| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
 
|
|
|
||
|
|
Anesth Analg 2003;97:29-34 © 2003 International Anesthesia Research Society
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionAppendix 1References |
|---|
Obstruction of the upper airway occurs frequently in anesthetized, spontaneously breathing children, especially in those with adenoidal hyperplasia. To improve airway patency, maneuvers such as chin lift (CL), jaw thrust (JT), and continuous positive airway pressure (CPAP) are often used. In this study, we examined the comparative efficacy of these maneuvers in children scheduled to undergo adenoidectomy. Sixteen children aged 2–9 yr were anesthetized with sevoflurane. During spontaneous breathing, the flows and pressures in the mask (ma), oropharynx (op), and esophagus (es) were measured simultaneously, and maximal pressure differences during inspiration (
P) were calculated. After baseline recording, CL and JT maneuvers were performed in random order without and with CPAP (5 cm H2O). The observed Pma - Pes of 12.3 ± 3.4 cm H2O at baseline decreased with all airway maneuvers (P < 0.05). This resulted from decreases of Pma - Pop (P < 0.05) and Pop - Pes (P < 0.05) in all interventions except CL, in which Pma - Pop remained similar. In contrast, significant improvements of minute ventilation and maximal inspiratory peak flow (P > 0.05) were observed only with JT (with and without CPAP). We conclude that CL may improve airway patency and ventilation, whereas JT with or without CPAP was the most effective maneuver to overcome airway obstruction in children with adenoidal hyperplasia. IMPLICATIONS: Airway maneuvers are often used in anesthetized children to relieve airway obstruction during spontaneous ventilation. Compared with chin lift and continuous positive airway pressure, the jaw thrust maneuver was the most effective to improve airway patency and ventilation in children undergoing adenoidectomy.
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
|---|
Inhaled induction under spontaneous breathing is an accepted and frequently used practice in pediatric anesthesia. However, the presence of partial or complete airway obstruction may represent a hazard.
In previous studies, we documented the effect of common airway maneuvers, such as chin lift (CL), jaw thrust (JT), and continuous positive airway pressure (CPAP), on airway patency in children with normal upper airway structures undergoing various elective non-ear-nose-throat procedures (1,2). In patients with tonsillar and adenoidal hyperplasia, JT with or without CPAP is effective in alleviating airway obstruction, whereas CL does not improve or even worsens airway patency (3,4). Nonetheless, the size of glottic opening increases in these patients irrespective of which airway maneuver is applied (5).
Therefore, we hypothesized that airway patency during the CL maneuver does not improve because of a persistent obstruction proximal to the oropharynx (above and below the soft palate), whereas during the JT maneuver, airway obstruction is reduced by an improved oral airway (below the soft palate). To test this hypothesis, local pressures were measured at the mask, at the level of the oropharynx, and in the esophagus by pressure-tip catheters to localize the site of obstruction in patients presenting for adenoidectomy.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
|---|
The Ethics Committee of the University Children’s Hospital, Beider Basel, approved the study, and written parental informed consent was obtained. Sixteen children (aged 2–9 yr) scheduled to undergo elective adenoidectomy were enrolled. For all patients, at least one parent witnessed their child snoring, with trouble breathing, apnea, or both. Patients with pulmonary disease, craniofacial dysmorphism, deformities of the chest or spine, or neuromuscular disorders were excluded from the study.
All patients received oral or rectal midazolam (0.3 mg/kg) 15 min before the induction of anesthesia. Routine clinical monitoring was applied. By using a circle system anesthetic machine, inhaled induction of anesthesia was performed with sevoflurane up to 8%. Then, throughout the remainder of the study, the inspiratory concentration was reduced to 5% sevoflurane in a mixture of 50% air and 50% oxygen with a total flow of 4 L/min.
