Tachykinins contribute to nerve-mediated contractions in the human esophagus.

BACKGROUND & AIMS: Tachykinins mediate nonadrenergic, noncholinergic excitation in the gastrointestinal tract, but their role in esophageal peristalsis remains unclear. METHODS: We used muscle strips from the distal third of human esophagus, obtained from patients undergoing esophagectomy for cancer, to investigate the contribution of tachykinins to nerve-mediated contractions. Isometric tension responses to agonists or electrical field stimulation were recorded in circular and longitudinal muscle strips. RESULTS: Tachykinins produced concentration-dependent increases in tension in circular and longitudinal muscle strips, with the following order of potency: beta-Ala(8)-neurokinin (NK) A (4-10) > NKB > substance P, suggesting NK(2) receptor involvement. The NK(2) receptor antagonist, SR48968 (1 micromol/L), inhibited responses to tachykinins in both muscles. Nerve activation produced on- and off-contractions in circular muscle and a duration-contraction in longitudinal muscle. Atropine (10 micromol/L)-insensitive nerve-evoked contractions were identified for the 3 types of responses. SR48968 produced concentration-dependent inhibition of atropine-insensitive on- and off-contractions but had no effect on the duration-contraction. At low stimulus frequency (1 Hz), on-contractions showed greater sensitivity to SR48968 than off-contractions. CONCLUSIONS: Nerve-mediated contractions in the human esophagus have a significant atropine-insensitive component. Tachykinins acting on NK(2) receptors can account for some, but not all, of this response, suggesting that other excitatory mechanisms also contribute.

Oropharyngeal dysphagia in esophageal cancer before and after transhiatal esophagectomy.

Although dysphagia is the predominant symptom of esophageal cancer, the nature of the swallowing deficit remains unclear, particularly regarding an oropharyngeal motor component. The present study examined the oropharyngeal swallow in patients with esophageal cancer before and following transhiatal esophagectomy. Videofluoroscopic data were obtained from ten patients with esophageal cancer before and following transhiatal esophagectomy as they swallowed 2-, 5-, and 10-cc aliquots of liquid and puree, and 0.5 and 1 tsp of solid. Each swallow was rated on 36 parameters by three independent judges. Swallow-related hyoid bone movement, computed from digitized segments of the videofluoroscopic data, was compared pre- and postsurgically. All patients showed at least mild abnormality of the oropharyngeal swallow preoperatively. Abnormalities involved all stages of swallowing in nine of the ten patients; however, the oral preparatory/oral stage was relatively more impaired than the pharyngeal stage in the majority of patients. Postsurgically, all patients exhibited at least a mild oropharyngeal swallowing impairment. New or increased postoperative deficits involved the pharyngeal stage of swallowing, whereas oral stage abnormalities were generally improved or unchanged following surgery. Swallow-related hyoid kinematics were highly variable both before and following surgery. Anterior hyoid bone excursion was significantly reduced postoperatively in one patient and significantly increased in one patient. Patients with esophageal cancer exhibit oropharyngeal dysphagia, with different profiles of abnormality before and following esophagectomy.

Pharmacological and molecular characterization of muscarinic receptor subtypes in human esophageal smooth muscle.

