Qualitative study of psychosocial factors impacting on Aboriginal women's management of chronic disease.

BACKGROUND: Aboriginal women are frequently called upon to support their families and other community members. At times, such supporting roles can be burdensome for these women. Many Aboriginal women live with chronic conditions. We explored the ways in which the women's caring roles impacted on how they maintained their own health. METHODS: The aim of this manuscript is to explore the psychosocial factors associated with the management of health and chronic disease in Aboriginal women. An interpretive phenomenological approach was used for the analysis of 72 in-depth semi-structured interviews. These interviews were conducted in four community controlled Aboriginal health services, in urban, rural and remote settings, across two states and a territory in Australia. RESULTS: Women living with chronic disease experience multiple challenges while caring for family, such as intergenerational trauma, mental health issues relating to addiction, domestic and family violence and incarceration. When these women become ill, they also have to take care of themselves. These women provided informal and unfunded care in response to a range of complex family and community problems. This continuous caring for family affected the women's ability to maintain their health and manage their own chronic conditions. CONCLUSION: The caring roles and responsibilities Aboriginal women have in their community impact on their health. Aboriginal women provide much needed refuge and support to family and the wider community. Underfunded and over-burdened formal support services are not meeting the needs of many Aboriginal women. Improved culturally secure resources and social services are required within communities to support Aboriginal women to successfully manage their own health.

Progenitor cells from patients with advanced phase chronic myeloid leukaemia respond to STI571 in vitro and in vivo.

STI571 targets p210(BCR-ABL) in chronic myeloid leukaemia (CML). In vitro, STI571 reduces self-replication (replating ability) by chronic-phase CML CFU-GM. Here, we studied CFU-GM in advanced-phase (accelerated and blast crisis) CML. The numbers and self-replication of CFU-GM in advanced phase were greater than in the chronic phase. Self-replication by CFU-GM from advanced phase patients was reduced by STI571 or IFN alfa to the same extent as in the chronic phase. The reduced replating ability induced by STI571 correlated with that induced by IFN alpha (r=0.73). STI571 treatment in vivo also reduced replating ability and the numbers of CFU-GM/ml of blood.

A multiphase CFD model of DAF process.

A Eulerian-Eulerian multiphase CFD model is employed for the air/water flow. A 3D structure grid is used to incorporate the air nozzle and tank geometry. The fixed frictionless wall boundary approximating the free surface acts as a sink to allow the air bubbles to escape. The air/water volume fraction in the flotation tank is evaluated to determine the effective air/water fluid density. The floc particle is then introduced and is tracked in the air/water fluid using a disperse Lagrangean model. Fate of these flocs depends on their sizes and density. Flocs therefore can either escape through the top water surface, settles in the main tank or breakthrough under the outlet weir. The CFD model is developed for a full scale DAF tank to predict the flow dynamic, particle removal and settled solid profile. The general flow pattern is compared with flow visualisation using the underwater camera. Comparison of average fluid velocities is carried out using acoustic Doppler velocimetry ADV measurement.

Treatment of spent filter backwash water using dissolved air flotation.

There is increasing interest in treating recovered spent filter backwash water in the drinking water industry. In the USA the Filter Backwash Recycling Rule will come into effect in the near future. The purpose of the Rule is to prevent the concentrated pathogenic agents, potentially in the filter backwash water, from being returned to the head of the water treatment works without some form of treatment or dilution. By treating this flow both public health and financial liability can be better managed by the operating utility. Dissolved Air Flotation (DAF) was investigated as a possible technology alternative to simple or advanced sedimentation techniques. This application is not widespread but sits somewhere in between the two normal applications of DAF as a high solids sludge thickener and a low turbidity clarification system. Given this a pilot plant program, supported by jar testing, was undertaken to determine the process capability and the design parameters for this application. DAF proved to be very suitable for backwash water recovery. DAF effluent turbidities of < 1.0 NTU could be easily obtained, when raw water turbidities were in excess of 50 NTU. Chemical requirements were low with only a single low dose of polymer required to bind the floc particles to form a solids matrix suitable for flotation. Flocculation contact times ranged from 0-10 minutes depending on the nature of the raw water. Recycle rates as low as 5% performed satisfactorily with no significant improvement when increased to 20%. Sludge solids of 3.5-9.6% dry solids were found and very low volumes of sludge, < 0.1% of the incoming flow make the DAF solids handling system very compact.

Pharmacokinetics of CAMPATH-1H in BMT patients.

