The effect of surgically implanted metallic bullet fragments on the intervertebral disc using a canine model☆.

PURPOSE: To characterize the gross, histologic, and systemic changes caused by implantation of metal fragments commonly used in commercial bullets into the intervertebral disc. BACKGROUND CONTEXT: Long-term complications of retained bullet fragments in the spine have been documented in the literature; however, the impact of different metal projectiles on the intervertebral disc has not been described. This study was performed to assess the local effects of the metallic bullet fragments on the intervertebral disc and their systemic effects regarding metal ion concentrations in serum and solid organs. STUDY DESIGN: Animal Model Study. METHODS: Funding for this project was provided by the Cervical Spine Research Society in the amount of $10,000. Copper, lead, and aluminum alloys from commercially available bullets were surgically implanted into sequential intervertebral discs in the lumbar spine of six canines. Kirschner wire implantation and a sham operation were performed as controls. Radiographs were performed to confirm the location of the bullets. Animals were sacrificed at 4, 6, and 9 months postimplantation. Whole blood, plasma, cerebrospinal fluid, kidney tissue, and liver tissue samples were analyzed for copper and lead concentrations. Histologic and gross samples were examined at the time of sacrifice. RESULTS: Significant tissue reactions were noted in the discs exposed to copper and lead. Copper resulted in significantly more severe disc degeneration than either the lead or aluminum alloy. In the short interval follow-up of this study, no statistically significant trend was observed in whole blood, plasma, cerebrospinal fluid, and tissue levels. CONCLUSION: This study demonstrates that the canine intervertebral disc is differentially susceptible to metallic fragments depending on the composition. Trends were noted for increasing levels of lead and copper in liver tissue samples although statistical significance could not be reached due to short time interval and small sample size. The metallic composition of retained fragments can be a determining factor in deciding on surgical intervention.

Flexor pulley system: anatomy, injury, and management.

Flexor pulley injuries are most commonly seen in avid rock climbers; however, reports of pulley ruptures in nonclimbers are increasing. In addition to traumatic disruption, corticosteroid-induced pulley rupture has been reported as a complication of treating stenosing tenosynovitis. Over the last decade, there have been 2 new developments in the way hand surgeons think about the flexor pulley system. First, the thumb pulley system has been shown to have 4 component constituents, in contrast to the classic teaching of 3 pulleys. Second, in cases of zone II flexor tendon injury, the intentional partial A2 and/or A4 pulley excision or venting is emerging as a component for successful treatment. This is challenging the once-held dogma that preserving the integrity of the entire A2 and A4 pulleys is indispensable for normal digit function.

Evidence-based medicine in hand surgery: clinical applications and future direction.

Evidence-based medicine empowers physicians to systematically analyze published data so as to quickly formulate treatment plans that deliver safe, robust, and cost-effective patient care. In this article, we sample some areas in hand and upper extremity surgery where the evidence base is strong enough that it has or should have unified treatment strategies; we identify some problems where good evidence has failed to unify treatment, and discuss problems for which evidence is still lacking but needed because treatment remains controversial. We also discuss circumstances in which level 4 evidence is more likely than randomized trials to guide treatment.

Smad1 expands the hemangioblast population within a limited developmental window.

Bone morphogenetic protein (BMP) signaling is an important regulator of hematovascular development. However, the progenitor population that responds to BMP signaling is undefined, and the relative role of downstream mediators including Smad1 is unclear. We find that Smad1 shows a distinctive expression profile as embryonic stem (ES) cells undergo differentiation in the embryoid body (EB) system, with peak levels in cell populations enriched for the hemangioblast. To test the functional relevance of this observation, we generated an ES cell line that allows temporal control of ectopic Smad1 expression. Continuous expression of Smad1 from day 2 of EB culture does not disturb hematopoiesis, according to colony assays. In contrast, a pulse of Smad1 expression exclusively between day 2 and day 2.25 expands the population of progenitors for primitive erythroblasts and other hematopoietic lineages. This effect correlates with increased levels of transcripts encoding markers for the hemangioblast, including Runx1, Scl, and Gata2. Indeed, the pulse of Smad1 induction also expands the blast colony-forming cell (BL-CFC) population at a level that is fully sufficient to explain subsequent increases in hematopoiesis. Our data demonstrate that Smad1 expression is sufficient to expand the number of cells that commit to hemangioblast fate.

BRCA1 inhibition of telomerase activity in cultured cells.

Telomerase, an enzyme that maintains telomere length, plays major roles in cellular immortalization and cancer progression. We found that an exogenous BRCA1 gene strongly inhibited telomerase enzymatic activity in human prostate and breast cancer cell lines and caused telomere shortening in cell lines expressing wild-type BRCA1 (wtBRCA1) but not a tumor-associated mutant BRCA1 (T300G). wtBRCA1 inhibited the expression of the catalytic subunit (telomerase reverse transcriptase [TERT]) but had no effect on the expression of a subset of other components of the telomerase holoenzyme or on the expression of c-Myc, a transcriptional activator of TERT. However, endogenous BRCA1 associated and partially colocalized with c-Myc; exogenous wtBRCA1 strongly suppressed TERT promoter activity in various cell lines. The TERT inhibition was due, in part, to suppression of c-Myc E-box-mediated transcriptional activity. Suppression of TERT promoter and c-Myc activity required the amino terminus of BRCA1 but not the carboxyl terminus. Finally, endogenous BRCA1 and c-Myc were detected on transfected mouse and human TERT promoter segments in vivo. We postulate that inhibition of telomerase may contribute to the BRCA1 tumor suppressor activity.

Acetylation in hormone signaling and the cell cycle.

The last decade has seen a substantial change in thinking about the role of acetylation in regulating diverse cellular processes. The correlation between histone acetylation and gene transcription has been known for many years. The cloning and biochemical characterization of the enzymes that regulate this post-translational modification has led to an understanding of the diverse role histone acetyltransferases (HATs) play in cellular function. Histone acetylases modify histones, transcription factors, co-activators, nuclear transport proteins, structural proteins and components of the cell cycle. This review focuses on the role of histone acetylases in coordinating hormone signaling and the cell cycle. Transition through the cell cycle is regulated by a family of protein kinase holoenzymes, the cyclin-dependent kinases (Cdks) and their heterodimeric cyclin partners. Recent studies have identified important cross-talk between the cell cycle regulatory apparatus and proteins regulating histone acetylation. The evidence for a dynamic interplay between components regulating the cell cycle and acetylation of target substrates provides an important new level of complexity in the mechanisms governing hormone signaling.