Diffuse esophageal spasm is an uncommon motility disorder that is found in less than 5% of patien... more Diffuse esophageal spasm is an uncommon motility disorder that is found in less than 5% of patients undergoing esophageal motility testing for dysphagia. It is defined manometrically by the presence of 20% or more simultaneous contractions in the distal esophageal body with normal peristalsis. This motility abnormality has been traditionally identified as occurring primarily in the smooth muscle portion of the distal esophagus yet, the term "diffuse" persists in the medical literature to identify DES. The aim of our study was to assess the diffuse or limited nature of this entity by evaluating the prevalence of simultaneous contractions in both proximal and distal esophagus in patients with DES. We reviewed esophageal motility tracings of 53 consecutive patients (32 F, 21 M) with DES and compared them with 53 age-matched patients with manometric normal studies. In the distal esophagus we found 195 simultaneous contractions (37% of swallows) with a median of 3 and range of ...
Purpose: BE is a premalignant lesion associated with adenocarcinoma of the esophagus. Several sma... more Purpose: BE is a premalignant lesion associated with adenocarcinoma of the esophagus. Several small endoscopic case studies have suggested a gender and ethnic predominance for BE. Currently no firm recommendations exist for determining endoscopic screening. Aim: To determine the demographic features of patients with dysplasia in BE.
Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) is a clinically av... more Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) is a clinically available tool that assesses the functional defect of various manometric abnormalities. The aim of our study was to evaluate esophageal bolus transit in patients with manometrically defined distal esophageal spasm (DES). Patients referred for esophageal function testing underwent combined MII-EM studies including 10 liquid and 10 viscous swallows. Individual swallows were classified using previously published manometric and impedance criteria. DES is traditionally defined as > or =20% simultaneous contractions in the distal esophagus. Diagnosis of esophageal transit abnormalities was defined by the presence of > or =30% incomplete liquid or > or =40% incomplete viscous swallows. Data from 71 patients (43 female, mean age 57 yr, range 16-85) with a manometric diagnosis of DES were analyzed. During liquid swallows, patients with chest pain had higher (p < 0.05) distal esophageal ...
OBJECTIVE: Nutcracker esophagus (NE) is defined as the presence of peristaltic contractions in wh... more OBJECTIVE: Nutcracker esophagus (NE) is defined as the presence of peristaltic contractions in which the average distal esophageal amplitude is greater than 180 mm Hg. The underlying mechanism responsible for these abnormalities is not known. The aim of this study was to test the hypothesis that NE might be caused by a defect in the inhibitory pathway controlling esophageal peristalsis.
Multichannel intraluminal impedance (MII) allows assessment of intraoesophageal bolus transit. In... more Multichannel intraluminal impedance (MII) allows assessment of intraoesophageal bolus transit. In the supine position, bolus transit is produced almost exclusively by peristaltic contractions; in the upright position, gravity also contributes to bolus transit. MII and peristaltic pressures were measured in four positions (0, 30, 60 and 90 degrees ) using ten swallows (5 cc each) of both water and viscous liquid with body position determined by random choice. Tracings were analysed for total bolus transit time: time interval between bolus entry at 20 cm above and bolus exit at 5 cm above the lower oesophageal sphincter (LOS) and contraction amplitudes at 5 and 10 cm above the LOS. Statistical comparison of mean values of all four body positions was done using anova and Bonnferoni post-test. Ten normal subjects (five females and five males, age 24-45 years) completed the study. At each body position, liquid material transited faster (P &amp;amp;lt; 0.001) than viscous material. Both liquid and viscous materials transited at lower inclinations (0 and 30 degrees ) significantly slower than at higher inclinations (60 and 90 degrees ). There was an almost perfect inverse linear correlation between angle of inclination and bolus transit time for both liquid (r = -0.99) and viscous (r = -1.00) boluses (Spearman correlation r &amp;amp;gt; 0.99 and P &amp;amp;lt; 0.02 for both substances). Contraction amplitudes for liquid vs viscous material were not significantly different at a given degree of inclination. Mean distal oesophageal amplitude declined with increasing inclination. Combined MII-OM identifies and quantifies the effects of gravity on the dichotomy between specific pressures measured by OM and function assessed as transit measured by MII.
