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Current difficulties and the possible future directions in scar assessment.

The quantitative assessment of the results of burn management is notoriously difficult. With the focus changing from survival to cosmetic and functional outcome, the scar assessments are increasingly important. The scar is a sum of the injury and all subsequent interventions on the way to healing. As such it is a complex structure, abnormal in its colour, depth, contour and pliability. To develop a quantitative system we believe it is vital to be able to track accurately an area of injury through time. Further, that physiological data acquired by a number of measurement tools be fused accurately to the morphologically correct information.

Adolescent↗

High intensity ultrasound increases distensibility of calcific atherosclerotic arteries.

To assess the effect of high intensity ultrasound energy on atherosclerotic arteries, the pressure-volume relation of stenoses in 14 atherosclerotic human cadaver arteries was measured before and after intraarterial application of ultrasound energy. The pressure-volume relation was measured by inflating a 3-mm angioplasty balloon within each artery with use of a syringe equipped with pressure and volume transducers. To minimize potential effects of balloon inflations on compliance, balloon inflation pressure was set at less than or equal to 3 atm before ultrasound application. Ultrasound energy was applied by using a titanium wire probe at a frequency of 20 kHz for 2 min. After exposure to ultrasound, arterial distensibility (measured as volume at 1 atm of balloon pressure) increased by a mean value of 82 +/- 60 microliters. These data suggest that ultrasound energy probably increases the pliability of atherosclerotic lesions by interrupting calcified plaque. This effect may enhance in vivo distensibility and render calcified atherosclerotic lesions more amenable to balloon angioplasty.

Angiography↗

Morphological survey of a new pericardial valve prosthesis (Pericarbon): long-term animal experimental model.

A long-term experimental morphological study was carried out in 22 adult sheep to evaluate a new pericardial valve prosthesis (Pericarbon), which had been implanted in the tricuspid or mitral position. This prosthetic device differs substantially from others in that its construction design consists of two sheets of glutaraldehyde-fixed bovine pericardium and a low-profile flexible plastic stent (Delrin) covered by a pyrolytic carbon coated dacron fabric; one pericardium sheet forms the three cusp valve and is sutured to the second, which lines the inner surface of the plastic stent. Twenty animals were sacrificed at fixed intervals, while 2 are still living at about 3 years post-surgery. Tricuspid explants (mean duration, 295 days) showed significant fibrous sheathing and a mean calcium X-ray score of 1.75. Mitral medium-term explants (mean duration, 325 days) had fairly well preserved pliability and a mean calcium X-ray score of 2.5. Long-term explants (mean duration, 467 days) were all stiffened by calcification (mean score, 3.75). None of the explants had tears or perforations. Medium or long-term mechanical failure was not observed. A significant host tissue reaction took place in the tricuspid but not in the mitral position. Calcification mainly involved the collagen fibres and increased progressively with time. Ultrastructural studies invariably disclosed fair preservation of graft tissue structures, surface reendothelization and initial nuclei of calcification within the collagen fibres. These morphological findings confirm the potential advantages of this new prosthetic device and warrant long-term clinical trials to test its actual durability.

Animals↗

Design of scaffolds for blood vessel tissue engineering using a multi-layering electrospinning technique.

Aiming to develop a scaffold architecture mimicking morphological and mechanically that of a blood vessel, a sequential multi-layering electrospinning (ME) was performed on a rotating mandrel-type collector. A bi-layered tubular scaffold composed of a stiff and oriented PLA outside fibrous layer and a pliable and randomly oriented PCL fibrous inner layer (PLA/PCL) was fabricated. Control over the level of fibre orientation of the different layers was achieved through the rotation speed of the collector. The structural and mechanical properties of the scaffolds were examined using scanning electron microscopy (SEM) and tensile testing. To assess their capability to support cell attachment, proliferation and migration, 3T3 mouse fibroblasts and later human venous myofibroblasts (HVS) were cultured, expanded and seeded on the scaffolds. In both cases, the cell-polymer constructs were cultured under static conditions for up to 4 weeks. Environmental-scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), histological examination and biochemical assays for cell proliferation (DNA) and extracellular matrix production (collagen and glycosaminoglycans) were performed. The findings suggest the feasibility of ME to design scaffolds with a hierarchical organization through a layer-by-layer process and control over fibre orientation. The resulting scaffolds achieved the desirable levels of pliability (elastic up to 10% strain) and proved to be capable to promote cell growth and proliferation. The electrospun PLA/PCL bi-layered tube presents appropriate characteristics to be considered a candidate scaffold for blood vessel tissue engineering.

