CD154, a marker of antigen-specific stimulation of CD4 T cells, is associated with response to treatment in patients with chronic HCV infection.

CD4 T-cell function is crucial for the eradication of HCV, and insufficient function is observed in chronic carriers. The monitoring of T-cell responses is complicated by the scarcity of antigen-specific T cells and the relative inefficiency of virus-specific T cells to produce effector cytokines. CD154 is a marker of activation expressed on T cells induced through their T-cell receptor. We analysed CD4 T-cell responses in 72 patients with chronic or resolved HCV infection (23 treatment naïve, 49 treatment experienced, including 16 who had achieved a sustained response). In an additional prospective protocol, 20 of the chronically infected patients were analysed before and after 8-12 weeks of combination therapy with peg-interferon-α and ribavirin. T-cell responses were measured by detecting the expression of CD154 and Th1 cytokines after stimulation with recombinant HCV proteins and were correlated with pretreatment status and outcome of therapy. Broader T-cell responses were observed in treatment naïve than in experienced patients, while the outcome of a preceding therapy regimen did not influence T-cell responses. In the prospective cohort, an on-treatment increase in CD154+ cytokine- T-cell activity was associated with response to treatment, while a decrease was observed in nonresponders. Stronger antigen-independent activity of CD154+ cytokine+ T cells was observed in responders than in nonresponders. Our data indicate that CD154 as a marker of activation of CD4 T cells is a suitable tool for the analysis of T-cell responses in patients with HCV infection.

Fracture healing and callus innervation after peripheral nerve resection in rats.

The effects of femoral and sciatic nerve resection on fracture healing and innervation of the fracture callus were studied using a stable fracture model. In 34 rats the right tibia was subjected to a standardized closed fracture and stabilized with a modular intramedullary nail. In half of the animals, resection of 1 cm of the femoral and sciatic nerves was performed (nerve resection group), whereas the other animals had sham operations (sham group). To avoid unequal load-bearing between the two groups, all fractured hindlimbs were immobilized in a plaster of Paris cast. The trial was terminated after 5 weeks of fracture healing. Callus size was scored radiographically, and bone mineralization was measured by 85-strontium incorporation. Seven rats from each group had immunohistochemical examination for neural regeneration and ingrowth. Antisera for protein gene product 9.5, neurofilaments, neural growth associated protein 43/B-50, calcitonin gene related peptide, and substance P were used. The mechanical properties of the healing fractures were recorded in a three-point cantilever bending test. After 5 weeks, the normally innervated, fractured tibias had regained approximately 50% strength compared with the unfractured side, in comparison with only 20% in the animals that had nerve resection. Although the fracture calluses were mechanically weaker, they were significantly larger in the nerve resection group, indicating defects in tissue composition or organization rendered by the nerve injury. The mineralization rate, as measured by 85-strontium incorporation, was the same in the two groups. However, the nerve resection did not provide complete denervation but changed the innervation pattern of the healing fracture, as the density of sensory nerve fibers immunostaining for substance P and neurofilaments was less in the group with femoral and sciatic nerve resection. The results suggest that intact innervation is essential for normal fracture healing because nerve injury induced a large, but mechanically insufficient, fracture callus.

Improved method for examination of microvascular structures in bone tissue.

Scanning electron microscopy of methylmethacrylate vascular corrosion casts was used for the morphologic examination of the microvascular system in bone. The methylmethacrylate used for vascular casting was prepared by prepolymerization with ultraviolet light. To approximate the viscosity of blood in the microcirculation, where the hematocrit of blood is lower than in the rest of the circulation, a viscosity between that of plasma and full blood was chosen for the casting material. Neither the ultraviolet prepolymerization of methylmethacrylate nor the choice of a viscosity this low has been used in microcorrosion casting in bone before. Further preparation of the tissue followed 2 directions: (1) complete maceration and decalcification of the specimens, thereby exposing all the vascular structures for detailed examination. By this procedure, it was possible to show detailed and sharp impressions of the vascular bed, and to show, for the first time, the vascular loop from a cutting cone; and (2) maceration without decalcification of the specimens, which is suitable for examination of relations between the microvascular system and the bone tissue. This technique enables studies of the role of the vascular system in bone remodeling and of the involvement of vascular structures in bone disorders. This improved technique for examination of microvascular structures in bone enables detailed studies of the vascular system and its relation to active remodeling sites in bone.

[Primary aneurysmal bone cyst. Evaluation of the symptomatology, treatment and prognosis based on 21 patients]. / Den primaere aneurysmatiske knoglecyste. En evaluering af symptomatologi, behandling og prognose på basis af 21 patienter.

PABC is a rather rare, non-malignant osteolytic bone disease, affecting children and young people. Most frequently, it is localized to the metaphyses of the long bones. The present material consists of 21 cases, treated in the Orthopaedic Hospital in Aarhus between 1973 and 1991. Nineteen patients were treated with curettage of the cyst followed by bone grafting to the cavity. Six (31%) had recurrences. Five were operated again without any recurrence. The last patient has not yet received any further treatment. Two patients were initially treated by bone resection. No postoperative complications occurred. Curettage of PABC followed by bone grafting is recommended as the treatment of choice, in spite of the recurrence rate mentioned above. Because of the risk of recurrence after this treatment, regular follow-up examinations are necessary until healing has occurred i order to treat a possible local recurrence in time.

Efficacy of a fibrin sealant on healing of extraction wounds.

In 61 patients, bilateral lower impacted third molars were removed. In 30 patients, a fibrin sealant was placed in the alveolus on one side immediately following the operation, while the other side functioned as control. In 31 patients, penicillin was added to the fibrin sealant, and the combination was placed in the alveolus on one side, the other side being the control. No difference with regard to bleeding, pain and swelling during the first postoperative week could be found. There was no difference between the sides regarding the incidence of postoperative infection and the healing of the alveoli after a 1-month control period.