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Biomedical subjects

D H Solomon

Publications and source records attributed to D H Solomon.

At least 127 records · Page 7Linked to original sources
PubMed1984

A radioimmunoassay of 3,5-dimethyl-3'-isopropyl-L-thyronine.

A simple, sensitive, and specific RIA has been developed to measure 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) in unextracted serum. The RIA employs a DIMIT-binding antibody obtained from a rabbit immunized with DIMIT-human serum albumin conjugate and [125I]T3 as the radioligand. 8-Anilino-1-naphthalene sulfonic acid and barbital buffer (0.075 M; pH 8.6) were used to minimize serum binding of DIMIT and [125I]T3. The detection threshold of the RIA was 0.03 microgram/dl. Recovery of nonradioactive DIMIT added to serum averaged 104%. 3,5,3'-Triiodothyroacetic acid cross-reacted maximally (78%) in the RIA, followed by T3 (56%), 3,5-diethyl-3'-isopropyl thyronine (43%), 3,3'-diiodothyronine (T2; 12%), tetraiodothyroacetic acid (6.7%), 3'-monoiodothyronine (T1; 0.54%), 3.5-T2 (0.34%), 3-T1 (0.26%), and T4 (0.25%); rT3, 3',5'-T2, thyronine, iodotyrosines, and KI cross-reacted 0.1% or less. The coefficient of variation averaged 7.4% within an assay and 9.0% between assays. After ip administration of DIMIT to the rat, the mean serum DIMIT concentration rose in a dose-related fashion from less than 0.12 microgram/dl in the controls to 44 micrograms/dl in those receiving 200 micrograms/100 g BW daily for 3 days; serum T4 and TSH levels declined significantly in animals receiving 3.2 micrograms DIMIT/(100 g BW X day) or more. After a single ip injection of DIMIT to the rat, serum DIMIT levels increased from a control value of 0.04 to 9.8 micrograms/dl at 2 h and then decreased progressively, with a half-life approximating 7.2 h. Serum TSH was suppressed for up to 24 h, while serum T4 and T3 were suppressed for up to 48 h after the injection. Concentrations of DIMIT 15 h after a dose of 10 micrograms, ip, to approximately 150-g rats were (nanograms per g; mean +/- SE) 19 +/- 2.3 in serum, 30 +/- 3.5 in liver, 23 +/- 2.4 in kidney, 19 +/- 4.7 in heart, 16 +/- 3.4 in skeletal muscle, and 20 +/- 3.0 in brain. DIMIT administration to pregnant rats [3 micrograms/(100 g BW X day) for 3 days, im] resulted in mean +/- SE DIMIT concentrations (micrograms per dl) of 0.51 +/- 0.14 in maternal serum, 0.57 +/- 0.04 in fetal serum, and 0.46 +/- 0.07 in amniotic fluid. A DIMIT dose of 10 micrograms/(100 g BW X day) for 3 days in maternal rats resulted in mean DIMIT concentrations (micrograms per dl) of 1.8 +/- 0.06 in maternal serum, 1.4 +/- 0.10 in fetal serum, and 1.3 +/- 0.17 in amniotic fluid.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Effect of 3,5,3'-triiodothyronine-induced hyperthyroidism on iodothyronine metabolism in the rat: evidence for tissue differences in metabolic responses.

