Place du kinésithérapeute dans le traitement de la dyspnée

Dyspnoea is the most frequent complaint in respiratory diseases. During clinical care, the physiotherapist is often in front of a dyspneic patient.So the physiotherapist has an important place in care of the dyspneic patients, first time for the evaluation, and then for the treatment. He is also a major interlocutor in a multidisciplinary staff.This article aims to show evaluation tools of the dyspnoea which allow to cover the various domains of the dyspnoea, and then the different physiotherapy’s methods which allow to decrease it.     

Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure.

OBJECTIVES: This study sought to investigate whether torasemide inhibits the enzyme involved in the myocardial extracellular generation of collagen type I molecules (i.e., procollagen type I carboxy-terminal proteinase [PCP]). BACKGROUND: Torasemide has been reported to reduce myocardial fibrosis in patients with chronic heart failure (HF). METHODS: Chronic HF patients received either 10 to 20 mg/day oral torasemide (n = 11) or 20 to 40 mg/day oral furosemide (n = 11) in addition to their standard HF therapy. At baseline and after 8 months from randomization, right septal endomyocardial biopsies were obtained to analyze the expression of PCP by Western blot and the deposition of collagen fibers (collagen volume fraction [CVF]) with an automated image analysis system. The carboxy-terminal propeptide of procollagen type I (PICP) released as a result of the action of PCP on procollagen type I was measured in serum by radioimmunoassay. RESULTS: The ratio of PCP active form to PCP zymogen, an index of PCP activation, decreased (p < 0.05) in torasemide-treated patients and remained unchanged in furosemide-treated patients. A reduction (p < 0.01) in both CVF and PICP was observed in torasemide-treated but not in furosemide-treated patients. Changes in PCP activation were positively correlated (p < 0.001) with changes in CVF and changes in PICP in patients receiving torasemide. CONCLUSIONS: These findings suggest the hypothesis that the ability of torasemide to reduce myocardial fibrosis in chronic HF patients is related to a decreased PCP activation. Further studies are required to ascertain whether PCP may represent a new target for antifibrotic strategies in chronic HF.     

Do minitransplants have minicosts? A cost comparison between myeloablative and nonmyeloablative allogeneic stem cell transplant in patients with acute myeloid leukemia

Allogeneic hematopoietic stem cell transplantation (SCT) is a widely used, cost-intensive procedure. Although pretransplant nonmyeloablative (NMA) or reduced-intensity conditioning regimens appear very promising, prospective studies comparing this approach with the conventional myeloablative (MA) approach in specific hematologic diseases are necessary, especially in patients in whom the conventional approach is not contraindicated. Cost may be an important factor in the decision-making process. We compared the costs of MA and NMA transplants in patients with acute myeloid leukemia (AML). We estimated 1-year resource utilization in 12 consecutive MA patients (median age: 39 years) and in 11 consecutive NMA patients (median age: 58 years) who underwent HLA-identical sibling SCT for AML. Resources care expenses were valued using the average daily rate for personnel costs, supplies, and room costs. Other data were directly collected from the patients' charts. Despite a trend for lower costs in NMA patients during the first 6 months, costs during the 6-12-month period were significantly higher after NMA due to late complications and readmissions (P=0.03). Finally, mean 1-year costs were not different in MA and NMA patients (P=0.75). Prospective studies comparing conventional and NMA approaches in homogeneous populations should include economic items.     

Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor: identification of pathways regulating B-cell survival

