Intestinal cytokine response after gut ischemia: role of gut barrier failure

OBJECTIVE: To investigate the effect of intestinal ischemia with and without a reperfusion injury on intestinal cytokine production and gut permeability. SUMMARY BACKGROUND DATA: In humans and in animal models, the gut has been implicated as a cytokine-producing organ after ischemia/reperfusion (I/R)-type injuries. Because of the limitations of in vivo models, it has been difficult to demonstrate directly that the gut releases cytokines after an I/R injury or whether there is a relation between the magnitude of the ischemic process and the cytokine response. METHODS: Ileal mucosal membranes from rats subjected to sham or 45 or 75 min of superior mesenteric occlusion (SMAO) or 45 minutes of SMAO and 30 minutes of reperfusion (SMAO 45/30) were mounted in the Ussing chamber system. Levels of tumor necrosis factor-alpha and interleukin-6 were serially measured in the mucosal and serosal reservoirs of the Ussing system, as was mucosal permeability as reflected by the passage of bacteria or phenol red across the ileal membrane. In a second group of experiments, Escherichia coli C25 was added to the mucosal reservoir to determine if the cytokine response would be increased. RESULTS: Mucosal and serosal levels of tumor necrosis factor-alpha were equally increased after SMAO, with the highest levels in the 75-minute SMAO group. The highest levels of interleukin-6 were found in rats subjected to 75 minutes of SMAO or SMAO 45/30; the serosal levels of interleukin-6 were four to sixfold higher than the mucosal levels. The addition of E. coli C25 resulted in a significant increase in the amount of interleukin-6 or tumor necrosis factor-alpha recovered from the mucosal reservoir. Increased ileal membrane permeability was observed only in rats subjected to 75 minutes of SMAO or SMAO 45/30. CONCLUSION: These results directly document that the levels of tumor necrosis factor-alpha and interleukin-6 released from the gut increase after an ischemic or I/R injury, such as SMAO, and that there is a relation between the magnitude of the gut ischemic or I/R insult and the cytokine response.     

No dose-dependent tubulotoxicity of 5-aminosalicylic acid: a prospective study in patients with inflammatory bowel diseases

BACKGROUND AND AIMS: Elevated levels of renal tubular markers in the urine are found in 20-30% of patients with chronic inflammatory bowel diseases. We investigated whether this reflects a dose-dependent tubulotoxicity of 5-aminosalicylic acid (5-ASA). PATIENTS AND METHODS: In an open, prospective, multicenter study 18 patients with Crohn's disease and 29 with ulcerative colitis were treated with 3 g 5-ASA or more daily as the sole drug for 6 weeks. Clinical activity (CDAI, CAI) and renal tubular markers [beta-N-acetyl-D-glucosaminidase (beta-NAG) and other proteins in urine] were monitored. We examined whether the proportion of patients with elevated beta-NAG is more than 15% higher (absolute difference) than that prior to treatment. RESULTS: The proportion decreased from 19.2% to 12.8% in the intention-to-treat analysis (n=47) and from 24.3% to 13.5% in the per-protocol analysis (n=37), which was not more than 15% higher than at baseline. Mean CDAI decreased from 222 to 146 and mean CAI from 7.3 to 3.1 (intention-to-treat analysis). Response to therapy was shown by 61% of patients with Crohn's disease and 66% of patients with ulcerative colitis. The cumulative dose of 5-ASA was not correlated with beta-NAG level in the urine. CONCLUSION: This study largely rules out that 5-ASA at 3 g or higher per day for 6 weeks induces renal tubular damage. Elevated renal tubular markers reflect inflammatory activity or an extraintestinal manifestation of inflammatory bowel diseases.     

Management of Demented Patients with Urinary Incontinence: A Case Study

Objective: To assess whether a demented patient with urinary incontinence (UI) could learn to use an adapted version of timed voiding (i.e., instead of being led by a caregiver, the patient learns to perform timed voiding by herself). Indeed, UI affects a large number of patients with dementia and creates a substantial burden to the caregiver. UI is the most common complaint at the time of institutionalization and it is often the cause of premature institutionalization. Timed voiding is a promising intervention, but one whose effectiveness remains to be demonstrated. Additionally, timed voiding has the disadvantage of being constraining for caregivers, requiring them to be present to stimulate the patient to urinate at each of the scheduled occasions. Method: The present intervention required the patient to learn (1) to associate an auditory signal from a timer to the action of urination, (2) to reprogram the timer, using the spaced retrieval technique. An ABAB paradigm was used to assess the effectiveness of this program to eliminate urinary accidents. Results: The results of the intervention showed that the use of the timer was effective in helping the patient to reduce her urinary leaks from 1.5 diurnal accidents per week to zero during four months. Conclusion: UI in patients with dementia seems treatable. Such intervention could contribute to delay institutionalization of patients with dementia through maintaining their autonomy and reducing the burden of caregivers.     

