Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
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The incidence of pregnant women with thyroid dysfunction has been reported to be around 0.1-0.4%. Graves' disease accounts for more than half of these disorders. The main cause of thyroid disease in pregnancy and puerperium is autoimmune dysfunction. Whether there may be goitre or exophthalmus present, clinical signs as inappropriate weight gain, high systolic pressure, palpitation (greater than or equal to 110/min), emotional lability, fatigue, acceleration of suppression of the Achilles' tendon reflex should induce changes in the biochemical thyroid function tests. Parameters for the diagnosis and management for hyperthyroidism are serum levels of free T4 and TSH, while those of T3, reverse T3, and TSH are for hypothyroidism. Serum anti-microsomal antibodies and anti-thyroglobulin antibodies which have no effect on the fetus are also good markers for severity. The transplacental transfer of maternal TSH receptor antibodies consisting of stimulatory and inhibitory immunoglobulins and maternal thyroid-binding inhibiting immunoglobulins play roles in the development of transient neonatal hyper- or hypothyroidism. Fetal control is achieved by optimal maternal management. Untreated hyperthyroidism may be associated with fetal malformations. This risk may be reduced by antithyroid drug treatment of up to 150 mg/day of propylthiouracil which has less chance of placental passage and less secretion into the mother's milk than methyl-mercapto-imidazol. Maternal thyroid function should be kept in the upper limit of normal range, taking into consideration the fetal dysfunction induced by over-administration of the drug which passes through placenta. Children of hypothyroid women taking inadequate replacement therapy manifested lower IQ values compared to the progeny of euthyroid or hypothyroid women taking adequate therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Thyroid disease]. 170 36

An 11-year-old boy with asthma had been receiving a controlled release theophylline preparation. He was prescribed fluvoxamine for a depressive disorder and within a week complained of severe headaches, tiredness and vomiting. His serum theophylline concentration had increased from 14.2 mg/L (shortly before fluvoxamine was started) to 27.4 mg/L. Fluvoxamine was withdrawn and theophylline concentrations decreased. Clomipramine was substituted for fluvoxamine with no further problems, and a later theophylline concentration was 13.7 mg/L. Competitive inhibition of hepatic microsomal enzymes by fluvoxamine may have been responsible for the elevated theophylline concentrations and toxicity observed in this case.
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PMID:Toxic interaction between fluvoxamine and sustained release theophylline in an 11-year-old boy. 179 25

Skeletal muscle has an inherent biochemical phenotypic plasticity that provides the possibility for it to be remodeled into a "heart-like" muscle for use in cardiac-assist devices. The purpose of this study was to chronically stimulate skeletal muscle electrically to transform the biochemical capacities of the three major subcellular systems (i.e., metabolic, calcium regulating, and contractile) to resemble those of heart muscle. The latissimus dorsi muscle (LDM) of mongrel dogs weighing 22-27 kg was stimulated via the thoracodorsal nerve at 2 Hz for 6-8 wk. This stimulation protocol reduced the phosphorylase (glycogenolytic) and phosphofructokinase (glycolytic) activities by 70%. The aerobic (citrate synthase activity) and fatty acid oxidative (3-hydroxyacyl-CoA dehydrogenase activity) capacities were not significantly increased by chronic stimulation and remained at about one-fourth those in the canine heart. The calcium-dependent sarcoplasmic reticulum adenosinetriphosphatase (ATPase) activity in the microsomal fraction, which was sixfold greater in the nonstimulated LDM than in the heart, was reduced by electrical stimulation to a level similar to that of the dog heart. The contractile capacity was evaluated by determining the percentage of types I and II fibers, the myofibrillar ATPase activity, and the proportion of myosin isoforms. The transformed muscle was comprised of 93 +/- 2% type I fibers, a myofibrillar ATPase activity similar to that in heart with primarily a slow-twitch muscle myosin isoform. In conclusion, electrical stimulation of canine LDM at 2 Hz for 6-8 wk resulted in two of the three biochemical systems, which confer physiological expression and fatigue resistance to muscle being transformed to resemble those of the myocardium.
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PMID:Biochemical transformation of canine skeletal muscle for use in cardiac-assist devices. 214 Aug 28

