The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic factors for various types of cancer. In this study, we assessed the association of NLR and PLR with the prognosis of small-cell lung cancer (SCLC) in patients who received the standard treatment. METHODS: We retrospectively reviewed patients who were diagnosed with SCLC and treated with platinum-based chemotherapy between July 2006 and October 2013 in Gyeongsang National University Hospital Regional Cancer Center and Changwon Samsung Hospital. RESULTS: In total, 187 patients were evaluated. Compared with low NLR (<4), high NLR (⩾4) at diagnosis was associated with poor performance status, advanced stage, and lower response rate. Median overall survival (OS) and progression-free survival (PFS) were worse in the high-NLR group (high vs low, 11.17 vs 9.20 months, P=0.019 and 6.90 vs 5.49 months, P=0.005, respectively). In contrast, PLR at diagnosis was not associated with OS or PFS (P=0.467 and P=0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase, and NLR at diagnosis were independent prognostic factors for OS and PFS. CONCLUSIONS: NLR is easily measurable and reflects the SCLC prognosis. A future prospective study is warranted to confirm our results.

Common stress and serum cortisol and IL-12 levels in missed abortion.

To investigate stress levels, serum cortisol levels, and changes in IL-12 concentration in patients with missed abortion. Patients with missed abortion (n = 48) were age and gestational age-matched with normal early pregnancy cases (n = 48). All subjects completed a stress evaluation survey questionnaire about common stressors. Venous blood samples were collected at 07.00 hours, and serum cortisol and IL-12 concentrations were measured by electrochemiluminescence immunoassay and ELISA methods, respectively. Missed abortion patients demonstrated a significantly higher number of common stressors and higher serum cortisol levels compared to controls (both p < 0.05). Dilation and curettage did not lead to significant differences in serum cortisol and IL-12 levels (p > 0.05). Stress and immunity alterations of the immune system may contribute to the aetiology of missed abortion.

Cancel all Hollidays for SLX4 mutations: identification of a new Fanconi anemia subtype, FANCP.

SLX4, a coordinator of structure-specific endo-nucleases, is mutated in a new Fanconi anemia subtype Stoepker et al. (2011) Nature Genetics 43:138-141. Mutations of the SLX4 gene in Fanconi anemia Kim et al. (2011) Nature Genetics 43:142-146.

Responses of wild plant species to polycyclic aromatic hydrocarbons in soil.

Responses of plants to polycyclic aromatic hydrocarbons (PAHs) contamination were determined with fifty-five Korean wild plants. Responsiveness of species was evaluated based on germination and shoot weight and shoot length of plants grown in soil spiked with four PAHs (pyrene, fluorene, phenanthrene and fluoranthene). Seeds of test plants were germinated with mixtures of PAHs of 0, 10, 30, 100, 300 mg kg(-1) spiked in soil. Seed germination of test plants changed when subjected to PAHs. As compared to control germination percentages ranged from 0 (completely inhibited) to 242.9% (highly promoted) of control at 300 mg kg(-1) of PAHs. In germination responses, Fabaceae plants were much less affected (105% of control) compared to species belonging to Caryophyllaceae (18.7% of control), which showed highly susceptible responses. Results demonstrated that seed germination was affected by species-specific responses to PAHs. In seedling growth experiments on Bromus tectorum and Veronica persica, species classified as highly susceptible in germination experiments, a low No Observed Effect Concentration (NOEC) of 10 mg kg(-1) was observed. On the other hand, NOEC was 100 mg kg(-1) in Bromus japonicus and Cerastium holosteoides var. hallaisanense, which were also classified as highly susceptible by the germination experiment. However, most species classified as susceptible showed high NOEC of greater than 10 mg kg(-1). EC(50) values of test species ranged from 2.87 x 10(2) (Humulus japonicus) to 8.05 x 10(81) mg kg(-1) (Bidens bipinnata) based on shoot length. The wide range of EC(50) for shoot weight suggests that shoot weight is more appropriate as an endpoint for PAHs toxicity than shoot length for determining the susceptibility of plant species to PAHs. It was confirmed that dose-response of plants to PAHs spiked soil can be used to estimate critical concentration of PAHs inhibiting early establishment of plants in contaminated fields.

Pericardial effusion in a dog concurrent with carcinoma of unknown primary origin.

