Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of adrenalectomy and hypophysectomy in the management of postmenopausal patients with metastatic breast carcinoma is reserved for highly selected patients. As an alternate approach, a pharmacologic method of inhibiting adrenal cortical secretion was developed which consisted of the daily administration of 1000 mg of aminoglutethimide to block steroidogensis and either dexamethasone (2.0-3.0 mg/day) or hydrocortisone (40-60 mg/day) as replacement glucocorticoid. This regimen markedly suppressed plasma levels of DHA-S, androstenedione, estrone, and estradiol, and urinary levels of aldosterone. Of 50 patients treated, 19 (38%) demonstrated either a complete (8/19) or a partial (11/19) objective disease remission which lasted for 18.05 +/- 3.1 months (mean +/- SEM). In 10 (20%) patients, there was stabilization of disease (7.8 +/- 1.2 months), accompanied by symptomatic relief of bone pain in six (12%). There was disease progression in 20 (40%) patients. The acute side effects of aminoglutethimide therapy were significant and consisted of transient lethargy (41.5%) and a cutaneous rash (35.8%). Chronic toxicity was negligible. The medical adrenalectomy regimen of aminoglutethimide plus glucocorticoid offers a suitable alternative to surgical adrenalectomy or hypophysectomy in the management of postmenopausal patients with metastatic breast carcinoma.
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PMID:Medical adrenalectomy with aminoglutethimide: clinical studies in postmenopausal patients with metastatic breast carcinoma. 64 74

An experimental model of clinical liver failure, using total devascularization of the liver is described in the pit. The survival time was 1495 +/- 75 (SEM) minutes. Clinically the pigs showed a uniform course. They became lethargic after eight to ten hours and following a period of increasing drowsiness they became comatose. The immediate cause of death was cardio-vasculary collaps. The ammonium ion concentration in the blood increased to 696 +/- 57 umol/l and in cerebrospinal fluid to 664 +/- 57 umol/l. Cerebrospinal fluid glucose concentration was significantly decreased.
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PMID:Total devascularization of the Liver: an experimental model of acute liver failure. 106 34

Although beta blockers are effective for the treatment of angina pectoris, chronic adverse effects produced by these agents--including lethargy, fatigue, and male impotence--can adversely affect patient acceptance and treatment compliance. To assess the clinical effects of switching from anti-anginal treatment with beta blocker only (phase I) to half-dose beta blocker plus the calcium blocker nifedipine (phase II) or nifedipine alone (phase III), 18 patients with chronic stable angina pectoris and side effects to beta blockers were evaluated in a 12-week, open-label trial. Three patients did not complete the study, one secondary to new unstable angina and two secondary to nifedipine side effects. Of the 15 patients completing the trial (13 men and two women; mean age, 54 +/- 5 [SEM] years), all sequentially participated in the one-month phases. Weekly angina frequency assessed from patient diaries was significantly less for treatment with nifedipine only (phase III) as compared with beta blocker (phase I) (1.7 +/- 1 versus 3.9 +/- 1 episodes per week), while phase II was not significantly different. Exercise test time was maintained throughout all phases (phase I, 457 +/- 39; phase II, 458 +/- 40; and phase III, 498 +/- 48 seconds, p not significant). All 15 patients in phase I (100 percent) had side effects to beta blockers, but these side effects were lessened in 12 patients (80 percent) in phase II and 13 patients (86 percent) in phase III, with total alleviation of symptoms in two patients (13 percent) in phase II, and eight patients (53 percent) in phase III. Thus, in patients with side effects to beta blockers, switching to nifedipine is associated with a significant reduction in beta blocker adverse symptoms and equal anti-anginal efficacy.
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PMID:Alternative medical treatment for patients with angina pectoris and adverse reactions to beta blockers. Usefulness of nifedipine. 287 34

Bilirubin inhibits in vitro oxidative phosphorylation and glycolysis. This study investigated the in vivo effect of bilirubin on cerebral oxygen, glucose, and lactate uptake in newborn piglets. Seventeen 2- to 4-day-old piglets were divided into three groups and examined as follows: group 1 = control (C); group 2 = control with sulfisoxazole; and group 3 = experimental, given bilirubin with sulfisoxazole. In the experimental group, bilirubin was infused for 4 h. The cerebral bilirubin content in the bilirubin-infused group was 11.0 +/- 1.4 nmol/g of cerebral cortex (mean +/- SEM), consistent with levels found in infants with kernicterus. However, this level of brain bilirubin had no major, acute effects on cerebral uptake of oxygen, glucose, or lactate despite producing lethargy and ataxia which were consistent with bilirubin intoxication. This suggests that mitochondrial changes may not be involved in vivo in acute bilirubin encephalopathy.
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PMID:The in vivo effect of bilirubin and sulfisoxazole on cerebral oxygen, glucose, and lactate metabolism in newborn piglets. 365 36

