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     

The proapoptotic 9-2 isozyme of 2-5 (A) synthetase cannot substitute for the sperm functions of the proapoptotic protein, Bax.

The 9-2 isozyme of 2-5 (A) synthetase has cellular proapoptotic functions that are mediated not by enzyme activity but by the Bcl-2 homology domain 3 present in its unique carboxyl-terminal region. Another proapoptotic cellular protein is Bax, whose absence in the Bax(-/-) mice causes male sterility due to abnormal sperm differentiation. In this study, we examined whether transgenic 9-2 expression can substitute for the in vivo reproductive function of Bax. To achieve this goal, a sperm-specific promoter was used to drive the expression of 9-2 in the sperm of transgenic mice. By selective cross-breeding, the transgene was transferred to Bax(-/-) mice to generate the experimental mouse line (Bax(-/-), 9-2(+/+)). The male experimental mice were sterile, and their testes maintained the structural abnormality found in Bax(-/-) mice. Thus, the male reproduction functions of Bax could not be replaced by the 9-2 isozyme of 2-5 (A) synthetase.     

Fibrin glue in initial treatment of epistaxis in hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease).

The purpose of the present study was to evaluate the haemostatic efficacy of fibrin sealant in patients with hereditary haemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease suffering epistaxis. A retrospective observational study of patients with HHT who were admitted to an emergency room for anterior or posterior epistaxis during May 2000-March 2003. A total of 24 patients were evaluated, of whom 15 were managed with foam nasal packing during May 2000-March 2002 and another nine were treated during March 2002-March 2003 with 0.3 ml fibrin sealant spray (Quixil; Omrix, Belgium). The immediate and the distant results were compared. Immediate haemostasis was achieved in all seven patients treated with fibrin glue, with good healing of bleeding sites, no secondary bleeding, no inflammation, and no plaque or crists. Twelve months of follow-up monitoring (until October 2003) of atrophic changes of nasal mucosa, bleeding frequency and intensity proved absence of atrophy of nasal mucosa and decreased bleeding frequency. In this group, the bleeding episode duration averaged 2 min 35 s since the moment of admittance. In the nasal packing group, we found local swelling, pain, and slow healing of the bleeding site with accidental atrophy of nasal mucosa and no effect on further bleeding frequency and intensity. Removal of nasal packing frequently initiates secondary bleeding. The rates of these side effects were higher in comparison with the fibrin glue group. The bleeding episode duration was also longer. In patients with HHT suffering profuse epistaxis, fibrin glue is more effective and convenient for the patients as compared with foam nasal packing. It is also safer, since it lacks the complications that usually accompany packing as swelling, atrophy of the nasal mucosa, and secondary bleeding provoked by the removal of the pack.     

Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure

Renal function was evaluated in 104 patients with severe chronic heart failure whom we treated with captopril or enalapril. Seventy patients showed no change or an improvement in renal function (group A), and 34 patients developed functional renal insufficiency (group B). Before converting-enzyme inhibition, group B patients received higher doses of furosemide (p less than 0.02) and had lower central venous pressures (p less than 0.05) than group A patients. After 1 to 3 months of converting-enzyme inhibition, an excessive reduction in left ventricular filling pressure (to less than 15 mm Hg) or mean arterial pressure (to less than 60 mm Hg) was noted in 28 of 34 (82%) patients in group B but in only 22 of 70 patients in group A (31%) (p less than 0.001). At the end of the study, drug-induced azotemia resolved after a reduction in the dosage of diuretics, despite unaltered treatment with captopril and enalapril. Hence, the deterioration of renal function after converting-enzyme inhibition in heart failure is not a toxic or immunologic reaction to therapy but results from specific hemodynamic events that can be ameliorated by sodium repletion.     