We studied the effect of T3-induced hyperthyroidism on the outer ring (5' or 3') monodeiodination of T4 (to T3) and 3',5'-diiodothyronine [3',5'-T2; to 3'-monoiodothyronine (3'-T1)] and on the inner ring (3 or 5) monodeiodination of 3,5-T2 (to 3-T1) by various rat tissues. Weight-matched pairs of male Sprague-Dawley rats were given either saline or T3 (20 micrograms/100 g BW daily) ip for 3 days. The metabolism of the iodothyronines was studied on day 4 in homogenates of the tissues in the presence of 25 mM dithiothreitol. Hyperthyroidism was associated with a significant (P less than 0.05) increase in T4 to T3 monodeiodinating activity in the liver (mean, 95%), kidney (mean, 60%), and heart (mean, 153%), but not in skeletal muscle, small intestine, spleen, testis, cerebral cortex, or cerebellum. The monodeiodinating activity converting 3',5'-T2 to 3'-T1 was greatly increased (P less than 0.05) in the heart (mean, 750%), spleen (mean, 462%), and skeletal muscle (mean, 167%), but not in liver, kidney, small intestine, testis, cerebral cortex, or cerebellum. In the case of liver and kidney, however, there was evidence of an activation of 3',5'-T2 monodeiodinating activity, as suggested by a significant increase in the activity in the absence of added dithiothreitol. The monodeiodination of 3,5-T2 to 3-T1 increased significantly only in the cerebral cortex (mean, 525%) and liver (mean, 69%) and not in any other tissue. The time course of the above-mentioned changes in iodothyronine metabolism was studied in groups of rats (five per group) given T3 (20 micrograms 100 g BW-1 day-1) 6-72 h before death. Significant increases in 3',5'-T2 (to 3'-T1) monodeiodination in the heart and 3,5-T2 (to 3-T1) monodeiodination in the cerebral cortex were evident within 6 h of T3 administration. Changes in T4 to T3 monodeiodinating activity in the kidney and liver, however, did not become statistically significant until 24 and 72 h, respectively. The various effects of T3 on the tissues became maximal between 48 and 72 h after the initiation of T3 treatment. Our data suggest that most tissues, including some that have been considered unresponsive to thyroid hormones, e.g. brain and spleen, demonstrate substantial metabolic changes after T3 administration. The tissue responses are variable in degree; in some instances, they are specific for the substrate and type of tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

A study of cardiac effects of thyroid hormones: evidence for amelioration of the effects of thyroxine by sodium ipodate.

We studied the effects of daily ip administration of T4 (200 micrograms/100 g BW) or T3 (50 micrograms/100 g) to the rat (six per group) for 3 days with or without sodium ipodate (6 mg/100 g), propylthiouracil (PTU; 2 mg/100 g), propranolol (0.5 mg/100 g), or amiodarone (2.5 mg/100 g) on cardiac weight, 3',5'-diiodothyronine (3',5'-T2) to 3'-monoiodothyronine monodeiodinating activity (MA), mitochondrial alpha-glycerophosphate dehydrogenase (alpha GPD), and/or cytosolic ornithine decarboxylase (ODC). T4 treatment caused a 28% increase in cardiac weight, about an 11-fold increase in 3',5'-T2 MA, about a 27% increase in alpha GPD activity, and about a 129% increase in ODC activity. Administration of ipodate with T4 abolished all effects of T4 on the heart. PTU abolished the effect of T4 on alpha GPD and markedly reduced its effect on 3',5'-T2 MA and ODC activity; it had little effect on cardiac hypertrophy caused by T4 treatment. Propranolol reduced the increase in cardiac weight following T4 administration from 28% to 11%, but had a modest or no effect on T4-induced changes in other metabolic variables studied. Amiodarone also reduced the effect of T4 on heart weight, but had little or no influence on 3',5'-T2 MA, the only metabolic variable studied. T3 treatment of the rat caused a 35% increase in heart weight, about a 15-fold increase in 3',5'-T2 MA, about a 35% increase in alpha GPD, and about a 100% increase in ODC activity. Ipodate and PTU reduced the increase in 3',5'-T2 MA following T3 administration, but had no appreciable influence on heart weight, alpha GPD, and/or ODC activity. Propranolol and amiodarone had no significant effect on any of the changes studied after T3 administration. It was concluded that: 1) ipodate markedly lessens or abolishes the effects of T4 on the heart; 2) propranolol and amiodarone decrease cardiac hypertrophy in response to T4 administration, but have little or no effect on metabolic changes due to T4; 3) PTU curtails the metabolic effects of T4 on the heart but has little effect on cardiac hypertrophy; 4) none of the drugs studied affects cardiac changes occurring after T3 administration. The changes observed in 3',5'-T2 MA after ipodate and PTU treatment may have been a result of direct interaction of the drugs with the deiodinase.

