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Cardiology 1985Results of recent clinical trials on secondary prevention of ischemic heart disease indicate that judicious, long-term administration of adrenergic beta blockers and...
Results of recent clinical trials on secondary prevention of ischemic heart disease indicate that judicious, long-term administration of adrenergic beta blockers and platelet-active drugs such as aspirin and Persantine (dipyridamole) would seem to yield protection against mortality associated with acute myocardial infarction, including sudden death. These drugs are beneficial also in prevention of recurrent myocardial infarction, especially among patients with unstable angina. These drugs should be considered as soon as the diagnosis of myocardial infarction or unstable angina is confirmed clinically. In terms of primary prevention of ischemic heart disease and cerebrovascular disease (stroke), the results of the Hypertension Detection and Follow-Up Program provide an excellent set of data on the efficacy of rigorous treatment of hypertension, especially those with mild hypertension. To be effective, treatment must start before there is evidence of target end organ damage, such as left ventricular hypertrophy. Recent data from the Australian Therapeutic Trial in Mild Hypertension also confirms these findings.
Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Aspirin; Cardiovascular Diseases; Clofibrate; Coronary Disease; Dextrothyroxine; Dipyridamole; Double-Blind Method; Drug Therapy, Combination; Estrogens; Humans; Hypertension; Myocardial Infarction; Niacin; Sulfinpyrazone
PubMed: 2866843
DOI: 10.1159/000173890 -
Clinical Pharmacology and Therapeutics Dec 1984Studies have shown that pharmaceutic preparations of the stereo isomers of thyroxine differ with respect to thyromimetic potency and lipid level-lowering effects. We...
Studies have shown that pharmaceutic preparations of the stereo isomers of thyroxine differ with respect to thyromimetic potency and lipid level-lowering effects. We applied a stereospecific assay for dextrothyroxine (DT4) and levothyroxine (LT4) to determine whether the biologic effects observed after the administration of DT4 (Choloxin; Flint Laboratories) resulted from inherent biologic activity of DT4, conversion of DT4 to LT4 in vivo, or LT4 contamination of Choloxin tablets. Choloxin was administered in a dose of 8 mg/day for 5 mo to nine athyreotic subjects who were then treated with pharmaceutic LT4 (Synthroid), 0.2 mg/day for an additional 5 mo. Analysis showed that LT4 contamination of Choloxin tablets ranged from 0.50% to 2.30%. This degree of contamination resulted in physiologically significant doses of LT4 in the 8 mg/day doses of Choloxin. During the treatment with two different lots of Choloxin, serum LT4 accounted for 33% to 53% of the measurable serum total thyroxine. The degree of LT4 contamination in Choloxin tablets was sufficient to account for the observed serum LT4 levels and casts doubt on the conclusions derived from previous studies in which Choloxin was used as the source of "DT4."
Topics: Adolescent; Adult; Aged; Analysis of Variance; Cholesterol; Chromatography, High Pressure Liquid; Dextrothyroxine; Drug Contamination; Female; Humans; Hypothyroidism; Male; Middle Aged; Radioimmunoassay; Stereoisomerism; Thyroidectomy; Thyrotropin; Thyroxine; Triglycerides
PubMed: 6499357
DOI: 10.1038/clpt.1984.257 -
Endocrinology Oct 1984Serum sex hormone-binding globulin (SHBG) concentration is increased in patients with thyrotoxicosis. SHBG is also present in rabbit serum, although it does not bind...
Serum sex hormone-binding globulin (SHBG) concentration is increased in patients with thyrotoxicosis. SHBG is also present in rabbit serum, although it does not bind estradiol-17 beta (E2). Studies were carried out in female rabbits to determine the effects of thyroid hormone on SHBG. Serum concentrations of L-T4 cholesterol, E2, progesterone, free and total testosterone (T), and SHBG were measured in immature female rabbits (8-10 weeks of age). Rabbits were ovariectomized or subjected to sham surgery at puberty (age, 14-16 weeks) and restudied 6 weeks later. Values for serum T4, T, percent free T, free T, E2, progesterone and cholesterol were similar in ovariectomized and sham treated rabbits. Serum SHBG concentration progressively decreased in all rabbits from immaturity to age 20-22 weeks and values remained constant thereafter. Ovariectomy did not affect this age-related decrease in serum SHBG concentration. The 20- to 22-week-old ovariectomized and sham-operated rabbits were treated daily with either 30 micrograms/kg L-T4 or 150 micrograms/kg D-T4 for 2 weeks. This dose of L-T4 induced a 10-25% loss of BW, whereas D-T4 treatment did not, strongly suggesting that the L-T4 but not the D-T4-treated rabbits were hypermetabolic. D-T4 and L-T4 induced similar increases in serum SHBG (D-T4, delta 132 nM; L-T4, delta 146 nM). The increase in serum SHBG activity in response to D-T4 or L-T4 was reversible, since serum SHBG concentration returned to pretreatment values 5 weeks after thyroid hormone therapy was discontinued. The 27- to 29-week-old rabbits were then treated for 2 weeks with D-T4 (150 micrograms kg-1 day-1). Serum SHBG concentration significantly increased, and there were negative correlations between the thyroid hormone-induced increase in SHBG activity and both the percent free T and free T (P less than 0.01). D-T4 administration significantly lowered the serum cholesterol concentration without altering BW.