After completion of the induction of anesthesia, the tip of a custom-built 5F silicone catheter mounted with two micro pressure transducers (Camtip®; Camtech, Sandvika, Norway) was advanced transnasally into the esophagus (6). The distal transducer was located at the tip of the catheter, and the proximal transducer was located 14 cm (in children with a height <120 cm) or 16 cm (in children with a height >120 cm) above the distal transducer. The design of the catheter was based on anthropometric data (7) and our own pilot studies. Meticulous care (by visual control) was taken to ensure correct catheter positioning with the proximal transducer located at the level of the middle pharyngeal constrictor muscle just below the uvula (oropharynx). In addition, adequate positioning of the distal transducer was ensured by the absence of direct artifacts elicited by cardiac motion (8). The catheter was guided from the nares across the cheek, where it laid underneath the soft cushion of the face mask (Vital Signs, Inc., Totowa, NJ).
The head of each child was extended on a prefabricated foam cushion to obtain an angle of 110° between the horizontal surface of the operating table and the line connecting the lateral corner of the eye and the tragus (9). Data acquisition was performed during steady-state anesthesia at least 15 min after the induction of anesthesia. After baseline (BL) recordings were made, CL and JT maneuvers with or without CPAP were performed in random order. Airway maneuvers were consistently performed as follows:
- BL: the anesthesiologist held the mask against the face and applied gentle pressure, but the chin was not supported (BL0).
- CL: the anesthesiologist lifted the chin at the inferior border of the mental protuberance with his left hand until the upper and lower rows of teeth were in close contact; however, care was taken not to protrude the mandible (CL0).
- JT: the anesthesiologist displaced the jaws at the mandibular angles with both hands upward and anterior to open the mouth (JT0).
- CPAP: by closing the pop-off valve in the circle system, a pressure of 5 cm H2O was applied to BL, CL, and JT (BL5, CL5, and JT5).
Gas flow was measured immediately proximal to the face mask by using a dual-hotwire anemometer with a dead space of 1 mL (Florian; Acutronic Medical Systems, Hirzel, Switzerland). The same equipment was also used to measure the pressure at the face mask. Pressure and flow measurement devices were calibrated before each experiment. The flow measurement device was calibrated with room air. A correction factor of 0.742 was used to account for the gas mixture actually used during the experiment. Data recordings were made over 30 s, and all data were stored simultaneously in a digital format (Labview; National Instruments Corp., Austin, TX). Reported results are the means of three consecutive respiratory cycles after a steady-state period of 20 s.
Pressure recordings showed sinusoidal waves with peaks and troughs corresponding to inspiration and expiration (Fig. 1). The difference between the maximal and minimal pressure values during inspiration reflected the inspiratory pressure amplitude measured at the mask (Pma), the oropharynx (Pop), and the esophagus (Pes). The differences between these pressure amplitudes in corresponding respiratory cycles were calculated: Pes - Pma, Pop - Pma, and Pes - Pop.
|
Tidal volume was calculated from flow measurements, the accuracy of which may have been impaired because pressure-dependent air leaks at the face mask can occur. To compensate for these variable leaks, an algorithm was applied (Appendix 1). In addition, maximal inspiratory airway resistance was calculated between the esophagus and the oropharynx (Res-op), the oropharynx and the mask (Rop-ma), and the esophagus and the mask (Res-ma) by dividing the maximal pressure difference by the maximal flow during inspiration.
All data were analyzed for normal distribution by the Shapiro-Wilk test; accordingly, data with a normal distribution were analyzed by repeated-measures analysis of variance, and data not having a normal distribution were analyzed by the Friedman test. Post hoc multiple comparison tests were performed with the Bonferroni correction or Wilcoxon’s signed rank test, as applicable. P < 0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
|---|
Eight boys and 8 girls were included in the study: age, 5.4 ± 1.8 yr; weight, 20.2 ± 4.9 kg; and height, 113 ± 12 cm. According to the parents, 14 children had nocturnal snoring, 6 had chronic mouth breathing, and 1 had episodes of apnea.
