The effect of pressurized carbon dioxide as a temporary plasticizer and foaming agent on the hot stage extrusion process and extrudate properties of solid dispersions of itraconazole with PVP-VA 64.

The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of itraconazole and polyvinylpyrrolidone-co-vinyl acetate 64 (PVP-VA 64) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer as well as to produce a foamed extrudate. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. The physicochemical characteristics of the extrudates with and without injection of carbon dioxide were evaluated with reference to the morphology of the solid dispersion and dissolution behaviour and particle properties. Carbon dioxide acted as plasticizer for itraconazole/PVP-VA 64, reducing the processing temperature during the hot stage extrusion process. Amorphous dispersions were obtained and the solid dispersion was not influenced by the carbon dioxide. Release of itraconazole from the solid dispersion could be controlled as a function of processing temperature and pressure. The macroscopic morphology changed to a foam-like structure due to expansion of the carbon dioxide at the extrusion die. This resulted in increased specific surface area, porosity, hygroscopicity and improved milling efficiency.     

USH2A mutation analysis in 70 Dutch families with Usher syndrome type II

Usher syndrome type II (USH2) is characterised by moderate to severe high-frequency hearing impairment, progressive visual loss due to retinitis pigmentosa and intact vestibular responses. Three loci are known for USH2, however, only the gene for USH2a (USH2A) has been identified. Mutation analysis of USH2A was performed in 70 Dutch USH2 families. Ten mutations in USH2A were detected, of which three are novel, c.949C>A, c.2242C>T (p.Gln748X) and c.4405C>T (p.Gln1468X). Including 9 previously published Dutch USH2a families, estimates of the prevalence of USH2a in the Dutch USH2 population were made. Mutations were identified in 62% of the families. In 28% both mutated alleles were identified, whereas in 34% the mutation in only one allele was found. It is estimated that about 28% of the Dutch USH2 families have a different causative gene. Analysis of deduced haplotypes suggests that c.1256G>T (p.Cys419Phe) is a Dutch ancestral mutation, occurring in 16% of the alleles.     

Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19

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Homeless projects show value of electronic records

Across the country, clinicians who have established health care outreach programs for the homeless are using computerized patient records to improve the quality of care delivered. Automated records are enabling providers to offer consistent case management to homeless patients who see many different doctors at many sites, including shelters and mobile clinics. The experience of those involved in these charitable efforts could provide valuable lessons for those attempting to phase in electronic records for the general population.     

A germline homozygote deletion of the glutathione-S-transferase Mu1 gene predisposes to bladder cancer

INTRODUCTION AND OBJECTIVES: Numerous studies have shown smoking and specific occupational exposures to be risk factors for bladder cancer. The risk of bladder cancer may be modified by the activity of carcinogen metabolizing enzymes. The glutathione-S-transferase Mu1 enzyme (GSTM1) detoxifies arylepoxides which are formed after exposure to certain polycyclic aromatic hydrocarbons and possibly aromatic amines. Approximately 40% of Caucasians lack GSTM1 activity due to a homozygous deletion of the GSTM1 locus on chromosome 1p13 (GSTM1 0/0 genotype). The aim of this study was to evaluate the combined effect of smoking and GSTM1 genotype on the risk of bladder cancer. MATERIALS AND METHODS: Sixty-one patients with transitional cell carcinoma of the bladder and 69 controls matched for age and sex were enrolled from the outpatient clinic. Lifestyle information was collected with a standardized questionnaire. DNA was extracted from white blood cells. The GSTM1 genotype was determined by a PCR-based method. RESULTS: 92% of the 61 patients had a history of smoking compared with 81% of the controls. There was a significant dose-response relationship for pack-years of smoking (trend test: p = 0.003). The proportion of GSTM1 0/0 genotype among patients was 62% compared with 43% among controls (odds ratio = 2.1; 95% CI 1.1-4. 3). The expected interaction between smoking and GSTM1 genotype was not observed. CONCLUSIONS: This study confirms the findings that a germline homozygous deletion of the GSTM1 gene predisposes to bladder cancer. An interaction with smoking was not found.