Preparation of supramolecular polymers by copolymerization of monomers containing quadruple hydrogen bonding units with regular monomers

The invention relates to the synthesis of polymers contg. self-complementary quadruple H groups by copolymg. monomers contg. a quadruple H bonding group with ³1 monomers of choice. The resulting polymers show unique new characteristics due to the presence of addnl. phys. interactions between the polymer chains that are based on multiple H bonding interactions (supramol. interactions). Thus, 2-isocyanatoethyl methacrylate (7.0 mL) was added to a soln. of 6-(1-ethylpentyl)isocytosine (13.4 g) in dry pyridine (150 mL), the reaction mixt. was stirred under Ar at 80° for 4 h to give a monomer, and was polymerizable with 2-hydroxyethyl methacrylate in the presence of ATRP initiators, CuBr, and bipyridine

Preparation of supramolecular polymers by copolymerization of monomers containing quadruple hydrogen bonding units with regular monomers

The invention relates to the synthesis of polymers contg. self-complementary quadruple H groups by copolymg. monomers contg. a quadruple H bonding group with ³1 monomers of choice. The resulting polymers show unique new characteristics due to the presence of addnl. phys. interactions between the polymer chains that are based on multiple H bonding interactions (supramol. interactions). Thus, 2-isocyanatoethyl methacrylate (7.0 mL) was added to a soln. of 6-(1-ethylpentyl)isocytosine (13.4 g) in dry pyridine (150 mL), the reaction mixt. was stirred under Ar at 80° for 4 h to give a monomer, and was polymerizable with 2-hydroxyethyl methacrylate in the presence of ATRP initiators, CuBr, and bipyridine

The Rasch-built Pompe-specific activity (R-PAct) scale.

We constructed a patient-based interval scale using Rasch analysis, specifically suited to quantify the effects of Pompe disease on patient's ability to carry out daily life activities and their social participation: Rasch-built Pompe-specific Activity scale. Between July 2005 and April 2011, 186 patients aged 16 or older, participated to develop this scale. External construct validity was determined through correlations with the MRC sumscore and Rotterdam Handicap Scale. Furthermore, test-retest reliability was determined in a subgroup of 44 patients. Finally, individual person-level responsiveness was used to determine the proportion of patients demonstrating significant improvement or deterioration during their natural disease course, or during treatment with enzyme replacement therapy. Of the original 49 items, 31 were removed after investigation of model fit, internal reliability, threshold examination, item bias, and local dependency. The remaining 18 items were ordered on a linearly weighted scale and demonstrated good discriminative ability (Person Separation Index 0.96), external construct validity (intraclass correlation coefficient (ICC) for MRC sumscore 0.82, and for the Rotterdam handicap scale 0.86), reliability of person's location (ability comparison: ICC 0.95), and responsiveness. We therefore conclude that the R-PAct scale enables us to accurately detect limitations in activities and social participation throughout the entire disease spectrum in patients with Pompe disease. Copyrigh

Long-term follow-up of 17 patients with childhood Pompe disease treated with enzyme replacement therapy

Objectives: Pompe disease is a progressive metabolic myopathy for which enzyme replacement therapy (ERT) was approved in 2006. While various publications have examined the effects of ERT in classic-infantile patients and in adults, little has been published on ERT in children with non-classic presentations. Study design: This prospective study was conducted from June 1999 to May 2015. Seventeen patients from various countries participated. Outcome measures comprised muscle function (6-minute walk test, quick motor-function test (QMFT)), muscle strength (hand-held dynamometry; manual muscle testing), and lung function (FVC sitting and supine). For each outcome measure, we used linear mixed-effects models to calculate the difference at group level between the start of therapy and 7 years of ERT. Patients’ individual responses over time were also evaluated. Results: Eleven males and six females started ERT at ages between 1.1 and 16.4 years (median 11.9 years); 82% of them carried the common c.-32-13T > G GAA gene variant on one allele. At group level, distance walked increased by 7.4 percentage points (p < 0.001) and QMFT scores increased by 9.2 percentage points (p = 0.006). Muscle strength scores seemed to remain stable. Results on lung function were more variable. Patients’ individual data show that the proportion of patients who stabilized or improved during treatment ranged between 56 and 69% for lung function outcomes and between 71 and 93% for muscle strength and muscle function outcomes. Conclusions: We report a positive effect of ERT in patients with childhood Pompe disease at group level. For some patients

Discontinuation of enzyme replacement therapy in adults with Pompe disease: Evaluating the European POmpe Consortium stop criteria

