Monte Carlo and analytical calculation of proton pencil beams for computerized treatment plan optimization

Proton pencil beams in water, in a format suitable for treatment planning algorithms and covering the radiotherapy energy range (50-250 MeV), have been calculated using a modified version of the Monte Carlo code PTRAN. A simple analytical model has also been developed for calculating proton broad-beam dose distributions which is in excellent agreement with the Monte Carlo calculations. Radial dose distributions are also calculated analytically and narrow proton pencil-beam dose distributions derived. The physical approximations in the Monte Carlo code and in the analytical model together with their limitations are discussed. Examples showing the use of the calculated set of proton pencil beams as input to an existing photon treatment planning algorithm based on biological optimization are given for fully 3D scanned proton pencil beams; these include intensity modulated beams with range shift and scanning in the transversal plane.     

Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the Lewis rat

Acute, monophasic experimental allergic encephalomyelitis (EAE) in the Lewis rat shows pathological similarities to the human disease multiple sclerosis (MS). Rats that recover from EAE are essentially resistant to disease reinduction, unlike MS in which relapses are frequently associated with common bacterial and viral infections. As macrophage-derived interleukin (IL)-12 is a critical component of innate resistance to bacterial infection and appears to directly activate encephalitogenic T cells in vivo, the ability of this cytokine to reinduce paralysis in EAE was examined. Paralytic disease was exacerbated by intraperitoneal IL-12 administration and could be reinduced up to 1 week after recovery from the primary clinical episode. Concomitant with worsening of initial clinical signs and relapse was an increase in the ratio of macrophages to T cells in brain stem perivascular cuffs and the expression of inducible nitric oxide synthase in cells with both macrophage and microglial morphology. These findings suggest that IL-12 may contribute to macrophage-mediated disease exacerbation and relapse in patients with MS.     

Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor

Chronic bone infection, as attends periodontitis, is often complicated by severe osteolysis. While LPS is believed to be central to the pathogenesis of the osteolytic lesion, the mechanisms by which this bacteria-derived molecule promotes bone resorption are unknown. We find that LPS induces bone marrow macrophages (BMMs) to express c-src, a protooncogene product that we demonstrate is a specific marker of commitment to the osteoclast phenotype. We next turned to possible soluble mediators of LPS-induced c-src. Of a number of osteoclastogenic cytokines tested, only TNF-alpha mirrors the c-src-enhancing effect of LPS. Suggesting that LPS augmentation of c-src is TNF-mediated, endotoxin sequentially induces BMM expression of TNF, followed by c-src. TNF and c-src expression, by cultured BMMs derived from LPS-injected mice, reflects duration of exposure to circulating endotoxin, intimating that endotoxin's effect in vivo is also mediated by TNF. Consistent with these findings, thalidomide (which antagonizes TNF action) attenuates c-src induction by LPS. An anti-TNF antibody blocks LPS enhancement of c-src mRNA, validating the cytokine's modulating role in vitro. Using BMMs of TNF receptor-deleted mice, we demonstrate that TNF induction of c-src is transmitted through the cytokine's p55, but not p75, receptor. Most importantly, LPS administered to wild-type mice prompts osteoclast precursor differentiation, manifest by profound osteoclastogenesis in marrow cultured ex vivo, and by a profusion of marrow-residing cells expressing the osteoclast marker tartrate resistant acid phosphatase, in vivo. In contrast, LPS does not substantially enhance osteoclast proliferation in mice lacking the p55TNF receptor, confirming that LPS-induced osteoclastogenesis is mediated by TNF in vivo via this receptor. Thus, therapy targeting TNF and/or its p55 receptor presents itself as a means of preventing the osteolysis of chronic bacterial infection.     

Comparison of supports for the direct synthesis of hydrogen peroxide from H2 and O2 using Au–Pd catalysts

The direct synthesis of hydrogen peroxide from H₂ and O₂ using a range of supported Au–Pd alloy catalysts is compared for different supports using conditions previously identified as being optimal for hydrogen peroxide synthesis, i.e. low temperature (2 °C) using a water–methanol solvent mixture and short reaction time. Five supports are compared and contrasted, namely Al₂O₃, -Fe₂O₃, TiO₂, SiO₂ and carbon. For all catalysts the addition of Pd to the Au only catalyst increases the rate of hydrogen peroxide synthesis as well as the concentration of hydrogen peroxide formed. Of the materials evaluated, the carbon-supported Au–Pd alloy catalysts give the highest reactivity. The results show that the support can have an important influence on the synthesis of hydrogen peroxide from the direct reaction. The effect of the methanol–water solvent is studied in detail for the 2.5 wt% Au–2.5 wt% Pd/TiO₂ catalyst and the ratio of methanol to water is found to have a major effect on the rate of hydrogen peroxide synthesis. The optimum mixture for this solvent system is 80 vol.% methanol with 20 vol.% water. However, the use of water alone is still effective albeit at a decreased rate. The effect of catalyst mass was therefore also investigated for the water and water–methanol solvents and the observed effect on the hydrogen peroxide productivity using water as a solvent is not considered to be due to mass transfer limitations. These results are of importance with respect to the industrial application of these Au–Pd catalysts.     

Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice

BACKGROUND: Previous studies have demonstrated that human monoclonal and polyclonal anticardiolipin antibodies have thrombogenic properties in vivo. Using such a model in which these antibodies have been shown to increase both the size of an induced thrombus and the duration of time in which such a clot lasts, we investigated whether hydroxychloroquine alters the dynamics of such thrombus formation. METHODS AND RESULTS: Three groups of nine mice were injected with purified immunoglobulin G (IgG) from a patient with the antiphospholipid syndrome (IgG-APS) and then fed with hydroxychloroquine at various doses (100, 6, and 3 mg/kg body wt). Three control groups of mice were also studied, including mice injected with IgG-APS and then fed with placebo, as well as two other groups injected with IgG from normal human serum and fed either hydroxychloroquine or placebo. A standardized thrombogenic injury was subsequently induced in the femoral vein of each mouse and the area (size) of thrombus measured as well as the total period of time that thrombus was present. Mice treated with hydroxychloroquine and IgG-APS showed significantly smaller thrombi that persisted for a shorter period of time compared with animals treated with IgG-APS and placebo. CONCLUSIONS: Hydroxychloroquine significantly diminished both thrombus size and total time of thrombus formation in mice previously injected with IgG-APS.     

Hypocalcemic-induced tetany that causes triceps and bilateral quadriceps tendon ruptures

Small-cell carcinoma (also known as oat-cell carcinoma) is a rare tumor that previously concerns the lung; small-cell carcinoma of the bladder is extremely rare (0.5% of all bladder malignancies). The Authors report here the case of a 78th years old man. Fourteen months before our observation he was submitted to a partial cystectomy for a small-cell carcinoma of the bladder cupola. There was no evidence of extra-vesical location at that moment and the patient was not submitted to any adjuvant therapy. At the moment of our observation the disease was very advanced and the patient died in a few time. The Authors discuss about the therapy of bladder small-cell carcinoma in the few cases described by the literature and about the survival of those patients. A radical surgical treatment in association with an adjuvant chemo- or radiotherapy appears as a better way to treat these patients. On account of this case the Authors agree with this choice and conclude that only a combined treatment can allow a better survival.     

Successful weight loss in a self-taught, self-administered program

There is little evidence concerning the effectiveness of self-help materials for weight control. The purpose of this research was to evaluate a self-help weight-loss program. Obese (body fat > or = 25.0%, range = 25.0-48.6%, mean +/- SEM = 36.5 +/- 1.3%) men (n = 14) and women (n = 21) were given a workbook detailing a behavior modification approach to weight loss that emphasizes self-monitoring of diet and exercise behaviors, and then sent home for 6 months to learn how to lose weight on their own. A group of 9 controls (CONT) who did not get a workbook were used for comparison. ANOVA showed that the experimental group (EXP) lost 8.1 +/- 0.9 (mean +/- SEM) kg body weight, 6.4 +/- 0.8 kg fat, and 3.9 +/- 0.6% body fat; all significant over time (p < 0.001) and different from the CONT (p < 0.0001) who showed no change in these variables. The EXP also reduced their fat intake (% of joules) from 36.1 +/- 1.0% to 27.9 +/- 1.3% (p < 0.0001), increased their carbohydrate intake from 45.7 +/- 1.2% to 50.0 +/- 1.7% (p < 0.007) and their protein intake from 16.3 +/- 0.05% to 20.7 +/- 0.7% (0 < 0.03), all of which were significantly different (p < 0.03) than the CONT who did not change. Dietary fiber increased in the EXP from 19.8 +/- 1.4 to 27.3 +/- 2.2 g/d (p < 0.001) even with a significant reduction in energy intake (11.3 +/- 0.6 vs. 8.9 +/- 0.5 Mj/d; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Isolation of Shigella dysenteriae serotypes 11, 12, and 13 from patients with diarrhea in Bangladesh

Nine isolates of bacteria biochemically resembling Shigella dysenteriae but not belonging to the 10 recognized serotypes were isolated from patients with diarrhea in Bangladesh. Further studies suggested that two, one, and six isolates belonged to the recently recognized S. dysenteriae serotypes 11, 12, and 13, respectively.