Topics: Animals; Castration; Cholesterol; Dextrothyroxine; Estradiol; Female; Progesterone; Rabbits; Sex Hormone-Binding Globulin; Thyroxine
PubMed: 6541121
DOI: 10.1210/endo-115-4-1446 -
The American Journal of Medicine Sep 1984In an attempt to compare the cholesterol-lowering effects of equivalent doses of D- and L-thyroxine, 10 euthyroid, hypercholesterolemic subjects were treated with graded... (Comparative Study)
Comparative Study
In an attempt to compare the cholesterol-lowering effects of equivalent doses of D- and L-thyroxine, 10 euthyroid, hypercholesterolemic subjects were treated with graded doses of each medication in a cross-over design using thyrotropin suppression following thyrotropin-releasing hormone administration as the end-point. The mean thyrotropin-suppressive dose of D-thyroxine was 2.4 +/- 0.66 mg per day, which resulted in mean reductions of 10 percent in total plasma cholesterol, 10 percent in plasma low-density lipoprotein cholesterol, and 11 percent in plasma high-density lipoprotein cholesterol. The mean thyrotropin-suppressive dose of L-thyroxine was 135 +/- 46 micrograms per day, which resulted in mean reductions of 7 percent in total plasma cholesterol, 6 percent in plasma low-density lipoprotein cholesterol, and 14 percent in plasma high-density lipoprotein cholesterol. The reductions in total, low-density, and high-density cholesterol achieved with D-thyroxine were not significantly different from those achieved with L-thyroxine. Neither medication produced a significant increase in heart rate or ventricular ectopy as determined by Holter monitoring. These data do not support the belief that D-thyroxine has a preferential cholesterol-lowering effect in humans when compared with equivalent doses of L-thyroxine. In addition, both D- and L-thyroxine reduced plasma high-density lipoprotein cholesterol.
Topics: Adult; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dextrothyroxine; Dose-Response Relationship, Drug; Female; Heart Rate; Humans; Hypercholesterolemia; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Thyrotropin; Thyroxine; Triglycerides
PubMed: 6475988
DOI: 10.1016/0002-9343(84)90107-4 -
Progress in Cardiovascular Diseases 1984The pathogenesis of arteriosclerosis is not yet fully understood. The growing body of scientific information strongly indicates that the plasma lipoproteins are playing... (Review)
Review
The pathogenesis of arteriosclerosis is not yet fully understood. The growing body of scientific information strongly indicates that the plasma lipoproteins are playing a crucial role in the development of this disease. We now have conclusive information that dietary cholesterol can produce arteriosclerosis in animals and its removal from the diet can result in regression of these lesions. Most importantly, we know that reducing plasma cholesterol in humans will prevent mortality and morbidity related to the clinical sequelae of arteriosclerosis. A diet can be prescribed that can produce profound reductions in lipoprotein levels in many individuals. The rate of success in achieving modifications that reduce plasma cholesterol is very high. Most patients over time find a diet with reduced cholesterol and saturated fat to be quite palatable. As food suppliers become more active in emphasizing low fat, low cholesterol products, and as restaurants see a demand for healthier entrees, the task for the physician and nutritionist will become much easier. Achieving sustained weight reduction is a much more difficult problem, but this too can be accomplished in many patients if the health professionals maintain a hopeful supportive approach. Ultimately, it is the patient's responsibility to bring about these lifestyle changes. It is the physician's and nutritionist's job to monitor the process and provide sound information and encouragement. For individuals with severe lipoprotein disorders such as familial hypercholesterolemia where diet therapy is helpful but not adequate, the use of medications is now indicated (bile acid binding resins and nicotinic acid). Other medications that promise additional effectiveness and safety are under development (Compactin, Mevinolin). It is our belief that control of coronary heart disease and stroke requires appropriate treatment of lipoprotein disorders and the methods for a strong beginning in this endeavor are at hand.
Topics: Adult; Aged; Anabolic Agents; Bile Acids and Salts; Child; Cholestyramine Resin; Clofibrate; Colestipol; Dextrothyroxine; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dietary Proteins; Drug Therapy, Combination; Energy Intake; Estrogens; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipoproteinemias; Hypolipidemic Agents; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Middle Aged; Neomycin; Niacin; Probucol; Progestins; Triglycerides
PubMed: 6330792
DOI: 10.1016/0033-0620(84)90017-3 -
Presse Medicale (Paris, France : 1983) Mar 1984
Comparative Study
Topics: Adult; Aged; Dextrothyroxine; Female; Humans; Hypothyroidism; Male; Middle Aged; Solutions; Tablets
PubMed: 6231564
DOI: No ID Found -
Atherosclerosis Feb 1984Eight subjects, belonging to a large family kindred repeatedly showing the electrophoretic pattern of the "double pre-beta lipoproteinemia", were studied. In seven of...
