Andrew J. Russ

Role of Platelet-Rich Plasma in Acceleration of Bone Fracture Healing

Platelet-rich plasma (PRP) is a common therapy for acceleration of maxillofacial and spinal fusion bone-graft healing. This study analyzes the therapeutic role of PRP during long-bone fracture healing evaluated Lewis rats. Following creation of unilateral open femur fractures, either 500 &mgr;L thrombin-activated PRP (PRP treated group) or 500 &mgr;L saline (control group) were applied once to the fracture site. Fracture healing was analyzed after 1 and 4 weeks. Following 4 weeks of fracture healing, radiographic analysis demonstrated higher callus to cortex width ratio (P < 0.05) in the PRP group (PRP: 1.65 ± 0.06; control: 1.48 ± 0.05). Three-point load bearing showed increased bone strength following PRP treatment (PRP: 60.85 ± 6.06 Newton, control: 47.66 ± 5.49 Newton). Fracture histology showed enhanced bone formation in the PRP group. Immunohistochemistry and Western-blotting demonstrated healing-associated changes in transforming growth factor (TGF)-β1 and bone morphogenetic protein (BMP)-2. Our results suggest that PRP accelerates bone fracture healing of rat femurs via modulation of TGF-β1 and BMP-2 growth factor expression.

Laparoscopy Improves Short-term Outcomes After Surgery for Diverticular Disease

BACKGROUND & AIMS Observational studies and small randomized controlled trials have shown that the use of laparoscopy in colon resection for diverticular disease is feasible and results in fewer complications. We analyzed data from a large, prospectively maintained, multicenter database (National Surgical Quality Initiative Program) to determine whether the use of laparoscopy in the elective treatment of diverticular disease decreases rates of complications compared with open surgery, independent of preoperative comorbid factors. METHODS The analysis included data from 6970 patients who underwent elective surgeries for diverticular disease from 2005 to 2008. Patients with diverticular disease were identified by International Classification of Diseases, 9th revision codes and then categorized into open or laparoscopic groups based on Current Procedural Terminology codes. Preoperative, intraoperative, and postoperative data were analyzed to determine factors associated with increased risk for postoperative complications. RESULTS Data were analyzed from 3468 patients who underwent open surgery and 3502 patients who underwent laparoscopic procedures. After correcting for probability of morbidity, American Society of Anesthesiology class, and ostomy creation, overall complications (including superficial surgical site infections, deep incisional surgical site infections, sepsis, and septic shock) occurred with significantly lower incidence among patients who underwent laparoscopic procedures compared with those who received open operations. CONCLUSIONS The use of laparoscopy for treating diverticular disease, in the absence of absolute contraindications, results in fewer postoperative complications compared with open surgery.

Suppression of T-cell expansion by melanoma is exerted on resting cells.

BackgroundImmunotherapeutic cancer protocols often rely on the ability to promote proliferative expansion of tumor-specific T-cell, but the influence of cancer on in vivo T-cell expansion remains largely undefined.MethodsThe ability of control and B16F10 melanoma-bearing C57BL/6 mice to expand lymphocytic choriomeningitis virus antigen-specific T-cell populations in response to acute viral infection was compared by using flow cytometric assays of splenocytes.ResultsThe ability to expand virus-specific CD8+ and CD4+ T-cells was globally and markedly suppressed in tumor-bearing mice. Expanded cytotoxic T lymphocytes (CTLs) retained in vivo and in vitro functionality, suggesting that melanoma growth did not induce T-cell anergy. The magnitude of suppressed proliferative expansion was proportional to the extent of tumor burden. Melanoma-induced suppression of CTL expansion was correlated with upregulated apoptotic activity and hampered the induction of memory precursor effector cells. Adoptive transfer of resting LCMV antigen-specific T-cells before or after tumor establishment demonstrated that a critical period of in vivo exposure of resting T-cells to growing melanoma was responsible for the induction of suppressed expansion. This suppression was durable; surgical resection of melanoma after in vivo exposure to resting T-cells but before antigenic stimulation did not restore full expansion.ConclusionsThese data suggest that growing melanoma tumors exert a global, antigen-independent influence on resting T-cells that fundamentally reprograms their ability to undergo proliferative expansion in response to subsequent antigenic stimulation. This finding may have direct implications for T-cell-based immunotherapeutic strategies.

Melanoma-induced suppression of tumor antigen-specific T cell expansion is comparable to suppression of global T cell expansion

We have observed that in vivo interaction between melanoma and resting T cells promotes suppression of antigen-driven proliferative T cell expansion. We hypothesized that this suppression would affect tumor antigen-specific T cell populations more potently than tumor-unrelated T cell populations. A B16F10 cell line was stably transfected to express low levels of the lymphocytic choriomeningitis virus (LCMV) glycoprotein GP33 (B16GP33). Mice bearing B16F10 or B16GP33 tumors were infected with LCMV, and proliferative expansion of LCMV epitope-specific T cell populations was quantified. In vitro and in vivo assays confirmed low levels of antigenic GP33 expression by B16GP33 tumors. Suppressed expansion of GP33-specific T cells was equivalent between mice bearing B16F10 and B16GP33 tumors. These observations suggest that the ability of growing melanoma tumors to impair antigen-driven proliferative expansion of activated T cells is global and not antigen-specific, and provide further insight into the influence of cancer on activated T cell homeostasis.

Gammopathy-associated Acrosclerosis as a Cause of Flexion Contractures in an Older Adult Patient: A Case Report and Literature Review

BACKGROUND This article describes an 87-year-old woman with progressive debilitating flexion contractures involving both hands. In addition, a similar scariform process in this patient extended to involve the upper and lower extremities. The patient had an established history of an IgG monoclonal gammopathy of undetermined significance (MGUS). Her contraction deformities were treated surgically. This is the first known reported case of gammopathy-associated acrosclerosis eventuating in bilateral hand contractures. IgG lambda paraprotein may evoke fibrocyte hypercellularity and sclerosis. Recent studies have used chemotherapy and peripheral stem cell transplantation in the treatment of severe sclerosing reactions associated with MGUS. This more recent approach reflects the inherent basis of the fibrosis, at least in scleromyxedema, and is one that is reflective of a clonal B-cell lymphoproliferative disorder.