To examine the relation of obesity and weight loss to the formation of gallstones according to pertinent clinical and research issues.

To review changes in the medical complications of drug abuse that have occurred since the authors reviewed them 25 years ago.

To describe the pathogenesis of gastrointestinal cytomegalovirus (CMV) disease, the types and locations of gastrointestinal lesions, the clinical settings in which they occur, and the specific methods available to diagnose and treat the disease.

To outline the preferable approach to the management of patients with nonfamilial colorectal polyps.

The field of cardiac pacing has expanded rapidly in recent years. Engineering improvements and microprocessor technology have resulted in a vast increase in pacemaker technology. The "high-tech" edge of cardiac pacing often discourages all but the pacemaker specialist from approaching a malfunctioning pacemaker. Electrocardiographic signs of pacemaker malfunction can be grouped into four categories: failure to output, failure to capture, undersensing, and inappropriate pacemaker rate. For each of these categories, there may be true malfunctions and pseudomalfunctions. In addition, environmental sources of electromagnetic interference, both within and outside the hospital environment, can result in pacemaker malfunction. Approaching pacemaker malfunction with these categories in mind should help minimize confusion.

To describe the major pathophysiologic mechanisms underlying inherited and secondary hypercoagulable states and to evaluate the frequency, natural history, diagnosis, and management of the various clinical disorders.

One quarter to one third of Americans are overweight; as many as 40% of women and 24% of men are trying to lose weight at any given time; many have tried a variety of methods, such as diets, exercise, behavior modification, and drugs. In controlled settings, participants who remain in weight loss programs usually lose approximately 10% of their weight. However, one third to two thirds of the weight is regained within 1 year, and almost all is regained within 5 years. For many overweight persons, achieving and maintaining a healthy weight is a lifelong challenge. Successful weight loss improves several cardiovascular risk factors and diabetic control; effects on mortality are not clear. Several epidemiologic studies have found that weight loss is associated with increased mortality but the reasons for weight loss were not known. Survey data also confirm that many Americans who are not overweight, particularly young women, are trying to lose weight, which may have adverse physical and psychological consequences. Because of the importance of these issues, research on weight and on weight loss and control should assume a high priority on the nation's health agenda.

To summarize published studies analyzing the effects of long-term change in body weight on all-cause mortality and have not been reported elsewhere in these proceedings.

Six published observational epidemiologic studies have reported evidence of reduced mortality rates in persons who have lost weight. In two studies, the reported protective effects of weight loss on mortality could not be justified by the data. In two other studies, weight loss was associated with both increased and decreased longevity in different subgroups. Only one study provided information on whether the weight loss was voluntary, but this study found similar effects of weight loss regardless of volition. These studies provided only limited information on the magnitude of weight loss associated with changes in longevity and no information on the types of methods used to achieve weight loss. Because of difficulties in studying long-term health outcomes related to obesity treatment, randomized, controlled trials are unlikely to provide a practical study design for this issue. Properly designed observational studies will probably provide the most useful information on the effects of voluntary weight loss on longevity.

Voluntary weight loss in obese patients consistently reduces negative emotions such as depression and anxiety in the short term. Dieting by persons of normal weight is associated with low self-esteem and depressive symptoms. Dieting is linked to the development and maintenance of eating disorders such as anorexia nervosa and bulimia nervosa, although the precise nature of this association is unclear. Dieting cannot be a sufficient causal condition and must combine with other still undetermined vulnerabilities to cause eating disorders. Identification of these risk factors must precede the development of effective programs to prevent eating disorders.

Weight loss reduces many of the health hazards associated with obesity including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, sleep apnea, hypoxemia and hypercarbia, and osteoarthritis. Potential adverse effects of weight loss include a greater risk for gallstone formation and cholecystitis, excessive loss of lean body mass, water and electrolyte problems, mild liver dysfunction, and elevated uric acid levels. Less consequential problems such as diarrhea, constipation, hair loss, and cold intolerance may also occur. The short-term adverse effects are not severe enough to contraindicate weight loss, nor do they outweigh its short-term benefits.

Community-based approaches to weight control including worksite interventions, intervention by home correspondence, and multimodal community strategies are reviewed. Community-based programs have shown the ability to treat large numbers of obese persons, many of whom probably would not spontaneously seek professional care. Community-based approaches produce modest weight losses at lower costs than do clinical interventions. Although no community program has yet to reduce the prevalence of obesity in the general population, this area is relatively new and deserves further study. Recommended areas for future research include strategies for recruitment to community programs and primary prevention of weight gain.

The rising incidence of obesity in the United States has given physicians an increased role in its treatment. Although unsupervised programs can produce significant weight losses, the lack of medical supervision increases the potential for health problems. As with other lifestyle changes (for example, smoking cessation and blood pressure control), even minimal physician involvement may enhance outcome. In published clinical trials, the absence of contact with health professionals among control group participants may account in part for their poor success at weight loss or for their weight gain. Smaller trials examining the value of physician advice and encouragement among dieting patients have shown promising results. Physicians should monitor the health of obese and overweight patients during and after weight loss as is appropriate for the patient, depending on caloric levels, rate of weight loss, weight-loss goals, and intercurrent health events. Medical supervision is necessary for patients on very-low-calorie diets, for severely obese patients (body mass index > 35), and for patients with other health problems.

