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In the Diabetes Prevention Program, a median weight loss of 5. Similarly, bariatric surgery has repeatedly reversed diabetes to normal glucose tolerance — Certain forms of cancer are significantly increased in individuals who are overweight , Males face increased risk for neoplasms of the colon, rectum, and prostate. In women, cancers of the reproductive system, including breast , endometrium , and gallbladder, are more common.

Women who gained 25 kg or more after age 18 were at increased risk of breast cancer RR 1. Women who gained 10 kg or more after menopause were also at increased risk for breast cancer compared with women whose weight remained stable. Breast cancer is not only related to total body fat but also may have a more important relationship to central body fat This relationship to body fat may also help explain why breast cancer risk is increased at age 75 in women in the highest vs the lowest quartile of BMI Circulating, unconjugated estradiol may mediate the relationship between increased body fat and breast cancer , as well as the relationship between increased body fat and the risk of endometrial cancer Many studies show that as BMI increases, there is an increased risk for heart disease , and heart failure Weight gain also strongly affects this risk at any initial BMI.

That is, at all levels of initial BMI and within BMI categories there was a graded increase in risk of heart disease with increasing waist circumference. Similarly, within waist circumference categories there was an increased risk of heart disease with increasing BMI Central adiposity, as reflected in waist circumference, is also a strong predictor of the risk for CVD When increased central adiposity is added to other components of the metabolic syndrome, the prediction is even higher.

However, when BMI is adjusted for waist circumference as a continuous variable, waist circumference accounted for essentially all of the risk for the metabolic syndrome. In a meta-analysis including 10 studies, indices of abdominal obesity including WHR and waist circumference were better discriminators than BMI of cardiovascular risk factors, including T2DM, hypertension, and dyslipidemia Both atrial fibrillation , and congestive heart failure , have a higher risk in subjects who are overweight. In the Multi-Ethnic Study of Atherosclerosis, the risk of congestive heart failure in obesity was associated with elevated levels of inflammatory markers interleukin-6 and C-reactive protein and albuminuria This appears to contradict the curvilinear relationship of BMI to body weight 41 , 88—91 , A simple way to eliminate this bias is to match the start of exposure to the start of follow-up.

The same is true regarding the effect of obesity on the risk of mortality 43 , — Alternatively, the obesity paradox may reflect some capacity of the individual with obesity to overcome cardiovascular risk. Still another explanation for this paradox may be the difference between what BMI tells us and what the underlying fat distribution is doing. In a recent study, Padwal et al.

If fat is the culprit, then measuring BMI may lead to an erroneous conclusion Hypertension is a global public health problem. Hypertension is the most important of 67 risk factors for worldwide risk of coronary heart disease, stroke, renal disease, and all-cause mortality Furthermore, antihypertensive therapy results in reductions of incidence of stroke, myocardial infarction, and heart failure Among hypertensive individuals who reduced their BP levels following a successful weight-loss intervention, those who maintained weight loss also maintained lower BP levels, and those who regained weight returned to their baseline BP levels In a meta-analysis of 25 studies, Neter et al.

In contrast to the relatively benign effects of excess weight on most components of respiratory function, overweight predisposes to obstructive sleep apnea OSA , which can be severe and life-threatening OSA is more common in men than women. An increased snoring index and increased maximal nocturnal sound intensity are characteristic. Nocturnal oxygen saturation is significantly reduced A study of obese patients with diabetes using polysomnography showed that Independently of obesity, OSA is associated with features of the metabolic syndrome, including hypertension, T2DM, and increased cardiovascular risk, possibly mediated by stress responses and hypoxia.

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Excess daytime sleepiness is an important consequence and can be a risk for driving and other tasks that require alertness Obesity is associated with an increased risk of gallbladder disease. In a meta-analysis of gallbladder disease and obesity, Aune et al. Fatty liver disease is often associated with obesity NASH is diagnosed when there is evidence of hepatocellular injury most often in the context of fatty liver and is of greater concern because it poses a genuine risk of progression to fibrosis, cirrhosis, greater risk for hepatocellular carcinoma, and cirrhosis-related liver failure.

