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Workaholism surfaced some years ago as a veritable addiction in the wide sense of the term, dependence. It differs from other sorts of dependence in that it is very often viewed in a positive perspective in the sense that it conveys to the person concerned the illusion of well-being, as well as a motivation and dedication in their professional activity. During the past 30 years, several authors have attempted to define this concept and to determine its characteristics. Robinson believes that workaholics have an approach to life whereby their work feeds on time, energy and physical activity. This provokes consequences that affect their physical health and interpersonal relationships. They have a tendency to live in the future rather than in the present. For Scott, Moore and Micelli , the compulsion for work is not necessarily viewed as being detrimental to one's health. Spence and Robbins highlight the notion of the pleasure experienced at work in their theoretical approach. The prevalence of the dependence on work is estimated at between 27 and 30% in the general population. It is correlated to the number of hours of work per week and tends to be higher as annual revenue increases. The sex ratio is 1, and the parents of children 5 to 18 years of age are the most susceptible to considering themselves workaholics. The physical and psychological consequences of professional exhaustion are characterized primarily by the decrease in self-esteem, symptoms of fatigue, anxiety, depression, irritability and the manifestation of physical problems including cardiovascular ailments, as evidenced by hypertension, as well as heart and kidney complications. All the theoretical point of views, from the psychoanalytical models to the contemporary models, highlight self esteem as being the centerpiece of the question regarding the problem of workaholism. In fact, the narcissism articulated from the sociological evolution of our western way of life permits us to delineate the psychic identity of the individual better, and therefore, to understand this reconstructive attempt of one's self better. In characterizing the personality traits of workaholic individuals, the doctor/therapist is required to deal with this new form of dependence as early as possible, in order to anticipate and avert the numerous personal, professional, social, relational and sanitary complications. Faced with this large prevalence of dependence on work, it seems important to us to look for a symptomatology that would emanate a signal of workaholism so as to envisage and propose to workaholic patients a specific course of action that would be adapted to their needs.
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PMID:[Workaholism: between illusion and addiction]. 2085 May 99

Since over-nutrition accelerates the development of obesity, progression to type 2 diabetes, and the associated co-morbidity and mortality, there has been a keen interest in therapeutic interventions targeting mechanisms that may curb appetite, increase energy expenditure or at least attenuate insulin resistance. Over the past decade, numerous peri-mitochondrial targets in the de novo lipid synthesis pathway have been linked to an increase in energy expenditure and the drug development industry has pursued the gene products involved as candidates to develop drugs against. The basis of this link, and specifically the premise that lowering tissue and cellular malonyl-CoA can increase energy expenditure, is scrutinised here. The argument presented is that fuel switching as effected by changes in cellular malonyl-CoA concentrations will not trigger the mitochondria to increase energy expenditure because: (1) an increase in beta-oxidation by lowering respiratory exchange ratio (indicative of the metabolic fuel consumed) does not equal an increase in energy expenditure (how rapidly fuel is consumed); (2) the ATP:oxygen ratios (i.e. ATP energy made:oxygen required for the reaction) are similar when metabolising lipids (2.8) vs glucose (3.0); (3) substrate availability (NEFA) does not drive energy expenditure in vivo; and (4) the availability of ADP in the mitochondrial matrix determines the rate of energy expenditure, not the availability of fuel to enter the mitochondrial matrix. To increase mitochondrial energy expenditure, work must be done (exercise) and/or the mitochondrial proton leak must be enhanced, both of which increase availability of ADP. In fact, despite the historic taboo of chemical uncoupling, this mechanism validated in humans is closest on task to increasing whole-body energy expenditure. Chemical uncoupling mimics the naturally occurring phenomenon of proton leak, accelerating the metabolism of glucose and lipids. However, it is completely non-genomic (i.e. the target is a location, not a gene product) and is not associated with addiction or mood alterations common to satiety agents. A significant hurdle for drug development is to discover a safe mitochondrial uncoupler and to formulate it potentially as a pro-drug and/or oral pump, to avoid the issue of overdosing experienced in the 1930s. The potential therapeutic impact of such a compound for an over-nutritioned patient population could be profound. If effective, the mitochondrial uncoupler mechanism could resolve many of the associated diseases such as type 2 diabetes, hypertension, obesity, depression, sleep apnoea, non-alcoholic steatohepatitis, insulin resistance and hyperlipidaemia, therefore becoming a 'disease-modifying therapy'.
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PMID:Targeting energy expenditure via fuel switching and beyond. 2095 61