Amiodarone↗
PubMed1984

A competitive ligand binding assay for measurement of thyroid hormone-binding inhibitor in serum and tissues.

A competitive ligand-binding assay (CLBA) is described for measurement of an inhibitor(s) of serum binding of T4 in ether extracts of serum and in homogenates and extracts of tissues. The CLBA is based on the effect of thyroid hormone binding inhibitor (THBI) on partition of a constant amount of radiolabeled ligand [(125I]T4) between fixed amounts of serum and an anti-T4 antibody. The method is convenient, rapid, sensitive, and reproducible. The coefficient of variation averaged 8.9% within an assay and 12.8% between assays. Several fatty acids, e.g. arachidonic acid, lauric acid, linolenic acid, and linoleic acid, had potent THBI activity in the CLBA; arachidonic acid was more potent than the other fatty acids. Since oleic acid cross-reacted substantially with T4-binding sites on anti-T4, its THBI activity was examined by an equilibrium dialysis method; it was about 77% as potent as arachidonic acid. Arachidic, myristic, palmitic, and stearic acids, choleserol, various phospholipids and triglycerides (triolein and tripalmitin) had little or no THBI activity in the CLBA. THBI activity was detected in the sera of 50% (60% when serum T4 was low and 42% when it was normal) of 34 patients with nonthyroid illnesses (NTI) when studied by CLBA and in 59% (67% when serum T4 was low and 53% when it was normal) of patients when determined by the inhibitory ratio (normalized dialysis ratio/normalized binding ratio). THBI values obtained by the CLBA correlated significantly (r = 0.58; P less than 0.001) with those obtained by the inhibitory ratio method. The dose-response curve of an ether extract of pooled sera of hospitalized patients was parallel to that of arachidonic acid in the CLBA. Among various rat tissues, the small intestine had the most THBI activity in both homogenates and ether extracts of homogenates. Ether (2 vol) extracted about 63% of the THBI activity in small intestine homogenate at pH 5.2. THBI activity was demonstrable in all particulate fractions (especially mitochondria and endoplasmic reticulum) of small intestine homogenate; cytosol contained little or no THBI activity. THBI activity changed little after treatment of small intestine homogenate with trypsin or protease inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Alcoholism.

After heart disease and cancer, alcoholism is America's third largest health problem; it affects 10 million people, costs $ 60 billion, and is implicated in 200 000 deaths annually. Alcohol is involved in 50% of deaths by motor vehicle and fire, 67% of murders, and 33% of suicides. It contributes to morbidity in certain malignancies and to many diseases of the endocrine, cardiovascular, hematopoietic, gastrointestinal, and nervous systems. The fetal alcohol syndrome occurs in a third of the infants born to women who drink more than 150 g of ethanol daily during pregnancy; another third of the infants become mentally retarded. The prevalence of alcoholism is lower in elderly than in middle-aged persons, but detection is difficult and vulnerability to harm is great in the elderly, due to both pharmacokinetic factors and increased tissue sensitivity. Alcohol and aging are additive in their harmful effects. Although modern medical treatment is helpful, alcoholics are frequently misdiagnosed and mismanaged by health professionals. Total abstinence from alcohol should be a primary goal of treatment.

Age Factors↗
PubMed1983

Pathogenesis of hyperthyroidism.

Graves' disease is the most frequent cause of hyperthyroidism in the United States. It occurs predominantly in a genetically predisposed population. Autoimmune abnormalities constitute a major component of the disease. Immunoglobulins of patients with Graves' disease manifest a number of thyroid-targeted activities, including a thyroid-stimulating activity that is related to interaction of immunoglobulin G (IgG) with the TSH receptor. That hyperthyroidism in Graves' disease is caused by thyroid-stimulating IgGs is an attractive hypothesis but the evidence in favor of the hypothesis is still insufficient. A better alternative hypothesis is not available, however.

Adult↗
PubMed1982

An inhibitor of the binding of thyroid hormones to serum proteins is present in extrathyroidal tissues.

