Tsuneki Sugihara

Midface advancement by gradual distraction

Midface osteotomy was performed on 5 young adult sheep aged 10-12 months. In 4 animals midface advancement by gradual distraction was performed using an external device; one animal served as a control. The midface was advanced by 2 mm per day for 21 days. The amount of advancement was 36 mm in the nasofrontal area and 43 mm on the lateral aspect of the maxilla. After the period of active distraction the midface was maintained with external fixation for an additional 6 weeks to allow for ossification. Radiographs were obtained immediately postoperatively, after 21 days of distraction, and at the end of the 6 week fixation period. New bone formation in the distracted area was obvious radiographically, clinically and histologically. In conclusion, midface advancement by osteotomy and gradual distraction is possible in the sheep model and may offer controlled correction of deformity, obviating the need for the bone grafting.

Keloid-Derived Fibroblasts Are Refractory to Fas-Mediated Apoptosis and Neutralization of Autocrine Transforming Growth Factor-β1 Can Abrogate this Resistance

The pathogenesis of keloid remains poorly understood. As no effective therapy for keloid is as yet available, an insight into its pathogenesis may lead to novel approaches. Apoptosis has been found to mediate the decrease in cellularity during the transition between granulation tissue and scar. Here, we report that in contrast to hypertrophic scar-derived and normal skin-derived fibroblasts, keloid-derived fibroblasts are significantly resistant to both Fas-mediated and staurosporine-induced apoptosis. The caspases-3, -8, and -9 were not activated indicating that the block in the apoptotic pathway in keloid is upstream of the caspases. There were no significant differences in the level of expression of Fas, Bcl-2, and Bax between the three groups but addition of transforming growth factor (TGF)-beta1 significantly inhibited Fas-mediated apoptosis in hypertrophic scar-derived and normal skin-derived fibroblasts and neutralization of autocrine TGF-beta1 with anti-TGF-beta1 antibody abrogated the resistance of keloid-derived fibroblasts. Anti-apoptotic activity was not observed with TGF-beta2. This is the first study linking refractory Fas-mediated apoptosis to cellular phenotype in keloids and indicating a pivotal role for the anti-apoptotic effect of TGF-beta1 in this resistance. Hence, it becomes important to treat keloids as a separate entity different from hypertrophic scars and enhancement of Fas-sensitivity could be a promising therapeutic target.

Preferential Impairment of Nitric Oxide–Mediated Endothelium-Dependent Relaxation in Human Cervical Arteries After Irradiation

BACKGROUND Vascular abnormalities are a major cause of postoperative complications in irradiated tissues. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxation may be involved. We examined the endothelium-dependent relaxation and morphology of the endothelium in irradiated human cervical arteries. METHODS AND RESULTS Irradiated arteries were taken from the neck region of patients who had radiation therapy. Arteries from patients who did not receive radiation therapy were used as controls. Endothelium-dependent relaxation to acetylcholine and A23187 was impaired in irradiated arteries. Norepinephrine-induced contraction and sodium nitroprusside-induced relaxation were unchanged. In control arteries, N(omega)-nitro-L-arginine and indomethacin each caused a partial inhibition of endothelium-dependent relaxation. In irradiated arteries, the impaired endothelium-dependent relaxation was unaffected by these agents, but it was abolished by high K(+). Acetylcholine produced similar degrees of hyperpolarization in control and irradiated arteries. Immunohistochemical examination for endothelial nitric oxide synthase indicated no expression in the endothelium of irradiated arteries. Electron scanning microscopy showed morphologically intact endothelial cells in irradiated arteries. CONCLUSIONS In irradiated human cervical arteries, the nitric oxide- and prostacyclin-mediated endothelium-dependent relaxation, but not endothelium-derived hyperpolarizing factor-mediated relaxation, are specifically impaired, without significant morphological damage of the endothelium. The impaired nitric oxide-mediated relaxation was associated with a lack of endothelial nitric oxide synthase expression. Our results suggest the importance of impaired endothelial function in irradiated human blood vessels, which may partly explain the development of vascular stenosis and poor surgical wound healing in irradiated tissues.

