Polyfluoroalkyl chemicals in pooled blood serum from infants, children and adults in Australia

Polyfluoroalkyl chemicals (PFCs) have been used worldwide for more than 50 years in a wide variety of industrial and consumer products. Limited data exist on human exposure to PFCs in the Southern Hemisphere. Human blood serum collected in southeast Queensland, Australia, in 2006−2007 from 2420 donors was pooled according to age (cord blood, 0−0.5, 0.6−1, 1.1−1.5, 1.6−2, 2.1−2.5, 2.6−3, 3.1−3.5, 3.6−4, 4.1−6, 6.1−9, 9.1−12, 12.1−15, 16−30, 31−45, 46−60, and >60 years) and gender and was analyzed for eight PFCs. Across all pools, perfluorooctane sulfonate (PFOS) was detected at the highest mean concentration (15.2 ng/mL) followed by perfluorooctanoate (PFOA, 6.4 ng/mL), perfluorohexane sulfonate (PFHxS, 3.1 ng/mL), perfluorononanoate (PFNA, 0.8 ng/mL), 2-(N-methyl-perfluorooctance sulfonamide) acetate (Me-PFOSA-AcOH, 0.66 ng/mL), and perfluorodecanoate (PFDeA, 0.29 ng/mL). Perfluorooctane sulfonamide was detected in only 24% of the pools, and 2-(N-ethylperfluorooctane sulfonamide) acetate was detected in only one. PFOS concentrations were significantly higher in pools from adult males than from adult females (p = 0.002); no gender differences were apparent in the pools from children (<12 years old). The highest mean concentrations of PFOA, PFHxS, PFNA, PFDeA, and Me-PFOSA-AcOH were found in children <15 years, while PFOS was highest in adults >60 years. Investigation into the sources and exposure pathways in Australia, in particular for children, is necessary as well as continued biomonitoring to determine the potential effects on human concentrations as a result of changes in the PFC manufacturing practices, including the cessation of production of several PFCs.

Serum polybrominated diphenyl ethers (PBDE) in pooled serum are higher in children (2-5 years of age) than in infants and adults

Background: Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in many products and have been detected in human samples worldwide. Limited data show that concentrations are elevated in young children. Objectives: We investigated the association between PBDEs and age with an emphasis on young children from Australia in 2006–2007. Methods: We collected human blood serum samples (n = 2,420), which we stratified by age and sex and pooled for analysis of PBDEs. Results: The sum of BDE-47, -99, -100, and -153 concentrations (Σ4PBDE) increased from 0–0.5 years (mean ± SD, 14 ± 3.4 ng/g lipid) to peak at 2.6–3 years (51 ± 36 ng/g lipid; p < 0.001) and then decreased until 31–45 years (9.9 ± 1.6 ng/g lipid). We observed no further significant decrease among ages 31–45, 45–60 (p = 0.964), or > 60 years (p = 0.894). The mean Σ4PBDE concentration in cord blood (24 ± 14 ng/g lipid) did not differ significantly from that in adult serum at ages 15–30 (p = 0.198) or 31–45 years (p = 0.140). We found no temporal trend when we compared the present results with Australian PBDE data from 2002–2005. PBDE concentrations were higher in males than in females; however, this difference reached statistical significance only for BDE-153 (p = 0.05). Conclusions: The observed peak concentration at 2.6–3 years of age is later than the period when breast-feeding is typically ceased. This suggests that in addition to the exposure via human milk, young children have higher exposure to these chemicals and/or a lower capacity to eliminate them. Key words: Australia, children, cord blood, human blood serum, PBDEs, polybrominated diphenyl ethers. Environ Health Perspect 117:1461–1465 (2009). doi:10.1289/ehp.0900596

Selective accumulation of virus-specific CD8+ T cells within the peripheral blood stem cell compartment

