The effect of temporal HU variations on the uncertainty of dose recalculations performed on MVCT images

Over the course of radiation therapy, a patient's anatomy may change substantially. The relatively recent addition of frequent in-room imaging to assist with patient localization has provided a database of images that may be used to recalculate dose distributions for adaptive radiotherapy purposes. The TomoTherapy Hi-Art II unit (Accuray Inc., Sunnyvale, CA, USA) uses a helical scanning geometry and a megavoltage (MV) beam to acquire volumetric patient images. This study evaluated the uncertainty of dose calculations performed on megavoltage CT (MVCT) images as a function of temporal Hounsfield Unit (HU) variations observed in the imaging system over three years on two machines. A baseline error between dose calculations performed on kVCT and MVCT images was established using a series of phantoms. This baseline error ranged from -1.4% to 0.6%. Materials of differing densities were imaged and MVCT numbers were measured periodically. The MVCT number of solid water varied from 5 to 103 HU and consistently increased prior to target replacement. Finally, the dosimetric uncertainty of the temporal HU variation was assessed using MVCT images of typical head and neck, lung and prostate cancer patients. Worst-case MVCT recalculation errors could approach 5%, 7% and 10% for the head and neck, lung and prostate images, respectively. However, if a tolerance of ±30 HU were maintained for the MVCT number of solid water, dosimetric errors were limited to ±2.5%, ±3% and ±4%, respectively.     

Recovery of visual functions after early acquired occipital damage

Plasticity of visual systems after early brain damage has been extensively studied in animal models but poorly documented in children after visual pathway lesions. This report describes the visual recovery of a male child who had a bilateral occipital lobe infarction at the age of 2 years 6 months, 10 days after colon resection for Hirschsprung disease. In the acute phase he had severe visual impairment without visual response. Some weeks later he could perceive movement. Since then, progressive recovery of his visual acuity and oculomotor abilities has been accompanied by a progressive reduction of the visual field defect. At 6 years 8 months, visual recognition acuity was 10/10 in both eyes and neuro-ophthalmological examination was normal, except for persistence of the visual field defect in the upper hemifield and a selective impairment of higher visual functions (recognition of object presented in a hard-to-decode way [e.g. overlapping figures], or use of complex visuospatial skills). The functional recovery observed in this patient confirms the adaptive plasticity of developing visual systems after early brain lesions. It suggests that in humans, as in animal models, processes related to cerebral plasticity may take place years after a brain lesion has been sustained.     

Increased spermine oxidase expression in human prostate cancer and prostatic intraepithelial neoplasia tissues

BACKGROUND: Inflammation has been strongly implicated in prostate carcinogenesis, but the precise molecular mechanisms linking inflammation and carcinogenic DNA damage are not known. Induction of the polyamine catabolic enzyme, spermine oxidase (SMO) has been linked to increased reactive oxygen species (ROS) and DNA damage in human gastric and lung epithelial cells and suggest direct mechanistic links between inflammation, SMO activity, ROS production, and epithelial carcinogenesis that are likely relevant in prostate cancer. METHODS: Tissue microarrays consisting of matched normal and diseased specimens from patients diagnosed with prostate cancer, prostatic intraepithelial neoplasia (PIN), or proliferative inflammatory atrophy (PIA), as well as unaffected individuals, were stained for SMO expression and analyzed using image analysis techniques and TMAJ software tools. RESULTS: Average SMO staining was significantly higher in prostate cancer and PIN tissues compared to patient-matched benign tissues. Benign tissues from prostate cancer, PIN, and PIA patients also exhibited significantly higher mean SMO expression versus tissues from prostate disease-free patients. CONCLUSIONS: Tissues from patients diagnosed with prostate cancer and PIN exhibit, on average, locally increased SMO expression in regions of prostatic disease and higher overall SMO expression in prostatic epithelial cells compared to healthy individuals. Further studies are warranted to directly examine the role of SMO-produced ROS in prostate carcinogenesis.     

