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Human papillomaviruses (HPVs) cause more than 4.5% of all cancer in the world and more than half of these cases are attributed to human papillomavirus type 16 (HPV16). Prophylactic vaccines are available but antiviral drugs are not. Novel targets for therapy are urgently needed. Alternative RNA splicing is extensively used by HPVs to express all their genes and HPV16 is no exception. This process must function to perfection since mis‐splicing could perturb the HPV gene expression program by altering mRNA levels or by generating dysfunctional mRNAs. Cis‐acting RNA elements on the viral mRNAs and their cognate cellular trans‐acting factors control papillomavirus RNA splicing. The precise but delicate nature of the splicing process renders splicing sensitive to interference. As such, papillomavirus RNA splicing is a potential target for therapy. Here we summarize our current understanding of cis‐acting HPV16 RNA elements that control HPV16 mRNA splicing via cellular proteins and discuss how they may be exploited as targets for therapy to papillomavirus infections and cancer. [ABSTRACT FROM AUTHOR]

Laryngeal papilloma (LP) is a rare benign disease, caused by recurrent multisite papillomas that are referred to as recurrent respiratory papillomatosis (RRP). RRP is caused primarily by two types of human papillomavirus (HPV): HPV6 and HPV11. The immune dysregulation within the microenvironment of the lesions has been shown to likely play a role in the development of RRP. The present study aimed at analyzing the transcriptional profile of immune response genes and cancer‐related genes in the LP microenvironment. We used the NanoString® nCounter® analysis system to study expression of 730 genes among seven paired samples of LP and healthy laryngeal (HL) tissue. qRT‐PCR and flow cytometric analysis was performed to confirm identified transcripts and follow‐up scores of infiltrating immune cells, respectively. In total, 113 differentially expressed transcripts were detected of which 37 showed increased expression levels and 76 decreased expression levels in the LP samples compared to the HL samples (fold change ≥ 2). Transcripts with increased expression levels included S100As (A7, A8, and A12), CEACAM1, neutrophil activation associated cytokines (IL8), chemokines (CXCL6), and IL receptors, e.g., IL4R. Transcripts with decreased expression in LP were associated with innate and adaptive immunity. Overall, HPV6 and 11 were present in 67% and 33% of the patients, respectively. There was a significant increase in neutrophils and a significant decrease in CD8+ T cells in LP. LP samples display an immune profile characterized by enhanced expression of neutrophilic markers and significantly reduced T cell‐associated markers [ABSTRACT FROM AUTHOR]

Here we show that treatment of the HPV16‐positive tonsillar cancer cell line HN26 with DNA alkylating cancer drug melphalan‐induced p53 and activated apoptosis. Melphalan reduced the levels of RNA polymerase II and cellular transcription factor Sp1 that were associated with HPV16 DNA. The resulting inhibition of transcription caused a rapid loss of the HPV16 early mRNAs encoding E6 and E7 as a result of their inherent instability. As a consequence of HPV16 E6 and E7 down‐regulation, the DNA damage inflicted on the cells by melphalan caused induction of p53 and activation of apoptosis in the HN26 cells. The BARD1‐negative phenotype of the HN26 cells may have contributed to the failure to repair DNA damage caused by melphalan, as well as to the efficient apoptosis induction. Finally, nude mice carrying the HPV16 positive tonsillar cancer cells responded better to melphalan than to cisplatin, the chemotherapeutic drug of choice for tonsillar cancer. We concluded that the short half‐life of the HPV16 E6 and E7 mRNAs renders HPV16‐driven tonsillar cancer cells particularly sensitive to DNA damaging agents such as melphalan since melphalan both inhibits transcription and causes DNA damage. What's new? In most tonsillar cancers involving human papillomavirus 16 (HPV16) infection, the p53 tumor suppressor is rendered nonfunctional by HPV16 E6 protein. As a result, tumor cells escape apoptosis and HPV replication proceeds unhindered. Here, the authors explored the ability of DNA‐damaging drugs to reverse these effects by liberating p53 in HPV‐positive tonsillar cancer cells. The data show that efficient reactivation of p53 and apoptosis requires degradation of HPV16 E6 and E7 mRNAs, as well as induction of the DNA damage response (DDR). The authors identify two drugs, melphalan and actinomycin D, that exert these dual effects in tonsillar cancer cells. [ABSTRACT FROM AUTHOR]

