Prophylactic use of bevacizumab to avoid anterior segment neovascularization following proton therapy for uveal melanoma.

PURPOSE: To investigate whether the prophylactic use of bevacizumab reduces the rate of rubeosis after proton therapy for uveal melanoma and improves the possibility to treat ischemic, reapplicated retina with laser photocoagulation. DESIGN: Comparative retrospective case series. METHODS: Uveal melanoma patients with ischemic retinal detachment and treated with proton therapy were included in this institutional study. Twenty-four eyes received prophylactic intravitreal bevacizumab injections and were compared with a control group of 44 eyes without bevacizumab treatment. Bevacizumab injections were performed at the time of tantalum clip insertion and were repeated every 2 months during 6 months, and every 3 months thereafter. Ultra-widefield angiography allowed determination of the extent of retinal ischemia, which was treated with laser photocoagulation after retinal reapplication. Main outcome measures were the time to rubeosis, the time to retinal reattachment, and the time to laser photocoagulation of ischemic retina. RESULTS: Baseline characteristics were balanced between the groups, except for thicker tumors and larger retinal detachments in the bevacizumab group, potentially to the disadvantage of the study group. Nevertheless, bevacizumab prophylaxis significantly reduced the rate of iris rubeosis from 36% to 4% (log-rank test P = .02) and tended to shorten the time to retinal reapplication until laser photocoagulation of the nonperfusion areas could be performed. CONCLUSIONS: Prophylactic intravitreal bevacizumab in patients treated with proton therapy for uveal melanoma with ischemic retinal detachment prevented anterior segment neovascularization, until laser photocoagulation to the reapplied retina could be performed.

Effect of a temperature increase in the non-noxious range on proton-evoked ASIC and TRPV1 activity.

Acid-sensing ion channels (ASICs) are neuronal H(+)-gated cation channels, and the transient receptor potential vanilloid 1 channel (TRPV1) is a multimodal cation channel activated by low pH, noxious heat, capsaicin, and voltage. ASICs and TRPV1 are present in sensory neurons. It has been shown that raising the temperature increases TRPV1 and decreases ASIC H(+)-gated current amplitudes. To understand the underlying mechanisms, we have analyzed ASIC and TRPV1 function in a recombinant expression system and in dorsal root ganglion (DRG) neurons at room and physiological temperature. We show that temperature in the range studied does not affect the pH dependence of ASIC and TRPV1 activation. A temperature increase induces, however, a small alkaline shift of the pH dependence of steady-state inactivation of ASIC1a, ASIC1b, and ASIC2a. The decrease in ASIC peak current amplitudes at higher temperatures is likely in part due to the observed accelerated open channel inactivation kinetics and for some ASIC types to the changed pH dependence of steady-state inactivation. The increase in H(+)-activated TRPV1 current at the higher temperature is at least in part due to a hyperpolarizing shift in its voltage dependence. The contribution of TRPV1 relative to ASICs to H(+)-gated currents in DRG neurons increases with higher temperature and acidity. Still, ASICs remain the principal pH sensors of DRG neurons at 35°C in the pH range ≥6.

High-momentum proton removal from 16 O and the (e,e'p) cross section

The cross section for the removal of high-momentum protons from 16O is calculated for high missing energies. The admixture of high-momentum nucleons in the 16O ground state is obtained by calculating the single-hole spectral function directly in the finite nucleus with the inclusion of short-range and tensor correlations induced by a realistic meson-exchange interaction. The presence of high-momentum nucleons in the transition to final states in 15N at 60¿100 MeV missing energy is converted to the coincidence cross section for the (e,e¿p) reaction by including the coupling to the electromagnetic probe and the final state interactions of the outgoing proton in the same way as in the standard analysis of the experimental data. Detectable cross sections for the removal of a single proton at these high missing energies are obtained which are considerably larger at higher missing momentum than the corresponding cross sections for the p-wave quasihole transitions. Cross sections for these quasihole transitions are compared with the most recent experimental data available.

Two nucleon induced Lambda decay and the proton to neutron induced ratio

We reanalyze the decay mode of Lambda hypernuclei induced by two nucleons modifying previous numerical results and the interpretation of the process. The repercussions of this channel in the ratio of neutron to proton induced Lambda decay is studied in detail in connection with the present experimental data. This leads to ratios that are in greater contradiction with usual one pion exchange models than those deduced before.

