Michael D. Schuffler

Severe idiopathic constipation is associated with a distinctive abnormality of the colonic myenteric plexus.

We analyzed the clinical, radiographic, esophageal manometric, and pathologic features of 26 women with severe, idiopathic constipation. Twenty-four patients were between 19 and 39 yr of age. Stool frequency was once every 5-28 days. On barium enema examination, 9 of 24 patients had colons of increased length and 4 of these 9 patients had colons of increased width (greater than 10 cm). Radionuclide solid-meal gastric-emptying studies were normal in 23 patients tested. Esophageal manometry demonstrated high-amplitude waves in 10 of 22 patients and long-duration waves in 3 of these 10 patients. Rectal biopsy specimens showed normal submucosal neurons in all patients and melanosis coli in 6. Twelve patients underwent subtotal colectomies for constipation. Conventional light microscopy using hematoxylin and eosin serial sections showed (a) melanosis coli in 4 patients; (b) normal smooth muscle in 11; (c) thinning of the circular muscle in 1; and (d) no apparent abnormalities of the myenteric plexus in any. In contrast, silver stains of the myenteric plexus showed (a) quantitatively reduced numbers of argyrophilic neurons in 10 patients; (b) morphologically abnormal argyrophilic neurons in 11; (c) decreased numbers of axons in 11; and (d) increased numbers of variably sized nuclei within ganglia in all 12. A coded analysis of the silver stains of colons from 8 patients with constipation and 19 control cases demonstrated that the pathologic abnormalities of severe idiopathic constipation could be differentiated from controls. Thus, severe idiopathic constipation is associated with a pathologically identifiable abnormality of the myenteric plexus. This abnormality appears different from anything previously described in intestinal pseudoobstruction.

The polymicrobial origin of intestinal infections in homosexual men

To determine the microbial cause and the clinical and pathologic correlates of anorectal and intestinal symptoms in homosexually active men, we performed comprehensive microbiologic studies, anoscopy, sigmoid-oscopy, and rectal biopsy in men examined in a clinic for sexually transmitted diseases. Enteric pathogens were found in 95 of 119 consecutive homosexual men with anorectal or intestinal symptoms and in 29 of 75 randomly selected homosexual men without such symptoms (P less than 0.001). The syndromes of proctitis, proctocolitis, and enteritis were differentiated on the basis of predominant symptoms and findings on anoscopy and sigmoidoscopy. Neisseria gonorrhoeae, herpes simplex virus, Chlamydia trachomatis (non-lymphogranuloma venereum serotypes), and Treponema pallidum were associated with 80 per cent of cases with symptomatic proctitis. Known causes of colitis, including Campylobacter jejuni, Campylobacter fetus fetus, Shigella flexneri, Chl. trachomatis (lymphogranuloma venereum serotypes), Entamoeba histolytica, and Clostridium difficile, were identified in 60 per cent of the cases of proctocolitis. Giardia lamblia was the only agent significantly correlated with enteritis. These data demonstrate that intestinal symptoms in homosexual men are attributable to a complex spectrum of microorganisms, but that careful clinical classification can serve as a guide to the selection of microbiologic studies and to a rational initial choice of therapy.

Pathology of neuromuscular disorders of the small intestine and colon

A variety of pathological abnormalities of the smooth muscle and myenteric plexus result in clinical syndromes of disordered small intestinal and colonic motility. These pathological abnormalities have been noted by conventional light microscopy and by utilization of Smiths technique for visualizing the myenteric plexus with silver. We have classified the neuromuscular disorders into two major categories, i.e., those affecting the myenteric plexus and those affecting the smooth muscle. The classification is further developed based on the variety of clinicopathological features of the various disorders. Although we can now identify the underlying pathology of these motor disorders and thus understand these illnesses better than we did a decade ago, we have much more to learn. With the great strides being made to understand the normal structure, function, and development of the myenteric plexus and smooth muscle, there is hope that we will be able to learn much more about the etiology and pathogenesis of these neuromuscular disorders in the decade to come.

