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Dr. House je o holi chodící doktor, který nesnáší pláště. Prodělal svalovou mrtvici, po které prožívá nesnesitelné bolesti. Velice často užívá vicodin, který má jeho bolavou nohu zklidnit. Tento lék je ale velice návykový a House si na něj vytvořil závislost. Používá často nevybíravé a ne příliš standardní metody a často se v diagnóze mýlí. Jeho omyly ale nemají fatální důsledek a většinou vedou k pozdějšímu úplnému vyléčení.
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