Small bowel transplantation in the dog using cyclosporine.

The effect of the new immunosuppressant cyclosporine on survival after total small intestinal allotransplantation (TSIA) was studied in a canine model. Successful TSIA was performed in 34 dogs. Eleven dogs were treated with cyclosporine, 25 mg/kg/day i.m., starting the day before the operation and continuing for four weeks. Thereafter the same dose was given orally. Thirteen dogs were given oral cyclosporine only, 25 mg/kg/day from the day after transplantation. Ten dogs served as controls. The dogs treated with intramuscular and oral cyclosporine survived a mean of 103.8 +/- 39.4 days (mean +/- S.E.M.). The longest survivor died after 432 days. Survival in this group was significantly longer than that of the control dogs, which survived 12.5 +/- 4.6 days. The orally treated dogs survived 30.4 +/- 7.6 days. All control dogs, and seven of the orally treated dogs, but only two of the intramuscularly treated dogs, died of acute rejection. It is concluded that cyclosporine is effective in prolonging survival after TSIA in the dog and reduces the incidence of acute rejection.

Identification and quantification of aberrant crypt foci and microadenomas in the human colon.

The objective of the present study was to determine whether aberrant crypt foci (ACF) similar to those observed in the colons of experimental animals exposed to colon carcinogens could be identified and quantified in the human colon. Twenty-seven colon resections from patients affected by familial adenomatous polyposis (FAP, five cases), colorectal cancer (CRC, 12 cases), and benign diseases of the large bowel (BD, 10 cases) were collected from a pathology repository or immediately after operation. Ten or more 1-cm2 formalin-fixed, methylene-blue--stained samples of colonic mucosa from each colon were scored under light microscopy for ACF. The number of ACF per cm2 and the number of crypts per ACF for each colon were calculated. The average number of ACF per cm2 in the FAP group (20 +/- 19, mean +/- SD) was significantly higher (P less than 0.01) than those of the CRC (0.37 +/- 0.41) and BD (0.18 +/- 0.35) groups. At least one ACF was found in every colon resection from CRC patients and in six out of 10 colon resections from the BD group. The average number of crypts per ACF ranged from five to 35 with absolute values from 1 to over 100. Fifty-five histologic specimens, 43 with ACF of various size and 12 without, were prepared by sectioning the colon parallel to the mucosal surface. There was a close correlation between the number of crypts per ACF in each specimen as scored by methylene-blue and histologic examination. Twenty-six aberrant crypt foci displayed dysplasia as evident by histologic analysis. In these instances we feel the term microadenoma is appropriate and, using this unique approach of examining the human colon, they can be easily identified and quantified. These lesions may well be precursors for adenomatous polyps and colorectal cancer.

Canine small bowel transplantation. A study of the immunological responses.

A canine small bowel allograft model was used to determine the effects of radiation to the graft in modifying the immunological effects of the passenger leukocytes. When untreated allografts were transplanted, death of the recipient animals occurred at a mean of nine days. The allograft was well-preserved and showed no signs of rejection. The reasons for attributing death to graft-versus-host (GVH) disease are discussed. When allografts were treated with 150 rads prior to transplantation, allograft rejection occurred, with death of the recipient animals at a mean of 9.2 days. This was the only group in which cell-mediated immunity developed. When allografts were treated with 50 rads, prolonged survival of the recipients to a mean of 28 days was noted. It is postulated that in this group a balance was struck between the allograft rejection reaction and GVH disease, with prolongation of allograft survival.

Histopathological features of congenital fundus lesions in familial adenomatous polyposis.

We report the light and electron microscopic findings for two lesions from two patients who died of complications of familial adenomatous polyposis. In the first case microscopy of a small (100 to 200 mu), uniformly dark lesion (the commonest type seen in this condition) showed enlarged retinal pigment epithelial cells with an increased number of pigment granules. This is consistent with the term "hypertrophy of the retinal pigment epithelium", currently used to describe these lesions. In the second case we sectioned a larger (1000 to 1500 mu), oval, grey lesion from the posterior pole. The pigment epithelium was normal, but between it and outer retina was an unusual choristoma consisting largely of myelinated axons and astrocytes.

