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Background In Ethiopia, HBV and HIV are co-circulating. Since patients are not routinely tested for HBV, the use of antiretroviral drugs could contribute to unintended HBV drug resistance and surface gene variability during HIV coinfection.Methods A total of 161 hepatitis B surface antigen (HBsAg)-positive sera from 58 HIV-coinfected and 103 drug-naive HBV-monoinfected individuals were characterized for HBV drug resistance and immune escape HBsAg variants. HBV polymerase/surface gene fragment of 716 bp was analysed by direct sequencing.Results In 34 out of 161 study subjects (21.1%) HBV drug resistance mutations (DRMs) were detected with a frequency of 3.1% rtL80F/I, 0.6% rtA181V, 1.2% rtT184S, 6.2% rtV173L, 10.6% rtL180M, 10.6% rtM204V/I and 8.1% rtI233V. The prevalence of the major DRMs in HBV–HIV-coinfected individuals was significantly higher than monoinfected individuals (41.4% versus 10.7%). Lamivudine selected DRMs, that is, rtL180M (29.3%) and rtM204V/I (29.3%) and rtV173L (15.5%) were more prevalent in HBV–HIV-coinfected individuals but absent in HBV-monoinfected individuals. Despite the finding that rtL180M and rtM204V/I were higher among ART-experienced individuals, the overall prevalence of DRMs (48.0% versus 36.4%) showed no significance difference among antiretroviral therapy (ART) status. The study also revealed higher frequency and heterogeneity of putative and known immune escape HBsAg mutations both in the major hydrophilic region (MHR; 68.3%) and outside the MHR (82.5%) of the surface gene. In particular, the ‘a’ determinant surface gene mutations (sT125S, sA128V, sQ129H/R, sT131I, sC137S, sT143M, sD144D/E, sG145R, sT148P) and the majority of clustered/multiple as well as drug selected immune escape HBsAg mutations were more prevalent in HBV–HIV-coinfected individuals.Conclusions HIV therapy without HBV co-management in Ethiopia fosters emergence and circulation of HBV variants of public health importance. It is highly recommended to include HBV testing and co-management as part of routine HIV care programmes for a better ART selection.

Induced pluripotent stem cells (iPSCs) have the ability to differentiate into any specialized somatic cell type, which makes them an attractive tool for a wide variety of scientific approaches, including regenerative medicine. However, their pluripotent state and their growth in compact colonies render them difficult to access and, therefore, restrict delivery of specific agents for cell manipulation. Thus, our investigation focus was set on the evaluation of the capability of layer-by-layer (LbL) designed microcarriers to serve as a potential drug delivery system to iPSCs, as they offer several appealing advantages. Most notably, these carriers allow for the transport of active agents in a protected environment and for a rather specific delivery through surface modifications. As we could show, charge and mode of LbL carrier application as well as the size of the iPSC colonies determine the interaction with and the uptake rate by iPSCs. None of the examined conditions had an influence on iPSC colony properties such as colony morphology and size or maintenance of pluripotent properties. An overall interaction rate of LbL carriers with iPSCs of up to 20% was achieved. Those data emphasize the applicability of LbL carriers for stem cell research. Additionally, the potential use of LbL carriers as a promising delivery tool for iPSCs was contrasted to viral particles and liposomes. The identified differences among those delivery tools have substantiated our major conclusion that LbL carrier uptake rate is influenced by characteristic features of the iPSC colonies (most notably colony size) in addition to their surface charges.

Das plötzliche Erscheinen des schweren akuten respiratorischen Syndroms (SARS) im Jahre 2003 zeigte der ganzen Welt, dass sich trotz des hohen Standards der medizinischen Versorgung in betroffenen Ländern eine hochinfektiöse neu entstandene Erkrankung rasch weltweit ausbreiten konnte. Durch stringente Anwendung und Verbesserung von Infektionskontrollmaßnahmen konnten eine weitere Ausbreitung von SARS verhindert und die Krankheit zunächst beherrscht werden. Zwischenzeitlich wurden entscheidende Fortschritte in der Kenntnis über die Struktur und weitere Eigenschaften des SARS-Corona-Virus (SARS-CoV) einschließlich des möglichen Virusreservoirs und der Ausbreitungswege erzielt. Validierte diagnostische Tests stehen jetzt zur Verfügung und werden verbessert. Effektive Vakzinen und antivirale Substanzen sind in Entwicklung. Von hoher Wichtigkeit, um gegen einen erneuten Ausbruch von SARS gewappnet zu sein, bleiben neben der genauen Kenntnis des viralen Krankheitserregers und seines möglichen weiteren Verhaltens die stetige Wachsamkeit, frühzeitige Erkennung und sofortige Isolierung von SARS-Verdachtsfällen.

