70:117-123, 1976 Copyright © 1976 by The Williams & Wilkins Co.
Vol. 70, No.1 Printed in U.S.A.
GASTROENTEROLOGY
CLINICAL TRENDS AND TOPICS FACTORS DETERMINING PRESSURE MEASUREMENT ACCURACY BY INTRALUMINAL ESOPHAGEAL MANOMETRY WYLIE J. DODDS, M.D., JOHN J. STEF, M.E.M.S., AND WALTER J. HOGAN, M.D. Departments of Radiology and Medicine, The Medical College of Wisconsin, Milwaukee, Wisconsin
Measurement accuracy represents an important problem for all physicians using esophageal pressure determinations for clinical or investigative assessment of esophageal motor function. Although intraluminal manometry is generally regarded as providing sophisticated quantitative assessment of esophageal motility, the examination, as currently performed, often yields only semiquantitative information. Inaccurate esophageal pressure measurement causes two major problems: (1) measurement artifact, and (2) measurement insensitivity. In some circumstances, apparent differences in esophageal pressure values between subject groups may represent measurement artifact rather than real physiological or pathological differences. In contrast, measurement insensitivity may obscure real differences in esophageal pressures existing between subject populations, causing such differences to go unrecognized. Clearly, reduction or elimination of measurement inaccuracy is desirable. We believe that the instrumentation and methodology are now available to achieve accurate quantitation of esophageal pressure activity. Esophageal pressure values obtained by manometry are determined by several different factors, including: recording system performance fidelity, recording technique, scoring method, and conditions existent during manometry. All these factors must be dealt with satisfactorily in order to achieve precise esophageal pressure measurements.
Instrumentation In the late nineteenth centrury esophageal pressure studies were first performed by Kronecker and Meltzer 1 using intraluminal balloons. The balloon method underwent modification,2, a but remained the major technique for recording esophageal motor activity until the early 1950's. Because this cumbersome method featured amplitude lag at high frequencies, and sphincter pressure varied with different balloon diameters,4-6 investigators sought other recording methods. In the 1950's Ingelfinger's group in Boston,7, 8 Code Received March 5, 1975. Accepted July 25, 1975. This work was supported, in part, by the Clinical Research Centers Program of the Division of Research Sources, National Institutes of Health, and by United States Public Health Service Research Grant No.1 ROl AM 15540.
and co-workers at the Mayo Clinic,9, 10 and others 11, 12 began to record intraluminal esophageal pressure using noninfused, open-tipped, water-filled catheters. Widely used for over a decade, this method was subsequently shown to record inaccurately due to mucosal sealing of the catheter recording orifices. Although several reports 12 -15 briefly described infused catheter, a technique in the 1950's, the catheter infusion method did not become established until the mid 1960's.5, 16, 17 Initially, the infusion technique was used primarily for measuring resting pressure within the lower esophageal sphincter. Slow infusion rates of a few microliters per minute were considered sufficient to achieve recording accuracy. For the first time, meaningful correlations were found between sphincter pressure and symptoms of gastroesophageal reflux,s, 17 and between sphincter pressure and sphincter strength. 18 In 1970 Pope 19 demonstrated that the slow infusion technique, seemingly satisfactory for measuring resting sphincter pressure, was inadequate for accurate measurement of transient peristaltic pressure peaks within the esophageal body_ From in vitro model data, he suggested that a catheter infusion rate of 2.4 ml per min was needed to record esophageal body peristaltic pressure peaks accurately. Using this infusion rate, regional peristaltic pressure amplitudes were shown to be reproducible in normal subjects. 19 Subsequently, Stef and co-workers 2o -ao demonstrated that Harvard pump infusion rate settings up to 12 ml per min were necessary to achieve recording accuracy in the proximal, striated muscle portion of the esophagus. From this work, and from the studies of others, 19,24-27 several important concepts have emerged relating to the recording performance of infused catheter manometric systems. 1. Recording fidelity is governed not only by recording system performance, but also by the character of the pressure event being recorded. For esophageal pressure waves, recording fidelity is inversely related to wave amplitude (Amp), and directly related to wave duration (Dur). On infusion manometry, recording fidelity is determined primarily by the total compliance (Camp) or deformability of the recording system 2a, 27 and the catheter infusion rate (lR). These relationships are readily formulated as follows:
