Liver Transplantation to Provide Low-Density-Lipoprotein Receptors and Lower Plasma Cholesterol in a Child with Homozygous Familial Hypercholesterolemia

A six-year-old girl with severe hypercholesterolemia and atherosclerosis had two defective genes at the low-density-lipoprotein (LDL) receptor locus, as determined by biochemical studies of cultured fibroblasts. One gene, inherited from the mother, produced no LDL receptors; the other gene, inherited from the father, produced a receptor precursor that was not transported to the cell surface and was unable to bind LDL. The patient degraded intravenously administered 125I-LDL at an extremely low rate, indicating that her high plasma LDL-cholesterol level was caused by defective receptor-mediated removal of LDL from plasma. After transplantation of a liver and a heart from a normal donor, the patient's plasma LDL-cholesterol level declined by 81 per cent, from 988 to 184 mg per deciliter. The fractional catabolic rate for intravenously administered 125I-LDL, a measure of functional LDL receptors in vivo, increased by 2.5-fold. Thus, the transplanted liver, with its normal complement of LDL receptors, was able to remove LDL cholesterol from plasma at a nearly normal rate. We conclude that a genetically determined deficiency of LDL receptors can be largely reversed by liver transplantation. These data underscore the importance of hepatic LDL receptors in controlling the plasma level of LDL cholesterol in human beings. (N Engl J Med 1984; 311: 1658–64.). © 1984, Massachusetts Medical Society. All rights reserved

2013 ACC/AHA Guideline Recommends Fixed-Dose Strategies Instead of Targeted Goals to Lower Blood Cholesterol

The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines recently issued the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. This new guideline endorses a paradigm shift in strategies for reducing atherosclerotic cardiovascular disease (ASCVD) events by lowering blood cholesterol. Whereas previous guidelines focused on therapy to decrease low-density lipoprotein and non-high-density lipoprotein cholesterol to specific target levels, the new guideline instead proposes implementation of cholesterol-lowering treatment using evidenced-based intensity of statin therapy without such targets. The guideline also provides a new risk estimator for primary prevention decisions, including stroke outcomes and data on African Americans, which will significantly increase the number of patients recommended for outcome-related benefits of cholesterol-lowering therapy. The first section of this paper reviews the process by which the task force developed the new evidence-based guideline, the major findings and recommendations, and their implications. The second section primarily focuses on the question of how much low-density lipoprotein cholesterol should be lowered and on additional considerations in risk assessment

2013 ACC/AHA Guideline Recommends Fixed-Dose Strategies Instead of Targeted Goals to Lower Blood Cholesterol

The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines recently issued the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. This new guideline endorses a paradigm shift in strategies for reducing atherosclerotic cardiovascular disease (ASCVD) events by lowering blood cholesterol. Whereas previous guidelines focused on therapy to decrease low-density lipoprotein and non-high-density lipoprotein cholesterol to specific target levels, the new guideline instead proposes implementation of cholesterol-lowering treatment using evidenced-based intensity of statin therapy without such targets. The guideline also provides a new risk estimator for primary prevention decisions, including stroke outcomes and data on African Americans, which will significantly increase the number of patients recommended for outcome-related benefits of cholesterol-lowering therapy. The first section of this paper reviews the process by which the task force developed the new evidence-based guideline, the major findings and recommendations, and their implications. The second section primarily focuses on the question of how much low-density lipoprotein cholesterol should be lowered and on additional considerations in risk assessment

