Patent Application
20060018528
The present invention relates to devices and methods for imaging, characterizing, diagnosing, and treating junctions between internal body areas and for analyzing, measuring, and monitoring pressure/volume relationships of body areas. In particular, the devices and methods of the present invention find use in distinguishing normal, non-hernia, reflux, and hernia patients for diagnostic purposes, drug screening, and selecting and monitoring appropriate interventions.
The primary determinant of gastroesophageal reflux is esophogastric junction (EGJ) incompetence permitting excessive reflux of gastric juice into the esophagus. Reflux events may occur in the context of transient lower esophageal sphincter relaxations (tLESRs), strain induced reflux, or free reflux during periods of either low LES pressure or deglutitive relaxation (see, e.g., Dent J, et al., 1980, J Clin Invest 65:256-67; Dodds W J, et al., 1982, N Engl J Med 307:1547-52; Barham C P, et al., 1995, Gut 36:505-10; Mittal R K, et al., 1995, Gastroenterology 109:601-10; each herein incorporated by reference in their entireties). tLESRs account for up to 90% of reflux episodes in asymptomatic controls and in symptomatic GERD patients without hiatus hernia (HH) (see, e.g., Dent J, et al., 1980, J Clin Invest 65:256-67; van Herwaarden M A, et al., 2000, Gastroenterology 119:1439-46; Schoeman M N, et al., 1995 Gastroenterology 108:83-91; each herein incorporated by reference in their entireties). In contrast, GERD patients with HH exhibit a more heterogeneous reflux pattern with reflux episodes frequently occurring during periods of low LES pressure, straining, and even swallow-induced LES relaxation (see, e.g., van Herwaarden M A, et al., 2000, Gastroenterology 119:1439-46; Barham C P, et al., 1995, Gut 36:505-10; each herein incorporated by reference in their entireties). The EGJ opens at lower pressures and to a greater diameter during LES relaxation in HH patients compared to asymptomatic normal subjects (see, e.g., Pandolfino J E, et al., 2002, Am J Physiol Gastrointest Liver Physiol 282:G1052-8; herein incorporated by reference in its entirety). A qualitative difference exists in the air/liquid content of refluxate between normal subjects and GERD patients (see, e.g., Sifrim D, et al., 1996 Gastroenterology 110:659-68; Sifrim D, et al., 1999 Gut 44:47-54; each herein incorporated by reference in their entireties). Although tLESRs are a dominant mechanism of reflux in normal controls and in reflux patients when evaluated as a heterogeneous group, unique mechanistic considerations amongst GERD patients exist with HH (see, e.g., Mittal R K, et al., 1995 Gastroenterology 109:601-10; van Herwaarden M A, et al., 2000 Gastroenterology 2000;1 19:1439-46; Kahrilas P J, et al., 2000 Gastroenterology 2000;118:688-95; Sloan S, et al., 1991 Gastroenterology 100:596-605; Jones M P, et al., 2002 Neurogastroenterol Motil 14;625-63 1; each herein incorporated by reference in their entireties). Factors that may contribute to increased compliance of the EGJ include radial disruption of the crural diaphragm, integrity of the phrenoesophageal ligament, grade of gastroesophageal flap valve or thickness of the LES smooth muscle (see, e.g., Hill L D, et al., 1996 Gastrointest Endosc 44:541-7; Pehlivanov N, et al, 2001 Am J Physiol Gastrointest Liver Physiol 280:G1093-8; each herein incorporated by reference in their entireties).
What is needed are improved devices and methods for imaging the EGJ, and improved methods of diagnosing and treating GERD and related conditions.
The present invention relates to systems, devices, and methods for imaging, characterizing, diagnosing, monitoring changes in, and treating junctions between internal body areas. In particular, the systems, devices and methods of the present invention find use in distinguishing normal, non-hernia, reflux, and hernia patients for diagnostic purposes, drug screening, selecting and monitoring appropriate interventions. The systems, devices, and methods of the present invention also find use in many other applications. A number of exemplary applications are illustrated herein. One skilled in the art will appreciate additional applications of the systems, devices, and methods of the present invention.