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equals or exceeds the upstroke rise rate of the pressure complex being recorded. 22, 23 This fact establishes a Amp Camp simple test whereby the manometrist may check the 2. The major cause of recording error on infusion recording characteristics of his infused catheter system. 23 manometry is recording system compliance. , 27 Eso- The rate of pressure rise within the infused system is phageal contractions create circularly oriented forces recorded during catheter occlusion (fig. 1). Comparison which tend to seal a catheter recording orifice, thereby of the resultant pressure rise rate, measured in mm Hg causing inaccurately low pressure recording. Recording per sec, with peristaltic pressure rise rates known to accuracy, however, can be obtained by infusing the occur in the human esophagus (fig. 2) reveals whether or catheter at a rate sufficiently rapid to prevent sealing. not the recording system tested has the capability for During the critical interval of a rapid pressure transient, high fidelity esophageal pressure recording. 23 To insure however, recording system compliance reduces the effec- recording accuracy, a pressure rise rate ~ 150 mm Hg per tive catheter infusion rate. Total system compliance sec is needed in the thoracic esophagus, whereas a rate ~ includes the compliances of the infusion pump, mano- 500 mm Hg per sec is desirable in the cervical esophagus. metric catheter, and volume displacement transducer to If the recording system rise rate is too low, the system which the catheter is connected. Although polyvinyl will not track esophageal pressure rises accurately. In catheters are slightly distensible, the major villain this case, system performance may be improved by: (1) causing compliance in currently used infusion systems decreasing compliance, i.e. using greased syringes or a is the infusion pump.23 During pressure transients, better pump, or (2) increasing infusion rate (fig. 3). We conventional infusion pumps fail to deliver fluid at the believe that the inherent pressure rise rate value of a infusion rate selected, and account for up to 85% of total system represents a more precise indicator of system system compliance. Pump compliance has two compo- performance than the infusion rate setting, and suggest nents: the infusion syringe and the pump gear train. that rise rate values be included in future investigative During pressure transients, fluid dissects along the studies using esophageal manometry. syringe barrel, causing small fluid losses. Additionally, A few workers have used subminiature intraluminal gear train play is taken up during dynamic loading. transducers to record esophageal pressure. 10, 24, 26, 31-34 In These compliances can be reduced, but not eliminated, 1953, Butin et al. 32 reported their experience using a by using greased syringes and heavy duty pumps. A Gauer 35 differential transformer for esophageal motility recent report describes a new hydraulic infusion system, studies. A strain gage intraluminal transducer was which virtually eliminates pump compliance, thereby described by Millhon and co-workers 34 in 1968. During achieving accurate recording of esophageal pressure the past several years, transducer pressure probes suitawaves at an infusion rate of about 0.5 ml per min or less. 28 When infusion pump compliance is minimized, A mm catheter compliance becomes the major compliance Hg source in the manometric system. Catheter compliance 200 depends upon the type of material, wall thickness, luminal diameter, and length of the manometric catheter. Consequently, catheter compliance is decreased by using minimally elastic, thick walled catheters of the B !! shortest length and smallest internal diameter feasible. ~ 100 Deformability of modern volume displacement trans~ ducers is negligible; fluid displacement of about 0.05 ~l causes pressure rises in the 100 mm Hg range. 