An unusual manifestation of esophageal moniliasis. Report of two cases.

Most previous reports of esophageal moniliasis have described diffuse changes in the esophagus. The authors describe two cases involving a localized polypoid lesion in the esophagus in patients with Candida infection. The pathogenesis is discussed.

Surgery based on misdiagnosis of adenomatous polyposis. The Canadian Polyposis Registry experience.

The histopathology of 304 patients registered in the Canadian Familial Polyposis Registry (CFPR) with a diagnosis of supposed adenomatous polyposis (AP) was reviewed. The diagnosis was changed in 17 (5.6 percent) of these patients. Group 1 consisted of nine patients who had adenocarcinomas plus multiple tubular adenomas (seven) or metaplastic polyps (two). Eight patients who had no colon cancer comprised Group 2. In these patients, the diagnosis was changed to lymphoid polyposis (2), metaplastic polyps (3), isolated adenomas (2), or juvenile polyposis (1). All 17 patients had had previous colonic resections. Following the change in diagnosis, this treatment was considered inappropriate in 11 patients. Treatment, prognosis, and follow-up of patients and affected family members depend on the type of polyposis syndrome diagnosed. Correct histologic assessment of polyps prior to initial surgery is essential.

The ferning and nitrazine tests of amniotic fluid between 12 and 41 weeks gestation.

Most studies investigating the usefulness of ferning and nitrazine methods for detecting the presence of amniotic fluid following ruptured amniotic membranes have employed samples from vaginal pooling. Reported accuracies are 84 to 100% for the ferning test and 87 to 97% for the nitrazine test. Our study was designed to determine if these tests are applicable throughout gestation. Samples were obtained from amniocenteses between 14 and 42 weeks. Part I: Of 112 samples allowed to dry on a slide for 3 minutes only, 86.6% were ferning positive and 100% were nitrazine positive. Flame-drying increased the presence of ferning to 96.4%. Part II: 363 samples were allowed to dry completely for up to 10 minutes. All samples were ferning and nitrazine positive. Part III: 17 samples were tested for ferning and nitrazine at 1 hour, and again at 1 week. Sixty-six samples were tested within 1 week and again at 2 weeks. All samples remained ferning and nitrazine positive. Therefore optimal analysis of suspected amniotic fluid occurs when specimens are air-dried for 10 minutes. These tests may be reliably performed at gestations of 12 to 41 weeks.

Pharyngeal rhabdomyoma: a clinico-pathological study.

Adult extracardiac rhabdomyomas are rare with only 33 head and neck cases being reported in the world literature. In this select group, only nine cases have been found in the pharynx. We present two cases of pharyngeal rhabdomyoma focusing on the imaging findings, surgical approaches and more specifically on the histopathological and electron microscopic diagnosis of this interesting lesion. It is important to differentiate this tumor from other neoplasms, including granular cell myoblastoma, rhabdomyosarcomas, hamartomas, and fetal rhabdomyomas.

Surveillance in relatives of patients with adenomatous polyposis.

Registry ascertainment of kindreds with adenomatous polyposis (AP) reduces the incidence of colorectal carcinoma by medical monitoring for offspring and siblings of affected patients. Due to its pleiomorphic genotype and a 50% risk for AP in each patient's progeny, early screening is mandatory. Flexible sigmoidoscopy, averaging from puberty to age 48, annually or every two years, is one diagnostic technique that does not result in excess patient discomfort or cost. Timely examination is facilitated when eye anomalies, osteomas, or epidermoid cysts are present in childhood as potential clinical markers for AP. Denial, misperceptions, and fear may impede surveillance in the absence of education by the registry health care team.

Structure and function of small bowel allografts in the dog: immunosuppression with cyclosporin A.