In certain embodiments, the present invention provides a device for imaging a junction between internal body areas comprising a bag configured to receive an imaging agent such that the size of the bag is proportional to the amount of the imaging agent received by the bag, wherein the bag is configured to engage the junction such that the imaging agent permits imaging of the junction. In certain preferred embodiments, the imaging permits the calculation of the cross sectional area of the junction. In certain preferred embodiments, the imaging permits the calculation of the cross sectional area of the junction at specific degrees of inflation of the bag. In other preferred embodiments, the imaging permits the measurement of liquid passing through the junction and the pressure exerted by the EGJ on the bag. In certain preferred embodiments, the results of a therapeutic intervention can be assessed by measuring the change in the pressure exerted on the bag by the EGJ during and after a therapeutic intervention.
In preferred embodiments, the junction is an esophogastric junction. In other preferred embodiments, the junction comprises a sphincter muscle.
In preferred embodiments, the composition of the bag is polyethylene. In other preferred embodiments, the imaging agent is provided to the bag through a barostat assembly. In yet other preferred embodiments, the barostat assembly provides the imaging agent to the bag under a predetermined pressure such that the bag assumes the pressure. In preferred embodiments, when filled with a specific amount of fluid, the bag is configured to exert a distension pressure upon the junction. In most preferred embodiments, a cold liquid is used to fill the bag and cool the lining of the junction during the application of thermal energy thereto.
In preferred embodiments, the device further comprises a manometric catheter, and the pressure of the liquid within the bag is measured with the manometric catheter.
In preferred embodiments, the device is used to diagnose an illness (e.g., GERD). In other preferred embodiments, the device is used to image the effect of a drug. In yet other preferred embodiments, the device further comprises an endoscopic tube. In yet other preferred embodiments, the device is configured to analyze and/or perform endoscopic lithotripsy. In preferred embodiments, the device is configured to apply thermal energy to shrink the junction therapeutically.
In certain embodiments, the present invention provides a system for imaging a junction between body areas comprising, a barostat component comprising a radioopaque imaging agent; a bag component connectable to the barostat via tubing, the bag component configured to receive the imaging agent through the tubing, the bag further configured to engage the junction; and an imaging component configured to measure cross-sectional area of the junction as a function of pressure within the bag. In preferred embodiments, the barostat component provides the imaging agent to the bag component under a predetermined pressure such that the bag assumes the pressure. In preferred embodiments, the bag component is made of polyethylene.
In preferred embodiments, the system further comprises a manometric catheter configured to measure pressure within the bag component. In preferred embodiments, the system further compres an endoscopic tube. In preferred embodiments, the system further comprises a thermal energy component selected from the group consisting of a laser energy component, a radiofrequency energy component, a microwave energy component, and an ultrasound energy component. In other preferred embodiments, the thermal energy component is configured to delivery thermal energy in a manner perpendicular to the axis of the bag.
In certain embodiments, the system is used within a method of analyzing a body area of a subject, wherein the system is provided, and the body area is contacted with the bag component. In preferred embodiments, the body area comprises an esophogastric junction. In preferred embodiments, the body area comprises a sphincter muscle. In preferred embodiments, the method further comprises the step of measuring a cross-sectional area of the junction as a function of pressure within the bag. In preferred embodiments, the method further comprises the step of diagnosing a disease or condition based on data obtained from the system. In yet other preferred embodiments, the disease or condition is GERD. In yet other preferred embodiments, the disease or condition is GERD with hiatus hernia. In still other preferred embodiments, the disease or condition is GERD without hiatus hernia. In preferred embodiments, the disease or condition is female stress urinary incontinence. In preferred embodiments, the disease or condition is fecal incontinence.
In preferred embodiments, the method further comprises the step of monitoring a medical procedure by monitoring the imaging component. In preferred embodiments, the medical procedure comprises a surgery. In still other preferred embodiments, the surgery comprises endoscopic lithotripsy. In preferred embodiments, the medical procedure comprises a drug therapy. In yet other preferred embodiments, the drug therapy comprises application of a drug selected from the group consisting of an anti-cancer agent, ranitidine, cimetidine, famotidine, nizatidine, omeprazole, lansoprozole, rabeprazole, esomeprazole, and metoclopramide. In preferred embodiments, the medical procedure comprises application of a thermal energy selected from the group consisting of laser energy, radiofrequency energy, microwave energy, and ultrasound energy.
In certain embodiments, the present invention provides a system for imaging a body area comprising, a barostat component comprising a radioopaque imaging agent; a bag component connectable to the barostat via tubing, the bag component configured to receive the imaging agent through the tubing, the bag further configured to engage the junction; an imaging component configured to analyze the body area as function of pressure within the bag; and a therapeutic component.
