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 course of schizophrenia: Some remarks on a yet unsolved problem of retrospective data collection

Summary The retrospective assessment of symptoms and syndromes is a basic measure in research of the longitudinal course of schizophrenia. In spite of its importance there have been few studies evaluating the standard of quality of instruments for retrospective data collection. Combining retrospectively and cross-sectionally collected data on schizophrenic symptomatology in a cohort study over a period of 5 years revealed a significant underestimation of symptoms when assessed in retrospect. The need for studies on the validity of instruments for the retrospective assessment of symptoms is stressed.     

Cytostatic and immunosuppressive treatment of ocular Beh?et syndrome

Ocular symptoms of Beh?et's syndrome in 16 patients and the results of cytostatic and immunosuppressive therapy with cyclosporin A (6 patients), chlorambucil (6 patients), and a combination of cyclophosphamide and procarbacin (4 patients) are described. The clinical course and therapeutic outcome were compared to the patients' visual acuity and the duration of the disease prior to institution of cytostatic therapy. Average follow-up was 4.6 years, maximum 9 years. The principal ocular symptom in all patients was hemorrhagic, occlusive periphlebitis. Other symptoms, in descending order of frequency, were chorioretinitis, iridocyclitis, complicated cataract, secondary glaucoma and exudative retinal detachment. The patients in whom cytostatic therapy was instituted no later than 6 months after onset of the disease showed an improvement in or stabilization of visual acuity, as well as a clear reduction in signs of intraocular inflammation and frequency of recurrence. No improvement in visual acuity or ocular symptoms was achieved in cases where the disease was very advanced, despite cytostatic-immunosuppressive therapy. The results support early institution of immunosuppressive therapy in cases with Beh?et's syndrome where severe, irreversible damage has not yet occurred and in which vision is threatened in both eyes. However, due consideration must be given to the potential risks of immunosuppressive therapy, in particular the risk of a malignant tumor.     

Differential Stripping: Determination of the Amount of Topically Applied Substances Penetrated into the Hair Follicles

The determination of penetration pathways of topically applied substances into the skin is the subject of several investigations. Recently, follicular penetration has become a major focus of interest. To date, a direct, non-invasive quantification of the amount of topically applied substance penetrated into the follicles had not been possible. The development of such a method was the aim of this study. Therefore, the advantages of both stripping techniques, tape stripping and cyanoacrylate skin surface biopsy, were combined and evaluated. Tape stripping was used to remove the part of the stratum corneum that contained the topically applied dye. Subsequently, the follicular contents were ripped off by cyanoacrylate skin surface biopsy. The combined method termed "differential stripping" was evaluated in vitro and in vivo , and the amount of topically applied fluorescent dye penetrated into the hair follicles was quantified after different penetration times. After 30 min, 5% of the recovered concentration of sodium fluorescein was found in the follicular infundibula, where it was still detectable after 48 h. Altogether, the results of this investigation revealed that differential stripping is a new method that can be used to study the penetration of topically applied substances into the follicular infundibula non-invasively and selectively.     

Endovaskuläre Brachytherapie als neue Therapieoption zur Prophylaxe der Rezidivstenose nach peripherer Katheterintervention

The therapeutic concept of irradiation of the vessel wall for prevention of restenosis after endovascular procedures is based on increasing knowledge about the pathophysiology of the process leading to restenosis. There is until now only a limited number of studies concerning the use of brachytherapy (BT) in the peripheral circulation, which is in contrast to the already large experience in the coronary circulation. In the peripheral trials the radiation dose was administered by a remote afterloader using a gamma source. According to the available data, vascular BT is a promising technology with the potential to reduce the restenosis rate. The Vienna-2-Trial was the first randomised study to demonstrate the efficacy of endovascular BT for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty. However, we have to await further supportive data from ongoing clinical trials before definitive recommendations can be given. Currently, endovascular BT seems already justified in patients with recurrent interventions or after long-segment femoropopliteal angioplasty because of the high risk of restenosis in these patients. The next years will demonstrate the ultimate role of endovascular BT in comparison to the rapidly evolving field of drug-eluting stents.     

Neue Entwicklungen in der systemischen Psoriasistherapie

The current standard systemic therapeutic modalities for psoriasis have many potential side effects. Progress made in the understanding of the pathophysiology of psoriasis as a T‐cell‐mediated dermatosis provide options for new more precise therapeutic approaches. These immunological therapeutic strategies involve the inhibition/depletion of activated T‐lymphocytes, the inhibition of antigen presentation and thus the regulation of T‐cell activation, the inhibition of adhesion of inflammatory cells, the inhibition of effects of proinflammatory mediators and the administration of antiinflammatory cytokines. This article summarizes these new systemic therapeutic approaches. Clinical results in the early studies have been mixed. In the next years further results of phase II‐ and phase III‐studies may be expected, which should allow better assessment of the potential of those particular approaches. Some of these approaches could lead to the approval of new drugs to treat psoriasis and to enhance or replace already existing therapeutic options. Furthermore results of therapeutic experiments should contribute to a better understanding of the disease. As we learn which mechanisms are more or less important for the disease, we will be better able to plan intervention strategies.