3T3 Cells↗

Collagen composite hydrogels for vocal fold lamina propria restoration.

Chronic voice impairment due to scarring of the vocal fold (VF) lamina propria (LP) can be debilitating in terms of quality of life. Due to the dependence of normal VF vibration on proper VF geometry, an implant inserted to restore appropriate shape and pliability to scarred LP should ideally maintain its insertion-dimensions while being replaced by newly synthesized extracellular matrix (ECM). In the present study, collagen-alginate and collagen-hyaluronan (HA) composite hydrogels were investigated for their ability to support ECM synthesis by VF fibroblasts with limited hydrogel compaction and/or resorption. Collagen-HA composites showed significant mass loss over 28 days of culture, with little evidence of new matrix production. Collagen-alginate composites, in contrast, resisted scaffold compaction and mass loss for at least 42 days in culture while allowing for ECM synthesis. Collagen-alginate hydrogels appear to be promising materials for VF restoration, warranting further investigation.

Alginates↗

Application of tissue ultrasound palpation system (TUPS) in objective scar evaluation.

One of the characteristics of hypertrophic scarring is its raised appearance. Its maturation often results in increased thickness. Therapists usually rely on subjective observation and palpation to document scar thickness. The result of these subjective assessments may reflect only the superficial scar thickness but is unable to measure the whole scar volume and thickness under the skin surface. Measurement of scar thickness using ultrasound imaging has been previously reported, but has not been commonly used in clinics due to its complex operation method and high cost. In this study, we have adopted a newly developed and user-friendly Tissue ultrasound palpation system (TUPS) for the assessment of scar thickness. It consists of a finger size palpation probe, connected to an ultrasound transducer and an in-series load cell to measure the thickness of the soft tissue over the human body. The method of operation is easy and it can be used to measure skin thickness on various parts of the body, thus reflecting the skin thickness. The reliability of the TUPS in clinical application was tested on 30 subjects with a hypertrophic scar at a local hospital. Three raters implemented two assessments on each subject to study its test-retest and inter-rater reliabilities. It was then used to assess 100 subjects with various severity of hypertrophic scar caused by trauma, scald, burn or surgery. They were assessed using TUPS as well as the Vancouver Scar Scale (VSS) for rating scar thickness, pliability, pigmentation and vascularity. Two-way mixed intra-class correlation showed a high test-retest reliability with Intraclass Correlation Coefficient (ICC)=0.98 and inter-rater reliability ICC=0.84. Fair positive correlations with VSS thickness score and VSS total score r=0.34 (p<0.05) and 0.42 (p<0.05), respectively. A significant difference between two scar type groups (50 burn scald scars and 50 surgical scars) was demonstrated (d.f.=52.94, t=3.99, p<0.01). TUPS was proved to have high inter-rater, test-retest reliability and it had a moderate correlation with the VSS that clinicians used for assessment of the scar. This system is recommended for clinical assessment of scar thickness.

Adolescent↗

Prevalence of hypertrophic scar formation and its characteristics among the Chinese population.