Tobacco addiction is the leading cause of preventable disease, disability, and death in Canada and is the most significant of the modifiable cardiovascular risk factors. Tobacco addiction is a principal contributor to the development of coronary artery disease (CAD) and its consequences, including sudden cardiac death, acute myocardial infarction, and heart failure. Its prevention and treatment should be accorded high priority. In fact, 30% of all CAD deaths are attributable to smoking. The identification and documentation of the smoking status of all patients, and the provision of cessation assistance, should be a priority in every cardiovascular setting. Systematic approaches to the identification and treatment of smokers can dramatically enhance the likelihood of cessation-the most cost-effective of all the interventions to prevent the development or progression of CAD. It is the view of the Canadian Cardiovascular Society that all patients in every medical setting-private office, outpatient clinic, or hospital-should have their smoking status systematically identified and documented and be offered specific assistance in initiating a cessation attempt. The provision of unambiguous, nonjudgemental advice regarding the importance of cessation and assistance with the initiation of a smoking cessation attempt should be seen as a fundamental responsibility of any cardiovascular clinician who encounters smokers in any setting. All cardiovascular specialists should be familiar with the principles and practice of smoking cessation. It is important for cardiovascular specialists to be as familiar with the initiation of smoking-cessation pharmacotherapy as they are with the pharmacological management of hypertension and hyperlipidemia.
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PMID:Smoking cessation and the cardiovascular specialist: Canadian Cardiovascular Society position paper. 2145 59

Obesity is a world wide epidemic; it is becoming more usual to be overweight or obese than to be normal weight. Obesity increases the risk of an extensive range of diseases such as cardiovascular disease, diabetes mellitus type 2, hypertension, depression and some types of cancer. Adipose tissue is more than a storage organ for surplus energy - it is also a setting for complex metabolic processes and adipose tissue releases substances that interact with other parts of the body to influence several systems including food intake and energy metabolism. The endocannabinoid system (ECS) is one of the signalling systems that control feeding behaviour. The ECS is implicated in many functions, such as pain, memory, addiction, inflammation, and feeding, and could be considered a stress recovery system. It also seems to integrate nutrient intake, metabolism and storage maintaining homeostatic balance. The ECS is a recently discovered system, and research indicates hyperactivity in obesity. The aim of this thesis is to elaborate on the relationships of this widespread system and its elements in adipose tissue in obesity. Study I is a 4 weeks rat intervention study to investigate whether weight independent effect of Rimonabant treatment exists. We found that food intake-tolerance development could be circumvented by cyclic administration of Rimonabant and implications of weight independent effects of treatment. Study II is a cross-sectional study to establish the expression of cannabinoid receptor 1 from various adipose tissue depots of lean and obese persons. In this study we conclude, that the subcutaneous adipose tissue express more CBR1 than the visceral depot in lean, but comparable levels in obese. Study III is a 10 weeks human intervention study to asses the effects on the ECS of 10% weight loss. We found reduction in the ECS in obesity that normalised with weight loss. Our results clearly show the presence of all the components of the ECS in human adipose tissue, and suggest that the ECS is reduced in adipose tissue in obesity. Our results do not support the hypothesis of hyperactivity of the ECS in human obesity. Possible future treatment of obesity with CBR1 antagonist could involve cyclic treatment of specific peripheral compounds.
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PMID:Investigations of the endocannabinoid system in adipose tissue: effects of obesity/ weight loss and treatment options. 2146 69

