Surgical management of severe scoliosis with high risk pulmonary dysfunction in Duchenne muscular dystrophy: patient function, quality of life and satisfaction.

In a previous study, the authors reported the clinical and radiological results of Duchenne muscular dystrophy (DMD) scoliosis surgery in 14 patients with a low FVC of <30%. The purpose of this study was to determine if surgery improved function and QOL in these patients. Furthermore, the authors assessed the patients' and parents' satisfaction. %FVC increased in all patients after preoperative inspiratory muscle training. Scoliosis surgery in this group of patients presented no increased risk of major complications. All-screw constructions and fusion offered the ability to correct spinal deformity in the coronal and pelvic obliquity initially, intermediate and long-term. All patients were encouraged to continue inspiratory muscle training after surgery. The mean rate of %FVC decline after surgery was 3.6% per year. Most patients and parents believed scoliosis surgery improved their function, sitting balance and quality of life even though patients were at high risk for major complications. Their satisfaction was also high.

Importance of a psychiatric approach in cosmetic surgery.

BACKGROUND: Some studies have suggested that certain types of psychiatric problems may be more prevalent in patients undergoing cosmetic surgery than in the general population. OBJECTIVE: In this study, 140 patients undergoing cosmetic surgery took a screening test before surgery. The results were statistically analyzed to evaluate the importance of a psychiatric approach in cosmetic surgery. METHODS: At the first visit to the clinic, an interview was carried out in the presence of a psychiatrist. If needed, a secondary evaluation was performed on those patients with suspected psychological disorders. RESULTS: Preoperative screening led to the diagnosis of psychiatric disorders in 45 of 140 patients (32%). Final psychiatric diagnoses included neuroses such as body dysmorphic disorder and depression/depressive states. CONCLUSIONS: It is sometimes beneficial to prioritize psychiatric treatment instead of focusing solely on surgical treatment to achieve better outcomes in patients undergoing cosmetic surgery who have psychiatric disorders. Preoperative psychiatric screening should be routine in the practice of cosmetic surgery.

Synergistic effects of FGF-2 with insulin or IGF-I on the proliferation of human auricular chondrocytes.

Chondrocyte preparation with the safety and efficiency is the first step in cartilage regenerative medicine. To prepare a chondrocyte proliferation medium that does not contain fetal bovine serum (FBS) and that provides more than a 1000-fold increase in cell numbers within approximately 1 month, we attempted to use the medium containing 5% human serum (HS), but it exerted no more than twofold increase in 2 weeks. To compensate for the limited proliferation ability in HS, we investigated the combinational effects of 12 factors [i.e., fibroblast growth factor (FGF)-2, insulin-like growth factor (IGF)-I, insulin, bone morphogenetic protein-2, parathyroid hormone, growth hormone, dexamethasone, 1alpha25-dihydroxy vitamin D3, L-3,3',5'-triodothyronine, interleukine-1 receptor antagonist, 17beta-estradiol, and testosterone] on the proliferation of human auricular chondrocytes by analysis of variance in fractional factorial design. As a result, FGF-2, dexamethasone, insulin, and IGF-I possessed promotional effects on proliferation, while the combination of FGF-2 with insulin or IGF-I synergistically enhanced the proliferation. Actually, the chondrocytes increased 7.5-fold in number in 2 weeks in a medium containing 5% HS with 10 ng/ml FGF-2, while the cell number synergistically gained a 10-12-fold increase with 5 microg/ml insulin or 100 ng/ml IGF-I in the same period. The proliferation effects were more enhanced at a concentration of 100 ng/ml for FGF-2, and especially for the combination of 100 ng/ml FGF-2 and 5 microg/ml insulin (approximately 16-fold within 2 weeks). In the long-term culture with repeated passaging, this combination provided more than 10,000-fold within 8 weeks (i.e., passage 4). Thus, we concluded that such a combination of FGF-2 with insulin or IGF-I may be useful for promotion of auricular chondrocyte proliferation in a clinical application for cartilage regeneration.

Inhibition of hair follicle growth by a laminin-1 G-domain peptide, RKRLQVQLSIRT, in an organ culture of isolated vibrissa rudiment.

We established a serum-free organ culture system of isolated single vibrissa rudiments taken from embryonic day 13 mice. This system allowed us to test more than 30 laminin-derived cell adhesive peptides to determine their roles on the growth and differentiation of vibrissa hair follicles. We found that the RKRLQVQLSIRT sequence (designated AG-73), which mapped to the LG-4 module of the laminin-alpha1 chain carboxyl-terminal G domain, perturbed the growth of hair follicles in vitro. AG-73 is one of the cell-binding peptides identified from more than 600 systematically synthesized 12 amino acid peptides covering the whole amino acid sequence of the laminin-alpha1, -beta1, and -gamma1 chains, by cell adhesion assay. Other cell-adhesive laminin peptides and a control scrambled peptide, LQQRRSVLRTKI, however, failed to show any significant effects on the growth of hair follicles. The AG-73 peptide binds to syndecan-1, a transmembrane heparan-sulfate proteoglycan. Syndecan-1 was expressed in both the mesenchymal condensation and the epithelial hair peg of developing vibrissa, suggesting that AG-73 binding to the cell surface syndecan-1 perturbed the epithelial-mesenchymal interactions of developing vibrissa. The formation of hair bulbs was aberrant in the explants treated with AG-73. In addition, impaired basement membrane formation, an abnormal cytoplasmic bleb formation, and an unusual basal formation of actin bundles were noted in the AG-73-treated-hair matrix epithelium, indicating that AG-73 binding perturbs various steps of epithelial morphogenesis, including the basement membrane remodeling. We also found a region-specific loss of the laminin-alpha1 chain in the basement membrane at the distal region of the invading hair follicle epithelium, indicating that laminins play a part in hair morphogenesis.

