PubMed Health⌕ Search

Biomedical subjects

D H Solomon

Publications and source records attributed to D H Solomon.

At least 19 recordsLinked to original sources
PubMed1992

Cognitive function in non-demented older adults with hypothyroidism.

PURPOSE: (1) to evaluate objectively changes in cognitive function and electrophysiologic characteristics associated with hypothyroidism of varying severity and duration in primarily older persons; (2) to determine whether these changes are reversible when a euthyroid state has been attained after treatment with thyroid hormone. SUBJECTS AND METHODS: We enrolled 54 non-demented hypothyroid patients (31-99, mean 68.6 +/- 16.4 years) with biochemical evidence of hypothyroidism (38 had overt and 14 had minimal hypothyroidism) and 30 euthyroid controls (31-96, mean 63.7 +/- 18.4 years) screened for good general health. We evaluated attention, orientation, memory, learning, visual-spatial abilities, calculation, language, visual scanning, and motor speed using standardized neuropsychological tests. Electrophysiological measures of neurocognitive function included the P300 latency component of the auditory Event-Related Potentials (ERP) and conduction speed from eye to cortex, the P100 latency component of the Patterned Visual-Evoked Potential (PVEP). All patients were studied when hypothyroid. A subset of patients with minimal initial test abnormalities were available to be retested when euthyroid, 5 and 9 months after onset of thyroid replacement therapy. RESULTS: Hypothyroid patients showed significantly lower scores on the Mini-Mental Status Test (MMS) and on five of 14 neuropsychological tests as compared to controls. The neuropsychological tests affected were copying a cube (visual-spatial function), the Inglis Paired Associates Learning Test-Low and Medium association items (memory and learning), Animal Naming (word fluency/production), and the Trail Making A test (attention, visual scanning and psychomotor function. Hypothyroidism also was associated with longer P100 latencies of PVEPs to 20' checks, but showed no significant differences in PVEP P100 latency to 50' checks, nor in the latency of the auditory ERP component P300. There was a statistically significant correlation between a laboratory index of the severity of hypothyroidism (serum T4) and the Inglis Medium Association items and Animal Naming. There was a statistically significant improvement after 5 months of treatment on three of the timed performance tests that previous studies have shown to be most sensitive to brain dysfunction. CONCLUSION: Hypothyroidism in non-demented older adults is associated with impairments in learning, word fluency, visual-spatial abilities, and some aspect of attention, visual scanning, and motor speed. The MMS by itself was sensitive in differentiating hypothyroid patients with cognitive deficits from controls, while electrophysiological measures did not generally differentiate the hypothyroid patients from normal controls. The MMS was not sensitive to treatment effects, but treatment was associated with significant improvements in three of the most sensitive measures of cognitive dysfunction.

Adult↗
PubMed1992

Metabolism of 3,5,3'-triiodothyronine sulfate by tissues of the fetal rat: a consideration of the role of desulfation of 3,5,3'-triiodothyronine sulfate as a source of T3.

We have recently demonstrated that serum concentration of 3,5,3'-triiodothyronine sulfate (T3S) is markedly elevated in the human newborn at a time when serum 3,5,3'-triiodothyronine (T3) is very low. The present study explores the ability of maternal (19-21 d pregnant) and near-term fetal Sprague-Dawley rat tissues to 1) monodeiodinate T3S and T3 in both the outer and the inner ring and 2) desulfate T3S to T3. Maternal liver microsomes metabolized T3S exceedingly efficiently (compare fetus p less than 0.05). Eighty percent or more of T3S was consumed during its incubation with 360 micrograms/mL microsomes for 2 h. The majority of the consumption of T3S by adult liver microsomes occurred by its 5'-monodeiodination to I-; little inner-ring monodeiodination to 3,3'-diiodothyronine was demonstrable. In fetal liver microsomes, however, over 75% of the substrate T3S remained unchanged after a 2-h incubation. T3 was metabolized similarly moderately by fetal and maternal liver microsomes. Brain microsomes metabolized T3S poorly in both the mother and the fetus. Over 90% of substrate T3S remained unchanged after a 2-h incubation in each case. Interestingly, brain microsomes metabolized T3 more rapidly than T3S (p less than 0.05). In the fetus, desulfation of T3S to T3 was clearly evident only in microsomes from the liver and the brain; in the adult, it was plentiful in many tissues. Fetal liver and brain tissues metabolize T3S poorly, and both actively desulfate T3S to T3. These data and those indicating high serum T3S in the fetus suggest that T3S is a local source of T3 in critical tissues in the fetus and possibly in adults with the low T3 syndrome.

