Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I evaluation of a weekly schedule of anguidine was undertaken as an alternative to the present continuous daily schedules. The dose ranged from 1.5 to 7.5 mg/m2 given as an infusion over 3 hours. No myelosuppression was noted at any dose level. The toxic effects included nausea and vomiting, hypotension, CNS symptoms (confusion, hallucinations, and psychomotor seizures), chills, fever, and diarrhea. A dose of 5 mg/m2 of anguidine produced acceptable toxicity.
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PMID:Phase I evaluation of a weekly schedule of anguidine. Southeastern Cancer Study Group Committee on Gastrointestinal Malignancies. 52 34

Nineteen patients with advanced cancer were entered into a phase I clinical trial of Tumor Necrosis Factor (TNF) which was designed to determine the pharmacokinetic profile, safety, and maximal tolerated dose (MTD) of the recombinant human cytokine in vivo. TNF was administered by continuous infusion for 24 hours followed by pharmacokinetics and a 120-hour infusion repeated every 3 weeks. The initial dose was 40 micrograms/m2 and was ultimately escalated to 200 micrograms/m2. A total of forty 5-day cycles were administered to 18 of these patients; and all were evaluable for toxicity. Toxicities in this trial included fever, chills, rigors, hypotension, headaches, seizures, lethargy, weight loss, and malaise. At all dose levels, but more significantly at the highest doses, hematological toxicities were observed and grade 3 neurotoxicity (headache and confusion), and hypotension were noted. Two patients expired during the study, and this was felt to be related to septic episodes. Because of these severe toxicities, 160 micrograms/m2 was defined as the MTD. At 160 micrograms/m2 peak serum levels occurred within 5-20 minutes of initiation and were not detectable 1 hour later. No anti-tumor responses were observed. No measurable plasma levels of TNF were observed with the administration of doses of 80 micrograms/m2. This dose level could be further studied in phase II studies alone and in combination with other agents, utilizing a continuous infusion schedule.
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PMID:A phase I pharmacokinetic study of recombinant human tumor necrosis factor administered by a 5-day continuous infusion. 142 28

The application of recombinant DNA technology to the production of tumor necrosis factor has resulted in the availability of large quantities of a highly purified protein product. This product has been evaluated extensively in preclinical studies, which have documented a direct cytostatic and cytotoxic effect on human tumor cells, as well as a variety of immunomodulatory effects on various immune effector cells, including neutrophils, macrophages, and T cells. In addition, a number of anti-infective and metabolic effects have been documented. In addition to its in vitro effects, rTNF has been shown to have antitumor activity in vivo in preclinical studies involving both transplantable murine tumors and human tumor xenografts. Such observations have led to the evaluation of rTNF as a potential antineoplastic agent in humans. Both single- and multiple-dose phase I studies have confirmed that rTNF can be safely administered to patients with advanced malignancies in a dose range associated with anticancer effect without concomitant serious toxicities such as shock and cachexia. The most commonly observed clinical toxicities include constitutional symptoms, such as fever, chills, headache, and fatigue, and toxicities, which can be at least partially controlled with concomitant administration of nonsteroidal anti-inflammatory drugs, such as acetaminophen and meperidine. Hypotension, which occurs at high doses administered by short intravenous infusion, can usually be prevented by prehydration with intravenous fluids or otherwise controlled by the administration. An intense local inflammatory reaction at the injection site as well as thrombocytopenia appear to be the dose-limiting toxicities after subcutaneous and intramuscular administration. Neurologic toxicity is infrequent, except following continuous intravenous infusion, where it may manifest as transient focal neurologic deficits or seizure. Prolonged administration of rTNF at higher doses may be associated with transient, subclinical decreases in diffusing capacity. Patients with underlying cardiopulmonary disease should be excluded from rTNF therapy in future clinical studies until the end-organ toxicities of this agent are better defined. For at least one preparation of rTNF there appears to be no evidence for the formation of antibodies to rTNF in patients who receive multiple administrations of the agent. Pharmacokinetic studies have shown a relatively rapid clearance following intravenous infusion with a half-life of 15 to 30 min and dose-dependent pharmacokinetics. rTNF can be detected in the serum following intramuscular or subcutaneous injection at only relatively high doses, suggesting a decreased bioavailability with the routes of administration. Early phase I studies defined tolerable dose ranges for each route of administration and began to explore immunomodulatory and metabolic effects of rTNF.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recombinant human TNF-alpha: preclinical studies and results from early clinical trials. 155 Aug 75

