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Zusammenfassung Einleitung Das West-Nil-Virus (WNV) ist ein weit verbreitetes Flavivirus, das hauptsächlich zwischen Vögeln von verschiedenen Mückenarten (z. B. Culex, Aedes) übertragen wird, aber auch auf Säugetiere einschließlich Menschen übertragen werden kann. Das Krankheitsspektrum reicht von asymptomatischen Infektionen bis hin zu infektiöser Enzephalitis. Risikofaktoren für schwere Erkrankungen sind Alter, Herz-Kreislauf-Erkrankungen und ein immungeschwächter Zustand. Anamnese und klinischer Befund Hier berichten wir über einen 60-jährigen männlichen Patienten, der 2 Jahre nach seiner Nierentransplantation aufgrund einer hypertensiven Nephropathie mit schwerem Fieber an das Universitätsklinikum Halle (Saale) überwiesen wurde. Untersuchungen und Diagnose Es konnte zunächst kein Infektionsfokus gefunden werden. Am 6. Tag im Verlauf seiner Krankheit entwickelte der Patient neurologische Symptome, sodass der Verdacht auf eine virale Enzephalitis gestellt wurde. Therapie und Verlauf Die im Raum stehende virale Enzephalitis wurde mit Aciclovir parenteral anbehandelt. Nach initialer Reduktion der Immunsuppression wurde eine koinzidente Funktionsverschlechterung des Nierentransplantats mit Methylprednisolon behandelt. Eine WNV-Infektion wurde aufgrund kürzlich aufgetretener Fälle bei Menschen in der näheren Umgebung der Stadt Leipzig vermutet. Es konnte WNV der Linie 2 im Urin des Patienten durch RT-PCR und im Verlauf eine Serokonversion von anti-WNV-IgM zu anti-WNV-IgG nachgewiesen werden. Die Behandlung mit Aciclovir wurde u. a. daraufhin abgebrochen. Der Patient erholte sich vollständig und die transplantierte Niere erlangte wieder eine angemessene Funktion. Die Biopsie des Transplantats zeigte keine relevante Abstoßung. Folgerung Dieser Fall unterstreicht die Notwendigkeit, seltenere Krankheitsursachen wie die WNV-Infektion insbesondere in Risikogruppen zu berücksichtigen. WNV kann mittels PCR im Blut und Liquor früh im Verlauf der Infektion nachgewiesen werden, wird aber auch über einen längeren Zeitraum im Urin ausgeschieden. Eine Serokonversion zu anti-WNV-IgG und -IgM kann gezeigt werden, aber die serologische Kreuzreaktivität in der Flavivirus-Familie muss berücksichtigt werden.

Ocular manifestations of syphilis with visual impairment symptoms may occur already at the stage of secondary syphilis. They may also be the only manifestation of syphilis and mimic other diseases of the eye. Therefore, in all patients with uveitis, optic neuritis, optic atrophy, acute ocular muscle paresis, or loss of visual acuity, syphilis infection should be ruled out, even if the medical history does not initially raise suspicion. Ocular involvement should be treated as neurosyphilis. Delayed diagnosis and inadequate therapy are often associated with irreversible consequences for the affected patient. As with any syphilis infection, HIV infection should be considered and excluded, especially in the case of ocular manifestations.

Evaluation of skin diseases can be challenging for non-dermatologists. Even obvious well-characterized skin pathologies might be misleading and thus treatment can fail. Particularly the differentiation of surgical treated entities is important, for example the management of a wound healing disturbance profoundly differs from that of a pyoderma gangrenosum. This article outlines several easily mistaken pairs of dermatologic entities on one hand and surgical on the other. For example, a livedo vasculopathy can be confused with a leg ulcer, a nail melanoma with a simple hematoma and finally a hidradenitis suppurativa with an axillary abscess. Typical clinical signs and anamnestic data may often lead to the right diagnosis also assisted by the simple fact to “keep it in mind“.

Livedoid vasculopathy (LV) has been shown to be associated with hypercoagulability. However, relevant genetic and exogenous thrombophilic factors are not fully determined.To evaluate the frequency of hyperhomocysteinaemia (HHCE) and genotypes of hypercoagulative factors in LV patients.Plasma homocysteine level was measured in 42 LV patients. Polymorphism of MTHFR (677C T and 1298A C), PAI1 (-675 5G/4G and -844A G), and F2 (20210G A), and the F5 Leiden mutation, as well as biochemical parameters for hypercoagulability, were analysed.Of the LV patients, 62% revealed mild HHCE. Polymorphisms of MTHFR were observed in 75% and 56% and the PAI1 -675 5G/4G polymorphism in 100% and 83% of patients with and without HHCE, respectively. All LV patients with renal failure had mild HHCE. A high level of comorbidity of hypertension (99%) and diabetes type 2 (44%) were noted.HHCE seems to play a major pathogenetic role in LV. A high prevalence of further procoagulative factors might support the view that LV is a "complex disease".

