Forensic analysis of explosions: Inverse calculation of the charge mass.

Forensic analysis of explosions consists of determining the point of origin, the explosive substance involved, and the charge mass. Within the EU FP7 project Hyperion, TNO developed the Inverse Explosion Analysis (TNO-IEA) tool to estimate the charge mass and point of origin based on observed damage around an explosion. In this paper, inverse models are presented based on two frequently occurring and reliable sources of information: window breakage and building damage. The models have been verified by applying them to the Enschede firework disaster and the Khobar tower attack. Furthermore, a statistical method has been developed to combine the various types of data, in order to determine an overall charge mass distribution. In relatively open environments, like for the Enschede firework disaster, the models generate realistic charge masses that are consistent with values found in forensic literature. The spread predicted by the IEA tool is however larger than presented in the literature for these specific cases. This is also realistic due to the large inherent uncertainties in a forensic analysis. The IEA-models give a reasonable first order estimate of the charge mass in a densely built urban environment, such as for the Khobar tower attack. Due to blast shielding effects which are not taken into account in the IEA tool, this is usually an under prediction. To obtain more accurate predictions, the application of Computational Fluid Dynamics (CFD) simulations is advised. The TNO IEA tool gives unique possibilities to inversely calculate the TNT equivalent charge mass based on a large variety of explosion effects and observations. The IEA tool enables forensic analysts, also those who are not experts on explosion effects, to perform an analysis with a largely reduced effort.

Polychlorinated biphenyl exposure and corticosterone levels in seven polar seabird species.

The role of polychlorinated biphenyls (PCBs) on exposure-related endocrine effects has been poorly investigated in wild birds. This is the case for stress hormones including corticosterone (CORT). Some studies have suggested that environmental exposure to PCBs and altered CORT secretion might be associated. Here we investigated the relationships between blood PCB concentrations and circulating CORT levels in seven free-ranging polar seabird species occupying different trophic positions, and hence covering a wide range of PCB exposure. Blood ∑7PCB concentrations (range: 61-115,632 ng/g lw) were positively associated to baseline or stress-induced CORT levels in three species and negatively associated to stress-induced CORT levels in one species. Global analysis suggests that in males, baseline CORT levels generally increase with increasing blood ∑7PCB concentrations, whereas stress-induced CORT levels decrease when reaching high blood ∑7PCB concentrations. This study suggests that the nature of the PCB-CORT relationships may depend on the level of PCB exposure.

Real-world experience with adjuvant fec-d chemotherapy in four Ontario regional cancer centres.

BACKGROUND: The efficacy of adjuvant chemotherapy with fec-d (5-fluorouracil-epirubicin-cyclophosphamide followed by docetaxel) is superior to that with fec-100 alone in women with early-stage breast cancer. As the use of fec-d increased in clinical practice, health care providers anecdotally noted higher-than-expected toxicity rates and frequent early treatment discontinuations because of toxicity. In the present study, we compared the rates of serious adverse events in patients who received adjuvant fec-d chemotherapy in routine clinical practice with the rates reported in the pacs-01 trial. METHODS: We retrospectively reviewed all patients prescribed adjuvant fec-d for early-stage breast cancer at 4 regional cancer centres in Ontario. Information was collected from electronic and paper charts by a physician investigator from each centre. Data were analyzed using chi-square tests, independent samples t-tests, one-way analysis of variance, and univariate regression. RESULTS: The 671 electronic and paper patient records reviewed showed a median patient age of 52.2 years, 229 patients (34.1%) with N0 disease, 508 patients (75.7%) with estrogen or progesterone receptor-positive disease (or both), and 113 patients (26%) with her2/neu-overexpressing breast cancer. Febrile neutropenia occurred in 152 patients (22.7%), most frequently at cycle 4, coincident with the initiation of docetaxel [78/152 (51.3%)]. Primary prophylaxis with hematopoietic growth factor support was used in 235 patients (35%), and the rate of febrile neutropenia was significantly lower in those who received prophylaxis than in those who did not [15/235 (6.4%) vs. 137/436 (31.4%); p < 0.001; risk ratio: 0.20]. CONCLUSIONS: In routine clinical practice, treatment with fec-d is associated with a higher-than-expected rate of febrile neutropenia, in light of which, primary prophylaxis with growth factor should be considered, per international guidelines. Adoption based on clinical trial reports of new therapies into mainstream practice must be done carefully and with scrutiny.

