Ileal Biopsy Specimens Research Articles

A case of sporadic intestinal cryptosporidiosis diagnosed by endoscopic biopsy.

Sporadic intestinal cryptosporidiosis is not easily diagnosed and might be overlooked. We present here a case of this disease in a 23-year-old Japanese military man with 3 days of abdominal pain, watery diarrhea, and nausea. The frequency of his diarrhea was more than 10 times per day. After his diarrheal bowel symptoms subsided, a colonoscopy was performed because inflammatory bowel disease was suspected. Although the endoscopic findings indicated non-specific ileitis, intestinal cryptosporidiosis was suspected from the histology of ileal biopsy specimens, and this was confirmed ultrastructurally. At that time, however, the patient was on active duty, and thus it was not possible to confirm this as a definitive diagnosis by an adequate stool examination for cryptosporidium. Routine practitioners should be encouraged to carefully inspect patients for this disease, supported by detailed knowledge of it and its diagnosis. If stool-examination results are negative or are not obtained at first, histological diagnosis by endoscopic biopsy could be a useful way to screen for intestinal cryptosporidiosis. Furthermore, stool or histological examination should be performed in recovered patients because the oocysts may continue to be shed for 1 to 4 weeks after the symptoms disappear. Therefore, endoscopic and histological examinations may be useful tools for the early diagnosis of intestinal cryptosporidiosis, although admittedly they are invasive procedures.

Reduced ileal expression of OSTα-OSTβ in non-obese gallstone disease

Cholelithiasis is a multifactorial process, and several mechanisms have been postulated. A decreased expression of the ileal apical sodium-dependent bile acid transporter (ASBT) and of the cytosolic ileal lipid binding protein (ILBP) was recently described in female non-obese patients. The role of the recently identified organic solute transporters alpha and beta (OSTalpha, OSTbeta) in gallstone pathogenesis remains unclear. Therefore, we performed analysis of OSTalpha-OSTbeta in gallstone patients according to body weight. Ileal mucosal biopsies were collected during routine colonoscopy from female gallstone carriers (n = 19) and controls (n = 34). OSTalpha-OSTbeta mRNA expression was measured using the LightCycler sequence detection system; protein was analyzed by immunohistochemistry and Western blot. The mRNA expression of OSTalpha-OSTbeta was significantly reduced (OSTalpha: 3.3-fold, P = 0.006; OSTbeta: 2.6-fold, P = 0.03) in normal-weight but not overweight gallstone carriers compared with controls. OSTalpha-OSTbeta protein levels also showed a reduction by 40-67%. The expression of OSTalpha-OSTbeta correlated positively with ASBT (r = 0.65, 0.58, respectively), ILBP (r = 0.77, 0.67), and the farnesoid X receptor (r = 0.58, 0.50). Fibroblast growth factor-19 showed a 2.8-fold reduction (P = 0.06), and liver receptor homolog-1 showed a 2-fold reduction (P = 0.04) in non-obese patients. In conclusion, an impaired function of all three ileal bile acid transporters may lead to low ileal bile acid reabsorption and an altered bile acid pool composition and therefore may contribute to the formation of gallstones in non-obese patients.

Normal Variation in Intraepithelial Lymphocytes of the Terminal Ileum

The number of intraepithelial lymphocytes (IELs) is often increased in the terminal ileum of patients with immune-mediated inflammatory diseases of the colon. However, data regarding their number in normal ileal mucosa of asymptomatic patients are lacking. We aimed to establish the acceptable range of IELs in biopsy specimens of normal ileal mucosa. Ileal mucosal biopsy specimens obtained during colonoscopy of 61 asymptomatic patients without endoscopic or pathologic evidence of colitis were immunostained for CD3 to assess the number of IELs present in each specimen. CD3+ lymphocytes were counted in 3 well-oriented villi and results expressed as the average for each biopsy specimen. The study group included 25 males and 36 females, ranging in age from 10 to 84 years (mean, 44.4 years). The mean +/- SD number of ileal CD3+ cells per 100 enterocytes for the group was 3.8 +/- 2 (median, 3; range, 0-9). In addition, there was a significant inverse relationship between the number of villus IELs and increasing age. Occasional IELs (approximately 4/100 villus enterocytes) are normally present in ileal biopsy specimens from asymptomatic patients without colitis. One should avoid overinterpreting the importance of occasional IELs in ileal biopsy specimens from asymptomatic patients.