3. A third important concept concerning recording fidelity is system frequency response. With infused catheter systems, low catheter frequency response represents an important factor which limits recording 1.0 2.0 fidelity. The frequency response for polyvinyl catheters TIME (sec.) is flat to only 1 to 2 Hz.25 Fortunately, the maximal freFIG. 1. Schematic of catheter occlUSIOn test for measuring inherent quency response of esophageal pressure events is less pressure rise rate. During catheter infusion, each catheter in the than 1 Hz.29 Consequently, an infused catheter system manometric recording assembly may be occluded with the thumb at its has the potential to achieve accurate esophageal pres- distal orifice (A) or proximally with a clamp (B). The first method sure recording when the system is optimally utilized. 23 determines performance of the entire infusion system, whereas the The infused catheter system, however, is not capabel second method determines system performance exclusive of the of accurate pharyngeal recording. 30 Pharyngeal pres- manometric catheter. No infusion rate is given for the schematic sure transients occur at frequencies up to 5 Hz, a range pressure tracing because the actual pressure curve varies for different recording systems depending on compliance. For conventional syringejust beyond the recording capability of infused catheter pump infusion systems, pressure rise rate is often nonlinear above 100 system. mm Hg. In the example shown, the AP/At for the primary slope is 100 4. Another important concept is pressure rise rate mm Hg per sec. Average slopes can also be measured to include the (ilP/ilt). Recording fidelity is achieved only when the higher pressure ranges, but in practice such AP/At values are quite inherent pressure rise rate of an infused catheter system similar to the rise rate of the primary slope. Recording Fidelity
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FIG. 2. Regional peristaltic pressure rise rates. Schematic represent ation of peristaltic pressure sequence associated with a wet swallow (WS ). The pressure curves were drawn from mean values obtained in healthy young adults. 23 The dotted lines indicate the pressure rise rate slope. Regional rise rate values given as x ± 1 so are shown on the right. For a given esophageal region, an infusion system rise rate 2 so above the mean regional value is likely to achieve recording fidelity. Inspection of the data suggests that a system rise rate of 150 mm Hg per sec is needed in the thoracic esophagus, whereas a capability of 500 mm H g per sec is desirable for the cervical esophagus.
ble for esophageal manometry have become available commercially (Esophageal Probe 31, Honeywell Biomedical; Mikro-tip Pressure Transducer, Millar Instruments, Inc.). Experience with these transducers, however, is limited (References 23, 26 and RK Goyal, Personal Communication) and such instrumentation has not yet achieved either general acceptance or use. The major advantage of intraluminal transducers is that their high frequency response, flat to several thousand Hz, far exceeds the response necessary for accurate esophageaF3 as well as pharyngeal pressure recording. 30 Additionally, the cumbersome plumbing required for infused catheter manometry is eliminated. Because hydraulic effects are absent, pressures can be recorded accurately with the subject in any position. Disadvantages of intraluminal transducer systems include some base line drift, the potential for temperature sensitivity, and inflexibility in manometric assembly configuration. Durability during daily usage has yet to be established. Nevertheless, the technology is available to perfect reliable intraluminal transducers suitable for esophageal pressure recording. High fidelity esophageal pressure recording is now possible using either a "well tuned" infused catheter system or an intraluminal transducer system. 23 Regardless of the system used, accurate esophageal pressure recording should permit more meaningful evaluation of esophageal function in both health and disease. Once
normal regional peristaltic pressure values, corrected for age and sex, are determined, high fidelity manometry is likely to be effective for diagnosing hitherto unsuspected esophageal motor abnormalities. Rather than simply assessing gross motor dysfunction, such as decreased incidence, regional absence, or total absence of peristalsis, high fidelity esophageal manometry may diagnose subtle quantitative abnormalities of peristaltic contraction strength. Analogous to arterial hypertension and hypotension, esophageal disorders featuring hypertensive or hypotensive peristaltic pressure amplitudes can be anticipated.