The physical interactions between B cells and stromal cells from the lymphoid tissue microenvironment are critical to the survival of normal and malignant B cells. They are principally mediated by integrins expressed on B cells and counterreceptors on stromal cells. Specifically, alpha4beta1 integrin engagement rescues B cells from physiological or drug-induced apoptosis. Therefore, in order to understand the mechanisms by which integrins prevent apoptosis in leukemia B cells, we compared the temporal gene expression profiles induced by beta1-integrin ligation with fibronectin (Fn) or adhesion by poly-L-Lysine in serum-starved precursor B leukemia cells. Among the 38 selected differentially expressed genes, 6 genes involved in adhesion (VAV2, EPB41L1, CORO1A), proliferation (FRAP1, CCT4), and intercellular communication (GJB3) were validated by real-time quantitative polymerase chain reaction (RT-Q-PCR). Gene expression modulation could also be validated at the protein level for 5 other genes. We show that integrin stimulation up-regulated FBI-1 expression but inhibited CD79a, Requiem, c-Fos, and caspase 7 induction when the cells underwent apoptosis. We further demonstrate that Fn stimulation also inhibits caspase 3 activation but increases XIAP and survivin expression. Moreover, integrin stimulation also prevents caspase activation induced by doxorubicin. Therefore, we identified genes modulated by adhesion of human precursor B leukemia cells that regulate proliferation and apoptosis, highlighting new pathways that might provide insights into future therapy aiming at targeting apoptosis of leukemia cells.     

Use of a single-item screening tool to detect clinically significant fatigue, pain, distress, and anorexia in ambulatory cancer practice

Fatigue, pain, distress, and anorexia are four commonly encountered symptoms in cancer. To evaluate the usefulness of a single-item screening for these symptoms, 597 ambulatory outpatients with solid tumors were administered a self-report screening instrument within the first 12 weeks of chemotherapy. Patients rated the severity of each symptom on a 0-10 scale, at its worst over the past three days, with higher ratings associated with higher symptom levels. From this sample, 148 patients also completed a more comprehensive assessment of these symptoms. Two criteria were used to determine optimal cut-off scores on the screening items: 1) the sensitivity and specificity of each screening item to predict clinical cases using receiver-operating characteristics analysis and 2) the proportion of patients at each screening score who reported that some relief of the target symptom would significantly improve their life. Optimal cut-off scores ranged from 4 to 6 depending on the target symptom (area under the curve range=0.68-0.88). Use of single-item screening instruments for fatigue, pain, distress, and anorexia may assist routine clinical assessment in ambulatory oncology practice. In turn, such assessments may improve identification of those at risk of morbidity and decreased quality of life due to excess symptom burden.     

Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload

DMT1 mediates the pH-dependent uptake of Fe(2+) from the diet in duodenal enterocytes and in most other cells. It transfers iron from the endosomes to the cytosol following the uptake of the transferrin-transferrin receptor complex. DMT1 mutations are responsible for severe hypochromic microcytic anemia in rodents and in 2 human patients described recently. We report a compound heterozygote for 2 new DMT1 mutations, associated with microcytic anemia from birth and progressive liver iron overload. The first mutation is a GTG deletion in exon 5, leading to the V114 in-frame deletion in transmembrane domain 2, and the second is a G --> T substitution in exon 8 leading to the G212V replacement in transmembrane domain 5. Together with the 2 previously reported cases, this patient defines a new syndrome of congenital microcytic hypochromic anemia, poorly responsive to oral iron treatment, with liver iron overload associated paradoxically with normal to moderately elevated serum ferritin levels.     

A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients

Adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoid proliferative disease that exists under diverse clinical forms ranging from chronic to acute. Although leukemic cells from patients with ATL exhibit an intrinsic resistance to chemotherapy, monoclonal antibodies directed against CD25 (interleukin 2 receptor alpha [IL-2Ralpha] antibody) have been used as specific therapeutic agents. However, significant clinical results with these antibodies have been demonstrated only in chronic forms of ATL. In contrast to resting T cells, human T-cell lymphotropic virus type 1 (HTLV-1)-infected cells constitutively express high levels of surface transferrin receptor (TfR). Herein, we report the characterization of a new monoclonal antibody (mAb A24) directed against the human TfR and the evaluation of its capacity to block the proliferation of ATL cells ex vivo. We determined that A24 binds TfR with an equilibrium constant (K'd) of 2.7 nM and competes with transferrin for binding to TfR. A24 also inhibited [55Fe]-transferrin uptake in activated T cells and blocked T-cell proliferation. Moreover, A24 reduced and impaired TfR expression and recycling, respectively. Most important, we showed that A24 blocked the ex vivo proliferation of malignant T cells from both acute and chronic forms of ATL, through induction of programmed cell death. Therefore efficient therapeutic tools to treat acute forms of ATL might be derived from A24.