Nutrient supply and nucleus pulposus cell function: effects of the transport properties of the cartilage endplate and potential implications for intradiscal biologic therapy.

OBJECTIVE: Intradiscal biologic therapy is a promising strategy for managing intervertebral disc degeneration. However, these therapies require a rich nutrient supply, which may be limited by the transport properties of the cartilage endplate (CEP). This study investigated how fluctuations in CEP transport properties impact nutrient diffusion and disc cell survival and function. DESIGN: Human CEP tissues harvested from six fresh cadaveric lumbar spines (38-66 years old) were placed at the open sides of diffusion chambers. Bovine nucleus pulposus (NP) cells cultured inside the chambers were nourished exclusively by nutrients diffusing through the CEP tissues. After 72 h in culture, depth-dependent NP cell viability and gene expression were measured, and related to CEP transport properties and biochemical composition determined using fluorescence recovery after photobleaching and Fourier transform infrared (FTIR) spectroscopy. RESULTS: Solute diffusivity varied nearly 4-fold amongst the CEPs studied, and chambers with the least permeable CEPs appeared to have lower aggrecan, collagen-2, and matrix metalloproteinase-2 gene expression, as well as a significantly shorter viable distance from the CEP/nutrient interface. Increasing chamber cell density shortened the viable distance; however, this effect was lost for low-diffusivity CEPs, which suggests that these CEPs may not provide enough nutrient diffusion to satisfy cell demands. Solute diffusivity in the CEP was associated with biochemical composition: low-diffusivity CEPs had greater amounts of collagen and aggrecan, more mineral, and lower cross-link maturity. CONCLUSIONS: CEP transport properties dramatically affect NP cell survival/function. Degeneration-related CEP matrix changes could hinder the success of biologic therapies that require increased nutrient supply.

ERK1/2 signaling pathway in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons.

Sensitization of esophageal nociceptive afferents by inflammatory mediators plays an important role in esophageal inflammatory nociception. Our previous studies demonstrated that esophageal mast cell activation increases the excitability of esophageal nodose C-fibers. But the intracellular mechanism of this sensitization process is still less clear. We hypothesize that extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway plays an important role in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons. Mast cell activation and in vivo esophageal distension-induced phosphorylations of ERK1/2 were studied by immuno-staining and Western blot in esophageal nodose neurons. Extracellular recordings were performed from nodose neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Nerve excitabilities were compared by action potentials evoked by esophageal distensions before and after mast cell activations with/without pretreatment of mitogen-activated protein kinases (MAPK)/ERK kinase inhibitor U0126. The expressions of phospho-ERK1/2 (p-ERK1/2) in the same nodose ganglia were then studied by Western blot. Mast cell activation enhances in vivo esophageal distension-induced phosphorylation of ERK1/2 in nodose neurons. This can be prevented by pretreatment with mast cell stabilizer cromolyn. In ex vivo esophageal-vagal preparations, both mast cell activation and proteinase-activated receptor 2 (PAR2)-activating peptide perfusion increases esophageal distension-induced mechano-excitability of esophageal nodose C-fibers and phosphorylation of ERK1/2 in nodose neurons. Pretreatment with MAPK/ERK kinase inhibitor U0126 prevents these potentiation effects. Collectively, our data demonstrated that mast cell activation enhances esophageal distension-induced mechano-excitability and phosphorylation of ERK1/2 in esophageal nodose C-fiber neurons. This reveals a new intracellular pathway of esophageal peripheral sensitization and inflammatory nociception.

Characterization of mast cell subtypes, distribution, and antigen-induced activation in the guinea pig esophagus.