Both liver fat and fibrosis were increased as a function of time in nonhuman primates fed a high-fructose diet vs nonhuman primates without the added fructose NAFLD is considered by some to be the hepatic manifestation of the metabolic syndrome The prevalence of fatty liver in the United States has been increasing steadily from to with obesity as an independent predictor In a meta-analysis of 21 studies 13 of which were prospective , Li et al.

Moreover, there was a dose response to rising BMI, with the relative risk increasing 1. Another meta-analysis found that for each 1 unit increase in waist circumference, the odds ratio of NAFLD increased 1. The prevalence is greater in Hispanic than white populations and less in blacks than whites. Aune et al. The summary relative risk for a 5-unit increment in BMI was 1. The summary relative risk per 5-unit increase in BMI was 1. The relative risks were 1. The study also associated increased risk with BMI in young adulthood, WHR, and weight gain from age 21 to 25 to midlife, but the analyses included few studies.

Osteoarthritis is likewise significantly increased in individuals who are overweight or obese. The osteoarthritis that develops in the knees and ankles may be directly related to the trauma associated with the degree of excess body weight However, the increased osteoarthritis in non—weight-bearing joints suggests that some components of the excess weight may alter cartilage and bone metabolism independent of weight bearing. Increased rates of osteoarthritis account for a significant component of the cost of overweight and for the associated disability Okoro et al.

A narrative analysis of 22 reviews on pregnancy in women with obesity showed that gestational diabetes, preeclampsia, gestational hypertension, depression, instrumental and cesarean birth, and surgical-site infection are more likely to occur in pregnant women with obesity compared with women with a healthy weight. Obesity in pregnancy is also linked to greater risk of preterm birth, large-for-gestational-age babies, fetal defects, congenital anomalies, and perinatal death.

Additionally, breastfeeding initiation rates are lower, and there is greater risk of early breastfeeding cessation in women with obesity compared with healthy-weight women. The idea that single food items or diets are able to promote and maintain weight loss has stimulated numerous studies to investigate different proportions of dietary fat, protein, or carbohydrates as weight-loss diets Table 3. Underlying all of these dietary approaches, however, is the fact that to lose weight, energy balance must be negative.

Although calories are the essential component of energy balance, and reducing them is important for weight loss, food consists of more than calories. When choosing a diet, it is important to select foods that you enjoy and substitute lower calorie healthy foods that can improve the quality of your diet. Macronutrient composition aside, a reduction of energy intake is still an essential component of the effectiveness of any diet. In the Diabetes Prevention Program, calorie reduction was the major predictor of weight loss Reduced intake in fat was the second predictor, and physical activity was only an important predictor when the calorie intake was unchanged Although this calculation would predict linear weight loss, weight loss is not linear; it is curvilinear.

At the initial stage, weight loss tends to be more rapid, and then slows until it reaches a plateau — The initial reduction of calorie intake initiates a number of compensatory mechanisms, which tend to drive food intake up and reduce weight loss — Several factors contribute to the different patterns of response during weight loss. The first is the initial rate of weight loss In the Look AHEAD trial, a multicenter clinical trial in individuals with diabetes, those in the highest tertile of initial weight loss in the first 2 months had nearly twice as much weight loss at 4 and 8 years compared with those in the lowest tertile of weight loss in the first 2 months.

This could be explained by the fact that adherence to any dietary program is critical to successful weight loss , — Genetic variation can also influence weight loss, as can the biological response to different diets , Another analysis, which examined eight clinical trials in overweight or adults with obesity, reported that the FTO genotype did not modify the response to diet Using genetic profiles may thus be of value in the future for developing personalized dietary regimens for managing obesity, but more evidence is needed for any clinical applications.

Carbohydrates, such as sugar or high-fructose corn syrup, create additional challenges to a weight-loss diet, because added sugar in beverages provides extra energy with reduced satiety, thus increasing the total energy intake In a meta-analysis, Nordmann et al. In a meta-analysis of longer trials by Tobias et al.

This is in line with a meta-analysis by Bueno et al. This analysis included 32 studies subjects total , which provided all food to the subjects. This analysis does not support the concept of a metabolic advantage for lower carbohydrate, higher fat diets, suggesting that any benefits of such diets probably involve differences in energy intake.

