Search

Treatment must be conducted after proper assessment of diabetic foot wounds. This implies appropriate foot care and the use of proper footwear from the perspectives of prophylaxis and walking. Diabetic foot wounds have some wound impairment factors, including peripheral neuropathy (PN), peripheral arterial disease (PAD), and infection; such wounds comprise combinations of these lesions. An additional goal besides wound healing is gait salvage. Here, we propose a simple new four-level classification of diabetic foot ulcerations, which we have termed the Kobe classification, in order to assess the wounds more easily and treat them systematically; the classification is as follows: Type I, mainly PN; Type II, mainly PAD; Type III, mainly infection; Type IV, PN+PAD+infection.

Objective: We investigated the role of the angiosome concept in endovascular therapy (EVT) for limb salvage., Background: The angiosome concept is clinically useful in bypass surgery for critical limbs ischemia (CLI). However, comparison with direct and indirect flow to the site of ulceration based on angiosome concept regarding freedom from amputation has not been systematically studied for the patient with CLI undergoing EVT., Methods: We analyzed 203 limbs in 177 consecutive patients (male = 127, age = 70 +/- 11 years) with ischemic ulceration that was Rutherford 5 or 6 (5 in 145 limbs and 6 in 58 limbs; pretreatment ankle-brachial index = 0.74 +/- 0.27), who underwent EVT alone without bypass surgery. We classified these patients into direct and indirect groups depending on whether feeding artery flow to the site of ulceration was successfully acquired or not acquired based on the angiosome concept. Freedom from amputation was compared between the direct and the indirect groups by Kaplan-Meier analysis., Results: The overall limb salvage rate was 82% (167/203). Skin perfusion pressure was significantly higher in the direct group (67 +/- 25 mm Hg) than in the indirect group (41 +/- 20 mm Hg, P = 0.002). The limb salvage rate was also significantly (P = 0.03) higher in the direct group (86%) than in the indirect group (69%) for up to 4 years after the procedure. The number of vessels with run-off flow did not influence the limb salvage rate in either the direct group (P = 0.84) or the indirect group (P = 0.90)., Conclusion: Acquiring direct flow based on the angiosome concept is important for limb salvage by EVT in patients with CLI., (Copyright 2010 Wiley-Liss, Inc.)

Harvesting the radial forearm flap may cause circulatory problems in the donor arm. To investigate the influence on donor hands after radial forearm flap harvesting, we assessed the process of circulatory changes prospectively by measuring skin perfusion pressure (SPP) that is clinically useful in detecting vascular lesions. The records of 17 patients (14 men and 3 women aged 59.7+/-11.8 years) who had undergone free radial forearm flap transfer for head and neck reconstruction, between December 2005 and April 2007, were analysed. SPP in the thumb (finger I), the middle finger (III) and the little finger (V) was measured in the 17 patients preoperatively and 1 month and 3, 6, 9 and 12 months postoperatively. All statistical tests were two sided, with a significance level defined as p<0.05. Preoperatively, baseline SPP was more dominant in finger I than in finger V. Postoperatively, SPP changed significantly in both fingers, while it showed no change in finger III and tended to be higher in finger I than in the other two. Harvesting the free radial forearm flap reduces skin perfusion in the fingers of the donor arm and, we assume, leads to a re-distribution of blood flow to the fingers, with the residual ulnar artery still supplying more blood flow to finger I than to finger V. This suggests the presence of an autoregulating mechanism whereby blood perfusion to the fingers is controlled by the physiological demands of individual fingers., ((c) 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Dermatofibrosarcoma protuberans (DFSP) of the scalp is a rare soft tissue sarcoma. A 22-year-old male with DFSP, who had undergone several surgical excisions and radiotherapy, presented with a mild left lower-limb paresis. An MRI scan demonstrated a huge mass extending throughout the frontoparietal convexity. A macroscopically complete removal of the mass was performed. Despite this, there were several recurrences; thereafter, the patient underwent surgery, stereotactic radiosurgery and chemotherapy. The histological findings demonstrated a DFSP that both abutted and occasionally invaded the adjacent brain cortex, while extending along the Virchow-Robin spaces. Due to the highly infiltrating characteristics of DFSP, another approach, such as the use of molecular-targeted agents, will be required to significantly improve the clinical outcome.

Purpose: The purpose of this study was to clarify the "healing capacity" of wounds of the oral mucosa in comparison to those of the skin, and to evaluate the wound healing mechanism of oral mucosa using a cytobiological approach from the aspect of energy metabolism in oral keratinocytes., Materials and Methods: Samples of epidermal and oral keratinocytes collected at surgery and of cultured oral keratinocytes were used to analyze (1) by gas chromatography the composition of fatty acids (16:0, 18:2, 20:4) in the cell membranes of keratinocytes, (2) by immunohistochemical staining of GLUT-1 antibody and specific PAS staining the localization of glucose metabolism, and (3) by RT-PCR and Western blotting the expression of GLUT-1 mRNA and of protein in the keratinocytes of the basal and parabasal layers of each epithelial tissue., Results: 1. The % composition of palmitic acid (16:0) was significantly higher in buccal mucosal keratinocytes (27.18+/-3.74%) and in the gingiva (23.00+/-1.40%) than in the epidermis (17.54+/-0.37%). 2. Immunohistochemical staining showed GLUT-1 protein in the skin to be expressed only in the bulge region of hair follicles and in the epidermal basal layer, and observed nearly throughout all epithelial cell layers in the oral mucosa. 3. PAS-positive cells were observed among differentiation-enhanced cells in the upper prickle layer in the oral mucosa. 4. The same results were obtained from RT-PCR and a Western blotting analysis., Conclusion: The present study demonstrated definite cytobiological evidence that the oral mucosa surpasses the skin in regard to its wound healing capacity.

