Hypercholesterolemia and microvascular dysfunction: interventional strategies

Hypercholesterolemia is defined as excessively high plasma cholesterol levels, and is a strong risk factor for many negative cardiovascular events. Total cholesterol levels above 200 mg/dl have repeatedly been correlated as an independent risk factor for development of peripheral vascular (PVD) and coronary artery disease (CAD), and considerable attention has been directed toward evaluating mechanisms by which hypercholesterolemia may impact vascular outcomes; these include both results of direct cholesterol lowering therapies and alternative interventions for improving vascular function. With specific relevance to the microcirculation, it has been clearly demonstrated that evolution of hypercholesterolemia is associated with endothelial cell dysfunction, a near-complete abrogation in vascular nitric oxide bioavailability, elevated oxidant stress, and the creation of a strongly pro-inflammatory condition; symptoms which can culminate in profound impairments/alterations to vascular reactivity. Effective interventional treatments can be challenging as certain genetic risk factors simply cannot be ignored. However, some hypercholesterolemia treatment options that have become widely used, including pharmaceutical therapies which can decrease circulating cholesterol by preventing either its formation in the liver or its absorption in the intestine, also have pleiotropic effects with can directly improve peripheral vascular outcomes. While physical activity is known to decrease PVD/CAD risk factors, including obesity, psychological stress, impaired glycemic control, and hypertension, this will also increase circulating levels of high density lipoprotein and improving both cardiac and vascular function. This review will provide an overview of the mechanistic consequences of the predominant pharmaceutical interventions and chronic exercise to treat hypercholesterolemia through their impacts on chronic sub-acute inflammation, oxidative stress, and microvascular structure/function relationships

Prospectus, March 30, 2011

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Reading and Ownership

First paragraph: ‘It is as easy to make sweeping statements about reading tastes as to indict a nation, and as pointless.’ This jocular remark by a librarian made in the Times in 1952 sums up the dangers and difficulties of writing the history of reading. As a field of study in the humanities it is still in its infancy and encompasses a range of different methodologies and theoretical approaches. Historians of reading are not solely interested in what people read, but also turn their attention to the why, where and how of the reading experience. Reading can be solitary, silent, secret, surreptitious; it can be oral, educative, enforced, or assertive of a collective identity. For what purposes are individuals reading? How do they actually use books and other textual material? What are the physical environments and spaces of reading? What social, educational, technological, commercial, legal, or ideological contexts underpin reading practices? Finding answers to these questions is compounded by the difficulty of locating and interpreting evidence. As Mary Hammond points out, ‘most reading acts in history remain unrecorded, unmarked or forgotten’. Available sources are wide but inchoate: diaries, letters and autobiographies; personal and oral testimonies; marginalia; and records of societies and reading groups all lend themselves more to the case-study approach than the historical survey. Statistics offer analysable data but have the effect of producing identikits rather than actual human beings. The twenty-first century affords further possibilities, and challenges, with its traces of digital reader activity, but the map is ever-changing

Schoolbooks and textbook publishing.

In this chapter the author looks at the history of schoolbooks and textbook publishing. The nineteenth century saw a rise in the school book market in Britain due to the rise of formal schooling and public examinations. Although the 1870 Education and 1872 (Scotland) Education Acts made elementary education compulsory for childern between 5-13 years old, it was not until the end of the First World War that some sort form of secondary education became compulsory for all children

THE ASSOCIATION OF AN INCREASED URINARY CALCIUM-TO- CREATININE RATIO, AND ASYMPTOMATIC GROSS AND MICROSCOPIC HEMATURIA IN CHILDREN

The role of hypercalciuria for the evaluation of unexplained asymptomatic gross and microscopic hematuria in children remains unclear, as evidenced by conflicting reports in the literature. We study the function of hypercalciuria in these patients, and determine whether routine evaluation of urine for hypercalciuria and treatment with thiazide diuretics, based on the results of a urinary calcium-to-creatinine ratio, is necessary. We also wanted to compare the yield of a urinary calcium-to-creatinine ratio in patients with gross and microscopic hematuria subgroups. Between 1991 and 1998 we treated 96 patients with microscopic hematuria (group 1) and 46 with gross hematuria (group 2). All patients had isolated unexplained hematuria. Patients with organic and anatomical causes, including urinary tract infection and other urinary symptoms, were excluded from the study. Nephrological urine and serum analyses in patients with hematuria were otherwise normal, as were all imaging studies. Group 1 included 50 males and 46 females, with a mean age of 7.6 years (range 1 to 14), and a spot urinary calcium-to-creatinine ratio was done in 79. Group 2 included 35 males and 11 females, with a mean age of 8.5 years (range 8 months to 14 years), and a spot urinary calcium-to-creatinine ratio was done in 43. A ratio of 0.2 or greater was considered hypercalciuria. The season of presentation was noted to determine any pattern. There were no seasonal variations regarding presentation. Followup of 34 patients in group 1 and 15 group 2, with a mean followup of 10.6 months (range 1 month to 8 years), was available. A total of 28 (82.3%) patients in group 1 and 15 (71.4%) group 2 had complete resolution of hematuria. However, there were 6 patients in both groups who had persistent hematuria but remained totally asymptomatic. Hydrochlorothiazide was used in only 2 patients in group 1 and 1 group 2 due to intractable hematuria on expectant management, a markedly increased urinary calcium-to-creatinine ratio and positive family history of urolithiasis. Although we cannot establish a direct cause and effect relationship, hypercalciuria is detected in a substantial number of cases of unexplained gross and microscopic hematuria. However, based on our study we do not recommend treatment with thiazide diuretics in all patients diagnosed with hypercalciuria, as hematuria resolved in a majority with observation or expectant treatment and minor dietary modification. We reserve treatment with thiazide diuretics only for those patients with intractable hematuria, a markedly increased urine calcium-to-creatinine ratio and family history of urolithiasi