Recording Technique The importance of recording technique primarily concerns sphincter pressure recordings during resting conditions and peristalsis. Because the lower esophageal sphincter (LES), 36-38 and possibly the upper esophageal sphincter (UES},39 make oscillatory, oral-aboral movements in rhythm with respiration, the sphincter pressure measured depends on recording technique. The conventional station pull-through method for measuring resting LES pressure features incremental withdrawal of a recording sensor through the sphincter, pausing for 15 sec or longer at each sensor station (fig. 4A) . Several studies suggest that the resultant pressure tracing is partially artifactual because the sphincter makes respiratory movements relative to the pressure sensor. 38, '0 For this reason, station pull-through tracings often provide only an approximation of true LES pressure . Pressure oscillations recorded from the sphincter segment are caused primarily by respiratory sphincter movement rather than transmitted pressure from the surrounding abdominal or thoracic cavity .38 An alternate method for recording resting sphincter pressure is a rapid, continuous withdrawal technique during susmm Hg
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TIME (sec.) FIG. 3. Obtaining satisfactory performance of the infused catheter manometric system . In this example, the manometrist wants to record esophageal peristalsis accurately in the thoracic esophagus. For this purpose the recording system should be able to generate a rise rate of 150 mm Hg per sec (dotted line), as discussed in the legend of figure 2. Initial testing of the manometric system infused at 1.6 ml per min, however, reveals an inherent LlP/Llt of only 50 mm Hg per sec . Greasing the infusion syringe improves performance, but the desired LlP/Llt of 150 mm Hg per sec is still not reached. Increasing the infusion rate to 3.2 ml per min, however, now yields the desired rise rate.
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CLINICAL TRENDS AND TOPICS A. Station Pull·through Technique mm
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FIG. 4. Pressure tracings of resting lower esophageal sphincter (LES) pressure obtained using two different pull·through techniques: Expirations and distance of the recording sensor from the nares are shown along the bottom of each part of the figure. The pressure inversion point is notated as PIP. A. Conventional station pull-through technique. Intrinsic LES pressure, taken as the LES to gastric pressure gradient, is often scored from Station pull-through-tracings as the difference between mean maximal LES pressure (a') and mean gastric pressure. Others score LES pressure at end expiration (b') or end inspiration (c'). Note, however, that end expiration LES pressure is a trough distal to PIP and a peak proximal to PIP. The converse is true of end inspiratory pressure. Measurements a, b, and c yield three different values. B. Rapid pull-through technique. The LES pressure tracing obtained by rapid pull-through provides precise end points for measurement, and the reasonable methods of scoring LES pressure are reduced to one (d).
pended respiration. 6, 41-44 This technique yields a smooth curve without oscillations (fig. 4B). Theoretically, the continuous withdrawal method provides an accurate longitudinal profile of pressure distribution within the LES.44 Of course, the recording system used must be capable of recording the LES pressure profile accurately. Another problem relevant to recording methodology concerns the radial pressure asymmetry demonstrated to exist in both the LES 45-47 and UES. 48 Unless taken into account, radial pressure asymmetry may cause spurious between pull-through variations in resting sphincter pressure. Several methods have been developed to deal with this problem. Waldeck and co-workers 41 ,42 use a single catheter with four radial orifices. This method always records the lowest radial sphincter pressure "seen" by any of the four recording orifices. Kaye and co-workers 49 describe a transducer device which measures mean radial sphincter pressure. Lastly, mean, low,
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or high radial sphincter pressure may be determined by using multiple fused catheters with radially oriented recording orifices. Using this latter method, Dodds and co-workers50 have shown that resting LES pressure in normal subjects is reproducible when measured on two or more occasions. A third problem relating to recording technique is sphincter motion during sphincter relaxation. During primary peristalsis, both the LES38.51-53 and UES54 make dramatic oral excursions relative to recording sensors anchored at resting sphincter position. Although sphincter relaxation does in fact accompany peristalsis, manometric recordings of sphincter relaxation obtained by conventional methods are primarily artifactual. 38 A true recording of sphincter relaxation would be recorded only if the sphincter were fixed in position or if the sensor tracked the sphincter during its movement. Except with LES fixation after hiatal hernia repair, these conditions probably seldom exist during clinical manometry. Two partial solutions, however, are available to substantiate sphincter relaxation. First, manometric assembly design may include several closely spaced recording orifices which, when placed immediately proximal to a sphincter, transiently record from the sphincter segment during its peristaltic oral excursion. Second, a rapid pullthrough maneuver may be performed during the anticipated interval of sphincter relaxation.
