Radiobiological basis, incidence and kinetics of acute mucosal reaction after different fractionation schemes

The paper is presented essential practical knowledge about acute mucosal reactions as an effect of radiation therapy in patients with head and neck cancers. The authors have presented their own experience with mucosal reactions in the course of different fractionation schedules. The practical use of Accumulated Dose in Time and Dose-Time Ratio as a parameters of the risk, intensity and overall heaviness of radiation mucositis is proposed

Acute and consequential mucosal radiation reactions in patients with head and neck cancer treated by continuous accelerated irradiation (CAIR)

Acute mucosal and late radiation responses on continuous accelerated irradiation (CAIR) were evaluated and compared with a conventional treatment (control arm) in 85 patients with head and neck cancer. Confluent mucositis was significantly more severe and maximum score lasting longer in CAIR than in control arm. In the CAIR group 5 (22%) late effects (osteo- and soft tissue necrosis) occured early during 2–4 month of follow-up compare to 5% (1 patient) in control group. There was significant correlation between severity of acute reactions and these late effects in CAIR arm, suggesting that they were consequential. The risk of consequential effects could be predicted by proposed time-area units system of integral acute mucosal reaction

Determinación de edades en Otariidae y Phocidae (Carnivora) sobre piezas dentarias, técnicas alternativas

The periodic depositing of layers of cement and dentine on the mammal’s teeth it is very useful to determine the absolute age. The different events produced during the life cycle as moult, sexual maturity, nursing and feeding are reflected on the amount and type of cement and dentine deposits on the teeth. The aim of this contribution is to determine through the application of different techniques the age of specimens of Phocidae and Otariidae (Mammalia) housed on different collections in Argentina; in order to compare the results obtained with the use of different techniques and to incorporate a crucial datum to each studied specimen. The different techniques were tested, improved and then were performed on 335 specimens of Arctocephalus gazella, Arctocephalus australis, Otaria byronia, Mirounga leonina, Leptonychotes weddellii, Lobodon carcinophagus e Hydrurga leptonyx. The techniques used were: root external rings counting, dentine and cement line counting, both undecalsified as decalsified. Our results showed that not all techniques are effective for all species and for all teeth, effectiveness depends i.e. on the teeth size,  on the way on the cement is deposited. Finally, we recommend which techniques are more effective for each species. The external ring and dentine line counting techniques with and without decalsification are more suitable for Arctocephalus, the dentine line counting by decalsification is recommendable for O. byronia, while in focids is better to used the line cements counting with previuos decalcificaction in postcanines.La depositación periódica de capas de esmalte, cemento y dentina en los dientes de los mamíferos es de gran utilidad para la determinación de edades absolutas. Los diferentes sucesos que se producen durante la vida del animal como la muda, la madurez sexual, período de lactancia y de alimentación, se reflejan muchas veces en la cantidad y tipo de depósito de dentina en las piezas dentarias. Los objetivos de este trabajo son: determinar, con diferentes técnicas aplicables sobre dientes, las edades absolutas de ejemplares de Phocidae y Otariidae (Mammalia) alojados en diferentes colecciones de la Argentina; comparar los resultados obtenidos con el empleo de las distintas técnicas; y añadir un dato relevante a cada ejemplar estudiado. Se compararon, ajustaron, y aplicaron las técnicas a un total de 335 ejemplares de las siguientes especies: Arctocephalus gazella, Arctocephalus australis, Otaria byronia, Mirounga leonina, Leptonychotes weddellii, Lobodon carcinophagus, e Hydrurga leptonyx. Las tecnicas aplicadas fueron: el conteo de anillos externos de la raíz, el conteo de líneas de dentina y de cemento tanto sin descalcificar como descalcificado. Los resultados mostraron que no todas las técnicas son aplicables a todas las especies, ni para todas las piezas dentarias, dependiendo en parte del tamaño de las piezas y de la forma en que el cemento se deposita. Finalmente recomendamos cuáles técnicas son más efectivas para cada especie estudiada. La técnica de conteo de anillos externos y lineas de dentina con y sin descalcificación es conveniente para los Arctocephalus, mientras que la del conteo de líneas de dentina por descalcificación es recomendable para O. byronia, en los fócidos se recomienda el conteo de líneas de cemento con previa descalcificación en poscaninos

Non-Invasive Exploration of Neonatal Gastric Epithelium by Using Exfoliated Epithelial Cells

Background & Aims: In preterm infants, exfoliated gastric epithelial cells can be retrieved from aspirates sampled through the naso-gastric feeding tube. Our aims were to determine (1) whether the recovery of exfoliated cells is feasible at any time from birth through the removal of the nasogastric tube, (2) whether they can be grown in culture in vitro, and (3) whether the physiological state of exfoliated cells expressing H+/K+-ATPases reflects that of their counterparts remaining in situ at the surface of the gastric epithelium in neonatal rat pups. Methods: In infants, gastric fluid aspirates were collected weekly after birth or every 3 hours over 24-h periods, and related to clinical parameters (Biocollection PROG/09/18). In rat pups submitted to a single fasting/refeeding cycle, we explored circadian exfoliation with the cellular counter-parts in the gland. All samples were analyzed by confocal imaging and Enzyme-Linked Immunosorbent Assay. Results: Epithelial cells were identified by microscopy using membrane-bound anti-H+/K+ ATPases antibody, assessed for nucleus integrity, and the expression of selected proteins (autophagy, circadian clock). On 34 infants, the H+/K+-ATPasepositive cells were consistently found quiescent, regardless of gestational age and feeding schedule from day-5 of life to the day of removal of the naso-gastric tube. By logistic regression analysis, we did find a positive correlation between the intensity of exfoliation (cellular loss per sample) and the postnatal age (p,0.001). The H+/K+ ATPase-positive cell

Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation

Chemotherapy plus bevacizumab is currently considered as the standard 1st line treatment of advanced colorectal cancer (ACC). Whereas GI perforation is a known side effect of bevacizumab, the development of GI ulcers has not been reported. We identified 18 patients with ACC who participated in a phase III multicentre trial which included chemotherapy and bevacizumab, who developed a GI ulcer (n = 6), perforation (n = 8) or both (n = 4). The risk of developing a symptomatic GI ulcer or perforation was 1.3% and 1.6%, respectively. Central review of the histology specimens showed ulceration and/or granulation tissue with neovascularisation. The majority (89%) of events developed early during treatment. Given these observations, as well as the relationship between VEGF and mucosal injury healing, we suggest that GI ulcers may occur as a side effect of treatment with bevacizumab and may herald perforation

Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study.

BACKGROUND: Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter. METHODS: Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1-6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1-6), followed by TMZ maintenance therapy (TMZ/RT→TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability. RESULTS: Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated. CONCLUSIONS: Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study