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     

Optimal intensity for respiratory muscle endurance training in patients with spinal cord injury.

OBJECTIVE: Respiratory muscle endurance of able-bodied persons, assessed by normocapnic hyperpnoea at 70% of their maximal voluntary ventilation, usually ranges from 10 to 20 minutes. The aim of this study was to determine the level of ventilation that patients with paraplegia and tetraplegia can sustain for 10-20 minutes to later be used as the guideline for respiratory muscle endurance training. DESIGN: Pilot study; cross-over setting. SUBJECTS: Two groups, 8 patients with paraplegia and 6 with tetraplegia. METHODS: Respiratory muscle endurance tests were performed at 3 different intensities of normocapnic hyperpnoea, i.e. 20%, 40% and 60% maximal voluntary ventilation. Subjects performed partial re-breathing from a bag to assure normocapnia. Respiratory endurance was separately analysed for patients with paraplegia and tetraplegia. RESULTS: Mean respiratory endurance times were 46.0, 18.9 and 4.2 minutes at 20%, 40% and 60% maximal voluntary ventilation in patients with tetraplegia and 51.8, 38.8 and 12.2 minutes in patients with paraplegia. The duration differed significantly at 60% maximal voluntary ventilation between the groups. CONCLUSION: Minute ventilation to perform respiratory muscle endurance training can be set at around 40% of maximal voluntary ventilation for patients with tetraplegia and around 60% of maximal voluntary ventilation for patients with paraplegia, as these levels can be sustained for 10-20 minutes.     

Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation

Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor.     

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.     

HUMAN LONGINGS AND MASCULINE TERRORS: MASCULINITY AND SEPARATION FROM MOTHER

ABSTRACT The paper explores two literary texts - Dostoevsky's novel Crime and Punishment and Euripides'play Bacchae - from the point of view of immature masculinity and the catastrophe that can follow if the boy fails to achieve a genuine separation from the maternal object. The author examines the masculine anxieties and defences that arise when the boy fails to work through the Oedipus complex and instead retreats to a dyadic relation with mother which excludes the father. This retreat involves a denial of reality and the creation of a paranoid world in which his own wishes to take possession of mother can be experienced by him as an intrusion by the mother into his own masculine identity and ultimately as castration by the mother. Attempts to resolve this threat to masculinity include the use of anal defences and tyrannical states of mind in the creation of a pseudo-masculinity.
The movement into the male Oedipus complex necessarily involves a psychological state in which the externality of the oedipal-object mother is continually in danger of being blurred by the shadow cast by the pre-oedipal mother. (Thomas Ogden 1992)     

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.