[The abdominal catastrophe]

Patients with an abdominal catastrophe are in urgent need of early, interdisciplinary medical help. The treatment plan should be based on medical priorities and clear leadership. First priority should be given to achieve optimal oxygenation of blood and stabilization of circulation during all treatment-phases. The sicker the patient, the less invasive the (surgical) treatment should to be, which means "damage control only". This short article describes 7 important, pragmatic rules that will help to increase the survival of a patient with an abdominal catastrophe. Preexisting morbidity and risk factors must be included in the overall risk-evaluation for every therapeutic intervention. The challenge in patients with an abdominal catastrophe is to carefully balance the therapeutic stress and the existing resistance of the individual patient. The best way to avoid abdominal disaster, however, is its prevention.

ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy

Anticancer drug therapy activates both molecular cell death and autophagy pathways. Here we show that even sublethal concentrations of DNA-damaging drugs, such as etoposide and cisplatin, induce the expression of autophagy-related protein 5 (ATG5), which is both necessary and sufficient for the subsequent induction of mitotic catastrophe. We demonstrate that ATG5 translocates to the nucleus, where it physically interacts with survivin in response to DNA-damaging agents both in vitro and in carcinoma tissues obtained from patients who had undergone radiotherapy and/or chemotherapy. As a consequence, elements of the chromosomal passenger complex are displaced during mitosis, resulting in chromosome misalignment and segregation defects. Pharmacological inhibition of autophagy does not prevent ATG5-dependent mitotic catastrophe, but shifts the balance to an early caspase-dependent cell death. Our data suggest a dual role for ATG5 in response to drug-induced DNA damage, where it acts in two signalling pathways in two distinct cellular compartments, the cytosol and the nucleus.

Driving and emergency braking may be impaired after tibiotalar joint arthrodesis: conclusions after a case series.

PURPOSE To assess whether reaction time (RT) and movement time (MT), as the two components of the total brake response time (TBRT) and brake force (BF) are different in patients with a foot joint arthrodesis in comparison to controls. METHODS The study was a comparative case series in a driving simulator under realistic driving conditions. Mobile patients without a walker, ≥6 months after surgery who were driving a car and had no neurological co-morbidity, knee or hip joint prosthesis were included in the study. The selection criteria resulted in 12 patients with right tibiotalar joint arthrodesis (TTJA) and 12 patients with another right foot joint arthrodesis (OFJA), who were compared to 17 individuals without any ankle-joint pathology. For TBRT, an empirical safe driving threshold of 700 ms was used. The outcome measures were RT, MT, TBRT, BF and McGuire score. RESULTS MT (p = 0.034) and TBRT (p = 0.026) were longer in TTJA patients in comparison with the controls. Also, more patients with TTJA than patients with OFJA and controls exceeded the safe driving threshold (p = 0.028). The outcomes in OFJA patients and in controls were comparable. The McGuire score was similar between the TTJA and OFJA patients (p = 0.26). CONCLUSIONS Significantly slower MT and TBRT, and significantly more patients exceeding the safe driving threshold, were observed after a tibiotalar-joint arthrodesis in comparison to the controls. Patients with OFJAs were not significantly different from the controls. Driving and emergency braking may be impaired after tibiotalar-joint arthrodesis.

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.

Ground reaction force profiles after partial and pancarpal arthrodesis in dogs

OBJECTIVES: To evaluate and compare long-term functional outcome after partial carpal arthrodesis and pancarpal arthrodesis in dogs using kinetic gait analysis. METHODS: Fourteen dogs with 19 partial carpal or pancarpal arthrodeses were retrospectively examined and underwent force-plate gait analysis. Mean times since surgery were 29.4 and 24.4 months for pancarpal and partial carpal arthrodesis respectively. Vertical and braking-propulsive ground reaction force profiles were compared between treatment groups, and to those of normal dogs (control group) using Kruskal-Wallis one-way analysis of variance. RESULTS: With the exception of time to vertical peak that occurred earlier in dogs with pancarpal than in dogs with partial carpal arthrodesis (p <0.01), there was no difference between the two treatment groups. Several parameters differed significantly between operated and healthy dogs (p <0.01): vertical impulses were significantly lower in both treatment groups, braking forces and impulses were also reduced after both techniques. Propulsive forces and impulses were only reduced in dogs with pancarpal arthrodesis. When comparing gait parameters of sound limbs of unilateral operated dogs to those of control dogs, braking forces and impulses (p <0.01; p <0.05) were significantly higher in the sound legs of unilateral operated dogs. CLINICAL SIGNIFICANCE: Long-term outcome after partial carpal and pancarpal arthrodesis is good and comparable to each other. Propulsive action may be altered more in dogs with pancarpal arthrodesis.

Toxic effects of brake wear particles on epithelial lung cells in vitro

ABSTRACT: BACKGROUND: Fine particulate matter originating from traffic correlates with increased morbidity and mortality. An important source of traffic particles is brake wear of cars which contributes up to 20% of the total traffic emissions. The aim of this study was to evaluate potential toxicological effects of human epithelial lung cells exposed to freshly generated brake wear particles. RESULTS: An exposure box was mounted around a car's braking system. Lung cells cultured at the air-liquid interface were then exposed to particles emitted from two typical braking behaviours ("full stop" and "normal deceleration"). The particle size distribution as well as the brake emission components like metals and carbons was measured on-line, and the particles deposited on grids for transmission electron microscopy were counted. The tight junction arrangement was observed by laser scanning microscopy. Cellular responses were assessed by measurement of lactate dehydrogenase (cytotoxicity), by investigating the production of reactive oxidative species and the release of the pro-inflammatory mediator interleukin-8. The tight junction protein occludin density decreased significantly (p < 0.05) with increasing concentrations of metals on the particles (iron, copper and manganese, which were all strongly correlated with each other). Occludin was also negatively correlated with the intensity of reactive oxidative species. The concentrations of interleukin-8 were significantly correlated with increasing organic carbon concentrations. No correlation was observed between occludin and interleukin-8, nor between reactive oxidative species and interleukin-8. CONCLUSION: These findings suggest that the metals on brake wear particles damage tight junctions with a mechanism involving oxidative stress. Brake wear particles also increase pro-inflammatory responses. However, this might be due to another mechanism than via oxidative stress.