Vasopressor use after initial damage control laparotomy increases risk for anastomotic disruption in the management of destructive colon injuries

Background

Management of destructive colon injuries during damage control (DC) laparotomy is debated. The authors reviewed a single institution's experience with destructive colon injuries to identify risk factors for anastomotic failure after colon reconstruction.

Methods

The authors identified all trauma patients sustaining destructive colon injuries between 2002 and 2011 from their medical center's trauma registry. Anastomotic leak was defined as suture or staple line disruption or enteral fistula formation.

Results

Of 171 identified patients, 68 had DC procedures, 41 (60%) had subsequent anastomoses performed during the same hospitalization, and 27 (40%) were diverted. The colon anastomotic leak rate in patients who underwent DC laparotomy was higher than in patients who were reconstructed at the primary operation in a non-DC setting (17% vs 6%, P = .09). The use of vasopressors after the initial DC operation more than quadrupled the leak rate to 50% (P = .02).

Conclusions

Colonic anastomotic disruptions yield deadly consequences, and diversion rather than anastomosis should be used in patients who require vasopressor support after the initial DC procedure.     

Vertebral fractures and trabecular microstructure in men with prostate cancer on androgen deprivation therapy

Androgen deprivation therapy (ADT), a treatment for prostate cancer, is associated with bone loss and fractures. Dual‐energy X‐ray absorptiometry (DXA)–measured bone mineral density does not assess vertebral fractures (VF). High‐resolution micro‐magnetic resonance imaging (HR‐MRI) assesses bone microarchitecture and provides structural information. To determine if VF identification increased the diagnosis of osteoporosis beyond DXA and if HR‐MRI demonstrated skeletal deterioration in men with VF, we cross‐sectionally studied 137 men aged ≥ 60 years with nonmetastatic prostate cancer on ADT for ≥ 6 months. Vertebral fracture assessment (VFA) by DXA was confirmed with X‐rays. HR‐MRI of the wrist included bone volume to total volume (BV/TV), surface density (trabecular plates), surface/curve ratio (plates/rods), and erosion index (higher depicts deterioration). VF were found in 37% of men; the majority were unknown. Seven percent of participants were classified as osteoporotic by hip or spine DXA. Thirty‐seven percent of men without osteoporosis by DXA had VF identified, suggesting that 90% of patients with clinical osteoporosis would have been misclassified by DXA alone. By ANOVA comparison across VF grades, the BV/TV, surface density, and spine, hip, and wrist DXA were lower, and erosion index was higher in men with moderate‐severe VF compared with lesser grades (all p < 0.05). By unadjusted ROC analysis, the addition of HR‐MRI to DXA at the spine, hip, and femoral neck added substantially (AUC increased 0.831 to 0.902, p < 0.05) to prediction of moderate‐severe vertebral fracture. HR‐MRI indices were associated with spine, hip, and wrist DXA measures (p < 0.01). Longer duration of ADT was associated with lower BV/TV, surface density, and surface/curve ratio (p < 0.05). ADT for men with prostate cancer is associated with silent VF. DXA alone leads to misclassifications of osteoporosis, which can be avoided by VF assessment. HR‐MRI provides a novel technique to assess deterioration of structural integrity in men with VF and adds micro‐structural information. © 2013 American Society for Bone and Mineral Research     

Social Competence Intervention Program (SCIP): A pilot study of a creative drama program for youth with social difficulties

This study explored the effects of participation in the Social Competence Intervention Program (SCIP), an innovative creative drama-based group intervention, of children diagnosed with autism spectrum disorder (ASD), nonverbal learning disability (NLD) and/or attention deficit hyperactivity disorder (ADHD). Eighteen participants in SCIP were compared to a clinical control group of 16 on changes in measures of social perception, social competence, and naturalistic observed social behavior. Hierarchical multiple regression model was used for all primary quantitative analyses. Interviews were conducted post-treatment to provide qualitative data. The treatment group showed significant improvement in key domains of observed social behavior in a natural setting compared to the clinical control group. Parents and children in the SCIP condition reported multiple positive changes in social functioning. These findings provide preliminary support for the use of a creative drama program for children with social competence deficits related to social perception problems.     

Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained

Key points

• Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents.
• Little is known about the effects of high‐intensity interval training (HIT) or of purely anaerobic resistance training on AHN.
• Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats.
• We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity.
• Our results confirm that sustained aerobic exercise is key in improving AHN.

Abstract

Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high‐intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low‐response trainer (LRT) and high‐response trainer (HRT) adult male rats to various forms of physical exercise for 6–8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin‐positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non‐significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength. Furthermore, RT had no effect on proliferation (Ki67), maturation (doublecortin) or survival (bromodeoxyuridine) of new adult‐born hippocampal neurons in adult male Sprague–Dawley rats. Our results suggest that physical exercise promotes AHN most effectively if the exercise is aerobic and sustained, especially when accompanied by a heightened genetic predisposition for response to physical exercise.

