A phase I clinical, pharmacologic, and biologic study of thrombopoietin and granulocyte colony-stimulating factor in children receiving ifosfamide, carboplatin, and etoposide chemotherapy for recurrent or refractory solid tumors: a Children's Oncology Group experience.

PURPOSE: Ifosfamide, carboplatin, and etoposide (ICE) are associated with grade III/IV dose-limiting thrombocytopenia. The Children's Oncology Group conducted a phase I dose escalation, pharmacokinetic, and biological study of recombinant human thrombopoietin (rhTPO) after ICE in children with recurrent/refractory solid tumors (CCG-09717) to assess the toxicity and maximum tolerated dose of rhTPO administered at 1.2, 2.4, or 3.6 microg/kg per dose. EXPERIMENTAL DESIGN: Children received ifosfamide 1,800 mg/m2 on days 0 to 4, carboplatin 400 mg/m2 on days 0 to 1, and etoposide 100 mg/m2 on days 0 to 4. rhTPO was administered i.v. on days +4, +6, +8, +10, and +12 at 1.2, 2.4, or 3.6 microg/kg per dose.RESULTS: rhTPO was well tolerated and maximum tolerated dose was not reached. Median time to platelet recovery > or =100,000/microL of rhTPO at 1.2, 2.4, and 3.6 microg/kg/d was 24 days (22-24 d), 25 days (23-29 d), and 22 days (16-37 d), respectively. Patients required a median of 2 days of platelet transfusions (0-7 days). Mean (+/- SD) rhTPO maximum serum concentrations were 63.3 +/- 9.7 and 89.3 +/- 15.7 ng/mL and terminal half-lives were 47 +/- 13 and 64 +/- 42 hours after 2.4 and 3.6 microg/kg/d, respectively. There was a significant increase in colony-forming unit megakaryocyte upon WBC count recovery. CONCLUSIONS: rhTPO was well tolerated. Time to hematologic recovery and median number of platelet transfusions seem to be improved compared with historical controls receiving ICE + granulocyte colony-stimulating factor (CCG-0894).     

Simulation of Diffusion-Controlled Growth of Interdependent Nuclei under Potentiostatic Conditions

The problem of diffusion-controlled growth following an instantaneous nucleation event was studied within the framework of a new numerical model, considering the spatial distribution of hemispherical nuclei on the electrode surface and the mutual influence of growing nuclei via the collision of 3D diffusion fields. The simulation of the diffusion-controlled growth of hexagonal and random ensembles was performed at the overpotential-dependent number density of nuclei. The diffusion flow to each nucleus within a random ensemble was simulated by the finite difference method using the derived analytical expressions for the surface areas and the volumes formed at the intersection of 3D diffusion fields with the side faces of a virtual right prism with a Voronoi polygon base. The implementation of this approach provides an accurate calculation of concentration profiles, time dependences of the size of nuclei, and current transients. The results, including total current density transients, growth exponents, and nucleus size distribution, were compared with models developed within the concept of planar diffusion zones, the mean-field approximation and the Brownian dynamics simulation method, as well as with experimental data from the literature. The prospects of the model for studying the initial stages of electrocrystallization were discussed.     

Theoretical and Experimental Models to Evaluate the Possibility of Corrosion Resistant Concrete for Coastal Offshore Structures

This study built theoretical and practical models to evaluate the corrosion resistance of concrete for coastal offshore structures in Vietnam. A mathematical model was developed in the form of a system of nonlinear partial differential equations characterizing the diffusion “free calcium hydroxide” in a solid of a concrete structure. The model describes the process of non-stationary mass conductivity observed in the “concrete structure—marine environment” system under non-uniform arbitrary initial conditions, as well as combined boundary conditions of the second and third kind, taking into account the nonlinear nature of the coefficients of mass conductivity k and mass transfer β. It was shown that the solution of the boundary value problem of non-stationary mass conductivity allows us to conclude about the duration of the service life of a concrete structure, which will be determined by the processes occurring at the interface: in concrete—mass conductivity, depending on the structural and mechanical characteristics of hydraulic structures, and in the liquid phase—mass transfer, determined by the conditions of interaction at the interface of the indicated phases.     

Quality of life versus semen parameters

INTRODUCTION: Psychological factors are believed to play an important role in infertility and its treatment Psychological problems may be considered to be risk factors and the cause of reduced infertility, as well as contribute to an unsuccessful outcome of infertility treatment. OBJECTIVES: The aim of the study was to investigate the correlation between semen parameters and quality of life in male patients with fertility problems. MATERIAL AND METHODS: 70 patients with infertility treated in Andrology Clinic were divided into two groups according to semen parameters: bad and good quality of semen. The quality of life has been with the help of Campbell questionnaires. RESULTS: Significantly lower questionnaire score in bad quality of semen group has been observed, in comparison with normozoospermic men. High correlation between concentration, motility and morphology in comparison with the quality of life has been observed in the studied group of patients. CONCLUSION: The quality of life is directly associated with semen parameters such as concentration, motility and morphology of sperm.     

