Peer Victimization Trajectories at the Adolescent Transition: Associations Among Chronic Victimization,Peer-Reported Status,and Adjustment

The current study demonstrated that chronic peer victimization, as compared to time-limited victimization, is particularly associated with peer status and peer-reported adjustment at the adolescent transition. Using a cohort sequential design, a sample of 653 adolescents (48% female, 87% Caucasian) in Grades 6–8 were assessed at 3 annual time points; data captured indices of peer victimization, likeability, popularity, and several peer-reported indices of internalizing (e.g., sadness, worry) and externalizing (e.g., anger, fighting) symptoms across Grades 6–10. Four trajectories of victimization experiences were identified—chronic, high decreasing, low increasing, and low stable—suggesting instability in victimization experiences over time. Adolescents who experienced chronic victimization, as compared to those with low-stable, decreasing, or increasing levels of victimization, were rated by peers more often on indices of maladjustment and less often on measures of popularity and likeability. Findings highlight negative associations with chronic victimization and underscore the need for targeted interventions to prevent chronic victimization. Overall, findings further emphasize the role of chronicity in victimization and highlight the importance of identifying chronic victims for intervention and prevention efforts.     

Towards human ex vivo organ perfusion models to elucidate drug pharmacokinetics in health and disease

Abstract

To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions of ADME profiles earlier in the drug development process are very valuable. Good prediction of intestinal absorption and renal and biliary excretion remain especially difficult, as there is an interplay of active transport and metabolism involved. To study these processes, including enterohepatic circulation, ex vivo tissue models are highly relevant and can be regarded as the bridge between in vitro and in vivo models. In this review the current in vitro, in vivo and in more detail ex vivo models for studying pharmacokinetics in health and disease are discussed. Additionally, we propose novel models, i.e., perfused whole-organs, which we envision will generate valuable pharmacokinetic information in the future due to improved translation to the in vivo situation. These machine-perfused organ models will be particularly interesting in combination with biomarkers for assessing the functionality of transporter and CYP450 proteins.     

Understanding and improving airway management in companion animals – Part 2

This article reviews alternatives to endotracheal tubes for airway management in veterinary patients under anaesthesia. Anaesthesia has had many improvements over the past few decades and now airway management is finally catching up and so veterinary anaesthetists have a wider choice of options. As in other areas of anaesthesia, airway management should not be a one-size-fits-all approach. Patient and procedure should be considered before selecting the most appropriate airway device.     

Understanding and improving airway management in companion animals - part 1

Airway Management, briefly taught within the veterinary nursing curriculum, is performed many times a day and a vital part of the anaesthesia process. Students are shown how to place an endotracheal tube, taught little about dead-space and airway resistance but, although there are many publications on the pitfalls of intubation, it is often sub-optimally managed in a busy clinic. To provide excellent, safe airway management for our patients, we must understand the history, mechanics and pitfalls about the process: It is only then can we truly apply better techniques in order to improve both care and safety to our patients.     

Primary cardiac sarcomas may develop from resident or bone marrow‐derived mesenchymal stem cells: use of immunohistochemistry including CD44 and octamer binding protein 3/4

Hegyi L, Thway K, Fisher C & Sheppard M N
(2012) Histopathology  61, 966–973 Primary cardiac sarcomas may develop from resident or bone marrow‐derived mesenchymal stem cells: use of immunohistochemistry including CD44 and octamer binding protein 3/4 Aims: To provide evidence that cardiac sarcomas ‘not otherwise specified’ express markers that might indicate their cellular origin or identify any lines of differentiation. Methods and results: We reviewed all 11 cases of primary undifferentiated cardiac sarcomas found in the archives of the Royal Marsden and Royal Brompton Hospitals, London, UK during the period 2000–2009. Five cases with appropriate consent and archived material were investigated using immunohistochemistry. We found that the spindle, pleomorphic or occasionally epithelioid cell sarcomas showed no lineage‐specific differentiation other than partial myofibroblastic or ‘myoid’ differentiation (all cases). All tumours showed some degree of cytoplasmic positivity for the mesenchymal stem cell marker CD44. In contrast, no nuclear octamer binding protein 3/4 (Oct3/4) expression was seen in any of the tumours, although very patchy cytoplasmic positivity was seen in some tumours. Conclusions: The cytoplasmic positivity for CD44 and the absence of nuclear Oct3/4 suggest that the cells of these sarcomas may represent ‘daughter’ stem cells that no longer have the capacity for tumour initiation, but have subsequently developed new lines of partial differentiation. Primary cardiac sarcomas may arise from mesenchymal stem cells with the ability to generate tumours with multilineage differentiation.     

