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)

Busulfan (BU) is a widely used myeloablative and antineoplastic agent in clinical bone marrow transplantation (BMT). The lower incidence of BU-associated toxicities and lower therapeutic effectiveness in young children given BU doses based on body weight (ie, 16 mg/kg) is associated with altered pharmacokinetics of BU; the area under the curve (AUC) of BU concentration versus time is significantly less in these patients than those observed in older children and adults. To optimize BU dosage in young BMT recipients, we developed a dosage regimen based on body surface area (BSA) and determined BU pharmacokinetics and BU-associated toxicities. Seven children (median age, 3.9 years, range, 1.1 to 5.7) undergoing allogeneic or autologous BMT for leukemia received 40 mg/m2/dose BU every 6 hours for 16 doses; BU concentrations were measured in the plasma, and AUCs were determined for each patient after the first and 13th doses. Expressed as a function of body weight, the median BU dosage was 26.4 mg/kg (range, 24.3 to 28.2), a 60% increase over the BU dosage based on body weight. Four patients developed mucositis, and one of them also developed nonfatal hepatic veno-occlusive disease (VOD). No patients receiving 40 mg/m2 BU developed neurotoxicity (eg, seizures) or interstitial pneumonitis. Prompt and sustained engraftment was observed in the allogeneic BMT recipients, and late graft failure was not seen. The mean BU AUCs were 1,105 mumol/L.min (range, 790 to 2,080) after the first dose and 1,022 mumol/L.min (range, 632 to 1,860) after the 13th dose of BU, comparable to the AUCs in adults given 16 mg/kg of BU. These studies suggest that, in young children, BSA-based dosing of BU (40 mg/m2) provides drug exposures (AUCs) closer to adult values with acceptable toxicities and may improve therapeutic effects.
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PMID:Optimization of busulfan dosage in children undergoing bone marrow transplantation: a pharmacokinetic study of dose escalation. 142 15

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

This report describes vaccine-induced canine distemper virus (CDV) infection in four European mink (Mustela lutreola) induced by the administration of a multivalent, avian-origin vaccine. Clinical signs consisting of seizures, ataxia, facial twitching, oculonasal discharge, hyperkeratosis of footpads, and anorexia developed 16-20 days postvaccination. Conjunctival smears from one animal were positive for CDV antigen by direct fluorescent antibody testing, confirming the clinical diagnosis. The four mink died 16-26 days postvaccination. Gross and microscopic lesions that were diagnostic for CDV infection included interstitial pneumonia, lymphoid depletion, nonsuppurative encephalitis, and dermatitis. Vaccine-strain virus was isolated from tissues of three animals. Cases of vaccine-induced distemper in mustelids using avian-origin vaccine have seldom been reported.
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PMID:Vaccine-induced canine distemper in European mink, Mustela lutreola. 936 45

We analyzed plasma pharmacokinetics of busulfan in 64 children and young adults (age 2.8-26; median 11 years) with homozygous beta-thalassemia transplanted with bone marrow from HLA-identical sibling donors. A uniform conditioning regimen was employed, using busulfan 14 or 16 mg/kg in 12 divided doses, and cyclophosphamide 120 or 200 mg/kg. Three sets of parameters were examined in this homogenous patient population: (1) factors that affect the plasma kinetics of busulfan, such as age and pre-transplant liver status defined by liver function tests, ferritin levels and liver biopsy; (2) busulfan-related toxicity: occurrence of veno-occlusive disease, seizures and idiopathic interstitial pneumonitis; and (3) the relationship between busulfan exposure and transplant outcome: engraftment delay or rejection, aplasia, occurrence of mixed chimeras and mortality. Kinetic analysis of first and 10th dose (using area under the curve (AUC), maximum and minimum concentration) as comparable, showing no sign of accumulation or decline in busulfan plasma levels over time. Age and liver status did not influence busulfan metabolism. No relationship was found between busulfan exposure and toxicities or transplant outcome. We conclude that busulfan monitoring is not predictive in children and young adults with homozygous beta-thalassemia receiving busulfan and high-dose cyclophosphamide along with histocompatable sibling donor marrow.
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PMID:Relationship of plasma pharmacokinetics of high-dose oral busulfan to the outcome of allogeneic bone marrow transplantation in children with thalassemia. 942 69