Purpose: Various autografts and synthetic materials such as titanium plates have been used for orbital floor reconstruction; however, no consensus on reconstruction methods has been reached. We have used iliac cancellous bone for this reconstruction with good results., Patients and Methods: Patients (n = 101) enrolled in this study underwent orbital floor reconstruction of pure blowout fracture with an approximate 1 mm thinned and trimmed iliac cancellous bone without fixation of the graft. The results were assessed by CT; diplopia exceeding an angle of 45 degrees was evaluated as a poor outcome., Results: Postoperatively, diplopia appeared in 15 patients and disappeared in 86 patients. At 6-month follow-up, CT showed that the morphology of the orbit was well maintained and no shedding or improper positioning of the grafted bone was observed in any of the patients. Moreover, CT images demonstrated ossification of the transplanted bone graft., Conclusions: The method encompassing the use of the medulla of the iliac bone has several merits: 1) the graft bone is sufficiently pliable and flexible to fit the gently curving orbital floor; 2) being soft, it is easy to cut. Furthermore, no complication attributable to its fragility is observed at short- and long-term follow-up. The 1 mm thin medullar bone graft derives its robustness from its beamed structure. We consider the medulla of the iliac bone fitting autosomal material for the reconstruction of the orbital floor.

Antiphopholipid syndrome (APS) is a major cause of ischemic stroke in young adults. In our study, stroke patients with antiphospholipid antibodies (APL) were significantly younger and were more likely to be women than stroke patients without APL. Valvular heart disease, neurological complications, and hematological disorders were more frequent in the APL-positive group. The mean value of thrombin-antithrombin III complex was significantly lower in the APL-positive group. beta2-Glyoprotein I (beta2-GPI) is the antigen primarily responsible for APL. At the DNA level, 4 different types of allelic polymorphisms have been detected in beta2-GPI. The allele at position 247 has codes for either valine (V) or leucine (L), which results in genotypic expression of VV, VL, or LL. In our study, the V and VL genotypes were more frequent in patients with cerebral infarction than in normal controls. The VL genotype was more frequent among patients aged less than 60 years than in those aged more than 60 years. The mean values of beta-thromboglobulin and platelet factor 4 in patients with the VL genotype were significantly higher than those with the LL genotype. The results suggested that V247 beta2-GPI allele is one of the genetic risk factors for the development of cerebral infarction through platelet activation.

The pathophysiology of chronic wounds differ from that of acute wounds, and the etiology has various, for example decubitus, diabetes, insufficient venous circulation, radiation, et al. Now, for diabetic foot ulcers with/without PAD, internist (diabetologist, interventionalist), radiologist, vascular surgeon, orthopedic surgeon, dermatologist, plastic surgeon tackle this difficult problem respectively. But it is far from total medical care as a team medicine. In this mini-review, I want to introduce our project for diabetic foot ulcers and gangrene with /without PAD, presenting our cases. I shall be happy if I can be of any help to any neurogenic foot problems in Hansen's disease.

Various causes of cerebrovascular complications exist in patients with malignant tumor. The pathogenesis of thrombosis in malignancy is complex and it has not been completely clarified as yet. A hypercoagulable state in these patients occurs through several interactive processes between the cancer cells and the patient. Tumor cells can directly and indirectly enhance activation of coagulation cascade. Trousseau's syndrome is a paraneoplastic neurologic syndrome which is caused by remote effects of cancers. Tumor cells produce cytokines which promote coagulation and suppress anticoagulant activities, thereby causing stroke in cancer patients. Brain tends to be a target organ of stroke in the conditions of disseminated intravascular coagulopathy (DIC) in cancer patients. Nonbacterial thrombotic endocarditis (NBTE) is characterized by the presence of relatively acellular aggregates of fibrin and platelets attached to normal heart valves. NBTE can be found in DIC. Paradoxical embolism due to patent foramen ovale in patients with deep vein thrombosis is also one of the cause of cerebral infarction. Stroke can occur under various setting of cancer chemotherapy. Tamoxifen increases the risk of stroke in patients with breast cancer. In paticular, it has been reported that the combination of chemotherapy and tamoxifen for breast cancer patients frequently produces thrombotic episodes. Patients with head and neck cancer treated with local radiotherapy have a high risk of developing significant carotid stenosis, and an increased risk of stroke. Malignancy as a risk factor for stroke is becoming increasingly recognized by physicians caring for these patients. The probability of stroke occurring in an individual patient depends on several factors such as intrinsic medical problems, the type of cancer, the clinical stage, performance status, and the treatment modalities employed. Understanding these factors is important for stroke prevention and provision in this population.

