Two patients with acute thrombocytopenia following gold administration and five-year follow-up

Thrombocytopenia is a well-known side effect following intramuscular gold therapy in patients with rheumatoid arthritis. Thrombocytopenia may occur at any time and it can be irreversible and sometimes fatal despite cytotoxic or immunosuppressive therapy. We describe two patients who presented with haemorrhagic diathesis on the day after the administration of aurothioglucose. The thrombocytopenia in these patients was caused by aurothioglucose-induced antibody-mediated platelet destruction. Both patients made an uneventful recovery and the platelet count returned to normal within severa

Variation in structure and properties of poly(glycerol adipate) via control of chain branching during enzymatic synthesis

Poly (glycerol adipate) (PGA) can be produced from divinyl adipate and unprotected glycerol by an enzymatic route to generate a polymer with relatively low molar mass (12 kDa). PGA bears a pendant hydroxyl group which imparts a hydrophilic character to this water insoluble polymer. We have examined the effect of synthesis temperature on polymer characteristics through various techniques including FT-IR, 1H and 13C NMR, surface and thermal analysis, both to expand the data already present in the literature about this material and to understand better its properties for potential pharmaceutical applications. The use of a lipase (Novozym 435) as a catalyst suppresses cross-linking at the pendant glyceryl hydroxyl through steric hindrance at the active site, thus producing polymers with low degrees of branching (5–30%), and removes the need for any pre- or post-polymerization protection/deprotection reactions. Careful temperature control during synthesis can give polymers with reproducible molecular weights and reduced amounts of polymer branching compared to synthesis at higher temperatures. Due to the ability of the synthetic route to produce a range of structures, PGA generated by enzymatic routes may emerge as a useful biodegradable polymer platform to engineer solid dispersions or nanoparticles for healthcare applications

Modelling bacterial growth of Lactobacillus curvatus as a function of acidity and temperature.

Models that describe the effect of acidity, temperature, and the combined effect of these variables on the growth parameters of Lactobacillus curvatus are developed and validated. Growth parameters (lag time, specific growth rate, and maximum population density) were calculated from growth data at different temperature-acidity combinations. Experiments were set up to assess the quantitative effects of temperature and acidity on the growth parameters rather than for parameter estimation solely. The effect of acidity is monitored at several constant temperature values. Models are set up and fitted to the data. The same procedure is used at constant acidity values to model the effect of temperature. For lag time, specific growth rate, and maximum population density, the effect of temperature could be multiplied with the effect of acidity to obtain combinatory models that describe the effect of both controlling factors on the growth parameters. Lag time measurements showed large deviations, and therefore the lag time models developed can only be used to estimate the order of magnitude of lag time

Modification of Cu surface with picosecond laser pulses

High purity, mirror-polished polycrystalline Cu surface was treated with single picosecond laser pulses at fluence levels close to the single-pulse modification threshold. The induced surface topography and sub-surface changes were examined with scanning and transmission electron microscopy, respectively. The analysis showed an increased absorption of laser energy on the microscopic surface topography inhomogeneities, even at a fluence level below the modification threshold. Many features, like spikes, bubbles, spheres, as well as small periodic ripples at the bottom of scratches, reveal a significant influence of melting and eruptive relaxation of the absorbed laser energy on the final appearance of the surface. Further, it was found that thermal stresses result in twinning to a depth of few tens of nanometers under the surface. Voids at this depth have been observed as well. The results of the observations provide new insights into the early stages of the picosecond laser pulse modification of metals, especially metals with a weak electron–phonon couplin

Trends in Incidence, Treatment and Survival of Stage II T4 Colon Cancer Patients

Surgical oncolog

Local recurrence in patients with rectal cancer diagnosed between 1988 and 1992: a population-based study in the west Netherlands

Contains fulltext : 123804.pdf (publisher's version ) (Closed access

What does cell therapy manufacturing cost? A framework and methodology to facilitate academic and other small-scale cell therapy manufacturing costings.

Contains fulltext : 220591.pdf (Publisher’s version ) (Open Access)BACKGROUND AIMS: Recent technical and clinical advances with cell-based therapies (CBTs) hold great promise in the treatment of patients with rare diseases and those with high unmet medical need. Currently the majority of CBTs are developed and manufactured in specialized academic facilities. Due to small scale, unique characteristics and specific supply chain, CBT manufacturing is considered costly compared to more conventional medicinal products. As a result, biomedical researchers and clinicians are increasingly faced with cost considerations in CBT development. The objective of this research was to develop a costing framework and methodology for academic and other small-scale facilities that manufacture cell-based therapies. METHODS: We conducted an international multi-center costing study in four facilities in Europe using eight CBTs as case studies. This study includes costs from cell or tissue procurement to release of final product for clinical use. First, via interviews with research scientists, clinicians, biomedical scientists, pharmacists and technicians, we designed a high-level costing framework. Next, we developed a more detailed uniform methodology to allocate cost items. Costs were divided into steps (tissue procurement, manufacturing and fill-finish). The steps were each subdivided into cost categories (materials, equipment, personnel and facility), and each category was broken down into facility running (fixed) costs and operational (variable) costs. The methodology was tested via the case studies and validated in developer interviews. Costs are expressed in 2018 euros (€). RESULTS: The framework and methodology were applicable across facilities and proved sensitive to differences in product and facility characteristics. Case study cost estimates ranged between €23 033 and €190 799 Euros per batch, with batch yield varying between 1 and 88 doses. The cost estimations revealed hidden costs to developers and provided insights into cost drivers to help design manufacturing best practices. CONCLUSIONS: This framework and methodology provide step-by-step guidance to estimate manufacturing costs specifically for cell-based therapies manufactured in academic and other small-scale enterprises. The framework and methodology can be used to inform and plan cost-conscious strategies for CBTs.01 juli 202