Lymphomatoid granulomatosis, a rare condition in children, affects the lungs primarily but may have significant extrapulmonary manifestations, especially in the central nervous system. We report a case of lymphomatoid granulomatosis with onset after the completion of chemotherapy for childhood acute lymphoblastic leukemia. Two months after treatment ended, the 7-year-old girl developed splenomegaly, cervical adenopathy, and bilateral interstitial pulmonary infiltrates. She improved on cefotaxime but experienced a seizure 1 month later. A computed tomography scan of the head was normal, but her pulmonary infiltrates had become nodular. A computed tomography-guided biopsy of 1 of the nodules revealed cellular interstitial pneumonitis. One month later, she had persistent pulmonary infiltrates, marked splenomegaly, and new seizures. Magnetic resonance imaging of the head revealed cerebral nodules. Itraconazole was begun, and the pulmonary infiltrates resolved. Five months after her initial symptoms, she developed tonic pupil and a decreased level of consciousness. Dexamethasone was initiated. Needle biopsies of the brain were carried out, yielding the diagnosis of severe chronic inflammatory changes focally consistent with granuloma. The child redeveloped splenomegaly and fever, and then suffered an acute decompensation with hypoxemia, tachypnea, splenomegaly, and cardiac gallop. Open-lung biopsy revealed lymphomatoid granulomatosis. Lymphoma-directed therapy was initiated, and the patient had complete resolution of pulmonary and cerebral nodules 5 months later. No intrathecal chemotherapy was administered, and radiation therapy was not necessary. Neuropsychological testing obtained after completion of therapy revealed an improvement in attention, coordination, and fine motor speed over time. She is now in good health and attending school.
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PMID:Lymphomatoid granulomatosis after childhood acute lymphoblastic leukemia: report of effective therapy. 1133 32

Cocaine use has increased considerably during the last twenty years and several related complications can be identified. Clinical features of cocaine intoxication are variable, but predominantly involve cardiovascular events. Chest pain is the most main complaint; myocardial ischemia must be ruled out. Other cardiovascular manifestations are left ventricular dysfunction, arrhythmia, endocarditis and aortic dissection. Non-cardiac complications include neurological (seizures, stroke, cerebral hemorrhage), respiratory (asthma, interstitial pneumonitis, pulmonary edema), renal (acute renal failure, rhabdomyolysis) and obstetrical disorders. Detection of cocaine in the urine provides the diagnosis. Symptomatic treatment is generally given, combining conventional treatment of the complication and broad use of benzodiazepines.
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PMID:[Acute complications in cocaine users]. 1221 80

Addiction is a chronic relapsing disorder characterized by repetitive and compulsive drug-seeking behavior and drug abuse despite negative health or social consequences. Cocaine addiction is a significant worldwide public health problem, which has somatic, psychological, psychiatric, socio-economic and judicial complications. Some of the most frequent complications are cardiovascular effects (acute coronary syndrome, cardiac arrhythmias, increased blood pressure); respiratory effects (fibrosis, interstitial pneumonitis, pulmonary hypertension, alveolar haemorrhage, asthma exacerbation; emphysema), neurological effects (strokes, aneurysms, seizures, headaches); risk for contracting HIV/AIDS, hepatitis B and C, sexual transmitted disease and otolaryngologic effects. Other complications are not discussed here. The vast majority of studies indicate that there are cognitive deficits induced by cocaine addiction. Attention, visual and working memories, executive functioning are affected in cocaine users. Psychiatric complications found in clinical practice are major depressive disorders, cocaine-induced paranoia, cocaine-induced compulsive foraging and panic attacks.
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PMID:[Complications of cocaine addiction]. 1964 39

