To investigate the prevalence of osteoarthritis (OA) of the knee in elderly subjects, we studied the Frarningham Heart Study cohort, a population-based group. During the eighteenth biennial examination, we evaluated the cohort members for OA of the knee by use of medical history, physical examination, and anteroposterior (standing) radiograph of the knees. Radiographs were obtained on 1,424 of the 1,805 subjects (79?b). Their ages ranged from 63-94 years (mean 73). Radiographs were read by a radiologist who specializes in bone and joint radiology, and were graded 0-4 according to the scale described by Kellgren and Lawrence. OA was defined as grade 2 changes (definite osteophytes), or higher, in either knee. Radiographic evidence of OA increased with age, from 27% in subjects younger than age 70, to 44% in subjects age 80 or older. There was a slightly higher prevalence of radiographic changes of OA in women than in men (34% versus 31 %); however, there was a significantly higher proportion of women with symptomatic disease (11% of all women versus 7% of all men; P = 0.003). The age-associated increase in OA was almost entirely the result of the marked age-associated increase in the incidence of OA in the women studied. This study extends current knowledge about OA of the knee to include elderly subjects, and shows that the prevalence of knee OA increases with age throughout the elderly years.

These results and other corroborative cross-sectional data show that obesity or as yet unknown factors associated with obesity cause knee osteoarthritis.

Weight loss reduces the risk for symptomatic knee osteoarthritis in women.

Objective. Knee osteoarthritis (OA) is highly prevalent, especially in the elderly. Preventive strategies require a knowledge of risk factors that precede disease onset. The present study was conducted to determine the longitudinal risk factors for knee OA in an elderly population.Methods. A longitudinal study of knee OA involving members of the Framingham Study cohort was performed. Weight-bearing knee radiographs were obtained in 1983-1985 (baseline) index increased the risk of OA (OR = 1.6 per 5-unit increase, 95% CI 1.2-2.2), and weight change was directly correlated with the risk of OA (OR = 1.4 per 10-lb change in weight, 95% CI 1.1-1.8). Physical activity increased the risk of OA (for those in the highest quartile, OR = 3.3, 95% CI 1.4-7.5). Smokers had a lower risk than did nonsmokers (for those who smoked an average of 1 1 0 cigarettedday, OR = 0.4, 95% CI 0.2-0.8). Factors not associated with the risk of OA included chondrocalcinosis and a history of hand OA. Weight-related factors affected the risk of OA only in women.Conclusion. Elderly persons at high risk of developing radiographic knee OA included obese persons, nonsmokers, and those who were physically active. The direction of weight change correlated directly with the risk of developing OA.Osteoarthritis (OA) is the most common joint disease, especially in the elderly. However, partly because of the slow time course of disease development, no substantial longitudinal studies of risk factors for the disease have been performed. Knowledge of the risk factors for knee OA has been derived from crosssectional studies.Similar to many chronic diseases, the pathogenesis of OA is likely to be multifactorial. Risk factors consistently associated with the disease in cross-sectional studies include older age, female sex, and being overweight (1). In cross-sectional studies, the OA could develop first, leading a person to become sedentary and to gain weight. We have reported that higher weight in early life predisposes patients to knee OA (2), and that weight loss lowers the risk of developing symptomatic knee OA (3). Both results were based on a one-time assessment of OA occurrence (3). We (4) and others ( 5 )

Objective. To determine the incidence of radiographic knee osteoarthritis (OA) and symptomatic OA (symptoms plus radiographic OA), as well as the rate of progression of preexisting radiographic OA in a population-based sample of elderly persons.Methods. Framingham Osteoarthritis Study subjects who had knee radiographs and had answered questions about knee symptoms in 1983-1985 were reexamined in 1992-1993 (mean 8. l-year interval) using the same protocol. Subjects were defined as having new (incident) radiographic OA if they developed grade 2 2 OA (at least definite osteophytes or definite joint space narrowing). New symptomatic OA was present if subjects developed a combination of knee symptoms and grade 2 2 OA. Progressive OA was diagnosed when radiographs showing grade 2 disease at baseline showed grade 2 3 disease on followup.Results. progressive disease occurred slightly more often in women (relative risk = 1.4; 95% CI 0.8-2.5) but rates did not vary by age in this sample. Among women, approximately 2 % per year developed incident radiographic disease, 1 % per year developed symptomatic knee OA, and about 4% per year experienced progressive knee OA.Conchsion. In elderly persons, the new onset of knee OA is frequent and is more common in women than men. However, among the elderly, age may not affect new disease occurrence or progression.Symptomatic knee osteoarthritis (OA) affects -6% of the adult population and occurs in almost 10% of those over age 65 (1). It accounts for the majority of total knee replacements in the United States, and recent evidence suggests that it accounts for as much lower extremity physical disability in the elderly as any other disease (2). For a disease so common and with such an enormous impact on affected persons and on society, remarkably little is known about its incidence and progression in the population. While the prevalence of knee OA has now been studied, the development of OA over time and the rate of progression of both radiographic and symptomatic disease are poorly characterized. Evaluations of etiologic factors, secular trends in disease, and comparisons of disease rates across populations are best performed with information on the rate of incident or new disease.There has been only one population-based incidence study of knee OA that incorporated serial radiographs of the knees and questions about symptoms. This important 12-year followup study of subjects from Holland (3) evaluated only 258 subjects and found low incidence rates.Studies of disease progression have been more