Isolated Ileal Erosions in Patients With Mildly Altered Bowel Habits

This study evaluated 28 patients to characterize the morphologic features associated with typical Crohn disease (CD). All patients had similar complaints, an endoscopically normal colon, and small isolated, aphthoid erosions in the terminal ileum. The mean length of follow-up was 5.8 years. Of 28 patients, 25 (89%) were female (mean age, 32.3 years). Four patients were ingesting nonsteroidal anti-inflammatory drugs. All 28 lesions were morphologically similar, with focal lamina propria edema, mild active inflammation, and crypt disarray. Most had a lymphoid aggregate within the region of edema. Erosion was identified histologically in 21 cases. Following colonoscopy, symptoms resolved in all 28 patients. Typical, full-blown CD developed in 8 patients (29%) after a mean interval of 3.6 years. CD lesions were morphologically identical to non-CD lesions. Most focal ileal erosions in patients with mildly altered bowel habits are idiopathic and clinically insignificant. They represent early CD in approximately 30% of patients. The interval between initial examination and typical CD can be long. Pathologists should remain diagnostically vigilant when examining ileal biopsy specimens obtained from patients with previous abnormal ileal biopsy findings, regardless of the interval. Persistent, mild morphologic abnormalities have a high likelihood of being CD.

The Value of Myenteric Plexitis to Predict Early Postoperative Crohn’s Disease Recurrence

Early ileocolonoscopy allows detection of recurrence after surgically induced remission of Crohn's disease (CD). Unequivocal histologic markers predicting recurrence have not been identified. We assessed the predictive value of neural lesions for early endoscopic CD recurrence and long-term reintervention risk. Ileocolonic resection specimens from 59 patients with CD and 21 control patients were histologically scored for typical inflammatory bowel disease lesions, neural hypertrophy, and presence and severity of inflamed ganglia and nerve bundles. Endoscopic recurrence was determined at 3 months in all patients and at 1 year in 32 patients as part of 2 prospective clinical trials. Myenteric plexitis of the proximal resection margin was present in 32 patients with CD (54%) in absence of surrounding inflammation. Patients with this feature had a higher endoscopic recurrence (Rutgeerts score >/=2) at 3 months (75% vs 41%; odds ratio, 4.36; 95% confidence interval, 1.44-13.23; P = .008) and at 1 year (93% vs 59%; odds ratio, 9.80; 95% confidence interval, 1.04-92.70; P = .041) and had a trend toward an earlier reintervention (mean, 7.00 vs 5.30 years; P = .174). The severity of myenteric plexitis in the proximal resection margin correlated with the severity of endoscopic recurrence at 3 months (r = 0.334, P = .010) and 1 year (r = 0.560, P = .001). Myenteric plexitis was the only consistent predictor of endoscopic recurrence. The presence of myenteric plexitis in proximal margins of ileocolonic resection specimens is predictive of early endoscopic CD recurrence.

CD23-Mediated IgE Transport Across Human Intestinal Epithelium: Inhibition by Blocking Sites of Translation or Binding

