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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Addictive Behaviors 3 (1978), S. 65-70 
    ISSN: 0306-4603
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine , Psychology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Addictive Behaviors 4 (1979), S. 345-348 
    ISSN: 0306-4603
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine , Psychology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 26 (1993), S. S3 
    ISSN: 1573-7217
    Keywords: breast cancer ; cisplatin ; cyclophosphamide ; etoposide ; mitoxantrone ; stem cell transplantation ; thiotepa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have evaluated tandem cycles of a tri-drug combination, termed CVP (cyclophosphamide, etoposide [VP-16], and cisplatin [Platinol]), at four levels in more than 300 patients with various types of tumors. Tandem CVP appears to be at least therapeutically equivalent to alternatives. A second potentially noncross-resistant combination of mitoxantrone and thiotepa (MT), with or without etoposide, has been used in sequence following CVP to improve long-term, disease-free survival in patients who have multiple metastatic sites, who relapse shortly after adjuvant therapy, or who show other unfavorable clinical features. A combination of MT and etoposide (MVT) achieved an overall response rate of 61% in 32 patients with metastatic or refractory breast cancer. The etoposide was then eliminated to decrease the major toxicities of this regimen. MT was subsequently given to 37 evaluable patients prior to bone marrow infusion. The overall response rate was 48.5%. Thirty patients with metastatic breast cancer were then treated with induction therapy, a cycle of CVP, and then a cycle of MT. Given the low complete remission (CR) rate to induction therapy in these patients, the CR rate achieved with CVP-MT was encouraging. Further studies are ongoing.
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 2015-01-27
    Description: Background and Purpose— Diffusion MRI is a promising, clinically feasible imaging technique commonly used to describe white matter changes after stroke. We investigated the sensitivity of diffusion MRI to detect microstructural alterations in gray matter after sensorimotor cortex stroke in adult male rats. Methods— The mean diffusivity (MD) and mean kurtosis of perilesional motor cortex were compared with measures in the contralesional forelimb area of sensorimotor cortex at 2 hours, 24 hours, 72 hours, or 25 days after surgery. MD and mean kurtosis were correlated to the surface densities of glia, dendrites, and axons. Results— Perilesional mean kurtosis was increased at 72 hours and 25 days after stroke, whereas MD was no longer different from contralesional sensorimotor cortex at 24 hours after stroke. There was a significant increase in the density of glial processes at 72 hours after stroke in perilesional motor cortex, which correlated with perilesional MD. Conclusions— These data support that mean kurtosis and MD provide different but complimentary information on acute and chronic changes in perilesional cortex. Glia infiltration is associated with pseudonormalization of MD in the perilesional motor cortex at 72 hours after lesion; however, this association is absent 25 days after lesion. These data suggest that there are likely several different, time-specific microstructural changes underlying these 2 complimentary diffusion measures.
    Keywords: Cerebrovascular disease/stroke, Imaging, Morphology, CT and MRI, Behavioral Changes and Stroke
    Print ISSN: 0039-2499
    Electronic ISSN: 1524-4628
    Topics: Medicine
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  • 5
    Publication Date: 2012-05-10
    Description: BACKGROUND: Detailed information about how patients with head and neck carcinoma (HNC) are treated across practice settings does not exist. The authors conducted a prospective, observational study to examine the patterns of care for a series of patients with newly diagnosed HNC in the United States and to test 2 hypotheses: 1) There is no difference in the pattern of care between community and academic settings; and 2) the results of major randomized clinical trials will change the pattern of care in both practice settings within 1 year of publication in peer-reviewed journals. METHODS: Patients aged ≥18 years were enrolled in the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN) after providing written informed consent if they had a confirmed diagnosis of new HNC and were scheduled to receive treatment other than surgery alone. RESULTS: Between 2005 and 2010, 100 centers enrolled 4243 patients, including 2612 patients (62%) from academic investigators and 1631 patients (38%) from community centers. Initial treatments were radiation with concurrent chemotherapy (30%) or cetuximab (9%), adjuvant radiotherapy (21%), induction chemotherapy (16%), and other (24%). Intensity modulated radiation therapy was the dominant radiation technique (84%). Single-agent cisplatin was prescribed in nearly half of patients and more often in academic centers (53% vs 43% of patients; P 〈 .0001). Single-agent cetuximab was the next most common drug used (19%) and was prescribed more frequently in community settings (24% vs 17%; P = .0001). The data rejected the 2 prospective hypotheses. CONCLUSIONS: LORHAN documented differences in patient characteristics and treatments between community and academic settings for a large series of patients in the United States. Cancer 2012. © 2012 American Cancer Society.
