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. 1972 Oct;51(10):2663–2668. doi: 10.1172/JCI107084

The Pathogenesis of Esophageal Dysfunction in Scleroderma and Raynaud's Disease

Sidney Cohen 1,2, Robert Fisher 1,2, William Lipshutz 1,2, Robert Turner 1,2, Allen Myers 1,2, Ralph Schumacher 1,2
PMCID: PMC332965  PMID: 5056661

Abstract

To determine the pathogenesis of esophageal dysfunction in scleroderma and Raynaud's disease, the lower esophageal sphincter (LES) was tested with: (a) methacholine acting directly at the cholinergic receptor on the muscle; (b) edrophonium, a cholinesterase inhibitor, enhancing the effect of released acetylcholine; and (c) gastrin I, acting through the release of acetylcholine. 10 patients with Raynaud's disease and 22 patients with scleroderma were compared with 20 normals and 20 patients with isolated LES incompetence. The mean basal LES pressure in normals was significantly greater than that recorded in both patients with scleroderma and Raynaud's disease. Six patients having scleroderma with normal peristalsis had an LES pressure significantly greater than that noted in 16 patients having scleroderma with abnormal peristalsis. In all groups, the per cent increase in LES pressure was similar when tested by direct muscle stimulation by methacholine. The response to agents that acted indirectly through intact cholinergic nerves differed in these groups. The LES response to gastrin I distinguished patients with normal peristalsis from those with abnormal peristalsis. The patients with normal peristalsis, either with scleroderma or with Raynaud's disease showed only a partial reduction in their response to gastrin I. The response to gastrin I was markedly reduced only in patients with abnormal peristalsis. These data indicate that in patients with scleroderma and Raynaud's disease, the LES response to direct muscle stimulation by methacholine was intact while the response to gastrin I and edrophonium was diminished.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atkinson M., Summerling M. D. Oesophageal changes in systemic sclerosis. Gut. 1966 Aug;7(4):402–408. doi: 10.1136/gut.7.4.402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beani L., Bianchi C., Crema A. The effect of catecholamines and sympathetic stimulation on the release of acetylcholine from the guinea-pig colon. Br J Pharmacol. 1969 May;36(1):1–17. doi: 10.1111/j.1476-5381.1969.tb08298.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cohen S., Lipshutz W. Hormonal regulation of human lower esophageal sphincter competence: interaction of gastrin and secretin. J Clin Invest. 1971 Feb;50(2):449–454. doi: 10.1172/JCI106512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cohen S., Lipshutz W., Hughes W. Role of gastrin supersensitivity in the pathogenesis of lower esophageal sphincter hypertension in achalasia. J Clin Invest. 1971 Jun;50(6):1241–1247. doi: 10.1172/JCI106601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. D'Angelo W. A., Fries J. F., Masi A. T., Shulman L. E. Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med. 1969 Mar;46(3):428–440. doi: 10.1016/0002-9343(69)90044-8. [DOI] [PubMed] [Google Scholar]
  6. DE TAKATS G., FOWLER E. F. Raynaud's phenomenon. JAMA. 1962 Jan 6;179:1–8. doi: 10.1001/jama.1962.03050010003001. [DOI] [PubMed] [Google Scholar]
  7. GIFFORD R. W., Jr The clinical significance of Raynaud's phenomenon and Raynaud's disease. Med Clin North Am. 1958 Jul;42(4):963–970. doi: 10.1016/s0025-7125(16)34246-8. [DOI] [PubMed] [Google Scholar]
  8. Jacobowitz D., Nemir P., Jr The autonomic innervation of the esophagus of the dog. J Thorac Cardiovasc Surg. 1969 Nov;58(5):678–passim. [PubMed] [Google Scholar]
  9. Kosterlitz H. W., Lydon R. J., Watt A. J. The effects of adrenaline, noradrenaline and isoprenaline on inhibitory alpha- and beta-adrenoceptors in the longitudinal muscle of the guinea-pig ileum. Br J Pharmacol. 1970 Jun;39(2):398–413. doi: 10.1111/j.1476-5381.1970.tb12903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lipshutz W., Hughes W., Cohen S. The genesis of lower esophageal sphincter pressure: its identification through the use of gastrin antiserum. J Clin Invest. 1972 Mar;51(3):522–529. doi: 10.1172/JCI106840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lipshutz W., Tuch A. F., Cohen S. A comparison of the site of action of gastrin I on lower esophageal sphincter and antral circular smooth muscle. Gastroenterology. 1971 Oct;61(4):454–460. [PubMed] [Google Scholar]
  12. Neschis M., Siegelman S. S., Rotstein J., Parker J. G. The esophagus in progressive systemic sclerosis. A manometric and radiographic correlation. Am J Dig Dis. 1970 May;15(5):443–447. doi: 10.1007/BF02283872. [DOI] [PubMed] [Google Scholar]
  13. Paton W. D., Vizi E. S. The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip. Br J Pharmacol. 1969 Jan;35(1):10–28. doi: 10.1111/j.1476-5381.1969.tb07964.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. STEVENS M. B., HOOKMAN P., SIEGEL C. I., ESTERLY J. R., SHULMAN L. E., HENDRIX T. R. APERISTALSIS OF THE ESOPHAGUS IN PATIENTS WITH CONNECTIVE-TISSUE DISORDERS AND RAYNAUD'S PHENOMENON. N Engl J Med. 1964 Jun 4;270:1218–1222. doi: 10.1056/NEJM196406042702303. [DOI] [PubMed] [Google Scholar]
  15. Saladin T. A., French A. B., Zarafonetis C. J., Pollard H. M. Esophageal motor abnormalities in scleroderma and related diseases. Am J Dig Dis. 1966 Jul;11(7):522–535. doi: 10.1007/BF02233564. [DOI] [PubMed] [Google Scholar]
  16. TREACY W. L., BAGGENSTOSS A. H., SLOCUMB C. H., CODE C. F. SCLERODERMA OF THE ESOPHAGUS. A CORRELATION OF HISTOLOGIC AND PHYSIOLOGIC FINDINGS. Ann Intern Med. 1963 Sep;59:351–356. doi: 10.7326/0003-4819-59-3-351. [DOI] [PubMed] [Google Scholar]
  17. TUFFANELLI D. L., WINKELMANN R. K. Systemic scleroderma, A clinical study of 727 cases. Arch Dermatol. 1961 Sep;84:359–371. doi: 10.1001/archderm.1961.01580150005001. [DOI] [PubMed] [Google Scholar]
  18. Willerson J. T., Thompson R. H., Hookman P., Herdt J., Decker J. L. Reserpine in Raynaud's disease and phenomenon. Short-term response to intra-arterial injection. Ann Intern Med. 1970 Jan;72(1):17–27. doi: 10.7326/0003-4819-72-1-17. [DOI] [PubMed] [Google Scholar]

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