Antidepressants are known to have no significant ability to cause addiction. However, a recent study showed many individuals with mood disorders self-medicated with antidepressants to relieve symptoms. We report here a male physician, diagnosed five years ago with major depressive disorder, with insomnia, anxiousness, and chest heaviness. He began self-medicating with 150 mg of venlafaxine daily, without any monitoring. During his most recent severe depressive episode, he was taking up to 1,500 mg of venlafaxine daily. Without this medication, he experienced discontinuation syndrome, which included severe anxiety, chest heaviness, and breathing difficulty, and which he judged as indicating a more severely depressed state. He also experienced overdose symptoms, such as hypertension and tachycardia. He attempted suicide with drugs that he possessed. In conclusion, careful monitoring is needed when treating patients with venlafaxine, because its discontinuation syndrome is similar to symptoms of major depressive disorder, and suicidality may result from an overdose.
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PMID:Uncontrolled self-medication with venlafaxine in a patient with major depressive disorder. 2151 42

Physicians' adoption of buprenorphine/naloxone treatment is hindered by concerns over feasibility, cost, and lack of comfort treating patients with addiction. We examined the use of buprenorphine/naloxone in a community practice by two generalist physicians without addiction training, employing a retrospective chart review. From 2006-2010, 228 patients with opiate abuse/dependence were treated with buprenorphine/naloxone using a home-induction protocol. Multiple co-morbidities including diabetes (23% of patients), hypertension (36%), Hepatitis C (43%), and depression (74%) were concurrently managed. In this diverse sample, 1/228 experienced precipitated withdrawal during induction. Of the convenience subsample analyzed (n = 28), 82% (+/-10%) had negative urine drug tests for opioids; 92% (+/-11%) were negative for cocaine; 88% (+/-12%) were positive for buprenorphine. This case series demonstrated feasibility and safety of a low-cost buprenorphine/naloxone home induction protocol employed by generalists. Concurrent treatment of multiple comorbidities conforms with the patient-centered medical home ideal. Randomized trials of this promising approach are needed.
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PMID:A case series of buprenorphine/naloxone treatment in a primary care practice. 2201 57

In addition to being present in tumor cells, many targets of signal transduction inhibitors are also found in normal tissue. Side effects attributable to the mechanism of action of molecular targeted agents thus represent "on-target" modulation in normal tissues. These mechanism-based toxicities can be pharmacodynamic effects of pathway inhibition and, in tumors depending on the inhibited pathway for proliferation, might be biomarkers of efficacy. The development of rash with tyrosine kinase inhibitors or monoclonal antibodies targeting the epidermal growth factor receptor is associated with superior outcomes in lung, head and neck, colorectal, and pancreatic cancer studies. Correlated with superior efficacy in retrospective analyses of large studies in advanced colorectal, breast, and renal cell carcinoma, arterial hypertension as an adverse event of antiangiogenic agents may also be a marker of effective target inhibition. An association between hypothyroidism and the activity of multitargeted tyrosine kinase inhibitors has been identified in renal cell carcinoma patients. Tumor growth addiction to the specific pathway that is effectively targeted may be the link between a mechanism-based toxicity and efficacy. The biological basis for this correlation can be pharmacological, with higher drug exposure being associated with greater toxicity and antitumor activity, and can also be genetic, because single nucleotide polymorphisms play an important role in drug pharmacokinetic and pharmacodynamic processes. Investigators have proposed that interpatient differences and associated toxicities can be exploited for dose selection and titration, and clinical trials are currently exploring intrapatient "dosing-to-toxicity" strategies. Ultimately, the predictive value of a side effect of molecular targeted therapies requires validation in prospective trials.
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PMID:Toxicity as a biomarker of efficacy of molecular targeted therapies: focus on EGFR and VEGF inhibiting anticancer drugs. 2213 23

