Tikva Yermiahu

Lycopene and 1,25‐dihydroxyvitamin d3 cooperate in the inhibition of cell cycle progression and induction of differentiation in hl‐60 leukemic cells

Lycopene, the major tomato carotenoid, has been found to inhibit proliferation of several types of cancer cells, including those of breast, lung, and endometrium. By extending the work to the HL-60 promyelocytic leukemia cell line, we aimed to evaluate some mechanistic aspects of this effect. Particularly, the possibility was examined that the antiproliferative action of the carotenoid is associated with induction of cell differentiation. Lycopene treatment resulted in a concentration-dependent reduction in HL-60 cell growth as measured by [3H]thymidine incorporation and cell counting. This effect was accompanied by inhibition of cell cycle progression in the G0/G1 phase as measured by flow cytometry. Lycopene alone induced cell differentiation as measured by phorbol ester-dependent reduction of nitro blue tetrazolium and expression of the cell surface antigen CD14. Results of several recent intervention studies with beta-carotene, which have revealed no beneficial effects of this carotenoid, suggest that a single dietary component cannot explain the anticancer effect of diets rich in vegetables and fruits. Thus another goal of our study was to examine whether lycopene has the ability to synergize with other natural anticancer compounds, such as 1,25-dihydroxyvitamin D3, which when used alone are therapeutically active only at high and toxic concentrations. The combination of low concentrations of lycopene with 1,25-dihydroxyvitamin D3 exhibited a synergistic effect on cell proliferation and differentiation and an additive effect on cell cycle progression. Such synergistic antiproliferative and differentiating effects of lycopene and other compounds found in the diet and in plasma may suggest the inclusion of the carotenoid in the diet as a cancer-preventive measure.

The need for routine pre-operative coagulation screening tests (prothrombin time PT/partial thromboplastin time PTT) for healthy children undergoing elective tonsillectomy and/or adenoidectomy

In some medical centers, the routine pre-operative evaluation of healthy children undergoing elective tonsillectomy and/or adenoidectomy (T and A) includes coagulation screening tests (PT, prothrombin Time; PTT, partial thromboplastin time; and INR, international normalized ratio). In this retrospective study, we determined whether there is a positive correlation between prolonged PT/PTT/INR tests in healthy children, with no prior medical history of coagulation problems, and bleeding during surgery and/or bleeding in the month following surgery. We reviewed the records of 416 elective T and A surgeries performed at the Soroka University Medical Center in Beer-Sheva, Israel, over the course of 1999. One hundred and twenty-one (29.1%) patients had preoperative prolonged PT values but only four (3.3%) of these patients experienced light bleeding during surgery. Seven (5.8%) of the 121 patients with prolonged PT tests experienced bleeding episodes during the 1st month subsequent to the surgery. Of the 65 (15.6%) patients who had prolonged pre-operative INR values, only three (4.6%) experienced light bleeding during surgery. Two (3.1%) patients with prolonged INR values experienced light bleeding during the 1st month subsequent to surgery. Sixty-one (14.7%) patients had prolonged first preoperative PTT values, only five of whom (8.2%) experienced light bleeding during surgery. Two (3.3%) of the 61 with prolonged PTT values experienced light bleeding during the 1st month subsequent to surgery. We therefore concluded that pre-operative coagulation screening tests provide low sensitivity and low bleeding predictive value. As such, routine coagulation tests before T &A are not indicated unless a medical history of bleeding tendency is suspected.

Cytology of middle ear fluid during acute otitis media.

Background. Limited information is available on the cellular characteristics of the middle ear fluid (MEF) during acute otitis media (AOM). Objectives. To determine the white blood cell (WBC) composition of the MEF in AOM before and during antibiotic therapy. Materials and methods. Total WBC and differential counts were determined in the MEF of 96 infants and children (ages 2 weeks to 3 years) with AOM who were receiving antibiotics. WBC counts were reported as number of WBC/mg MEF (mean ± sd). Results. One hundred forty-five MEF samples were obtained by tympanocentesis at enrollment (Day 1), and 36 samples were collected on Days 4 to 5 after initiation of antibiotic therapy. Sixty-one percent of the patients were <1 year of age, and 38% were receiving antibiotic therapy at enrollment. Twenty-eight MEF samples were paired (same ear, Day 1 and Days 4 to 5). One hundred twelve pathogens were isolated from 95 of 145 (66%) culture-positive samples obtained on Day 1: 67 Haemophilus influenzae, 40 Streptococcus pneumoniae and 5 others. MEF WBC counts were lower on Day 1 in patients who had received previous antibiotic therapy than in those who had not (432.4± 412.8 vs. 590.5 ± 436.8, P = 0.03). WBC counts were higher on Day 1 in culture-positive than in culture-negative samples (603.9 ± 504.9 vs. 421.4 ± 373.4, P = 0.02). WBC counts were higher on Day 1 in MEF samples positive for S. pneumoniae than in those positive for H. influenzae (799.2 ± 641.5 vs. 506.4 ± 401.9, P = 0.04). There were no differences in the number of neutrophil WBC present in the samples obtained on Day 1 vs. Days 4 to 5 or between samples positive vs. samples negative for bacterial pathogens. Conclusions. WBC counts were higher in the MEF of patients with culture-positive AOM than in those with culture-negative AOM and in those with AOM caused by S. pneumoniae.