Each year in Hong Kong, about 350,000 surgical procedures are conducted for various types of conditions. Previous review indicated that the prevalence of hypertrophic scar among Caucasians ranged from 15% to 63% and that the incidence was even higher among non-Caucasians. This study aims to find out the prevalence rate of hypertrophic scar among the Hong Kong Chinese population after standardized surgical procedures. A systematic and objective scar measurement protocol is implemented in this study. The spectrocolorimeter, Miniscan XE plus was used to measure the scar pigmentation based on the theory of the CIE colour model. The tissue ultrasound palpation system (TUPS) was employed to measure scar thickness. From May 2001 to December 2003, 154 patients, who received surgical intervention at the Department of Orthopaedics and Traumatology of a large regional hospital, were invited to join a scar-screening test. One hundred and fifteen patients (74.67%) were found to have signs of hypertrophic scar based on thickness, pliability, pigmentation and vascularity (using the Vancouver scar scale (VSS) score). One hundred and one patients consented to have more comprehensive scar assessment. Results indicated that the scar thickness was 4.91+/-1.03 mm. Compared with the adjacent normal skin, the color of hypertrophic scar was significantly different in terms of lightness (d.f.=100, t=-19.36, p<0.01), redness (d.f.=100, t=15.75, p<0.01) and yellowness (d.f.=100, t=-11.48, p<0.01) using paired t-test analysis. Fourtysix point five percent and 33.7% among patients reported pain (2.19+/-2.74) and itchiness (1.47+/-2.53) over the scar. The objective scar assessments showed that more than 70% of scars had increase in thickness and pigmentation after surgery. More than 40% of patients reported pain and itchiness. The results showed that more than 70% of the scars in the HK Chinese population had become hypertrophic in terms of pigmentation, thickness and physical symptoms such as pain and itchiness 1 month after the surgical intervention. More long-term follow up study should be done to find out the prevalence and that it is essential to provide early intervention before the scar becomes problematic in management.

Adolescent↗

BIOSA bileaflet pericardial valve: experimental study in sheep model.

BACKGROUND: BIOSA is a single sheet, two-cuspal-shaped ("bileaflet") glutaraldehyde fixed bovine pericardial valve prosthesis (BP), designed to minimize stress and prevent mechanical failure. We tested this device in the adult sheep model. METHODS: Seven BIOSA and two Baxter Carpentier-Edwards (Perimount) pericardial BPs, 25 mm in size, were implanted in the tricuspid position of adult sheep. A mid term BIOSA explant (81 days) died of infective endocarditis. The remaining BPs were divided in three early explants (0-3 days: two BIOSA and one Perimount) and five late explants (162-189 days: four BIOSA and one Perimount). Protocol of the study included gross examination, mammography X-ray (score 0-4), histology, scanning (SEM) and transmission (TEM) electron microscopy and atomic absorption spectroscopy. RESULTS: (a) Early explants: The mesothelium was detached, collagen-elastic fibers and pericardiocytes of the fibrosa showed optimal preservation. Calcium content in BIOSA BPs was 6.22 mg/g dry weight (mean) versus 7.75 mg/g of the Perimount BP. (b) Late explants: At naked eye all BPs showed regular cusp pliability and coaptation, without tears, perforations, fibrous pannus or calcific deposits. X-ray was either negative (three BPs) or exhibited score 1 (two BPs). Microscopic features were excellent both in terms of collagen-elastic fibers preservation and absence of inflammation. The calcium content was 4.95 mg/g dry weight (mean) in BIOSA BPs versus 5.29 mg/g in the Perimount BP. CONCLUSIONS: Tissue characteristics of BIOSA BPs were optimal, without difference with Perimount BPs and in this animal model no case of structural valve deterioration occurred in the long term.

Animals↗

EcR and Usp, components of the ecdysteroid nuclear receptor complex, exhibit differential distribution of molecular determinants directing subcellular trafficking.