Monitoring disease activity using GH and IGF-I in the follow-up of 501 patients with acromegaly

Context The aims of treatment in patients with acromegaly are to achieve serum GH/IGF‐I concentrations associated with cure or normalization of mortality and alleviation of symptoms. Objective and methods Using the West Midlands Acromegaly database (n = 501) we investigated the reliability of basal fasting GH in predicting nadir or mean GH during oral glucose tolerance test (OGTT) or GH day curve (GHDC), respectively, the degree of discordance between disease activity measured by GH and IGF‐I values and the effect of radiotherapy on the above relationships. In total 773 OGTT and 507 GHDC were performed. Results Basal fasting GH was strongly correlated with nadir/mean GH on OGTT/GHDC (r = +0·87, P < 0·0001, r = +0·93, P < 0·0001, respectively). A basal GH < 2·5 µg/l was associated with a nadir/mean GH during OGTT/GHDC < 2·5 µg/l in 98·6% and 88·2% of cases, respectively. Elevated IGF‐I was seen in 32·4% and 46·4% of patients with GH nadir values during OGTT < 1 and < 2·5 µg/l, respectively, and in 21·2% and 45·9% of GHDC with mean GH < 1 and < 2·5 µg/l, respectively. Radiotherapy increased the discordance in GH and IGF‐I as markers of disease activity at GH < 2·5 µg/l (elevated IGF‐I‐values when OGTT nadir GH < 2·5 µg/l: radiotherapy 55·5%vs. no radiotherapy 36·9%, P = 0·002). Conclusions There is a close relationship between a basal fasting GH < 2·5 µg/l and nadir/mean GH < 2·5 µg/l during OGTT/GHDC. There is a large discordance between disease activity when assessed by GH and IGF‐I which is further increased by radiotherapy. These observations illustrate the challenge of defining appropriate biochemical end‐points to achieve control of disease and normalization of mortality in acromegaly.     

Symptomatic bronchoconstriction after short-term inhalation of sulfur dioxide

We studied the relationship between duration and concentration of exposure in SO2-induced bronchoconstriction in 8 asthmatic subjects. On separate days, we administered SO2 in humidified air through a mouthpiece at 2 concentrations (0.5 and 1.0 ppm) for 3 time periods (1, 3, and 5 min) during eucapnic hyperpnea (60 L/min). Humidified air was administered for 5 min as a control. Bronchoconstriction was assessed by measurement of specific airway resistance (SRaw). The magnitude of the bronchoconstrictor response to both concentrations of SO2 increased progressively over the 3 time periods studied. The mean (+/- SE) increase in SRaw (in L x cm H2O/L/s) and percent increase above baseline (in parentheses) after each exposure to SO2 were as follows: 2.5 +/- 0.3 (34%) after 0.5 ppm for 1 min; 7.5 +/- 4.7 (93%) after 1.0 ppm for 1 min; 13 +/- 3.2 (173%) after 0.5 ppm for 3 min; 31.4 +/- 7.4 (395%) after 1.0 ppm for 3 min; 19.6 +/- 4.0 (234%) after 0.5 ppm for 5 min; 44.1 +/- 9.8 (580%) after 1.0 ppm for 5 min; 3.5 +/- 1.5 (46%) after humidified air for 5 min. For the group, the increases in SRaw caused by inhalation of both concentrations of SO2 for 1 min were small. However, 2 of 8 subjects did develop large increases in SRaw and chest tightness after inhalation of 1.0 ppm for 1 min. Seven of 8 subjects developed wheezing, chest tightness, or dyspnea and used an inhaled bronchodilator after inhalation of 0.5 ppm for 3 and 5 min and 1.0 ppm for 3 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)