Dysphagia is common in both Parkinson&amp;amp;#39;s disease (PD) and progressive supranuclear... more Dysphagia is common in both Parkinson&amp;amp;#39;s disease (PD) and progressive supranuclear palsy (PSP). Although it is believed to be more common in PSP, there are no controlled data and no comparison of swallowing function between these two disorders. Our aim was to assess dysphagia and swallow function in patients with PSP and PD. Seven patients with PSP were matched to seven patients with PD on the basis of disease duration. Self-rated dysphagia, movement disorder disability, modified barium swallow results, and abnormalities noted on manometry of the lower esophageal sphincter, esophageal body, upper esophageal sphincter, and pharynx were compared between the two groups. Neither severity nor duration of dysphagia differed between the two groups. Patients with PSP had a significantly greater degree of disability [median (range) Hoehn &amp;amp;amp; Yahr score, 4 (3-5) vs. 2 (1-2); P &amp;amp;lt; 0.002]. Manometric abnormalities were similar for the two groups. Oral-phase abnormalities on modified barium swallow were significantly more frequent in PSP (four patients with PSP vs. no patients with PD; p &amp;amp;lt; 0.005). Pharyngeal abnormalities did not differ. Modified barium-swallow scores correlated well with self-reported dysphagia severity for patients with PSP (r = 0.93; p &amp;amp;lt; 0.05) but not for those with PD (r = 0.42; p = NS). The frequency of abnormalities noted during the oral phase was significantly increased in PSP. It is hypothesized that the sensory information conveyed due to this may account for the better correlation between symptoms and swallowing abnormalities and the belief that swallowing problems are more common in PSP.
Gastroesophageal reflux disease (GERD) is known to cause a variety of symptoms that lead a patien... more Gastroesophageal reflux disease (GERD) is known to cause a variety of symptoms that lead a patient to seek otolaryngologic care. New advances in the treatment of GERD have enabled otolaryngologists to eliminate most of the signs and symptoms caused by acid reflux. Omeprazole, the most recent pharmacologic advancement, has been reported to be universally successful in controlling acid release from the stomach of patients with GERD. This report describes a series of patients with GERD for whom high-dose omeprazole therapy was not successful in completely reducing gastric acid levels of GERD symptomatology.
Esophageal manometry is a specialized procedure used to evaluate lower and upper esophageal sphin... more Esophageal manometry is a specialized procedure used to evaluate lower and upper esophageal sphincter pressure, esophageal body contraction amplitude, and peristaltic sequence. The procedure is clinically useful in evaluation of a patient with nonstructural dysphagia, unexplained or noncardiac chest pain, a compendium of symptoms suggested because of gastroesophageal reflux disease, and in the preoperative evaluation for antireflux surgery. Manometric findings in 95 normal subjects evenly distributed across age groups were reported in 1987, and are the values still used in our and most laboratories today. The subsequent review will offer our &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;view&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; on the clinical utility of esophageal manometry, on the basis of years of experience and performance techniques that have remained constant over decades.
