Two common mutations (D9N, N291S) in lipoprotein lipase: a cumulative analysis of their influence on plasma lipids and lipoproteins in men and women.

We assessed the effect of two common mutations in the lipoprotein lipase gene (LPL), D9N and N291S, which have been shown to modulate plasma lipids in a wide spectrum of patients. A total of 1114 men and 1 144 women from the Framingham Offspring Study (FOS) were analyzed for these two LPL variants. Subsequently, the association with fasting plasma lipids and risk of coronary artery disease (CHD) was determined. We extended our study by calculating weighed means of lipids and lipoproteins in carriers and non-carriers for these LPL mutations in patients with genetic dyslipidemias, CHD patients and healthy controls. In the FOS sample, the D9N and N291S alleles were associated with lower high-density lipoprotein-cholesterol (HDL-C) (delta = - 0.07 mmol/ 1, p = 0.03) and a trend towards increased triglycerides (delta = 0.25 mmol/ 1, p = 0.07). In women, a trend towards the high triglyceride, low HDL-C phenotype was evident (delta = - 0.02 mmol/1 for HDL-C and delta = 0.14 mmol/l for triglycerides, respectively). Cumulative analysis of other studies of male carriers of the D9N and N291S revealed higher levels of triglycerides (D291N; 2.60(1.85) mmol/l vs. 1.62(1.18) mmol/l: p < 0.0001) (D9N; 1.94 (1.19) mmol/l vs. 1.74(1.17) mmol/l: p < 0.001) and lower HDL-C (N291S; 1.04(0.32) mmol/l vs. 1.15(0.28) mmol/l: p < 0.0001) (D9N; 1.08(0.24) mmol/l vs. 1.16(0.28) mmol/l: p < 0.0001). In females, results differed with higher TG levels (N291S; 1.70(0.99) mmol/l vs. 1.10(0.63) mmol/l: p < 0.001) (D9N; 1.08(0.76) mmol/l vs. 0.96(0.51) mmol/l: p < 0.01) and lower HDL-C levels (N291S; 1.27(0.33) mmol/l vs. 1.51(0.32) mmol/l: p < 0.0001); however, the HDL-C levels for D9N carriers were similar to non-carriers (D9N; 1.52(0.29) mmol/l vs. 1.53(0.35) mmol/l: p = 0.83). Our data provide evidence that common variants of the LPL gene are significant modulators of lipid and lipoprotein levels in both men and women.

Intermittent claudication. A risk profile from The Framingham Heart Study.

BACKGROUND: Intermittent claudication identifies persons at increased risk for death and disability. METHODS AND RESULTS: Using 38-year follow-up data for the original cohort in the Framingham Heart Study, we developed an intermittent claudication risk profile. Intermittent claudication occurred in a total of 381 men and women. Age, sex, serum cholesterol, hypertension, cigarette smoking, diabetes, and coronary heart disease were associated with an increased risk for claudication and were included in the profile. A pooled logistic regression model was used to compute the probability of intermittent claudication for specified levels of risk factors. CONCLUSIONS: The intermittent claudication risk profile allows physicians to identify high-risk individuals during a routine office visit and can be used to educate patients about modifiable risk factors, particularly smoking and blood pressure. Improved compliance with risk factor modification strategies may result in a beneficial impact on survival.

Uric acid excretion: quantitative assessment from spot, midmorning serum and urine samples.

Uric acid excretion can be measured in milligrams of urinary uric acid per decilitre of glomerular filtrate by obtaining the product of urinary uric acid and serum creatinine concentrations and dividing by the urine creatinine (all concentrations in mg/dL). In 29 normal adult men, the excretion rate in spot, midmorning samples was 0.4 +/- 0.1 (SD) mg of uric acid per decilitre of glomerular filtrate. Eight of 36 untreated gouty men excreted acid at a rate more than three standard deviations above normal. Excretion of uric acid is conveniently and physiologically assessed by this simple method.

Pancreatic cyst complicated by major arterial erosion and gastrointestinal haemorrhage.

Uncommonly, pancreatic cysts are complicated by the erosion of certain adjacent arteries and serious gastrointestinal haemorrhage. This diagnosis should be entertained in any patient with chronic pancreatitis who presents with unexplained gastrointestinal blood loss, whether acute or chronic, a pulsatile mass in the epigastrium, and an associated bruit. Selective caeliac axis angiography may not only confirm the diagnosis, but provide precise anatomical information as a guide to the surgeon in planning treatment. The surgical treatment of choice is transcystic ligation of the bleeding vessel, followed by internal cyst drainage.