Effects of cisapride on the esophageal motor function of patients with progressive systemic sclerosis or mixed connective tissue disease.

In a double-blind crossover study lower esophageal sphincter pressure and distal esophageal motility were studied in 10 patients with progressive systemic sclerosis or mixed connective tissue disease, following a single intravenous dose of cisapride or placebo. The measurements were carried out under basal conditions and 30 min after intravenous administration of 10 mg cisapride or placebo. No effects on lower esophageal sphincter pressure or distal esophageal motility were observed.     

Anorectal motility in systemic scleroderma

We prospectively compared esophageal and rectal motility data from 7 patients with progressive systemic sclerosis (4 females, 3 males) to esophageal recordings in 22 and anorectal recordings in 9 healthy controls. All patients with sclerosis exhibited motility disturbances in the lower esophageal sphincter (LES): LES resting pressure, LES relaxation amplitude and duration, and the number of incomplete LES relaxations were significantly different compared to the controls. All patients had alterations of anorectal motility: resting pressure, maximal squeeze pressure, and sphincter relaxation amplitude following balloon distension of the rectum were significantly decreased as compared to the control subjects. We conclude that esophageal and anorectal manometry are comparable in their sensitivity to differentiate between patients with systemic sclerosis and normal subjects.     

Esophageal function in progressive systemic sclerosis.

A prospective study was performed in 13 consecutive patients with systemic progressive sclerosis (PSS). For the diagnosis of impaired esophageal peristalsis cineradiography and manometry are equally useful. Esophageal suction biopsy allows the diagnosis of esophagitis but not of scleroderma. Mild to severe esophageal involvement was observed in 12 patients. In only one patient the esophagus was virtually normal. Dysfunction of the esophageal body may occur early in the course of the disease while incompetence of the lower esophageal sphincter is observed on an average after 7 to 8 years. Both impairment of peristalsis and pressure of the lower esophageal sphincter may lead to delayed esophageal clearance. Relaxation of LES is normal even in the absence of primary peristalsis. Extensive esophageal damage including severe gastroesophageal reflux may be present in the absence of esophageal symptoms.     

The Role of Nifedipine Therapy in Achalasia: Results of a Randomized, Double-Blind, Placebo-Controlled Study

Utilizing the rationale that the calcium channel blocker nifedipine decreases lower esophageal sphincter pressure, we performed a double-blind, placebo-controlled, crossover trial of sublingual nifedipine in achalasia, a disorder whose treatment depends on reduction in lower esophageal sphincter pressure. Ten patients participated in this trial, completed diaries, underwent manometric determinations of lower esophageal sphincter pressure, and had testing of esophageal emptying rates by a solid-meal radionuclide method. Nifedipine, titrated to a dose of 10-30 mg before meals, was well tolerated. Compared with placebo, nifedipine significantly reduced the frequency of dysphagia, but some symptoms of dysphagia, regurgitation, or nocturnal cough were still present most days. Nifedipine significantly reduced lower esophageal sphincter pressure by 28%, a value approximately one-half that achieved by successful pneumatic dilatation or myotomy. Esophageal emptying rates, as determined by the radionuclide method, were unchanged by nifedipine. We concluded that 1) nifedipine reduces symptoms of achalasia, but substantial symptoms do remain during such therapy; 2) the suboptimal effect results from the limited, although statistically significant, effect of nifedipine on reduction of lower esophageal sphincter pressure; and 3) although we believe that nifedipine may be recommended as treatment for achalasia in the subset of patients whose overall medical condition places them at high risk for forceful dilatation or surgery, it cannot be recommended as a standard alternative to these other modalities.     

Effects of famotidine on upper gastrointestinal motility in patients with progressive systemic sclerosis

The effects of famotidine on human upper gastrointestinal motility were investigated, together with the relationship of gastric alkalinization and serum gastrin levels to changes produced by famotidine. Intravenous famotidine (20 mg), at a dose level in which an inhibitory effect on acetylcholinesterase activity is not recognized, was given to 13 patients with progressive systemic sclerosis but no other disorders. Gastric phasic motor activity was not changed significantly, but the lower esophageal sphincter pressure was elevated significantly in comparison with 15 controls given physiological saline, even when gastric phasic motor activity was taken into consideration. Gastric alkalinization with 7% sodium bicarbonate did not significantly increase the sphincter pressure in all 7 subjects so treated. No significant correlation was recognized between the serum gastrin level, the lower esophageal sphincter pressure, and the gastric motility index in any of the 3 groups. It was, therefore, concluded that intravenous administration of famotidine affected upper gastrointestinal motility, especially the lower esophageal sphincter pressure, through an as yet unknown mechanism other than inhibition of acetylcholinesterase activity, gastric alkalinization, or elevation of serum gastrin levels.     