Esophageal peristalsis is dependent on activation of muscarinic receptors, but little is known about the roles of specific receptor subtypes in the human esophagus. We examined muscarinic receptor expression and function in human esophageal smooth muscle obtained from patients undergoing resection for cancer. [(3)H]Quinuclidinyl benzylate (QNB)-specific binding was similar in longitudinal muscle (B(max) = 106 +/- 22 fmol/mg of protein, K(d) = 68 +/- 9 pM) and circular muscle (B(max) = 81 +/- 16 fmol/mg of protein, K(d) = 79 +/- 15 pM). Subtype-selective antagonists inhibited [(3)H]QNB similarly in muscle from both layers. Further analysis of antagonist inhibition of [(3)H]QNB binding showed a major site (60-70%) with antagonist affinity profile consistent with the M2 subtype and a second site that could not be classified. Reverse transcription-polymerase chain reaction and immunoblotting demonstrated the presence of all five known muscarinic receptor subtypes, and immunocytochemistry on acutely isolated smooth muscle cells confirmed the expression of each subtype on the muscle cells. Subtype-selective antagonists had similar inhibitory effects on carbachol-evoked contractions in longitudinal muscle and circular muscle strips with pA(2) values of 9.5 +/- 0.1 and 9.6 +/- 0.2 for 4-diphenylacetoxy-N-methylpiperidine methiodide, 7.1 +/- 0.1 and 7.0 +/- 0.2 for pirenzepine, and 6.2 +/- 0.2 and 6.4 +/- 0.2 for methoctramine, respectively. We conclude that human esophageal smooth muscle expresses muscarinic receptor subtypes M1 through M5. The antagonist sensitivity profile for muscle contraction is consistent with activation of the M3 subtype.

Human esophageal smooth muscle cells express muscarinic receptor subtypes M(1) through M(5).

Receptor characterization in human esophageal smooth muscle is limited by tissue availability. We used human esophageal smooth muscle cells in culture to examine the expression and function of muscarinic receptors. Primary cultures were established using cells isolated by enzymatic digestion of longitudinal muscle (LM) and circular muscle (CM) obtained from patients undergoing esophagectomy for cancer. Cultured cells grew to confluence after 10-14 days in medium containing 10% fetal bovine serum and stained positively for anti-smooth muscle specific alpha-actin. mRNA encoding muscarinic receptor subtypes M(1)-M(5) was identified by RT-PCR. The expression of corresponding protein for all five subtypes was confirmed by immunoblotting and immunocytochemistry. Functional responses were assessed by measuring free intracellular Ca(2+) concentration ([Ca(2+)](i)) using fura 2 fluorescence. Basal [Ca(2+)](i), which was 135 +/- 22 nM, increased transiently to 543 +/- 29 nM in response to 10 microM ACh in CM cells (n = 8). This response was decreased <95% by 0.01 microM 4-diphenylacetoxy-N-methylpiperidine, a M(1)/M(3)-selective antagonist, whereas 0.1 microM methoctramine, a M(2)/M(4)-selective antagonist, and 0.1 microM pirenzepine, a M(1)-selective antagonist, had more modest effects. LM and CM cells showed similar results. We conclude that human smooth muscle cells in primary culture express five muscarinic receptor subtypes and respond to ACh with a rise in [Ca(2+)](i) mediated primarily by the M(3) receptor and involving release of Ca(2+) from intracellular stores. This culture model provides a useful tool for further study of esophageal physiology.

Delayed rectifier and Ca(2+)-dependent K(+) currents in human esophagus: roles in regulating muscle contraction.

We have examined K(+) channels and their function in human esophageal smooth muscle using perforated patch recording, RT-PCR to identify channel mRNA, and muscle contraction to study the effects of channel blockers. Depolarization revealed at least two types of currents: a 4-aminopyridine (4-AP)-sensitive transient delayed rectifier K(+) (K(V)) and a Ca(2+)-dependent K(+) (K(Ca)) current. K(Ca) current was active at positive potentials and was blocked by tetraethylammonium (TEA), iberiotoxin, and charybdotoxin but was insensitive to 4-AP. The mRNA encoding the gene products of Kv1.2 and Kv1.5 was identified in muscle and dissociated cells, consistent with these channel types contributing to K(V) current. 4-AP increased resting tension of muscle strips, suggesting a role for K(V) in setting the membrane potential. TEA, but not 4-AP, augmented the amplitude and duration of electrically evoked contraction, effects that were abolished by nifedipine. Here we provide the first description of macroscopic K(+) currents in human esophagus. K(V) channels participate in regulation of resting tension, whereas the K(Ca) channel limits depolarization and contraction during excitation.

Intrasphincteric botulinum toxin versus pneumatic dilatation for achalasia: a cost minimization analysis.

