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)

Eighty-seven cats with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of mitoxantrone, a dihydroxyquinone derivative of anthracene, which was administered at 21-day intervals at dosages ranging from 2.5 to 6.5 mg/m2 of body surface, IV. Eleven of these cats were treated concurrently with radiation but were evaluated separately. Each cat was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the cat developed progressive disease, or until the cat's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. Although the primary purpose of this study was to determine a clinically useful dosage and to characterize the toxicoses associated with mitoxantrone administration, each cat was monitored for response to treatment. Forty-nine cats had been refractory to 1 or more treatment modalities prior to inclusion in this study. The most common signs of toxicosis after treatment with mitoxantrone were vomiting, anorexia, diarrhea, lethargy, sepsis secondary to myelosuppression, and seizures. Two cats died of complications that may have been attributed to mitoxantrone: 1 of cardiomyopathy and the other of pulmonary edema of an undetermined cause. Older cats were more likely to develop signs of toxicosis after the third or fourth mitoxantrone treatment than younger cats (P < or = 0.05). Cats with signs of toxicosis during the 21-day interval after administration of the first dose of mitoxantrone were significantly (P < or = 0.05) more likely to develop signs of toxicosis during the 21-day interval between the second and third doses of mitoxantrone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toxicoses and efficacy associated with administration of mitoxantrone to cats with malignant tumors. 832 Jan 52

Human status epilepticus (SE) is consistently associated with cognitive problems, and with widespread neuronal necrosis in hippocampus and other brain regions. In animal models, convulsive SE causes extensive neuronal necrosis. Nonconvulsive SE in adult animals also leads to widespread neuronal necrosis in vulnerable regions, although lesions develop more slowly than they would in the presence of convulsions or anoxia. In very young rats, nonconvulsive normoxic SE spares hippocampal pyramidal cells, but other types of neurons may not show the same resistance, and inhibition of brain growth, DNA and protein synthesis, and of myelin formation and of synaptogenesis may lead to altered brain development. Lesions induced by SE may be epileptogenic by leading to misdirected regeneration. In SE, glutamate, aspartate, and acetylcholine play major roles as excitatory neurotransmitters, and GABA is the dominant inhibitory neurotransmitter. GABA metabolism in substantia nigra (SN) plays a key role in seizure arrest. When seizures stop, a major increase in GABA synthesis is seen in SN postictally. GABA synthesis in SN may fail in SE. Extrasynaptic factors may also play an important role in seizure spread and in maintaining SE. Glial immaturity, increased electronic coupling, and SN immaturity facilitate SE development in the immature brain. Major increases in cerebral blood flow (CBF) protect the brain in early SE, but CBF falls in late SE as blood pressure falters. At the same time, large increases in cerebral metabolic rate for glucose and oxygen continue throughout SE. Adenosine triphosphate (ATP) depletion and lactate accumulation are associated with hypermetabolic neuronal necrosis. Excitotoxic mechanisms mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors open ionic channels permeable to calcium and play a major role in neuronal injury from SE. Hypoxia, systemic lactic acidosis, CO2 narcosis, hyperkalemia, hypoglycemia, shock, cardiac arrhythmias, pulmonary edema, acute renal tubular necrosis, high output failure, aspiration pneumonia, hyperpyrexia, blood leukocytosis and CSF pleocytosis are common and potentially serious complications of SE. Our improved understanding of the pathophysiology of brain damage in SE should lead to further improvement in treatment and outcome.
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PMID:Pathophysiological mechanisms of brain damage from status epilepticus. 838 2

