibly OSA. In this paper the surgical procedures of uvulopalatopharyngoplasty (UPPP), nasal surgery, and maxillofacial surgery are discussed and analyzed as they relate to the resolution of snoring, UARS, and OSA. There are many methodological problems in the published literature that make this analysis difficult. We feel that surgical therapy should be comparable to CPAP therapy, fulfilling the same analytical criteria in regard to measurement of severity and improvement of the disorder, as well as an equally sustained effect. Operative risk and side effects need to be clearly stated. Guidelines for future data collection and clinical trials of surgical procedures are proposed, and we recommend randomized prospective multicenter protocols and a registry of patients undergoing surgery for OSA so that long-term follow-up can be achieved.

Airway Obstruction↗

Lactate accumulation during moderate hypoxic hypoxia in neocortical rat brain.

Neocortical metabolism was studied during moderate hypoxic hypoxia, reoxygenation, and postmortem periods in anesthetized normocapnic rats using 1H nuclear magnetic resonance (NMR) spectroscopic imaging. Rats were prepared with unilateral common carotid occlusion to determine the ipsilateral metabolic effects of inadequate cerebral blood flow (CBF) response to hypoxia. No difference in brain metabolism between the two hemispheres was found during the control period. Hypoxic hypoxia (PaO2 = 54.1 +/- 5.8 mm Hg) resulted in a significant rise in neocortical lactate peak in both hemispheres, with an additional marked rise in the clamped side compared to the unclamped side (53 +/- 27 vs. 22 +/- 13% of postmortem value, p < 0.001). These lactate changes were not reversible within 30 min of reoxygenation in the clamped hemisphere. No changes in neocortical lactate peak were observed while elevating arterial lactate via intravenous lactate infusion without hypoxia. In addition, hypoxic hypoxia resulted in an apparent decrease in neocortical water and N-acetyl aspartate (NAA) signals, which were related to a shortening in T2 relaxation times. It is concluded that neocortical lactate is an early metabolic indicator during moderate hypoxic hypoxia in normocapnic conditions.

Animals↗

Inspiratory coactivation of the genioglossus enlarges retroglossal space in laryngectomized humans.

To investigate the relationship between the electrical activity of the genioglossus (GG-EMG) and associated tongue movement, seven laryngectomized subjects breathing through a tracheal stoma (without pressure or flow change in the upper airway) were studied in the supine position. Tongue movement, with the use of lateral fluoroscopy, and GG-EMG expressed as a percentage of maximum voluntary genioglossal activation were monitored simultaneously during 1) spontaneous inspiration (SI), 2) resistive loaded inspiration (LI), and 3) rapid inspiration (RI). Tongue position during each maneuver was compared with its position during spontaneous expiration. Peak GG-EMG during the three maneuvers was significantly different from each other (SI: 5.4 +/- 1.6, LI: 11.9 +/- 1.8, and RI: 51.6 +/- 9.4 (SE) %, respectively). Associated forward movement of the posterior aspect of the tongue was minimum during SI; however, significant movement was observed during LI, and this was increased during RI. Significant covariance existed between peak GG-EMG and this movement. Genioglossal coactivation with inspiration enlarges the glossopharyngeal airway, particularly in its caudal part. In subjects with intact upper airways, this activation may protect or enhance upper airway patency in an effort-dependent manner.

Aged↗

Abnormal autonomic stress responses in obstructive sleep apnoea are reversed by nasal continuous positive airway pressure.

Obstructive sleep apnoea (OSA) is associated with abnormalities in autonomic stress tests, which are tests of cardiovascular response in the autonomic nervous system (ANS). The level of abnormality has been related to the level of overnight arterial oxygen saturation (Sa,O2). We have studied ANS function pre- and post-treatment with nasal continuous positive airway pressure (nCPAP) in six males with moderately severe or severe OSA (apnoea/hypopnoea index (AHI) median 51 (range 14-74 events.h-1 of sleep). Tests consisted of heart rate responses to Valsalva manoeuvre, deep breathing, and change of posture from lying to standing. In addition, systolic blood pressure (SBP) response to standing and diastolic blood pressure (DBP) response to handgrip were studied. Each abnormal test (compared to published normal values) scored +1.0 and each marginal test result (90-95% confidence interval for normals) scored +0.5. A total score was calculated for the five tests performed in the evening and morning (maximum score 10 per patient). Patients had been receiving treatment for more than 1 year (median 471 (389-624) days) and objective compliance was monitored by a clock counter in the nCPAP machines. Five of six patients had regularly used nCPAP (mean 7.8 h.night-1) and all showed a normalization in ANS test score: pre-nCPAP 2 (1-4.5), post-nCPAP 0.2 (0-0.5) (p < 0.05, Wilcoxon signed rank test). One poorly compliant subject (No. 6; nCPAP 3 h.night-1) had a deterioration in ANS test score: 1 pre-nCPAP to 1.5 post-nCPAP. The improvement in ANS test score in the five compliant patients was positively correlated with an improvement in mean Sa,O2 during sleep posttreatment. We conclude that successful treatment of obstructive sleep apnoea leads to normalization of impaired autonomic stress responses.

