Two cases of adult Still''s disease with atypical rash

Previous studies on baseline pulmonary function testing (PFT) abnormalities in patients with inflammatory bowel disease (IBD) are conflicting because most of them have incorporated patients suffering from both ulcerative colitis (UC) and Crohn's disease (CD). The aim of the study is to investigate whether any PFT abnormalities could be detected in a large group of IBD patients and whether there are differences between the two IBD entities. A total of 132 patients, 47 with CD (mean age 35 years) and 85 with UC (mean age 40 years) were studied. Pulmonary function tests (PFTs), lung transfer factor for carbon monoxide (TLCO) were examined and compared with those of 36 healthy controls. No significant difference of mean values of spirometric indices, TLCO and ABG was found between the two groups of patients and controls, or between patients with CD and UC. However, nine (19%) patients with CD and 15 (17.6%) with UC had a reduction in TLCO, a percentage significantly higher than in controls (P < 0.05). The majority of the patients with TLCO reduction were in an active phase of disease (P < 0.05). Our results suggest that there is no difference in routine PFTs between UC and CD patients, as well as between both these groups and normal controls. However, TLCO abnormalities related to the degree of disease activity are found in patients with both UC and CD.     

Elevation of phospholipase A2 protein in sera of patients with Crohn's disease and ulcerative colitis

The protein mass of group II phospholipase A2 (PLA2) levels were immunochemically measured in sera of 43 patients with Crohn's disease (CD), 43 patients with ulcerative colitis (UC), and 35 healthy volunteers, and compared with PLA2 enzymatic activity. Serum immunoreactive group II PLA2 (IR-PLA2 II) levels of active CD patients were significantly higher than those of the controls and inactive CD patients. Serum IR-PLA2 II levels were also significantly greater in patients with severe UC and moderate UC than in the controls and patients with mild UC. Serum IR-PLA2 II levels were found to be closely correlated with serum PLA2 activity in patients with CD and UC. Serum IR-PLA2 II levels and PLA2 activity decreased by antiinflammatory treatment in six patients with CD and two with UC. These results suggest that serum IR-PLA2 II levels can be a useful parameter in the evaluation of disease activity of CD and UC, and that elevated PLA2 enzymatic activity in sera of patients with CD and UC is attributable to increased protein concentration of group II PLA2, in agreement with our previous results.     

Inflammatory bowel diseases in children]

From an incidence cohort diagnosed during 1962-1987 we identified all patients with onset of IBD before the age of 15 in order to describe the course and to compare course and prognosis with adult onset IBD. The mean incidence of IBD among children below 15 years was 2.2/10(5), 2.0 for ulcerative colitis (UC), and 0.2 for Crohns disease (CD). At diagnosis, UC children had more extensive disease compared to adults (p < 0.05). Abdominal pains were also more frequent. The cumulative colectomy probability was 6% after one year and 29% after 20 years, not different from adults. Regarding disease activity, it was found that 60-70% of UC patients were in remission in the first 10 years of disease, for CD about 50% were in remission. One UC patient developed carcinoma of the sigmoid colon. Time between onset and development of carcinoma was 12 years. For CD no differences in clinical appearance at diagnosis and course between children and adults were found. No deaths occurred among CD patients. Three CD patients were found to have severe growth retardation already at diagnosis. In conclusion, the incidence of IBD is low in childhood. At diagnosis children with UC have more widespread disease than adults. Children with CD do not differ in clinical presentation, course or prognosis compared to adult onset CD. However, growth retardation is a problem among CD patients.     

