Using CT to diagnose traumatic lumbar hernia

OBJECTIVE: The objective of this study was to determine the CT findings of traumatic lumbar hernia in 15 patients and to discuss the mechanism and treatment of injury. CONCLUSION: CT can reveal traumatic lumbar hernia and show both the anatomy of disrupted muscular layers and the presence of herniated intraabdominal viscera or retroperitoneal fat.     

Tolerance and efficacy of conformal radiotherapy for hepatocellular carcinoma in cirrhotic patients. Results of the French RTF1 phase II trial]

PURPOSE: While some patients presenting with hepatocellular carcinoma (HCC) benefit from curative therapies (transplantation, surgery, percutaneous ablation), others are only candidates for palliative options such as chemoembolization or symptomatic care. Although conventional external-beam radiotherapy of the liver is regarded as little efficient and potentially toxic in cirrhotic patients, 3-dimensional conformal radiotherapy (CRT), by decreasing the amount of normal liver included in the radiation portal, allows dose escalation to occur without increasing the risk of radiation-induced hepatitis. This trial was designed to assess the efficacy and tolerance of CRT for small-size HCC in cirrhotic patients. PATIENTS AND METHODS: Prospective phase II trial including stage A/B cirrhotic patients with small-size HCC not suitable for curative treatments; CRT consisted in a standard fractionation radiation, with a total dose of 66 Gy. RESULTS: Twenty-seven patients were included, 15 of whom had previously been treated for HCC; mean age was 68. Among the 23 assessable patients, 18 (78%) presented with complete response, 3 (13%) with partial response, and 2 with no response. Acute complications occurred in 24 patients, and were mainly acceptable (grade 1/2: 22 patients, grade 3/4: 11 patients, 4 (15%) of whom had clinical and/or hematological toxicities). Only 2 (9%) grade 3/4 clinical and/or hematological late toxicities are reported. CONCLUSION: CRT is a non-invasive curative technique highly suitable for small-size HCC in cirrhotic patients; further investigations are needed to compare it to the other available treatments, and to integrate it into the curative therapeutic algorithm of HCC.     

Carbon monoxide: a new pharmaceutical agent?

Small amounts of carbon monoxide (CO) are continuously produced in mammals. The intracellular levels of this gaseous molecule can markedly increase under stressful conditions following the induction of heme oxygenases (HO), ubiquitous enzymes responsible for the catabolism of heme. The development of a technology concerning the CO-releasing molecules (CO-RMs) that control the delivery and action of CO under different pathological conditions represents a major step forward in the development of CO-based pharmaceuticals with therapeutic applications. CO is important for the homeostatic control of cardiovascular functions. Abnormal metabolism and function of CO contribute to the pathogenesis and development of hypertension. Another vascular disease in which the role of CO has been evaluated is pulmonary arterial hypertension. Important results have been reported in which CO prevents intimal hyperplasia by arresting hyperproliferative vascular smooth muscle cells as well as increased mobilization and recruitment of bone-marrow-derived progenitor cells. Transplantation has been a field of research, in which most studies have investigated the beneficial properties of CO-RMs. CO gas and CO-RMs have produced promising results in the preservation of organs for transplantation. The anti-inflammatory properties of CO and CO-RMs have been demonstrated in a multitude of animal models of inflammation, suggesting a possible therapeutic application for inflammatory diseases. Despite therapeutic benefit in animal model studies, the efficacy of CO in humans remains unclear. Further studies are expected to better understand the pharmacokinetics as well as long- and short-term effects of CO-RMs.     

Simulation of 125I-based radioprobing experiments to study DNA quadruplex structure and topology

Purpose: Certain guanine-rich DNA sequences have the capacity to fold into four-stranded structures stabilized by the stacking of square planar arrangements of four hydrogen-bonded guanine bases. However both the overall topology of folding and the more detailed three dimensional structure of these quadruplexes is difficult to determine or predict, and they can be polymorphic, altering radically depending on environmental conditions. Radioprobing experiments, in which Auger electrons emitted during the decay of a ¹²⁵I-containing base induce strand cleavage in a distance- and structure-dependent manner, have provided possible means of determining these details. Here we have used a combination of computer simulation methods to study the information obtained by one such experiment, reported in 2004.

Method: Models were constructed of three quadruplex topologies considered in the experiment, and one other topology proposed more recently. Molecular Dynamics simulations were used to equilibrate these structures and monitor how they evolved over several nanoseconds in solution. Snapshots from the trajectories were then subjected to Monte Carlo track structure prediction, from which theoretical cleavage patterns have been extracted.

Results: The four topologies were found to yield quite different cleavage patterns, which allow the presence of particular conformations in an experiment to be predicted.

Conclusion: Radioprobing, which is usable in biologically relevant environments, is sensitive enough to distinguish with some confidence between alternative folding topologies in a DNA structure. Monte Carlo track structure simulation can reinforce or question conclusions drawn from experiment, and Molecular Dynamics used with various restraints provides a practical means of guiding a model towards one that yields cleavage patterns closer to those found experimentally.     

Acute psycho-physiological responses to perceptually regulated hypoxic and normoxic interval walks in overweight-to-obese adults

ObjectivesWe investigated psycho-physiological responses to perceptually regulated interval walks in hypoxia versus normoxia in obese individuals.DesignWithin-participants repeated measures.MethodsTen obese adults (BMI = 32 ± 3 kg/m^?2) completed a 60-min interval session (15 × 2 min walking at a rating of perceived exertion of 14 on the 6–20 Borg scale with 2 min of rest) either in hypoxia (FiO₂ = 13.0%, HYP) or normoxia (NOR). A third trial replicating the HYP speed pattern was carried out in normoxia as a control (CON). Exercise responses were analysed comparing the average of 1st to 3rd exercise bouts to those of the 4th–6th, 7th–9th, 10th–12th and 13th–15th exercise bouts (block 1 versus 2, 3, 4 and 5).ResultsTreadmill speed was slower during block 4 (6.14 ± 0.67 versus 6.24 ± 0.73 km/h^?1) and block 5 (6.12 ± 0.64 versus 6.25 ± 0.75 km/h^?1) in HYP compared to NOR or CON (p = 0.009). Compared to NOR and CON, heart rate was +6–10% higher (p = 0.001), whilst arterial oxygen saturation (?12–13%) was lower (p < 0.001) in HYP. Perceived limb discomfort was lower in HYP and CON versus NOR (?21 ± 4% and ?34 ± 6%; p = 0.004).ConclusionsIn overweight-to-obese adults, perceptually regulated interval walks in hypoxia versus normoxia leads to progressively slower speeds along with lower limb discomfort and larger physiological stress than normoxia. Walking at the speed adopted in hypoxia produces similar psycho-physiological responses at the same absolute intensity in normoxia.