Adult↗

Hyperpnoea during and immediately after exercise in man: evidence of motor cortical involvement.

1. The neurophysiological basis for the increase in breathing associated with exercise remains obscure. The present study uses positron emission tomography (PET) to measure relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during and immediately following exercise. 2. Male volunteers underwent H2(15)O PET scanning during two complementary studies. Firstly, six subjects performed right leg exercise, adequate to increase oxygen uptake 2.5-fold. Secondly, five different subjects were scanned immediately following bicycle exercise (adequate to increase oxygen uptake 5-fold) while breathing was still increased. In each study, as a control, scanning was also performed during matched passive isocapnic positive pressure ventilation; additionally, in the first study, passive right leg movement was performed. 3. Increases in relative rCBF were obtained in each individual and co-registered with their magnetic resonance image of the brain defining individual gyral morphology. 4. During exercise, individual and group analysis revealed significant relative rCBF increases in the left and right superomedial primary motor cortex (the motor cortical 'leg' areas) and also in the left and right superolateral primary motor cortex in areas previously shown to be associated with volitional breathing. After exercise, there was no significant increase in relative rCBF in the superomedial areas but such increases were still present bilaterally in the superolateral areas which had been activated during the exercise. Other relative rCBF increases were also found, both during and after exercise, in cortical and subcortical areas known to be involved in motor control. 5. The results from PET scans during and after exercise, taken together, provide evidence for motor cortical involvement in the exercise-related hyperpnoea in man.

Adult↗

Imagination of dynamic exercise produced ventilatory responses which were more apparent in competitive sportsmen.

1. The cardiorespiratory response to imagination of previously performed treadmill exercise was measured in six competitive sportsmen and six non-athletic males. This was compared with the response to a control task (imaging letters) and a task not involving imagination ('treadmill sound only'). 2. In athletes, imagined exercise produced increases in ventilation which varied within and between subjects. The mean maximal increase (11.71 min-1) was approximately 20% of the ventilatory response to actual exercise. This was primarily due to treadmill speed-related increases in respiratory frequency (mean maximal increase, 14.8 breaths min-1) and resulted in significant reductions in end-tidal PCO2 (mean maximal fall, 7 mmHg). These effects were greater (P < 0.01) than any observed during the control tasks. 3. Changes in heart rate (mean increase, 12 beats min-1) were not significantly different from those observed during the control tasks (P > 0.2). 4. In non-athletes, imagination of exercise produced no changes in cardiorespiratory variables. No significant differences were detected in subjective assessments of movement imagery ability between athletes and non-athletes (P = 0.17). 5. This study demonstrates that ventilatory effects, when observed, are specific to imagination of exercise. The greater likelihood of generating ventilatory responses in highly trained athletes, experienced in 'rhythmic' sports, may be related to awareness of breathing and its role in exercise imagination strategy. A volitional component of the response cannot be discounted.

Adult↗

Muscular metabolism during oxygen supplementation in patients with chronic hypoxemia.

