Wound matrix attachment regulates actin content and organization in cells of the granulation tissue

Actin cytoskeletal polymerization is associated with a pro-proliferative, pro-survival state. We hypothesized that the actin polymerization of wound cells is increased in the presence of wound matrix attachment and is decreased after disruption of this attachment. Musculocutaneous flap and wound splinting models were used to investigate the effect of wound matrix attachment on the actin cytoskeleton. Disruption of wound matrix attachment was accomplished by incision of the wound matrix/dermis interface (wound matrix release) and/or desplinting. Polymerized actin was assayed with phalloidin labeling of wound specimens 24 hours after disruption of attachment and a method to quantify the content and organization of polymerized actin in granulation tissue was used. Disruption of wound matrix attachment decreased the content of polymerized actin, the actin staining intensity, and the actin fiber organization in the granulation tissue of both the flap and splint models. Disruption of wound matrix attachment decreased actin polymerization and fiber organization in the granulation tissue. Our data support the concept that the state of wound matrix attachment regulates the actin cytoskeleton of wound cells.     

A framework for systematically improving occupational therapy expert opinions on work capacity

Aim:  To present an evidence-based framework to improve the quality of occupational therapy expert opinions on work capacity for litigation, compensation and insurance purposes.
Methods:  Grounded theory methodology was used to collect and analyse data from a sample of 31 participants, comprising 19 occupational therapists, 6 medical specialists and 6 lawyers. A focused semistructured interview was completed with each participant. In addition, 20 participants verified the key findings.
Results:  The framework is contextualised within a medicolegal system requiring increasing expertise. The framework consists of (i) broad professional development strategies and principles, and (ii) specific strategies and principles for improving opinions through reporting and assessment practices.
Conclusions:  The synthesis of the participants' recommendations provides systematic guidelines for improving occupational therapy expert opinion on work capacity.     

Thymoglobulin-Associated Cd4+ T-Cell Depletion and Infection Risk in HIV-Infected Renal Transplant Recipients

HIV-infected patients are increasingly referred for kidney transplantation, and may be at an increased risk for rejection. Treatment for rejection frequently includes thymoglobulin. We studied thymoglobulin's effect on CD4+ T-cell count, risk of infection and rejection reversal in 20 consecutive HIV-infected kidney recipients. All patients used antiretroviral therapy and opportunistic infection prophylaxis. Maintenance immunosuppression consisted of prednisone, mycophenolate mofetil and cyclosporine. Eleven patients received thymoglobulin (7 for rejection and 4 for delayed/slow graft function) while 9 did not. These two groups were similar in age, gender, race, donor characteristics and immunosuppression. Mean CD4+ T-cell counts remained stable in patients who did not receive thymoglobulin, but became profoundly suppressed in those who did, decreasing from 475 +/- 192 to 9 +/- 10 cells/microL (p < 0.001). Recovery time ranged from 3 weeks to 2 years despite effective HIV suppression. Although opportunistic infections were successfully suppressed, low CD4+ T-cell count was associated with increased risk of serious infections requiring hospitalization. Rejection reversed in 6 of 7 patients receiving thymoglobulin. We conclude that thymoglobulin reverses acute rejection in HIV-infected kidney recipients, but produces profound and long-lasting suppression of the CD4+ T-cell count associated with increased risk of infections requiring hospitalization.     

Disarticulation resections of the mandible: a prospective review of 16 cases.

PURPOSE: This article provides a review of the disarticulation resection of the mandible for various benign and malignant tumors and non-neoplastic processes. In so doing, the author proposes a classification to describe extension of pathology into the condylar region, thereby requiring its sacrifice. Recommendations are also proposed for preservation versus sacrifice of the meniscus when performing a disarticulation resection of the mandible. Finally, complications are evaluated in this type of mandibular resection. PATIENTS AND METHODS: This review is based on the author's accumulated clinical data obtained from performing disarticulation resections on 16 patients who presented with 10 different pathologic diagnoses. Disarticulation resections are performed for 3 different patterns of extension of pathologic processes into the condylar region, designated as type I, type II, and type III by the author. These designations reflect the radiographic involvement of the condyle or subcondylar region of the mandible by the pathologic entity. The designations of type II and type III extensions are diagnosis dependent, whereas type I extension is independent of diagnosis. RESULTS: Five patients in this series presented with type I condylar extension, 2 patients presented with type II condylar extension, and 9 patients presented with type III condylar extension. The meniscus required sacrifice in 3 of the 16 patients. Complications occurred in 3 of 16 patients and included 1 dislocation of the plate into the middle cranial fossa, 1 dislocation of the plate inferiorly and posteriorly to the mastoid process, and 1 cutaneous exposure of the plate. CONCLUSIONS: Disarticulation resections are rarely required variants of segmental resection of the mandible, and they are required by a variety of pathologic processes of the jaws and contiguous structures. The placement of a reconstruction bone plate with an affixed condylar prosthesis is well tolerated by patients and is associated with few complications. These reconstruction bone plates favorably support facial form, symmetry, and occlusion such that many patients delay their definitive bony reconstruction. Because these condyles are temporary prostheses, the surgeon should consider their removal with bony reconstruction of the disarticulation defect as soon as possible after the ablative surgery.     

