Tumor-induced mechanical hyperalgesia involves CGRP receptors and altered innervation and vascularization of DsRed2 fluorescent hindpaw tumors

Functional and anatomical relationships among primary afferent fibers, blood vessels, and cancers are poorly understood. However, recent evidence suggests that physical and biochemical interactions between these peripheral components are important to both tumor biology and cancer-associated pain. To determine the role of these peripheral components in a mouse model of cancer pain, we quantified the change in nerve and blood vessel density within a fibrosarcoma tumor mass using stereological analysis of serial confocal optical sections of immunostained hind paw. To this end we introduced the Discoma coral-derived red fluorescent protein (DsRed2) into the NCTC 2472 fibrosarcoma line using the Sleeping Beauty transposon methodology, thus providing a unique opportunity to visualize tumor-nerve-vessel associations in context with behavioral assessment of tumor-associated hyperalgesia. Tumors from hyperalgesic mice are more densely innervated with calcitonin gene related peptide (CGRP)-immunoreactive nerve fibers and less densely vascularized than tumors from non-hyperalgesic mice. As hyperalgesia increased from Day 5 to 12 post-implantation, the density of protein gene product 9.5 (PGP9.5)-immunoreactive nerves and CD31-immunoreactive blood vessels in tumors decreased, whereas CGRP-immunoreactive nerve density remained unchanged. Importantly, intra-tumor injection of a CGRP1 receptor antagonist (CGRP 8-37) partially blocked the tumor-associated mechanical hyperalgesia, indicating that local production of CGRP may contribute to tumor-induced nociception through a receptor-mediated process. The results describe for the first time the interaction among sensory nerves, blood vessels and tumor cells in otherwise healthy tissue, and our assessment supports the hypothesis that direct tumor cell-axon communication may underlie, at least in part, the occurrence of cancer pain.     

Comparative biomechanical study on three miniplates osteosynthesis systems for stabilisation of low condylar fractures of the mandible

Open reduction and fixation of low condylar fractures of the mandible can be achieved by many osteosynthesis systems that differ in size, shape, and site of placement according to the surgical approach. We investigated the maximum load and rigidity of 4 osteosynthesis systems: the standard double 4-hole straight miniplates, the inverted y-miniplate (with and without self-drilling screws), and the TriLock Delta condyle trauma plate. The standard double 4-hole straight miniplate osteosynthesis achieved the best fixation and resistance in view of a mean (SD) maximum load of 539.8 (100.2) N, followed by the inverted y-miniplate with the self-drilling screws (246.5 (23.8) N), the inverted y-miniplate with standard screws (242.4 (27.2) N), and finally the TriLock Delta plate (167.4 (39.2) N). Analysis of the slope of the force–displacement diagram from 80 N to 100 N in each group showed that the TriLock Delta miniplate had the highest values for rigidity (17.3 (5.1) N/μm), followed by the inverted y-miniplate groups with self-drilling screws (14.1 (6.4) N/μm), and with standard screws (12.6 (2.5) N/μm). The double 4-hole straight miniplate osteosynthesis had the lowest rigidity (8.7 1.4) N/μm). Despite the significant difference in the maximum load between the double 4-hole miniplates and other investigated osteosynthesis patterns, all groups had sufficient load for the fixation of low condylar fractures of the mandible when postoperative bite forces and the slowly increasing voluntary clenching during healing were considered.     

Infection and rejection risk after cardiac transplantation with induction vs. no induction: a multi‐institutional study

Data from Cardiac Transplant Research Database (CTRD) were analyzed from 1999 to 2006 to examine the effects of different induction strategies at the time of cardiac transplantation. A total of 2090 primary heart transplants were categorized by induction with interleukin‐2 receptor blocker (IL‐2RB), antithymocyte globulin (ATG), or no induction (NI). Probabilities for rejection and infection were estimated with parametric time‐related models. Using these models, hazard was calculated for two theoretical patient profiles, one at lower risk for rejection and higher risk of infection (Profile 1) and higher risk for rejection and lower risk of infection (Profile 2). Of the 2090 transplants, 49.8% (1095) did not receive induction, 27.3% (599) received IL‐2RB, and 18.0% (396) received ATG. Profile 1 patients had lower hazard for rejection with IL‐2RB compared to ATG and NI (p < 0.01), but at the cost of increased risk of infection (5.0 vs. 1.8 vs. 1.6, respectively, at four wk, p < 0.01). Profile 2 patients experienced a fivefold decreased hazard for rejection when treated with IL‐2RB compared with ATG and NI (p < 0.01). In patients at high risk of infection, IL‐2RB reduced risk of rejection but at the expense of increased hazard for infection.     

Establishing a Role for Vancomycin Powder Application for Prosthetic Joint Infection Prevention—Results of a Wear Simulation Study

Topical vancomycin powder (VP) has shown efficacy and safety in decreasing post-operative spine infections. VP use in arthroplasty has not been established. Concerns remain for third-body wear with the addition of crystalline substrate at the implant interface. The study's purpose was to compare wear behavior of CoCr on UHMWPE to identical wear couples with VP. A six-station wear simulator was utilized and cyclic articulations were run for 10 million cycles (Mc). UHMWPE wear was measured using photography, stereomicroscopy, and gravimetric measurement. There were no differences in wear mark length (P = 0.43), width (P = 0.49), or gravimetric wear at 10 Mc (P = 0.98). VP and control groups lost 0.32 and 0.33 mg, respectively. VP may have a role in PJI prevention. A well-designed clinical study is needed.     