Epidemiological aspects of inflammatory bowel disease in a north Italian population: a 4-year prospective study

OBJECTIVE: To determine the incidence and clinical characteristics at presentation of inflammatory bowel disease (IBD) in a defined area of north Italy. DESIGN: A 4-year prospective population-based epidemiological study. SETTING: An area in Lombardia defined by the National Health Service scheme with about 294,000 inhabitants, two referral hospitals and 259 general practitioners (GPs). PATIENTS: Subjects presenting to a GP with symptoms compatible with IBD underwent a diagnostic work-up at one of the referral hospitals. Those with ulcerative colitis (UC), Crohn's disease (CD) or indeterminate colitis diagnosed according to a defined protocol were included, as were residents of the area with IBD diagnosed elsewhere. Rigid case ascertainment methods were used. Patients were followed for one year; 125 patients were identified. RESULTS: The patient ascertainment rate was constant over the 4 years; UC was diagnosed in 82 patients, CD in 40, and indeterminate colitis in three. The mean annual incidence of IBD for the whole period was 10.6/10(5) inhabitants (95% confidence limits, 7.2-15.1), 7.0/10(5) for UC (4.3-10.7) and 3.4/10(5) (1.6-6.3) for CD. The mean interval between onset of symptoms and diagnosis was under 6 months. The clinical characteristics of our patients were similar to those of north European and American series. CONCLUSION: The incidence of IBD was higher than previously observed in Italy but was still lower than in some north European countries and in the USA. Our data could be used as a basis for future longitudinal studies and in international comparative investigations.     

Changes in neuropeptide-containing nerves in human colonic mucosa with inflammatory bowel disease

The distribution abnormality of vasoactive intestinal polypeptide-containing nerves (VIP-nerves) and substance P-containing nerves (SP-nerves) was immunohistochemically investigated in the colonic mucosa with inflammatory bowel disease (IBD) in relation to colonic glands and blood vessels in the lamina propria. In active ulcerative colitis (UC), VIP- and SP-nerves decreased in severe inflammatory lesions. VIP-nerves were almost absent particularly around crypt abscesses. Even in resolving and quiescent UC, VIP-nerves still decreased, depending on the decrease of glands and blood vessels. On the other hand, both nerves increased in some hypervascular lesions. In the uninvolved mucosa of UC, they did not change their distribution. In Crohn's disease, the distribution abnormality of both nerves resembled that of UC. These results suggest that the changes in VIP- and SP-nerve distributions in the mucosa with IBD are subsequent to mucosal inflammation and damage. However, these peptides are known to be immunoregulators, and their distribution abnormalities may induce the disorder of immunoregulation in the IBD mucosa and cause the mucosal damage and/or chronicity.     

Thrombophilia and inflammatory bowel disease: does factor V mutation have a role?

BACKGROUND: An increased tendency for thromboembolism is a well known problem of inflammatory bowel disease (IBD). Microvascular thrombosis has also been claimed as a pathogenic factor in IBD. Recently a point mutation in the gene coding factor V (FV Leiden) has been identified in various thromboembolic diseases, but the role in IBD is unknown. OBJECTIVE: To determine the frequency of FV Leiden in IBD patients and compare with a group of controls. METHODS: Sixty-three IBD patients [43 ulcerative colitis (UC) patients and 20 Crohn's disease (CD) patients] and 36 healthy controls were included in the study. Only one of the UC patients had a history of cerebral thromboembolism. The extracted DNA from frozen blood was subjected to polymerase chain reaction for the amplification of FV gene. The amplicons were hybridized both with the mutant and wild-type probes to detect FV mutation. Readings of optical density above 0.3 were considered as positive results. According to the patterns of ELISA, heterozygosity and homozygosity for normal and mutant alleles were determined. RESULTS: Eight (18%) of UC patients were heterozygous normal and one (2%) patient had homozygous mutation. Eight (45%) of the 20 CD patients had a heterozygous pattern and one (5%) had a homozygous pattern. In the control group four (11%) subjects showed a heterozygous genotype. FV Leiden was found to be statistically more frequent in CD patients (P < 0.005) (odds ratio 6.5, 95% confidence interval 1.3-18.), but not in the UC patients as compared with controls (P> 0.05). There was no significant correlation between FV Leiden presence and disease activity, gender or disease duration for both UC and CD. CONCLUSION: The results suggest that FV Leiden is more frequent in CD patients, but not in the UC patients as compared with controls. The high rate of factor V mutation in our CD patients suggests the need for further studies to confirm a relationship between this mutation and aetiology of the disease.     

