Small-Inte, stinal Mucosa in Pseudoobstruction Syndromes MICHAEL D. SCHUFFLER, MD, LAWRENCE R. KAPLAN, MD, and LINDA JOHNSON, BS, MT, ASCP

The purpose of this investigation was to determine the frequency and severity of small intestinal mueosal damage in pseudoobstruction syndromes. One hundred eighty-nine interpretable biopsies from 12 patients were blindly reviewed by two investigators. The underlying disorders were scleroderma in 7 and idiopathic intestinal pseudoobstruction in 5. All 12 had small-intestinal dilatation on small-bowel series. Eight of the 12 patients had biopsies characterized by moderate to severe mucosal damage; 3 of these had some biopsies which were flat. The damage did not correlate with: (1) types and numbers of organisms recovered from small intestinal aspirates; (2) duration of illness; (3) degree of dilatation of the proximal small bowel; (4) concentrations of deconjugated bile salts in small intestinal fluid; or (5) amount of fat absorbed in fat-balance studies. We conclude that mucosal damage is common in pseudoobstruction syndromes. The pathogenesis o f the damage and its relationship to intraluminal bacteria remain undefined.

Intestinal pseudoobstruction is a disorder characterized by signs and symptoms of intestinal obstruction in the absence of an occluding lesion of the intestinal lumen (1). Pseudoobstruction may either be an acute or a chronic disorder. Causes of the chronic disorder include s c l e r o d e r m a (2), amyloidosis (3), and idiopathic intestinal pseudoobstruction (liP) (4). liP, in turn, may be caused by either functional or structural abnormalities of the smooth muscle (5) or myenteric plexus (6) of the intestine. Patients with chronic intestinal pseudoobstruc-

From the Departments of Medicine and Laboratory Medicine of the University of Washington School of Medicine and the United States Public Health Service Hospital, Seattle, Washington. This study was supported in part by Grant 5 RO 1 AM 16059 (The Pathogenesis of Human Alimentary Mucosal Disease) from the Public Health Service and by Federal Health Programs Service Project SEA 76-41-75. A portion of this work was conducted through the Clinical Research Center of the University of Washington, supported by Grant RR-37 from the National Institutes of Health. Address for reprint requests: Dr. Michael D. Schuffler, Chief, Division of Gastroenterology, United States Public Health Service Hospital, Box 3145, Seattle, Washington 98114.

tion frequently have malabsorption (4, 7-14) and may undergo small-intestinal biopsy as part of a diagnostic evaluation (4, 8-10, 14, 15). It is important, therefore, to know what the appearance of the small-intestinal mucosa is in this condition in order to avoid confusion with other entities. There are many reports of the small-intestinal mucosa in scleroderma (14-20) and IIP (41 8-10, 21, 22), but only in the minority is the mucosa reported to be abnormal (23-25). During the evaluation of a patient with IIP, we discovered that the majority of her biopsies were flat. Since she did not respond to a gluten-flee diet and since her brother had only mild mucosal damage in spite of having an identical clinical illness, we concluded that she did not have celiac sprue and that her mucosal damage was secondary to her disease. Two cases of pseudoobstruction previously reported from this institution also had mucosal damage, albeit not as severe (25). These three patients stimulated us to do the present study, in which we evaluated the frequency and severity of small-intestinal mucosal damage in 12 patients with intestinal pseudoobstruction.

