Hiroshi Iioka

Difference of Molecular Response to Ischemia???Reperfusion of Rat Skeletal Muscle as a Function of Ischemic Time: Study of the Expression of p53, p21WAF-1, Bax Protein, and Apoptosis

The authors investigated the expression of p53, p21WAF-1, Bax protein, and apoptosis to elucidate the cellular response to ischemia–reperfusion of skeletal muscle using the rat lower limb model. The rat left lower limb was dissected in the inguinal region, isolating the bony femoral muscles, and the femoral vessels were clamped to produce an ischemic condition. After 3 or 6 hours, the clamps were removed and the gastrocnemius muscle was resected at various times up to 72 hours after reperfusion. Five specimens of the muscle were obtained at each time point from 5 rats. When any rat died during the study, additional rats were used until 5 specimens could be obtained from 5 rats at each time point. The expression of three proteins was detected by Western blot analysis. The apoptotic cells were detected using terminal deoxytransferase-mediated dUDP (deoxyuridine[-5′]diphosphate) nick-end labeling assay. Histopathological study showed severe interstitial edema and leukocyte infiltration at 6 hours of ischemia compared with 3 hours of ischemia. Moreover, at 6 hours of ischemia, muscle fiber fragmentation was observed at 72 hours after reperfusion whereas no fragmentation was found at 3 hours of ischemia. At 3 hours of ischemia, p53 and p21WAF-1 accumulated after reperfusion, and there was a time lag in the time of onset of elevation and the peak time point between these two proteins. The level of Bax protein did not elevate and the rate of apoptotic cells did not increase. At 6 hours of ischemia, p53 and p21WAF-1 also accumulated, but the kinetics of p21WAF-1 were similar to that of p53 in the time of onset of elevation and the peak time point after reperfusion. In addition, the level of Bax protein increased and apoptosis was induced. These results demonstrated that p53 and p21WAF-1 accumulated after 3 and 6 hours of ischemia of skeletal muscle during reperfusion. Moreover, it was demonstrated that the kinetics of induced p53, p21WAF-1, and Bax protein differ between 3 hours and 6 hours of ischemia, and it is speculated that this difference plays an important role in determining the consequence of the cell exposed to ischemia.

Mortality and Recurrence Rate After Pressure Ulcer Operation for Elderly Long-term Bedridden Patients

We operated on 16 sacral pressure ulcers in elderly and long-term residential patients who were immobile as a result of cerebral vascular disease. The mean age of patients was 76 years. Eight ulcers were treated with local fascial flaps and 8 by simple closure. The follow-up period was from 1 to 4 years. Recurrence and mortality rates were examined retrospectively. In the 16 patients, recurrence occurred in 37.5%, and 43.8% died without recurrence. The recurrence rate was 37.5% for local fascial flaps and 37.5% for simple closure. Overall mortality was 68.8% in the follow-up period. Because postoperative death was common, we should not only focus on reducing local pressure but also pay attention to any underlying disease. Because of this high mortality rate, the least invasive procedure possible should be used. Because the recurrence rate of simple closure was the same as for local fascial flaps, simple closure should be considered as a reconstructive method.

Hard-palate mucosal graft in the management of severe pincer-nail deformity.

It is well recognized that a hard-palate mucosal graft offers adequate support with less shrinkage than full-thickness skin grafts and minimum keratinization, even when grafted under dry conditions.1–3 In addition, its thickness and firmness are similar to those of the nail bed. We thought that these characteristics of hard-palate mucosa may be applicable to nail-bed defects, and chose to use the graft as a covering material for the repair of a nail-bed defect after resecting subungual exostosis.4 We found that compared with a free-skin graft, the hard-palate mucosal graft provided good coverage of the nail-bed defect. As in most clinics, we encounter various types of nail deformities on a daily basis, including pincer nail. A severe case of pincer nail reveals a tubelike deformity of the nail plate in which the overcurvature increases along the axis from in a proximal-to-distal direction.5 The nail bed and nail-bed tissue generally shrink, especially at distal sites, resulting in a very narrow nail bed.6 To correct the pincer-nail deformity, the narrow nail bed must be spread. However, in severe cases, the shrunken nail-bed tissue may not be large enough to cover the entire area of the spread nail bed, which results in a nail-bed defect. In this case, a material that offers less shrinkage, provides rigid support, and maintains a flattened and spread nail bed must be used to cover the defect. We describe the use of a hard-palate mucosal graft in the correction of severe pincer-nail deformity.

Usefulness and Limitations of Artificial Dermis Implantation for Posttraumatic Deformity

We have previously reported the use of artificial dermis implantation to cover exposed major vessels and to correct a depressed region after tissue resection and bone deformity with satisfactory results. In this paper, we present cases with depressed lesions and adhesive lesions after trauma, treated with artificial dermis implantation. Artificial dermis (Terudermis®, Terumo Co. Ltd., Tokyo, Japan) was implanted in 12 cases of posttraumatic deformity. Eight of the 12 cases involved a depressed lesion, and the other four involved adhesive lesions. There was no postoperative infection or allergic reaction in any of the patients. Improvement of the deformity was obtained in all cases, but the degree of volume reduction in traumatic cases is likely to be more severe than that in the non-traumatic cases previously reported. In conclusion, artificial dermis implantation is an easy, safe, and useful method to correct a posttraumatic deformity, such as a depression or an adhesion, although it is important to note that depressions require overcorrection in order to obtain satisfactory results, as compared with non-traumatic cases treated with artificial dermis.