The Svalbard glaucous gull as bioindicator species in the European arctic: insight from 35 years of contaminants research.

Biomonitoring survey conducted with glaucous gulls from Svalbard have demonstrated that this top-predator-scavenger species accumulates a wide array of chemicals of environmental concern, including organohalogens, trace elements, organometals, and several non-halogenated and non-metallic-compounds. Among these contaminants are those subjected to global bans or restrictions in North America and Europe (e.g., legacy OC's, penta-, and octa-PBDE technical mixtures and mercury). In addition, some currently produced chemicals were found in gulls that lack and global use regulation (e.g., deca-PBDE , HBCD, and other non-PBDE BFR additives, siloxanes, and selected PFASs). Svalbard glaucous gulls are also exposed to contaminant metabolites that, at time, are more bioactive than their precursors (e.g., oxychlordane, p,p'-DDE, OH- and MeSo2-PCBs, and OH-PBDEs) Concentrations of legacy OCs (PCBs, DDTs, CHLs, CBzs, dieldrin, PCDD/Fs, and mirec) in tissues, blood, and eggs of Svalbard glaucous gulls have displayed the highest contamination levels among glaucous gull populations that inhabit Greenland (Cleemann et al. 2000) Jan Mayen (Gabrielsen et al. 1997), Alaska (Vander Pol et al. 2009), and the Canadian Arctic (Braune et a. 2005). To date, measurements obtaines on more novel organohalogens (e.g., OH- and MeSo2-containing metabolites, BFRs and PFASs) in Svalbard glaucous gull samples generally confirm that the spatial and trophodynamic trends of the legacy OC concentrations, whereas no clear trend emerges from surveys of trace elements and organometals. Using the glaucous gull as biosentinel species provides clear evidence that Svalbard and the European Arctic environment is exposed to a complex mixture of legacy and more recently introduced PBT-like substances.

Organohalogen and metabolically-derived contaminants and associations with whole body constituents in Norwegian Arctic glaucous gulls.

Comprehensive surveys of organohalogen contaminants have been conducted in various tissues and blood of glaucous gulls (Larus hyperboreus), a top scavenger-predator species in Svalbard in the Norwegian Arctic. However, the physico-chemical properties of organohalogens (e.g., type and degree of halogenation and the presence or absence of additional phenyl group substituents) that may influence toxicokinetics, and subsequently tissue-specific accumulation, have yet to be studied in this species. We investigated the concentrations, total body burdens, and compositional patterns of legacy chlorinated compounds (PCBs and chlordanes (CHLs)), metabolically-derived PCBs (methylsulfonyl (MeSO(2))- and OH-PCBs), brominated flame retardants (polybrominated diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs), total-hexabromocyclododecane (HBCD)), and PBDE metabolites and/or naturally-occurring compounds with similar structures (MeO- and OH-PBDEs) in liver, blood and whole body homogenate samples of adult glaucous gulls (n=19) from Svalbard. Further, we examined the distribution of these organohalogens and metabolites in relation to whole body composition of glaucous gulls, i.e., the total water, protein, lipid and mineral contents in whole homogenate carcasses. The total body burden of organohalogens and metabolites in glaucous gulls ranged between 3.3 and 33.0 mg. Compound class distribution showed that the relative proportions of sum (Sigma) OH-PCB and SigmaOH-PBDE to the total organohalogen concentrations were significantly highest in blood. Conversely, the SigmaCHL and SigmaPCB showed generally higher proportions in the lipid-rich liver as well as in whole body homogenates. No significant difference in the compositional patterns of individual congeners/compounds was found among tissues/blood, with the exception of the classes comprised of less polar brominated compounds (PBDEs, PBBs and total-(alpha)-HBCD). Total proteins isolated from the whole body homogenates of glaucous gulls were significantly associated to the proportions of SigmaOH-PCB and SigmaPBDE. A non-significant positive association was found between total lipids and the SigmaPCB proportions. The present study suggests that both protein association and lipid solubility are important concomitant factors to be considered in the toxicokinetics and fate of contaminants as a function of chemical structure and properties, e.g., chlorination, bromination and the presence of other phenyl substituents such as OH group. An enhanced, selective retention of these organohalogen classes in given tissues/body compartments may thus lead to site-specific toxicological actions and adverse effects in the highly-contaminated Svalbard glaucous gulls.