Comparative studies of esophageal function in systemic sclerosis.

Three modalities for assessing esophageal dysfunction in patients with systemic sclerosis were prospectively compared. Seventeen patients underwent (a) esophageal manometry with measurement of distal esophageal peak contraction pressure amplitude, percentage of peristaltic waves, and lower esophageal sphincter pressure; (b) cine-esophagography with scoring based on residual contrast and the character of visualized waves; and (c) esophageal transit scintigraphy with quantification of residual swallowed tracer. Highly significant correlations were found between scintigraphic residual and cine-esophagography score, between scintigraphic residual and manometric amplitude, and indeed between all pairs of measured esophageal function parameters except those involving lower esophageal sphincter pressure. In addition, scintigraphy and cine-esophagography showed comparable ability to discriminate between patients with abnormal and normal esophageal motor function. Symptoms did not significantly correlate with quantitative parameters, nor did they have diagnostic discriminating ability. Induction of Raynaud's phenomenon in a subgroup of patients had no detectable effect on esophageal function. It was concluded that these three diagnostic modalities are approximately equivalent in their ability to detect esophageal dysmotility in systemic sclerosis and measure its severity.     

Metoclopramide response in patients with progressive systemic sclerosis. Effect on esophageal and gastric motility abnormalities

Twelve patients with progressive systemic sclerosis (four with CREST [calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia] variant) underwent systematic evaluation to assess the esophagogastric effects of metoclopramide hydrochloride in this patient population. Esophageal manometry, esophageal radionuclide scintigraphy, solid-phase gastric emptying, and 24-hour esophageal pH monitoring were performed in all patients with and without metoclopramide. Metoclopramide improved lower esophageal sphincter pressure and reduced the gastric emptying delay and gastroesophageal reflux in most patients but had a less consistent effect improving esophageal transit or esophageal body pressures. Metoclopramide should be strongly considered in the pharmacologic approach to the gastroesophageal reflux-related complications of this disease.     

Effects of famotidine on upper gastrointestinal motility in patients with progressive systemic sclerosis.

The effects of famotidine on human upper gastrointestinal motility were investigated, together with the relationship of gastric alkalinization and serum gastrin levels to changes produced by famotidine. Intravenous famotidine (20 mg), at a dose level in which an inhibitory effect on acetylcholinesterase activity is not recognized, was given to 13 patients with progressive systemic sclerosis but no other disorders. Gastric phasic motor activity was not changed significantly, but the lower esophageal sphincter pressure was elevated significantly in comparison with 15 controls given physiological saline, even when gastric phasic motor activity was taken into consideration. Gastric alkalinization with 7% sodium bicarbonate did not significantly increase the sphincter pressure in all 7 subjects so treated. No significant correlation was recognized between the serum gastrin level, the lower esophageal sphincter pressure, and the gastric motility index in any of the 3 groups. It was, therefore, concluded that intravenous administration of famotidine affected upper gastrointestinal motility, especially the lower esophageal sphincter pressure, through an as yet unknown mechanism other than inhibition of acetylcholinesterase activity, gastric alkalinization, or elevation of serum gastrin levels.     

Esophagitis in progressive systemic scleroderma. Prevalence and risk factors in forty-six patients]

