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Clinical tests, a questionnaire on life style and mental health, and physical fitness tests were conducted on 3,132 individuals (1,796 men and 1,336 women) to find the relationships between physical fitness level and life style, mental health, or cardiovascular risk factors among Japanese. Individuals with an advanced physical fitness level also exhibited optimum mental health: the odds ratio (OR) and 95% confidence interval (CI) for their sensation of fatigue (fast recovery) was 1.16 (95% CI = 1.00 to 1.35) and that for mood recovery (fast) was 1.29 (95% CI = 1.12 to 1.49). Among those with an advanced physical fitness level, the following were rare (OR): daily smoking [0.78]; obesity (over 120%) [0.73 (95% CI = 0.62 to 0.87)]; thick subcutaneous fat (over 20 mm on the back) [0.77 (95% CI = 0.66 to 0.90)]; high blood sugar level [0.64 (95% CI = 0.50 to 0.82)]; and hypertension [0.67 (95% CI = 0.49 to 0.91)]. These are risks for circulatory diseases. These data show that risk factors associated with cardiovascular disease are more common in those with a low physical fitness level.
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PMID:A comparative epidemiological study on the effects of physical fitness on health level. 895 15

Thirty-five years ago, Lois and Theodore Zucker reported the discovery of a genetic mutation in the rat that resulted in juvenile-onset obesity, increased food intake, decreased energy expenditure, and insulin resistance. The mutation was called fatty (fa). The fatty gene is passed on to successive generations by an autosomal recessive mode of inheritance. In the intervening years, much work has been done to characterize the many abnormalities of this animal model of obesity. Nearly 10 years ago, we reviewed the evidence for a central nervous system mechanism in the etiology of obesity in the fatty Zucker rat. Since that time, the discovery of novel peptides and genes has revolutionized the study of the etiology of genetically linked obesities. In this review, we update the evidence for a central nervous system mechanism of obesity in Zucker rats by focusing on the possible role of neuropeptide Y (NPY) and leptin in the etiology of obesity. We also discuss the role of glucocorticoids and insulin in the regulation of NPY.
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PMID:Evidence for a central mechanism of obesity in the Zucker rat: role of neuropeptide Y and leptin. 908 55

Dexfenfluramine increases serotonergic activity by stimulating serotonin (5-hydroxytryptamine; 5-HT) release into brain synapses, inhibiting its reuptake into presynaptic neurons and by directly stimulating postsynaptic serotonin receptors. On the basis of the serotonin hypothesis of appetite control, these actions would be expected to reduce appetite and, consequently, bodyweight. Studies conducted in animals and in overweight patients with and without associated disorders have confirmed the weight-reducing efficacy and good tolerability of dexfenfluramine. In 3-month clinical studies in obese patients, weight reductions with dexfenfluramine 15mg twice daily combined with dietary support were significantly higher than those achieved with placebo and similar to those with ephedrine/caffeine 20/20mg 3 times daily, sibutramine 10mg once daily and fluoxetine 60 mg/day. Furthermore, dexfenfluramine recipients with non-insulin-dependent diabetes mellitus, hyperlipidaemia or hypertension consistently show improvements in glycaemic control, blood lipid profiles and blood pressure. 12-month trial results indicate that most weight loss occurs in the initial 6 months and appears to be maintained for a further 6 months. Weight regain after withdrawal of treatment in 12-month studies demonstrates that dexfenfluramine is effective in maintaining a stable bodyweight at a lower level than placebo and in limiting food intake over this time period. Commonly reported adverse events with dexfenfluramine include diarrhoea, tiredness, dry mouth and somnolence; these symptoms are generally mild and transient. Approximately 7 and 10% of dexfenfluramine recipients in short and long term studies withdrew because of adverse events. Dexfenfluramine was better tolerated than ephedrine/caffeine and fluoxetine in short term studies. Obesity is a chronic condition that is accompanied by a number of metabolic complications. It is a significant health problem in developed countries, and as a major risk factor for many chronic diseases, including diabetes and cardiovascular disease, the economic burden of this condition is considerable. As with other chronic conditions, there is a role for pharmacological intervention in patients with severe obesity. However, drugs should be considered as only one component of a weight-control programme, since additional lifestyle modification is required to maintain weight loss. The promising data on the long term efficacy and tolerability of dexfenfluramine as well as its favourable effects on risk factors associated with obesity requires confirmation in long term studies. In the meantime, dexfenfluramine should be considered a valuable adjunct to a reduced-calorie diet in the management of severe obesity, particularly in patients with associated disorders and those unsuccessful with conventional weight loss measures. Available data support the use of the drug for up to 1 year to maintain weight loss and thus dexfenfluramine should be considered for long term administration.
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PMID:Dexfenfluramine. An updated review of its therapeutic use in the management of obesity. 911 19

