Biomedical subjects

John Warner

Publications and source records attributed to John Warner.

5 recordsLinked to original sources

PubMed2026

From genes to trajectories: mapping genetic influences on Huntington's disease progression.

MOTIVATION: There are many diseases with established genetic factors, such as Huntington's disease (HD), that are characterized by variable rates of progression. However, beyond the contribution of the known genetic factors - in this case the Huntingtin (HTT) gene - the impact of the full human genome on the natural progression of such diseases throughout a patient's life remains largely unknown. The increased availability of genome wide association (GWA) data in HD gene expansion carriers (HDGECs), combined with the clinical assessment scores on the same set of patients, has provided a perfect opportunity to assess the potentially broader genetic impact on the natural progression of HD. RESULTS: We present a genetics-driven, probabilistic disease progression model designed to identify and investigate the ways in which a range of genetic factors affect the natural progression of HD. When applied to a clinico-genomic HD dataset, our model identified several single nucleotide polymorphisms (SNPs) with previously unreported effects on disease progression that act at distinct stages and with varying magnitudes. This discovery may shed light on the potential mechanistic impact of previously unidentified genes on HD that may have implications for clinical management. As increasing amounts of GWA data become available more generally, we anticipate that this modeling framework will be broadly applicable to other diseases with strong genetic components. AVAILABILITY AND IMPLEMENTATION: The source code for IHDPM is available at https://github.com/BiomedSciAI/IHDPM.

Huntington Disease↗

PubMed2002

Switching from conventional to extrafine aerosol beclomethasone dipropionate therapy in children: a 6-month, open- label, randomized trial.

BACKGROUND: In adults with asthma, hydrofluoralkane-134a beclomethasone dipropionate (HFA-BDP) extrafine aerosol provides equivalent asthma control at half the daily dose of conventional chlorofluorocarbon (CFC)-BDP. OBJECTIVE: We sought to compare the efficacy and tolerability of switching from CFC-BDP to HFA-BDP at half the daily dose in children with stable asthma. METHODS: This 6-month, open-label, randomized, multicenter study enrolled 520 children aged 5 to 11 years with well-controlled asthma receiving inhaled CFC-BDP or budesonide 200 to 800 microg/d x. (Four hundred fifty-two patients were using doses within the recommended range of 200-400 microg and were analyzed separately.) During a 4-week run-in period, patients used CFC-BDP plus a spacer (CFC-BDP+S) at approximately the same dose as they were using before study entry. Patients were then randomized in a 1:3 ratio to continue on CFC-BDP+S or switch to HFA-BDP Autohaler at half the daily dose. RESULTS: The change from baseline in morning peak expiratory flow was significantly greater in patients receiving 100-200 microg of HFA-BDP compared with those receiving 200-400 microg of CFC-BDP+S at weeks 7 to 8 (8.5 and 0.4 L/min, respectively; P =.014), with continuing improvement in both groups over 6 months (12.2 and 12.4 L/min, respectively, at month 6). There were no significant differences between treatments in mean change from baseline in FEV(1), percentage of days or nights without asthma symptoms, and daily beta-agonist use over the 6-month treatment period. The proportion of patients who had one or more asthma exacerbations, the incidence of adverse events, and the percentage change from baseline in 24-hour urinary free cortisol levels were similar in the 2 treatment groups. CONCLUSIONS: This study confirms that asthma control can be well maintained in children when switching from CFC-BDP+S to an HFA-BDP Autohaler at doses as low as 100 to 200 microg/d.

Administration, Inhalation↗

PubMed2002

The prevalence and management of asthma in primary-aged schoolchildren in the south of England.

A postal questionnaire survey of headteachers in 149 Infant, Junior and Primary schools (response rate: 63.8%) indicated poor asthma record keeping and a need for regular staff training in asthma. Dealing with an emergency was a major concern of headteachers. In 25 of the schools surveyed, an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was distributed to parents of children in Years 3 and 4 (7-9 years). Headteacher-reported asthma prevalence was 11.9% in these schools, while ISAAC parental reports indicated a current or previous diagnosis of asthma in 24.3% children, with 17.8% receiving asthma treatment and 18.9% reporting wheeze in the previous 12 months. Of six wheezing children per Year 3/4 class, one was receiving no treatment for asthma, three had experienced four or more attacks of wheeze in the previous year with one wheezing child per two Year 3/4 classes experiencing more than 12 such attacks. Four in six children experienced exercise-related wheeze, while only one in five schools allowed asthma medication at Physical Education lessons. A whole school policy on asthma together with some regularly updated staff education and training by an asthma-trained nurse would address many of the issues raised in this study.

Analysis of Variance↗

PubMed2002

Growth, systemic safety, and efficacy during 1 year of asthma treatment with different beclomethasone dipropionate formulations: an open-label, randomized comparison of extrafine and conventional aerosols in children.

OBJECTIVE: To assess the long-term safety of hydrofluoroalkane 134a (HFA)-beclomethasone dipropionate (BDP) extrafine aerosol administered by the Autohaler compared with chlorofluorocarbon (CFC)-BDP administered by a press-and-breathe metered-dose inhaler (pMDI) and spacer (+S) in the treatment of children with asthma. METHODS: This 12-month, open-label, randomized, multicenter study enrolled 300 children who were aged 5 to 11 years and had well-controlled asthma on inhaled CFC-BDP or budesonide; 256 patients were using doses within the recommended range (200-400 microg) and were analyzed separately. Patients were randomized in a 1:3 ratio to continue on CFC-BDP+S at approximately the same dose as they were using before study entry or switch to HFA-BDP at half the daily dose. RESULTS: Asthma control was well maintained in the HFA-BDP group as evidenced by lung function tests and asthma symptoms compared with CFC-BDP+S at approximately twice the dose. There were no significant differences between the HFA-BDP 100 to 200 microg and CFC-BDP+S 200 to 400 microg treatment groups in mean change from baseline in height (5.23 cm vs 5.66 cm at month 12, respectively) or mean growth velocity from day 1 to month 12 (5.27 cm/y vs 5.71 cm/y, respectively). There were no significant differences between groups in adrenal function tests or markers of bone metabolism. CONCLUSIONS: In this long-term study in children with asthma, extrafine HFA-BDP provided long-term maintenance of asthma control at approximately half the dose compared with CFC-BDP+S. There were no clinically meaningful differences between HFA-BDP extrafine aerosol and conventional CFC-BDP+S with regard to growth or other systemic effects.

Administration, Inhalation↗

PubMed2002

Contamination problem with sentinel node localization procedure: a case study.

Lymphoscintigraphy for sentinel node (SN) localization was performed on a 60-y-old man with a melanoma on his back. Skin contamination occurred as a result of the radiopharmaceutical dose administration. Skin contamination could result in a misinterpretation of the SN location. Careful observation of the procedure avoided a misinterpretation with this study.

Artifacts↗