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MATERIALS A N D M E T H O D S This series c o m p r i s e s 12 p a t i e n t s with i n t e s t i n a l pseudoobstruction. Two patients, cases 6 and 10, were included as patients J.M. and L.C. in a previous report (25). The other 10 cases were consecutive referrals to the principal investigator during the years 1972-1976. All 12 patients had symptoms of chronic intestinal obstruction. They had attacks of abdominal pain, distention, vomiting, and weight loss, and radiographically, all had dilatation of the small intestine without luminal obstruction. This was confirmed in 8 patients who came to surgery or autopsy. The underlying disorders were scleroderma in seven and IIP in 5. The diagnosis of liP was based on criteria previously reported (26). Cases 1 and 8 were a sister and brother whose IIP was caused by degeneration of the myenteric plexus (6), whereas cases 2 and 5 had a form of liP caused by smooth-muscle degeneration (5). No full-thickness tissue was available on case 4, so that we do not know what form of IIP she had. Raynaud's phenomenon was present in 6 of the 7 patients with scleroderma and 5 of the 6 had sclerodactyly. The sixth had no sclerodactyly, but did have subungual telangiectasias and pulmonary fibrosis. The patient without Raynaud's phenomenon or sclerodactyly had tight skin over the wrists and forearms, a lower esophageal sphincter pressure of 1 mm Hg, free gastroesophageal reflux, and esophageal aperistalsis. Other clinical information is summarized in Table 1. Methods. Each patient was evaluated on the Clinical Research Center of the University of Washington. Approval for this investigation was given by the Human Sub-

jects Review Committee of the University, and each patient gave informed consent. With the exception of one patient who tolerated no oral intake, all patients had fat-balance studies. The actual fat ingested was calculated by a dietitian and varied between 30 and 96 g per day. After 2 days of equilibration, stools were collected for 3 days and the fat content was analyzed by the method of Van de Kamer (27). The percentage of fat absorbed per day was calculated by the formula: daily intake - daily output x 100 daily intake Small-Bowel Biopsies and Cultures. Following an overnight fast, each patient swallowed a hydraulic biopsy tube (Quinton Instrument Company, Seattle, Washington) to which was glued a 16 F aspiration tube. The assembly, which was gas sterilized prior to use, was guided into the small intestine under fluoroscopic control. In all but one patient the tube assembly was advanced to the ligament of Treitz. In two cases the tube could be advanced to a loop beyond Treitz, and in one patient the tube could not be advanced beyond the third part of the duodenum. After the assembly reached its most distal point, a sterile syringe was attached to the aspiration tube. Five to ten ml of fluid were withdrawn and discarded. A second sterile syringe was then attached and 3-5 ml of fluid were aspirated. The syringe was capped and handed to one of the investigators who immediately processed it. The aspirate was inoculated directly into fluid media and onto a variety of solid agar plates. A direct Gram stain was done.

TABLE 1. CLINICAL CHARACTERISTICS*

Age

Sex

Duration of symptoms (years)

1 57 2 15 3 65 4 63 5 31 6** 62 7 64 8 60 9 43 10tt 58 11 51 12 47 Normal values

F F F F F M M M M F F M

45 6 3 13 13 4 14 40 1 27 6 1

Case no.

Primary disease

IIP$ IIPw Scl IIP82 IIPw Scl Scl IIP$ Scl Scl Scl Scl

Weight (kg)

Previous weight (kg)

37 30 38 54 42 54 46 36 42 61 48 69

50 36 48 90 54 62 70 60 60 70 54 93

Albumin (q/lOOml)

Folate (ng/ml)

Schilling test? (% excreted/ 24 hr)

4.3 4.0 2.3 2.3 4.4 3.7 3.8 4.0 4.0 4.0 4.4 3.7 3.7-5.8

10 14 24 -3.8 15 36 50 3 6 11 8 5-21

9.0 16.0 6.0 1.0 7.0 7.0 2.9 0.53 0.0 22.6 12.0 29.0 > 15

*In all tables the cases are arranged in the order of severity of mucosal changes and not in the order in which patients were evaluated. tIntrinsic factor administered with radioactive vitamin B12. $IIP= idiopathic intestinal pseudoobstruction secondary to degeneration of the myenteric plexus. w secondary to degeneration of the smooth muscle. 82 of unknown pathology. **Patient J.M. in reference 25. ttPatient L.C. in reference 25.

