The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis

Background The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed serving as a connector between the nervous and immune system. This connection is called the “cholinergic inflammatory pathway.” Through stimulation of the acetylcholine receptors located upon the macrophages, the “unspecific” immune system can be directly influenced. Methods The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model. Results After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals (34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6, IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis. Conclusion The vagal nerve is therefore an important modulator of the immune system. W. Kessler and T. Traeger contributed equally to this work Best of Forum Papers presented at the Annual Meeting of the German Society of Surgery, 2–5 May 2006, Berlin, Germany     

Spinal epidural hematoma. Report of a case and review of the literature

We report the case of a thoracic epidural hematoma at the T7-T9 level which occurred after placement of spinal epidural catheter for continuous anaesthesia in acute pancreatitis. The male patient felt a sudden back pain after six days of successful analgesia and became paraplegic 24 hours afterwards. An emergency laminectomy and removal of the hematoma were performed; however, the patient recovered only incompletely.We discuss the clinical signs and symptoms of spinal epidural hematoma as well as its diagnostics and therapy. The controversial views from the literature concernings its etiology are critically reviewed.     

Regelungssystematische Vorschläge zur Umsetzung der Richtlinie 2004/23/EG (Geweberichtlinie)

Ohne Zusammenfassung     

Apparent superiority of H2-receptor stimulation and simultaneousβ-blockade over conventional treatment withβ-sympathomimetic drugs in post-acute myocardial infarction: Cardiac effects of impromidine — a new specific H2-receptor agonist — in the surviving catecholamine-insensitive myocardium

Left ventricular infarction (AMI) was produced in experimental animals and the contractile response to -adrenergic and H₂-histaminergic stimulation by isoproterenol and impromidine tested in the isolated perfused heart preparation. Adenylate cyclase activity as well as binding characteristics of [³H]-dihydroalprenolol ([³H]-DHA), [³H]-methyl-tiotidine ([³H]-TIOT) and [³H]-quinuclidinyl benzilate ([³H]-QNB) to cardiac ₁-, H₂- and cholinergic muscarinic receptors were determined in sarcolemmal membrane preparations of the right ventricle of the same hearts. In addition, an attempt was made to elucidate the therapeutic value of post-AMI treatment with impromidine in the presence and absence of-sympathomimetic, in contrast to administration of prenalterol and the conventional therapy with -sympathomimetic drugs, e.g. dobutamine. Three days post-AMI the dose-response curve for isoproterenol of right ventriculardP/dt _max was significantly depressed, while the inotropic effect of impromidine was not impaired. Stimulation of adenylate cyclase activity by isoproterenol was reduced by 80% whereas impromidine and NaF stimulation rates were unaltered. Receptor-binding studies indicated a 90% loss and 10-times lowered affinity (K _D) of the remaining -receptors while specific [³H]-TIOT- and [³H]-QNB-binding was unchanged.Administration of dobutamine increased mortality rates and extension of infarct size, led to a further decrease in contractile response to isoproterenol, induced complete insensitivity of adenylate cyclase to isoproterenol stimulation and caused pronounced additional reduction of number and affinity of [³H]-DHA-binding sites. In contrast, all above alterations were prevented by treatment with either prenalterol or combined administration of impromidine plus metoprolol. It is concluded, that these alterations in the non-ischemic, uninvolved myocardium post-AMI are the result of catecholamine-induced specific damage of sarcolemmal -receptors. Furthermore, treatment with H₂-agonists in combination with -blocking agents may have beneficial effects, whereas conventional therapy with -sympathomimetic drugs tends to worsen the already depressed function of the -adrenergic stimulation mechanism.Supported by grants Ba 666/1 and Ba 666/2-2 from the Deutsche Forschungsgemeinschaft (DFG).Data presented in this paper are part of a doctoral thesis by Dr S.B. Felix.     

Cadmium in beavers translocated from the Elbe river to the rhine/meuse estuary,and the possible effect on population growth rate

Beavers (Castor fiber) from the Middle Elbe region were re-introduced in the Biesbosch, The Netherlands, an estuary contaminated with cadmium (Cd) by the rivers Rhine and Meuse. The Middle Elbe region was also polluted with Cd, but the beavers released in the Biesbosch originated from two relatively clean habitats within this region. The Biesbosch population grew slower than other released beaver populations in Europe, and it was hypothesized that Cd intoxication was responsible for this. The beavers fed primarily on the bark and leaves of willow and poplar trees, which contained great concentrations of Cd. The average Cd concentration in the food (6.9 g/g_dry) was above the maximum tolerable concentration for large domestic herbivores. The Cd concentrations of the kidneys and hair of the beavers were correlated with those in the bark of the trees. The Cd concentration in the hair increased threefold after the release in the Biesbosch, and the geometric mean Cd kidney concentration was 55 g/g_dry. Using three different models, an average Cd kidney concentration in the beavers of >100 g/g_dry was predicted in the Biesbosch in the near future. Such a concentration causes kidney damage in some other mammals. Beaver kidneys from the Mulde, a tributary of the Elbe, contained on average 467 g Cd/g_dry, the greatest concentration reported in herbivores. Nevertheless, the fertility along the Mulde was high, due to the fact that it is an otherwise optimal beaver habitat. Furthermore, the low fertility in the Biesbosch was due to a small fraction of successful breeding pairs. We conclude that the initial low population growth rate in the Biesbosch was probably not caused by contamination with Cd. However, future effects on the individual (reproductive) life span cannot be ruled out.     

