RESUMEN
Clozapine is the drug of choice for treatment-resistant schizophrenia. Prompted by a patient who developed reversible clozapine-induced myocarditis after long-term treatment with clozapine for several years for chronic-resistant schizophrenia, we undertook a review of the relevant literature. Concerning the myocarditis, the patient recovered rapidly by withdrawal of clozapine and with supportive management. Psychiatric stabilisation of the patient was at least possible with a combination of quetiapine (600 mg) and amisulpride (800 mg). Well-designed studies with the aim to specifically investigate treatment options after clozapine are limited and clinical possibilities are discussed in this paper. Olanzapine and combinations using non-clozapine atypical neuroleptics have partly shown improvement, whereas evidence for successful augmentation with mood stabilisers, anticonvulsants or electroconvulsive therapy in treatment-resistant schizophrenia is limited.
Asunto(s)
Antipsicóticos/efectos adversos , Clozapina/efectos adversos , Miocarditis/inducido químicamente , Amisulprida , Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Dibenzotiazepinas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Fumarato de Quetiapina , Esquizofrenia/tratamiento farmacológico , Sulpirida/análogos & derivados , Sulpirida/uso terapéuticoRESUMEN
Fibroblast cultures from two Werner syndrome patients were analyzed by spectral karyotyping. There were multiple, pseudodiploid clones in both cultures, mostly marked by random balanced reciprocal translocations. One of the cultures contained a clone with three-way exchanges involving chromosomes 2, 3, and 16. Duplication-deficiencies were exceptional, as were completely normal metaphases. The most frequent breakpoint occurred at 16q22 which corresponds to FRA16B, possibly reflecting difficulties of WS cells in replicating AT-rich repetitive DNA structures. Both cultures ceased proliferation after eight in vitro passages, but a single clone with exceptional growth potential emerged in one of the senescing cultures. Due to its identical translocations, the derivation of this near tetraploid clone (with tetrasomy for all autosomes except chromosomes 4 and 6) could be traced to the most prevalent pseudodiploid clone of the parental mass culture. Our study confirms the existence of variegated translocation mosaicism as the cytogenetic hallmark of WS fibroblast cultures and suggests that tetraploidization in combination with certain chromosome rearrangements and selective chromosome dosage may overcome the severely limited in vitro lifespan of WS fibroblasts.