Summary: Invasive fungal diseases (IFD) are a primary cause of morbidity and mortality in patients with haematological malignancies. These infections are mostly life‐threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other Non‐Aspergillus moulds are increasingly identified in case of documented IFD. For definite diagnosis of IFD, a combination of diagnostic tools have to be applied, including conventional mycological culture and non‐conventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. Although varying widely in cancer patients, the risk of invasive fungal infection is highest in those with allogeneic stem cell transplantation and those with acute leukaemia and markedly lower in patients with solid cancer. Since the last edition of Diagnosis of Invasive Fungal Diseases recommendations of the German Society for Hematology and Oncology in 2012, integrated care pathways have been proposed for the management and therapy of IFDs with either a diagnostic driven strategy as opposed to a clinical or empirical driven strategy. This update discusses the impact of this additional evidence and effective revisions. [ABSTRACT FROM AUTHOR]

We prospectively evaluated a multiplex real-time PCR assay (SeptiFast, SF) in a cohort of patients undergoing allo- BMT in comparison to an in-house PCR method ( IH- PCR). Overall 847 blood samples (mean 8 samples/patient) from 104 patients with haematological malignancies were analysed. The majority of patients had acute leukaemia (62%) with a mean age of 52 years (54% female). Pathogens could be detected in 91 of 847 (11%) samples by SF compared to 38 of 205 (18.5%) samples by BC, and 57 of 847 (6.7%) samples by IH- PCR. Coagulase-negative staphylococci (n=41 in SF, n=29 in BC) were the most frequently detected bacteria followed by Escherichia coli (n=9 in SF, n=6 in BC). Candida albicans (n=17 in SF, n=0 in BC, n=24 in IH- PCR) was the most frequently detected fungal pathogen. SF gave positive results in 5% of samples during surveillance vs in 26% of samples during fever episodes. Overall, the majority of blood samples gave negative results in both PCR methods resulting in 93% overall agreement resulting in a negative predictive value of 0.96 (95% CI: 0.95-0.97), and a positive predictive value of 0.10 (95% CI: −0.01 to 0.21). SeptiFast appeared to be superior over BC and the IH- PCR method. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To determine viral load of human papillomavirus type 6 (HPV6), physical state of HPV6-DNA, and transcription level of HPV6 E7-mRNA in laryngeal papilloma and in adjacent healthy mucosa.Study Design: Case series.Methods: A papilloma biopsy was collected from each of 25 adult patients with respiratory recurrent papillomatosis. From 14 of the 25 patients, we first collected a biopsy from healthy mucosa of the false vocal fold and another from the papilloma. Quantity of HPV6 and E7-mRNA was measured by polymerase chain reaction.Results: For the papilloma, the median load of HPV6 was 41 copies/cell, and the lowest amount was 5.4 copies/cell. Human papillomavirus type 6 was detected in 50% (7/14) of the healthy mucosa, with a median of 1.1 copies/cell, and the highest amount was 6.6 copies/cell. Overall, viral load was higher in papilloma than in healthy mucosa (P < 0.05). The average HPV6 E2/E7-DNA ratio was 1.3, indicating an episomal state. Human papillomavirus type 6-mRNA was detected in all HPV6-DNA-positive samples. The transcription median ratio of HPV6-mRNA/HPV6-DNA was 1.5 in papilloma and 3.8 in healthy mucosa.Conclusion: The amount of HPV6-DNA was consistently higher in the papilloma than in healthy mucosa. The transcription level of HPV6 E7 mRNA was similar in the papilloma and in normal mucosa. We suggest that interfering with replication of HPV6 and suppression of HPV6 to fewer than five copies/cell may be curative. [ABSTRACT FROM AUTHOR]

