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)

Ten patients, who were admitted to the Intensive Coronary Care Unit during a one year period with symptomatic bradycardia while on combination therapy with oral diltiazem and beta-blocker agents, are described. The important features of this adverse reaction to drug combination were that it appeared mainly in a relatively elderly age group and with presenting symptoms of lethargy, dizziness, syncope, chest pain, and (in one patient with poor left ventricular function) pulmonary edema. It was not dose dependent and occurred even in very low doses of each drug. Electrophysiologic abnormalities were localized to the sinus node in all 10 patients and the primary rhythm disorders were junctional escape rhythm, sinus bradycardia, and sinus pause. These rhythm abnormalities resolved within 24 h following withdrawal of the offending drugs. Temporary pacemaker insertion was necessary in four patients. The duration of drug combination used before the acute episode range from within hours to up to 2 years. In conclusion, although combination diltiazem/beta blocker therapy is very effective in ischemic syndrome, caution is advised when this combination is used especially in the elderly or in patients with left ventricular dysfunction or antecedent sinoatrial or atrioventricular conduction abnormality.
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PMID:Symptomatic bradycardia induced by the combination of oral diltiazem and beta blockers. 168 24

Recombinant gamma interferon (r-GIFN) demonstrates in vitro and in vivo characteristics that contrast with those of alpha and beta interferons. It has relatively weak antiviral properties, yet relatively potent immunomodulatory effects. A phase I trial was performed with r-GIFN (specific activity 2.6 X 10(6) IU/mg protein), administered as a continuous intravenous (IV) infusion over 24 hours for five days (Cl X 5) and repeated every 28 days. This schedule was chosen based on the short half-life of r-GIFN in animal systems and the in vitro augmentation of biologic effects with continuous exposure to interferons. Twenty-one patients with refractory solid tumors received 46 evaluable courses of therapy. The dose-limiting toxicities included fever, flu-like symptoms, cardiovascular toxicity, and neurotoxicity. The cardiovascular toxicity included hypotension and one episode of cardiac ischemia with chest pain. Neurotoxicity consisted of lethargy and confusion. These toxicities were reversible, and although dose-limiting, occurred sporadically throughout all dosage levels. Mild to moderately severe non-dose-limiting toxicities included nausea and vomiting, leukopenia, and liver function abnormalities. Other infrequent toxicities included hypocalcemia, diarrhea, constipation, and alopecia. The maximally tolerated dose of r-GIFN on this schedule is 0.5 X 10(6) IU/m2/d. Partial responses were seen in one patient with metastatic melanoma and in one patient with renal cell carcinoma. Toxicity and antitumor activity were seen at doses where interferon serum levels could not be detected by radioimmunoassay. In addition, the toxicity and antitumor activity seen were at much lower doses than previously described for shorter infusion schedules of other recombinant gamma interferon preparations. Differences in biologic activity of interferon preparations and/or differences in scheduling may account for this variability. Although this study defines a recommended phase II dose of r-GIFN based on the maximally tolerated dose, the optimal therapeutic index may exist at a lower dosage level.
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PMID:A phase I clinical trial of recombinant DNA gamma interferon. 310 84

A 52-year-old man with myxedema was evaluated for anterior chest pain that was considered to be compatible with myocardial ischemia. The night after admission he developed extreme bradycardia, hypotension, and apneic episodes lasting up to 25 s. Continuous positive airway pressure and administration of medroxyprogesterone acetate prevented further episodes and relieved much of the somnolence and lethargy that had contributed to the evidence for myxedema. Alveolar hypoventilation caused by decreased sensitivity to carbon dioxide, inadequate central neural drive, peripheral muscle force, and obesity all may have contributed to the apnea. Chest pain has not recurred, and results of electrocardiography have remained normal following full thyroid hormone replacement. The early recognition of myxedema causing sleep apnea will allow specific treatment to avoid the cardiovascular risks related to prolonged apnea and will help avoid confusion with other etiologies of cardiovascular abnormalities.
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PMID:Extreme bradycardia during sleep apnea caused by myxedema. 363 55