In previous studies in rodent models of food allergy, we identified that sensitization induces expression of CD23 on intestinal epithelial cells and results in enhanced IgE-dependent transepithelial antigen uptake; further studies in CD23-/- mice provided evidence that CD23 is involved in protected transport of antigen into the body. Little information exists in humans on receptor-mediated immunoglobulin (Ig)E transport across epithelia. The present study was designed to examine expression of CD23 by human epithelial cells, determine its isoform and regulation by interleukin (IL) 4, and identify the role of CD23 in transepithelial IgE transport. Epithelial expression of CD23 was studied in cell lines, ileal biopsy specimens, and explanted fetal intestine. Bidirectional transport of IgE was measured across filter-grown cells, either normal cells or those transfected with antisense CD23 oligonucleotides, or in the presence of blocking antibody. Expression of the low-affinity IgE receptor was demonstrated in cultured epithelial cells as well as in situ cells in human intestine. CD23b was the isoform expressed by HT29, T84, and Caco-2 cells. IL-4 up-regulated the expression of epithelial CD23. IgE was transported in both the basal-to-apical direction and the apical-to-basal direction across filter-grown epithelial cells, a process that was inhibited by transfection of cells with CD23 antisense oligonucleotides or pretreatment with nonspecific IgE or anti-CD23 antibody. These findings provide evidence that CD23 encodes a functional IgE receptor on human intestinal epithelial cells and that this epithelial receptor is likely to play an important role in food allergies.

Isolated Ileal Erosions in Patients With Mildly Altered Bowel Habits A Follow-up Study of 28 Patients

This study evaluated 28 patients to characterize the morphologic features associated with typical Crohn disease (CD). All patients had similar complaints, an endoscopically normal colon, and small isolated, aphthoid erosions in the terminal ileum. The mean length of follow-up was 5.8 years. Of 28 patients, 25 (89%) were female (mean age, 32.3 years). Four patients were ingesting nonsteroidal anti-inflammatory drugs. All 28 lesions were morphologically similar, with focal lamina propria edema, mild active inflammation, and crypt disarray. Most had a lymphoid aggregate within the region of edema. Erosion was identified histologically in 21 cases. Following colonoscopy, symptoms resolved in all 28 patients. Typical, full-blown CD developed in 8 patients (29%) after a mean interval of 3.6 years. CD lesions were morphologically identical to non-CD lesions. Most focal ileal erosions in patients with mildly altered bowel habits are idiopathic and clinically insignificant. They represent early CD in approximately 30% of patients. The interval between initial examination and typical CD can be long. Pathologists should remain diagnostically vigilant when examining ileal biopsy specimens obtained from patients with previous abnormal ileal biopsy findings, regardless of the interval. Persistent, mild morphologic abnormalities have a high likelihood of being CD.

Cytologic diagnosis ofLawsonia intracellularisproliferative ileitis in a Japanese snow macaque (Macaca fuscata)

Diffuse ileal thickening and ileocecocolic lymphadenomegaly were observed during exploratory laparotomy in a 2-year-old male Japanese snow macaque (Macaca fuscata) that had flu-like signs and diarrhea. Cytologic examination of ileal biopsy imprints revealed many mature, mildly karyolytic neutrophils and fewer well-differentiated lymphocytes, eosinophils, macrophages, and plasma cells in a background containing amorphous, necrotic material. Tightly cohesive sheets of moderately pleomorphic epithelial cells also were seen. The cytologic diagnosis was chronic, active, mixed inflammation with atypical epithelial cells and necrosis. Histologically, the mucosal and crypt epithelium was moderately hyperplastic with a loss of goblet cells, increased mitoses, and frequent crypt abscesses. Within the lamina propria and extending into the submucosa was a marked neutrophilic infiltrate, with low numbers of lymphocytes, histiocytes, plasma cells, and eosinophils. The histologic diagnosis was chronic, diffuse, marked suppurative and lymphocytic ileitis. Warthin-Starry silver staining of the ileal biopsy and imprint specimens demonstrated numerous pleomorphic, curved bacilli consistent with Lawsonia intracellularis. Polymerase chain reaction (PCR) and immunohistochemistry confirmed the identity of the infectious agent. L intracellularis infection may be underdiagnosed because silver stain is required to visualize the organism with light microscopy and because the pathognomonic crypt hyperplasia may be complicated by secondary pathologic changes. Application of silver stain to cytologic specimens should be considered when distal intestinal lesions associated with hyperplastic epithelium, with or without inflammation, hemorrhage, or necrosis, are identified in animals with clinical signs of enteritis, especially in frequently affected species or in stressed or young animals.

The proportion of Th1 cells, which prevail in gut mucosa, is decreased in inflammatory bowel syndrome.