BACKGROUND: Pericardial effusion (PE) due to secondary metastasis has rarely been reported in dogs. CASE DESCRIPTION: This case describes clinical signs and further diagnostics regarding metastatic carcinoma of unknown primary origin (CUP) in refractory PE of a dog. FINDINGS/TREATMENT AND OUTCOME: A nine-year-old, castrated male Shih Tzu dog was referred for evaluation of cough and dyspnea. On presentation, tachypnea, intermittent cough, and muffled heart sounds were noted. Thoracic radiography, electrocardiography, and echocardiography confirmed a PE. No mass lesion was detected at the heart base, aorta, or right atrium (RA). Analysis of the PE showed hemorrhagic cytology, and an idiopathic hemorrhagic PE was tentatively diagnosed. The dog responded to conservative treatment with steroid and diuretics, but the clinical sign recurred. Further evaluation with multi-detector computed tomography (MDCT) was non-diagnostic. The dog died 457 days after initial presentation. Necropsy and histopathology revealed metastatic CUP origin. CONCLUSION: This case illustrated a rare cause of recurrent PE in dogs.

Correction: Musashi RNA-binding protein 2 regulates estrogen receptor 1 function in breast cancer.

The original version of this article contained error in Figure 2e. In Figure 2e, the 6th colony image of T47D cells treated with shMSI2 was inadvertently replaced with a duplicate of 7th colony image. However, the conclusions reported in the manuscript are not affected by figure replacement. The authors regret that these errors were made and apologize for the confusion and inconvenience. The correct version of this figure panel appears in the Author Correction associated with this Article.

Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia.

BACKGROUND: This randomized, double-blind, prospective study was undertaken to evaluate the effects of magnesium sulphate on anaesthetic requirements and postoperative analgesia in patients undergoing total i.v. anaesthesia (TIVA). METHODS: Fifty patients who underwent gynaecological surgery were randomly divided into two groups. Before induction of anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and then 15 mg kg(-1) h(-1) i.v. by continuous infusion. The control group (Group S) received the same amount of isotonic saline. TIVA (propofol+remifentanil) was administered under bispectral index monitoring during anaesthesia induction and maintenance. Rocuronium was administered before orotracheal intubation and during surgery when the train-of-four count was 2 or more. After operation, patient-controlled analgesia with a solution of ketorolac and morphine was used and the consumption of this solution was recorded. Pain scores at rest and upon movement were evaluated 30 min, 4, 24, and 48 h after surgery. RESULTS: Patients in Group M required less rocuronium than those in Group S [mean (SD) 0.44 (0.09) vs 0.35 (0.07) microg kg(-1) min(-1), P<0.05]. The total amounts of propofol and remifentanil administered were similar in the two groups. Postoperative pain scores, cumulative analgesic consumption, and shivering incidents were significantly lower in Group M (P<0.05). Mean arterial pressure just after intubation and during the immediate postoperative period was also significantly lower in Group M (P<0.05). CONCLUSIONS: I.v. magnesium sulphate during TIVA reduced rocuronium requirement and improved the quality of postoperative analgesia.

Calf-contouring surgery of gastrocnemius hypertrophy: selective neurectomy of the sural nerve.

Generally, Asians tend to have obese calves that are shorter and thicker than those of Caucasians. The cause of the enlarged calves is either an excess of subcutaneous fat or calf muscular hypertrophy, but some patients have both conditions. These features are accentuated by the contraction of the calf muscles when patients stand in tiptoe position or wear high heels. In the case of calf muscular hypertrophy without excessive subcutaneous fat, manipulation of the calf muscle is an effective method for reducing calf circumference. From January 2005 to December 2006, the authors performed selective sural neurectomy for 20 patients who complained of obese calves. Using a popliteal incision, the sural nerve branches to the medial and/or lateral gastrocnemius muscles were dissected from the posterior tibial nerve. Using a nerve stimulator, the branches with the most contractile portions were resected in 1 cm lengths at the distal ends. One medial branch was resected in 15 patients, and two branches were resected in 5 patients. In the case of a lateral neurectomy, only one branch was resected. Ultrasound-assisted liposuction was combined for five patients who also showed excessive subcutaneous fat. The patients ranged in age from 19 to 29 years (mean, 23 years). The follow-up period varied from 6 to 18 months. The circumferential change was checked 6 months postoperatively 15 cm below the medial condyle and 15 cm above the medial malleolus. These average circumferences were reduced, respectively, from 36.6 and 32.5 cm to 35.5 and 32.2 cm. In gait analysis performed at 6 months postoperatively, the calf muscle power was slightly reduced to 95% of the preoperative state, but still remained above the normal range. Subjectively, no patient complained of muscle weakness or gait disturbance. One patient showed lower leg edema after mountain climbing that subsided after 1 day of rest. The authors believe a selective neurectomy technique can be an effective method for treating obese calves.

Musashi RNA-binding protein 2 regulates estrogen receptor 1 function in breast cancer.