Diabetes affects the structural and functional integrity of many organ systems, including the gas... more Diabetes affects the structural and functional integrity of many organ systems, including the gastrointestinal tract. It has been demonstrated that diabetes is associated with spontaneous gastric ulceration, and enhanced susceptibility of the gastric mucosa to injury. However, the intracellular events that regulate these processes are poorly understood. In light of our observation that in healthy adult rats, acute gastric mucosal injury results in a marked induction in EGFR tyrosine kinase (Tyr-k) activity (Histol. Histopathol. 12: 491-501, 1997), we compared gastric mucosal EGFR Tyr-k between streptozotocininduced (50 mg/kg; i.v.) 3-month old diabetic rats and their healthy counterparts. The gastric mucosa was analyzed 3 weeks after induction of diabetes, when blood glucose concentrations were between 300 and 400 mg/dL. Results revealed a 40-50% higher EGF-R Tyr-k activity in the gastric mucosa of diabetic rats than in their healthy counterparts. This was accompanied by a 400-600% increase in the relative concentration of EGFR as well as the extent of tyrosine phosphorylation of the receptor and other proteins. Recent results from this laboratory suggest that the membranebound TGF-ct may play a critical role in regulating EGFR Tyr-k activity in the gastric mucosa (Am. J. Physiol. 273: G389-G398, 1997) through a autocrine/juxtacrine mechanism. To determine whether a similar mechanism may also be responsible for the induction EGFR Tyr-k in the gastric mucosa of diabetic rats, mucosal membrane and cytosolic fractions were analyzed for TGF-ot levels by Western-immunoblot. We observed that the relative concentration of the 14 kDa precursor form of TGF-ct in gastric mucosal membranes, but not in the cytosol, was 600-700% higher in diabetic rats when compared with the corresponding preparations from their healthy counterparts. Our results demonstrate that diabetes produces a marked increase in EGFR Tyr-k activity in the gastric mucosa, which could partly be the result of increased production of the enzyme and/or a greater accumulation of TGF-tx in mucosal membranes.
The effects of age and gender on the upper esophageal sphincter&amp;amp;amp;amp;amp;amp;amp;a... more The effects of age and gender on the upper esophageal sphincter&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s (UES) and pharyngeal manometric parameters were investigated in 84 healthy subjects (45 men, 39 women, mean age = 44 years, range = 18-91). Manometric recordings were performed with solid-state circumferential transducers. Subjects older than 60 years (n = 23) showed a significant lower UES resting pressure. In addition, during water swallows they had a higher UES residual pressure, shorter UES relaxation interval and UES relaxation duration, and a decreased UES relaxation rate. Furthermore, pharyngeal contraction had significant higher amplitude and longer duration in subjects older than 60 years during water swallows. Some of these findings were also observed during cookie and pudding swallows. Women had a higher UES resting pressure and a longer UES relaxation interval than men. The observed changes with increasing age indicate loss of basal tone and decreased compliance of the UES. Increased pharyngeal contraction amplitude and its prolonged duration in the elderly might be compensatory to this. These physiologic effects of age and gender on UES and pharyngeal parameters should be taken into account during analysis of manometric studies.
Repetitive, spontaneous contractions of the proximal esophagus have recently been identified as a... more Repetitive, spontaneous contractions of the proximal esophagus have recently been identified as a feature of achalasia. This article documents similar findings in six patients with Parkinson&amp;amp;#39;s disease. Parkinson&amp;amp;#39;s disease and achalasia share many common features neurologically. Both have Lewy bodies in the esophageal myenteric plexuses and the substantia nigra, in addition to evidence of degeneration of the dorsal motor nucleus of the vagus. The esophageal features radiologically and manometrically are also similar. Repetitive proximal esophageal contractions may represent another link between these diseases. They have also been reported in scleroderma. We speculate that the common link between all three disease processes may be poor distensibility of the esophagus.
American Journal of Physiology Gastrointestinal and Liver Physiology, Feb 1, 1998
The human esophagus is composed of striated muscle proximally and of smooth muscle distally with ... more The human esophagus is composed of striated muscle proximally and of smooth muscle distally with a transition zone between the two. Striated muscle contracts much faster than smooth muscle. The change in pressure over time (dP/dt) of the contraction amplitude should therefore be higher in proximal than in distal esophagus, reflecting the presence of striated muscle proximally. There were 34 normal esophageal manometries of patients analyzed for swallow amplitude and dP/dt in the pharynx and esophagus. An additional 11 healthy controls were similarly studied. Amplitudes in pharynx and proximal and distal esophagus were not different. The mid-esophagus had a pressure trough (P &amp;amp;lt; 0.001). The dP/dt in the pharynx was much higher than that in the esophagus (P &amp;amp;lt; 0.001). The dP/dt of proximal and distal esophagus were of the same order of magnitude. The manometric behavior of the striated muscle portion of the proximal esophagus differs from that seen in the pharynx and shows similar characteristics to distal esophageal smooth muscle.