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PSEUDOOBSTRUCTION Dilutions of the specimen fluid were made using trypticase soy yeast broth as the diluent. The specimen was plated with a special loop calibrated to deliver 0.001 ml. The undiluted specimen and dilutions of 10-3 , 10-6 , and 10-9 were plated onto blood agar, MacConkey agar (without crystal violet), chocolate agar, and special prereduced anerobic plates supplemented with vitamin K and hemin (Columbia agar as base). After inoculation, the prereduced anerobic plates were put under flowing CO2, until all media were plated; they were then immediately placed in an anerobic atmosphere using gas exchange (85% nitrogen, 10% hydrogen, 5% CO2). The anerobic media were incubated for 48-72 hr prior to examination. Aerobic organisms were identified by standard microbiologic procedures. Anerobic organisms were identified by a combination of Gram stain, colonial morphology, biochemical tests, and/or gas-liquid chromotography (Hewlett-Packard 5830-A gas chromotograph with flame ionization detector). Glucose, mannitol, sucrose, lactose, maltose, trehalose, and rhaminose were the basic sugars used. Tests for indol, nitrate, esculin hydrolysis, and motility were always done, and when indicated, tests for gelatin liquefaction, lecithinase, and lipase were also done. Small-intestinal biopsies were taken with the hydraulic biopsy tube at 3- to 4-cm intervals in the intestinal segment extending from the most distal point reached with the tube to the second part of the duodenum. The biopsies were fixed in Bouin's solution, processed for serial lightmicroscopic sections, and stained with hemat0xyiin and eosin (28). Two patients did not have peroral small-intestinal biopsies; their tissue was obtained from the surgically resected duodenum in case 2 and the resected proximal jejunum in case 11. A portion of some of the fluid samples was analyzed for deconjugated bile sales (25). The slides of all 12 patients were coded, mixed, and blindly reviewed by two of the investigators (MDS and LRK). The biopsies were interpreted as normal or mildly, moderately, or s e v e r e l y abnormal, according to the criteria of Perera et al (28). Briefly, a normal biopsy contained four contiguous finger-like villi and a single row of crypts. Surface epithelial cells were columnar and contained only occasional lymphocytes. The lamina propria did not have an excessive number of round cells and acute inflammatory cells were absent. A severely abnormal biopsy was one in which villi were absent or virtually absent. In addition, the biopsy usually had abnormal surface epithelial cells, markedly elongated crypts (mitoses often reaching close to the surface), increased lymphocytes within the epithelial lining, and increased round cells in the lamina propria. A mildly abnormal biopsy was one in which there were small deviations from normal: although some villi were normal, others, on well-oriented sections, were shorter than normal. These villi were often blunted and broadened and the crypts were elongated, ie, mitoses were seen at points 25-50% along the way from the bottom of the crypt to the top of a villus. The mildly abnormal biopsy was often, but not always, accompanied by changes in epithelial cells, such as loss of nuclear polarity and/or increased lymphocytes within the epithelial cell lining. The moderately severe biopsy was characterized by shorter villi and longer crypts, ie, mitoses were Digestive Diseases, Vol. 23, No. 9 (September 1978)