The number of esophageal mucosa mast cells (MCs) increases in allergic and inflammation conditions in the esophagus, but their role in these conditions is less clear. MCs are derived from bone marrow, migrate and mature in the peripheral tissues. Two subsets of MCs have been characterized as mucosal MC (MMC) and connective tissue MC (CTMC) defined by anatomic location, granule contents, and functions. Whether esophageal MCs share typical features with either MMC or CTMC has yet to be determined. This study characterized esophageal MCs subtypes, distribution, antigen-induced sensitization, and degranulation as measured by MC staining and histamine release assay. Immunofluorescent double staining of MC tryptase and chymase were performed in the esophagus, intestine, and skin from normal and ovalbumin (OVA) actively sensitized guinea pigs. Histamine release was measured in the esophagus from OVA-sensitized guinea pigs following in vitro antigen challenge. Similar to the MCs in the intestine and skin, esophageal MCs contained three subtypes, which included 62% MCtc (tryptase+/chymase+), 17% MCc (chymase+/tryptase-), and 21% MCt (tryptase+/chymase-). In contrast to the ileal MCs, which were distributed all over the mucosa, submucosa, and serosa, MCs in the esophagus almost all (more than 98%) lined along the lamina propria. OVA active sensitization significantly increased the esophageal MC subtype MCtc. OVA in vitro challenge of the esophagus from sensitized guinea pig significantly decreased tryptase-positive MC subtypes MCtc and MCt, and released a significant amount of tissue histamine content. In conclusion, MCs in the guinea pig esophagus have unique features in immunophenotypes, distribution, and degranulation response to OVA challenge with the release of significant amounts of proteases and histamine into the tissue. These characteristics may indicate that OVA in vitro challenge in OVA-sensitized guinea pig esophagus could be a good model to study the role of esophageal MCs in allergic and inflammation conditions.

5-Hydroxytryptamine selectively activates the vagal nodose C-fibre subtype in the guinea-pig oesophagus.

The afferent neurons innervating the oesophagus originate from two embryonic sources: neurons located in vagal nodose ganglia originate from embryonic placodes and neurons located in vagal jugular and spinal dorsal root ganglia (DRG) originate from the neural crest. Here, we address the hypothesis that 5-hydroxytryptamine (5-HT) differentially stimulates afferent nerve subtypes in the oesophagus. Extracellular recordings of single unit activity originating from nerve terminals were made in the isolated innervated guinea-pig oesophagus. Whole cell patch clamp recordings (35 degrees C) were made from the primary afferent neurons retrogradely labelled from the oesophagus. 5-Hydroxytryptamine (10 micromol L(-1)) activated vagal nodose C-fibres (70%) in the oesophagus but failed to activate overtly vagal jugular nerve fibres and oesophagus-specific spinal DRG neurons. The response to 5-HT in nodose C-fibre nerve terminals was mimicked by the selective 5-HT(3) receptor agonist 2-methyl-5-HT (10 micromol L(-1)) and nearly abolished by the 5-HT(3) receptor antagonists ondansetron (10 micromol L(-1)) and Y-25130 (10 micromol L(-1)). In patch clamp studies, 2-methyl-5-HT (10 micromol L(-1)) activated a proportion of isolated oesophagus-specific nodose capsaicin-sensitive neurons (putative cell bodies of nodose C-fibres). We conclude that the responsiveness to 5-HT discriminates placode-derived (vagal nodose) C-fibres from the neural crest-derived (vagal jugular and spinal DRG) afferent nerves in the oesophagus. The response to 5-HT in nodose C-fibres is mediated by the 5-HT(3) receptor in their neuronal membrane.

Regional activation in the rat brain during visceral stimulation detected by c-fos expression and fMRI.

AIM: The aim of the study was to determine and compare the areas of brain activated in response to colorectal distention (CRD) using functional magnetic resonance imaging (fMRI) and c-fos protein expression. METHODS: For fMRI study (3.0 T magnet), anaesthetized rats underwent phasic CRD, synchronized with fMRI acquisition. Stimulation consisted of eight cycles of balloon deflation (90 s) and inflation (30 s), at 40, 60 or 80 mmHg of pressure. For c-fos study two sets of experiments were performed on anaesthetized rats: comparing (A) brain activation in rats with the inserted colorectal balloon (n = 5), to the rats without the balloon (n = 5); and (B) rats with inserted balloon (n = 10), to the rats with inserted and distended balloon (n = 10). The pressure of 80 mmHg was applied for 2 h of 30 s inflation and 90 s deflation, alternating cycles. RESULTS: Functional MRI revealed significant activation in the amygdala, hypothalamus, thalamus, cerebellum and hippocampus. Significant increase in c-fos expression was observed in amygdala and thalamus in the first set of experiments, and hypothalamus and parabrachial nuclei in the second. CONCLUSION: The two methods are not interchangeable but appeared to be complementary: fMRI was more sensitive, whereas c-fos had much greater resolution.

Iminium ion chemistry of mitosene DNA alkylating agents. Enriched 13C NMR and isolation studies.