Pre-illness dietary factors in inflammatory bowel disease

BACKGROUND: The effect of environmental factors has been demonstrated in the pathogenesis of inflammatory bowel disease (IBD). Nutrition may be one of them. AIM: To investigate the pre-illness diet in patients with recent IBD in comparison with matched population and clinic controls. METHODS: Quantified dietary histories were obtained from 87 patients with recent IBD (54 ulcerative colitis (UC) and 33 Crohn's disease (CD)) and 144 controls. Odds ratios (OR) for IBD were derived for intake levels of various foods. RESULTS: A high sucrose consumption was associated with an increased risk for IBD (OR 2.85 (p = 0.03) against population controls and 5.3 (p = 0.00) against clinic controls). Lactose consumption showed no effect while fructose intake was negatively associated with risk for IBD (NS). Similar trends were noted in UC and CD. A high fat intake was associated with an increased risk for UC; this was particularly marked for animal fat (OR 4.09, p = 0.02) and cholesterol (OR 4.57, p = 0.02). A high intake of fluids (p = 0.04), magnesium (p = 0.04), vitamin C, and fruits (NS) was negatively associated with the risk for IBD, while a positive association was found for retinol (p = 0.01). Most of the findings were similar in UC and CD except for potassium and vegetable consumption which showed a negative association only with risk for CD. CONCLUSIONS: An association was found between pre-illness diet and subsequent development of UC and CD. The effect of dietary components may be primary or modulatory.     

Small intestine in lymphocytic and collagenous colitis: mucosal morphology, permeability, and secretory immunity to gliadin

There is a recognised association between the "microscopic" forms of colitis and coeliac disease. There are a variety of subtle small intestinal changes in patients with "latent" gluten sensitivity, namely high intraepithelial lymphocyte (IEL) counts, abnormal mucosal permeability, and high levels of secretory IgA and IgM antibody to gliadin. These changes have hitherto not been investigated in microscopic colitis. Nine patients (four collagenous, five lymphocytic colitis) with normal villous architecture were studied. Small intestinal biopsies were obtained by Crosby capsule; small intestinal fluid was aspirated via the capsule. IEL counts were expressed per 100 epithelial cells, and intestinal IgA and IgM antigliadin antibody levels were measured by ELISA. Small intestinal permeability was measured by the lactulose:mannitol differential sugar permeability test. IEL counts were normal in all cases, median 17, range 7-30. Intestinal antigliadin antibodies were measured in six cases and were significantly elevated in two patients (both IgA and IgM). Intestinal permeability was measured in eight cases and was abnormal in two and borderline in one. These abnormalities did not overlap: four of nine patients had evidence of abnormal small intestinal function. Subclinical small intestinal disease is common in the two main forms of microscopic colitis.     

Serogroup conversion of Vibrio cholerae

The aim was to analyse the abdominal scintigraphy pattern in patients with seronegative spondylarthropathy (SSp), ulcerative colitis (UC) and Crohn's disease (CD). A total of 117 patients with defined histological lesions of inflammatory bowel disease (IBD) (68 UC and 49 CD), 32 patients with active SSp [European Spondylarthropathy Study Group (ESSG) 1991 criteria] without clinical evidence of IBD and 21 controls without IBD or SSp were studied. All patients with SSp and controls received similar doses of non-steroidal anti-inflammatory drugs. Abdominal scintigraphy images were obtained at 30 and 120 min after injection of 99m-technetium hexamethyl propylene amine oxime (99mTc-HMPAO)-labelled leucocytes. The 99mTc-HMPAO-labelled leucocyte scan was positive in 17 patients with SSp (53.1%), 45 patients with UC (66.1%) and 33 patients with CD (67.3%). Rectum and sigma involvement was more frequent in patients with UC (68.8%) than in patients with SSp (23.5%) or CD (33.3%) (P < 0.05) [odds ratios (OR): 7.1 and 4.4, respectively]. Terminal ileum involvement was more frequent in patients with CD (63.6%) than in patients with SSp (23.5%) or UC (8.8%) (P < 0.05) (OR: 5.6 and 17.9, respectively). The 99mTc-HMPAO-labelled leucocyte scan shows an increased uptake in patients with SSp without evidence of IBD. Perhaps these patients represent one end of the spectrum of IBD, but rectal and terminal ileum involvement were less frequent in patients with SSp than in patients with UC or CD.     