Scoring Method Another factor affecting esophageal pressure determination is the method used to score the manometric pressure tracings. For example, small but significant differences in peristaltic wave velocity e){ist, depending on whether wave velocity is calculated from pressure wave onset or wave peaks. 55 Differences in scoring method also cause significant differences in LES pressure values measured from sphincter tracings obtained by the station pull-through technique (fig. 4A). LES pressure on such tracings has been scored as end expiratory, end inspiratory, or as mean pressure. Some workers refer maximal LES pressure to gastric pressure, whereas others use atmospheric pressure as zero reference. At present, a single method is not universally accepted as a standard. 56 Each method yields a different value,5 probably none of which is entirely accurate. 40 Further, these methods generate considerable intra-observer and interobserver scoring error. 44 , 57 Tracings of resting LES pressure obtained by the continuous withdrawal technique (fig. 4B) seem to minimize observer scoring error. 44 Because of the difficulties and vagaries inherent in sphincter pressure measurement, blind scoring design is desirable for investigative studies evaluating sphincter pressure. Without blind scoring, inadvertent observer bias is likely, particularly when anticipated differences or changes in sphincter pressure are small. The problems and disagreements concerning the best method for recording and scoring esophageal sphincter pressure clearly need resolution. We support Ingelfinger's suggestion that: "Much could be accomplished, one suspects, if both medical and surgical investiga-
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tors would agree on standardized methods for measuring esophageal pressure. "58
Study Conditions Accrued evidence indicates that esophageal pressures are determined, in part, by the specifics of the manometric examination. Peristaltic variables such as pressure wave amplitude, duration, and velocity depend on the swallowing modality and character of a swallowed bolus. Peristaltic variables are influenced by bolus volume,55 consistency!9 and temperature. 60 For example, peristalsis in normal subjects following a wet swallow features a greater incidence, higher pressure wave amplitude, and slower wave velocity than peristalsis associated with a dry swallow. 55. 61 Historically, dry swallows were used at manometry to induce peristalsis. Wet swallows, however, are a more reliable method than dry swallows for inducing peristalsis,55 and also serve to normalize the manometric and roentgen examinations of esophageal motor function. 62 Peristalsis may also be affected by changes in intra-abdominal pressure. When a bolus is present, increases in abdominal pressure cause increased peristaltic wave amplitude, increased wave duration, and decreased wave speed. 63 These findings further demonstrate that the quantitative features of peristalsis are not fixed, but rather are partially a function of the conditions existing during manometry. Sphincter pressure is also affected by the specific conditions existent during manometry. LES pressure, for instance, is influenced by intra-abdominal pressure, 64-67 subject position,68 and manometric assembly diameter.43, 69-72 Generally, LES pressure increases with large assembly diameters.43, 71 Assembly diameter also affects UES pressure and peristaltic pressure amplitudes in the esophageal body. 72 These observations appear to be best explained by radial stretch, which affects the length-tension characteristics of circular esophageal muscle. Presently, the specifics of esophageal manometry remain unstandardized and often unspecified. It is hoped that a consensus will emerge in the future concerning items such as optimal swallowing modality and assembly diameter. For the present, esophageal pressure values should be referred to the specific conditions of the manometric examination, especially swallowing modality and assembly