Gemcitabine and carboplatin in intensively pretreated patients with metastatic breast cancer

Background: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. Patients and Methods: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. Results: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombo-cytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. Conclusion: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2). Copyright (c) 2008 S. Karger AG, Basel

High efficacy and low toxicity of weekly docetaxel given as first-line treatment for metastatic breast cancer

Background: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer. Patients and Methods: All patients received docetaxel, 35 mg/m(2) weekly for 6 weeks, followed by 2 weeks of rest. Subsequent cycles ( 3 weeks of treatment, 2 weeks of rest) were given until a maximum of 5 cycles or disease progression. Premedication consisted of 8 mg dexamethasone intravenously 30 min prior to the infusion of docetaxel. Results: Fifty-four patients at a median age of 58 years with previously untreated MBC were included in the study. A median of 10 doses ( median cumulative dose 339 mg/m(2)) was administered ( range: 2 - 18). The overall response rate was 48.1% ( 95% CI: 34 - 61%, intent-to-treat). Median survival was 15.8 months and median time to progression was 5.9 months ( intent-to-treat). Hematological toxicity was mild with absence of neutropenia-related complications. Grade 3 neutropenia was observed in 3.7% of patients and grade 3 and 4 anemia was observed in 5.6 and 1.9% of patients, respectively. Conclusion: The weekly administration of docetaxel is highly efficient and safe as first-line treatment for MBC and may serve as an important treatment option specifically in elderly patients and patients with a reduced performance status. Copyright (C) 2005 S. Karger AG, Basel

Metabolic drift in the aging brain.

Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication

Health-seeking behaviour, diagnostics and transmission dynamics in the control of visceral leishmaniasis in the Indian subcontinent.

Countries in the Indian subcontinent have committed to reducing the incidence of kala-azar, a clinical manifestation of visceral leishmaniasis, to below 1 in 10,000 by 2020. We address the role of timing of use and accuracy of diagnostics in kala-azar control and elimination. We use empirical data on health-seeking behaviour and health-system performance from the Indian state of Bihar, Bangladesh and Nepal to parameterize a mathematical model. Diagnosis of cases is key to case management, control and surveillance. Treatment of cases prevents onward transmission, and we show that the differences in time to diagnosis in these three settings explain the observed differences in incidence. Shortening the time from health-care seeking to diagnosis is likely to lead to dramatic reductions in incidence in Bihar, bringing the incidence down to the levels seen in Bangladesh and Nepal. The results emphasize the importance of maintaining population and health-system awareness, particularly as transmission and disease incidence decline. We explore the possibility of diagnosing patients before the onset of clinical kala-azar (before 14 days fever), and show that this could have a marked impact on incidence, even for a moderately sensitive test. However, limited specificity (that results in false positives) is a major barrier to such a strategy. Diagnostic tests of high specificity used at an early stage of active infection, even if sensitivity is only moderate, could have a key role in the control of kala-azar, and prevent its resurgence when paired with the passive health-care system and tests of high sensitivity, such as the test for rK39 antibody response

Late pleistocene sedimentation history of the Shirshov Ridge, Bering Sea

The analysis of the lithology, grain-size distribution, clay minerals, and geochemistry of Upper Pleistocene sediments from the submarine Shirshov Ridge (Bering Sea) showed that the main source area was the Yukon–Tanana terrane of Central Alaska. The sedimentary materials were transported by the Yukon River through Beringia up to the shelf break, where they were entrained by a strong northwestward-flowing sea current. The lithological data revealed several pulses of ice-rafted debris deposition, roughly synchronous with Heinrich events, and periods of weaker bottom-current intensity. Based on the geochemical results, we distinguished intervals of an increase in paleoproductivity and extension of the oxygen minimum zone. The results suggest that there were three stages of deposition driven by glacioeustatic sea-level fluctuations and glacial cycles in Alaska

Quantitative Analysis of Honey Bee Blood-Ethanol Levels Following Exposure to Ethanol Vapors

The use of invertebrate models has allowed researchers to examine the mechanisms behind alcoholism and its effects with a cost-effective system. In that respect, the honey bee is an ideal model species to study the effects of ethanol (EtOH) due to the behavioral and physiological similarities of honey bees with humans when alcohol is consumed. Although both ingestion and inhalation methods are used to dose subjects in insect EtOH model systems, there is little literature on the use of the EtOH vapor-exposure method for experiments using honey bees. The experiment presented here provides baseline data for a dose EtOH-hemolymph response curve when using EtOH vapor-inhalation dosing with honey bees (Apis mellifera). Bees were exposed to EtOH vapors for 0, 1, 2.5, or 5 min, and hemolymph was collected 1 min post EtOH exposure. Hemolymph samples were analyzed using gas chromatography (GC) for hemolymph EtOH concentration. The ethanol-hemolymph level of the bees increased linearly with exposure time. The results provide a dosing guide for hemolymph EtOH level in the honey bee model ethanol-inhalation system, and thus makes the honey bee model more robust.&nbsp

The Use of Dwarf Octopus (Octopus joubini) As A Model for Hands-On Research Experience in Comparative Psychology

The Laboratory of Comparative Psychology and Behavioral Biology at Oklahoma State University has been developing comparative psychology teaching exercises for over 30 years. In this paper, we provide suggestions for using the dwarf octopus (Octopus joubini) to teach students about the importance of observation, and the relationship of observation in the creation of ethograms and experimental design. Throughout this paper, students learn how to properly make an observation of a novel animal, create an ethogram, and conduct an experiment. We present a sample observation activity and three additional experiments, during which students will observe and record behaviors and environmental conditions. Students learn saltwater tank upkeep, time management, creation and coding of operational definitions, attention to changes in animal behavior, and the experimental process. These observation studies allow students to observe and record behavioral data to understand comparative psychology and experimental design.  &nbsp

An experimental investigation on mass transfer in presence of chemical reactions on a graphite cylinder in crossflow

In connection with analyses of hypothetical massive air ingress accidents in HTGR ($\underline{H}$igh $\underline{T}$emperature $\underline{G}$as-Cooled $\underline{R}$eactor), in which it is assumed that the air is transported through the hot region of graphite core support posts, experiments on mass transfer and in-pore diffusion with homogeneous and heterogeneous chemical reactions were performed on a graphite cylinder in crossflow. Two BLMR ($\underline{B}$oundary $\underline{L}$ayer $\underline{M}$ass transfer controlled $\underline{R}$egime) runs and two runs in an intermediate regime between BLMR and IPDR ($\underline{I}$n-$\underline{P}$ore-$\underline{D}$iffusion controlled $\underline{R}$egime) were executed at atmospheric pressures, Reynolds numbers ranging from 533 to 2490, and cylinder temperatures from 848°C to 1120°C. The nuclear grade graphite cylinder having a diameter of 100 mm and a porosity of 21.2 % was corroded in a nitrogen gas flow containing approximately 5 % oxygen. Mean and local mass transfer coefficients and corrosion rates were obtained to examine the influences of the chemical reactions on the mass transfer. As a result it can be concluded that the chemical reactions and small changes in shape do not significantly influence the mass transfer under conditions to be expected in HTGR air ingress accidents and that thus the analogy between heat and mass transfer can be used for safety calculations