Paget disease of bone: mapping of two loci at 5q35-qter and 5q31.

Paget disease of bone is characterized by focal increases of the bone-remodeling process. It is the second most common metabolic bone disease after osteoporosis. Genetic factors play a major role in the etiology of Paget disease of bone, and two loci have been mapped for the disorder: PDB1 and PDB2. The gene(s) causing the typical form of the disorder remains to be characterized. To decipher the molecular basis of Paget disease of bone, we performed genetic linkage analysis in 24 large French Canadian families (479 individuals) in which the disorder was segregating as an autosomal dominant trait. After exclusion of PDB2, a genomewide scan was performed on the three most informative family nuclei. LOD scores >1.0 were observed at seven locations. The 24 families were then used to detect strong evidence for linkage to chromosome 5q35-qter. Under heterogeneity, a maximum LOD score of 8.58 was obtained at D5S2073, at straight theta= .1. The same characteristic haplotype was carried by all patients in eight families, suggesting a founder effect. A recombination event in a key family confined the disease region within a 6-cM interval between D5S469 and the telomere. The 16 other families, with very low conditional probability of linkage to 5q35-qter, were further used, to map a second locus at 5q31. Under heterogeneity, a maximum LOD score of 3.70 was detected at D5S500 with straight theta=.00. Recombination events refined the 5q31 region within 12.2 cM, between D5S642 and D5S1972. These observations demonstrate the mapping of two novel loci for Paget disease of bone and provide further evidence for genetic heterogeneity of this highly prevalent disorder. It is proposed that the 5q35-qter and 5q31 loci be named "PDB3" and "PDB4," respectively.

Extensive F-18 FDG uptake in metastatic spindle cell carcinoma of the lung.

A 77-year-old man with stage IIB squamous cell carcinoma of the lung underwent right upper lobectomy. One month later he was examined for right chest pain, dyspnea, cough, and weakness. A roentgenogram showed nondiagnostic diffuse opacification of his right lung cavity. An F-18 FDG positron emission tomographic (PET) study revealed extensive uptake in the right pleural area, left adrenal gland, right axilla, and soft tissues consistent with extensive local recurrence and metastatic disease. Biopsy of a right chest soft tissue lesion showed spindle cell carcinoma, a rare variant of squamous cell carcinoma.

Inhibition of antioxidants and hyperthermia enhance bleomycin-induced cytotoxicity and lipid peroxidation in Chinese hamster ovary cells.

Regional hyperthermia has potential for human cancer treatment, particularly in combination with systemic chemotherapy or radiotherapy. Heat enhances the cytotoxic effect of certain anticancer agents such as bleomycin, but the mechanisms involved in cell killing are currently unknown. Bleomycin generates reactive oxygen species. It is likely that hyperthermia itself also increases oxidative stress in cells. We evaluate whether oxidative stress has a role in the mechanism of cell death caused by bleomycin and heat in Chinese hamster ovary cells. Heat (41 to 44 degrees C) increased cytotoxicity of bleomycin, evaluated by clonogenic cell survival. Decreased levels of cellular antioxidants should create an imbalance between prooxidant and antioxidant systems, thus enhancing cytotoxic responses to heat and to oxidant-generating drugs. We determine the involvement of four major cellular antioxidant defenses, superoxide dismutase (SOD), the glutathione redox cycle (GSH cycle), catalase, and glutathione S-transferase (GST), in cellular sensitivity to bleomycin, alone or combined with hyperthermia. These cellular defenses were inhibited by diethyldithiocarbamate, l-buthionine sulfoximine, aminotriazole, and ethacrynic acid, respectively. We show that levels of antioxidants (SOD, GSH cycle, and GST) affect cellular cytotoxic responses to bleomycin, at normal and elevated temperatures (41 to 44 degrees C), suggesting the involvement of oxidative stress. Bleomycin and iron caused oxidative damage to membrane lipids in intact cells, at 37 and 43 degrees C. Lipid peroxidation was evaluated by fluorescence detection of thiobarbituric acid-reactive products. There was an increase in damage to membrane lipids when the antioxidant defenses, SOD and catalase, were inhibited. The differing effects of antioxidant inhibitors on bleomycin-induced cytotoxicity and membrane lipid damage suggest that different mechanisms are involved in these two processes. However, free radicals appear to be involved in both cases. The marked sensitization of cells by diethyldithiocarbamate, to both bleomycin-induced cytotoxicity and lipid peroxidation, suggests that superoxide could be involved in both of these processes.