Forty-six patients with progressive systemic sclerosis (37 women and 9 men) were successively evaluated by endoscopy, manometry, and esophageal pH monitoring. Fourteen patients (30.4 percent) had erosive esophagitis. Twenty-four patients were symptomatic; nineteen patients complained of dysplagia. Erosive esophagitis was significantly more frequent in symptomatic patients than in asymptomatic patients (50.0 percent vs 9 percent, P less than 0.01) and especially in patients complaining of dysphagia (57.9 percent vs 11.1 percent, P less than 0.01). Erosive esophagitis was not correlated with symptoms of gastroesophageal reflux. Abnormal esophageal motility was found in 34 patients (73.9 percent). Occurrence of erosive esophagitis was not linked with esophageal dysmotility. In patients with erosive esophagitis lower esophageal sphincter pressures were significantly lower than those in patients without erosive esophagitis. Twenty-four hr-pH monitoring showed pathological gastroesophageal reflux in 20 patients (43.5 percent). Erosive esophagitis was more frequent in patients with pathological gastroesophageal reflux than in patients with normal gastroesophageal reflux (50.0 percent vs 15.4 percent, P less than 0.02) especially in patients with pathological supine nighttime gastroesophageal reflux (61.5 percent vs 18.2 percent, P less than 0.01). Our data suggest that symptoms, dysphagia, diminished lower esophageal sphincter pressures, and pathologic nighttime gastroesophageal reflux are reliable predictors of the presence of erosive esophagitis in patients with progressive systemic sclerosis.     

Manometric evaluation of esophageal function in progressive systemic sclerosis with special regard to the disease severity

A study was conducted to elucidate the relation between the severity of progressive systemic sclerosis (PSS) and the grade of esophageal function disorder, the extent of which was estimated using esophageal manometry. Fifty two patients with PSS were divided into the mild, moderate and severe groups according to the severity score established by the PSS Research Group supported by The Ministry of Health and Welfare of Japan. Primary peristaltic pressure in the esophageal body at 25 to 35cm from the incisors as well as lower esophageal sphincter pressure (LESP), which represents the function of the smooth muscle of the esophagus, were significantly decreased in parallel with the increasing severity of PSS. In contrast, there was no significant difference in upper esophageal sphincter pressure (UESP) or in primary peristaltic pressure at 20cm from the incisors, indicating that the function of striated muscle of the esophagus was not impaired. In addition, even in the mild PSS group without dysphagia (19 cases), primary peristaltic pressure in the esophageal body at 25 to 35cm from incisors was found to be significantly decreased in comparison with the control. Hence, esophageal manometry was useful for early detection of the pathophysiological state of the esophageal function in PSS.     

Manometric evaluation of esophageal function in progressive systemic sclerosis with special regard to the disease severity.

A study was conducted to elucidate the relation between the severity of progressive systemic sclerosis (PSS) and the grade of esophageal function disorder, the extent of which was estimated using esophageal manometry. Fifty two patients with PSS were divided into the mild, moderate and severe groups according to the severity score established by the PSS Research Group supported by The Ministry of Health and Welfare of Japan. Primary peristaltic pressure in the esophageal body at 25 to 35cm from the incisors as well as lower esophageal sphincter pressure (LESP), which represents the function of the smooth muscle of the esophagus, were significantly decreased in parallel with the increasing severity of PSS. In contrast, there was no significant difference in upper esophageal sphincter pressure (UESP) or in primary peristaltic pressure at 20cm from the incisors, indicating that the function of striated muscle of the esophagus was not impaired. In addition, even in the mild PSS group without dysphagia (19 cases), primary peristaltic pressure in the esophageal body at 25 to 35cm from incisors was found to be significantly decreased in comparison with the control. Hence, esophageal manometry was useful for early detection of the pathophysiological state of the esophageal function in PSS.     

Lower esophageal rings as a cause of dysphagia in progressive systemic sclerosis—Coincidence or consequence?

Lower esophageal rings were found in five of 40 consecutive patients seen with progressive systemic sclerosis. Three of these five patients had diffuse skin involvement and two had the CREST variant of progressive systemic sclerosis. All of the patients with lower esophageal rings had intermittent esophageal obstruction (initially attributed to esophageal dysmotility), but so did five of seven patients with esophageal strictures without lower esophageal rings. Esophageal bougienage relieved this symptom in four of the five patients with rings in which it was performed. Persistent relief of these obstructive symptoms (6–36 months) in the patients with rings was in contrast to the recurrent dilatations that have been needed in the group of patients with peptic strictures. In contrast to esophageal aperistalsis and/or stricture formation, the lower esophageal ring, perhaps as a consequence of chronic gastroesophageal reflux, may be a more treatable cause of dysphagia in patients with progressive systemic sclerosis.     