Animals↗
PubMed1992

A study of the characteristics of the rat placental iodothyronine 5-monodeiodinase: evidence that it is distinct from the rat hepatic iodothyronine 5'-monodeiodinase.

Recent studies have demonstrated that rat liver type I iodothyronine 5'-monodeiodinase (5'-MD) characteristically contains selenocysteine. The present study was undertaken to characterize rat placental type III iodothyronine 5-MD and to compare it with 5'-MD. Solubilized rat placental microsomes were delipidated by carboxymethyl cellulose-Sephadex chromatography. Phospholipids and proteins were recovered in two distinct peaks, which did not show 5-MD activity. 5-MD activity was recovered fully, however, by combining the two components (phospholipids and protein) and partially after the addition of exogenous phospholipids to protein. Tissue selenoproteins were labeled by injection of radioactive selenium (75Se; 50 microCi, iv; on days 5, 10, and 15 of gestation) to pregnant rats. Subcellular fractions of maternal and fetal tissues were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. No specific seleno-labeled proteins were evident in the microsomes of placenta or maternal or fetal brain. A 27- to 29-kilodalton (kDa) band previously suggested to be 5'-MD was observed, however, in maternal liver and kidney microsomes. Aurothioglucose inhibited rat placental 5-MD, but the dose required for 50% inhibition was over 50-fold greater than that for Se-containing hepatic 5'-MD (430 vs. 8 nM). The mechanism of the inhibition was noncompetitive for 5-MD, whereas it was competitive for 5'-MD. A synthetic peptide of 16 amino acids corresponding to the carboxy-terminal portion of 5'-MD was synthesized, and rabbits were immunized with the peptide-BSA conjugate. Western blots studies using the rabbit antiserum showed one specific 29-kDa band in rat liver microsomes. However, no specific bands were observed in 5-MD-rich placental or fetal brain microsomes. Bromoacetyl T3 (BrAcT3) was a potent inhibitor of rat placental 5-MD. Affinity labeling of solubilized rat placental microsomes with [125I]BrAcT3 showed a predominant band of 31 kDa, distinct from the 27- to 29-kDa band found in liver and kidney. The labeling of the 31-kDa band was enhanced by 10 mM dithiothreitol, inhibited 60% by 150 microM T3, and prevented by 40 microM aurothioglucose. A dominant affinity-labeled 31-kDa band was also observed in fetal brain microsomes. Some tissues without 5-MD activity (testes and spleen) also showed weak binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Evidence that the human placental 5-monodeiodinase is a phospholipid-requiring enzyme.