The maximal pressure differences recorded during inspiration are shown in Table 1. The largest Pes - Pma was observed during BL0. Although Pes - Pma was significantly decreased with the application of CL, the JT maneuver resulted in a significant further decrease of Pes-ma. Moreover, when CPAP was applied, Pes-ma decreased significantly with all interventions.
|
Detailed analysis of the airway pressure proximal to the oropharynx (
Pop-ma) and distal to the oropharynx (Pes-op) revealed the following: 1) All interventions except CL resulted in a significant decrease of Pop-ma when compared with BL0. 2) The application of CPAP decreased Pop-ma under all conditions. 3) The Pes-op decreased with all interventions when compared with BL0. 4) At BL0, BL5, JT0, and JT5, the Pop-ma and Pes-op were of a similar magnitude; in contrast, at CL0 and CL5, a large proportion (approximately 70%) of Pes - Pma resulted from Pop-ma. Calculated airway resistances are shown in Figure 2.
|
Respiratory variables of all children are shown in Table 2. Compared with BL0, maximal inspiratory flow and minute ventilation increased significantly during the JT maneuver (with and without CPAP). In contrast, the CL maneuver (with and without CPAP) did not result in improved ventilation. CPAP application resulted in a significant increase of the respiratory rate. Complete airway obstruction was observed in three subjects at BL0; CL0 resolved the airway obstruction in two of these children, but two children had a new episode of airway obstruction.
|
Heart rates did not differ among the six maneuvers. The mean heart rates (SD) of the 16 subjects were the following: BL0, 112 bpm (10 bpm); CL0, 112 bpm (11 bpm); JT0, 110 bpm (11 bpm); BL5, 112 bpm (10 bpm); CL5, 111 bpm (11 bpm); and JT5, 111 bpm (10 bpm).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
|---|
The results of this study document the frequent occurrence of partial and complete airway obstruction in anesthetized, spontaneously breathing children undergoing adenoidectomy. Resistance proximal and distal to the oropharynx contributed to this obstruction with a similar magnitude. Although the CL maneuver reduced resistance only distal to the oropharynx, CPAP and the JT maneuver improved airway patency both proximal and distal to the oropharynx. However, JT was the only maneuver that resulted in improved ventilation.
Airway obstruction can occur at various anatomic levels of the upper airway, depending on the condition (e.g., sleep, unconsciousness, or anesthesia) (9–12). During anesthesia with inhaled anesthetics or propofol, obstruction distal to the oropharynx is most likely caused by the posterior displacement of the hyoid bone, which leads to a downfolding of the epiglottis that reduces the airway dimension; this is because the rims approach the posterior pharyngeal wall during inspiration (10,13). In addition, anterior displacement of the aryepiglottic cartilages obstructing the laryngeal inlet, a characteristic finding in infants with laryngomalacia (14), can also contribute in anesthetized children (15).
In children, obstruction in the oropharynx is usually caused by large tonsils that cause a decrease in the transverse diameter of the airway during anesthesia (3). Proximal to the oropharynx, obstruction can occur in the nasal or the oral airway (above or below the soft palate). Even a complete obstruction in one of these airways will probably not cause any substantial decrease of overall airflow as long as the other remains open. In children with partial or complete obstruction of the nasal airway caused by adenoid hyperplasia, the patency of the oral airway is crucial. All children in this study had large adenoids and clinical signs of nasal airway obstruction and were therefore at risk of developing complete obstruction when the oral airway was compromised. To study the occurrence of obstruction proximal and distal to the oropharynx and its response to the described maneuvers, we positioned pressure transducers in the esophagus, the oropharynx, and the mask.
Spontaneous breathing under the BL condition, BL0, was characterized by a large difference in the inspiratory pressure amplitude between the mask and the esophagus, well above the physiologic intrapleural pressure swings (range of 2–4 cm H2O) required to overcome the viscoelastic forces of the lung in patients with unobstructed airways (16). These large esophageal pressure amplitudes indicated partial airway obstruction, whereas the absence of airflow in some of the patients gave evidence of total airway obstruction. The pressure differences proximal and distal to the oropharynx were of similar magnitude, suggesting that increased resistances proximal and distal to the oropharynx were contributing equally. The obstruction distal to the oropharynx corroborates with previous findings under anesthesia (3,10,13). The obstruction proximal to the oropharynx can be explained only by impaired airway patency in both the nasal and oral airways. Thus, we speculate that the oral and nasal airways were simultaneously obstructed in these patients: the oral airway by the tongue approaching the soft and hard palate and the nasal airway by adenoidal tissue. These findings in anesthetized children are in agreement with the reported correlation between the size of the adenoids in children and the severity of obstructive sleep apnea (17).