Background: In treating patients with anophthalmic orbits, it is essential to achieve a long-lasting natural appearance and comfortable retention of eye prostheses. In 1992, the authors developed a therapeutic strategy based on a simple algorithm for treating the three common symptoms of acquired anophthalmic orbit: severe eye socket contracture is surgically treated with a radial forearm free flap transfer, upper lid depression is treated with lipoinjection, and lower lid retraction is treated with an auricular cartilage graft., Methods: From 1992 to 2004, 18 acquired anophthalmic orbits (11 enucleated and seven exenterated) were treated at Kobe University Hospital based on the authors' therapeutic strategy. Aesthetic outcomes were evaluated according to patient and surgeon satisfaction., Results: Sixteen patients underwent auricular cartilage grafts, eight received radial forearm free flap transfers, and seven were treated with lipoinjection. Optional revisional surgery was carried out in four cases. The aesthetic outcome was assessed as good in six patients, moderate in eight patients, and poor in four patients; the last four had undergone total maxillectomy with orbital exenteration or had eyelid defects because of previous cancer surgery., Conclusions: The authors' therapeutic strategy for acquired anophthalmic orbit is simple and, with slight modification, fitting for most cases, although it necessitates innovative surgery in cases with orbital rim and/or eyelid defects.

There have been few reports about the characteristics of the pigmentary arrangement of congenital melanocytic nevi (CMN) and nevus spilus (NS). Though the lines of Blaschko, which don't correspond to other lines such as Langer's lines and skin dermatomes, are well known to be followed by some rare pigmentary disorders, the relationship between these two disorders and the lines of Blaschko has not been discussed. Therefore, through an examination of 200 cases, we investigated whether or not the arrangement of CMN and NS follow the lines of Blaschko. Thirty-nine out of 92 cases (42.4%) of CMN and 67 out of 108 cases (62.0%) of NS were considered to follow the lines of Blaschko. Today, the idea is widely accepted that two functionally different cells proliferate during early embryogenesis of the skin which is caused from mosaicism and, as a result, the lines of Blaschko appear visually. In our results, we found that there were some cases of CMN and NS which showed a relationship with the lines of Blaschko, which is meaningful considering that the lesions and the lines are both related to pigmentary gene anomalies. The result was compared with CMN and NS by the chi(2) test. NS showed a predominant tendency to follow the lines with a significant difference (P = 0.0055). This may indicate that the lines of Blaschko reflect more clearly the proliferation of the epidermal cells than other cells in growth of the skin of the embryo. Further studies are required to elucidate the reason why some cases follow these lines and others do not.

We fabricated ex vivo produced oral mucosa equivalent (EVPOME) from patients' oral mucosal keratinocytes without using animal-derived serum or feeder layer cells. To confirm the clinical benefits of 1) early initiation of epithelialization, 2) a short period until complete healing and 3) negligible scar contracture, the mechanism of wound healing after EVPOME transplantation for oral mucosal defects was analyzed histopathologically. Transplantation was performed on 15 patients (eight men and seven women; aged between 51 and 76 years, mean, 66.6 years). Two patients had squamous cell carcinoma of the tongue, nine had leukoplakia (four in the tongue only, two in the gingiva only, one in the buccal mucosa, and two in two or more areas), and four had hypoplasia in the alveolar ridge. The mean interval between punch-biopsy for the fabrication of EVPOME and its transplantation for the reconstruction of oral mucosal defects was 28.5 days, by which time EVPOME with a mean size of 6.5 cm(2) and a cell count of 8.6 x 10 5-plex th; could be obtained. The underlying disease, past history, and smoking history of the patients did not constitute negative factors for EVPOME fabrication. About 10 days after transplantation, EVPOME began uniting with the surrounding epithelium. The mean duration required for the wound to be completely covered (28.2 days) was much shorter than after transplantation of only an acellular allogenic dermal matrix (AlloDerm), and showed only slight scar formation, similar to that observed after artificial dermis (Terdermis) transplantation. Presence of laminin-1, 5 and type IV collagen in the basement membrane of EVPOME was confirmed, and the arrangement and positioning of keratinocytes were preserved during the degradation of perlecan and anchoring fibrils (type VII collagen) for remodeling, i.e., the period of the most active remodeling of EVPOME transplantation. Only a few fibroblasts were observed in the lamina propria during this period, suggesting that keratinocyte-derived cytokines, rather than fibroblast-derived cytokines, play an important role in the early stages of mucosal wound healing after EVPOME transplantation. The efficacy of EVPOME is associated with closely related to the presence of the keratinocyte-derived system and the usefulness of AlloDerm that sustains keratinocytes.

