Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds

Human skin wounds (66) inflicted between 20 h and 7 months prior to biopsy were studied. In order to identify the type of cellular differentiation of the fibroblastic cells in the granulation tissue, alpha-smooth muscle actin and desmin were immunohistochemically localized. The value of any presumed time-dependent appearance and/or disappearance of positively stained cells was tested for the estimation of wound age. In skin specimens with a wound age less than 5 days (n =15) no typical granulation tissue had developed and no alpha-actin-positive myofibroblasts could be detected. The first appearance of positively reacting myofibroblasts was noted in a 5-day-old wound. In 57% of the lesions with a wound age between 5 and 31 days (25 out of 44 cases) typical granulation tissue formation was present and myofibroblasts with positive reaction for alpha-smooth muscle actin could be identified. Numerous positively reacting cells could generally be found in wounds aged between 16 and 31 days, but also in wounds less than 16 days old. In 29% of the cases with a wound age of more than 31 days (2 out of 7 cases) alpha-sma-positive myofibroblasts also occured. Fibroblastic cells positive for desmin could not be seen at all in our series. Our results demonstrate the appearance of alpha-sma-positive myofibroblasts with the initial formation of typical granulation tissue in human skin lesions as early as approximately 5 days after wounding. In contrast to recent experimental results these cells remained detectable in wounds aged more than 2 months in some cases. The immunohistochemical detection of actin-positive cells, therefore, demonstrates whether an unknown skin wound is aged approximately 5 days or more. Even though a time-dependent decrease of myofibroblasts in human granulation tissue after 31 days in human wounds seems probable, the extended presence (up to about 2 months) of these cells allows no further exact age determination of older wounds

A mathematical model for fibro-proliferative wound healing disorders

The normal process of dermal wound healing fails in some cases, due to fibro-proliferative disorders such as keloid and hypertrophic scars. These types of abnormal healing may be regarded as pathologically excessive responses to wounding in terms of fibroblastic cell profiles and their inflammatory growth-factor mediators. Biologically, these conditions are poorly understood and current medical treatments are thus unreliable. In this paper, the authors apply an existing deterministic mathematical model for fibroplasia and wound contraction in adult mammalian dermis (Olsenet al., J. theor. Biol. 177, 113–128, 1995) to investigate key clinical problems concerning these healing disorders. A caricature model is proposed which retains the fundamental cellular and chemical components of the full model, in order to analyse the spatiotemporal dynamics of the initiation, progression, cessation and regression of fibro-contractive diseases in relation to normal healing. This model accounts for fibroblastic cell migration, proliferation and death and growth-factor diffusion, production by cells and tissue removal/decay. Explicit results are obtained in terms of the model processes and parameters. The rate of cellular production of the chemical is shown to be critical to the development of a stable pathological state. Further, cessation and/or regression of the disease depend on appropriate spatiotemporally varying forms for this production rate, which can be understood in terms of the bistability of the normal dermal and pathological steady states—a central property of the model, which is evident from stability and bifurcation analyses. The work predicts novel, biologically realistic and testable pathogenic and control mechanisms, the understanding of which will lead toward more effective strategies for clinical therapy of fibro-proliferative disorders

Abrogation of chronic rejection in a murine model of aortic allotransplantation by prior induction of donor-specific tolerance

Aortic allotransplantation in mice has been well established as a model of choice to study the evolvement of chronic rejection, the etiopathology of which is believed to be that of immune origin. This has prompted the postulation that prior induction of donor-specific tolerance would attenuate or abrogate the underlying events that culminate in posttransplant arteriosclerosis. To study the effects of donor-specific tolerance on chronic rejection, we performed orthotopic liver transplantation without immunosuppression in mice 30 days before aortic allotransplantation across C57Bl/10J (H2b)→C3H (H2(k)) strain combinations (group III). Aortic allografting in syngeneic (group I; C3H→C3H) and allogeneic (group II, C57Bl/10J→C3H) animals served as controls. No morphological changes were evidenced in the transplanted aortas in group I animals. Contrarily, aortic allografts in group H animals underwent a self-limiting acute cellular rejection, which resolved completely and was succeeded by day 30 after transplantation by histopathological changes pathognomonic of chronic rejection. There was evidence for diffuse myointimal thickening, progressive concentric luminal narrowing, and patchy destruction of internal elastic membranes resulting in massive vascular obliteration by day 120 after transplantation. It was of interest that no arteriosclerotic changes were observed for the duration of follow-up (up to 120 days after transplantation) in transplanted aortas (liver donor-type) harvested from animals in group III. However, vasculopathy was prominent in third-party aortic grafts transplanted into tolerant recipients. Taken together, these data suggest that prior induction of tolerance abrogates the development of chronic rejection; this protection seems to be donor specific

Staphylocoques et autres bactéries à gram positif: Détection de la pénicillinase de Staphylococcus aureus : quand cela paraît flou.

