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Concordance of familial characteristics in Crohn's disease and ulcerative colitis.

The diagnosis of inflammatory bowel disease (IBD) in a proband increases the probability of a parallel IBD diagnosis in a family member. In this study, we were able to confirm the IBD diagnosis in 35 (9.9 percent) of the relatives of 352 registry probands. To confirm a proband's report of a positive family history of IBD, efforts were made to directly contact all first-degree relatives regardless of their IBD status (parents, siblings, and children). Consent to contact family members was obtained from the proband, who furnished the registry personnel with names, addresses, and phone numbers. We then attempted to contact each identified relative by phone. After verbal consent was obtained, family members were asked if they had been diagnosed with IBD. This diagnosis was confirmed by contacting the relative's physician. A McNemar (chi 2 Mc) matched-pair analysis was used to analyze concordance between the proband and the affected family member. Within the CD/CD (Crohn's disease) concordant pairs, sex was a significant risk factor. Sex was not a significant risk factor within the UC/UC (ulcerative colitis) concordant pairs. In the concordant surgery pairs, no surgical procedure was a significant risk factor for the prediction of a similar surgical procedure for the affected relative. In concordant extraintestinal complications, only the appearance of a skin rash was significantly related to the appearance of a skin rash in the affected relative.

Colitis, Ulcerative↗

Elevation of interleukin-6 in inflammatory bowel disease is macrophage- and epithelial cell-dependent.

Local interleukin-6 (IL-6) activity was studied using colonic mucosal tissues in inflammatory bowel disease (IBD) and inflammatory control patients. Active IBD specimens exhibited significantly higher IL-6 activity than control specimens in both cultures of isolated lamina propria mononuclear cells (LPMC) and mucosal tissues with an increased number of IL-6-producing cells. However, the activity in inactive IBD or inflammatory controls did not differ from controls. Northern blot analysis demonstrated IL-6 messenger RNA in LPMC and colonic epithelial cells isolated from active IBD specimens but not in control cells. Furthermore, immunofluorescent microscopic study of active IBD specimens showed more conspicuous staining of IL-6 in infiltrating LPMC (mostly CD68+ cells) and colonic epithelial cells. These results suggest that elevation of local IL-6 activity may be a characteristic feature of active IBD and both macrophages and colonic epithelial cells are the major cell types responsible for this phenomenon.

Adenocarcinoma↗

Plain abdominal radiographs in children with inflammatory bowel disease.

The value of plain abdominal radiography in children with inflammatory bowel disease (IBD) has not been ascertained. We reviewed the scout radiographs prior to first barium examination in 100 children with IBD [53 Crohn, 47 ulcerative colitis (UC) and scout films prior to excretory urography in 50 patients who had no clinical evidence of intestinal disease (controls)]. The films were reviewed without clinical information, and the abnormalities on each film scored according to severity and location. Criteria included: mural thickening, dilatation and mucosal abnormalities of the small bowel and colon, as well as abnormal quantity and/or distribution of feces in the colon. Eighty percent (40/50) of the films in the control group were interpreted as normal. Abnormalities suggestive of IBD were present in 73% of the IBD group (76% Crohn and 72% UC). Thirty-one percent of the films in the IBD group had a moderately abnormal score (greater than or equal to 3) or markedly abnormal score (greater than or equal to 5) at presentation. The most reliable radiographic findings were: mucosal abnormality in the colon and small bowel and an abnormal stool pattern (feces completely absent or only present in one colonic segment). The clinical presentation of IBD in childhood is often vague and nonspecific. Abnormalities in plain films of the abdomen are common in these patients and may be helpful in suggesting the presence and, to a great degree, the severity of disease in these children.

Adolescent↗

Salivary SIgA and SIgA 1 in coeliac disease, inflammatory bowel disease and controls.

Levels of secretory IgA1 (SIgA1) in the saliva have not been measured previously in either coeliac disease (CD) or inflammatory bowel disease (IBD). Saliva was collected from coeliacs, IBD patients and controls. The concentration of total SIgA in saliva was measured by enzyme linked immunosorbent assay (ELISA) with an anti-human SIgA antibody as the bound phase and human SIgA isolated from colostrum as the standard. The concentration of SIgA1 was determined using an ELISA with a lectin with a high affinity for human SIgA1. The IBD patients have a significantly higher concentration of SIgA1 than the controls. The rate of secretion of saliva and %SIgA1 was significantly lower in coeliacs than in the control and IBD groups. The rate of secretion of SIgA1 was significantly higher in the IBD than in the coeliacs. We describe hitherto unreported levels of SIgA1 in CD and IBD.

