Chemotherapy of brain tumors

This is a review of chemotherapy options for patients with brain tumors, both at the time of initial diagnosis and at recurrence. Gliomas, the most common malignant brain tumors, represent the main focus of the review; chemotherapeutic options for supratentorial, brain stem, and optic track gliomas are discussed.     

Measles virus expressed Helicobacter pylori neutrophil-activating protein significantly enhances the immunogenicity of poor immunogens

Helicobacter pylori neutrophil-activating protein (NAP) is a toll-like receptor 2 (TLR2) agonist and potent immunomodulator inducing Th1-type immune response. Here we present data about characterization of the humoral immune response against NAP-tagged antigens, encoded by attenuated measles virus (MV) vector platform, in MV infection susceptible type I interferon receptor knockout and human CD46 transgenic (Ifnarko-CD46Ge) mice. Immunogenicity of MV expressing a full-length human immunoglobulin lambda light chain (MV-lambda) was compared to that of MV expressing lambda-NAP chimeric protein (MV-lambda-NAP). MV-lambda-NAP immunized Ifnarko-CD46Ge mice developed significantly higher (6–20-fold) anti-lambda ELISA titers as compared to the MV-lambda-immunized control animal group, indicating that covalently-linked NAP co-expression significantly enhanced lambda immunogenicity. In contrast, ELISA titers against MV antigens were not significantly different between the animals vaccinated with MV-lambda or MV-lambda-NAP. NAP-tagged antigen expression did not affect development of protective anti-measles immunity. Both MV-lambda and MV-lambda-NAP-immunized groups showed strong virus neutralization serum titers in plaque reduction microneutralization test. These results demonstrated that MV-encoded lambda-NAP is highly immunogenic as compared to the unmodified full-length lambda chain. Boost of immune response to poor immunogens using live vectors expressing NAP-tagged chimeric antigens is an attractive approach with potential application in immunoprophylaxis of infectious diseases and cancer immunotherapy.     

Epigenetic alterations induced by ambient particulate matter in mouse macrophages

Respiratory mortality and morbidity has been associated with exposure to particulate matter (PM). Experimental evidence suggests involvement of cytotoxicity, oxidative stress, and inflammation in the development of PM‐associated pathological states; however, the exact mechanisms remain unclear. In the current study, we analyzed short‐term epigenetic response to PM₁₀ (particles with aerodynamic diameter less than 10 μm) exposure in mouse ascitic RAW264.7 macrophages (BALB/C Abelson murine leukemia virus‐induced tumor). Ambient PM₁₀ was collected using a high volume sampler in Little Rock, AR. Analysis revealed that PM₁₀ was composed mainly of Al and Fe, and the water soluble organic fraction was dominated by aliphatic and carbohydrate fragments and minor quantities of aromatic components. Exposure to PM₁₀ compromised the cellular epigenome at concentrations 10–200 µg/ml. Specifically, epigenetic alterations were evident as changes in the methylation and expression of repetitive element‐associated DNA and associated DNA methylation machinery. These results suggest that epigenetic alterations, in concert with cytotoxicity, oxidative stress, and inflammation, might contribute to the pathogenesis of PM‐associated respiratory diseases. Environ. Mol. Mutagen. 55:428–435, 2014. © 2014 Wiley Periodicals, Inc.     

Role of No Scalpel Vasectomy in Male Sterilization

No Scalpel Vasectomy (NSV) is a modern method of delivery, ligation and excision of vas deference without use of a knife. It provides a permanent sterilization option for male. It is a safe, effective method of vasectomy with low complication and greater patient compliance. To evaluate effectiveness and its acceptance of the procedure data were collected on men who accepted NSV between Jan??2008 to Mar??09. Demographic information, motivating factors, educational status and surgical complications were recorded. The cases were done in rural hospitals & Primary health centers as camp procedure. A total of 649 vasectomies performed using NSV method from Jan??08 to Mar??09. The mean age of the acceptors was 35?years with 4 numbers of children on average. Complications included bleeding during surgery in 4 cases (0.6%), haematoma in one case (0.2%), and superficial wound infection occurred in two cases (0.3%) and scrotal pain in 4 cases (0.6%). NSV is an effective, minimal access method of vas delivery, ligation and excision. It provides safe and effective contraceptive option to male population with minimal complications. Doctors, health workers along with the simplicity of procedure and early return to work are great motivating factors. It is easily performed as camp procedure in a simple medical setup. Doctors can be effectively trained hands on during the camp procedure.     