The left lung from a dog was removed, ventilated with negative pressure, and perfused with venous blood. Pulmonary arterial, venous, and alveolar pressures could be varied over a large range. The distribution of blood flow in the lung was measured with Xe133. Under these conditions, there was no blood flow above the level at which alveolar equaled arterial pressure (measured at the arterial cannula). Below this level there was a linear increase in blood flow down the lung when the venous pressure was kept low. Raising the venous pressure made the distribution of flow more uniform below the level at which venous and alveolar pressures were equal although flow still increased down this zone. The flow distribution could be completely accounted for by the mechanical effects of the pressure inside and outside the blood vessels which each behaved like a Starling resistance. It was possible to simulate the flow distributions found in man in various physiological and diseased states. pulmonary; hydrostatic effect; Starling resistance Submitted on November 15, 1963

The compliance of the total respiratory system and its components was studied in 24 normal and 12 obese spontaneously breathing unanesthetized subjects. The mean compliance of the total respiratory system was .119 l/cm H2O in normal individuals, but was .052 l/cm H2O in obese subjects. The difference indicated an increased elastic resistance to distention. The compliance of the lung in obese individuals was not different from that of the normals. The compliance of the chest wall was .224 l/cm H2O in normal subjects and was .077 l/cm H2O in obese individuals. In contrast to normal subjects, total respiratory compliance was markedly reduced by recumbency in obese individuals. This was entirely due to a further increase in the resistance of the chest wall. A significant correlation was demonstrated between vital capacity and total respiratory compliance in normal and obese subjects. It has been estimated that of the increase in the mechanical work of breathing in obesity is due to elastic work done on the chest wall. Submitted on November 2, 1959

Previous studies have shown that the free fatty acids (FFA) of blood plasma are renewed much more rapidly than the other plasma lipids (1-3). It has been calculated that, if oxidized, they could satisfy the requirements of oxidative metabolism in the postabsorptive state in man at rest (3). Measurements of arteriovenous (A-V) differences have shown that sufficient FFA are taken up by the heart in the postabsorptive state to account for much of its oxidative metabolism, provided they are all oxidized (4-5). Similar observations related to skeletal muscle have been difficult to evaluate because of the multiple sources of venous blood draining limbs (6). Measurements of radioactivity in expired CO2 after injection of C14-labeled fatty acids suggest that, in man (3) and in dogs (7), oxidation of circulating FFA accounts for 25 to 50% of energy metabolism in the postabsorptive state at rest. Such quantitative evaluations have been complicated by recycling of FFA between blood and tissues, recycling of triglyceride fatty acids from the liver, and slow equilibration of labeled CO2 derived from oxidation of labeled FFA with the body pool of CO2.We thought that many of these problems could be minimized if such studies were done during exercise, since blood flow would be directed primarily to workinig muscle. Thus, steady-state conditions might be reached earlier and permit more reliable calculation of the contribution of plasma FFA to total body metabolism. Further-* Supported by grants H-6285 and H-2554 from the U. S. Public Health Service, the Health Foundation of the Arrowhead Area, and the San Mateo County Heart Association, Calif.t Junior Research Fellow, San Francisco Heart Association.t Lederle International Fellow, 1962. more, since energy metabolism during exercise can be considered essentially that of skeletal muscle, such studies would measure utilization of FFA by muscle in vivo.The efflux of FFA from plasma is increased during exercise (8-11), presumably a result of augmented blood flow to working muscles (10-11). Basu, Passmore, and Strong (12) have shown that the concentration of FFA in plasma from antecubital veins is elevated when men walk 3 to 4 miles per hour for more than 30 to 60 minutes. This suggests that the turnover rate of FFA is considerably increased during such exercise. We have chosen this model for our studies. The results show that the turnover rate of FFA is indeed increased and strongly suggest that FFA are the major circulating metabolites burned by working muscle in the postabsorptive state. METHODSExperimental subjects and procedures. Six members of a wrestling team, aged 23 to 30, volunteered as subjects. All were participating in a strenuous program of training and were in excellent physical condition. The nature and purpose of the study were explained to them in detail. They reported to the laboratory in the morning after fasting for 12 to 15 hours. Four received water as desired during the study. Two were first fed a fat-free breakfast containing 80 g of carbohydrate and 20 g o...