Portal and systemic bacteraemia and endotoxaemia in liver disease.

Using a percutaneous transhepatic technique, blood was obtained from the portal veins of 30 patients with various hepatic disorders and examined for the presence of bacteria and endotoxin. Simultaneous samples also were drawn from hepatic and peripheral veins. In three cases, portal vein cultures grew diphtheroids, which were of doubtful significance, while all hepatic and peripheral cultures were sterile. Endotoxin was detected in seven portal vein samples; in none of these patients were the hepatic or peripheral blood samples positive. In three cases, only peripheral blood samples were positive for endotoxin. It was concluded that portal bacteraemia occurs as infrequently in patients with liver disease as in those without. Portal endotoxaemia was detected in patients with all degrees of liver disease but, even in patients with moderately severe portal hypertension, the liver may remain an effective filter of endotoxin.     

Significance of interleukin-6 in patients with inflammatory bowel disease

The significance of interleukin-6 (IL-6) in patients with inflammatory bowel disease (IBD) was studied by measuring the IL-6 level in serum and colonic tissue by means of an enzyme-linked immunosorbent assay (ELISA), and by examining its localization using an immunohistochemical method. The serum IL-6 level reflected the degree of disease activity, and the extent of affected area, and was also correlated with the serum C-reactive protein (CRP) level. In the colonic mucosa of active IBD, the tissue IL-6 level was markedly elevated, and immunoreactive products of anti-IL-6 antibody were present in infiltrative mononuclear cells in the lamina propria. This indicates that IL-6 production in these cells is enhanced at the site of affected intestine. These results, together with its biological activity and the type of cell producing it, suggest that IL-6 is an available marker to assess disease conditions of IBD and that it might be also involved in the pathophysiology of IBD.     

Microalbuminuria in inflammatory bowel disease.

Microalbuminuria independently predicts the development of nephropathy and increased cardiovascular morbidity and mortality in diabetic patients, but it may be an indicator of the acute phase response. This study examined microalbuminuria as a marker of the acute phase response in patients with inflammatory bowel disease and correlated it with the disease activity in 95 patients with inflammatory bowel disease (ulcerative colitis (n = 52), Crohn's disease (n = 43)) determined by the simple index of Harvey and Bradshaw. Fifty patients were in complete clinical remission and 45 patients had active disease. Microalbuminuria was detected in all patients with inflammatory bowel disease (147 (17) v 18 (2) microgram/min, inflammatory bowel disease v controls mean (SEM), p < 0.007). Patients with active inflammatory bowel disease had higher concentrations of microalbuminuria compared with patients in remission (206 (19) v 65 (8) microgram/min, mean (SEM), p < 0.0001). Eight patients with active inflammatory bowel disease who were sequentially followed up with measurements of microalbuminuria had significantly lower values, when the disease was inactive (active inflammatory bowel disease 192 (44) v inactive inflammatory bowel disease 64 (14) microgram/min, p < 0.03). There was a significant correlation with the simple index of Harvey and Bradshaw (r = 0.818, p < 0.0001). Microalbuminuria values were significantly lower in inflammatory bowel disease patients in remission, maintained with olsalazine compared with those patients maintained with mesalazine and salazopyrine, but no significant difference was seen in values of microalbuminuria in active inflammatory bowel disease patients receiving different salicylates. This study also measured serum amyloid-A as an indicator of the acute phase response in the same patients. Serum amyloid-A was significantly increased in active disease compared with inactive disease (151 (43) v 33 (7) or controls 11 (2) micrograms/ml, p < 0.05). In conclusion microalbuminuria is present in abnormal amounts in all patients with active inflammatory bowel disease, and values fall when the disease is quiescent. Microalbuminuria is probably a consequence of an acute phase response and provides a simple, rapid, and inexpensive test, which has the potential to monitor inflammatory bowel disease activity and response to treatment.     

Fibromyalgia in inflammatory bowel disease.