BACKGROUND: Pneumatic dilatation or intrasphincteric botulinum toxin injection provide effective symptom relief for patients with achalasia. Although intrasphincteric botulinum toxin injection is simple and safe, its efficacy may be short-lived. Pneumatic dilatation lasts longer, but esophageal perforation is a risk. We compared treatment costs for pneumatic dilatation and intrasphincteric botulinum toxin injection using a decision analysis model to determine whether the practical advantages of intrasphincteric botulinum toxin injection outweigh the economic impact of the need for frequent re-treatment. METHODS: Probability estimates for intrasphincteric botulinum toxin injection were derived from published reports. Probability estimates for the pneumatic dilatation strategy were obtained by retrospective review of our 10-year experience using the Rigiflex dilator. Direct, "third-party payer" costs were determined in Canadian dollars. RESULTS: Intrasphincteric botulinum toxin injection was significantly more costly at $5033 compared with $3608 for the pneumatic dilatation strategy, yielding an incremental cost of $1425 over the 10-year period considered. Sensitivity analysis showed that pneumatic dilatation is less expensive across all probable ranges of costs and probability estimates. The intrasphincteric botulinum toxin injection strategy is less costly if life-expectancy is less than 2 years. CONCLUSIONS: Intrasphincteric botulinum toxin injection is more costly than pneumatic dilatation for the treatment of achalasia. The added expense of frequent re-treatment with intrasphincteric botulinum toxin injection outweighs the potential economic benefits of the safety of the procedure, unless life-expectancy is 2 years or less.

Myogenic mechanism for peristalsis in the cat esophagus.

A myogenic control system (MCS) is a fundamental determinant of peristalsis in the stomach, small bowel, and colon. In the esophagus, attention has focused on neuronal control, the potential for a MCS receiving less attention. The myogenic properties of the cat esophagus were studied in vitro with and without nerves blocked by 1 microM TTX. Muscle contraction was recorded, while electrical activity was monitored by suction electrodes. Spontaneous, nonperistaltic, electrical, and mechanical activity was seen in the longitudinal muscle and persisted after TTX. Spontaneous circular muscle activity was minimal, and peristalsis was not observed without pharmacological activation. Direct electrical stimulation (ES) in the presence of bethanechol or tetraethylammonium chloride (TEA) produced slow-wave oscillations and spike potentials accompanying smooth muscle contraction that progressed along the esophagus. Increased concentrations of either drug in the presence of TTX produced slow waves and spike discharges, accompanied by peristalsis in 5 of 8 TEA- and 2 of 11 bethanechol-stimulated preparations without ES. Depolarization of the muscle by increasing K(+) concentration also produced slow waves but no peristalsis. We conclude that the MCS in the esophagus requires specific activation and is manifest by slow-wave oscillations of the membrane potential, which appear to be necessary, but are not sufficient for myogenic peristalsis. In vivo, additional control mechanisms are likely supplied by nerves.

Characterization and regulation of Ca2+-dependent K+ channels in human esophageal smooth muscle.

We examined the properties of K+ channels in smooth muscle cells dissociated from human esophagus using patch-clamp recording in the cell-attached configuration. The predominant channel observed had a conductance of 224 +/- 4 pS, and current reversal was dependent on K+ concentration. Channel activity was voltage dependent and increased with elevation of intracellular free Ca2+ concentration ([Ca2+]i), consistent with this being the large-conductance Ca2+-dependent K+ (KCa) channel. ACh as well as caffeine caused transient increases in KCa channel activity, and the effects of ACh persisted in Ca2+-free solution, indicating that Ca2+ release from stores contributed to channel activation. Simultaneous patch clamp and fluorescence revealed that KCa channel activity was well correlated with elevation of [Ca2+]i. The functional role of KCa channels in esophagus was studied by measuring ACh-induced contraction of strips of muscle. Tetraethylammonium and iberiotoxin, blockers of KCa channels, increased ACh-induced contraction, consistent with a role for K+ channels in limiting excitation and contraction. These studies are the first to characterize KCa channels and their regulation in human esophageal smooth muscle.