T lymphocytes and their cytokines have an important role in the regulation of immune responses in the gut and in the pathogenesis of intestinal inflammation such as in Crohn's disease. The aim of this study was to analyse the Th1/Th2 cytokine profile (IFN-gamma, IL-2, IL-4 and IL-10) in intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) in Crohn's disease (CD) and ulcerative colitis (UC) in relation to healthy controls (C). Colonic and ileal biopsy specimens were obtained from controls (n = 13) and patients with CD (n = 32). Colonic biopsies were obtained from patients with UC (n = 11). Intracytoplasmic IFN-gamma, IL-2, IL-4 and IL-10 were determined by flow cytometry after PMA-ionomycin stimulation in IEL and LPL. In colonic LPL, a significant proportional decrease of IFN-gamma and IL-2 producing CD3+ cells was observed in patients with CD and UC compared to controls. In ileal LPL, a similar tendency was found although differences were not significant. In IEL no differences in cytokine profiles could be observed. Flow cytometric analysis of intracytoplasmic cytokines at single cell level showed a proportional decrease of IFN-gamma and IL-2 producing T cells in colonic lamina propria in patients with inflammatory bowel disease.

Role of microcirculatory disorders in the morphogenesis of fissured ulcers in children with terminal ileitis

Structure and ultrastructure of ileal biopsy specimens were studied in 6 children with Crohn's disease in order to investigate the morphogenesis of fissures. Microcirculatory disorders lead to the formation of microinfarctions which are shaped as long fissures due to tissue vascular architectonics and peristaltic movements of the intestine.

Tumor necrosis factor α antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis

Background & Aims: Anti–tumor necrosis factor α monoclonal antibody treatment (infliximab) reduces clinical signs and symptoms in patients with Crohn's disease. The effects of infliximab on mucosal histopathologic abnormalities in Crohn's ileocolitis were studied. Methods: Thirteen patients with steroid-refractory Crohn's disease were treated with a single infusion of infliximab (5–20 mg/kg), and 5 were treated with placebo. Ileal and colonic biopsy specimens of all patients were collected before and 4 weeks after therapy. Severity of inflammation was assessed by a histological score. Immunohistochemical stainings with antibodies against HLA-DR, CD68, tumor necrosis factor α, intercellular adhesion molecule 1, lymphocyte function–associated antigen, CD4, CD8, and interleukin 4 were performed. Results: Total histological activity score was reduced significantly in both ileitis and colitis after infliximab. This is caused by a virtual disappearance of the neutrophils and a reduction of mononuclear cells. Mucosal architecture returned to normal in 4 patients at 4 weeks. The number of lamina propria mononuclear cells decreased because of a global reduction of CD4 + and CD8 + T lymphocytes and CD68 + monocytes. Aberrant colonic epithelial HLA-DR expression completely disappeared. The percentage of intercellular adhesion molecule 1 and lymphocyte function–associated antigen 1–expressing and interleukin 4– and tumor necrosis factor–positive lamina propria mononuclear cells sharply decreased. Conclusions: Infliximab dramatically decreases histological disease activity in Crohn's ileocolitis. Signs of active inflammation nearly disappear accompanied by a profound down-regulation of mucosal inflammatory mediators. GASTROENTEROLOGY 1999;116:22-28

Overexpression of an unstable intrinsic factor–cobalamin receptor in Imerslund–Gräsbeck syndrome

Two sisters with Imerslund–Gräsbeck syndrome who presented with clinical features of cobalamin deficiency are described. Intrinsic factor–cobalamin receptor (IFCR) activity and protein levels were determined in ileal biopsy specimens by using radioisotope assay and immunoblotting, respectively. IFCR activities in ileal homogenates expressed as femtomoles of ligand binding per milligram of protein were 38 ± 4 in control tissue, 494 ± 24 in patient 1, and 94 ± 7 in patient 2. However, when assayed in the presence of IFCR antiserum, the ligand binding was inhibited by >90% in both normal control and the patients with Imerslund–Gräsbeck syndrome. Immunoblotting of total membranes from the biopsy specimen of these 2 patients failed to detect an immunoreactive band of molecular mass of 185 kilodaltons. These findings are at variance with reports of decreased IFCR activity and indicate a new phenotype in which an active but an unstable receptor is overexpressed in Imerslund–Gräsbeck syndrome. GASTROENTEROLOGY 1998;115:173-176