Study Objective Because the incidence rate of renal impairment is 2-10% for patients treated with high-dose methotrexate and renal impairment develops in 0-12.4% of patients treated for osteosarcoma, we sought to evaluate the efficacy of glucarpidase, a recently approved drug that rapidly hydrolyzes methotrexate to inactive metabolites, which allows for nonrenal clearance in patients with delayed renal methotrexate elimination. Design Pooled analysis of efficacy data from four multicenter single-arm compassionate-use clinical trials using protocols from 1993 to 2007. Patients Of 476 patients with renal toxicity and delayed methotrexate elimination who were treated with intravenous glucarpidase for rescue after high-dose methotrexate, 169 patients had at least one preglucarpidase (baseline) plasma methotrexate concentration greater than 1 μmol/L and one postglucarpidase methotrexate concentration measurement by high-performance liquid chromatography and were included in the efficacy analysis; renal recovery was assessed in 436 patients who had at least one recorded preglucarpidase and postglucarpidase serum creatinine concentration measurement. Measurements and Main Results Efficacy was defined as rapid and sustained clinically important reduction ( RSCIR) in plasma methotrexate concentration, with a concentration of 1 μmol/L or lower at all postglucarpidase determinations. Median age of efficacy-evaluable patients was 20 years (range 5 weeks-84 years). Osteosarcoma (36%), non-Hodgkin lymphoma (27%), and acute lymphoblastic leukemia (20%) were the most frequent underlying diagnoses. Median preglucarpidase serum methotrexate was 11.7 μmol/L. At the first (median 15 minutes) through the last (median 40 hours) postglucarpidase measurement, plasma methotrexate concentrations demonstrated consistent 99% median reduction. RSCIR was achieved by 83 (59%) of 140 patients. A total of 64% of patients with renal impairment greater than or equal to Common Terminology Criteria for Adverse Events grade 2 recovered to grade 0 or 1 at a median of 12.5 days after glucarpidase administration. Conclusion Glucarpidase caused a clinically important 99% or greater sustained reduction of serum methotrexate levels and provided noninvasive rescue from methotrexate toxicity in renally impaired patients. [ABSTRACT FROM AUTHOR]

The chromosomal translocation t(8;14)(q24;q32) with juxtaposition of MYC to enhancer elements in the immunoglobulin heavy chain (IGH) gene locus is the genetic hallmark of the majority of Burkitt lymphoma and a subset of Diffuse large B‐cell lymphoma patients. Around 3% of adult B‐lineage acute lymphoblastic leukemia (ALL) patients show this aberration. Flow cytometry mostly reveals a “mature B‐ALL” or “Burkitt‐type” ALL immunophenotype. Using long‐distance PCR for t(8;14)/MYC‐IGH fusion, we investigated bone marrow, peripheral blood and a few other samples with suspected Burkitt‐ALL or mature B‐ALL and identified 133 MYC‐IGH‐positive cases. The location of the chromosomal breaks in the IGH joining and the 8 different switch regions was determined using a set of long‐distance PCRs. The chromosomal breakpoints with the adjacent MYC regions on 8q24 were characterized by direct sequencing in 49 cases. The distribution of chromosomal breaks among the IGH joining and switch regions was the following: JH 23.3%, M 21.8%, G1 15.0%, G2 7.5%, G3 3.8%, G4 4.5%, A1 12.8%, A2 3.8%, E 7.5%. Two breakpoint clusters near MYC were delineated. There was no clear correlation between the degree of somatic hypermutation and the chromosomal break locations. Epstein Barr virus was detected in 5 cases (4%). This detailed and extensive molecular analysis illustrates the molecular complexity of the MYC‐IGH translocations and the detected distribution of breakpoints provides additional evidence that this translocation results from failed switch and VDJ recombinations. This study may serve as a model for the analysis of other IGH translocations in B‐cell lymphoma. Highlights: Establishes an extensive map of MYC‐IGH translocations with previously unmatched accuracy.Shows an unexpectedly high frequency of MYC translocations to the Ce switch region.Reveals complex MYC translocations in a switch‐rearranged IGH gene locus.Investigates correlations between somatic hypermutation and IGH and MYC break location.Provides a map of the most frequently mutated amino acids in the MYC protein. [ABSTRACT FROM AUTHOR]

We provide evidence that the human papillomavirus (HPV) E2 protein regulates HPV late gene expression. High levels of E2 caused a read-through at the early polyadenylation signal pAE into the late region of the HPV genome, thereby inducing expression of L1 and L2 mRNAs. This is a conserved property of E2 of both mucosal and cutaneous HPV types. Induction could be reversed by high levels of HPV-16 E1 protein, or by the polyadenylation factor CPSF30. HPV-16 E2 inhibited polyadenylation in vitro by preventing the assembly of the CPSF complex. Both the N-terminal and hinge domains of E2 were required for induction of HPV late gene expression in transfected cells as well as for inhibition of polyadenylation in vitro. Finally, overexpression of HPV-16 E2 induced late gene expression from a full-length genomic clone of HPV-16. We speculate that the accumulation of high levels of E2 during the viral life cycle, not only turns off the expression of the pro-mitotic viral E6 and E7 genes, but also induces the expression of the late HPV genes L1 and L2. [ABSTRACT FROM AUTHOR]