Colorectal inflammation and increased cell proliferation associated with oral sodium phosphate bowel preparation solution.

Evidence is emerging that sodium phosphate (NaP), a commonly used oral cathartic agent, causes aphthoid ulcers or focal active colitis (FAC) in the colon and rectum. The aims of this study were (1) to assess the incidence of such ulcers diagnosed endoscopically ("aphthoid ulcers"), (2) to assess the incidence of histologically detected FAC and neutrophilic infiltration overlying lymphoid follicles ("aphthoid lesions"), and (3) to determine whether this effect of NaP is associated with epithelial cell proliferation. Aphthoid ulcers, unexplained by other diagnoses, were found in 18 of 687 consecutive patients (2.6%) who underwent colonoscopic examination after oral NaP preparation during a 12-month period; biopsy specimens showed FAC or aphthoid lesions. FAC was present in 11 of 316 patients (3.5%) who had biopsies but were endoscopically normal. Eight patients with aphthoid ulcers in the rectosigmoid showed no abnormalities when reexamined by flexible sigmoidoscopy after an interval as short as 7 days (range, 7 to 56 days). Mucosal biopsy specimens from these patients were assessed for apoptosis and epithelial proliferation by determining the MIB-1 labeling index (LI). The LI was increased by 136% after NaP preparation (55 +/- 6) compared with biopsy specimens obtained from the same patients during reexamination without NaP preparation (23 +/- 6, P = .01). This correlated with the number of apoptotic bodies per 10 colonic crypts (1.2 +/- 0.3 v 0.5 +/- 0.2, respectively). To determine whether these proliferative changes represent a response to mucosal ulceration, rectosigmoid biopsy specimens were compared in two additional patient groups: an NaP group in whom no gross lesions were evident and a no-NaP group who were not exposed to NaP. Although more modest, similar changes in the LI (42 +/- 4 and 30 +/- 3, respectively, P = .03) and in the occurrence of apoptotic bodies per 10 colonic crypts (1.3 +/- 0.4 and 0.4 +/- 0.1, respectively) were observed. We conclude that use of NaP is associated with increased colorectal crypt epithelial cell proliferation. This proliferative response to NaP exposure is evident in the absence of colonoscopically or other histologically recognizable abnormalities. In a proportion of patients, aphthoid ulcers, FAC, or aphthoid lesions serve as markers of mucosal damage by NaP.

Pharmacological and molecular characterization of muscarinic receptors in cat esophageal smooth muscle.

The muscarinic receptor subtypes that mediate cholinergic responses in cat esophageal smooth muscle were examined. Antagonist effects on carbachol-induced and nerve-evoked contractions were studied in vitro using muscle strips from the distal esophagus. Antagonists displayed similar relative selectivities in suppressing carbachol and nerve-mediated responses as follows: 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) > zamifenacin > para-fluoro-hexahydrosiladiphenidol > pirenzepine > AF-DX 116 > methoctramine, indicating that these responses are mediated by the same receptor subtype. 4-DAMP, pirenzepine and methoctramine effects on carbachol responses gave pA2 values characteristic of the M3 receptor in both the circular muscle (9.25 +/- 0.12, 6.79 +/- 0.09 and 6.04 +/- 0.11, respectively) and longitudinal muscle (9.46 +/- 0.14, 7.25 +/- 0.07 and 6.10 +/- 0.06, respectively). Reverse transcription-polymerase chain reaction analysis was done using primer sequences based on the cloned human muscarinic receptor subtypes. Messenger RNA for the m3 receptor was readily identified, whereas m2 was not detected in esophageal muscle, but was present in cardiac muscle. Sequence homology between the amplified products from cat tissue and the corresponding human m2 and m3 receptors genes were 93% and 89%, respectively. In the cat esophagus, the M3 receptor mediates functional responses and messenger RNA for the corresponding molecular form of this receptor is abundant in this tissue.

A cost-utility analysis comparing omeprazole with ranitidine in the maintenance therapy of peptic esophageal stricture.

