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     

Replication of Marburg virus in human endothelial cells. A possible mechanism for the development of viral hemorrhagic disease.

Marburg and Ebola virus, members of the family Filoviridae, cause a severe hemorrhagic disease in humans and primates. The disease is characterized as a pantropic virus infection often resulting in a fulminating shock associated with hemorrhage, and death. All known histological and pathophysiological parameters of the disease are not sufficient to explain the devastating symptoms. Previous studies suggested a nonspecific destruction of the endothelium as a possible mechanism. Concerning the important regulatory functions of the endothelium (blood pressure, anti-thrombogenicity, homeostasis), we examined Marburg virus replication in primary cultures of human endothelial cells and organ cultures of human umbilical cord veins. We show here that Marburg virus replicates in endothelial cells almost as well as in monkey kidney cells commonly used for virus propagation. Our data support the concept that the destruction of endothelial cells resulting from Marburg virus replication is a possible mechanism responsible for the hemorrhagic disease and the shock syndrome typical of this infection.     

Crisis debriefing of a jury after a murder trial

The importance of crisis debriefing for those involved in major accidents, violent crimes, and natural disasters has been demonstrated. Similar debriefing may be warranted for jurors exposed to disturbing material in criminal cases. The authors describe a debriefing session for jurors after the murder trial of a man whose truck had collided with a school bus, killing 27 people. The graphic evidence of the accident, the high levels of emotion of the survivors and the victims' relatives, and the intense community and national attention to the trial placed the jurors under considerable stress. The debriefing enabled the jurors to express their feelings of anger, guilt, and frustration and to begin to accept their role in the event.     

Radioresponsiveness, sublethal damage repair and stem cell rate in spheroids from three human tumor lines: comparison with xenograft data.

Dose-control curves after fractionated irradiation were generated for small oxic spheroids from the two human glioma cell lines, U87 and A7, as well as the squamous cell carcinoma line FaDu. These data were fitted by the linear quadratic model assuming Poisson statistics. The alpha/beta values of A7, U87, and FaDu spheroids, respectively were 10.3 (8.1-12.9) Gy, 17.8 (15.1-21.1) Gy, and 37.9 (29.1-51.5) Gy. These data were compared with those previously published by Suit et al. (31) and Zietman et al. (40) for 6 mm xenografts of U87 and FaDu after fractionated irradiation and for A7 after single dose irradiation under clamped conditions. A good agreement in the alpha/beta values was observed for U87 and Fadu xenografts and spheroids assuming an oxygen enhancement ratio (OER) of 2.7. In addition, the ranking according to the single doses needed to control 50% of the tumors agreed for xenografts and spheroids from the three cell lines. U87 was the most resistant line in both model systems, followed by A7 and FaDu. However, the absolute values of alpha and beta, obtained from the direct fit to the dose-control data were only about half as high for U87 and FaDu xenografts than for the spheroids. Monte Carlo simulations showed that this discrepancy can be explained by a greater tumor heterogeneity of the xenografts. While the number of critical stem cells or spheroid rescuing units equaled the number of cells per spheroid for the three cell lines, the percentage of tumor rescuing units for Fadu and U87 xenografts was estimated to be below 1%. In a next step, survival curves were generated for exponentially growing cells of the three lines. A7 cells were significantly more radioresistant when plated on tissue plastic than in soft agar. Using the most resistance-promoting colony assay conditions for each cell line, a good agreement was observed for the alpha and SF2Gy values calculated from the colony and spheroid control data. This study shows that the spheroid model can quantitatively predict the repair capacity of sublethal damage as well as the rank order of radiation sensitivity of in vivo tumors.     

Antidiuretic-hormone-induced morphological changes in the ampullary epithelium of the frog semicircular canal

Summary Morphological changes induced by in vitro treatment with arginine-vasotocin, the frog antidiuretic hormone, were studied in the ampullary epithelium of the frog semicircular canal. Morphological changes appeared only in the apical side of the dark cells, while the basal part of these cells and the other cells lining the semicircular canal did not show any change. Changes consisted of the appearance of numerous small vesicles in the apical cytoplasm and the development of microvilli on the apical plasma membrane of the dark cells. These results suggest that arginine-vasotocin could play a role in the regulation of endolymph section.     

An Absent Ophthalmic Artery or Carotid Siphon Signal on Transcranial Doppler Confirms the Presence of Severe Ipsilateral Internal Carotid Artery Disease

Transcranial Doppler ultrasound provides a useful adjunct to extracranial ultrasound in the diagnosis of carotid bifurcation disease. Previous studies have shown that collateral flow patterns and diminished flow velocities in the ipsilateral middle cerebral artery correlate with hemodynamically significant carotid disease. In a series of 7,054 carotid duplex and transcranial Doppler examinations, 12.5% (95% confidence interval [CI]: 8.7, 16.4) of 287 ophthalmic arteries ipsilateral to an apparent carotid occlusion had no detectable flow signal, compared with 0.5% (95% Cl: 0.3, 0.7) of 6,767 ophthalmic arteries ipsilateral to a nonoccluded carotid artery (p < 0.001 ). Carotid siphon signals were not detectable in 24.4% (95% Cl: 19.4, 29.4) of arteries ipsilateral to the carotid occlusion, versus 1.0% (95% Cl: 0.8, 1.3) ipsilateral to nonoccluded carotid arteries (p < 0.001 ). A significant number of absent ophthalmic artery and carotid siphon signals (5.7 and 8.7%, respectively) were also found in patients with 80 to 99% extracranial carotid stenosis. A subset of 216 studies with angiographic correlation confirmed the high association of these transcranial Doppler findings with severe stenosis or occlusion of the internal carotid artery. Primary ophthalmological disease or siphon occlusion did not explain these findings. An absent ophthalmic artery or carotid siphon signal on transcranial Doppler examination is believed to represent a failure to detect slow flow distal to severe carotid bifurcation lesions. As a sign of ipsilateral carotid occlusion, the sensitivities of absent ophthalmic artery and carotid siphon signals are quite low (12.5 and 24.4%, respectively). The high specificities of 99.5 and 99.0%, however, make these findings useful in confirming the diagnosis of presumptive carotid occlusion by carotid duplex ultrasound.     

Vécus psychologiques des démarches d'assistance médicale à la procréation

Assisted Reproductive Technologies (ART) come along with important emotional and psychological burden, as well as the physical constraints, for both the woman and her partner. Couples entering ART programs are usually infertile ones, but some specific settings, like serodiscordant couples where the male partner is HIV positive, involving fertile couples. These couples are usually well-adjusted and motivated ones. During the treatments, waiting for the outcome, and the unsuccessful cycles are among the most stressfull experiences. Common reactions are stress, anxiety and depression, but for some couples, the difficulties are so great that they discontinue the program after only one attempt. When parents, the couples usually experience good parenting competencies, and the “precious” children, despite a greater genetic risk, usually have a normal development, but some specific psychological difficulties may arise, that may request a specific help.