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Biomedical subjects

Paul S Phillips

Publications and source records attributed to Paul S Phillips.

12 recordsLinked to original sources
PubMed2006

Genetic risk factors associated with lipid-lowering drug-induced myopathies.

Lipid-lowering drugs produce myopathic side effects in up to 7% of treated patients, with severe rhabdomyolysis occurring in as many as 0.5%. Underlying metabolic muscle diseases have not been evaluated extensively. In a cross-sectional study of 136 patients with drug-induced myopathies, we report a higher prevalence of underlying metabolic muscle diseases than expected in the general population. Control groups included 116 patients on therapy with no myopathic symptoms, 100 asymptomatic individuals from the general population never exposed to statins, and 106 patients with non-statin-induced myopathies. Of 110 patients who underwent mutation testing, 10% were heterozygous or homozygous for mutations causing three metabolic myopathies, compared to 3% testing positive among asymptomatic patients on therapy (P = 0.04). The actual number of mutant alleles found in the test group patients was increased fourfold over the control group (P < 0.0001) due to an increased presence of mutation homozygotes. The number of carriers for carnitine palmitoyltransferase II deficiency and for McArdle disease was increased 13- and 20-fold, respectively, over expected general population frequencies. Homozygotes for myoadenylate deaminase deficiency were increased 3.25-fold with no increase in carrier status. In 52% of muscle biopsies from patients, significant biochemical abnormalities were found in mitochondrial or fatty acid metabolism, with 31% having multiple defects. Variable persistent symptoms occurred in 68% of patients despite cessation of therapy. The effect of statins on energy metabolism combined with a genetic susceptibility to triggering of muscle symptoms may account for myopathic outcomes in certain high-risk groups.

AMP Deaminase↗
PubMed2006

Clinical perspectives of statin-induced rhabdomyolysis.

Fear of muscle toxicity remains a major reason that patients with hyperlipidemia are undertreated. Recent evaluations of statin-induced rhabdomyolysis offer new insights on the clinical management of both muscle symptoms and hyperlipidemia after rhabdomyolysis. The incidence of statin-induced rhabdomyolysis is higher in practice than in controlled trials in which high-risk subjects are excluded. Accepted risks include age; renal, hepatic, and thyroid dysfunction; and hypertriglyceridemia. New findings suggest that exercise, Asian race, and perioperative status also may increase the risk of statin muscle toxicity. The proposed causes and the relationship of drug levels to statin rhabdomyolysis are briefly reviewed along with the problems with the pharmacokinetic theory. Data suggesting that patients with certain metabolic abnormalities are predisposed to statin rhabdomyolysis are presented. The evaluation and treatment of patients' muscle symptoms and hyperlipidemia after statin rhabdomyolysis are presented. Patients whose symptoms are related to other disorders need to be identified. Lipid management of those whose symptoms are statin-related is reviewed including treatment suggestions.

Asian People↗
PubMed2005

The effects of geology and the impact of seasonal correction factors on indoor radon levels: a case study approach.

Geology has been highlighted by a number of authors as a key factor in high indoor radon levels. In the light of this, this study examines the application of seasonal correction factors to indoor radon concentrations in the UK. This practice is based on an extensive database gathered by the National Radiological Protection Board over the years (small-scale surveys began in 1976 and continued with a larger scale survey in 1988) and reflects well known seasonal variations observed in indoor radon levels. However, due to the complexity of underlying geology (the UK arguably has the world's most complex solid and surficial geology over the shortest distances) and considerable variations in permeability of underlying materials it is clear that there are a significant number of occurrences where the application of a seasonal correction factor may give rise to over-estimated or under-estimated radon levels. Therefore, the practice of applying a seasonal correction should be one that is undertaken with caution, or not at all. This work is based on case studies taken from the Northamptonshire region and comparisons made to other permeable geologies in the UK.

Air Pollutants, Radioactive↗
PubMed2004

Surface calcification of silicone plate intraocular lenses in patients with asteroid hyalosis.