Distinct cytokine patterns in early and chronic ileal lesions of Crohn's disease

BACKGROUND & AIMS: Chronic intestinal lesions of patients with Crohn's disease (CD) are associated with a T helper (Th) 1-type cytokine profile, including high levels of interleukin 2 (IL-2) and interferon gamma (IFN-gamma). However, the mechanisms involved in the pathogenesis of the early mucosal lesions are poorly known. The aim of this study was to examine the pattern of Th1- and Th2-type (IL-4, IL-5, and IL-13) cytokines in the early ileal lesions occurring in patients with CD 3 months after ileal resection and ileocolonic anastomosis. Cytokines were also examined in the chronic ileal lesions to look for cytokine patterns related to disease progression. METHODS: Ileal biopsy specimens were obtained from 17 patients with CD and 11 controls. Mucosal IL-2, IFN-gamma, IL-4, IL-5, and IL-13 messenger RNA (mRNA) was evaluated by competitive reverse-transcription polymerase chain reaction. RESULTS: The early ileal lesions of patients with CD were associated with a significant increase of IL-4 mRNA and a decrease of IFN-gamma mRNA compared with the normal mucosa of patients with CD or controls. A Th1-type pattern was observed in the chronic ileal lesions. CONCLUSIONS: Divergent cytokine patterns are observed during different clinical stages of CD. These observations need to be considered in the development of newer specific therapeutic agents to prevent CD recurrences. (Gastroenterology 1997 Jul;113(1):118-26)

Leucocyte typing, cytokine expression, and epithelial turnover in the ileal pouch in patients with ulcerative colitis and familial adenomatous polyposis.

Conventional histopathology, leucocyte typing, cytokine mRNA expression, and crypt cell turnover were compared in ileal pouch biopsy specimens from patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Biopsy specimens were taken from 17 patients with UC and seven with FAP at a median interval of 19 months (range 2-120) after ileostomy closure. All contained both epithelium and lamina propria. Cryostat sections were stained for lymphocyte subtypes (CD3, CD4, CD8), macrophages (CD68), common leucocyte antigen (CD45), and Ki-67, using a three stage immunoperoxidase reaction. Cytokine mRNA expression for interleukins 2 and 6, tumour necrosis factor alpha, and interferon gamma was studied using an in situ hybridisation technique. Lymphocyte subtype and macrophage populations in epithelium and lamina propria were similar in UC and FAP. The labelling index (Ki-67) was significantly increased in biopsy specimens from patients with UC (UC median = 43.3 (interquartile range (IQR) 38.9-48.2) v FAP 34.9 (29.9-35.2), p < 0.05). There was little or no epithelial mRNA expression for any cytokine in any of the specimens. Lamina propria mRNA expression for interleukin 2 was significantly increased in UC (UC median (IQR) 10.7 (5.4-14.2) cells per unit area v FAP 2.8 (1.5-6.6) p < 0.05) but not for tumour necrosis factor alpha, interleukin 6, and interferon gamma. While static morphological assessment (leucocyte type, conventional histopathological examination) was similar, tests of cell function (mRNA expression and labelling index) were different in ileal pouches in patients with UC compared with FAP. The study also showed that mRNA expression occurred almost entirely in the lamina propria.

