RESUMO
The high resolution of modern DNA arrays has the implification of unintended coincidental detection of gene deletions predisposing to late-onset neurological and oncological disorders. Here, we report the case of an 18-year-old girl with mild intellectual disability, facial dysmorphisms, and a microdeletion of approximately 6.3 Mb on 22q12.1q12.3 including NF2, the gene for neurofibromatosis type 2, and CHEK2, a modifier gene for breast cancer. Subsequent magnetic resonance imaging of the brain showed she had already developed bilateral vestibular schwannomas. The challenge of DNA arrays and the consequences for genetic counselling and informed consent will be discussed in the light of this unique case with a microdeletion including both a high risk and a moderate risk cancer predisposition gene.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Achados Incidentais , Neuroma Acústico/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Adolescente , Quinase do Ponto de Checagem 2 , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Feminino , Humanos , Imageamento por Ressonância Magnética , Neurofibromina 2/genética , Neuroma Acústico/diagnóstico , Proteínas Serina-Treonina Quinases/genética , Fatores de RiscoAssuntos
Infecção Hospitalar/etiologia , Doenças em Gêmeos , Infecções por Bactérias Gram-Negativas/etiologia , Hidrocefalia/cirurgia , Recém-Nascido Prematuro , Meningites Bacterianas/etiologia , Ralstonia pickettii , Derivação Ventriculoperitoneal/efeitos adversos , Infecção Hospitalar/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Hidrocefalia/microbiologia , Recém-Nascido , Meningites Bacterianas/tratamento farmacológicoRESUMO
We report on two patients with morphine-related seizures associated with either intrathecal or intracerebroventricular administration. Both patients had a history of malignant tumor and both experienced the seizures following bolus application of morphine, while even higher dosages were well tolerated when continuously infused. Seizures occurred without signs of intoxication. Initiation of intrathecal morphine therapy and bolus application should be performed carefully and only when constant monitoring is provided for at least 12 h. Animal data and possible mechanisms for morphine-related seizures are discussed.
Assuntos
Analgésicos Opioides/administração & dosagem , Epilepsia/induzido quimicamente , Morfina/administração & dosagem , Adulto , Idoso , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Carcinoma de Células Escamosas/fisiopatologia , Neoplasias de Cabeça e Pescoço/fisiopatologia , Humanos , Injeções Intraventriculares , Injeções Espinhais , Masculino , Morfina/efeitos adversos , Morfina/uso terapêutico , Dor Intratável/tratamento farmacológico , Neoplasias da Bexiga Urinária/fisiopatologiaRESUMO
KT-362 is an antiarrhythmic and antihypertensive agent with vasodilating activity. Since it carries a homoveratryl group in the side chain, an obvious relation exists to the verapamil-type calcium antagonists. Replacement of the fused aromatic moiety in KT-362 with thiophene provided 8-[N-[2-(3,4-dimethoxyphenyl) ethyl]-beta-alanyl]-5,6,7,8-tetrahydrothieno[3,2-b][1,4] thiazepine (1). Compound 1 shows a negative chronotropic activity in spontaneously beating right atria (IC50 = 23 microM, n = 7), and a negative inotropic effect in papillary muscles (IC50 = 2.7 microM, n = 7) and left atria (IC50 = 4 microM, n = 6) of the guinea-pig heart. The decrease of contractility in papillary muscles could be antagonized by increasing the extracellular calcium concentration. Compound 1 was found to affect high (IC50: 70 +/- 5 microM) and low (IC50: 129 +/- 34 microM) voltage-activated calcium channel currents as well as voltage-activated sodium channel currents (IC50: 80 +/- 13 microM) in chick dorsal root ganglion neurons. In addition nicotine-induced currents were potently inhibited (IC50: 6 +/- 0.7 microM) in bovine chromaffin cells.
