Partial versus maximal forced exhalations in COPD: enhanced signal detection for novel therapies.

BACKGROUND: Evaluation of novel compounds for COPD often relies on FEV1 for signal detection. Partial forced exhalations from end-tidal inspiration (PEFV) might complement FEV1 in identifying such a signal. We examined the prevalence of bronchodilator response (BDR) using PEFV and FEV1 in patients with COPD. METHODS: 110 consecutive COPD patients were tested prospectively with PEFV and maximal expiratory flow before and after inhalation of a short-acting ß2 agonist (salbutamol, 400 µg). Partial flow at 800 ml above residual volume was derived from the PEFV (PF800). Significant changes in PF800 and/or FEV1 were set at the upper 95% confidence interval after placebo (n = 28). RESULTS: Four groups were identified by the presence (+) or absence (-) of a BDR: Group 1 [PF800 (-)FEV1(-)] when no change was observed (n = 31), Group 2 [PF800(+)FEV1(-)] when PF800 alone improved (n = 31), Group 3 [PF800(-)FEV1(+)] when FEV1 alone improved (n = 26), and Group 4 [PF800(+)FEV1(+)] when both variables improved (n = 18). There were 35 non-responders in any parameter, and 75/110 subjects who showed a response in at least one parameter. The changes in PF800 and FEV1 were not correlated suggesting these assess different airway generations. CONCLUSIONS: The use of PF800 increased detection of a BDR in COPD compared to FEV1 alone and may reflect small airway responses. The PEFV maneuver is simple, repeatable and may avoid some of the theoretical disadvantages of FEV1. The role of PF800 for evaluating novel anti-inflammatory agents remains to be determined.

Specificity of amino acid regulated gene expression: analysis of genes subjected to either complete or single amino acid deprivation.

Amino acid deprivation activates the amino acid response (AAR) pathway that enhances transcription of genes containing an amino acid response element (AARE). The present data reveal a quantitative difference in the response to deprivation of individual amino acids. The AAR leads to increased eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation and ATF4 translation. When HepG2 cells were deprived of an individual essential amino acid, p-eIF2alpha and activating transcription factor 4 were increased, but the correlation was relatively weak. Complete amino acid starvation in either Earle's balanced salt solution or Krebs-Ringer bicarbonate buffer (KRB) resulted in activation of transcription driven by a SNAT2 genomic fragment that contained an AARE. However, for the KRB, a proportion of the transcription was AARE-independent suggesting that amino acid-independent mechanisms were responsible. Therefore, activation of AARE-driven transcription is triggered by a deficiency in any one of the essential amino acids, but the response is not uniform. Furthermore, caution must be exercised when using a medium completely devoid of amino acids.

Effect of changing the gravity vector on respiratory output and control.

We studied the respiratory output in five subjects exposed to parabolic flights [gravity vector 1, 1.8 and 0 gravity vector in the craniocaudal direction (Gz)] and when switching from sitting to supine (legs bent at the knees). Despite differences in total respiratory compliance (highest at 0 Gz and in supine and minimum at 1.8 Gz), no significant changes in elastic inspiratory work were observed in the various conditions, except when comparing 1.8 Gz with 1 Gz (subjects were in the seated position in all circumstances), although the elastic work had an inverse relationship with total respiratory compliance that was highest at 0 Gz and in supine posture and minimum at 1.8 Gz. Relative to 1 Gz, lung resistance (airways plus lung tissue) increased significantly by 52% in the supine but slightly decreased at 0 Gz. We calculated, for each condition, the tidal volume changes based on the energy available in the preceding phase and concluded that an increase in inspiratory muscle output occurs when respiratory load increases (e.g., going from 0 to 1.8 Gz), whereas a decrease occurs in the opposite case (e.g., from 1.8 to 0 Gz). Despite these immediate changes, ventilation increased, going to 1.8 and 0 Gz (up to approximately 23%), reflecting an increase in mean inspiratory flow rate, tidal volume, and respiratory frequency, while ventilation decreased (approximately -14%), shifting to supine posture (transition time approximately 15 s). These data suggest a remarkable feature in the mechanical arrangement of the respiratory system such that it can maintain the ventilatory output with small changes in inspiratory muscle work in face of considerable changes in configuration and mechanical properties.

Effect of gravity and posture on lung mechanics.

