Analysis of skeletal muscle microcirculation in a porcine polytrauma model with haemorrhagic shock

Polytraumatised patients with haemorrhagic shock are prone to develop systemic complications, such as SIRS (systemic inflammatory response syndrome), ARDS (acute respiratory distress syndrome) and MOF (multiple organ failure). The pathomechanism of severe complications following trauma is multifactorial, and it is believed that microcirculatory dysfunction plays an important role. The aim of this study was to determine the changes in the microcirculation in musculature over time during shock and subsequent resuscitation in a porcine model of haemorrhagic shock and polytrauma. Twelve pigs (German Landrace) underwent femur fracture, liver laceration, blunt chest trauma, and haemorrhagic shock under standard anaesthesia and intensive care monitoring. Microcirculation data were measured from the vastus lateralis muscle using a combined white light spectrometry and laser spectroscopy system every 15 min during the shock and resuscitation period, and at 24, 48, and 72 h. Oxygen delivery and oxygen consumption were calculated and compared to baseline. The relative haemoglobin, local oxygen consumption, and saturation values in the microcirculation were observed significantly lower during shock, however, no changes in the microcirculatory blood flow and microcirculatory oxygen delivery were observed. After resuscitation, the microcirculatory blood flow and relative haemoglobin increased and remained elevated during the whole observation period (72 h). In this study, we observed changes in microcirculation during the trauma and shock phases. Furthermore, we also measured persistent dysfunction of the microcirculation over the observation period of 3 days after resuscitation and haemorrhagic shock. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1377–1382, 2018.

     

Smoking and the developing brain: Altered white matter microstructure in attention‐deficit/hyperactivity disorder and healthy controls

Brain white matter (WM) tracts, playing a vital role in the communication between brain regions, undergo important maturational changes during adolescence and young adulthood, a critical period for the development of nicotine dependence. Attention‐deficit/hyperactivity disorder (ADHD) is associated with increased smoking and widespread WM abnormalities, suggesting that the developing ADHD brain might be especially vulnerable to effects of smoking. This study aims to investigate the effect of smoking on (WM) microstructure in adolescents and young adults with and without ADHD. Diffusion tensor imaging was performed in an extensively phenotyped sample of nonsmokers (n = 95, 50.5% ADHD), irregular smokers (n = 41, 58.5% ADHD), and regular smokers (n = 50, 82.5% ADHD), aged 14–24 years. A whole‐brain voxelwise approach investigated associations of smoking, ADHD and their interaction, with WM microstructure as measured by fractional anisotropy (FA) and mean diffusivity (MD). Widespread alterations in FA and MD were found for regular smokers compared to irregular and nonsmokers, mainly located in the corpus callosum and WM tracts surrounding the basal ganglia. Several regions overlapped with regions of altered FA for ADHD versus controls, albeit in different directions. Irregular and nonsmokers did not differ, and ADHD and smoking did not interact. Results implicate that smoking and ADHD have independent effects on WM microstructure, and possibly do not share underlying mechanisms. Two mechanisms may play a role in the current results. First, smoking may cause alterations in WM microstructure in the maturing brain. Second, pre‐existing WM microstructure differences possibly reflect a risk factor for development of a smoking addiction. Hum Brain Mapp 36:1180–1189, 2015. © 2014 Wiley Periodicals, Inc.     

Associations between high callous–unemotional traits and quality of life across youths with non-conduct disorder diagnoses

Research regarding callous–unemotional (CU) traits in non-conduct disorder (CD) diagnoses is sparse. We investigated the presence of high CU traits and their associations with quality of life (QoL) in a clinically referred sample of youths with non-CD diagnoses. Parents of 1018 children referred to a child and adolescent psychiatric clinic and rated their child’s CU traits and QoL. Experienced clinicians derived DSM-IV-TR diagnoses based on systematic clinical evaluations of these children. High CU traits compared to low CU traits were present in 38.5 % of the sample, and more often in boys than girls (69.4 vs. 30.6 %, p = .004), and were associated with more police contacts (12.2 vs. 3.5 %, p < .001). Logistic regression analyses revealed that those with diagnoses of autism spectrum disorder (odds ratio; OR = 1.61; 95 % CI 1.24–2.09; p < .001) and disruptive behavior disorder not otherwise specified/oppositional defiant disorder (OR = 4.98; 95 % CI 2.93–8.64; p < .001), but not attention-deficit/hyperactivity disorder (OR = 1.01; 95 % CI .79–1.31; p = .94), were more likely to have high than low CU traits. Those with anxiety/mood disorders were more likely to have low than high CU traits (OR = .59; 95 % CI .42–82; p = .002). In all diagnostic groups, high CU compared to low CU traits were associated with significantly lower QoL, while controlling for gender, age, and comorbidity. As such, high CU traits significantly modify QoL in non-CD disorders.     

