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PubMed1999

[Pathological bone density in chronic inflammatory bowel diseases--prevalence and risk factors].

INTRODUCTION: Osteopenia and osteoporosis are frequent but often underestimated complications in inflammatory bowel disease. In patients with IBD, several factors could contribute to osteopenia, but the pathogenetic mechanisms are still not completely understood. We carried out a prospective study to evaluate the prevalence and possible etiologic factors for osteopenia and subsequent osteoporosis in IBD-patients. METHODS: 140 patients with inflammatory bowel disease (Crohn's disease n = 125, ulcerative colitis n = 15) underwent clinical and spine radiological assessments. Lumbar bone mineral densities were measured by dual energy X-ray absorptiometry (DXA). Markers of bone formation and resorption and vitamin D were assessed in n = 95 patients. Patients were asked about medication, previous or actual intestinal stenosis, smoking and intestinal resection. A lactose-H2-breath test was undertaken if lactose intolerance was clinically suspected. RESULTS: Compared to age- and sex-matched healthy controls (Z-score), the prevalence of osteopenia (Z < -1) was 62%, while osteoporosis (Z < -2) occurred in 38%. The mean bone density of IBD-patients was osteopenic with no significant differences between Crohn's disease (Z = -1.24) and ulcerative colitis (Z = -1.25). Osteoporotic fractures were seen in three patients (2.1%). Crohn's disease patients with osteoporosis showed a significant lower body mass index (BMI) than patients with normal bone density. 52.9% of patients with manifest osteoporosis underwent systemic steroid treatment in the preceding year, but only 34% of those with normal bone density. Except hemoglobin, none of the biochemical markers showed a significant difference between osteoporosis, osteopenia and patients with normal bone density. CONCLUSION: The results show a high prevalence of osteopenia and osteoporosis in IBD. Since osteoporosis is often associated with low body mass index, multiple intestinal resections and previous systemic steroid treatment, we suggest a bone densitometry in these patients. Since etiology of osteoporosis in IBD is multifactorious and not completely understood, there is still no standard treatment. The effect of osteoanabolic and antiresorptive agents must be evaluated in further studies.

Adolescent↗
PubMed1999

Inflammatory bowel disease in horses: 11 cases (1988-1998).

OBJECTIVE: To determine clinical and surgical abnormalities in, and long-term outcome of, horses that undergo surgery because of colic secondary to inflammatory bowel disease (IBD). DESIGN: Retrospective study. ANIMALS: 11 horses. PROCEDURE: Medical records of horses that had undergone abdominal surgery and in which IBD had been diagnosed on the basis of histologic examination of intestinal biopsy specimens were reviewed. RESULTS: 5 horses were examined because of acute colic and 6 were examined because of chronic colic. At surgery, all 11 horses had edematous or hemorrhagic bowel segments suggestive of IBD. In addition, 6 horses had circumferential mural bands (CMB) causing constriction of the small (4 horses) or large (2) intestine. Intestinal resections were performed in 7 horses. All 11 horses survived surgery and were discharged from the hospital; 10 horses were still alive at the time of follow-up (1.5 to 7 years after surgery). CLINICAL IMPLICATIONS: Results suggest that IBD is an uncommon cause of colic in horses. Surgical resection of segments of intestine with constrictive CMB may relieve clinical signs of colic. Horses with IBD that had surgery had a good prognosis for long-term survival.

Acute Disease↗
PubMed2000

[Chronic inflammatory bowel disease--pathogenic concepts and therapeutic perspectives].

Chronic inflammatory bowel disease (IBD) is considered to be a consequence of inappropriate upregulation of immune reactions evoked by the colonic microflora. Abnormalities observed in IBD may be explained, at least in part, by an unfavourable balance between pro- and anti-inflammatory cytokines. Conventional drug treatment of IBD may soon be replaced by more selective inhibitors that act centrally in the inflammatory process. Immunoneutralisation with chimeric anti-tumour necrosis factor-alpha (TNF alpha) antibodies reduces treatment refractory IBD, including fistular Chrons' disease, but recombinant human TNF alpha-receptor fusion proteins may be equally effective with potentially fewer side effects. This view also applies to chimeric antibodies directed against cytokines or adhesion molecules. Potentially more promising are antisense oligonucleotides and matrix-metalloproteinase inhibitors. Whether sustained remission can be achieved probably depends on successful unravelling of the aetiology of IBD.