The central autonomic network (CAN) is an integral component of an internal regulation system through which the brain controls visceromotor, neuroendocrine, pain, and behavioral responses essential for survival. It includes the insular cortex, amygdala, hypothalamus, periaqueductal gray matter, parabrachial complex, nucleus of the tractus solitarius, and ventrolateral medulla. Inputs to the CAN are multiple, including viscerosensory inputs relayed on the nucleus of the tractus solitarius and humoral inputs relayed through the circumventricular organs. The CAN controls preganglionic sympathetic and parasympathetic, neuroendocrine, respiratory, and sphincter motoneurons. The CAN is characterized by reciprocal interconnections, parallel organization, state-dependent activity, and neurochemical complexity. The insular cortex and amygdala mediate high-order autonomic control, and their involvement in seizures or stroke may produce severe cardiac arrhythmias and other autonomic manifestations. The paraventricular and other hypothalamic nuclei contain mixed neuronal populations that control specific subsets of preganglionic sympathetic and parasympathetic neurons. Hypothalamic autonomic disorders commonly produce hypothermia or hyperthermia. Hyperthermia and autonomic hyperactivity occur in patients with head trauma, hydrocephalus, neuroleptic malignant syndrome, and fatal familial insomnia. In the medulla, the nucleus of the tractus solitarius and ventrolateral medulla contain a network of respiratory, cardiovagal, and vasomotor neurons. Medullary autonomic disorders may cause orthostatic hypotension, paroxysmal hypertension, and sleep apnea. Neurologic catastrophes, such as subarachnoid hemorrhage, may produce cardiac arrhythmias, myocardial injury, hypertension, and pulmonary edema. Multiple system atrophy affects preganglionic autonomic, respiratory, and neuroendocrine outputs. The CAN may be critically involved in panic disorders, essential hypertension, obesity, and other medical conditions.
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PMID:The central autonomic network: functional organization, dysfunction, and perspective. 841 66

Significant hypothermia is an increasing clinical problem that requires a rapid response with properly trained personnel and techniques. Although the clinical presentation may be such that the victim appears dead, aggressive management may allow successful resuscitation in many instances. Initial management should include CPR if the victim is not breathing or is pulseless. Further core heat loss should be prevented by removing wet garments, insulating the victim, and ventilating with warm humidified air/oxygen to help stabilize core temperature. Core temperature and cardiac rhythm should be monitored in the prehospital setting, if possible, and CPR should be continued during transport. In-hospital management should consist of rapid core rewarming in the severely hypothermic victim with heated humidified oxygen, centrally administered warm IV fluids (43 C), and peritoneal dialysis until extracorporeal rewarming can be accomplished. Postresuscitation complications should be monitored; they include pneumonia, pulmonary edema, cardiac arrhythmias, myoglobinuria, disseminated intravascular thrombosis, and seizures. The decision to terminate resuscitative efforts must be individualized by the physician in charge.
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PMID:Hypothermia. 843 36

Generalized convulsive status epilepticus (GCSE) is accompanied by a marked increase in plasma catecholamines. This produces a number of changes in general systemic physiology including hypertension, tachycardia, cardiac arrhythmias, hyperglycemia, acidosis, and hyperpyrexia. If SE is stopped quickly, these changes are self-correcting and do not produce an increased risk of neuropathology. However, if seizures continue, many of the early physiologic changes reverse, and late status epilepticus is marked by hypotension, hypoglycemia, pulmonary edema and a continued acidosis and elevation of body temperature. Prevention of serious hypoglycemia, maintenance of adequate systemic blood pressure to provide adequate cerebral perfusion, and normalizing the body temperature will minimize or prevent neuropathologic sequelae to SE of extended duration.
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PMID:Systemic effects of generalized convulsive status epilepticus. 846 91

Aspirin overdose may result in acid-base disturbances, electrolyte abnormalities, pulmonary edema, chemical hepatitis, seizures, and mental status alteration, but myocardial depression has not been reported following aspirin overdose in children. In addition to these more typical features, the 13-month-old boy reported here developed clinical, radiographic, and echocardiographic evidence of myocardial impairment with pulmonary edema and moderately severe global left ventricular dysfunction (estimated shortening fraction of 23%). Complete resolution of the myocardial dysfunction was demonstrated on follow-up echocardiography as the child recovered from the aspirin intoxication. This case suggests that myocardial dysfunction can occur as a result of toxic aspirin ingestion, and that it may contribute to salicylate-induced pulmonary edema.
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PMID:Transient myocardial dysfunction in a child with salicylate toxicity. 853 Jul 86