Measures for relieving partial or complete upper airway obstruction include airway maneuvers such as CL, JT, and CPAP. CL and JT resulted in a decrease of the pressure difference between the esophagus and the oropharynx. Both maneuvers exert tension to the strap muscles that lead to a forward displacement of the hyoid bone. As a result, the epiglottis is drawn anteriorly away from the posterior pharyngeal wall by the hyoepiglottic ligament (10,13), resulting in an increase of the cross-sectional diameter of the upper airway (1,3,5,18).
Contrary to their effect distal to the oropharynx, CL and JT differentially influenced airway patency proximal to the oropharynx. Compared with the BL0 level, the CL maneuver did not decrease the resistance proximal to the oropharynx. Moreover, in some patients, the novel occurrence of complete airway obstruction was noted when CL was applied. This finding is in agreement with data obtained in unconscious children, where CL was insufficient to guarantee a free airway in more than 50% of patients (19). The observed deterioration of airway patency during CL in a substantial number of patients may be due to a decreased cross-sectional area of the oral airway. In patients without large adenoids, this increase of oral airway resistance is easily compensated for by the increase of the cross-sectional area of the nasal airway during CL (1,20). In contrast, the significantly reduced airway resistance proximal to the oropharynx induced by the JT maneuver may be caused by the opening of the mouth, the forward displacement of the mandibular angles, and the downward displacement of the chin producing increased oral airway dimensions between the soft palate and the dorsum of the tongue.
CPAP uniformly decreased the pressure differences proximal and distal to the oropharynx during BL, CL, and JT. On the basis of findings obtained in both adult (21) and pediatric populations (3), this mainly correlated with increased lateral and anterior-posterior airway dimensions. Patients with relevant obstructions during the CL maneuver may benefit especially from this pneumatic strut effect of CPAP.
The tidal breathing pattern was significantly influenced by all airway maneuvers examined in this study (Table 2). Minute ventilation and tidal volume increased when JT was applied without CPAP. However, the simultaneous application of JT with 5 cm H2O of CPAP resulted in decreased minute ventilation and tidal volume. This observation corroborates previous findings, in which increasing levels of CPAP of up to 10 cm H2O could cause a decrease in tidal volume (2). It is possible that the imposed expiratory resistive load caused by CPAP cannot be compensated for and results in a decreased respiratory drive.
Several limitations of this study must be noted. 1) All results were obtained under a deep level of anesthesia (sevoflurane 5%). This was necessary to avoid emergence reactions due to the JT maneuver that could elicit painful stimuli by exerting pressure at the mandibular angles. An adequate and constant depth of anesthesia is a mandatory prerequisite for a rational comparison of the effect of various airway maneuvers. The absence of an emergence reaction can be assumed on the basis of the observation of stable heart rates throughout the study. 2) The placement of the microtip pressure transducers in the oropharynx and the esophagus, along with the pressure measurement in the mask, allowed the discrimination of obstructions proximal and/or distal to the oropharynx. Thus, obstruction at the oropharyngeal level—in children, most likely caused by large tonsils—could not be assessed with the design in this study.