Chronic Intestinal Pseudo-obstruction: A Report Of 27 Cases And Review Of The Literature

Twenty-seven cases of chronic intestinal pseudo-obstruction are reported. The causes of pseudo-obstruction were progressive systemic sclerosis in 14, hollow visceral myopathy in 4, visceral neuropathy in 2, sclerosing mesenteritis in 1, and jejunal diverticulosis in 1. No identifiable cause was found in five. Chronic pseudo-obstruction is a long-term illness characterized by vomiting, abdominal distention, abdominal pain and weight loss. Involvement is often present throughout the intestine so that patients may present with a variety of symptoms deriving from the esophagus, stomach, small intestine, and colon. Hollow visceral myopathy and visceral neuropathy are usually familial and urologic involvement is sometimes present in the former. Abnormalities of smooth muscle function can be discerned by radiography and esophageal manometry. The pattern and distribution of the abnormalities are helpful in differentiating pseudo-obstruction from true mechanical obstruction. They may also be helpful in differentiating one form of pseudo-obstruction from another. The majority of cases have identifiable pathology within either the smooth muscle or myenteric plexus of the bowel wall. The natural history of pseudo-obstruction is variable. Remissions and exacerbations occur and may be unrelated to anything that is done therapeutically. The illness is unresponsive to any drug known to have an effect on intestinal motility. Antibiotic treatment of small intestinal bacterial overgrowth and selected surgical procedures may occasionally be palliative. Many patients develop malnutrition and require home parenteral nutrition in order to survive.

Herpes simplex virus proctitis in homosexual men. Clinical, sigmoidoscopic, and histopathological features.

Acute herpes simplex virus (HSV) infection was detected in 23 of 102 consecutively examined, sexually active male homosexuals who presented with anorectal pain, discharge, tenesmus, or hematochezia, as compared with 3 of 75 homosexual men without gastrointestinal symptoms (P less than 0.01). Findings that were significantly more frequent in men with HSV proctitis than in men with proctitis due to other infectious causes included fever (48 per cent), difficulty in urinating (48 per cent), sacral paresthesias (26 per cent), inguinal lymphadenopathy (57 per cent), severe anorectal pain (100 per cent), tenesmus (100 per cent), constipation (78 per cent), perianal ulcerations (70 per cent), and the presence of diffuse ulcerative or discrete vesicular or pustular lesions in the distal 5 cm of the rectum (50 per cent). Serologic evidence indicated that 85 per cent of the men with symptomatic HSV proctitis were having their first episode of HSV-2 infection. The diagnosis of HSV proctitis is suggested by the presence of severe anorectal pain, difficulty in urinating, sacral paresthesias or pain, and diffuse ulceration of the distal rectal mucosa.

Intestinal Pseudo-Obstruction as the Presenting Manifestation of Small-Cell Carcinoma of the Lung: A Paraneoplastic Neuropathy of the Gastrointestinal Tract

A 58-year-old woman who had presented with intestinal pseudo-obstruction died 9 months later from rapidly progressive neurologic symptoms and autonomic insufficiency. Her gastric emptying had been markedly delayed and transit of markers had been slowed throughout the small bowel. A 5-hour manometric recording of the antrum and duodenum had shown absence of the normal interdigestive motor complex, which was replaced by irregular contractile activity of reduced amplitude. A small-cell carcinoma of the lung was found at autopsy. Pathologic study of the gut showed widespread degeneration of the myenteric plexus, which was infiltrated by plasma cells and lymphocytes and contained significantly reduced numbers of neurons. The extra-intestinal nervous system had neuronal loss and lymphocytic infiltrates in dorsal root ganglia. Thus, a gastrointestinal neuropathy causing intestinal pseudo-obstruction may be the presenting manifestation of a paraneoplastic syndrome associated with small-cell carcinoma.

