Inositol phosphate formation in arterial smooth muscle from rabbits with perinephritis hypertension

Total inositol phosphate formation was measured in the aorta and femoral artery from rabbits at 1, 2 and 6 weeks after kidney wrapping, at which times the mean arterial pressures were 88 +/- 4, 96 +/- 3 and 126 +/- 7 mmHg against a control pressure of 74 +/- 3 mmHg. Noradrenaline-stimulated (10(-7) to 10(-4) mol/l) inositol phosphate formation was increased in the aorta and femoral artery from hypertensive rabbits at 2 weeks (aorta noradrenaline 10(-6) mol/l sham, 105 +/- 14%; hypertensive, 164 +/- 20% of control). Noradrenaline-stimulated inositol phosphate formation was unchanged at 1 and 6 weeks in the aorta. Endothelin-stimulated inositol phosphate formation was unchanged at 2 weeks. Basal inositol phosphate formation was not significantly different in normotensive and hypertensive animals. In perinephritis hypertension there is an alteration in phosphatidylinositol metabolism in arterial smooth muscle. This occurs at the time when the blood pressure is rising rapidly. This alteration may affect a specific phosphatidylinositol pool that is linked to the alpha-adrenoceptor but not to the endothelin receptor.     

Burden of disability in a post war birth cohort in the UK.

STUDY OBJECTIVE--To report the prevalence of physical disability in a national sample of 43 year old men and women, and examine the relationship between disability and the consumption of hospital care. To assess the contribution of childhood health and social circumstances to the risk of adult disability, and the socioeconomic consequences of disability. DESIGN--The assessment of disabilities of physical movement was based on criteria developed by OPCS for their national survey of disability. The analysis used data on socioeconomic circumstances from childhood to 43 years and on serious illness in the first 25 years of life collected prospectively on members of the MRC National Survey of Health and Development, the 1946 birth cohort study. SETTING--England, Wales, and Scotland. PARTICIPANTS--A general population sample of 3235 men and women aged 43 years. MAIN RESULTS--Seven per cent of cohort survivors at 43 years were physically disabled and a further 3% reported difficulties although they were not assessed as disabled according to OPCS criteria. The prevalence of severe disability at this age was similar to that derived from the OPCS survey but the prevalence of mild disability was substantially greater. Disability was associated with a greater use of hospital care in recent years and throughout life. Those who had experienced a serious illness in earlier life were over twice as likely to be disabled; certain conditions, such as polio, were associated with a particularly high relative risk. Those who had had a socially disadvantaged start to life were more likely to be physically disabled at 43 years but the strength of this relationship was considerably weakened by adjustment for later social factors, suggesting that social disadvantage throughout life, or during adult life, increased the risk of disability. Taking these results into account the relative impact of disability on income and employment was found to be greatest for those from the unskilled and semi-skilled classes. CONCLUSIONS--The prevalence of physical disability among those in early middle age may be greater than previously estimated. The strong links between childhood ill health and adult disability and its association with high levels of hospital care support longstanding recommendations for better coordination between child and adult health services. Social disadvantages affects the risk of disability and its financial and employment consequences.     

Effects of a p38 MAP kinase inhibitor on bone ingrowth and tissue differentiation in rabbit chambers

The effects of an oral p38 mitogen-activated protein kinase (MAPK) inhibitor and polyethylene particles separately and together on tissue differentiation in the bone harvest chamber (BHC) in rabbits over a 3-week treatment period were investigated. The harvested tissue was analyzed histomorphometrically for markers of bone formation (percentage of bone area), osteoblasts (alkaline phosphatase staining), and osteoclasts (CD51, the alpha chain of the vitronectin receptor). Polyethylene particles decreased the percentage of bone ingrowth and staining for alkaline phosphatase. The p38 MAPK inhibitor alone decreased alkaline phosphatase staining. When the oral p38 MAPK inhibitor was given and the chamber contained polyethylene particles, there was a suppression of bone ingrowth and alkaline phosphatase staining. In contrast to oral non-steroidal anti-inflammatory drugs (NSAIDs) and local Interleukin-1 receptor antagonist (IL-1ra) administration, the oral p38 MAPK inhibitor alone did not suppress bone formation when given during the initial phase of tissue differentiation. Particle-induced inflammation and the foreign body reaction were not curtailed when the p38 MAPK inhibitor was given simultaneously with particles. Additional experiments are needed to establish the efficacy of p38 MAPK inhibitor administration on mitigating an established inflammatory and foreign body reaction that parallels the clinical situation more closely.     

