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  • 1
    ISSN: 1540-8167
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Introduction: Previous studies have suggested that paroxysmal atrial fibrillation (PAF) of vagal origin often occurs at night and PAF of sympathetic origin occurs during the daytime; however, autonomic tone after spontaneous termination of PAF has not been determined. The aim of this study was to evaluate by heart rate variability (HRV) analysis the relationship between the time of PAF onset and autonomic tone before and after PAF. Methods and Results: Twenty-three patients ( 65 ± 2 years) who underwent 24-hour ambulatory monitoring, had one or more episodes of PAF (〉30 min), and had maintained normal sinus rhythm for 〉60 min before/after PAF were enrolled in this study. Mean duration of PAF was 6.2 ± 1.2 hours. HRV parameters were analyzed in a 10-minutes section at 60 minutes, 20 minutes, and immediately before the onset of PAF and after its termination. PAF began at night in 14 patients (group N) and during the daytime in 9 patients (group D). In group N, the high-frequency (HF) component and low-frequency (LF) component showed a significant decrease after PAF; PAF was preceded by a gradual increase in HF and LF. Changes in the LF/HF ratio, however, did not occur before or after PAF. Conversely, group D showed a significant increase in the LF/HF ratio before PAF and a decrease in LF and the LF/HF ratio after PAF, but no changes in HF. These changes in HRV parameters were not influenced by the duration or termination time of PAF. Conclusion: This study suggests that the autonomic nervous system plays an important role in both the initiation and termination of PAF. Furthermore, the time of PAF onset influences the autonomic tone at the initiation and termination of PAF. (J Cardiovasc Electrophysiol, Vol. 14, pp. 559-564, June 2003)
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  • 2
    ISSN: 1540-8167
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Connexin43 Expression in DCM. Introduction: Gap junction alterations recently have been implicated in chronic heart failure, but direct evidence between gap junction manifestation in nonischemic dilated cardiomyopathy (DCM) is lacking. The current study examines whether qualitative changes or altered distribution of gap junctional connexin43 (Cx43) are related to global ventricular function and ventricular arrhythmia in DCM. Methods and Results: We investigated 31 DCM patients (52 ± 15 years) and 5 control subjects (55 ± 10 years). Expression of Cx43 proteins was qualitatively and quantitatively determined using immunoconfocal microscopy in right ventricular biopsy specimens from each patient. The expression level of Cx43 protein was defined as the proportion of tissue area occupied by Cx43 (percent tissue area) in each test area. Cx43 immunoreactive signal expressed as percent tissue area was not correlated with the change in left ventricular ejection fraction (P = 0.17). Of 31 DCM patients, 23% subsequently developed sustained ventricular tachycardia (VT), which allowed retrospective division of the samples into two groups: non-VT and VT. Left ventricular ejection fraction was comparable in both groups, but the percent tissue area in the VT groups was significantly decreased compared with that of the non-VT groups (P = 0.03). Furthermore, Cx43 protein was distributed heterogeneously in the VT groups (P 〈 0.0001). Conclusion: Heterogeneous reduction of Cx43 protein may result in development of malignant ventricular arrhythmia in DCM.
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  • 3
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim: This study was aimed to confirm the usefulness of allogeneic cultured dermal substitute (CDS) in the treatment of skin defects after excision of skin cancer. Methods: Eleven elderly patients (mean age of 76.3 year old) with skin cancer were included in this study. Most of the patients had basic disease such as diabetes or ASO. Allogeneic CDS used in the study were produced at Kitasato University. The CDS were applied to skin defects with exposing bone or tendon after oncological surgery, and changed once or twice a week until the open wound became suitable for autologous skin grafting or healed completely. Results: Healthy granulation tissue was formed to cover the exposed bone or tendon in all cases. Only in one case, the treatment with allogeneic CDS was abandoned owing to undesirable infection. In eight cases, appropriate wound beds acceptable for autologous skin graft were prepared. In other two cases, the skin defect became smaller and eventually closed without skin graft. In ten cases with or without skin graft, undesirable scar contracture was not observed over prolonged follow-up. Conclusions: Elderly patients with skin cancer provide reconstructive surgeons with challenging problems when bone or bare tendon is exposed after oncological surgery. Flap transfer might be complicated especially when the patients suffered from a basic disease such as diabetes or ASO. This study has confirmed that the use of allogeneic CDS is a safe and reliable method to achieve wound healing in those high-risk patients.