1. The possible contribution of endogenous endothelin (ET) to the pathogenesis of seizure-associated pulmonary oedema was examined in mechanically ventilated rats after intravenous bolus injection of the gamma-aminobutyric acid (GABA) antagonist, bicuculline (1.2 mg kg-1). 2. Recurrent seizure activity elicited by bicuculline injection led to rapidly developing pulmonary oedema. Within 4 min after bicuculline application (1.2 mg kg-1), arterial O2 partial pressure (PaO2) significantly dropped from 17.49 +/- 1.20 kPa to 7.51 +/- 2.21 kPa (P < 0.01) and arterial CO2 partial pressure (PaCO2) significantly increased from 4.64 +/- 0.56 kPa to 8.15 +/- 0.99 kPa (P < 0.01). Gradually a progressive acidosis developed. Moreover, mean arterial blood pressure (MABP) and end-inspiratory airway pressure (Paw) rapidly increased. 3. Concomitantly there was a time-dependent increase of big ET-1 and ET-1 levels in bronchoalveolar lavage (BAL) as determined by combined reverse phase high performance liquid chromatography (h.p.l.c.) and radioimmunoassay. BAL levels of both peptides increased up to 8 min after bicuculline injection and slowly decreased subsequently. In contrast, BAL from animals injected with vehicle did not contain detectable amounts of ET. 4. Pretreatment with the endothelin-converting enzyme inhibitor, phosphoramidon (5.4 mg kg-1, i.v.) for 5 min significantly (P < 0.001) reduced peak ET-1 levels in BAL fluid by 65.4 +/- 9.9% at 8 min after bicuculline injection. Simultaneously it afforded protection from hypoxia. PaCO2 did not increase and PaO2 decreased only slightly from 14.63 +/- 1.00 kPa to 12.97 +/- 0.61 kPa (P > 0.05) after phosphoramidon pretreatment. In contrast, vehicle-treated animals that received bicuculline showed both significant hypercapnia as well as profound hypoxia. Phosphoramidon significantly diminished the maximum increase in Paw by 76.7 +/- 12.4% (P <0.005), but only slightly affected the MABP. Phosphoramidon pretreatment had no effect on the acidosis.5. Pretreatment with the ETA receptor antagonist, BQ-123 (1 mg kg-1, i.v.), for 5 min did not affect the levels of ET-1 in the BAL fluid at 8 min after bicuculline injection but did ameliorate the development of hypoxia. No hypercapnia developed and Pa02 decreased only moderately from 16.65 +/-0.25 kPa to 14.19 +/-2.15 kPa (P>0.05) in BQ-123-treated animals. In contrast, vehicle-treated animals that received bicuculline exhibited significant hypercapnia as well as profound hypoxia. BQ-123 significantly reduced the increase in Paw by 51.3 +/- 12.8% (P < 0.01). It affected MABP only slightly and had no effect on the acidosis.6. These results suggest that ET peptides play a significant role in this model of neurogenic pulmonary oedema and may act as mediators of respiratory distress. The deleterious effects of endogenous ET in this model are primarily mediated via the ETA receptor, for they were inhibited by the ETA receptor antagonist, BQ-123. ETA receptor antagonists may therefore be of potential therapeutic value in respiratory distress.
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PMID:A role for endothelin in bicuculline-induced neurogenic pulmonary oedema in rats. 854 73

The pathogenesis of neurogenic pulmonary edema has been debated for many years. Whether cardiogenic mechanisms and increased pulmonary vascular pressures are primary or even necessary for the production of pulmonary edema has been argued. We used postictal pulmonary edema to study this problem in a sheep model of neurogenic pulmonary edema with bicucullin-induced status epilepticus. Seizure-induced increases in pulmonary vascular pressures were averted with a reservoir system to maintain left atrial pressure (LAP) and pulmonary artery pressure (PAP) at preseizure levels. No increase in lung lymph flow occurred during seizures, in contrast to the doubling of lung lymph flow that occurred during seizures when ictal pulmonary vascular hypertension was not blocked. These data support a primary role of pulmonary vascular pressure increases in the production of neurogenic pulmonary edema.
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PMID:Postictal pulmonary edema requires pulmonary vascular pressure increases. 861 70