Background: In patients with perianal extramammary Paget's disease, wide local excision is recommended. In the reconstruction of the resulting large defects not only the closure of the defect but also the preservation of anogenital function need to be considered., Methods: We used bilateral V-Y advancement posterior thigh fasciocutaneous flaps for reconstructing three large anogenital defects, including the total anal canal, resulting from wide local excisions attributed to extramammary Paget's disease. A temporary anus was constructed at the same time to allow the wound of the reconstructed anus to heal. After the surgery, the course of bowel function was followed up through interviews and manometric examinations., Results: All defects were successfully reconstructed with the flaps, and bowel function recovered satisfactorily. Manometric examinations were carried out in two cases; anal pressures were recorded regularly and used as parameters of the recovery of bowel function before closing the artificial anus. Eventually, the patients recovered the function of defecation., Conclusions: We recommend the bilateral V-Y advancement posterior thigh fasciocutaneous flaps together with manometric studies as one of the most effective techniques for managing large anogenital defects. The use of sensate flaps, the restoration of original structures and manometric studies are conducive to successful outcomes.

Background: Reconstruction of eye globe-sparing total maxillectomy defects is one of the major challenges to reconstructive surgeons. In 1994, the authors developed an uncomplicated and easy reconstructive method, where a titanium mesh is applied for the support of orbital contents, a radial forearm free flap for covering the mesh and the cheek lining, and an obturator prosthesis for palatal and dental rehabilitation., Methods: Five patients who underwent primary reconstruction with the authors' method after globe-sparing maxillectomy with loss of the orbital floor from 1994 to 1999 and who were followed up for more than 5 years were retrospectively reviewed for (1) the presence of diplopia, (2) the shape of the reconstructed orbital floor assessed by coronal section magnetic resonance imaging, and (3) the presence of infection/exposure of the titanium mesh., Results: Only one of the five patients developed slight diplopia. Coronal magnetic resonance imaging showed that the orbital floor restored with titanium mesh had in all cases maintained a proper shape and position for more than 5 years. No infection or exposure of the titanium mesh had developed in any of the cases, despite exposure to irradiation of not less than 30 Gy. All the patients had well-retentive obturator prostheses., Conclusion: This long-term follow-up study demonstrated that the authors' method attained a long-lasting successful outcome functionally and is the method of choice for reconstruction after globe-sparing total maxillectomy.

The modulatory effects of ultraviolet B (UVB) irradiation on cutaneous inflammatory responses are well known but their mechanism remains obscure. It has been proposed that regulated upon activation normal T-cell expressed and secreted protein (RANTES), which is one of the chemokines produced by epidermal keratinocytes, might play an important role in the pathogenesis of cutaneous inflammatory disorders, such as atopic dermatitis and psoriasis vulgaris. This study was designed to determine whether UVB irradiation could affect the production of RANTES that is induced in cultured normal human epidermal keratinocytes upon stimulation by inflammatory cytokines. We measured levels of the transcript of the gene for RANTES in cultured keratinocytes and of RANTES itself in culture supernatants by semiquantitative reverse transcription and the polymerase chain reaction and by an enzyme-linked immunosorbant assay (ELISA), respectively. Neither the transcript nor RANTES itself was detected without prior stimulation of cells by tumor necrosis factor alpha (TNF-alpha) and/or interferon gamma (IFN-gamma) and production of RANTES was not induced by UVB (100 J/m2) irradiation alone. Cells were irradiated with UVB just before addition of TNF-alpha and IFN-gamma to the medium and then cells and culture supernatants were harvested 12, 24, and 36 h later. In both irradiated and non-irradiated cells, RANTES mRNA was first detected at 12 h and the level increased subsequently. RANTES itself was detected at 24 h, with a higher level at 36 h. At all time points examined, UVB irradiation inhibited the production of RANTES mRNA and of the protein itself. These results suggest that suppression of the production of RANTES by epidermal keratinocytes might be involved in the modulatory effects of UVB irradiation on cutaneous inflammation.

In order to more clarify the delayed wound healing in diabetes mellitus, we cultured the human epidermal keratinocytes in both 6 mM (control group) and 12 mM glucose (high-glucose group) of "complete" MCDB 153 medium. Hyperglycaemia slowed the rate of their proliferation and inhibited their DNA synthesis and the production of total proteins. By 1 month after primary seeding in high-glucose group, the cells ceased their proliferation, whereas the cells in control group grew for more than 40 days. Mean population doublings in high-glucose group was 5.27 (vs. 7.25 in control, P = 0.001), and mean population doubling time during 1 month in high glucose group was 5.43 days (vs. 3.65 days in control, P = 0.02). They indicate that prolonged exposure to high glucose decreases the replicative life span of human epidermal keratinocytes in vitro. Furthermore, analysis of fatty acid contents in membrane phospholipids with thin-layer and gas chromatography showed no difference between the cultured keratinocytes in both conditions. Immunocytochemical staining of glucose transporter 1 shows that 28.1% of cells in high-glucose group were almost twice positive of those in control group (13.2%, P = 0.008). The mechanism of the ill effects of high glucose on epidermal keratinocytes is not so far clear, but it indicates the possibility of any direct effect of hyperglycaemia on glucose metabolism without changing lipid metabolism on cell membrane. The high-glucose group presented in this report can be available as an in vitro valuable study model of skin epidermal condition on diabetes mellitus.