Ecdysteroids coordinate development, reproduction and other essential biological processes in insects and other arthropods through the receptor which is a heterodimer of two members of the nuclear receptors superfamily, the ecdysteroid receptor (EcR) and the Ultraspiracle (Usp). Although the transcriptionally active EcR/Usp heterocomplex is believed to be the only functional form of the receptor, there are data indicating that EcR may be involved in the mediation of the non-genomic effects outside of the nucleus. Since the nucleocytoplasmic shuttling could be a key element determining participation of the single nuclear receptor molecule both in the genomic and non-genomic functions we have analyzed nuclear import and export properties of the EcR and Usp from Drosophila melanogaster. We show for the first time that both receptors exhibit differential distribution of the nuclear localization and nuclear export signals (NLSs and NESs). In particular, the Usp which exhibits exclusively nuclear localization in all cell types analyzed, contains apparently only NLS activity within the DNA-binding domain. In contrast, the three known EcR isoforms (A, B1 and B2) are mosaics of elements which can potentially mediate their nucleocytoplasmic shuttling. We have found two active NESs in ligand binding domain and NLS activity within the DNA-binding domain of all isoforms. Simultaneously we demonstrate that B1 and A isoforms possess an additional NLS activity localized in AB regions. We speculate that this characteristic, along with the previously reported structural pliability of the EcR molecule, allows the single receptor to evoke many different genomic as well as non-genomic ecdysteroid-dependent responses.

Active Transport, Cell Nucleus↗

Pediatric video laryngo-stroboscopy.

OBJECTIVE: Laryngo-stroboscopy remains as the clinical gold standard for assessing properties of the glottal phonatory and valvular function. This includes deficits of closure as well as mucosal wave irregularities secondary to abnormal zones of pliability and symmetry. Per-oral stroboscopy has technical limitations in children due to the size of the telescope and issues of patient compliance. However, flexible laryngoscopy is readily performed in newborns and young children. This paper describes the use of a new trans-nasal, digital flexible laryngoscope, which allows for laryngo-stroboscopy in children. METHODS AND RESULTS: A prospective longitudinal series was done on 25 children ages 19 months-13 years (mean age, 7.0 years) with this new technology. All 25 were successfully examined. CONCLUSIONS: New technological advancements in the design of digital flexible endoscopes has allowed for laryngo-stroboscopy, and therefore, provides the potential for expanding the population of children with vocal disorders in whom stroboscopic imaging is possible. Larger studies will be necessary to determine its limitations related to age, development, and disease. As the study of pediatric voice disorders continues to evolve, accurate diagnosis is essential to apply state of the art non-operative and phonosurgical interventions. Further longitudinal studies are currently underway to continue to refine techniques of pediatric voice assessment and to define limitations of this new technology.

Adolescent↗

Comparison of deltopectoralis flap and free radial forearm flap in reconstruction after oral cancer ablation.

Defects in the head and neck resulting from ablation of oral cancer frequently lead to disabling functional and cosmetic deformities. Rehabilitation of patients with oral cancer can be an emotionally and technically challenging endeavor. Selection of the donor tissue is clearly dependent upon the defect that is to be reconstructed. The donor tissue should be of sufficient bulk and pliability to facilitate reestablishing contour and function. Regional flap and free flap have been the mainstays of reconstruction for surgical defects after ablation of oral cancer. The records of 77 patients in whom 49 deltopectoral (DP) flaps and 28 free radial forearm flaps (FRFF) were used were analyzed. The success rate of the DP flap was 89.8% and of the FRFF was 96.4%. The minor complication rate at the transplant site (fistula, dehiscence, hematoma) for the DP flaps was 22.4% and for the FRFFs was 14.3%. Overall complication rate at the transplant site for DP flaps was 32.7% and for the FRFFs was 17.9%. The incidence of partial loss of the donor-site skin graft was 4.1% for the DP flaps and 10.7% for the FRFFs. Overall complication rate at the donor site for DP flaps was 10.2% and for the FRFFs was 39.3%. DP flaps had better aesthetic and functional results at the donor site, than FRFFs. However, the DP flap is a staged procedure and results in prolonged hospitalization. In contrast to FRFF, performing a DP flap avoids the difficult technique of microanastomosis, and therefore reduces the donor-site complication rate and the operation time. Therefore, free flaps can not be routinely substituted for regional flaps, but they represent better reconstructive alternatives for specific and selected patients.

Adult↗

Lamina propria replacement therapy with cultured autologous fibroblasts for vocal fold scars.

