Mid-term outcomes after distally locked-to-standard primary stem exchange in 29 hip-prosthesis patients

AbstractBackgroundCementless locked femoral stems are used for revision surgery in patients with bone loss to induce spontaneous bone reconstruction, allowing subsequent replacement by a standard primary stem. The small number of patients and short follow-ups available to date preclude a valid assessment of this strategy.HypothesisAfter distally locked stem revision, replacement by a standard primary stem does not induce complications, and the quality of the bone reconstruction allows strong fixation of a regular primary stem.Materials and methodsWe retrospectively evaluated 29 patients in whom a distally locked femoral stem was replaced by a standard primary stem between 1998 and 2010 (cemented in 27, cementless in 2 cases). The reason for the procedure was stem breakage, stem migration, or thigh pain. Mean patient age was 63years (range, 39–78years). Outcomes were evaluated based on the Postel-Merle d’Aubigné [PMA] score and Harris Hip Score [HHS]. In addition, radiographs were obtained to assess prosthesis fixation and the Hofmann cortical index measured the bone reconstruction.ResultsThe distally locked stem was removed via a postero-lateral approach without femoral osteotomy in all the 29 cases. In one patient, an intra-operative fracture occurred during femoral preparation. Mean follow-up after the exchange procedure was 75months (range, 3–188months). Postoperative ccomplications occurred in 9 (32%) patients and consisted of chronic infection in 2 patients (after 3 and 76months), post-traumatic peri-prosthetic fractures treated with internal fixation in 3 patients (after 100, 138, and 182months), aseptic loosening in 3 patients (after 13, 39, and 122months), and recurrent instability in one patient (after 63months). All cause revision stem survival after 75months was 72% (95% confidence interval, 47%–87%). In the 19 patients who still had their revision stem at last follow-up, the mean PMA score was 16.7 (range, 13–18) and the mean HHS was 88.2 (range, 59–99). The Hofmann index remained unchanged [36.5% (range, 28%–58%) before the exchange and 32.9% (range, 20%–57%) after the exchange; P=0.129].DiscussionThis study confirms the feasibility of substituting a distally locked stem with a standard primary stem. No specific complications occurred and no technical difficulties arose when extracting the long stems. However, the 32% complication rate and, more specifically, the occurrence of loosening in 10% (3/29) of patients mandates caution in the use of this technique, which should not be proposed routinely, and suggests a need for considering cementless fixation of the standard primary stem.Level of evidenceLevel IV, retrospective study

Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption we performed a population based genome-wide association study of ‘age at first tooth’ and ‘number of teeth’ using 5998 and 6609 individuals respectively from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2,446,724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of fifteen independent loci, with ten loci reaching genome-wide significance (p<5x10−8) for ‘age at first tooth’ and eleven loci for ‘number of teeth’. Together these associations explain 6.06% of the variation in ‘age of first tooth’ and 4.76% of the variation in ‘number of teeth’. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including a SNP in the protein-coding region of BMP4 (rs17563, P= 9.080x10−17). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development

One-year prospective comparative study of three large-diameter metal-on-metal total hip prostheses: Serum metal ion levels and clinical outcomes

SummaryIntroductionThe good clinical outcomes and low wear obtained with 28-mm metal-on-metal implants for total hip replacement prompted the development of large-diameter heads that more closely replicated the normal hip anatomy, with the goal of improving prosthesis stability. However, the blood release of metal ions due to wear at the bearing surfaces and the high rate of groin pain seen with large-diameter implants are causing concern. To determine whether these events are related to the geometry and metal composition of the prosthesis components, we conducted a prospective study of clinical outcomes and serum chromium and cobalt levels 1 year after implantation of three different acetabular cups.HypothesisSerum levels of metal ions are comparable with different types of large-diameter metal-on-metal total hip prostheses.Patients and methodsWe compared 24 Durom™ cups (D), 23 M2a Magnum™ cups (M2a), and 20 Conserve Total™ (C) cups regarding serum chromium and cobalt levels, Postel-Merle d’Aubigné (PMA) scores and Oxford Hip Scores (OHS), as well as radiographic cup orientation and position at 1-year follow-up. Mean age was 66 years (45–85 years), mean body mass index was 28 Kg/m2 (18–45), patients were almost equally divided between males and females, and the reason for hip replacement was primary hip osteoarthritis in 65 patients and avascular necrosis in two. Metal ions were assayed in serum from blood drawn through non-metallic catheters, using mass spectrometry.ResultsDislocation occurred in two patients (one D and one M2a) and revision to change the bearing couple was required in two patients in the D group. Serum cobalt levels in the C group were significantly higher (P=0. 0003) than in the two other groups (7.5μg/L versus 2. 7μg/L with D and 2. 2μg/L with M2a). Clinical outcomes were better in the M2a group (PMA, 17.7 [16–18]; and OHS, 15.2 [12–30]; P<0.05). The PMA score and OHS were 17.5 (16–18) and 18.2 (12–42), respectively, with D; and 16.75 (10–18) and 22. 2 (12–42), respectively, with C cups. When all three cup models were pooled, serum ion levels were higher in patients with pain than without pain (chromium, 7.1μg/L versus 2.1μg/L [P=0.002], and cobalt, 8μg/L versus 2.6μg/L [P=0.0004]).DiscussionSerum chrome and cobalt levels increased after metal-on-metal total hip replacement, and the increase was greater with large-diameter implants than previously reported with 28-mm implants. Persistent pain was significantly associated with higher metal ion levels, with a probable cobalt cut-off of about 8μg/L. Differences in modular head-neck concepts may explain the observed variations.Level of evidenceIII, prospective comparative study