Most of the available appetite-suppressant drugs act on noradrenergic and possibly dopaminergic receptors to produce satiety. A smaller number increase excess neuronal serotonin levels by blocking serotonin reuptake or by increasing its release. All these drugs produce significantly greater weight loss than does placebo in most studies. Abuse is a problem with amphetamine, methamphetamine, and benzphetamine, whereas other drugs have minimal or no potential for abuse. Weight loss can be sustained for up to 36 months. Net weight loss, compared with placebo, ranges from 2 to 10 kg, and weight regain after terminating drug treatment proves that drugs do not work when not taken. The stigma of obesity, the public opprobrium toward obese persons, and regulatory rigidity have led to unjustified distrust in the potential of drug treatment for obesity.

Physically active men and women may be less likely than their sedentary peers to become overweight. Caloric restriction in overweight persons produces larger weight losses than does exercise, although more of the weight loss by dieting is from lean body mass. The addition of exercise to diet intervention produces more weight loss than does dieting alone. Exercise has a favorable effect on body fat distribution, with a reduction in waist-to-hip ratio with increased exercise. Exercise is especially important in maintaining weight loss in overweight persons. Several prospective studies have shown that overweight men and women who are active and fit have lower rates of morbidity and mortality than overweight persons who are sedentary and unfit. Therefore, exercise is of benefit to overweight persons, even if it does not make them lean. Exercise is recommended as an important part of a weight control program.

Behavior modification applied to the treatment of obesity has evolved from the environmental control of eating behavior to a broader approach characterized by systematic manipulation of all factors associated with eating and exercise patterns. This approach has shown success in helping obese persons lose modest amounts of weight. The average length of treatment is 18 weeks, and the average weight loss is 9.9 kg. About 66% of these weight losses are maintained at 52 weeks of follow-up. Because obesity is a chronic condition with a substantial potential for relapse, longer-term treatments are needed. In the future, behavioral modification is likely to be further combined with other treatment methods.

Diet composition can play a role in obesity treatment because it can influence energy intake and nutrient balance. The greatest potential effect of diet composition occurs not during weight reduction but during maintenance of a reduced body weight. During weight reduction, the extent of negative energy balance is the greatest determinant of the amount and rate of weight loss, and any effects of diet composition are likely to be very small. Conversely, during the maintenance period after weight reduction, maintenance energy requirements are reduced and the rate of fat oxidation may be low. Prevention of fat storage and regain of body weight can be achieved either by increasing fat oxidation (for example, by increasing exercise) or by reducing the fat content of the habitual diet. The treatment with the greatest chance for success combines a reduced-fat diet with aerobic exercise.

Recent studies of the treatment of obesity by moderate and severe caloric restriction show that patients treated in randomized trials using a conventional 1200 kcal/d reducing diet, combined with behavior modification, lose approximately 8.5 kg in 20 weeks. They maintain approximately two thirds of this weight loss 1 year later. Patients treated under medical supervision using a very-low-calorie diet (400 to 800 kcal/d) lose approximately 20 kg in 12 to 16 weeks and maintain one half to two thirds of this loss in the following year. Both dietary interventions are associated with increasing weight regain over time, although regain can be minimized with the recognition that obesity, in many cases, is a chronic condition that requires continuing care. Patients who participate in a formal weight-loss maintenance program, exercise regularly, or both are likely to achieve the best long-term results.

Data voluntarily supplied by industry were examined to evaluate the success of commercial weight loss programs and products. Information about the safe loss of weight, the maintenance of this lowered weight, and resultant health benefits were reviewed. Information was received from companies that produce over-the-counter preparations designed for persons with a small weight loss goal and from physician-supervised programs for morbidity obese persons placed on very-low-calorie diets. Regardless of the products used, successful weight loss and control was limited and required individualized programs consisting of restricted caloric intake, behavior modification, and exercise. Although some manufacturers of physician-supervised weight loss products for obese persons hav defined the effectiveness of their programs with controlled clinical studies, other industry programs have only begun to accurately assess their effectiveness or safety. Given the importance to public health of reducing obesity, rigorous studies on current weight control practices should be pursued aggressively.

The medical hazards of obesity are discussed. Risks include insulin resistance, diabetes mellitus, hypertriglyceridemia, decreased levels of high-density lipoprotein cholesterol, and increased levels of low-density lipoprotein cholesterol. Obesity is also associated with gallbladder disease and some forms of cancer as well as sleep apnea, chronic hypoxia and hypercapnia, and degenerative joint disease. Obesity is an independent risk factor for death from coronary heart disease. A central distribution of body fat enhances the risk for most of these conditions.