Ceramide is an integral part of the extracellular lipid bilayer of the stratum corneum (SC) that forms the permeability barrier of the skin. The production of SC ceramides is catalyzed by sphingomyelinase (SMase) and glucocerebrosidase (GCase). Acid-ceramidase (acid-CDase) catalyzes the hydrolysis of ceramide in the SC. We examined the effects of T helper (Th)1 and Th2 cytokines on levels of transcripts of genes for acid-CDase, acid-SMase, and GCase, on levels of ceramide, and on the extent of transepidermal water loss (TEWL) in the human epidermis in an effort to determine whether these cytokines affect the permeability barrier functions. Levels of transcripts for acid-SMase and GCase and the amount of ceramide in human epidermal sheets were enhanced by tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma and these effects were inhibited in the presence of interleukin (IL)-4. In epidermal keratinocytes cultured under submerged conditions, however, no similar inhibitory effects of IL-4 were observed. Consistent with these results, TEWL was suppressed by TNF-alpha and IFN-gamma, and these effects were also inhibited by IL-4. The balance between Th1 and Th2 might affect the construction and/or the repair of the epidermal permeability barrier via regulation of the production of ceramide.

The restoration of velopharyngeal function after extensive soft palate resection to treat malignant oropharyngeal tumors is a major challenge to reconstructive surgeons. The authors had previously reconstructed soft palatal defects routinely with the folded forearm flap. A patient who had more than half of the soft palate excised experienced postoperative velopharyngeal dysfunction. To restore efficient velopharyngeal function, pharyngoplasty was additively applied where the folded ridge of the forearm flap was sutured to the posterior pharyngeal wall in an inverse manner of the pharyngeal flap technique. The essence of the procedure was positive narrowing of the nasopharyngeal space. Five patients who underwent this pharyngoplasty and another five who did not were evaluated for postoperative functions of speech intelligibility and of nasal regurgitation during oral feeding. The velopharyngeal movements of all patients were examined under a nasopharyngeal endoscope. The evaluations demonstrated that this surgical procedure afforded satisfactory results. This positive narrowing pharyngoplasty technique is simple, easy, and minimally invasive to the remaining healthy tissue, and it is the method of choice for the reconstruction of the soft palate after malignant tumor resection.

Background: Antiphospholipid syndrome is important as a cause of ischemic stroke, although clinical characteristics of the syndrome are not well documented., Methods: We analyzed differences in clinical characteristics between 40 antiphospholipid-antibody (aPL)-positive and 40 aPL-negative stroke patients., Results: Stroke patients with aPL were significantly younger and were more likely to be women in comparison with stroke patients without aPL. Valvular heart disease, neurological complications and hematological disorders were more frequent in the aPL-positive group. The mean value of thrombin-antithrombin III complex was significantly lower in the aPL-positive group. Cerebral infarctions in the carotid system were less and large-artery lesions more frequent in the aPL-positive patients., Conclusions: Stroke patients with aPL have clinical characteristics distinct from stroke patients without aPL., (Copyright 2005 S. Karger AG, Basel.)

We report the case of a 76 year-old male with multiple subcutaneous nodules, but without joint symptoms or deformities, who was diagnosed histopathologically with rheumatoid nodulosis after resection of the nodules. Rheumatoid nodulosis is a disease characterized by multiple subcutaneous nodules that are histopathologically similar to rheumatoid nodules, a high titer of rheumatoid factor, and radiologically detectable cystic bone lesions, but with none or few of the systemic manifestations orjoint activity of rheumatoid arthritis (RA). It is considered to be a benign variant of RA. This rare disease must be considered when a case of multiple subcutaneous nodules is encountered, even in aged males withoutjoint symptoms or deformities.

Oral-facial-digital syndrome type 1 (OFD1) is an X-linked dominant disease characterized by malformations of the face, oral cavity, and digits. Thus far, 18 small mutations in the OFD1 gene have been reported. Here, we describe, in one Japanese sporadic female OFD1 case, the presence of a novel pair of deletion mutations: a 4,094-bp deletion encompassing exon 7 to intron 9, and a 14-bp deletion in intron 9, both of which are present in her paternal X-chromosome. The first deletion, the largest known to affect OFD1, was revealed by identifying four novel transcripts that all lacked exons 7-9. The most likely cause of the double deletion is two unequal recombinations between homologous sequences. Identification of the 4,094-bp deletion was made possible only by analyzing OFD1 mRNA, underscoring the utility of mRNA analysis in the mutational analysis of OFD1.

New circulation in the free flap reestablished at the recipient site is the key to successful microvascular reconstructive surgery. This study is the first evaluation of long-term circulatory changes in nine free radial forearm flap transfers. Postoperatively, color Doppler studies revealed that the flow volume through the arterial pedicle increased rapidly during the first 3 days, gradually increased until day 14 (exceeding flow volume through the facial artery of the unoperated contralateral side), then decreased slightly until the sixth month. The pulsatility index, representing vascular resistance downstream, decreased successively. Ohm's law explains that this flow increase is caused by reduced vascular resistance downstream, attributed to changes in the vascularity of the transferred flap and in the recipient bed. The authors believe the circulatory changes are determinants of the clinical properties of the flap. This study addresses the importance of clarifying the events that transpire at the macroscopic circulatory level in the transferred free flap.