The absence of cellular immunity is central to the pathogenesis of herpesvirus-mediated diseases after allogeneic hemopoietic stem cell transplantation (HSCT). For both bone marrow (BM)– and granulocyte-colony stimulating factor–mobilized peripheral blood stem cells (PBSCs) HSCT, donor-derived Epstein-Barr virus (EBV) and cytomegalovirus (CMV) peptide–specific CD8+ T cells clones undergo early expansion and persist long-term, with additional diversification arising from novel antigen-specific clones from donor-derived progenitors. Whether BM or PBSC is the superior source of antiviral CD8+ T cells is unclear. Given that PBSC has largely replaced BM as a source of stem cells for HSCT, it is unlikely that herpesvirus effector T-cell reconstitution will ever be compared prospectively. PBSC grafts contain 10 to 30 times more T cells than BM and a randomized study found proven viral infections were more frequent in BM than PBSC recipients, suggesting viral-specific T-cell immunity is enhanced in PBSC. Recently Moss showed in lung cancer patients that herpesvirus-specific BM-derived CD8+ T cells have unique homing properties relative to herpesvirus-specific CD8+ T cells present in unmobilized peripheral blood (PB). Immunodominant EBV-lytic peptide–specific CD8+ T cells were enriched in BM but were reduced for CMV peptide–specific CD8+ T cells relative to PB. EBV-latent peptide–specific CD8+ T cells were equivalent, which has relevance in the context of posttransplantation lymphoproliferative disorder for which impaired EBV-latent CD8+ T-cell immunity is a risk-factor. A comparison of herpesvirus-specific cellular immunity in PBSC versus PB has yet to be performed.

A brief history of haemotopoietic stem cell Ex vivo expansion

Haematopoiesis is the process by which a hierarchy of mature and progenitor blood cells are formed. These cell populations are all derived from multipotent haematopoietic stem cells (HSC), which reside in the bone marrow ‘niche’ of adult humans. Over the lifetime of a healthy individual, this HSC population replenishes between 1010-1011 blood cells on a daily basis. Dysregulation of this system can lead to a number of haematopoietic diseases, including aplastic anaemias and leukaemias, which result in, or require for disease resolution, bone marrow cell depletion. In 1956, E. Donnall Thomas demonstrated that haematopoiesis could be restored by transplanting bone marrow-derived cells from one man into his identical twin brother, who was suffering from advanced leukaemia. His success drew significant interest in academic research and medicine communities, and 12 years later, the first successful allogeneic transplant was performed. To this day, HSCs remain the most studied and characterised stem cell population. In fact, HSCs are the only stem cell population routinely utilised in the clinic. As such, HSCs function as a model system both for the biological investigation of stem cells, as well as for their clinical application. Herein, we briefly review HSC transplantation, strategies for the ex vivo cultivation of HSCs, recent clinical outcomes, and their impact on the future direction of HSC transplantation therapy.

Increased generation of platelet-derived microparticles following percutaneous transluminal coronary angioplasty

