Myostatin inhibits proliferation but not differentiation of trout myoblasts

The muscle growth in mammals is regulated by several growth factors including myostatin (MSTN), a member of the transforming growth factor-beta (TGF-beta) superfamily. To date, it is unknown in fish whether MSTN could have any effect on proliferation or differentiation of myogenic cells. Using culture of trout satellite cells, we showed that mstn1a and mstn1b mRNA are expressed in myoblasts and that their expression decreased in differentiating myoblasts. We also demonstrated that a treatment with huMSTN decreased the proliferation of IGF1-stimulated myoblasts in a dose-dependent manner. By contrast, treatment of myoblasts with 100 nM of huMSTN for three days, did not affect the percentage of positive cells for myogenin neither the percentage of nuclei in myosin positive cells. Moreover, our results clearly indicated that huMSTN treatment had no effect on MyoD and myogenin protein levels, which suggests that huMSTN did not strongly affect MyoD activity. In conclusion, we showed that huMSTN inhibited proliferation but not differentiation of trout myoblasts, probably resulting from a lack of huMSTN effect on MyoD activity. Altogether, these results show high interspecies differences in the function of MSTN.     

Effects of growth on maxillary distraction osteogenesis in cleft lip and palate

PurposeThe objective was to analyze the effects of growth on the long-term result of maxillary distraction osteogenesis (DO) in cleft lip and palate (CLP).Patients and methodsRetrospective study of 24 CLP cases with long-term follow-up operated for maxillary DO using the Polley and Figueroa technique: 10 patients were distracted during growth, while 14 patients were operated after their growth spurt. Preoperative (T0), 6–12 months postoperative (T1), and ≥4 years postoperative (T2) cephalometric radiographs were evaluated. A classical cephalometric analysis was used to assess the treatment stability, and a Procrustes superimposition method was performed to assess local changes in the maxilla and the mandible.ResultsAt T0, the mean age was of 11.9 ± 1.4 years for growing patient, and 17.9 ± 3.5 years for patient treated after their growth spurt (P < 0.001). Between T0 and T1, a greater increase of the SNA was shown in growing patients (P = 0.036), but the relapse was more important between T1 and T2, with a significant decrease of the SNA (P = 0.002) and ANB (P = 0.032) compared to the patients treated after their growth spurt. Although not significant, growing patients showed greater rotations of their palatal plane and mandibular plane.ConclusionsMaxillary DO in CLP does not correct the growth deficit inherent to the pathology. Overcorrection of at least 20% is advised during growth.     

Medical treatment for sphincter of oddi dysfunction:Can it replace endoscopic sphincterotomy?

AIM:To report the results of a medical management of sphincter of oddi dysfunction(SOD) after an intermediate follow-up period.METHODS:A total of 59 patients with SOD(2 men and 57 women,mean age 51 years old) were included in this prospective study.After medical treatment for one year,the patients were clinically re-evaluated after an average period of 30 mo.RESULTS:The distribution of the patients according to the Milwaukee's classification was the following:11 patients were type 1,34 were type 2 and 14 were type 3.Fourteen patients underwent an endoscopic sphincterotomy(ES) after one year of medical treatment.The median intermediate follow-up period was 29.8 ± 3 mo(3-72 mo).The initial effectiveness of the medical treatment was complete,partial and poor among 50.8%,13.5% and 35%,respectively,of the patients.At the end of the follow-up period,37 patients(62.7%) showed more than 50% improvement.The rate of improvement in patients who required ES was not significantly different compared with the patients treated conservatively(64.2% vs 62.2%,respectively).CONCLUSION:Our study confirms that conservative medical treatment could be an alternative to endoscopic sphincterotomy because,after an intermediate follow-up period,the two treatments show the same success rates.     

Prospective study using anterior approach did not show association between Modic 1 changes and low grade infection in lumbar spine

Introduction

The modern literature is producing a rapidly growing number of articles which highlight the relationship between infection and lumbar disc degeneration. However, the means by which samples are collected is questionable. Posterior approach surgery is not free from skin contamination. The possibility of intraoperative contamination of disc biopsies cannot be excluded.

Objective

The objective of this study was to determine if an association existed between lumbar disc degeneration and chronic infection of the intervertebral disc.

Materials and methods

313 patients (186/127, F/M) with chronic low back pain secondary to degenerative disc disease which was resistant to medical treatment were included in a single-centre prospective study. All underwent a lumbar anterior video-assisted minimally invasive fusion or disc prosthesis in L4–L5 and/or L5–S1 via an anterior retroperitoneal approach. The patients MRI scans demonstrated in Pfirrmann's classification grade IV or V disc degeneration; 385 disc drives were taken. In terms of Modic changes, 303 Modic 1, 58 Modic II and 24 absence of Modic change, respectively. All underwent intraoperative biopsy, performed according to a strict aseptic protocol. The biopsies were then cultured for 4 weeks with specialised enrichment cultures and subjected to histopathological analysis.

Results

The mean age was 47 ± 8.6 years sterile cultures were obtained in 379 samples (98.4 %) and 6 were positive (1.6 %). The cultured bacteria were: Propionibacterium acnes (n:2), Staphylococcus epidermidis (n:2), Citrobacter freundii (n:1), and Saccharopolyspora hirsuta (n:1). Histopathological analysis did not demonstrate any evidence of a neutrophilia. There were no delayed or secondary infections.

Discussion and conclusion

Unlike the posterior approach where contamination is common, the anterior video-assisted approach allows a biopsy without skin contact. This approach to the spine is the most effective way to eliminate the risk of contamination. Our results confirm the absence of any relationship between infection and disc degeneration. We suggest that the 6 positive samples in our study may be related to contamination. The absence of infection at 1-year followup is an additional argument in favour of our results. In conclusion, our study shows no association between infection and disc degeneration. The pathophysiology of disc degeneration is complex, but the current literature opens new perspectives.

