Treatment of Burkitt's/Burkitt-like lymphoma in adolescents and adults: a 20-year experience from the Norwegian Radium Hospital with the use of three successive regimens.

BACKGROUND: Burkitt's/Burkitt-like lymphoma (BL/BLL) are highly aggressive lymphomas mainly affecting children and young adults. We report the results in adolescent and adult patients with the use of three successive regimens. PATIENTS AND METHODS: Forty-nine patients aged 15-70 years admitted to the Norwegian Radium Hospital in the period 1982-2001 with a diagnosis of BL/BLL on histological review and who were given chemotherapy with curative intent are included in this analysis. Up to 1987 patients were given doxorubicin-based chemotherapy supplemented with intravenous and intrathecal methotrexate (MmCHOP). From 1987 to 1994, patients who obtained complete remission upon this regimen were consolidated with high-dose therapy with stem-cell support (MmCHOP + HDT). In 1995 we introduced as frontline therapy the German Berlin-Frankfurt-Munster (BFM) regimen. RESULTS: By intention to treat analyses, the progression-free survival rates for patients who received MmCHOP (n=13), MmCHOP + HDT (n=17) or BFM therapy (n=19) are 30.8%, 70.6% and 73.7%, respectively. In the groups of patients who received either the BFM regimen or MmCHOP + HDT, all patients who obtained complete remission upon induction therapy are continuously disease free. There was no treatment-related death. CONCLUSIONS: BL/BLL in adolescents and adults can successfully be treated with 5-day blocks of intensified chemotherapy such as the BFM regimen or CHOP/methotrexate-based chemotherapy consolidated with high-dose therapy. Using the BFM regimen, continuous remissions are obtained without additional myeloablative chemotherapy.     

Low perfusion pressure during CPB may induce cerebral metabolic and ultrastructural changes

Background. Recently we reported on cerebral metabolic changes suggesting ischemia in piglets during nitroprusside-induced low-pressure CPB. We here investigated whether a mean arterial pressure (MAP) of 40–45 mmHg could provoke similar changes by a NO-independent intervention. Methods. Piglets underwent 60 minutes normothermic followed by 90 minutes hypothermic CPB. The LP-group (n=8) had MAP of 40–45 mmHg by phentolamine while the HP-group (n=8) had MAP of 60–80 mmHg by norepinephrine. Cerebral glucose, lactate, pyruvate and glycerol were determined. In the last two animals of each group, cerebral tissue was examined by electron microscopy. Results. Cerebral lactate was higher in the LP-group than the HP-group during normothermic CPB. Compared with baseline, cerebral glucose of the LP-group decreased whereas lactate/pyruvate-ratio, lactate and glycerol-concentrations increased during normothermic CPB. In the HP-group these parameters remained unchanged. Electron microscopy showed 31.2% and 8.3% altered mitochondria in the cortical micrographs taken from the LP- and the HP-group, respectively (p<0.001). Conclusion. MAP below 45 mmHg during CPB was associated with cerebral biochemical and morphological changes consistent with anaerobic metabolism and subcellular injury.     

The Arts and Health Communication in Uganda: A Light Under the Table

This qualitative interview study brings the voices of 27 public health leaders, health communication experts, and artists who work in public health in Uganda together to articulate the principles and practices that make the country a shining example of effective, evidence-based use of the arts for health communication. The specific aim of the study was to identify best practices, theoretical foundations, and other factors that contribute to the success of arts-based health communication campaigns in Uganda.

The study presents four primary themes related to use of the arts for health communication in Uganda: (1) the arts empower health communication; (2) the arts engage people emotionally; (3) effective programs are highly structured; and (4) professionalism is critical to program effectiveness. The findings suggest that the arts humanize, clarify, and empower health communication. The arts can attract attention and engage target populations, reduce hierarchical divisions and tensions that can challenge communication between health professionals and community members, make concepts clearer and more personally and culturally relevant, and communicate at an emotional level wherein concepts can be embodied and made actionable. The findings articulate why and how the arts are an effective means for health communication and can guide best practices.     

