A phase I/II study of gemcitabine during radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma

The purpose of this phase I/II, open-label, single-arm trial is to investigate the safety, tolerability, maximum tolerated dose and preliminary efficacy of the potential radiosensitizer gemcitabine, administered concomitantly to radiotherapy, in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Six doses of weekly gemcitabine were administered intravenously, concomitantly to 6 weeks of hyperfractionated radiotherapy. Successive cohorts received increasing doses of 140, 175 and 200 mg/m2 gemcitabine, respectively, following a 3 + 3 dose-escalation schedule without expansion cohort. Dose-limiting toxicities (DLT) were monitored during treatment period. Clinical response was assessed using predefined case report forms and radiological response was assessed using the modified RANO criteria. Quality of life (QoL) was assessed using PedsQL questionnaires. Between June 2012 and December 2016, nine patients were enrolled. Treatment was well tolerated, and no DLTs were observed up to the maximum dose of 200 mg/m2. All patients experienced reduction of tumor-related symptoms. QoL tended to improve during treatment. PFS and MOS were 4.8 months (95% CI 4.0–5.7) and 8.7 months (95% CI 7.0–10.4). Classifying patients according to the recently developed DIPG survival prediction model, intermediate risk patients (n = 4),

Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study

Introduction: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. Methods: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. Results: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28–84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). Conclusion: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted

Bacterial adhesion to modified polyrethanes

+160hlm.;24c

Bacterial deposition in a parallel plate and a stagnation point flow chamber: Microbial adhesion mechanisms depend on the mass transport conditions

Deposition onto glass in a parallel plate (PP) and in a stagnation point (SP) flow chamber of Marinobacter hydrocarbonoclasticus, Psychrobacter sp. and Halomonas pacifica, suspended in artificial seawater, was compared in order to determine the influence of methodology on bacterial adhesion mechanisms. The three strains had different cell surface hydrophobicities, with water contact angles on bacterial lawns ranging from 18 to 85 degrees. Bacterial zeta potentials in artificial seawater were essentially zero. The three strains showed different adhesion kinetics and the hydrophilic bacterium H. pacifica had the greatest affinity for hydrophilic glass. On average, initial deposition rates were two- to threefold higher in the SP than in the PP flow chamber, possibly due to the convective fluid flow toward the substratum surface in the SP flow chamber causing more intimate contact between a substratum and a bacterial cell surface than the gentle collisions in the PP flow chamber. The ratios between the experimental deposition rates and theoretically calculated deposition rates based on mass transport equations not only differed among the strains, but were also different for the two flow chambers, indicating different mechanisms under the two modes of mass transport. The efficiencies of deposition were higher in the SP flow chamber than in the PP flow chamber: 62±4 and 114±28% respectively. Experiments in the SP flow chamber were more reproducible than those in the PP flow chamber, with standard deviations over triplicate runs of 8% in the SP and 23% in the PP flow chamber. This is probably due to better-controlled convective mass transport in the SP flow chamber, as compared with the diffusion-controlled mass transport in the PP flow chamber. In conclusion, this study shows that bacterial adhesion mechanisms depend on the prevailing mass transport conditions in the experimental set-up used, which makes it essential in the design of experiments that a methodology is chosen with mass transport conditions resembling the problem under investigation

The Effect of Dissolved Organic Carbon on Bacterial Adhesion to Conditioning Films Adsorbed on Glass from Natural Seawater Collected during Different Seasons

Adhesion of three marine bacterial strains, i.e. Marinobacter hydrocarbonoclasticus, Psychrobacter sp. and Halomonas pacifica with different cell surface hydrophobicities was measured on glass in a stagnation point flow chamber. Prior to bacterial adhesion, the glass surface was conditioned for 1 h with natural seawater collected at different seasons in order to determine the effect of seawater composition on the conditioning film and bacterial adhesion to it. The presence of a conditioning film was demonstrated by an increase in water contact angle from 15° on bare glass to 50° on the conditioned glass, concurrent with an increase in the amount of adsorbed organic carbon and nitrogen, as measured by X-ray photoelectron spectroscopy. Multiple linear regression analysis on initial deposition rates, with as explanatory variables the temperature, salinity, pH and concentration of dissolved organic carbon (DOC) of the seawater at the time of collection, showed that the concentration of DOC was most strongly associated with the initial deposition rates of the three strains. Initial deposition rates of the two most hydrophilic strains to a conditioning film, increased with the concentration of DOC in the seawater, whereas the initial deposition rate of the most hydrophobic strain decreased with an increasing concentration of DOC

