Development of a Software for Quantitative Evaluation Radiotherapy Target and Organ-at-Risk Segmentation Comparison

Modern radiotherapy requires accurate region of interest (ROI) inputs for plan optimization and delivery. Target delineation, however, remains operator-dependent and potentially serves as a major source of treatment delivery error. In order to optimize this critical, yet observer-driven process, a flexible web-based platform for individual and cooperative target delineation analysis and instruction was developed in order to meet the following unmet needs: (1) an open-source/open-access platform for automated/semiautomated quantitative interobserver and intraobserver ROI analysis and comparison, (2) a real-time interface for radiation oncology trainee online self-education in ROI definition, and (3) a source for pilot data to develop and validate quality metrics for institutional and cooperative group quality assurance efforts. The resultant software, Target Contour Testing/Instructional Computer Software (TaCTICS), developed using Ruby on Rails, has since been implemented and proven flexible, feasible, and useful in several distinct analytical and research applications.     

The role of iodine in thyroid autoimmunity: from chickens to humans: a review.

Evidence has been presented to support the idea that iodine plays an important role in autoimmune thyroiditis. Excessive amounts induce thyroiditis in genetically susceptible animal strains, while intrathyroidal depletion of iodine prevents disease in strains susceptible to severe thyroiditis. While the mechanisms by which iodine promotes thyroiditis is unknown, several hypotheses have been proposed. (1) T and/or B cells may react specifically to iodinated portions of thyroglobulin (Tg) so that severe iodine depletion renders Tg non-immunogenic. (2) A defect in the iodine processing machinery in thyroid epithelial cells of a susceptible person or animal may, in the presence of iodine, result in elevated levels of oxygen or iodine radicals, which could damage membrane lipids or proteins. (3) Defective iodine processing may result in the iodination of lipid or proteins (other than Tg) which could act either as immunogens or polyclonal activators.     

Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration.

BACKGROUND AND PURPOSE: Tissue hardness (induration), pain and tenderness are common late adverse effects of curative radiotherapy for early breast cancer. The purpose of this study was to test the efficacy of IH636 grape seed proanthocyanidin extract (GSPE) in patients with tissue induration after high-dose radiotherapy for early breast cancer in a double-blind placebo-controlled randomised phase II trial. PATIENTS AND METHODS: Sixty-six eligible research volunteers with moderate or marked breast induration at a mean 10.8 years since radiotherapy for early breast cancer were randomised to active drug (n = 44) or placebo (n = 22). All patients were given grape seed proanthocyanidin extract (GSPE) 100 mg three times a day orally, or corresponding placebo capsules, for 6 months. The primary endpoint was percentage change in surface area (cm(2)) of palpable breast induration measured at the skin surface 12 months after randomisation. Secondary endpoints included change in photographic breast appearance and patient self-assessment of breast hardness, pain and tenderness. RESULTS: At 12 months post-randomisation, > or =50% reduction in surface area (cm(2)) of breast induration was recorded in 13/44 (29.5%) GSPE and 6/22 (27%) placebo group patients (NS). At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of external assessments of tissue hardness, breast appearance or patient self-assessments of breast hardness, pain or tenderness. CONCLUSIONS: The study failed to show efficacy of orally-administered GSPE in patients with breast induration following radiotherapy for breast cancer.     