Whether or not multiple venous anastomoses reduce the risk of free-flap failure is a subject of controversy. We report here, for the first time, on the importance of selecting 2 separate venous systems of the flap for dual anastomoses. The efficacy of multiple anastomoses was verified through a retrospective review of 310 cases of the free radial forearm flap transfer. Dual anastomoses of separate venous systems (the superficial and the deep) showed a lower incidence of venous insufficiency than single anastomosis did (0.7% versus 7.5%; P < 0.05). On the other hand, dual anastomoses of a sole venous system showed no significant difference in the incidence of venous insufficiency compared with single anastomosis (11.5% versus 7.5%; P = 0.48). Our results suggest that dual venous anastomoses of separate venous systems is conducive to reduced risk of flap failure and affords protection against venous catastrophe through a self-compensating mechanism that obviates thrombosis of either anastomosis.

We report a case of Churg-Strauss syndrome (CSS) with necrosis of the fingers and toes and liver infarction. A 59-year-old man with asthma suddenly noticed that his fingers and toes felt unusually cold. This condition worsened progressively, and some digits became necrotic within several weeks. Laboratory studies revealed hypereosinophilia and an extremely elevated serum level of IgE. Digital subtraction angiography of the extremities revealed extensive irregular narrowing of small and medium-sized arteries in the extremities. Abdominal computed tomography (CT) revealed an area of low density at the periphery of the right lobe of the liver. Angiography revealed irregular narrowing of small arteries that corresponded to the ischemic area. A nerve conduction study suggested sensory nerve neuropathy. The preceding asthma, acute onset of digital necrosis, liver infarction, neuropathy, and hypereosinophilia strongly suggested a diagnosis of CSS. The patient was treated with 40 mg of prednisolone and 120 micro g of intravenous prostaglandin E1 daily, and all the digits that had turned black and necrotic were amputated. After the amputation, the dose of prednisolone was gradually reduced, and no new lesions appeared on the skin or in the liver. The rare possible complications of CSS, including necrosis of digits and liver infarction, should not be ignored.

We describe a very rare case of midface fracture where the zygomatic bone had been completely avulsed. The fragment was preserved in a frozen state for 40 days, then replanted and the graft was taken. The conditions favourable for the taking of the freeze-preserved zygomatic graft were: (1) an appropriate preservation method, (2) conservation of the periosteum on the zygomatic bone, (3) diversity of the haemodynamics of the zygomatic membranous bone, (4) immobilization of the zygoma by rigid fixation, and (5) a rich blood supply at the recipient site.

The risk for free flap thrombosis is greatly influenced by blood flow. Postoperative hemodynamic changes in vascular pedicles of the microvascular skin flap have not been reported, however. This study focuses on the intraoperative and postoperative changes in the flow volume in the vascular pedicles of the free forearm flap examined by color Doppler ultrasonography. The arterial flow volume increased continuously until day 7, compared with which, the volume after flap elevation was 36%. On day 1, it reached only 52%. In the venous pedicle, the flow volume through the cutaneous vein was only 37% compared with that through the radial vena comitans after flap elevation, whereas the volume through both veins was equal on day 7. Drastic changes in the flow explain the possible vascular occlusion during the early postoperative period in the free forearm flap transfer.

The aim of this study was to determine the optimal stage of development at which transplant human ex vivo-produced oral mucosa equivalents (EVPOMEs) in vivo. EVPOMEs were generated in a serum-free culture system, without the use of an irradiated xenogeneic feeder layer, by seeding human oral keratinocytes onto a human cadaveric dermal equivalent, AlloDerm. EVPOMEs were cultured for 4 days submerged and then for 7 or 14 days at an air-liquid interface to initiate stratification before transplantation into SCID mice. AlloDerm, without epithelium, was used as a control. Mice were killed on days 3, 10, and 21 posttransplantation. Epithelium of the transplanted EVPOMEs was evaluated with the differentiation marker keratin 10/13. Dermal microvessel ingrowth was determined by immunohistochemistry with a mouse vascular marker, lectin binding from Triticum vulgaris. The presence and stratification of the epithelium were correlated with revascularization of the underlying dermis. The microvessel density of AlloDerm without epithelium was less than that of EVPOMEs with an epithelial layer. Microvessel density of the dermis varied directly with the degree of epithelial stratification of the EVPOMEs. The EVPOMEs cultured at an air-liquid interface for 7 days had the optimal balance of neoangiogenesis and epithelial differentiation necessary for in vivo grafting.

The free radial forearm flap has two drainage veins, the cutaneous and the deep, but no established consensus has been reached on the selection of the drainage pedicle. In our study, the flow volumes of the veins were examined by colour Doppler ultrasonography after 20 forearm flaps had been raised. The volume through the deep vein was significantly higher than that through the cutaneous vein (p < 0.01). In comparing the total flow (both veins open), the flow rate through the deep vein alone (cutaneous vein occluded) was over 80% in 13 cases, 60%-80% in seven, and under 60% in none; that through the cutaneous vein alone (deep vein occluded) was 60%-80% in eight, 40%-60% in eight, under 40% in four, and over 80% in none. Our results show the importance of the deep vein, as indicated by its high drainage capacity from the early stages of flap transfer.