long-term Outcome of Pressure Sores Treated with Flap Coverage

&NA; This article provides our experience with 45 ischial sores and 24 sacral sores in 53 paraplegic patients between 1990 and 1995. Data were evaluated as to the sites of sores and types of the transferred flaps. Types of the transferred flaps were categorized into the fasciocutaneous flap and the myocutaneous or muscle Hap. In the treatment of 45 ischial sores, 18 were reconstructed with the fasciocutaneous flaps and 27 with the myocutaneous or muscle flaps. In the treatment of 24 sacral sores, 23 were reconstructed with the fasciocutaneous flaps and 1 with the myocutaneous flap. The recurrence rate was analyzed by percent pressure sore free survival (%PSFS) by the Kaplan‐Meier method. Overall, the ischial sores provided a higher recurrence rate than sacral sores; however, there was no significant difference in the %PSFS between the sites of sores. The group of the sores reconstructed with the fasciocutaneous flap demonstrated significant or marginally significant better results in the %PSFS (total of ischial and sacral, p = 0.0155; ischial, p = 0.0555) compared with the group of the sores reconstructed with the myocutaneous or muscle flap. These findings indicated that the use of the fasciocutaneous flap is expected to provide a better longterm result in surgical reconstruction of pressure sores than the myocutaneous or muscle flap. (Plast. Reconstr. Surg. 100: 1212, 1997.)

Functional and morphological damage of endothelium in rabbit ear artery following irradiation with cobalt60

The relaxant actions of acetylcholine and A23187 were examined in the rabbit central ear artery at different intervals following exposure to different doses of radiation with a cobalt60 unit. The artery was irradiated with a dose of 10 Gy, 20 Gy and 45 Gy. Radiation caused dose‐ and time‐dependent impairment of the endothelium‐dependent relaxations. The impaired endothelium‐dependent relaxations occurred as early as 1 week postirradiation and persisted throughout the experimental period (10 weeks). The endothelium‐independent response to sodium nitroprusside was well preserved up to 6 weeks after irradiation. The contractile response to noradrenaline was unaltered by irradiation throughout the experimental period, but in contrast to control vessels, an increase in the sensitivity to noradrenaline in the presence of the nitric oxide synthase (NOS) inhibitor NG‐nitro‐L‐arginine was not observed in the irradiated vessels. The impaired endothelium‐dependent relaxations in the irradiated vessels were not improved by pretreatment with the NOS substrate L‐arginine, the cyclo‐oxygenase inhibitor indomethacin or the free radical scavengers superoxide dismutase and catalase. Scanning electron microscopy indicated morphologically intact endothelial cells within the first 4 weeks after irradiation. Western blot analysis showed a significant decrease in the expression of endothelial NOS (eNOS) in the irradiated vessels. These data indicate that endothelial cell function is specifically impaired in the irradiated vessels before morphological endothelial cell damage can be detected. This impairment may be related to diminished eNOS expression.

Functional reconstruction of the tongue and deglutition muscles following extensive resection of tongue cancer