See Hall and Guo, Another strategy for reducing energy density besides reducing dietary fat intake is to substitute foods with higher water content. One trial has compared a reduced-fat diet to a diet with extra fruits and vegetables with lower energy density. In this trial, the addition of fruits and vegetables led to greater weight loss compared with lowering fat only Diets with a higher intake of fruits and vegetables evolved into the Volumetrics diet The efficacy of the Volumetrics diet warrants further investigation.

The glycemic index is based on the rise in blood glucose in response to test foods , A meta-analysis by Thomas et al. Additionally, both total and low-density lipoprotein LDL cholesterol fell more with low—glycemic index diets. The long-term effects of low—glycemic index diets warrant further evaluation. Fasting glucose may provide a clue to dietary selection.

Hjorth et al. However, those who adhered to a higher protein diet lost more weight. When this study used urinary nitrogen loss as a measure of protein intake, those with the greater increase in protein intake lost significantly more weight Mediterranean-style diets are characterized by enhanced consumption of olive oil, nuts, whole grain, fruits, and vegetables.

In diabetic individuals, the Mediterranean diet produced a greater weight loss during 4 years than did a low-fat diet Another meta-analysis reported that Mediterranean diets reduced body weight 2. In a meta-analysis, Avenell et al. In a 6-month intervention, the daily use of a commercially available portion-control plate was effective in promoting weight loss among patients with obesity and T2DM when compared with a usual-care dietary group. A meta-analysis of six studies using meal replacements showed more weight loss than low-calorie diets at 3 months Data from another trial showed that portion control can increase diet quality while maintaining significant weight loss during 18 months Several RCTs have compared diets head-to-head , , , , We summarize these in Table 4 , , — These studies show improvements in hemoglobin A1c HbA1c in patients with T2DM and improvements in triglycerides and HDL cholesterol in the groups assigned to the low-carbohydrate diet arms.

One trial randomized individuals with obesity to one of four popular diets, including the Atkins diet , The Ornish diet , the Weight Watchers diet , and the Zone diet Adherence to the diets was the single most important criterion of success in these trials. In one study, a low-fat diet was compared with a low-carbohydrate diet Atkins diet and a Mediterranean-style diet Compared with the low-fat diet, individuals assigned to the Mediterranean diet and low-carbohydrate diet had significantly greater weight loss and maintenance by 24 months In a meta-analysis of numerous popular diets that included 48 unique trials, low-carbohydrate diets performed equally with low-fat diets after 12 months, with the low-carbohydrate diets resulting in 7.

The foods in all four diets were the same, although they differed in quantity. At the end of 6 months, 12 months, and 2 years, the weight loss was similar for all four diets ; however, those who achieved the largest increase in protein intake lost more weight The similarity of the mean weight loss in all four diet groups obscures the wide range of individual weight losses shown in Fig.

Weight change from baseline to 6 months for each individual participant in the four dietary assignment groups ranked from the largest loser on the left to the most weight gain on the right. In a meta-analysis, Gudzune et al. The Jenny Craig diet resulted in a 4. The Nutrisystem diet resulted in a 3. The Atkins diet not technically a commercial program, but one with affiliated diet products resulted in 0. The differences in the amount of weight loss among various commercial diets were relatively small, and the long-term effects of these diets on weight control and chronic disease risk are still unclear.

One study , assigned participants to weight loss with a VLCD for 4 weeks before randomizing them to either a control diet or study diet supplemented with The study reported that body weight in the low-fat diet group and the control-diet group was similar after an average of 7. However, those who maintained the lowest quintile of fat intake were 1. A recent comprehensive meta-analysis indicated that long-term effects of low-fat diets on body weight depended on the intensity of intervention in the comparison group.

When compared with other dietary interventions of similar intensity, evidence from RCTs does not support low-fat diets over other dietary interventions The National Weight Control Registry identifies additional strategies for maintaining weight loss , which include engaging in higher levels of physical activity e.

Prediction of weight gain may also be related to the ability to metabolize carbohydrates. Subjects who had a higher positive carbohydrate balance on day 15, were inactive, and ate an isocaloric high-carbohydrate diet gained less fat mass during a 4-year follow-up period Diets with many different macronutrient compositions can result in short-term weight loss. However, weight loss reaches a plateau within the first 3 to 6 months.

After that, weight is regained and often returns to baseline by 1 to 2 years. Maintenance of long-term weight loss is strongly influenced by the ability to adhere to the dietary program. Behavioral support can significantly improve outcomes.