Musashi RNA-binding protein 2 (MSI2) has important roles in human cancer. However, the regulatory mechanisms by which MSI2 alters breast cancer pathophysiology have not been clearly identified. Here we demonstrate that MSI2 directly regulates estrogen receptor 1 (ESR1), which is a well-known therapeutic target and has been shown to reflect clinical outcomes in breast cancer. Based on gene expression data analysis, we found that MSI2 expression was highly enriched in estrogen receptor (ER)-positive breast cancer and that MSI2 expression was significantly correlated with ESR1 expression, including expression of ESR1 downstream target genes. In addition, MSI2 levels were associated with clinical outcomes. MSI2 influenced breast cancer cell growth by altering ESR1 function. MSI2 alters ESR1 by binding specific sites in ESR1 RNA and by increasing ESR1 protein stability. Taken together, our findings identified a novel regulatory mechanism of MSI2 as an upstream regulator of ESR1 and revealed the clinical relevance of the RNA-binding protein MSI2 in breast cancer.

Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the intracranial hemorrhage in two dogs: a case report.

Two dogs with generalized seizures were evaluated. The dogs were diagnosed with traumatic intracranial hemorrhages based on the history, neurological examinations, and magnetic resonance imaging (MRI) of the brain. Treatment was started with oxygen, prednisolone and anticonvulsant agents. No further seizure activity was observed after treatment in both dogs, however cushing reflex was detected in case 1 and a left-sided hemi-paresis was detected in case 2. Further supportive treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF) was attempted. No abnormal signs were noted in either of the dogs and no recurrence was noted 16 and 14 months later, in case 1 and 2, respectively. These cases indicate that a combination of rhG-CSF treatment with previous therapy could be used in dogs with traumatic brain injury.

Conjugated polyelectrolyte nano field emission adlayers.

Here we report on a straightforward and rapid means of enhancing the field electron emission performance of nascent vertically aligned multi-walled carbon nanotubes by introducing a polar zwitterionic conjugated polyelectrolyte adlayer at the vacuum-emitter interface. We attribute the observed 66% decrease in turn-on electric field to the augmented emitter micro-morphology and shifted surface band structure. The composite emitters can be optically modulated by exploiting the absorption cross-section of the solution cast adlayer, which increases the local carrier concentration which broadens the effective electrostatic shape of the emitter during optical excitation. Assessment via scanning anode field emission microscopy reveals a 25% improvement in DC time stability, a significant reduction in long-term hysteresis shift, and a threefold increase in bandwidth during pulsed mode operation.

Vascular effects of synthetic or natural progestagen combined with conjugated equine estrogen in healthy postmenopausal women.

BACKGROUND: Synthetic, not natural, progestagen may negate the favorable effects of estrogen. Nonetheless, observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estrogen and users of estrogen combined with synthetic progestin. METHODS AND RESULTS: In a double-blind study, we randomly assigned 20 healthy postmenopausal women to micronized progesterone (MP) 200 mg or medroxyprogesterone acetate (MPA) 10 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and the remaining 5 days off cyclically during 2 months, followed by crossover to the alternate therapy. CEE+MP and CEE+MPA significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P=0.004 by ANOVA) by a similar degree (P=0.863). Both therapies significantly decreased E-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 levels from baseline values (P<0.001, P=0.048, and P=0.016 by ANOVA, respectively) by a similar degree (P=0.977 for ICAM-1 and P=0.541 for VCAM-1, respectively). CEE+MPA decreased E-selectin levels more than CEE+MP did (P=0.040). Both therapies significantly decreased monocyte chemoattractant protein-1 levels from baseline values (P<0.005 by ANOVA) by a similar degree (P=0.194). Both therapies significantly decreased tissue factor antigen and increased tissue factor activity levels from baseline values (P=0.003 and P<0.001 by ANOVA, respectively) by a similar degree (P=0.652 for antigen and P=0.173 for activity). Both therapies significantly lowered plasma plasminogen activator inhibitor-1 levels from baseline values (P<0.001 by ANOVA) by a similar degree (P=0.533). CONCLUSIONS: CEE+MP and CEE+MPA provide similar improvement in endothelium-dependent vasodilator responsiveness and effects on markers of inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal women.

Phase I study of infusional paclitaxel in combination with the P-glycoprotein antagonist PSC 833.

