Extracellular heat shock protein 70 levels in tumour-bearing dogs and cats treated with radiation therapy and hyperthermia.

Hyperthermia is a form of a cancer treatment which is frequently applied in combination with radiotherapy (RT) to improve therapy responses and radiosensitivity. The mode of action of hyperthermia is multifactorial; the one hand by altering the amount of the blood circulation in the treated tissue, on the other hand by modulating molecular pathways involved in cell survival processes and immunogenic interactions. One of the most dominant proteins induced by hyperthermia is the major stress-inducible heat shock protein 70 (Hsp70). Hsp70 can be found in the blood either as a free-protein (free HSP70) derived from necrotic cells, or lipid-bound (liposomal Hsp70) when it is actively released in extracellular vesicles (EVs) by living cells. The aim of the study was to evaluate the levels of free and liposomal Hsp70 before and after treatment with RT alone or hyperthermia combined with radiotherapy (HTRT) in dogs and cats to evaluate therapy responses. Peripheral blood was collected from feline and canine patients before and at 2, 4, 6 and 24 h after treatment with RT or HTRT. Hsp70 enzyme-linked immunosorbent assays (ELISAs) were performed to determine the free and liposomal Hsp70 concentrations in the serum. The levels were analysed after the first fraction of radiation to study immediate effects and after all applied fractions to study cumulative effects. The levels of free and liposomal Hsp70 levels in the circulation were not affected by the first singular treatment and cumulative effects of RT in cats however, after finalizing all treatment cycles with HTRT free and liposomal Hsp70 levels significantly increased. In dogs, HTRT, but not treatment with RT alone, significantly affected liposomal Hsp70 levels during the first fraction. Free Hsp70 levels were significantly increased after RT, but not HTRT, during the first fraction in dogs. In dogs, on the other hand, RT alone resulted in a significant increase in liposomal Hsp70, but HTRT did not significantly affect the liposomal Hsp70 when cumulative effects were analysed. Free Hsp70 was significantly induced in dogs after both, RT and HTRT when cumulative effects were analysed. RT and HTRT treatments differentially affect the levels of free and liposomal Hsp70 in dogs and cats. Both forms of Hsp70 could potentially be further investigated as potential liquid biopsy markers to study responses to RT and HTRT treatment in companion animals.

Association of perinatal risk factors with neurological outcome in neonates with hypoxic ischemic encephalopathy.

OBJECTIVE: Neonates exposed to perinatal insults typically present with hypoxic ischemic encephalopathy (HIE). The aim of our study was to analyze the association between known risk factors for HIE and the severity of encephalopathy after birth and neurological outcome in neonates during the first 4 d of life. METHODS: Retrospective cohort study including 174 neonates registered between 2011 and 2013 in the National Asphyxia and Cooling Register of Switzerland. RESULTS: None of the studied perinatal risk factors is associated with the severity of encephalopathy after birth. Fetal distress during labor (OR, 2.06; 95% CI, 1.02-4.25, p = .049) and neonatal head circumference (HC) above 10th percentile (p10) at birth (OR, 1.33; 95% CI, 1.05-1.69, p = .02) were associated with neurological benefit in the univariate analysis. Fetal distress on maternal admission for delivery was the only risk factor for neurological harm in the univariate (OR, 0.26; 95% CI, 0.12-0.57, p < .01) and the multivariate analysis (OR, 0.15; 95% CI, 0.04-0.67, p = .013). We identified two different patient scenarios: the probability for neurological benefit during the first 4 d of life was only 20% in neonates with the combination of all the following risk factors (gestational age >41 weeks, chorioamnionitis, fetal distress on maternal admission for delivery, fetal distress during labor, sentinel events during labor, HC below 10th percentile), whereas in the absence of these risk factors the probability for neurological benefit increased to 80%. CONCLUSIONS: We identified a constellation of risk factors that influence neurological outcome in neonates with HIE during the first 4 d of life. These findings may help clinicians to counsel parents during the early neonatal period. (ClinicalTrials.gov NCT02800018).

Novel hyperthermia applicator system allows adaptive treatment planning: Preliminary clinical results in tumour-bearing animals.