In preferred embodiments, the therapeutic component is a therapeutic drug. In preferred embodiments, the therapeutic component provides a cooling component to reduce the temperature of the imaging agent. In preferred embodiments, the therapeutic component is selected from the group consisting of laser energy, radiofrequency energy, microwave energy, and ultrasound energy.
In preferred embodiments, the system is configured for fiber-optic delivery of the laser energy. In other preferred embodiments, the laser energy is delivered at a range of about 70 to 110 degrees from the axis of the fiber-optic. In preferred embodiments, the therapeutic drug is selected from the group consisting of an anti-cancer agent, ranitidine, cimetidine, famotidine, nizatidine, omeprazole, lansoprozole, rabeprazole, esomeprazole, and metoclopramide.
In certain embodiments, the system is used within a method of treating a subject comprising treating the subject with a thermal energy emitting component; and monitoring the treating by detecting the imaging component. In preferred embodiments, the subject suffers from or is suspected of suffering from a condition selected from the group consisting of GERD, female stress urinary incontinence, fecal incontinence, and cancer.
The present invention provides imaging devices for imaging body areas, methods for measuring the dimensions of body areas (e.g., cross sectional area), and monitoring of therapeutic applications thereof. The devices and systems of the present invention also find use in any application where pressure/volume relationships of body areas are to be measured, monitored, or analyzed. In preferred embodiments, the imaging devices are used in the imaging of junctions between internal body areas (e.g., EGJ, pyloric junction sphincter, duodenum junction, jejunum junction, ileum junction, colon opening, rectal opening, oral opening, ureter pelvic junction, trachea /lung junction, gall bladder openings, ureter bladder opening, or any opening or junction between internal body areas). The system, devices, and methods also find use in any situation where a pressure/volume relationship is relevant, including, but not limited to removal of skin flaps, wound closings, breast or other augmentation or implant processes, etc. The illustrated and preferred embodiments discuss these devices, methods and applications in the context of imaging the EGJ and methods of diagnosing gastric related illnesses (e.g., GERD).
In preferred embodiments, the devices of the present invention find use within medical functions as a means for imaging and diagnosing illnesses, conditions, and tissue properties involving a junction between internal body areas (e.g., GERD). The imaging devices of the present invention provide numerous advantages over prior art imaging techniques including, but not limited to, improved imaging of junctions between internal body areas, improved ability to diagnose junction related illnesses, improved ability to profile the mechanical characteristics of a junction, improved ability to calculate the cross sectional area of a junction, improved ability to visualize junctions, and improved ability to monitor therapeutic applications thereof.
The imaging devices of the present invention function under the principle that the profiling of a junction between internal body areas in response to varied distension pressures permits a mechanical characterization of the junction. The diagnostic devices of the present invention enable compliance and opening pressures of the junction to be measured, thereby permitting assessment of the therapeutic. Characterization of a junction between internal body areas permits improved diagnoses, therapy monitoring, and treatment options for junction related disorders.
Imaging Devices
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Uses of the Imaging Devices
The imaging devices of the present invention are not limited to particular uses (e.g., profiling internal body areas, diagnostic applications, therapeutic applications). In preferred embodiments, the imaging devices are useful in general imaging and analysis of a body area.
In preferred embodiments, the imaging devices of the present invention are used in profiling the opening characteristics (e.g., pressure/volume) of an internal body area (e.g., EGJ, pyloric junction sphincter, duodenum junction, jejunum junction, ileum junction, colon opening, rectal opening, oral opening, ureter pelvic junction, trachea/lung junction, gall bladder openings, ureter bladder opening, or any opening or junction between two internal body areas). For example, measurements (e.g., cross sectional area) of an internal body area may be made as a function of various distension pressures from the imaging bag so as to generate an operating profile of the internal body area.
In preferred embodiments, the imaging devices of the present invention are useful in visualizing internal body areas and making diagnoses (e.g., diagnosing GERD, esophogastric cancer, detecting tumor formation, cancer, colon cancer, diagnosing female urinary stress incontinence, fecal (anal) incontinence, etc.).
In preferred embodiments, the imaging devices are useful in therapeutic applications. In preferred embodiments, the imaging devices of the present invention are used in conjunction with an endoscope or enteroscope for treatment purposes (e.g., esophagogastroduodenoscopy, endoscopic lithotripsy, colonoscopy, drug delivery, tumor removal). For example, in some embodiments, the imaging devices may be used to deliver drugs useful in treating GERD (e.g., H2 receptor antagonists, ranitidine, cimetidine, famotidine, nizatidine, proton pump inhibitors, omeprazole, lansoprozole, rabeprazole, esomeprazole, prokinetics, metoclopramide, etc.) or cancer (e.g., anti-cancer drugs).