    Print ISSN: 0008-543X
    Electronic ISSN: 1097-0142
    Topics: Biology , Medicine
    Published by Wiley-Blackwell on behalf of The American Cancer Society.
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  • 6
    Publication Date: 2014-01-07
    Description: Haloperidol is an efficacious antipsychotic drug that has serious, unpredictable motor side effects that limit its utility and cause noncompliance in many patients. Using a drug–placebo diallel of the eight founder strains of the Collaborative Cross and their F 1 hybrids, we characterized aggregate effects of genetics, sex, parent of origin, and their combinations on haloperidol response. Treating matched pairs of both sexes with drug or placebo, we measured changes in the following: open field activity, inclined screen rigidity, orofacial movements, prepulse inhibition of the acoustic startle response, plasma and brain drug level measurements, and body weight. To understand the genetic architecture of haloperidol response we introduce new statistical methodology linking heritable variation with causal effect of drug treatment. Our new estimators, "difference of models" and "multiple-impute matched pairs", are motivated by the Neyman–Rubin potential outcomes framework and extend our existing Bayesian hierarchical model for the diallel ( Lenarcic et al. 2012 ). Drug-induced rigidity after chronic treatment was affected by mainly additive genetics and parent-of-origin effects (accounting for 28% and 14.8% of the variance), with NZO/HILtJ and 129S1/SvlmJ contributions tending to increase this side effect. Locomotor activity after acute treatment, by contrast, was more affected by strain-specific inbreeding (12.8%). In addition to drug response phenotypes, we examined diallel effects on behavior before treatment and found not only effects of additive genetics (10.2–53.2%) but also strong effects of epistasis (10.64–25.2%). In particular: prepulse inhibition showed additivity and epistasis in about equal proportions (26.1% and 23.7%); there was evidence of nonreciprocal epistasis in pretreatment activity and rigidity; and we estimated a range of effects on body weight that replicate those found in our previous work. Our results provide the first quantitative description of the genetic architecture of haloperidol response in mice and indicate that additive, dominance-like inbreeding and parent-of-origin effects contribute strongly to treatment effect heterogeneity for this drug.
    Print ISSN: 0016-6731
    Topics: Biology
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  • 7
    Publication Date: 2017-05-02
    Description: Regulation of the formation and rewiring of neural circuits by neuropeptides may require coordinated production of these signaling molecules and their receptors that may be established at the transcriptional level. Here, we address this hypothesis by comparing absolute expression levels of opioid peptides with their receptors, the largest neuropeptide family, and by characterizing coexpression (transcriptionally coordinated) patterns of these genes. We demonstrated that expression patterns of opioid genes highly correlate within and across functionally and anatomically different areas. Opioid peptide genes, compared with their receptor genes, are transcribed at much greater absolute levels, which suggests formation of a neuropeptide cloud that covers the receptor-expressed circuits. Surprisingly, we found that both expression levels and the proportion of opioid receptors are strongly lateralized in the spinal cord, interregional coexpression patterns are side specific, and intraregional coexpression profiles are affected differently by left- and right-side unilateral body injury. We propose that opioid genes are regulated as interconnected components of the same molecular system distributed between distinct anatomic regions. The striking feature of this system is its asymmetric coexpression patterns, which suggest side-specific regulation of selective neural circuits by opioid neurohormones.—Kononenko, O., Galatenko, V., Andersson, M., Bazov, I., Watanabe, H., Zhou, X. W., Iatsyshyna, A., Mityakina, I., Yakovleva, T., Sarkisyan, D., Ponomarev, I., Krishtal, O., Marklund, N., Tonevitsky, A., Adkins, D. L., Bakalkin, G. Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits.