Adult↗

Effect of DA-6034, a derivative of flavonoid, on experimental animal models of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034, 7-carboxymethyloxy-3', 4', 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD: two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3 to approximately 3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 mg/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.

Acetic Acid↗

Immunohistochemical expression of cyclin D1, cyclin E, p21/waf1 and p27/kip1 in inflammatory bowel disease: correlation with other cell-cycle-related proteins (Rb, p53, ki-67 and PCNA) and clinicopathological features.

BACKGROUND AND AIMS: The expression patterns of cyclins D1 and E as well as cyclin-dependent kinase inhibitors p21/waf1 and p27/kip1 and their correlation with clinical parameters and other cell cycle regulators was investigated in inflammatory bowel disease (IBD). PATIENTS AND METHODS: These molecular markers were localized immunohistochemically using the monoclonal antibodies anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21 (4D10) and anti-p27 (1B4) in 70 patients with IBD, 30 patients with colorectal cancer and eight healthy subjects. Data were analyzed statistically using the software program. RESULTS: Cyclin D1 expression was higher in both UC and CD compared with the healthy control group. In addition, CD cyclin D1 expression was higher compared with UC cases and colorectal carcinomas. Cyclin D1 expression was correlated with disease activity and cell proliferation in UC cases. A positive relationship of cyclin D1 with p27/kip1 in both UC and CD was detected. Cyclin E expression was higher in UC, CD and carcinomas compared with healthy control group and its expression correlated with proliferative activity in both UC and CD cases. p21/waf1 expression was higher in IBD cases compared with that of the control group, while a decreased p21/waf1 expression in the group of carcinomas was noted. This expression was correlated with disease activity in UC and the proliferative activity in both UC and CD. The expression of cyclins D1 and E as well as p21/waf1 was also correlated with the existence of dysplastic lesions. A lower p27/kip1 expression in the group of carcinomas compared with IBD cases and healthy controls was found. CONCLUSIONS: The expression patterns of cyclin D1, cyclin E, p21/waf1 and p27/kip1 in IBD may indicate their contribution in epithelial cell turnover and their possible implication in IBD-related dysplasia-carcinoma.

Carcinoma↗

Inflammatory bowel disease and the lung: is there a link between surgery and bronchiectasis?

PURPOSE: One-third of patients with inflammatory bowel disease (IBD) has extracolonic manifestations. Inflammatory bowel-associated pulmonary disease is one of the less commonly recognized and more recently described manifestations. Here, we report the experience of our patients with inflammatory bowel-associated bronchiectasis. METHODS: A retrospective analysis of case notes of patients with IBD and respiratory manifestations was undertaken. Relevant demographic, clinical, radiological, and pulmonary physiology laboratory results were reviewed. RESULTS: Ten patients with IBD and bronchiectasis were identified. Eight developed respiratory symptoms after surgery for IBD. Five of the ten had ulcerative colitis. Their lung function abnormality is mild to moderate in severity. Small airways disease (forced expiratory flow between 25-75% is <50%) was evident in seven of the ten patients. CONCLUSIONS: This preliminary study supports an association between surgery for IBD and development of symptomatic lung disease, particularly bronchiectasis, in susceptible patients. The pulmonary manifestations of IBD in some patients may only become clinically significant after surgery and the withdrawal of medical treatment.

Aged↗

Investigation of association of the DLG5 gene with phenotypes of inflammatory bowel disease in the British population.