Using postal randomization to replace telephone randomization had no significant effect on recruitment of patients

OBJECTIVE: To test the effect of postal randomization on recruitment of patients into a randomized trial in primary care. STUDY DESIGN AND SETTING: General practices used a telephone service to randomize patients in our trial. Delays in the start of recruitment at some sites led us to modify the randomization procedure. When new practices took part patients completed and posted baseline materials to the Trial Secretary in York who performed the randomization and informed those concerned of the allocation. RESULTS: Of the 647 practices who were invited to take part, 130 (45%) of 288 agreed to participate using telephone randomization and 155 (43%) of 359 using the postal method. These practices recruited 553 patients from November 2002 to October 2004 across 11 sites in the United Kingdom. The postal method reduced the number of patients recruited by a factor of 0.86 (95% confidence interval=0.62-1.20), or 14%. The number of general practitioners working in a practice significantly increased patient recruitment by a factor of 1.12 (1.05-1.20), whereas practice distance from hospital significantly decreased recruitment by a factor of 0.98 (0.97-0.99). CONCLUSION: Postal randomization had no significant effect on recruitment of patients into our trial.     

Dietary patterns throughout adult life are associated with body mass index, waist circumference, blood pressure, and red cell folate

Dietary patterns are important in the prevention of chronic disease; however, there are few studies that include repeat measures of dietary patterns. The objective of this study was to assess the relations between dietary patterns during adult life (at ages 36, 43, and 53 y) and risk factors for chronic disease at age 53 y. Participants of a longitudinal study of health completed a 5-d food diary at 3 occasions during adult life (n = 1265). Factor analysis was used to identify dietary patterns and a pattern score was calculated from the consumption of the food items in each dietary pattern. Means and 95% CI for dietary pattern scores were calculated for each risk factor category using random effects models adjusted for socio-demographic and health-related behaviors. In women, the fruit, vegetables, and dairy pattern was inversely associated with BMI (P < 0.004), waist circumference (P = 0.0007), blood pressure (P = 0.02), and was positively associated with red cell folate (P < 0.03). The ethnic foods and alcohol pattern was also inversely associated with blood pressure (P = 0.008), whereas the meat, potatoes and sweet foods pattern was positively associated with glycated hemoglobin (P = 0.01). In men, a mixed pattern was inversely associated with waist circumference (P = 0.02) and blood pressure (P = 0.01), whereas there were no significant associations with the ethnic foods and alcohol pattern. Specific dietary patterns throughout adult life were associated with chronic disease risk factors.     

Life course body size and lipid levels at 53 years in a British birth cohort

OBJECTIVES: To investigate the association between growth in height and change in body mass index (BMI) during the life course on lipid levels at 53 years. METHODS: 2311 men and women from a British cohort study were included in analyses. Non-fasting total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels were measured at 53 years. Height and BMI at 2, 4, 7, 11, 15 and 36 years in relation to the lipid outcomes at 53 years were assessed using multiple regression models. The effects of z scores of height and BMI at 2 years and yearly rates of change (velocities) in height and BMI between 2-7, 7-15 and 15-36 years were also considered. RESULTS: Total cholesterol level decreased by 0.119 mmol/l (95% CI -0.194 to -0.045) per SD increase in height at 2 years and by 0.073 mmol/l (95% CI -0.145 to -0.001) for every SD increase in height velocity between 15 years and adulthood. Similar, but weaker associations were seen for LDL cholesterol. The relationships between leg length and total and LDL cholesterol were stronger than the relationship with trunk length. Higher BMI at 36 and 53 years and greater BMI increases between 15-36 and 36-53 years were associated with higher total and LDL cholesterol and lower HDL cholesterol levels. The effects of growth could not be explained by birth weight or lifetime socioeconomic status. CONCLUSIONS: Early life exposures, which restrict height growth in infancy, resulting in shorter adult leg length, may influence lipid levels in adult life.