Antibodies↗
PubMed2000

[Pharmacotherapy of inflammatory bowel disease].

Inflammatory bowel disease (IBD) encompasses ulcerative colitis and Crohn's disease. Since the etiology of both diseases, is undetermined the causal therapy do not exist. Medical treatment has focused on nonspecific suppressions of the inflammatory process. There are four groups of IBD drugs: anti-inflammatory medicaments, immunomodulators, antidiarrheal agents, and biologic therapy. In a last year immunosuppressives become the very essential IBD drugs. Azathioprine is drug of choice for chronically active Crohn's disease; methotrexate become the second line immunosuppressive drug. It appears that anti-TNG monoclonal antibodies, cA2 (infliximab) may produce rapid control of active Crohn's disease and achieve tissue healing. Topically acting glucocorticosteroids are a safer than standard glicocorticosteroids in ileocolonic Crohn's disease. Cyclosporin is becoming a drug of choice in severely active ulcerative colitis. Anti-inflammatory agents, sulfasalazine and 5-ASA drugs are recommended in treatment mild and moderately active IBD and as maintenance treatment in ulcerative colitis. Corticosteroids still have the main role in the treatment of active IBD. There is no convincing data for efficacy of corticosteroids as maintenance therapy.

Humans↗
PubMedDate not supplied

Increased gut permeability in juvenile chronic arthritides. A multivariate analysis of the diagnostic parameters.

OBJECTIVE: This study was aimed at evaluating intestinal permeability (IP) in patients with oligoarticular juvenile idiopathic arthritis (o-JIA), spondyloarthropathy (SpA) associated with inflammatory bowel disease (IBD) and other forms of juvenile-onset chronic arthritiis (OIA) using the lactulose/mannitol (L/M) test in comparison with other non-invasive parameters of gut involvement. METHODS: A series of 26 children affected with o-JIA and 14 with either SpA/IBD or OIA were assessed for IP. The urinary L/M ratio was measured by gas chromatography. The erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and faecal alpha 1 antitrypsin concentrations were also evaluated. Ten o-JIA patients displayed active arthritis while in 16 the disease was under control. Among the OIA patients, 11 were affected with psoriatic arthritis and the remaining 3 with chronic reactive arthritis. 14 patients with SpA-IBD had active synovitis or spine inflammation. 14 eo-pJCA and 22 OIA and SpA-IBD patients, respectively, were receiving NSAID therapy. RESULTS: The mean L/M ratios for the Spa-IBD (0.07 +/- 0.02, mean +/- SD), OIA (0.05 +/- 0.02) and o-JIA (0.04 +/- 0.02) patients were significantly higher (p < 0.001, p = 0.022 and p = 0.01, respectively) than those found in controls (0.02 +/- 0.01). Logistic regression analysis disclosed a positive correlation between the L/M ratio and the presence of gastrointestinal manifestations (p = 0.011). The type of disease (p = 0.28), the disease activity in the JCA patient group (p = 0.24) and NSAID administration (p = 0.210) did not seem to significantly influence the L/M ratio. CONCLUSIONS: All of the subtypes of juvenile chronic arthritides that we studied displayed an increased IP. Hence, gut wall inflammation (albeit asymptomatic) may also be present in o-JIA patients. The SpA-IBD patients with gastrointestinal symptoms displayed the highest mean L/M ratio values. The L/M test seemed to correlate with histopathological features of the gut mucosa. The L/M ratio was shown to be a highly sensitive but poorly specific test for predicting gut inflammatory disease compared to other non-invasive screening tests.