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There are variations among individuals in the response to each diet, which are larger than the difference in mean weight loss between comparison diets. Clinicians should consider genetic differences regarding dietary response to weight loss, as personalized dietary regimens might improve the efficacy of long-term weight-loss regimens. Current data indicate that some but not all individuals can achieve modest long-term weight loss with any one of the diets evaluated herein.

Additional research is needed to identify optimal diets for weight control and long-term health, which should extend beyond macronutrient composition and examine food quality and overall dietary patterns, as well as factors that can improve long-term compliance. The Nurses Health Study and Health Professionals Follow-up Study reported that improving diet quality was associated with less weight gain, especially in younger women or individuals who are overweight There is a significant body of evidence supporting the effect of physical activity in both short-term and long-term weight loss in adults , , — The main components of energy expenditure by order of magnitude are resting energy expenditure, physical activity, and the thermic effect of food.

Resting energy expenditure is the amount of energy required for a hour period by the body during resting conditions. Physical activity is composed of both nonexercise activity thermogenesis and thermogenesis due to volitional activity of muscle groups. The thermic effect of food is the amount of energy above the resting rate used for processing and storing food.

Energy expenditure from physical activity is directly related to body weight. However, it is unclear to what extent reductions in energy expenditure from physical activity relate to the epidemic of obesity that has developed during the last 30 years. Most measurements of energy expenditure are not precise or easy to use. Therefore, reliable longitudinal data are lacking.

Two recent studies have concluded that the current epidemic of obesity is more the result of an increase of energy intake than a decrease in energy expenditure — , but this is not the universal opinion There is an important genetic component associated with the extent to which individuals engage in physical activity Although most research on the effects of physical activity on body weight has focused on aerobic types of physical activity, there is also evidence suggesting that resistance exercise may have some effect on weight loss. Resistance exercise may influence body weight by increasing lean body mass, which will result in an increase in resting metabolic rate.

However, the vast majority of data indicate that resistance exercise only results in minimal reductions in body weight or body fatness — This relationship only existed with moderate- to vigorous-intensity physical activity and not with low-intensity physical activity. These data imply that there is an intensity threshold of physical activity that is necessary to affect body weight and prevent excessive weight gain.

Despite the benefit of physical activity in weight loss, physical activity appears to decline during adolescence and remains low in most adults , In a longitudinal study of adolescent girls, the level of activity declined in both black and white girls each year during adolescence. By age 17, black girls engaged in almost no spontaneous physical activity and white girls only engaged in very modest amounts of spontaneous physical activity We do not have a comparable study in adolescent males. There is keen interest in the influence of sedentary behavior on a variety of health-related outcomes, including overweight and obesity.

Much of the early literature in this area focused on the association between television viewing as an indicator of sedentary behavior and the risk of obesity. Television viewing is positively associated with the risk of gaining weight and the development of obesity , Studies on obesity have evaluated exercise as a sole treatment, in combination with diets, and as a way to maintain weight loss. Table 5 — has been adapted from this study with the addition of two newer trials, one 16 months long and one 8 months long.

The effects from diet are significantly greater than those from exercise, but increasing physical activity may have important benefits on improving BP and cardiometabolic risk factors. These studies are the gold standard and are notable for the frequency of contact, the emphasis on individualizing therapy, and the long-term emphasis on maintaining weight loss. The best outcomes are with frequent, face-to-face interventions. However, incorporating this in primary care is challenging. In a meta-analysis of behavioral weight-loss programs, LeBlanc et al.

Lifestyle interventions may also be effective for preventing weight regain , Patients who participated in group sessions every other week for 1 year after weight reduction maintained 13 kg of their The most successful patients monitor their weight frequently and respond quickly to small increases in weight Self-monitoring involves recording the type and amount of foods and beverages consumed, along with their calorie content and weight gain.

Self-monitoring helps patients identify their eating patterns including times and places associated with consumption and also helps patients select targets for reducing calorie intake Table 6. Techniques of stimulus control teach patients to manage external cues, such as the sight or smell of food, as well as times, places, and events associated with eating , By decreasing exposure to problem foods, patients are less likely to overeat.

