The effects of PTH,loading and surgical insult on cancellous bone at the bone–implant interface in the rabbit

Enhancing the quantity and quality of cancellous bone with anabolic pharmacologic agents may lead to more successful outcomes of non-cemented joint replacements. Using a novel rabbit model of cancellous bone loading, we examined two specific questions regarding bone formation at the bone–implant interface: (1) does the administration of intermittent PTH, a potent anabolic agent, and mechanical loading individually and combined enhance the peri-implant cancellous bone volume fraction; and, (2) does surgical trauma enhance the anabolic effect of PTH on peri-implant bone volume fraction. In this model, PTH enhanced peri-implant bone volume fraction by 30% in loaded bone, while mechanical loading alone increased bone volume fraction modestly (+ 10%). Combined mechanical loading and PTH treatment had no synergistic effect on any cancellous parameters. However, a strong combined effect was found in bone volume fraction with combined surgery and PTH treatment (+ 34%) compared to intact control limbs. Adaptive changes in the cancellous bone tissue included increased ultimate stress and enhanced remodeling activity. The number of proliferative osteoblasts increased as did their expression of pro-collagen 1 and PTH receptor 1, and the number of TRAP positive osteoclasts also increased. In summary, both loading and intermittent PTH treatment enhanced peri-implant bone volume, and surgery and PTH treatment had a strong combined effect. This finding is of clinical importance since enhancing early osseointegration in the post-surgical period has numerous potential benefits.     

Association of orexin receptor polymorphisms with antipsychotic-induced weight gain

Objectives: Antipsychotic-induced weight gain (AIWG) is a common side effect of treatment with antipsychotics such as clozapine and olanzapine. The orexin gene and its receptors are expressed in the hypothalamus and have been associated with maintenance of energy homeostasis. In this study, we have analysed tagging single nucleotide polymorphisms (SNPs) in orexin receptors 1 and 2 (HCRTR1 and HCRTR2) for association with AIWG. Methods: Schizophrenia or schizoaffective disorder subjects (n?=?218), treated mostly with clozapine and olanzapine for up to 14 weeks, were included. Replication was conducted in a subset of CATIE samples (n?=?122) treated with either olanzapine or risperidone for up to 190 days. Association between SNPs and AIWG was assessed using analysis of covariance (ANCOVA) with baseline weight and duration of treatment as covariates. Results: Several SNPs in HCRTR2 were nominally associated with AIWG in patients of European ancestry treated with either clozapine or olanzapine (P<0.05). In the replication analysis two SNPs rs3134701 (P?=?0.043) and rs12662510 (P?=?0.012) were nominally associated with AIWG. None of the SNPs in HCRTR1 were associated with AIWG. Conclusion: This study provides preliminary evidence supporting the role of HCRTR2 in AIWG. However, these results need to be confirmed in large study samples.     

Characterisation of the cell suspension harvested from the dermal epidermal junction using a ReCell® kit

Background

The use of non-cultured autologous cells to promote wound healing and in reconstructive procedures is increasing. One common method for preparing these cells is the use of the ReCell^® device. However, despite its current clinical use, no characterisation of the cell suspension produced using a ReCell^® device has been published.

Objective

To characterise the ReCell suspension that is applied to wounds for cell type, viability, yield, stability and proliferative potential.

Methods

The ReCell^® device was used to harvest cells from a 2 cm² piece of split-thickness skin isolated using a dermatome. The resulting cell suspension was analysed for cell yield, cell type, viability over time, proliferative potential and reproducibility.

Results

Average viable cell yield was 1.7 × 10⁶/cm² of tissue, with 75.5% of the total cell isolate viable. Total viable cell number was not significantly reduced after 4 h storage at 22 °C or 4 °C, and was stable for 24 h at 4 °C. Proliferative potential was assessed using a colony forming assay, with 0.3% of viable cells isolated forming keratinocyte colonies. Predominantly the suspension contained keratinocytes (64.3 ± 28.8%) and fibroblasts (30.3 ± 14.0%), with a small population of melanocytes also identified (3.5 ± 0.5%). Finally, the supernatant contained low total protein (0.92 mg/ml) and the supernatant had no significant effects on cell viability or growth when applied ex vivo.

Conclusions

These results suggest the ReCell^® device provides a method for the preparation of a cell suspension with high viability and proliferative potential, containing viable melanocytes and no apparent toxic cell debris. Further work on the sustained viability of these cells in vivo, and in particular after application to the wound, will be important to better understand the potential of the ReCell^® device in the clinic.     