Gel filtration (GFI) of the solubilized human placental microsomes (SHPMP) performed in an Ultrogel AcA-34 column in the presence of 1 mM 3-(3-cholamidopropyl)dimethylammonio-1-propane sulfonate (CHAPS) plus 10 mM n-octyl-beta-D-glucopyranoside (beta-OG) demonstrated two main protein peaks. The 5-Monodeiodinase (5-MD) activity measured by the conversion of [125I]T3 to [125I]3,3'-diiodothyronine in a 2- to 18-h incubation at 37 C in the presence of 10 mM dithiothreitol was detected only in the first peak, and the specific activity was increased about 9 times over that of the starting SHPM. The fractions containing most of the 5-MD activity were filtered through a second Ultrogel AcA34 column (GFII) in the presence of 2 mM CHAPS plus 20 mM beta-OG. In these conditions, 5-MD activity was detected in low amounts only in the second peak. Cation exchange chromatography on carboxymethylcellulose-Sephadex with a starting buffer of pH 5 containing 2 mM CHAPS plus 20 mM beta-OG, followed by a pH 8 buffer, showed a very small OD peak at the void volume (P) and a second peak with about 95% of the protein (E). However, no 5-MD activity was detectable in either peak, while a nearly complete restoration of the enzyme was achieved when P and E were mixed. 5-MD was also completely restored by combination of P with the first inactive peak of GFII. When P was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no distinct protein bands were observed. After ethanol-ether extraction and digestion with H2SO4 and H2O2, inorganic phosphate was detectable only in P, suggesting the presence of phospholipids. We next studied the effect of phosphatidyl serine (PS), phosphatidyl choline (PC), or phosphatidyl ethanolamine (PE) on 5-MD activity of E (5 micrograms protein/mL). The 5-MD activity was recovered in a dose-response manner with all phospholipids studied, but PS was the most effective agent for reconstitution. At 1 microgram/mL, 5-MD activity, expressed as a percentage of the total P plus E activity, was 101% for PS, 35% for PC, and 20% for PE. The addition of rat liver or kidney microsomes (80 micrograms/mL) to E (5 micrograms/mL) provided recoveries of 79% and 48%, respectively, of the total P plus E activity. The following conclusions were reached. 1) Phospholipids are essential for the 5-MD activity of SHPMP. 2) CHAPS and beta-OG may extract phospholipids from the membranes without denaturation of the 5-MD.(ABSTRACT TRUNCATED AT 400 WORDS)

Cholic Acids↗
PubMed1991

Further studies on the long-term treatment of Graves' hyperthyroidism with ipodate: assessment of a minimal effective dose.

We have previously described that sodium ipodate (500 mg/day, p.o.) is effective in normalizing serum T3 and T4 levels in most patients with Graves' hyperthyroidism. In this study, we examined serum T3, T4, and rT3 levels in 14 hyperthyroid patients with Graves' disease during treatment with a lower dose (500 mg, every other day, p.o.) of sodium ipodate for a period of 3-30 weeks (mean 15.5 weeks). Three types of responses were observed. In group I (4 patients), both serum T3 and T4 were in the normal range at the end of treatment [baseline: mean +/- SEM T3, 6.8 +/- 0.96 nmol/L (normal 0.92-3.0)] and T4 [256 +/- 44 nmol/L (normal 62-167); post-ipodate: T3, 2.0 +/- 0.46 nmol/L and T4 107 +/- 28 nmol/L]. In group II (n = 5), either serum T3 (3 patients) or serum T4 (2 patients) did not become normal (baseline: T3 7.7 +/- 1.1 and T4 228 +/- 3.9; post-ipodate: T3 2.9 +/- 0.57 and T4 188 +/- 27 nmol/L). In group III (5 patients), neither serum T3 nor serum T4 returned to normal following ipodate treatment (baseline: T3 11.9 +/- 1.8 and T4 260 +/- 23; post-ipodate: T3 7.5 +/- 0.49 and T4 322 +/- 17 nmol/L). The mean serum rT3 concentration increased during ipodate treatment to a peak value of 100% above baseline and remained elevated (20-75% above baseline) throughout the study. Some improvement in hyperthyroidism was suggested by increase in body weight during ipodate treatment in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

1 alpha,25-dihydroxyvitamin D3-induced regulation of protein kinase C gene expression during HL-60 cell differentiation.