In conclusion, the results of this study document that partial or total obstruction occurs frequently in anesthetized children scheduled to undergo adenoidectomies. Airway maneuvers such as CL, JT, and CPAP exert varying effects on airway patency and tidal breathing. CL without CPAP does not improve oral airway patency. JT with and without CPAP is the most effective maneuver to decrease upper airway obstruction.
|
Appendix 1 |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
|---|
The diagram (Fig. 3) shows how tidal volume was calculated from the measurements. The measured flow values were averaged for eight samples. This led to a smooth flow signal, especially for the end of expiration, where flow measurements showed vibrations of 65 Hz. The average flow was corrected with an estimate of the leak rate and integrated over inspiration time.
|
Evidently the resulting tidal volume was influenced by the leak-rate estimation. Leak-rate estimation was determined assuming that mask leak was the only significant loss of air. Therefore, the long-term (at least five breath cycles) average of the leak rate-compensated flow signal had to be close to 0. The leak-flow estimation assumed that it was proportional to the square root of the pressure difference at the mask border. This assumption is consistent with the physical law for calculating flow through a narrow hole. The leak-flow factor kv depends on the size of the leak hole and can change during measurements as the result of small changes in the mask position. Therefore, the leak-flow factor had to be continuously estimated.
The leak flow-factor was estimated as follows. The beginning and end of a breathing cycle were determined from zero crossing of the flow signal. The compensated flow values were integrated (summed) over a complete breathing cycle. If breathing is constant and leak compensation perfect, the value at the end of a cycle approximates 0. A value different from 0 indicates that there must be an uncompensated leak, and a new leak-flow factor can be estimated. An instantaneous adaptation of the leak-flow factor to the new estimate is reasonable only under constant conditions. Because this is not realistic, the leak-flow factor was modified only toward the new estimate. The percentage of modification determines the speed of adaptation; although adding only a small percentage of the difference to the new estimate means that there is a slow adaptation to leak-flow change, it also means that the leak-flow estimation works well under inconsistent breathing patterns. A reasonable adaptation speed for these measurements was aimed at achieving a good leak-flow estimate after 10 breathing cycles.
|
Acknowledgments |
|---|
This study was supported by a grant (3200-056034.98) from the Swiss National Science Foundation. Jeremy Geiduschek was on paid sabbatical leave by the University of Washington School of Medicine, Department of Anesthesiology.
The authors would like to thank C. Affolter for his assistance in computational analysis, Björn Gjersøe for the provision and construction of the micro pressure transducers, Joan Etlinger for editorial assistance, and Jürg Hammer for his constructive support.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
|---|
- Reber A, Wetzel SG, Schnabel K, et al. Effect of combined mouth closure and chin lift on upper airway dimensions during routine magnetic resonance imaging in pediatric patients sedated with propofol. Anesthesiology 1999; 90: 1617–23.[Web of Science][Medline]
- Reber A, Geiduschek JM, Bobbia SA, et al. The effect of continuous positive airway pressure on the measurement of thoracoabdominal asynchrony and minute ventilation in children anesthetized with sevoflurane and nitrous oxide. Chest 2002; 122: 473–8.
[Abstract/Free Full Text] - Reber A, Paganoni R, Frei FJ. Effect of common airway manoeuvres on upper airway dimensions and clinical signs in anaesthetized, spontaneously breathing children. Br J Anaesth 2001; 86: 217–22.
[Abstract/Free Full Text] - Reber A, Bobbia SA, Hammer J, Frei FJ. Effect of airway opening manoeuvers on thoraco-abdominal asynchrony in anaesthetized children. Eur Respir J 2001; 17: 1239–43.
[Abstract/Free Full Text] - Meier S, Geiduschek J, Reber A, et al. The effect of chin lift, jaw thrust and continuous positive airway pressure on the size of the glottic opening and on stridor in anesthetized, spontaneously breathing children. Anesth Analg 2002; 94: 494–9.
[Abstract/Free Full Text] - Skatvedt O. Continuous pressure measurements in the pharynx and esophagus during sleep in patients with obstructive sleep apnea syndrome. Laryngoscope 1992; 102: 1275–80.[Web of Science][Medline]
- Strobel CT, Byrne WJ, Ament ME, Euler AR. Correlation of the esophageal lengths in children with height: application of the Tuttle test without prior oesophageal manometry. J Pediatr 1979; 94: 81–4.[Web of Science][Medline]
- Chartrand DA, Jodoin C, Couture J. Measurement of pleural pressure with oesophageal catheter-tip micromanometer in anaesthetized humans. Can J Anaesth 1991; 38: 518–21.