The effects of supplemental oxygen (O2) versus air on working calf muscle metabolism were studied in seven patients with stable chronic obstructive pulmonary disease (COPD) and chronic hypoxemia (PaO2 = 57 +/- 3 SE mm Hg) and seven age-matched control subjects. Oxygen and air were randomly administrated at 24-h intervals, and O2 flow rate was adjusted to correct hypoxemia (PaO2 = 87 +/- 4 mm Hg) in the COPD group. The relative concentrations of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and the intracellular pH (pHi) were determined with 31P magnetic resonance spectroscopy at rest, during a graded standardized and localized exercise protocol (360 active plantar flexions), and during recovery. In resting muscle no significant effect of added O2 was demonstrable in each group with regard to pHi, Pi/PCr, and ATP/(PCr+Pi+PME) ratios. Mechanical data were similar between the two groups and between the two tests during the whole exercise. The indices of muscular oxidative metabolism (Pi/PCr and pHi at the end of exercise and recovering PCr resynthesis rate) were impaired in the COPD group compared with that in the control group during air (all p < 0.05). All these parameters were significantly improved with added O2 in the COPD group (p < 0.05), whereas no similar effects were observed in the control group. However, these beneficial effects were incomplete since the exercising Pi/PCr ratio remained higher in the COPD group than in the control group during added O2. This energetic muscular impairment could correspond to tissular damage related to chronic hypoxemia.

Aged↗

Respiratory monitoring in sleep apnea syndrome.

This review provides a critical analysis of current respiratory monitoring techniques in diagnosis of sleep apnea syndrome. The correct analysis of polysomnography requires knowledge of the limitations of the means of recording used. These limitations, for invasive and noninvasive techniques, are discussed in terms of calculation, differentiation and scoring of respiratory events. Aims and means are stated for monitoring and scoring in research as well as in clinical practice.

Diagnosis, Differential↗

Individuality of breathing patterns during hypoxia and exercise.

Breathing was recorded via a pulsed ultrasonic flowmeter in 11 healthy subjects, at rest and during steady-state exercise (at 50% of their maximal O2 consumption) at both sea level (200 m) and simulated altitude (4,500 m in a hypobaric chamber). The pattern of breathing was quantified breath by breath in terms of classical respiratory variables (tidal volume and inspiratory and expiratory times), and the shape of the entire airflow profile was quantified by harmonic analysis. Statistical tests were used to compare the within-individual with the between-individual variations. In comparing the sea level vs. altitude rest (16% increase in ventilation) and sea level vs. altitude exercise (40% increase in ventilation) airflow profiles, we found a significantly greater resemblance within the individual than between individuals. Comparisons of sea level rest and exercise (295% increase in ventilation) and altitude rest and exercise (375% increase in ventilation) revealed no similarity within individuals. Despite airflow profile changes between rest and exercise, it is still possible to attest to a diversity of flow profile between individuals during exercise. Hypoxia at rest or during exercise does not alter the phenomenon of the individuality of breathing patterns.

Adult↗

Metabolism and aerobic capacity of skeletal muscle in chronic respiratory failure related to chronic obstructive pulmonary disease.

The calf muscle energy metabolism of 8 stable chronic obstructive pulmonary disease (COPD) patients with chronic respiratory failure (arterial oxygen tension (Pao2) 7.7 +/- 0.4 kPa or 58 +/- 3 mmHg) was studied, using 31-phosphorus magnetic resonance spectroscopy (31P MRS). MRS spectra were acquired at rest and during the course of 360 pedal movements at 20, 35 and 50% of the maximal voluntary contraction (MVC) and during recovery. Eight healthy age-matched subjects served as the control group. No significant differences between groups were observed in resting muscle, as regards intracellular pH, Pi/PCr ratio (Pi: inorganic phosphate; PCr: phosphocreatine) and the relative ATP expressed as the ratio beta ATP/PCr + Pi + PME (PME: phosphomonoester). Although effective power outputs were similar for both groups at each work level, COPD patients exhibited a higher Pi/PCr ratio than health controls (3.34 +/- 0.89 vs 0.49 +/- 0.05 at 50% MVC; p less than 0.01) and a lower pHi (6.65 +/- 0.11 vs 7.06 +/- 0.02 at 50% MVC; p less than 0.01). PCr resynthesis during recovery was slower in patients than in control subjects (t1/2 PCr 1.27 +/- 0.26 min vs 0.47 +/- 0.05 min; p less than 0.05). These results suggest impairment of aerobic capacity in a non-ventilatory working muscle, which may be due to hypoxaemia in patients with chronic respiratory failure.

Aged↗

Impairment of muscular metabolism in chronic respiratory failure. A human 31P MRS study.