Platelet-derived microparticles (PMPs) which are produced during platelet activation contribute to coagulation1 and bind to traumatized endothelium in an animal model2. Such endothelial injury occurs during percutaneous transluminal coronary angioplasty (PTCA), a procedure which restores the diameter of occluded coronary arteries using balloon inflations. However, re-occlusions subsequently develop in 20-25% of patients3, although this is limited by treatment with anti-platelet glycoprotein IIb/IIIa receptor drugs such as abciximab4. However, abciximab only partially decreases the need for revascularisation5, and therefore other mechanisms appear to be involved. As platelet activation occurs during PTCA, it is likely that PMPs may be produced and contribute to restenosis. This study population consisted of 113 PTCA patients, of whom 38 received abciximab. Paired peripheral arterial blood samples were obtained from the PTCA sheath: 1) following heparinisation (baseline); and 2) subsequent to all vessel manipulation (post-PTCA). Blood was prepared with an anti-CD61 (glycoprotein IIIa) fluorescence conjugated antibody to identify PMPs using flow cytometry, and PMP results expressed as a percentage of all CD61 events. The level of PMPs increased significantly from baseline following PTCA in the without abciximab group (paired t test, P=0.019). However, there was no significant change in the level of PMPs following PTCA in patients who received abciximab. Baseline clinical characteristics between patient groups were similar, although patients administered abciximab had more complex PTCA procedures, such as increased balloon inflation pressures (ANOVA, P=0.0219). In this study, we have clearly demonstrated that the level of CD61-positive PMPs increased during PTCA. This trend has been demonstrated previously, although a low sample size prevented statistical significance being attained6. The results of our work also demonstrate that there was no increase in PMPs after PTCA with abiciximab treatment. The increased PMPs may adhere to traumatized endothelium, contributing to re-occlusion of the arteries, but this remains to be determined. References: (1) Holme PA, Brosstad F, Solum NO. Blood Coagulation and Fibrinolysis. 1995;6:302-310. (2) Merten M, Pakala R, Thiagarajan P, Benedict CR. Circulation. 1999;99:2577-2582. (3) Califf RM. American Heart Journal.1995;130:680-684. (4) Coller BS, Scudder LE. Blood. 1985;66:1456-1459. (5) Topol EJ, Califf RM, Weisman HF, Ellis SG, Tcheng JE, Worley S, Ivanhoe R, George BS, Fintel D, Weston M, Sigmon K, Anderson KM, Lee KL, Willerson JT on behalf of the EPIC investigators. Lancet. 1994;343:881-886. (6) Scharf RE, Tomer A, Marzec UM, Teirstein PS, Ruggeri ZM, Harker LA. Arteriosclerosis and Thrombosis. 1992;12:1475-87.

Increased platelet-derived microparticles in the coronary circulation of percutaneous transluminal coronary angioplasty patients

Platelet-derived microparticles that are produced during platelet activation are capable of adhesion and aggregation. Endothelial trauma that occurs during percutaneous transluminal coronary angioplasty (PTCA) may support platelet-derived microparticle adhesion and contribute to development of restenosis. We have previously reported an increase in platelet-derived microparticles in peripheral arterial blood with angioplasty. This finding raised concerns regarding the role of plateletderived microparticles in restenosis, and therefore the aim of this study was to monitor levels in the coronary circulation. The study population consisted of 19 angioplasty patients. Paired coronary artery and sinus samples were obtained following heparinization, following contrast administration, and subsequent to all vessel manipulation. Platelet-derived microparticles were identified with an anti-CD61 (glycoprotein IIIa) fluorescence-conjugated antibody using flow cytometry. There was a significant decrease in arterial platelet-derived microparticles from heparinization to contrast administration (P 0.001), followed by a significant increase to the end of angioplasty (P 0.004). However, there was no significant change throughout the venous samples. These results indicate that the higher level of platelet-derived microparticles after angioplasty in arterial blood remained in the coronary circulation. Interestingly, levels of thrombin–antithrombin complexes did not rise during PTCA. This may have implications for the development of coronary restenosis post-PTCA, although this remains to be determined.

Models of survivorship care provision in adult patients with haematological cancer : an integrative literature review

Purpose: Increasing numbers of haematology cancer survivors warrants identification of the most effective model of survivorship care to survivors from a diverse range of haematological cancers with aggressive treatment regimens. This review aimed to identify models of survivorship care to support the needs of haematology cancer survivors. Methods: An integrative literature review method utilised a search of electronic databases (CINAHL, Medline, PsycInfo, PubMed, EMBASE, PsycArticles, Cochrane Library) for eligible articles (up to July 2014). Articles were included if they proposed or reported the use of a model of care for haematology cancer survivors. Results: Fourteen articles were included in this review. Eight articles proposed and described models of care and six reported the use of a range of survivorship models of care in haematology cancer survivors. No randomised controlled trials or literature reviews were found to have been undertaken specifically with this cohort of cancer survivors. There was variation in the models described and who provided the survivorship care. Conclusion: Due to the lack of studies evaluating the effectiveness of models of care, it is difficult to determine the best model of care for haematology cancer survivors. Many different models of care are being put into practice before robust research is conducted. Therefore well-designed high quality pragmatic randomised controlled trials are required to inform clinical practice.