In preferred embodiments, the system includes a laser (e.g., side firing laser, lateral firing laser) or other heating component (e.g., a heating component emitting radiofrequency, microwave energy, or ultrasound energy) configured for treating tissue (e.g., to cause scar formation or collagen contraction). A preferred method of using a lateral-firing laser device is described in more detail in U.S. Pat. No. 5,437,660, herein incorporated by reference in its entirety.
Laser and radiofrequency energy is commonly used, for example, in the treatment of herniated or ruptured spinal discs so as to relieve pressure against nerves, and to shrink shoulder capsule so as to prevent shoulder dislocation. In cosmetic and dermatologic procedures, laser energy is applied to the skin to cause shrinkage and growth of the new collagen in tissues lying beneath the epidermis to treat wrinkles or to coagulate unattractive blood vessels beneath the skin. To prevent thermal damage to the epidermis, a coolant, such as a cryogenic gas, ambient air, a fluid spray, a refrigerated, transparent gel or a cooled fluid circulated through a container with quartz or fused silica windows, can be applied to the surface of the skin to cool the epidermis. Laser energy can safely be transmitted through aqueous liquids. The laser may be provided as part of an endoscope, hydrostat, or with any other part of the system or may be provided as a separate component. In preferred embodiments, imaging systems are provided such that energy (e.g., laser energy) transmitted along a catheter may be directed at tissue through an energy emitter (e.g., fiber optic laser delivery component) that is substantially surrounded by an imaging big filled with a fluid coolant (e.g., chilled de-ionized water, chilled saline, and cryogenic-state gas). In preferred embodiments, a cold liquid medium is preferred, as that the liquid medium serves as a cooling agent during application of laser or other thermal energy to the junction.
The imaging system, when used with the laser or other heating component, permits real-time monitoring of therapy to assist in achieving the best outcome. In preferred embodiments, the imaging system is configured such that the pressure exerted by an opening (e.g., EGJ) may be monitored before and after the administration of a therapy (e.g., laser energy). As such, the imaging system permits a user to, for example, apply a therapy (e.g., laser energy), monitor the effect of the therapy by measuring the pressure exerted by the opening, and reapply the therapy until a desired opening pressure is reached.
Utilization of laser or other thermal energy within a cold liquid medium contained in a bag or balloon inflated within the junction assists in preventing thermal injury to the endothelial lining of the EGJ or other junction, while permitting the laser energy to pass through the endothelial lining to shrink the collagen in the underlying tissues by photomechanical cross linking (see, e.g., U.S. patent application Ser. Nos. 20030060813 and 20040120668; each herein incorporated by reference in their entireties). The devices and systems of the present invention may be integrated with one or more portions of the devices and systems described in U.S. patent application Ser. Nos. 20030060813 and 20040120668 to provide enhanced systems for modifying tissues surrounding a duct, hollow organ or body cavity.
In preferred embodiments, the imaging devices are useful in assisting in wound closing (e.g., removing skin flaps through stretching). In preferred embodiments, the imaging devices are useful in prosthetic surgery (e.g., breast augmentation).
In preferred embodiments, the imaging devices are useful in the screening and monitoring of drugs. For example, the effect of a drug on a certain internal body position (e.g., the EGJ) may be monitored and imaged with the imaging devices.
In preferred embodiments, the imaging devices of the present invention are useful in generating a profile of the esophogastric junction (EGJ) leading to a diagnosis of gastroesophageal reflux disease (GERD). For example, liquid flow through and into (e.g., reflux) the EGJ may be measured as varying amounts of distention pressure is applied from the imaging bag. Such a profile permits an understanding of the mechanical properties of the EGJ and permits distinction between various illnesses (e.g., distinguishing between GERD patients with and without hiatus hernia). In preferred embodiments, the imaging devices assist, for example, in explaining the distinct reflux profile observed in HH patients (e.g., a mechanistic difference in EGJ opening characteristics rather than of LES relaxation per se). In preferred embodiments, the imaging devices are used in exploring the mechanical properties of the relaxed EGJ in an opening diameter range (>10 mm) and a distensive pressure range (10-30 mmHg) greater than believed to be physiologically important in GERD.