Abbreviations

AHN

adult hippocampal neurogenesis

BDNF

brain‐derived neurotrophic factor

BrdU

bromodeoxyuridine

HIT

high‐intensity interval training

HRT

high‐response trainer

LRT

low‐response trainer

RW

running wheel

Sed

sedentary

TBS

Tris‐buffered saline

V˙O2max

maximal oxygen uptake

     

Upregulation of GAD65 mRNA in the medulla of the rat model of metabolic syndrome

Although alterations in the function of the neurotransmitter system have been implicated in the pathology of Alzheimer's disease (AD), the mechanisms that underlie this pathological change are not well understood. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key protease in the generation of beta-amyloid, an important trigger protein in the pathogenesis of AD. The expression and activity of BACE1 are increased in the brains of sporadic AD patients, and a role for BACE1 in neurotransmission has been suggested recently. This study examines whether BACE1 plays a role in regulated exocytosis in PC12 cells. Treatment of PC12 cells with a beta-secretase inhibitor reduced stimulus-dependent secretion of neurotransmitters, suggesting a potential role of BACE1 in regulated exocytosis. Using transfected human growth hormone as a reporter for a regulated secretory pathway in PC12 cells, we found that the transient overexpression of BACE1 increased basal secretion in the absence of a stimulus and reduced stimulus-dependent secretion in intact PC12 cells. In digitonin-permeabilized PC12 cells, an overexpression of BACE1 enhanced the Ca2+-independent and ATP-independent component of the secretory pathway. Furthermore, expression of the glycosylation-deficient mutant of BACE1, BACE1N354Q, led to an elevation of basal secretions over that by BACE1 wild-type, suggesting a role of BACE1 glycosylation in basal secretion. These results demonstrate an unknown role for BACE1 in secretion, and suggest that elevated levels of BACE1 in AD brains may contribute to the altered neurotransmitter pathology of AD through stimulation of spontaneous basal secretion under resting conditions.     

A Rifapentine-Containing Inhaled Triple Antibiotic Formulation for Rapid Treatment of Tubercular Infection

Purpose

The potential for rifapentine-containing oral therapeutic regimens to significantly shorten the current six-month anti-tubercular treatment regimen is confounded by high plasma protein binding of rifapentine. Inhaled aerosol delivery of rifapentine, a more potent anti-tubercular antibiotic drug, in combination with other first-line antibiotics may overcome this limitation to deliver a high drug dose at the pulmonary site of infection.

Methods

A formulation consisting of rifapentine, moxifloxacin and pyrazinamide, with and without leucine, was prepared by spray-drying. This formulation was assessed for its physico-chemical properties, in vitro aerosol performance and antimicrobial activity.

Results

The antibiotic powders, with and without leucine, had similar median aerodynamic diameters of 2.58?±?0.08 μm and 2.51?±?0.06 μm, with a relatively high fine particle fraction of 55.5?±?1.9% and 63.6?±?2.0%, respectively. Although the powders were mostly amorphous, some crystalline peaks associated with the δ polymorph for the spray-dried crystalline pyrazinamide were identified.

Conclusions

Stabilisation of the powder with 10% w/w leucine and protection from moisture ingress was found to be necessary to prevent overt crystallisation of pyrazinamide after long-term storage. In vitro biological assays indicated antimicrobial activity was retained after spray-drying. Murine pharmacokinetic studies are currently underway.     

Characterization of Open-Cell Sponges via Magnetic Resonance and X-ray Tomography

The applications of polymeric sponges are varied, ranging from cleaning and filtration to medical applications. The specific properties of polymeric foams, such as pore size and connectivity, are dependent on their constituent materials and production methods. Nuclear magnetic resonance imaging (MRI) and X-ray micro-computed tomography (µCT) offer complementary information about the structure and properties of porous media. In this study, we employed MRI, in combination with µCT, to characterize the structure of polymeric open-cell foam, and to determine how it changes upon compression, µCT was used to identify the morphology of the pores within sponge plugs, extracted from polyurethane open-cell sponges. MRI T₂ relaxation maps and bulk T₂ relaxation times measurements were performed for 7° dH water contained within the same polyurethane foams used for µCT. Magnetic resonance and µCT measurements were conducted on both uncompressed and 60% compressed sponge plugs. Compression was achieved using a graduated sample holder with plunger. A relationship between the average T₂ relaxation time and maximum opening was observed, where smaller maximum openings were found to have a shorter T₂ relaxation times. It was also found that upon compression, the average maximum opening of pores decreased. Average pore size ranges of 375–632 ± 1 µm, for uncompressed plugs, and 301–473 ± 1 µm, for compressed plugs, were observed. By determining maximum opening values and T₂ relaxation times, it was observed that the pore structure varies between sponges within the same production batch, as well as even with a single sponge.