International audienc

A new method for the evaluation of the end-to-end distance of the knee ligaments and popliteal complex during passive knee flexion

Background: Accurate knowledge about the length variation of the knee ligaments (ACL, PCL, MCL and LCL) and the popliteal complex during knee flexion/extension is essential for modelling and clinical applications. The aimof the present study is to provide this information by using an original technique able to faithfully reproduce the continuous passive knee flexion–extension kinematics and to reliably identify each ligament/tendon attachment site. Methods: Twelve lower limbs (femur, tibia, fibula, patella)were tested and set inmotion (0–120°) using an ad hoc rig. Tibio-femoral kinematics was obtained using an optoelectronic system. A 3D digital model of each bone was obtained using low-dosage stereoradiography. Knee specimens were dissected and the insertion of each ligament and popliteal complex were marked with radio opaque paint. ACL, PCL and MCL were separated into two bundles. Bone epiphyses were CT-scanned to obtain a digital model of each ligament insertion. Bones and attachment site models were registered and the end-to-end distance variation of each ligament/tendon was computed over knee flexion. Results: A tibial internal rotation of 18°±4° with respect to the femur was observed. The different bundles of the ACL, MCL and LCL shortened, whereas all bundles of the PCL lengthened. The popliteal complex was found to shorten until 30° of knee flexion and then to lengthen. Conclusion: The end-to-end distance variation of the knee ligaments and popliteal complex can be estimated during knee flexion using a robust and reliable method based on marking the ligaments/tendon insertions with radiopaque paint. Level of evidence: Level IVThanks to Ann-Laure Pollastri for her technical support and to Louis Dagneaux for helping during the experimental session. The authors also thank the ParisTech BiomecAM chair program on subject-specific musculoskeletal modelling. This research was approved by the ethics committee of the human anatomy lab of the University of Caen (Basse Normandie, France)

Radiographic Outcomes of Adult Spinal Deformity Correction : A Critical Analysis of Variability and Failures Across Deformity Patterns

International audienceStudy Design: Multicenter, prospective, consecutive, surgical case series from the International Spine Study Group.Objectives: To evaluate the effectiveness of surgical treatment in restoring spinopelvic (SP) alignment.Summary of Background Data: Pain and disability in the setting of adult spinal deformity have been correlated with global coronal alignment (GCA), sagittal vertical axis (SVA), pelvic incidence/lumbar lordosis mismatch (PI-LL), and pelvic tilt (PT). One of the maingoals of surgery for adult spinal deformity is to correct these parameters to restore harmonious SP alignment.Methods: Inclusion criteria were operative patients (age greater than 18 years) with baseline (BL) and 1-year full-length X-rays. Thoracic and thoracolumbar Cobb angle and previous mentioned parameters were calculated. Each parameter at BL and 1 year was categorized as either pathological or normal. Pathologic limits were: Cobb greater than 30 , GCA greater than 40 mm, SVA greater than 40 mm, PI-LL greater than 10 , and PT greater than 20 . According to thresholds, corrected or worsened alignment groups of patients were identified and overall radiographic effectiveness of procedure was evaluated by combining the results from the coronal and sagittal planes

Clinical Improvement Through Surgery for Adult Spinal Deformity: What Can Be Expected and Who Is Likely to Benefit Most ?

Study Design: Multicenter, prospective, nonconsecutive, surgical case series from the International Spine Study Group. Objectives: To evaluate the extent of clinical improvement after surgery for adult spinal deformity (ASD) based on minimal clinically important difference (MCID) and baseline measures. Summary of Background Data: For ASD, evaluation of surgical treatment success using clinical scores should take into account baseline disability and pain and the improvement defined relative to the MCID. Methods: Inclusion criteria included operative patients (age O18 years) with baseline and 2-year SRS-22 scores. Normative values for the SRS scores were included and improvement for patients was expressed in number of MCIDs. At baseline, patients were classified by differences in activity and pain scores from normative values in four groups: ‘‘worst,’’ ‘‘severe,’’ ‘‘poor,’’ and, ‘‘moderate.’’ At 2 years after surgery, patients were classified into four groups based on their change in SRS score as follows: ‘‘no improvement or deterioration,’’ ‘‘mediocre,’’ ‘‘satisfactory,’’ or ‘‘optimal.’’ Distinction among curve types was also performed based on the SRS-Schwab ASD classification. Results: A total of 223 patients (age 5 55 15 years) were included. At baseline, for 77% of the patients, the worst scores were in Activity or Pain. At baseline, the distribution was 36%‘‘worst,’’ 28%‘‘severe,’’ 19% ‘‘poor,’’ and 17% ‘‘moderate.’’ Patients with sagittal malalignment only were more likely to be in the ‘‘worst’’ state (54%). The overall distribution of improvement was as follows: 24% no improvement or deterioration, 17% mediocre, 25%satisfactory, and 33%optimal. Forty-one percent of baseline ‘‘moderate’’ patients achieved no improvement. Of the baseline ‘‘worst’’ patients, 20% achieved no improvement, and 36% and 19% achieved ‘‘satisfactory’’ and ‘‘optimal’’ improvement, respectively. Conclusion: Overall, 24% of patients did not experience improvement after surgery. Patients with baseline severe disability were more likely to perceive improvement than patients with less disability.This study was supported by the International Spine Study Group and partially funded via a grant received from Depuy Synthes (Grant # NCT00738439) and the Scoliosis Research Society