diameter. Unless these details are provided, esophageal pressure values are as ambiguous as a gas pressure measured at an unspecified gas temperature and volume. Conclusion Accuracy in esophageal pressure measurement is determined by instrumentation performance, recording technique, and scoring method. The specific procedural details of manometry, such as swallowing modality, subject position, and recording assembly diameter also dictate the actual pressure values recorded. All the above factors must be considered to achieve precise esophageal pressure values. We believe that the instrumentation, techniques, and methods are currently available to elevate esophageal manometry to a truly
quantitative examination of esophageal motor activity. 73 After peristaltic pressure values in normal subjects are established, manometric diagnosis of subtle esophageal motility disturbances featuring hypotensive or hypertensive peristaltic pressures may become commonplace. Development and standardization of methods to record and score esophageal sphincter pressure accurately are also needed. Improved methods will undoubtedly result in more reproducible data, less investigator disagreement, and wider acceptance of significant results. REFERENCES 1. Kronecher H, Meltzer S: Der Schluckmechanismus, seine Erregung and seine Hemmung. Anat Physiol (Physiol Abstr) (suppl):328-362, 1893 2. Ingelfinger F J, Abbott WO: Intubation studies of the human small intestine: Diagnostic significance of motor disturbances. Am J Dig Dis 7:468-474, 1940 3. Hightower NC Jr, Code CF, Maher FT: A method for the study of gastro-intestinal motor activity in human beings. Proc Staff Meet Mayo Clin 24:453-462, 1949 4. Brody DA, Quigley JP: Registration of digestive tract intraluminal pressure. Methods Med Res 4:109-123, 1951 5. Pope CE II: A dynamic test of sphincter strength: its application to the lower esophageal sphincter. Gastroenterology 52:779-786, 1967 6. Rinaldo JA Jr, Levey JF: Correlation of several methods for recording esophageal sphincter pressures. Am J Dig Dis 13:882-890, 1968 7. Sanchez GC, Kramer P, Ingelfinger FJ: Motor mechanisms of the esophagus, particularly of its distal portion. Gastroenterology 25:321-332, 1953 8. Ingelfinger FJ, Kramer P, Sanchez GC: Gastroesophageal vestibule, its normal function and its role in cardiospasm and gastroesphageal reflux. Am J Med Sci 228:417-425, 1954 9. Creamer B, Andersen HA, Code CF: Esophageal motility in patients with scleroderma and related diseases. Gastroenterologia 86:763-775, 1956 10. Hightower NC Jr: The physiology of symptoms: swallowing and esophageal motility. Am J Dig Dis 3:562-583, 1958 11. Sleisenger MH, Davidson M, Pert JH, Almy TP: Recent advances in physiology of the esophagus. N Y State J Med 55:2747-2754, 1955 12. Texter EC Jr, Smith HW, Moeller HC, Barborka CJ: Intraluminal pressures from the upper gastrointestinal tract: correlations with motor activity in normal subjects and patients with esophageal disorders. Gastroenterology 32: 1013-1024, 1957 13. Quigley JP,. Brody DA: A physiologic and clinical consideration of the pressures developed in the digestive tract. Am J Med 13:73-81, 1952 14. Lorber SH, Shay H: Technical and physiological considerations in measuring gastrointestinal pressures in man. Gastroenterology 27:478-487, 1954 15. Pert JH, Davidson M, Almy TP, Sleisenger MH: Esophageal catheterization studies. 1. The mechanism of swallowing in normal subjects with particular reference to the vestibule (esophago-gastric sphincter). J Clin Invest 38:397-406, 1959 16. Harris LD, Winans CS, Pope CE II: Determination of yield pressures: a method for measuring anal sphincter competence. Gastroenterology 50:754-760, 1966 17. Winans CS, Harris LD: Quantitation of lower esophageal sphincter competence. Gastroenterology 52:773-778, 1967 18. Cohen S, Harris LD: Lower esophageal sphincter pressure as an index of lower esophageal sphincter strength. Gastroenterology 58: 157 -162, 1970 19. Pope CE II: Effect of infusion on force of closure measurements in the human esophagus. Gastroenterology 58:616-624, 1970
