Replicative multivirus infection with cytomegalovirus, herpes simplex virus 1, and parvovirus B19, and latent Epstein-Barr virus infection in the synovial tissue of a psoriatic arthritis patient.

BACKGROUND: Psoriatic arthropathy occurs as complicating feature in about 5-7% of psoriasis patients. Infectious mechanisms including viral antigens have been suggested by serologic data as CD8 T cellular specifity towards viral epitopes. OBJECTIVE AND RESULTS: We here reported a case of a 32-year-old male psoriatic arthritis patient, where we could demonstrate simultaneous infection with cytomegalovirus (CMV), herpes simplex virus type I (HSV1) and parvovirus B19 (B19), as well as latent Epstein-Barr virus (EBV) infection within the synovial tissue by immunohistochemistry (CMV, parvovirus B19, HSV1, EBV-LMP) and DNA-in situ-hybridization (CMV). Serologic examination revealed positive EBV and parvovirus B19-IgG-antibodies, but no antibody response to HSV1 and CMV. CONCLUSION: This case is of special interest, since replicative viral infections have not yet been demonstrated localised in the psoriatic arthritis synovia. Thus, with particular regard to the limited information of the serologic data and the possible need of immuno suppressive therapy direct synovial testing for viral antigenes may be considered in psoriatic arthritis patients.     

Pulmonary tuberculosis due to bacille Calmette-Guérin

Summary Immunotherapy using bacille Calmette-Guérin (BCG) has gained increasing acceptance in the management of superficial bladder cancer. Systemic reactions after intravesical instillation of BCG are rare. However, when the therapy is complicated, the lung often becomes involved. Since the pathogenesis of lung infiltrates after immunotherapy is unknown, we report on a patient who developed a lung infiltrate after receiving BCG immunotherapy for bladder cancer. The infectious etiology was established by culture confirmation of a BCG strain in the broncheoalveolar lavage fluid.Abbreviation BCG bacille Calmette-Guérin     

Über die prednisolonähnliche Wirkung von Corticosteronderivaten

Zusammenfassung Es wird über die Prüfung zweier Derivate des Corticosterons an 67 bzw. 34 Patienten eines dermatologischen Krankengutes berichtet. Die klinische Wirksamkeit des einen Pr?parates war deutlich geringer als die von Prednisolon, w?hrend die des anderen dem therapeutischen Effekt von Prednisolon entsprach.

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Summary The results of a clinical trial with two derivatives of corticosterone in 67 resp. 34 dermatological cases are described. The efficiency of the first substance was significantly less than that of prednisolone, while the other one was equally efficient as prednisolone.

     

Charcot-Marie-Tooth neuropathy type 2 and P0 point mutations: two novel amino acid substitutions (Asp61Gly; Tyr119Cys) and a possible "hotspot" on Thr124Met

Mutations in the gene for the major protein component of peripheral nerve myelin, myelin protein zero (MPZ, P0), cause hereditary disorders of Schwann cell myelin such as Charcot-Marie-Tooth neuropathy type 1B (CMT1B), Dejerine-Sottas syndrome (DSS), and congenital hypomyelinating neuropathy (CHN). More recently, P0 mutations were identified in the axonal type of CMT neuropathy, CMT2, which is different from the demyelinating variants with respect to electroneurography and nerve pathology. We screened 49 patients with a clinical and histopathological diagnosis of CMT2 for mutations in the P0 gene. Three heterozygous single nucleotide changes were detected: two novel missense mutations, Asp61Gly and Tyr119Cys, and the known Thr124Met substitution, that has already been reported in several CMT patients from different European countries. Haplotype analysis for the P0 locus proved that our patients with the 124Met allele were not related to a cohort of patients with the same mutation, all of Belgian descent and all found to share a common ancestor. Our data suggest that P0 mutations account for a detectable proportion of CMT2 cases with virtually every patient harbouring a different mutation but recurrence of the Thr124Met amino acid substitution. The high frequency of this peculiar genotype in the European CMT population is presumably not only due to a founder effect but Thr124Met might constitute a mutation hotspot in the P0 gene as well.     

Vorschlag für eine Konsensus-Klassifikation der periprothetischen Membran gelockerter Hüft- und Knieendoprothesen

After 10 years, loosening of total joint endoprostheses occurs in about 3 to 10 percent of all patients, requiring elaborate revision surgery. A periprosthetic membrane is routinely found between bone and loosened prosthesis. Further histomorphological examination allows determination of the etiology of the loosening process. Aim of this study is the introduction of clearly defined histopathological criteria for a standardized evaluation of the periprosthetic membrane. Based on histomorphological criteria and polarized light microscopy, four types of the periprosthetic membrane were defined: periprosthetic membrane of wear particle type (type I), periprosthetic membrane of infectious type (type II), periprosthetic membrane of combined type (type III), periprosthetic membrane of indifferent type (type IV). Periprosthetic membranes of 268 patients were analyzed according to the defined criteria. The correlation between histopathological and microbiological diagnosis was high (89%, p<0,001), the inter-observer reproducibility was sufficient (95%). This classification system enables a standardized diagnostic procedure and therefore is a basis for further studies concerning the etiology of and pathogenesis of prosthesis loosening.     