The anterior rectus sheath, efficacious in reconstructive surgery, is used in oromandibular reconstruction with the free rectus abdominis musculocutaneous flap. This study describes reconstruction with this sheath in 20 patients: to preserve only the swallowing function in 10 patients (formation of the bulge of the reconstructed oral floor and prevention of its sinking); to preserve both swallowing and articulation in 5 patients (formation of the bulge of the reconstructed tongue and prevention of its sinking, concurrent with a money-pouch-like reconstruction of the tongue, laryngeal suspension, and neuroanastomosis); and to prevent exposure of the reconstruction plate, replacing the resected mandibular continuity in 5 patients. The purpose of reconstruction was achieved in all patients. The vascularized free rectus abdominis musculocutaneous flap with a firm anterior rectus sheath may be the first choice for these types of reconstruction., (Copyright 2003 Wiley-Liss, Inc.)

To investigate whether the striatal dopamine receptor function is involved in the development of vascular parkinsonism (VP), a positron emission tomography (PET) study was conducted on 9 patients with VP by using [11C] N-methylspiperone as the tracer. The rate of binding availability in the striatal dopamine D2 receptor (k3) was determined semiquantitatively, and the values were compared to the predicted normal values based on the results from 7 normal volunteers. Of 9 patients with VP, the normalized D2 receptor binding [%k3] was more than 90% in 5 patients, 89 to 87% in 3, and 75% in one. These values showed no evident correlation with the Hoehn and Yahr stage. The laterality of the striatal %k3 did not correspond to that of the parkinsonism. Thus, the striatal dopamine D2 receptor binding was not severely impaired and did not correlate with the neurological status in patients with VP. This may indicate that striatal dopamine D2 receptor function is not primarily associated with the development of the parkinsonism in VP.

We reported a 74-year-old male case of progressive supranuclear palsy (PSP) who responded to tandospirone citrate, a serotonin receptor (5-HT1A) agonist. The patient manifested postural instability and gait disturbance at 71 years. Additionally, he showed vertical gaze paresis, regidity of the neck, extremities and trunk, bradykinesia and mild cognitive impairment. A brain MRI revealed moderate atrophy of bilateral frontal/temporal lobes and of midbrain tegmentum one year after the onset. The patient had been diagnosed as PSP and treated with L-DOPA. However, L-DOPA therapy showed only transient response for a few months. His symptoms deteriorated gradually, and he became unable to sit, stand up or walk by himself. Tandospirone citrate was additionally administered at 30 mg/day. Rigidity and bradykinesia were remarkably improved in two weeks after the start of tandospirone treatment. He became able to stand up and walk a short distance with supports in four weeks. Cognitive disturbance was also slightly improved. Tandospirone citrate was effective on our case of PSP, especially on rigidity. Our findings suggest that combination of levodopa and tandospirone citrate is a useful therapy for PSP.

The interaction between melanocytes and keratinocytes in epidermal tissue suggest a bidirectional interchange between these two cell types. Although keratinocytes appear to affect melanocyte function, there are no reported effects of melanocytes on keratinocytes. Using cell strains, we examined the effect of melanocytes on keratinocyte proliferation. Two conditioned medium techniques were used: one was a co-culture system, where both cell types, grown on separate surfaces shared a common volume of medium. The second was simply feeding keratinocytes melanocyte-conditioned medium. Mixed cultures (both cell types together in a monolayer) where also studied. Our results showed that melanocyte-conditioned medium and melanocytes in co-culture significantly stimulated keratinocyte proliferation as measured by bromodeoxyuridine incorporation assay. However, growth of both cell types together in culture did not affect the growth rate of either cell type. Our results showed that cultured human melanocytes produce one or more soluble factors that stimulate the growth of cultured keratinocytes.

Background: Cerebral vasospasm is a poor resulting outcome of a ruptured cerebral aneurysm; to clarify the mechanism of vasospasm it is important to improve this outcome. C-type natriuretic peptide (CNP) is present in the brain as a cerebral vasodilator; it is also an endothelium-derived relaxing factor produced via cGMP. We speculated that CNP might be an inhibitor of cerebral vasospasm after subarachnoid hemorrhage (SAH)., Methods: To clarify the role of CNP in cerebral vasospasm after SAH, we conducted 1 week monitoring of CNP concentrations in the plasma and cerebrospinal fluid (CSF) of 26 patients who had undergone clipping within 24 hours of the occurrence of SAH, and divided them into group A (positive for angiographic spasm) and group B (negative for angiographic spasm). We also examined CNP concentrations in the CSF of patients who were receiving spinal anesthesia for small orthopedic operations, as reference patients., Results: The CNP concentration in the CSF on day 1 was higher than in the reference patients and decreased in both test groups, but we did not observe any significant difference between the groups. CNP concentrations in the plasma did not change in either group., Conclusions: CNP concentrations in the CSF were high in the acute phase after SAH, whereas plasma CNP concentrations remained constant. However, our findings did not support our hypothesis because we did not find any relationship between vasospasm and changes in CNP concentrations in the CSF.