Enzyme replacement therapy for Pompe disease received market authorization in 2006. To implement this costly treatment in the Netherlands in the most sensible way, a multidisciplinary expert committee was installed. We evaluated decision making in adult patients in relation to the European POmpe Consortium stop criteria. Of 125 adult Pompe patients, 111 started treatment; subsequently treatment stopped in 24 patients (21%). In 10 patients, treatment was discontinued for medical or personal reasons, as defined in the six stop criteria (median treatment duration: 2.1 years, range: 0.3–14.6 years). Three of these patients continued follow-up (follow-up: 1.3–8.0 years), these patients did not display a more rapid decline after discontinuation. In 14 of 24 patients, therapy ended at time of death. In 10 patients death was related to Pompe disease (median treatment duration: 7.2 years, range: 0.4–10.3 years). All 10 patients were severely affected at start of treatment, treatment had elicited positive effects in eight. The European POmpe Consortium guidelines worked well in decision making on stopping treatment. However, (re)evaluation of the rationale for continuation of treatment in advanced disease stage is not addressed. We suggest to add this to the treatment evaluation and to handle treatment decisions in a multidisciplinary expert team

Temperature and Frequency Dependence of Complex Conductance of Ultrathin YBa2Cu3O7-x Films: A Study of Vortex-Antivortex Pair Unbinding

We have studied the temperature dependencies of the complex sheet conductance of 1-3 unit cell (UC) thick YBa2Cu3O7-x films sandwiched between semiconducting Pr0.6Y0.4Ba2Cu3O7-x layers at high frequencies. Experiments have been carried out in a frequency range between: 2 - 30 MHz with one-spiral coil technique, 100 MHz - 1 GHz frequency range with a new technique using the spiral coil cavity and at 30 GHz by aid of a resonant cavity technique. The real and imaginary parts of the mutual-inductance between a coil and a film were measured and converted to complex conductivity by aid of the inversion procedure. We have found a quadratic temperature dependence of the kinetic inductance, L_k^-1(T), at low temperatures independent of frequency, with a break in slope at T^dc_BKT, the maximum of real part of conductance and a large shift of the break temperature and the maximum position to higher temperatures with increasing frequency. We obtain from these data the universal ratio T^dc_BKT/L_k^-1(T^dc_BKT) = 25, 25, and 17 nHK for 1-, 2- and 3UC films, respectively in close agreement with theoretical prediction of 12 nHK for vortex-antivortex unbinding transition. The activated temperature dependence of the vortex diffusion constant was observed and discussed in the framework of vortex-antivortex pair pinning. PACS numbers: 74.80.Dm, 74.25.Nf, 74.72.Bk, 74.76.BzComment: PDF file, 10 pages, 6 figures, to be published in J. Low Temp. Phys.; Proc. of NATO ARW: VORTEX 200

Effects of a higher dose of alglucosidase alfa on ventilator-free survival and motor outcome in classic infantile Pompe disease: an open-label single-center study

Background: Though enzyme-replacement therapy (ERT) with alglucosidase alfa has significantly improved the prospects for patients with classic infantile Pompe disease, some 50 % of treated infants do not survive ventilator-free beyond the age of 3 years. We investigated whether higher and more frequent dosing of alglucosidase alfa improves outcome. Methods: Eight cross-reactive immun

Positive association between physical outcomes and patient-reported outcomes in late-onset Pompe disease: a cross sectional study

BACKGROUND: Pompe disease is a rare, progressive metabolic myopathy. The aim of this study is to investigate the associations of physical outcomes with patient-reported outcome measures (PROMs) in late-onset Pompe disease. METHODS: We included 121 Dutch adult patients with Pompe disease. Physical outcomes comprised muscle strength (manual muscle testing using Medical Research Council [MRC] grading, hand-held dynamometry [HHD]), walking ability (6-min walk test [6MWT]), and pulmonary function (forced vital capacity [FVC] in upright and supine positions). PROMs comprised quality of life (Short Form 36 health survey [SF-36]), participation (Rotterdam Handicap Scale [RHS]) and daily-life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale). Analyses were cross-sectional: the time-point before, and closest to, start of Enzyme Replacement Therapy was chosen. Associations between PROMs and physical outcomes were investigated using linear regression models. RESULTS: RHS and R-PAct scores were better in patients with higher FVC supine and upright, HHD, MRC and 6MWT scores, accounting for the effect of sex, disease duration, use of wheelchair and ventilator support. While the SF-36 Physical Component Summary (PCS) was correlated positively with FVC upright, HHD, MRC and 6MWT scores, there was no significant relationship between the SF-36 Mental Component Summary (MCS) and any of the physical outcomes. CONCLUSIONS: Participation, daily-life activities, and the physical component of quality of life of adult Pompe patients are positively correlated to physical outcomes. This work serves as a first step towards assessing how changes over time in physical outcomes are related to changes in PROMs, and to define the minimal change in physical outcomes required to make an important difference for the patient