Patient preferences on the use of technology in cancer surveillance after curative surgery: A cross-sectional analysis

Background

Advances in communication technology have enabled new methods of delivering test results to cancer survivors. We sought to determine patient preferences regarding the use of newer technology in delivering test results during cancer surveillance.

Complete response to therapy: why do primary central nervous system lymphoma patients not return to work?

Journal of Neuro-Oncology - Evidence supporting routine postoperative antiepileptic drug (AED) prophylaxis following oncologic neurosurgery is limited, and actual practice patterns are largely...     

Cutis laxa,exocrine pancreatic insufficiency and altered cellular metabolomics as additional symptoms in a new patient with ATP6AP1-CDG

Congenital disorders of glycosylation (CDG) are genetic defects in the glycoconjugate biosynthesis. > 100 types of CDG are known, most of them cause multi-organ diseases. Here we describe a boy whose leading symptoms comprise cutis laxa, pancreatic insufficiency and hepatosplenomegaly. Whole exome sequencing identified the novel hemizygous mutation c.542 T > G (p.L181R) in the X-linked ATP6AP1, an accessory protein of the mammalian vacuolar H⁺-ATPase, which led to a general N-glycosylation deficiency. Studies of serum N-glycans revealed reduction of complex sialylated and appearance of truncated diantennary structures. Proliferation of the patient's fibroblasts was significantly reduced and doubling time prolonged. Additionally, there were alterations in the fibroblasts' amino acid levels and the acylcarnitine composition. Especially, short-chain species were reduced, whereas several medium- to long-chain acylcarnitines (C14-OH to C18) were elevated. Investigation of the main lipid classes revealed that total cholesterol was significantly enriched in the patient's fibroblasts at the expense of phophatidylcholine and phosphatidylethanolamine. Within the minor lipid species, hexosylceramide was reduced, while its immediate precursor ceramide was increased. Since catalase activity and ACOX3 expression in peroxisomes were reduced, we assume an ATP6AP1-dependent impact on the β-oxidation of fatty acids. These results help to understand the complex clinical characteristics of this new patient.     

Combined DNA methylation and gene expression profiling in gastrointestinal stromal tumors reveals hypomethylation of SPP1 as an independent prognostic factor

Gastrointestinal stromal tumors (GISTs) have distinct gene expression patterns according to localization, genotype and aggressiveness. DNA methylation at CpG dinucleotides is an important mechanism for regulation of gene expression. We performed targeted DNA methylation analysis of 1.505 CpG loci in 807 cancer‐related genes in a cohort of 76 GISTs, combined with genome‐wide mRNA expression analysis in 22 GISTs, to identify signatures associated with clinicopathological parameters and prognosis. Principal component analysis revealed distinct DNA methylation patterns associated with anatomical localization, genotype, mitotic counts and clinical follow‐up. Methylation of a single CpG dinucleotide in the non‐CpG island promoter of SPP1 was significantly correlated with shorter disease‐free survival. Hypomethylation of this CpG was an independent prognostic parameter in a multivariate analysis compared to anatomical localization, genotype, tumor size and mitotic counts in a cohort of 141 GISTs with clinical follow‐up. The epigenetic regulation of SPP1 was confirmed in vitro, and the functional impact of SPP1 protein on tumorigenesis‐related signaling pathways was demonstrated. In summary, SPP1 promoter methylation is a novel and independent prognostic parameter in GISTs, and might be helpful in estimating the aggressiveness of GISTs from the intermediate‐risk category.     

Surfactant reduces extravascular lung water and invasion of polymorphonuclear leukocytes into the lung in a piglet model of airway lavage

Acute respiratory distress syndrome (ARDS) in newborns and young infants is linked with an inflammatory response of the lungs which affects the capillary-alveolar permeability, epithelial integrity and type I and II pneumocyte function. Abundant extravascular lung water with a high protein content inactivates surfactant together with the enzymatic action of polymorphonuclear leukocytes (PMNL). We asked if a decrease in extravascular lung water and a reduction in lung infiltration with PMNL could be achieved by surfactant administration (Curosurf) within 6 h of mechanical ventilation when given in a newborn piglet model of repeated airway lavage. Improvements in gas exchange and lung mechanics were predominantly caused by resorption of extravascular lung water rather than by the reopening of alveolar atelectases. PMNL were significantly reduced in the bronchoalveolar lavage fluid after 6 h of mechanical ventilation. However, acute phase cytokines (IL-6, TNF-alpha) remained unchanged, except for IL-8 which increased after administration of surfactant. We conclude that the decrease in extravascular lung water and in infiltration with PMNL following surfactant administration is accomplished within 6 h through mechanisms different from attenuation of pro-inflammatory cytokines. Surfactant treatment for newborn and infant ARDS might therefore improve fluid overload and atelectasis and reduce PMNL infiltration.     

