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Biomedical subjects

C P Tsakona

Publications and source records attributed to C P Tsakona.

10 recordsLinked to original sources

Changes in maternal plasma macrophage-colony stimulating factor levels during normal pregnancy.

An enzyme-like immunosorbent assay and a blood autoanalyser were used to determine macrophage-colony stimulating factor (M-CSF) levels and the absolute number and percentage of circulating monocytes in 80 normal women with singleton pregnancies at 12-40 weeks' gestation, and ten healthy non-pregnant volunteers. The mean values of M-CSF and absolute number and percentage of circulating monocytes of the control group were 367 U/ml (SD 43) and 389 x 10(6)/l (SD 180) and 5.3% (SD 1.7) respectively. In pregnancy, M-CSF was significantly higher than non-pregnant controls only after 28 weeks' gestation. The absolute number and the percentage of circulating monocytes increased significantly with gestation after 16 weeks. There was no significant association between the concentration of M-CSF and the number or percentage of circulating monocytes. These data suggest that during pregnancy there is an up-regulation of M-CSF and monocytes.

Adult↗

Serum macrophage colony-stimulating factor (M-CSF) levels correlate with clinical response to interferon-alpha in patients with early-stage B-CLL.

Interferon-alpha (IFN-alpha) reduces peripheral lymphocyte counts in B-CLL (CLL). In eight patients with stage 0 CLL on IFN-alpha therapy, peripheral lymphocyte counts fell to 61.7 +/- 19.5% of baseline at week 2 (P < 0.01), while serum M-CSF levels rose from 455 +/- 183 U/ml to 686 +/- 110 U/ml (P < 0.05). Neopterin levels also showed a significant rise. M-CSF levels were correlated with clinical response in these patients. Increased production of M-CSF and the activation of mononuclear phagocytes may be involved in clinical responses to IFN-alpha in early-stage CLL.

Biopterins↗

Myeloperoxidase activity and nuclear segmentation of maternal neutrophils during normal pregnancy.

Myeloperoxidase (MPO) activity and nuclear segmentation of neutrophils were measured in peripheral blood samples from 90 normal pregnant women, arranged in nine groups of ten each, every four weeks at 8-40 weeks gestation and from 25 non-pregnant healthy female controls. A blood autoanalyser (Technicon H*1) was used to determine the mean peroxidase index (MPXI) and the lobularity index (LI) of circulating neutrophils. Mean MPXI levels in pregnancy decreased with gestation to a minimum at 20 weeks' gestation and increased thereafter to reach non-pregnant levels at 36 weeks. Mean LI values did not change significantly with gestation, but were significantly lower throughout pregnancy compared to controls. There was no significant association between MPXI and LI. It could be postulated that the fall in MPXI during mid-gestation is due to degranulation of neutrophils and the subsequent rise at the end of pregnancy could be a consequence of enhanced MPO activity under the influence of oestrogens. Low LI suggests the production of immature neutrophils during pregnancy.

Cell Nucleus↗

Recombinant interferon alfa 2a in the treatment of patients with early stage B chronic lymphocytic leukaemia.

18 patients with early stage, previously untreated B-CLL were given interferon alfa (IFN alpha) 2a. 3 MU thrice weekly, subcutaneously. The peripheral lymphocyte count decreased in all patients. Response was delayed in three patients until they had received a median of 5 months therapy, one of whom had an initial transient increase in lymphocytes. Two patients normalized their blood lymphocyte counts, but neither achieved complete remission (CR). Responses were transient in eight patients lasting a median of 5 months (3-21). Binding anti-IFN alpha antibodies were present in 9/17 patients tested (53%). Low titre binding antibodies (< 533 IBU/ml) were not associated with LHR, but high titre antibodies (> 4401 IBU/ml) were. Two of 12 patients assessed had a > 3 g/l increase in baseline serum IgG levels during IFN alpha therapy, one of whom reverted to pretreatment levels in association with LHR. Haematological toxicity was moderate, other than in two patients, one of whom developed autoimmune haemolytic anaemia and the other thrombocytopenia. We conclude that IFN alpha lowers the lymphocyte count in early stage CLL, that the response may be delayed and that anti-IFN alpha antibodies may play a role in a proportion of those in whom the response is transient.

Adult↗

Low-dose recombinant alfa-2a-interferon: a feasible maintenance therapy in acute myeloid leukaemia in the older patient.