Paraneoplastic visceral neuropathy as a cause of severe gastrointestinal motor dysfunction

The purpose of this study was to define the cause of severe gastrointestinal motor dysfunction in 7 patients with lung cancer. Six patients had small cell carcinoma and 1 patient had pulmonary carcinoid. Their ages ranged from 58 to 74 yr. All had intestinal pseudoobstruction and obstipation/constipation; 6 of 7 patients had gastroparesis; 4 of 4 patients had esophageal peristaltic abnormalities; and 2 patients had neurogenic bladders, autonomic insufficiency, and peripheral neuropathy. Five of 7 patients had dilated small bowel with 4 of them showing slow transit of barium; 2 of 7 patients had dilated colons; and 3 of 7 patients had slow colonic transit. Five patients died 4-9 mo after onset of gastrointestinal symptoms, and 2 survived. Post-mortem or surgical samples of the esophagus, stomach, small bowel, and colon showed neuron and axon degeneration and dropout, lymphoplasmacytic infiltration, and glial cell proliferation within the myenteric plexus of 6 patients. The antrum from the seventh patient had inflammatory cells within the myenteric plexus but without neuron dropout. Neuron numbers were significantly less than normal in each area of the gastrointestinal tract. Thus, we conclude that lung cancer may be complicated by severe gastrointestinal motor dysfunction resulting from visceral neuropathy of the myenteric plexus, a paraneoplastic effect of the cancer.

Infections with Campylobacter jejuni and Campylobacter-like Organisms in Homosexual Men

In studies of the cause of gastrointestinal symptoms in homosexual men, Campylobacter jejuni was recovered from 10 of 158 men with, and 2 of 75 men without, intestinal symptoms. In addition, a heterogeneous group of Campylobacter-like organisms was identified in 26 symptomatic and 6 asymptomatic homosexual men, but in none of 150 heterosexual men and women. Infections with Campylobacter-like organisms, like infections with C. jejuni, were significantly associated with the sexual practice of anilinctus and were usually associated with diarrhea, abdominal cramps, and hematochezia; proctocolitis seen at sigmoidoscopy; increased numbers of leukocytes seen on rectal smears; acute inflammatory changes seen on rectal biopsy specimens; and a serum antibody response to the infecting organism.

Chronic Idiopathic Intestinal Pseudo-Obstruction Caused by a Degenerative Disorder of the Myenteric Plexus: The Use of Smith's Method to Define the Neuropathology

In this paper we report the pathologic basis of chronic idiopathic intestinal pseudo-obstruction in a patient who had a subtotal colectomy and ileorectal anastomosis for severe obstipation. Conventional light microscopy of the resected intestine showed an increased thickness of the longitudinal muscle, minimal amounts of smooth muscle fibrosis, and normal smooth muscle cells. The morphology of the myenteric plexus was difficult to interpret with this technique, but quantification of colonic neurons revealed a significantly decreased number compared with controls. Silver stains of the myenteric plexus by Smiths method showed: (a) patchy loss of nerve tracts with replacement by Schwann cells, (b) degeneration and decreased numbers of both argryophilic and argyrophobic neurons, (c) fragmentation and dropout of many axons, and (d) increased thickness and disorganized spatial arrangement of other axons. The pathology of this intestinal neuropathy could be missed by conventional light microscopy and may be apparent only when a silver technique is used to visualize the myenteric plexus.

Chronic intestinal pseudoobstruction as a complication of Duchenne's muscular dystrophy

We report a case of Duchennes muscular dystrophy complicated by intestinal pseudoobstruction. The patient had recurrent attacks of nausea, vomiting, and abdominal distention for many years, and abdominal films repeatedly showed a dilated and fluid-filled small intestine and colon. Barium studies showed an esophageal diverticulum, reduced esophageal and gastric motility, and a dilated small bowel and colon. Pathologically, the entire gastrointestinal tract had smooth muscle fibrosis, but this was most marked in the esophagus and stomach. We conclude that Duchennes muscular dystrophy may involve intestinal smooth muscle and produce pseudoobstruction.