Influence of the smoking habit in the surgery of inflammatory bowel disease

The smoking habit is a key factor in the development of inflammatory bowel disease (IBD), but little information exists as to the relationship between smoking habit, the need of surgery and its complications. OBJECTIVES: To investigate the relationship between smoking habit, the need of surgery, their complications and clinical recurrence after surgery in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We studied a group of 62 patients (22 with UC and 40 with CD) with previous surgery. We analyzed the clinical and surgical characteristics of the disease. Smoking habit was established by a personal interview. This group of patients was compared with another control group of 202 patients (133 with UC and 69 with CD) with IBD without previous surgery. RESULTS: Smoking habit was similar between operated and non-operated patients for both UC (73% and 80% non-smokers) and CD (67% and 63% smokers) The number and type of complications after surgery were not related with smoking habit. In CD patients, although the recurrences did not depend on the smoking habit, they did occur earlier in smokers than in non smokers (83.6 +/- 21 vs 155 +/- 50 weeks, p = ns). CONCLUSIONS: The smoking habit does not seem to influence significantly the need of surgery and post surgical development of IBD, although in CD the smokers seems to present recurrence before non smokers.     

Epidemiological study on the incidence of inflammatory bowel disease in 4 Spanish areas. Spanish Group on the Epidemiological Study of Inflammatory Bowel Disease

BACKGROUND: The incidence of inflammatory bowel disease (IBD) shows marked geographical variations. The aim of this study was to determine and compare the incidence of IBD in four Spanish areas: Sabadell (Northeast), Vigo (Northwest), Mallorca island and Motril (South). PATIENTS AND METHODS: Prospective survey based on inception cohorts over a two-years period (1 October 1991 to September 1993). Subjects were the patients resident in these areas and diagnosed of IBD according to a standard protocol for case ascertainment and definition. RESULTS: Altogether 328 cases were identified, of whom 191 were diagnosed as ulcerative colitis (UC), 135 as Crohn's disease (CD) and 2 as indeterminate colitis. The overall adjusted incidence rate per 100,000 persons between ages 15-64 years of UC and CD were respectively 9.8 and 5.2 in Sabadell, 7.7 and 5.0 in Vigo, 7.8 and 5.8 in Mallorca and 4.3 and 6.5 in Motril. The Incidence rate ratio showed no significant differences for either conditions among these areas. The global adjusted incidence rate of UC in Spanish areas (8.0; IC 95%: 6.3-9.7) was significantly lower to that of Northern European countries while that of CD (5.5; IC 95%: 4.1-6.9) was between that of Northern and Southern Europe with no significant differences. CONCLUSIONS: The incidence of IBD did not show differences among the Spanish areas, and rates are between 2 and 6 times higher than those previously reported. The incidence of UC is significantly lower than that observed in the North of Europe, while for CD the incidence is between that of Northern and Southern Europe.     

Anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. Anti-cardiolipin (aCL) antibodies have been shown to be associated with thrombosis. Recently, the antibodies against the anti-cardiolipin cofactor beta2-glycoprotein I (a(beta2)GPI) have been found with higher specificity for thrombosis. The presence of these antibodies was assessed in 128 patients with IBD [83 with ulcerative colitis (UC) and 45 with Crohn's disease (CD)] and 100 healthy controls (blood donors). Patients with UC and CD had a significantly higher prevalence of aCL (18.1% and 15.6%, respectively) than healthy controls (HC) (3%). Eleven IBD patients (8.6%) but no HC had a(beta2)GPI. None of the IBD patients with a history of thrombosis had aCL and only one of them (a UC patient with deep vein thrombosis of the right leg) had a high titer of IgG a(beta2)GPI. In conclusion, these data show that both aCL and a(beta2)GPI are significantly associated with IBD but further studies are needed to determine the significance of our findings.     