Fifteen 8-month-old fennec foxes imported from Sudan showed fever, mucopurulent ocular discharge, diarrhea, severe emaciation, seizures, and generalized ataxia, and died. Three of the 15 animals were presented for diagnostic investigation. Severe dehydration, brain congestion, and gastric ulcers were observed in all animals. In one animal, the lungs had failed to collapse and were multifocally dark red in appearance. Histopathologically, there were lymphohistiocytic meningoencephalitis with malacia, mild interstitial pneumonia, lymphoid depletion of lymphoid tissues and organs, and intestinal villous atrophy with intralesional coccidia. There were many intracytoplasmic and/or intranuclear inclusion bodies in the epithelial cells of the medullary velum, lungs, liver, kidneys, trachea, pancreas, stomach, gall bladder, urinary bladder, and ureters, and in macrophages of malacia foci and lymphocytes and macrophages of lymphoid organs. Additionally, intestinal coccidia were confirmed to be Isospora species by a fecal test. To our knowledge, this is the first report of canine distemper with intestinal coccidiosis in fennec fox.
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PMID:Canine distemper virus infection in fennec fox (Vulpes zerda). 2029 71

To gain insights into the pathogenicity of Imjin virus (MJNV), a newfound hantavirus isolated from the Ussuri white-toothed shrew (Crocidura lasiura), groups of Syrian hamsters (Mesocricetus auratus) of varying ages (<1, 5, 10, 14, 21, 35 and 56 days) were inoculated by the intraperitoneal route with 1000 pfu of MJNV strains 04-55 and 05-11. MJNV-infected Syrian hamsters, aged 21 days or less, exhibited reduced activity, weight loss, respiratory distress, hind-limb paralysis and seizures. Death ensued 1 to 6 days after onset of clinical disease. MJNV RNA was detected in brain and other major organs by RT-PCR and real time-PCR. Histopathological examination showed alveolar hemorrhage, interstitial pneumonia and severe pulmonary congestion; focal hepatic necrosis and portal inflammation; and acute meningoencephalitis. By immunohistochemistry, MJNV antigen was detected in pulmonary microvascular endothelial cells and glial cells. Older hamsters (35 and 56 days of age) developed subclinical infection without histopathological changes. Future studies are warranted to determine the pathophysiologic bases for the differential age susceptibility of Syrian hamsters to lethal MJNV disease.
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PMID:Lethal disease in infant and juvenile Syrian hamsters experimentally infected with Imjin virus, a newfound crocidurine shrew-borne hantavirus. 2637 Oct 66

Pharmacological and cellular treatment of cancer is changing dramatically with benefits for patient outcome and comfort, but also with new toxicity profiles. The majority of adverse events can be classified as mild or moderate, but severe and life-threatening complications requiring ICU admission also occur. This review will focus on pathophysiology, symptoms, and management of these events based on the available literature.While standard antineoplastic therapy is associated with immunosuppression and infections, some of the recent approaches induce overwhelming inflammation and autoimmunity. Cytokine-release syndrome (CRS) describes a complex of symptoms including fever, hypotension, and skin reactions as well as lab abnormalities. CRS may occur after the infusion of monoclonal or bispecific antibodies (MABs, BABs) targeting immune effectors and tumor cells and is a major concern in recipients of chimeric antigen receptor (CAR) modified T lymphocytes as well. BAB and CAR T-cell treatment may also be compromised by central nervous system (CNS) toxicities such as encephalopathy, cerebellar alteration, disturbed consciousness, or seizures. While CRS is known to be induced by exceedingly high levels of inflammatory cytokines, the pathophysiology of CNS events is still unclear. Treatment with antibodies against inhibiting immune checkpoints can lead to immune-related adverse events (IRAEs); colitis, diarrhea, and endocrine disorders are often the cause for ICU admissions.Respiratory distress is the main reason for ICU treatment in cancer patients and is attributable to infectious agents in most cases. In addition, some of the new drugs are reported to cause non-infectious lung complications. While drug-induced interstitial pneumonitis was observed in a substantial number of patients treated with phosphoinositol-3-kinase inhibitors, IRAEs may also affect the lungs.Inhibitors of angiogenetic pathways have increased the antineoplastic portfolio. However, vessel formation is also essential for regeneration and tissue repair. Therefore, severe vascular side effects, including thromboembolic events, gastrointestinal bleeding or perforation, hypertension, and congestive heart failure, compromise antitumor efficacy.The limited knowledge of the pathophysiology and management of life-threatening complications relating to new cancer drugs presents a need to provide ICU staff, oncologists, and organ specialists with evidence-based algorithms.
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PMID:New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management. 2840 43


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