The human promyelocytic leukemia cell line HL-60 differentiates in vitro when treated with various inducers. It has previously been shown that protein kinase C (PKC) isozymes are modulated during granulocytic differentiation of HL-60 cells induced by dimethyl sulfoxide or retinoic acid (M. Makowske, R. Ballester, Y. Cayre, and O.M. Rosen, J. Biol. Chem., 263: 3402-3410, 1988; K. Hashimoto, A. Kishimoto, H. Aihara, I. Yasuda, K. Mikawa, and Y. Nishizuka, FEBS Left., 263: 31-34, 1990). HL-60 responds to 1 alpha, 25-dihydroxyvitamin D3 (1,25-(OH)2D3) or to 12-O-tetradecanoylphorbol-13-acetate by giving rise to monocytic cells. In the present study, we demonstrate that treatment of HL-60 cells with 1,25-(OH)2D3 causes dramatic increases in PKC-alpha and PKC-beta protein levels detected by immunoblotting with PKC isoform-specific antibodies and in Ca(2+)- and phospholipid-dependent protein kinase activity. We also observed a transient increase in the steady-state levels of PKC-alpha and PKC-beta mRNA species in Northern blotting experiments, with maximal induction occurring 48 h after addition of 1,25-(OH)2D3. Analyses of 1,25-(OH)2D3-induced PKC mRNA expression by nuclear run-on transcription experiments suggest that the observed increases in PKC mRNA levels may occur by a posttranscriptional mechanism(s). In contrast to the transient increases in PKC mRNA levels, the increases in PKC Mr 80,000 protein species and in PKC enzyme activity were progressive in HL-60 cells treated with 1,25-(OH)2D3 between 1 and 5 days, thus implying the existence of a further up-regulation of PKC proteins occurring at the translational and/or posttranslational levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗
PubMed1990

Carotid endarterectomy for elderly patients: predicting complications.

OBJECTIVE: To determine whether the complication or death rate from carotid endarterectomy can be predicted from hospital and physician structural variables, such as the hospital's teaching status or the number of endarterectomies done by the surgeon per year. DESIGN: Survey of medical records. After controlling for the severity of the patient's condition on the basis of data in the medical record at the time of the endarterectomy, regression analyses were used to predict the postoperative stroke, heart attack, and 30-day death rate as a function of patient, physician, and hospital characteristics. SETTING: Three geographic areas (states or large parts of states; average population, 3 million) in the United States. PATIENTS: Random sample of 1302 patients 65 years of age or older having carotid endarterectomy in 1981. INTERVENTION: Carotid endarterectomy. MEASUREMENTS AND MAIN RESULTS: Of 1302 patients, 11.3% had a postoperative stroke or heart attack or died within 30 days of the operation. Patient age, race, income, and gender; physician volume, board certification status, and age; and hospital size, for-profit status, ownership, and teaching status were not significantly related to the postoperative complication or death rate. If the surgeon was a graduate of a foreign, but not a Western European or Canadian, medical school, however, the average complication or death rate rose from 10.4% to 19.6% (P less than 0.05). CONCLUSIONS: The effectiveness of carotid endarterectomy depends heavily on its complication rate. Because complications after surgery cannot, in general, be predicted from structural variables, referring physicians cannot rely solely on the surgeon's experience and qualifications when recommending a carotid endarterectomy. The surgeon's and the hospital's actual postoperative complication and death rate should be considered.

Age Factors↗
PubMed1990

Predicting the appropriate use of carotid endarterectomy, upper gastrointestinal endoscopy, and coronary angiography.

BACKGROUND AND METHODS: In a nationally representative population 65 years of age or older, we have demonstrated that about one quarter of coronary angiographies and upper gastrointestinal endoscopies and two thirds of carotid endarterectomies were performed for reasons that were less than medically appropriate. In this paper we examine whether specific characteristics of patients (age, sex, and race), physicians (age, board-certification status, and experience with the procedure), or hospitals (teaching status, profit-making status, and size) predict whether a procedure will be performed appropriately. RESULTS: In general, we found that little of the variability in the appropriateness of care (4 percent or less) could be explained on the basis of standard, easily obtainable data about the patient, the physician, or the hospital. For all three procedures, however, performance in a teaching hospital increased the likelihood that the reasons would be medically appropriate (P = 0.09 for angiography, P = 0.30 for endoscopy, and P less than 0.01 for endarterectomy). In addition, angiographies were more often performed for appropriate reasons in older or more affluent patients (P less than 0.01 for both). Being treated by a surgeon who performed a high rather than a low number of procedures decreased the likelihood of an appropriate endarterectomy by one third, from 40 to 28 percent (P less than 0.01). CONCLUSIONS: Appropriateness of care cannot be closely predicted from many easily determined characteristics of patients, physicians, or hospitals. Thus, for the present, if appropriateness is to be improved it will have to be assessed directly at the level of each patient, hospital, and physician.

