Relationship between vitamin D status and bone mineralization,mass, and metabolism in children with osteogenesis imperfecta: Histomorphometric study

The effect of low vitamin D levels in children with bone fragility disorders has not been examined in detail. In this study, we evaluated the relationship between vitamin D status and parameters of skeletal mineralization, mass, and metabolism in a group of pediatric osteogenesis imperfecta (OI) patients. This retrospective study consisted of 71 patients with a diagnosis of OI type I, III, or IV (ages 1.4 to 17.5 years; 36 girls) who had not received bisphosphonate treatment before iliac bone biopsy. Serum 25‐hydroxyvitamin D [25(OH)D] levels ranged from 13 to 103 nmol/L and were less than 50 nmol/L in 37 patients (52%). None of the OI patients had radiologic signs of rickets or fulfilled the histomorphometric criteria for the diagnosis of osteomalacia (ie, elevated results for both osteoid thickness and mineralization lag time). Serum 25(OH)D levels were negatively correlated with age and serum parathyroid hormone levels but were not correlated with any parameter of bone mineralization (ie, osteoid thickness, mineralization lag time, or bone‐formation rate per bone surface) or bone mass (ie, lumbar spine areal bone mineral density, iliac bone volume per tissue volume, or iliac cortical width). We found no evidence that serum 25(OH)D levels in the range from 13 to 103 nmol/L were associated with measures of bone mineralization, metabolism, or mass in children with OI. © 2011 American Society for Bone and Mineral Research     

Preaortic left primitive iliac vein: two case studies

Although congenital abnormalities of the inferior vena cava (IVC) are rare, they can lead to serious hemorrhagic complications, especially during aortoiliac surgery. The most frequent complications include the double IVC, left-sided IVC, and the left retroaortic renal vein isolated or associated with a preaortic renal vein forming a periaortic venous collar. Preaortic primitive iliac vein represents an exceptional anatomic entity and only a few cases have been reported in previously published data (Ruemenapf et?al., J Vasc Surg 1998;27:767-771; Schiavetta et?al., J Vasc Surg 1998;28:719-722; Shindo et?al., Ann Vasc Surg 2000;14:393-396; Balbridge and Canos, Arch Surg 1987;122:1184-1188; Honkasalo et?al., Acta Chir Scand 1983;149:717-719; Brener et?al., Arch Surg 1974;108:159-165; Vohra and Leiberman, Eur J Vasc Surg 1991;5:209-211; McClure and Huntington, Am Anat Memoirs 1929;15:1-55). In this study, we report two cases of preaortic left primitive iliac vein. The first patient was a male who was operated on for an aortobiiliac aneurysm. The second was of a female patient who was operated on for an interaortocaval lymphadenopathy that resulted from ganglion curettage performed for ovarian cancer.     

Challenges and potential solutions to meeting accrual goals in a Phase II chemoprevention trial for prostate cancer

ObjectiveThe goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer.MethodsWe developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented.ResultsBetween January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n = 3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n = 113) declining to participate due to patient related factors and 14% (n = 29) eliminated due to protocol-related criteria for exclusion. Ninety-four (94) subjects consented to participate with 34% of these subjects (n = 74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies.ConclusionA contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials.     

Effect of vertebral cement augmentation with polymethylmethacrylate on intervertebral disc and bone tissue

Vertebral cement augmentation is reported to be a safe and effective technique for providing stabilization and pain relief. However, adjacent intervertebral discs may be at risk of accelerated degeneration as a result of aggravated nutritional constraints. Therefore, we investigated the effects of injecting polymethylmethacrylate (PMMA) into three adjacent lumbar vertebrae on intervertebral disc and vertebral bone tissue in 12 skeletally mature sheep. After 6 and 12 months of augmentation, the sheep were euthanized and their spines were processes for histological evaluation. Semiquantitative histomorphological analysis of discs and endplates was conducted using published criteria. Histomorphological changes in the augmented bone were assessed qualitatively. Approximately 80% of the length of the endplates was in contact with PMMA. However, there was no significant difference between the histopathological score of the discs adjacent to augmented vertebrae and the score of the control discs. Bone tissue reaction to PMMA was characterized by a thin fibrous tissue layer and occasional foreign-body reactions. New bone formation was present in all augmented vertebrae. Concerns about aggravation of disc degeneration as a result of vertebral cement augmentation seem to be unsubstantiated. Furthermore, adverse effects of PMMA cement on bone biology do not seem to be a relevant issue.     

Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep

Purpose: To present the long‐term follow‐up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike‐waves during slow wave sleep (CSWS). Methods: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. Key Findings: After a mean duration of follow‐up of 15.6 years (range, 8–23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short‐lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long‐term outcome correlated best with duration of CSWS. Significance: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.     

Protection against TNFα-dependent liver toxicity by intraperitoneal liposome delivered DsiRNA targeting TNFα in vivo

Tumor necrosis factor-alpha (TNFα) is a classic proinflammatory cytokine implicated in the pathogenesis of several autoimmune and inflammatory diseases including viral encephalitis. Macrophages being major producers of TNFα are thus attractive targets for in vivo RNA interference (RNAi) mediated down regulation of TNFα. The application of RNAi technology to in vivo models however presents obstacles, including rapid degradation of RNA duplexes in plasma, insufficient delivery to the target cell population and toxicity associated with intravenous administration of synthetic RNAs and carrier compounds. We exploited the phagocytic ability of macrophages for delivery of Dicer-substrate small interfering RNAs (DsiRNAs) targeting TNFα (DsiTNFα) by intraperitoneal administration of lipid-DsiRNA complexes that were efficiently taken up by peritoneal macrophages and other phagocytic cells. We report that DsiTNFα-lipid complexes delivered intraperitoneally altered the disease outcome in an acute sepsis model. Down-regulation of TNFα in peritoneal CD11b+ monocytes reduced liver damage in C57BL/6 mice and significantly delayed acute mortality in mice treated with low dose LPS plus d-galactosamine (D-GalN).