From a database of 4,129 patients with sleep-disordered breathing (SDB), we found 207 subjects (43 women) that still complained of daytime tiredness, fatigue, and/or sleepiness despite treatment. In 25 subjects the sleepiness developed 1 to 36 months following treatment and was related to noncompliance (8 subjects), significant weight increase and/or inappropriate treatment (10 subjects), or development of new medical problems (7 subjects). In the remaining 182 subjects, sleepiness was noted within 1 month after what was judged appropriate treatment for SDB. In this group, the reason for persistent complaint was divided into four categories: 1) inappropriate treatment as a result of not using the measurement of esophageal pressure (Pes) in the initial diagnosis (41 subjects), 2) nonfunctional treatment (3 subjects), 3) associated narcolepsy-like syndrome (2 subjects), and 4) emergence of obesity and/or periodic leg movements as significant factors (135 subjects). The 135 subjects in this last category could be subdivided into three subgroups: 1) younger subjects, severely overweight with lower mean nocturnal saturated arterial oxygen (SaO2) values; 2) older subjects, of normal weight, with high numbers of periodic leg movements (PLM); and 3) moderately overweight subjects, with a combination of PLM and lower mean SaO2 values than expected. Treatments were aimed at eliminating the identified problems; they included standard medications for PLM and nasal bilevel positive airway pressure (BiPAP) for low SaO2 measurements. These treatments were not effective in specific cases, and stimulant medications had to be prescribed.
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PMID:Tiredness and somnolence despite initial treatment of obstructive sleep apnea syndrome (what to do when an OSAS patient stays hypersomnolent despite treatment). 912 68

The object of this study was to examine whether eating behavior, food preference, gastric emptying, and gut hormone patterns are altered after jejunoileal bypass (JIB) in patients with severe obesity. Eight obese [mean (+/- SD) body mass index (BMI; in kg/m2) 42.9 +/- 4] subjects were studied prospectively before and 9 mo after JIB with eight age- and sex-matched normal-weight control subjects. Total energy intake, data from the universal eating monitor (VIKTOR), eating motivation measured by visual analog scales, a food-preference checklist, a forced-choice list, solid-phase gastric emptying, and postprandial concentrations of cholecystokinin, motilin, and neurotensin were studied. BMI was reduced by 29% after JIB. Compared with normal subjects, the JIB patients showed a reduced desire to eat, decreased hunger, and reduced prospective consumption before a test meal. After surgery, obese subjects selected fewer food items and showed a reduced preference for high-carbohydrate and high-fat items before a test meal. There was a trend from an accelerated toward a decelerated eating pattern in obese subjects after JIB. After JIB, gastric emptying of obese subjects was slowed and similar to that in control subjects. Obese subjects had lower postprandial cholecystokinin concentrations that were lower than those of control subjects both before and after JIB. Postprandial concentrations of neurotensin were higher after JIB. We conclude that after JIB, the desire to eat and preference for high-carbohydrate and high-fat items is reduced, resulting in decreased energy intake. That gastric emptying is prolonged and gut hormone patterns are altered with low postprandial plasma cholecystokinin and high neurotensin plasma concentrations may at least partly account for these observations.
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PMID:Reduced food intake after jejunoileal bypass: a possible association with prolonged gastric emptying and altered gut hormone patterns. 920 88