Arthritis, Juvenile↗
PubMedDate not supplied

Interleukin-4 inhibits the increased production of vascular endothelial growth factor by peripheral blood mononuclear cells in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF), a potent angiogenic, permeability-enhancing cytokine plays an important role in tissue repair and chronic inflammatory disorders. Peripheral blood mononuclear cells (PBMCs) and the inflamed mucosa have been demonstrated to be main sources of the recently described circulating VEGF in patients with inflammatory bowel disease (IBD). There is no current information about the influence of immunoregulatory cytokines on VEGF in IBD. The present study examines the effect of interleukin-4 on the increased VEGF production of PBMCs in patients with IBD. METHODOLOGY: Unstimulated PBMCs from 17 patients with Crohn's disease, 16 patients with ulcerative colitis and 8 healthy controls were cultured with or without IL-4. VEGF production was measured in the supernatant using an enzyme-linked immunosorbent assay. RESULTS: IL-4 led to a significant reduction of the VEGF production by PBMCs of both active Crohn's disease patients (471.7 +/- 377.5 pg/mL vs. 208.2 +/- 123.2 pg/mL, P = 0.018, n = 7) and active ulcerative colitis patients (177.1 +/- 79.4 pg/mL vs. 87.4 +/- 77.2 pg/mL, P = 0.008, n = 9). IL-4 inhibited significantly the VEGF production by PBMCs of patients with inactive Crohn's disease (179.2 +/- 133.9 pg/mL vs. 87.7 +/- 56.6 pg/mL, P = 0.005, n = 10). There was no significant difference of VEGF release by PBMCs cultured with IL-4 in patients with active Crohn's disease or active ulcerative colitis compared with PBMCs cultured without IL-4 in patients with inactive disease and healthy controls (112.6 +/- 41.9 pg/mL, n = 8). CONCLUSIONS: IL-4 has been shown to reduce the increased VEGF production of PBMCs in patients with IBD to normal levels. The known defective immunosuppressive effect of IL-4 in IBD may contribute to the pathogenic cascade leading to inflammation by VEGF mediated mechanisms.

Adult↗
PubMed2000

Antineutrophil cytoplasmic antibodies (ANCAs) in patients with inflammatory bowel disease show no correlation with proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme: a Singapore study.

INTRODUCTION: The pathogenic importance of antineutrophil cytoplasmic antibodies (ANCAs) in inflammatory bowel disease (IBD) is unclear and target antigen localisation studies may lend insight to the specific pathogenic mechanisms of IBD. In this pilot study, we looked at occurrence of ANCA in Asian IBD patients. In ANCA-positive samples, we analysed for the presence of target antigens i.e. proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme. MATERIALS AND METHODS: This prospective study was carried out from July 1997 to February 1998. Sera were screened for ANCAs with indirect immunofluorescent test and tested with an enzyme immunoassay (ELISA) kit which provides a semi-quantitative assay for human IgG autoantibodies against 6 antigens: proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme. RESULTS: A total of 75 patients were studied: 50 with IBD and 25 controls with functional bowel disease. Ten had Crohn's disease (CD) and 40 had ulcerative colitis (UC). There was no racial predilection among the Chinese, Malays or Indians. In CD, 1 was positive for cytoplasmic ANCA (cANCA) and 2 for perinuclear ANCA (pANCA). In UC, 4 were positive for pANCA, 15 for atypical perinuclear ANCA (apANCA) and 1 for cANCA. In the CD and UC population, the proportion positive for ANCA was 30% and 50%, respectively. There was no ANCA detected among the controls. Of those ANCA-positive IBD patients (n:23), only 1 demonstrated anti-myeloperoxidase antibodies. No antibodies were detected against the other 5 antigens tested. CONCLUSIONS: This pilot Singapore study concludes that there is no significant ANCA association with proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme.

Adult↗
PubMed2001

The incidence of deep venous thrombosis and pulmonary embolism among patients with inflammatory bowel disease: a population-based cohort study.