Kinematically complete analysis of the CLAS data on the proton structure Function F2 in a Regge-Dual model

The recently measured inclusive electron-proton cross section in the nucleon resonance region, performed with the CLAS detector at the Thomas Jefferson Laboratory, has provided new data for the nucleon structure function F2 with previously unavailable precision. In this paper we propose a description of these experimental data based on a Regge-dual model for F2. The basic inputs in the model are nonlinear complex Regge trajectories producing both isobar resonances and a smooth background. The model is tested against the experimental data, and the Q2 dependence of the moments is calculated. The fitted model for the structure function (inclusive cross section) is a limiting case of the more general scattering amplitude equally applicable to deeply virtual Compton scattering. The connection between the two is discussed.

Proton emission off nuclei induced by kaons in flight

We study the (K-, p) reaction on nuclei with a 1 GeV/c momentum kaon beam, paying special attention to the region of emitted protons having kinetic energy above 600 MeV, which was used to claim a deeply attractive kaon nucleus optical potential. Our model describes the nuclear reaction in the framework of a local density approach and the calculations are performed following two different procedures: one is based on a many-body method using the Lindhard function and the other is based on a Monte Carlo simulation. The simulation method offers flexibility to account for processes other than kaon quasielastic scattering, such as K- absorption by one and two nucleons, producing hyperons, and allows consideration of final-state interactions of the K-, the p, and all other primary and secondary particles on their way out of the nucleus, as well as the weak decay of the produced hyperons into pi N. We find a limited sensitivity of the cross section to the strength of the kaon optical potential. We also show a serious drawback in the experimental setup-the requirement for having, together with the energetic proton, at least one charged particle detected in the decay counter surrounding the target-as we find that the shape of the original cross section is appreciably distorted, to the point of invalidating the claims made in the experimental paper on the strength of the kaon nucleus optical.

Small, stable shuttle vectors based on the minimal pVS1 replicon for use in gram-negative, plant-associated bacteria.

The minimal replicon of the Pseudomonas plasmid pVS1 was genetically defined and combined with the Escherichia coli p15A replicon, to provide a series of new, oligocopy cloning vectors (5.3 to 8.3 kb). Recombinant plasmids derived from these vectors were stable in growing and nongrowing cells of root-colonizing P. fluorescens strains incubated under different environmental conditions for more than 1 month.

Whole anterior segment proton beam radiotherapy for diffuse iris melanoma.

AIM: To report the results of whole anterior segment proton beam radiotherapy (PBR) for diffuse iris melanoma. METHODS: Between 2000 and 2011, 12 patients with iris melanoma received PBR to the entire iris and ciliary body. RESULTS: Patients had a mean age of 57 years and a median follow-up of 3.5 years (range 1-11.6 years). Tumour iris involvement was 1-4 h in five patients, 5-8 h in four and 9-12 h in three. Angle involvement was 6-8 h in five patients and 9-12 h in seven. The visual acuity (VA) before treatment was 6/5-6/6 in six patients, 6/8-6/9 in three and 6/18-6/38 in three. No tumour recurrence occurred during the follow-up period. Glaucoma treatment was required in 11 of 12 patients. The visual acuity at the last follow-up was 6/5-6/9 in five patients, 6/18-6/24 in three, 6/60-1/60 in two and no light perception in two. Four patients developed varying non-severe degrees of limbal stem cell deficiency, which was treatable with conservative measures. CONCLUSIONS: Whole anterior segment PBR is a useful alternative to enucleation for diffuse iris melanoma. Most patients will need treatment for glaucoma and some may require treatment for tear-film instability and/or stem cell failure.

Scleritis after proton therapy in uveal melanoma [Skleritis nach Protonentherapie bei Aderhautmelanom]

BACKGROUND: Sclera is a very radioresistant tissue and scleritis after proton therapy has not been described so far. HISTORY AND SIGNS: Four female patients, aged between 31 and 74 years, were treated with proton therapy for uveal melanoma (height range: 2.2 - 3.5 mm), located in the macula, the superior equator and 2 in the ciliary body. All patients had a history of a previous or active inflammatory disease and developed scleritis after radiotherapy. THERAPY AND OUTCOME: Two patients had infectious scleritis and were treated with adequate antibiotic therapy. After systemic corticotherapy, 3 patients recovered completely; the remaining patient was managed with additional immunosuppressive treatment as well as a conjunctival and scleral graft, but has not become pain free yet. CONCLUSION: Scleritis is a possible complication after proton therapy, probably on an ischemic basis, where there is a predisposing factor such as inflammatory systemic disease.