Pairs of mongrel dogs received orthotopic total small bowel allografts. Half were treated with the immunosuppressive agent cyclosporin A and the other half were not. Ten untreated dogs survived a mean of 12.5 days (range from 7 to 25 days). They lost up to 30% of their initial body weight and rejection with hemorrhagic necrosis was usually the cause of graft failure. The mean survival of 11 dogs treated with cyclosporin A was 90.6 days (range 9 to 286 days) with early deaths being due to pneumonia or volvulus. Intestinal mucosa appeared normal, but there was some smooth muscle hypertrophy. Reconnection of lymph vessels was complete in all dogs examined more than 21 days after allografting. Two dogs survived for 203 and 221 days, respectively, and one dog remains alive and well 287 days after operation. The long-term survivors remained healthy, with steady body weights, formed stools, normal plasma protein values and xylose absorption curves that did not differ from those of autografted dogs. Roentgenography after a barium meal and follow-through study showed normal mucosa. The transit time was around 60 minutes (normal 150 minutes). Late, acute episodes of rejection occurred in two dogs, when blood levels of cyclosporin A were low (less than 400 ng/ml). Bowel mucosa showed ulceration and villous atrophy, with lymphoid infiltration, leading to malabsorption as a terminal event. Cyclosporin A is effective in increasing the duration of survival in dogs with small bowel allografts while maintaining essentially normal bowel structure and good function.

Transient oligohydramnios in a severely hypovolemic gravid woman at 35 weeks' gestation, with fluid reaccumulating immediately after intravenous maternal hydration.

Oligohydramnios is known to accompany chronically hypovolemic maternal conditions, usually preeclampsia, pregnancy-induced hypertension, and intrauterine growth retardation. A case is presented in which an acute maternal hypovolemic situation with oligohydramnios was treated vigorously with intravenous fluid hydration; ultrasonography documented immediate reaccumulation of normal amniotic fluid volume.

Bile aspiration: an experimental study in rabbits.

It has been shown that bile injected intratracheally in rabbits produces severe pulmonary edema, atelectasis, and focal hemorrhages. The authors investigated the effect of a number of solutions, including physiological concentration of bile, hydrochloric acid pH 1.0, bile salt diluted to 1%, and bile at 100% concentrations. Whenever the bile concentration exceeded 3%, none of the test animals survived. It is not possible to apply directly the results of an experimental animal study to humans. However, the severity of the pulmonary changes produced force the conclusion that bile is a potentially dangerous aspirate in humans.

Single-patient randomised clinical trial. Use in determining optimum treatment for patient with inflammation of Kock continent ileostomy reservoir.

A single-patient randomised clinical trial was used to determine optimum treatment for a patient with inflammation of her continent ileostomy. The trial proved to be feasible and acceptable to both patient and clinician. As a result, both the diagnosis of inflammation and the efficacy of metronidazole in treating it were confirmed. The trial design, in which multiple courses of active and control treatments are given to one patient, may be useful in other clinical situations to determine the most effective therapy in an individual case.

Small intestinal villous adenoma and celiac disease.

We describe the first patient with presumed celiac disease to present with a jejunal villous adenoma. Small bowel adenocarcinoma complicating celiac disease probably arises from adenoma, although this has not been previously addressed. The literature concerning factors in celiac disease predisposing to small intestinal epithelial neoplasia is reviewed.

Management of patients with polyps containing malignancy removed by colonoscopic polypectomy.

The management of malignant colonic polyps removed colonoscopically has been a controversial subject. A continuing series is reported of 36 patients with 37 malignant polyps removed by colonoscopic polypectomy (CP) between 1976 and 1982. Fourteen polyps contained carcinoma in situ (CIS); 13 were treated by CP alone; one was treated by CP and colectomy. Nineteen polyps contained invasive carcinoma; 13 were treated by CP alone; six were treated by CP and colectomy. Four patients had sessile polyps resected piecemeal, in which accurate staging was impossible. Two were treated with CP alone, and two had CP plus colectomy. All patients were followed with yearly colonoscopy and/or barium enema. Follow-up has been six to 84 months (mean 36 months). Twenty-seven patients whose polyps were treated by CP alone have had no evidence of recurrent tumor at the polypectomy site. Of the nine patients undergoing colectomy, six had residual tumor at the polypectomy resection site. No patients had involved lymph nodes. Our current approach to this problem is based on the degree of invasion and the status of the resection margins. Polyps containing CIS can safely be treated with CP alone. Polyps with invasive carcinoma and clear resection margins should be treated with CP and either colectomy or frequent repeat colonoscopy. This decision is a clinical one and must involve input from both the clinician and the pathologist. Those polyps whose resection margins are involved or where piecemeal excision precludes accurate pathologic assessment should undergo colectomy.