BACKGROUND: There is an impression mostly from specialty clinics that patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolic disorders. Our aim was to determine the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) from a population-based database of IBD patients and, to compare the incidence rates to that of an age, gender and geographically matched population control group. METHODS: IBD patients identified from the administrative claims data of the universal provincial insurance plan of Manitoba were matched 1:10 to randomly selected members of the general population without IBD by year, age, gender, and postal area of residence using Manitoba Health's population registry. The incidence of hospitalization for DVT and PE was calculated from hospital discharge abstracts using ICD-9-CM codes 451.1, 453.x for DVT and 415.1x for PE. Rates were calculated based on person-years of follow-up for 1984-1997. Comparisons to the population cohort yielded age-adjusted incidence rate ratios (IRR). Rates were calculated based on person-years of follow-up (Crohn's disease = 21,340, ulcerative colitis = 19,665) for 1984-1997. RESULTS: In Crohn's disease the incidence rate of DVT was 31.4/10,000 person-years and of PE was 10.3/10,000 person-years. In ulcerative colitis the incidence rates were 30.0/10,000 person-years for DVT and 19.8/10,000 person-years for PE. The IRR was 4.7 (95% CI, 3.5-6.3) for DVT and 2.9 (1.8-4.7) for PE in Crohn's disease and 2.8 (2.1-3.7) for DVT and 3.6 (2.5-5.2) for PE, in ulcerative colitis. There were no gender differences for IRR. The highest rates of DVT and PE were seen among patients over 60 years old; however the highest IRR for these events were among patients less than 40 years. CONCLUSION: IBD patients have a threefold increased risk of developing DVT or PE.

Adult↗
PubMed2001

Rapid imaging of experimental colitis with (99m)Tc-interleukin-8 in rabbits.

UNLABELLED: Radiolabeled autologous leukocytes (WBCs) are the gold standard for imaging inflammatory bowel disease (IBD). For the rapid and adequate management of patients with IBD, there is need for a new agent at least as good as radiolabeled WBCs, but easier to prepare and without its inherent risks. In this study, the potential of interleukin-8 (IL-8) labeled with (99m)Tc using hydrazinonicotinamide (HYNIC) to image IBD was investigated in a rabbit model of acute colitis and compared with that of (99m)Tc-HMPAO-labeled granulocytes. METHODS: In rabbits with chemically induced acute colitis, inflammatory lesions were scintigraphically visualized after injection of either IL-8 or purified granulocytes, both labeled with (99m)Tc. Gamma camera images were acquired at 2 min and at 1, 2, and 4 h after injection. Four hours after injection, the rabbits were killed, and the uptake of the radiolabel in the dissected tissues was determined. The dissected colon was imaged and the inflammatory lesions were scored macroscopically. For each affected colon segment, the colitis index (affected colon-to-normal colon uptake ratio, CI) was calculated and correlated with the macroscopically scored severity of inflammation. RESULTS: Both agents visualized the colitis within 1 h after injection. (99m)Tc-HYNIC-IL-8 images of the colonic abnormalities were more accurate and the intensity of uptake in the affected colon continuously increased until 4 h after injection, whereas no further increase 1 h after injection was noticed scintigraphically for (99m)Tc-HMPAO-granulocytes. The absolute uptake in the affected colon was much higher for IL-8 than for the radiolabeled granulocytes with the percentage injected dose per gram (%ID/g) 0.41 +/- 0.04 %ID/g and 0.09 +/- 0.05 4 %ID/g h after injection, respectively. With increasing severity, the CI at 4 h after injection for (99m)Tc-HYNIC-IL-8 was 4.4 +/- 0.6, 13.5 +/- 0.5, and 25.8 +/- 1.0; for granulocytes, the CI at 4 h after injection was 1.5 +/- 0.1, 3.4 +/- 0.2, and 6.4 +/- 0.5, respectively. The CI correlated with the severity of the inflammation (r = 0.95, P < 0.0001 for IL-8; r = 0.95, P < 0.0001 for granulocytes). CONCLUSION: Within 1 h after injection, visualization of the extent of colonic inflammation in vivo was possible with (99m)Tc-HYNIC-IL-8 and (99m)Tc-HMPAO-granulocytes. Within 2 h after injection, (99m)Tc-IL-8 allowed a good evaluation, and within 4 h after injection, a meticulous evaluation of the severity of IBD. Although (99m)Tc-HMPAO-granulocytes were able to delineate the extent of IBD within 2 h after injection, an accurate estimation of severity of inflammation was not possible. (99m)Tc-HYNIC-IL-8 is an inflammation-imaging agent that showed promising results in this study. (99m)Tc-IL-8 can be prepared off-the-shelf and yields excellent imaging with high target-to-background ratios.