Management of psychopharmacologic agents in children and adolescents

This article summarizes the ways in which a clinician should think about medication use in children and describes practical usage of the most frequently used child psychopharmacologic agents.Leena Ranade, M.D., and Aftab Qadir, M.D., were Fellows in Child Psychiatry, State University of New York at Stony Brook at the time of writing this article.     

Cognitive functioning and psychiatric symptomatology in patients with chronic hepatitis C.

Hepatitis C virus (HCV) infection is a major public-health-care problem, with over 170 million infected worldwide. Patients with chronic HCV infection often complain of various cognitive problems as well as symptoms of depression, anxiety, and fatigue. Relatively little is known, however, about the specific cognitive deficits that are common among HCV patients, and the influence of psychiatric symptomatology on cognitive functioning. In the current study of 21 chronically infected HCV patients, we assessed subjective cognitive dysfunction, depression, anxiety, and fatigue and compared these symptom areas to cognitive tests assessing visuoconstruction, learning, memory, visual attention, psychomotor speed, and mental flexibility. Results revealed that cognitive impairment ranged from 9% of patients on a visuoconstruction task to 38% of patients on a measure of complex attention, visual scanning and tracking, and psychomotor speed, and greater HCV disease severity as indicated by liver fibrosis was associated with greater cognitive dysfunction. Objective cognitive impairment was not related to subjective cognitive complaints or psychiatric symptomatology. These findings suggest that a significant portion of patients with chronic HCV experience cognitive difficulties that may interfere with activities of daily living and quality of life. Future research using cognitive measures with HCV-infected patients may assist researchers in identifying if there is a direct effect of HCV infection on the brain and which patients may be more likely to progress to cirrhosis and hepatic encephalopathy.     

Regional gene therapy for full-thickness articular cartilage lesions using naked DNA with a collagen matrix.

A novel gene therapy approach for treating damaged cartilage is proposed that involves placing endotoxin-free cDNA containing the gene for bone morphogenetic protein-2 (BMP-2) in type I collagen sponges and then transferring the naked plasmid DNA construct to the injury site. A full-thickness cartilaginous defect in rabbits implanted with plasmid containing a marker gene (beta-galactosidase) showed expressed protein as detected by immunostaining. At 1 week postimplantation, mesenchymal cells subjacent to the defect had incorporated the implanted naked plasmid DNA and, once transfected, served as local bioreactors, transiently producing the gene product. Plasmids containing the gene for BMP-2 implanted in collagen sponges in cartilage lesions stimulated hyalinelike articular cartilage repair at 12 weeks postimplantation, nearly equivalent in quality to that induced by collagen sponges with recombinant BMP-2 protein. Our approach circumvents the risks of inflammation and immunogenic response associated with the use of viral vectors. Naked plasmid DNA as a vehicle for transferring therapeutic genes has been shown to be effective in a therapeutic model within rabbit articular cartilage and appears to be safe and cost effective.     

Allografts of tumor nuclear transplantation embryos: differentiation competence.

The developmental potential of nuclei can be studied by nuclear transplantation. Although amphibian blastula nuclei and other early embryonic nuclei are totipotent, to our knowledge no nucleus from an adult cell has ever been shown to be totipotent by this procedure. Transfer of Lucké renal carcinoma nuclei into enucleated eggs results in prefeeding swimming tadpoles. Inasmuch as these tadpoles die, rescue of this pluripotential tissue was attempted by grafting fragments of triploid tumor nuclear transplant tadpoles to the tails of normal diploid Rana pipiens hosts. Grafts of tumor nuclear transplant tadpole tissue were histologically indistinguishable from grafts of normally fertilized embryos and developed normal-appearing structures such as complete eyes, well-differentiated neural tissues, kidney tubules, and gut epithelium. Moreover, histological differentiation in tumor nuclear transplant grafts was comparable to that observed in 50-day-old normal larvae. Grafting enhanced the survival of tumor nuclear transplant tissue from no more than 14 days as part of the donor tadpole to 40 days at which time the grafts were harvested as healthy tissue. Thus, both differentiation and survival of tumor nuclear transplant tissue were augmented with the grafting procedure. Cytophotometric analysis of ploidy was used to confirm the tumor origin of the donor tissue.