Dosimetry study of [I-131] and [I-125]- meta-iodobenz guanidine in a simulating model for neuroblastoma metastasis.

The physical properties of I-131 may be suboptimal for the delivery of therapeutic radiation to bone marrow metastases, which are common in the natural history of neuroblastoma. In vitro and preliminary clinical studies have implied improved efficacy of I-125 relative to I-131 in certain clinical situations, although areas of uncertainty remain regarding intratumoral dosimetry. This prompted our study using human neuroblastoma multicellular spheroids as a model of metastasis. 3D dose calculations were made using voxel-based Medical Internal Radiation Dosimetry (MIRD) and dose-point-kernel (DPK) techniques. Dose distributions for I-131 and I-125 labeled mIBG were calculated for spheroids (metastases) of various sizes from 0.01 cm to 3 cm diameter, and the relative dose delivered to the tumors was compared for the same limiting dose to the bone marrow. Based on the same data, arguments were advanced based upon the principles of tumor control probability (TCP) to emphasize the potential theoretical utility of I-125 over I-131 in specific clinical situations. I-125-mIBG can deliver a higher and more uniform dose to tumors compared to I-131 mIBG without increasing the dose to the bone marrow. Depending on the tumor size and biological half-life, the relative dose to tumors of less than 1 mm diameter can increase several-fold. TCP calculations indicate that tumor control increases with increasing administered activity, and that I-125 is more effective than I-131 for tumor diameters of 0.01 cm or less. This study suggests that I-125-mIBG is dosimetrically superior to I-131-mIBG therapy for small bone marrow metastases from neuroblastoma. It is logical to consider adding I-125-mIBG to I-131-mIBG in multi-modality therapy as these two isotopes could be complementary in terms of their cumulative dosimetry.

Detection of temporal lobe seizures and identification of lateralisation from audified EEG.

OBJECTIVE: To investigate the accuracy of human listeners in identifying epileptic seizures and seizure lateralisation from audified EEG signals. METHODS: EEG data from 17 temporal lobe epilepsy patients (9 male, 8 female; aged 23-55) was converted to audio format by 60× time compression. Using a subset of 19% of the data, five auditory participants (2 female, 3 male; aged 23-58) were trained to identify seizures and their lateralisation by listening to audified EEG signals from difference electrodes P3-T5 and P4-T6. Following training, seizure detection performance of the auditory participants was tested using the remaining data. RESULTS: Allowing a 5s auditory time margin for successful detection, the mean sensitivity of the five auditory participants was 89.6% (SD 8.3%) with a false detection rate of only 0.0068/h (SD 0.0077/h). The mean accuracy of seizure lateralisation identification was 77.6% (SD 7.1%). CONCLUSIONS: With a limited amount of training, humans can detect seizures and seizure lateralisation from audified EEG signals of electrodes P3-T5 and P4-T6 with accuracy comparable to visual assessment of full EEG traces (21 electrodes) by an expert encephalographer. SIGNIFICANCE: A more efficient and accurate clinical tool for assessing EEG data based on audification may be developed, which will improve diagnosis and treatment of epilepsy.

Accumulation of manganese in Neisseria gonorrhoeae correlates with resistance to oxidative killing by superoxide anion and is independent of superoxide dismutase activity.

As a facultative aerobe with a high iron requirement and a highly active aerobic respiratory chain, Neisseria gonorrhoeae requires defence systems to respond to toxic oxygen species such as superoxide. It has been shown that supplementation of media with 100 microM Mn(II) considerably enhanced the resistance of this bacterium to oxidative killing by superoxide. This protection was not associated with the superoxide dismutase enzymes of N. gonorrhoeae. In contrast to previous studies, which suggested that some strains of N. gonorrhoeae might not contain a superoxide dismutase, we identified a sodB gene by genome analysis and confirmed its presence in all strains examined by Southern blotting, but found no evidence for sodA or sodC. A sodB mutant showed very similar susceptibility to superoxide killing to that of wild-type cells, indicating that the Fe-dependent SOD B did not have a major role in resistance to oxidative killing under the conditions tested. The absence of a sodA gene indicated that the Mn-dependent protection against oxidative killing was independent of Mn-dependent SOD A. As a sodB mutant also showed Mn-dependent resistance to oxidative killing, then it is concluded that this resistance is independent of superoxide dismutase enzymes. Resistance to oxidative killing was correlated with accumulation of Mn(II) by the bacterium. We hypothesize that this bacterium uses Mn(II) as a chemical quenching agent in a similar way to the already established process in Lactobacillus plantarum. A search for putative Mn(II) uptake systems identified an ABC cassette-type system (MntABC) with a periplasmic-binding protein (MntC). An mntC mutant was shown to have lowered accumulation of Mn(II) and was also highly susceptible to oxidative killing, even in the presence of added Mn(II). Taken together, these data show that N. gonorrhoeae possesses a Mn(II) uptake system that is critical for resistance to oxidative stress.

