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1.  Early migration characteristics of a hydroxyapatite-coated femoral stem: an RSA study 
International Orthopaedics  2009;35(4):483-488.
Measurement of early stem subsidence can be used to predict the likelihood of long-term femoral component loosening and clinical failure. Data that examines the early migration pattern of clinically proven stems will provide clinicians with useful baseline data with which to compare new stem designs. This study was performed to evaluate the early migration pattern of a hydroxyapatite-coated press-fit femoral component that has been in use for over ten years. We enrolled 30 patients who underwent THA for osteoarthritis. The median age was 70 years (range, 55–80 years). Patients were clinically assessed using the Harris hip score. Radiostereometric analysis was used to evaluate stem migration at three to four days, six months, one year and two years. We observed a mean subsidence of 0.73 mm at six months, 0.62 mm at one year and 0.58 mm at two years and a mean retroversion of 1.82° at six months, 1.90° at one year and 1.59° at two years. This data suggests that subsidence is confined to the first six months after which there was no further subsidence. The results from this study can be compared with those from novel cementless stem designs to help predict the long-term outcome one may expect from new cementless stem designs.
PMCID: PMC3066322  PMID: 20012862
2.  Outcome of Extracorporeal Membrane Oxygenation for Early Primary Graft Failure After Pediatric Heart Transplantation 
We sought to analyze the indications and outcome of extracorporeal membrane oxygenation (ECMO) for early primary graft failure and determine its impact on long-term graft function and rejection risk.
Early post-operative graft failure requiring ECMO can complicate heart transplantation.
A retrospective review of all children requiring ECMO in the early period after transplantation from 1990 to 2007 was undertaken.
Twenty-eight (9%) of 310 children who underwent transplantation for cardiomyopathy (n = 5) or congenital heart disease (n = 23) required ECMO support. The total ischemic time was significantly longer for ECMO-rescued recipients compared with our overall transplantation population (276 ± 86 min vs. 242 ± 70 min, p < 0.01). The indication for transplantation, for ECMO support, and the timing of cannulation had no impact on survival. Hyperacute rejection was uncommon. Fifteen children were successfully weaned off ECMO and discharged alive (54%). Mean duration of ECMO was 2.8 days for survivors (median 3 days) compared with 4.8 days for nonsurvivors (median 5 days). There was 100% 3-year survival in the ECMO survivor group, with 13 patients (46%) currently alive at a mean follow-up of 8.1 ± 3.8 years. The graft function was preserved (shortening fraction 36 ± 7%), despite an increased number of early rejection episodes (1.7 ± 1.6 vs. 0.7 ± 1.3, overall transplant population, p < 0.05) and hemodynamically comprising rejection episodes (1.3 ± 1.9 vs. 0.7 ± 1.3, overall transplant population, p < 0.05).
Overall survival was 54%, with all patients surviving to at least 3 years after undergoing transplantation. None of the children requiring >4 days of ECMO support survived. Despite an increased number of early and hemodynamically compromising rejections, the long-term graft function is similar to our overall transplantation population.
PMCID: PMC3117294  PMID: 19679252
extracorporeal membrane oxygenation; child; heart transplantation; right-sided heart failure; left-sided heart failure; hypertension pulmonary
3.  Implications of incising the ventricular septum in double outlet right ventricle and in the Ross–Konno operation☆ 
Incision into the ventricular septum in complex biventricular repair is controversial, and has been blamed for impairing left ventricular function. This retrospective study evaluates the risk of a ventricular septal incision in patients undergoing double outlet right ventricle (DORV) repair and Ross–Konno procedure.
From January 2003 to September 2007, 11 patients with DORV had a ventricular septum (VS) incision and 12 DORV patients did not. Sixteen patients had a Ross–Konno, and 16 had an isolated Ross procedure. The ventricular septal incision was made to match at least the diameter of a normal aortic annulus. In DORV, the VSD was enlarged superiorly and to the left. In the Ross–Konno, the aortic annulus was enlarged towards the septum posteriorly and to the left.
The median follow-up for the study is 19 months (1 month–4 years). For DORV, there were no significant differences in discharge mortality ( p = 0.22), late mortality ( p = 0.48), or late mortality plus heart transplant ( p = 0.093). Although patients with DORV and VSD enlargement have a more complex postoperative course, there were no differences in ECMO use ( p = 0.093), occurrence of permanent AV block ( p = 0.55), left ventricular ejection fraction (LVEF) ( p = 0.40), or shortening fraction (LVSF) ( p = 0.50). Similarly, for the Ross–Konno there were no significant differences in discharge mortality ( p = 0.30), late mortality ( p = NS), LVEF (p = 0.90) and LVSF ( p = 0.52) compared to the Ross, even though the Ross–Konno patients were significantly younger ( p < 0.0001).
