166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy.

166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical. METHODS: After two 1.1-GBq administrations of 166Ho-DOTMP, data from whole-body counting using a gamma-camera or uptake probe were assessed for reproducibility of whole-body retention in 12 patients with multiple myeloma. The radiation-absorbed dose to normal organs was estimated using MIRD methodology, applying residence times and S values for 166Ho. Marrow dose was estimated from measured activity retained after 18 h. The activity to deliver a therapeutic dose of 25 Gy to the marrow was determined. Methods based on region-of-interest (ROI) and whole-body clearance were evaluated to estimate kidney activity, because the radiotracer is rapidly excreted in the urine. The dose to the surface of the bladder wall was estimated using a dynamic bladder model. RESULTS: In clinical practice, gamma-camera methods were more reliable than uptake probe-based methods for whole-body counting. The intrapatient variability of dose calculations was less than 10% between the 2 tracer studies. Skeletal uptake of 166Ho-DOTMP varied from 19% to 39% (mean, 28%). The activity of 166Ho prescribed for therapy ranged from 38 to 67 GBq (1,030-1,810 mCi). After high-dose therapy, the estimates of absorbed dose to the kidney varied from 1.6 to 4 Gy using the whole-body clearance-based method and from 8.3 to 17.3 Gy using the ROI-based method. Bladder dose ranged from 10 to 20 Gy, bone surface dose ranged from 39 to 57 Gy, and doses to other organs were less than 2 Gy for all patients. Repetitive administration had no impact on tracer biodistribution, pharmacokinetics, or organ dose. CONCLUSION: Pharmacokinetics analysis validated gamma-camera whole-body counting of 166Ho as an appropriate approach to assess clearance and to estimate radiation-absorbed dose to normal organs except the kidneys. Quantitative gamma-camera imaging is difficult and requires scatter subtraction because of the multiple energy emissions of 166Ho. Kidney dose estimates were approximately 5-fold higher when the ROI-based method was used rather than the clearance-based model, and neither appeared reliable. In future clinical trials with 166Ho-DOTMP, we recommend that dose estimation based on the methods described here be used for all organs except the kidneys. Assumptions for the kidney dose require further evaluation.     

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution.

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates geared to simplified preparation without biochemical blood handling. In this initial article, we describe the conceptual and technical evolution from fibrin glues to platelet concentrates. This retrospective analysis is necessary for the understanding of fibrin technologies and the evaluation of the biochemical properties of 3 generations of surgical additives, respectively fibrin adhesives, concentrated platelet-rich plasma (cPRP) and PRF. Indeed, the 3-dimensional fibrin architecture is deeply dependent on artificial clinical polymerization processes, such as massive bovine thrombin addition. Currently, the slow polymerization during PRF preparation seems to generate a fibrin network very similar to the natural one. Such a network leads to a more efficient cell migration and proliferation and thus cicatrization.     

Sciatic Neuropathy: Case Report and Discussion of the Literature on Postoperative Sciatic Neuropathy and Sciatic Nerve Tumors

Sciatic nerve injury and dysfunction is not an uncommon cause of lower extremity symptoms in a musculoskeletal practice. We present the case of a man who presented with lower extremity weakness, pain, and cramps, and was initially diagnosed at an outside institution with bilateral S1 radiculopathies and recommended for spine surgery. He came to us for a second opinion. Electrodiagnostic testing revealed an isolated sciatic neuropathy and the patient was referred for imaging, which showed a sciatic nerve sheath tumor. Review of the literature on sciatic neuropathies shows that there can be many possible etiologies of sciatic nerve dysfunction, but that hip arthroplasty continues to be the leading risk factor. Sciatic nerve tumors are not commonly described in the literature and their definitive management remains unclear.     

The National Summit on Preconception Care: A Summary of Concepts and Recommendations

The Centers for Disease Control and Prevention (CDC) and 35 partner organizations have engaged in developing an agenda for Preconception Health. A summit was held in June 2005 to discuss the current state of knowledge regarding preconception care and convene a select panel to develop recommendations and action steps for improving the health of women, children, and families through advances in clinical care, public health, and community action. A Select Panel on Preconception Care, convened by CDC, deliberated critical related issues and created refined definition of preconception care. The panel also developed a strategic plan with goals, recommendations, and action steps for improving preconception health. The recommendations and action steps are specific to the implementation of health behavior, access, consumer demand, research, and surveillance activities for monitoring and improving the health of women, children and families. The outcome of the deliberations is the CDC publication of detailed recommendations and action steps in the Morbidity and Mortality Weekly Report series, Recommendations and Reports.

     

Educating African American men about the prostate cancer screening dilemma: a randomized intervention.

