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The interpretation of results measured by quantitative ultrasound (QUS) of the heel depends on the population studied. We measured estimated bone mineral density (BMD) of the heel using the Hologic Sahara sonometer. People were studied at county fairs, health fairs, and churches. Subjects were not on treatments that would affect bone density, other than calcium supplementation. This included 823 Caucasian women, 131 African American women, and 301 Caucasian men. In contrast to women, for Caucasian men the squared term for age was not significant, and a straight line of decline was the best fit for estimated BMD. African American women had a standard deviation larger than that reported by Hologic for Caucasian women. We compared a history of self-reported fractures with a subject's estimated BMD. An estimated BMD of 0.57 gm/cm 2 included 75% of all fractures. This cutoff point was associated with increased fracture prevalence in subjects over age 50, relative risk of 1.4. This result corresponds to the Hologic data T-score of –0.2. When used as a screening tool for osteoporosis fracture risk, an estimated BMD of 0.57 gm/cm 2 seems reasonable in those subjects over age 50.

The side effects of nonsteroidal anti-inflammatory drugs (NSAID) include problems involving peptic ulceration, renal function, and liver disease. Publications have stressed the need to monitor patients for these problems and the rheumatology community across the country has echoed these concerns in continuing education activities to physicians over the years. The American College of Rheumatology (ACR) disseminated recommendations for nonsteroidal anti-inflammatory drugs (NSAID) monitoring in rheumatoid arthritis (RA) patients. We used this as an example of expert opinion for monitoring of NSAID and compared it with the frequency of monitoring by primary care physicians using NSAID for various diseases. We asked whether the rheumatology community's efforts were successful over time to enhance NSAID monitoring by primary care physicians. Physicians across the United States, using a computerized medical record, allowed data to be extracted from their medical practices. Dates of NSAID prescriptions and laboratory test monitoring for any diagnosis were analyzed. Those tests included a CBC, hepatic panel, and renal tests. The frequency of baseline tests performed within 3 months before starting a NSAID by internists was 30% compared with 6% by family practitioners in private practice and 1% in academic family practice centers before publication of the ACR guideline. After dissemination of the guidelines in 1996, the frequency of baseline testing by these groups was lower. Follow-up monitoring within 3 months of starting a NSAID was also low (24, 3, and 2% respectively) and did not improve after ACR guideline publication. Publication and dissemination of the ACR guidelines, and other efforts, did not improve rates of monitoring. The rheumatology community needs to re-evaluate the effectiveness of programs that teach safe use of rheumatologic medications by primary care physicians.

The interpretation of results measured by quantitative ultrasound (QUS) of the heel depends on the population studied. We measured estimated bone mineral density (BMD) of the heel using the Hologic Sahara sonometer. People were studied at county fairs, health fairs, and churches. Subjects were not on treatments that would affect bone density, other than calcium supplementation. This included 823 Caucasian women, 131 African American women, and 301 Caucasian men. In contrast to women, for Caucasian men the squared term for age was not significant, and a straight line of decline was the best fit for estimated BMD. African American women had a standard deviation larger than that reported by Hologic for Caucasian women. We compared a history of self-reported fractures with a subject's estimated BMD. An estimated BMD of 0.57 gm/cm2 included 75% of all fractures. This cutoff point was associated with increased fracture prevalence in subjects over age 50, relative risk of 1.4. This result corresponds to the Hologic data T-score of -0.2. When used as a screening tool for osteoporosis fracture risk, an estimated BMD of 0.57 gm/cm2 seems reasonable in those subjects over age 50.

Optimal information that should be included in ultrasound (US) heel bone mineral density (BMD) reports is not known. If additional information about further evaluation of patients with low heel BMD were included in reports, would responses for treatment improve? We screened people at health fairs using the Sahara heel US machine. For those with a T-score of/= 1.0, letters were sent to their primary care physician notifying them of the result. Physicians were randomly assigned to (1) a standard letter, which recommended central bone density screening (dual X-ray absorptiometry [DXA]) and treatment if the BMD was low; or (2) an extended letter, which also outlined treatment strategies based on recommended subsequent central DXA scan results for a T-score of1.50 and also if2.00. The extended letter only increased the frequency of DXA testing from 30.1 to 37.2% (not a significant increase). Of 88 people with heel BMD/= 1.00 and not previously on any treatment, 25 of 45 (56%) were treated (calcium, estrogens, bisphosphonates, or calcitonin or a combination) after physicians received a standard letter and 30 of 43 (70%) after an extended letter (one-sided p = 0.084). Of people with T/= 1.9, and initially taking nothing more than calcium, 5 of 36 (13.9%) received additional treatment after physicians received a standard letter vs 9 of 41 (22.0%) after an extended letter (one-sided p = 0.180). For those with T/= 1.0 because of the screen 25 of 197 (12.7%) received additional treatment. One hundred forty-six of 194 (75%) individuals and received treatment with calcium or other medications, and 74 of 173 (43%) of individuals before screening and 141 of 195 (72%) after physicians received letters took calcium. Physicians regarded calcium alone as adequate treatment in many cases. There was no marked increase in treatment when additional information was provided to physicians regarding evaluation and treatment for low US heel BMD results.