Making a ventricular septal incision in DORV repair and in the Ross–Konno operation does not increase mortality and does not impair the LV function. The restriction of the VSD remains an important issue in the management of complex DORV. These encouraging results need to be confirmed by larger series.
PMCID: PMC3117298  PMID: 19269838
Double outlet right ventricle; Ventricular septal defect; Ross–Konno
4.  Long-Term Outcome of Palliation with Internal Pulmonary Artery Bands After Primary Heart Transplantation for Hypoplastic Left Heart Syndrome 
Pediatric cardiology  2009;30(4):419-425.
The purpose of this study was to describe the long-term outcome of infants with hypoplastic left heart syndrome (HLHS) who underwent placement of internal pulmonary artery bands as part of a transcatheter palliation procedure followed by primary heart transplantation. Transcatheter palliation included stenting of the ductus arteriosus, decompression of the left atrium by atrial septostomy, and internal pulmonary artery band placement. Cardiac hemodynamics, pulmonary artery architecture, and pulmonary artery growth since transplantation are described. Nine infants with HLHS had internal pulmonary artery bands placed and underwent successful heart transplant. No infant required reconstruction of the pulmonary arteries at the time of transplant. At 1 year after transplant, all of the recipients had normal mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient. Pulmonary angiography performed at 1 year after transplant demonstrated no distortion of pulmonary artery anatomy with significant interval growth of the branch pulmonary arteries. There was 100% survival to hospital discharge after transplant in this cohort of infants. Transcatheter placement of internal pulmonary artery bands for HLHS offers protection of the pulmonary vascular bed while preserving pulmonary artery architecture and growth with good long-term outcome.
PMCID: PMC3117302  PMID: 19365660
Congenital heart disease; Heart catheterization; Heart transplant; Infant
5.  Case Report: Cementless Stem Stabilization after Intraoperative Fracture: A Radiostereometric Analysis 
We present the case of a patient with intraoperative femoral fracture during THA, which was repaired using cerclage fixation and insertion of an hydroxyapatite-coated cementless stem. The patient was evaluated postoperatively using radiostereometry during a 2-year course, and despite a large amount of subsidence and rotation, stabilization occurred and was maintained by 6 months. By evaluating the pattern of stem migration after intraoperative fracture, this case shows, even in the presence of instability, a successful clinical outcome can be achieved using an hydroxyapatite-coated cementless stem.
PMCID: PMC2816748  PMID: 19760467
6.  Reintervention after Mobile-bearing Oxford Unicompartmental Knee Arthroplasty 
Medial compartment osteoarthritis is a common disorder that often is treated by unicompartmental knee arthroplasty (UKA). Although the Oxford 3 prosthesis is commonly used based on revision rate and cumulative survival, our experience suggests that although there may be adequate implant survival rates, we observed a worrisome and undisclosed reintervention rate of nonrevision procedures.
We describe the frequency and cause of repeat intervention subsequent to implanting this device.
Between 1998 and 2005, 398 patients underwent UKA using the Oxford 3 prosthesis. The minimum followup was 12 months (mean, 43 months; range, 12–102 months).
Forty of the 398 (10%) patients had 55 (13.8%) repeat anesthetics (reintervention). There were 38 nonrevision reinterventions. Revision was performed in 15 patients (3.8%), but two patients had a second revision (17 revisions or 4.3%). We revised the UKA to a second UKA in seven of the 15 cases but two subsequently were rerevised to a TKA; eight were revised directly to a TKA.
Although our data confirm the reported revision rates for this prosthesis, we observed a substantial reintervention rate. Most of the reinterventions are minor and are diagnosed frequently and treated arthroscopically. If revision is required, a second UKA may be considered and performed successfully in patients with isolated loosening of one component.
Level of Evidence
Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC2807008  PMID: 19768516
7.  Dinoflagellate Spliced Leader RNA Genes Display a Variety of Sequences and Genomic Arrangements 
Molecular Biology and Evolution  2009;26(8):1757-1771.