A system of nonspecific defense in chronic inflammatory bowel diseases--pathophysiologic and therapeutic aspects]

Monocytes/macrophages are a prominent feature of the inflammatory infiltrate in inflammatory bowel disease (IBD). Progress in the development of monoclonal antibodies has provided a powerful means to identify and study various subsets of macrophages in the intestinal mucosa. In both Crohn's disease and ulcerative colitis distinct macrophage populations have been found being prominent in active disease, but absent from normal mucosa. Studies of our group show that the Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 (27E10 epitope) can be immunolocalized in the majority of granulocytes and macrophages in active but not inactive IBD. Serum MRP8/14 concentrations are significantly increased in patients with active IBD compared with patients suffering from inactive/mild disease. In vitro studies revealed that IL-13, IL-10 and IL-4 strongly suppress secretion of monocytic proteins. Differential responses of monocytes and macrophages towards the inhibitory effects of TH2-cytokines can be observed in both patients with IBD and control groups. Combined treatment with TH2-cytokines may effectively suppress the response of activated monocytes/macrophages thus being of potential therapeutic benefit for patients with IBD.     

Sensitive diagnosis of cardiac allograft rejection by detection of cytokine transcription in situ

BACKGROUND & AIMS: Interleukin 12 (IL-12) is a heterodimeric, macrophage-derived cytokine that is elevated in Crohn's disease (CD). Epstein-Barr virus-induced gene 3 (EBI3) is a recently characterized human glycoprotein that is homologous to the 40-kilodalton chain of IL-12 and forms a heterodimer with the 35-kilodalton chain of IL-12. We investigated the expression of EBI3 in colonic mucosa of normal control subjects, patients with ulcerative colitis (UC), and patients with CD. METHODS: Colonic tissue was analyzed for messenger RNA (mRNA) expression by quantitative polymerase chain reaction and for protein expression by immunohistology and Western blotting. RESULTS: EBI3 mRNA was present in intestinal biopsy specimens from healthy subjects and patients with CD but was elevated only in active UC. EBI3 levels in UC specimens correlated with histological scores of activity and T-cell infiltration. EBI3-positive cells that had a shape consistent with that of macrophages were identified in the lamina propria, and protein was detected by Western blotting. CONCLUSIONS: EBI3 is a novel IL-12-related cytokine that is expressed by macrophage-like cells in normal intestine and CD and has enhanced expression in active UC but not in active CD.     

Diagnostic accuracy of serological assays in pediatric inflammatory bowel disease

BACKGROUND & AIMS: Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease (IBD) types in the pediatric age group. The aim of this study was to test the diagnostic accuracy of modified assays for perinuclear (p) antineutrophil cytoplasmic antibodies (ANCAs) and anti-Saccharomyces cerevisiae antibodies (ASCAs) in patients with pediatric ulcerative colitis (UC) and Crohn's disease (CD) and in those without IBD. METHODS: With observers blinded to patients' diagnoses, serum specimens were analyzed for immunoglobulin (Ig) A and IgG ASCAs and ANCAs by enzyme-linked immunosorbent assay. The perinuclear location of ANCAs visualized by indirect immunofluorescence was confirmed by its disappearance after administration of deoxyribonuclease. RESULTS: IgA and IgG ASCA titers were significantly greater and highly specific for CD (95% for either, 100% if both positive). pANCA was 92% specific for UC and absent in all non-IBD controls. The majority of patients with CD positive for pANCA had a UC-like presentation. Disease location, duration, activity, complications, and treatment with immunosuppressive drugs did not have an impact on the ASCA or pANCA assay results. After resection, UC patients remained pANCA positive, in contrast to patients with CD, in whom ASCA titers decreased toward normal values postoperatively. CONCLUSIONS: ASCA and pANCA assays are highly disease specific for CD and UC, respectively. These serological tests can assist clinicians in diagnosing and categorizing patients with IBD and may be useful in making therapeutic decisions.     

Use of technetium-tagged white blood cells in patients with Crohn's disease and ulcerative colitis: is differential diagnosis possible?

