Keloid-derived fibroblasts are refractory to Fas-mediated apoptosis and neutralization of autocrine transforming growth factor-beta1 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.

Technique for selective microangiography of skin flaps with high contrast and fine detail.

The technical factors of microangiography were studied, and the authors found that the main limiting factors in resolution were the injection pressure of the contrast medium and the thickness of the materials. A gentle manual hand pressure injection, with the aid of visual monitoring under the operating microscope, were keys to obtaining beautiful microangiograms.

Inner ear abnormalities in Kabuki make-up syndrome: report of three cases.

Three patients, a female and two males, 28, 15, and 14 years of age, with Kabuki make-up syndrome (KMS) were studied for middle and inner ear abnormalities by using CT scanning of the petrous bones. All three patients had bilateral dysplasia of the inner ear, i.e., hypodysplasia of the cochlea, vestibule, and semicircular canals (so-called Mondini dysplasia), whereas their middle ears had no abnormalities. Audiometry demonstrated a sharp decrease in hearing of the high tone range, bilateral in one and unilateral in another, while the third patient was noncooperative. In view of these findings, it would be advisable to study each individual with KMS and hearing impairment for possible inner ear abnormalities.

Gluteus maximus adipomuscular turnover or sliding flap in the surgical treatment of extensive sacral chordomas.

Two cases with extensive posterior peritoneal defects after high sacral amputation for sacral chordoma are presented. An adipomuscular flap as a modification of the conventional gluteus maximus muscle flap was designed to obliterate an extensive residual posterior peritoneal dead space. The deep adipose tissue beneath the superficial fascia left on the gluteus maximus muscle was effectively used to provide more volume to the flap. The adipomuscular flap was turned over into the posterior peritoneal defect in the first case, and the flap was slid into the cavity in the other case. The adipomuscular flap eventually enabled the successful reconstruction of the posterior peritoneal defect, and the volume of the flap was well maintained behind the rectum, according to the postoperative magnetic resonance imaging findings in both cases.

Functional alveolar ridge reconstruction with prefabricated iliac crest free flap and osseointegrated implants after hemimaxillectomy.

We achieved functional alveolar ridge reconstruction after hemimaxillectomy using a prefabricated iliac crest flap. The iliac crest was vascularized secondarily by a long rectus abdominis muscle flap with its inferior epigastric vessels intact to obtain an ideal anatomic location between the maxillary defect and microvascular anastomosis site. The iliac crest was tightly resurfaced with a split-thickness skin graft as well. After a bony surgical delay, the prefabricated iliac crest flap was microsurgically transferred to the face. Three osseointegrated implants were placed in the prefabricated iliac crest, and a dental prosthesis was worn with immobilization and stability. Our procedure enabled recovery of a satisfactory facial appearance and excellent masticatory function.

Clinical application of expanded free flaps based on primary or secondary vascularization.

Prefabricated free flaps using an expansion technique were used for four reconstructive cases, including two leg reconstructions and two facial reconstructions. In this series, the prefabricated free flaps created by using the expander were classified into two types: the expanded flap based on the conventional vascular pedicle, which is called the expanded flap with primary vascularization; and the expanded flap based on the vascular pedicle in the carrier, which is called the expanded flap with secondary vascularization. The expanded flap with primary vascularization that is created in the trunk has a good indication for leg reconstruction, because it provides an wide and thin flap with minimal donor site morbidity. The expanded flap with secondary vascularization created in the pectoral region has a good indication for facial reconstruction, because it provides good color and texture matches. Although there are some disadvantages in the tissue expansion technique, the prefabricated free flaps using the expander are very effective in facial and leg reconstruction.

A fiberscopic analysis of velopharyngeal movement before and after primary palatoplasty in cleft palate infants.

There have been few studies done on the abnormal function of velopharyngeal muscles in unrepaired cleft palate infants. To examine and assess velopharyngeal movement before primary palatoplasty offers supposedly any valuable information for the successful operation and the restoration of excellent velopharyngeal function. We designed to investigate and analyze velopharyngeal movement before and after primary palatoplasty in 26 cleft palate infants with a fine nasopharyngeal fiberscope. We found three different patterns of velopharyngeal movement in unrepaired cleft palate infants when crying or strangulation reflex occurred: (1) posterior movement type (10 cases, 38.5 percent), where the soft palates moved only posteriorly and cephalically and did not move medially; (2) medial movement type (10 cases, 38.5 percent), where the soft palates moved only medially and did not move posteriorly or cephalically; and (3) posteromedial movement type (6 cases, 23.0 percent), where the soft palates moved both posteriorly and cephalically as well as medially. Postoperative velopharyngeal closure was classified into three patterns: (1) the soft palate type, in which the soft palate mainly operates; (2) the lateral wall type, in which compensational medial movement of the lateral pharyngeal wall is mainly observed; and (3) the mixed type, in which both the soft palate and the lateral pharyngeal wall operate. Also, we demonstrated a close relationship between velopharyngeal movement before and after primary palatoplasty in cleft palate infants. In total, 10 of 16 cleft palate infants with the posterior movement type or posteromedial movement type, in which posterior movement of the soft palates was observed before primary palatoplasty, postoperatively showed the soft palate type of velopharyngeal closure. On the other hand, only 2 of 10 cleft palate infants with the medial movement type, in which the soft palates did not move posteriorly but medially before primary palatoplasty, postoperatively showed the soft palate type of velopharyngeal closure. The Fisher's exact probability test clarified that cleft palate infants with the posterior movement type or posteromedial movement type were more likely to show postoperatively the soft palate type of the velopharyngeal closure compared with those with the medial movement type (p = 0.051). This is the first trial to examine velopharyngeal movement in unrepaired cleft palate infants. Our findings indicate the probability that velopharyngeal closure mechanism in repaired cleft palate infants is able to be predicted by velopharyngeal movement behavior before primary palatoplasty. Next, we must clarify a correlation between preoperative velopharyngeal movement and postoperative velopharyngeal function and speech outcome.

