Differences in gait patterns, pain, function and quality of life between males and females with knee osteoarthritis: a clinical trial

Background  

The aim of this study was to gain a deeper understanding of the gender differences in knee osteoarthritis (OA) by evaluating the differences in gait spatio-temporal parameters and the differences in pain, quality of life and function between males and females suffering from knee OA.     

Evaluating tissue changes with ultrasound during radiofrequency ablation

The purpose of this study was to estimate tissue changes during radiofrequency (RF) ablation by correlating echo frequency shifts and temperature elevations. Experiments were performed on phantoms (tissue mimicking gel) and in-vitro turkey breast. Heating was performed with a modified RF-ablation system. Intermittent RF was applied and the temperature at the electrode tip was continually measured by an embedded thermocouple. Various voltages (10-30V) were applied to achieve a wide range of temperature elevations between 10 and 80 degrees C and ablation sizes between 5 and 27 mm in width. B-mode images and raw data were acquired every 5 s by a modified ultrasound imaging system. The raw data from each line and frame was processed using an algorithm to measure spectral shifts of the echo signals in the power spectrum. The phantom experiments showed positive frequency shifts as the temperature rose, with dependency on the heating rate. A linear relationship (R(2) > 0.96) was found between the RF-applied voltage and the width of the heated area, defined by frequency changes larger than 0.05 MHz. In-vitro experiments showed a correlation (R(2) = 0.84) between the width of the coagulated area and the maximal width of the region with more than 0.12 MHz frequency shifts, but a lower correlation (R(2) = 0.4) between the width of the coagulated area and the temperature elevation. In conclusion, correlation was found between echo frequency shifts and temperature elevations and between echo frequency shifts and the width of the ablated area during intermittent RF ablation. Our results suggest that, with further refinement and validation, ultrasound could be used to measure RF heating and its induced coagulation.     

Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior

The accurate execution of DNA replication requires a strict control of the replication licensing factors hCdt1 and hCdc6. The role of these key replication molecules in carcinogenesis has not been clarified. To examine how early during cancer development deregulation of these factors occurs, we investigated their status in epithelial lesions covering progressive stages of hyperplasia, dysplasia, and full malignancy, mostly from the same patients. Abnormal accumulation of both proteins occurred early from the stage of dysplasia. A frequent cause of unregulated hCdc6 and hCdt1 expression was gene amplification, suggesting that these components can play a role per se in cancer development. Overexpression of hCdt1 and hCdc6 promoted rereplication and generated a DNA damage response, which activated the antitumor barriers of senescence and apoptosis. Generating an inducible hCdt1 cellular system, we observed that continuous stimulus by deregulated hCdt1 led to abrogation of the antitumor barriers and resulted in the selection of clones with more aggressive properties. In addition, stable expression of hCdc6 and hCdt1 in premalignant papilloma cells led to transformation of the cells that produced tumors upon injection into nude mice depicting the oncogenic potential of their deregulation.     

Prophylaxis against Soman Inhalation Toxicity in Guinea Pigs by Pretreatment Alone with Human Serum Butyrylcholinesterase

Human butyrylcholinesterase (HuBChE) has previously been shownto protect mice, rats, and monkeys against multiple lethal toxicdoses of organophosphorus (OP) anticholinesterases that werechallenged by iv bolus injections. This study examines the conceptof using a cholinesterase scavenger as a prophylactic measureagainst inhalation toxicity, which is the more realistic simulationof exposure to volatile OPs. HuBChE-treated awake guinea pigswere exposed to controlled concentration of soman vapors rangingfrom 417 to 430 µg/liter, for 45 to 70 s. The correlationbetween the inhibition of circulating HuBChE and the dose ofsoman administered by sequential iv injections and by respiratoryexposure indicated that the fraction of the inhaled dose ofsoman that reached the blood was 0.29. HuBChE to soman molarratio of 0.11 was sufficient to prevent the manifestation oftoxic signs in guinea pigs following exposure to 2.17 theinhaled LD50 dose of soman (ILD50, 101 µg/kg). A slightincrease in HuBChE:soman ratio (0.15) produced sign-free animalsafter two sequential respiratory exposures with a cumulativedose of 4.5 ILD50. Protection was exceptionally high and farsuperior to the currently used traditional approach that consistedof pretreatment with pyridostigmine and postexposure combinedadministration of atropine, benactyzine, and an oxime reactivator.Quantitative analysis of the results suggests that in vivo sequestrationof soman, and presumably other OPs, by exogenously administeredHuBChE, is independent of the species used or the route of challengeentry. This assuring conclusion significantly expands the databaseof the bioscavenger strategy that now offers a dependable extrapolationfrom animals to human.     

Escalation and Intensification of Radiotherapy for Stage III Non-small Cell Lung Cancer: Opportunities for Treatment Improvement

In this overview we review and model how radiotherapy tumour control and complication rates vary with dose, fractionation, schedule duration, irradiated volume and use of chemotherapy for stage III non-small cell lung cancer (NSCLC), and use the modelling to study the effectiveness of different NSCLC dose-escalation approaches being developed in the UK. Data have been collated for pneumonitis, lung fibrosis, early and late oesophagitis, cord and cardiac complications, and local progression-free survival at 30 months. Dependences of the various end points on treatment-related factors are catalogued and analysed using the linear-quadratic incomplete repair model to account for dose and fractionation effects, making linear corrections for differences in schedule duration, and loosely characterising volume effects using parallel- and series-type concepts. Tolerance limits are calculated for the different end points and distilled into ranges of prescribed dose likely to be tolerable when delivered in 2.5 and 4 week radiation and 6 week chemoirradiation schedules using conformal techniques. Worthwhile (～20%) gains in 30 month local progression-free survival should be achievable at safely deliverable levels of dose escalation. The analysis suggests that longer schedules may be more beneficial than shorter ones, but this finding is governed by the relative rates of tumour and oesophageal accelerated proliferation, which are quite imprecisely known. Consequently escalated 2.5, 4 and 6 week schedules are being developed; each should lead to useful improvements in local control but it is not yet known which schedule will be most effective.     

Atracurium Resistance in a Critically Ill Patient

A previously healthy 25-year-old man with metastatic testicular teratocarcinoma became resistant to atracurium-induced neuromuscular blockade as evidenced by train-of-four (TOF) monitoring combined with clinical assessment. Subsequently he had an adequate response with a standard dosage of pancuronium. During the first 10 days of neuromuscular blockade, the atracurium requirements escalated from 0.31 to 1.7 mg/kg/hour, guided by TOF monitoring, movement, and spontaneous respirations. The infusion was discontinued but later reinstituted. Despite a total atracurium loading dose of 1.4 mg/kg followed by an infusion rate titrated to 1.7 mg/kg/hour, inadequate paralysis persisted. Atracurium was terminated and an intravenous infusion of pancuronium 0.10 mg/kg/hour was started. Over the next 3 days the pancuronium infusion was titrated down to a range of 0.04-0.06 mg/kg/hour, followed by a maintenance infusion of 0.01-0.05 mg/kg/hour for 5 days. A pharmacokinetic alteration, such as increased metabolism or elimination, may have caused the atracurium resistance.