Eight subjects, belonging to a large family kindred repeatedly showing the electrophoretic pattern of the "double pre-beta lipoproteinemia", were studied. In seven of them thyroid function, serum lipids and apolipoprotein A-I were determined before and after treatment with dextro-thyroxine, preparation almost free of levo-thyroxine. In most of the patients, total-T4 levels and free-T4 Index were in the lower normal range, but basal TSH levels and the TSH response to TRH were normal. Dextro-thyroxine was effective in reducing both serum total cholesterol and triglycerides, but the percentage decrease in serum triglycerides was definitely greater than that of serum total cholesterol. This marked, unexpected hypotriglyceridemic effect is similar to that observed in a group of obese, hypertriglyceridemic hypothyroid patients treated with levo-thyroxine. Besides serum total cholesterol and triglycerides, the VLDL cholesterol/triglycerides ratio and the electrophoretic "slow moving" pre-beta component were also significantly reduced after treatment, suggesting that dextro-thyroxine can remove efficiently "remnant" VLDL particles from the plasma. Following dextro-thyroxine therapy, the relatively low pretreatment values of apolipoprotein A-I were significantly increased, being restored to normal.
Topics: Adult; Aged; Apolipoprotein A-I; Apolipoproteins; Dextrothyroxine; Family; Female; Humans; Lipids; Lipoproteins, VLDL; Male; Middle Aged; Thyroid Gland
PubMed: 6424687
DOI: 10.1016/0021-9150(84)90022-4 -
Clinical Nuclear Medicine Jan 1984Two patients are reported who presented with clinical hyperthyroidism, increased serum thyroid function studies, and depressed radioactive iodine uptake, secondary to...
Two patients are reported who presented with clinical hyperthyroidism, increased serum thyroid function studies, and depressed radioactive iodine uptake, secondary to chronic ingestion of D-T4. Symptoms abated, and function studies returned to normal, following discontinuation of D-T4. This uncommon effect of D-T4 may be more prevalent than is generally realized and must be recognized as another potential cause of low radioiodine uptake in patients with clinical hyperthyroidism.
Topics: Aged; Dextrothyroxine; Female; Humans; Hypercholesterolemia; Hyperthyroidism; Iodine Radioisotopes; Middle Aged; Thyroid Function Tests
PubMed: 6697613
DOI: 10.1097/00003072-198401000-00007 -
General and Comparative Endocrinology Jan 1984Binding studies were conducted using in vitro-labeled quail liver nuclei to identify and characterize receptors for L-triiodothyronine (T3). Saturation binding... (Comparative Study)
Comparative Study
Binding studies were conducted using in vitro-labeled quail liver nuclei to identify and characterize receptors for L-triiodothyronine (T3). Saturation binding experiments were analyzed by Scatchard analysis and indicated a single class of high-affinity, limited-capacity T3 binding sites. These receptors exhibited binding specificity as demonstrated by competition experiments between labeled T3 and unlabeled thyroid hormones or hormone analogs. Binding specificity was virtually identical in quail and rat liver nuclei. Thus, apparent differences between mammals and birds, in regard to the biological potency of T4 versus T3, are not apparent at the level of the nuclear T3 receptor.
Topics: Aging; Animals; Binding Sites; Binding, Competitive; Cell Nucleus; Coturnix; Dextrothyroxine; Kinetics; Liver; Male; Quail; Receptors, Cell Surface; Receptors, Thyroid Hormone; Thyroxine; Triiodothyronine
PubMed: 6325294
DOI: 10.1016/0016-6480(84)90228-4 -
The American Journal of Medicine May 1983Drug therapy should be instituted only after appropriate diet treatment has been started and adequate baseline lipid and lipoprotein values are established. Nicotinic...
Drug therapy should be instituted only after appropriate diet treatment has been started and adequate baseline lipid and lipoprotein values are established. Nicotinic acid is useful in treating most lipoprotein disorders and the cutaneous flushing that develops during the early part of treatment is usually alleviated by aspirin. Cholestyramine and colestipol are nonabsorbable resins whose use is limited to type II hyperlipoproteinemia. Clofibrate is primarily effective in lowering triglyceride levels, but its clinical use has considerably declined following the World Health Organization study results that reported increased morbidity and mortality rates among patients receiving this drug. Based on the finding of increased mortality among a subset of patients participating in the Coronary Drug Project, dextrothyroxine is only recommended for treating patients who do not have clinically evident atherosclerotic heart disease. Probucol lowers total and low-density lipoprotein cholesterol levels, but has the undesirable effect of simultaneously reducing high-density lipoprotein levels.
Topics: Bile Acids and Salts; Clofibrate; Dextrothyroxine; Humans; Hyperlipidemias; Hypolipidemic Agents; Niacin; Probucol
PubMed: 6846378
DOI: No ID Found