Aged↗
PubMed1990

American Thyroid Association guidelines for use of laboratory tests in thyroid disorders.

Selection of appropriate laboratory determinations will enable the clinician to diagnose thyroid dysfunction readily in the majority of patients. At the present time, estimation of free thyroxine and a "sensitive" thyrotropin assay are recommended as the principal laboratory tests for thyroid disease. A decrease in serum free thyroxine estimate and a raised level of serum thyrotropin confirm the diagnosis of hypothyroidism caused by thyroid gland failure. An increase in free thyroxine estimate combined with a serum sensitive thyrotropin level suppressed to less than 0.1 mU/L establishes the diagnosis of thyrotoxicosis. In sick patients, a normal or raised serum free thyroxine estimate together with a normal level of serum thyrotropin suggests that the patient has neither hypothyroidism nor thyrotoxicosis. Patients with severe illnesses, generally in the intensive care unit, and those treated with certain drugs, as well as individuals with unusual thyroid disorders, may present with confusing laboratory findings. An understanding of the regulation of the thyroid hormone system and/or judicious consultation with an endocrinologist should enable the clinician to diagnose thyroid disease, if present, in such patients.

Female↗
PubMed1990

Does inappropriate use explain small-area variations in the use of health care services?

We studied the relationship of the appropriateness of the use of coronary angiography, carotid endarterectomy, and upper gastrointestinal tract endoscopy to their rates of use in 23 adjacent counties in one state. We measured appropriateness by means of a detailed review of the medical records of Medicare beneficiaries who had the procedures performed in 1981, using present criteria derived by an expert panel. Use rates per 10,000 Medicare enrollees in a county varied from 13 to 158 for coronary angiography, 5 to 41 for carotid endarterectomy, and 42 to 164 for upper gastrointestinal tract endoscopy. Inappropriate use varied by county from 8% to 75% for coronary angiography, from 0% to 67% for carotid endarterectomy, and from 0% to 25% for endoscopy. For coronary angiography, inappropriate use accounted for 28% of the variance in the county rate. For the other two procedures, no significant correlations were found between inappropriateness of use and rate of use. We conclude that little of the variation in the rates of use of these procedures can be explained by inappropriate use.

Aged↗
PubMed1990

Serum thyrotropin in hospitalized psychiatric patients: evidence for hyperthyrotropinemia as measured by an ultrasensitive thyrotropin assay.

In order to gather further insight into the basis for high serum T4 and/or T3 of psychiatric illnesses, we studied thyroid function in 84 consecutive newly hospitalized psychiatric patients (HPP) in a 12-week period. Serum T4 and T3 were measured by immunoassay and thyrotropin (thyroid-stimulating hormone [TSH]) by an ultrasensitive immunoradiometric assay. Serum T4 was in the normal range in 64 (76%) and elevated in 20 (24%); free T4 index was elevated in 13 of 75 (16%), total T3 in 12 of 60 (20%), free T3 index in seven of 56 (13%), and TSH in 14 of 84 (17%) cases so studied. Serum TSH was subnormal in only one case (1%). Among the 14 patients with elevated serum TSH, serum free T4 index was normal in 12 and elevated in two. High serum T4 (or free T4 index) and high serum TSH were not correlated significantly by chi 2 analysis. None of the patients with elevated TSH demonstrated goiter or antithyroglobulin or antimicrosomal antibodies. On repeat testing 7 to 21 days after admission, serum TSH (and/or T4) normalized in the three of five patients studied. Serum TSH response to 500 micrograms intravenous (IV) thyrotropin-releasing hormone (TRH) was normal (serum TSH post-TRH, 8 to 28 microU/mL) in two patients with elevated TSH and T4, one patient with normal TSH and high T4, and one patient with normal TSH and T4. One patient with suppressed serum TSH (0.1 microU/mL) had elevated serum T4 (16.9 micrograms/dL, normal 4.8 to 11.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells.