An observational study of sun and heat protection during Canada Day outdoor celebration, 2003

Attendance at summer outdoor mass gatherings may lead to heat- and sun-related illness. The purposes of this study were: (1) to estimate the proportion of people in attendance at the 2003 Canada Day celebration in the National Capital Region who used sun and heat protective items; (2) to identify factors associated with the utilization of these protective items; and (3) to provide research data to public outdoor event organizers when developing evidence-based plans for safer events. A naturalistic observational cross-sectional method was used to gather information at the 2003 Canada Day celebration in the National Capital Region on attendees' demographics, the sun and heat protective items they used and the protective resources available at the event sites. Of the 398 observed attendees, the proportion using any one of the protective items ranged from 3 percent (an open umbrella) to 51.5 percent (sunglasses). Females were more likely to use protective items more than males, and adults more likely than children. Planners of public outdoor events should consider the factors that influence the utilization of sun and heat protective behaviours and the environmental modifications that would allow participants to make safe choices.     

Plazomicin: an investigational therapy for the treatment of urinary tract infections

Introduction: Living in the ever-expanding era of multidrug-resistant (MDR), extensively drug-resistant (XDR), and even pandrug-resistant Gram-negative microorganisms, the medical community is facing the approaching fear of the “End of Antibiotics.” Plazomicin is a next-generation aminoglycoside designed to evade all clinically relevant aminoglycoside-modifying enzymes, the main mechanism of aminoglycoside resistance. A newer aminoglycoside active against several MDR-XDR microorganisms is herein presented and discussed.

Areas covered: Herein, the authors present the currently available information on plazomicin. This includes the current knowledge concerning plazomicin’s: mechanisms of action, in vitro activity and interactions, its pharmacokinetics, its clinical efficacy in complicated urinary tract infections (cUTIs) and acute pyelonephritis, and its toxicity issues.

Expert opinion: Plazomicin was developed to evade all clinically relevant aminoglycoside-modifying enzymes. Unfortunately, ribosomal enzymatic modification by ribosomal 16S-rRNA methyltransferases confers broad-spectrum high-level aminoglycoside resistance. Still, plazomicin demonstrates high activity against the Enterobacteriaceae including extended spectrum beta lactamase and most carbapenemase producers, as well as several of the non-fermenters. When compared to levofloxacin, the in vivo activity of plazomicin in complicated urinary tract infections (cUTIs) and in acute pyelonephritis in humans was very promising. Furthermore, regarding safety, no clinically significant effects on renal, vestibular, or cochlear function have been observed both at Phase I and II studies in humans, with mild to moderate adverse events being dose related. However, the authors believe that the real position of plazomicin in the MDR-XDR world will be revealed once pending Phase III studies are completed.     

Using big data to retrospectively validate the COMPASS-CAT risk assessment model: considerations on methodology

Journal of Thrombosis and Thrombolysis - External validation is a prerequisite in order for a prediction model to be introduced into clinical practice. Nonetheless, methodologically intact external...     

Tamoxifen induced hepatotoxicity in breast cancer patients with pre-existing liver steatosis: the role of glucose intolerance

OBJECTIVE: Tamoxifen induced hepatotoxicity has not been investigated in breast cancer patients with pre-existing liver steatosis. The aim of our study was to investigate the most common predisposing factors for non-alcoholic fatty liver disease in breast cancer patients with liver steatosis, treated with adjuvant tamoxifen therapy, in order to evaluate their role in the appearance of tamoxifen induced hepatotoxicity. METHODS: Clinical and laboratory evaluation, including an oral glucose tolerance test, was done in 60 women with breast cancer and liver steatosis before the beginning of adjuvant tamoxifen treatment and every 6 months during treatment. Tamoxifen induced hepatotoxicity was defined as abnormal liver function tests during tamoxifen treatment whereas these test results were below the normal range at baseline control. Statistical evaluation of data was performed using parametric methodology (the chi-squared test, and Student's t-test, P < 0.05). RESULTS: Twenty-six patients (43.3%) exhibited tamoxifen induced hepatotoxicity (group A) whereas 34 (56.7%) did not (group B). The mean overall follow-up period for the whole group was 37.5 months (SD 27.8, range 6-120 months) and did not differ between the two groups (P = 0.055). There was significant statistical difference in body mass index (BMI) and baseline fasting glucose, cholesterol and triglyceride levels between the two groups. Eighteen of 26 patients (69.2%) from group A had impaired glucose tolerance compared with only 8/34 patients (23.5%) from group B (P < 0.001), a finding observed even in BMI matched patients from the two groups (62.5% vs 12.5%, P = 0.002). CONCLUSIONS: Tamoxifen induced hepatotoxicity is observed in a great proportion of breast cancer patients with pre-existing liver steatosis, especially those with higher BMI and higher glucose and lipid levels at baseline control. Glucose intolerance before the beginning of tamoxifen treatment seems to be a predictor of the hepatotoxicity, unrelated to baseline BMI.