Percutaneous fixation of acetabular fractures: computer-assisted determination of safe zones, angles and lengths for screw insertion

Introduction

Percutaneous retrograde screw fixation for acetabular fractures is a demanding procedure due to the complex anatomy of the pelvis and the varying narrow safe bony corridors. Limited information is available on optimal screw placement and the geometry of safe zones for screw insertion in the pelvis.

Methods

Three-dimensional reconstructions of 50 consecutive CT scans of polytrauma patients (35 males, 15 females) were used to introduce three virtual CAD bolts (representing screws) into the anterior column (superior ramus of the pubic bone), posterior column (the ischial bone) and the supraacetabular region, as performed during percutaneous screw fixation. The three-dimensional (3D) position of these screws was evaluated with a computer software (MIMICS) after virtual optimal insertion. The 3D position, the narrowest zone and the distance to the hip joint of the two columns and the supraacetabular region were defined.

Results

The mean maximal screw length for the three virtual screws measured between 107.4 and 148?±?18.7?mm. The narrowest zone of the pelvic bone (superior pubic ramus) had a width of 9.2?±?2.4?mm. The average distances between the bolts and the hip joint were 3.9 and 19.4?±?7.4?mm. For the anterior column (superior pubic ramus) screw, the mean lateral angle to the sagittal midline plane was 39.0?±?3.2° and the mean posterior angle to the transversal midline plane was 15.1?±?4.0°. The mean supraacetabular screw angles measured 22.4?±?3.4° (medial), 35.3?±?4.6° (cranial) and the mean angles for the ischial screw were 12.0?±?5.4° (posterior) and 18.4?±?4.0° (lateral).

Conclusions

The zones for safe screw positioning are very narrow, making percutaneous screw fixation of the acetabulum a challenging procedure. The predefined angles for the most frequently positioned percutaneous screws may aid in preoperative planning, decrease operative and radiation times and help to increase safe insertion of screws.     

The role of shame in distinguishing perpetrators of intimate partner violence in U.S. veterans

Increasing attention is being paid to the fact that exposure to traumatic stressors in military combat may lead to perpetration of intimate partner violence (IPV). Because shame has been identified as a factor in posttraumatic stress disorder (PTSD), the current cross-sectional study examined the relationship in U.S. veterans between IPV and PTSD, depression, guilt, and shame. We hypothesized that shame would be the strongest correlate of perpetration of IPV and that shame would mediate the relationship between PTSD and IPV. Participants were 264 primarily male and Caucasian mixed-era veterans presenting for psychological treatment at a Veterans Affairs hospital. They completed standard measures of depression, PTSD symptoms, shame, and guilt and a local checklist was used to dichotomize the sample regarding IPV. Discriminant analysis indicated that shame contributed most (standardized canonical discriminant function coefficient = .44) to distinguishing perpetrators of IPV. In addition, the results were consistent with shame as a mediator of the relationship between PTSD and IPV. These results are in line with studies indicating that shame is linked to IPV perpetration in nonveteran samples (Harmon, 2002; Rand, 2004; Schibik, 2002) and suggests that shame may be an important aspect of the relationship between PTSD and IPV.     