The value of four-detector row spiral computed tomography for the diagnosis of pulmonary embolism

Although spiral computed tomography (CT) is being used increasingly as the first-line imaging procedure in the diagnostic workup of patients with clinically suspected pulmonary embolism (PE), the diagnostic value of negative findings, at least when using the four-detector row scanners, is still controversial. A total of 702 consecutive patients with clinical symptoms suggestive of PE underwent four-slice CT. Patients with negative findings received the determination of D-dimer. Those with positive D-dimer underwent further diagnostic workup to confirm or rule out the diagnosis of PE. Those with negative D-dimer were followed-up to 6 months to detect the development of symptomatic venous thromboembolism (VTE). The CT test was interpreted as negative in 536 patients (76.3%). These patients had the D-dimer determination, which was positive in 279 and negative in the remaining 257 patients. Of the former, PE subsequently was documented in 55 patients (19.7%). Of the latter, symptomatic VTE in the follow-up period developed in three patients (1.17%; 95% confidence interval, 0.24 to 3.38%). In conclusion, when using the four-detector row, the negative predictive value of CT findings in patients with clinically suspected PE and positive D-dimer is low. In contrast, it is safe to withhold anticoagulation from patients with negative findings and negative D-dimer.     

Relationship between serum complement and different lipid disorders

Inflammatory and lipid factors share an important role in atherosclerosis. Recent studies showed the concomitant presence and increase of complement components and lipid both in the atherosclerotic plaque and the circulating blood. The aim of this study was to examine the relationship between the complement system and lipid disorders. We evaluated the circulating complement terminal complex C5b-9, a clear sign of complement activation, in three groups of 30 patients the first with hypercholesterolemia, the second with hypertriglyceridemia (associated with low values of HDL-cholesterol), the third with low levels of HDL-cholesterol compared with an equivalent group of matched normolipemic subjects. We found a significant increase of sC5b-9 in each group of patients compared with controls. The mean sC5b-9 level in the hypercholesterolemic population was 366.2±141.2 ng/ml (P<0.01), 395.4±118.2 ng/ml in the hypertrygliceridemic group (P<0.01), 414.8±126.4 ng/ml in the low HDL-chol subjects (P<0.01), and 182.0±40.8. ng/ml in the control group. Regression analysis showed a significant direct correlation between sC5b-9 and triglycerides (r=0.64), and a significant inverse correlation between sC5b-9, HDL-chol (r=0.74), and apo-A1 (r=0.68); no significant relationship was found between sC5b-9 and cholesterol. We suggest that complement activation is associated with the various lipid disorders and is more important in those dyslipidemic conditions in which other factors may be involved. In particular, hypertriglyceridemia may be associated with endothelial and fibrinolytic disturbances, and the decrease of HDL may induce the failure of the regulatory proteins transported by the same HDL. Received: 31 March 2001 / Accepted: 3 February 2002     

Falcipain‐2 inhibitors

Malaria, particularly that one caused by Plasmodium falciparum, remains a serious health problem in Africa, South America, and many parts of Asia where it afflicts about 500 million people and is responsible for the death of more than one million children each year. The main reasons for the persistence of malaria are the emergence of resistance to common antimalarial drugs, inadequate control of mosquito vectors, and the lack of effective vaccines. Therefore, the identification and characterization of new targets for antimalarial chemotherapy are of urgent priority. This review is focused on inhibitors of falcipain‐2, a cysteine protease from P. falciparum, which represents one of the most promising targets for antimalarial drug design. Falcipain‐2 is a key enzyme in the life cycle of P. falciparum since it degrades hemoglobin, at the early trophozoite stage, and cleaves ankyrin and protein 4.1, the cytoskeletal elements vital to the stability of red cell membrane, at the schizont stage. The main classes of falcipain‐2 inhibitors are peptides or peptidomimetics bearing the most popular pharmacophores of cysteine protease inhibitors, such as vinyl sulfones, halomethyl ketones, and aldehydes. Furthermore, many other chemotypes have been identified as inhibitors of falcipain‐2, such as isoquinolines, thiosemicarbazones, and chalcones. These inhibitors represent all classes, which, to the best of our knowledge, have been disclosed in journal articles to date. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 1, 136–167, 2010