Extrathyroidal tissues of man and the rat contain a potent inhibitor of the binding of thyroid hormones to serum proteins and to an anion-exchange resin. The inhibitor is heat-labile and nondialyzable. It acts by reducing the binding affinity of thyroid hormones to serum proteins, not by reducing the number of binding sites. The tissue inhibitor is similar in several characteristics to an inhibitor described previously in the serum of some critically ill patients, suggesting that the tissue inhibitor may leak into the circulation in severe illnesses.

Animals↗
PubMed1982

Effect of patient age on duration of medical encounters with physicians.

The authors analyzed the USC/DRME Practice Study data to determine if the characteristics of physician patient encounters change with patient age. The only significant change observed was a decline in encounter time for patients 65 years of age and older compared with those 45 through 64 years of age. This decrease was significant for raw data and for data weighted for the number of physicians of various types and standardized for complexity of case mix in various age groups, also for both nonhospital and hospital encounters and for almost all classes of encounters. Three types of generalists and four types of medical subspecialists were studied; encounter times for all types were, for patients 65 and older, either the same as or less than those for patients 45 through 64. The observed phenomenon may reflect a conscious decision on the part of some physicians to allot less time to elderly patients.

Age Factors↗
PubMed1982

Specific nuclear binding sites of triiodothyronine and reverse triiodothyronine in rat and pork liver: similarities and discrepancies.

The specific binding of [125I]T3 and [125I]rT3 to nuclear extracts of rat and pork liver was studied. The Ka values of the binding of T3 and rT3 to nuclear extracts were similar (0.65 +/- 0.12 vs. 0.68 +/- 0.10 x 10(9) M-1; P = NS), but the maximal binding capacity for T3 was smaller than that for rT3 (333 +/- 36 vs. 1209 +/- 338 fmol/mg DNA; P less than 0.05). The amount of nonradioactive T4 required to cause a 50% displacement of [125I]T3 from the nuclear binding sites was, on a molar basis, 27 times greater than that of T3 in the case of pork liver and 110 times greater than that of T3 in the case of rat liver. Similarly, rT3-binding sites were highly specific. Relative to rT3, 16- and a 100-fold greater molar excesses of T4 were required to cause a 50% displacement of [125I[rT3 from the nuclear binding sites in pork and rat liver, respectively. Similarly, 700--2150 times more rT3 than T3 was required to obtain a 50% displacement of [125I]T3; in contrast, 50--250 times more T3 than rT3 was needed to displace 50% specifically bound [125I]rT3. Reduced glutathione and other sulfhydryl (SH)-reducing agents increased, whereas oxidized glutathione and SH-oxidizing or -binding agents decreased the binding of [125I]T3 and [125I]rT3 to nuclear extracts, with one exception. Dithiothreitol, a potent SH-reducing agent, reduced the binding of rT3 whereas it increased the binding of T3 to the nuclear binding sites. A 48-h fast was associated with a significant reduction in the maximal binding capacity of nuclear extracts for T3 (control vs. fasting rats, 589 +/- 92 vs. 339 +/- 50 fmol T3/mg DNA; P less than 0.05) and rT3 (1620 +/- 162 vs. 693 +/- 102 fmol rT3/mg DNA; P less than 0.005) without changes in affinity. The data suggest that 1) there exist specific high affinity, low capacity nuclear rT3-binding sites in rat and pork liver which are distinct from the nuclear T3 receptors, and 2) rT3- and T3-binding sites are reduced in parallel during starvation.

Animals↗
PubMed1981

Short- and long-term residents of nursing homes.

This article analyzes reported data on length of stay of discharged patients from the 1977 National Nursing Home Survey. Assuming that patients admitted to nursing homes are one of two types, short-stayers and long-stayers, the statistically best-fitting proportions and expected lengths of stay for the two types are derived. The results are applied to statistics on characteristics of resident and discharged patients to find admission characteristics that differentiate the two groups. Because long-stayers and short-stayers have quite different characteristics, nursing home statistics will be very different if one bases them on discharges or a cross-section of residents. For example, we estimate that short-stay patients represent 61 per cent of discharges but only 9 per cent of residents. A further application shows that, including deaths in hospitals, almost half of discharged patients die, rather than the usually cited figure of 25 per cent.

Aged↗