     

Pedicle subtraction osteotomy in the thoracic spine and thoracolumbar junction: a retrospective series of 28 cases

Purpose

Pedicle subtraction osteotomy is a well-described surgical technique for treatment of kyphotic deformity in the spine. It is not widely used for treatment of thoracic kyphosis. We present the first documented series of 28 patients who underwent this procedure in 3 international centers. These patients presented with severe deformity with a wide range of aetiologies.

Indications

Kyphosis larger than 70 degrees, which is demonstrably rigid based on dynamic imaging.

Materials and methods

28 patients underwent surgery following pre-op neurological and radiographic assessment to fully assess the deformity. A triangular osteotomy was carried out using intraoperative navigation techniques. The patients were assessed post-operatively again with clinical and radiographic parameters at regular follow-up.

Results

The mean ODI score after surgery was 24.7 (16–42) while the pre-op was 53.4 (38–76). Mean thoracic kyphosis was improved from 64.2° (±20.1°) to 41.1° (±17.4°) resulting in a mean sagittal correction of 23.1°. Mean segmental correction at the PSO for all 28 cases was 17.8° (±8.1°). Stratified by region we found different values for the PSO correction: between T1 and T5 (6 cases) it was 17.5° (±5.4°) and between T6 and T9 (4 cases) 18.2° (±4.7°) and between T10 and L1 (18 cases) 26.2° (±5.2°). FBI index was 22.3° pre-op and improved to 7.8° post-op. Calculations were performed with Microsoft excel (2011 Microsoft, Redmond, WA).

Conclusions

Global sagittal balance was statistically improved in this series as demonstrated by FBI and C7 SVA correction.

     

Chemoembolization in hepatocellular carcinoma: multivariate analysis of survival prognostic factors after the first session

AIM: The aim of the study was to determine whether simple routine parameters evaluating the first session of transarterial chemoembolization (variation in alfa-fetoprotein concentration, tumor lipiodol uptake, and post-embolization syndrome) can predict survival of patients treated for hepatocellular carcinoma. METHODS: Seventy-two patients treated with transarterial chemoembolization and evaluated one month after the first sessions with CT scan were included. Transarterial chemoembolization session included hepatic arteriography, lipiodol and doxorubicin (50 mg) emulsion injection, followed by gelatin sponge embolization. The following variables were studied in univariate and multivariate analysis: 6 recorded at the first session (age, cirrhosis etiology, Child-Pugh class, tumor number, largest lesion size, and alpha-fetoprotein concentration), and 5 recorded after the first session (variation in alfa-fetoprotein concentration, tumor lipiodol uptake, post-embolization syndrome, mean interval between each session, and associated treatment). RESULTS: Mean follow-up was 22.7 months (4-106). Mean survival was 30.4 months (95% CI: 23. 3-37.5). Actuarial survival at 1, 2, 3 and 5 years was respectively 65.5%, 44%, 29.5%, and 18%. The only independent prognostic factors in multivariate analysis were the Child Pugh class and the mean interval between sessions (P<0.001 and<0.01 respectively). None of our criteria evaluating the first TACE session significantly influenced survival. CONCLUSION: The 3 parameters (variation in alpha-fetoprotein concentration, tumor lipiodol uptake and post-embolization syndrome) after the first transarterial chemoembolization did not predict survival. They could not be used to determine which patient could benefit from repeated transarterial chemoembolization sessions.     

Lack of evidence for reduced plasma apo B48 catabolism in patients with heterozygous familial hypercholesterolemia carrying the same null LDL receptor gene mutation

Increasing evidence suggests that remnants of chylomicrons and very low density lipoprotein (VLDL) also known as triglyceride-rich lipoproteins (TRL) are directly related to the pathogenesis of atherosclerosis. While studies in animals suggest that low density lipoprotein (LDL) receptor deficiency delays clearance of chylomicron remnants, human data supporting this hypothesis are conflicting. The objective of this study was to compare the fractional catabolic rate (FCR) and production rate (PR) of TRL apolipoprotein B48, the principal structural protein of intestinally derived chylomicron remnants, between familial hypercholesterolemic (FH) heterozygotes and non-FH controls. This was achieved by examining the kinetics of TRL apo B48 labelled with a stable isotope (L-(5,5,5-D3)leucine) in five normolipidemic males (age: 24.7 +/- 1.3 years; body mass index (BMI): 23.9 +/- 1.4 kg/m2) and six genetically defined FH heterozygous males (age: 29.7 +/- 9.9 years; (BMI): 22.0 +/- 4.3 kg/m2) carrying the same null LDL receptor gene mutation. All participants were apo E3 homozygotes. During the kinetic study, the subjects consumed 1/30 of their daily food intake every 30 min over a 15 h period. No significant difference was observed between FH heterozygotes and controls for FCR of TRL apo B48 (7.9 +/- 2.1 versus 7.9 +/- 2.6 pools per day, P = 0.99) while the TRL apo B48 pool size (10.5 +/- 5.4 versus 5.7 +/- 2.4 mg, P = 0.03) and PR (1.1 +/- 0.3 versus 0.6 +/- 0.3 mg kg(-1) per day, P = 0.02) were significantly higher among FH than in controls. In conclusion, this study shows no evidence for reduced plasma apo B48 catabolism in patients with heterozygous FH carrying the same null LDL receptor gene mutation and suggests that the plasma levels of intestinally derived TRL are elevated in FH due to an increased production rate.