Eleven patients with acute myeloid leukaemia (AML) in first complete remission (CR) were treated with alfa-2a-interferon (for short 'interferon') maintenance therapy, at a dose of 3 MU twice to thrice weekly subcutaneously. Adjustments were made to maintain neutrophil counts > 1 x 10(9)/l and platelet counts > 100 x 10(9)/l. A transient fall in haemoglobin, neutrophil and platelet counts was noted in all 9 evaluable patients. Median time to nadir was 7 weeks. Initial dosage reductions were necessary in 5 patients, 3 of whom were later able to tolerate the starting dose. No episodes of infection or bleeding were documented during therapy and no red cell or platelet transfusions were necessary. At the time of writing (median follow-up of 31 weeks), 7 patients continue in CR, 6 of whom remain on interferon. One patient discontinued interferon on developing sicca syndrome. Other than in this patient, side effects were minor. Mean dose administered was 6.7 MU/patient/week. We conclude that low-dose IFN maintenance therapy is well tolerated in older patients with AML in first CR.

Aged↗

Does treatment with haemopoietic growth factors affect the incidence of bacteraemia in adult lymphoma transplant recipients?

Eighty-six consecutive adult patients undergoing ABMT colony-stimulating factor for lymphoma in three (CSF) trials were studied retrospectively to investigate whether the administration of CSFs had a beneficial impact on the incidence of bacteraemia. Forty-nine patients did not receive CSFs and 51% of them developed bacteraemia during the recovery phase. Nineteen patients received M-CSF post-ABMT, 9 G-CSF and 9 GM-CSF; 40%, 33% and 22%, respectively, developed bacteraemia during the recovery phase. Ninety per cent of all infections (Gram +ve and Gram -ve) and 100% of the Gram -ve ones occurred when the absolute neutrophil count (ANC) was < or = 0.1 x 10(9)/l. This period of maximum risk, i.e. the total number of consecutive days with ANC < 0.1 x 10(9)/l, was not shortened by CSFs; however, a decrease in the incidence of bacteraemia was detected in the CSF-treated patients during the above period and this might be a result of enhanced phagocytic function. The incidence of bacteraemia appeared to be related to the type of lymphoma (p < 0.02) regardless of CSF administration: 28 of 59 patients with Hodgkin's disease developed bacteraemia (46.7%) versus 6 of 27 patients (22.2%) with non-Hodgkin's lymphoma.

Adult↗

Patterns of primary degranulation as indicated by the mean myeloperoxidase index (MPXI) during bacteraemia in lymphoma transplants treated with growth factors.

The pattern of changes in neutrophil myeloperoxidase (MPO) before, during and after bacteraemia was studied in 34 patients recovering from autologous bone marrow transplantation for relapsed Hodgkin's disease and non Hodgkin's lymphomas. Thirteen patients received haemopoietic growth factors (7 received M-CSF, 3 received G-CSF and 3 GM-CSF). The mean peroxidase index (MPXI) produced as part of a routine FBC performed by a flow cytochemistry blood autoanalyser (Technicon H*1) was used as a parameter to assess the MPO and subsequently the azurophil degranulation. The manufacturer's normal values for MPXI range from -10 to +10. Median MPXI on the day of documented bacteraemia was just below normal in the control and M-CSF groups (-10.8 and -8.9 respectively), but it was much below normal in the G-CSF (-16.5, P < 0.05) and even lower in the GM-CSF group (-39.6, P < 0.02); this correlated well with the decreased bacteraemia incidence in the last two groups. Although contact of neutrophils with bacterial chemoattractants resulted in primary degranulation in all groups, the pattern of changes in MPO content was different, suggesting that neutrophils primed in vivo with various haemopoietins respond to the challenge of microbial agents via different pathways.

Bacteremia↗

Use of flow cytochemistry via the H*1 in FAB identification of acute leukaemias.

Blood samples from 40 adult patients with untreated acute leukaemia were processed through the Technicon H*1 blood autoanalyser which gives a complete white cell differential count using flow cytochemistry and provides white cell cytograms as well. We examined the differences in the percentage differential counts and the white cell cytograms of various FAB types of acute leukaemia in an attempt to estimate the usefulness of this easily obtainable data for the identification of acute leukaemias. Differentiation of the 33 acute myeloid leukaemia (AML) cases from the 7 acute lymphoblastic leukaemia (ALL) cases was possible on the basis of lymphocyte percentage (AML mean 29.6 vs. ALL mean 67.1, p < 0.01), monocyte percentage (AML mean 12.5 vs. ALL mean 3.3, p < 0.001), mean peroxidase activity value (AML mean -12.6 vs. ALL mean -0.6, p < 0.01) and the absence of IG flag (circulating immature granulocytes) in ALL. Interestingly, the FAB subtypes of AML could be distinguished from each other on the basis of characteristic patterns of cell distribution in the peroxidase cytogram when the total white cell count was over 10 x 10(9)/l. Even with lower counts the differences were distinctive providing that circulating blasts were present.

Adult↗