The anti-anginal effects of KB-944 (Fostedil), a new calcium ion antagonist with a half life of approximately 23-28 hr, were evaluated in 20 patients with exertional angina pectoris in a placebo-controlled single-blind dose titration trial. Ambulatory monitoring and multistage treadmill exercise with computer-assisted electrocardiographic analysis was performed after 2 weeks of placebo therapy and after two 2-weekly periods of KB-944 therapy. The mean (+/- SEM) exercise time to the development of angina on treadmill walking increased from 6.9 +/- 0.4 min on placebo to 9.4 +/- 0.5 min on KB-944 100 mg/day (P less than 0.001) and 9.7 +/- 0.8 min on KB-944 200 mg/day (P less than 0.001 vs placebo and not significant vs KB-944 100 mg/day). The time to the development of 1 mm ST-segment depression of 5.3 +/- 0.4 min on placebo increased to 6.5 +/- 0.5 and 6.6 +/- 0.5 min on KB-944 100 and 200 mg/day, respectively (P less than 0.01 vs placebo). The heart rate at rest of 77 +/- 3 beats/min on placebo was reduced to 68 +/- 3 beats/min on KB-944 100 mg/day (P less than 0.001) and 71 +/- 2 beats/min on KB-944 200 mg/day (P less than 0.01). The maximal heart rate and the rate-pressure product were not altered by KB-944 therapy. One patient developed unstable angina during the treatment phase of KB-944 200 mg/day and was withdrawn. Five patients complained of dyspepsia and one of headache and lethargy during KB-944 200 mg/day. One patient developed ventricular tachycardia during treadmill testing while on KB-944 200 mg/day. The 24-hr ambulatory monitoring data confirmed the findings of exercise testing. KB-944 (Fostedil) in a dose of 100 mg once daily was well tolerated as compared to KB-944 200 mg once daily and both the doses were equally effective. The drug merits further evaluation for the treatment of exertional angina pectoris.
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PMID:Ambulatory monitoring and exercise testing in the evaluation of a new long-acting calcium ion antagonist KB-944 (Fostedil) for the treatment of exertional angina pectoris. 390 75

We reviewed clinical data in 33 patients with transient hyperammonemia of the newborn (THAN): six previously unreported cases and 27 from the literature. Thirteen neonates with urea cycle enzyme deficiencies (UCED) served for comparison. No differences were found in the incidence of perinatal complications, route of delivery, Apgar scores, sex, or incidence or time of onset of seizures. On the other hand, neonates with THAN had significantly lower birth weights (mean +/- SEM 2282 +/- 78 gm vs 3336 +/- 222 gm, P less than 0.001) and gestational ages (35.1 +/- 0.5 weeks vs 39.6 +/- 0.5 weeks, P less than 0.001). Mean time of onset of respiratory distress (3.9 +/- 1.4 hours vs 71.5 +/- 26.1 hours, P less than 0.001), ventilatory support (P less than 0.001), lethargy (P less than 0.005), and coma (P less than 0.005) occurred earlier in THAN. Distinctive laboratory findings in patients with THAN included abnormal chest radiographic findings and plasma ammonium concentrations that were higher (1871 +/- 209 microM vs 973 +/- 169 microM, P less than 0.02) at an earlier age. Respiratory distress occurred in all but one patient with THAN before 24 hours; in contrast, only 62% of infants with UCED had respiratory symptoms, and none before 30 hours. In this retrospective study, the clinical presentation alone differentiated THAN from UCED.
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PMID:Differentiation of transient hyperammonemia of the newborn and urea cycle enzyme defects by clinical presentation. 405 69

A patient with carbamyl phosphate synthetase deficiency had four episodes of hyperammonemia, up to 226 microM, associated with valproate (VPA) treatment. These were accompanied by vomiting, lethargy, and coma. A group of epileptic patients receiving VPA remained asymptomatic but had significantly higher mean plasma ammonium levels when compared to epileptic patients receiving other anticonvulsants: 33.6 +/- 1.9 (SEM) versus 23.6 +/- 1.5 microM. Thus, VPA caused symptomatic hyperammonemia in a patient with an impairment in urea synthesis and resulted in mildly elevated ammonium levels in epileptic patients. These data suggest that ammonium levels should be monitored in patients receiving VPA who exhibit signs of vomiting or lethargy.
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PMID:Valproate-induced hyperammonemia. 680 93