BACKGROUND AND AIMS: Mutations in the DLG5 gene are associated with an increased risk of inflammatory bowel disease (IBD) in some European populations. Initial investigation of a British IBD population showed evidence of association of one of three DLG5 variants, R30Q, in a family-based collection but not in a case-control cohort. We have now examined the association of the R30Q polymorphism in a large cohort of British IBD cases, tested for interaction between the DLG5 and CARD15 genes and assessed possible association of DLG5 with clinical features of Crohn's disease (CD) and ulcerative colitis (UC). MATERIALS AND METHODS: DLG5 R30Q and the CARD15 polymorphisms, Arg702Trp, Gly908Arg and Leu1007fs were genotyped in 1,148 IBD cases and 749 controls. DLG5 R30Q was also analysed in cases stratified by CARD15 genotype, disease subtype and smoking history. RESULTS/FINDINGS: No significant difference in frequencies of the R30Q variant was observed between IBD cases (9.9%) and controls (10.1%) or in cases analysed separately as CD and UC. There was also no significant difference in the frequency of R30Q between CD cases carrying risk-associated CARD15 alleles and those that did not. The frequency of R30Q was higher in CD cases with ileal disease than cases without (p=0.042) and higher in CD cases who had smoked than in nonsmokers (p=0.009). INTERPRETATION/CONCLUSION: The R30Q variant in the DLG5 gene does not appear to be associated with an overall increase in the risk of disease in a British IBD cohort, but differences in its frequency in subgroups of CD patients warrant further investigation.

Case-Control Studies↗

Evaluation of venous thromboembolism and coagulation-fibrinolysis markers in Japanese patients with inflammatory bowel disease.

BACKGROUND: Arterial or venous thromboembolism is rarely encountered clinically as an extradigestive tract complication in inflammatory bowel disease (IBD). However, it is one of the important prognostic factors for IBD patients. The present study was designed to evaluate the relationship between pulmonary embolism (PE) and deep vein thrombosis (DVT) with coagulation-fibrinolysis markers in patients with active IBD. METHODS: In 47 consecutive cases hospitalized due to active IBD [26 with Crohn's disease (CD) and 21 with ulcerative colitis (UC)], we evaluated the disease severity, blood tests, pulmonary ventilation-perfusion scan (V/Q scan), and magnetic resonance venography (MRV) or conventional venography. RESULTS: PE was diagnosed by V/Q scan in 5 (2 with CD and 3 with UC; 10.6%). DVT was diagnosed in 5 (2 with CD and 3 with UC; 10.6%). Of the 47 patients, 8 (17.0%) had venous thromboembolism (either PE or DVT), and 2 of them (4.3%) had both conditions. In UC patients, the thrombosis group was in more severe stages based on endoscopic grading than the nonthrombosis group. In all patients, the thrombosis group were older (50.3 +/- 14.3 years) than the nonthrombosis group (29.2 +/- 11.7 years). Furthermore, the thrombosis group had higher thrombin-antithrombin III complex (13.1 +/- 17.7 ng/ml) and d-dimer (964 +/- 1402 ng/ml) values than the nonthrombosis group (5.3 +/- 5.5 ng/ml, P=0.0245, and 207 +/- 192 ng/ml, P=0.0016, respectively). There were no significant differences in leukocyte and platelet counts, C-reactive protein, and fibrinogen between the two groups. CONCLUSIONS: A high incidence of venous thromboembolism was suggested in Japanese patients with active IBD. We should be careful with thrombosis in treatment of IBD patients, especially those who are of older age and in more severe stages.

Adult↗

Infectious bursal disease virus recovery from Vero cells transfected with RNA transcripts is enhanced by expression of the structural proteins in trans.

Positive sense RNA transcripts of infectious bursal disease (IBD) virus genome segments A and B have previously been shown to be infectious. In this study we demonstrate that recovery of IBD virus from the transfection of Vero cells with positive sense RNA transcripts of genome segments A and B was enhanced by expression of the viral structural proteins VP2 with VP3 or by expression of viral polyprotein VP243 from DNA plasmids in trans. Expression of individual viral proteins VP2, VP3, or VP4 alone from DNA plasmids did not enhance IBD virus recovery. Earliest virus recovery from transfection of positive sense RNA transcripts of genomic segments A and B was at 36 h and mean titers were 10(1.8) pfu/ml. IBD virus was recovered 6 hours after transfection in cells concurrently expressing either VP2 with VP3 or VP243 and mean titers were 10(8.5) pfu/ml or 10(9.2) pfu/ml, respectively. Likewise, expression of the viral polyprotein from DNA plasmid increased the permissiveness of Vero cells for infection with non-culture adapted IBD virus. The titer of recovered non-culture adapted virus from 10(3.3) pfu/ml to 10(10.3) pfu/ml with expression of the viral polyprotein. This report is the first to describe a reverse genetics model for IBD virus with high efficiency of virus recovery for non-culture adapted strains.