Acute Disease↗
PubMed2001

[Epidemiology of chronic inflammatory bowel disease in Gijón, Asturias].

AIMS: To determine several aspects of the epidemiology of chronic inflammatory bowel disease (IBD), including distribution of the various forms of IBD, sex, age at diagnosis considering lag-time to diagnosis, criteria used in the diagnosis, the relationship between educational level and activity, familial aggregation, phenotype (site and clinical type), number of admissions and mean hospital stay/year, surgical requirements and mortality. PATIENTS AND METHODS: We carried out a retrospective (1954-1993) and prospective (1994-97) descriptive epidemiologic population study, in the fifth health district of Gijón in Asturias (Spain), with 225,798 inhabitants. A total of 595 patients diagnosed with chronic IBD according to the diagnostic criteria described by Lennard-Jones and Truelove for Crohn's disease (CD) and ulcerative colitis (UC) and according to Ashley B. Price's criteria for indeterminate colitis (IC) were studied. In all patients a complete clinical follow-up was performed. RESULTS: During the study period, we diagnosed 595 patients with IBD [305 patients with UC (51.3%), 272 (45.7%) patients with CD and 18 (3%) with IC]. Sex distribution was 287 females (48.2%) and 308 males (51.8%), with a male/female ratio of 1.07. Mean age at presentation was 38.79 +/- 17.44 years (UC: 43.37 +/- 17.55; CD: 33.98 +/- 16.16; IC: 33.73 +/- 13.48), p = 0.000. Age at onset prior to diagnosis was as follows: UC: 42.03; CD: 30.47; IC: 30.99 (p = 0.000). Diagnostic criteria used in UC was symptomatic in 99.01% (p = ns), endoscopic in 95.04% (p = 0.000), and pathologic in 87.21% (p = 0.000); in CD diagnostic criteria used was radiologic in 85.29% (p = 0.000). A total of 29.1% of patients with UC and 66.7% of those with CD had higher education (p = 0.0005). Family history was found in 9.8%. Anatomical site was as follows: in UC: rectum 21%, 28.2% rectum and sigmoid, 22.3% left colitis, 4.2% distal to hepatic flexure and 24% pancolitis; in CD: 32.72% terminal ileum, 19.11% colon, 37.13% ileo-colon, 11.02% extensive intestinal and 3.67% gastro-duodenal. A total of 8.37% of patients with UC and 14.51% of those with CD had been hospitalized during the previous 4 years; mean hospital stay was 1.63 days in UC and 2.27 days in CD. The mean surgical requirements were 0.54 +/- 1.08 (31.59%); UC: 0.11 +/- 0.36 (10.2%); CD: 1.04 +/- 1.38 (56.25%), p = 0.000. The mortality rate was 48.73 deaths/1,000 inhabitants (UC: T = 65.57; CD: T = 33.08; IC:T= 0) p = ns. The standardized mortality ratio was 4.83 (UC: 6.51; CD: 3.28). CONCLUSIONS: We highlight the uniformity of the distribution of IBD in relation to types of disease and sex. Patients with CD had a higher level of education. Genetic components play an important role in these diseases and familial aggregation was high, especially in CD. Complicated situations are infrequent in this group of patients. Morbidity was higher in patients with CD as reflected by surgical requirements and hospital stay. Mortality was lower in CD than in UC.

Adolescent↗
PubMed2001

Tumor necrosis factor-alpha in serum of patients with inflammatory bowel disease as measured by a highly sensitive immuno-PCR.