Diffuse esophageal spasm is an uncommon motility disorder that is found in less than 5% of patien... more Diffuse esophageal spasm is an uncommon motility disorder that is found in less than 5% of patients undergoing esophageal motility testing for dysphagia. It is defined manometrically by the presence of 20% or more simultaneous contractions in the distal esophageal body with normal peristalsis. This motility abnormality has been traditionally identified as occurring primarily in the smooth muscle portion of the distal esophagus yet, the term "diffuse" persists in the medical literature to identify DES. The aim of our study was to assess the diffuse or limited nature of this entity by evaluating the prevalence of simultaneous contractions in both proximal and distal esophagus in patients with DES. We reviewed esophageal motility tracings of 53 consecutive patients (32 F, 21 M) with DES and compared them with 53 age-matched patients with manometric normal studies. In the distal esophagus we found 195 simultaneous contractions (37% of swallows) with a median of 3 and range of ...
Purpose: BE is a premalignant lesion associated with adenocarcinoma of the esophagus. Several sma... more Purpose: BE is a premalignant lesion associated with adenocarcinoma of the esophagus. Several small endoscopic case studies have suggested a gender and ethnic predominance for BE. Currently no firm recommendations exist for determining endoscopic screening. Aim: To determine the demographic features of patients with dysplasia in BE.
Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) is a clinically av... more Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) is a clinically available tool that assesses the functional defect of various manometric abnormalities. The aim of our study was to evaluate esophageal bolus transit in patients with manometrically defined distal esophageal spasm (DES). Patients referred for esophageal function testing underwent combined MII-EM studies including 10 liquid and 10 viscous swallows. Individual swallows were classified using previously published manometric and impedance criteria. DES is traditionally defined as > or =20% simultaneous contractions in the distal esophagus. Diagnosis of esophageal transit abnormalities was defined by the presence of > or =30% incomplete liquid or > or =40% incomplete viscous swallows. Data from 71 patients (43 female, mean age 57 yr, range 16-85) with a manometric diagnosis of DES were analyzed. During liquid swallows, patients with chest pain had higher (p < 0.05) distal esophageal ...
OBJECTIVE: Nutcracker esophagus (NE) is defined as the presence of peristaltic contractions in wh... more OBJECTIVE: Nutcracker esophagus (NE) is defined as the presence of peristaltic contractions in which the average distal esophageal amplitude is greater than 180 mm Hg. The underlying mechanism responsible for these abnormalities is not known. The aim of this study was to test the hypothesis that NE might be caused by a defect in the inhibitory pathway controlling esophageal peristalsis.
Multichannel intraluminal impedance (MII) allows assessment of intraoesophageal bolus transit. In... more Multichannel intraluminal impedance (MII) allows assessment of intraoesophageal bolus transit. In the supine position, bolus transit is produced almost exclusively by peristaltic contractions; in the upright position, gravity also contributes to bolus transit. MII and peristaltic pressures were measured in four positions (0, 30, 60 and 90 degrees ) using ten swallows (5 cc each) of both water and viscous liquid with body position determined by random choice. Tracings were analysed for total bolus transit time: time interval between bolus entry at 20 cm above and bolus exit at 5 cm above the lower oesophageal sphincter (LOS) and contraction amplitudes at 5 and 10 cm above the LOS. Statistical comparison of mean values of all four body positions was done using anova and Bonnferoni post-test. Ten normal subjects (five females and five males, age 24-45 years) completed the study. At each body position, liquid material transited faster (P &amp;amp;lt; 0.001) than viscous material. Both liquid and viscous materials transited at lower inclinations (0 and 30 degrees ) significantly slower than at higher inclinations (60 and 90 degrees ). There was an almost perfect inverse linear correlation between angle of inclination and bolus transit time for both liquid (r = -0.99) and viscous (r = -1.00) boluses (Spearman correlation r &amp;amp;gt; 0.99 and P &amp;amp;lt; 0.02 for both substances). Contraction amplitudes for liquid vs viscous material were not significantly different at a given degree of inclination. Mean distal oesophageal amplitude declined with increasing inclination. Combined MII-OM identifies and quantifies the effects of gravity on the dichotomy between specific pressures measured by OM and function assessed as transit measured by MII.