OBJECTIVES: To develop a canine model of vocal fold scar and to evaluate its treatment with lamina propria replacement therapy using autologous cultured fibroblasts. MATERIALS AND METHODS: Full thickness of the lamina propria layer in canine vocal folds was injured with a laser. Fibroblasts were cultured and expanded in the laboratory from a buccal mucosal biopsy. The scarred vocal folds were treated with 3 weekly injections of fourth, fifth, and sixth passage autologous fibroblasts. Mucosal waves and acoustic parameters were measured at baseline, after scarification, and several months after injection therapy. Histologic evaluation of the vocal folds for fibroblasts, collagen, elastin, reticulin, and hyaluronic acid was performed. RESULTS: Nine beagle dogs were used, and 1 animal served as control. Vocal fold scarring resulted in absent or severely limited mucosal waves and significantly worse acoustic parameters. Significant improvements in mucosal waves and acoustic parameters were obtained after lamina propria replacement therapy. After therapy, mucosal waves became normal in 4 animals and near normal in the other 4. No statistical difference was found in mucosal waves between baseline and post-therapy. All animals tolerated therapy without complications. The treated vocal folds demonstrated an increased density of fibroblasts, collagen, and reticulin, a decreased density of elastin, and no change in hyaluronic acid. CONCLUSIONS AND SIGNIFICANCE: Therapeutic options for vocal fold scars are limited. Lamina propria replacement therapy in the form of autologous cultured fibroblasts improves mucosal pliability and returns normal or near normal mucosal waves in experimentally scarred vocal folds. This novel therapeutic modality may hold new promise for treating vocal fold scars.

Animals↗

Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil.

Rho-kinase is a key regulator of cytoskeletal events and a promising drug target in the treatment of vascular diseases and neurological disorders. Unlike other protein kinases, Rho-kinase requires both N- and C-terminal extension segments outside the kinase domain for activity, although the details of this requirement have been elusive. The crystal structure of an active Rho-kinase fragment containing the kinase domain and both the extensions revealed a head-to-head homodimer through the N-terminal extension forming a helix bundle that structurally integrates the C-terminal extension. This structural organization enables binding of the C-terminal hydrophobic motif to the N-terminal lobe, which defines the correct disposition of helix alphaC that is important for the catalytic activity. The bound inhibitor fasudil significantly alters the conformation and, consequently, the mode of interaction with the catalytic cleft that contains local structural changes. Thus, both kinase and drug conformational pliability and stability confer selectivity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Radial forearm free flap for reconstruction of the oral cavity: clinical experience in 55 cases.

OBJECTIVE: Since the advent of modern microvascular techniques, the radial forearm free flap (RFFF) has become a reliable method for reconstruction of defects within the oral cavity. The purpose of the present study was to evaluate our experience with the use of the RFFF for the reconstruction of oral cavity defects after tumor resection. STUDY DESIGN: During a 9-year period, 103 consecutive patients were treated in our department for the reconstruction of oral defects after tumoral ablation by means of microvascularized free flaps. Fifty-five patients were reconstructed by means of the RFFF. Patients were treated for benign (n = 1) and malignant (n = 54) entities. All the patients underwent an abdominal split-thickness skin graft for the closure of the donor site. RESULTS: Fifty-five patients underwent reconstruction by means of the RFFF after resection of the oral cavity. Squamous cell carcinoma was present in 54 patients. A mean age of 55.5 years was observed (range 16-78). Thirty-nine patients (70.9%) were men and 16 (29.1%) women. Primary reconstruction was achieved in 52 patients (96.3%). A fasciocutaneous graft was used in all of the cases, with a mean size of 7.39 x 5.17 cm. The mean flap ischemic time was 56.02 minutes. During the immediate follow-up period, revision of the vascular anastomosis was necessary in 18.9% of the cases owing to flap ischemia. CONCLUSION: Our results revealed that the RFFF is a reliable method for reconstructing a wide range of oral cavity defects with an acceptable low morbidity rate. It provides adequate bulkiness and pliability, resulting in adequate reconstruction of a wide variety of defects within the oral cavity.

