Effects of hip brace on coxa valga in nonambulatory children with cerebral palsy: A randomized controlled trial.

BACKGROUND: Coxa valga, measured as the neck-shaft angle (NSA) or head-shaft angle (HSA), is regarded as a potential risk factor for hip dislocation in patients with cerebral palsy. We investigated the effects of a novel hip brace on coxa valga. METHODS: A prospective, multicenter, assessor-blinded, randomized controlled trial was conducted from July 2019 to November 2021. Children with cerebral palsy aged 1 to 10 years with Gross Motor Function Classification System levels IV and V were recruited. The study group wore a hip brace for at least 12 hour a day. A lower strap of the hip brace was designed to prevent coxa valga biomechanically. The effectiveness of the hip brace on coxa valga was assessed by measurement of the NSA and head-shaft angle at enrollment and 6 and 12 months after enrollment. RESULTS: Sixty-six participants were enrolled, and 33 patients were assigned to each group. Changes in the mean NSA of both sides and the NSA of left side showed significant differences between the 2 groups over 12 months (mean NSA of both sides, -1.12 ± 3.64 in the study group and 1.43 ± 3.75 in the control group, P = .023; NSA of the left side, -1.72 ± 5.38 in the study group and 2.01 ± 5.22 in the control group, P = .008). CONCLUSIONS: The hip brace was effective in preventing the progression of coxa valga and hip displacement, suggesting that the prevention of coxa valga using hip brace is a contributing factor in prevention of hip displacement.

Autologous cardiomyotissue implantation promotes myocardial regeneration, decreases infarct size, and improves left ventricular function.

BACKGROUND: Cell therapy for myocardial infarction (MI) may be limited by poor cell survival and lack of transdifferentiation. We report a novel technique of implanting whole autologous myocardial tissue from preserved myocardial regions into infarcted regions. METHODS AND RESULTS: Fourteen rats were used to optimize cardiomyotissue size with peritoneal wall implantation (300 µm identified as optimal size). Thirty-nine pigs were used to investigate cardiomyotissue implantation in MI induced by left anterior descending balloon occlusion (10 animals died; male-to-female transplantation for tracking with in situ hybridization for Y chromosome, n=4 [2 donors and 2 MI animals]; acute MI implantation cohort at 1 hour, n=13; and healed MI implantation at 2 weeks, n=12). Assessment included echocardiography, magnetic resonance imaging, hemodynamics, triphenyltetrazolium chloride staining, and histological and molecular analyses. Tracking studies demonstrated viable implants with donor cells interspersed in the adjacent myocardium with gap junctions and desmosomes. In the acute MI cohort, treated animals compared with controls had improved perfusion by magnetic resonance imaging (1.2±0.01 versus 0.86±0.05; P<0.01), decreased MI size (magnetic resonance imaging: left ventricle, 2.2±0.5% versus 5.4±1.5%, P=0.04; triphenyltetrazolium chloride: anterior wall, 10.3±4.6% versus 28.9±5.8%, P<0.03), and improved contractility (dP/dt, 1235±215 versus 817±817; P<0.05). In the healed MI cohort, treated animals had less decline in ejection fraction between 2 and 4 week assessment (-3±4% versus -13±-4%; P<0.05), less decline in ±dP/dt, and smaller MI (triphenyltetrazolium chloride, 21±11% versus 3±8%; P=0.006) than control animals. Infarcts in the treated animals contained more mdr-1(+) cells and fewer c-kit(+) cells with a trend for decreased expression of matrix metalloproteinase-2 and increased expression of tissue inhibitor of metalloproteinase-2. CONCLUSION: Autologous cardiomyotissue implanted in an MI area remains viable, exhibits electromechanical coupling, decreases infarct size, and improves left ventricular function.

Transendocardial and transepicardial intramyocardial fibroblast growth factor-2 administration: myocardial and tissue distribution.

Effective local delivery to the heart remains an obstacle to successful therapeutic application of a number of drugs and biological agents. This study was designed to study and optimize the delivery characteristics of transendocardial intramyocardial (IM) administration, determine myocardial deposition and retention over time, and compare it to transepicardial IM injection. Thirty-nine pigs were used for the study (15 for catheter optimization, 15 for transendocardial IM delivery, and 9 for transepicardial IM delivery). (125)I-Fibroblast growth factor-2 (FGF2) (25 microCi) was used as the prototype molecule. Tissue and myocardial distribution was determined at 1 and 24 h and 7 days. Using 1-h (125)I-FGF2 myocardial deposition as a parameter for delivery efficiency, the optimal needle length and delivery volume for transendocardial based delivery were determined to be 6 mm and 0.1 ml, respectively. Using these parameters for endocardial delivery, (125)I-FGF2 cardiac activity was 18.01 +/- 3.84% of delivered activity at 1 h, 11.65 +/- 5.17% at 24 h, and 2.32 +/- 0.87% at 7 days in ischemic animals. Studies in nonischemic animals produced similar results. For transepicardial delivery, (125)I-FGF2 cardiac-specific activity was 23.14 +/- 12.67% for the 6-mm needle, declining to 12.32 +/- 8.50% at 24 h, and did not significantly differ from values obtained following transendocardial delivery. Thus, optimized transendocardial intramyocardial delivery using Biosense guidance results in efficient delivery of FGF2 to the target myocardium that is comparable with transepicardial delivery, both providing markedly higher myocardial deposition and retention and lower systemic recirculation of FGF2 than intracoronary, intrapericardial, or intravenous delivery. However, myocardial distribution is limited to injection sites.

Proteome analysis of human liver tumor tissue by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-mass spectrometry for identification of disease-related proteins.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide and is a leading cause of death. To contribute to the development and improvement of molecular markers for diagnostics and prognostics and of therapeutic targets for the disease, we have largely expanded the currently available human liver tissue maps and studied the differential expression of proteins in normal and cancer tissues. Reference two-dimensional electrophoresis (2-DE) maps of human liver tumor tissue include labeled 2-DE images for total homogenate and soluble fraction separated on pH 3-10 gels, and also images for soluble fraction separated on pH 4-7 and pH 6-9 gels for a more detailed map. Proteins were separated in the first dimension by isoelectric focusing on immobilized pH gradient (IPG) strips, and by 7.5-17.5% gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels in the second dimension. Protein identification was done by peptide mass fingerprinting with delayed extraction-matrix assisted laser desorption/ionization-time of flight-mass spectrometry (DE-MALDI-TOF-MS). In total, 212 protein spots (117 spots in pH 4-7 map and 95 spots in pH 6-9) corresponding to 127 different polypeptide chains were identified. In the next step, we analyzed the differential protein expression of liver tumor samples, to find out candidates for liver cancer-associated proteins. Matched pairs of tissues from 11 liver cancer patients were analyzed for their 2-DE profiles. Protein expression was comparatively analyzed by use of image analysis software. Proteins whose expression levels were different by more than three-fold in at least 30% (four) of the patients were further analyzed. Numbers of protein spots overexpressed or underexpressed in tumor tissues as compared with nontumorous regions were 9 and 28, respectively. Among these 37 spots, 1 overexpressed and 15 underexpressed spots, corresponding to 11 proteins, were identified. The physiological significance of the differential expressions is discussed.