Metabolite and diffusion changes in the rat brain after Leksell Gamma Knife irradiation.

Our study describes the time course of necrotic damage to the rat brain resulting from Leksell Gamma Knife (LGK) irradiation at a dose that was previously considered to be subnecrotic. A lesion induced in the rat hippocampus by 35 Gy irradiation was monitored by MRI, MRS, and DW-MRI for 16 months. T2-weighted images revealed a large hyperintense area with an increased apparent diffusion coefficient of water (ADCw), which occurred 8 months after irradiation, accompanied by metabolic changes (increase of lactate (Lac) and choline (Cho), and decrease of creatine (Cr) and N-acetyl aspartate (NAA), as determined by MRS) that indicated an edema. In two animals, the hyperintensity persisted and a postnecrotic cavity connected to enlarged lateral ventricles developed. In the rest of the animals, the hyperintensity started to decrease 9 months post-irradiation (PI), revealing hypointense areas with a decreased ADCw. Histology confirmed the MRI data, showing either scar formation or the development of a postnecrotic cavity.     

Magnetic resonance relaxometry in monozygotic twins discordant and concordant for schizophrenia.

T1 and T2 relaxation times were examined in four pairs of monozygotic (MZ) twins discordant and concordant for schizophrenia with low and high genetic loading for the illness and five healthy control MZ twin pairs. Patients with schizophrenia (n = 11) showed significant prolongation in T1 relaxation times in the globus pallidus (GP) bilaterally (P < 0.005, Bonferroni corrected) when compared to 14 healthy MZ twins.     

Lenvatinib for the treatment of kidney cancer

Introduction: Sequential administration of single targeted agents has evolved as the dominant paradigm in advanced RCC treatment. Lenvatinib plus everolimus is the first combination therapy in advanced RCC to show improvement in efficacy compared to monotherapy in advanced RCC while maintaining manageable toxicity profile.

Areas covered: This review gives a brief overview of the contemporary clinical data on lenvatinib including its mechanism of action, pharmacokinetics, efficacy and safety profile in combination with everolimus. The clinical applications of lenvatinib in combination with everolimus are addressed within the context of the current competitive therapeutic landscape of RCC.

Expert commentary: Lenvatinib is a new VEGF receptor-targeted tyrosine kinase inhibitor approved in combination with everolimus for second-line therapy in patients with advanced renal cell carcinoma progressing on a first-line VEGF receptor-targeted tyrosine kinase inhibitor. The combination of lenvatinib with everolimus significantly improved progression-free survival compared with everolimus with a hazard ratio of 0.40 and increased objective response to 43%. Optimal sequence of therapy targeting the tumor and the immune system remains a challenge and further investigation is warranted.     

The photosensitization of uveal melanoma cells by ionizing radiation

A study of the character of changes in melanoma cells "in vitro" subjected to successive beta-radiation and light energy of low intensity has revealed a more expressed loss of cells as compared with a "pure" ionizing action. Essential differences in the cells density in the monolayer appear already by the 3d-8th day and reach the maximum 2-3 weeks later. The dynamics of changes in the cells density isn't connected with the cellular type of the tumor and initial density isn't connected with the cellular type of the tumor and initial density of their distribution in the monolayer. The duration of the culture existence becomes shorter. If monolayers not subjected to the action perished after 54.0 +/- 6.2 days, after beta-radiation 35.2 +/- 2.4 days later, then after combined action they perished 17.2 +/- 2.6 days later. Thus, the effect was revealed that is actually opposite to a recently discovered phenomenon of photoreactivation of ionizing injury. Despite difficulty of interpreting possible mechanisms of the discovered phenomenon, it is already possible to suggest about its possibility to be used in treatment of pigmentary new formations.     