Zusammenfassung Zerebrale Infektionen mit Aspergillus-Spezies zeigten in der Vergangenheit eine ausgesprochen ungünstige Prognose mit einer Letalität von nahezu 100 %. Um die Diagnose einer zerebralen Aspergillose zweifelsfrei zu belegen, ist meist eine Hirnbiopsie erforderlich. Weiterentwickelte Diagnostikverfahren, insbesondere die Magnetresonanztomografie mit Diffusionswichtung und der Nachweis von Aspergillus-spezifischer DNS mittels PCR, haben in den letzten Jahren die Qualität der indirekten Diagnostik wesentlich verbessert. Ein wesentlicher Grund für die sehr ungünstige Prognose der zerebralen Aspergillose in der Vergangenheit dürfte die nur unzureichende Penetration der meisten verfügbaren Antimykotika gewesen sein. Im Gegensatz zu Amphotericin B, den Echinocandinen und den Azolen Itraconazol und Posaconazol weist Voriconazol bei einem sehr geringen Molekulargewicht eine vergleichsweise sehr gute ZNS-Penetration auf. In der bisher umfangreichsten Studie zur zerebralen Aspergillose führte eine Therapie mit Voriconazol bei 81 Patienten zu einer Ansprechrate von 35 % und einer Überlebensrate von 31 %. Zusätzliche neurochirurgische Interventionen waren in dieser Studie sowie in einer erweiterten Analyse von 120 Patienten mit einer signifikant besseren Überlebenswahrscheinlichkeit assoziiert. Aufgrund der Vielzahl der unterschiedlichen neurochirurgischen Eingriffe ist derzeit jedoch unklar, welches Verfahren für welche klinische Situation am besten geeignet ist. [ABSTRACT FROM AUTHOR]

Summary Immunocompromised patients have a high risk for invasive fungal diseases (IFDs). These infections are mostly life-threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Empirical treatment is regarded as the standard of care for granulocytopenic patients who remain febrile despite broad-spectrum antibiotics. However, this strategy can bear a risk of overtreatment and subsequently induce toxicities and unnecessary treatment costs. Pre-emptive antifungal therapy is now increasingly used to close the time gap between delayed initiation for proven disease and empirical treatment for anticipated infection without further laboratory or radiological evidence of fungal disease. Currently, some new non-invasive microbiological and laboratory methods, like the Aspergillus-galactomannan sandwich-enzyme immunoassay ( Aspergillus GM-ELISA), 1,3-β- d-glucan assay or PCR techniques have been developed for a better diagnosis and determination of target patients. The current diagnostic approaches to fungal infections and the role of the revised definitions for invasive fungal infections, now IFDs, will be discussed in this review as well as old and emerging approaches to empirical, pre-emptive and targeted antifungal therapies in patients with haemato-oncological malignancies. [ABSTRACT FROM AUTHOR]

Summary Endogenous endophthalmitis caused by filamentous fungi has been infrequently described and its prognosis in immunocompromised patients is largely unknown. Patients were identified through a single-centre database containing patients with endophthalmitis. Cases published since 2002 were reviewed. Clinical and treatment features as well as outcomes were analysed. Six patients were identified from the database. Underlying conditions were haematological malignancies (HM) and/or allogeneic haematopoietic stem cell transplantation (HSCT). Three patients underwent vitrectomy. None of the patients survived and the median time from first evidence of endophthalmitis until death was 33 days. The median time from first evidence of an invasive fungal infection to endophthalmitis was only 5 days. Fifty-six patients were identified from the literature. The majority of these patients underwent vitrectomy (27) or enucleation (10) and received intraocular antifungal therapy (28). Only 13 (23%) of 56 patients experienced an improved vision. The survival rate was 52% in all 56 patients but was significantly less in patients with HM or post-HSCT when compared with all others (26% vs. 70%, respectively; P = 0.003). Endogenous endophthalmitis caused by filamentous fungi is frequently associated with a permanent decrease or loss of vision. This type of fungal infection carries a particular poor prognosis in patients with profound immunosuppression, requiring improved treatment strategies. [ABSTRACT FROM AUTHOR]

The article presents a study on the influence of interleukin 15 (IL-15) on the outcome in primary adult acute lymphoblastic leukemia (ALL). The study was made among 87 patients who were part of the German Multicenter Acute Lymphoblastic Leukemia (GMALL) wherein their samples of bone marrow were taken. It reveals that high expression of IL-15 was related with shorter relapse-free survival (RFS). It adds that IL-15 plays a critical role in the failure of contemporary ALL antileukemic therapy.

