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Subsequent Decades (subsequent + decade)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Genetic determinants for activated fluoropyrimidine chemotherapy

DRUG DEVELOPMENT RESEARCH, Issue 2 2006
William H. GmeinerArticle first published online: 5 JUN 200
Abstract Fluoropyrimidines (FPs) remain widely used for the treatment of diverse malignancies more than four decades following the initial report of 5-fluorouracil (5FU), the archetypal FP, as a novel compound with potential anti-neoplastic activity. Subsequent decades of research have enriched our understanding of the biochemical mechanisms that are important for FP activation as well as the genetic determinants that are predictive of the likely success, or failure, of FP chemotherapy for a particular individual. The concept that chemotherapy should be customized to complement the genetic profiles of cancer patients has become increasingly important as genotyping of tumor samples has become possible and as the number of available anticancer drugs has increased. Significant progress has been made in identifying the gene expression profiles for cancer patients who are likely to benefit from treatment with FPs. In this review, we will summarize the results of retrospective clinical studies correlating response to FP chemotherapy with the expression of specific genes, such as TS and DPD. We will also present a summary of FPs in current clinical use, including orally bioavailable FPs such as capecitabine, as well as FPs that are in pre-clinical development, such as FdUMP[10]. Refinement of a target population through pharmacogenetic analysis and development of novel FPs that evoke very high response rates in this target population will likely result in the use of FP regimens in the coming era when cancer becomes a largely manageable disease. Drug Dev. Res. 67:119,129, 2006. © 2006 Wiley-Liss, Inc. [source]

Oral ciprofloxacin plus colistin: prophylaxis against bacterial infection in neutropenic patients.

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2001
A strategy for the prevention of emergence of antimicrobial resistance
Following a 2-year study, the combination of oral ciprofloxacin and colistin has been used continuously for 10 years without the emergence of resistance. During a 2-year period (1987,1989), we compared ciprofloxacin + colistin (CIP + COL) with neomycin + colistin (NEO + COL) in a randomized trial , combinations chosen because of the potential for prophylaxis of Gram-negative infection by ciprofloxacin, with colistin given to reduce the risk of emergence of resistance. Sixty-four patients with similar demographics in each arm were evaluable for efficacy analysis. Patients on CIP + COL had a significantly lower proportion of neutropenic days with fever (P < 0·001) and neutropenic days on intravenous antibiotics (P < 0·001) than patients on NEO + COL. A total of 54 (15 bacteriologically documented) pyrexial episodes occurred in patients on CIP + COL and 77 (41 bacteriologically documented) in patients on NEO + COL. Only two Gram-negative bacterial infections occurred in the CIP + COL arm compared with 16 in the NEO + COL arm. No Staphylococcus aureus infections occurred in the CIP + COL group compared with 10 in the other patients. Two CIP-resistant Gram-negative bacilli were isolated from patients on CIP + COL compared with 13 NEO-resistant Gram-negative bacilli from patients on NEO + COL. Following a subsequent decade of unchanged use of this prophylactic strategy in neutropenic patients, a 2-year follow-up study between 1 January 1998 and 31 December 1999 showed 66 significant infections during 350,400 neutropenic episodes. Eight of the 111 (7·2%) isolates were with ciprofloxacin-resistant organisms, involving 2% of the neutropenic episodes, indicating that the strategy of combining colistin with ciprofloxacin has been effective in the prevention of Gram-negative sepsis in neutropenic patients without the emergence of significant resistance despite widespread concurrent hospital and community use of the quinolones. [source]

"PROTECTION AND REAL WAGES": THE HISTORY OF AN IDEA

THE JAPANESE ECONOMIC REVIEW, Issue 4 2006
RONALD W JONES
Few economics articles have achieved the celebrity that still attaches to the paper, "Protection and Real Wages", by Wolfgang Stolper and Paul Samuelson in (1941). In this paper I discuss how the Stolper-Samuelson theorem has been re-interpreted over subsequent decades, and how attempts to generalize the theorem to higher dimensions have met with qualified results. The theorem leads to a simple proposition in political economy: in competitive models any productive factor can have its real return increased by a non-transparent policy whereby relative commodity prices are altered if there are enough commodities and joint production, is not too severe. [source]

Emanuel Miller Lecture: Early onset depressions , meanings, mechanisms and processes

THE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 12 2008
Ian M. Goodyer
Background:, Depressive syndromes in children and adolescents constitute a serious group of mental disorders with considerable risk for recurrence. A more precise understanding of aetiology is necessary to improve treatment and management. Methods:, Three neuroactive agents are purported to be involved in the aetiology of these disorders: serotonin, brain-derived neurotrophic factor and cortisol. A literature review was conducted to determine their contributions to the emergence of unipolar depressions in the adolescent years. Results:, Serotonin, brain-derived neurotrophic factor and cortisol may operate in concert within two distinct functional frameworks: atypical early epigenesis arising in the first few years of life and resulting in the formation of a vulnerable neuronal network involving in particular the amygdala and ventral prefrontal cortex. Individuals with this vulnerability are likely to show impaired mood regulation when faced with environmental demands during adolescence and over the subsequent decades; and acquired neuroendangerment, a pathological brain process leading to reduced synaptic plasticity, in particular in the hippocampus and perhaps the nucleus accumbens and ventral tegmentum. This may result in motivational, cognitive and behavioural deficits at any point in the lifespan most apparent at times of environmental demand. Conclusions:, The characteristics, course and outcome of a depressive episode may depend on the extent of the involvement of both atypical early neurogenesis and acquired neuroendangerment. [source]