Interaction between thiol-modifying agents and P1075, a KATP channel opener, in rat isolated aorta

In vascular smooth muscle, openers of ATP-dependent potassium channels (K _ATP channels), such as P1075 (N-cyano-N’-(1,1-dimethylpropyl)-N’’-3-pyridylguanidine), produce relaxation. In this study we have investigated the effects of thiol-modifying agents on the binding of P1075 and on the ⁸⁶Rb⁺ efflux stimulating and vasorelaxant effects of the opener in rat aortic rings. The increase in ⁸⁶Rb⁺ efflux induced by P1075 was taken as a qualitative measure of K⁺ channel opening. The hydrophilic SH-group-oxidizing substance, thimerosal (1 to 100μM), abolished specific binding of [³H]-P1075 with an IC₅₀ value of 7.6±1.2μM; at 30μM, the half time for inhibition was 38min. Two other thiol-oxidizing agents, PMB (4-hydroxy-mercuribenzoic acid) and DTBNP (2,2’-dithio-bis(5-nitropyridine)), inhibited binding up to 86% and 44%, respectively. The disulphide bond reducing substance, DTT (1,4-dithiothreitol, 0.1 to 1mM), reduced [³H]-P1075 binding by up to 20% and partially reversed the inhibitory effect of thimerosal. In ⁸⁶Rb⁺ efflux experiments, thimerosal (3 to 100μM) concentration-dependently increased basal efflux but inhibited P1075-stimulated tracer efflux with an IC₅₀ value of 7±1μM. The inhibitory effect occurred with a half-time of approximately 8min and was essentially reversed by DTT. In rings precontracted with noradrenaline, thimerosal inhibited the vasorelaxant effect in a noncompetitive manner, shifting the concentration-relaxation curves to the right and reducing maximum relaxation.The data show that oxidation of thiol groups interferes with the binding of the K _ATP channel opener, P1075; concomitantly, the ⁸⁶Rb⁺ efflux stimulating and the vasorelaxant effects are inhibited. Reduction of disulphide bonds by DTT has only minor effects on the action of P1075. Collectively, the results suggest that intact thiol groups are essential for the functioning of the K_ATP channel in rat aorta. The different kinetics governing the inhibition of opener binding and of opener-stimulated ⁸⁶Rb⁺ efflux suggest that the SH-groups involved in the two processes differ in their accessibility to thimerosal and/or in their reactivity. Received: 7 April / Accepted: 9 July 1997     

Age, socioeconomic status, and health

Analysts dispute what roles biomedical, psychosocial, and other factors play in determining the duration of morbidity and disability over the life course. Cross-sectional data from two national surveys of adults aged 25 years and over not only show, however, that age and socioeconomic status (SES) are significant predictors of self-reported physical health; they also demonstrate that the relation of age to health varies with SES features. Longitudinal research is needed to test the finding that enduring functional limitations in terms of time are actually compressed in higher SES groups. To improve well-being in our society, moreover, requires specifying why SES differences occur, and perhaps ultimately reducing socioeconomic inequality itself.     

Reaming versus non-reaming in medullary nailing: Interference with cortical circulation of the canine tibia

Summary Medullary nails have only been used with reluctance in the treatment of open fractures since reaming interferes with the cortical circulation. The technique of interlocking offers the interesting possibility of inserting a relatively stiff nail which does not necessarily require reaming. The effects of reaming prior to nail insertion upon the cortical circulation was investigated in the canine tibia. Intravital staining with procion red was used to trace areas of disturbed circulation. Nail insertion without reaming provided clear advantages for the bone's blood supply, while reaming disturbed perfusion in two-thirds of the cortical area and regionally extended through the entire thickness of the cortex. The disturbance without reaming was limited to the inner layer of the cortex and involved only one-third of the cortical cross-section.     

The Rigiflex TTS: A New Method to Dilate Benign Esophageal Stenosis

Abstract: This paper dicusses the use of esophageal dilatation with a Rigiflex TTS balloon. This method was used 45 times on 11 patients affected by anastomotic or a severe grade peptic esophageal stenosis. Fluoroscopic guidance was used in 36 procedures (80%) without effecting the mean duration of the treatment (12 minutes). The results were considered satisfactory when these goals had been achieved: a) dilatation of the stenosis over 15 mm; b) a dysphagia free-time of more than 6 months. A satisfactory result was achieved in 10 patients (90.9%), without deaths and major complications. 5 patients received 1 dilatation and the other 5 needed, 3-3-4-7–11 procedures respectively to obtain a satisfactory result. On these basis we consider that its great efficacy, security and tolerability depend on the following characteristics of the Rigiflex TTS balloon: 1) “radial” dilatation; 2) the possibility of introducing the balloon through the operative channel of the fiberscope; 3) direct visualization of the stenosis during dilatation. The following disadvantages with this method are: the absence of a tactile sensation of dilatation and the elevated cost of the instrument. We conclude that the Rigiflex TTS balloon is an important alternative to guide-wire techniques, especially for the treatment of severe esophageal strictures.