identified at points at least 50% of the distance from the bottom of a crypt to a top of a villus. Epithelial cell abnormalities (cuboidal and/or vacuolated cells), loss of nuclear polarity, increased numbers of surface lymphocytes, and increased round cells in the lamina propria usually accompanied this change of villus architecture. Biopsies had to be well oriented and free of traumatic, tangential, Brunner's, and shallowness artifacts (28) to be considered interpretable. If a biopsy had significant artifacts present, we judged that biopsy to be uninterpretable. If there was disagreement between the two investigators, it was resolved by jointly reviewing the sections and coming to an agreement. In order to obtain a single value which would reflect the overall mucosal injury in each patient, we used a method in which we assigned a score to each biopsy: normal = 1 ; mild = 2; moderate = 3; and severe = 4. The total score of each patient was divided by the number of interpretable biopsies to give a "mucosal score." For example, case 3 had 1 mild, 3 moderate, 3 severe, and 2 u n i n t e r p r e t a b l e b i o p s i e s . T h e m u c o s a l s c o r e of c a s e 2 = (1 x 2) + (3 • 3) + (3 • 4) = 23/7 = 3.3 We analyzed the data by the method of least-squares linear regression to determine whether mucosal injury was related to the types and numbers of organisms isolated, the percentage of fat absorbed, the serum levels of folate and albumin, the duration of illness, and the concentrations of intraluminal deconjugated bile salts. The small-bowel series of each patient was reviewed. A mean width of the proximal small intestine was determined by averaging the values of the widest diameter of the duodenum and the widest diameter of the jejunum. We then determined whether mucosal injury was related to the degree of dilatation of the proximal small bowel. We also analyzed whether fat absorption was related to the degree of intestinal dilatation. RESULTS S m a l l - B o w e l Biopsies. F r o m t h e 12 p a t i e n t s , 203 b i o p s i e s w e r e o b t a i n e d o f w h i c h 189 w e r e interpretable. Mucosal damage was usually present but was highly variable, the mucosal scores ranging f r o m 1.1 to 3.7 ( T a b l e 2). A t o n e e n d o f t h e s p e c t r u m , 14 o f 16 b i o p s i e s f r o m o n e p a t i e n t w e r e n o r mal. A t t h e o p p o s i t e e n d , t h e m a j o r i t y o f b i o p s i e s w e r e fiat a n d n o n e w a s n o r m a l . N i n e p a t i e n t s h a d at least one normal biopsy (Figures la-e). The patients with IIP had more damage (mean s c o r e = 2.8) t h a n t h e p a t i e n t s w i t h s c l e r o d e r m a ( m e a n s c o r e = 1.9), b u t this d i f f e r e n c e w a s n o t stat i s t i c a l l y significant (t = 1.93; P > 0.05). S m a l l - B o w e l CultureS. A w i d e v a r i e t y o f o r g a n i s m s w e r e r e c o v e r e d f r o m t h e p r o x i m a l small int e s t i n e ( T a b l e 3). A l l b u t o n e p a t i e n t h a d E. coli. A n e r o b i c o r g a n i s m s w e r e r e c o v e r e d in 5 p a t i e n t s ; 2 had bacteroides. Two additional patients had organ i s m s on G r a m s t a i n t h a t d i d n o t g r o w o n c u l t u r e .

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TABLE 2. SMALL BOWEL BIOPSY RESULTS* Case

Normal

Mild

Moderate

Severe

Uninterpretable

1 2 3 4 5 6 7 8 9 10 11 12

0 0 0 0 1 1 3 6 7 14 8 14

1 0 1 4 3 16 10 5 10 10 3 2

5 11 3 6 5 6 6 2 0 0 0 0

17 6 3 0 0 0 0 0 0 0 0 0

1 0 2 1 1 1 0 4 0 3 0 1

Interpre- . table

23 17 7 10 9 23 19 13 17 24 11 16

Mucosal score

3.7 3.4 3.3 2.6 2.4 2.2 2.2 1.7 1.6 1.4 1.3 1.1

*The n u m b e r s in c o l u m n s 2-7 represent the n u m b e r of biopsies placed in each category after blind review.

The only organism recovered (on two separate occasions) from case 1 was Torulopsis glabrata. The total numbers of organisms and other relevant data are shown in Table 4. The mucosal scores did not correlate with the types or numbers of organisms present, the duration of obstructive symptoms, the serum levels of albumin or folate, the intraluminal c o n c e n t r a t i o n s of d e c o n j u g a t e d bile salts, or the diameter of the proximal small bowel as measured on small-bowel series. Fat absorption varied from 46% in 2 patients to 93% in 1 patient. Fat absorption did not correlate with the severity of mucosal damage. There was, however, an inverse relation between fat absorption and the diameter of the proximal small intestine (y = 132.1 - ll.8x; r = -0.72; P < 0.02). DISCUSSION The principal purpose of this investigation was to determine to what extent small-intestinal mucosal damage is present in several forms of intestinal pseudoobstruction. We studied one form caused by scleroderma, a second caused by a degenerative disorder of smooth muscle, and a third caused by a degenerative disorder of the myenteric plexus. The latter two are part of the spectrum of IIP. Almost all previous studies dealing with IIP and small-intestinal scleroderma have stated that the villous architecture is normal in these diseases (4, 8-10, 1422). One study, however, reported mild damage in a case of IIP (23), and another reported an "atrophic" mucosa in scleroderma (24). Only one other report s h o w e d p h o t o g r a p h s clearly d o c u m e n t i n g small-intestinal mucosal injury (25).