The volume-pressure relationship of the lung was studied in six subjects on changing the gravity vector during parabolic flights and body posture. Lung recoil pressure decreased by approximately 2.7 cmH(2)O going from 1 to 0 vertical acceleration (G(z)), whereas it increased by approximately 3.5 cmH(2)O in 30 degrees tilted head-up and supine postures. No substantial change was found going from 1 to 1.8 G(z). Matching the changes in volume-pressure relationships of the lung and chest wall (previous data), results in a decrease in functional respiratory capacity of approximately 580 ml at 0 G(z) relative to 1 G(z) and of approximately 1,200 ml going to supine posture. Microgravity causes a decrease in lung and chest wall recoil pressures as it removes most of the distortion of lung parenchyma and thorax induced by changing gravity field and/or posture. Hypergravity does not greatly affect respiratory mechanics, suggesting that mechanical distortion is close to maximum already at 1 G(z). The end-expiratory volume during quiet breathing corresponds to the mechanical functional residual capacity in each condition.

[Anesthesia induction with sevoflurane in adult patients with predictive signs of difficult intubation]. / Induction anesthésique avec le sévoflurane chez le patient adulte avec des signes prédictifs d'une intubation difficile.

OBJECTIVE: This work was carried out to study induction with sevoflurane in adult patients with predictive signs of difficult intubation. STUDY DESIGN: Randomised prospective study. PATIENTS AND METHODS: The study had two parts. Part I: 15 patients without predictive signs of difficult intubation but with a cervical collar. Eight patients were anaesthetised with propofol 3 mg.kg-1 and fentanyl 2 micrograms.kg-1, seven with sevoflurane 8%. Part II: 20 patients with predictive signs of difficult intubation anaesthetised with sevoflurane 8%. RESULTS: In part I, all patients were intubated, the time for intubation was longer with sevoflurane, 6 vs 4 min. They were apneic only in the propofol group. After intubation, 7 cases of coughing (4 severe) occurred in the propofol group and 3 moderate coughing in the sevoflurane group. In part II, one patient experienced considerable agitation after oral airway insertion and was excluded. Other patients were intubated with sevoflurane. Seven patients were intubated with a bougie, three patients through an intubating LMA and one patient with a rigid bronchoscope. The other patients were intubated with a Macintosh blade. The mean time for intubation was 10 +/- 7 min and end tidal sevoflurane concentration after intubation was 4 +/- 0.6%. After intubation, 7 cases of coughing (3 severe) occurred but no desaturation < 95%. No significant haemodynamic variations occurred. CONCLUSION: Induction with sevoflurane 8% allowed tracheal intubation without major incidents. All patients breathed spontaneously. Sevoflurane can be recommended for induction in cases of predictive difficult intubation.

Effect of gravity on chest wall mechanics.

Chest wall mechanics was studied in four subjects on changing gravity in the craniocaudal direction (G(z)) during parabolic flights. The thorax appears very compliant at 0 G(z): its recoil changes only from -2 to 2 cmH(2)O in the volume range of 30-70% vital capacity (VC). Increasing G(z) from 0 to 1 and 1.8 G(z) progressively shifted the volume-pressure curve of the chest wall to the left and also caused a fivefold exponential decrease in compliance. For lung volume <30% VC, gravity has an inspiratory effect, but this effect is much larger going from 0 to 1 G(z) than from 1 to 1.8 G(z). For a volume from 30 to 70% VC, the effect is inspiratory going from 0 to 1 G(z) but expiratory from 1 to 1.8 G(z). For a volume greater than approximately 70% VC, gravity always has an expiratory effect. The data suggest that the chest wall does not behave as a linear system when exposed to changing gravity, as the effect depends on both chest wall volume and magnitude of G(z).

Changes in lower limb volume in humans during parabolic flight.

Variations in gravity [head-to-foot acceleration (Gz)] induce hemodynamic alterations as a consequence of changes in hydrostatic pressure gradients. To estimate the contribution of the lower limbs to blood pooling or shifting during the different gravity phases of a parabolic flight, we measured instantaneous thigh and calf girths by using strain-gauge plethysmography in five healthy volunteers. From these circumferential measurements, segmental leg volumes were calculated at 1, 1.7, and 0 Gz. During hypergravity, leg segment volumes increased by 0.9% for the thigh (P < 0.001) and 0.5% for the calf (P < 0.001) relative to 1-Gz conditions. After sudden exposure to microgravity following hypergravity, leg segment volumes were reduced by 3.5% for the thigh (P < 0.001) and 2.5% for the calf (P < 0.001) relative to 1.7-Gz conditions. Changes were more pronounced at the upper part of the leg. Extrapolation to the whole lower limb yielded an estimated 60-ml increase in leg volume at the end of the hypergravity phase and a subsequent 225-ml decrease during microgravity. Although quantitatively less than previous estimations, these blood shifts may participate in the hemodynamic alterations observed during hypergravity and weightlessness.

Pulmonary diffusing capacity and pulmonary capillary blood volume during parabolic flights.