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Science Inc
    Wound repair and regeneration 12 (2004), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The authors have developed a CDS by culturing fibroblasts on the two-layered spongy matrix of hyaluronic acid (HA) and atelo-collagen (Col). This CDS is designed to promote wound healing by synergistic effect of fibroblasts and matrix. Both HA and Col molecules seem to function biologically in the process of wound healing. HA molecules play a critical role in several cellular functions such as migration and proliferation by promoting adhesion and disadhesion between the cell and the tissue substrate. Besides providing structural support and strength to the new tissue, Col molecules have a profound effect on the cells within and on its matrix. Col and Col-derived peptides act as chemoattractants for fibroblasts in vitro and may have a similar activity in vivo. Fibroblasts seeded on the Col surface of two-layered spongy matrix were found to attach, proliferate, and release vascular endothelial growth factor (VEGF) as well as fibronectin. The cryopreserved CDS was found to keep the original potency to release VEGF after thawing followed by re-culturing. Multi-center's clinical research using allogeneic CDS has been proceeded as a national millennium project for regenerative medicine. These products are able to be stored in a freezer and transported to other hospitals in a frozen state. The clinical evaluation involving 180 cases has been already conducted using allogeneic cryopreserved CDS at 30 hospitals across Japan since April 2001. The results obtained in our clinical study suggest that this type of allogeneic CDS is able to provide an effective therapy for patients with severe full-thickness skin defects. These excellent clinical evaluations seem to be closely related to the results obtained in this fundamental study, especially related to the potency of cryopreserved allogeneic CDS to release VEGF and fibronectin.
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  • 5
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study was designed to try the application of autologous cultured dermal substitute (CDS) in conjunction with patient's own epidermis. The autologous CDS was prepared by seeding cultured autolougus fibroblasts on the spongy matrix of hyaluronic acid and atelo-collagen. A 9-year-old man with a giant congenital pigmented nevus (intradermal type) was included in this clinical study. A part of nevus (30 cm × 10 cm) was excised superficially at a thickness of 20/1000 inches, and followed by second excision to remove nevus at a level of full-thickness skin. The autologous CDS was applied to the debrided wound surface. The split-thickenss skin obtained by first excision was preserved at 4 °C. After 1 week, the epidermis was obtained from the preserved split-thickness skin using dispase, and followed by grafting on the wound bed, which was prepared by applying autologous CDS. This patient's own epidermis was found to take permanently, achieving an excellent clinical results.
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  • 6
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim: Recently, various types of cultured skin substitutes have been developed and some of them are used clinically. This study was designed to evaluate the efficacy of allogenic cultured dermal substitute which was applied to burn injuries in clinical trials such as deep dermal burns and dermal burns. Methods: Allogenic cultured dermal substitute (CDS) was simply applied to the burn wound, over which covering materials were applied to protect CDS. Results: The application of CDS to deep dermal burns was proved to facilitate healthy granulation tissue formation at early stage and epithelialization from the outer margins. When CDS applied to the debrided wound surface of dermal burns, an excellent wound bed was generated which was suitable for the graft take of an autologous patch. Conclusion: CDS provides an excellent epithelialization and granulation for burn wounds.