BACKGROUND: Studies have suggested that scans with technetium-tagged white blood cells (WBC-Tc99m) may be equal to endoscopy in the assessment of extent and activity of inflammatory bowel disease (IBD). OBJECTIVE: We have retrospectively examined the accuracy of WBC-Tc99m scans in differentiating continuous from discontinuous colitis in pediatric IBD. MATERIALS AND METHODS: There were 207 children in the study (96 boys, 111 girls, median age 13 years). This included 29 controls - children with no gastrointestinal disease (NL) who underwent WBC-Tc99m scans for other medical problems. Scans were obtained at 30 minutes and 2-4 hours following injection. Scans were interpreted as showing continuous colitis, discontinuous colitis, or no colitis. RESULTS: In the 77 children with active Crohn's disease (CD) of the colon, the scans revealed discontinuous uptake in 63 children and continuous uptake in 14. In the 29 children with ulcerative colitis (UC), 23 scans showed continuous uptake and 6 revealed discontinuous uptake. Two of these 6 showed focal activity near the appendix, and subclinical appendicitis could not be excluded. Another child was bleeding and the scan could have been misinterpreted as showing small- bowel inflammation. In the last three patients, skip areas were clearly identifiable. In none of these last three patients were the biopsies typical of CD (i. e., no granuloma was identified) nor was inflammation patchy. In summary, of the 106 scans showing inflammation, 6 were classified into the wrong group. CONCLUSION: These data show that WBC-Tc99m scanning can be useful in distinguishing discontinuous from continuous colitis.     

Cultured astrocytes express functional receptors for galanin

OBJECTIVE: Inflammatory bowel disease (IBD) is characterized by T cell activation. Activated T cells shed interleukin-2 receptors (IL-2R) in a soluble form. A positive correlation between sIL-2Ralpha (CD25) and disease activity is well documented in IBD, whereas IL-2Rgamma (CD132) has not been investigated in this respect. Sera from 42 patients with ulcerative colitis (UC), 34 with Crohn's disease (CD), 31 healthy volunteers, and 12 patients with infectious enterocolitis were obtained. METHODS: Disease activity was scored according to a semiquantitative score for UC and CD. sIL-2R alpha chain and gamma chain were assessed by sandwich ELISA techniques using monoclonal antibodies specific for CD25 and CD132, respectively. RESULTS: The concentration of IL-2Ralpha chain (CD25) was found to be median 3.8 ng/ml in healthy volunteers versus 7.0 ng/ml in UC patients (p < 0.001), and 9.6 ng/ml in CD patients (p < 0.001). With respect to IL-2Rgamma (CD132), significantly higher amounts were found in CD patients: 6.6 ng/ml as compared with healthy controls <1.0 ng/ml (p < 0.004). A Kruskal-Wallis test revealed a significant correlation between alpha chain and disease activity in CD (p < 0.001), and further significantly higher gamma chain levels were found in active CD (p = 0.03). For UC patients, a statistically significant increase of the alpha chain with increasing disease activity (p < 0.01) was observed, whereas no significant changes of the gamma chain levels were found (p > 0.05). A difference of gamma chain levels were found between CD and UC in moderate and severe disease activity (p < 0.05). Further analyses revealed that mesalazine did not influence the IL-2Ralpha or -gamma concentration either in UC or in CD patients. CONCLUSION: An increased circulating level of the soluble common gamma chain (CD132) seems to be found in CD, and an overlap exists between CD and UC.     

Computed tomography and granulocyte scintigraphy in active inflammatory bowel disease. Comparison with endoscopy and operative findings

The accuracy of computed tomography (CT) and [99mTc]HMPAO granulocyte scintigraphy (GS) for detection of bowel localization, inflammatory activity, and complications in acute inflammatory bowel disease (IBD) was prospectively studied in 32 patients. Of each bowel segment, findings on CT and GS were scored by one blinded observer. Findings on operation or endoscopy served as the gold standard. In Crohn's disease (CD, 17 patients), CT detected bowel pathology (sensitivity 71%, specificity 98%), abscesses (sensitivity and specificity 100%), and fistulas (sensitivity 80%, specificity 100%). In CD, GS had a sensitive of 79% and a specificity of 98% for detection of inflammatory activity. The detection of complications with GS was poor. Segmental inflammatory activity correlated with endoscopy-operative findings for CT (r = 0/86, P < 0.0001) and GS (r = 0.86, P < 0.0001). In ulcerative colitis (UC, 15 patients), GS predicted proximal extension of bowel involvement better than CT. In CD, CT is Superior to GS for localization of both active and fibrostenotic bowel disease, and in detection of the abscesses and fistulas. In UC, GS showed proximal extension more accurately than CT.     

