Effect of blockade of TNF-alpha and interleukin-1 action on bone resorption in early postmenopausal women.

After acute estrogen withdrawal in postmenopausal women, administration of anakinra or etanercept, specific blockers of IL-1 and TNF-alpha, respectively, reduced the rise in bone resorption markers to about one half of that in controls. This is consistent with an important role for these immune cytokines in mediating the effect of estrogen deficiency on bone. INTRODUCTION: Studies in rodents have implicated increased production of interleukin (IL)-1 beta and TNF-alpha as mediators of bone loss after ovariectomy, but their roles are unclear in humans whose immune system differs markedly from that of rodents. MATERIALS AND METHODS: We administered transdermal estradiol, 0.1 mg/d, for 60 days to 42 early postmenopausal women. Estrogen treatment was discontinued, and subjects were randomly assigned to intervention groups receiving 3 wk of injections with 0.9% saline, anakinra 100 mg/d, or etanercept 25 mg/twice weekly. Bone turnover was assessed by measuring serum carboxyl-terminal telopeptide of type 1 collagen (CTX) and amino-terminal telopeptide of type 1 collagen (NTX), markers for bone resorption, and serum amino-terminal propeptide of type 1 collagen (P1NP), a marker for bone formation. Results were expressed as percent change in markers from baseline (last 2 days of estrogen treatment and days 20 and 21 of intervention). RESULTS: The percent changes from baseline during intervention for serum CTX, urine NTX, and serum PINP, respectively, were 43.3 +/- 8.0%, 12.0 +/- 7.1%, and -41.0 +/- 2.5% for the control group; 25.9 +/- 6.3%, 9.5 +/- 4.0%, and -37.8 +/- 3.0% for the anakinra group; and 21.7 +/- 5.0%, 0.32 +/- 3.82%, and -34.5 +/- 3.9% for the etanercept group. Compared with the control group, the blunting of the increase in serum CTX fell just below the level of significance (p=0.10) after anakinra treatment, whereas the blunting of the increase in serum CTX (p=0.034) and in urine NTX (p=0.048) were significant after etanercept treatment. Other changes were not significant. CONCLUSIONS: The data are consistent with a role for TNF-alpha, and possibly for IL-1 beta, in mediating increased bone resorption during estrogen deficiency in women. Although either cytokine blocker reduced serum CTX by about one half, the effect of combined blockade could not be tested because of concerns about toxicity. The data do not exclude direct or indirect contributory roles for RANKL or for other cytokines.     

Initial experience with Tc-99m-HM-PAO in the study of brain tumors

A preliminary study of the distribution of the 99mTc complex of hexamethylpropylene amine oxime (HM-PAO) in 12 patients with brain neoplasms before, during, and after radiotherapy has been performed. Untreated brain tumors were found to exhibit a range of 99mTc-HM-PAO uptake, varying from areas of markedly increased isotope activity to photopenic areas, when compared to normal brain tissue. A ratio of 99mTc-HM-PAO tumor uptake to contralateral normal tissue uptake was calculated prior to and during radiotherapy. This ratio tended to return towards unity in lesions responding to therapy. A predictable alteration in whole brain 99mTc-HM-PAO uptake during radiotherapy was not demonstrated. Unlike the radiolabeled amines, 99mTc-HM-PAO localizes in primary tumors, probably indicating that its uptake mechanism is independent of non specific amine receptors. 99mTc-HM-PAO may be useful in the study of brain tumor physiology and response to therapy.     

A Community-based Study of Prolonged Fatigue and Chronic Fatigue

Previous estimates of the prevalence of fatigue and chronic fatigue have derived largely from treated populations and have been biased by differential access to health-care treatment linked with gender, racial/ethnic and social class status. This study involves a community-based prevalence study of prolonged fatigue and chronic fatigue. It addresses: (1) the rate of prolonged fatigue and chronic fatigue in a socioeconomically and ethnically diverse sample of 28,673 adults in Chicago; and (2) establishes the relative prevalence of prolonged fatigue and chronic fatigue across race/ethnicity, socio-economic status and gender. Univariate and multivariate statistical techniques were utilized to delineate the overall rate of prolonged fatigue and chronic fatigue in the Chicago population and its relative prevalence by gender, race/ethnicity, and social class. Findings indicated that fatigue is common in urban populations, but that prolonged fatigue and chronic fatigue occur in about 5.00 to 7.68 percent and 2.72 to 4.17 percent, respectively, of the sample of the population. Highest levels of fatigue were consistently found among women and those with lower levels of education and occupational status.     