&NA; The authors describe their experience with functional restoration of tongue and deglutition muscles at the floor of the mouth after an extensive resection of tongue cancer. Five patients underwent immediate tongue reconstruction using a reinnervated rectus abdominis myocutaneous free flap in which the included tenth intercostal nerve was coapted to the remaining hypoglossal nerve. The rectus sheath strips attached on both cut ends of the muscle were used to create the firm tendinous insertions between the mandible and hyoid bone based on the anatomic findings of the extrinsic tongue and suprahyoid muscles. The postoperative course was uneventful in all patients. All patients presented with good tongue bulk without obvious atrophy. Three patients with subtotal glossectomy demonstrated good cooperative mobility of the reconstructed and remaining tongue and had solid or semisolid/soft diet. However, two patients with total glossectomy did not show satisfactory rehabilitation of the reconstructed tongue. Postoperative electromyographic assessment in two patients showed good functional recovery of the grafted muscle. The cine‐magnetic resonance imaging deglutition study in one patient with 80‐percent tongue resection demonstrated sufficient elevation of the dorsal base of the reconstructed tongue, contraction of the reconstructed deglutition muscles, complete glossopalatal closure, and elevation of the hyoid bone and larynx during the deglutition. This reconstructive technique is strongly recommended for the patients who have undergone subtotal glossectomy to provide physiological functional recovery of the reconstructed tongue synchronizing with the remaining tongue. (Plast. Reconstr. Surg. 102: 993, 1998.)

Altered expressions of HOX genes in human cutaneous malignant melanoma

HOX genes act as master genes to control morphogenesis. In human, HOX genes form 4 clusters composing 9 to 11 HOX genes (39 genes in total) on different chromosomes. We hypothesized that aberrant expression of HOX genes was associated with development and subsequent progression of melanoma and that the 39 HOX gene expression pattern determined the sites where melanoma grew. The expression levels of 39 HOX genes in 15 human cutaneous melanoma specimens and 7 nevus pigmentosus specimens were quantified by a comprehensive analysis system based on the real‐time RT‐PCR method. We found that the expression levels of HOXA11, A13, B9, D12 and D13 in melanoma were higher than those in nevus pigmentosus and that the expression levels of HOXA11, B2 and C13 were significantly different between pT4 melanoma and pT1 to pT3 melanoma. It was most notable that the expression levels of HOXA1, A2, C4 and B13 in melanoma with distant metastasis were higher than those in melanoma without it. On the other hand, we found no relationship between HOX genes expression patterns and the growing sites of melanoma. These results indicated that the misexpressions of some specific HOX genes were implicated in melanoma genesis and metastasis but had no linkage with melanoma sites.

SURGICAL MANAGEMENT OF MAXILLECTOMY DEFECTS BASED ON THE CONCEPT OF BUTTRESS RECONSTRUCTION

Few published large series have described a surgical approach to maxillary skeletal reconstruction on the basis of the extent of maxillectomy.

Superiority of the fasciocutaneous flap in reconstruction of sacral pressure sores.

The gluteal maximus muscle has been used in the treatment of sacral pressure sores since the 1970s. However, it is noted that the muscle portion of the transferred flap shows highly atrophic degeneration and the muscle itself is not suitable tissue for covering the pressure-bearing area. We have managed various fasciocutaneous flaps as the first choice for reconstruction of sacral pressure sores and obtained good results. The fasciocutaneous flap has an anatomical structure that resists physical stimulation or external pressure and an abundant blood supply via its fascial plexus. In addition, if we use a gluteal maximus myocutaneous flap at first, some fasciocutaneous flaps are compromised because of the design and blood supply. We suggest that the fasciocutaneous flap has the first priority and is superior to the gluteal maximus myocutaneous and muscle flaps in reconstruction of sacral pressure sores.

The extensibility in human skin: variation according to age and site.

Normal skin extensibility in the living body of 94 healthy male subjects ranging in age from 3 months to 73 years was determined quantitatively with the Bio-Skin Tension Meter at 12 sites. In comparison with the age of 20-29 years, the skin extensibility, particularly in the age group of less than 2 years, was significantly high. However, no significant difference from the age groups of 12-14, 15-19, 30-49 and over 50 years was found at any site. Correlation by age was noted at the extremities, excluding the posterior upper arm and at the lower abdomen, with the extensibility of the group less than 1 year as the maximum value, decreasing gradually down to 3-5 or 6-8 years. At the cheek, shoulder, anterior chest, and posterior upper arm, however, no correlation with age was noted.