[Abdominal vacuum therapy for the open abdomen - a retrospective analysis of 82 consecutive patients]. / Intraabdominelle Vakuumtherapie des offenen Abdomens - Eine retrospektive Analyse von 82 konsekutiven Patienten.

BACKGROUND: The therapy for open abdomen remains challenging. Abdominal vacuum therapy seems to simplify the treatment and to enable a direct fascial closure in a high percentage of the patients. PATIENTS AND METHODS: A retrospective analysis of 82 consecutive patients who underwent abdominal vacuum therapy between January 2005 and December 2007 was undertaken. Indications, -duration of treatment, complications as well as rate and type of abdominal wall closure were evaluated. RESULTS: The 82 consecutive patients consisted of 46 % female and 54 % male patients with a median age of 65.5 years. The most frequent diagnoses were colorectal carcinoma (24 %, n = 28, colon n = 18 and rectum n = 10), inflammatory bowel dis-ease (13 %), perforated peptic ulcer (9 %), necrotising pancreatitis (7 %), peritoneal carcinosis (5 %), ileus (5 %) and mesenteric ischaemia (4 %). The predominant indication for vacuum therapy was peritonitis (88 %). Vacuum therapy treatment was applied for a median of 6 days (range: 1-73 days). 18 patients (22 %) received intraabdominal foam dressings without the fenestrated polyurethane layer. In 70 % of all cases the abdominal vacuum therapy was performed without complications. 16 patients (19.5 %) developed intestinal fistulas. However, fistulas were not observed among the patients who were treated with foam dressings without a polyurethane layer. Abdominal bleeding was observed in 8 patients (10 %) and a persistent abdominal compartment syndrome was seen in one patient. Nine patients (11 %) died during hospitalisation. After completion of the intraabdominal vacuum therapy, -direct fascial closure was feasible in 35 patients (43 %). In 47 patients (57 %) an absorbable synthetic mesh was required for fascial closure. Symptomatic incisional hernias -occurred in 22 % of the patients. CONCLUSION: Abdominal vacuum therapy simplifies the treatment of patients with abdominal catastrophes such as peritonitis or necrotising pancreatitis. The cost-effective intraperitoneal use of a foam dressing without a fenestrated polyurethane layer was possible without an increased rate of fistulas. This retrospective analysis demonstrates that abdominal vacuum therapy can be performed without complications in the majority of patients. Furthermore, direct fascial closure is possible in almost half of the patients.

Protective role of HO-1 for alcohol-dependent liver damage.

BACKGROUND/AIMS: Alcoholic liver disease is continuously increasing in developed countries being a leading cause of death worldwide. Chronic ethanol consumption induces oxidative stress by accumulation of reactive oxygen intermediates (ROI) while reducing the cellular antioxidant defense. Induction of heme oxygenase-1 (HO-1) may protect primary human hepatocytes (hHeps) from such damage. Thus, the aim of this study was to investigate the potential of polyphenols to protect hHeps from ethanol-dependent oxidative damage. METHODS: hHeps were isolated by collagenase perfusion. ROI and cellular glutathione (GSH) were measured by fluorescent-based assays. Cellular damage was determined by lactate dehydrogenase (LDH) leakage and staining for apoptosis and necrosis. Nuclear translocation of Nrf2 and HO-1 expression were analyzed by Western blot. RESULTS: Ethanol and TGF-ß rapidly increase ROI and reduce GSH in hHeps, causing apoptosis with a release of approximately 40% total LDH after 72 h. Similar to incubation with hemin preincubation and co-incubation of cells with nifedipine, verapamil and quercetin significantly reduce oxidative stress and resulting cellular damage, in a dose-dependent manner, by initiating nuclear translocation of Nrf2 which in turn induces HO-1 under the control of p38 and ERK. Blocking of HO-1 activity with ZNPP9 reverses the protective effect of all three substances. CONCLUSION: Our results suggest that increasing HO-1 activity in hHeps protects them from oxidative stress-dependent damage. As polyphenols have great potential to induce HO-1 expression, they may play an important role for future therapeutic strategies to protect liver from oxidative stress-dependent damage observed during chronic alcohol consumption.

Attenuation of lethal graft-versus-host disease by inhibition of nitric oxide synthase.