- Boidin MP. Airway patency in the unconscious patient. Br J Anaesth 1985; 57: 306–10.
[Abstract/Free Full Text] - Safar P, Escarraga LA, Chang F. Upper airway obstruction in the unconscious patient. J Appl Physiol 1959; 14: 760–4.
[Abstract/Free Full Text] - Hudgel DW, Hendricks C. Palate and hypopharynx: sites of inspiratory narrowing of the upper airway during sleep. Am Rev Respir Dis 1988; 138: 1542–7.[Web of Science][Medline]
- Marcus C, McColley SA, Carrol JL, et al. Upper airway collapsibility in children with obstructive sleep apnea syndrome. J Appl Physiol 1994; 77: 918–24.
[Abstract/Free Full Text] - Hammer J, Reber A, Trachsel D, Frei FJ. Effect of jaw-thrust and continuous positive airway pressure on tidal breathing in deeply sedated infants. J Pediatr 2001; 138: 826–30.[Web of Science][Medline]
- Baxter MR. Congenital laryngomalacia. Can J Anaesth 1994; 41: 332–9.[Web of Science][Medline]
- Reber A, Paganoni R, Frei FJ. Airway obstruction due to arytenoid prolapse in a child. Acta Anaesthesiol Scand 1999; 43: 104–6.[Web of Science][Medline]
- Rodarte JR, Rehder K. Dynamics of respiration. In: Fishman AP, section ed. The respiratory system. Macklem PT, Mead J, volume eds. Volume 3: Mechanics of breathing. Baltimore: American Physiology Society, 1986: 131–44.
- Brooks LJ, Stephens BM, Bacevice AM. Adenoid size is related to severity but not the number of episodes of obstructive apnea in children. J Pediatr 1998; 132: 682–6.[Web of Science][Medline]
- Reed WR, Roberts JL, Thach BT. Factors influencing regional patency and configuration of the human infant upper airway. J Appl Physiol 1985; 58: 635–44.
[Abstract/Free Full Text] - Roth B, Magnusson J, Johansson I, et al. Jaw-lift: a simple and effective method to open the airway in children. Resuscitation 1998; 39: 171–4.[Web of Science][Medline]
- Isono S, Tanaka A, Sho Y, et al. Advancement of the mandible improves velopharyngeal airway patency. J Appl Physiol 1995; 79: 2132–8.
[Abstract/Free Full Text] - Schwab RJ, Pack AI, Gupta KB, et al. Upper airway and soft tissue structural changes induced by CPAP in normal subjects. Am J Respir Crit Care Med 1996; 154: 1106–16.[Abstract]
This article has been cited by other articles:
|
|
 |
|
  Y.-C. P. Arai, M. Nakayama, N. Kato, Y. Wakao, H. Ito, and T. Komatsu The Effects of Jaw Thrust and the Lateral Position on Heart Rate Variability in Anesthetized Children with Obstructive Sleep Apnea Syndrome Anesth. Analg., June 1, 2007; 104(6): 1352 - 1355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 American Heart Association 2005 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) of Pediatric and Neonatal Patients: Pediatric Basic Life Support Pediatrics, May 1, 2006; 117(5): e989 - e1004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Part 11: Pediatric Basic Life Support Circulation, December 13, 2005; 112(24_suppl): IV-156 - IV-166. [Full Text] [PDF]
|
|
|
|
|
|
Y.-C. P. Arai, K. Fukunaga, W. Ueda, M. Hamada, H. Ikenaga, and K. Fukushima The Endoscopically Measured Effects of Airway Maneuvers and the Lateral Position on Airway Patency in Anesthetized Children with Adenotonsillar Hypertrophy Anesth. Analg., April 1, 2005; 100(4): 949 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-C. P. Arai, K. Fukunaga, S. Hirota, and S. Fujimoto The Effects of Chin Lift and Jaw Thrust While in the Lateral Position on Stridor Score in Anesthetized Children with Adenotonsillar Hypertrophy Anesth. Analg., December 1, 2004; 99(6): 1638 - 1641. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