PURPOSE: To report three cases in which a silicone-plate lens was explanted because of whitish deposits on the posterior optic surface. DESIGN: Observational case series with clinicopathological correlation. PATIENTS AND METHODS: In the three instances, the deposits were observed at least 2 years after uneventful cataract surgery. All of the patients had unilateral mild asteroid hyalosis in the concerned eye. After explantation of the lenses, gross and light microscopic analyses were performed. The posterior optic surfaces of the lenses also underwent scanning electron microscopy coupled with energy dispersive x-ray spectroscopy for analysis of the elemental composition of the deposits. RESULTS: Gross and light microscopic analyses revealed well-demarcated areas of whitish deposits on the posterior optic surface of the lenses, as well as multiple pits caused by Neodymium:yttrium aluminum garnet laser treatments. The deposits formed an amorphous layer with a "crustlike" appearance, which was confirmed by scanning electron microscopy. X-ray spectroscopy analyses demonstrated the composition of the deposits to be similar to hydroxyapatite. CONCLUSIONS: The material opacifying the lenses was probably derived from the asteroid bodies or from a similar process that results in this vitreous condition. We were unaware of this association between asteroid hyalosis and late postoperative dystrophic calcification of silicone lenses.

Aged↗
PubMed2002

Statin-associated myopathy with normal creatine kinase levels.

BACKGROUND: Muscle symptoms in patients who are treated with statins and have normal creatine kinase levels are not well understood. OBJECTIVE: To report biopsy-confirmed myopathy and normal creatine kinase levels associated with statin use. DESIGN: Case reports from preliminary analysis of an ongoing clinical trial. SETTING: Clinical research center in a community hospital. PATIENTS: Four patients with muscle symptoms that developed during statin therapy and reversed during placebo use. MEASUREMENTS: 1) Patients' ability to identify blinded statin therapy and 2) standard measures of functional capacity and muscle strength. RESULTS: All four patients repeatedly distinguished blinded statin therapy from placebo. Strength testing confirmed weakness during statin therapy that reversed during placebo use. Muscle biopsies showed evidence of mitochondrial dysfunction, including abnormally increased lipid stores, fibers that did not stain for cytochrome oxidase activity, and ragged red fibers. These findings reversed in the three patients who had repeated biopsy when they were not receiving statins. Creatine kinase levels were normal in all four patients despite the presence of significant myopathy. CONCLUSION: Some patients who develop muscle symptoms while receiving statin therapy have demonstrable weakness and histopathologic findings of myopathy despite normal serum creatine kinase levels.

Aged↗
PubMed2002

The cost-effectiveness of residential radon remediation programmes: assumptions about benefits stream profiles over time.

A recent cost-effectiveness analysis of a residential radon remediation programme considered and highlighted many areas of uncertainty in the parameters chosen for the analysis. One assumption not challenged in the study was the benefits stream profile adopted. There are several different ways of loading the benefits in terms of life years into the cost-effectiveness model and several of these are explored and the results are reported in this study. The benefits profile depends upon the lead-time to cancer manifestation post environmental carcinogen (radon) exposure. The literature reviewed suggests that there are many options for loading benefits to radon-induced lung cancer prevention programmes. In this study, the alternative benefits stream profiles are explored and their implications for the cost-effectiveness ratio are examined. Adopting different benefits stream profiles to the model results in a range of cost-effectiveness ratios from 14912.90 pounds per life year gained to 52416.27 pounds per life year gained. The preferred model is reported where the life years gained are assumed to be equally distributed over the last 15 years of the 40-year time horizon of the analysis (Y25-40) and the corresponding cost-effectiveness ratio is 37,943 pounds per life year gained.

Aged↗
PubMed2002

A critical comparison of the cost-effectiveness of domestic radon remediation programmes in three counties of England.

Radon remediation programmes in domestic dwellings were carried out in five areas, from three counties of England, and the total costs obtained. A single company, which abided by the Code of Practice of the Radon Council of Great Britain, carried out the remediation. The dose savings from the programmes were calculated and used to estimate the number of lung cancers averted. The data obtained allowed the cost-effectiveness of the remediation programmes in each area to be calculated. The remediation programmes in three areas (Northants 2, 3 and North Oxfordshire) were cost-effective whereas those in two areas (Northants 1 and North Somerset) were not. To be cost-effective, the Northants I and North Somerset areas would need to increase the number of householders that carried out remediation, if they were over the UK Action Level. Health policy makers should concentrate their resources on communities in areas where there is a significant proportion of dwellings above the UK Action Level and where the number of properties being remediated is low.

Air Pollution, Indoor↗