Preshaped Hydroxyapatite Tricalcium-Phosphate Implant Using Three-Dimensional Computed Tomography in the Reconstruction of Bone Deformities of Craniomaxillofacial Region

We prepared solid life-sized models and templates of implants based on three-dimensional computed tomography data in six cases with a bone deformity of the craniomaxillofacial region. After simulation surgery using these models and templates, the preshaped hydroxyapatite-tricalcium phosphate (HAP-TCP) implants were prepared to fill in the facial bone defects, and implantation was performed. Consequently, implants fitted the individual bone defects, and satisfactory facial contouring was obtained in five cases. In one case with severe cutaneous scarring in the grafted site, it was necessary to reduce the volume of the preshaped HAP-TCP implant during surgery. In conclusion, the three-dimensional, solid, life-sized model and template are useful for preoperative detailed simulation, and the use of preshaped HAP-TCP implants based on the template probably contributes to successful reconstruction of complex facial bone deformities and to the reduction of surgical invasion, resulting in achievement of better results.

Histological evaluation of grafted hard palate mucosa in the reconstruction of the upper eyelid

We have used a hard palate mucosal graft for reconstruction of the posterior lamella of the eyelid and in only one case was replacement required because of discomfort and pain. The stratum corneum of the hard palate mucosa may have been the cause.

Development of a novel therapeutic approach using a retinoic acid-loaded microneedle patch for seborrheic keratosis treatment and safety study in humans

Seborrheic keratosis is one of the most common skin benign tumors in humans with a high occurrence rate of 80%-100% in people > 50 years of age; however, its pathogenesis is still unclear. The standard treatment includes cryotherapy and laser surgery for physically removing lesions. Drug therapy for this condition has not been well established. We aimed to evaluate the use of all-trans retinoic acid (ATRA)-loaded microneedle (MN) patches as a simple, alternative therapeutic option to traditional surgical treatments. This therapeutic strategy was designed to induce the proliferation of basal keratinocytes and accelerate stratum corneum turnover, leading to the lesion falling off the surface of the skin. The MN patch induced epidermal hyperplasia and marked expression of heparin-binding epidermal growth factor-like growth factor mRNA and protein corresponding to ATRA activity in the skin of HR-1 hairless mice. The acceleration of stratum corneum turnover was also observed by the dansyl chloride method. The skin irritation study in mice and safety study in humans support the safety findings of our study. Overall, MN patches can offer an effective and safe means of ATRA delivery into the skin, and the ATRA-loaded MN patch appears to be an effective pharmaceutical product providing a novel therapeutic option for seborrheic keratosis.

Clinical study of a retinoic acid-loaded microneedle patch for seborrheic keratosis or senile lentigo.

Aims: Pigmented lesions such as of seborrheic keratosis and senile lentigo, which are commonly seen on skin of people > 50 years of age, are considered unattractive and disfiguring because of their negative psychological impact. Drug therapy using all‐trans retinoic acid (ATRA) is an attractive option for self‐treatment at home. We have developed an ATRA‐loaded microneedle patch (ATRA‐MN) and confirmed the pharmacological effects of ATRA‐MN application in mice. Here, we describe a clinical study to evaluate the safety and efficacy of ATRA‐MN in subjects with seborrheic keratosis or senile lentigo. Main methods: ATRA‐MN was applied to the lesion site of each subject for 6 h once per week for 4 weeks. The skin irritation reaction was scored to assess adverse reactions and blood tests were performed to evaluate the presence of systemic adverse reactions. To assess the treatment effect using ATRA‐MN, the desquamation and whitening ability of the investigational skin was observed. Key findings: Desquamation of the stratum corneum was observed following four ATRA‐MN applications at 1‐week intervals, but ATRA‐MN applications did not induce severe local or systemic adverse effects. Significance: These results showed that ATRA‐MN treatment is promising as a safe and effective therapy for seborrheic keratosis and senile lentigo.

Chronic expanding hematoma in the temporal region.

A rare case of chronic expanding hematoma in the right temporal region that developed into a large mass over the course of 12 years is reported. The patient, who had a history of blunt trauma to her right temporal region at the age of 4 months, noticed a slowly growing mass at the same site over the last few months. Computed tomography revealed a well-circumscribed subcutaneous tumor. The tumor was completely resected. Histopathologically, the diagnosis of chronic expanding hematoma was confirmed.

Successful free osteocutaneous scapular flap transfer for mandibular reconstruction in a 93-year-old patient.

With the extension of the average life span and the development of surgical technique, anesthesia, and pre- and postoperative management, operations for elderly patients have become more widely accepted. In the field of plastic surgery, free-flap transfers using microvascular techniques have become a common surgical procedure in reconstruction of the head and neck region after surgical removal of a cancer. There have been several reports of free-flap transfer in patients older than 90 years, but the authors know of no reports of free osteocutaneous flap transfer for mandibular reconstruction, which is a very invasive free-flap surgery, for such patients. The mandible plays a significant role in various kinds of dynamic functions, such as mastication, deglutition, and articulation. Disorder of these functions causes a deterioration in the patients quality of life. The authors have performed a mandibular reconstruction using an osteocutaneous scapular free flap after resection of a gingival cancer invading the mandibular bone in a 93-year-old Japanese woman. In our case, an osteocutaneous scapular free flap, which permits the patient rapid rehabilitation of the lower leg, is thought to be a good choice because it allows the patient to get out of bed as quickly as possible in the postoperative period to minimize additional complications.