Plasma membranes were isolated from lapine synovial cells grown in monolayer culture using discontinuous sucrose gradient centrifugation techniques. 5′nucleotidase was detected in great abundance while glucose-6 phosphate dehydrogenase and cytochrome oxidase were present at low to undetectable levels. Plasma membranes incubated at 37°C for 60 min with [3H]-arachidonyl-phosphatidylinositol/phosphatidylserine synthesized [3H]-diacylglycerides. Little if any [3H]-diacylglyceride synthesis was measured when [3H]-arachidonyl-phosphatidylcholine or [3H]-arachidonyl-phosphatidylethanolamine were used as substrates. These results are consistent with a plasma membrane-associated phosphatidylinositol-specific phospholipase C from lapine synovial cells in culture.

The relative benefits and risks of reserpine and guanethidine were compared in patients with thiazide-treated mild to moderate hypertension (diastolic pressure 95-115 mm Hg). Forty-nine ambulant patients )30 men, 19 women) were treated throughout the study with hydrochlorothiazide, 50 mg/day. In this double blind crossover study each drug was added in graded increments until a predetermined therapeutic response was obtained, blood pressure measurements and side effect scores were evaluated biweekly. Major conclusions of the study were: 1) guanethidine, as well as reserpine, will reduce mild to moderate blood pressures to normal; 2) in most cases, side effects which did occur while taking guanethidine or reserpine were well tolerated and neither drug was clearly superior. Side effects associated with larger doses of guanethidine employed in severe hypertension were absent or only slightly bothersome. Thus, guanethidine apppears to have a good benefit-to-risk ratio in the therapy of mild to moderate hypertension and offers a number of advantages over drugs commonly used in this syndrome. This study refutes the common belief that guanethidine must be reserved only for the treatment of more severe degrees of hypertension.

Inhibition of prostaglandin E2 synthesis partially ameliorates some aspects of synovitis, but joint destruction still progresses. Other aspects of phospholipid metabolism may play a role in synovial tissue pathophysiology. Products of phosphatidylinositol metabolism can activate intracellular processes in response to extracellular stimuli. We asked whether this pathway is activated in synoviocytes in monolayer tissue culture by the addition of hydroxyapatite (HA) crystals in medium. These crystals are found in pathological human synovial fluid. These crystals are associated with the secretion of degradative enzymes and with a destructive arthritis in humans. Rabbit synoviocyte cultures, previously incubated with [3H]inositol to label inositol phospholipids, were stimulated with the addition of hydroxyapatite (180 micrograms/ml) to the cultures. There was enhanced intracellular accumulation of [3H]inositol monophosphate (30-100%) after 4 h. This indicated an increased phospholipase C activity. The radioactivity in [3H]inositol bis- and trisphosphates was too low to reliably measure. The use of [32P]Pi allowed detection of these compounds. In the presence of HA, incorporation of [32P]Pi into phosphatidylinositol, phosphatidylinositol monophosphate, and phosphatidylinositol bisphosphate was increased. In addition, cultures exposed to [32P]Pi during stimulation with HA had an increased content of [32P]inositol monophosphate, bisphosphate, and trisphosphate.

Although the use of methotrexate (MTX) is gaining acceptance in the treatment of several connective tissue diseases, there is little evidence of its therapeutic value in systemic lupus erythematosus (SLE). We examined the response to MTX in patients with steroid-resistant SLE in an open, unblinded study. Of 10 SLE patients treated with MTX (7.5 mg/weekly), 7 showed improvement. The other 3 stopped therapy because of lack of response or because of side effects. Improvements were noted within 3 months in responding patients. These promising observations suggest that controlled studies of MTX for the treatment of SLE are justified.