BACKGROUND: Until there is a definitive demonstration that early diagnosis and treatment of prostate cancer reduces disease-related mortality, it is imperative to promote informed screening decisions by providing balanced information about the potential benefits and risks of prostate cancer screening. Within a community/academic collaboration, we conducted a randomized trial of a printed booklet and a videotape that were designed for African American (AA) men. The purpose of the trial was to determine the effect of the interventions on knowledge, decisional conflict, satisfaction with the screening decision, and self-reported screening. METHODS: Participants were 238 AA men, ages 40 to 70 years, who were members of the Prince Hall Masons in Washington, DC. Men were randomly assigned to the (a) video-based information study arm, (b) print-based information study arm, or (c) wait list control study arm. Intervention materials were mailed to men at home. Assessments were conducted at baseline, 1 month, and 12 months postintervention. Multivariate analyses, including ANCOVA and logistic regression, were used to analyze group differences. RESULTS: The booklet and video resulted in a significant improvement in knowledge and a reduction in decisional conflict about prostate cancer screening, relative to the wait list control. Satisfaction with the screening decision was not affected by the interventions. Self-reported screening rates increased between the baseline and the 1-year assessment, although screening was not differentially associated with either of the interventions. In exploratory analyses, prostate-specific antigen testing at 1 year was more likely among previously screened men and was associated with having low baseline decisional conflict. CONCLUSIONS: This study represents one of the first randomized intervention trials specifically designed to address AA men's informed decision making about prostate cancer screening. We have developed and evaluated culturally sensitive, balanced, and disseminable materials that improved knowledge and reduced decisional conflict about prostate cancer screening among AA men. Due to the high incidence and mortality rates among AA men, there is a need for targeted educational materials, particularly materials that are balanced in terms of the benefits and risks of screening.     

Prevalence and risk behaviors of Chinese men who seek same-sex partners via the internet in Hong Kong.

To examine the prevalence of Internet sex networking among men who have sex with men (MSM) in Hong Kong and risk behaviors associated with the behavior, a telephone survey of 15,230 Hong Kong Chinese men aged 18-60 was conducted. Of the 283 active MSM (having engaged in some MSM behaviors in the last 6 months) identified, 17.7% had networked for MSM partners via the Internet in the last 6 months. Younger age (odds ratio [OR] for age < or = 25 vs. age >25 = 4.67, 95% confidence interval [CI] = 2.35-9.28) and being an anal-sex MSM (OR = 4.72, 95% CI=2.36-9.44) were independent predictors of Internet sex networking. Being an Internet sex networker was associated with some risk behaviors such as having contracted a sexually transmitted disease (adjusted OR = 4.79, 95% CI = 1.34-17.11), having had > or = 3 MSM partners (adjusted OR = 4.74, 95% CI = 2.20-10.23), and having engaged in anal sex (adjusted OR = 3.95, 95% CI = 1.89-8.23). HIV prevention programs for MSM should thereby include Internet-based interventions.     

Primary angiitis of the central nervous system: MRI features and clinical presentation

We report the MRI features in a series of four patients with primary angiitis of the central nervous system (PACNS). Based on MRI features, clinical presentation, paraclinical investigations and laboratory tests, including cerebrospinal fluid (CSF) analysis, various differentials were considered. In two patients with MRI findings of cortical, subcortical and deep white matter lesions, lack of mass effect, focal areas of bleed and heterogeneous parenchymal, leptomeningeal or pial enhancement and a normal magnetic resonance angiography, a differential diagnosis of primary angiitis of the CNS was also considered. In all patients, an open brain biopsy was advised to establish a definitive diagnosis of PACNS. Here, we briefly discuss the MRI features, correlation with clinical presentation and paraclinical parameters for the diagnosis of this entity. We also briefly review the literature.     

Thermodynamic stability of wild-type and mutant p53 core domain

Some 50% of human cancers are associated with mutations in the core domain of the tumor suppressor p53. Many mutations are thought just to destabilize the protein. To assess this and the possibility of rescue, we have set up a system to analyze the stability of the core domain and its mutants. The use of differential scanning calorimetry or spectroscopy to measure its melting temperature leads to irreversible denaturation and aggregation and so is useful as only a qualitative guide to stability. There are excellent two-state denaturation curves on the addition of urea that may be analyzed quantitatively. One Zn²⁺ ion remains tightly bound in the holo-form of p53 throughout the denaturation curve. The stability of wild type is 6.0 kcal (1 kcal = 4.18 kJ)/mol at 25°C and 9.8 kcal/mol at 10°C. The oncogenic mutants R175H, C242S, R248Q, R249S, and R273H are destabilized by 3.0, 2.9, 1.9, 1.9, and 0.4 kcal/mol, respectively. Under certain denaturing conditions, the wild-type domain forms an aggregate that is relatively highly fluorescent at 340 nm on excitation at 280 nm. The destabilized mutants give this fluorescence under milder denaturation conditions.