A hypomorphic myogenin allele reveals distinct myogenin expression levels required for viability, skeletal muscle development, and sternum formation.
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The myogenic basic helix-loop-helix transcription factor myogenin plays an essential role in the differentiation of skeletal muscle and, secondarily, in rib and sternum formation during mouse development. However, virtually nothing is known about the quantitative requirements for myogenin in these processes. Here, we describe the generation of mice carrying a hypomorphic allele of myogenin, which expresses myogenin transcripts at approximately one-fourth the level of the wild-type myogenin allele. The hypomorphic allele in combination with wild-type and myogenin-null alleles was used to create an allelic series. Embryos representing the complete range of genotypes from homozygous wild type to homozygous null were analyzed for their viability, ability to form normal ribs and sternum, and extent of skeletal muscle differentiation. Embryos carrying the hypomorphic myogenin allele over a wild-type allele were normal. In embryos bearing homozygous hypomorphic alleles, the sternum developed normally and extensive skeletal muscle differentiation occurred. However, muscle hypoplasia and reduced muscle-specific gene expression were apparent in these embryos, and the mice were not viable as neonates. When the hypomorphic allele was placed over a myogenin-null allele, the resulting embryos had sternum defects resembling homozygous myogenin-null embryos, and there was severe muscle hypoplasia. Our results demonstrate that skeletal muscle formation is highly sensitive to the absolute levels of myogenin and that correct sternum formation, skeletal muscle differentiation, and viability each require distinct threshold levels of myogenin. (+info)
Minimally invasive aortic valve replacement through a transverse sternotomy: a word of caution.
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OBJECTIVES: To compare aortic valve replacement (AVR) using a minimally invasive approach through a transverse sternotomy with the established approach of median sternotomy. DESIGN: Retrospective, case-control study. PATIENTS: Fourteen high risk patients (median age 78, Parsonnet score of 18%) who underwent AVR performed through a minimally invasive transverse sternotomy were compared with a historical group of patients matched for age, sex, and Parsonnet score who underwent AVR performed through a median sternotomy by the same surgeon. OUTCOME MEASURES: Cross clamp time, total bypass time, intensive care stay, postoperative in-hospital stay, morbidity, and mortality. RESULTS: There were two deaths in the minimally invasive group and none in the control group (NS). The cross clamp and total bypass times were longer in the minimally invasive group (67 and 92 minutes v 46 and 66 minutes, p < 0.001). There was a higher incidence of re-exploration for bleeding (14% v 0%) and paravalvar leaks (21% v 0%) in the minimally invasive group but these differences were not significant. The minimally invasive group had a longer postoperative in-hospital stay (p = 0.025). The incidence of mortality or major morbidity was 43% (six of 14) in the minimally invasive group and 7% (one of 14) in the matched pairs (p = 0.013). CONCLUSIONS: AVR can be performed through a transverse sternotomy but the operation takes longer and there is an unacceptably high incidence of morbidity and mortality. (+info)
Retinoid signaling is required for chondrocyte maturation and endochondral bone formation during limb skeletogenesis.
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Retinoids have long been known to influence skeletogenesis but the specific roles played by these effectors and their nuclear receptors remain unclear. Thus, it is not known whether endogenous retinoids are present in developing skeletal elements, whether expression of the retinoic acid receptor (RAR) genes alpha, beta, and gamma changes during chondrocyte maturation, or how interference with retinoid signaling affects skeletogenesis. We found that immature chondrocytes present in stage 27 (Day 5.5) chick embryo humerus exhibited low and diffuse expression of RARalpha and gamma, while RARbeta expression was strong in perichondrium. Emergence of hypertrophic chondrocytes in Day 8-10 embryo limbs was accompanied by a marked and selective up-regulation of RARgamma gene expression. The RARgamma-rich type X collagen-expressing hypertrophic chondrocytes lay below metaphyseal prehypertrophic chondrocytes expressing Indian hedgehog (Ihh) and were followed by mineralizing chondrocytes undergoing endochondral ossification. Bioassays revealed that cartilaginous elements in Day 5.5, 8.5, and 10 chick embryo limbs all contained endogenous retinoids; strikingly, the perichondrial tissues surrounding the cartilages contained very large amounts of retinoids. Implantation of beads filled with retinoid antagonist Ro 41-5253 or AGN 193109 near the humeral anlagens in stage 21 (Day 3.5) or stage 27 chick embryos severely affected humerus development. In comparison to their normal counterparts, antagonist-treated humeri in Day 8.5-10 chick embryos were significantly shorter and abnormally bent; their diaphyseal chondrocytes had remained prehypertrophic Ihh-expressing cells, did not express RARgamma, and were not undergoing endochondral ossification. Interestingly, formation of an intramembranous bony collar around the diaphysis was not affected by antagonist treatment. Using chondrocyte cultures, we found that the antagonists effectively interfered with the ability of all-trans-retinoic acid to induce terminal cell maturation. The results provide clear evidence that retinoid-dependent and RAR-mediated mechanisms are required for completion of the chondrocyte maturation process and endochondral ossification in the developing limb. These mechanisms may be positively influenced by cooperative interactions between the chondrocytes and their retinoid-rich perichondrial tissues. (+info)
Sternal wound infections in patients after coronary artery bypass grafting using bilateral skeletonized internal mammary arteries.