The expression profile of a panel of RNA-binding proteins (heterogeneous ribonucleoprotein (hnRNP) A1, hnRNP C1/C2, hnRNP H, hnRNP I, ASF/SF2, SR proteins, HuR and U2AF65) and markers of differentiation, proliferation and neoplasia (cytokeratin (CK) 13, CK-14, proliferating cell nuclear antigen (PCNA), Syndecan-1 and p16INK4a) were analyzed in 50 formalin fixed paraffin embedded cervical tissues using immunohistochemistry. The samples included histologically normal cervical epithelium, human papillomavirus (HPV) induced low-grade and high-grade pre-malignant lesions and cervical cancers. All samples were tested for HPV DNA using nested PCR. Forty-nine of the 50 tissue samples tested positive for HPV, 27 tissue samples (54%) were HPV-16 positive and 4 samples (8%) were HPV-18 positive. The immunohistochemistry results detected different expression levels of the various proteins in basal epithelial cells in histologically normal epithelium followed by an increase in expression in the intermediate layers, whereas the superficial layers remained negative for all tested RNA-binding proteins. Expression of all RNA-binding proteins increased in neoplastic lesions and highest expression was detected in cervical cancers. p16INK4a had a stronger association with high-grade lesions when compared with the RNA-binding proteins. The expression profile of the RNA-binding proteins is similar to PCNA expression in histologically normal epithelium as well as in lesions (low-grade and high-grade) and cervical cancers. As PCNA expression has been suggested to mimic HPV E6/E7 expression in cervical epithelium, the results suggest the RNA-binding protein analyzed here regulate HPV early gene expression directly and late gene expression indirectly. J. Med. Virol. 81:897-907, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Recently, improved response and survival rates in patients treated with voriconazole and neurosurgery for central nervous system (CNS) aspergillosis have been reported. We assessed retrospectively the outcome in 17 patients with definite or probable CNS aspergillosis treated with amphotericin B alone ( n = 15) or in combination with 5-fluorocytosine ( n = 3) or itraconazole ( n = 2). Four patients underwent neurosurgery. The mortality rate was 100% with a median survival of only 10 days (range: 3–60) after onset of first symptoms or first radiological evidence of CNS aspergillosis. In conclusion, treatment with amphotericin B and itraconazole has negligible efficacy in CNS aspergillosis. [ABSTRACT FROM AUTHOR]

Killer-immunoglobulin-like receptors (KIR) or C-type lectin-like receptors are heterogeneously expressed on NK cells and small subsets of T cells and might provide a new diagnostic tool for LGL lymphoproliferations (LGLL). We investigated the diagnostic impact of these cell surface molecules in T- and NK-type LGLL. Using three-color flow cytometry we examined the expression patterns of KIR (CD158a/b/e/i), CD85j, lectin-like receptors (CD94, CD161, NKG2A/D) and natural cytotoxicity receptors (NKp30/44/46) in 13 patients with LGLL (10 T-, 3 NK-LGLL) and compared them to those of the corresponding lymphocyte subsets in 20 control subjects. The presence of clonal TCR-gamma rearrangements and of Epstein Barr virus- (EBV) DNA were evaluated by PCR. All patients exhibited an altered expression of NK-associated markers. KIR were either lacking (6/13) or overexpressed (7/13). CD94 expression was significantly higher in all LGLL. NKG2A expression was significantly higher in NK-LGLL. Absence or overexpression was observed for NKG2A in T-LGLL and CD161 in most T/NK-LGLL. In NK-LGLL expression of NKp30 and NKp46 was significantly decreased, whereas CD85j was overexpressed. We consistently found a skewed expression pattern of novel NK markers as a pathological feature of LGLL. These antigens should be included in the diagnostic workup of this rare disease. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Overexpression of the embryonic transcription factor, Wilms’ tumour protein 1 (WT1), is common in acute myeloid leukaemias (AML). Mutations of Wilms’ tumour gene 1 ( WT1) in AML are rare and WT1 expression may be increased by other transcription factors. PAX2, PAX8 and GATA-1 are known physiological regulators of WT1. In the present study, we analysed either bone marrow or blood samples of 43 AML patients for the expression levels of WT1, PAX2, PAX8 and GATA-1 by real-time reverse transcription polymerase chain reaction (LightCycler). Bone marrow samples of patients without haematological malignancies and stem cell preparation samples from healthy donors and lymphoma patients served as controls. PAX2 expression was found in 11 of 43 AML samples, with a clear correlation of PAX2 with WT1 expression levels observed. PAX8 expression was found in two additional samples. GATA-1 expression was detectable in 41 of 43 AML samples and also in all control samples; no significant differences between these groups were observed and no correlation of GATA-1 expression with WT1 expression levels was apparent. In conclusion, PAX2, and possibly PAX8, appears to be a candidate for the upregulation of WT1 in a proportion of AML, whereas GATA-1 expression cannot be explained as an inducer of WT1. In two-thirds of leukaemias from our series, the basis of WT1 upregulation cannot be explained by the simple upregulation of the known WT1 activators. [ABSTRACT FROM AUTHOR]