In preferred embodiments, the imaging devices are used in exploring the mechanical characteristics of EGJ opening in GERD patients and normal subjects at physiological apertures and intraluminal pressures. In preferred embodiments, the monitoring of a treatment enables a user (e.g., physician) to assess changes in and the status of the EGJ or other junction after a therapeutic application (e.g., application of a particular drug dosage, sufficiency of a laser energy, radiofrequency (RF), microwave or ultrasound energy application, or the sufficiency of any other therapeutic application).
The following examples are provided to demonstrate and further illustrate certain preferred embodiments of the present invention and are not to be construed as limiting the scope thereof.
Seven normal subjects (NL) (4 males, 23-33 years old) without reflux symptoms, 7 patients with GERD and HH (HH) (5 males, 28-53 years old) and 9 GERD patients without HH (NHH) (5 males, 24-48 years old) were studied. Patients were classified as HH or NHH based on upper endoscopy results. The endoscopic criterion for HH was that the position of the SCJ was ≧2 cm proximal to the center of the hiatal impression after aspirating excess air from the stomach. Presence or absence of HH was confirmed with fluoroscopy using the criterion of persistent rugal folds proximal to the hiatus between dilute barium swallows. The HH subjects had axial displacement ranging from 2.0 cm to 4.4 cm based on fluoroscopic measurements. Non hiatus hernia patients had <1 cm axial herniation during endoscopy and subsequent fluoroscopy. As shown in Table 1, GERD was defined by the presence of ≧Los Angeles A esophagitis on current or recent endoscopy (HH, 5/7; NHH 2/9) and/or abnormal 24 hour ambulatory pH monitoring using a cutoff value of 4.2% total time pH <4 (HH, 2/7, NHH, 9/9). At the time of the experimental study, all patients were in symptomatic remission as a result of maintenance treatment with a proton pump inhibitor (n=12) or nonprescription therapy (n=4) and none were taking any medication known to affect esophageal contractility. None of the subjects had a history of surgical manipulation of the EGJ. Table 1. Study subject demographics.
*Total % time pH < 4 greater than 4.2%
This Example describes the manometric procedures used in experiments conducted in some embodiments the present invention. Subjects underwent baseline manometry before or shortly after the hydrostat protocol, but never on the same day. Manometry was done using a water-perfused system (Dentsleeve Pty. Ltd, Parkside, South Australia). The manometric catheter was an 8-lumen silicone rubber extrusion with a 6 cm sleeve sensor and 7 side-hole recording sites. Each side-hole channel was connected to an extracorporeal pressure transducer and perfused with sterile water at 0.15 ml/min using a low compliance perfusion pump (Dentsleeve Mark II, 16 channel model); the sleeve channel was perfused at 0.6 ml/min. Output of the pressure transducers was connected to a computer polygraph set at a sampling frequency of 40Hz (Neomedix systems Pty Ltd, Warriedwood, NSW, Australia) and processed using Gastromac software (Neomedix systems Pty Ltd, Warriedwood, NSW, Australia). The transducers were calibrated at 0 and 70 mmHg prior to recording using externally applied pressure. Response characteristics of each side-hole manometric channel exceeded 200 mmHg/s. Basal LES pressure was measured at end expiration during a 5-minute baseline period. Relaxation pressure was defined as the mean LES pressure during maximal deglutitive relaxation. All manometric pressure values were referenced to intragastric pressure.
This Example describes the hydrostatic instrumentation used in some embodiments of the present invention.
Hydrostat bags were designed so that when fully distended they had a cylindrical shape, 2 cm in diameter and 10 cm in length. The length of the bag ensured that position could be maintained across the EGJ during distention without need for repositioning. Hydrostat bags were end-mounted on the polyvinyl tubing with nylon surgical suture over a plastic tie point. In addition, a single sensor solid-state manometric catheter (Medical Measurements Inc., Hackensack, N.J.) was incorporated into the assembly positioned such that the sensor was within the hydrostat bag, 1 cm beyond the distal end of the polyvinyl tubing. Prior to use, the entire system was checked for leaks ex-vivo by inflation to 40 mmHg.