Cheek reconstruction with an expanded prefabricated musculocutaneous free flap: case report.

We present a case of reconstruction of the left cheek with a prefabricated musculocutaneous flap. A pedicled serratus anterior muscle flap was transferred to the left chest, deep to skin. The muscle flap and overlying skin were expanded. The expanded, prefabricated musculocutaneous flap was then transferred as a free flap to the left cheek defect.

Penetration of flomoxef into human maxillary and mandibular bones.

Penetration of flomoxef into the maxillary and mandibular bones was assayed clinically to provide data about its usefulness for the prevention of postoperative infection after maxillofacial surgery. Twenty-one patients undergoing maxillofacial surgery at our department were given flomoxef 2 g dissolved in 20 ml of physiological saline intravenously over 3 minutes during operation, and the serum, maxillary and mandibular concentrations were measured 1, 3, and 6 hours after injection by the band culture method using Escherichia coli 7437 as the indicator strain. The mean concentrations were 53.4, 16.1, and 2.6 micrograms/ml, respectively, in the serum, 17.6, 7.8, and 1.0 micrograms/g in maxillary bone, and 16.4, 4.2, and 0.9 micrograms/g in mandibular bone. The mean bone:serum ratios at 1, 3, and 6 hours were 33.0%, 48.2%, and 36.8%, respectively, for maxillary bone, and 30.7%, 26.2%, and 35.7% for mandibular bone. When compared with previously reported data on the bone:serum ratios in jaw of various other intravenous antibiotics, our results show that penetration of flomoxef into maxillary and mandibular bone is extremely high. As all the intramaxillary and intramandibular concentrations exceed its MIC80 values against clinical isolates of bacteria frequently isolated in cases of infection in the oral and maxillofacial region, it is apparent that one intravenous shot of flomoxef 2 g allows penetration of the drug into the maxillary and mandibular bones at effective concentrations. Flomoxef is therefore potentially useful for the prevention and treatment of infections in the oral and maxillofacial region, as it has excellent penetration into the maxillary and mandibular bones.

Cleft lip mongolian spot: mongolian spot associated with cleft lip.

BACKGROUND: Mongolian spots in the cleft area of cleft lip have been found in some Japanese children. OBJECTIVE: Our purpose was to study the frequency of cleft lip mongolian spot in children with cleft lip of various severity. METHODS: Sixty-six babies with unilateral cleft lip were divided into three groups: namely, those with microform cleft lip (10 subjects), incomplete cleft lip (30 subjects), and complete cleft lip (26 subjects). The incidence of cleft lip mongolian spot in the three groups was studied. RESULTS: Thirty-six babies (55%) had a cleft lip mongolian spot. The mongolian spot was observed in no patients with microform cleft lip, in 18 patients (60%) with incomplete cleft lip, and in 18 patients (69%) with complete cleft lip. CONCLUSION: Cleft lip mongolian spot appears in high incidence when the cleft goes beyond the vermilion border.

Primary correction of the unilateral cleft lip nose.

The details of surgical techniques for primary correction of the unilateral cleft lip nose and their results for 45 cases are reported. The technique employed an infracartilaginous incision on the affected side, thus allowing direct suturing of the alar cartilage onto the lateral cartilage. For the post-operative evaluation, the nasal form in both frontal and bottom views was scored for five items. In overall evaluation, the grades of "Good," "Fair," and "Poor" were derived from the total scores of five items. In the postoperative results (range of follow-up: 24 months to 84 months), 24 cases were rated "Good" (53.3%), 13 cases "Fair" (28.9%), and 8 cases "Poor" (17.8%). Thirty cases appear not to need secondary correction (66.6%). The technique is useful because the alar cartilages and lateral cartilages can be accurately sutured, and relatively stable results can be obtained.

Umbilical endometriosis.

A 41-year-old woman with umbilical endometriosis is presented. The umbilical lesion is repeatedly painful and there is a bloody discharge simultaneous with the menstrual period. Treatment of umbilical endometriosis is by excision. Hormonal therapy results in its incomplete regression. Umbilical endometriosis is a very rare disease, but should be considered in the differential diagnosis of umbilical tumors.