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  • 7
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Failure of re-epithelialization characterizes the pathophysiology of chronic wounds. However, the mechanism of this failure has not been fully clarified. During the re-epithelialization of acute wounds, migrating epidermal cells up-regulate integrins α5β1, αvβ5, αvβ6 and these integrins play an important role in the re-epithelialization process. Laminin-1 is a basement membrane component which appears during the late phase of the re-epithelialization process. In this study, with 6 specimens from burn patients (acute wounds, control) and 11 specimens from patients with pressure ulcers, we examined the expression of α5β1 in the migrating epidermis, laminin-1 at the dermal-epidermal junction and fibronectin in the dermis by an immunohistochemical method. We then compared the findings for α5β1 with histological, laminin-1 and fibronectin distribution findings. In 8 out of the 11 pressure ulcer specimens, the expression of α5β1 significantly decreased or was negative while it increased in the control. The degree of expression correlated well with histological findings of epidermal elongation over the wound bed. Moreover, fibronectin distribution in all the pressure ulcer specimens decreased considerably while it increased in three out of the six burn specimens. A statistically significant correlation was found between the distance at which the cells were positively stained for α5β1 and the distance at which they were negatively stained for laminin-1 in both the burn (control) and pressure ulcer specimens. Our data demonstrated that the decrease in α5β1 expression correlated with the failure in re-epithelialization of chronic wounds (pressure ulcers). It was also suggested that the decrease in fibronectin distribution was responsible for the failure of the re-epithelialization process.
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  • 8
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim: Multi-center's clinical study for the application of the cultured dermal substitute (CDS) composed of hyaluronic acid and collagen spongy matrix with allogenic cultured fibroblasts1 is in progress since 2001. In this study, effect of the CDS for the treatment of fresh DDB wounds was tested. Methods: Six cases of second-degree burns, diagnosed as DDB by observation of blood stream of the dermal capillary using Compact Micro Vision System (Hi-Scope®, Hi Rox Co., Japan), were treated with the cultured allogenic fibroblasts, CDS. Results: The epithelialization of the wounds was obtained on 8.2 ± 2.6 (mean ± SD) days after the application. Conclusion: The results of our clinical experiences suggest that the allogenic cultured fibroblasts have beneficial effect on the wound healing of the DDB.
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  • 9
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim: A treatment of extensive burn contracture in children needs to repeat the autologous skin graft. This study was designed to evaluate the application of autologous CDS to prepare the proper wound bed acceptable for the split-thickness autologous skin graft. Methods: Prior to the clinical study, the master cell banking system was established using a small piece of skin derived from each patient. The autologous CDS was prepared by plating the patient's own fibroblasts, cultured from the master cells, on a spongy matrix of hyaluronic acid and atelo-collagen. The CDS was applied on the skin defects left behind surgical excision to release scar contracture. The split-thickness autologous skin graft (6∼8/1000 inch) was applied on the wound bed, prepared by using the CDS. Results: The clinical trials were conducted in 5 cases. When the autologous CDS was applied on the skin defect, exposing subcutaneous fatty tissue, the highly vascularlized wound bed was prepared within about 1 week. Although a split-thickness skin graft was very thin, the severe contracture was not observed over a period of several months. Conclusion: The application of autologous CDS is promising for the treatment for extensive burn scar contracture in children.
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  • 10
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim: Clinical researches using allogeneic CDS, developed in the R & D Center for Artificial Skin of Kitasato University, have been carried out in 30 medical centers across Japan. The clinical results in our hospital, especially focusing on the treatment of refractory ulcers and dermal burns, were reported in this study. Methods: The CDS was prepared by plating cultured fibroblasts on a spongy matrix of hyaluronic acid and atelo-collagen. The CDS was used in 13 clinical trials, including 6 refractory ulcers, 4 dermal burns, 1 skin defect left behind preparing skin flaps, and 2 skin defects left behind removal of scar. The use of CDS in conjunction with a conventional ointment-gauze dressing was repeated at an interval of 4 to 7 days over a period of 2 to 6 weeks. Results: The successful application with CDS was achieved in all cases. Especially, in case of refractory ulcers, failed to heal even by using trafermin (Fiblast spray®) or other ointments, a complete healing was achieved in one case and wound size reduction was observed in other 5 cases within 6 weeks. Conclusions: Our results suggest that the CDS is effective in the treatment of refractory ulcers and other skin defects. The excellent clinical results seem to be related to the cytokines released from the CDS.
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