Prognostic factors in patients with bladder carcinoma treated with definitive irradiation

An analysis was performed of 116 patients with bladder carcinoma who completed definitive radiotherapy at a single institution. Patients were analyzed for survival and local control. The overall 5-year survival rate was 34%. A multivariate analysis of survival showed disease stage, hemoglobin level, histologic grade, and total dose to be significant factors in outcome. The local control rates for Stage A, B, C, and D patients were 26%, 36%, 18%, and 0%, respectively. The multivariate analysis revealed disease stage and pretreatment hemoglobin level to be significant predictors of local control. In patients unsuitable for surgery or current combined technique protocols, high-dose irradiation may offer some patients survival and local control. Furthermore, prognostic factors in this study may aid in the stratification necessary for current protocol designs.     

Feasibility of RNA collection for micro-array gene expression analysis in the treatment of cervical carcinoma: a scientific correlate of RTOG C-0128

PURPOSE: To determine the feasibility of RNA collection in a multi-institutional cooperative group setting to be utilized for micro-array gene expression analysis, and to describe the methodology. METHODS: RTOG C0128, a phase I-II, protocol was designed to look at the safety and efficacy of external beam radiation therapy to 45 Gy with concomitant 5-FU and cisplatin chemotherapy, brachytherapy to deliver 85 Gy to point A, and Celecoxib at 400 mg twice daily for 1 year. Patients had the option of participating in a tissue collection portion of the protocol to be utilized for micro-array gene expression analysis before treatment and at the time of the first implant. RNA quality was determined by two parameters: the absorbance ratio at 260 nm/280 nm, and by the ratio of the integrated peak of 28S RNA to 18S RNA after gel electrophoresis. RESULTS: From August 2001 to March 2004, 84 patients were accrued to the trial, and tissue was obtained prior to initiation of therapy on 34 patients (40%). FIGO stages for the patients who provided tissue were IB (23%), II (57%), and IIIA-IVA (20%). Additionally, biopsies were obtained at the time of the first implant from 22 of the accrued patients making paired samples available on 26% for RNA extraction and micro-array gene expression analysis. The mean +/- SEM amount of tissue obtained pretreatment was 97 +/- 13 mg compared with 51 +/- 8 mg for tissue obtained at the time of the first implant (P = 0.009). The mean total RNA extracted from the samples prior to treatment was 119 +/- 19 microg versus 35 +/- 6 microg at the time of the first procedure (P = 0.001). The RNA quality was assessed via the absorbance ratio at 260 nm divided by 280 nm. The mean values pretreatment and at first implant were 1.87 +/- 0.07 versus 1.66 +/- 0.11, respectively (P = 0.002); however, the integrated peak of 28S RNA to 18S RNA after gel electrophoresis was not significantly different (P = 0.26). CONCLUSIONS: RNA extraction for gene expression analysis can be successfully performed in the multi-institutional cooperative group setting. Fresh tissue samples were obtained on 40% of accrued patients prior to treatment. The amount of biopsy material and the quantity of RNA extracted were greater prior to treatment compared with the first implant. The quality of RNA was superior prior to treatment as measured by the ratio of absorbance at 260/280 nm. These results indicate that gene expression analysis is feasible in the cooperative group setting utilizing amplification techniques for the RNA. Hopefully, this will allow for improvement in prognosis, therapeutic development, and correlation with acute and late toxicities in patients with cancer.     

A comparative SEM-study on the teeth of 10 anuran species

Teeth of 10 anuran species have been investigated by means of scanning electron microscopy (SEM). Generally a great variability of the structure of dentine crowns and the zone of division was noted not only between the single species, but also within one species on the same dentigerous bone. 4 species (Hyla cinerea, Rana ridibunda, R. hosei, Ptychadena spec.) mostly have more or less bladed bicuspid and clearly divided teeth corresponding to the "Lissamphibia"-pattern. 2 species (Xenopus laevis, X. spec.) exhibit conical spike-like teeth with a trace of a dividing zone similar to those observed in late stage larvae of Urodela. One species (Ceratophrys cranwelli) shows undivided bladed monocuspid teeth. It is assumed that the 2 species of Dendrobatidae (Dendrobates tricolor, D. anthonyi) examined have no zone of division. Its occurrence in Gastrotheca riobambae and in the few juvenile D. tricolor available is still doubtful. Results are discussed regarding the variability of tooth structures (dentine crown, zone of division, pedicel) and the occurrence of 2 types of monocuspid teeth in the Amphibia as well as its possible bearing upon phylogeny and systematics of this group.