Described herein is a study of the reductive alkylation chemistry of mitosene antitumor agents. We employed a 13C-enriched electrophilic center to probe the fate of the iminium ion resulting from reductive activation. The 13C-labeled center permitted the identification of complex products resulting from alkylation reactions. In the case of DNA reductive alkylation, the type and number of alkylation sites were readily assessed by 13C NMR. Although there has been much excellent work done in the area of mitosene chemistry and biochemistry, the present study provides a number of new findings: (1) The major fate of the iminium ion is head-to-tail polymerization, even in dilute solutions. (2) Dithionite reductive activation results in the formation of mitosene sulfite esters as well as the previously observed sulfonate adducts. (3) The mitosene iminium ion alkylates the adenosine 6-amino group as well as the guanosine 2-amino group. The identification of the latter adduct was greatly facilitated by the 13C-label at the electrophilic center. (4) The mitosene iminium ion alkylates DNA at both nitrogen and oxygen centers without any apparent base selectivity. The complexity of mitosene reductive alkylation of DNA will require continued adduct isolation studies.

Substance P binding in gastrointestinal tract of nondiabetic BB rat and changes in diabetic BB rat over time.

Our aim was to determine sites of substance P binding in the gut of the BB rat and examine changes in SP binding in the diabetic rat, over time. Specific binding of [125I]substance P was localized in sections of nondiabetic gut using emulsion autoradiography and quantitated in diabetic and nondiabetic gut using film autoradiography. High levels of SP binding were located in esophageal muscularis mucosa, circular muscle of the stomach and colon, deep muscular plexus, and in the circular muscle adjacent to the plexus in the ileum. The myenteric plexus demonstrated moderate to high levels of binding. Specific binding increased in the antrum and pylorus at three weeks and in the jejunum and distal colon at four weeks of diabetes but decreased in the distal ileum at two to four weeks of diabetes. Changes persisted at four to six months. These results contribute to understanding changes in the control of intestinal motility in diabetes.

Action of substance P and interaction of calcitonin gene-related peptide and substance P on the cat antral circular muscle.

The actions of substance P (SP) and calcitonin gene-related peptide (CGRP) and their interaction were examined in vitro in the feline antrum and colon. Circular muscle contraction was seen in the antrum to both peptides, but only to SP in the proximal colon. Antral contraction was enhanced when both peptides were given together. This interaction was inhibited by tetrodotoxin or atropine. SP acted at the antrum via a smooth muscle neurokinin receptor which is not a (NK)-1 receptor. SP binding was displaced by neurokinin A but not by the NK-1 receptor antagonist, CP-96345. The colonic response was inhibited by CP-96345. Immunohistochemistry revealed SP-like immunoreactivity (SP-LI) in fibers in the antral myenteric plexus and circular muscle, while CGRP-like immunoreactivity (CGRP-LI) was seen in the myenteric plexus only, without co-localization. These studies supported the hypothesis that SP acted via the NK-2 receptor at the feline circular muscle in the antrum to induce contraction and at the NK-1 receptor in the proximal colon. CGRP enhanced the effect of SP via a cholinergic pathway.

Polymorphism of the glycogen synthase gene and non-insulin-dependent diabetes mellitus in Chinese population.

OBJECTIVE: To investigate the possible association between the Xbal polymorphism of the glycogen synthase gene and non-insulin-dependent diabetes mellitus (NIDDM) in Chinese population. METHODS: 216 NIDDM patients and 106 healthy controls were studied. DNA fragment containing Xbal restriction site was amplified by the polymerase chain reaction, digested by the Xbal enzyme and compared by gel electrophoresis with a positive control from Finland. RESULTS: The Xbal polymorphism was found in 18 of 216 Chinese patients (8.3%) and was also found in 10 of 106 controls (9.4%) (P > 0.05). CONCLUSIONS: The results suggest that the Xbal polymorphism of the glycogen synthase gene could not be used as a genetic marker for NIDDM in Chinese population of Henan Han nationality.

Nitric oxide synthase (NOS) expression in the myenteric plexus of streptozotocin-diabetic rats.