The diaphragm is the primary muscle of inspiration, and as such uncompromised function is essential to support the ventilatory and gas exchange demands associated with physical activity. The normal healthy diaphragm may fatigue during intense exercise, and diaphragm function is compromised with aging and obesity. However, more insidiously, respiratory diseases such as emphysema mechanically disadvantage the diaphragm, sometimes leading to muscle failure and death. Based on metabolic considerations, recent evidence suggests that specific regions of the diaphragm may be or may become more susceptible to failure than others. This paper reviews the regional differences in mechanical and metabolic activity within the diaphragm and how such heterogeneities might influence diaphragm function in health and disease. Our objective is to address five principal areas: 1) Regional diaphragm structure and mechanics (GAF). 2) Regional differences in blood flow within the diaphragm (WLS). 3) Structural and functional interrelationships within the diaphragm microcirculation (DCP). 4) Nitric oxide and its vasoactive and contractile influences within the diaphragm (MBR). 5) Metabolic and contractile protein plasticity in the diaphragm (SKP). These topics have been incorporated into three discrete sections: Functional Anatomy and Morphology, Physiology, and Plasticity in Health and Disease. Where pertinent, limitations in our understanding of diaphragm function are addressed along with potential avenues for future research.
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PMID:Diaphragm structure and function in health and disease. 921 1

Sleep-related breathing disorders (SRBD) include several disorders gradually developing from simple and loud snoring through upper airway resistance syndrome and sleep apnoea up to the Pickwickian syndrome. They are manifestant as a respiratory distress and apnoeic episodes, desaturation of oxygen in the blood and interruption of sleep. These symptoms are demonstrated in a case of a patient with the Pickwickian syndrome. SRBD may result in severe secondary life-threatening cardiovascular complications (nocturnal arrhythmias, sudden cardiac death, stroke and pulmonary oedema). They may contribute also to the development of important disorders of public health such as hypertension, obesity, and traffic accidents resulting from hypersomnolence and fatigue. (Tab. 1, Fig. 3, Ref. 46.)
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PMID:[Sleep-related breathing disorders--an interdisciplinary topic in undergraduate and postgraduate medical education]. 926 12

Many types of drugs are used by athletes to improve performance. This paper reviews the literature on 3 categories of drugs: those that enhance performance as stimulants (amphetamines, ephedrine, and cocaine), those that are used to reduce tremor and heart rate (beta-blockers) and those involved in bodyweight gain or loss (anabolic-androgenic steroids, growth hormone, beta 2-agonists, and diuretics). Limitations of research on these drugs as they relate to performance enhancement are also discussed. The numerous studies that have assessed the effects of amphetamines on performance report equivocal results. This may be due to the large interindividual variability in the response to the drug and the small sample sizes used. Most studies, however, show that some individuals do improve exercise performance when taking amphetamines, which may be attributed to their role in masking fatigue. As a stimulant, ephedrine has not been found to improve performance in the few studies available. More recently, ephedrine has been purported to be effective as a fat burner and used by athletes to maintain or improve muscle mass. Although research on individuals with obesity supports the use of ephedrine for fat loss, no studies have been done on athletes. The few studies of cocaine and exercise suggest that little to no performance gains are incurred from cocaine use. Moreover, the sense of euphoria may provide the illusion of better performance when, in actuality, performance was not improved or was impaired. beta-Blockers have been found to reduce heart rate and tremor and to improve performance in sports that are not physiologically challenging but require accuracy (e.g. pistol shooting). However, there is evidence that some individuals may be high responders to beta-blockers to the extent that their heart rate response is so blunted as to impair performance. Although equivocal, several studies have reported that anabolic-androgenic steroids increase muscle size and strength. However, most studies are not well controlled and use insufficient drug doses. One recent well controlled study did find an increase in muscle mass and strength with supraphysiological doses, and the improvements were greater in participants who were also resistance training. There is little information available on the effects of growth hormone on muscle mass or performance in athletes, although data suggest that growth hormone administration does not increase muscle protein synthesis. beta 2-Agonists, such as clenbuterol and salbutamol, when administered orally appear to improve muscular strength due to their potential role in increasing muscle mass. However, studies have not been done using athletes. Diuretics results in a loss of body water and hence bodyweight that can be advantageous for sports with strict bodyweight classifications. There is insufficient evidence on possible performance decrements in the field that could result from dehydration induced by the diuretics. Overall, the most significant concern in studies of drug use is the large inter-individual variability in responses to a drug. Further studies are needed to understand why some individuals are more responsive than others and to assess whether the responses are consistent for a given individual. Most studies of drug effectiveness have not used athletes. The effectiveness of many drugs may be reduced in highly trained athletes because there is a lower margin for improvement.
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PMID:Drugs and sport. Research findings and limitations. 942 62

Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality. Decreased expression of leptin or of functional leptin receptors results in hyperphagia, decreased energy expenditure, and obesity. It is unclear, however, whether defective leptin-dependent signal transduction directly promotes any of the conditions that frequently complicate obesity. Abnormalities in tumor necrosis factor alpha expression have been noted in each of the above comorbid conditions, so leptin deficiency could promote these complications if leptin had immunoregulatory activity. Studies of rodents with genetic abnormalities in leptin or leptin receptors revealed obesity-related deficits in macrophage phagocytosis and the expression of proinflammatory cytokines both in vivo and in vitro. Exogenous leptin up-regulated both phagocytosis and the production of proinflammatory cytokines. These results identify an important and novel function for leptin: up-regulation of inflammatory immune responses, which may provide a common pathogenetic mechanism that contributes to several of the major complications of obesity.
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PMID:Leptin regulates proinflammatory immune responses. 943 11

To analyse the effect of obesity on exercise-derived heat dissipation, lean and obese Zucker rats were exercised on an inclined treadmill until they would no longer run with gentle prodding. We measured their oxygen consumption, water vapour loss, the concentrations of adenosine tri- and diphosphate, creatine phosphate, and lactate in quick-frozen leg muscles, and the temperature of muscle, skin and blood in the aorta. We determined blood flow to leg muscle, fat and skin by measuring the entrapment of fluorescent microspheres. From the measurements we calculated heat flow rates between hind leg muscle, blood, fat and skin and the environment. The obese rats weighed twice as much as the lean (340-400 g and 175-200 g respectively) and ran half as fast (113 +/- 7 m versus 257 +/- 17 m). The differences between the two groups for basal oxygen consumption (lean: 6.7 +/- 0.9 micromol/min, obese: 5.0 +/- 1.9 micromol/min) and exercising oxygen consumption (lean: 37.8 +/- 5.6 micromol/min, obese: 22.2 +/- 3.8 micromol/min) were not significant. Both groups stopped running after the same time at their maximal speed (lean: 4.5 +/- 0.3 min, obese: 4.2 +/- 0.2 min). During exercise, lean rats had higher increases in core temperature (lean: 0.7 degrees C, obese: 0.4 degrees C) and muscle temperatures (lean: 1.3 degrees C, obese: 0.7 degrees C) than the obese rats. The calculated heat flows indicated a predominant conductive transfer of heat from muscle through the skin in lean rats but a higher proportion of heat transfer to the blood in obese rats. It is concluded that muscle heat accumulation did not cause fatigue in either case.
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PMID:Hind leg heat balance in obese Zucker rats during exercise. 944 91


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