Toll-like receptor 9 contributes to recognition of Mycobacterium bovis Bacillus Calmette-Guérin by Flt3-ligand generated dendritic cells

Recognition of mycobacteria by the innate immune system is essential for the development of an adaptive immune response. Mycobacterial antigens stimulate antigen presenting cells (APCs) through distinct Toll-like receptors (TLRs) resulting in rapid activation of the innate immune system. The role of TLRs during infection with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) has been evaluated for TLR2 and TLR4 only. Surprisingly, despite the fact that immune stimulatory CpG-motifs have been originally derived from BCG, for the vaccine strain the role of TLR9 has not been addressed before. To identify the set of TLRs involved in the recognition of BCG, we infected bone marrow-derived macrophages and bone marrow-derived dendritic cells (Flt3-ligand generated DCs) from TLR2, TLR3, TLR4, TLR7, TLR9, MyD88 knockout, TLR2/4 and TLR2/4/9 multiple knockout mice. The degree of activation and stimulation was determined by TNFα, IL-6 and IL-12p40 ELISA. Activation of DCs was measured by surface expression of the costimulatory molecule CD86. We observed the most dramatic reduction of the inflammatory response for TLR2-deficient antigen presenting cells. Both macrophages and DCs produce markedly decreased amounts of TNFα and IL-6 in the absence of TLR2 whereas no significant reduction could be observed for TLR3, 4, 7, 9 single TLR-knockouts. However, IL-12 production in DCs appears not exclusively dependent on TLR2 and only in TLR2/4/9-deficient DCs BCG-induced IL-12 is reduced to background levels. Similarly, up-regulation of CD86 is abolished only in TLR2/4/9-deficient DCs supporting a role of TLR9 in the recognition of M. bovis BCG by murine dendritic cells.     

False-positive results of plasma PCR for cytomegalovirus DNA due to delayed sample preparation

Positive results by cytomegalovirus (CMV) PCR of plasma are considered predictive of active CMV infection in kidney allograft recipients. To assess whether contamination with leukocyte-derived CMV DNA can distort the results, aliquots of whole-blood samples from 60 CMV immunoglobulin G-positive patients with leukocyte CMV DNAemia were stored for up to 24 h at room temperature (RT) and at 4 degrees C before plasma preparation. Native and ultrafiltered plasma samples were tested by CMV and beta-globin PCRs. Among 30 latently infected patients (negative for CMV pp65 antigens), low baseline rates (10%) and levels (median number of copies, 10 [per 10 microl]) of CMV plasma DNAemia in native plasma samples increased significantly over time (after 4 h at RT, 37% [P < 0.001]; median number of copies, 45 [P < 0.001]). Similar effects were found during storage at 4 degrees C. Ultrafiltration reduced the levels of CMV plasma DNAemia, but by 6 h of storage the levels were significantly elevated as well. CMV and beta-globin DNA kinetics in plasma were parallel. In contrast, 30 actively infected patients (pp65 positive) had high baseline rates (87% in native samples) and levels (median number of copies, 75) of CMV plasma DNAemia. No significant effects of storage or ultrafiltration and no concordance with beta-globin DNA kinetics were seen. In conclusion, delayed preparation of plasma samples bears a significant risk of false-positive CMV PCR results, probably due to leukocyte lysis. This has important implications in the clinical setting and for PCR standardization.     

Clinical Significance of Epithelial Peptide Antibiotics

Although the epithelium of macro-organisms is constantly exposed to microbial threats, infections are rather rare. Antimicrobial substances produced by epithelial cells may explain the high natural resistance of the exposed epithelia. Gene-encoded antimicrobial peptides that are believed to kill micro-organisms via pore formation have been found in the surface cells and secretions of plants and insects, and in the skin of frogs. The tongues and lungs of cattle are usually free of infection, and the first mammal-derived epithelial antimicrobial peptides, which belong to the so-called beta-defensin family, were discovered in bovine trachea and tongue. These beta-defensins are induced by infections and inflammatory agents, and are upregulated in specific anatomical sites of the epithelia, where infections occur. Recent studies have revealed that human epithelia also express beta-defensins: the tissues of the urogenital tract constitutively express human beta-defensin-1 (HBD-1), and a second human beta-defensin, HBD-2, is produced in skin and lung upon stimulation of epithelial cells with infectious or inflammatory agents. This brief review summarises our current knowledge about epithelial antimicrobial peptides, and discusses their possible role and relevance in the clinic. This includes the possibility of defective production in patients with recurrent infections, the therapeutic use of synthetic antimicrobial peptides, and the induction of their synthesis as an alternative strategy to prevent infections.