A Phase I trial of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NSC 286193, tiazofurin) was conducted using a 5-day continuous infusion schedule. Twenty-four patients with advanced cancer were entered on this trial. Dose levels ranged from 360 to 2350 mg/sq m/day for 5 days. Neurotoxicity was dose limiting and occurred in six patients. Neurotoxicity was expressed as confusion, lethargy, or obtundation and was associated with focal neurological deficits in four of six patients: hemiparesis, three; cortical blindness and bilateral upper extremity weakness, one. Neurotoxicity was not clearly dose related, occurring at 900 mg/sq m/day for 5 days (two patients), 1100 mg/sq m/day for 5 days (two patients), 1850 mg/sq m/day for 5 days, and 2350 mg/sq m/day for 5 days (one patient each). Other toxicities seen were myelosuppression, desquamation of palms and soles, malar erythema, and hyperpigmentation, stomatitis, chest pain, drug fever, and increased serum creatine phosphokinase. Administered drug [71.5 +/- 11.2% (SE)] was recovered intact in the urine within 24 h of administration. Terminal-phase mean harmonic half-life was 8.0 h. The unpredictable neurotoxicity seen following continuous infusion therapy with tiazofurin suggests that Phase II trials of this schedule are not indicated until better understanding of the biochemical effects of tiazofurin is achieved.
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PMID:Phase I clinical study with pharmacokinetic analysis of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NSC 286193) administered as a five-day infusion. 398 12

Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, TCAR) is a synthetic C-nucleoside that demonstrated significant in vivo activity against a variety of animal tumors as well as in vitro activity against human tumor-derived cell lines. Thirteen patients were treated with TCAR administered as a 5-day continuous infusion in this Phase I trial. Seventeen complete cycles were administered in three dose levels ranging from 550 to 1450 mg/M2. Dose-limiting toxicities were myelosuppression and neurotoxicity including severe lethargy. Other toxicities including superficial skin peeling, myalgias, and tearing were seen at all doses. One patient had chest pain on day 4 resulting in stopping the drug, however, there was no evidence of cardiac or pericardial disease. Uric acid levels rose within one day in the absence of allopurinol treatment. There were no treatment related deaths. HPLC measurement of drug levels demonstrated steady-state plasma levels during the infusion, and a half-life following the infusion of 7.7 +/- 0.6 hours. Minor abnormalities in renal function were associated with dramatic changes in pharmacokinetics and toxicity. No clinical responses were observed in this trial.
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PMID:Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion. 408 42

Eleven academic institutions were selected to study mitoxantrone administered on a schedule of 10 mg/m2/d for five days initially and later at 12 mg/m2/d for five days, each given as a 30 minute intravenous (IV) infusion each day. Patients with acute or chronic leukemia were stratified by leukemic type and clinical status and included one group of patients considered to be in relapse after complete remission from previous chemotherapy and another group of patients considered refractory to standard induction and/or salvage chemotherapy. During the initial treatment schedule, complete remissions were obtained in two of seven patients with acute nonlymphoblastic leukemia, in one of three patients with acute lymphoblastic leukemia, but in none of the patients with chronic granulocytic leukemia in blast crisis. The durations of remission for these three patients were 22, 57, and 78 days, respectively. An increase in mitoxantrone dose to 12 mg/m2/d produced complete remissions in 8 of 19 evaluable patients with acute nonlymphoblastic leukemia, in one of ten patients with refractory acute nonlymphoblastic leukemia, and in one of four patients with chronic granulocytic leukemia in blast crisis. Each of these patients required only a single course of mitoxantrone to achieve remission; the median time to remission was 37 days (range 18 to 64 days). Remission duration ranged from 35 days (chronic granulocytic leukemia) to 186 days, with the median duration for those patients with acute nonlymphoblastic leukemia achieving remission being 135 days. Of the six patients with acute lymphoblastic leukemia, none achieved remission at the higher dose level. Drug-related gastrointestinal toxicity included mucositis (25%), diarrhea (21%), and nausea and vomiting (61%). Systemic infection (nonfatal) was experienced by 21% of patients and alopecia by 17%. Other side effects that occurred occasionally were hepatic dysfunction, decreased renal function, confusion, lethargy, anxiety, and fever. Possible drug-related phlebitis developed in one patient, and a single episode of minor epistaxis was reported in another. Cardiovascular toxicity was low. At a mitoxantrone dose of 10 mg/m2/d for five days, one patient developed hypotension, and one episode of congestive heart failure was reported in another. At the higher dose of 12 mg/m2/d, no drug-related hypotension, congestive heart failure, tachycardia, or chest pain were reported. These data indicate that mitoxantrone is a promising single drug for the treatment of acute nonlymphoblastic leukemia and possibly for acute lymphoblastic leukemia.
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PMID:Mitoxantrone in the treatment of relapsed and refractory acute leukemia. 638 65

