Biomedical subjects

Michael J World

Publications and source records attributed to Michael J World.

4 recordsLinked to original sources

PubMed2006

Variation in the lipoprotein lipase gene influences exercise-induced left ventricular growth.

The adult heart relies predominantly on fatty acids (FA) for energy generation, and defects in FA catabolism cause dramatic left ventricular (LV) growth in early age. Since lipoprotein lipase (LPL) is the key enzyme in plasma triglyceride catabolism and is highly expressed in the myocardium, we investigated an association between the functional LPL gene serine 447 stop (S447X) variant and exercise-induced LV growth. The S447X variant was genotyped in 146 British Army recruits undergoing a 10-week exercise programme. Over the training period, X447 allele carriers showed less LV growth than S447 homozygotes (SS, 5.8+/-0.7%; SX, 2.2+/-1.5%; P=0.03) and a decrease in systolic blood pressure (DeltaSBP: SS, 1.9+/-1.3 mmHg; SX, -5.7+/-2.2 mmHg; P=0.015). Although LPL genotype did not significantly predict LV growth with DeltaSBP in statistical modelling (LPL, P=0.14; DeltaSBP, P=0.06), regression analysis indicated that LPL S447X genotype effect on DeltaSBP accounted for only 20% of the effect on LV growth. In multivariate analysis, LPL, peroxisome-proliferator-activated receptor alpha and angiotensin-converting enzyme genotypes were independent predictors of cardiac growth. Thus, LPL S447X genotype influenced exercise-induced changes in LV mass and SBP. Change in blood pressure accounted for a proportion of LV growth. These data suggest that increased myocardial FA availability may reduce exercise-induced LV growth.

Adult↗

PubMed2002

Peroxisome proliferator--activated receptor alpha gene regulates left ventricular growth in response to exercise and hypertension.

BACKGROUND: Left ventricular hypertrophy (LVH) occurs as an adaptive response to a physiological (such as exercise) or pathological (valvular disease, hypertension, or obesity) increase in cardiac work. The molecular mechanisms regulating the LVH response are poorly understood. However, inherited defects in fatty acid oxidation are known to cause severe early-onset cardiac hypertrophy. Peroxisome proliferator--activated receptor alpha (PPARalpha) regulates genes responsible for myocardial fatty acid oxidation and is downregulated during cardiac hypertrophy, concomitant with the switch from fatty acid to glucose utilization. METHODS AND RESULTS: The role of PPARalpha in left ventricular growth was investigated in 144 young male British Army recruits undergoing a 10-week physical training program and in 1148 men and women participating in the echocardiographic substudy of the Third Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Augsburg study. A G/C polymorphism in intron 7 of the PPARalpha gene significantly influenced left ventricular (LV) growth in response to exercise (P=0.009). LV mass increased by 6.7 +/- 1.5 g in G allele homozygotes but was significantly greater in heterozygotes for the C allele (11.8 +/- 1.9 g) and in CC homozygotes (19.4 +/- 4.2 g). Likewise, C allele homozygotes had significantly higher LV mass, which was greater still in hypertensive subjects, and a higher prevalence of LVH in the Third MONICA Augsburg study. CONCLUSIONS: We demonstrate that variation in the PPARalpha gene influences human left ventricular growth in response to exercise and hypertension, indicating that maladaptive cardiac substrate utilization can play a causative role in the pathogenesis of LVH.

Adaptation, Physiological↗

PubMed2002

Left ventricular mass: reliability of M-mode and 2-dimensional echocardiographic formulas.

The study of left ventricular (LV) hypertrophy is hindered by problems with LV mass measurement by echocardiography. Both the M-mode and 2D area-length formulas for calculating LV mass assume a fixed geometric shape, which may be a source of error. We examined this hypothesis by using cardiovascular magnetic resonance images to eliminate the confounding effects of acoustic access and image quality. LV mass was measured directly in 212 healthy subjects by means of a standard 3D cardiovascular magnetic resonance technique. LV mass was also calculated by using the cube-function and area-length formulas with measurements from the magnetic resonance images. A comparison of serial measurements was made by examining the changes in LV mass by all 3 techniques in those completing an exercise program (n=140). The cube-function technique showed a consistent underestimation of LV mass of 14.3 g, and there were wide 95% limits of agreement (+/-57.6 g and +/-46.3 g for cube-function and area-length techniques, respectively) when compared with 3D measurement. There were similarly wide limits of agreement for the change in mass (+/-55.2 g and +/-44.8 g for cube-function and area-length, respectively). The assumption of geometric shape in the cube-function and area-length formulas resulted in significant variation in LV mass estimates from direct measurement by using a 3D technique. The technique cannot be recommended either at a single time point or for serial studies in small populations; 3D imaging techniques, such as cardiovascular magnetic resonance, are preferable.

Cardiac Volume↗

PubMedDate not supplied

Bioterrorism: the need to be prepared.

Postal distribution of anthrax spores in October 2001 in the USA resulted in cases of pulmonary anthrax. In consequence, interest and concern about terrorist attacks on civilian populations using biological weapons have increased, particularly when one recent authoritative assessment suggested that an attack using some form of unconventional weapon on a Western city was 'inevitable'. This article reviews the steps necessary to minimise the probability of a successful attack. Despite best endeavours, the possibility remains that significant numbers of casualties will arise, emphasising the need to plan for reception, triage, decontamination and treatment of patients. The medical Royal Colleges could assist the education of the wider medical community about aspects of pathology hitherto considered to be primarily military but which have now become important for civilian physicians.

Bioterrorism↗