Decreased activity of intestinal and urinary intrinsic factor in Gräsbeck-Imerslund disease

Background/Aims: The pathogenesis of inherited intestinal cobalamin malabsorption (Gräsbeck-Imerslund disease) remains unknown. The authors studied whether the disease corresponds to a defective expression and/or function of the intrinsic factor-cobalamin receptor in the ileum. Methods: Intrinsic factor-cobalamin receptor activity was measured using radioisotope assay and gel-filtration exclusion chromatography in ileal biopsy specimens and urine concentrates from 4 patients with Gräsbeck-Imerslund disease and 5 controls. Results: Receptor activity was 164 ± 13 fmol/mg of protein in control biopsy specimens and <2.6 fmol/mg protein in specimens from patients. The association constant was estimated to be 3.8 ± 0.4 (nmol/L) −1 in controls. A dramatic decrease in receptor activity was also observed in urine concentrate from patients with an association constant of 1.9 and 3.3 (nmol/L) −1. Isoelectrofocusing of the cross-linked intrinsic factor-cobalamin receptor complex showed an isoelectric point at 4.8 in a patient as well as in control samples. Conclusions: It is concluded that Gräsbeck-Imerslund disease is related to decreased intrinsic factor-receptor activity in intestinal mucosa; the receptor assay in urine can be helpful for diagnosis.

Diarrheogenic bacterial enteritis in acquired immune deficiency syndrome: A light and electron microscopy study of 52 cases

Diarrhea, the etiology of which often is obscure, is a major complication of human immunodeficiency virus (HIV) disease. Diarrheogenic bacterial infections (eg, enteropathogenic Escherichia coli) are diagnosed traditionally by stool analysis rather than by examination of endoscopic biopsy specimens. Although E coli rarely have been associated with diarrhea in HIV/acquired immunodeficiency syndrome (AIDS) patients, neither have they routinely been sought. Endoscopic ileal and colorectal biopsy specimens from AIDS-positive patients with chronic diarrhea were analyzed by light and transmission electron microscopy (TEM). The surface epithelium of many large intestinal biopsy specimens previously diagnosed with, for example, nonspecific colitis, regularly showed disarray, degeneration, and necrosis, often with polymorphonuclear neutrophils (PMNs) and eosinophils, irregular cell aggregates, cell shedding, and defects. The crypts were not involved nor were consistent changes noted in the lamina propria. Closer scrutiny of 52 of these biopsy specimens showed gram-negative coliform bacteria intimately associated with histopathology in four distinct patterns. In 22 biopsy specimens, including two from infants, four morphological types of bacilli were observed that adhered to and effaced the brush border in the classic manner with cytoskeletal rearrangement and pedestals. Other bacterial morphologies and/or patterns of epithelial interaction also were observed (ie, thin bacilli intercalated between microvilli [n = 7], loosely associated bacilli [n = 21], and enterocyte invasion by long rods [n = 2]). Three patients also had minor ileal involvement. Infection was greatest in the right colon and coinfections (eg, microsporidia, Mycobacterium avium complex, adenovirus, and especially cytomegalovirus) were documented in 37% (19 of 52) of specimens. Diarrheogenic bacterial infections, some of the E coli type, may be an important cause of diarrhea in HIV disease. Their precise characterization is needed so that stool samples, not endoscopic biopsy specimens, can be used for diagnosis.

Histologic detection of trophozoites of Giardia lamblia in the terminal ileum.

The occurrence of trophozoites of Giardia lamblia in mucosal biopsy specimens obtained from the terminal ileum and associated histologic changes are reported. In this retrospective histologic analysis an average of 3.2 (range, 1-7) Giardia-positive biopsy specimens obtained from the terminal ileum of 32 subjects was examined. Colonization was defined as sparse (1-10 trophozoites per specimen), intermediate (10-30 trophozoites per specimen), or heavy (more than 30 trophozoites). The number of intraepithelial lymphocytes (IEL) was assessed and the results expressed as the number of IEL/100 epithelial cells. Grade of villous flattening was determined semiquantitatively. The number of lymphoid follicles per biopsy specimen was counted, and the degree of mucosal inflammation determined semiquantitatively. Ileal mucosa biopsy specimens from 32 Giardia-free cases, classified histologically as normal, served as control. Twelve of the patients were female, and twenty male. The mean age was 46 years (range, 20-68 years). Light colonization with G. lamblia was observed in 13 (40.6%) patients, intermediate in 6 (18.8%), and heavy colonization in 13 (40.6%; range, 2-215 trophozoites/case). Normal villous architecture was seen in all cases. The numbers of lymphocytes and granulocytes in the lamina propria were considered to be within the normal range in all patients with giardiasis and in all controls. The occurrence of lymphoid follicles and the content in IEL did not differ significantly in Giardia-positive and -negative cases. G. lamblia can colonize the terminal ileum and may therefore be detected in biopsy specimens obtained from this area. Owing to the absence of associated histologic changes a search for the parasites themselves has to be made in the specimen.