Nitric oxide (NO) is an important inhibitory neurotransmitter in the gut. Alterations in NO mediated responses have been described in diabetic animals. The presence of nitric oxide synthase (NOS) reflects the potential for NO synthesis and is found in neurons in the myenteric plexus. The aim of this study was to determine changes in nitric oxide synthase (NOS) expression in the myenteric plexus of the gastrointestinal tract of diabetic rats at three months of streptozotocin-induced diabetes, compared to age matched controls, using immunohistochemistry. Diabetic animals showed a decrease in NOS expression in the antrum, with 59.1 +/- 7.3% of neurons being positive for NOS in diabetes compared to 81.2 +/- 4.7% in controls (P < 0.05). NOS expression in duodenum, ileum, and colon of diabetic animals was not statistically different from controls. Decreased expression of NOS in antrum may contribute to altered gastric emptying observed in diabetics.

The clinical usefulness of routine stacked multiplanar reconstruction in helical abdominal computed tomography.

RATIONALE AND OBJECTIVES: The authors evaluate the usefulness of stacked multiplanar reconstructions in routine, thick-section abdominal computed tomography. MATERIALS AND METHODS: Twenty-five routine, thick-section contrast abdominal CTs performed with equivalent technique were reformatted by multiplanar reconstructions in sagittal and coronal planes sequentially from side-to-side and front-to-back. The image sets were submitted, first axial images only followed by axial plus multiplanar reconstructions (MPRs), to 5 separate physician readers including 2 radiologists and 3 nonradiologists. These readers graded the visualization of a variety of normal and up to 5 pathologic lesions per patient on a scale of 1 to 5 (5 = best). RESULTS: The addition of sagittal and coronal multiplanar reconstructions significantly improved the visualization of all normal anatomic structures (mean axial only, 3.8; mean axial plus MPR, 4.1; P < 0.0001). In addition, most pathologic lesions were statistically better visualized with the addition of multiplanar reconstructions (mean axial images only, 3.9; mean axial plus MPR, 4.1; P < 0.0001). All five readers found improved visualization in nearly every category with the addition of the multiplanar reconstructions. However, in only 7% of cases, did a reviewer find new diagnostic information with the addition of MPR images. CONCLUSIONS: Stacked multiplanar reconstructions of routine, thick-section abdominal CT has clinical value in both the display of normal anatomic and pathologic lesions. Further studies, however, are required to confirm these findings before it is commonly used.

Distribution of beta-adrenoceptor subtypes in gastrointestinal tract of nondiabetic and diabetic BB rats. A longitudinal study.

The effects of aging and diabetes on the distribution of beta-adrenoceptor subtypes in the gut were investigated in the BB rat. [125I]Cyanopindolol binding to 10-micron sections was evaluated using film autoradiography. Cyanopindolol binding to beta-, beta 1-, and beta 2-adrenoceptors was displaced by 1 microM propranolol, 50 nM ICI-89-406, and 100 nM ICI-118-551, respectively. beta-Adrenoceptor binding was highest in the circular muscle of proximal colon and lowest in the pylorus of 4- to 5-month-old rats. Aging (8- to 10-month-old vs. 4- to 5-month-old rats) was associated with increased beta-adrenoceptor binding in the pylorus and reduced binding in the proximal colon. Diabetes had a time-dependent effect on the level of beta-adrenoceptor binding. It was increased in the antral and pyloric stomach but longer periods of diabetes caused a reduction in beta-adrenoceptor binding in the pylorus. Those in the intestine were reduced time-dependently and involved beta 1- or beta 2-adrenoceptors or both.

Effect of celiac ganglionectomy on tachykinin innervation, receptor distribution and intestinal responses in the rat.

Substance P (SP) is an important neurotransmitter in the control of intestinal motility and is found in both the enteric and sympathetic nervous systems. This study examined the effect of celiac ganglionectomy on (1) mechanical properties of the circular muscles of the duodenum, ileum and proximal colon, (2) circular muscle responses to SP and neurokinin A. (3) distribution of substance P-like immunoreactive nerves, and (4) the distribution of neurokinin 1 and neurokinin 2 receptors. Celiac ganglionectomy resulted in an effective sympathectomy as evidenced by a marked decrease in norepinephrine content and tyrosine hydroxylase staining in the duodenum, ileum and proximal colon. The in vitro length/tension characteristics of the circular muscle of the duodenum, ileum and colon were unchanged after ganglionectomy. In all regions of the gut studied, substance P and neurokinin A caused dose-dependent contractions that were unaltered by celiac ganglionectomy. Immunohistochemistry revealed moderate substance P-like immunoreactive fibers in the myenteric plexus, submucosal plexus and circular muscle of the ileum, while in the colon, substance P-like immunoreactivity was intense in the myenteric plexus, and moderate in the circular muscle. In vitro autoradiography showed minimal binding of SP (NK1 receptor) or neurokinin A (NK2 receptor) in the ileum and significantly greater binding in the circular muscle layer of the colon. Celiac ganglionectomy did not affect substance P-like immunoreactivity, or NK1 or NK2 receptor binding. A greater contractile response to neurokinins was seen in the colon than in the duodenum or ileum, which paralleled the receptor density. The studies demonstrate that surgical celiac ganglionectomy, unlike chemical sympathectomy, does not affect the substance P innervation, receptor density or physiological responses of the intestine. The greater contractile response of the colon than the ileum parallels the greater receptor density rather than the peptide content as determined by immunhistochemistry.