A Longitudinal Investigation of Changes to Social Resources Associated With Psychological Distress Among Kurdish Torture Survivors Living in Northern Iraq

Social resources can buffer against psychological distress following potentially traumatic events. Psychological distress can also lead to social resource deterioration. This longitudinal study evaluated whether baseline psychological distress symptoms and changes in these symptoms were associated with changes in social resources 5 months later among 96 adult male (52.6%) and female treatment‐seeking torture survivors residing in Kurdistan, Iraq. Adapted versions of the Hopkins Symptom Checklist‐25, Harvard Trauma Questionnaire, and a traumatic grief measure were used. Locally derived scales measured perceived social support, social integration, and frequency of social contact. Multinomial logistic regression models assessed the association between symptoms and loss or gain in social resources. We hypothesized that higher mental health symptoms would relate to decreased social resources. Higher baseline depression (adjusted conditional odds ratio [ACOR] = 1.14), posttraumatic stress disorder (PTSD; ACOR = 1.09), and traumatic grief symptoms (ACOR = 1.14) increased the odds of loss of social integration. For some, higher traumatic grief symptoms were associated with increased social integration (ACOR = 1.17). Increased anxiety (ACOR = 1.23) and PTSD symptoms (ACOR = 1.07) was associated with declines in social contact; decreased depression (ACOR = 1.06) and PTSD symptoms (ACOR = 1.04) were related to gaining social contact. This study highlights the complex relationship between mental health symptoms and losses and gains in social resources among torture survivors.     

Long-Term toxicity studies in Canine of E10A, an adenoviral vector for human endostatin gene

E10A, a recombinant adenovirus type 5 vector carrying the human endostatin gene, may be a promising gene therapy drug in the treatment of solid tumors by antiangiogenesis, but a preclinical safety evaluation of E10A has not yet been performed. With high and low doses equivalent to 30 and 7.5 times the human curative dose, respectively, intramuscular injections of E10A were given once daily, 6 days/week, for 3 months, followed by a 1-month recovery period. As of 4 months, all experimental animals appeared generally healthy: normal behavior and eating habits, no nausea, vomiting, or salivation, no abnormal changes in urination or defecation, and increased body weight with the time of experiment. Urinalysis, hemogram, blood biochemistry, electrocardiogram, macroscopic and microscopic studies of organs and tissues were done before treatment, at month 3 of treatment, and 1 month posttreatment. At all time points, no significant abnormal toxic effects were noted. Preliminary investigation of E10A immunotoxicity in dogs indicated that anti-adenoviral antibodies were generated, in a dose- and time-independent manner, after E10A injection. Our data demonstrated that, long term, high-dose intramuscular administration of recombinant human endostatin-carrying adenovirus (E10A) was not notably toxic and might be safe for clinical therapeutic use, although additional long-term toxicity studies by other administration routes are still necessary.     

Anterior cruciate ligament reconstruction using hamstring autograft in over-40 patients. Does preoperative arthritic changes matter?

Introduction

The purpose of this study was to assess the effect of osteoarthritis on the outcome of arthroscopic anterior cruciate ligament (ACL) reconstruction, and to assess the effect of the procedure on the progression of osteoarthritis.

Material and methods

Forty-two patients, age above 40, presenting by symptomatic instability secondary to rupture of the ACL were enrolled in a prospective cohort study. Cases were divided into two groups according to the absence of osteoarthritic changes (group I, 19 patients) or presence of osteoarthritic changes (group II, 23 patients) in preoperative radiographs. ACL anatomic single bundle reconstruction by the anteromedial portal technique using hamstring autograft fixed by biodegradable interference fit screws was done for all patients, and a fixed postoperative rehabilitation protocol was applied. Data were recorded and statistical analysis of the preoperative, 1 year follow up, and final follow up (average 41 months in group I and 42 months in group II) results of both groups was conducted.

Results

The average patient age at the time of operation was 44.5 years in group I versus 46.4 years in group II. The follow-up median pain scores, ROM, modified Lysholm scores were significantly better in group I compared to group II. On the contrary, the difference between preoperative and 1 year postoperative scores and the percentage of improvement of the modified Lysholm score were significantly higher in group II. Deterioration of the radiographic grade of osteoarthritis in the final follow-up was declared in 15.8 % of patients of group I and in 21.7 % of patients of group II (P?=?0.71). Age, concomitant meniscus injury, and presence of preoperative arthritic changes, and cartilage defect had no statistically significantly effect on the success rate. Patients who had ACL reconstruction more than 2 years after injury and those with higher body mass index (BMI) had worse outcome than those who had earlier reconstruction and lower BMI.

Conclusion

Patients having preoperative mild to moderate arthritic changes will indeed benefit from ACL reconstruction at short term, although their overall functional outcome seemed to be inferior to the outcome of non-arthritic patients. However, osteoarthritic changes deteriorate over time in both groups especially when there is preoperative mild to moderate arthritic changes.