Prognostic factors in malignant glioma: Influence of the overexpression of oncogene and tumor-suppressor gene products on survival

Despite the use of multimodal therapy, higher-grade glioma is stilluniformly fatal in the adult population. There is a considerable differencebetween the length of survival in each given patient, even within the sametumor type and malignancy grade group, suggesting that there are factorsthat might differentially influence outcome. To identify such factors, 107patients with anaplastic or malignant glioma were retrospectivelyinvestigated. Clinical parameters and paraclinical data on the p53, mdm2,and EGFR genes at the DNA or protein level were evaluated by univariateanalysis and Cox proportional hazards regression modeling. Kaplan-Meiersurvival estimation demonstrated that immunohistochemical positivity formdm2 protein in patients with anaplastic astrocytoma or with glioblastomamultiforme was associated with a shorter survival time (p = 0.02).P53 gene mutations and immunopositivity for the epidermal growth factorreceptor (EGFR) protein were not significantly related to poor prognosis.The Cox proportional hazards model revealed immunohistochemical positivityfor p53, mdm2, or for both of them, the presence of postoperativeirradiation, and the extent of surgical resection of tumor to be variablessignificantly associated with prolonged survival. EGFR overexpression, ageover 60 years, and Karnofsky performance score below 40 points did notsignificantly shorten survival time. In conclusion, the present studyidentified immunohistochemically detected mdm2-protein overexpression as astatistically significant negative prognostic parameter in patients bearinganaplastic or malignant glioma. Association analysis of variables revealed apossible correlation between mdm2 and p53, which is also consistent with thebiological interaction mode of both proteins in vivo.     

Einführung von Operationschecklisten als Teil des Risikomanagements

For approximately the past 10 years the aspects of quality and risk management have spread widely not only into the realm of hospitals but also into overall general medicine, which is viewed by many physicians as a paradigmatic change. The required use of the WHO operating room (OR) checklist has in the meantime become routine procedure in many hospitals but with varying degrees of acceptance. Current data reaffirm the positive effect of the checklist in lowering complication and mortality rates. This effect can be directly traced to a higher level for safety culture in the OR.     

Improved laparoscopic treatment of symptomatic urachal anomalies

Purpose

Remaining urachal anomalies are seldom found but can result in long-standing recurrent symptoms and repeated surgery. In this single-centre study, we evaluated the laparoscopic approach of excision of the urachus leaving the umbilicus untouched.

Methods

Twenty-one patients were operated on for persisting symptomatic urachal anomalies between 1998 and 2011. Patients included 8 males and 13 females (mean 28.5 years, range 15–72 years). Patients’ histories, surgical data and demographic data were prospectively collected and analysed. During follow-up, patients were evaluated using the total body image and cosmesis questionnaire (BIQ).

Results

Excision of the urachus was carried out in 18 cases in a laparoscopic three-trocar technique and in 3 cases using single-site surgery. In all cases, the infected umbilicus was left untouched. Mean surgical time of all procedures was 55.7 min (31–106 min). Histopathology confirmed an urachal anomaly in all cases. The former discharging or infected umbilicus healed without any complications. Sixteen patients could be included for the BIQ. Total body image score after surgery was 5.49 with a score of 5.0 being the most satisfactory result possible. The total cosmetic score was 21.37 close to the maximum score of 24.

Conclusions

The laparoscopic treatment of urachal anomalies using a three-trocar technique or the single-site surgery technique is both safe and effective. In our opinion, the excision of the umbilicus should be avoided. It simplifies the procedure and leads to satisfactory cosmetic results.     

Pretransplant Sensitization Against Angiotensin II Type 1 Receptor Is a Risk Factor for Acute Rejection and Graft Loss

The angiotensin II type 1 receptor (AT₁R) is an emerging target of functional non‐HLA antibodies (Ab). We examined the potential of determining the degree of presensitization against AT₁R as a risk factor for graft survival and acute rejection (AR). The study included 599 kidney recipients between 1998 and 2007. Serum samples were analyzed in a blinded fashion for anti‐AT₁R antibodies (AT₁R‐Abs) using a quantitative solid‐phase assay. A threshold of AT₁R‐Ab levels was statistically determined at 10 U based on the time to graft failure. An extended Cox model determined risk factors for occurrence of graft failure and a first AR episode. AT₁R‐Abs >10 U were detected in 283 patients (47.2%) before transplantation. Patients who had a level of AT₁R‐Abs >10 U had a 2.6‐fold higher risk of graft failure from 3 years posttransplantation onwards (p = 0.0005) and a 1.9‐fold higher risk of experiencing an AR episode within the first 4 months of transplantation (p = 0.0393). Antibody‐mediated rejection (AMR) accounted for 1/3 of AR, whereby 71.4% of them were associated with >10 U of pretransplant AT₁R‐Abs. Pretransplant anti‐AT₁R‐Abs are an independent risk factor for long‐term graft loss in association with a higher risk of early AR episodes.