Goal setting helps patients make objective, measurable changes in eating, activity, and related behaviors , They are guided in setting specific targets for calorie intake, minutes of physical activity, and frequency of self-monitoring. Problem solving teaches patients to analyze challenges they have in adhering to their diet and activity prescriptions , , Patients learn to identify a number of possible solutions to the problem, pick the most promising one, and then implement it.

They learn to identify cognitive distortions e.

The structured behavioral programs, as described above, produce an average loss of 7 to 10 kg in the first 6 months but with great variability. Patients require a high-intensity intervention to achieve these losses; lower intensity treatment is not as effective Individuals with the best attendance and greatest consistency in keeping self-monitoring records achieve the largest weight losses Sherwood et al.


Appel et al. The weight loss was generally well maintained at 24 months 4. Perri et al. Several studies that used structured dietary interventions i. Tate et al. In a 1-year follow-up study, Tate et al. Harvey-Berino et al.

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In 6 months, the on-site program resulted in 8. These studies underscore the importance of patients keeping records of their food intake and physical activity and receiving feedback from a trained interventionist. Educational instruction i. These studies also suggest that the most successful Internet programs are those in which therapists provide weekly e-mail feedback to patients. However, on-site behavioral programs still provide better results The reduced efficacy of Internet programs, however, is offset by the potentially greater accessibility and affordability of this approach, compared with traditional behavioral treatment.

Despite their popularity, little is known about the effectiveness of smart-phone applications for weight management. A recent study that compared usual primary care with or without the MyFitnessPal application revealed essentially no weight-loss difference between the two approaches during 6 months Medications for managing obesity have a long and checkered history Treatment in the 18th century included soap 6 , 17 and vinegar mixed with a number of purgatives Some treatments also used tobacco, a strategy people still use today to prevent weight gain.

In the late 19th and early to midth century, three major groups of medications came into use: thyroid hormone, dinitrophenol, and amphetamine. Clinicians prescribed both thyroid extract and dinitrophenol a product of the aniline dye industry until negative side effects became evident Amphetamine became popular after when Nathanson noted that 10 of 40 patients treated with amphetamine for narcolepsy had marked loss of appetite and weight. However, the abuse potential of amphetamines soon became apparent , and clinicians stopped prescribing them as a way to manage obesity.

Aminorex, another member of the amphetamine-like group, emerged in Austria and Switzerland in , but it was removed from the market in due to associated pulmonary hypertension Table 7 lists several drugs for obesity management that were associated with significant detrimental side effects From the end of World War II through , there was considerable research on monoaminergic drugs.

Researchers discovered that injecting norepinephrine into the central nervous system of experimental animals reduced food intake and activated thermogenesis. This resulted in a search for thermogenic drugs that could work through monoaminergic receptors. During this period, researchers also synthesized many derivatives of amphetamine for treating obesity , along with serotonergic drugs and multiple monoamine reuptake inhibitors. The discovery of leptin in 20 marks the beginning of modern approaches to identifying drugs for treating obesity.

Leptin is a peptide made primarily in adipose tissue. Its absence is associated with massive obesity in animals and human beings. Treatment with leptin reverses the obesity caused by leptin deficiency, indicating that there is a clear-cut molecular—genetic mechanism and a highly effective treatment of at least one type of obesity. However, because leptin failed to show adequate weight loss in obese persons who are not leptin deficient, trials were stopped , The discovery of leptin opened a flood of research to discover new treatments, some of which were withdrawn from the market due to health risks In Table 8 we list medications that are FDA approved for weight management in patients with obesity and divide them into two groups.

First are the agents approved for long-term treatment of obesity. See Bray and Ryan, The FDA approved them using only data from small, short-term studies, and there are no cardiovascular outcome studies for these agents. Also important to note, these drugs are all contraindicated for pregnant women, as is weight loss per se.

Because weight loss can increase fertility, all women in a weight-management program that use medications should be cautioned about the need for contraception. If pregnancy does occur while a patient is taking any of these medications, the patient should immediately stop the medication and contact a medical professional.

More detailed information is in Figs. Diagram of the sites within the central nervous system where medications can have their effects. See Apovian et al. Orlistat is a potent and selective inhibitor of pancreatic lipase that reduces intestinal digestion of fat. Data are from Dong et al. Orlistat is the only medication the FDA approved for weight management in adolescents with obesity Adherence to orlistat use falls off rapidly after initial prescription Orlistat can cause small but significant decreases in fat-soluble vitamins, and clinicians should advise patients to take vitamin supplements.