This Example describes an experimental protocol used in some embodiments of the present invention. After an overnight fast, the hydrostat catheter was passed orally with the patient in a sitting position such that the end of the catheter was at least 50 cm distal to the incisors. The subject was then placed in a supine position under a fluoroscope (Easy Diagnostics, Phillips Medical Systems, Shelton, Conn., USA) and shielded below the umbilicus with a lead apron. The assembly was positioned under fluoroscopy such that the bag was within the stomach. Pressure within the hydrostat bag was heavily dependent on hydrostatic considerations. Prior to experimentation the height of the hydrostat bottle was adjusted in relation to the patient such that there was no flow of contrast within the system. Intragastric pressure was then measured for a one-minute period. Guided by fluoroscopy, the bag was then unfolded, positioned straddling the EGJ, and secured in position to the subject's cheek with tape.
This Example describes the EGJ anatomy and distensibility (e.g., compliance) observed via use of the systems of the present invention. EGJ opening dimensions were imaged in both posterior-anterior (PA) and lateral projections during deglutitive relaxation as a function of hydrostat distension pressure. Distention pressure was increased in 2 mmHg increments up to 12 mmHg (see
This Example describes the mechanical simulation of air and water flow through the EGJ in some embodiments of the present invention. In order to estimate the impact of observed EGJ opening apertures on flow of air and water across the EGJ the barostat and hydrostat was set up to measure flow through 1 cm lengths of polyurethane tubing. Tubing sizes were selected so as to encompass the average opening apertures of the three subject groups observed during 4mmHg distension (the average pressure increment observed during tLESRs). The barostat was used to measured air flow rates and the hydrostat was used to measure water flow rates. Air and water flow rates through the simulation tubing were measured for 20 seconds and mean flow rate reported. The maximal barostat inflation rate was measured to be 57 ml/sec without any outflow restriction. Therefore, flow rates were extrapolated using a liquid:air viscosity ratio of 55:1 when maximal flow rate was exceeded.
This Example describes the data analysis used in experiments conducted in some embodiments of the present invention. Maximal deglutitive opening diameter at the narrowest point within the EGJ was measured from digitized videofluorographic images using Macintosh video and NIH image software. A vertebra was used as a spatial reference and the 10 mm length of the proximal tie ring on the hydrostat assembly was used to correct for magnification (see
All results are summarized as mean ±SEM unless specified otherwise. One-way ANOVA was used to compare the manometric parameters among the three groups. Student's paired t-test was used to compare the manometric parameters between groups with p<0.0253 considered significant. ANOVA was used to compare differences in EGJ opening cross sectional area among subject groups at each distensive pressure. Slope of the area pressure relationship was calculated using simple regression analysis. Least square regression analysis was used to determine the correlation between the slope of the area/pressure relationship and the basal LES pressure. A p value <0.05 was considered significant.
This Example describes the manometric measures of EGJ function as measured in some embodiments of the present invention. Manometric data for each group are shown in Table 2. Using ANOVA, no significant difference existed in mean basal LES pressure among the three groups. An unpaired t-test revealed a significant difference in LES pressure between NL and HH patients (p<0.005). Neither ANOVA nor an unpaired t-test revealed any significant differences in LES relaxation pressure or intragastric pressure among the three subject groups.
*p < 0.005 when compared to normal subjects
This Example describes the EGJ opening during low-pressure distension as measured in some embodiments of the present invention. The smallest EGJ opening aperture during deglutitive relaxation occurred at the level of the diaphragmatic hiatus in all subjects. Radial asymmetry was noted in the normal subjects during pressure distention with the lateral diameter being greater than the PA (
By ANOVA analysis, EGJ cross-sectional opening areas at pressures ≦0 mmHg (intragastric pressure) were significantly greater in HH compared to both NL and NHH patients (P<0.05) (
This Example describes the simulation of air and water flow through the EGJ as measured in some embodiments of the present invention. Extrapolating from
*Diameter of tubing simulating cross-sectional area of each study group with distention pressures of 4 mmHg.
†Given the fact that 57 ml/sec was the greatest flow rate attainable with the barostat, air flow rates were extrapolated from liquid flow rates using a liquid:air viscosity ratio of 55:1.
All publications and patents mentioned in the above specification are herein incorporated by reference. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention that are obvious to those skilled in the relevant fields are intended to be within the scope of the following claims.
This application claims priority to U.S. Provisional Application 60/565,769 filed Apr. 27, 2004, and herein incorporated by reference in its entirety. This work was supported, in part, by grant RO1 DC00646 from the Public Health Service and K23 DK62170-01. The government may have certain rights in the invention.
| Number | Date | Country | |
|---|---|---|---|
| 60565769 | Apr 2004 | US |