The effects of acute exposure to methylene chloride (dichloromethane) are due to its central nervous system depressant properties, which have resulted in fatalities. Manifestations of acute exposure include mental confusion, fatigue, lethargy, headache and chest pain. Metabolic conversion of methylene chloride to carbon monoxide may place persons with preexisting coronary artery disease at increased risk. Sequelae following chronic exposure are unknown, but data suggest serious long-term effects. The Environmental Protection Agency considers methylene chloride to be a probable human carcinogen.
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PMID:Methylene chloride toxicity. 846 11

The symptoms caused by or relating to orthostatic hypotension (over 20 mmHg systolic blood pressure) were evaluated using a questionnaire in 72 patients with primary chronic autonomic failure, 32 of whom had pure autonomic failure (PAF, and 40 multiple system atrophy (MSA). The most common posturally related symptoms were dizziness (84% PAF, 83% MSA), syncope (91% PAF, 45% MSA), visual disturbances (75% PAF, 53% MSA) and suboccipital/paracervical 'coat-hanger' neck pain (8 l% PAF, 53% MSA). Chest pain occurred mainly in patients with PAF (44% PAF, 13% MSA). Improvement occurred with sitting or lying flat. Non-specific symptoms (weakness, lethargy and fatigue) were common in both groups (91% PAF, 85% MSA); six patients (one PAF, five MSA) had these symptoms only. Postural symptoms (mainly dizziness and neck pain) were worse in the morning and with warm temperature, straining, exertion, arm movements and food ingestion; they were more common in PAF. Compensatory autonomic symptoms, such as palpitations and sweating, did not occur in either group. In conclusion, orthostatic hypotension caused symptoms of cerebral hypoperfusion (syncope, dizziness and visual disturbances); neck pain, presumably due to muscle hypoperfusion, also occurred frequently. These symptoms were exacerbated by various factors in daily life and were relieved by returning to the horizontal. Non-specific symptoms (such as fatigue) also were common. In MSA, despite substantial orthostatic hypotension, fewer patients had syncope, visual disturbance and neck pain; the reasons for this are unclear. Lack of these features does not exclude the need to assess and investigate orthostatic hypotension and possible autonomic failure.
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PMID:Symptoms associated with orthostatic hypotension in pure autonomic failure and multiple system atrophy. 1055 35

According the literature atrio-ventricular blockade (AVB) is the most frequent and well-known symptom of Lyme carditis. Typical signs of complete AVB include fatigue, lethargy and syncope- Morgagni-Adams-Stokes syndrome (MAS). The authors present their results and experience with 5 patients selected from a long-term study (conducted between 1987 and 1998) comprising 58 patients who developed MAS. The authors tried to evaluate the changes especially in the cardiovascular system. They correlated the clinical state with ECG findings, as well as with the levels of the Borrelia burgdorferi antibodies. The following results were obtained: 1) all patients had typical syncope, 2) the clinical course was not complicated (except one patient who developed ventricular fibrillation), 3) two patients had frequent symptomatic and asymptomatic arrhythmia including chest pain and episodic rest dyspnea, 4) subjective difficulties (usually palpitations) correlated with ECG findings (Lown 3a, 3b). The authors also looked for any relationship between clinical difficulties and levels of antibodies. The results obtained with an early permanent pacemaker were less favourable than those reported in the literature. Despite early treatment 2 patients had repeated palpitations and ECG correlates during the next years.
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PMID:Borrelia burgdorferi as a cause of Morgagni-Adams-Stokes syndrome. Long time follow-up study. 1066 10

We report a case of angiosarcoma involving the right ventricle. The patient was seen in our Cardiology Department and subsequently referred to our unit for surgery. He gave a 1-week history of lethargy, chest pain, breathlessness on exertion, fevers, and night sweats. Echocardiography and computed tomography of the chest showed a large pericardial effusion with multiple densities, raising suspicions of a hemorrhagic effusion. Surgical exploration showed an epicardial mass. Histopathology revealed angiosarcoma.
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PMID:Angiosarcoma of the right ventricle: a rare encounter. 1253 13


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