Preoperative localization of parathyroid lesions in hyperparathyroidism: relationship between technetium-99m-MIBI uptake and oxyphil cell content.

UNLABELLED: The aim of this study was to assess the relationship between parathyroid oxyphil cell content and early or late phases of uptake of 99mTc-MIBI, a radioisotope preferentially retained in mitochondria-rich cells. METHODS: This study is a retrospective, single-blind analysis of all double-phase 99mTc-MIBI parathyroid scintigraphy studies performed before surgery in our institution between 1990 and 1995. A total of 18 parathyroid lesions in 14 patients were reviewed. This sample included 11 cases of primary hyperparathyroidism (8 adenomas, 1 adenocarcinoma and 2 hyperplasias) and 3 cases of tertiary hyperparathyroidism secondary to chronic renal failure. RESULTS: Uptake of 99mTc-MIBI in the early phase of scintigraphy was associated with larger parathyroid lesions (1.61 +/- 1.61 ml versus 0.33 +/- 0.27 ml; p < 0.02) and higher serum calcium levels (3.00 +/- 0.41 mM versus 2.67 +/- 0.14 mM; p < 0.02). More importantly, we found that a parathyroid oxyphil cell content greater than 25% was more often associated with a positive uptake of 99mTc-MIBI in the late phase of the test (positive late uptake in 78% of lesions with a high oxyphil cell content versus 33% in lesions with an oxyphil cell content between 1% and 25% and 0% in lesions with no oxyphil cells; p < 0.04). CONCLUSION: These findings suggest that the late retention of 99mTc-MIBI in double-phase scintigraphy is related to parathyroid oxyphil cell content.

False-positive 201thallium study in Wolff-Parkinson-White syndrome.

Wolff-Parkinson-White syndrome (WPW) is known to cause abnormal rest electrocardiogram and stress tests. Consequently, the diagnosis of coronary artery disease (CAD) may be difficult in patients with WPW. Previous reports have described false positive stress 201thallium studies in WPW, but the absence of CAD has rarely been confirmed by coronary angiography. A case of false positive stress 201thallium scintigraphy confirmed by angiography is presented. Left ventricular contractile asynchrony can explain the defects observed in myocardial perfusion scintigraphy. The importance of the defects relates to the length of the delta wave.

Massive hydrothorax complicating peritoneal dialysis. Isotopic investigation (peritoneopleural scintigraphy).

Massive hydrothorax occurring during continuous ambulatory peritoneal dialysis is a rare complication that may appear at any time during the course of the treatment. Most of the time, it is right-sided and is more frequent in female patients. A case is presented that was investigated by peritoneopleural scintigraphy. A rapid accumulation of the radiopharmaceutical over the right hemithorax was observed. To explain that finding, a macroscopic diaphragmatic defect was suspected. Different therapeutic approaches are presented.

A novel microporous polyurethane vascular graft: in vivo evaluation of the UTA prosthesis implanted as infra-renal aortic substitute in dogs.