OBJECTIVE: Studies of the rheumatological complications of inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) have focused on peripheral arthritis and spondylitis, and less is known about soft tissue rheumatism, specifically the fibromyalgia syndrome (FM). Our aim was to estimate the prevalence of FM and assess pain thresholds in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Seventy-two patients with UC and 41 with CD attending consecutively at the Gastroenterology Outpatient Clinic were assessed for the presence of FM and tenderness thresholds. FM was diagnosed according to the American College of Rheumatology 1990 criteria. Tenderness was measured by manual palpation and with a dolorimeter. One hundred twenty healthy subjects served as controls. RESULTS: FM was documented in 30 of 113 patients with IBD (30%), specifically in 49% of patients with CD and 19% with UC (p = 0.001); in controls the rate was 0%. Subjects with CD exhibited more tenderness and reported more frequent and more severe FM associated symptoms than subjects with UC. Patients with CD had a higher tender point count, 11.3 (+/- 6.5), than those with UC, 6.4 (+/- 5.7) (p = 0.001); in healthy controls, the count was 0.1 (+/- 0.5). Tenderness thresholds (kg) were lower in CD 2.9 (+/- 1.7) than UC 3.9 (+/- 2.0) (p = 0.005) and controls 5.8 (+/- 0.9). CONCLUSION: FM is common in IBD, particularly Crohn's disease. The lower pain threshold in Crohn's disease may suggest a disease-specific effect. Recognizing FM in patients with IBD will prevent misdiagnosis and ensure correct treatment.     

Hyposplenism in inflammatory bowel disease.

Splenic function was assessed in 35 patients with ulcerative colitis and 20 patients with Crohn's disease. Hyposplenism was diagnosed if there were Howell-Jolly bodies in the peripheral blood film or if there was prolongation of clearance from the peripheral blood of injected 51-Cr-labelled heat-damaged red blood cells. Thirteen of the patients with ulcerative colitis had hyposplenism as compared with only one patient with Crohn's disease. Conversely, heat-damaged red cell clearance values faster than the normal range were found in six out of the 20 patients with Crohn's disease. Four patients with hyposplenism and ulcerative colitis developed life-threatening septicaemia in the early postcolectomy period, two of these being further complicated by disseminated intravascular coagulation.     

Pharmacogenomics in inflammatory bowel disease.

Inherited variations in the nucleotide sequence of genes influence how individual patients respond to drugs. Most commonly, clinically significant genetic variations consist of single nucleotide polymorphisms (SNPs) within genes that affect drug disposition or drug targets. Up to now, relatively few clinically important examples of inherited traits that affect drug responses have been studied in detail. However, one of the well-characterized examples is highly relevant to inflammatory bowel disease therapeutics, that of thiopurine methyltransferase pharmacogenetics. Individuals with 2 normal alleles of the gene encoding thiopurine methyltransferase metabolize and clear thiopurines such as azathioprine and 6-mercaptopurine rapidly. Individuals with 1 normal and 1 variant allele are intermediate, whereas those with 2 variant alleles clear thiopurines very slowly. Intermediate and slow metabolizers are predisposed to have high active thiopurine drug levels and develop bone marrow suppression. Genomic era technology permits determination of large numbers of SNPs in large numbers of individuals. This capability is allowing the field of pharmacogenomics to become one of the most productive interfaces in translational biomedical research at present. By using high-throughput SNP genotyping, combined with careful phenotypic characterization of disease, pharmacogenomic research carries the potential of identifying individual biomarkers that predict the relative likelihood of benefit or risk from a therapeutic intervention. If this promise can be realized, pharmacogenomics will deliver the opportunity for personalized medicine.     

Thromboembolism in inflammatory bowel disease.

