Blastic plasmacytoid dendritic cell neoplasm: the first report of two cases treated by 5‐Azacytidine

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy which was first included as an independent cutaneous lymphoma in the 2008 World Health Organisation (WHO) classification (1). BPDCN usually has an extremely poor prognosis, with quick relapses after chemotherapy (2; 3). Here, we report two cases of patients diagnosed in 2011 with BPDCN and myelodysplasia, and who were treated for the first time with 5‐azacytidine (5‐Aza); a drug approved by the Food and Drug Administration (FDA) and mainly used in the treatment of myelodysplastic syndrome (Kaminskas E, et al. 2005 Clin Cancer Res, 11, 3604–8). The first case was an 81‐year‐old man who presented with unusual CD10+, CD56‐ immunohistochemistry and 45X, ‐Y abnormality using fluorescent in situ hybridization (FISH) analysis. The second case was a 78‐year‐old woman who manifested monosomy 13 and chromosome instability due to D13S319 locus deletion in 13q14 as determined by FISH. Both patients showed excellent responses of their skin lesions after one cycle of chemotherapy, and their hematological disease was stabilized; however, pulmonary sepsis set in, followed by neutropenia after the fourth and the fifth cycle of treatment, that is, eight and 9 months postdiagnosis, respectively, leading to patient death.     

Amélioration de la perfusion des organes vitaux par la valve d’impédance inspiratoire et le concept de pompe respiratoire : rationnel physiologique et application clinique

Objective

In this article, we review the effects of the respiratory pump to improve vital organ perfusion by the use of an inspiratory threshold device.

Data sources

Medline and MeSH database.

Study selection

All papers with a level of proof of I to III have been used.

Data extraction

The analysis of the papers has focused on the physiological modifications induced by intrathoracic pressure regulation.

Data synthesis

Primary function of breathing is to provide gas exchange. Studies of the mechanisms involved in animals and humans provide the physiological underpinnings for “the other side of breathing”: to increase circulation to the heart and brain. We describe studies that focus on the fundamental relationship between the generation of negative intrathoracic pressure during inspiration through a low-level of resistance created by an impedance threshold device and the physiologic effects of a respiratory pump. A decrease in intrathoracic pressure during inspiration through a fixed resistance resulting in an intrathoracic pressure of −7 cmH₂O has multiple physiological benefits including: enhanced venous return, cardiac stroke volume and aortic blood pressure; lower intracranial pressure; resetting of the cardiac baroreflex; elevated cerebral blood flow oscillations and increased tissue blood flow/pressure gradient.

Conclusion

The clinical and animal studies support the use of the intrathoracic pump to treat different clinical conditions: hemorrhagic shock, orthostatic hypotension, septic shock, and cardiac arrest.     

Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma

Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas strictly localized to the CNS, occurring mainly in elderly patients with comorbidities. Current treatment in fit patients relies on high-dose methotrexate and high-dose cytarabine. The aim of this study was to evaluate the efficacy and feasibility of this treatment in elderly patients and to assess potential prognostic factors associated with survival. We conducted a retrospective study in two centers between January 2008 and September 2015 including 35 elderly immunocompetent patients who received first-line treatment with high-dose methotrexate. With a median follow-up of 19.8 months (range: 1.7–73.4 months), median overall survival (OS) was 39.5 months (95% confidence interval (95% CI): 18.3–60.7) and median progression-free survival (PFS) was 25.8 months (95% CI: 5.2–46.4). In univariate analysis, administration of high-dose cytarabine and achieving a relative dose intensity for methotrexate >?75% were associated with increased OS (p?=?0.006 and p?=?0.003, respectively) and PFS (p?=?0.003 and p?=?0.04, respectively) whereas comorbidities, defined by a CIRS-G score ≥?8, were associated with decreased OS and PFS (p?=?0.02 and p?=?0.04, respectively). A high MSKCC score was associated with decreased OS (p?=?0.02). In multivariate analysis, administration of high-dose cytarabine was associated with increased OS and PFS (p?=?0.02 and p?=?0.007, respectively). Comorbidities and relative dose intensity for methotrexate are important for the prognosis of elderly patients with PCNSL. These results must be confirmed in prospective trials.     

Characterization of two angiotensin II binding sites in cultured mouse spinal cord neurones

Characteristics of angiotensin II (AII) binding have been determined in cultured mouse spinal cord neurones using [125I]AII and [3H]AII. The Scatchard plot of equilibrium binding was curvilinear and could be described by postulating the existence of two different classes of independent binding sites (Kd1 = 0.43 nM, Bmax1 = 12.5 fmol/1.5 X 10(6) cells; Kd2 = 25.6 nM, Bmax2 = 220 fmol/1.5 X 10(6) cells). These values are in close agreement with the Kd values obtained from kinetic studies. The high affinity binding sites appeared to be similar to the single class of sites described in other studies. The relative inhibition potency of AII-related peptides was studied. Sar1,-Leu8-AII was the most potent in inhibiting specific AII binding. The characteristics of the two AII binding sites suggest that they correspond to two receptors as described in a previous electrophysiological approach using this model in our laboratory. Taken together, these data confirm that this model of neurones in primary culture is a unique and very attractive model of receptor studies. The classical criteria necessary for positive identification of a ligand-receptor have been satisfied: saturability, reversibility, specificity and most importantly correlation of the binding parameters and biological effects of AII.     

Silicalites and Mesoporous Silica Nanoparticles for photodynamic therapy

The synthesis of silicalites and Mesoporous Silica Nanoparticles (MSN), which covalently incorporate original water-soluble photosensitizers for PDT applications is described. PDT was performed on MDA-MB-231 breast cancer cells. All the nanoparticles showed significant cell death after irradiation, which was not correlated with (1)O(2) quantum yield of the nanoparticles. Other parameters are involved and in particular the surface and shape of the nanoparticles which influence the pathway of endocytosis. Functionalization with mannose was necessary to obtain the best results with PDT due to an active endocytosis of mannose-functionalized nanoparticles. The quantity of mannose on the surface should be carefully adjusted as a too high amount of mannose impairs the phototoxicity of the nanoparticles. Fluorescein was also encapsulated in MCM-41 type MSN in order to localize the nanoparticles in the organelles of the cells by confocal microscopy. The MSN were localized in lysosomes after active endocytosis by mannose receptors.