The purpose of this study was to determine the effects of recombinant human GH (rhGH; 0.025 mg/kg.day) and one of two doses of recombinant human insulin-like growth factor-I (rhIGF-I; 0.015 and 0.060 mg/kg, twice daily) on body composition in elderly women. Sixteen healthy elderly women (mean age +/- SEM, 71.9 +/- 1.3 yr) were randomly assigned to receive either rhGH (GH; n = 5), low dose rhIGF-I (n = 6), or high dose rhIGF-I (n = 5). A 2-week predrug baseline period was followed by 4 weeks of hormone treatment, with a standardized diet fed throughout. All groups experienced a significant increase in serum IGF-I and IGFBP-3 levels over the treatment period, accompanied by significant decreases in IGF-II (P < 0.05). Fat mass decreased in all groups, with significant increases in lean body mass and nitrogen retention occurring in the high dose IGF and GH groups. Total body water did not change, whereas increases observed in intracellular fluid approached significance (P = 0.06). These anabolic changes were accompanied by numerous negative side-effects in the GH and high dose IGF groups, including headaches, lethargy, joint swelling/pain, and bloatedness. The low IGF dose was well tolerated. These results demonstrate that the administration of rhGH and rhIGF-I for 4 weeks results in anabolic changes in body composition in elderly women.
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PMID:The effects of recombinant human insulin-like growth factor-I and growth hormone on body composition in elderly women. 753 17

The gallbladder of the insectivorous hibernating bats (Pipistrellus pipistrellus et Rhinolophus ferrumequinum) in fullness, shows a fundus, a corpus and a neck. Its wall is formed by three layers: mucous membrane, with simple columnar epithelium on a thin basal lamina, beneath which is a "lamina propria" of connective tissue with blood and lymphatic vessels; lamina muscularis, constituted by three of four parallel bundles of smooth muscle cells, arranged in circular pattern; serous membrane of loose connective tissue, with precollecting lymphatic vessels and covered by mesothelial cells. By SEM the luminal surface of mucous membrane shows more or less prominent folds delimiting irregular areas with hexa-pentagonal outlines of the apical region of epithelial cells. This latter present a convex dome aspect with numerous microvilli, not changed significantly, during the different year periods. In summer and autumn the epithelial cells are characterized by developed organelles in supranuclear cytoplasm. During the prehibernating period, chiefly the cytoplasm shows multivesicular and heterogeneous dense bodies. In summer, autumn and initial hibernating period, epithelial cell cytoplasm presents microvilli with prominent "antennulae microvilares", numerous light micropinocytosis vesicles, little rough vesicles in apical portion. The mitochondria, grouping in supranuclear and basal cytoplasm, in lethargy, are characterized by small matrix osmiophilic granules. The epithelial cells are held together near the apical surface by tight and gap junctions, and some rare desmosomes only in Rhinolophus f.e. The cell membranes are deep pleated or interdigitate with wide intercellular spaces during the prehibernating period and experimental arousing, while in lethargy and summer months these present linear outline with scanty invaginations. The Authors compared these morphological aspects of bat gallbladder with other micromammalia's one, underline particularly the functional role of dense bodies, wide intercellular spaces and apical micropinocytosis vesicles. The different seasonal ultrastructural characteristics of epithelial cells are considered in close relation to an absorbing function connecting with balance of different metabolisms.
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PMID:[Structure and seasonal aspects of the bat gallbladder]. 794 8

Interleukin-1 (IL-1) may be involved in gut permeability to macromolecules and gut glutamine metabolism during endotoxemia. We developed a sensitive radioimmunoassay specific for mouse IL-1 alpha (detection limit of 100 pg/ml, or 5 pM) and measured intestinal levels of IL-1 alpha in response to endotoxin. CD-1 mice (N = 190) were randomized to intraperitoneal (ip) or intravenous (i.v.) lipopolysaccharide (LPS) infusion (15 micrograms/g or 1.5 micrograms/g Escherichia coli 0111:B4 LPS) or saline. Mice were sacrificed at Time 0, 30 min, 1 hr, 2.5 hr, 4 hr, 6 hr, 12 hr, and 24 hr (3 mice/group/time point). Small bowel (SB) and large bowel (LB) were harvested and compared to liver. Duodenum, upper jejunum, midjejunum, terminal ileum, cecum, ascending colon, and sigmoid were analyzed in separate experiments. Tissues were frozen, weighed, and homogenized, the homogenates were centrifuged, and the supernates were assayed for immunoreactive IL-1 alpha. IL-1 alpha was expressed as pg/g wt +/- SEM (lowest detectable amount = 1000 pg/g wet tissue (WT)). SB but not LB from normal controls had constitutively elevated levels of IL-1 alpha (6177 +/- 1640 pg/g WT). LPS ip or i.v. produced lethargy, diarrhea, and a dramatic elevation of IL-1 alpha levels in both SB and LB. In SB, IL-1 alpha was elevated compared to baseline at 1 hr (19201 +/- 626 pg/g WT) and reached a fivefold maximal increase at 2.5 hr (31775 +/- 503 pg/g WT) following 15 micrograms/g ip.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal production of interleukin-1 alpha during endotoxemia in the mouse. 841 68


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