Contributions of cell kill and posttreatment tumor growth rates to the repopulation of intracerebral 9L tumors after chemotherapy: An MRI study

The drought of progress in clinical brain tumor therapy provides an impetus for developing new treatments as well as methods for testing therapeutics in animal models. The inability of traditional assays to simultaneously measure tumor size, location, growth kinetics, and cell kill achieved by a treatment complicates the interpretation of therapy experiments in animal models. To address these issues, tumor volume measurements obtained from serial magnetic resonance images were used to noninvasively estimate cell kill values in individual rats with intracerebral 9L tumors after treatment with 0.5, 1, or 2 × LD10 doses of 1,3-bis(2-chloroethyl)-1-nitrosourea. The calculated cell kill values were consistently lower than those reported using traditional assays. A dose-dependent increase in 9L tumor doubling time after treatment was observed that significantly contributed to the time required for surviving cells to repopulate the tumor mass. This study reveals that increases in animal survival are not exclusively attributable to the fraction of tumor cells killed but rather are a function of the cell kill and repopulation kinetics, both of which vary with treatment dose.

Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: Reversal by D1 antagonists

The conditioning of cocaine's subjective actions with environmental stimuli may be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of learning factors in persistent addictive behavior as well as the neurobiological basis of this phenomenon, rats were trained to associate discriminative stimuli (SD) with the availability of i.v. cocaine vs. nonrewarding saline solution, and then placed on extinction conditions during which the i.v. solutions and SDs were withheld. The effects of reexposure to the SD on the recovery of responding at the previously cocaine-paired lever and on Fos protein expression then were determined in two groups. One group was tested immediately after extinction, whereas rats in the second group were confined to their home cages for an additional 4 months before testing. In both groups, the cocaine SD, but not the non-reward SD, elicited strong recovery of responding and increased Fos immunoreactivity in the basolateral amygdala and medial prefrontal cortex (areas Cg1/Cg3). The response reinstatement and Fos expression induced by the cocaine SD were both reversed by selective dopamine D1 receptor antagonists. The undiminished efficacy of the cocaine SD to elicit drug-seeking behavior after 4 months of abstinence parallels the long-lasting nature of conditioned cue reactivity and cue-induced cocaine craving in humans, and confirms a significant role of learning factors in the long-lasting addictive potential of cocaine. Moreover, the results implicate D1-dependent neural mechanisms within the medial prefrontal cortex and basolateral amygdala as substrates for cocaine-seeking behavior elicited by cocaine-predictive environmental stimuli.

Anti-mosquito midgut antibodies block development of Plasmodium falciparum and Plasmodium vivax in multiple species of Anopheles mosquitoes and reduce vector fecundity and survivorship

The mosquito midgut plays a central role in the sporogonic development of malaria parasites. We have found that polyclonal sera, produced against mosquito midguts, blocked the passage of Plasmodium falciparum ookinetes across the midgut, leading to a significant reduction of infections in mosquitoes. Anti-midgut mAbs were produced that display broad-spectrum activity, blocking parasite development of both P. falciparum and Plasmodium vivax parasites in five different species of mosquitoes. In addition to their parasite transmission-blocking activity, these mAbs also reduced mosquito survivorship and fecundity. These results reveal that mosquito midgut-based antibodies have the potential to reduce malaria transmission in a synergistic manner by lowering both vector competence, through transmission-blocking effects on parasite development, and vector abundance, by decreasing mosquito survivorship and egg laying capacity. Because the intervention can block transmission of different malaria parasite species in various species of mosquitoes, vaccines against such midgut receptors may block malaria transmission worldwide.

Challenges, Strengths and Opportunities Related to Implementing Comprehensive Evidence-Based Guidelines on Breast Cancer Survivorship Care by Primary Care Physicians and Nurse Practitioners in Southeastern Ontario

