日本消化器外科学会雑誌第26巻第2号

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1 Key words: severe idiopathic chronic constipation, Auerbach's plexus, number of ganglion cell, nuclear area oi ganglion cell, muscarinic acetylcholine receptor

2 stool FiS. I Transit time curves of radiopaque markers in each part of the colon. Open circles are number of the residual markers in the constipation group (n= 6), closed circles are that in the control (n=5). Total transit time markedly delayed in each part of the constipated colon. Points and bars indicate meanf SD. Transverse colon Descending colon ileorectostomy, Table 1 Clinical review of 20 patients with severe idiopathic constipation Patients duration of number symptoms \years, colorectostomycolonic prervrous post op. laxative symptoms caliber (cm) operation t/7 t/7 t/7 t/7 hysterectomy t/5 lvert It. hemicolectomy t/5 L/3 LS. t/7 t/5 LS. t/5 LS. t/7 I.S. t/s t/7 appendectomy t/5 t/7 appendectomy t/5 lvert I.S. t/7 appendectomy lvert D: Abdominal distension, P : Abdominal pain, N : Nausea, lax. : various mixture of laxatives, I.S.: internal sphincterotomy,

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4 Fig. 2 A-plexus of the sigmoid colon. HE stainx 200. Nerve cells are reduced in number and show an enlargement of cell bedies in the constipated colon (B) comparing to the control (A). Fig. 3 Degenerative changes of nerve cells in the constipated colon. HE stain x400. A : Giant ttansformation of nerve cells with vacuolar degeneration. B: Gliosis of the A- plexus. An arrow shows disappearing nerve cell with satellite glial cells indicating neuronophagia.

5 E Fig. 4 Transverse section of the sigmoid colon. NSE stain x200. NSE positive neurons in the A-plexus and nerve fibers in the circular muscle layer are definitely reduced in the constipated (B) as compared to the control (A). 15(207) Fig. 5 Number of the myenteric ganglion cells per entire circumference of the colon. group A n=8 Table 2 Number and size of the ganglion cells in each part of the constipated colon. The number of the nerve cells per entire circumference gradually increased toward the anal side. But no significant difference was seen in the nerve cell size estimated by the nuclear area among four diffent parts of the colon Case I Case 2 Case 3 Number Area Number Area Number Area Transverse colon Number: Number of ganglion cells per entire circumference Area: Nuclear area of ganglion cell (p' )

6 Table 3 Number and size of the myenteric gan. glion cells of the sigmoid colon Fig. 6 Nuclear area of nerve cells of the myenteric plexus of the colon. Fig. 7 Distribution curves of nuclear area. Points indicate mean values of each specimens. Number Area meantsd gni P< 0.01

7 - log concentration of oxotremorine (n) E Fig. 8 Scatchard analyses of specific ('Hl QNB binding. Open circles are from the control group and closed circles are from the constipation group. l Bound ONB (Jmoles) Fig. 9 Dose-response curves of contractions to oxotremorine. Each maximal contraction of the muscle was taken as 100% and values were calculated as percentages of this contraction. Points and bars indicate mean values and standard deviation Table 4 Muscarinic acetylcholine receptor binding in controls and con' stipation group B max (f mol/mg protein) Control n=5 Constipation n=5 Bmax: maximum specific binding. KD: dissociation constant. Values are meant SD. protein conteng Qc/ms wet wt)

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11 Hirofumi Niwamoto, Shuichi Ohashi* and Eizo Okamoto The First Department of Surgery, Hyogo College of Medicine *Department of Surgery, Takarazuka Municipal Hospital To clarify the functional role of the myenteric plexus in the pathogenesis of severe idiopathic constipation, morphologic studies were carried out on resected specimens of 20 patients treated by subtotal colectomy. The number of myenteric nerve cells of the entire circumference of the colon calculated by an image analyzer was lm + 32 in the constipated patients, which was significantly lower than the in the control. Conversely, the size of the nerve cells represented by the nuclear area was p2 in the constipated group, which was significantly higher than the p2 in the control. The amount of muscarinic acetylcholine receptor measured by [3H] quinuclidinyl benzilate binding assay was significantly higher in the constipated groups (477.0 a 79.6 fmol/mg protein) than in the control (291.6 t37.2 fmol/mg protein). Coincidentally, the dose response curve of the fresh muscle strip to oxotremorine, an agonist of acetylcholine, shifted markedly to the left, indicating the existence of denervation supersensitivity of Cannon. This study suggests that a decrease in cholinergic excitatory neurons and a relative increase in inhibitory neurons of the myenteric plexus may play a significant role in the pathophysiology of severe idiopathic constipation. Reprint requests: Hirofumi Niwamoto The First Department of Surgery, Hyogo College of Medicine 1-l Mukogawa-cho, Nishinomiya, 663 JAPAN

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