PURPOSE: PSC 833 (valspodar) is a second-generation P-glycoprotein (Pgp) antagonist developed to reverse multidrug resistance. We conducted a phase I study of a 7-day oral administration of PSC 833 in combination with paclitaxel, administered as a 96-hour continuous infusion. PATIENTS AND METHODS: Fifty patients with advanced cancer were enrolled onto the trial. PSC 833 was administered orally for 7 days, beginning 72 hours before the start of the paclitaxel infusion. Paclitaxel dose reductions were planned because of the pharmacokinetic interactions known to occur with PSC 833. RESULTS: In combination with PSC 833, maximum-tolerated doses were defined as paclitaxel 13.1 mg/m(2)/d continuous intravenous infusion (CIVI) for 4 days without filgrastim, and paclitaxel 17.5 mg/m(2)/d CIVI for 4 days with filgrastim support. Dose-limiting toxicity for the combination was neutropenia. Statistical analysis of cohorts revealed similar mean steady-state concentrations (C(pss)) and areas under the concentration-versus-time curve (AUCs) when patients received paclitaxel doses of 13.1 or 17.5 mg/m(2)/d for 4 days with PSC 833, as when they received a paclitaxel dose of 35 mg/m(2)/d for 4 days without PSC 833. However, the effect of PSC 833 on paclitaxel pharmacokinetics varied greatly among individual patients, although a surrogate assay using CD56+ cells suggested inhibition of Pgp was complete or nearly complete at low concentrations of PSC 833. Responses occurred in three of four patients with non-small-cell lung cancer, and clinical benefit occurred in five of 10 patients with ovarian carcinoma. CONCLUSION: PSC 833 in combination with paclitaxel can be administered safely to patients provided the paclitaxel dose is reduced to compensate for the pharmacokinetic interaction. Surrogate studies with CD56+ cells indicate that the maximum-tolerated dose for PSC 833 gives serum levels much higher than those required to block Pgp. The variability in paclitaxel pharmacokinetics, despite complete inhibition of Pgp in the surrogate assay, suggests that other mechanisms, most likely related to P450, contribute to the pharmacokinetic interaction. Future development of combinations such as this should include strategies to predict pharmacokinetics of the chemotherapeutic agent. This in turn will facilitate dosing to achieve comparable CPss and AUCs.

Vascular effects of estrogen in type II diabetic postmenopausal women.

OBJECTIVES: We assessed the effects of estrogen on vascular dilatory and other homeostatic functions potentially affected by nitric oxide (NO)-potentiating properties in type II diabetic postmenopausal women. BACKGROUND: There is a higher cardiovascular risk in diabetic women than in nondiabetic women. This would suggest that women with diabetes do not have the cardioprotection associated with estrogen. METHODS: We administered placebo or conjugated equine estrogen, 0.625 mg/day for 8 weeks, to 20 type II diabetic postmenopausal women in a randomized, double-blinded, placebo-controlled, cross-over design. RESULTS: Compared with placebo, estrogen tended to lower low-density lipoprotein (LDL) cholesterol levels by 15 +/- 23% (p = 0.007) and increase high-density lipoprotein (HDL) cholesterol levels by 8 +/- 16% (p = 0.034). Thus, the ratio of LDL to HDL cholesterol levels significantly decreased with estrogen, by 20 +/- 24%, as compared with placebo (p = 0.001). Compared with placebo, estrogen tended to increase triglyceride levels by 16 +/- 48% and lower glycosylated hemoglobin levels by 3 +/- 13% (p = 0.295 and p = 0.199, respectively). However, estrogen did not significantly improve the percent flow-mediated dilatory response to hyperemia (17 +/- 75% vs. placebo; p = 0.501). The statistical power to accept our observation was 81.5%. Compared with placebo, estrogen did not significantly change E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1 or matrix metalloproteinase-9 levels. Compared with placebo, estrogen tended to decrease tissue factor antigen and increase tissue factor activity levels by 7 +/- 46% and 5 +/- 34%, respectively (p = 0.321 and p = 0.117, respectively) and lower plasminogen activator inhibitor-1 levels by 16 +/- 31% (p = 0.043). CONCLUSIONS: The effects of estrogen on endothelial, vascular dilatory and other homeostatic functions were less apparent in type II diabetic postmenopausal women, despite the beneficial effects of estrogen on lipoprotein levels.

The P-glycoprotein antagonist PSC 833 increases the plasma concentrations of 6alpha-hydroxypaclitaxel, a major metabolite of paclitaxel.