Comparison of effects of nifedipine,propantheline bromide,and the combination on esophageal motor function in normal volunteers

Both intracellular calcium ions and neural input are important in esophageal smooth muscle contraction. The aim of this study was to compare the effects of well-tolerated doses of the calcium-channel blocker, nifedipine (20 mg sublingually/buccally) with the anticholinergic, propantheline bromide (15 mg orally) and the combination of these two agents on esophageal motor function. Seven healthy volunteers underwent manometric evaluation after nifedipine, propantheline bromide, the combination, and placebo on different days. Lower esophageal sphincter pressure decreased significantly (P<0.05 vs basal and placebo) by 32% after nifedipine, but fell only 21% after propantheline bromide. After the combination lower esophageal sphincter pressure fell by 45% (P<0.05 vs basal and placebo and nifedipine alone). Contraction amplitude in the body of the esophagus decreased significantly (P<0.05 vs basal and placebo) by 26% after propantheline bromide, but fell only 11% after nifedipine. The combination led to a decrease of 37% in contraction amplitude, but this was not significantly different from that obtained with propantheline bromide alone. No drug or combination had any effect on other manometric parameters. These data show that in the normal subjects studied with the above doses: (1) nifedipine has a greater effect than propantheline bromide on the lower esophageal sphincter; (2) propantheline bromide has a greater effect than nifedipine on esophageal contraction amplitude; and (3) the combination of nifedipine and propantheline bromide has an enhanced effect on both lower esophageal sphincter pressure and esophageal contraction amplitude.     

Progressive systemic sclerosis of the internal anal sphincter leading to passive faecal incontinence.

Two female patients aged 62 and 44 years with progressive systemic sclerosis and passive faecal incontinence are described. Both had the typical gut motility disorders of dysphagia, heartburn, and constipation. Anorectal physiology tests showed a low resting pressure in both and an absent rectoanal inhibitory reflex in one. In both patients anal endosonography showed a thin internal anal sphincter with changed reflectivity suggestive of fibrosis. In both patients anorectal sensation and pudendal nerve function were normal. Histological examination of the rectum in one patient showed collagenous replacement of the rectal muscularis propria with prominent atrophy of the musculature. This study suggests that the internal sphincter may be selectively affected by progressive systemic sclerosis, which may lead to passive faecal incontinence.     

Radionuclide esophageal transit in progressive systemic sclerosis

Twenty-three patients with progressive systemic sclerosis (PSS) were studied by radionuclide esophageal transit (RT) and esophageal manometry. Twenty-two patients had abnormal manometry ranging from lower esophageal sphincter incompetence to aperistaltism. Of these 22 patients, twenty (91%) had abnormal RT with prolongation of transit time. A characteristic RT pattern showing stagnation of the radionuclide in the distal and middle segments of the esophagus was demonstrated in 82% of the patients with advanced sclerodermatous involvement of the esophagus. Fifteen of the 19 controls (79%) studied had a normal RT. Four showed prolongation of transit time without stagnation. We conclude that RT is a safe, noninvasive, highly sensitive method which might be used as an alternative to esophageal manometry. However, it may lack specificity.     

Influence of age on lower esophageal sphincter pressure]

We studied the effect of aging on lower esophageal sphincter (LES) pressure of 52 normal subjects, 129 patients with Chagas' disease and 63 patients with systemic sclerosis. Three groups were compared: with ages between 10 to 29 years, 30 to 49 years and 50 to 70 years. We used a perfused catheter and the station pull-through (SPT) technique, at end expiratory phase. There was no difference in LES pressure between the three groups in normal subjects (p = 0.72) and patients with systemic sclerosis (p = 0.33). In Chagas' disease the patients with ages between 50 to 70 years had LES pressure (17 +/- 8 mmHg, mean +/- SD) lower (p = 0.03) than patients with ages between 10 to 29 years (22 +/- 9 mmHg). We conclude that in Chagas' disease the patients with ages over 50 years have LES pressure lower than patients with ages under 30 years, what does not happen with normal subjects nor systemic sclerosis patients.     