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20. Stef JJ, Linehan JH, Dodds WJ, Hogan WJ: Pressure measurements in clinical esophageal motility studies: an analysis of the infused catheter technique (abstr.). Proc Ann ConfEngl Med BioI 14:220, 1972 21. Stef JJ: Intraluminal pressure measurements during esophageal peristalsis: an analysis of the infused catheter technique. Master's Thesis in Mechanical Engineering, 1973 22. Stef JJ, Dodds WJ, Hogan WJ, Linehan JH: Esophageal manometry: component analysis of systems used to record intraluminal pressure. Proceedings of the Fourth International Symposium on Gastrointestinal Motility. Vancouver, Mitchell Press, Ltd, 1974 P 337-346 23. Stef JJ, Dodds WJ, Hogan WJ, Linehan JH, Stewart ET: Intraluminal esophageal manometry: an analysis of variables affecting recording fidelity of peristaltic pressures. Gastroenterology 67:221-230, 1974 24. Code CF, Schlegal JF: The pressure profile of the gastro-esophageal sphincter in man: an improved method of detection. Mayo Clin Proc 33:406-414, 1958 25. Code CF, Schlegel JF: Motor action of the esophagus and its sphincters. In Handbook of Physiology, Sect 6: Alimentary Canal, Vol IV Motility. Washington DC, American Physiological Society, 1968, p 1824 26. Hollis JB, Castell DO: Amplitude of esophageal peristalsis as determined by rapid infusion. Gastroenterology 63:417-422, 1972 27. Zabinski MP, Spiro HM, Biancani P: Influence of perfusion rate and compliance on esophageal manometry. J Appl Physiol 38: 177 -180, 1975 28. Dodds WJ, Stef JJ, Arndorfer RC, Linehan JH, Hogan WJ: Improved infusion system for esophageal manometry (abstr). Clin Res 22:602, 1974 29. Farrar JT, Davidson M: Measurement of Gastrointestinal Motility in Man. In Methods in Medical Research. vol 8, chap IV. Edited by HD Bruner. Chicago, The Year Book Publishers, Inc., 1968, p 200-221 30. Dodds WJ, Hogan WJ, Lydon SB, Stewart ET, Stef JJ, Arndorfer RC: Quantitation of pharyngeal motor function in normal human subjects. J Appl Physiol (in press), 1975 31. Code CF, Hightower NC Jr, Morlock CG: Motility of alimentary canal in man: Review of recent studies. Am J Med 13:328-351, 1952 32. Butin JW, Olsen AM, Moersch HJ, Code CF: A study of esophageal pressures in normal persons and patients with cardiospasm. Gastroenterology 23:278-293, 1953 33. Code CF, Wilkinson GR Jr, Sauer WC: Normal and some abnormal colonic motor patterns in man. Ann N Y Acad Sci 58:317-335, 1954 34. Millhon WA, Hoffman DE, Jarvis P, Cross CJ, Millhon JS, Crites NA: Preliminary report on Millhon-Crites intraesophageal motility probe. Am J Dig Dis 13:929-933, 1968 35. Gauer OH, Gienapp E: A miniature pressure-recording device. Science 112:404-405, 1950 36. Berridge FR, Friedland GW, Tagart REB: Radiological landmarks at the oesophagogastric junction. Thorax 21:499-510, 1966 37. Dodds WJ, Stewart ET, Hodges D, Zboralske FF: Movement of the feline esophagus associated with respiration and peristalsis. An evaluation using tantalum markers. J Clin Invest 52:1-13, 1973 38. Dodds WJ, Stewart ET, Hogan WJ, Stef JJ, Arndorfer RC: Effect of esophageal movement on intraluminal esophageal pressure recording. Gastroenterology 67:592-600, 1974 39. Goyal RK, Sangree MH, Hersh T, Spiro HM: Pressure inversion point at the upper high pressure zone and its genesis. Gastroenterology 59:754-759, 1970 40. Winans CS: Alteration of lower esophageal sphincter characteristics with respiration and proximal esophageal balloon distention. Gastroenterology 62:380-388, 1972