In principle, target inactivation analysis provides a means of determining the molecular weights (Mr) and states of aggregation of proteins in native environments where they are functionally active. We applied this irradiation technique to the rat liver microsomal membrane proteins: cytochrome b5, epoxide hydrolase, flavin-containing monooxygenase, NADH-ferricyanide reductase, NADPH-cytochrome P-450 reductase, and seven different forms of cytochrome P-450. Catalytic activities, spectral analysis of prosthetic groups, and sodium dodecyl sulfate-polyacrylamide electrophoresis/peroxidase-coupled immunoblotting were used to estimate apparent Mr values in rat liver microsomal membranes. Except in one case (cytochrome P-450PCN-E), the estimated Mr corresponded most closely to that of a monomer. Purified cytochrome P-450PB-B, NADPH-cytochrome P-450 reductase and epoxide hydrolase were also subjected to target inactivation analysis, and the results also suggested monomeric structures for all three proteins under these conditions. However, previous hydrodynamic and gel-exclusion results clearly indicate that all three of these proteins are oligomeric under these conditions. The discrepancy between target inactivation Mr estimates and hydrodynamic results is attributed to a lack of energy transfer between monomeric units. Thus, while P-450PCN-E may be oligomeric in microsomal membranes, target inactivation analysis does not appear to give conclusive results regarding the states of aggregation of these microsomal proteins.
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PMID:Target inactivation analysis applied to determination of molecular weights of rat liver proteins in the purified state and in microsomal membranes. 311 94

Cimetidine is known to impair the hepatic microsomal oxidation of diazepam, reducing its clearance and prolonging its half-life. We studied the clinical importance of this effect in 10 patients, who were receiving long-term treatment with diazepam for anxiety, tension, or difficulty in sleeping, in an eight-week double-blind controlled study during which the diazepam dosage remained constant. The study was in four two-week phases: base-line or adaptation, coadministration of cimetidine (300 mg) or matching placebo four times daily, crossover to the opposite treatment (placebo or cimetidine), and recovery treatment with diazepam alone. During the cimetidine phase, plasma concentrations of diazepam plus desmethyldiazepam rose an average of 57 per cent (P less than 0.005), then fell when cimetidine was withdrawn. However, there were no significant changes in scores on the digit-symbol-substitution test, a tracking task, or a reaction-time test. Clinical self-ratings indicated no increases in sedation, fatigue, or drowsiness. Patients experienced shortening of sleep latency (P less than 0.05) and an increase in self-rated depth or soundness of sleep (P less than 0.001) during the cimetidine period, but there were no changes in sleep duration or in the number of nocturnal awakenings. Although coadministration of cimetidine to diazepam-treated patients causes a large increase in plasma diazepam and desmethyldiazepam concentrations, the increase is of minimal clinical importance.
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PMID:Clinical importance of the interaction of diazepam and cimetidine. 642 9

A case of hyperthyroidism associated with pancytopenia has been reported. A 51-year-old woman was hospitalized for the investigation of struma, peripheral edema and fatigue. Hormonal studies revealed hyperfunction of the thyroid gland. Hematological examinations showed normocytic normochromic anemia, leukopenia and thrombocytopenia with hyperplastic bone marrow and increased serum iron levels. Elevations of the anti-thyroidal antibody and anti-microsomal antibody, and a decrease in CH50 titer were observed. A Coombs' test and anti-leukocytic antibody and anti-thrombocytic antibody tests were negative. The numbers of erythrocyte and thrombocyte were normalized after the administration of methimazole for three months as were the findings of the bone marrow and the serum iron level. However, leukopenia was maintained due to the effect of methimazole. It should be suggested that the etiology of pancytopenia might be due to hyperthyroidism. Although the mechanism of pancytopenia in a patient with hyperthyroidism is unclear, it might be related to the reduced life-span of whole blood components and/or partially to the autoimmune mechanism.
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PMID:[Case of hyperthyroidism with pancytopenia]. 666 44

A 47-year-old housewife was admitted to our hospital because of general fatigue and constipation suggesting hypothyroidism. For 3 years before admission, general fatigue, arrhythmia, dry skin, drowsiness, cold intolerance and hypermenorrhea occurred insidiously. She had habitually taken considerable amounts of seaweed every day, e.g. more than 50 g of " Kombu " for more than 5 years and at least 1 g of " Wakame " for 6 months. On admission, serum thyroxine (T4) was 1.3 micrograms/dl, serum triiodothyronine (T3) was 47 ng/dl, TSH was 132 microunits/ml, and 123I thyroidal uptake was 60% at 3 hr. and 75% at 24 hr. Anti-thyroglobulin hemagglutination antibodies and anti-thyroid microsomal hemagglutination antibodies were both negative. When seaweed was omitted from her diet, T4 rose to 6.3 micrograms/dl and T3 rose to 113 ng/dl, whereas TSH lowered to 11 microunits/ml in 2 weeks. The seaweed-free diet was continued and 4 months later, when she had become euthyroid, an open biopsy of the thyroid gland was carried out. Histological examination of the specimen revealed a marked colloid deposition without characteristic features of Hashimoto's disease. Five months after admission, with the daily administration of 100 mg potassium iodide (KI), the effects of inorganic iodide on thyroid function had begun to be seen. On the 16th day of the KI regimen, palpitation and tachycardia (pulse rate 160/min.) with multifocal ventricular premature beat appeared, and T4 on the 11th day was 5.9 micrograms/dl, which was clearly lower than the pretreatment level of 8.4 micrograms/dl. KI was discontinued on the 16th day, and one week after the withdrawal, T4, T3 and TSH all returned to the pretreatment level. For more than 3 years on a seaweed-free diet, she remained euthyroid without any thyroid regimen. To see the effects of inorganic iodide on thyroid function after this long period on a seaweed-free diet, KI was again administered. One hundred mg/day KI for 14 days followed by 200 mg/day for 21 days had virtually no effect on T4, T3 and free T4 and she remained well. None of the perchlorate discharge tests performed on 3 occasions during the 6 month period after the initiation of the seaweed-free diet showed a discharge.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A case of iodide myxedema observed for 3 years under a low iodide diet--especially on the restoration of the mechanism of escape from the Wolff-Chaikoff effect]. 674 70