BACKGROUND: Recent studies have suggested that patients receiving omeprazole for prophylaxis against peptic esophageal stricture recurrence have less dysphagia and require fewer repeat dilations than patients receiving ranitidine. OBJECTIVE: To estimate the incremental utility gain and associated incremental cost of omeprazole compared with those of ranitidine for the maintenance therapy of patients with peptic stricture who required esophageal dilation. METHODS: Decision analysis using SMLTREE software was used to compare the incremental cost-utility of omeprazole 20 mg once daily with that of ranitidine 150 mg bid for one year. Variables were estimated from the literature, hospital data, and utility analyses involving patients with peptic stricture and health professionals. The primary outcome measure was cost per quality-adjusted life-years (QALYs) gained. RESULTS: The incremental cost of omeprazole compared with that of ranitidine was $556 per patient treated. The incremental utility gain of omeprazole was 0.0112 QALYs. Overall, the incremental cost:utility ratio of omeprazole in the maintenance therapy of patients with peptic stricture was $49,600 per QALY gained. A sensitivity analysis revealed that the estimates with the greatest impact on the cost:utility ratio were disutility associated with dysphagia and dilation, the probability of requiring redilation and the cost of medications. CONCLUSIONS: Omeprazole 20 mg once daily is associated with greater utility and higher cost than ranitidine 150 mg bid when used as prophylaxis against stricture recurrence. Omeprazole may be considered clinically and economically sufficient enough to warrant widespread use in this setting.

Regulation of intracellular calcium in human esophageal smooth muscles.

We have investigated sources of Ca2+ contributing to excitation of human esophageal smooth muscle, using fura 2 to study cytosolic free Ca2+ concentration ([Ca2+]i) in dispersed cells and contraction of intact muscles. Acetylcholine (ACh) caused an initial peak rise of [Ca2+]i followed by a plateau accompanied by reversible contraction. Removal of extracellular Ca2+ or addition of dihydropyridine Ca2+ channel blockers reduced the plateau phase but did not prevent contraction. Caffeine also caused elevation of [Ca2+]i and blocked responses to ACh. Undershoots of [Ca2+]i were apparent after ACh or caffeine. Blockade of the sarcoplasmic reticular Ca(2+)-ATPase by cyclopiazonic acid (CPA) reduced the ACh-evoked increase of [Ca2+]i and abolished the undershoot, indicating involvement of Ca2+ stores. When contraction was studied in intact muscles, removal of Ca2+ or addition of nifedipine reduced, but did not abolish, carbachol (CCh)-induced contraction. Elevation of extracellular K+ caused contraction that was inhibited by nifedipine, although CCh still elicited contraction. CPA caused contraction and suppressed the CCh-induced contraction, whereas ryanodine reduced CCh-induced contraction. Our studies provide evidence that muscarinic excitation of human esophagus involves both release of Ca2+ from intracellular stores and influx of Ca2+.

Regional differences in cholinergic activity of muscle fibers from the human gastroesophageal junction.

Muscles of the gastroesophageal junction that contribute to the lower esophageal sphincter (LES) include clasplike semicircular fibers on the right and slinglike oblique gastric fibers on the left. This study examined whether in vitro differences between the sling and clasp muscles could account for the in vivo asymmetry of LES pressure and its cholinergic contribution. Isometric tension was recorded from muscle strips of the sling, clasp, and circular layers of the esophagus and gastric fundus isolated from surgical specimens. The sling developed less spontaneous tension (8.9 +/- 4.3 mN/mm2) than the clasp (25.0 +/- 7.4 mN/mm2, P < 0.01) but showed a fivefold greater increase in response to carbachol. Eserine (1 microM) increased tension in the sling muscle (64.5 +/- 29.7%), but not in the clasp, whereas 1 microM atropine or 1 microM tetrodotoxin had no significant effect in either muscle. In both muscles, tension was reduced by 10 microM sodium nitroprusside. Sling or clasp muscle differed from circular muscle of the esophagus or gastric fundus in spontaneous tension, carbachol response, or responses to electrical stimulation. Thus the clasp muscle develops greater spontaneous tension, whereas the sling is more sensitive to cholinergic stimulation, providing a potential explanation for the in vivo asymmetry of the LES pressure and its response to cholinergic blockade.