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41. Waldeck F: A new procedure for functional analysis of the lower' esophageal sphincter (LES). Pfluegers Arch 335:74-84, 1972 42. Waldeck F, Jennewein HM, Siewert R: The continuous withdrawal method for the quantitative analysis of the lower oesophageal sphincter (LES) in humans. Eur J Clin Invest 3:331-337, 1973 43. Kaye MD, Showalter JP: Measurement of pressure in the lower esophageal sphincter. The influence of catheter diameter. Am J Dig Dis 19:860-863, 1974 44. Dodds WJ, Hogan WJ, Stef JJ, Miller WN, Lydon SB, Arndorfer RC: A rapid pull-through technique for measuring lower esophageal sphincter pressure. Gastroenterology 68:437-443, 1975 45. Kaye MD, Showalter JP: Manometric configuration of the lower esophageal sphincter in normal human subjects. Gastroenterology 61:213-223, 1971 46. Winans CS: Manometric asymmetry of the lower esophageal high pressure zone (abstr). Gastroenterology 62:830, 1972 47. Dodds WJ, Miller WN, Hogan WJ, Arndorfer RC, Lydon SB, Stef JJ: Influence of extrinsic forces on intraluminal lower esophageal sphincter pressure (abstr). Gastroenterology 68:885, 1975 48. Winans CS: The pharyngoesophageal closure mechanism: a manometric study. Gastroenterology 63:768-777, 1972 49. Kaye MD, Showalter JP, Rock KC, Johnson E: A circumferentially-sensitive miniature transducer for study of human esophageal motility (abstr). Gastroenterology 64:752, 1973 50. Dodds WJ, Hogan WJ, Miller WN, Barreras RF, Arndorfer RC, Stef JJ: Relationship between serum gastrin concentration and lower esophageal sphincter pressure. Am J Dig Dis 20:201-207, 1975 51. Nauta J: The closing mechanism between the esophagus and the stomach. Gastroenterologia >16:219-241, 1956 52. Johnson HD: Active and passive opening of the cardia and its relation to the pathogenesis of hiatus hernia. Gut 7:392-401,1966 53. Clark MD, Rinaldo JA Jr, Eyler WR: Correlation of manometric and radiologic data from the esophagogastric area. Radiology 94:261-270, 1970 54. Sokol EM, Heitmann P, Wolf BS, Cohen BR: Simultaneous cine radiographic and manometric study of the pharynx, hypopharynx, and cervical esophagus. Gastroenterology 51:960-974, 1966 55. Dodds WJ, Hogan WJ, Reid DP, Stewart ET, Arndorfer RC: A comparison between primary peristalsis following wet and dry swallows. J Appl Physiol 35:851-857, 1973 56. Fox JE, Beck IT: A method of translating esophageal pressure tracings to digital data for computer evaluation. Am J Dig Dis 18:757-766, 1973 57. Fox JE, Vidins EI, Beck IT: Observer variation in esophageal pressure assessment. Gastroenterology 65:884-888, 1973 58. Ingelfinger FJ: The sphincter that is a sphinx. N Engl J Med 284: 1095-1096, 1971 59. Ingelfinger FJ: Esophageal Motility. Physiol Rev 38:533-584,1958 60. Winship DH, Viegas De Andrade SR, Zboralske FF: Influence of bolus temperature on human esophageal motor function. J Clin Invest 49:243-250, 1970 61. Hollis JB, Castell DO: The effect of bolus size and cholinergic stimulation of human esophageal peristalsis (abstr). Clin Res 22:361, 1974 62. Hogan WJ, Dodds WJ, Stewart ET: Comparison of roentgenology and intraluminal manometry for evaluating oesophageal peristalsis (abstr). Rendiconti di Gastroenterologia 5(2):28,1973 63. Dodds WJ, Hogan WJ, Stewart ET, Stef JJ, Arndorfer RC: Effects of increased intra-abdominal pressure on esophageal peristalsis. J Appl Physiol 37:311-315, 1974 64. Lind JF, Warrian WG, Wankling WJ: Responses of the gastroesophageal junctional zone to increases in abdominal pressure. Can J Surg 9:32-38, 1966 65. Cohen S, Harris LD: Does hiatus hernia affect competence of the
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gastroesophageal sphincter? N Engl J Med 284:1053-1056, 1971 66. Henderson RD, Rodney K: Tone of the gastroesophageal junction: its response to abdominal compression and to swallowing. Can J Surg 14:328-334, 1971 67 . Dodds WJ, Hogan WJ, Miller WN, Stef JJ, Arndorfer RC, Lydon SB: Effect of increased intraabdominal pressure on lower esophageal sphincter pressure. Am J Dig Dis 20:298-308, 1975 68. Babka JC, Hager GW, Castell DO : The effect of body position on lower esophageal sphincter pressure . Am J Dig Dis 18:441-442, 1973 69 . Biancani P , Spiro HM, Bejar J : Pressure-diameter characteristics of component and incompetent human lower esophageal sphincter (LES) (abstr) . Gastroenterology 64 : 6~8 , 1973
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