Localization of Arhg, a Member of the Ras Homolog Gene Family, to 11p15.5-11p15.4 by Fluorescence Insitu Hybridization

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Human E2F5 gene is oncogenic in primary rodent cells and is amplified in human breast tumors

E2F transcription factors (E2F1 to 6) are central players in the control of animal cell proliferation as regulators of genes involved in cell cycle progression and in transformation. In this report, we have investigated the potential involvement of the E2F5 gene in tumorigenesis. We show that E2F5 can promote the formation of morphologically transformed foci in primary baby rat kidney cells (BRK) when it is overexpressed in the presence of its heterodimeric partner DP1 and activated RAS. This suggests that E2F5 behaves like a MYC-type cooperating oncogene in functional assays, prompting us to monitor potential amplifications of the E2F5 gene in primary human tumors. We mapped the human E2F5 gene to 8q21.1-21.3 equidistant from the MOS (8q12) and MYC (8q24) oncogenes. Since the long arm of chromosome 8 is frequently the site of increased gene copy number (ICN) in breast cancer, we screened 442 breast tumor DNAs for gains of E2F5, MOS, and MYC genes. The three genes showed ICN, albeit at variable incidence and levels of amplification, with the ICN of E2F5 occurring concomitantly with those of MOS and/or MYC in almost half of the cases. Moreover, a marked increase of the 2.5-kb E2F5 transcript was also detected in some tumors and tumor cell lines. In conclusion, the evidence that sustained unregulated expression of E2F5 can cooperate with other oncogenes to promote cell transformation in functional assays, together with the detection of chromosomal amplifications and overexpressions of the E2F5 gene in breast tumors, provides the first indications that E2F5 deregulation may have a role in human tumor development. Genes Chromosomes Cancer 28.126-130, 2000. (C) 2000 Wiley-Liss, Inc

Human E2F5 gene is oncogenic in primary rodent cells and is amplified in human breast tumors

E2F transcription factors (E2F1 to 6) are central players in the control of animal cell proliferation as regulators of genes involved in cell cycle progression and in transformation. In this report, we have investigated the potential involvement of the E2F5 gene in tumorigenesis. We show that E2F5 can promote the formation of morphologically transformed foci in primary baby rat kidney cells (BRK) when it is overexpressed in the presence of its heterodimeric partner DP1 and activated RAS. This suggests that E2F5 behaves like a MYC-type cooperating oncogene in functional assays, prompting us to monitor potential amplifications of the E2F5 gene in primary human tumors. We mapped the human E2F5 gene to 8q21.1-21.3 equidistant from the MOS (8q12) and MYC (8q24) oncogenes. Since the long arm of chromosome 8 is frequently the site of increased gene copy number (ICN) in breast cancer, we screened 442 breast tumor DNAs for gains of E2F5, MOS, and MYC genes. The three genes showed ICN, albeit at variable incidence and levels of amplification, with the ICN of E2F5 occurring concomitantly with those of MOS and/or MYC in almost half of the cases. Moreover, a marked increase of the 2.5-kb E2F5 transcript was also detected in some tumors and tumor cell lines. In conclusion, the evidence that sustained unregulated expression of E2F5 can cooperate with other oncogenes to promote cell transformation in functional assays, together with the detection of chromosomal amplifications and overexpressions of the E2F5 gene in breast tumors, provides the first indications that E2F5 deregulation may have a role in human tumor development. Genes Chromosomes Cancer 28.126-130, 2000. (C) 2000 Wiley-Liss, Inc

C8, a new member of the convertase family.

A novel subtilisin-like protein, PC8, was identified by PCR using degenerate primers to conserved amino acid residues in the catalytic region of members of the prohormone convertase family. PC8 was predicted to be 785 residues long and was structurally related to the mammalian convertases furin, PACE4, PC1 and PC2, sharing more than 50% amino acid identity over the catalytic region with these family members. PC8 possessed the catalytically important Asp, His, Asn and Ser amino acids, the homo B domain of this family of enzymes and a C-terminal hydrophobic sequence indicative of a transmembrane domain. Structurally, PC8 is more related to furin and PACE4 than to PC1 or PC2. Like furin and PACE4, PC8 mRNA was found to be widely expressed; this is in contrast with PC1 and PC2, which have a restricted distribution. Two transcripts, of 4.5 and 3.5 kb, were detected in both human cell lines and rat tissues. Unlike furin and PACE4, both of which map to chromosome 15, PC8 maps to chromosome 11q23-11q24, suggesting that this gene may have resulted from an ancient gene duplication event from either furin or PACE4, or conversely that these genes arose from PC8