Provision of survivorship care for patients with haematological malignancy at completion of treatment: a cancer nursing practice survey study

Purpose Many haematological cancer survivors report long-term physiological and psychosocial effects, which persist far beyond treatment completion. Cancer services have been required to extend care to the post-treatment phase to implement survivorship care strategies into routine practice. As key members of the multidisciplinary team, cancer nurses’ perspectives are essential to inform future developments in survivorship care provision. Methods This is a pilot survey study, involving 119 nurses caring for patients with haematological malignancy in an Australian tertiary cancer care centre. The participants completed an investigator developed survey designed to assess cancer care nurses’ perspectives on their attitudes, confidence levels, and practice in relation to post-treatment survivorship care for patients with a haematological malignancy. Results Overall, the majority of participants agreed that all of the survivorship interventions included in the survey should be within the scope of the nursing role. Nurses reported being least confident in discussing fertility and employment/financial issues with patients and conducting psychosocial distress screening. The interventions performed least often included, discussing fertility, intimacy and sexuality issues and communicating survivorship care with the patient’s primary health care providers. Nurses identified lack of time, limited educational resources, lack of dedicated end-of-treatment consultation and insufficient skills/knowledge as the key barriers to survivorship care provision. Conclusion Cancer centres should implement an appropriate model of survivorship care and provide improved training and educational resources for nurses to enable them to deliver quality survivorship care and meet the needs of haematological cancer survivors.

What are the barriers of quality survivorship care for haematology cancer patients? Qualitative insights from cancer nurses

Purpose: Many haematological cancer survivors report long-term physiological and psychosocial effects beyond treatment completion. These survivors continue to experience impaired quality of life (QoL) as a result of their disease and aggressive treatment. As key members of the multidisciplinary team, the purpose of this study is to examine the insights of cancer nurses to inform future developments in survivorship care provision. Methods: Open text qualitative responses from two prospective Australian cross-sectional surveys of nurses (n=136) caring for patients with haematological cancer. Data were analysed thematically, using an inductive approach to identify themes. Results: This study has identified a number of issues that nurses perceive as barriers to quality survivorship care provision. Two main themes were identified; the first relating to the challenges nurses face in providing care (‘care challenges’), and the second relating to the challenges of providing survivorship care within contemporary health care systems (‘system challenges’). Conclusions: Cancer nurses perceive the nature of haematological cancer and its treatment, and of the health care system itself, as barriers to the provision of quality survivorship care. Care challenges such as the lack of a standard treatment path and the relapsing or remitting nature of haematological cancers may be somewhat intractable, but system challenges relating to clearly defining and delineating professional responsibilities and exchanging information with other clinicians are not. Implications for Cancer Survivors: Addressing the issues identified will facilitate cancer nurses’ provision of survivorship care, and help address haematological survivors’ needs with regard to the physical and psychosocial consequences of their cancer and treatment.

Haematology and Plasma Biochemistry of Wild Black Flying-Foxes, (Pteropus alecto) in Queensland, Australia

This paper establishes reference ranges for hematologic and plasma biochemistry values in wild Black flying-foxes (Pteropus alecto) captured in South East Queensland, Australia. Values were found to be consistent with those of other Pteropus species. Four hundred and forty-seven animals were sampled over 12 months and significant differences were found between age, sex, reproductive and body condition cohorts in the sample population. Mean values for each cohort fell within the determined normal adult reference range, with the exception of elevated levels of alkaline phosphatase in juvenile animals. Hematologic and biochemistry parameters of injured animals showed little or no deviation from the normal reference values for minor injuries, while two animals with more severe injury or abscessation showed leucocytosis, anaemia, thrombocytosis, hyperglobulinemia and hypoalbuminemia.

British Society of Haematology, Slide Session presented at the Annual Scientific Meeting, Brighton 2009

P>Seven cases were discussed by an expert panel at the 2009 Annual Scientific Meeting of the British Society of Haematology. These cases are presented in a similar format to that adopted for the meeting. There was an initial discussion of the presenting morphology, generation of differential diagnoses and then, following display of further presenting and diagnostic information, each case was concluded with provision of a final diagnosis.