PURPOSE: Overexpression of P-glycoprotein (Pgp) is one mechanism of drug resistance in cancer chemotherapy. A Phase I trial was conducted using PSC 833, a Pgp antagonist, in combination with paclitaxel in patients with refractory cancer. The objective of this study was to assess the effect of PSC 833 on the metabolism of paclitaxel and characterize the differences in 6alpha-hydroxypaclitaxel pharmacokinetics. In addition, we examined the possibility of enhanced cytotoxicity of paclitaxel by the coexistence of 6alpha-hydroxypaclitaxel. EXPERIMENTAL DESIGN: Patients received paclitaxel 35 mg/m(2)/day by continuous intravenous infusion (CIVI) x 4 days without PSC 833 in cycle 1 and escalating doses of paclitaxel (13.1, 17.5, or 21.3 mg/m(2)/day CIVI x 4 days) with 5 mg/kg PSC 833 by mouth every 6 h x 7 days in cycle 2. Plasma samples were analyzed for both paclitaxel and its major metabolite with high-performance liquid chromatography methods. Using human liver microsomes, we studied the effect of PSC 833 on the metabolism of paclitaxel. In addition, the in vitro cytotoxicity of 6alpha-hydroxypaclitaxel alone and in combination with paclitaxel was evaluated. RESULTS: Twenty-one of 22 patients had a metabolite peak (6alpha-hydroxypaclitaxel) observed in the chromatogram of plasma samples from cycle 2 when they received paclitaxel in combination with PSC 833. This metabolite was not detectable in plasma obtained during the first cycle when they received paclitaxel without PSC 833. During cycle 2, the mean concentrations of 6alpha-hydroxypaclitaxel and paclitaxel were 0.10 +/- 0.074 and 0.079 +/- 0.041 microg/ml, respectively. A moderate association was observed between total bilirubin and 6alpha-hydroxypaclitaxel concentrations (P = 0.015, r = 0.52; n = 21). Human liver microsome experiments showed that a PSC 833 concentration as high as 10 microM did not affect the production of 6alpha-hydroxypaclitaxel. Paclitaxel cytotoxicity in HL60 and K562 human leukemia cells was increased in the presence of noncytotoxic concentrations of 6alpha-hydroxypaclitaxel. CONCLUSIONS: PSC 833 increases the plasma concentration of 6alpha-hydroxypaclitaxel during paclitaxel therapy. Inhibition of cytochrome P-450 3A4 by PSC 833 may explain this in part, although other mechanisms cannot be excluded.

Chemopreventive effect of green tea (Camellia sinensis) among cigarette smokers.

Chemopreventive effects of green tea and coffee among cigarette smokers were examined in 52 clinically healthy male subjects between 20 and 52 years of age. Blood specimens were obtained from nonsmokers (group I), smokers (group II), smokers consuming green tea (group III), and smokers drinking coffee (group IV). The mean number of cigarette smoking years (> 10 cigarettes/day) in groups II-IV ranged from 13.4 to 14.7 years. Daily intake of green tea and coffee was 2-3 cups/day for 6 months (groups III and IV). The frequencies of sisterchromatid exchange (SCE) in mitogen-stimulated peripheral lymphocytes from each experimental group were determined and analyzed statistically. SCE rates were elevated significantly in smokers (9.46 +/- 0.46) versus nonsmokers (7.03 +/- 0.33); however, the frequency of SCE in smokers who consumed green tea (7.94 +/- 0.31) was comparable to that of nonsmokers, implying that green tea can block the cigarette-induced increase in SCE frequency. Coffee, in contrast, did not exhibit a significant inhibitory effect on smoking-induced SCE.

Implantation of penile prosthesis in a patient with severe corporeal fibrosis induced by cavernosal injection therapy.

Implantation of a penile prosthesis in men with complicated fibrosis of corpus cavernosum is very difficult and even impossible. Cavernosal dilation requires sharp intracavernosal dissection to implant prosthesis, however complete removal of the fibrotic tissue is often impossible. We introduce a new technique using electric resection and electrovaporization of fibrotic tissue for implantation of penile prosthesis in a patient with severe corporeal fibrosis.

Mode of action of sesame lignans in protecting low-density lipoprotein against oxidative damage in vitro.

We investigated the antioxidant properties of sesaminol, a major component of sesame oil, on the oxidative modification of human low-density lipoprotein (LDL) in vitro. Sesaminol inhibited the Cu2+-induced lipid peroxidation in LDL in a concentration-dependent manner with an IC50 36.0 +/- 10.0 nM. Sesaminol was a more effective scavenger than either alpha-tocopherol or probucol in reducing the peroxyl radicals derived from 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in aqueous solution. In addition, as determined by the secondary products of lipid peroxidation identified by using immunochemical methods, sesaminol completely inhibited the formation of 4-hydroxy-nonenal (4-HNE)- and malondialdehyde (MDA)-adducts in a concentration-dependent manner. Probucol and alpha-tocopherol at the same concentration exhibited a lesser inhibitory effect. Our findings suggest that sesaminol is a potentially effective antioxidant that can protect LDL against the oxidation.