Small cell carcinomas (SmCCs) of the uterine cervix are rare tumors. The knowledge regarding protein expression of several checkpoint candidates of cell cycle regulation is limited. Surgically treated SmCCs were selected from our files for immunohistochemical staining (neuroendocrine markers, p53, p16, p14, and cyclin D1). Polymerase chain reaction analysis, using general primers, was performed for human papillomavirus analysis. Nine of 677 tumors (1.3%) were classified as SmCCs after Grimelius staining (8/9 tumors positive) and immunohistochemical reaction against neurone-specific enolase, chromogranin A, synaptophysin (7/9 positive tumors), and CD 56 (8/9 positive tumors). All specimens were positive for at least two of the above. Two SmCCs were p53 positive and one case was p14 positive. Cyclin D1 staining was completely negative. All cases showed strong nuclear and/or cytoplasmic p16-immunostaining. Seven tumors represented human papillomavirus positivity for high-risk types. Four patients died of the tumor after a median time of 36.7 months (range, 15-56 months), representing a 5-year survival rate of 56%. The results suggest that p16 is up-regulated or accumulated in the SmCCs of the uterine cervix, probably caused by infection with human papillomavirus. p14 inactivation is of high prevalence in SmCCs and detection rate of p53 is similar to other histologic types of cervical carcinomas.

We assessed epidemiologic, clinical and laboratory features of aseptic meningitis during one season of multiserotype enteroviral meningitis in East Germany in 70 consecutive patients with aseptic meningitis admitted to the Children’s University Hospital Leipzig.

Epigenetic immune cell counting provides a potentially more robust platform to diagnose immune defects in adults and newborns.

Al-Ali: Novartis: Consultancy, Honoraria, Research Funding. Westerman:Intrinsic Life Sciences: Employment, Membership on an entity's Board of Directors or advisory committees. Hehme:Novartis: Employment. Niederwieser:Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau.

Abstract 1307

42 consecutive pts (23 male/19 female, median age 57 [range:18-70] years) with AML who underwent allogeneic HCT from February, 2008 - February, 2009 at the University of Leipzig were included. Each patient was assessed 10 days prior to and at a median of 3 (range: 3-5) months after HCT. Donors were matched related in 8 (19%) and matched unrelated (MUD) in 34 (81%) pts. Preparative regimen consisted of 12 Gy TBI/cyclophosphamid 120 mg/kg (ATG was included for unrelated HCT) in 13 (31%) and fludarabin 30 mg/m2/day for 3 days/2 Gy TBI) in 29 (69%) pts. Acute GvHD > grade II was present in 13 (31%) and chronic GvHD in 17 (40%) pts. HFE genotype prior to and after HCT was assessed by PCR technique. Body iron was assessed by serum ferritin (sf) (normal values < 400ng/mL). Serum hep was measured by hepcidin C-ELISA at Intrinsic LifeSciences LLC, La Jolla, CA.(normal values: male 29-254 ng/mL, female: 17-286 ng/mL). Hep levels of 21 age-and gender-matched healthy volunteers (6 m/15 f, median age 57 years) were used as a control.Median serum hep was much higher in pts both prior to [median 358 (range:56-1096) ng/ml] and after HCT [median 398 (range:172-941) ng/ml] compared with the control group [median 52 (range:8.3-131) ng/ml] (p<0.0001). Age and gender had no influence on hep values. Similarly, liver function, interval between diagnosis and HCT, number of chemotherapies, conditioning regimen, antibiotic- or antifungal-treatments had no impact on hep level. Iron overload was already seen in all pts prior to HCT with a median sf of 1945 (range: 617-6981) ng/mL after a median number of 22 units BT. Although after HCT the number of BT mounted to a median of 30 units (p<0.0001), sf with a median of 2260 ng/mL remained elevated comparable to the level prior to HCT. Lower hep levels significantly correlated with fewer BT (p=0.001), but surprisingly not with sf values. Hep correlated inversely with the degree of anemia (p=0.002). Mutations in the HFE gene were found in 19 (46%) pts prior to HCT (heterozygosity (het) for H63D, n=11, het C282Y, n=3, het S65C, n=1, and homozygosity (homo) for H63D, n=4) and in 15 (37.5%) pts after HCT reflecting donor genotype (het for H63D,n=12, het C282Y, n=1, compound-het, n=1). Mutations in the HFE gene were not associated with lower hep levels.After HCT, 19 (45%) pts showed a decline in hep level of 155 (range: 394.8-9.5) ng/ml and 23 (55%) pts had an increase in hep levels of 138 (range: 43.3- 620.9) ng/ml compared with pre-transplantaion levels. None of the above mentioned parameters could predict or correlate with these changes in serum hep. Iron overload prior to HCT strongly correlated with later extensive chronic GvHD (p=0.003) and tended to correlate with limited GvHD (p=0.06). On the other hand, hep levels at any time point did not correlate with acute or later chronic GvHD.Serum hepcidin is highly elevated in pts with AML prior to as well as after allogeneic HCT compared with healthy controls mainly because of frequent blood transfusions leading to elevated iron stores. This suggests that hepcidin synthesis and upregulation remain intact despite intensive chemotherapy and HCT. Hepcidin normally binds to ferroportin, leading to intracellular retention of iron in macrophages and to a reduction of extracellular serum iron. This may explain why serum hepcidin correlates with blood transfusions but not with serum ferritin values. Actually, overexpression of hepcidin may play an important protective role in this setting as it may prevent an increased ferroportin-mediated iron export from macrophages thereby reducing the severity of parenchymal iron loading and damage.Westerman: INTRINSIC LIFESCIENCES LLC: Consultancy, Employment, Equity Ownership. Hehme:Novartis: Employment. Niederwieser:Novartis: Speakers Bureau. Al-Ali:Novartis: Research Funding.

Abstract 4047