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.     

Carotid endarterectomy in patients with chronic renal insufficiency: a recent series of 184 cases

BACKGROUND: The published results of carotid endarterectomy (CEA) in chronic renal insufficiency (CRI) patients are contradictory, mostly because of the relatively small number of patients in these studies. To better assess the neurologic complications and mortality, we reviewed a recent and substantially larger series of CRI patients who underwent CEAs. METHODS: From March 2000 to March 2003, 675 consecutive primary CEAs were performed in 609 patients (346 men, 57%) under general anesthesia. Asymptomatic carotid artery stenosis accounted for 71% of cases. CRI (serum creatinine level > or = 1.5 mg/dL) was detected in 166 patients (27%) who underwent 184 CEAs. The remaining 443 patients (73%) had 491 CEAs. RESULTS: Patients with CRI were different in age (76 +/- 8 years vs 72 +/- 9 years, P < .001), male gender (73% vs 51%, P < .001), coronary artery disease (50% vs 28%, P < .001), and diabetes mellitus incidence (38% vs 27%, P < .02). No significant difference in stroke rates was observed between the CRI patients and the control group (1.2% vs 0.5%). The mortality rate for CRI patients was 3%, whereas it was 0% for the control group ( P < .002). The 143 CRI patients with serum creatinine levels from 1.5 to 2.9 mg/dL had a 0.7% mortality rate, whereas it was 17% for 23 patients with serum creatinine levels of 3 mg/dL or more ( P < .001). The stroke rate for the former group was 0.7% and 4.3% for the latter group (NS). Asymptomatic (16) and symptomatic (7) patients with serum creatinine levels of 3 mg/dL or more had mortality rates of 13% and 28%, respectively, with P = .6. CONCLUSION: The high mortality rate observed in patients with serum creatinine levels of 3 mg/dL or more after CEA calls for a nonoperative approach in the management of asymptomatic patients.     

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.     

Combining automated attenuation-based tube voltage selection and iterative reconstruction: a liver phantom study

Objectives

To determine the value of combined automated attenuation-based tube-potential selection and iterative reconstructions (IRs) for optimising computed tomography (CT) imaging of hypodense liver lesions.

Methods

A liver phantom containing hypodense lesions was imaged by CT with and without automated attenuation-based tube-potential selection (80, 100 and 120 kVp). Acquisitions were reconstructed with filtered back projection (FBP) and sinogram-affirmed IR. Image noise and contrast-to-noise ratio (CNR) were measured. Two readers marked lesion localisation and rated confidence, sharpness, noise and image quality on a five-point scale (1 = worst, 5 = best).

Results

Image noise was lower (31–52 %) and CNR higher (43–102 %) on IR than on FBP images at all tube voltages. On 100-kVp and 80-kVp IR images, confidence and sharpness were higher than on 120-kVp FBP images. Scores for image quality score and noise as well as sensitivity for 100-kVp IR were similar or higher than for 120-kVp FBP and lower for 80-kVp IR. Radiation dose was reduced by 26 % at 100 kVp and 56 % at 80 kVp.

Conclusions

Compared with 120-kVp FBP images, the combination of automated attenuation-based tube-potential selection at 100 kVp and IR provides higher image quality and improved sensitivity for detecting hypodense liver lesions in vitro at a dose reduced by 26 %.

Key Points

? Combining automated tube voltage selection/iterative CT reconstruction improves image quality. ? Attenuation values remain stable on IR compared with FBP images. ? Lesion detection was highest on 100-kVp IR images.     

The efficacy of dietary intervention on urinary risk factors for stone formation in recurrent calcium oxalate stone patients

PURPOSE: Nutrition is suggested to be the major environmental risk factor in idiopathic calcium oxalate stone disease. The study was designed to evaluate the effect of dietary intervention on urinary risk factors for recurrence in calcium oxalate stone formers. MATERIALS AND METHODS: A total of 76 men and 31 women with idiopathic calcium oxalate stone disease collected 24-hour urine on their habitual, self-selected diets and after 7 days on a balanced standardized diet according to the recommendations for calcium oxalate stone formers. RESULTS: On the usual diet, a urine volume of less than 2.0 l per 24 hours was present in 57.9%, hypercalciuria in 25.2%, hypomagnesuria in 18.7%, hyperoxaluria in 14.0%, hyperuricosuria in 41.3% and hypocitraturia in 57.0% of patients. The frequency of metabolic abnormalities and the risk of calcium oxalate stone formation decreased significantly on the ingestion of the balanced diet, due to the significant increase in urinary volume, pH and citrate excretion and the significant decrease in urinary calcium and uric acid excretion. No change occurred in urinary oxalate and magnesium excretion. CONCLUSIONS: The evaluation of urinary risk profiles of the patients on their usual dietary habits revealed a high risk for calcium oxalate stone formation. A low fluid intake and an increased intake of protein and alcohol were identified as the most important dietary risk factors. The shift to a nutritionally balanced diet according to the recommendations for calcium oxalate stone formers significantly reduced the stone forming potential.