Use of positron emission tomography and evoked potentials in the detection of cortical afferents from the gastrointestinal tract.

OBJECTIVE: Positron emission tomography permits precision identification of the cerebral regions involved in physiologic functions. As the cerebral localization for visceral sensation has not been identified, our aim was to examine the cerebral viscerotopic representation for rectal sensation. METHODS: Cerebral-evoked potentials were measured in five healthy volunteers who underwent rectal balloon distension. Simultaneously, cerebral blood flow was measured using positron emission tomography with 15H2O. RESULTS: A cerebral-evoked potential occurred with rectal balloon distension. An increase in cerebral blood flow was noted in the pre- and postcentral gyrus and the thalamus. CONCLUSION: The techniques for measuring cerebral-evoked potentials and cortical blood flow are useful in the delineation of the cerebral regions subserving visceral sensation.

[An immunohistochemical study on human leucocyte antigen-DR in Hashimoto thyroiditis and Graves disease].

By using anti-human leucocyte antigen (HLA)-DR antibodies with the help of avidin-biotin complex immunohistochemical method, the authors studied the number and distribution of HLA-DR positive thyroid cells in thyroid glands from sixteen patients with Hashimoto thyroiditis, fourteen patients with Graves disease, and six controls. The correlation between the degree of thyroid cells HLA-DR expression and the values of serum thyroglobulin antibodies and thyroid peroxidase antibodies determined with radioimmunoassay was also analyzed in order to find the relation of aberrant HLA-DR expression on thyroid cells with thyroid autoimmune reaction. Normal thyroid cells did not express HLA-DR antigens, but HLA-DR antigens were often found in some thyroid cells from patients with Hashimoto thyroiditis or with Graves disease. The number of HLA-DR positive thyroid cells was significantly greater in Hashimoto thyroiditis than in Graves disease. HLA-DR positive thyroid cells were localized in areas harbouring infiltrating lymphocytes. The degree of thyroid HLA-DR expression correlated closely with the values of serum thyroglobulin antibodies and thyroid peroxidase antibodies in Hashimoto thyroiditis and Graves disease. These results suggest that infiltrating lymphocytes may facilitate HLA-DR expression on thyrocytes. The occurrence of serum thyroglobulin antibodies and thyroid peroxidase antibodies in Hashimoto thyroiditis and Graves disease may have a close relationship with aberrant HLA-DR expression by thyrocytes which were apt to be damaged by autoimmune attack.

Effect of transcutaneous nerve stimulation on esophageal function in normal subjects--evidence for a somatovisceral reflex.

Transcutaneous stimulation (TNS) at esophageal acupuncture points decreases lower esophageal sphincter (LES) pressures in patients with achalasia. We examined the effect of TNS on esophageal motility and vasoactive intestinal peptide (VIP) levels in normal subjects. TNS was applied to either hand or foot (placebo) in 10 volunteers. Esophageal and LES pressures were recorded and blood was drawn for VIP analysis. Hand TNS improved LES relaxation and percent of peristaltic contractions to swallows, and decreased the number of spontaneous contractions. Foot TNS decreased only spontaneous contractions while LES pressures and VIP levels were unchanged. We conclude that a somatovisceral pathway involving the esophagus exists.

Questioning the clinical significance of upper gastrointestinal cytomegalovirus disease following heart transplantation.