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Our results indicate that mucosal damage is common in the above forms of pseudoobstruction. Even if all the biopsies with mild injury are excluded from analysis and we include only the moderate and severe changes as being reliable markers of mucosal damage, we are left with 8 of 12 patients having such damage. If we exclude the 2 previously reported patients, then 7 of the 10 remaining cases have mucosal damage and 3 of the 7 have biopsies which are flat. Our study differs in one important respect from previous studies of IIP and scleroderma, and this may explain why we found abnormalities whereas previous studies did not. Our patients had an average of 16 interpretable small-bowel biopsies per patient (range = 7-24) in contrast to an average of 1 biopsy per patient in the previous reports. Since damage is patchy, it could have been missed in previous studies. We do not understand the pathogenesis of the mucosal injury. Even when the 3 patients having flat biopsies (cases 1-3) are compared with the 4 having minimal or no changes (cases %12), none of the factors analyzed provide a reason for why the two groups differ. The 3 patients with flat biopsies did not have celiac sprue. Case 1 did not respond to 3 months of a gluten-free diet, and her brother' s mucosa was for the most part normal in spite of his having an identical clinical illness. Case 2, with a motor abnormality of the entire intestine, and case 3, with scleroderma, both showed dramatic weight gains and cessation of diarrhea following a course of antibiotics, a response typical of bacterial overgrowth but not of celiac sprue. Digestive Diseases, Vol. 23, No. 9 (September 1978)

PSEUDOOB STRUCTION

h

d

e

Fig 1. Small intestinal mucosa from five patients with intestinal pseudoobstruction. (a) Case 11; the mucosa is normal. (b) Case 9; mild abnormality; the villi are slightly shortened and blunted. (c) Case 5; moderate abnormality; the villi are shortened and the crypts are elongated. (d) Case 2; moderate abnormality; a few stubby villi remaining; the crypts are elongated, and there are increased cells in the lamina propria. (e) Case 1; severe abnormality; the mucosa is flat and indistinguishable for celiac sprue. (H&E, x 144)

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TABLE 3. MUCOSAL SCORES VS BACTERIA ISOLATED*

Case

Mucosal score Group 1

1

2

3

4

5

6

3.7

3.4

3.3

2,6

2.4

2.2

6.3

6.7 7.8? 6.0

5.1

9.3

6.3

E. coli Klebsiella sp. Streptococcus fecalis Nonhemolytic Streptococcus Pseudomonas aeruginosa Acinetobacter Lactobacillus

7

8

9

10

11

12

2.2

1.7

1.6

1.4

1.3

1.1

5.0

4.5

6.0

5.0

7.3

4.4

3.0

2+ 4.8

9.0 3.0 4.8

6.0

Group 2 Bacteroide s

9.0 5.0

Proprionibacterium Clostridium sp. Veillonella alcalescens Actinomyces sp.

6.9 1+

6.0 6.0 7.6

Unidentified yeasts

1+

6.0

G-anerobic rod Group 3

Torulopsis glabrata

6.0

6.0

7.2

8.0

Candida albicans Streptococcus viridans

4.5

3.5 7.1

4.8? 4.7

Diptheroids

9.0

Hemophilus parainfluenza

4.7

6.3

*Bacteria are reported as the log of organisms/ml of intestinal contents except in cases 6 and I0 in which semiquantitative values are also shown. For the purpose of analysis, the bacteria are arranged in 3 groups; in group 1 are aerobic bacteria often found in feces; in group 2 are anerobes; in group 3 are fungi, yeasts, and aerobic pharyngeal flora. fTwo different colony types. TABLE 4. SUMMARY OF DATA

Case

Mucosal score

Fat absorption (% o f intake)

1 2 3 4 5 6 7 8 9 10 11 12

3.7 3.4 3.3 2.6 2.4 2.2 2.2 1.7 1.6 1.4 1.3 1.1

82 N.D. 46 81 65 81 85 73 46 83 67 93

Group 1 bacteria *

Group 2 bacteria *

0 6.3 7.8 5.0 9.3 6,3 5.0 4.5 6.1 5.0 82 9.3 4.0

0 0 6.5 0 0 5.0 0 6.9 6.0 1 + 82 0 0

Total bacteria t 7 8 7.9 5.0 9.3 6.4 5.0 9.0 7.2 5.0 82 9.3 4.0

Mean diameter upper intestine (cm )$

Deconjugated bile salts (raM)