The magnitude of the thyroid-stimulating hormone (TSH) response induced by thyrotropin-releasing hormone (TRH) helps identify patients whose thyroid is failing. Many of these patients have been found to have Hashimoto's thyroiditis, symptomless autoimmune thyroiditis (SAT), and subclinical hypothyroidism. While patients with SAT are clinically euthyroid, what might be "symptomless" for the endocrinologist might be a syndrome presenting with psychiatric symptoms to the psychiatrist. As a preliminary test of this hypothesis, we tested 100 consecutive admissions to a psychiatric hospital who complained of depression or lack of energy. Fifteen (15%) of 100 patients were identified from the baseline thyroxin (T4), triiodothyronine (T3) resin uptake (RU), T3 radioimmunoassay (T3RIA), TSH, and TRH test who met criteria for either subclinical, mild, or overt hypothyroidism. Of these 15 patients, 9 (60%) had positive thyroid microsomal antibodies with titers of greater than or equal to 1:10. Our data suggest that SAT is not symptomless and may be an important diagnosis to consider in the evaluation of depressed, anergic, or atypical patients.
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PMID:"Symptomless" autoimmune thyroiditis in depression. 681 Apr 1

Various diseases often occur after delivery but the systemic examinations have not been studied before. Thyroid dysfunction frequently (4.4%) occurs after delivery through an immune rebound mechanism. If postpartum women complain of the symptoms caused by thyrotoxicosis (palpitation, weight loss, increased sweating, finger tremor, fatigue) or hypothyroidism (edema, cold intolerance, hoarseness, sleepiness, fatigue), it is essential to examine thyroid hormones, thyroid stimulating hormone, anti-thyroid microsomal antibody (MCHA) and anti-TSH receptor antibody. To predict who will develop postpartum thyroid dysfunction, the measurement of MCHA during pregnancy is useful because 62% of the subjects with positive MCHA show thyroid dysfunction after delivery. The individuals at high risk of postpartum onset of Graves' thyrotoxicosis can be found early in their pregnancy by the detection of thyroid stimulating antibody (TSAb). Other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, autoimmune hypophysitis and so on, also could develop after delivery. These findings indicate that laboratory tests in the postpartum period are essential to diagnose postpartum onset of autoimmune diseases and the measurement of autoantibodies in early pregnancy is useful for prediction of their onset in the postpartum period.
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PMID:[Postgravid health care and laboratory tests]. 855 72

The silicone implant controversy wavers between reassuring epidemiological studies and about 300 case reports of patients developing a definite or incomplete/atypical connective tissue disease (CTD) after receiving a silicone gel-filled breast implant (SBI). Since Hashimoto's thyroiditis (HT) is rarely reported in this context, we report here two new cases of HT associated with a history of bilateral cosmetic SBIs. The first patient was a 45-year-old white woman who had SBIs in 1976. In 1991 she developed HT, evolving to thyroid deficiency which was compensated with levothyroxine treatment. In addition, the patient complained of fatigue, arthralgia, morning stiffness and developed a sicca syndrome necessitating artificial tears. The 1995 evaluation disclosed the presence of antinuclear antibodies at a titre of 1/640, and high level anti-thyroid microsomal antibodies (1/256,000). Gamma globulins rose to 22.6%. Thyroid ultrasonography showed an enlarged thyroid gland with a diffusely hypoechogenic pattern. The implants were painful, and in 1996 they were removed. Microscope examination of the fibrous capsule surrounding the prostheses showed extremely dense connective tissue with fibrosis. The second patient was a 55-year-old white woman who had SBIs in 1984. In 1995, she developed HT with clinical pain and tenderness of the thyroid gland, with mild hyperthyroidism and positive antithyroglobulin antibodies, and was given corticosteroid treatment for 5 months. In 1996, the implants were again painful and the patient developed positive antinuclear antibodies with a titre of 1/200. Ultrasonography showed a heterogeneous thyroid gland, and implant removal was advised. Hashimoto's thyroiditis is recognized as a subset of chronic auto-immune thyroiditis, and its association with SBI is rare. In these 2 observations, an association without relation is possible, but a future survey of similar cases seems warranted.
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PMID:[Hashimoto's thyroiditis and silicone breast implants: 2 cases]. 930 36


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