Diurnal variation in DLCO and non-standardized study procedures may cause a false positive safety signal in clinical trials.

Diffusing capacity for carbon monoxide (DLCO) was measured in a phase I single ascending dose study after inhalation of AZD8154 or placebo in healthy participants at baseline (DLCO) and follow-up (DLCO) 6 days after dosing. Initially, DLCO timepoint was 2 h earlier than the DLCO timepoint and clinically significant decreases in DLCO (absolute change up to 19% from baseline and DLCO values less than 70) were observed then. The observed reduction in DLCO was confirmed as a false positive finding after alignment of DLCO timings.

Characterisation of pharmacokinetics, safety and tolerability in a first-in-human study for AZD8154, a novel inhaled selective PI3Kγδ dual inhibitor targeting airway inflammatory disease.

Aims: This 3-part, randomised, phase 1 first-in-human study (NCT03436316) investigated the safety, tolerability and pharmacokinetics (PK) of AZD8154, a dual phosphoinositide 3-kinase (PI3K) γδ inhibitor developed as a novel inhaled anti-inflammatory treatment for respiratory disease.

Methods: Healthy men, and women of nonchildbearing potential, were enrolled to receive single and multiple ascending inhaled doses of AZD8154 in parts 1 and 3 of the study, respectively, while part 2 characterised the systemic PK after a single intravenous (IV) dose. In part 1, participants received 0.

What to Do with a Second Chance in Life? Long-Term Experiences of Non-carriers of Huntington's Disease.

Little is known about how people's lives are influenced when going from a 50% risk status of Huntington's disease (HD) to no risk after performing predictive testing. In this study, 20 interviews were conducted to explore the long-term (> 5 years) experiences after receiving predictive test results as a non-carrier of HD. The results showed a broad variety of both positive and negative reactions.

More appreciation of life or regretting the test? Experiences of living as a mutation carrier of Huntington's disease.

Little is known about how the knowledge of being a mutation carrier for Huntington's disease (HD) influences lives, emotionally and socially. In this qualitative study 10 interviews were conducted to explore the long term (>5 years) experiences of being a mutation carrier. The results showed a broad variety of both positive and negative impact on the carriers' lives.

Gene expression analysis identifies a genetic signature potentially associated with response to alpha-IFN in chronic phase CML patients.

Microarray-based gene expression analysis was performed on diagnostic chronic phase CML patient samples prior to interferon treatment. Fifteen patient samples corresponding to six cytogenetic responders and nine non-responders were included. Genes differentially expressed between responder and non-responder patients were listed and a subsequent leave-one-out cross validation (LOOV) procedure showed that the top 20 genes allowed the highest prediction accuracy.

Detailed assessment of copy number alterations revealing homozygous deletions in 1p and 13q in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is characterized by over-expression of cyclin Dl as a result of the characteristic t(11;14)(q13;q32). However, this translocation alone has proven not to be sufficient for lymphomagenesis, suggesting the involvement of additional alterations. We have characterized 35 cases of MCL by array comparative genomic hybridization with an average resolution of 0.

Immunosuppressive drugs in islet xenotransplantation: a tool for gaining further insights in the mechanisms of the rejection process.

Background: The aim of the present study was to examine the effect of tacrolimus (TAC) and prednisolone (PRE) in islet xenotransplantation and to use the immunosuppressive effects of these drugs and others to further characterize the mechanisms behind islet xenograft rejection.

Methods: Fetal porcine islet-like cell clusters (ICCs) were transplanted under the kidney capsule in Lewis rats. The animals were treated with TAC, cyclosporine A (CsA) plus 15-deoxyspergualin (DSG), CsA plus sirolimus (SIR) or CsA plus leflunomide (LEF), with or without the addition of PRE.

A distinct Th1 immune response precedes the described Th2 response in islet xenograft rejection.

Previous studies using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) have demonstrated that islet xenograft rejection in mice is dominated by Th2-associated cytokines, i.e., interleukin (IL)-4 and IL-10.