Summary. An unusual course was observed in a patient with indolent T-prolymphocytic leukaemia (T-PLL) who subsequently developed mycosis fungoides (Mf), lymphomatoid papulosis (LyP) and cutaneous CD30+ anaplastic large cell lymphoma (ALCL). Polymerase chain reaction analysis demonstrated identical monoclonal T-cell receptor-β and -γ gene rearrangements in all the different clinical entities. Furthermore, cytogenetic studies revealed the same aberrant clone with trisomy of chromosome 8 in T-PLL and ALCL cells. This unique observation suggests that in T-PLL, the leukaemic cells might undergo secondary transformation, subsequently resulting in different phenotypes of cutaneous T-cell lymphoma. [ABSTRACT FROM AUTHOR]

CD82 (KAI1) is a member of the tetraspan transmembrane protein family which has been cloned from lymphoblastoid variant cell lines. However, a role for CD82 in early normal and malignant haemopoiesis has not yet been characterized. We studied the CD82 expression in 33 normal donor samples and 98 leukaemias by fluorescence activated cell sorting (FACS) and reverse transcriptase polymerase chain reaction (RT-PCR). We demonstrated that CD82 was moderately expressed in the vast majority of normal granulocytes and monocytes. In contrast, only about one third of the peripheral blood lymphocytes were weakly CD82 positive (CD82+). Interestingly, judgement of the CD82 transcription and expression in various leukaemias revealed that CD82 was overexpressed in chronic myeloid leukaemia (CML) patients in accelerated or blastic phase (CML-AP/BP) as well as in acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL) patients. Analysis of AML patients with CD34+/CD82+ blasts prompted us to expand our studies on haemopoietic CD34+ progenitor cells. Intriguingly, 84–95% of the CD34+ cells isolated from healthy bone marrow, cord blood or peripheral blood were highly CD82+. CD82 was abundantly expressed on primitive as well as on committed haemopoietic progenitor cells. After in vitro induction of myeloid differentiation in CD34+ peripheral blood progenitor cells (PBPC), the expression of CD82 decreased to levels similar to those found on peripheral blood granulocytes. These observations suggest for the first time a role for CD82 in normal and malignant haemopoiesis. [ABSTRACT FROM AUTHOR]

Hydroxyethyl starch (HES) is usually considered to be associated with limited side effects. Generalized foamy cell macrophage syndrome after HES therapy has rarely been reported since Schaefer first described it as ‘hydrops lysosomalis generalisatus’ in 1982. We present a 19-yr-old male who received large amounts of HES. A bone marrow and a liver biopsy were performed because of persistent thrombocytopenia and liver dysfunction. We found severe infiltration of foamy cell degenerated macrophages in both organ systems, indicating that sequelae of HES therapy have to be included in the differential diagnosis of bone marrow and liver dysfunction. [ABSTRACT FROM AUTHOR]

Discusses the case of intramedullary abscess in a patient with disseminated Scedosporium apiospermum infection. Re-induction of chemotherapy; Resistance to antifungal agents.

Deals with the diagnosis of rhabdomyosarcoma. Details on the immunophenotyping of bone marrow aspirate; Cells that were visible in stained smears.