The effect of three different Korean Traditional Medicines (KTM) was studied on several functional parameters of adult human cells in culture. The cells were non-transformed strains of normal, skin epidermal cells (keratinocytes) from adult humans. Aqueous extracts of the herbal medicines were tested using two types of cell strains: one type was essential fatty acid deficient (EFAD) cells which grow rapidly in medium that was low in calcium and had no essential fatty acids; the second type was a cell strain grown in medium supplemented with essential fatty acid (EFA-supplemented). These cells had much slower, in vivo skin growth rates, and the fatty acid composition resembled that measured in epidermal biopsy tissue. The KTMs chosen for this study were tae-gang-hual-tang (for treating osteoarthritis), hual-ak-tang (for pain relief) and sip-zeon-tae-bo-tang (for fortifying immune systems). Because high proliferation rates usually correlate with skin inflammation and because many of the chemotactic agents mediating inflammatory response are modified fatty acids, this study focused on cell growth rate and membrane fatty acid composition as signals for the effects of the herbal medicines. By monitoring growth rate, these experiments measured both a stimulatory and a regulatory effect on the growth of keratinocytes. Some toxicity was seen at the highest doses of the KTMs. These effects were modeled mathematically, and the results showed varying effects on growth rate depending on dose and herbal recipe. The fitting parameters were discussed as they relate to biological function. The experimental design was also discussed and alternatives were suggested.

The authors report the rare case of a patient with neurocutaneous vascular hamartomas mimicking Cobb syndrome. An 8-year-old boy was admitted to the authors' hospital with progressive urinary disturbance and upper back pain. Multiple skin nevi had been noted at the child's birth. Radiological examination revealed multiple cavernous angiomas in the spinal cord in the same metamere in which the skin nevi had been observed and also in the left cerebral hemisphere. His symptoms gradually improved without surgical intervention. Four years later he was readmitted because of a cerebral hemorrhage involving the left cerebral peduncle. Nonsurgical treatment was chosen because his symptoms promptly improved. To the best of the authors' knowledge, this is the first case of multiple cavernous angiomas in the brain and spinal cord associated with skin nevi. The authors discuss this clinical entity and the significance of the disease.

Merkel cell carcinoma is characterized by specific neuroendocrine features and the expression of several neuropeptides. We report a case of Merkel cell carcinoma with post-surgical hyponatremia in an 85-year-old Japanese woman. A tumor on the left cheek histopathologically showed the characteristics of Merkel cell carcinoma together with Bowen's disease. Although an increased level of ACTH was found both in the tumor and in the peripheral blood, the postoperative hyponatremia in our patient seems more likely to have been caused by the stress of the operation and indapamide, considering that the ACTH level in the tumor was much lower than those in other ectopic ACTH-producing tumors in previous reports.

The present study endeavored to differentiate Alzheimer's disease (AD) from vascular dementia (VaD) by comparing the metabolic and hemodynamic parameters. Positron emission tomographic (PET) studies were carried out in 13 patients with probable AD and 20 patients with VaD. PET findings were not included in the diagnostic criteria of AD or VaD. Using oxygen-15 labeled compounds, cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), cerebral blood volume, and vascular transit time (VTT) were measured quantitatively during the resting state. To evaluate vascular reactivity (VR), CBF was also measured during 7% CO2 inhalation. Regional CBF from the parietal cortex positively correlated with the neuropsychological scores in both AD and VaD groups. The typical parietotemporal pattern of hypoperfusion and hypometabolism was observed in the AD group, whereas the frontal lobe including the cingulate and superior frontal gyri were predominantly affected in the VaD group. The occipital cortex was preserved in both groups. A significant increase of the OEF was found in the parietotemporal areas in the AD group. No significant prolongation was seen with VTT. There was a marked difference in VR between the two groups: VR was depleted in the VaD group, whereas VR was normal in the AD group. The increased OEF with preserved vascular reserve seen in AD may implicate participation of a vascular factor in the pathogenesis of AD, possibly at the capillary level. Thus, PET provides important functional information in discriminating AD from VaD by comparing the patterns of hypoperfusion and/or hypometabolism, and in the understanding of the underlying hemodynamic pathophysiology.

Background: The rate of recurrence of basal cell carcinoma (BCC) in the periorbital region is higher than that in other areas because of the spread of the tumor along barrier structures., Objective: A better understanding of the biological behavior of BCC in this area, in particular as it relates to the lacrimal system, should improve the outcome of surgery., Methods: A study was made of two cases of BCC that developed in the periorbital region and invaded the lacrimal system., Results: The tumors were found to have invaded the lacrimal system along the mucosal epithelium. Magnetic resonance imaging (MRI) did not suggest any abnormalities in this area. In one patient, the tumor had infiltrated the nasal cavity without destruction of the periorbital bone and nasal cartilage. A preoperative fiberscopic examination clearly demonstrated the involvement of the nasal cavity in this case., Conclusion: The lacrimal system is often invaded by BCC that originates from the periorbital region. Physicians and surgeons need to be well aware of the possibility of such aggressive infiltration by BCC.