ABSTRACT
A 66-year-old female patient with the initial diagnosis of acute myeloid leukemia is reported. Paraneoplastic syndrome manifested as hypernatremia due to central diabetes insipidus (CDI), which could be controlled with the administration of desmopressin. After initiation of the induction therapy, the required desmopressin administration could be reduced and terminated. In the further course, the early increasing polyuria and hypernatremia indicated the primary refractory acute myeloid leukemia.
Subject(s)
Diabetes Insipidus, Neurogenic , Hypernatremia , Leukemia, Myeloid, Acute , Neoplasms, Second Primary , Humans , Female , Aged , Polyuria/diagnosis , Hypernatremia/diagnosis , Deamino Arginine Vasopressin/therapeutic use , Diabetes Insipidus, Neurogenic/diagnosis , Leukemia, Myeloid, Acute/complications , Neoplasms, Second Primary/complicationsABSTRACT
We describe for the first time the misinterpretation of a wearable cardioverter defibrillator in the arrhythmia recognition algorithm with subsequent fatal outcome of a multi-morbid patient with an ischemic cardiomyopathy and a highly reduced left ventricular pump function (30 %). The patient's death was preceded by a life-threatening shockable rhythm which was repeatedly documented, but ultimately not correctly recognized by the system and therefore not treated.
Subject(s)
Algorithms , Death, Sudden, Cardiac/etiology , Defibrillators/adverse effects , Diagnosis, Computer-Assisted/adverse effects , Electric Injuries/etiology , Electric Injuries/diagnosis , Equipment Design , Equipment Failure , Fatal Outcome , Humans , Male , Medical Errors/adverse effects , Medical Errors/prevention & control , Middle Aged , Therapy, Computer-Assisted/methods , Treatment FailureABSTRACT
As deregulation of RAS signaling is important in the pathogenesis of myeloid leukemias, molecular targeting of RAS signaling may be a promising therapeutic strategy. Farnesyl transferase inhibitors (FTIs) are the most promising class of these new cancer therapeutics. Several FTIs have entered phase II clinical trials in acute myeloid leukemia (AML). Since geranylgeranylation of K-RAS and N-RAS in the presence of FTIs may represent an important mechanism of FTI resistance, 6 geranylgeranyl transferase-I inhibitors (GGTIs) were screened alone and in combination with FTI for growth inhibition of myeloid leukemia cells. Significant growth inhibition (>70%) in myeloid cell lines was observed for GGTI-286 (9/19), GGTI-298 (14/19), GGTI-2147 (16/19) and FTI L-744,832 (17/17). GGTI treatment of NB-4 cells resulted in an accumulation of cells in G(0)/G(1), whereas FTI L-744,832 primarily caused an increase in G(2)/M. FTI and GGTIs both induced apoptosis. In all cases, FTI/GGTI cotreatment led to synergistic cytotoxic effects in both myeloid cell lines (5/5) and primary AML cells (6/6). This synergy coincided with increased apoptosis. FTI/GGTI cotreatment caused an accumulation of unprocessed N-RAS and inactive N-RAS-RAF complexes. Our results suggest that alternative geranylgeranylation of N-RAS may represent an important mechanism of resistance to FTI monotherapy in myeloid leukemia cells.