Background Many breast cancer survivors continue to have a broad range of physical and psychosocial problems after breast cancer treatment. As cancer centres move forward with earlier discharge of stable breast cancer survivors to primary care follow-up it is important that comprehensive evidence-based breast cancer survivorship care is implemented to effectively address these needs. Research suggests primary care providers are willing to provide breast cancer survivorship care but many lack the knowledge and confidence to provide evidence-based care. Purpose The overall purpose of this thesis was to determine the challenges, strengths and opportunities related to implementing comprehensive evidence-based breast cancer survivorship guidelines by primary care physicians and nurse practitioners in southeastern Ontario. Methods This mixed-methods research was conducted in three phases: (1) synthesis and appraisal of clinical practice guidelines relevant to provision of breast cancer survivorship care within the primary care practice setting; (2) a brief quantitative survey of primary care providers to determine actual practices related to provision of evidence-based breast cancer survivorship care; and (3) individual interviews with primary care providers about the challenges, strengths and opportunities related to provision of comprehensive evidence-based breast cancer survivorship care. Results and Conclusions In the first phase, a comprehensive clinical practice framework was created to guide provision of breast cancer survivorship care and consisted of a one-page checklist outlining breast cancer survivorship issues relevant to primary care, a three-page summary of key recommendations, and a one-page list of guideline sources. The second phase identified several knowledge and practice gaps, and it was determined that guideline implementation rates were higher for recommendations related to prevention and surveillance aspects of survivorship care and lowest related to screening for and management of long-term effects. The third phase identified three major challenges to providing breast cancer survivorship care: inconsistent educational preparation, provider anxieties, and primary care burden; and three major strengths or opportunities to facilitate implementation of survivorship care guidelines: tools and technology, empowering survivors, and optimizing nursing roles. A better understanding of these challenges, strengths and opportunities will inform development of targeted knowledge translation interventions to provide support and education to primary care providers.

Commutation tables for joint annuities & survivorship assurances, based on the Carlisle mortality at 3, 3 1/2, 4, 5, and 6 per cent interest, with tables of annuities & assurances on single lives, and other useful tables, and an introduction on their construction & use.

Mode of access: Internet.

Traité de Porphyre, touchant l'abstinence de la chair des animaux : avec la vie de Plotin par ce philosophe, et une dissertation sur les genies /

Mode of access: Internet.

Proceedings of the Congressional total abstinence society,

From the Washington ed.

Intemperance among literary men. An address, delivered before the Portland Young Men's Total Abstinence Society, on Sunday evening, July 31, in the Park Street Church and repeated, by request, on Sunday evening, Aug. 7, in the First Parish Church.

Mode of access: Internet.

The Washingtonian reform : an address, delivered before the Hingham Total Abstinence Society, June 16, 1844 /

"Published by request of the Government of the Society."

Traité de Porphyre, touchant l'abstinence de la chair des animaux : avec la vie de plotin.

Mode of access: Internet.

A second declaration of independence; or, The manifesto of all the Washington total abstinence societies of the United States of America.

Cover-title.

Combined acamprosate and naltrexone, with cognitive behavioural therapy is superior to either medication alone for alcohol abstinence: A single centres' experience with pharmacotherapy

Aims: To compare treatment outcomes amongst patients offered pharmacotherapy with either naltrexone or acamprosate used singly or in combination, in a 12-week outpatient cognitive behavioural therapy (CBT) programme for alcohol dependence. Methods: We matched 236 patients across gender, age group, prior alcohol detoxification, and dependence severity and conducted a cohort comparison study of three medication groups (CBT+acamprosate, CBT+naltrexone, CBT+combined medication) which included 59 patients per group. Outcome measures included programme attendance, programme abstinence and for those who relapsed, cumulative abstinence duration (CAD) and days to first breach (DFB). Secondary analyses compared the remaining matched 59 subjects who declined medication with the pharmacotherapy groups. Results: Across medication groups, CBT+ combined medication produced the greatest improvement across all outcome measures. Although a trend favoured the CBT+ combined group, differences did not reach statistical significance. Programme attendance: CBT + Acamprosate group (66.1%), CBT + Naltrexone group (79.7%), and in the CBT + Combined group (83.1%). Abstinence rates were 50.8, 66.1, and 67.8%, respectively. For those that did not complete the programme abstinent, the average number of days abstinent (CAD) were 45.07, 49.95, and 53.58 days, respectively. The average numbers of days to first breach (DFB) was 26.79, 26.7, and 37.32 days. When the focal group (CBT + combined) was compared with patients who declined medication (CBT-alone), significant differences were observed across all outcome indices. Withdrawal due to adverse medication effects was minimal. Conclusions: The addition of both medications (naltrexone and acamprosate) resulted in measurable benefit and was well tolerated. In this patient population naltrexone with CBT is as effective as combined medication with CBT, but the trend favours combination medication.