Thromboembolism represents a severe complication of inflammatory bowel disease occurring in young patient, with active disease. Deep venous thrombosis and pulmonary embolism are the most frequent thromboembolism manifestations. Arterial complications and unusual sites for thromboembolism are more rare. Overall, inflammatory bowel disease is a real prothrombotic state as almost all parameters of coagulation are enhanced. Anticoagulation during the episode of thromboembolism is mandatory, and sometimes may ameliorate the course of inflammatory bowel disease.     

Serum lysozyme in inflammatory bowel disease.

Serum lysozyme activity was measured in 18 patients with ulcerative colitis and 40 patients with Crohn's disease by both the turbidimetric and lysoplate method. Only one patient with ulcerative colitis and eight patients with Crohn's disease had increased serum lysozyme activity by either or both methods. Both methods appeared equally sensitive in detecting increased serum lysozyme activity. In Crohn's disease, the percent with elevated values increased with increase in disease activity.     

Pulmonary function in inflammatory bowel disease.

Pulmonary function has been assessed in patients with ulcerative colitis and Crohn's disease and compared with a healthy population. No statistically significant differences were found in the measurements observed within the three groups.     

Serum lysozyme in inflammatory bowel disease.

The mean concentrations of serum lysozyme were markedly higher in patients with Crohn's disease and ulcerative colitis than in normal controls, and mean levels tended to be slightly higher in those with Crohn's disease than in those with colitis. The significance of these differences is unclear but the overlap between values in normal individuals and those with inflammatory bowel disease prevents the measurement having any discriminant value.     

Serum lysozyme in inflammatory bowel disease.

Serum lysozyme (muramidase) concentrations were measured in three groups of patients: control, ulcerative colitis and proctitis, and Crohn's disease. The mean +/-SD for each group was: control, 7 +/- 2; ulcerative colitis and proctitis, 7 +/- 2; and Crohn's disease, 10 +/- 4. Although a significant difference was seen between values in patients with Crohn's disease and values observed in those with ulcerative colitis or control patients, an important overlap was found between these groups. Further studies are necessary to explain the disparate results between this study and previous reports.     

Adhesion molecules in inflammatory bowel disease.

The ability of leucocytes to adhere to endothelium is essential for leucocyte migration into inflammatory sites. Some of these adhesion molecules are released from the cell surface and can be detected in serum. The soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), E selectin, and vascular cell adhesion molecule 1 (VCAM-1) were studied in the serum of patients with Crohn's disease, ulcerative colitis, and healthy controls. A second blood sample was taken from patients with active disease after one month of treatment and a third two months after remission was achieved. Tissue expression of the same adhesion molecules was studied by immunohistology. Circulating VCAM-1 concentrations were significantly higher in patients with active ulcerative colitis (n = 11, median = 165 U/ml) compared with patients with inactive ulcerative colitis (n = 10, median = 117 U/ml, p < 0.005), active Crohn's disease (n = 12, median = 124 U/ml, p < 0.02), and controls (n = 90, median = 50 U/ml, p < 0.0001). Within each disease group there were no significant differences in E selectin or ICAM-1 concentrations between the active and inactive states, however, patients with active Crohn's disease had significantly higher ICAM-1 concentrations (n = 12, median = 273 ng/ml) than controls (n = 28, median = 168, p < 0.003). VCAM-1 concentrations fell significantly from pretreatment values to remission in active ulcerative colitis (p < 0.01). In Crohn's disease there was a significant fall in ICAM-1 both during treatment (p < 0.01) and two months after remission (p < 0.02). Vascular expression of ICAM-1 occurred more often and was more intense in inflamed tissue sections from patients with ulcerative colitis and Crohn's disease than from controls. Vascular labelling with antibody to E selectin also occurred more often in patients with active inflammatory bowel disease. In conclusion, increased circulating concentrations of selected adhesion molecules are associated with inflammatory bowel disease. There is also evidence of local upregulation, particularly of ICAM-1. Differential expression of adhesion molecules in tissue may play a part in the initiation of leucocyte migration and local inflammation; the function of circulating adhesion molecules is unknown, but may play a physiological part in blocking adhesion.