Dysphagia is common in both Parkinson&amp;amp;#39;s disease (PD) and progressive supranuclear... more Dysphagia is common in both Parkinson&amp;amp;#39;s disease (PD) and progressive supranuclear palsy (PSP). Although it is believed to be more common in PSP, there are no controlled data and no comparison of swallowing function between these two disorders. Our aim was to assess dysphagia and swallow function in patients with PSP and PD. Seven patients with PSP were matched to seven patients with PD on the basis of disease duration. Self-rated dysphagia, movement disorder disability, modified barium swallow results, and abnormalities noted on manometry of the lower esophageal sphincter, esophageal body, upper esophageal sphincter, and pharynx were compared between the two groups. Neither severity nor duration of dysphagia differed between the two groups. Patients with PSP had a significantly greater degree of disability [median (range) Hoehn &amp;amp;amp; Yahr score, 4 (3-5) vs. 2 (1-2); P &amp;amp;lt; 0.002]. Manometric abnormalities were similar for the two groups. Oral-phase abnormalities on modified barium swallow were significantly more frequent in PSP (four patients with PSP vs. no patients with PD; p &amp;amp;lt; 0.005). Pharyngeal abnormalities did not differ. Modified barium-swallow scores correlated well with self-reported dysphagia severity for patients with PSP (r = 0.93; p &amp;amp;lt; 0.05) but not for those with PD (r = 0.42; p = NS). The frequency of abnormalities noted during the oral phase was significantly increased in PSP. It is hypothesized that the sensory information conveyed due to this may account for the better correlation between symptoms and swallowing abnormalities and the belief that swallowing problems are more common in PSP.
Gastroesophageal reflux disease (GERD) is known to cause a variety of symptoms that lead a patien... more Gastroesophageal reflux disease (GERD) is known to cause a variety of symptoms that lead a patient to seek otolaryngologic care. New advances in the treatment of GERD have enabled otolaryngologists to eliminate most of the signs and symptoms caused by acid reflux. Omeprazole, the most recent pharmacologic advancement, has been reported to be universally successful in controlling acid release from the stomach of patients with GERD. This report describes a series of patients with GERD for whom high-dose omeprazole therapy was not successful in completely reducing gastric acid levels of GERD symptomatology.
Esophageal manometry is a specialized procedure used to evaluate lower and upper esophageal sphin... more Esophageal manometry is a specialized procedure used to evaluate lower and upper esophageal sphincter pressure, esophageal body contraction amplitude, and peristaltic sequence. The procedure is clinically useful in evaluation of a patient with nonstructural dysphagia, unexplained or noncardiac chest pain, a compendium of symptoms suggested because of gastroesophageal reflux disease, and in the preoperative evaluation for antireflux surgery. Manometric findings in 95 normal subjects evenly distributed across age groups were reported in 1987, and are the values still used in our and most laboratories today. The subsequent review will offer our &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;view&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; on the clinical utility of esophageal manometry, on the basis of years of experience and performance techniques that have remained constant over decades.