KIT activation in uterine cervix adenosquamous carcinomas by KIT/SCF autocrine/paracrine stimulation loops

ObjectivesUterine adenosquamous carcinoma (ASC) is an uncommon, yet, one of the most aggressive cervical cancer subtype. The successful treatment of some tumors, such as gastrointestinal stromal tumors (GISTs), by anti-KIT inhibitors fosters the study of this receptor tyrosine kinase in other malignancies. In the present study, we intended to molecularly characterize KIT in ASC.MethodsIn a series of 30 cases, we studied KIT (CD117), KIT phosphorylated / activated form, as well as KIT ligand, stem cell factor (SCF), by immunohistochemistry. We further screened for KIT hotspot mutations (exon 9, 11, 13 and 17) by PCR-SSCP and for KIT gene amplification by Quantitative real-time PCR in CD117 positive cases.ResultsWe observed CD117 expression in ～ 13% of cases, with ～ 7% co-expressing SCF, which resulted in KIT phosphorylation/activation. No KIT activating mutations or gene amplification were found, despite the presence of 4q aneuploidy in one case.ConclusionsThis is the first study assessing KIT activation and molecular alterations in a large series of rare ASC. Our findings showed the absence of KIT molecular alterations and suggested the presence of KIT activation in a small proportion of cases through KIT/SCF co-expression.     

Glyburide metabolism by placentas of healthy and gestational diabetics

The aim of this investigation was to determine the metabolism of glyburide (GL) by microsomes prepared from placentas obtained from uncomplicated pregnancies (UP), women with gestational diabetics (GD) on a diabetic diet, and those on a diet and GL. Term placentas were obtained from UP and GD. Crude microsomal fractions were prepared by differential centrifugation and stored at -80 degrees C. The activity of the microsomes in metabolizing glyburide to the trans-4-hydroxycyclohexyl glyburide (THCGL) and cis-3-hydroxycyclohexyl glyburide (CHCGL) was determined and quantified using high-performance liquid chromatography-mass spectrometer (HPLC-MS). The activity of the placental microsomes varied widely between individual placentas in each group. The median values (pmol.mg (-1) P.min (-1)) for the rates of THCGL formation were 0.34, 0.3, and 0.23 for placentas of UP, GD on diet, and GD on GL and a diet, respectively. The median values for CHCGL formation were 0.13 for UP, 0.11 for GD on a diet, and 0.10 (pmol.mg (-1) P.min (-1)) for GD on GL and a diet. A pool of individual microsomal fractions from each group was prepared and its activity revealed the following: greater formation of THCGL in the UP (0.36 +/- 0.10) than GD (0.22 +/- 0.03) ( P = 0.058 for GD on a diet, 0.04 for GD on GL). There was greater formation of CHCGL in UP (0.26 +/- 0.04) than GD (0.12 +/- 0.003) ( P < 0.006). There was no difference in GD on a diet and GD on GL plus diet. We concluded that the apparent differences in the formation of metabolites may be statistically significant, but it is unlikely to be of physiological importance, given the sample size and other experimental factors. Therefore, a more comprehensive investigation is underway.     

Molecular characteristics of rifampin and isoniazid resistant Mycobacterium tuberculosis strains from Beijing, China

Background China is one of the high burden countries of Mycobacterium tuberculosis （TB） infection globally, with high incidence and mortality. We studied the molecular characteristics of rifampin （RIF） and isoniazid （INH） resistant Mycobacterium tuberculosis strains from Beijing, China, in order to find out the genetic marker for rapid detection of specific drug resistance. Methods Forty pansusceptible and 81 resistant strains of Mycobacterium tuberculosis isolated from Beijing, China during 2002-2005 were analyzed. The modified rifampin oligonucleotide （RIFO） assay based on reverse line blot hybridization was used to detect mutations in the 81 bp hot-spot region of rpoB gene, which is associated with RIF resistance. The INH resistance associated genes, regulatory region mab-inhA （-15C/T） and structural gene katG S315T were detected by reverse line blot hybridization and PCR-restriction fragment length polymorphism （RFLP） method respectively. All the strains were typed by spoligotying and the Beijing genotype was further subdivided by NTF locus analysis. The distribution of drug resistance associated mutations in the above genes was compared in these groups. Results Sixty-five （91.5%） of 71 RIF resistant and 52 （92.9%） of 56 multidrug-resistant （MDR, i.e. resistant to at least RIF and INH） strains were found to harbor mutations in the rpoB hot-spot region. No mutation was detected in RIF sensitive strains. The specificity and sensitivity of the modified RIFO assay were 100% and 91.5%, respectively, katG315 AGC〉ACC and inhA-15C〉T mutations were found in 40 （60.6%） and 10 （15.2%） of 66 INH resistant strains, respectively; 7.6% of INH-resistant strains had mutations in both of these genes. Therefore, a combined use of both katG315 and inhA-15 identified 68.2% of INH-resistant strains. The Beijing genotype accounted for 91.7% of total strains and was further subdivided into ＂modern＂ （76.6%） and ＂ancestral＂ （23.4%） group. There is no significant difference between ＂ancestral＂ and ＂modern＂ group in prevalance of drug resistance-associated gene mutations. Conclusions The hot-spot region of rpoB gene can be used as genetic marker for detection of RIF resistant strains; a combined use of both katG315 and inhA-15 can improve the detection rate of I NH resistant strains; the Beijing genotype is prevalent in Beijing, China; the modified RIFO assay can be a practical tool for rapid detection of RIF resistant and MDR isolates in the routine diagnostic work.