Spliced leader (SL) trans-splicing is a common mRNA processing mechanism in dinoflagellates, in which a 22-nt sequence is transferred from the 5′-end of a small noncoding RNA, the SL RNA, to the 5′-end of mRNA molecules. Although the SL RNA gene was shown initially to be organized as tandem repeats with transcripts of 50–60 nt, shorter than most of their counterparts in other organisms, other gene organizations and transcript lengths were reported subsequently. To address the evolutionary gradient of gene organization complexity, we thoroughly examined transcript and gene organization of the SL RNA in a phylogenetically and ecologically diverse group of dinoflagellates representing four Orders. All these dinoflagellates possessed SL RNA transcripts of 50–60 nt, although in one species additional transcripts of up to 92 nt were also detected. At the genomic level, various combinations of SL RNA and 5S rRNA tandem gene arrays, including SL RNA–only, 5S rRNA–only, and mixed SL RNA–5S rRNA (SL–5S) clusters, were amplified by polymerase chain reaction for six dinoflagellates, containing intergenic spacers ranging from 88 bp to over 1.2 kb. Of these species, no SL–5S cluster was detected in Prorocentrum minimum, and only Karenia brevis showed the U6 small nuclear RNA gene associated with these mixed arrays. The 5S rRNA–only array was also found in three dinoflagellates, along with two SL–5S-adjacent arrangements found in two other species that could represent junctions. Two species contained multimeric SL exon repeats with no associated intron. These results suggest that 1) both the SL RNA tandem repeat and the SL–5S cluster genomic organizations are an “ancient” and widespread feature within the phylum of dinoflagellates and 2) rampant genomic duplication and recombination are ongoing independently in each dinoflagellate lineage, giving rise to the highly complex and diversified genomic arrangements of the SL RNA gene, while conserving the length and structure of the functional SL RNA.
PMCID: PMC2734150  PMID: 19387009
Dinoflagellate; SL RNA; complex genomic arrangement
8.  Hypermethylated cap 4 maximizes Trypanosoma brucei translation 
Molecular microbiology  2009;72(5):1100-1110.
Through trans-splicing of a 39-nt Spliced Leader (SL) onto each protein-coding transcript, mature kinetoplastid mRNA acquire a hypermethylated 5′-cap structure, but its function has been unclear. Gene deletions for three Trypanosoma brucei cap 2′-O-ribose methyltransferases, TbMTr1, TbMTr2, and TbMTr3, reveal distinct roles for four 2′-O-methylated nucleotides. Elimination of individual gene pairs yields viable cells, however attempts at double knockouts resulted in the generation of a TbMTr2−/−/TbMTr3−/− cell line only. Absence of both kinetoplastid-specific enzymes in TbMTr2−/−/TbMTr3−/− lines yielded substrate SL RNA and mRNA with cap 1. TbMTr1−/− translation is comparable to wildtype, while cap 3 and cap 4 loss reduced translation rates, exacerbated by the additional loss of cap 2. TbMTr1−/− and TbMTr2−/−/TbMTr3−/− lines grow to lower densities under normal culture conditions relative to wildtype cells, with growth rate differences apparent under low serum conditions. Cell viability may not tolerate delays at both the nucleolar Sm-independent and nucleoplasmic Sm-dependent stages of SL RNA maturation combined with reduced rates of translation. A minimal level of mRNA cap ribose methylation is essential for trypanosome viability, providing the first functional role for the cap 4.
PMCID: PMC2859698  PMID: 19504740
gene knockout; methyltransferase; ribose 2′-O-methylation; SL RNA; spliced leader; trans-splicing
9.  Histone acetylations mark origins of polycistronic transcription in Leishmania major 
BMC Genomics  2009;10:152.
Many components of the RNA polymerase II transcription machinery have been identified in kinetoplastid protozoa, but they diverge substantially from other eukaryotes. Furthermore, protein-coding genes in these organisms lack individual transcriptional regulation, since they are transcribed as long polycistronic units. The transcription initiation sites are assumed to lie within the 'divergent strand-switch' regions at the junction between opposing polycistronic gene clusters. However, the mechanism by which Kinetoplastidae initiate transcription is unclear, and promoter sequences are undefined.
The chromosomal location of TATA-binding protein (TBP or TRF4), Small Nuclear Activating Protein complex (SNAP50), and H3 histones were assessed in Leishmania major using microarrays hybridized with DNA obtained through chromatin immunoprecipitation (ChIP-chip). The TBP and SNAP50 binding patterns were almost identical and high intensity peaks were associated with tRNAs and snRNAs. Only 184 peaks of acetylated H3 histone were found in the entire genome, with substantially higher intensity in rapidly-dividing cells than stationary-phase. The majority of the acetylated H3 peaks were found at divergent strand-switch regions, but some occurred at chromosome ends and within polycistronic gene clusters. Almost all these peaks were associated with lower intensity peaks of TBP/SNAP50 binding a few kilobases upstream, evidence that they represent transcription initiation sites.
The first genome-wide maps of DNA-binding protein occupancy in a kinetoplastid organism suggest that H3 histones at the origins of polycistronic transcription of protein-coding genes are acetylated. Global regulation of transcription initiation may be achieved by modifying the acetylation state of these origins.
PMCID: PMC2679053  PMID: 19356248

Results 1-9 (9)