Staged management of giant abdominal wall defects: acute and long-term results

INTRODUCTION: Shock resuscitation leads to visceral edema often precluding abdominal wall closure. We have developed a staged approach encompassing acute management through definitive abdominal wall reconstruction. The purpose of this report is to analyze our experience with this technique applied to the treatment of patients with open abdomen and giant abdominal wall defects. METHODS: Our management scheme for giant abdominal wall defects consists of 3 stages: stage I, absorbable mesh insertion for temporary closure (if edema quickly resolves within 3-5 days, the mesh is gradually pleated, allowing delayed fascial closure); stage II, absorbable mesh removal in patients without edema resolution (2-3 weeks after insertion to allow for granulation and fixation of viscera) and formation of the planned ventral hernia with either split thickness skin graft or full thickness skin closure over the viscera; and stage III, definitive reconstruction after 6-12 months (allowing for inflammation and dense adhesion resolution) by using the modified components separation technique. Consecutive patients from 1993 to 2001 at a single institution were evaluated. Outcomes were analyzed by management stage, with emphasis on wound related morbidity and mortality, and fistula and recurrent hernia rates. RESULTS: Two hundred seventy four patients (35 with sepsis, 239 with hemorrhagic shock) were managed. There were 212 males (77%), and mean age was 37 (range, 12-88). The average size of the defects was 20 x 30 cm. In the stage I group, 108 died (92% of all deaths) because of shock. The remaining 166 had temporary closure with polyglactin 910 woven absorbable mesh. As visceral edema resolved, bedside pleating of the absorbable mesh allowed delayed fascial closure in 37 patients (22%). In the stage II group, 9 died (8% of all deaths) from multiple organ failure associated with their underlying disease process, and 96% of the remaining 120 had split-thickness skin graft placed over the viscera. No wound related mortality occurred. There were a total of 14 fistulae (5% of total, 8% of survivors). In the stage III group, to date, 73 of the 120 have had definitive abdominal wall reconstruction using the modified components separation technique. There were no deaths. Mean follow-up was 24 months, (range 2-60). Recurrent hernias developed in 4 of these patients (5%). CONCLUSIONS: The staged management of patients with giant abdominal wall defects without the use of permanent mesh results in a safe and consistent approach for both initial and definitive management with low morbidity and no technique-related mortality. Absorbable mesh provides effective temporary abdominal wall defect coverage with a low fistula rate. Because of the low recurrent hernia rate and avoidance of permanent mesh, the components separation technique is the procedure of choice for definitive abdominal wall reconstruction.     

Associations among psychosis,mood, anxiety,and posttraumatic stress symptoms: A network analysis

The associations among psychotic experiences (i.e., hallucinations and delusions), trauma exposure, and posttraumatic stress symptoms are complex and multidirectional. Using network analysis to understand how psychotic experiences and symptoms of posttraumatic stress disorder (PTSD) relate to one another may identify new interventional targets to treat comorbidity and its underlying pathological processes. This study aimed to use network analysis to examine the associations among psychotic experiences; negative symptoms of psychosis; and symptoms of PTSD, anxiety, and depression. In this population-based cohort study, 4,472 participants (36.7% male) were assessed for psychotic experiences, negative symptoms of psychosis, PTSD, anxiety, and depression at age 23 (M = 23.86 years, SD = 0.520) or 24 years (M = 24.03, SD = 0.848). Associations among symptoms were assessed via network analysis. Exploratory graph analysis identified three clusters of densely connected symptoms within the overall network: psychotic experiences; PTSD symptoms; and depressive and anxiety symptoms and negative symptoms of psychosis. Psychotic experiences had the strongest associations with other symptoms in the network, and symptoms of anxiety played a key role in bridging psychotic experiences, symptoms of PTSD, and depressive symptoms. Consistent with the stress reactivity and affective models for psychotic experiences, the results suggest that symptoms of anxiety and emotional distress (e.g., hyperarousal, panic) may have a key role in the development and maintenance of psychotic experiences and symptoms of PTSD. Targeting these symptoms may ameliorate symptom burden transdiagnostically.     

Attenuated Salmonella typhimurium with interleukin 2 gene prevents the establishment of pulmonary metastases in a model of osteosarcoma

Purpose

The current management of osteosarcoma (OS) entails an aggressive preoperative and postoperative chemotherapeutic regimen with limb salvage surgery. Despite these efforts, relapse-free survival is less than 60% in patients with classic OS, whereas most patients relapse with pulmonary metastases. In these studies, we sought to prevent the establishment of pulmonary metastases from OS with a single oral dose of SalpIL2.

Methods

Mice were administered attenuated Salmonella typhimurium with (SalpIL2) and without a gene for human interleukin 2 (Sal-NG) 7 days before challenge with 2 × 10⁵ OS cells via tail vein. Three weeks after injection, mice were harvested for splenic lymphocytes and tumor enumeration.

Results

Prophylaxis with attenuated SalpIL2 significantly reduces pulmonary metastases in number and volume (P < .0001 and P < .0001) with respect to saline controls. Furthermore, splenic natural killer cell populations were increased 396% with SalpIL2 (P < .0007) and 426% with Sal-NG (P < .0003) compared to nontreated groups.

Conclusions

Host natural killer response is greatly amplified and maybe partially responsible for the effective immune response against the formation of pulmonary metastases. A single oral dose of SalpIL2 may be a novel form of adjuvant therapy for patients after early detection of primary OS.