The role of fibric acid derivatives in the secondary prevention of coronary heart disease.

Fibric acid derivatives effectively lower triglycerides and raise high-density lipoprotein (HDL) cholesterol, but their effect on low-density lipoprotein (LDL) cholesterol is weakly beneficial (small decreases) to adverse (small increases) and varies according to the triglyceride level. Early primary prevention studies of atherosclerosis using the fibric acid derivative clofibrate showed only modest effects on atherosclerosis and an alarming increase in mortality in the intervention group. Although the Helsinki Heart Study later demonstrated that gemfibrozil decreased cardiac endpoints in primary prevention without increasing total mortality, the efficacy of fibric acid derivatives in both primary and secondary prevention of atherosclerosis has remained widely in doubt. Nevertheless, many patients with atherosclerosis have normal or even low LDL cholesterol, but elevated triglyceride, and low HDL cholesterol; furthermore, even aggressive LDL cholesterol lowering with HMG Co-A (3-hydroxy 3-methylglutaryl coenzyme A) reductase inhibitors (statins) fails to prevent the majority of atherosclerotic events. These findings have kindled increased interest in the use of fibric acid derivatives in atherosclerosis prevention, especially through treatment of non-LDL dyslipidemias. Recent studies with angiographic and clinical end-points have now provided evidence for a beneficial effect of at least some drugs in this class in the secondary prevention of atherosclerosis.

Thyroid palpation versus high-resolution thyroid ultrasonography in the detection of nodules.

Detection of thyroid nodules by physical examination and high-resolution ultrasonography was compared using small groups of blinded, experienced physician examiners working with a sample of 2441 persons from Estonia, most of whom were Chernobyl nuclear reactor clean-up workers. A random subsample of 113 (5%) persons was subjected to triple control examinations with both physical examination and high-resolution ultrasonography. Positive high-resolution ultrasonographic findings were considerably more reproducible among different observers than were positive physical examination findings. Agreement between methods was poor. Nodules were found in 169 (6.9%) subjects by physical examination and in 249 (10.2%) subjects by high-resolution ultrasonography. Physical examination found only 53 (21%) of the 249 nodules found by high-resolution ultrasonography. High-resolution ultrasonography did not confirm the existence of 115 (68%) of the 169 nodules found by physical examination. Only 6.4% of nodules less than 0.5 cm in diameter, as based on high-resolution ultrasonographic results, were detected by physical examination. Physical examination detection improved with increasing nodule size but was still only 48.2% for nodules larger than 2 cm. Physical examination was relatively effective in detecting nodules in the isthmus of the thyroid gland but much less so for nodules in the upper pole of the gland. Clinical evaluation and epidemiologic studies of nodular thyroid disease stand to benefit from the greater sensitivity and specificity of ultrasonographic examinations.

Regulation of aldose reductase gene expression in renal cortex and medulla of rats.

A role for aldose reductase-mediated production of polyol in the aetiology of diabetic nephropathy has been supported by both animal and clinical studies. In the renal medulla, the rate of polyol production is influenced in part by regulated changes in the level of aldose reductase gene expression. However, little is known about the expression of aldose reductase in the renal cortex. In this study, we evaluated the regulation of aldose reductase gene expression in the renal cortex and medulla in response to galactose feeding. Four groups of rats (n = 6) were treated for 9 weeks with control or galactose diet in the presence or absence of sorbinil, an aldose reductase inhibitor. In the renal medulla, galactose treatment produced a significant (p < 0.01) decrease in aldose reductase mRNA, to approximately 10% of control levels. Coadministration of sorbinil partially prevented the effect of galactose feeding on medullary aldose reductase mRNA (to 43% of control). Under basal conditions, the concentration of aldose reductase mRNA in the cortex was only 1% that of the renal medulla. Galactose feeding significantly reduced cortical aldose reductase mRNA by 29% relative to control (p < 0.01), and this was completely reversed by addition of sorbinil. Sorbinil administration to rats fed a control diet also decreased aldose reductase expression in the renal medulla and cortex. These results demonstrate that galactose feeding results in dynamic, polyol-dependent regulation of aldose reductase gene expression in the renal cortex as well as the medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Case report 631: Neo-osseous porosis (metaphyseal osteopenia) in polyglandular autoimmune (Schmidt) syndrome.

In summary, a case is reported of a patient with the radiographic findings of diffuse, symmetrical metaphyseal osteopenia of long bones. A constellation termed neo-osseous porosis, associated with polyendocrine failure (Schmidt syndrome) involving the thyroid gland, adrenal glands, and gonads has been described in this case. Neo-osseous porosis has been observed previously in idiopathic juvenile osteoporosis. This case represents the first instance in which this distinctive radiographic picture has been observed in the setting of specific (multiple) endocrine dysfunction disorders.