Systemic infection with Alaria americana (Trematoda).

Alaria americana is a trematode, the adult of which is found in mammalian carnivores. The first case of disseminated human infection by the mesocercarial stage of this worm occurred in a 24-year-old man. The infection possibly was acquired by the eating of inadequately cooked frogs, which are intermediate hosts of the worm. The diagnosis was made during life by lung biopsy and confirmed at autopsy. The mesocercariae were present in the stomach wall, lymph nodes, liver, myocardium, pancreas and surrounding adipose tissue, spleen, kidney, lungs, brain and spinal cord. There was no host reaction to the parasites. Granulomas were present in the stomach wall, lymph nodes and liver, but the worms were not identified in them. Hypersensitivity vasculitis and a bleeding diathesis due to disseminated intravascular coagulation and a circulating anticoagulant caused his death 8 days after the onset of his illness.

Ultrastructural evidence for piecemeal and anaphylactic degranulation of human gut mucosal mast cells in vivo.

One hundred and seventeen coded intestinal biopsies were examined by electron microscopy and evaluated for morphological evidence of mast cell and basophil secretion in situ. Sixty percent of the biopsies had evidence of secretion. Mast cell secretion was evident in control biopsies, many of which were obtained from uninvolved tissues of patients with inflammatory bowel disease. Biopsies of inflamed continent pouches from ulcerative colitis (UC) patients showed more mast cell secretion than noninflamed UC pouch biopsies. This evidence of mast cell secretion supports recent work that documents high constitutive levels of histamine in jejunal fluids of Crohn's disease patients and suggests a proinflammatory role for mast cells in inflammation associated with pouchitis.

Prophylactic mesalamine treatment decreases postoperative recurrence of Crohn's disease.

BACKGROUND & AIMS: Recurrence of Crohn's disease frequently occurs after surgery. A randomized controlled trial was performed to determine if mesalamine is effective in decreasing the risk of recurrent Crohn's disease after surgical resection is performed. METHODS: One hundred sixty-three patients who underwent a surgical resection and had no evidence of residual disease were randomized to a treatment group (1.5 g mesalamine twice a day) or a placebo control group within 8 weeks of surgery. The follow-up period was a maximum of 72 months. RESULTS: The symptomatic recurrence rate (symptoms plus endoscopic and/or radiological confirmation of disease) in the treatment group was 31% (27 of 87) compared with 41% (31 of 76) in the control group (P = 0.031). The relative risk of developing recurrent disease was 0.628 (90% confidence interval, 0.40-0.97) for those in the treatment group (P = 0.039; one-tail test) using an intention-to-treat analysis and 0.532 (90% confidence interval, 0.32-0.87) using an efficacy analysis. The endoscopic and radiological rate of recurrence was also significantly decreased with relative risks of 0.654 (90% confidence interval, 0.47-0.91) in the effectiveness analysis and 0.635 (90% confidence interval, 0.44-0.91) in the efficacy analysis. There was only one serious side effect (pancreatitis) in subjects in the treatment group. CONCLUSIONS: Mesalamine (3.0 g/day) is effective in decreasing the risk of recurrence of Crohn's disease after surgical resection is performed.

Human gut mucosal mast cells: ultrastructural observations and anatomic variation in mast cell-nerve associations in vivo.

One hundred and seventeen coded intestinal biopsy specimens were examined by electron microscopy. All surgical biopsies were obtained from uninvolved sites of patients with two inflammatory bowel diseases (ulcerative colitis or Crohn's disease) and from patients with preneoplastic and neoplastic diseases (adenocarcinoma, rectal polyp, familial polyposis). Biopsy sites included normal ileum, colon, and rectum as well as conventional ileostomies and continent pouches constructed from the ileum. The data reported here describe the ultrastructural anatomy of human gastrointestinal tract mucosal mast cells in vivo and their anatomic associations with enteric nerves.