Reagiert die Haut unter anderem mit Exanthemen auf eine Therapie, die den Rezeptor des epidermalen Wachstumsfaktors hemmt, ist dies ein gutes Zeichen fur den Behandlungserfolg. Trotzdem leiden die Patienten unter der Toxizitat. Wie lasst sie sich in den Griff bekommen?

High-dose steroids in combination with other immunosuppressant substances, usually azathioprine, are the therapy of choice in pemphigus vulgaris. Complete remission can be difficult to achieve, with mucosal lesions often recalcitrant. We describe two patients in whom gold in the form of sodium aurothiomalate was effective in resolving mucosal lesions. Initially both patients were treated with high-dose corticosteroids, one in combination with mycophenolate mofetil. Their oral lesions proved to be stubborn but responded well to intramuscular gold, which also showed a steroid-sparing effect, so that the dosage of corticosteroids could be reduced to a minimum. Sodium aurothiomalate was continued until both patients were in remission without any side effects.

SummaryIn thrombin-stimulated human platelets several proteins undergo rapid and transient changes in tyrosine phosphorylation. We demonstrate that a set of proteins of 27, 29, 31, 34, and 39 kDa is affected by released ADP and P2Y12 receptor signaling during platelet activation. AR-C69931MX, an antagonist of the Gi2-coupled P2Y12 ADP receptor, inhibits initial tyrosine phosphorylation of p27 and p31 and prevents subsequent dephosphorylation of p29, p34, and p39. Antagonists of the Gq-coupled P2Y1 ADP receptor have no effect. Precluding integrin αIIbβ3 outside-in signaling with RGDS or S1197 does not affect the increase in tyrosine phosphorylation of the set of proteins but inhibits their subsequent dephosphorylation. Besides the ADP analogue 2-MeS-ADP, other platelet agonists such as collagen and the TXA2-mimetic U46619 also induce p27 and p31 tyrosine phosphorylation in a P2Y12 receptor-dependent manner. Tyrosine phosphorylation of p27 and p31 in response to collagen, but not thrombin, is prevented by aspirin and the TXA2 receptor antagonist SQ29548, indicating that the effect of collagen strongly relies on TXA2 signaling. Furthermore, epinephrine, acting via inhibitory Gz-coupled α2A-adrenoceptors, bypasses the inhibitory effect of AR-C69931MX on thrombin-induced p27 and p31 tyrosine phosphorylation. Finally, we demonstrate that tyrosine phosphorylation of p27 and p31 downstream of P2Y12 receptors is due to the inhibition of adenylyl cyclase but not phosphoinositide 3-kinase (PI 3-K) activation. Elevating cAMP levels with PGI2 or forskolin precludes thrombin-induced p27 and p31 tyrosine phosphorylation. Moreover, direct inhibition of adenylyl cyclase by SQ22536 reverses the effect of AR-C69931MX. Our data indicate that the observed changes in tyrosine phosphorylation are the result of both primary Gq signaling, initiating the release of ADP, as well as subsequent P2Y12 receptor-mediated Gi coupling.

SummaryStimulating human platelets with thrombin induces the activation of the extra cellular signal-regulated kinase 2 (ERK2). We demonstrate that this effect is highly dependent on ADP secretion and P2Y12 receptor signalling. AR-C69931MX (10 µM), a specific antagonist of the Gi-coupled P2Y12 ADP receptor, inhibits ERK2 activation induced by thrombin. Antagonists of the Gq-coupled P2Y1 ADP receptor, A3P5P (500 µM) and MRS2179 (100 µM), have no effect. ADP and its more potent analogue 2-methylthio-ADP alone (both up to 100 µM) do not induce ERK2 activation. Furthermore, we show that the inhibitory effect of AR-C69931MX on ERK2 activation induced by 0.1 U/ml thrombin as well as on platelet aggregation can be bypassed by epinephrine (1 and 10 µM), whereas epinephrine alone has no effect. Epinephrine acts on platelets mainly via α2A-adrenergic receptors, which, like P2Y12 receptors, couple to inhibitory G proteins. In addition, 2-methylthioADP as well as epinephrine provoke ERK2 activation at a thrombin concentration that alone has no detectable effect (0.05 U/ml). Thromboxane A2 (TXA2), which, like ADP, is released by activated platelets, acts as a positive feedback mediator. Stimulating the Gq-coupled TXA2-receptor with U46619 (10 µM), which leads to ADP secretion and P2Y12 receptor dependent platelet aggregation, also induces P2Y12-related ERK2 activation. The inhibition of U46619-induced ERK2 activation and platelet aggregation by AR-C69931MX are also rescued by epinephrine. Pretreatment with aspirin inhibits ERK2 activation induced by 0.1 U/ml thrombin, but has no effect at high concentrations of thrombin. The combination of U46619 and thrombin, at concentrations which alone have no effect, provokes ERK2 activation, suggesting that thrombin and released TXA2 act synergistically. Our data indicate that both primary signalling through Gq, which evokes ADP secretion, as well as subsequent coupling via Gi by the P2Y12 receptor are required for ERK2 activation.