Adolescent↗

Reconstruction of right ventricular outflow and pulmonary artery with a composite pericardial monocusp patch: an experimental study.

A composite bovine pericardial monocusp patch was implanted in the right ventricular outflow tract of 30 dogs. The monocusp patch incorporates a molded sinus of Valsalva designed according to a computer-analyzed study of the normal anatomy. Twenty-two dogs survived the operation and were killed between 1 and 34 months postoperatively (mean, 19.5 +/- 3.5 months). Two implants showed signs of infective endocarditis 2 and 2.5 months, respectively, after operation; 1 was thrombosed at 7 months, and 1 was calcified 8 months postoperatively. In the remaining 18 animals, there was no stenosis, thrombosis, or degeneration of tissue in the monocusp. Macroscopic and microscopic studies of these grafts showed normal structure and pliability of the monocusp valve up to 34 months after operation.

Animals↗

The use of vein allografts as sidearms for intraaortic balloon insertion.

Femoral artery cannulation for intraaortic balloon counterpulsation may be attended by difficulties due to changes in the vessel wall and the inherent stiffness of Dacron grafts. A substitute technique utilizing venous allografts is described. The advantages are enumerated and are related to allograft pliability. Fifty-nine such procedures have been done without related complications.

Assisted Circulation↗

Morphological mural changes in the aorta in non-specific aortoarteritis (Takayasu's arteritis): assessment by intravascular ultrasound imaging.

OBJECTIVE: Non-specific aortoarteritis (Takayasu's arteritis) is a panarteritis of unknown aetiology which primarily involves the vessel walls. The imaging morphology of wall abnormalities has been infrequently studied and their intravascular ultrasound appearance is not reported in the literature. METHOD: We studied this morphology by intravascular ultrasound in nine patients in whom the diagnosis of Takayasu's arteritis was made by clinical and angiographic criteria. Intravascular ultrasound was performed by the transfemoral route. Images of the aorta were obtained in each patient. Qualitative and quantitative analysis was performed. RESULTS: All procedures were successful, without complication. Typical findings included thickening and altered echogenicity of the media, adventitia and peri-arterial tissues. The inner echogenic layer was thin. Pliability of aortic walls was lost in stenotic segments. Aortic calcification was seen in one patient. The aortic wall thickness was 0.17-0.58 cm. Angiograms showed skip areas of aortic involvement. Intravascular ultrasound showed wall changes even in the skip areas which were normal at angiography. CONCLUSION: Intravascular ultrasound shows changes in the aortic wall morphology in non-specific aortoarteritis. Our findings suggest that this disease involves contiguous aortic segments, producing wall and luminal changes in some areas and only wall changes in intervening areas.

Adolescent↗

Immunoregulation of malarial infection: balancing the vices and virtues.

Malaria continues to extract an incalculable cost on human morbidity and mortality throughout tropical and subtropical regions of the world, and effective control measures are urgently needed. Despite considerable efforts in recent years to develop subunit vaccines targeted at various stages of the Plasmodium life-cycle, the commercial availability of a vaccine is still a distant prospect. One of the underlying difficulties hindering successful vaccine design is our incomplete knowledge of the precise type(s) of immune response to aim for, and then how to achieve it. A greater appreciation of the mechanisms of protective immunity, on the one hand, and of immunopathology, on the other, should provide critical clues on how manipulation of the immune system may best be achieved. Ten years have passed since the identification of the Th1/Th2 paradigm for distinguishing CD4+ T cells according to cytokine secretion patterns which determine their function. This review summarises our progress towards understanding the broad spectrum of immune responsiveness to the blood stages of the malaria parasite during experimental infections in mice and highlights the way in which examination of rodent malarias provides a powerful tool to dissect the interaction of Th1 and Th2 cells during an immune response to an infectious disease agent. It is proposed that the pliability of rodent systems for investigating immunoregulation provides valuable insight into the balance between protection and pathology in human malaria and throws light on the factors involved in the modulation of vaccine-potentiated immunity.

Animals↗