Behavioral risk factors are among the preventable causes of health disparities, yet long-term change remains elusive. Many interventions are designed to increase self-efficacy, but little is known about the effect on long-term behavior change in older, low-income African Americans, especially when facing more problematic barriers. A cohort of 185 low-income African-Americans with hypertension reported barriers they encountered while undergoing a multiple behavior change trial from 2002 to 2006. The purpose of the present study was to explore the relationships between self-efficacy, barriers, and multiple behavior change over time. Higher self-efficacy seemed to be partially helpful for smoking reduction and increasing physical activity, but not for following a low-sodium diet. Addiction was indirectly associated with less reduction in smoking through lower self-efficacy. Otherwise, different barriers were associated with behavior change than were associated with self-efficacy: being "too busy" directly interfered with physical activity and "traditions" with low-sodium diet; however, they were neither the most frequently reported barriers, nor associated with lower self-efficacy. This suggests that an emphasis on self-efficacy alone may be insufficient for overcoming the most salient barriers encountered by older African Americans. Additionally, the most common perceived barriers may not necessarily be relevant to long-term behavioral outcomes.
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PMID:Self-efficacy and barriers to multiple behavior change in low-income African Americans with hypertension. 2232 10

Amphetamines or amphetamine-type stimulants (ATSs) refer to a group of pharmacological and -toxicological agents that have a common phenethylamine structural backbone and typically impart effects that include, but are not limited to, vasoconstriction, anorexia, central nervous system stimulation, and/or hallucinations. While differences in side chain chemistry can impart different pharmacological or toxicological effects, for some compounds, e.g., MDMA (Ecstasy), alterations of the phenyl part of the molecule impart other significant effects. ATSs are used both therapeutically and recreationally, with significant abuse and addiction potential. Therapeutically, these agents are mainly used to treat hyperactivity disorders or aid in weight loss. Toxicological effects include hypertension, arrhythmia, excitability, aggressiveness, psychoses, coma, and death.Traditional analytical methods to analyze amphetamines include gas chromatography-mass spectrometry where derivatization is often required to facilitate analysis. Besides sample preparation issues, it has been demonstrated that injection port chemistry in the GC can lead to misleading results with some members of the amphetamine class. To circumvent these issues, liquid chromatography-mass spectrometry (LC-MS/MS) offers the promise of a simpler sample preparation procedure and fewer analytical concerns. This chapter describes an LC-MS/MS technique for the analysis of 14 ATSs in blood, serum/plasma, and urine. The method is quantitative and has reporting limits in the low ng/mL range. Electrospray ionization is used in the positive ion mode. Two transitions for each compound are monitored along with ion ratios.
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PMID:Quantitation of amphetamine-type stimulants by LC-MS/MS. 2276 11

Pharmacological treatments of insomnia have become safer since the first benzodiazepine receptor agonist (BzRA) hypnotic was introduced in the 1960's. Though BzRAs could hardly cause a fatal condition even in cases of overdosing, they had inherited the arguments on addiction and withdrawal from the prior studies of barbiturate hypnotics that indicated they are strongly addictive. In the 2000s, it was repeatedly demonstrated that insomnia as well as sleep deprivation underlie the development and deterioration of comorbid diseases such as hypertension, cardiovascular diseases, diabetes and depression, and that the proper use of hypnotic drugs is unlikely to cause tolerance, addiction nor rebound phenomena, but likely to be associated with improvement of QOL. Thus, the 2005's consensus report on chronic insomnia by NIH has recommended general physicians to facilitate insomnia treatment to prevent the development of physical and/or mental disorders. The author reviewed in this article the efficacy and side effects of BzRA hypnotics, a hypnotic drug therapy combined with cognitive and behavioral interventions, uses of melatonin receptor agonist in general and sleep medicine practices, and future utilization of newly-developed orexin antagonists for insomnia treatment.
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PMID:[Present status and future of hypnotic drug treatment for insomnia]. 2284 12


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