Release of synaptosomal dopamine formed from tyrosine andl-dopa

The present report compares the synaptosomal release of [³H]dopamine, continuously forming from [³H]DOPA, with that of [¹⁴C]dopamine, forming from [¹⁴C]tyrosine as a marker of dopaminergic nerve endings. For the purpose of the comparison, synaptosomal (P₂) preparations from rat caudate nuclei were incubated withl-[³H]DOPA and [¹⁴C]tyrosine for 10 min and the particulates were rapidly separated from the medium postincubation. The separated fractions were analyzed for the level of double labelled (¹⁴C/³H) dopamine and the synaptosomal content of the labelled substrates. Of the total labelled dopamine formed, the fraction that was present in the medium, following the synaptosomal release, was determined. Tested were the release enhancing effects of various additions which included several known dopaminergic agents, serotonin and 5-hydroxytryptophan. The data show that the addition of dopamine to the incubation mixture to either 0.5 or 1.0 μM concentration markedly enhanced the release of labelled dopamine. Serotonin when added to 5.0 μM concentration also raised the medium content of labelled dopamine but it was ineffective at 1.0 μM. 5-Hydroxytryptophan, 1.0 or 5.0 μM, had no effect. For the comparison of the release enhancing effects of an addition of [¹⁴C]dopamine and [³H]dopamine, the corresponding release indices (release index = medium/total ratio of labelled dopamine in the presence of an addition divided by the same ratio in control (no addition) sample) were determined. The data indicate that the index of [¹⁴C]dopamine did not differ significantly from that of [³H]dopamine following the addition of either dopamine, serotonin or 5-hydroxytryptophan at any of the concentrations tested. A similar lack of difference between the index of [¹⁴C]dopamine and that of [³H]dopamine was observed following the addition of reserpine (1.8 μM), although a considerable enhancement of labelled dopamine release occurred. The addition of either amphetamine (9.1 μM) or amfonelic acid (9.1 μM) also enhanced labelled dopamine release but in their presence the index of [³H]dopamine was significantly higher than that of [¹⁴C]dopamine. Amfonelic acid preferentially raised the [³H]dopamine index at the lowest concentration of 0.91 μM that we have tested and also after only 5 min of incubation; coaddition of reserpine increased the [¹⁴C]dopamine release, thus abolishing the preferential effect of amfonelic acid on [³H]dopamine. When the incubation was performed without an addition (control sample), no difference (NS) was observed between the particulate to medium distribution of [¹⁴C]dopamine and that of [³H]dopamine after either 5, 10 or 15 min. The results suggest that (a) dopamine synaptosomally formed froml-DOPA may exist in a pool distinct from that dopamine arising from tyrosine hydroxylation and (b) the observed dopamine compartmentation may be due to some mechanism distinct from any possible participation of serotoninergic partivles. Also, the present results support the previously suggested existence of synaptosomal DOPA in pools.     

Effects of phencyclidine on synaptosomal dopamine continuously appearing from phenylalanine: Sensitivity to reserpine

In the present study some effects of phencyclidine on synaptosomal (P₂) synthesis and release of labelled dopamine, continuously appearing from [¹⁴C]phenylalanine, were investigated in vitro. Also examined was the sensitivity of such effects of phencyclidine to reserpine, acting either in vitro or in vivo. Synaptosomal (P₂) preparations from rat caudate nuclei were incubated with the drugs added at various concentrations in the presence of [¹⁴C]phenylalanine substrate. The particulates were quickly separated from the medium after incubation and the separated fractions were analyzed for labelled dopamine and the synaptosomal uptake of [¹⁴C]phenylalanine. Of the total labelled dopamine formed, the fraction that was present in the medium was determined and taken as a measure of the spontaneous or basal release and its enhancement by any drug addition. Phencyclidine (3.1–36.4 μM) stimulated both the total (medium plus particulates) formation and the synaptosomal release of labelled dopamine, while reserpine (0.09–1.80 μM) inhibited the formation and enhanced the release. A coaddition of reserpine (0.09–1.80 μM) and phencyclidine to the incubation medium blocked the stimulating effect of the latter drug on the labelled dopamine synthesis; the same experiments revealed furthermore, an inhibitory effect of phencyclidine (0.91–36.4 μM) on the synthesis, an effect that was additive to the inhibition due to reserpine alone. The enhancing effect of phencyclidine on labelled dopamine release was however maintained in the presence of reserpine. Phencyclidine (0.22–36.4 μM) also inhibited the formation of labelled dopamine and enhanced its release when the P₂ fraction was prepared from reserpine-pretreated rats (5.0 and 2.5 mg/kg, i.p., at 24 and 2 hr before the experiment). Reserpine (1.80 μM) itself, added in vitro to the same P₂ preparation, was without any significant effect. The phencyclidine congener Ketamine, with or without reserpine, had little effect either on the synthesis or the release. In none of the incubations did the addition of drugs affect the synaptosomal uptake of labelled phenylalanine.     

Role of enteric adenoviruses and rotaviruses in mild and severe acute enteritis

The role of enteric-type adenoviruses and rotaviruses in mild and severe acute gastroenteritis was investigated among children younger than 5 years of age seeking treatment at an urban hospital (UH) and at a rural health center (RHC) in India. There were 330 children at the UH and 340 at the RHC; 319 and 315 age matched nondiarrheal children served as controls for the respective groups. Rotavirus was detected in 15.2% of 330 cases and 1.9% of 319 controls at the UH (P less than 0.001) and in 16.5% of 340 cases and 2.9% of 315 controls at the RHC (P less than 0.001). RV excretion was 3- to 5-fold more common in severe compared with mild diarrhea at the UH and at the RHC (P less than 0.001). The detection rate for enteric-type adenoviruses was similar in patients and controls, respectively, at the UH (0.9%; 2.5%) and RHC (3.8%; 2.5%). At the RHC adenovirus types other than 40 and 41 were excreted by 8.8% of the patients and by only 1.0% of the controls (P less than 0.001). It is possible that the diarrheagenic role of adenoviruses may not be restricted to types 40 and 41.