Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: the Framingham Study

OBJECTIVE: To examine whether estrogen replacement therapy (ERT) prevents worsening of radiographic knee osteoarthritis (OA) in elderly women. METHODS: A total of 551 women ages 63-91 years (mean age 71) in the Framingham Study were followed up from biennial examination 18 (1983-1985) to examination 22 (1992-1993). Data on postmenopausal ERT were obtained every 2 years. Subjects were classified into 3 groups according to their estrogen use at biennial examination 18: never users (n = 349), past users (n = 162), and current users (n = 40). Women received anteroposterior weight-bearing knee radiographs at examinations 18 and 22. Using the Kellgren and Lawrence criteria, global radiographic knee OA was assessed, (grade range 0-4) and individual radiographic features, such as osteophytes and joint space narrowing, were scored from 0 to 3. Worsening was defined as either development of radiographic OA that was not present at baseline (incident OA) or progression of baseline radiographic OA by > or =1 Kellgren and Lawrence grade (progressive OA). Potential confounding factors included age, body mass index, weight change, smoking, knee injury, physical activity level, and bone mineral density at the femoral neck. RESULTS: During 8 years of followup, 17.4% of knee radiographic scores worsened by 1 grade and 5.8% by 2 or 3 grades among never users of ERT. Among current estrogen users, only 11.7% of knee radiographic scores worsened by 1 grade and none worsened by more than 1 grade. After adjusting for age and other potential confounding factors, the relative risk of incident radiographic knee OA in comparison with never users of estrogen was 0.8 (95% confidence interval [95% CI] 0.5-1.4) in past users and 0.4 (95% CI 0.1-3.0) in current users. Current use of estrogen also showed a trend toward decreased risk of progressive knee OA compared with never use (odds ratio [OR] 0.5, 95% CI 0.1-2.9). When both incident and progressive radiographic knee OA cases were combined, current ERT use had a 60% decreased risk compared with never use (OR 0.4, 95% CI 0.1-1.5). CONCLUSION: This is the first prospective cohort study to examine the effects of ERT on radiographic knee OA. The results indicate that current use of ERT had a moderate, but not statistically significant, protective effect against worsening of radiographic knee OA among elderly white women. These findings corroborate those of cross-sectional studies and point further to a potential benefit of female hormones in OA.     

Long-term sweat collection using salt-impregnated pads

To facilitate a study of the pharmacokinetics of drugs dissolved in sweat, a technique was devised for collecting sweat at a steady rate over an 8-day period. Three normal subjects each wore 4 absorbent pads applied to their skin under waterproof dressings for 8 days. The absorbent pads were either plain cotton or cotton impregnated with sodium chloride crystals. Each pad (3 cm x 3 cm) was applied to an area of skin (2 cm x 2 cm) defined by an adhesive template, and was removed daily, weighed, and replaced, to determine progressive uptake of sweat. Sweat uptake by plain cotton pads reached a plateau value within 2 to 3 days and did not significantly increase thereafter; in contrast, uptake by the salt-impregnated pads continued at a steady rate for the full 8 days of the study (mean rate 0.79 mg/cm2/hr, SD = 0.16, N = 6). This effect may be related to an osmotic gradient across the skin, but the physiologic mechanisms are not completely clear. This appears to be a convenient tool for the collection of sweat over long periods at a steady rate.     

Effect of cholesterol and cholestyramine feeding and of fasting on sterol synthesis in the liver, lleum, and lung of the guinea pig

The effects of feeding diest containing either cholesterol (0.24% w/w) or cholestyramine (2.5% w/w) and of fasting on sterol synthesis in the liver, ileum, and lung of both male and female guinea pigs have been studied by measuring the incorporation by tissue slices of 14C-labeled acetate into total digitoninpredipitable sterols. Cholesterol feeding significantly decreased (P less than 0.05) sterol synthesis in the liver, ileum, and lung of the males and in the ileum of females. Cholestyramine feeding stimulated the rate of hepatic sterol synthesis 13-fold but did not significantly affect sterologenesis in the ileum. Sterol synthesis in the lung was significantly increased (P less than 0.05) but to a much lesser extent than in the liver. Fatty acid synthesis in the liver, ileum, and lung was not significantly affected by either cholesterol or cholestyramine feeding. In guinea pigs fasted for 24 hr, sterol synthesis was inhibited in all three tissues, the most pronounced effect occurring in the liver. Only in the lung was fatty acid synthesis significantly decreased (P less than 0.001) by fasting. Cholesterol feeding resulted in increased concentrations of cholesterol in the plasma and liver. Cholestyramine feeding reduced plasma cholesterol concentration by 81% in females and by 64% in males. However, it did not significantly change the tissue cholesterol concentrations. Fasting resulted in a significant increase (P less than 0.05) in plasma cholesterol concentration but did not effect the concentration of cholesterol in the tissues. It was concluded that in the normal guinea pig, the feedback inhibition produced by both cholesterol and also possibly by bile acids suppresses sterol synthesis in the liver to very low rates compared to those in the small intestine, where sterologenesis is not only less sensitive to the cholesterol negative feedback system than that in the liver, but also is not subject to regulation by the bile acid negative feedback system.     

Colitis cystica profunda

Colitis cystica profunda is a benign disease of the colon. Its importance lies in differentiating it from mucus-producing adenocarcinoma. It has rarely been described in the surgical literature. A review of records of patients seen at the Mayo Clinic produced 66 clinical cases of localized colitis cystica profunda, and in 21 patients the diagnosis was confirmed histologically. Follow-up, which was available in all patients, ranged from 2 months to 29 years, with a mean follow-up of more than 8 years. The data suggest that local excision is the preferred initial therapy.     

Developmental characteristics of histamine methyltransferase and phenylethanolamine-N-methyl-transferase of rat brain

The specific activity of histamine methyltransferase of rat brain increases rapidly from the 16th until the 25th day of gestation (7 days after birth). The specific activity of phenylethanolamine-N-methyl-transferase shows a rapid increase during the 1st and the 2nd week after birth, the adult values being obtained by the end of the 2nd week.     

Analysis of three restriction fragment length polymorphisms in the human type II procollagen gene

Cloned genomic DNA sequences corresponding to various regions of the human type II procollagen gene were used to analyze the DNA from 78 normal volunteers. Southern hybridization experiments detected polymorphic HindIII, BamHI, and EcoRI sites. The presence of the polymorphic HindIII site results in a 7.0-kilobase (kb) band, and the absence of this site results in a 14.0-kb band. When present, the BamH1 polymorphic site yields a 4.8-kb band, and when absent, yields a 7.2-kb band. The presence of the EcoRI polymorphic site results in a 3.7-kb band, and its absence results in a 7.0-kb band. Each polymorphic site was mapped. Analyses of the data demonstrated that the sites are present in overall gene frequencies of .39 for HindIII, .04 for BamHI, and .02 for EcoRI. Gene frequencies of the polymorphic sites were also studied with respect to race. The polymorphic sites are present in a Hardy-Weinberg distribution in the study population. Study of an extended family demonstrated that the segregation of the HindIII polymorphic site is consistent with Mendelian inheritance.