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OBJECTIVES: This study evaluated the risks of sternal wound infections in patients undergoing myocardial revascularization using bilateral skeletonized internal mammary arteries (IMAs). BACKGROUND: The skeletonized IMA is longer than the pedicled one, thus providing the cardiac surgeon with increased versatility for arterial myocardial revascularization without the use of vein grafts. It is isolated from the chest wall gently with scissors and silver clips, and no cauterization is employed. Preservation of collateral blood supply to the sternum and avoidance of thermal injury enable more rapid healing and decrease the risk of sternal wound infection. METHODS: From April 1996 to August 1997, 545 patients underwent arterial myocardial revascularization using bilateral skeletonized IMAs. The right gastroepiploic artery was used in 100 patients (18%). The average age of the patients was 65 years; 431 (79%) were men and 114 (21%) were women; 179 (33%) were older than 70 years of age; 166 (30%) were diabetics. The average number of grafts was 3.2 per patient. RESULTS: The 30-day operative mortality rate was 2% (n = 11). There were six perioperative infarcts (1.1%) and six strokes (1.1%); 9 patients had sternal infection (1.7%) and 15 (2.8%) had superficial infection. Risk factors for sternal infection were chronic obstructive pulmonary disease and emergency operation. Superficial sternal wound infections were more common in women and in patients with chronic obstructive pulmonary disease, renal failure, or peripheral vascular disease. The 1-year actuarial survival rate was 97%. Two of the six late deaths were not cardiac-related. Late dehiscence occurred in three patients (0.6%). The death rate (early and late) of patients with any sternal complication was higher than that of patients without those complications (33% vs. 2.7%). CONCLUSIONS: Routine arterial myocardial revascularization using bilateral skeletonized IMAs is safe, and postoperative morbidity and mortality rates are low, even in elderly patients and those with diabetes. Chronic obstructive pulmonary disease and emergency operations were found to be associated with an increased risk of sternal infections, and the authors recommend avoiding the use of bilateral skeletonized IMAs in patients with these preoperative risk factors. (+info)
The development of the fetal sternum: a cross-sectional sonographic study.
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OBJECTIVE: To assess the relationship between gestational age and sonographic appearance of the various sternal components and establish growth during human gestation. DESIGN: A prospective cross-sectional study. METHODS: The study was performed on 252 consecutive normal singleton pregnancies from 19 weeks of gestation until term, using transabdominal high-resolution ultrasound techniques. The sternal length, as well as the number of ossification centers at each gestational age, were recorded. RESULTS: The first occasion at which a fetal human sternum could be visualized with two to three ossification centers was at 19 weeks' gestational age. The fifth ossification center was first visualized at 29 weeks' gestation. The mean +/- SE of sternal length varied from 15 +/- 0.98 mm (95% confidence interval (CI) 12.79-17.21) at 19-20 weeks, to 36.50 +/- 0.29 mm (95% CI 35.58-37.42) at 37-38 weeks' gestation. Sternal length as a function of gestational age was expressed by the regression equation: sternal length (mm) = -11.06 + 1.39 x gestational age (weeks). The correlation coefficient, r = 0.924 for sternal length, was found to be highly statistically significant (p < 0.0001). CONCLUSIONS: The presented data offer normative measurements of the fetal sternum which may be helpful in the prenatal diagnosis of congenital syndromes that include, among other manifestations, abnormalities of sternal development. (+info)
Injury to the first rib synchondrosis in a rugby footballer.
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Injuries to the first rib synchondrosis are uncommon in sport. The potential for serious complications following posterior displacement is similar to that seen with posterior sternoclavicular joint dislocation. Clinical examination and plain radiography may not provide a definitive diagnosis. Computerised tomography is the most appropriate imaging modality if this injury is suspected. Posterior dislocation of the first rib costal cartilage with an associated fracture of the posterior sternal aspect of the synchondrosis has not been previously reported. (+info)
Surgical aspects and techniques of lung volume reduction surgery for severe emphysema.
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Lung volume reduction surgery (LVRS) has become an accepted procedure for palliative treatment of diffuse, nonbullous emphysema. Single or multiple peripheral segmental wedge resections of the most destroyed areas of the lungs are performed with the use of stapling devices, in order to decrease hyperinflation and restore diaphragmatic function. Median sternotomy, videoendoscopy or anterior muscle sparing thoracotomies have been used as surgical approaches. The functional improvement after bilateral resections exceed those after a unilateral approach. LVRS has demonstrated its potential as an alternative to transplantation, and with growing experience, the indications for the procedure have been widened. In selected patients with peripheral lung cancer who have been considered unsuitable for a surgical resection, the combination of both tumour resection and LVRS has successfully been performed. In contrast to LVRS, laser surgery of the emphysematous lung has been abandoned in most institutions. (+info)
Sternal splitting approach to upper thoracic lesions located anterior to the spinal cord.
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The sternal splitting approach for upper thoracic lesions located anterior to the spinal cord is described. The sternal splitting approach can be effectively applied to lesions from the T-1 to T-3 levels. The aortic arch prevents procedures below this level. The approach is straight toward the T1-3 vertebral bodies and provides good surgical orientation. The sternal splitting approach was applied to five patients with metastatic spinal tumors at the C7-T3 levels and three patients with ossification of the posterior longitudinal ligament at the T1-3 levels. No postoperative neurological deterioration occurred. Two patients had postoperative hoarseness. The sternal splitting approach to the upper thoracic spine is recommended for hard lesions, extensive lesions requiring radical resection, and lesions requiring postoperative stabilization with spinal instrumentation. (+info)