Topical interleukin-8 antibody attracts leukocytes in a piglet lavage model

Objective Acute respiratory distress syndrome (ARDS) in young infants is linked with a pulmonary inflammatory response part of which are increased interleukin-8 (IL-8) levels and migration of polymorphonuclear leukocytes (PMNL) into lung tissue. A topical application of an antibody against IL-8 might therefore decrease PMNL migration and improve lung function.Design Randomized, controlled, prospective animal study.Setting Research laboratory of a university childrens hospital.Subjects and interventions Anesthetized, mechanically ventilated newborn piglets (n=22) underwent repeated airway lavage to remove surfactant and to induce lung inflammation. Piglets then received either surfactant alone (S, n=8), or a topical antibody against IL-8 admixed to surfactant (S+IL-8, n=8), or an air bolus injection (control, n=6).Measurements and results After 6 h of mechanical ventilation following intervention, oxygenation [S 169±51 (SD) vs S+IL-8 139±61 mmHg] and lung function (compliance: S 1.3±0.4 vs S+IL-8 0.9±0.4 ml/cmH₂O/kg; extra-vascular lung-water: S 27±9 vs S+IL-8 52±28 ml/kg) were worse in the S+IL-8 group because reactive IL-8 production [S 810 (median, range 447–2323] vs S+IL-8 3485 (628–16180) pg/ml; P<0.05) with facilitated migration of PMNL into lung tissue occurred. Moreover, antibody application caused augmented chemotactic potency of IL-8 [linear regression of migrated PMNL and IL-8 levels: S r²=0.30 (P=ns) vs S+IL-8 r²=0.89 (P=0.0002)].Conclusion Topical anti-IL-8 treatment after lung injury increases IL-8 production, PMNL migration, and worsens lung function in our piglet lavage model. This effect is in contrast to current literature using pre-lung injury treatment protocols. Our data do not support anti-IL-8 treatment in young infants with ARDS.Financial support: supported by Hübner-Stiftung im Stifterverband, Essen; and Deutsche Forschungsgemeinschaft, Bonn, grant KR 1863/1-1     

Mittheilung einiger Fälle von Meningea-Blutungen,nebst Bemerkungen über die Technik der Eröffnung des Schädels bei denselben

Ohne Zusammenfassung (Mit 2 Abbildungen.)     

Experimentelle Untersuchungen zum Einfluß der Ovarialhormone auf die Entwicklung der Rattenmandibula

Zusammenfassung Weiblichen Ratten des Wistar-Stammes wurden am 1. oder 2. Lebenstag die Ovarien entfernt. Intakte Wurfgeschwister dienten als Kontrolltiere. An den mazerierten Unterkiefern erfolgten Flächen- sowie Längen- und Streckenmessungen von der Geburt an bis zur Pubertät. Es zeigte sich, daß insgesamt die Wachstumsraten bei den neonatal ovarektomierten Tieren im Vergleich zur Kontrollgruppe geringer waren. Deutliche Unterschiede wurden vor allem an den Mandibularflächen und im Vertikaldurchmesser des Kondylarbereiches gefunden. Der Flächeninhalt der Mandibulae stieg im Untersuchungszeitraum auf das 6fache, die Fläche im Bereich der Kondylen vergrößerte sich im gleichen Zeitraum auf das 14fache. Aus den Ergebnissen kann gefolgert werden, daß das Wachstum der Mandibula durch die niedrige präpubertale Sekretion der Ovarialhormone stimuliert wird. Den stärkeren Einfluß üben aber wahrscheinlich andere Wuchsfaktoren, z. B. Wachstumshormon, Schilddrüsenhormone, Androgene und wahrscheinlich das Insulin aus.

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Summary Female rats of a Wistar strain were ovariectomized on the first day of life. Intact littermates served as controls. The growth of the mandibles was evaluated from birth till puberty by measuring the total area as well as the length and the distance between different points. The results demonstrated a generally lower mandibular growth in the neonatally castrated females as compared to the intact controls. Significant differences were mainly found in the total area of the mandible as well as in the vertical diameter of the condyles. Throughout the period of investigation, the total area of the mandibles increased 6fold and that of the condyles 14fold. The findings suggest that the relatively low oestrogen secretion during the prepubertal development stimulates mandibular growth, but that the predominant influence may be exerted by other growth factors, e. g. growth hormone, thyroid hormones, androgens and probably insulin.

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Résumé Des rates de la colonie Wistar furent ovariectomisées un ou deux jours après la naissance. Des soeurs intactes servirent de contrôle. Depuis la naissance jusqu'à la puberté, on mesura la croissance des mandibules, tant sur leur surface totale que sur leur longueur et on nota la distance séparant différents points donnés. Les résultats ont montré une croissance mandibulaire généralement inférieure chez les femelles châtrées, dans la période néonatale, par rapport aux femelles intactes du groupe de contrôle. On observa des différences significatives dans la surface mandibulaire, ainsi que dans le diamètre vertical de la région condylienne. La surface totale des mandibules augmenta de 6 fois et celle des condyles de 14 fois pendant la période d'observation. On pourrait conclure, au vu des résultats obtenus, que la croissance mandibulaire est stimulée par la sécrétion prépubérale relativement basse d'oestrogènes, mais que l'influence prédominante appartient probablement à d'autres facteurs de croissance, tels que l'hormone de croissance, les hormones thyroidiennes, les androgènes et probablement l'insuline.

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Herrn OMR Prof. Dr. med. habil.R. Fränkel zum 75. Geburtstag, vorgetragen beim Geburtstagssymposium in Reinhardsbrunn.