Animals↗

Serum angiogenin in inflammatory bowel disease.

Angiogenesis-promoting cytokines have been suggested to play an important role in inflammatory bowel disease (IBD) since they promote inflammation by increasing vascular permeability and mediate tissue repair by activating fibroblasts. The aim of the present study was to evaluate the serum levels of angiogenin, a potent angiogenic factor, in patients with ulcerative colitis (UC) and Crohn's disease (CD). Angiogenin serum levels were measured in 154 IBD patients (78 UC and 76 CD), in 18 cases with other causes of intestinal inflammation, and in 84 matched healthy controls using a commercially available enzyme-linked immunosorbent assay. Angiogenin levels were assessed in terms of disease activity, type, localization, and treatment. Mean (+/-SD) serum angiogenin levels were 526.5+/-224.1 ng/ml in UC patients, 508.8+/-228.5 ng/ml in CD patients, 394.6+/-137.6 ng/ml in healthy controls, and 448.1+/-167.8 ng/ml in patients with non-IBD intestinal inflammation. A statistically significant difference among the mean levels of angiogenin in the four groups was found (P = 0.0003). IBD patients with early disease had a significantly lower mean serum angiogenin compared with patients with late disease (P = 0.03). No significant association between angiogenin levels and disease activity, localization, disease type, or treatment was found. Serum angiogenin is elevated in patients with IBD. The increased serum angiogenin suggests that angiogenin may mediate angiogenesis and vascular permeability in the mucosa of patients with IBD.

Adult↗

Insulin-like growth factor binding protein 3 in inflammatory bowel disease.

Epithelial cell growth regulation has been reported to be altered in inflammatory bowel disease (IBD) patients. The cell growth regulatory factor, insulin-like growth factor binding protein 3 (IGFBP-3), may be partly responsible for this phenomenon. So far, IGFBP-3 levels have been assessed as values of total protein, which is a sum of bioactive intact 43- to 45-kDa protein and its inactive proteolytic cleavage fragments. We aimed to assess the levels of intact IGFBP-3 and its cleaving protease MMP-9 in IBD. Patients with IBD and controls were included. Total plasma IGFBP-3 concentration was measured in ELISA. Western blot analysis, which distinguishes between intact and cleaved IGFBP-3, was performed in order to determine the ratio of intact to total protein; this ratio was used to calculate the concentration of intact IGFBP-3. The profile of plasma proteases was evaluated in zymography and MMP-9 levels were determined in ELISA. The concentration of intact IGFBP-3 was significantly decreased in patients with moderate to severe IBD activity compared to those in remission or controls. Of note, a dramatic depletion of intact IGFBP-3 was found in 7.4% of patients with IBD. Zymography revealed that the dominant gelatinase was the pro-form of MMP-9. However, no differences in MMP-9 levels were noted between those with active disease and controls. The level of intact IGFBP-3 is decreased in IBD patients with moderate to severe disease activity. This decrease may be linked to altered IGFBP-3 production or to increased cleavage by proteases other than MMP-9.

Adult↗

Pancreatic autoantibodies in Greek patients with inflammatory bowel disease.

Pancreatic autoantibodies (PAbs) have been suggested as a specific but not sensitive marker for Crohn's disease (CD). The aim of this study was to assess the value of detecting PAbs in Greek patients with ulcerative colitis (UC) and CD. Sera were collected from 150 patients with IBD (73 with UC and 77 with CD), 31 cases with non-IBD intestinal inflammation, 16 cases with other autoimmune diseases, and 104 healthy controls. Determination of PAbs was performed by a standard indirect immunofluorescence technique. PAbs were detected in 18 of 73 (24.7%) samples from UC patients and in 32 of 77 (41.6%) samples from CD patients. The prevalence of positive PAbs was significantly higher in CD than in UC (P = 0.04). None of the 104 samples from healthy controls and the 31 cases with non-IBD intestinal inflammation had detectable PAbs. One patient with Sjogren's syndrome was PAbs positive. No association of PAbs with IBD activity, IBD localization, or medical treatment was found. Patients with stenotic CD had a significantly higher prevalence of PAbs positivity (60%) compared with patients with inflammatory (28.6%) and fistulizing (41.2%) disease (P = 0.02). The prevalence of PAbs in Greek CD patients was found to be similar to that in previous reports. In contrast to these studies we found also increased prevalence of PAbs in UC patients. These findings suggest that PAbs should be considered as a specific marker for IBD rather than for CD.