BACKGROUND: The significance of serum concentrations of tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of inflammatory bowel disease (IBD) is uncertain. We measured TNF-alpha in serum from IBD patients by immuno-PCR to analyze the relationship between TNF-alpha and pathophysiologic state in IBD. METHODS: Serum samples were collected from 54 healthy blood donors, 29 patients with ulcerative colitis (UC; 46 samples), and 7 patients with Crohn disease (CD; 8 samples). DNA label was generated by PCR amplification using biotinylated primer and was bound with streptavidin to biotinylated third antibody. TNF-alpha sandwiched by antibodies was detected by PCR amplification of the DNA label. RESULTS: TNF-alpha could be measured in all samples. The median serum concentration in IBD patients overall was approximately 390-fold higher than in healthy donors (median increase, 380-fold for UC, 640-fold for CD). The median serum TNF-alpha concentration was 1.7-fold higher in the active stage of UC than in the inactive stage (P <0.05), and this difference could be detected in individual patients. CONCLUSIONS: Sensitive measurement of serum TNF-alpha could provide an important pathophysiologic marker for the presence and activity of IBD.

Adult↗
PubMed2001

[Serum bone marker measurements in bone metabolism disorders associated with inflammatory bowel diseases].

Patients with inflammatory bowel disease (IBD) have decreased bone mineral density (BMD), which is usually much more remarkable in patients with Crohn's disease (CD) than those with ulcerative colitis (UC). The aim of the present study was to investigate the usefulness of serum beta-Crosslaps (bCL) and osteocalcin (OC) determinations to assess bone metabolism in patients with IBD. Forty-nine patients with IBD (23 UC, 26 CD) and 46 healthy controls were studied. Serum bCL and OC were measured by Elecsys immunoassay. Compared to controls (0.275 +/- 0.14 ng/ml) the mean bCL concentration was significantly higher in the CD (mean = 0.489 +/- 0.25 ng/ml; p < 0.001) and UC groups (mean = 0.439 +/- 0.3 ng/ml; p < 0.01). The mean OC concentration was significantly higher in the CD group (28.52 +/- 14.75 ng/ml) than in controls (21.42 +/- 7.43 ng/ml) but OC level was not significantly increased in the UC group (24.89 +/- 15.08 ng/ml). There was no significant difference in bCL or OC concentrations between the CD and UC groups. These results indicate that the accelerated bone resorption is not associated with increased bone formation in patients with IBD. These two marker of the bone metabolism could be a good laboratory parameter of bone pathology in patients with IBD, especially in CD.

Adult↗
PubMed2001

Self-care for the inflammatory bowel disease patient: what can the professional recommend?

The management of patients with inflammatory bowel disease (IBD) continues to present a challenge for gastroenterologists. IBD constitutes a significant burden for the affected individual because of both intestinal and systemic manifestations. The lack of a specific cause and a definitive cure for this condition, as well as the potential for associated malignancy, leave patients unsettled and fearful of the future. Many patients and their families are significantly impaired by the limitations that IBD places on their lives. These limitations are frequently overlooked, and extend well beyond the boundaries of traditional medical practice. Patients often seek to become active participants in the management of their disease. An approach that includes discussion and education on lifestyle issues affecting IBD patients should be part of our routine practice. This article reviews lifestyle and self-care factors relevant to the IBD patient, and what the gastroenterologist can recommend based on current evidence.

Adult↗
PubMed2001

Growth failure in the child with inflammatory bowel disease.

Once considered rare in pediatric practice, chronic inflammatory bowel disease (IBD) is now being recognized with increasing frequency in children of all ages. In IBD, growth failure may be the only clinical presentation; it is imperative to perform a detailed history and physical examination to search for other systemic and gastrointestinal manifestations of the disease. IBD can have a significant impact on linear growth, weight gain, and bone mineralization, and can cause delays in the onset of puberty. Delays in growth and sexual development can be early indicators of disease activity, and assessment of growth and development should be performed frequently. Nutritional therapy is important not only to correct undernutrition, but also as therapy for IBD. Delayed puberty can have a significant impact on the self-esteem of the adolescent patient and diminish final adult height. Loss of bone mineral density is especially significant during a period in which the majority of bone accretion is expected to occur. These issues present unique problems to the gastroenterologist caring for a child or adolescent with IBD and require specific types of monitoring and interventions.