    Print ISSN: 0892-6638
    Electronic ISSN: 1530-6860
    Topics: Biology
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  • 8
    Publication Date: 2017-05-02
    Description: Purpose: Ras/MEK/ERK pathway activation is common in oral cavity squamous cell carcinoma (OCSCC). We performed a neoadjuvant (preoperative) trial to determine the biomarker and tumor response of OCSCC to MEK inhibition with trametinib. Experimental Design: Patients with stage II–IV OCSCC received trametinib (2 mg/day, minimum 7 days) prior to surgery. Primary tumor specimens were obtained before and after trametinib to evaluate immunohistochemical staining for p-ERK1/2 and CD44, the primary endpoint. Secondary endpoints included changes in clinical tumor measurements and metabolic activity [maximum standardized uptake values (SUV max ) by F-18 fluorodeoxyglucose positron emission tomography/CT), and in tumor downstaging. Drug-related adverse events (AE) and surgical/wound complications were evaluated. Results: Of 20 enrolled patients, 17 (85%) completed the study. Three patients withdrew because of either trametinib-related ( n = 2: nausea, duodenal perforation) or unrelated ( n = 1: constipation) AEs. The most common AE was rash (9/20 patients, 45%). Seventeen patients underwent surgery. No unexpected surgical/wound complications occurred. Evaluable matched pre- and posttrametinib specimens were available in 15 (88%) of these patients. Reduction in p-ERK1/2 and CD44 expression occurred in 5 (33%) and 2 (13%) patients, respectively. Clinical tumor response by modified World Health Organization criteria was observed in 11 of 17 (65%) evaluable patients (median 46% decrease, range 14%–74%). Partial metabolic response (≥25% reduction in SUV max ) was observed in 6 of 13 (46%) evaluable patients (median 25% decrease, range 6%–52%). Clinical-to-pathologic tumor downstaging occurred in 9 of 17 (53%) evaluable patients. Conclusions: Trametinib resulted in significant reduction in Ras/MEK/ERK pathway activation and in clinical and metabolic tumor responses in patients with OCSCC. Clin Cancer Res; 23(9); 2186–94. ©2016 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 9
    Publication Date: 2012-08-04
    Description: At the Last Glacial Maximum (LGM), the salinity contrast between northern source deep water and southern source bottom water was reversed with respect to the contrast today. Additionally, Glacial Southern Source Bottom Water (GSSBW) was saltier than Antarctic Bottom Water (AABW), over and above the difference implied by the mean sea level change. This study examines to what extent cold temperatures, through their effect on ice formation and melting, could have caused these differences. Computational sensitivity experiments using a coupled ice shelf cavity–sea ice–ocean model are performed in a Weddell Sea domain, as a representative case study for bottom water formation originating from Antarctic continental shelves. Ocean temperatures at the domain open boundaries are systematically lowered to determine the sensitivity of Weddell Sea water mass properties to a range of cool ocean temperatures. The steady state salinities differ between experiments due to temperature-induced responses of ice shelf and sea ice melting and freezing, evaporation and open boundary fluxes. The results of the experiments indicate that reduced ocean temperature can explain up to 30% of the salinity difference between GSSBW and AABW, primarily due to decreased ice shelf melting. The smallest and most exposed ice shelves, which abut narrow continental shelves, have the greatest sensitivity to the ocean temperature changes, suggesting that at the LGM there could have been a shift in geographical site dominance in bottom water formation. More sea ice is formed and exported in the cold ocean experiments, but the effect of this on salinity is negated by an equal magnitude reduction in evaporation.
    Print ISSN: 0883-8305
    Electronic ISSN: 1944-9186
    Topics: Geosciences
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