L-selectin shows time and gender dependency in association with MODS

BACKGROUND: Recent investigations have demonstrated gender related immunologic alterations after trauma. These complications arise due to polymorphonuclear granulocytes (PMN) interacting with endothelium via L-selectin. Therefore, the purpose of this study was to investigate gender related differences in the expression of L-selectin in relation to posttraumatic multiple organ dysfunction syndrome (MODS). METHODS: Multiply injured patients were prospectively entered in the study. MODS was determined using the Denver score. The concentration of L-selectin on the surface of PMN was determined using flow cytometry during a 14 days' period. RESULTS: 48 patients were included in the study. The kinetics of L-selectin were different comparing male and female patients. Male patients with MODS initially showed a rapid decrease of surface L-selectin from 80 to 20 ng/ml. A return to admission levels was related to MODS. Male patients without MODS displayed elevated L-selectin levels up to 140 ng/ml. Female patients, however, all showed an initial rapid decrease of L-selectin to 20 ng/ml. Women who developed posttraumatic MODS had significantly increased levels up to 110 ng/ml before development of MODS developed. CONCLUSIONS: We feel that a gender related dimorphism in the initial L-selectin expression following trauma exists and is associated with MODS. These findings indicate new therapeutic means for the treatment of MODS. Therapies should be timely and gender dependently coordinated.     

Impact of in vivo complement activation and cryoglobulins on graft outcome of HCV-infected renal allograft recipients

BACKGROUND: Chronic hepatitis C virus (HCV) infection is closely associated with mixed cryoglobulinemia. Cryoglobulins can activate complement leading to vascular damage. We examined whether cryoglobulinemia and complement turnover is associated with HCV infection in renal transplant recipients and whether this has an adverse effect on graft outcome. METHODS: Sera and fresh plasma from 31 HCV-RNA-positive patients after renal transplantation (group I) were studied for cryoglobulins, complement hemolytic activity (CH50), and complement split product C3d. In total, 80 HCV-negative renal transplant recipients (group II) and 72 untreated patients with chronic hepatitis C (group III) without renal transplantation served as controls. RESULTS: Cryoglobulins were detected in 45, 28, and 26% of the patients in group I, II, and III, respectively. A high cryocrit ( > 5%) was present only in patients of group III (p < 0.01%). Mean CH50 values were lower and C3d levels higher in HCV-positive patients (group I and III) compared with HCV-negative patients (p < 0.0001). Cryoglobulins were not associated with extrahepatic manifestations or graft dysfunction, except in five patients of group III demonstrating cryoglobulinemic vasculitis. HCV-positive renal transplant recipients with signs of complement activation showed a significantly greater increase of serum creatinine (0.88 +/- 1.14 mg/dL) when compared with baseline than patients without complement activation (0.34 +/- 0.37 mg/dL; p = 0.035). There was also a tendency toward a higher extent of proteinuria in patients with complement activation (1.38 +/- 2.17 g/d vs. 0.50 +/- 0.77 g/d; p = 0.25, NS). CONCLUSIONS: Cryoglobulins are common in renal allograft recipients, but do not affect graft function. However, complement activation appears to be involved in chronic allograft dysfunction in HCV-infected recipients.     

Trauma care in Germany

Trauma Care in Germany fulfils all requirements to deal with injured young and mobile individuals as well as with an increasing number of injured elderly patient. Furthermore, it is prepared to cope with mass casualties of injured. As a public task the Trauma System in Germany is well organized and follows clear cut demands. To perform technical and medical therapy at highest available level as soon as possible, a ground system of physician staffed ambulances is supported by a network of physician-staffed HEMS all over Germany. Therefore, enormous efforts in financing, basic research and quality management have been undertaken during recent years to create such a sophisticated rescue system.