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     

Quantification of refractive error: comparison of autorefractor and focometer.

PURPOSE: The advantages of a focometer (FOCOMETER) over other methods of refraction for use in developing countries are that it is lightweight, compact, relatively inexpensive, fairly quick, and easy to use with minimal training. This clinical trial compared the repeatability, validity, and ease of use of the focometer with an autorefractor. METHODS: The refractive status of the right eye of 80 participants was determined with an autorefractor (Canon RK3). Three measurements were also taken with the focometer. RESULTS: The spherical equivalent (M) of the focometer was 0.25 D more positive than the autorefractor (p < 0.001) and 84% of measurements were within 0.75 D of the autorefractor. The autorefractor detected astigmatism in 91% (73) of the eyes, whereas the focometer identified only 32% (26). The design of the clock target restricts cylinder axis accuracy to the nearest 15 degrees . There was evidence of a learning effect for the focometer: the second and third measurements were more repeatable in the untrained group. There were no differences between the mean (1.03 +/- 2.28) and third focometer (-1.05 +/- 2.32) measurements (p = 0.34). However, using the third focometer measurement, 94% of participants had visual acuities of at least 6/12(-2). CONCLUSIONS: This study highlighted the focometer's restricted power range, inaccuracy of astigmatism and axis determination, and dependence on subject understanding and compliance. Therefore, in most clinical settings, the focometer would not be adequate for quantifying refractive error, but the focometer spherical equivalent was within acceptable limits of the autorefractor, and the visual acuity with lenses determined by the focometer indicates its potential usefulness in public health settings, especially where only spherical ready-made spectacles are dispensed. There may be more cost-effective ways to determine refractive error in these circumstances. A potentially important enhancement in focometer methodology that improves its ease of use was identified: use only the third measurement for each eye.     

Phase II trial of piroxantrone in patients with recurrent and metastatic squamous cell carcinoma of the head and neck

Summary Twenty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with piroxantrone 150 mg/m² intravenously every 21 days. There were no objective responses. The 95% upper confidence bound for response is 15%. Primary toxicity was hematologic.     

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.