The Struck-and-lost Factor in Alaskan Walrus Harvests, 1952-1972

Struck-and-lost rates during hunts for walruses, Odobenus rosmarus (Linnaeus), in Alaska from 1952 to 1972 did not vary from year to year. On average, 42% of the animals struck by bullets were lost (i.e., not retrieved). About 55% of the struck-and lost animals died immediately; the rest were wounded. Apparently, most of the wounded died soon after they were struck. The sex-age composition of the struck-and-lost animals was about the same as that in the harvest, and the proportion lost did not vary with the size of the group encountered. Claims of reduction in loss rates in recent years, based on improved firepower, are open to question. Considerable improvement in weapons took place also during the 21-year period of this study, but it merely increased the proportion of outright kills among the struck-and-lost animals. It did not reduce the proportion lost of the animals that were struck.Key words: walrus, Odobenus rosmarus, Alaska, harvests, struck-and-lostLe taux d'animaux frappés et perdus au cours de la chasse au morse, Odobenus rosmarus (Linnaeus) en Alaska de 1952 à 1972 n'a pas varié d'une année à l'autre. En moyenne, 42 p. cent des animaux frappés par les balles ont été perdus (c.-à-d. non récupérés). Environ 55 p. cent des animaux frappés et perdus sont morts sur le coup et 45 p. cent ont été blessés. Il semble que la plupart de ces derniers soient morts peu de temps après avoir été frappés. La composition selon le sexe et l'âge des animaux frappés et perdus était environ la même que celle des prises, et la proportion des animaux perdus ne variait pas avec la taille du groupe chassé. On peut remettre en question les affirmations des dernières années concernant une réduction du taux de perte causée par l'amélioration de la puissance de feu. Durant les 21 années de l'étude, les armes ont subi de grosses améliorations, mais celles-ci ont tout simplement fait augmenter la proportion des bêtes tuées sur le coup, parmi les animaux qui avaient été frappés et perdus. Les améliorations apportées aux armes n'ont pas réduit la proportion des animaux perdus parmi ceux qui avaient été frappés.Mots clés: morse, Odobenus rosmarus, Alaska, prises, frappés et perdu

Near-Infrared Spectral Monitoring of Triton with IRTF/SpeX II: Spatial Distribution and Evolution of Ices

This report arises from an ongoing program to monitor Neptune's largest moon Triton spectroscopically in the 0.8 to 2.4 micron range using IRTF/SpeX. Our objective is to search for changes on Triton's surface as witnessed by changes in the infrared absorption bands of its surface ices N2, CH4, H2O, CO, and CO2. We have recorded infrared spectra of Triton on 53 nights over the ten apparitions from 2000 through 2009. The data generally confirm our previously reported diurnal spectral variations of the ice absorption bands (Grundy & Young 2004). Nitrogen ice shows a large amplitude variation, with much stronger absorption on Triton's Neptune-facing hemisphere. We present evidence for seasonal evolution of Triton's N2 ice: the 2.15 micron absorption band appears to be diminishing, especially on the Neptune-facing hemisphere. Although it is mostly dissolved in N2 ice, Triton's CH4 ice shows a very different longitudinal variation from the N2 ice, challenging assumptions of how the two ices behave. Unlike Triton's CH4 ice, the CO ice does exhibit longitudinal variation very similar to the N2 ice, implying that CO and N2 condense and sublimate together, maintaining a consistent mixing ratio. Absorptions by H2O and CO2 ices show negligible variation as Triton rotates, implying very uniform and/or high latitude spatial distributions for those two non-volatile ices.Comment: 22 pages, 13 figures, 5 tables, to appear in Icaru

Improving coronary heart disease risk assessment in asymptomatic people: Role of traditional risk factors and noninvasive cardiovascular tests

At least 25% of coronary patients have sudden death or nonfatal myocardial infarction without prior symptoms.1 Therefore, the search for coronary patients with subclinical disease who could potentially benefit from intensive primary prevention efforts is critically important. The American Heart Association’s (AHA) Prevention V Conference, “Beyond Secondary Prevention: Identifying the High Risk Patient for Primary Prevention,” addressed ways to identify more patients who are asymptomatic and clinically free of coronary heart disease (CHD) but at sufficiently high risk for a future coronary event to justify more intensive risk reduction efforts.2 In this report, we amplify on key findings and recommendations of the AHA Prevention V conference, highlight new research since the conference, and propose an approach to the use of office-based testing and additional noninvasive procedures in selected patients to better define their coronary event risk. The recommendations are concordant with the recently released approach to risk assessment and management from the third report of the Adult Treatment Panel of the National Cholesterol Education Program (ATP-III).