Rare cases of severe liver injury have been reported with patients taking orlistat. A causal relationship has not been established, but patients who take orlistat should contact their health care provider if itching, jaundice, pale color stools, or anorexia develop Lorcaserin selectively targets the serotonin-2c receptors to reduce food intake , but it has low affinity for the serotonin-2b receptors on heart valves. They also showed improvements in cardiovascular risk factors — In preclinical toxicology studies in rats, there were more brain and mammary tumors.

This may reflect the fact that the drug does not reach the high concentrations in the central nervous system of human beings that is does in rats The molecular change extends the circulating half-life from 1 to 2 minutes to 13 hours. One study that administered daily subcutaneous injections of liraglutide at 1. Another larger trial reported that after 56 weeks, liraglutide reduced body weight by 8. In another trial , those receiving liraglutide for weight maintenance after initially losing weight from a low-calorie diet lost an additional 6.

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Furthermore, only about half of the placebo group was able to maintain the weight they lost due to diet. Liraglutide is contraindicated in people with a family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Clinicians should not prescribe liraglutide for patients with a history of pancreatitis and should discontinue liraglutide if acute pancreatitis develops. Two cardiovascular outcome trials studied liraglutide 1.

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In patients with T2DM, liraglutide lowered the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke Semaglutide lowered the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke Phentermine acts to reduce appetite through increasing norepinephrine in the hypothalamus. Topiramate may reduce appetite through its effect on GABA receptors. The patients in these two studies had higher risk profiles due to excess weight.

This weight loss is larger than observed in clinical trials with single drugs Improvements in BP, glycemic measures, HDL cholesterol, and triglycerides occurred with both the recommended and the top doses of the medication in these trials , Improvements in risk factors were related to the amount of weight loss.

In patients with OSA, this combination reduced the severity of symptoms Glaucoma is a rare side effect of topiramate, and the drug is contraindicated in glaucoma. Topiramate is a carbonic anhydrase inhibitor that often produces tingling in the fingers and may change the taste for carbonated beverages.

Other potential issues include risk of kidney stones associated with topiramate and increased heart rate in patients susceptible to phentermine. Bupropion is approved as a single agent for depression and for smoking cessation. It reduces food intake by acting on adrenergic and dopaminergic receptors in the hypothalamus. It has a modest effect on weight loss. In one study , weight loss at 56 weeks was 5. Treatment also improved waist circumference, fasting glucose, fasting insulin, homeostasis assessment model of insulin resistance HOMA-IR , and HDL cholesterol, but there was a transient increase in BP.

The study also reported significant improvements in weight, waist circumference, insulin, homeostatic model assessment of insulin resistance, HDL cholesterol, triglycerides, and quality of life. In a third study, weight loss at week 56 was 6. As in the other studies, there were improvements in cardiometabolic risk markers, weight-related quality of life, and control of eating. There was also improvement in triglycerides and HDL cholesterol compared with placebo. Because bupropion increases pulse and both bupropion and naltrexone increase BP, an ongoing study is examining cardiovascular outcomes There are no head-to-head comparisons of these medications.

The inclusion criteria and background lifestyle interventions differed across studies, so we must interpret results with caution. All five agents were associated with significantly greater weight loss at 1 year than placebo. We group the sympathomimetic drugs benzphetamine, diethylpropion, phendimetrazine, and phentermine together, because they are noradrenergic drugs that the FDA tested and approved before The U.

Drug Enforcement Agency classifies phentermine and diethylpropion as schedule IV drugs and benzphetamine and phendimetrazine as schedule III drugs. The FDA approved phentermine as a single agent in , and it remains the most commonly prescribed drug for weight loss in the United States There are few current data to evaluate its long-term efficacy.

In another 6-month study of phentermine, weight loss was 5. Finally, a study from Korea reported that after 12 weeks, mean weight loss for phentermine was 8. Weight loss with phentermine may not be greatly enhanced by increasing doses beyond 15 mg Phentermine is part of a group of drugs called sympathomimetic drugs.