DADOS-Survey: an open-source application for CHERRIES-compliant Web surveys

Background  

The Internet has been increasingly utilized in biomedical research. From online searching for literature to data sharing, the Internet has emerged as a primary means of research for many physicians and scientists. As a result, Web-based surveys have been employed as an alternative to traditional, paper-based surveys. We describe DADOS-Survey, an open-source Web-survey application developed at our institution that, to the best of our knowledge, is the first to be compliant with the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). DADOS-Survey was designed with usability as a priority, allowing investigators to design and execute their own studies with minimal technical difficulties in doing so.     

Duke Surgery Research Central: an open-source Web application for the improvement of compliance with research regulation

Background  

Although regulatory compliance in academic research is enforced by law to ensure high quality and safety to participants, its implementation is frequently hindered by cost and logistical barriers. In order to decrease these barriers, we have developed a Web-based application, Duke Surgery Research Central (DSRC), to monitor and streamline the regulatory research process.     

Sciatic artery aneurysms: report of three cases and review of the literature

Sciatic artery aneurysms (SAAs) develop in a persistent sciatic artery, which is a congenital anomalous continuation of the internal iliac artery and may be the major blood supply to the lower extremity. SAAs may appear clinically with rupture, thrombosis, distal embolization, or compression of the sciatic nerve. We have reviewed our three cases and the literature to delineate those factors that permit correct preoperative diagnosis and appropriate surgical intervention. Our three patients (aged 54 to 82 years) appeared with severe ischemia that resulted in above-knee amputations. The literature reveals 21 patients ranging in age from 35 to 84 years (58% were women). Twenty of those patients had operations, one of which resulted in death, and five in above-knee amputations. Unexplained sciatic or buttock pain, or a palpable "pulsating" buttock mass, suggests an SAA. The diagnosis is confirmed by angiography. The recommended treatment is femoropopliteal bypass grafting followed by ligature or percutaneous endovascular thrombosis of the aneurysm. Early diagnosis and correct surgical therapy are the keys to successful management of SAA.     

Clinical significance of technetium-99m methylene diphosphonate myocardial uptake: association with carcinoma of the prostate

Benign myocardial uptake of technetium-99m labelled phosphates, not related to cardiac or metabolic disorders, has been documented except in the case of^99mTc-methylene diphosphonate (MDP). The aim of this study was to assess the frequency of myocardial uptake and its possible association with malignant tumours in general and prostatic carcinoma in particular. We reviewed bone scintigrams performed with either^99mTc-hydroxydiphosphonate (HDP) or^99mTc-MDP over a period of more than 2 years for all patients with prostatic carcinoma and a matching group of patients suffering from other malignant and non-malignant disorders. A total of 965 scintigrams of 812 patients (males=559, females=253; age range 50–91 years, average age 69.2 years) were reviewed. Increased myocardial uptake was detected in 19 scintigrams (MDP=13, HDP=6) of 18 patients (17 males, one female). Most of the male patients with increased myocardial uptake had prostatic carcinoma (13/17) and were over 80 years of age (12/17). All patients were free of any cardiac or noncardiac disorder that might account for such uptake. When scintigraphy was repeated in the same patient, the uptake of^99mTc-HDP was more diffuse and of higher grade than that of^99mTc-MDP Benign myocardial uptake of^99mTc-MDP is more common than previously thought. Although uptake of radiophosphates is attributed to asymptomatic atherosclerotic changes associated with old age, a strong association with prostatic carcinoma exists which may indicate variations in the bone: soft tissue affinity of different MDP complexes.