We performed a retrospective review of patients who underwent esophagogastroduodenoscopy after heart transplantation to determine the clinical setting in which upper gastrointestinal cytomegalovirus disease is identified. No gastrointestinal cytomegalovirus disease was found prior to transplant 51 and this period (from transplant 1 to 50) correspond to a time when significantly fewer esophagogastroduodenoscopies included biopsy. Patients in whom cytomegalovirus was identified were more likely to have been CMV seronegative and to have received a heart from a seropositive donor (60% vs 20%, P = 0.029). In addition, patients with cytomegalovirus used aspirin more commonly (90% vs 31%, P = 0.001), and underwent esophagogastroduodenoscopy earlier after transplantation (123d vs 652d, P = 0.029). We conclude that factors that increase the use of esophagogastroduodenoscopy and biopsy in the early transplant period increase the likelihood of identifying cytomegalovirus in gastrointestinal tissue. However, the clinical course and significance of cytomegalovirus identified in the upper gastrointestinal tract in heart transplant patients may be difficult to discern.

Complications during pneumatic dilation for achalasia or diffuse esophageal spasm. Analysis of risk factors, early clinical characteristics, and outcome.

UNLABELLED: A retrospective cohort study was performed to assess risk factors, early clinical characteristics, and outcome of complications in patients undergoing pneumatic dilation. Of 178 patients with achalasia or diffuse esophageal spasm who underwent 236 dilations with a Browne-McHardy dilator, 16 patients experienced a complication (9.0%). Nine major complications developed: perforations (4), hematemesis (2), fever (2), and angina (1). A prior pneumatic dilation and use of inflation pressure > or = 11 PSI were independent risk factors by multivariate analysis for developing a complication. An esophagram immediately following the dilation identified three of the four perforations. Three postdilation findings were identified as indicators of patients with an increased risk of having developed a perforation: blood on the dilator, tachycardia, and prolonged chest pain lasting > 4 hr after dilation. In all patients incurring a major complication, one of the three indicators, or the complication itself was recognized within 5 hr of dilation. All patients with complications, including the four with perforation who received prompt surgical repair and esophagomyotomy, recovered uneventfully. The symptomatic relief of dysphagia in patients with perforation undergoing emergent surgical repair and esophagomyotomy was similar to patients undergoing elective esophagomyotomy. CONCLUSIONS: (1) Pneumatic dilation is a safe treatment of achalasia, with a 1.7% risk of perforation. (2) The risk of developing a complication is increased by having had a previous pneumatic dilation or by use of inflation pressures > or = 11 psi. (3) All patients with a major complication were identified within 5 hr after dilation. (4) Complications following pneumatic dilation, if recognized and treated promptly, were not associated with adverse, long-term sequelae.

Pneumatic dilatation or esophagomyotomy treatment for idiopathic achalasia: clinical outcomes and cost analysis.

The choice between pneumatic dilatation and surgical esophagomyotomy as the initial treatment for achalasia is controversial. The aims of this study were to determine the long term clinical outcome and costs of treating achalasia initially with pneumatic dilatation as compared to esophagomyotomy. Of 123 patients undergoing an initial pneumatic dilatation for achalasia at our institution from 1976 to 1986, 71 (58%) received no further treatment for achalasia during a mean follow up of 4.7 +/- 2.8 years. Only 15 of these 123 patients (12%) eventually underwent surgical esophagomyotomy (two for perforation during pneumatic dilatation, 13 for persistent or recurrent symptoms). The degree of dysphagia at follow up was improved to a similar degree in patients treated with an initial pneumatic dilatation as compared to patients treated with an initial esophagomyotomy. Patients with age > or = 45 years at time of initial pneumatic dilatation had fewer subsequent treatments for persistent or recurrent symptoms and had less dysphagia on follow up as compared to patients < 45 years. Subsequent pneumatic dilatations to treat persistent or recurrent symptoms were less beneficial than an initial pneumatic dilatation. The cost of esophagomyotomy was 5 times greater than the cost of pneumatic dilatation. When costs were analyzed to include subsequent treatments of symptomatic patients, the total expectant costs of treating with an initial esophagomyotomy remained 2.4 times greater than treating with an initial pneumatic dilatation. This study suggests that an initial pneumatic dilatation will be the only treatment needed for the majority of patients with achalasia. A treatment regimen starting with pneumatic dilatation has less overall costs than starting with esophagomyotomy. For each subsequent pneumatic dilatation, however, the clinical benefit leans toward surgery.