A novel microporous polyurethane blood conduit developed at the University of Texas at Arlington was implanted as an infra-renal substitute in dogs. The prosthesis was fabricated by precipitating a solution of the polymer with dry nitrogen onto a rotating mandrel. The grafts were sterilized either by gamma radiation (series I) or ethylene oxide (series II); they were implanted for the following prescheduled periods: 4, 24, 48 hours, and 1 week (short-term) and 2, 4 weeks, 3 and 6 months (medium-term). The thrombohematological characteristics of each animal were evaluated prior to implantation and confirmed that the index of blood coagulability was normal. In the short-term group, five out of eight grafts were patent and three were partially occluded; four grafts in the medium-term group were patent; one was partially occluded; and three were thrombosed at retrieval. One week after implantation, the prostheses were surrounded by an external capsule, which was present mainly at the two anastomoses. The external capsule covered the entire graft at 3 months. No kinking of the grafts was observed and the presence of a mild yellow stain related to bilirubin uptake was detected at 2 weeks, 1, 3, and 6 months. Histological studies have revealed the formation of a thin internal capsule at both anastomoses, 2 weeks postimplantation, which was not anchored to the graft wall. In the medium-term group, the thrombosed grafts failed to develop an internal capsule, whereas the patent graft exhibited a thick internal capsule made of neocollagenous tissue over the entire graft. This new microporous polyurethane prosthesis did not perform satisfactorily as an infra-renal substitute in dogs and its in vivo stability requires further assessment. Thus, the concept of a polyurethane with closed pores does not achieve what was anticipated.

Diffuse lung uptake of technetium-99m sulfur colloid in malaria.

Diffuse lung accumulation of colloid was seen on liver-spleen imaging in a patient during the acute stage of vivax malaria. A repeat study was performed following successful therapy and showed complete disappearance of lung uptake. Possible mechanisms for this unusual observation are discussed, with the conclusion that this phenomenon is probably related to increased reticuloendothelial system activity, due to a malaria-induced increase in the pulmonary macrophages.

Gallium-67 citrate accumulation in a mycotic popliteal artery aneurysm.

A 31-year-old man with bacterial endocarditis developed a mycotic popliteal aneurysm which presented clinically like an acute osteomyelitis. Bone and Ga-67 scanning played a major role in disclosing this unsuspected lesion. Various isotopic techniques proposed for the detection of mycotic aneurysm are reviewed. The potential usefulness of Ga-67 imaging in patients at risk of developing such lesions is discussed.

[Hepatobiliary scintigraphy using 99m Tc-DISIDA and obstructive cholangiopathy in children]. / Scintigraphie hépato-biliaire au disida-99mTc et cholangiopathies obstructives infantiles.

Technetium 99m-labeled diisopropyl iminodiacetic acid (99m Tc-DISIDA) hepatobiliary scintigraphy of 26 patients with pathologically proven infantile obstructive cholangiopathy are retrospectively studied according to two types of criteria. Those of type 1 consider 1) hepatocyte clearance 2) hepatobiliary transit time and 3) visualisation of intestinal activity. For biliary atresia, sensitivity of 88.2%, specificity of 88.9%, positive predictive value of 93.8% and negative predictive value of 80.0% were obtained. For neonatal hepatitis, those parameters were 57.1%, 94.7%, 80.0% and 85.7% respectively. Criteria of type 2 identify only biliary atresia. They consider 1) presence or absence of intestinal radioactivity through 24 hours and 2) birth weight. Sensitivity, specificity, positive and negative predictive values were 88.2%, 88.9%, 93.8% and 80.0% respectively. Even if all these values are inferior to many reported in literature, we consider that the two types of criteria are relatively sensitive and specific to detect biliary atresia. Even through there are a few false negatives, biliary scintigraphy does remain one of the most important diagnostic tests in the context of biliary atresia.

Ascites and right pleural effusion: demonstration of a peritoneo-pleural communication.

A 54-yr-old female with known liver cirrhosis presented with a right transudative pleural effusion and ascites. To find the source of pleural fluid, [99mTc]sulfur colloid was injected intraperitoneally and a serial imaging study revealed its passage to the right pleural space on 2-hr and 24-hr images. Mechanisms proposed in the formation of pleural effusion in liver cirrhosis are (a) lymphatic drainage and (b) diaphragmatic defect. Radioisotope migration speed may be a clue for differentiating these two mechanisms, being more rapid in the presence of a diaphragmatic defect.

Flip-flop phenomenon and dissection of extracranial carotid artery.

A case of extracranial carotid artery dissection investigated both by conventional brain imaging and by arteriography is presented. The radionuclide angiogram showed a flip-flop phenomenon on the left hemisphere. The implications, including clinical features, pathogenesis, diagnosis, and treatment are discussed. Dissection of extracranial carotid artery is a cause of carotid hypoactivity, and this phenomenon is associated directly with a flip-flop phenomenon on brain imaging.