The calf muscle metabolism of 7 patients with stable chronic respiratory failure (PaO2 below 65 Torr) was studied using 31P NMR spectroscopy. NMR spectra were acquired at rest, during the course of 360 pedal movements at 20, 35 and 50% of the maximal voluntary contraction (MVC) and during recovery. Eight normal aged-matched subjects served as a control group. In resting muscle, no significant differences were observed between both groups as regards intracellular pH, inorganic phosphate/phosphocreatine (Pi/PCr) and beta-ATP/PCr + Pi + phosphomonoester (PME) ratios. Although effective power outputs were similar for both groups at each work level, patients exhibited a higher Pi/PCr ratio than healthy controls (3.19 +/- 1.01 vs 0.49 +/- 0.05 at 50% MVC; p less than 0.01) and a lower pHi (6.65 +/- 0.11 vs 7.06 +/- 0.02 at 50% MVC; p less than 0.01). Moreover, PCr resynthesis during recovery was slower in patients than in control subjects (t1/2 PCr = 1.26 +/- 0.30 vs 0.47 +/- 0.05 min; p = 0.01). These results suggest impairment of aerobic capacity in a non-ventilatory working muscle, probably due to hypoxemia in patients with chronic respiratory failure.

Adenosine Triphosphate↗

[Can oximetry contribute to the detection of apnea? The use of a mathematical analysis of the oximetry signal].

The aim of this study was to test the efficacy of nocturnal oximetry as a means of continuous recording of SaO2 in the identification of apnoeic events in the recognition of non-apnoeic desaturation. The oscillations of SaO2 in relation to successive periods of apnoea during the course of the sleep apnoea syndrome (SAS) or with apnoeic episodes in patients with chronic airflow obstruction (BPCO) or restricted disease, were identified using a new delta index quantifying the variations of SaO2 during the night. 26 successive patients in whom there was an indication for nocturnal oximetry were included in a prospective study comparing nocturnal oximetry and polysomnography during 34 nights. In the apnoeic patients we found a strong correlation (r = .85. p. less than .01) between the apnoeic period and the delta index. In BPCO the number of apnoea was correlated with the delta index (r = .96. p. less than .01). A minimal threshold of the delta index fixed at 1.5 was satisfactory for detecting apnoea if the initial SaO2 was less than 93%. The value of the adequate for affected detection ought to be fixed at .8 (95% sensitivity) when the initial SaO2 was greater than 93%. A detection of apnoeic events thus seems possible by this method.

Apnea↗

Sequential combination of 5-fluorouracil, cis-platinum and irradiation in unresectable non-small cell lung cancer.

Twenty patients with unresectable non-small cell lung carcinoma, 15 stage III and 5 stage IV (supraclavicular lymphadenopathy) were treated with a combination of three courses of chemotherapy and hypofractionated irradiation followed after 3 weeks by split-course radiotherapy. Each course was repeated every 3 weeks with the following sequence. Cis-platin (CDDP) (20 mg/m2) was given in a 20-min infusion, followed by a 2-h infusion of 5-fluorouracil (5-FU) (400 mg/m2) on days 1, 2, 5 and 6. Radiation with a dose of 3 Gy on the target volume was given on days 3 and 4, after a 2-h infusion of 5-FU (400 mg/m2). Split course of irradiation consisted of 16 Gy in 5 fractions repeated after 3 weeks interval. The objective response rate was 75%. Median follow-up was 24 months, the median survival was 14 months. The 1-year survival was 53% and the 2-year survival was 16%.

Actuarial Analysis↗

[Oncogenes and bronchial cancer].

Oncogenes are genes for malignant transformation which correspond to changes, by genetic mutation, of genes which are present in all normal eukaryotic cells, called proto-oncogenes. The latter are involved in physiological functions often controlling growth and cell differentiation. Their mechanism of action and the activation of oncogenes are successively anticipated. These oncogenes are implicated in the majority of cancers and in particular in bronchial carcinoma: the myc-oncogenes (c-myc, N myc, L myc) are primarily activated in small cell carcinomas (CPC), the Ras genes (Ki Ras, Ha Ras) in epidermoid and adeno carcinomas. The intervention of growth factors such as bombesin in CPC and of their receptors such as epithelial growth factor (EGF) in non small cell bronchial carcinomas has been shown, as well as the role of cytogenic abnormalities (deletion of the short arm of chromosome 3). Their relation to oncogenes is discussed. The knowledge acquired on oncogenes in bronchial carcinoma should shed light on the pathogenesis of these cancers and find its next application in the diagnostic, prognostic and therapeutic field.

Bronchial Neoplasms↗