Monosomy 15 in chronic myelomonocytic leukemia. description of a case and review of the literature

We report a 89-year-old female diagnosed with chronic myelomonocytic leukemia (CMMoL) presenting with a monosomy 15. To our knowledge, this is the second reported case of CMMoL with monosomy 15. On the other hand, monosomy 15 in complex karyotypes is a frequent chromosome aberration in myelodysplastic syndromes, particularly in refractory anemia with excess of blasts.     

Impact of Cold Ischemia Time on the Function of Liver Grafts Preserved With Custodiol

ObjectiveThis study aimed to evaluate how cold ischemia time (CIT) interferes with liver graft function in the first 7 days after surgery for Custodiol (HTK) preserved organs.MethodsThis retrospective observational study analyzed the medical records of 38 transplantation patients at Hospital Leforte Liberdade, São Paulo, in 2018. The study population was divided into 2 groups (group A, CIT < 8 hours; group B, CIT > 8 hours). Postoperative parameters—such as international normalized ratio, total bilirubin, aspartate aminotransferase/alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GGT), lactate dehydrogenase, lactate, creatinine, red blood cell transfusion, need for hemodialysis, use of vasoactive drugs, endotracheal intubation time, length of stay in the intensive care unit (ICU), and length of hospital stay—were compared.ResultsGroup A (CIT < 8 hours) presented less need for red blood cell transfusions (odds ratio 0.29; confidence interval 0.06-0.98; P = .04), had a shorter hospital stay (P = .024), and had lower levels of total bilirubin (P = .05) and GGT (P = .05) in the first 7 postoperative days. The other variables showed no statistically significant difference.ConclusionIn livers preserved with Custodiol, CIT > 8 hours generated higher levels of total bilirubin and GGT in the postoperative period, in addition to higher hospital costs; greater need for red blood cell transfusions; and longer hospitalization, including longer stays in the ICU.     

Clonal proliferation of cyclin D1-positive mantle lymphocytes in an asymptomatic patient: an early-stage event in the development or an indolent form of a mantle cell lymphoma?

Mantle cell lymphoma (MCL) is a B-cell neoplasm with a relatively aggressive clinical course. There is a very small subgroup of patients who present with atypical lymphocytes in peripheral blood, with or without lymphocytosis, lymphadenopathy, or splenomegaly, and with an indolent clinical course. They frequently show mutated IgV(H) genes and CD5 negativity. We report an asymptomatic elderly patient who presented with a single submandibular lymphadenopathy. The biopsy showed immunophenotype and t(11;14)(q13;q32) consistent with MCL. The abnormal lymphoid population was also detected in peripheral blood and bone marrow. The patient has remained asymptomatic for 5 years without receiving any therapy. It is uncertain whether these cases represent an early-stage event in the development or an indolent form of MCL. The existence of such asymptomatic patients with an indolent clinical course should induce a strict clinical judgment in terms of therapeutic decisions.     

Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration.

The involvement of adenosine A(1) and A(2A) receptors in the motor effects of caffeine is still a matter of debate. In the present study, counteraction of the motor-depressant effects of the selective A(1) receptor agonist CPA and the A(2A) receptor agonist CGS 21680 by caffeine, the selective A(1) receptor antagonist CPT, and the A(2A) receptor antagonist MSX-3 was compared. CPT and MSX-3 produced motor activation at the same doses that selectively counteracted motor depression induced by CPA and CGS 21680, respectively. Caffeine also counteracted motor depression induced by CPA and CGS 21680 at doses that produced motor activation. However, caffeine was less effective than CPT at counteracting CPA and even less effective than MSX-3 at counteracting CGS 21680. On the other hand, when administered alone in habituated animals, caffeine produced stronger motor activation than CPT or MSX-3. An additive effect on motor activation was obtained when CPT and MSX-3 were coadministered. Altogether, these results suggest that the motor-activating effects of acutely administered caffeine in rats involve the central blockade of both A(1) and A(2A) receptors. Chronic exposure to caffeine in the drinking water (1.0 mg/ml) resulted in tolerance to the motor effects of an acute administration of caffeine, lack of tolerance to amphetamine, apparent tolerance to MSX-3 (shift to the left of its 'bell-shaped' dose-response curve), and true cross-tolerance to CPT. The present results suggest that development of tolerance to the effects of A(1) receptor blockade might be mostly responsible for the tolerance to the motor-activating effects of caffeine and that the residual motor-activating effects of caffeine in tolerant individuals might be mostly because of A(2A) receptor blockade.     

Functional analysis of gene expression in risperidone treated cells provide new insights in molecular mechanism and new candidate genes for pharmacogenetic studies

Risperidone is a potent antagonist of both dopamine and serotonin receptors. However, little is known about the underlying molecular mechanism by which risperidone acts. Although a number of genetic variants have been observed to correlate with treatment response there are no definitive predictors of response. We performed a genome-wide gene expression analysis (Human Genome U219 Array Plate) of a human neuroblastoma cell line (SK-N-SH) exposed to risperidone to identify molecular mechanisms involved in the cellular response to risperidone and thus identify candidate genes for pharmacogenetic studies. Our results revealed that cellular risperidone treatment is associated with a range of gene expression changes, which are time (6–48 h) and dose related (0.1–10 μM). We found that functional clusters of these changes correspond to Gene Ontology categories related to neural cell development functions, and synaptic structure and functions. We also identified Canonical Pathways related to these functional categories: neurogenesis and axon guidance; synaptic vesicle; and neurotransmitter signaling (dopamine, serotonin and glutamate). Finally, we identified candidate genes for pharmacogenetic studies related to the main risperidone secondary effects: motor disorders, cardiovascular disorders and metabolic disorders. Our results suggest that risperidone treatment affects the neurogenesis and neurotransmission of neuroblastoma cells, which is in agreement with the “initiation and adaptation” model to explain the mechanism of action of psychotropic drugs.