Bacterial Strains Isolated from Different Niches Can Exhibit Different Patterns of Adhesion to Substrata

Various mechanisms have been demonstrated to be operative in bacterial adhesion to surfaces, but whether bacterial adhesion to surfaces can ever be captured in one generally valid mechanism is open to question. Although many papers in the literature make an attempt to generalize their conclusions, the majority of studies of bacterial adhesion comprise only two or fewer strains. Here we demonstrate that three strains isolated from a medical environment have a decreasing affinity for substrata with increasing surface free energy, whereas three strains from a marine environment have an increasing affinity for substrata with increasing surface free energy. Furthermore, adhesion of the marine strains related positively with substratum elasticity, but such a relation was absent in the strains from the medical environment. This study makes it clear that strains isolated from a given niche, whether medical or marine, utilize different mechanisms in adherence, which hampers the development of a generalized theory for bacterial adhesion to surfaces

Ventriculoperitoneale-shuntdisfunctie bij kinderen

The clinical presentation of a ventriculoperitoneal shunt (VP-shunt) dysfunction depends on whether the cranial sutures are still unfused, and on the cause and severity of the VP-shunt obstruction. A suspicion of a VP-shunt dysfunction is always reason to consult with a neurosurgeon. A patient with a suspected VP-shunt dysfunction that presents with elevated intracranial pressure should be urgently assessed at the emergency department of a neurosurgical center. Conclusions about whether the ventricular system is enlarged should be based on comparison between the imaging made to demonstrate the VP-shunt dysfunction and a reference scan of the brain, made when the patient was in a good clinical condition. In a patient with small ventricles, but clinical indications of elevated intracranial pressure, a VP-shunt dysfunction can't be ruled out. In that case fundoscopy may be very valuable to rule out papilledema

Bacterial deposition to fluoridated and non-fluoridated polyurethane coatings with different elastic modulus and surface tension in a parallel plate and a stagnation point flow chamber

Deposition of three marine bacterial strains with different cell surface hydrophobicities from artificial seawater to polyurethane coatings on glass with different surface tensions and elastic modulus was studied in situ in a parallel plate (PP) and stagnation point (SP) flow chamber. Different surface tensions of the coatings were established by changing the amount of fluorine, whereas using more or less branched polymers made different elastic moduli. Surface tensions of the coating, derived from measured contact angles with liquids, ranged from 11.9 to 44.9 mJ m-2, while the elastic moduli, derived from force-distance curves as measured with an atomic force microscope were between 1.5 and 2.2 GPa. In both flow chambers, the most hydrophilic bacterium Halomonas pacifica adhered preferentially to the more hydrophilic, non-fluoridated coating, whereas the most hydrophobic bacterium Marinobacter hydrocarbonoclasticus showed a greater preference for the more hydrophobic coating. Bacterial adhesion in the PP flow chamber was not influenced by the elastic modulus of the coatings, but in the SP flow chamber bacteria adhered in higher numbers to hard surfaces than to coatings of lower elastic moduli

Multiple linear regression analysis of bacterial deposition to polyurethane coating after conditioning film formation in the marine environment

Many studies have shown relationships of substratum hydrophobicity, charge or roughness with bacterial adhesion, although bacterial adhesion is governed by interplay of different physico-chemical properties and multiple regression analysis would be more suitable to reveal mechanisms of bacterial adhesion. The formation of a conditioning film of organic compounds adsorbed from seawater affects the properties of substratum surfaces prior to bacterial adhesion, which is a complicating factor in studying the mechanism of bacterial adhesion. In this paper, the impact of conditioning films adsorbed from natural seawater to four polyurethane coatings with different hydrophobicity, elasticity and roughness was studied for three different marine bacterial strains in a multiple linear regression analysis. The water contact angle on hydrophobic coatings decreased on average by 8 degrees and increased on average by the same amount on hydrophilic coatings. These changes were accompanied by increased concentrations of oxygen and nitrogen on the surface as determined by X-ray photoelectron spectroscopy, indicative of adsorption of proteinaceous material. Furthermore, the mean surface roughness increased on average by 4 nm after conditioning film formation. Multiple linear regression analysis revealed that changes in deposition due to conditioning film formation of Marinobacter hydrocarbonoclasticus, Psychrobacter sp. SW5H and Halomonas pacifica in a stag nation-point flow chamber could be explained in a model comprising hydrophobicity and the prevalence of nitrogen-rich components on the surface for the most hydrophobic strain. For the two more hydrophilic strains, deposition was governed by a combination of surface roughness and hydrophobicity. Elasticity was not a factor in bacterial adhesion to conditioning films