Coordination of breathing and swallowing: effects of bolus consistency and presentation in normal adults.

Respiration and swallowing were recorded simultaneously by inductance plethysmography, submental electromyography, and a throat microphone in 10 normal subjects during eating and drinking tasks that included single boluses of varying volume (5-20 ml) and consistency presented with a syringe and cup, a 200-ml drink taken with and without the use of a straw, and a sandwich meal. Swallows were associated with a brief swallow apnea (SA) lasting approximately 1 s. Swallow effects on the duration or tidal volume of the preswallow, postswallow and swallow-associated breathing cycles varied depending on bolus characteristics and presentation. Expiration before and after the SA was the preferred pattern with all drinking and eating tasks. Inspiration followed SA in < 5% of single-bolus swallows, but this pattern increased significantly with a 200-ml drink administered by cup or by straw and during a sandwich meal (23.8 +/- 5.2, 27.0 +/- 2.6, and 16.3 +/- 2.7%, respectively. Hence, the swallow-associated breathing pattern seen with single-bolus swallows may not reflect that associated with regular eating and drinking behavior. This finding implies that the risk of aspiration may be reduced by teaching patients prone to aspiration to simplify the complex behavior of eating and drinking to a series of single-bolus swallows.

Predictors for frequent esophageal dilations of benign peptic strictures.

Recurrence of esophageal peptic stricture necessitating repeated dilation treatments remains a problem for many patients despite optimal acid suppressive therapy. The factors associated with frequent relapses are poorly understood. We studied retrospectively a population of 58 patients with benign peptic strictures and dysphagia treated by esophageal dilation and followed for 66.5 +/- 6.7 months. Data was collected for age, sex, heartburn, weight loss, esophagitis, Barrett's esophagus, number of dilation treatments during the first year of follow-up, frequency and number of subsequent dilation treatments, type of dilator used, and history of other concurrent treatments. Patients who lacked heartburn (P = 0.007) or who reported a history of weight loss (P = 0.006) at the time of their initial presentation required more frequent dilations during the first year of follow-up. The mean number of dilations in year 1 was 6.2 +/- 0.9 for patients lacking heartburn versus 3.2 +/- 0.5 for patients with heartburn (P = 0.004), and 9.0 +/- 1.8 for patients who reported weight loss versus 4.1 +/- 0.5 (P = 0.006) for those who did not. The patients requiring frequent treatment during their first year also required frequent subsequent dilations because of stricture recurrence (P < 0.0001). We did not demonstrate any relationship between the other factors studied and treatment frequency. These observations suggest that patients who require frequent retreatment for recurrent peptic stricture are more likely to provide a history of weight loss and less likely to complain of heartburn at initial presentation. The pattern of frequent repeat dilation for recurrent peptic strictures is established during the first year of follow-up.

Phasic contractions of the muscular components of human esophagus and gastroesophageal junction in vitro.

This study was performed to assess the repetitive phasic mechanical and (or) electrical activity of the muscle from different regions of the human gastroesophageal junction (GEJ). Muscle strips from the circular and longitudinal layers of the gastric fundus and esophagus and of the clasp and sling components of the GEJ were obtained from surgical specimens and prepared for in vitro recording of contractile or electrical activity. Phasic contractions occurred in all regions except the longitudinal muscle of the gastric fundus and that overlying the sling. Robust phasic activity (2.6 +/- 0.6 min-1) was most frequent (92% of specimens) in longitudinal muscle overlying the clasp, arising spontaneously in 67%. Stretch or carbachol stimulation increased the frequency of these contractions. Transmural electrical stimulation produced a transient cessation of phasic activity. Electrical recording showed slow waves with superimposed spiking coinciding with phasic contractions. These activities were unaltered by 1 microM atropine or 1 microM tetrodotoxin, but inhibited by 2 microM verapamil. In conclusion, several muscles of the human esophagus and GEJ manifest repetitive contractions in vitro, particularly the longitudinal muscle overlying the clasp muscle fibers. These oscillations are due to electrical slow waves, can potentially be modulated by intrinsic nerves, and may play a role in the intermittent phasic contractions of lower esophageal sphincter pressure in vivo.

