Elevated neutrophil to lymphocyte ratio is associated with poor long-term survival and graft failure after lung transplantation

PurposeWe aimed to assess the prognostic value of Neutrophil to Lymphocyte Ratio (NLR) on long-term outcomes and graft dysfunction after lung transplantation.MethodsWe retrospectively reviewed all patients receiving a lung transplant at our institution from 2011 to 2014. The primary exposure was elevated NLR at the time of transplant, defined by NLR>4. The primary outcomes were graft failure and three-year all-cause mortality. Multivariate logistic regression and Kaplan-Meier survival analysis were used to analyze outcomes.Results95 patients were included. 40 patients (42%) had an elevated NLR. Elevated NLR was associated with graft failure (OR: 4.7 [1.2–18.8], p = 0.02), and three-year mortality (OR: 5.4 [1.3–23.2], p = 0.03) on multivariate logistic regression. Patients with elevated NLR demonstrated significantly lower survival on Kaplan-Meier analysis (50% versus 74%, p = 0.02). The c-statistic for our multivariate model was 0.91.ConclusionElevated neutrophil to lymphocyte ratio is associated with poor long-term survival and graft failure after lung transplantation.     

Multiparameter assessment of the cell cycle effects of bioactive and cytotoxic agents.

This paper describes the use of the bromodeoxyuridine/propidium iodide method to assess the effects of bioactive and cytotoxic agents on the kinetic characteristics of acute myelogenous leukemia cells. By careful selection of gates, the following parameters can be measured simultaneously using only 50,000 cells: the proportion of cells in S-phase, the distribution of cells within the S-phase compartment, the relative rate of DNA synthesis, the relative distribution of S-phase times, the proportion of S0 cells, and the proportion of cells in G1 and G2/M. This method was used to demonstrate that while retinoic acid, alpha-interferon, and cytosine arabinoside may all "inhibit" DNA synthesis, the actual effects of these agents differ. Retinoic acid appears to arrest cells in G1 without affecting the rate of DNA synthesis, while alpha-interferon and cytosine arabinoside "inhibit" DNA synthesis by reducing the rate of synthesis per se.     

New non-cocaine-containing topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations

OBJECTIVE: To compare the effectiveness of three new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine, tetracaine-phenylephrine [tetraphen], and tetracaine-lidocaine-phenylephrine) to that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: The emergency department of an urban children's hospital. PARTICIPANTS: Children 1 year of age or older with a laceration /= 5 years of age using a visual analogue scale (VAS). Suture technicians, research assistants, and parents also scored pain using a seven-point Likert scale. In addition, suture technicians completed an anesthetic effectiveness scale. RESULTS: There was consistently no difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. A statistically significant difference was seen among anesthetics when comparing VAS and Likert scale scores of suture technicians and Likert scale scores of research assistants. Based on post hoc analyses, these statistically significant differences were between TAC and prilocaine-phenylephrine (suture technician VAS and Likert scale) and between TAC and tetracaine-lidocaine-phenyl-ephrine (suture technician Likert scale), but not between TAC and tetraphen. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.2 VAS units for each of the observer groups. Based on anesthetic effectiveness scale scores, the three new topical preparations collectively performed significantly better on the face and scalp than on the extremities (relative risk = 1.83; 95% confidence interval 1.20 < relative risk < 2.79). CONCLUSION: This study demonstrated the effectiveness and safety of three new non-cocaine-containing topical anesthetics. Consistently, there was no statistical difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. Tetraphen offers an effective alternative to TAC during laceration repair in children.     

氯仿重结晶棉酚的质量研究

报道了氯仿重结晶的棉酚的化学性质,样品在不同温度下干燥恒重后,经熔点、薄层层析、紫外光谱、红外光谱、X-射线衍射、热重量分析、元素(C,H,Cl)分析及棉酚合量测定等一系列的分析,确证了在60℃以下棉酚与氯仿成溶剂化物(solvate)。随着干燥温度的升高或在室温长时间的贮存,此现象逐渐消失,100℃真空干燥恒重后成为纯棉酚。     

Mode of action of iron (III) chelators as antimalarials: II. Evidence for differential effects on parasite iron-dependent nucleic acid synthesis

Iron chelation treatment of red blood cells infected with Plasmodium falciparum selectively intervenes with iron-dependent metabolism of malaria parasites and inhibits their development. Highly permeant hydroxamate iron chelator RSFileum2 affects all parasite stages when cultures are continuously exposed to drug, but affects primarily ring stages when assessed for irreversible effects, ie, sustained inhibition remaining after drug removal. On the other hand, the hydrophilic and poorly permeant desferrioxamine (DFO) affects primarily trophozoite/schizont stages when tested either in the continuous mode or irreversible mode. Unlike parasites, mammalian cells subjected to similar drug treatment show complete growth recovery once drugs are removed. Our studies indicate that parasites display a limited capacity to recover from intracellular iron depletion evoked by iron chelators. Based on these findings we provide a working model in which the irreversible effects of RSFs on rings are explained by the absence of pathways for iron acquisition/utilization by early forms of parasites. Trophozoite/schizonts can partially recover from RSFileum2 treatments, but show no DNA synthesis following DFO treatment even after drug removal and iron replenishment by permeant iron carriers. At trophozoite stage, the parasite uses a limited pathway for refurnishing its iron-containing enzymes, thus overcoming iron deprivation caused by permeant RSFileum2, but not by DFO because this latter drug is not easily removable from parasites. Their DNA synthesis is blocked by the hydroxamate iron chelators probably by affecting synthesis of ribonucleotide reductase (RNRase). Presumably in parasites, prolonged repression of the enzyme leads also to irreversible loss of activity. The action profiles of RSFileum2 and DFO presented in this study have implications for improved chemotherapeutic performance by combined drug treatment and future drug design based on specific intervention at parasite DNA synthesis.     

Liposomal delivery of methylphosphonate antisense oligodeoxynucleotides in chronic myelogenous leukemia [see comments]

Chronic myelogenous leukemia (CML) is a hematologic malignancy characterized by the presence of the Philadelphia (Ph) chromosome. Bcr- abl, the fusion gene associated with the Ph chromosome, expresses a p210bcr-abl protein that promotes a selective expansion of mature myeloid progenitor cells. Methylphosphonate (MP) oligodeoxynucleotides complementary to specific regions of the bcr-abl mRNA were incorporated in liposomes. We studied the effects of liposomal MP (L-MP) on the growth inhibition of CML-like cell lines. L-MP targeted to the breakpoint junctions of the bcr-abl mRNA inhibited the growth of CML cells. Fifty percent inhibition was achieved at approximately 1 mumol/L of L-MP oligonucleotide concentrations. The inhibitory effect was selective because growth inhibition was observed only with CML but not with control cell lines. Moreover, CML cell growth inhibition was dependent on the sequence of the MP oligodeoxynucleotides incorporated in the liposomes. The growth inhibition of CML cells by L-MP resulted from selective inhibition of the expression of the p210bcr-abl protein.