Ileal and colonic fatty acid profiles in patients with active Crohn's disease.

In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls the fatty acid distribution in the inflamed ileal mucosa was significantly characterised by (a) a decrease of 18:2 n6 and 18:3 n3 accompanied by a substantial increase of the highly polyunsaturated fatty acids 20:4 n6, 22:4 n6, and 22:6 n3 and (b) a higher unsaturation index of total fatty acids compared with controls. These changes were similar in the inflamed colon. Additionally, both the inflamed and the macroscopically normal colonic mucosa showed an increase of saturated (18:0) and a decrease of monounsaturated fatty acids (18:1 n9). Fatty acid profiles of ileum and colon showed side variations in controls, but not in the Crohn's disease group. These data suggest that in Crohn's disease changes in the distribution of polyunsaturated fatty acids seem to be the general feature of inflamed mucosa in small and large intestine. Results further suggest that colonic fatty acid metabolism in Crohn's disease is altered by degrees, showing changes in saturated and monounsaturated fatty acids as an additional, primary event.

Primary bile acid diarrhoea without an ileal carrier defect: quantification of active bile acid transport across the ileal brush border membrane.

Unexplained bile acid malabsorption associated with diarrhoea that responds to cholestyramine was first described in 1973 but convincing evidence of the proposed mechanism--a defective active ileal bile acid transport--has never been substantiated. Active bile acid transport was quantified in vitro using brush border membrane vesicles prepared from terminal ileal biopsy specimens from 10 patients who fulfilled the criteria of idiopathic bile acid diarrhoea. They were recruited from 181 patients with bile acid malabsorption of various causes. Transport was quantified as in vitro Na+ dependent bile acid transport (INBAT), expressed as pmol taurocholate/mg brush border membrane protein/15 seconds, and in vitro Na+ dependent bile acid local transport capacity (INBALTC), expressed as pmol taurocholate/g ileal biopsy tissue/15 seconds. The lowest INBAT and INBALTC values in the 10 patients with idiopathic bile acid diarrhoea were well above the 10th centile values of a control group of 132 patients. Both INBAT (mean (range) 88 (30-136)) and INBALTC (158 (85-268)) values were significantly higher in the 10 patients than in the control group (INBAT: mean (range) 63 (1-244), INBALTC: mean (range) 98 (1-408)). Quantification of active ileal bile acid transport in these 10 patients with idiopathic bile acid malabsorption suggests that a genetic (carrier) defect is rare in adults.

Adaptive Changes in Ileal Mucosal Nutrient Transport Following Colectomy and Endorectal Ileal Pull-Through With Ileal Reservoir

To study ileal mucosal function when used in an ileal reservoir or ileostomy, eight dogs underwent colectomy and endorectal ileal pull-through with creation of a lateral ileal reservoir. Ileal mucosal biopsy specimens were obtained at the initial operation, from the ileostomy and dormant ileal reservoir at the time of ileostomy closure, and from the reservoir 3 months later. Rates of uptake for four different substrates were determined by radioactive absorption techniques. Absorption of carbohydrates, amino acids, and bile acids was markedly decreased and of short-chain fatty acid mildly reduced in ileal reservoir mucosa compared with normal ileum, largely owing to a decrease in reservoir absorptive surface area from flattened villi. Reservoir uptake of the substrates evaluated within 3 months after operation was similar to that for normal colonic mucosa. Uptake of all measured substrates from ileostomy mucosa approximated that of normal ileum. The use of short ileal reservoirs and the avoidance of stasis may favor reduced bacterial growth and increased nutrient absorption.