Adult↗

Economically important non-oncogenic immunosuppressive viral diseases of chicken--current status.

Immunosuppressive viral diseases threaten the poultry industry by causing heavy mortality and economic loss of production, often as a result of the chickens' increased susceptibility to secondary infections and sub-optimal response to vaccinations. This paper aimed to present an up-to-date review of three specific economically important non-oncogenic immunosuppressive viral diseases of chickens, viz. chicken infectious anaemia (CIA), infectious bursal disease (IBD) and hydropericardium syndrome (HPS), with emphasis on their immunosuppressive effects. CIA and IBD causes immunosuppression in chickens and the socio-economic significance of these diseases is considerable worldwide. CIA occurs following transovarian transmission of chicken anaemia virus and has potential for inducing immunosuppression alone or in combination with other infectious agents, and is characterized by generalized lymphoid atrophy, increased mortality and severe anemia. The virus replicates in erythroid and lymphoid progenitor cells, causing inapparent, sub-clinical infections that lead to depletion of these cells with consequent immunosuppressive effects. The IBD virus replicates extensively in IgM(+) cells of the bursa and chickens may die during the acute phase of the disease, although IBD virus-induced mortality is highly variable and depends, among other factors, upon the virulence of the virus strain. The sub-clinical form is more common than clinical IBD because of regular vaccination on breeding farms. Infection at an early age significantly compromises the humoral and local immune responses of chickens because of the direct effect of B cells or their precursors. HPS is a recently emerged immunosuppressive disease of 3-6-weeked broilers, characterized by sudden onset, high mortality, typical hydropericardium and enlarged mottled and friable livers, with intranuclear inclusion bodies in the hepatocytes. The agent, fowl adenovirus-4, causes immunosuppression by damaging lymphoid tissues; the presence of IBD and CIA viruses may predispose for HPS or HPS may predispose for other viral infections. Synergism with CIA or other virus infections or prior immunosuppression is necessary to produce IBH-HPS in chickens and the susceptibility of chickens infected with fowl adenovirus varies throughout the course of CIA infection. The mechanism of immunosuppression has been studied in detail for certain chicken viruses at molecular levels, which will provides new opportunities to control these diseases by vaccination.

Adenoviridae Infections↗

Treatment of Extraintestinal Manifestations in Inflammatory Bowel Disease.

Extraintestinal manifestations (EIM) of inflammatory bowel disease (IBD) occur rather frequently and may be found in up to 30% of patients. However, surprisingly few randomized, controlled studies have been conducted that were specifically aimed at the treatment of EIM of IBD patients. Therefore, most therapies of EIM are empiric or deduced from studies in populations with other type of patients. EIM may be associated with active IBD. Treatment of active IBD is, therefore, the mainstay of treatment of EIM. Lifestyle modification as a means of therapy is a recent subject of study in chronic conditions, such as IBD. Based on epidemiologic and experimental findings, EIM of various tracts can be modified by optimizing alimentary intake, refraining from sedentary lifestyle, and adapting smoking habits. Not many new drugs for treatment of EIM have been developed during the past few years; the role of infliximab has been extended in particular in Crohn's disease-related EIM. Careful consideration of prescribed drugs remains necessary due to potential interaction with the course of IBD.

Journal Article↗

Targeting Therapy in Pediatric Inflammatory Bowel Disease.

Progress in our understanding of the interaction between the environment and the immune system in disease pathogenesis has led to major advancements in the area of inflammatory bowel disease (IBD) therapeutics. Biotechnology is keeping pace with these scientific advances. Current therapies target the various elements of the inflammatory cascade implicated in the pathogenesis of IBD. The anti-inflammatory and immunomodulatory properties of the pharmacologic therapies used in IBD vary from actions that are extremely broad to those that are cellular or cytokine specific. Despite the various therapeutic options available for IBD patients, chosen therapies should be based on the overall treatment goal for individual patients. Therapeutics can be broadly categorized as induction therapies (goal to treat active disease) and maintenance therapies (goal to prevent relapse of disease). The modern thinking behind drug development is that IBD therapy should be disease modifying so to avoid complications and alter the long term natural history of disease. This review will cover both current and emerging agents and highlight the pathogenesis of IBD and how it relates to therapeutic targets.