Esophageal motor disturbances in progressive systemic sclerosis

Ten patients with progressive systemic sclerosis (PSS) and esophageal symptoms (group 1) and 10 control subjects were studied. Esophageal electromanometry using the intermittent pull-through technique and catheter perfusion with distilled water were performed in all patients and individuals. The variables studied were pressure amplitude in the lower esophageal sphincter (LES) (mmHg) and deglutition wave amplitude (mmHg at 5, 10 and 15 cm above LES). In PSS patients, the average LES pressure was 18.5 +/- 4.6 mmHg, and in control subjects it was 27 +/- 6.5 mmHg (p < 0.01). Deglutition wave amplitude at 5, 10 and 15 cm above LES was 13.2 +/- 7.5 mmHg, 12 +/- 3.7 mmHg and 15 +/- 3.3 mmHg, respectively, in PSS patients. In control subjects, it was 67.6 +/- 12.5 mmHg, 58.6 +/- 20.9 mmHg and 52.4 +/- 21.4 mmHg (p < 0.001). In PSS patients, the pressure amplitude in LES and in the body of the esophagus was lower than in control subjects. In PSS patients, esophageal manometry showed the absence of normal peristalsis.     

Autoantibody profile in progressive systemic sclerosis as markers for esophageal involvement

We investigated the relationship between the severity and extent of esophageal involvement in patients with progressive systemic sclerosis (PSS) and the autoantibody profile. We studied 37 consecutive patients with PSS and compared their results to 25 healthy volunteers. Patients with PSS were separated into three subgroups: group 1 (antinuclear antibody [ANA] [+/-], anti-Sc170 antibody [Scl70] [-], and anticentromere antibody [ACA] [-]), group 2 (ANA [+], Scl70 [+], and ACA [-]), and group 3 (ANA [+], Scl70 [-], and ACA [+]). The lower esophageal sphincter pressure and the mean proximal esophageal amplitude were significantly lower in group 3 when compared with group 1, group 2, and the healthy controls. Distal esophageal aperistalsis was noted in 85% of group 3, 40% of group 2, and 30% of group 1. An involvement of esophageal motility was found in 100% of the patients with ACA. Our results suggest that esophageal involvement is more pronounced in patients with PSS with ACA as compared with patients with only Sc170 or ANA.     

Esophageal dysfunction in patients with progressive systemic sclerosis and mixed connective tissue diseases

Esophageal motility was studied in 37 patients with progressive systemic sclerosis (PSS), 12 patients with mixed connective tissue disease (MCTD) and 40 controls by the manometry method, using an open tube and continuous perfusion, and by radiological examination. Radiology was normal in 17 patients with PSS and five patients with MCTD, and abnormal in 15 patients with PSS and three with MCTD. The most frequent abnormality was slow transit time of barium. Manometry of the esophageal body was normal in 20 patients with PSS and six patients with MCTD, and abnormal in 17 patients with PSS and six with MCTD. Lack of contraction in the middle lower segments of the esophagus was the abnormality most frequently observed. Lower esophageal sphincter pressure was significantly lower among patients with PSS and MCTD than among the controls. Dysphagia was reported by ten patients with PSS and by six patients with MCTD. Radiology and manometry showed similar changes in PSS and MCTD, but dysphagia was more frequent among patients with MCTD.     

Cardiovascular autonomic function, autoantibodies, and esophageal motor activity in patients with systemic sclerosis and mixed connective tissue disease

OBJECTIVE: To study cardiovascular autonomic nerve function and presence of autoantibodies in relation to esophageal motor activity in patients with systemic sclerosis (SSc) and mixed connective tissue disease (MCTD). METHODS: Twenty-five patients with SSc (13 limited, 12 diffuse cutaneous disease; disease duration 1-19 yrs) and 6 patients with MCTD (disease duration 1-10 yrs) were studied. Cardiovascular autonomic function was assessed using 5 standard tests and autoantibody status determined. Esophageal motor activity and lower and upper esophageal sphincter pressures were recorded manometrically. RESULTS: Five patients with SSc had definite, 7 borderline, and 13 no autonomic dysfunction; 23 had antinuclear. 9 anti-Sc170, 4 anticentromere, and 1 U1snRNP antibodies. Contraction amplitudes in the smooth muscle as well as the striated muscle esophagus and lower esophageal sphincter pressures were significantly lower and autonomic dysfunction more frequent in patients with than in those without anti-Sc170 (6 of 9 vs 6 of 16 patients); upper esophageal sphincter pressures did not differ. All patients with MCTD had antinuclear antibodies, 5 had definite autonomic dysfunction; their lower esophageal sphincter pressures were significantly lower than in SSc patients without anti-Sc170 and anti-U1snRNP. CONCLUSION: Esophageal motor dysfunction may be associated with the presence of anti-Sc170 and anti-U1snRNP autoantibodies and prevail in patients with cardiovascular autonomic neuropathy.