Data from the Spacelab Life Sciences-1 (SLS-1) mission have shown sustained but moderate increase in pulmonary diffusing capacity (DL). Because of the occupational constraints of the mission, data were only obtained after 24 h of exposure to microgravity. Parabolic flights are often used to study some effects of microgravity, and we measured changes in DL occurring at the very onset of weightlessness. Measurements of DL, membrane diffusing capacity, and pulmonary capillary blood volume were made in 10 male subjects during the 20-s 0-G phases of parabolic flights performed by the "zero-G" Caravelle aircraft. Using the standardized single-breath technique, we measured DL for CO and nitric oxide simultaneously. We found significant increases in DL for CO (62%), in membrane diffusing capacity for CO (47%), in DL for nitric oxide (47%), and in pulmonary capillary blood volume (71%). We conclude that major changes in the alveolar membrane gas transfers and in the pulmonary capillary bed occur at the very onset of microgravity. Because these changes are much greater than those reported during sustained microgravity, the effects of rapid transition from hypergravity to microgravity during parabolic flights remain questionable.

A review of applications of recombinant DNA techniques in diagnosis and treatment of dental diseases.

The goal of regeneration in oral maxillofacial reconstruction is replacing the previous goal of repair. Many advances in treatment and diagnosis have taken place in medicine and dentistry with the advent of DNA technology. The purpose of this paper is to provide the dental practitioner an overview of some of the medical research using recombinant DNA technology and its potential use in dentistry.

Respiratory mechanics before and after late artificial surfactant rescue.

OBJECTIVE: To assess the effect of late administration of synthetic surfactant (Exosurf) on the ventilatory function of premature infants with hyaline membrane disease (HMD). METHODOLOGY: Prospective non-randomized study in the Neonatal Intensive Care Unit (NICU) of a major referral hospital. The patients included two groups of premature infants with a birthweight between 750 and 2000 g who developed HMD. In group 1 with moderate to severe HMD, 2 x 5 mL/kg doses of Exosurf were given 12 h apart (first dose given at a mean age of 18.7 +/- 3.4 h [mean +/- s.e.m.]). In group 2 with milder HMD, no surfactant was given. RESULTS: Significant reductions (P < 0.05) in the fraction of inspired oxygen (FIO2) occurred 6 h after surfactant administration (24 h of life) and by 48 h (64 h of life) in group 2. These improvements in gas exchange preceded improvements in passive respiratory compliance which occurred 24 h after surfactant (42 h of life) and by 72 h (88 h of life) in group 2 (P < 0.01). In both groups pulmonary resistance increased and was significant (P < 0.05) by 48 h (66 h of life) in group 1. CONCLUSIONS: Synthetic surfactant given as late as a mean age 18.7 +/- 3.4 h still improves gas exchange but these early improvements cannot be completely explained by modifications of respiratory compliance.

Is proximal airway pressure a good reflection of peripheral airspace pressure in infants and children models under HFJV?

This experimental study was carried out to determine if an alveolar positive end-expiratory pressure (PEEP) could occur during high frequency jet ventilation (HFJV) in infants, and if tracheal pressure is a good estimation of alveolar pressure. We used physical models simulating a 1.5 kg premature (P), a 3 kg newborn (N) and a 6 kg child (C) with normal compliance and normal resistance. Moreover, in the N model, we used two different resistances and lung compliance heterogeneity was studied in the P model. Pressure was measured simultaneously in the tube simulating trachea (Paw) and in the bottle simulating the lung (Palv). HFJV was performed either via an endotracheal tube (ETT) or via a long catheter as in laryngoscopy. The ratio of injection time upon cycle duration (Ti/Ttot) was 20% or 30%, jet frequency was altered from 150 to 300 min-1 and the driving pressure was set as in clinical practice (0.5 and 0.6 bar). PEEP occurred mainly in N (1.1 to 3.2 cm H2O) and C models (0 to 3.5 cm H2O). It was inversely related to expiratory time (Te). The end-expiratory pressure drop between Palv and Paw (delta EEP) was higher in N and increased from 0.5 to 2 cm H2O with the shortening of Te and with airway resistances, i.e. the presence of ETT. In the heterogeneous model, PEEP and delta EEP were greater in the higher compliance alveolus. This study shows that the end-expiratory Palv is underestimated by end-expiratory Paw.(ABSTRACT TRUNCATED AT 250 WORDS)

Laparoscopic excision of a benign gastric tumor.

A successful laparoendoscopic excision of a 3-cm leiomyoma of the stomach is reported. Review of related literature and suggested technique and methods for this procedure are described.

Respiratory muscle function in trained and untrained adolescents during short-term high intensity exercise.