Journal Article↗

Inflammatory bowel disease. Part I: Nature and pathogenesis.

Once regarded as medical curiosities, ulcerative colitis and Crohn's disease have achieved a remarkable change in status recently and today are among the more compelling of all human illnesses. The cause(s) of inflammatory bowel disease (IBD) are not known. Genetic, environmental, microbial, and immunologic factors are involved, but the precise mechanisms are obscure. The incidence of ulcerative colitis is relatively stable, while Crohn's disease continues to increase in frequency. In 10% to 15% of patients, it is hard to differentiate between ulcerative colitis and Crohn's colitis; however, problems with diagnosis usually resolve with time and repeated examinations. In part I of his two-part monograph on IBD, Dr. Kirsner addresses the nature and pathogenesis of the disease. Increased study of ulcerative colitis and Crohn's disease in recent years has generated new knowledge regarding their etiology. Part I focuses on microbial, immunologic, and genetic mechanisms and the inflammatory processes involved in the disease. In part II, which will be presented in next month's issue of Disease-a-Month, Dr. Kirsner deals with the clinical features, course, and management of IBD, based on the author's 55 years of experience with these problems and supplemented by critical examination of the recent (1988-1990) literature. Particular attention is directed to the symptoms and physical findings of ulcerative colitis and Crohn's disease, the laboratory, radiologic, endoscopic, and pathologic features, and the many systemic complications. The IBDs are mimicked by several enterocolonic infections and other conditions, making differential diagnosis necessary. Inflammatory bowel disease in children and the elderly conforms to conventional clinical patterns modified by the health circumstances of the respective age groups. Because the cause of IBD has not been established, current medical therapy is facilitative and supportive rather than curative. The principles of medical treatment are approximately the same for ulcerative colitis and Crohn's disease. Treatment emphasizes a program rather than a drug and also considers the individuality of the therapeutic response. A clearer understanding of dietary and nutritional needs, including hyperalimentation and electrolyte and fluid balance, aids treatment. Antidiarrheal and antispasmodic preparations and sedatives are prescribed for symptom relief. The bowel inflammation is controlled with sulfasalazine or the newer 5-amino salicylic acid (5-ASA) compounds, antibacterial drugs for complications of Crohn's disease and IBD, adrenocortical steroids, and the immunosuppressive compounds 6-mercaptopurine (6-MP), azathioprine, and cyclosporine, as determined in each patient. The surgical procedures available for treatment of ulcerative colitis include total proctocolectomy and ileostomy or ileoanal anastomosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Familial empiric risk estimates of inflammatory bowel disease in Ashkenazi Jews.

Genetic factors have been implicated in the etiology of inflammatory bowel disease (IBD) because of the increased occurrence of IBD in relatives. To further characterize the familial aggregation of IBD, we obtained family histories by interview on 188 IBD patients, including 154 Ashkenazi Jews (82%), ascertained through a Los Angeles gastroenterology practice. Thirty-three index cases (17.6%) had at least one affected first-degree relative; an additional 11 had more distant affected relatives. Thus, 23.4% of our sample had a positive family history. The quantification of empiric risk estimates for various classes of relatives has been quite limited and has been reported in only a few series. An important goal of our study was the determination of the specific empiric risk figures for relatives. We obtained uncorrected risk estimates of 2.5% to off-spring, 5.2% to siblings, and 2.9% to parents. Although the highest risk we observed is to siblings, IBD has a variable and often late age of onset, and it is likely that many relatives, particularly offspring, of patients in this sample have not reached the age at which they will manifest clinical disease. Thus, these uncorrected risks as well as those reported in the literature are an underestimate of the true empiric risks. To provide an estimate of the true lifetime risks, we utilized age-specific incidence data to calculate the following age-corrected empiric risk estimates for IBD: 8.9% to offspring, 8.8% to siblings, and 3.5% to parents. It is these latter age-corrected estimates that are most appropriate for both genetic counseling and genetic modeling.

Adolescent↗