These drugs produce central excitation, manifested as dry mouth, insomnia, or nervousness. This effect is most obvious shortly after the drug is started and wanes substantially with continued use. Sympathomimetic drugs may also increase heart rate and BP. The prescribing information usually recommends that the drugs not be given to individuals with a history of CVD — Lacking good quantitative measures of the effects of sympathomimetic drugs on heart rate and pulse, we recommend caution in prescribing drugs in this group. According to the Endocrine Society Guidelines , clinicians should not prescribe sympathomimetic drugs to persons with a history of CVD and elevated BP.

Those guidelines do not require that patients fail lifestyle therapy before clinicians prescribe medications. For patients who are overweight or obese, the Endocrine Society clinical practice guidelines on obesity pharmacotherapy recommended that providers consider body weight when prescribing medications for other chronic health conditions, so that at-risk patients can avoid medications that promote weight gain. The guideline recommends that patients use medications that are weight neutral or associated with weight loss.

In managing patients with obesity, the guideline also advises that providers review medications at every visit and discuss weight effects with patients, so that patients at risk for weight gain can share in the decision process when choosing medications. According to the Awareness, Care and Treatment in Obesity Management study , there are a number of misconceptions regarding obesity shared by providers and patients alike, specifically that obesity is not a disease, that patients have the primary responsibility for their problem and for its treatment, that prevention is more important than treatment, and that the risks of treatment should be low.

At present, the FDA has approved nine agents five for long-term use and four for short-term use. For newer drugs, the time since approval of these medications is too short to know whether and how they will be used. However, older data which predate the current medication landscape indicate there are some serious concerns about how diet medications are used, such as: patients using prescription weight-loss pills who do not meet the BMI criterion for these medications; family, friends, and other nonphysicians providing medications; the use of nonprescription diet products; using pills after they were withdrawn from the market; low 1-year persistent use rates; and co-using narcotic and antidepressants 35 , , , This legislation helped undercut the credibility of legitimate weight-management practices by allowing the promotion of agents that are often unsafe, ineffective, and have unproven health claims.

As long as the claim is not for disease treatment per se , and products are generally recognized as safe, they can be promoted for health claims. These agents are regulated by the U. Federal Trade Commission but not by the FDA, and thus they do not undergo the rigorous testing and review exercised by the FDA when it approves pharmaceutical preparations for patients who are overweight or obese. Blanck et al. Pillitteri et al. Many respondents thought that dietary supplements are safer than prescription drugs, and many overestimated the degree of regulatory screening of these products.

Golov, D. Read Article. The Magic Force , Foreword to Catalysis , ed. Hofmann and L. Gade Wiley-VCH, , xix-xxvii. Firenze University Press, , pp. Menachem Genack, Sterling Ethos, , pp. Lipscomb, Jr. Jianpeng Ma, Imperial College Press, , pp. The Joy of Chemistry , R. Hoffmann and B. Chemical and Engineering News 91 27 July 8, , p. Preface to Sierra, M. Foreword to Aromaticity and Other Conjugation Effects , ed. Bonding to Hydrogen , R. Hoffmann, American Scientist , Reflections on Art in Science , R. Passerelles , R. Hoffmann, Chemical Heritage, 30 2 , 37 Hoffmann, Angew.

That's Interesting , R. Hoffmann, American Scientist 99 , Empathy Is Global , R. One Shocked Chemist , R. Hoffmann, American Scientist 99, For the 60th Birthday of Eiichi Nakamura , R. Hoffmann, Guest Editorial in Chem. Asian J. Shakhashiri ed. Cava, M. Lakshmikantham, R.

Hoffmann, and R. Williams, Tetrahedron 67 , McGuire, American Scientist , 98, Honesty to the Singular Object , R. Margery Arent Safir. Suhrkamp Insel: Frankfurt , pp. McGuire, Science , , Sept. Hellwich and C. Siebert, Bellstein Journal of Organic Chemistry, 5 Foreword , R. Hoffmann in H. Dodziuk, ed. The Chemistry Is Right , R. The Tense Middle , R. Allison, D. Gediman, Henry Holt, New York, , pp.

Hoffmann, P. Schaefer III, Angew. Why Think Up New Molecules? Roald Hoffmann, American Scientist, 96 , Learning from Molecules in Distress , R. Hoffmann and H. Hopf, Angewandte Chemie , 47, A Passion for Chemistry and Art , R. For a Few Atoms More , R. Hoffmann, American Scientist 96 2 , Harris and P. Edwards, eds. Bensaude-Vincent and W.