We have previously demonstrated that administration of the nitric oxide (NO) synthesis inhibitor aminoguanidine (AG) to mice undergoing nonlethal graft-versus-host disease (GVHD) results in less destruction of host tissue and enhanced proliferative responses of splenic lymphocytes. Subsequently, we have determined whether the amelioration of GVHD pathology associated with inhibition of NO synthesis affects survival in a lethal GVHD model. Utilizing a C57BL/6 to C57BL/6xDBA2JF1 model, administration of parental lymph node lymphocytes instead of splenocytes results in 80-90% lethality by week 4 after GVHD induction. Administration of AG resulted in significantly decreased lethality coincident with decreased serum NO2- + NO3- levels. AG therapy had no effect on donor anti-host cytolytic T cell activity, which indicates that destruction of host tissue via this pathway was unaffected by the therapy. Histological evaluation of spleen, small intestine, bone, and mesenteric lymph node did not reveal any difference in the histological correlates of disease in the treated mice. AG increased various hematopoietic indices, including red blood cell count, white blood cell count, and hemoglobin, which indicates that the disruption of hematopoiesis during acute GVHD is mediated in part by NO. In addition, the number of GVHD mice with endogenous bacterial infections in the spleen and liver was significantly decreased in mice receiving AG therapy. These data indicate that NO plays a detrimental role during GVHD that appears to result in decreased hematopoietic indices and concomitant susceptibility to bacterial infection.

A prospective randomized trial comparing interleukin-2 receptor antibody versus antithymocyte globulin as part of a quadruple immunosuppressive induction therapy following orthotopic liver transplantation.

BACKGROUND: Quadruple immunosuppressive induction therapy has been shown to markedly reduce the incidence of acute rejection episodes without increasing the incidence of infectious complications after liver transplantation. However, the use of polyclonal antibody preparations (e.g. antithymocyte globulin [ATG]) is associated with side effects such as fever and tachycardia. To evaluate the efficacy and the safety of a monoclonal antibody directed against the interleukin-2 receptor (BT563) in comparison with ATG as part of a quadruple induction regimen, a prospective, randomized study was conducted. METHODS: Eighty consecutive adult recipients of primary orthotopic liver transplants were randomized to receive either BT563 (10 mg/day; days 0-12; n=39) or ATG (5 mg/kg/day; days 0-6; n=41) in addition to the standard immunosuppressive protocol consisting of cyclosporine, and prednisolone, and azathioprine. RESULTS: Patients treated with BT563 had a significantly lower incidence of steroid-sensitive rejection episodes (3 vs. 11; P<0.025) and also significantly fewer drug-related side effects (4 vs. 18, P<0.038) when compared with patients treated with ATG. The incidence of infectious complications was not different between the two groups. Patient survival did not differ significantly between the two groups (84.6% at 1, 2, and 3 years in the BT563 group and 90.2% at 1 year and 87.8% at 2 and 3 years for the ATG group). Analysis of graft function showed an advantage for the BT563 group in terms of postoperative bilirubin levels. However, no differences were observed in long-term follow-up between the two groups. CONCLUSIONS: Our results indicate that treatment with anti-interleukin-2 receptor antibody as part of quadruple induction therapy after orthotopic liver transplantation is safe and effective and shows fewer steroid-sensitive rejection episodes as well as fewer side effects when compared with quadruple induction therapy including ATG.

Upregulation of intraepithelial lymphocyte (IEL) function in the small intestinal mucosa in sepsis.

Host defense mechanisms preventing bacterial invasion are particularly important in the gastrointestinal tract, since most gram-negative infections originate from there. Intraepithelial lymphocytes (IEL) seem to play an important role in this immune surveillance of the intestine, although their function in sepsis is not fully understood. To evaluate the characteristics of IEL in sepsis, C57BL/6 mice received a non-lethal dose of LPS and IEL were harvested at various time points thereafter. Although IEL displayed no phenotypic changes after endotoxemia, they displayed enhanced cytolytic activity and increased proliferation after LPS injection In addition, IEL from septic mice showed enhanced gamma interferon (IFN-gamma) production after LPS administration. The production of IFN-gamma may have induced the increased intestinal NOS-2 mRNA expression which was observed after endotoxemia. In conclusion, endotoxemia leads to functional activation of IEL without phenotypic changes. The activation of IEL and the subsequently increased NOS-2 expression may be important mechanisms in maintaining the mucosal barrier after sublethal LPS challenge.

[Mesenteric artery occlusion as a rare complication of thromboangiitis obliterans]. / Mesenterialarterienverschluss als seltene Komplikation bei Thrombangiitis obliterans.

Mesenteric artery occlusions are rare complications of Thrombangiitis obliterans (Buerger's disease). We report on a 30-year old male with Thrombangiitis obliterans and mesenteric occlusion as a complication of this disease. Because of unclear abdominal pain, laparoscopy was performed which showed small bowel infarction and reduced liver perfusion. After small bowel resection and a second examination, ischemia of the intestinum continued. Angiography was performed, which showed central occlusion of the celiac trunk and the superior mesenteric artery. Relaparotomy with the embolectomy of the superior mesenteric artery, venous bypass from the sup.mes.art. to the hepatic arteries and repeated small bowel resection was performed. The patient recovered completely and was discharged from hospital after 3 weeks. After a further admission to the hospital 3 weeks later with abdominal pain caused by acute occlusion of the right colonic artery and severe ischemia of the right hemicolon, a right hemicolectomy was performed. Now, one year after the last hospital admission, the patient shows no sign of having any abdominal problems.