Effect of all-trans retinoic acid on procoagulant and fibrinolytic activities of cultured blast cells from patients with acute promyelocytic leukemia

The mechanisms underlying acute promyelocytic leukemia (APL) coagulopathy and its reversal by administration of all-trans retinoic acid (ATRA) have been investigated. Bone marrow promyelocytic blasts from nine patients with APL were cultured with or without ATRA 1 mumol/L. Cultured blasts (days 0, 3, 6, and 9) were washed, resuspended in phosphate buffer, lysed by freezing and thawing, and then assayed for procoagulant activity (PCA), elastase activity, tissue factor (TF) antigen, tissue-type plasminogen activator (t-PA) antigen and urokinase- type plasminogen activator (u-PA) antigen. PCA was determined by a recalcification assay. Elastase was measured by an amidolytic assay (S- 2484). TF, t-PA, and u-PA antigens were measured by an enzyme-linked immunosorbent assay (ELISA). Malignant promyelocytes isolated from the patients had increased levels of PCA and TF as compared with the control polymorphonucleates, and low levels of elastase, t-PA, and u- PA; the patient blast PCA level was significantly related to the degree of hypofibrinogenemia. In this system, blast PCA depended on the tissue factor and was significantly correlated to the TF antigen values. In the cultures without ATRA, PCA, TF, and u-PA progressively increased, whereas elastase and t-PA levels remained essentially unchanged. In the presence of ATRA, all parameters (except u-PA) decreased during the culture time. Thus, a major role of the promyelocytic blast cell PCA in the pathogenesis of M3-related coagulopathy is suggested; the ATRA effect on coagulopathy seems mainly mediated by a downregulation of the PCA.     

Declarative memory retention and emotional stimuli. A study of an Italian sample

Psychological and pharmacological studies in humans suggest that emotional arousal enhances long-term memory. In this paper we used, in an Italian sample, an adaptation of a paradigm previously utilized in American samples to study the relationship between emotion and long-term memory. Seventy-two healthy adults from different educational backgrounds were randomly assigned either to a neutral group or to an emotional arousal group and then told a short story, presented audio-visually. In both groups, the slides shown and the slide sequence were the same, and the images were accompanied by a narrative. The two versions of the story differed primarily in their emotional content. Shortly after viewing the slide presentation, the participants were asked to rate the emotionality of the narrative, and ten days later were submitted to a retention test. The emotionally-arousing version of the story was rated as more emotional than the neutral one. Compared with the members of the neutral group, the subjects in the arousal group recalled a significantly higher number of elements from the story. There was no overall difference between the two groups in performance on the recognition memory test. These results confirm that the emotional content of stimuli enhances long-term declarative memory of those stimuli, and indicate the possible usefulness of applying the paradigm utilized in this study to different clinical samples from various cultural backgrounds.     

An assessment of the operating characteristics of Coulter Counter Model S-Plus STKR

BACKGROUND AND METHODS. The operating performance of the Coulter Counter S Plus STKR was evaluated in two hospital laboratories in Rome and in Florence. Experimental design conformed to both the ICSH and NCCLS Standards for the evaluation of hematologic analyzers, and to the ECCLS guidelines for the multicenter evaluation of analyzers in clinical chemistry. RESULTS AND CONCLUSIONS. Cell counts in K3 EDTA were unchanged over 6 hours at room temperature and 72 hours at 4 degrees C, while MCV, MPV and leukocyte differentials were far less stable. Carry over, precision and linearity met the manufacturer's specifications, while a satisfactory relative accuracy was demonstrated by determining reference values on an adult reference group and by comparing the instrument with the previous model S Plus IV D. The accuracy of the leukocyte differentials was evaluated by the microscope reference method, and our results seemed to validate the hypotheses that the STKR model counts: i) eosinophils, basophils and banded neutrophils among GR; ii) variant lymphocytes among LY, and iii) various abnormal cells among mononuclear cells. However, in spite of this statistical significance, some difficulties in correctly classifying the mononuclear population were demonstrated.     

Lymphocyte subset counting by immunoperoxidase using an automated routine hematologic analyzer

Using monoclonal antibodies against CD2, CD4, CD8 and CD19 antigens and an automated biotin-avidin immunoperoxidase technique on whole blood samples, we evaluated the technical performance and clinical usefulness of lymphocyte subset counting by the routine hematology analyzer Technicon H*1. Statistical evaluation demonstrated excellent precision and very good correlation with the immunofluorimetric flow cytometer Ortho Spectrum III. Correlation between manual immunofluorescence at the microscope and the H*1 method was much poorer, owing to the high intrinsic imprecision of the manual method. Reference ranges obtained with the H*1 immunoperoxidase method in 44 healthy subjects closely matched those obtained with the Spectrum III. In 46 subjects with or at risk for HIV infection, we found with the H*1 method a significant decrease in CD4+ cells and in the CD4+/CD8+ cell ratio, which was progressively more marked in HIV- negative patients with lymphadenopathic syndrome, AIDS-related complex, and in patients with full-blown AIDS.     

Quantified-EEG in normal aging and dementias

The value of quantitative electroencephalography (q-EEG) in the differential diagnosis of multi-infarct dementia (MID) and dementia of Alzheimer's type (DAT) is controversial. To evaluate the possible diagnostic role of q-EEG in these two conditions we studied 18 healthy adults, 16 healthy elderly (HE), 29 DAT patients and 45 MID patients. MID patients showed a significant increase of delta activity on the occipital regions, a significant widespread increase of theta activity, a significant widespread decrease of alpha activity. DAT patients showed a significant widespread increase of delta and theta activity, a significant widespread decrease of alpha activity. Spectral profile analysis showed an asymptotic exponential peak frequency at 4.33 HZ, and the disappearance of dominant activity in DAT patients; a 1 Hz decrease of peak frequency with a preserved normal profile in MID patients. We conclude that q-EEG is a useful ancillary test to differentiate MID from DAT.     

Coronavirus disease 2019 (COVID-19): Focus on peripheral blood cell morphology

Numerous studies have shown peculiar morphological anomalies in COVID-19 patients' smears. We searched all the peer-reviewed scientific publications that explicitly reference the cytomorphological alterations on peripheral blood smears of patients with COVID-19. We extracted data from sixty-five publications (case reports, patient group studies, reviews, and erythrocyte morphology studies). The results show that frequent alterations concern the morphology of lymphocytes (large lymphocytes with weakly basophilic cytoplasm, plasmacytoid lymphocytes, large granular lymphocytes). Neutrophils display abnormal nuclei and cytoplasm in a distinctive cytomorphological picture. Besides a left shift in maturation, granulations can be increased (toxic type) or decreased with areas of basophilia. Nuclei are often hyposegmented (pseudo-Pelger-Huёt anomaly). Apoptotic or pycnotic cells are not uncommon. Monocytes typically have a large cytoplasm loaded with heterogeneous and coalescing vacuoles. Platelets show large and giant shapes. The presence of erythrocyte fragments and schistocytes is especially evident in the forms of COVID-19 that are associated with thrombotic microangiopathies. Such atypia of blood cells reflects the generalized activation in severe COVID-19, which has been demonstrated with immunophenotypic, molecular, genetic, and functional methods. Neutrophils, in particular, are involved in the pathophysiology of hyperinflammation with cytokine storm, which characterizes the most unfavorable evolution.