Acid inhibition on the first day of dosing : comparison of four proton pump inhibitors

RESUME Introduction: Les inhibiteurs de la pompe à protons sont actuellement considérés comme les médicaments de choix pour le traitement des affections peptiques comme l'ulcère gastroduodénal et l'oesophagite de reflux. La rapidité, ainsi que le degré d'inhibition de la sécrétion gastrique acide sont importants pour le contrôle optimal des symptômes ainsi que pour le traitement de ces affections. But : Le but principal de cette étude a été de comparer, chez les sujets asymptomatiques non infectés par H. pylori, par pH-métrie intragastrique de 24 heures, la rapidité et la durée de l'action antisécrétoire de doses uniques de rabéprazole 20 mg, d'oméprazole capsule 20 mg, d'oméprazole en comprimé MUPS (« Multiple Unit Pellet System ») 20 mg, de pantoprazole 40 mg et de lansoprazole 30 mg, respectivement. Matériel et méthodes : Cette étude, effectuée en double aveugle et randomisée, a été conduite de manière croisée chez 18 sujets H. pylori-négatifs. Une pH-métrie de 24 heures a été effectuée le jour de l'administration du médicament (dose unique de rabéprazole 20 mg, de lansoprazole 30mg, de pantoprazole 40 mg, d'oméprazole capsule 20 mg, d'oméprazole MUPS comprimé 20mg, ou de placebo). Résultats : Le pH intragastrique médian (3.4 vs. 2.9, 2.2, 1.9 et 1.8, respectivement; p≤ 0.03) et le temps avec un pH supérieur à 4 pendant les 24 heures suivant la prise du médicament (8.0 heures vs. 7.4, 4.9, 2.9, et 3.0, respectivement; p≤ 0.003) ont été statistiquement plus élevés avec le rabéprazole qu'avec le lansoprazole, le pantoprazole, l'oméprazole capsule, l'oméprazole comprimé MUPS, ou le placebo. Les valeurs du pH pendant les périodes diurnes et nocturnes étaient plus hautes avec le rabeprazole et le lansoprazole qu'avec le pantoprazole, l'oméprazole capsule, et l'oméprazole comprimé MUPS (p≤0.04). Conclusion : Le rabéprazole s'est montré le plus efficace de tous les inhibiteurs de pompe à protons étudiés durant le premier jour de l'administration du médicament. SUMMARY Background: Rapid and consistent acid suppression on the first day of dosing may be important in treating acid-related disorders. Aim: To compare the antisecretory activity and onset of action of single doses of rabeprazole, lansoprazole, pantoprazole, omeprazole capsule, omeprazole multiple unit pellet system (MUPS) tablet and placebo in healthy Helicobacter pylori-negative subjects. Methods: This cross-over, double-blind, randomized study was performed in 18 H. pylori-negative subjects. Twenty-four-hour intragastric pH monitoring was performed on the day of treatment (once-daily dose of rabeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, omeprazole capsule 20 mg, omeprazole MUPS tablet 20 mg or placebo). Results: The intragastric pH (3.4) and time at pH > 4 during the 24 h post-dose (8.0 h) were significantly greater with rabeprazole than with lansoprazole, pantoprazole, omeprazole capsule, omeprazole MUPS tablet or placebo (P ≤ 0.04 for rabeprazole vs. the others). Daytime and night-time pH values were higher with rabeprazole and lansoprazole than with pantoprazole, omeprazole capsule and omeprazole MUPS tablet (P ≤ 0.04). Conclusion: Rabeprazole was the most potent acid inhibitor of all the proton pump inhibitors tested during the first day of dosing.

Iridocyclectomy for neovascular glaucoma caused by proton-beam radiotherapy of pigmented ciliary adenocarcinoma.

PURPOSE: To report neovascular glaucoma after proton-beam radiotherapy of an adenocarcinoma of the pigmented ciliary epithelium and its successful treatment by iridocyclectomy. PATIENT AND METHODS: A 65-year-old man developed neovascular glaucoma 10 months after proton-beam radiotherapy of a small pigmented iridociliary tumour with a clinical differential diagnosis of uveal melanoma or adenocarcinoma. The diagnosis of 'toxic tumour syndrome' was made, and iridocyclectomy performed. RESULTS: Histopathology and immunohistochemistry of the specimen diagnosed an adenocarcinoma of the pigmented ciliary epithelium, with the presence of mitoses suggesting residual viable tumour cells. The rubeosis regressed, with normalization of the intraocular pressure. Phacoemulsification for radiation-induced cataract restored VA to 6/9, which was better than that recorded at initial referral, the patient having longstanding cellophane maculopathy. CONCLUSIONS: Neovascular glaucoma after radiotherapy of a small, pigmented, ciliary body tumour raises the possibility of adenocarcinoma. This 'toxic tumour syndrome' may respond to iridocyclectomy of the irradiated tumour.