4.1 8.8 6.4 4.0 6.4 5.5 3.9 4.3 5.6 4.5 5.8 4.7

0 N.D.w 0 N.D. 2.4 1.2 N.D. 0 3.4 0.3 N.D, N.D.

*Log10 of total bacteria/ml in either groups l or 2. ?Logt0 of total bacteria recovered in groups 1-3. ;Mean of widest diameter of duodenum plus widest diameter of jejunum (cm). w = not done. 82 (values not used in statistical analyses).

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PSEUDOOB STRUCTION

"

%

Fig 2. Surface epithelial cells from two patients with intestinal pseudoobstruction. (a) Case 2; the epithelial cells are flattened and there is lack of nuclear polarity; mucus (arrows) is adherent to the surface cells. (b) Case I; the epithelial cells are markedly vacuolated. (H&E, x576)

Our patients had large numbers of bacteria cultured from the proximal small bowel, an area which normally contains only small numbers of pharyngeal organisms (29). Whether the bacteria could have produced the mucosal injury is undetermined. Mucosal injury can accompany bacterial overgrowth in experimental animals with self-filling blind loops (30-33). The mucosal damage is apparent by electron microscopy (30, 32), and the severity of the abnormalities correlates with the degree of bacterial proliferation (32). A recent study suggested that the injury is caused by bacterial proteases (34). In one previous study of stasis syndrome in man, antibiotics improved fat absorption but did not produce an i m p r o v e d a p p e a r a n c e of the damaged small-bowel mucosa (25). Although we found no relation between mucosal damage and the bacteria isolated, this does not mean that no relation exists. It is possible that we did not recover fastidious anerobes and that such anerobes were responsible for the mucosal damage. It is also possible that the organisms isolated from a single aspirate did not reflect the bacterial popuDigestive Diseases, Vol. 23, No. 9 (September 1978)

lations present at other times. Furthermore, some of the organisms isolated could have contained injurious proteases whereas others did not. Can intestinal distention per se flatten the mucosa? Acute intestinal distention may result in shorter and broader villi (35), but it also results in shorter and broader crypts. The damaged mucosa in our patients contained normal or elongated crypts. In addition, we found no correlation between intestinal dilatation and the severity of mucosal injury. Small-intestinal mucosal damage may be a manifestation of kwashiorkor (36). Although our patients were underweight, they did not have the clinical manifestations of this disease. Hypoalbumihernia, which usually occurs in kwashiorkor, was present in only 2 patients, and they were not the 2 with the greatest damage. The importance of mucosal injury as a factor contributing to the malabsorption in 10 of our patients is also uncertain. It is reported that mucosal cell injury is a major determinant of the malabsorption associated with bacterial overgrowth (25). We found no correlation between the severity of fat malabsorption and the severity of mucosal injury. This does not necessarily mean that no relation exists. Because we only biopsied proximally and therefore did not determine how much of the small bowel was injured, we can only speculate that, as in celiac sprue (37), the severity of fat malabsorption might best correlate with the total length of damaged small intestine. We did find an inverse relation between fat absorption and the width of the proximal small intestine. If we assume that intestinal dilatation is a measure of ineffective intestinal propulsion and ineffective mixing, then it is possible that in pseudoobstruction poor mixing p e r s e is an important determinant of fat malabsorption, especially if it results in widening of and decreased penetrance of fatty acids through the unstirred water layer (38). Finally, the o c c u r r e n c e of mucosal injury in pseudoobstruction must figure in the differential diagnosis of an abnormal small-bowel biopsy obtained from a patient with small-intestinal symptoms. Pseudoobstruction is one more cause of an abnormal small-intestinal biopsy. ACKNOWLEDGMENTS The authors wish to thank Dr. Cyrus E. Rubin for his guidance and advice, Dr. David R. Saunders for his critical review of the manuscript, and Z6~ Jonak, Linda Esther, and Diane Simons for their technical assistance.