Besides general complications of immunosuppression such as increased susceptibility to opportunistic infections or malignancy, individual immunosuppressive agents are associated with specific side effects. Nephrotoxicity is the major side effect of cyclosporine (CsA). Various attempts have been made to minimize this toxicity, such as monitoring drug blood levels, modifying the protocol, and coadministering other agents. Other side effects caused by CsA are hepatotoxicity, hyperkalemia, hypertension, tremor, gum overgrowth, and hirsutism. Azathioprine (AZA) causes dose-related bone marrow suppression, commonly leading to leukopenia. Careful monitoring of complete blood cell count and dosage adjustment according to white blood cell count are usually adequate to prevent serious leukopenia. The side effects of corticosteroids are numerous and include slow wound healing and de novo insulin-dependent diabetes mellitus. Many complications are dose related, and with low dosage or discontinuation of steroids, their frequency rapidly decreases. Antilymphoblast and antithymocyte globulins (P-ALG) are foreign antibodies and may cause allergic-type reactions such as fever, chill, and hypotension. The initial side effect of monoclonal antibody (muromonab-CD3, OKT3) is similar to that of P-ALG. It includes high fever, shaking chills, headache, rigors, and hypotension. To prevent it, acetaminophen, an antihistamine, and a steroid usually are administered before injection. Because this agent is also associated with high frequency of pulmonary edema, it should not be given to any patient who has more than 3% body weight gain during the week prior to therapy. In rare case, it causes aseptic meningitis or encephalopathy, which is manifested by fever, severe headache, and seizure.
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PMID:Complications associated with immunosuppressive therapy and their management. 174 17

We describe an 18-month-old male infant suffering from the ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome and further delineate the clinical phenotype. Severe retardation of growth and psychomotor development, chill-like seizures, bronchial asthma, urticaria, a proneness to skin infections and transient nail dystrophy observed in our patient are non-obligatory manifestations of this disorder. Histological examination of the atrichia revealed poorly developed, shortened hair follicles and a complete absence of sebaceous glands. The sex ratio of published cases suggests an X-linked recessive inheritance. The marked clinical variability of the IFAP syndrome might be the expression of a contiguous gene defect.
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PMID:Further delineation of the ichthyosis follicularis, atrichia, and photophobia syndrome. 191 13

Cocaine abuse is associated with a constellation of serious medical complications. An unrecognized and recently described complication of cocaine use is rhabdomyolysis with acute renal failure. We describe the first patient identified in our institution with this entity, admitted to the medical services with oliguric acute renal failure. Three days prior to admission the patient had a cocaine snorting binge. He presented with bilateral flank pain, gross hematuria, vomiting and chills. No history of crush injury, prolonged immobilization and or seizures was reported. On admission the vital signs were normal, physical exam revealed periorbital edema and marked soft tissue neck swelling. Lab values: Bun 120 mgs%, Creat. 10.7 mgs%, Na 132 meq/lt, Co2 13mq/lt, Cl, 103meq/lt, Co2 13meq/lt, Ca 5.3 mgs%, CPK 30,800 U/L with a MM fraction of 98%, LDH 600 U/L, SGOT 300 U/L. The urine was dark red with a ph of 6.5 and 100 rbc/hpf. The anti-GBM antibody and blood cultures were negative. An abdominal sonogram was normal. He received peritoneal dialysis and was discharged on his 14th hospital day with a CPK of 2,800 U/L and decreasing azotemia. Cocaine associated rhabdomyolysis has only been recently described in the literature (AJM April, 88). Acute myoglobinuric renal failure needs to be added to the growing list of medical complications of cocaine use.
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PMID:Cocaine and rhabdomyolysis: report of a case and review of the literature. 207 48

An 81-year-old woman had chills, fever, nausea, vomiting, and epigastric pain. On day 3 she had hematuria and was treated with trimethoprim-sulfamethoxazole. On day 5 she had a cough, hypotension, anemia, azotemia, and elevated hepatic enzyme levels. Her condition deteriorated with thrombocytopenia, anuria requiring dialysis, edema, and hypoalbuminemia. Treatment with chloramphenicol and doxycycline was started on day 10. By day 11, she was in hypotensive shock; on day 12 she had seizures and died. Murine typhus was diagnosed by demonstration of antibodies to Rickettsia typhi by indirect immunofluorescence. Necropsy revealed interstitial pneumonia, pulmonary edema, hyaline membranes, alveolar hemorrhages, petechiae and vasculitis in the central nervous system, interstitial myocarditis, multifocal interstitial nephritis and hemorrhages, splenomegaly, portal triaditis, and mucosal hemorrhages in urinary tract. Immunofluorescent R. typhi were demonstrated in the lungs, brain, kidneys, liver, and heart. This unusual death occurred in an elderly patient without rash who was treated too late with antirickettsial drugs.
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PMID:Histopathology and immunohistologic demonstration of the distribution of Rickettsia typhi in fatal murine typhus. 249 81