Adolescent↗
PubMedDate not supplied

European genetic study on rheumatoid arthritis: is there a linkage of the interleukin-1 (IL-1), IL-10 or IL-4 genes to RA?

UNLABELLED: The genetic predisposition for rheumatoid arthritis (RA) is only partly explained by the HLA locus and most genetic factors involved in the susceptibility (and/or severity) of the disease await further identification. The first European genome scan in RA families provided suggestive evidence for linkage with a region (3.1/3q13) on chromosome 3, but many other potential RA susceptibility genes have yet to be analysed. AIMS: To perform a linkage analysis with microsatellite markers located in the vicinity of the interleukin-1 (IL-1) gene superfamily, the IL-10 gene and the IL-4 gene cluster which might be considered putative candidate loci for RA. METHODS: 107 Caucasoid European RA sibpairs from 90 nuclear families were genotyped for markers flanking the genes for the IL-1 superfamily, IL-10 and the IL-4 gene cluster. Linkage analysis based on the identity by descent (IBD) in affected siblings was analysed with the program SIBPALNA. Affected sibpairs were stratified according to the identity by state (IBS) for three markers in the HLA region (DRB1 oligotyping, D6S276 and TNFa microsatellites) and to the presence/absence of erosive disease on X-ray examination. RESULTS: Analysis of the whole family set showed an excess of allele sharing for markers of the IL-1 gene cluster (IBD 60%; P = 0.012) but not for IL-10 or IL-4. After stratification, the evidence of linkage to IL-1 was restricted to HLA concordant sibpairs (n = 32; IBD 70%; P = 0.006). Some evidence of linkage to IL-10 was also observed in HLA concordant sibpairs (IBD 66%; P = 0.03) and in sibpairs with erosive disease (n = 61; IBD 62%; P = 0.02). CONCLUSIONS: We found suggestive evidence of linkage of RA to the IL-1 locus. The increased linkage to IL-1 and IL-10 in HLA-identical sibs suggests a possible interaction between these cytokines and the HLA loci. Moreover IL-10 could interact with HLA factors in predisposing to erosive disease. These results need to be tested in additional families for consistency and replication.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Mode of inheritance of HLA-DRB1 shared epitope in Japanese familial rheumatoid arthritis.

OBJECTIVE: To clarify the mode of genetic contribution of the HLA-DR shared epitope (SE) to the pathogenesis of familial cases of Japanese rheumatoid arthritis (RA). METHODS: Fifty-three unrelated Japanese RA families that had more than 2 affected sibs were selected. The HLA-DR shared epitope typing was carried out by the PCR method and PCR-SSCP (single stranded DNA conformation polymorphism) method. Affected sib pair analysis was carried out using the MAPMAKER/SIB 2.0 program. The mode of inheritance was also calculated based on the sharing of genes identical by descent (IBD) between siblings in each of the 53 affected sib-pairs (propositus and the 2nd affected sib). RESULTS: The maximum LOD score of HLA-DR was 0.437, and the sharing of 2 IBDs, 1 IBD, and no IBDs between affected sibs were 0.330, 0.500, and 0.170, respectively. The sharing distribution of IBD was confirmed to be compatible with the dominant or additive mode since the observed gene frequency of SE was 0.255. CONCLUSION: The HLA-DR shared epitope participated in the pathogenesis of familial cases of Japanese RA. The SE contributes to this pathogenesis in either the dominant or additive mode of inheritance.

Adult↗
PubMed2003

Introduction and overview: recent advances in the immunotherapy of inflammatory bowel disease.