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REFERENCES 1. Moss AA, Goldberg HI: Intestinal pseudo-obstruction. CRC Crit Rev Clin Radiol Nucl Med 3:363-387, 1972 2. Treacy WL, Bunting WL, Gambill EE, Code CF: Scleroderma presenting as obstruction of the small bowel. Mayo Clin Proc 37:607-616, 1962 3. Legge DA, Wollaeger EE, Carlson HC: Intestinal pseudoobstruction in systemic amyloidosis. Gut 11:764-767, 1970 4. Maldonado JE, Gregg JA, Green PA, Brown AL: Chronic idiopathic intestinal pseudo-obstruction. Am J Med 49:203212, 1970 5. Schuflter MD, Lowe MC, Bill AH: Studies of idiopathic intestinal pseudo-obstruction. I. Hereditary hollow visceral myopathy: Clinical and pathological studies. Gastroenterology 73:327-338, 1977 6. Schuffler MD, Bird TD, Sumi SM, Cook A: A new familial neurological syndrome presenting as intestinal pseudo-obstruction. Gastroenterology 72:1128, 1977 7. Naish JM, Capper WM, Brown NJ: Intestinal pseudo-obstruction with steatorrhea. Gut 1:62-66, 1960 8. Pearson AJ, Brzechwa-Adjukiewicz A, McCarthy CF: Intestinal pseudo-obstruction with bacterial overgrowth in the small intestine. Dig Dis 14:200-205, 1969 9. Lukie BE, S a n d e r s MG: Chronic idiopathic intestinal pseudo-obstruction with malabsorption, a scleroderma-like disorder. Can Med Assoc J 109:1222-1227, 1973 10. Cockel R, Hill EE, Rushton DI, Smith B, Hawkins CF: Familial steatorrhea with calcification of the basal ganglia and mental retardation. Q J Med 42:771-783, 1973 11. Nahai F: Pseudo-obstruction of the small bowel. Bristol Med Chir J 84:209-212, 1969 12. Dyer NH, Dawson AM, Smith BF, Todd IP: Obstruction of the bowel due to lesion in the myenteric plexus. Br Med J 1:686-689, 1969 13. Hoskins LC, Norris HT, Gottlieb LS, Zamcheck N: Functional and morphologic alterations of the gastrointestinal tract in progressive systemic sclerosis (scleroderma). Am J Med 33:45%470, 1962 14. Meihoff WE, Hirschfield JS, Kern F, Jr: Small intestinal scleroderma with malabsorption and pneumatosis cystoides intestinalis. JAMA 204:102-106, 1968 15. Rosson RS, Yesner R: Peroral duodenal biopsy in progressive systemic sclerosis. N Engl J Med 272:391-394, 1965 16. Herrington JL, Jr: Scleroderma as a cause of small bowel obstruction. Arch Surg 78:17-24, 1959 17. Greenberger N J, Dobbins WO III, Rnppert RD, Jesseph JE: Intestinal atony in progressive systemic sclerosis (scleroderma). Am J Med 45:301-308, 1968 18. Horsewell RR, Hargrove MD, Jr, Peete WP, Ruffin JM: Scleroderma presenting as the malabsorption syndrome. A case report. Gastroenterology 40:580-582, 1961 19. Bluestone R, MacMahon M, Dawson JM: Systemic sclerosis and small bowel involvement. Gut 10:185-193, 1969 20. Heinz, ER, Steinberg AJ, Sackner MA: Roentgenographic

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21.

22.

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28. 29. 30.

31.

32.

33. 34.

35. 36.

37.

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Digestive Diseases, Vol. 23, No. 9 (September 1978)

Small-intestinal mucosa in pseudoobstruction syndromes.

Small-Inte, stinal Mucosa in Pseudoobstruction Syndromes MICHAEL D. SCHUFFLER, MD, LAWRENCE R. KAPLAN, MD, and LINDA JOHNSON, BS, MT, ASCP The purpos...
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