Ilizarov segmental bone transport of infected tibial nonunions requiring extensive debridement with an average distraction length of 9,5 centimetres. Is it safe?

ObjectivesTo evaluate the results of one stage radical debridement and segmental bone transport with circular fixator in the treatment of infected tibial non-union requiring extensive debridement with an average defect size of 8 cm and distraction length of 9,5 cm.DesignRetrospective study.SettingLevel I trauma centre at an academic university hospital.PatientsThirty patients with infected tibial non-union with an average of 2,9 previous failed operations after a mean 12,5 months post-injury were treated consecutively. The mean age was 39,5 years (R:16–68). After radical debridement and irrigation, all patients were treated with segmental bone transport using Ilizarov circular fixator. All patients except 3, managed with an open docking protocol without bone grafting. In 2 patients a planned ankle arthrodesis with transport was done.Main outcome measurementsBone union, resolution of infection, external fixation index (EFI), external fixation time (EFT), bone and functional results for this big defect size.ResultsUnion and eradication of infection was achieved in all patients. Mean follow-up was 32,5 months (R: 12–72 mo.) The average bone defect after debridement was measured 8.1 cm (R, 6–15). The total distraction length to restore the debridement defect and previous LLD was 9,5 cm (R, 6–15). The mean external fixation time was 13,7 months; the mean external fixation index was 1,49 mo./cm. One non-union, one refracture and one late valgus deformity was managed successfully with plating or nailing and all were healed uneventfully at the completion of the treatment. According to Paley & Maar and Katsenis criteria, the bone results were excellent in 24 and good in 6, functional scores were excellent in 21, good in 7, and fair in 2 patients. Minor complications were 1,36 per patient, major complications were 0,4 per patient and permanent complications were 0,2 per patient in the study group.ConclusionIn the management of large post-infectious bone defects requiring an average 9,5 cm distraction; segmental bone transport is safe in terms of union and eradication of infection. The EFI, EFT, complications, bone and functional results do not differ from the other published studies with smaller defect size.     

Reactive oxygen at the heart of metabolism

During heart development, the progression from a pluripotent, undifferentiated embryonic stem cell to a functional cardiomyocyte in the adult mammalian heart is characterised by profound changes in gene expression, cell structure, proliferative capacity and metabolism. Whilst the precise causal relationships between these processes are not fully understood, it is clear that the availability and cellular ability to utilise oxygen are critical effectors of cardiomyocyte differentiation and function during development. In particular, cardiomyocytes switch from a largely glycolytic-based production of ATP to predominantly β-oxidation of long-chain fatty acids to generate the cellular energy requirements. Whilst this transition occurs progressively during embryonic and foetal development, it is particularly abrupt over the period of birth. In the adult heart, many cardiopathologies are accompanied by a reversal to a more foetal-like metabolic profile. Understanding the mechanistic causes and consequences of the normal metabolic changes that occur during heart development and those in the pathological heart setting is crucial to inform future potential therapeutic interventions. It is becoming clear that reactive oxygen species (ROS) play critical roles in the regulation of redox-mediated molecular mechanisms that control cellular homoeostasis and function. ROS are generated as a consequence of metabolic processes in aerobic organisms. An overproduction of ROS, when not balanced by the cell's antioxidant defence mechanisms (termed “oxidative stress”), results in non-specific oxidation of proteins, lipids and DNA and is cytotoxic. However, the tightly regulated temporal and spatial production of ROS such as H₂O₂ acts to control the activity of proteins through specific post-translational oxidative modifications and is crucial to cellular function. We describe here the metabolic changes that occur in the developing heart and how they can revert in cardiopathologies. They are discussed in the light of what is currently known about the regulation of these processes by changes in the cellular redox state and levels of ROS production.     

Antibodies against the second extracellular loop of β1-adrenergic receptors induce endothelial dysfunction in conductance and resistance arteries of the Wistar rat

Autoantibodies against β₁-adrenoceptors (β₁-ARs) have been detected in the serum of patients with various cardiac diseases; however, the pathological impact of these autoantibodies (β₁-AABs) has only been evaluated in cardiac tissue. The purpose of the present study was to evaluate whether β₁-AABs have deleterious effects on vascular reactivity in rats.An enzyme-linked immunosorbent assay was used to detect β₁-AABs in sera from immunized rats over a period of 1–3 months using the peptidic sequence of the second extracellular loop of human β₁-AR. Functional studies were performed in thoracic aortic (TA) and small mesenteric artery (SMA) rings from immunized rats. Following pre-contraction with phenylephrine (0.3 μM and 3 μM for the TA and SMA respectively), cumulative concentration–response curves (CCRCs) to various β-AR agonists (isoproterenol, dobutamine, salbutamol, SR 58611A), acetylcholine, A23187, and sodium nitroprusside (SNP) were then plotted.The relaxations induced by dobutamine, SR 58611A, and acetylcholine were significantly impaired, but salbutamol-induced relaxations were not affected, in both vessels from immunized rats. A significant impairment of isoproterenol-induced relaxation was only observed in SMA. CCRCs to SNP were not modified in either of the vessels. A23187-induced relaxation was impaired in immunized rats. Following pretreatment with l-arginine, vasorelaxation to acetylcholine and SR 58611A was restored in immunized rats.This study demonstrates that immunization against the second extracellular loop of β₁-ARs has a deleterious impact on vasorelaxations in the TA and SMA of rats, involving alterations in endothelium-dependent NO signaling pathways.     

Carcinogenicity of acrylamide in B6C3F1 mice and F344/N rats from a 2-year drinking water exposure

Acrylamide is a component of roasted coffee and certain baked and fried carbohydrate-rich foods prepared at high temperatures. We have assessed the carcinogenicity of acrylamide in male and female B6C3F₁ mice and F344/N rats administered 0, 0.0875, 0.175, 0.35, or 0.70 mM acrylamide in the drinking water ad libitum for 2 years. Acrylamide caused significant dose-related decreasing trends in the body weights of F344/N rats. Acrylamide administration resulted in significant dose-related decreasing trends in survival in both sexes of B6C3F₁ mice and in female F344/N rats. Histopathological analyses indicated significant dose-related increases in Harderian gland and lung tumors in male and female B6C3F₁ mice. Male B6C3F₁ mice also had a significantly increased incidence of forestomach tumors, while female B6C3F₁ mice had significant dose-related increases in mammary gland, ovary, and skin tumors. In male and female F344/N rats, there were significant increases in thyroid tumors. Male F344/N rats also had significant dose-related increases in testes, heart, and pancreas tumors, while female F344 rats demonstrated significant increases in clitoral gland, mammary gland, oral cavity, and skin tumors. These results, combined with previous mechanistic studies, provide strong support for the concept that acrylamide is activated to a carcinogen through metabolism to glycidamide.