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Biomedical subjects

Adrian Williams

Publications and source records attributed to Adrian Williams.

11 recordsLinked to original sources
PubMed2006

The Parkinson-Control study: a 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease.

Dopamine agonists have been recommended as early treatment for Parkinson's disease (PD), alone or combined with levodopa. Piribedil is a non-ergot selective D(2)/D(3) agonist with alpha(2) antagonist properties shown to be effective in the treatment of PD. This 12-month international, randomized, double-blind trial aimed to assess the efficacy of piribedil 150 mg versus bromocriptine 25 mg, in early combination with levodopa in Stage I to III PD patients. Motor efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS III, Items 18-31) as improvement from baseline. Response rate was defined as a 30% improvement. Among the 425 randomly assigned patients, 178 were also included in a substudy on cognitive follow-up evaluated by a dysexecutive syndrome oriented battery. A relevant improvement in UPDRS III over the 12-month study duration was observed both in the piribedil and bromocriptine groups (-7.9 +/- 9.7 points from baseline versus -8.0 +/- 9.5; not significant [n.s.]) with a response rate of 58.4% and 55.3% (n.s.), respectively. Piribedil and bromocriptine resulted in similar improvement on all UPDRS III subscores. Piribedil patients required less levodopa dose increase than those on bromocriptine. Cognitive performance remained generally unchanged in both groups, with a significant effect of piribedil limited to the Wisconsin Card Sorting Test. An overall good tolerability of piribedil was observed. Early combination of piribedil 150 mg with levodopa resulted in significant long-term improvement of all motor symptoms in PD patients insufficiently controlled by levodopa alone. Taking into account both efficacy and acceptability in the long-term, piribedil proved in this bromocriptine controlled study to be an effective and safe treatment for PD.

Adult↗
PubMed2005

Nicotinamide: a double edged sword.

Enrichment of diet with Nicotinamide in the West was introduced in the 1940s to prevent the dietary deficiency disorder Pellagra. Pellagra was caused by a particular form of poor vegetarian diet leading to Nicotinamide and Tryptophan deficiency. Arguably Pellagra would have disappeared if dietary measures suggested at the time had been implemented before Nicotinamide was even discovered. Diets may sometimes now be too high in selected pyridines and inadvertently we have exchanged one neurodegenerative disease for another. Parkinson's disease triggered in contrast to Pellagra by a particular form of rich omnivorous diet. Moderation of Nicotinamide intake would be easy to begin with compared with other dietary manipulations as there is no behavior change necessary for individuals. A substantial amount of Nicotinamide can be removed when and where there is too much that has been introduced artificially and inserted where there is too little because meat is unaffordable.

Humans↗
PubMed2005

Inferring pathogen inactivation from the surface temperatures of compost heaps.

A sufficiently high composting temperature should inactivate many common pathogens likely to be present in solid animal waste. Monitoring core temperatures inside compost heaps is not straightforward, which means that heaps are not generally monitored. An alternative is to monitor surface temperatures and use those data to infer core temperatures, and thus whether pathogen inactivation has occurred. This paper describes two methods (thermal imaging and thermocouples) for the measurement of surface temperature, and a modelling approach using time series analysis to predict the temperatures obtained in the core of aerated heaps of composting pig farmyard manure (FYM) from surface temperature data. The model was able to predict core temperatures in the heap quite closely for a period of time for well insulated parts of the heap, although predictions were further from observed values close to the surface of the heap and the aeration pipe.

Agriculture↗
PubMed2004

Diagnosing restless legs syndrome (RLS) in primary care.

This paper represents a review of current opinion and information on the effective diagnosis of restless legs syndrome (RLS) in a primary care setting. RLS can be a distressing condition--it can cause serious sleep disturbance and has a significant impact on quality of life comparable to that of depression or type 2 diabetes. The prevalence of adults whose RLS is severe enough to warrant medical advice has been estimated to be approximately 3%, but only a small proportion of these patients currently report having been diagnosed in primary care, despite stating that they have presented to their GP. The benefits of increased understanding of the symptoms of RLS and how patients present in primary care are discussed, with emphasis on how this will help GPs more effectively diagnose and manage the patients affected. Guidelines on how to diagnose RLS in a primary care setting are given--when a patient presents with sleep disturbance, RLS should be routinely considered and, where existing, be readily diagnosed in a primary care setting on the basis of the patient's clinical history, a physical examination and with the aid of four questions based on the International RLS Study Group (IRLSSG) four essential diagnostic criteria.