The breathing pattern and respiratory muscle function were investigated in ten trained and ten untrained adolescents (aged 15-16 years) while undergoing an incremental intensity exercise test on a cycle ergometer up to 80% maximal oxygen consumption (VO2max), maintained to exhaustion. Before and after exercise, maximal inspiratory (PImax) and expiratory (PEmax) pressures were measured at residual volume and total lung capacity, respectively. During exercise, the breathing pattern [tidal volume (VT), respiratory frequency (fR), ventilation] and the relative contribution of ribcage and abdomen to VT were assessed using inductance plethysmography. Electromyographic activities of transversus abdominis (EMGtr) and diaphragm (EMGdi) muscles were recorded and analysed during exercise. There was a difference in the change in the pattern of breathing between the trained and the untrained group; fR increased significantly (P < 0.05) at 40% VO2max for the untrained group. Before exercise there was no difference in the maximal respiratory pressures. Up to 60% and 80% VO2max, transversus abdominis and diaphragm muscle activity increased significantly in the trained adolescents. However in this group, no evidence of respiratory muscle fatigue appeared: PImax, PEmax and the frequency spectrum of EMGtr and EMGdi were not altered by exercise up to exhaustion. In the untrained group, who had high ventilatory responses, expiratory muscle function was unchanged at the end of the exercise, but signs of inspiratory muscle fatigue appeared in that PImax was significantly decreased after exercise.

EMG study of respiratory muscles in humans immersed at different water temperatures.

The electromyograms of the rectus abdominis (EMGra) and of the diaphragm (EMGdi) have been recorded on human subjects immersed at two bath temperatures (TW), 25 and 40 degrees C. The recordings were obtained during a calibrated isometric contraction sustained for 20 s against a closed stopcock at functional residual capacity (FRC) level for EMGra (expiratory effort) and at pulmonary volume greater than 90% vital capacity for EMGdi and EMGra (inspiratory effort). After eliminating the electrocardiographic artifact, the EMG signal was processed to obtain its root-mean-square (rms) value and three parameters of its frequency spectrum, total energy (Etot), centroid frequency (fc), and high-to-low ratio (H/L). The results show that EMGdi is not modified by TW. On the other hand rms and Etot of EMGra are always increased at TW = 25 degrees C compared with TW = 40 degrees C, whereas fc and H/L decrease with temperature during the expiratory effort at FRC level but do not vary during inspiratory effort at high pulmonary volume. These results, compared with those previously published for cooled limb muscles, show that TW can elicit EMG alterations on the superficial respiratory muscles through two mechanisms, an intrinsic mechanism due to the local variation in muscle temperature and an extrinsic mechanism acting upon the control system of the muscle contraction. Linked alterations of the muscular mechanical activity probably account for the observed effects of TW on the statics and the dynamics of the pulmonary volumes.

Effects of water temperature on pulmonary volumes in immersed human subjects.

Pulmonary volumes and capacities have been measured at three water temperatures (Tw = 25, 34, 40 degrees C) in standing subjects immersed up to the shoulders. The comparison of data obtained in air with those obtained in thermoneutral immersion (Tw = 34 degrees C) confirms the results previously published in several studies. The comparison of data obtained in immersion at different Tw shows: 1. A significant decrease in vital capacity (VC) with bath temperature (VC 40 degrees C greater than VC 34 degrees C greater than VC 25 degrees C). The same decrease is observed in the inspiratory reserve volume (IRV) while the expiratory reserve volume (ERV), the residual volume (RV) and the functional residual capacity (FRC) do not vary. 2. A significant decrease in maximum breathing capacity (MBC) with bath temperature (MBC 40 degrees C greater than MBC 25 degrees C). 3. A significant increase in tidal volume (VT) in cold or hot water compared to thermoneutral water (VT40 degrees C greater than VT34 degrees C; VT34 degrees C less than VT25 degrees C) during quiet breathing. Breathing frequency does not change, thus ventilation (V) follows the same evolution as VT. The relative abdominal (ABD) contribution to VT, estimated by a double belt inductance plethysmograph, is reduced at Tw = 25 degrees C but unchanged at Tw = 40 degrees C compared to thermoneutral bath. Beside variations in the metabolic state, the variations of the pulmonary volumes as a function of Tw are estimated to be mainly due to alterations in respiratory muscles functioning.

A graphic analysis of respiratory heat exchange.

A new graphic representation of respiratory heat exchange is proposed using the concept of equivalent temperatures directly related to enthalpy values. On such a diagram it is possible to 1) compute the value of the heat exchange (delta H) knowing the inspired temperature (TI) and the partial pressure of water vapor (PIH2O) [or the relative humidity (rhI)] of inspired gas; 2) estimate the variation in delta H following a given variation in TI and PIH2O or, inversely, to choose the variation in TI and PIH2O necessary to obtain a given variation in delta H; 3) dissociate inspiratory and expiratory exchanges and to evaluate the efficiency of the respiratory heat exchange process in different environmental situations; and 4) easily compare the results of different studies published on respiratory heat exchanges in humans or other animal species.