Wound healing in denervated rat skin.

Recently, several reports have suggested that innervation influences wound healing. However, some investigators have reported that nerve injury prevented wound healing while others have suggested it had no influence on full-thickness skin wound healing. We created denervated skin areas on rats by dissection of the spinal hemicord. Subsequently, 15-mm-diameter skin defects were made symmetrically within the denervated area on the right side of the back and the normal innervated area on the left side. Biopsies were performed at 3, 7, and 14 days after wounding. We measured changes of the wound surface area, the rate of wound contraction, and the rate of epithelialization. The differences were not significant at 3 or 7 days after the operation. However, we could observe significantly delayed wound healing of the denervated skin areas compared to the normal areas at 14 days. Both wound contraction and epithelialization were delayed in the denervated groups. Our results suggest that sensory disturbance is a negative factor for skin wound healing.

Synergistic Effects of FGF-2 with Insulin or IGF-I on the Proliferation of Human Auricular Chondrocytes.

Chondrocyte preparation with the safety and efficiency is the first step in cartilage regenerative medicine. To prepare a chondrocyte proliferation medium that does not contain fetal bovine serum (FBS) and that provides more than a 1000-fold increase in cell numbers within approximately 1 month, we attempted to use the medium containing 5% human serum (HS), but it exerted no more than twofold increase in 2 weeks. To compensate for the limited proliferation ability in HS, we investigated the combinational effects of 12 factors [i.e., fibroblast growth factor(FGF)-2, insulin-like growth factor(IGF)-I, insulin, bone morphogenetic protein-2, parathyroid hormone, growth hormone, dexamethasone, 1α25-dihydroxy vitamin D3, L-3,3',5'-triodothyronine, interleukine-1 receptor antagonist, 17ß-estradiol, and testosterone] on the proliferation of human auricular chondrocytes by analysis of variance in fractional factorial design. As a result, FGF-2, dexamethasone, insulin, and IGF-I possessed promotional effects on proliferation, while the combination of FGF-2 with insulin or IGF-I synergistically enhanced the proliferation. Actually, the chondrocytes increased 7.5-fold in number in 2 weeks in a medium containing 5% HS with 10 ng/ml FGF-2, while the cell number synergistically gained a 10-12-fold increase with 5 µg/ml insulin or 100 ng/ml IGF-I in the same period. The proliferation effects were more enhanced at a concentration of 100 ng/ml for FGF-2, and especially for the combination of 100 ng/ml FGF-2 and 5 µg/ml insulin (approximately 16-fold within 2 weeks). In the long-term culture with repeated passaging, this combination provided more than 10,000-fold within 8 weeks (i.e., passage 4). Thus, we concluded that such a combination of FGF-2 with insulin or IGF-I may be useful for promotion of auricular chondrocyte proliferation in a clinical application for cartilage regeneration.

Experimental study on bone formation potential of cryopreserved human bone marrow mesenchymal cell/hydroxyapatite complex in the presence of recombinant human bone morphogenetic protein-2.

Secondary bone grafting in the alveolar cleft is one of the most important treatment modalities for patients with a cleft lip and palate. In children, however, harvesting a sufficient amount of bone graft from the donor site is difficult, and the procedure imposes a heavy burden on the patients. This problem may be resolved if autologous transplantation can be performed using a cell-hybrid type of artificial bone prepared with the patient's own bone marrow cells through a tissue engineering technique. In the current study, we examined the possibility of achieving such an autologous transplantation using cryopreserved human bone marrow cells. Human bone marrow cells were grown in culture and cryopreserved, and the cells preserved for 3 years and the cells preserved for 3 months were then thawed and recultivated. In one experiment, the recultivated cells were seeded onto a complex composed of porous hydroxyapatite and bone morphogenetic protein (BMP), and the complex was grafted subcutaneously in nude mice. In another experiment, the cells were seeded onto the porous hydroxyapatite and cultivated for 10 days before grafting in a medium supplemented with BMP. The bone formation potential of the cells was compared between these two experiments. Formation of mature bone was observed 2 weeks after transplantation in the former experiment, whereas only scarce bone formation was evident 4 weeks after transplantation in the latter experiment. It is therefore assumed that exposing the cultured human bone marrow cells to a high concentration of BMP in vivo strongly promotes bone formation.