Radiation Damage to the Erythrocyte Membrane: The Effects of Medium and Cell Concentrations

Human erythrocytes suspended in plasma, or in phosphate buffered saline (PBS), were exposed to ionizing radiation. Potassium leakage from irradiated erythrocytes is significantly higher in PBS than in plasma. The potassium leakage decreases when PBS is gradually replaced by plasma. These findings suggest that some of the plasma constituents have radioprotective properties. The potassium leakage per cell is independent of the hematocrit, Hct. The potassium leakage is attributed to the formation of radiation defects in the membrane. Analysis of the effect of radiation dose, plasma and cell concentrations on the product of the number and surface area of the radiation defects indicates that the radiation damage is mainly due to the direct formation of free radicals in the cell membrane. The radioprotective effect of plasma is attributed to surface reactions of these free radicals with plasma constituents adsorbed on the membrane.

Thalassemia intermedia and cavernous transformation of portal vein thrombosis in pregnancy

We report a rare case of a cavernous transformation of portal vein (CTPV) thrombosis accompanied by Thalassemia and thrombophilia during pregnancy that was successfully treated by low molecular weight heparin. The clinical presentation, diagnosis and the treatment are discussed.

Conversion of childhood acute lymphocytic leukemia (L2) with a double t(12;21) to juvenile myelomonocytic leukemia with a novel t(4;11)(p12;q23): a cytogenetic, morphologic, and immunophenotypic study

Here we describe a cytogenetic and flow-cytometric study of a case in which a conversion of childhood acute lymphocytic leukemia (ALL) into juvenile myelomonocytic leukemia (JMML) occurred. A 3-year-old boy diagnosed CALLA+, pre-B-ALL with double t(12;21) (by fluorescence in situ hybridization analysis), was treated as per the BFM protocol. A cytogenetic analysis performed at 17 months into treatment showed no t(12;21) in bone marrow (BM) cells; however, a novel translocation, namely, t(4;11), involving the p12 locus on chromosome 4 and the MLL gene at 11q23 was detected in monocytes. No cytogenetic abnormalities were found either in Epstein-Barr virus-transformed B cells or in phytohemagglutinin-stimulated T-lymphoid cells. Flow-cytometric analysis demonstrated an asynchronous expression of the antigenic determinants in populations of granulocytic and monocytoid cells: 60% of monocytes expressed low levels of CD14, an unusually high level of CD15, and no CD13 or HLA-DR antigens; 74% of myeloid cells expressed no CD13. Our results indicate that the transformation from B-cell ALL to JMML in this case occurred most probably in the granulocyte-erythroid-macrophage-megakaryocyte progenitor cells without involving the lymphoid cell line. To date, the child is 10 months off therapy and asymptomatic, with t(4;11) in only 3% of the cells.

Flow cytometry and morphology analysis of bone marrow in a child with brucellosis and hematologic manifestations.

Constitutional symptoms and pancytopenia are occasionally the initial presentation of pediatric brucellosis. Therefore, in endemic areas, in children with pancytopenia, both brucellosis and malignancy should be included in the deferential diagnosis. We report here a child with pancytopenia and hepatosplenomegaly as manifestations of brucellosis in whom bone marrow morphology and flow cytometry data revealed hemophagocytosis, left shift in myeloid cells and activation changes in antigenic properties of T and B lymphocytes and monocytes. The patient had an uneventful and complete recovery after appropriate antibiotic therapy. Our report demonstrates that bone marrow and flow cytometry findings in children with brucellosis may include significant reactive changes in hematopoiesis.

Acute myelogenous leukemia with splenic infarcts presenting as fulminant multi-organ failure.

A 60-year-old male was admitted with leukopenia, thrombocytopenia, splenic infarcts and a normal peripheral smear. Within few hours he rapidly deteriorated with fatal multi-organ failure. Autopsy revealed massive infiltration of leukemic cells in several organs. Acute myelogenous leukemia should be considered in a patient presenting with unexplained multiorgan failure.

Acute blast crisis with EBV-infected blasts, in a patient with chronic myeloid leukemia, and vasculitis.

Unless they undergo transplantation, all patients with chronic myeloid leukemia (CML) will eventually develope a late phase of acute blast crisis (ABC). Although additional chromosomal abnormalities to the Philadelphia (Ph) chromosome may herald ABC in many CML cases, the mechanisms leading to this fatal event are obscure. Viral etiology, including the Epstein-Barr virus (EBV) has never been implicated in the pathogenesis of ABC in CML. Iloprost is an analogue of epoprostenol (prostacyclin; PGI2) commonly used for the treatment of peripheral vascular diseases and acts via inhibition of platelet activation, and by vasodilation. A case of ABC with blasts of undetermined lineage showing EBV infection in a male patient with Ph positive CML is described here. This unusual event developed during a course of treatment with the prostacyclin analogue, iloprost administered for vasculopathic leg ulcers. The proliferating blasts stained positively by immunohistochemistry only for the leukocyte common antigen (LCA/CD-45), and the EBV-latent membrane protein 1 (LMP-1). The only chromosomal abnormality detected by cytogenetic analysis was the conventional Ph-chromosome. It is suggested that ABC in this case of CML, was associated with EBV-activated blasts of undetermined lineage.