Susceptibility locus for inflammatory bowel disease on chromosome 16 has a role in Crohn's disease, but not in ulcerative colitis

In the Western world, chronic inflammatory bowel disease (IBD) presents as two major clinical forms, Crohn's disease (CD) and ulcerative colitis (UC) [Targan, S.R. and Shanahan, F. (1994). In Retford, D.C (ed.), Inflammatory Bowel Disease: From Bench to Bedside. Williams and Wilkins, Baltimore]. Genetic epidemiological studies, the occurrence of rare syndromes associated with IBD, and animal models suggest that inherited factors play significant roles in the susceptibility to both forms of IBD [Yang, H.-Y. and Rotter, J.I. (1995) In Kirsner, J.B. and Shorter, R.G. (eds). Genetic Aspects of Idiopathic Inflammatory Bowel Disease. Williams and Wilkins, Baltimore, pp.301-331]. Recently, a genome-wide search on European families with multiple affected members with CD identified a putative susceptibility locus in the centromeric region of chromosome 16 [Hugot, J.-P. et al. (1996) Nature, 379, 821-823]. We have now tested this region in an independent set of US families, confirmed that this region is likely to contain a gene predisposing to CD, and further refined the chromosomal location of this gene. Most importantly with respect to this locus, our data also seem to indicate that there is heterogeneity both within the CD group, and between the CD and UC groups with respect to this locus. The susceptibility locus appears to be involved only in non-Jewish CD sibpairs and not in our Ashkenazi Jewish CD sibpairs. Additionally, we have tested sibpairs having either only UC or both UC and CD for involvement of this locus, and have found no evidence that this region predisposes to IBD in these patients.     

Medial collateral knee ligament healing. Combined medial collateral and anterior cruciate ligament injuries studied in rabbits

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA), particularly perinuclear ANCA (p-ANCA), have been found more frequently in sera from patients with ulcerative colitis (UC) than in sera from Crohn's disease (CD) or unclassified enterocolitis (UE) patients. This 2-center study examined sera from 102 pediatric patients with inflammatory bowel disease (IBD) to evaluate their diagnostic value and assess their relationship with disease features, distribution, activity and treatment. METHODS: The serum ANCA of 102 children with IBD were measured: 33 UC, 64 CD and 5 UE with various disease locations and degrees of activity. The mean age at the onset of symptoms was 10.7 years (1 to 16.3 years). Sera from 26 unaffected first degree relatives and 20 children without IBD were also investigated. ANCA were detected using indirect immunofluorescence of ethanol-fixed granulocytes. RESULTS: There were ANCA in the sera of 24/33 children with UC (73%), 9/64 with CD (14%) and 4/5 with UE (80%). p-ANCA were more frequent than cytoplasmic-ANCA in positive sera: UC = 67%, CD = 57% and UE = 75%. The presence of ANCA was 73% sensitive and 81% specific for a diagnosis of UC, compared to other IBD (p < 0.001). Three children with proved sclerosing cholangitis associated with UC were all positive. There was no link between ANCA-positive sera and disease activity, or other endoscopic or clinical criteria. ANCA were detected in 4/26 first degree relatives (15%) and in 1/20 control subjects (5%). CONCLUSIONS: Because of their sensitivity and specificity, ANCA may be helpful in the clinical assessment of patients with IBD, and especially those with UC. However, there is no link between the pressure of p-ANCA and the site of UC or its activity, so that it cannot be used to monitor medical treatment or surgical indications.