The use of dobutamine stress echocardiography for the evaluation of coronary artery disease is rapidly expanding. Despite its widespread use, the feasibility and safety of dobutamine stress echocardiography has not been sufficiently documented. Between November 1992 and June 1995, we performed 1000 dobutamine stress echocardiographies. There were 744 men and 256 women with a mean age of 59 +/- 11 years. Anti anginal medication was not routinely withdrawn before the test. The mean maximal dobutamine dose was 41,4 +/- 10 mu g/kg center dot min(-1). Atropine was given additionally in 440 patients, with a mean dose of 0.5 mg. In patients receiving beta-blockers additional atropine was more often necessary as compared to those not receiving beta-blockers (278/457 = 61% versus 162/543 = 30 %, p < 0.0001). Reasons for discontinuing dobutamine infusion were achievement of target heart rate (64 % of cases) and maximal dose (12 % of cases). In 791 (79,1 %) patients no side-effects of dobutamine stress echocardiography were noticed. Termination of the study because of adverse side-effects occurred in 6.6 %. A total of 103 (10,3 %) noncardiac side-effects were observed: dizziness or nausea 6.4 %, headache 1.7 %. In one patient a focal cerebral seizure occurred. 156 cardiac side-effects occurred: blood pressure decrease of more than 20 mm Hg in 25 patients, extreme palpitations in 16 patients and pulmonary edema in one case. Most common cardiac side-effects consisted of arrhythmias (11.4 %): 9.1 % ventricular and 2.3 % supraventricular arrhythmias. Most ventricular arrhythmias were less severe (uniform and multiform premature ventricular beats, ventricular bigeminy or couplets in 71 patients). Nonsustained ventricular tachycardia, with a maximum duration of 20 s, occurred in 18 patients. In one patient sustained ventricular tachycardia developed and progressed towards ventricular fibrillation. This patient could be successfully defibrillated. Supraventricular arrhythmias presented as new atrial fibrillation in 10 patients, supraventricular tachycardia in three patients, junctional rhythm with a short decline in heart rate in nine patients and a second-degree AV block in another case. Dobutamine stress echocardiography has proven to be a safe and feasible method in the diagnosis of coronary heart disease. Minor side-effects are common and sometimes unpleasant for the patient, but do not often require termination of the study. Severe side-effects are seldom (< 1 %), but nevertheless, adequate medical and technical (defibrillator) support should be rapidly available.
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PMID:[Feasibility and safety of dobutamine stress echocardiography: experiences with 1,000 studies]. 871 45

The murine monoclonal antibody muromonab CD3 (OKT3) is directed against the CD3 antigen on peripheral human T cells and effectively blocks all T cell function. Prophylaxis with muromonab CD3 (5mg intravenously once daily for 10 to 14 days) as induction therapy together with corticosteroids, azathioprine and delayed cyclosporin (sequential therapy) optimises early graft function by delaying the potentially nephrotoxic and hepatotoxic effects of cyclosporin until graft function is established. Although clinical data are limited (by inconsistencies in trial design and trial size), prophylactic muromonab CD3-based sequential therapy is significantly more effective than standard triple therapy in the prophylaxis of allograft rejection in renal and hepatic, but not cardiac, transplant recipients. Benefits are particularly notable in patients with delayed graft function. No significant between-treatment differences in patient survival have been observed. The overall efficacy of muromonab CD3- and polyclonal-based prophylactic regimens appears to be similar, although results vary between investigators and confirmation is needed. An anti-interleukin-2 monoclonal antibody-based prophylactic regimen improved graft and patient survival compared with muromonab CD3-based prophylaxis in hepatic transplant recipients. Antimuromonab CD3 antibodies may develop; however, muromonab CD3 may be successfully reused in patients with low titres. Preliminary pharmacoeconomic data suggest that mean drug costs are greater with quadruple immunosuppressive regimens containing muromonab CD3, antithymocyte globulin (ATG) or antilymphocyte globulin (ALG) than with triple therapy. Drug costs with prophylactic muromonab CD3-based regimens were similar or greater than those with polyclonal-based protocols. The first doses of muromonab CD3 are associated with the 'cytokine-release syndrome'. More severe first-dose events include aseptic meningitis, intragraft thromboses, seizures and potentially fatal pulmonary oedema. The incidence and/or severity of cytomegalovirus infection with prophylactic muromonab CD3 based immunosuppression is similar to or greater than that with triple therapy and ATG- or ALG-based regimens. However, the risk of infection and also the observed increase in lymphoproliferative disorders appears to be related to the degree of immunosuppression rather than to the drug itself Thus, sequential muromonab CD3-based therapy is more effective than standard triple therapy (in renal and hepatic transplant recipients) and appears to be similar to that of polyclonal-based regimens in the prophylaxis of transplant rejection. Although the routine use of prophylactic muromonab CD3 in low-risk patients with primary graft function does not appear to be justified, prophylactic muromonab CD3-based therapy has a role in patients at high risk of rejection.
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PMID:Muromonab CD3: a reappraisal of its pharmacology and use as prophylaxis of solid organ transplant rejection. 886 51


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