Intraoperative fluid balance during cardiopulmonary bypass: effects of different mean arterial pressures

INTRODUCTION: This study investigated whether two levels of mean arterial pressure (MAP) during cardiopulmonary bypass did influence per-operative fluid shifts. METHODS: Sixteen pigs underwent 60 minutes of normothermic cardiopulmonary bypass (CPB) followed by 90 minutes of hypothermic CPB. Eight animals had a MAP of 60-80mmHg by norepinephrine (HP group). Another 8 animals had a MAP of 40-45 mmHg by phentolamine (LP group). Blood chemistry, plasma/interstitial colloid osmotic pressures, plasma volume, fluid balance, fluid extravasation rate and tissue water content were measured or calculated. RESULTS: The plasma volume was significantly lower in the HP group compared with the LP group after 60 minutes of CPB. Net fluid balance was 0.18 (0.05) ml x kg(-1) x min(-1) in the HP group and 0.21 ml x kg(-1) x min(-1) in the LP group (P > 0.05) while fluid extravasation rate was 1.18 (0.5) and 1.13 (0.4) ml x kg(-1) x min(-1) in the HP group and the LP group during CPB (P > 0.05). CONCLUSION: Net fluid balance and fluid extravasation rate were similar in the animals with elevated and with lowered MAP during CPB.     

Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients

Here, we present results from a clinical trial employing a new vaccination method using dendritic cells (DCs) transfected with mRNA from allogeneic prostate cancer cell lines (DU145, LNCaP and PC-3). In all, 20 patients were enrolled and 19 have completed vaccination. Each patient received at least four weekly injections with 2 x 10(7) transfected DCs either intranodally or intradermally. Safety and feasibility of vaccination were determined. Immune responses were measured as delayed-type hypersensitivity and by in vitro immunoassays including ELISPOT and T-cell proliferation in pre- and postvaccination peripheral blood samples. Serum prostate-specific antigen (PSA) levels and bone scans were monitored. No toxicity or serious adverse events related to vaccinations were observed. A total of 12 patients developed a specific immune response to tumour mRNA-transfected DCs. In total, 13 patients showed a decrease in log slope PSA. This effect was strengthened by booster vaccinations. Clinical outcome was significantly related to immune responses (n = 19, P = 0.002, r = 0.68). Vaccination with mRNA-transfected DCs is safe and results in cellular immune responses specific for antigens encoded by mRNA derived from the prostate cancer cell lines. The observation that in some patients vaccination affected the PSA level suggests that this approach may become useful as a treatment modality for prostate cancer patients.     

Depletion of T lymphocytes from human bone marrow. Use of magnetic monosized polymer microspheres coated with T-lymphocyte-specific monoclonal antibodies

A new technique for depletion of T cells from bone marrow is presented. Bone marrow cells (BMC) were rosetted with magnetic monosized polystyrene microspheres coated with monoclonal antibodies (MAbs) specific for T cell CD2 and CD3 antigens. Rosetted T cells were subsequently removed from non-T cells with the aid of a magnet. This immunomagnetic separation procedure was carried out in less than 40 min and reproducibly removed T cells, leaving a maximum of 0.025% sheep-red-blood-cell (SRBC) rosette-forming cells and less than 0.02% T cells as detected by a T cell limiting dilution assay. The efficacy of the depletion procedure was further shown by flow cytometry data, by effective removal of cells from a T cell line added to the BMC prior to immunomagnetic separation, and by abrogation of interleukin 2 (IL-2)-producing capacity in T-cell-depleted BMC (BMC-T). The T cell depletion procedure provided a 43-74% recovery of non-T cells present in the Isopaque-Ficoll-isolated bone marrow mononuclear cell fraction and did not disturb the growth potential of stem cells, as assayed by hematopoietic stem cell assays.     

Mean arterial pressure about 40 mmHg during CPB is associated with cerebral ischemia in piglets

Objective. To investigate if a mean arterial pressure below 50 mmHg during CPB may lead to cerebral ischemia. Material and methods. Piglets with low mean arterial pressure by nitroprusside (LP-group) (n?=?6) were compared with piglets given norepinephrine to obtain high pressure (HP-group) (n?=?6) during normothermic and hypothermic CPB. Intracranial pressure, flow and markers of cerebral energy metabolism (microdialysis) were recorded. Results. Mean arterial pressure differed significantly between the groups and stabilized about 40–45 mmHg in the LP-group. Cerebral perfusion pressure decreased to 21.3 (7.7) mmHg in the LP-group and increased to 51.8 (11.2) mmHg in the HP-group at 150 min of CPB (P?<?0.001, between groups). During bypass the intracerebral glucose concentration decreased significantly in the LP-group. In this group the lactate/pyruvate ratio increased from 15.5 (5.3) to 64.5 (87.6) at 90 min and 45.0 (36.5) at 150 min (P?<?0.05) with no such changes in the HP-group. Similarly the cerebral glycerol concentration increased significantly in the LP-group, whereas glycerol remained stable in the HP-group. Conclusion. Mean arterial pressure about 40 mmHg during CPB is associated with cerebral ischemia.     

Targeting Telomerase with an HLA Class II-Restricted TCR for Cancer Immunotherapy

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