The prevalence of abnormal biochemical thyroid function reported here is substantial and confirms previous reports in smaller populations. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest elevations of TSH corresponded to changes in lipid levels that may affect cardiovascular health. Individual symptoms were not very sensitive, but patients who report multiple thyroid symptoms warrant serum thyroid testing. These results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement.

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Blood pressure rises rapidly upon waking and may be responsible, in part, for the increased incidence of myocardial infarction and stroke during the morning hours. Current formulations and dosing of antihypertensive drugs do not provide maximum coverage during this vulnerable period. This study was performed to demonstrate that propranolol CR (Innopran XL), a novel chronotherapeutic formulation of propranolol designed for nighttime dosing, has appropriate pharmacokinetics to provide maximum cardioprotective effect in the morning. Pharmacokinetics of propranolol CR and sustained-release propranolol after single and multiple doses were determined in normal male volunteers in this open-label, 2-period crossover study. The drugs were dosed in the evening and serial blood samples were taken for determination of propranolol concentration the next 24 to 72 hours. After a single 160-mg dose of propranolol CR administered at 10 pm, absorption was delayed by about 4 hours, after which plasma concentration rose steadily, reaching a peak at about 10:00 am. In contrast, after dosing with sustained release propranolol, plasma levels of propranolol began to rise almost immediately, reaching a plateau between 4:00 am and 10:00 am. During multiple dosing, steady-state trough plasma concentrations were achieved after 2 days with either drug. After the final dose, the plasma profiles of both drugs were similar to those observed in the single-dose study. Bioavailability was similar for both formulations of propranolol. Propranolol CR exhibited appropriate pharmacokinetics for a chronotherapeutic approach to the treatment of hypertension.

A B S T R A C T The feeding of cholesterol-rich diets alters the serum lipoproteins of a number of mammalian species. These lipoproteins are characterized by the presence of several classes of particles enriched in cholesteryl esters and apolipoprotein E (apo E). It was the aim of this study to determine whether one or more of these particles arises by de novo hepatic synthesis by characterizing nascent lipoproteins isolated from the hepatic Golgi apparatus of hypercholesterolemic rats. Characterization of these lipoproteins afforded the opportunity to assess morphologic, biochemical, and biophysical properties of newly synthesized lipoproteins before enzymatic alterations and apoprotein transfer known to occur after secretion into the plasma compartment. Golgi very low density lipoproteins (VLDL, d < 1.006 g/ml) from hypercholesterolemic rats contained nearly four times the total cholesterol mass found in control Golgi VLDL. They exhibited electrophoretic mobility intermediate between beta and pre-beta and were devoid of apo C. A second population of hepatic Golgi lipoproteins was isolated from hypercholesterolemic rats at 1.006-1.040 g/ml d. These low density lipoproteins were smaller than VLDL, displayed beta electrophoretic mobility, were enriched in cholesteryl esters, and contained apo E as well as apo B. The fatty acid composition of the core lipids of the nascent lipoproteins was found to reflect that of dietary triglyceride. The liver of the hypercholesterolemic rat thus plays an active role in dietary-induced hypercholesterolemia by synthesizing a modified VLDL and a low density lipoprotein resembling serum low density lipoprotein.Portions of this work were presented at the 62nd Annual

Previous studies have shown abnormal thyroid hormone profiles during cardiac arrest. We explored this association further by characterizing plasma thyroid hormone profiles in 473 patients with out-of-hospital cardiac arrest and correlating them with clinical outcomes. Paramedics collected blood at the end of attempted resuscitation regardless of success. Bloods were collected and processed in a similar manner from 18 control subjects randomly selected from the community. Total thyroxine and total triiodothyronine were lower and reverse triiodothyronine and thyrotropin were higher in cardiac arrest patients than control subjects (all p < 0.001). Except for reverse triiodothyronine, findings were similar for a subgroup of cardiac arrest patients considered to be previously healthy (n = 30). Being discharged alive was associated with total thyroxine, total triiodothyronine and reverse triiodothyronine concentrations closer to the control range and thyrotropin concentrations farther from it, namely higher. In a multivariate stepwise model, only total triiodothyronine and thyrotropin were significantly associated with outcome. Whether these profoundly abnormal profiles represent a pre-existing state or a sudden change of thyroid hormone concentrations cannot be answered with this retrospective study. These observations suggest that thyroid hormones may play a role in the etiology of cardiac arrest, its prognosis, or both.