rTNF was administered to 28 patients with advanced metastatic cancers by continuous intravenous infusion for 5 consecutive days every 2 weeks. The dose levels were 30, 40, 70, 110, 180 and 290 micrograms/M2/day. Groups of 3 patients were started at each successive dose level and then on subsequent courses treated with the next dose level through 4 escalations as tolerated. Tumor types were: colon cancer 14; adenocarcinoma of unknown primary, 2; renal cancer, 2; leiomyosarcoma, 2; lung cancer, 1; prostate cancer, 1; thymona, 1; bladder cancer; 1; parotid, 1; Kaposi's sarcoma 2; ovarian 1. Toxicities included fever and chills (usually within the first 8 hours of infusion), fatigue, headache, decreased performance status, hypotension and CNS. All patients experienced leukopenia and thrombocytopenia within 24 hours or less after start of infusion with return of baseline by 72 hours after rTNF was stopped. The fall in these counts averaged 50% and was not dose related. No major changes in liver or renal function, coagulation or blood lipids were seen. Major dose limiting toxicities were fatigue, confusion, thrombocytopenia, seizures, hypotension and decreased performance status. NK cell activity measured against K562 target cells was augmented from about 30% target cell lysis to about 70% target cell lysis over the first 7 days of treatment. Two patients, both with metastatic colon cancer showed transient, objective tumor regression which did not qualify as a partial response. One patient with ovarian cancer had a stable partial response but progressed after 13 courses of treatment. Continuous infusion of TNF can be safely administered to patients with a maximum tolerated dose of only between 30 and 40 micrograms/M2/day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase I trial of recombinant tumor necrosis factor (rTNF) administered by continuous intravenous infusion in patients with disseminated malignancy. 264 24

Twenty-six patients with recurrent respiratory papillomatosis have received interferon administered according to one or more of five experimental protocols currently ongoing or completed at the University of Iowa. Short-term side effects following interferon administration were common and included fever, headache, chills, fatigue, myalgias, and nausea. Two patients experienced neurotoxicity manifested as somnolence, confusion, or petit mal type or grand mal type seizures. Preliminary data show evidence for some growth retardation in patients receiving long-term interferon therapy. Laboratory evidence of toxicity in the form of decreased WBC, RBC, and platelet counts occurred in five patients, and increased liver enzymes occurred in 16 patients. Neither cardiovascular nor renal toxicity was noted.
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PMID:Side effects and toxicity of interferon in the treatment of recurrent respiratory papillomatosis. 367 59

Clinical features, findings of diagnostic studies, results of therapy, and prognostic factors were analyzed in 45 patients with brain abscesses. The number of patients diagnosed yearly has increased since CT scanning became available, but despite the enhanced sensitivity, the time from either onset of symptoms or hospital admission until initiation of therapy was not decreased and there was no dramatic effect upon morbidity or mortality in this series. Infections of paranasal sinuses, ears, lungs, and odontogenic foci were predisposing factors in approximately 70% of cases. Single abscesses, present in 75% of patients, were distributed equally in both hemispheres, with more than half in the frontal and parietal lobes. Common signs and symptoms included headache, fever, chills, seizures, nausea, vomiting, altered sensorium, nuchal rigidity, and localizing neurologic signs. Blood cultures were positive in 11%. Lumbar puncture rarely provided data from which a diagnosis could be established; CSF cultures were positive in only 7% of patients, and there was a 15% temporally associated incidence of brain herniation and death. Diagnostic information was most readily obtained using imaging techniques such as CT and 99mTc scanning, and arteriography was invasive and of no added value. CT scans are however, often initially negative in patients presenting with clinical signs of meningitis presumably following rupture of an abscess into the subarachnoid space, and the average time for changes to appear on CT scan is 9 days. It is, therefore, recommended that when the clinical assessment suggests the possibility of brain abscess the patient be treated empirically with antibiotics and that lumbar puncture be performed only after thoughtful assessment of the risk-to-benefit ratio for each patient. Causative organisms were isolated from more than 80% of abscesses despite prior antibiotic treatment; more than half grew a single pathogen, most commonly streptococci. Anaerobic and microaerophilic bacteria accounted for 62% of all isolates, and were the only organisms in 33% of patients. Computerized tomographic scans in 30 patients showed "ring-enhancing" lesions, nodular enhancement, or areas of low attenuation. Complete resolution of abscesses on CT scans rarely occurred during hospitalization and took as long as 5 months. Decrease in the size of abscesses on CT scan correlated well with clinical improvement and was seen within a week when abscesses were excised, but was often not obvious for 6 to 8 weeks if antibiotics were used alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Brain abscess. A study of 45 consecutive cases. 378


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