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.

[Experimental teratological studies on facial anomalies induced in mice by bis (dichloroacetyl) diamine. I. Establishment of an animal model of the median cleft face syndrome by the administration of bis (dichloroacetyl) diamine to mice].

Bis (dichloroacetyl) diamine (abbreviated as bisdiamine hereafter) was administered by oral intubation to pregnant Jcl: ICR and A/J mice at a dosage of 3,200 mg/kg/day at days 7.5 and 8.5, 8.5 and 9.5, 9.5 and 10.5 or 10.5 and 11.5 of gestation (VP = day 0). Fetuses were recovered at day 17.5 of gestation following maternal sacrifice. The numbers of resorptions, live fetuses and malformed fetuses were counted in the two strains of mice and the induced craniofacial anomalies were examined macroscopically and histopathologically. In both strains, median facial cleft, cleft palate, exencephalocele and open eyelids were commonly induced craniofacial anomalies. Bisdiamine-induced median facial cleft ranging in severity from minor midfacial disorganization to completely divided nose with a median cleft lip in Jcl: ICR and A/J was strikingly similar to a spectrum of midline defects of the median cleft face syndrome in humans. Histopathological examinations of severe median facial cleft in the two strains revealed that the bifurcated nasal septal cartilage showed irregular hypoplasia and that it was partly disorganized into several nodules of various shapes and sizes. These results indicate that bisdiamine treatment in mice provides a useful animal model of the median cleft face syndrome. Furthermore, higher frequency of median facial cleft and lower mortality in bisdiamine-treated Jcl: ICR indicate that bisdiamine treatment in Jcl: ICR is more effective than that in A/J to make an animal model of this syndrome.

[Experimental teratological studies on facial anomalies induced in mice by bis(dichloroacetyl)diamine. II. Pathogenesis of bis(dichloroacetyl)diamine-induced median cleft face syndrome in mice].

The present study was performed to clarify the pathogenesis of bis(dichloroacetyl)diamine (abbreviated as bisdiamine hereafter)-induced median cleft face syndrome in mice. Bisdiamine was administered by oral intubation to pregnant Jcl: ICR mice at a dosage of 3,200 mg/kg/day at days 7.5 and 8.5 of gestation (VP = day 0). Embryos were recovered at 4, 12, 24, 48, 72 and 96 hr after bisdiamine treatment at day 8.5 of gestation and morphological differences between the bisdiamine-treated and control embryos at the specific time intervals were quantitatively examined by the light and scanning electron microscopy. First, bisdiamine caused extensive death of cranial, mainly prosencephalic and mesencephalic, neural crest cells and neuroepithelial cells. Second, the former damage resulted in reduced numbers of mesenchymal cells in the frontonasal prominences and the latter resulted in dorsolateral deviation of the nasal placodes. Consequently, the medial nasal prominences were abnormally widely spaced and then, the median cleft face syndrome was induced. In addition, the findings suggesting that bisdiamine might cause aberrant movement of neural crest cells and/or mesenchymal cells were observed.

Plasticity and rigidity of differentiation of brain vesicles studied in quail-chick chimeras.

Transplantation of a piece of the alar plate of the prosencephalon or of the rhombencephalon of quail embryos into the roof of the mesencephalon of chick embryos was carried out at 7-10 somite stage. Results obtained were: the transplanted alar plate of the prosencephalon differentiated into tissue closely resembling the tectum when the transplants were integrated into the host mesencephalon; in all the cases, the alar plate of the rhombencephalon did not differentiate into tectum-like structure, but into rhombencephalic descendants. We conclude that the alar plate of the prosencephalon at 7-10 stage is not definitively determined and may retain an ability to differentiate into the optic tectum, whereas the prospective fate of the rhombencephalon has already been determined at 7-10 stage.

Changes in the subepithelial mesenchymal cell process meshwork in developing facial prominences in mouse embryos.

We examined temporal and spatial changes in the subepithelial mesenchymal cell process meshwork (CPM) in normally developing medial (MNP) and lateral nasal prominences (LNP) in mouse embryos by light and scanning electron microscopy. Marked changes were found only in the MNP during the fusion of the MNP and LNP. The CPM density in the prospective fusion area of the MNP gradually increased as the epithelial surfaces approached each other, attained its maximum just before contact, and decreased after contact. The CPM density in the prospective fusion area of the LNP changed only slightly even when the epithelial surfaces approached each other. The increase in CPM density paralleled that in the density of mesenchymal cell bodies. The LNP grew more actively toward the line of fusion than did the MNP during the progressive fusion of the two prominences. A larger number of fusion-associated epithelial morphological changes--the appearance of superficial protruding cells and cell degeneration--occurred in the MNP than in the LNP. These findings suggest that the increased CPM density is closely related to the growth of the facial prominences and the fusion-associated epithelial morphology and that the CPM plays an important role in the epithelial-mesenchymal interaction during the formation of the upper lip and primary palate.