Hyperthermia (HT) as an adjuvant to radiation therapy (RT) is a multimodality treatment method to enhance therapeutic efficacy in different tumours. High demands are placed on the hardware and treatment planning software to guarantee adequately planned and applied HT treatments. The aim of this prospective study was to determine the effectiveness and safety of the novel HT system in tumour-bearing dogs and cats in terms of local response and toxicity as well as to compare planned with actual achieved data during heating. A novel applicator with a flexible number of elements and integrated closed-loop temperature feedback control system, and a tool for patient-specific treatment planning were used in a combined thermoradiotherapy protocol. Good agreement between predictions from planning and clinical outcome was found in 7 of 8 cases. Effective HT treatments were planned and verified with the novel system and provided improved quality of life in all but 1 patient. This individualized treatment planning and controlled heat exposure allows adaptive, flexible and safe HT treatments in palliatively treated animal patients.

Effects of contour propagation and background corrections in different MRI flow software packages.

BACKGROUND: Velocity-encoded magnetic resonance imaging (VENC-MRI) is a commonly used technique in cardiac examinations. This technique utilizes the phase shift properties of protons moving along a magnetic field gradient. VENC-MRI offers a unique way of measuring the severity of valve regurgitation by directly quantifying the regurgitation flow volume. PURPOSE: To compare flow analysis results of different software programs and to assess the effect of background correction in sample patient cases. MATERIAL AND METHODS: A phantom was built out of Polymethyl methacrylate (PMMA) which provides tubes of different diameters. These tubes can be connected to an external water circuit to generate a water flow inside the tubes. Expected absolute flow quantities inside the tubes were determined from preset tube- and flow-parameters. Different flow conditions were measured with a VENC-MRI sequence and the images evaluated using different software packages. In a second step six randomly selected patients showing different degrees of aortic insufficiency were evaluated in clinical terms. RESULTS: The contour propagation algorithms used in the software packages performed differently even on static phantom geometry. In terms of clinical evaluation the software packages performed similarly. Enabling background correction or leaving out manual correction of propagated contours changed results for severity of aortic insufficiency. CONCLUSION: Turning on background correction and manual correction of propagated contours in MRI flow volume measurements is strongly recommended.

Tumour necrosis factor and interferon are selectively cytostatic in vitro for hormone-dependent and hormone-independent human breast cancer cells.

Since experimental studies have shown that tumour necrosis factor-alpha (TNF-alpha) has potent anti-tumour activity that can be potentiated with cytokines, we tested the efficacy of TNF-alpha with interferon-gamma (IFN-gamma) on different human breast cancer cell lines, particularly comparing hormone-dependent and -independent phenotypes. TNF-alpha inhibited the growth of hormone-dependent human MCF-7, ZR-75-1 and T47-D breast cancer cells with a half maximal concentration of 0.25 nM. In contrast, the growth of hormone-independent cells MDA-MB-231 and HS578T was not affected by TNF-alpha alone, but a synergistic inhibition was observed when using IFN-gamma and TNF-alpha together. The mRNA for the proto-oncogene C-MYC, as an intracellular indicator of cell activation, was significantly increased in MCF-7 cells in the presence of TNF-alpha. In MDA-MB-231 cells this mRNA was increased only in the presence of both TNF-alpha and IFN-gamma, without a change in the number of surface TNF receptors. These findings indicate that TNF-alpha treatment in combination with IFN-gamma may provide a successful approach to overcome the cellular heterogeneity of advanced breast tumours.

[A review of the palaeopathology of bone and joint diseases of the medieval period (author's transl)]. / Gelenkerkrankungen bei Skelettfunden aus dem Mittelalter.

Diseases of joints and bones, i.e. chronic Arthritits, Ankylosing, Spondylitis, Osteoarthritis are not unusual. One of the most common in bones is Arthritis. The skeletal tuberculosis is a rare finding. A Kyphosis or a collapsed vertebral is not synonymous with spinal tuberkulosis. Femur esp. the Tibia shows often a chronic Periotitis, it is perhaps caused by Lues. Pseudopathological changes are common and have often led to erroneous diagnoses.