Achalasia in Down's syndrome.

Gastrointestinal disorders, including motor disorders of the esophagus, occur more frequently in patients with Down's syndrome than in the general population. We recently diagnosed achalasia in a man with Down's syndrome, an association reported only once before. Of the 643 patients with achalasia treated at our institution over a 30-year period (1962-1992), a total of three had Down's syndrome. We report their clinical, radiological, and manometric findings. Achalasia may be underdiagnosed in patients with Down's syndrome because their intellectual impairment may interfere with their ability to report symptoms adequately. All three patients responded well to conventional treatment.

Nitric oxide mediates inhibitory nerve effects in human esophagus and lower esophageal sphincter.

The effect of inhibition of nitric oxide synthase on nonadrenergic, noncholinergic nerve-mediated responses in circular smooth muscle of the human esophageal body and lower esophageal sphincter (LES) was examined in vitro. Tissues were obtained from 10 patients (eight esophageal resection for cancer, two transplant donors). Muscle strips from the LES developed significant spontaneous tension (11.6 +/- 2.1 mN/mm2, N = 6) and relaxed in response to electrical stimulation. The nitric oxide synthase inhibitor, N omega-nitro-L-arginine (NNA), at 10(-5) M, inhibited the relaxation, but had no significant effect on the spontaneous tension (13.0 +/- 2.6 mN/mm2, P = 0.07). Esophageal body strips developed little spontaneous tension, demonstrated an "off" contraction following the cessation of the electrical stimulus, and when contracted with 10(-5) M carbachol, relaxed during electrical stimulation. NNA (10(-5) M) inhibited the off contraction and the relaxation seen after carbachol and unmasked a prominent intrastimulus contraction. This intrastimulus contraction was enhanced by eserine and inhibited by atropine and tetrodotoxin. NNA showed similar potency in the esophageal body and LES and its effects were reversed by L-arginine, but not D-arginine. The results indicate that nitric oxide is an important mediator for nonadrenergic, noncholinergic nerve effects in the human esophagus and lower esophageal sphincter.

Cholinergic responses in the cat lower esophageal sphincter show regional variation.

BACKGROUND/AIMS: The lower esophageal sphincter (LES) pressure in humans is asymmetric; the highest pressure and the most significant cholinergic contribution occurs toward the left. The basis of this asymmetry was examined using the cat as a model. METHODS: The LES pressure profile was determined using a manometry catheter with four ports oriented at right angles. The LES was dissected into right and left halves with the latter including a contribution from the oblique gastric sling fibers. Isometric tension responses were studied in vitro. RESULTS: In vivo, both the initial LES pressure (31.8 +/- 4.0 mm Hg) and the decrease (79.9% +/- 6.4%) after intravenous atropine (100 micrograms/kg) were greatest in the leftward direction. In vitro, both halves of the LES developed similar spontaneous tension, but the increase in tension to carbachol was twofold greater on the left than the right. Eserine increased and atropine decreased initial tension by 25%-30% in both. Strips from either side relaxed in response to electrical stimulation but the response was more complete in strips from the right, whereas sodium nitroprusside produced similar relaxation in both. CONCLUSIONS: Regional differences in the LES pressure and its cholinergic component can be accounted for by differences in the in vitro properties of the LES muscle fiber groups.

Hemorrhagic colitis caused by Escherichia coli O157:H7--unusual ultrasonographic and computed tomography findings.

Hemorrhagic colitis due to Escherichia coli O157:H7 occurs sporadically but widely throughout North America. Radiographically this condition may mimic ischemic colitis, inflammatory bowel disease, acute appendicitis or appendiceal abscess. Correlation of radiologic and clinical findings is required to ensure diagnostic accuracy and avoid unnecessary surgical intervention.