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Hoffmann, in Foundations of Chemistry , 6, 11 Shall We Change? The first French newspaper , Gazette afterwards called the Gazette de France , started in under the patronage and with the active co-operation of Cardinal Richelieu. The first weekly edition appeared in May The first page was entitled Gazette , the second Nouvelles ordinaires de divers endroits. It commonly began with foreign and with national news. Much of its earliest foreign news came directly from the Cardinal, and often in his own handwriting.

Its title later changed to Nouveau Mercure , and in to Mercure de France , a designation retained, with minor modification, until , when the paper finally ceased. It had many prominent contributors and in its circulation rose rapidly and reached a peak of 13, copies. Print media played a significant role in the formation of popular public opinion towards the monarchy and Old Regime.

Under the Old Regime, France had a small number of heavily censored newspapers which needed royal licenses to operate; papers without licenses had to operate underground. The increasing popularity of these revolutionary publications was reflected in the increased political activity of the French population, particularly those in Paris, where citizens flocked to coffeehouses to read pamphlets and newspapers and to listen to orators. While both papers presented republican arguments and anti-religious sentiments, the end result was a direct competition for support from the same readers.

After a short run, the paper was denounced in May by the Assembly citing its news briefs condemning the Civil Constitution of the Clergy. They resisted the National Guard with stolen arms and fifty people died during the confrontation. Both liberal and conservative publications together became the main communication medium; newspapers were read aloud in taverns and clubs and circulated amongst patrons.

During the conservative era of the Directory , from to , newspapers declined sharply in importance. The Declaration of the Rights of Man allowed for the freedom of the press but also allowed for the government to repress abuses of the press. The Moniteur Universel served as the official record of legislative debates. Jean-Paul Marat gained enormous influence through his powerful L'Ami du peuple with its attacks on scandals and conspiracies that alarmed the people until he was assassinated in In , all restrictions on the press were eliminated; by over newspapers had been founded, including in Paris alone.

During the conservative era of the Directory, from to , newspapers declined sharply in importance. When Napoleon took power in , only seventy-two papers were left in Paris, and he soon closed all but In , he took the final step: he allowed only four papers in Paris and one in each of the other departments; all of them closely censored. Napoleon utilized propaganda in a wide range of media including newspapers, art, theatres, and his famous bulletins. Napoleon ensured that his efforts were being met by not only censoring the majority of media content but by also creating and publishing his own works.

Under Napoleon, the organ of official information was the Moniteur Gazette nationale, ou le moniteur universal , which was founded in under the same general management as the Mercure. Both newspapers were sources of establishment messages and written for an establishment audience, with the Moniteur representing the majority view in the French assembly and the Mercure representing the minority. The restoration of the Bourbons in allowed for a free press. After , censorship was light, but there were restrictions such as the requirement to pay a large deposit with the government, And a stamp tax of five centimes on each copy.

A handful of newspapers were published, closely aligned with political factions. They were expensive, sold only by subscription, and served by a small elite. In the midth century, s, a series of technical innovations revolutionized the newspaper industry, and made possible mass production of cheap copies for a mass national readership.

The telegraph arrived in , and, about , the rotary press developed by Hippolyte Auguste Marinoni. Previously, publishers used expensive rag paper and slow hand-operated screw presses. Now they used much cheaper wood pulp paper, on high-speed presses. The cost of production fell by an order of magnitude.

The opening of the railway system in the s made rapid distribution possible between Paris and all the outlying cities and provinces. As result of the technical revolution, much greater quantities of news was distributed much faster, and more cheaply. In June La Presse became the first French newspaper to include paid advertising in its pages, allowing it to lower its price, extend its readership and increase its profitability; other titles soon copied the formula. The revolution of gave rise to many ephemeral papers.

Most of newspapers were suppressed; each party was allowed only one paper. The severity of the censorship relax in the s but did not end until the French Third Republic started in Le Correspondant founded in and published fortnightly, expressed liberal Catholic opinion, urged a restoration of freedom in France, resisted a growing anti-clericalism, and fought its conservative Catholic rival paper L'Univers.