An on-belt elemental analyser for the cement industry.

On-line control of raw mill feed composition is a key factor in the improved control of cement plants. A new and improved on-conveyor belt elemental analyser for cement raw mill feed based on neutron inelastic scatter and capture techniques has been developed and tested successfully in Adelaide Brighton's Birkenhead cement plant on highly segregated material with a depth range of 100 to 180 mm. Dynamic tests in the plant have shown analyser RMS total errors of 0.49, 0.52, 0.38 and 0.23 wt% (on a loss free basis) for CaO, SiO2, Al2O3 and Fe2O3 respectively, when 10-minute counting periods are used.

Functional caudate imaging in symptomatic Huntington's disease: positron emission tomography versus single-photon emission computed tomography.

Functional neuroimaging with positron emission tomography previously demonstrated reduced caudate glucose metabolism in virtually all symptomatic patients with Huntington's disease (HD). Single-photon emission computed tomography studies of brain blood flow also have shown caudate abnormalities in patients with HD. The present study compared these two functional imaging modalities in 6 patients with HD who had been symptomatic for fewer than 5 years. All patients had significantly impaired caudate-thalamus and caudate-whole-slice glucose metabolism ratios as measured by positron emission tomography. However, only 3 had clearly abnormal caudate-thalamus activity ratios and 2 had clearly abnormal caudate-whole-slice ratios on single-photon emission computed tomography. These findings indicate that single-photon emission computed tomography imaging of caudate blood flow is a less sensitive indicator of caudate dysfunction in early HD than is positron emission tomography imaging of caudate glucose metabolism.

Iron metabolism in Rhodobacter capsulatus. Characterisation of bacterioferritin and formation of non-haem iron particles in intact cells.

The water-soluble cytochrome b557 from the photosynthetic bacterium Rhodobacter capsulatus was purified and shown to have the properties of the iron-storage protein bacterioferritin. The molecular mass of R. capsulatus bacterioferritin is 428 kDa and it is composed of a single type of 18-kDa subunit. The N-terminal amino acid sequence of the bacterioferritin subunit shows 70% identity to the sequence of bacterioferritin subunits from Escherichia coli, Nitrobacter winogradskyi, Azotobacter vinelandii and Synechocystis PCC 6803. The absorbance spectrum of reduced bacterioferritin shows absorbance maxima at 557 nm (alpha band), 526 nm (beta band) and 417 nm (Soret band) from the six haem groups/molecule. Antibody assays reveal that bacterioferritin is located in the cytoplasm of R. capsulatus, and its levels stay relatively constant during batch growth under aerobic conditions when the iron concentration in the medium is kept constant. Iron deficiency leads to a decrease in bacterioferritin and iron overload leads to an increase. Bacterioferritin from R. capsulatus has an amorphous iron-oxide core with a high phosphate content (900-1000 Fe atoms and approximately 600 phosphates/bacterioferritin molecule). Mössbauer spectroscopy indicates that in both aerobically and anaerobically (phototrophically) grown cells bacterioferritin with an Fe3+ core is formed, suggesting that iron-core formation in vivo may not always require molecular oxygen.

Radio-iodobenzylguanidine for the scintigraphic location and therapy of adrenergic tumors.

Radioiodinated meta-iodobenzylguanidine, a recently developed radiopharmaceutical, has been shown to permit safe, noninvasive, sensitive, and specific scintigraphic location of pheochromocytomas of all types. The technique is especially efficacious in the case of extraadrenal primary lesions and locally recurrent and metastatic tumors. In addition to being taken up by pheochromocytomas, meta-iodobenzylguanidine may be used to image neuroblastomas, nonfunctioning paragangliomas, and carcinoid tumors. Lesions with high 131I-meta-iodobenzylguanidine uptake may respond to treatment with large doses of this radiopharmaceutical.

Foot skin ischaemia in atherosclerotic peripheral vascular disease.

Hyperbaric oxygen and the vasodilating effect of tolazoline hydrochloride were used to investigate atherosclerotic ischaemia of the skin of the foot. Ischaemic feet were divided into two subgroups each with a foot blood flow significantly higher than normal and significantly different from each other. The high blood flow in the ischaemic feet appears to have been an attempt to meet a tissue oxygen need. In some instances this need seems to have been satisfied but without obvious benefit to the ischaemic or anoxic skin. It is suggested that a local rather than a regional blood flow insufficiency is the cause of skin lesions in peripheral vascular disease.