Cells from the human leukemia cell line HL-60 undergo terminal differentiation when exposed to inducing agents. Differentiation of these cells is always accompanied by withdrawal from the cell cycle. Here we describe the isolation of a cDNA encoding a novel serine protease that is present in HL-60 cells and is down-regulated during induced differentiation of these cells. We have named this protease myeloblastin. Down-regulation of myeloblastin mRNA occurs with both monocytic and granulocytic inducers. Myeloblastin mRNA is undetectable in fully differentiated HL-60 cells as well as in human peripheral blood monocytes. We found that regulation of myeloblastin mRNA in HL-60 cells is serum dependent. Inhibition of myeloblastin expression by an antisense oligodeoxynucleotide inhibits proliferation and induces differentiation of promyelocyte-like leukemia cells.

Amino Acid Sequence↗
PubMed1989

Relation between surgeons' practice volumes and geographic variation in the rate of carotid endarterectomy.

We examined the relation between the number of operative procedures carried out by individual surgeons and the variation in the rate of carotid endarterectomy among Medicare beneficiaries in areas of high, average, and low use of the procedure in 1981. Rates ranged from 48 per 100,000 in the low-use area to 178 per 100,000 in the high-use area. Two variables accounted for most of the differences in the rates: the number of surgeons performing the procedure and the number of endarterectomies performed by surgeons with high practice volumes. Twice as many surgeons in the high-use area and 25 percent more in the average-use area performed carotid endarterectomy as compared with those in the low-use area. If the average number of cases per surgeon had been the same, the differences in the number of surgeons would have accounted for 36 percent and 15 percent, respectively, of the differences in use. Surgeons who performed 15 or more carotid endarterectomies during the year accounted for most of the variation in the rates. These high-volume surgeons represented 15 percent and 17 percent of the surgeons in the areas of high and average use, respectively, as compared with 4 percent of those in the low-use area. They accounted for 60 and 77 percent, respectively, of the additional endarterectomies. Three fourths of the surgeons performing carotid endarterectomies carried out fewer than 10, and 24 percent did only 1. We conclude that most of the geographic variation in the rate of carotid endarterectomy is caused by a few surgeons in high-use areas who perform large numbers of operations.

Carotid Arteries↗
PubMed1989

Glucocorticoid regulation of hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene expression.

The effect of adrenalectomy and triamcinolone treatment on mRNA encoding rat hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was studied. Adrenalectomy decreased both the kinase and the bisphosphatase activities of the bifunctional enzyme to about 30% of the values in livers of normal rats. Triamcinolone treatment restored both activities to normal by 24 h. These changes were caused by alterations in the concentration of the enzyme as determined by immunoblotting and by an assay that measures phosphoenzyme formation. Messenger RNA for liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was markedly decreased by adrenalectomy and was increased 15-fold by triamcinolone administration for 8 h. The rate of transcription of the bifunctional enzyme gene, measured in rat liver nuclei, was also decreased in adrenalectomy, and triamcinolone treatment increased this rate 5-fold within 8 h. Similarly, liver nuclear precursors of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA were decreased by adrenalectomy to 25% of the level in nuclei from normal rats. Triamcinolone treatment restored heterogeneous values by 2 h, while treatment for 30 h increased it 12-fold over the adrenalectomized levels. It was concluded that glucocorticoids regulate the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, at least in part, by modulating the transcription rate of the gene.

Adrenalectomy↗