Biologic properties in vitro of a recombinant human granulocyte- macrophage colony-stimulating factor

Recombinant human granulocyte-macrophage colony-stimulating factor (rH GM-CSF) was purified to homogeneity from medium conditioned by COS cells transfected with a cloned human GM-CSF cDNA and shown to be an effective proliferative stimulus in human marrow cultures for GM and eosinophil colony formation. The specific activity of purified rH GM- CSF in human marrow cultures was calculated to be at least 4 X 10(7) U/mg protein. Clone transfer experiments showed that this proliferation was due to direct stimulation of responding clonogenic cells. Acting alone, rH GM-CSF did not stimulate erythroid colony formation, but in combination with erythropoietin, increased erythroid and multipotential colony formation in cultures of peripheral blood cells. rH GM-CSF had no proliferative effects on adult or fetal murine hematopoietic cells, did not induce differentiation in murine myelomonocytic WEHI-3B cells, and was unable to stimulate the survival or proliferation of murine hematopoietic cell lines dependent on murine multi-CSF (IL 3). rH GM- CSF stimulated antibody-dependent cytolysis of tumor cells by both mature human neutrophils and eosinophils and increased eosinophil autofluorescence and phagocytosis by neutrophils. From a comparison of these effects with those of semipurified preparations of human CSF alpha and -beta, it was concluded that rH GM-CSF exhibited all the biologic activities previously noted for CSF alpha.     

Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia

The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (lung-resistance protein [LRP]) overexpressed in several P-glycoprotein- negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37%) cases, including 7 (33%) de novo AML, 13 (48%) secondary AML, 11 (38%) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35% of LRP+ patients as compared with 68% of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P =.0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.     

Primary 23-gauge vitreoretinal surgery for rhegmatogenous retinal detachment

AIM: To report the effectiveness and safety of primary 23-Gauge (G) vitreoretinal surgery for rhegmatogenous retinal detachment (RRD). METHODS: In this retrospective study, 49 eyes of 49 consecutive patients who underwent primary 23-G transconjunctival sutureless vitrectomy (TSV) for RRD between January 2007 and July 2009 at our institution were evaluated. RESULTS: Mean follow-up time was 8.9±7.7 months (1-28 months). Retinal reattachment was achieved with a single operation in 47(95.9%) of 49 eyes. In two eyes (4.1%), retinal redetachment due to new breaks was successfully treated with reoperation using the 23-G TSV system. Mean logMAR visual acuity was 2.01±0.47 preoperatively and 1.3±0.5 postoperatively (P<0.001, Paired t-test). Mean preoperative intraocular pressure (IOP) was 14.1±2.8mmHg. Mean postoperative IOP was 12.3±3.6mmHg at 1 day, 13.1±2.1mmHg at 1 week, 14.3±2.2mmHg at 1 month. Iatrogenic peripheral retinal break was observed in 1 eye (2.0%) intraoperatively. No sutures were required to close the scleral or conjunctival openings, and no eyes required convertion of surgery to 20-G vitrectomy. CONCLUSION: Primary 23-G TSV system was observed to be effective and safe in the treatment of RRD.     

远端与近端结肠癌在临床、病理和分子生物学特征上的区别

背景远端和近端结肠癌在起源,基因暴露,环境诱变及肠道菌群等方面均存在差异。然而这些差异很少被用来解释如何影响肿瘤的发生机制,特异的治疗响应及预后情况。研究系统性探索了远端与近端结肠癌的差异及这些差异的临床意义。资料与方法研究共纳入3 045例结肠癌患者的详细临床病理数据用于分析,这些患者资料均来源于PETACC3(关于结肠癌辅助化疗)临床试验。这些数据中,     

Intubation for patients with overdose: Time to move on from the Glasgow Coma Scale

Patients frequently present to the ED with drug overdose and reduced conscious level leading to coma. There is considerable practice variation around which patients require intubation. Indications include: (i) respiratory failure (including airway obstruction); (ii) to facilitate specific therapies or intubation as a therapy in itself; and (iii) for airway protection in the unprotected airway. We argue that intubating a patient purely for (iii) is outdated and that most patients can be safely observed. There is a paucity of good quality research in the area of drug overdose with reduced consciousness. Teaching may be outdated and based on the use of the Glasgow Coma Scale in head trauma. Current low quality research suggests observation is safe. We recommend that patients undergo an individualised risk assessment of the need for intubation. We propose a flow diagram to aid clinicians in safely observing comatose overdose patients. This can be applied if the drug is unknown, or there are multiple drugs involved.