Humans↗
PubMed2003

A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference.

STUDY OBJECTIVES: To investigate the link between extreme diurnal preference, delayed sleep phase syndrome, and a length polymorphism in Per3. DESIGN: Subjects were genotyped using polymerase chain reaction. PATIENTS OR PARTICIPANTS: Subjects with defined diurnal preference as determined by the Horne-Ostberg questionnaire and patients with delayed sleep phase syndrome. MEASUREMENTS AND RESULTS: The Per3 polymorphism correlated significantly with extreme diurnal preference, the longer allele associating with morningness and the shorter allele with eveningness. The shorter allele was strongly associated with the delayed sleep phase syndrome patients, 75% of whom were homozygous. CONCLUSION: The length of the Per3 repeat region identifies a potential genetic marker for extreme diurnal preference.

Adolescent↗
PubMed2003

pH-induced modifications to stratum corneum lipids investigated using thermal, spectroscopic, and chromatographic techniques.

The effects of nonphysiological pH on stratum corneum lipid content and structure have been studied. Human stratum corneum samples were soaked in solutions at pH 1, 2, 6, 11, or 12 for up to 24 h. After removal of the stratum corneum, the buffer solutions were analyzed for lipid composition using thin-layer chromatography analysis and the stratum corneum sheets were examined using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. The results demonstrate that only buffers of pH 11 or higher affect the stratum corneum lipids. No large difference in the contents of ceramides and cholesterol extracted by buffers of varying pH was observed. In contrast, free fatty acid extraction was pH dependent; amounts removed by 24-h treatment with pH 11 or 12 buffers were comparable, and were similar to amounts extracted with a methanol-chloroform mixture for 15 min. No appreciable changes in DSC and FTIR spectra were detected between untreated stratum corneum and stratum corneum samples treated with buffers at pHs in the range 1-6. For tissue treated with pH 11 and 12, the position of the endothermal melting peak T2 shifted from 72 to 74 degrees C on the DSC thermograms. Small changes in the broadness of spectral peaks at 2855 cm(-1) [attributable to upsilon(CH(2)) stretching of stratum corneum lipids and 1655 cm(-1) upsilon(C=O) stretching amide I band] can be seen in the FTIR spectra from the treated stratum corneum samples, although no shifts in peak positions were observed. Intensity changes in peaks from extraneous lipids [upsilon(C=O) stretching mode at 1735 cm(-1)] were observed after buffer treatments. The changes provoked by the alkaline buffers are not dramatic and it may be concluded that the stratum corneum appears remarkably resilient to extended exposure in both highly acidic (pH 1) and highly alkaline (pH 12) environments.

Adult↗
PubMed2002

The 3111 Clock gene polymorphism is not associated with sleep and circadian rhythmicity in phenotypically characterized human subjects.

Mutations in clock genes are associated with abnormal circadian parameters, including sleep. An association has been reported previously between a polymorphism (3111C), situated in the 3'-untranslated region (3'-UTR) of the circadian gene Clock and evening preference. In the present study, this polymorphism was assessed in: (1) 105 control subjects with defined diurnal preference, (2) 26 blind subjects with free-running circadian rhythms and characterized with regard to circadian period (tau) and (3) 16 delayed sleep phase syndrome patients. The control group was chosen from a larger population (n = 484) by Horne-Ostberg questionnaire analysis, from which three subgroups were selected (evening, intermediate and morning preference). Data from sleep diaries completed by 90% of these subjects showed a strong correlation between preferred and estimated timings of sleep and wake. The mean timings of activities for the evening group were at least 2 h later than the morning group. Genetic analysis showed that, in contrast with the previously published finding, there was no association between 3111C and eveningness. Neither was there an association between 3111C and tau, nor a significant difference in 3111C frequency between the normal and delayed sleep phase syndrome groups. To assess the effect of this polymorphism on messenger RNA (mRNA) translatability, luciferase reporter gene constructs containing the two Clock polymorphic variants in their 3'-UTR were transfected into COS-1 cells and luciferase activity measured. No significant difference was observed between the two variants. These results do not support Clock 3111C as a marker for diurnal preference, tau, or delayed sleep phase syndrome in humans.

Alleles↗