BACKGROUND: CAMPATH-1 (CD52)Abs are used in stem-cell transplantation for prevention of GvHD and rejection. The humanized Ab CAMPATH1H has recently replaced the rat Ab CAMPATH-1G. There was a concern whether it might have a longer half-life in vivo and, possibly, cause prolonged immunosuppression post-transplant. METHODS: Serum samples were collected pre- and post-transplant from patients receiving CAMPATH-1H at 10 mg/day according to two protocols: (A) from Day -5 to Day +4 (total dose, 100 mg), (B) from Day -10 to Day -6 (total dose, 50 mg). The Ab concentrations were measured using an immunofluorescence assay. RESULTS: Lymphocytes were substantially depleted by the second day of treatment and were below 0.1 x 10(9)/L by the day of transplant and for at least 1 month post-transplant. By Day 90 there was a greater recovery in Group B, to a median of 0.32 x 10(9)/L compared with 0.25 x 10(9)/L in Group A. By Day 180, both groups had recovered to approx 0.52 x 10(9)/L. Serum concentrations of CAMPATH-1H on the day of transplant were well above the level necessary for opsonization of lymphocytes. The peak Ab concentration was 6.1 micro g/mL in Group A and 2.5 micro g/mL in Group B. CAMPATH-1H could be detected in Group A for 23 days post-transplant, significantly longer than in Group B (11 days). The terminal half-life in the two groups was similar (range 15-21 days) and contrasts with the half-life of < 1 day previously estimated for CAMPATH-1G. There were no cases of graft failure and the incidence of GvHD was similar in the two groups. DISCUSSION: The humanized Ab CAMPATH-1H appears to persist in the circulation for longer than the original rat Ab CAMPATH-1G. This might contribute to delayed lymphocyte recovery and prohibit the use of early donor-lymphocyte infusions. A short course of treatment given early pre-transplant is likely to be preferable to the extended course given both pre- and post-transplant.

A phase I/II study of multiple-dose intravenous busulfan as myeloablation prior to stem cell transplantation.

Busulfan has been previously only available in an oral formulation due to its poor water solubility. We report the results of a phase I study of multiple escalating doses of intravenous busulfan (Spartaject Busulfan, Orphan Europe, Paris, France) for myeloablation prior to stem cell transplantation (SCT) in 12 patients with chronic myeloid leukemia, acute myeloid leukemia or acute lymphocytic leukemia. One patient received allogeneic SCT; the other 11 patients received autologous SCT. The first six patients received i.v. busulfan diluted in 50 ml of 0.9% normal saline and the last six patients received busulfan in a 500-ml 5% dextrose solution. All patients experienced profound myelosuppression and all but one demonstrated hematopoietic engraftment. Toxicity was mild or moderate and there were no toxic deaths attributable to busulfan. Of note, there were no cases of veno-occlusive disease of the liver. Busulfan plasma concentrations were determined by gas chromatography with electron capture detection and showed little intrapatient variability. In most cases there was no significant difference between the first and last dose PK parameters. These data suggest that dose adjustment based on first dose PK data could allow uniformity of busulfan dosing for patients receiving SCT.

The IFN-gamma response of the murine invariant chain gene is mediated by a complex enhancer that includes several MHC class II consensus elements.

IFN-gamma induces the expression of the MHC class II-associated invariant chain (IN) protein in a variety of cells of nonlymphoid origin. Here we analyze the transcription from the murine invariant chain gene and delimit the cis-acting sequences which confer IFN-gamma responsiveness in human fibroblasts. The major start of transcription of the gene is located 29 bp 3' of a TATA box and 85 bp 5' of the single ATG codon which opens the reading frame. To identify the regulatory elements of the murine IN promoter which respond to IFN-gamma, the 5' flanking region of the gene including its capsite and 85 bp of coding region have been cloned in front of the bacterial chloramphenicol acetyl transferase (CAT) gene. Examination of this construct and various 5' and 3' deletion mutants for IFN-gamma inducibility in transient transfection assays revealed that DNA sequences between -261 and -189 were essential and sufficient for the induction. Removal of sequences between -215 and -189 reduced inducibility of the IN-promoter and abolished the capacity of the element to transmit inducibility to a heterologous promoter. Single or multiple base changes in other parts of the element also abolished inducibility. Cotransfection of a 350 molar excess of the IFN-gamma response element with an inducible IN-CAT chimeric construct blocked inducibility, suggesting positive regulation. A protein binding to the central part of the IFN-gamma response element was detectable in gel retardation experiments; it was active only in extracts from IFN-gamma-treated cells.

Interferon-gamma, mitomycin C, and cycloheximide as regulatory agents of MHC class II-associated invariant chain expression.

The murine and human major histocompatibility complex class II-associated invariant chain genes are expressed in mature B cells and in antigen-presenting cells. Several pre-B cell lines and fibroblasts do not naturally contain invariant chain mRNA. Expression is inducible, however, by interferons and other agents interfering with proliferation. Mitomycin C induces the transcription of the gene in pre-B cells, but not in fibroblasts. Interferon-gamma acts in both types of cells. Cycloheximide inhibits the induction of the invariant chain mRNA by interferon-gamma, suggesting that protein synthesis is required. In fact, cycloheximide itself increases the transcriptional rate at the invariant chain gene, suggesting the existence of a labile repressor or an indirect action through cycloheximide arrest of the cell cycle. Lipopolysaccharide (LPS) activation of B lymphocytes causes a rapid decrease of the invariant chain mRNA level and of the amount of invariant chain protein due to rapid turnover. Also class II alpha and beta mRNA expression decreases after LPS treatment. The decrease of invariant chain protein is accompanied by increased surface expression of alpha and beta. The murine invariant chain gene transfected into human fibroblasts is regulated by the same agents and the same dose of agents as is the endogenous gene. The differentiation marker invariant chain thus seems to be transcribed from a gene that is accessible to regulation even in nonlymphoid cells and the expression of which is linked to states of nonproliferation. The sequence responsible for these responses is contained within the cloned genomic fragment and is conserved between mouse and man.