A method for modelling retinal detachment

A new method of retinal detachment simulation includes subretinal administration of ferromagnetic fluid with subsequent action from without by a permanent magnetic field. Retinal detachment was induced in 24 eyes of experimental animals. Of them, clinical picture of total high fibrous detachment of the retina was simulated in 16 eyes, and high rigid detachment occupying 2-3 quadrants of the eye fundus--in 8 eyes. Histologically, the induced retinal detachment was characterized by development of degenerative-proliferative processes in all eye coats. The proposed model allows to obtain different variants of "fresh" and "old" retinal detachments. It is highly reproducible, creates conditions for studying all aspects of pathogenesis of complicated forms of retinal detachment and for development of methods for its treatment.     

The AN69 ST haemodialysis membrane under conditions of two different extracorporeal circuit rinse protocols a comparison of thrombogenicity parameters.

BACKGROUND: Thrombogenicity is an important parameter of haemodialysis (HD) membrane biocompatibility. The surface of the polyacrylonitrile AN69 ST membrane is coated with a polyethylenimine. This modification allows heparin adsorption. The binding of heparin to the membrane surface occurs during priming of the extracorporeal circuit (ECC) by rinsing it with saline and heparin. Our aims were to assess and compare the thrombogenicity of the AN69 ST membrane under conditions of two extracorporeal circuit (ECC) rinse protocols-with and without unfractionated heparin (UFH). METHODS: In a prospective, crossover and randomized study, we examined 10 patients during HD after ECC preparation with either rinse protocols. Prior to HD and at 15, 60 and 240 min, we determined plasma levels of the thrombin-antithrombin complexes (TAT), platelet factor 4 (PF4), heparin concentration (antiXa) and thrombocyte count. Systemic anticoagulation was performed using UFH. RESULTS: During HD after ECC rinse without UFH, there was a significantly earlier and more marked increase in TAT compared with UFH-containing rinse (P <0.05). Using Spearman coefficient, we demonstrated a significant correlation between TAT and antiXa at 60 min (r = -0.534) and 240 min (r = -0.538). A comparison of the TAT/antiXa ratios between rinses at 60 min revealed a significantly higher increase in TAT following UFH-free rinse (P <0.05). There was no difference in PF4 between the rinses. Platelet count did not change significantly during HD using either rinse protocol. CONCLUSION: Based on plasma TAT levels, ECC priming with an UFH-containing solution reduces the thrombogenicity of the AN69 ST membrane. There is no significant difference between both types of priming concerning PF4 and thrombocyte count.     

Evidence to suggest adoption of water exchange deserves broader consideration: Its pain alleviating impact occurs in 90% of investigators

AIM: To determine variations in colonoscopy real-time insertion pain among investigators using three different insertion techniques.METHODS: From March 2013 through June 2014, 18-85-year-old diagnostic and 50-70-year-old screening patients were enrolled at each center to on-demand sedation colonoscopy with water exchange(WE), water immersion(WI) and insufflation with air or CO2 for insertion and withdrawal [air or carbon dioxide(AICD)]. Data were aggregated for analysis. Primary outcome: Variations in real-time maximum insertion pain(0 = none, 1-2 = discomfort, 10 = worst).RESULTS: One thousand and ninety-one cases analyzed: WE(n = 371); WI(n = 338); AICD(n = 382). Demographics and indications were comparable. The WE group had the lowest real-time maximum insertion pain score, mean(95%CI): WE 2.8(2.6-3.0), WI 3.8(3.5-4.1) and AICD 4.4(4.1-4.7), P 0.0005. Ninety percent of the colonoscopists were able to use water exchange to significantly decrease maximum insertion pain scores. One investigator had high insertion pain in all groups, nonetheless WE achieved the lowest real-time maximum insertion pain score. WE had the highest proportions of patients with painless unsedated colonoscopy(vs WI, P = 0.013; vs AICD, P 0.0005); unsedated colonoscopy with only minor discomfort(vs AICD, P 0.0005), and completion without sedation(vs AICD, P 0.0005).CONCLUSION: Aggregate data confirm superiority of WE in lowering colonoscopy real-time maximum insertion pain and need for sedation. Ninety percent of investigators were able to use water exchange to significantly decrease maximum insertion pain scores. Our results suggest that the technique deserves consideration in a broader scale.