Diabetes affects the structural and functional integrity of many organ systems, including the gas... more Diabetes affects the structural and functional integrity of many organ systems, including the gastrointestinal tract. It has been demonstrated that diabetes is associated with spontaneous gastric ulceration, and enhanced susceptibility of the gastric mucosa to injury. However, the intracellular events that regulate these processes are poorly understood. In light of our observation that in healthy adult rats, acute gastric mucosal injury results in a marked induction in EGFR tyrosine kinase (Tyr-k) activity (Histol. Histopathol. 12: 491-501, 1997), we compared gastric mucosal EGFR Tyr-k between streptozotocininduced (50 mg/kg; i.v.) 3-month old diabetic rats and their healthy counterparts. The gastric mucosa was analyzed 3 weeks after induction of diabetes, when blood glucose concentrations were between 300 and 400 mg/dL. Results revealed a 40-50% higher EGF-R Tyr-k activity in the gastric mucosa of diabetic rats than in their healthy counterparts. This was accompanied by a 400-600% increase in the relative concentration of EGFR as well as the extent of tyrosine phosphorylation of the receptor and other proteins. Recent results from this laboratory suggest that the membranebound TGF-ct may play a critical role in regulating EGFR Tyr-k activity in the gastric mucosa (Am. J. Physiol. 273: G389-G398, 1997) through a autocrine/juxtacrine mechanism. To determine whether a similar mechanism may also be responsible for the induction EGFR Tyr-k in the gastric mucosa of diabetic rats, mucosal membrane and cytosolic fractions were analyzed for TGF-ot levels by Western-immunoblot. We observed that the relative concentration of the 14 kDa precursor form of TGF-ct in gastric mucosal membranes, but not in the cytosol, was 600-700% higher in diabetic rats when compared with the corresponding preparations from their healthy counterparts. Our results demonstrate that diabetes produces a marked increase in EGFR Tyr-k activity in the gastric mucosa, which could partly be the result of increased production of the enzyme and/or a greater accumulation of TGF-tx in mucosal membranes.
The effects of age and gender on the upper esophageal sphincter&amp;amp;amp;amp;amp;amp;amp;a... more The effects of age and gender on the upper esophageal sphincter&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s (UES) and pharyngeal manometric parameters were investigated in 84 healthy subjects (45 men, 39 women, mean age = 44 years, range = 18-91). Manometric recordings were performed with solid-state circumferential transducers. Subjects older than 60 years (n = 23) showed a significant lower UES resting pressure. In addition, during water swallows they had a higher UES residual pressure, shorter UES relaxation interval and UES relaxation duration, and a decreased UES relaxation rate. Furthermore, pharyngeal contraction had significant higher amplitude and longer duration in subjects older than 60 years during water swallows. Some of these findings were also observed during cookie and pudding swallows. Women had a higher UES resting pressure and a longer UES relaxation interval than men. The observed changes with increasing age indicate loss of basal tone and decreased compliance of the UES. Increased pharyngeal contraction amplitude and its prolonged duration in the elderly might be compensatory to this. These physiologic effects of age and gender on UES and pharyngeal parameters should be taken into account during analysis of manometric studies.
Repetitive, spontaneous contractions of the proximal esophagus have recently been identified as a... more Repetitive, spontaneous contractions of the proximal esophagus have recently been identified as a feature of achalasia. This article documents similar findings in six patients with Parkinson&amp;amp;#39;s disease. Parkinson&amp;amp;#39;s disease and achalasia share many common features neurologically. Both have Lewy bodies in the esophageal myenteric plexuses and the substantia nigra, in addition to evidence of degeneration of the dorsal motor nucleus of the vagus. The esophageal features radiologically and manometrically are also similar. Repetitive proximal esophageal contractions may represent another link between these diseases. They have also been reported in scleroderma. We speculate that the common link between all three disease processes may be poor distensibility of the esophagus.
American Journal of Physiology Gastrointestinal and Liver Physiology, Feb 1, 1998
The human esophagus is composed of striated muscle proximally and of smooth muscle distally with ... more The human esophagus is composed of striated muscle proximally and of smooth muscle distally with a transition zone between the two. Striated muscle contracts much faster than smooth muscle. The change in pressure over time (dP/dt) of the contraction amplitude should therefore be higher in proximal than in distal esophagus, reflecting the presence of striated muscle proximally. There were 34 normal esophageal manometries of patients analyzed for swallow amplitude and dP/dt in the pharynx and esophagus. An additional 11 healthy controls were similarly studied. Amplitudes in pharynx and proximal and distal esophagus were not different. The mid-esophagus had a pressure trough (P &amp;amp;lt; 0.001). The dP/dt in the pharynx was much higher than that in the esophagus (P &amp;amp;lt; 0.001). The dP/dt of proximal and distal esophagus were of the same order of magnitude. The manometric behavior of the striated muscle portion of the proximal esophagus differs from that seen in the pharynx and shows similar characteristics to distal esophageal smooth muscle.
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