Ulcerative colitis (UC) and Crohn's disease (CD) comprise a series of inflammatory bowel disease (IBD) resulting from chronic upregulation of the mucosal immune system. Although the pathogenesis of IBD remains elusive, it appears that there is chronic activation of the immune and inflammatory cascade in genetically susceptible individuals. Current disease management guidelines have therefore focused on the use of antiinflammatory agents, aminosalicylates and corticosteroids. However, some patients are still refractory to these therapies. Recent advances in the understanding of the pathophysiological conditions of IBD have provided new immune system modulators as therapeutic tools. Cytapheresis has demonstrated effectiveness against UC and has practical use in Japan. Immunosuppressive agents including cyclosporin A and tacrolimus (FK506) have expanded the choice of medical therapies available for certain subgroups of patients. Furthermore, biological therapies have begun to assume a prominent role. Studies with chimeric monoclonal anti-TNF-alpha antibody treatment of CD have been reported with dramatic success. Another antiinflammatory cytokine therapy includes anti-IL-6 receptor, anti-IL-12, or toxin-conjugated anti-IL-7 receptor. Given the diversity of proinflammatory products under its control, NF-kappa B may be viewed as a master switch in lymphocytes and macrophages, regulating inflammation and immunity. In the murine 2,4,6-trinitrobenzen sulfonic acid (TNBS) colitis model, an antisense oligonucleotide to NF-kappa B p65 ameliorated inflammation even after induction of colitis. Recently, a clinical pilot trial of this agent demonstrated promising results. Accumulating evidence suggests that luminal bacterial flora is a requisite and central factor in the development of IBD. Probiotic therapies such as a nonpathogenic Escherichia coli strain have been well tolerated, but larger clinical trials are needed. In addition, novel therapeutic strategies targeting adhesion molecules and costimulatory molecules, or enhancing tissue repair, are under investigation. Although some still need more confirmatory studies, these immune therapies will provide new insights into cell-based and gene-based treatment against IBD in the near future.

Colitis, Ulcerative↗
PubMed2003

[Epidemiology in inflammatory bowel disease in five areas of Asturias. Spain].

AIMS: The epidemiologic analysis inflammatory bowel disease (IBD) is a powerful research tool to assess the contribution of environmental factors to its etiology. IBD has been reported to have varying frequencies in different parts of the world, and there seem to be significant differences in the disease pattern and clinical course. The aim of the present study was to assess the disease pattern of IBD in Asturias (Spain). PATIENTS AND METHODS: A descriptive epidemiological population based study, retrospective (1954-1993) and prospective (1994-97), was performed to study 1018 patients found, bigger than 14 years, to have IBD, in five areas of Asturias (Spain) (461.965 inhabitants). RESULTS: During the period of time studied, we diagnosed 1018 IBD [565 ulcerative colitis (55.5%), 415 (40.8%) Crohn's disease and 38(3.7%) indeterminate colitis], with 482 females (47.2%), 536 males (52.8%), and male/female: 1.11. Age at diagnosis were 39.49 +/- 1.08 (95% CI : 38.41 +/- 40.57); (UC: 43.95 +/- 1.47; CD: 33.53 +/- 1.51; IC: 38.26 +/- 5.14. p = 0.000. Age at onset previously at diagnosis for UC: 42.84 +/- 1.34; CD: 30.68 +/- 1.40; IC: 36.74 +/- 4.86 (p = 0.000). Diagnosis criteria: UC: syntomatic 97.34% (p = ns), endoscopy 96.63% (p = 0.000 pathology 90.26% (p = 0.000). CD: radiology 83.61% (p =0.000). Study level in CD: 57.57 (p = 0.0005). Family history: 8.4%. The most frequent involvement at diagnosis of UC was proctitis only, in 13.6%, 269% rectum and sigmoid 26% let colitis, 20% pancolitis, and in CD colon only, in 16.7%, 30.3% terminal ileum, 41.3% ileo-colon of the patients. This also helps to explain the differences in severity, need for surgery, and survival noted between community based studies. CONCLUSIONS: We highlight the uniformity of distribution of the inflammatory bowel disease in relation to types and sex. The high frequency of familial Crohn's disease suggests a genetic predisposition. Highlighting a bigger morbilidad for the Crohn's Disease reflected in the surgical requirements, but however with smaller mortality that in ulcerative colitis.

Adult↗