Serial procalcitonin responses in infection of children with secondary immunodeficiency.

PURPOSE: Procalcitonin has proven to be a sensitive inflammatory marker in non-neutropenic patients. The aim of this study was to determine and compare Procalcitonin with other inflammatory markers in the serum of immunosuppressed children with haematological malignancies; and to assess the predictive value of these mediators in distinguishing between bacterial and non-bacterial infection. METHODS & RESULTS: The study included 37 children with acute lymphoblastic leukaemia undergoing intensive chemotherapy. They were divided into 3 groups, A, B and C. Group A consisted of 29 neutropenic children with 94 febrile episodes, group B of 20 neutropenic children with 56 afebrile episodes and group C of 13 non-neutropenic children with 58 afebrile episodes. Serial serum levels of PCT, C-Reactive Protein, Neopterin, Interleukin-6 and NO2/NO3 were all determined on a day-to-day basis for 7 consecutive days. In serum the concentrations of CRP was determined by nephelometry, of PCT by immunoluminescence and of Neopterin, IL-6 and NO2/NO3 by ELISA method. CONCLUSIONS: According to our results the Procalcitonin concentration increased rapidly in patients with microbial infection; the response was detectable within 24 hs of the onset of fever due to microbial infections. Procalcitonin is a specific and sensitive marker of microbial infection in patients with neutropenic fever. The markers, C-Reactive Protein, Interleukin-6 and NO2/NO3 may not help to identify infections and distinguish the etiology of infection in neutropenic febrile children with acute lymphoblastic leukaemia.

Serum adenosine deaminase and procalcitonin concentrations in neutropenic febrile children with acute lymphoblastic leukaemia.

Neutropenia as a state of immunosuppression is probably the major problem in patients suffering from acute lymphoblastic leukaemia undergoing intensive chemotherapy. Fever is frequent in neutropenic patients and often related to infection. Clinically, the presence of infection in patients with neutropenia may be difficult to establish, because there are usually few signs of infection. The aim of this work was to study sensitive markers for early diagnosis of microbial infection in neutropenic children undergoing intensive chemotherapy as a treatment for acute lymphoblastic leukaemia. The study included three groups (A, B and C) of children with acute lymphoblastic leukaemia and neutropenia. Group A consisted of 29 children with febrile neutropenia and microbial infection, aged 1-14 years (5.8+/-2.9), 11 boys and 18 girls; Group B of 38 children with febrile neutropenia without microbial infection, aged 2-14 years (6.8+/-3.1), 14 boys and 24 girls; and Group C of 53 children with neutropenia without fever and without infection, aged 1-14 years (5.9+/-2.1), 21 boys and 32 girls. Blood samples were collected upon admission and before the start of any antimicrobial treatment. The samples were used for blood culture, serological tests, leukocyte count and analysis of levels of C-reactive protein, procalcitonin, total adenosine deaminase (ADA) activity and its isoenzymes, ADA-1 and ADA-2. According to our results the procalcitonin levels and total ADA activity discriminated best between neutropenic febrile (Groups A and B) and neutropenic afebrile episodes (Group C). In conclusion, this study suggests procalcitonin and total ADA activity as two easily measurable and cost effective markers for the assessment of immune response in febrile neutropenic patients with acute lymphoblastic leukaemia.

Serum procalcitonin, adenosine deaminase and its isoenzymes in the aetiological diagnosis of pneumonia in children.

A prospective study was undertaken to assess the usefulness of leukocyte count, serum C-reactive protein (CRP), procalcitonin (PCT), and the activities of total adenosine deaminase (tADA) and its isoenzymes ADA1 and ADA2, in the aetiological diagnosis of pneumonia in children. The study included three groups. Group A consisted of 23 children with bacterial pneumonia, group B of 50 children with viral and mycoplasmal pneumonia and group C of 46 healthy children. On the first day of admission in the clinic, blood samples were collected before the start of antimicrobial treatment, for culture, serological tests, leukocyte count and for the determination of CRP and PCT levels as well as tADA activity and its isoenzymes ADA1 and ADA2. According to our results, the mean leukocyte count and the mean concentrations of PCT and CRP were significantly higher in the children of group A than those in groups B and C. The admission serum PCT concentration has a higher sensitivity, specificity and positive predictive value for bacterial pneumonia than either CRP or the leukocyte count. The mean serum tADA, ADA1 and ADA2 activity in children of group A was not significantly different from those in group C, while the difference between groups B and C was statistically significant. In conclusion, we found that CRP is a good marker for screening various infectious diseases, but it cannot be used to distinguish between bacterial and viral infections. Serum PCT measurement might be a useful tool for the physician for the aetiological diagnosis of pneumonia in children. Measurements of serum tADA and ADA2 activity may provide useful additional diagnostic information on the aetiology of pneumonia so that appropriate antibiotic therapy can be given promptly. Further studies with larger patients groups are required to confirm our results.

Adenosine deaminase activity and its isoenzyme pattern in patients with juvenile rheumatoid arthritis and systemic lupus erythematosus.

Adenosine deaminase (ADA) is involved in purine metabolism and plays a significant role in the mechanisms of the immune system. The aim of this study was to investigate the activity of total ADA (tADA) and its isoenzymes ADA1 and ADA2 in serum and peripheral blood lymphocytes (PBLs) of children with juvenile rheumatoid arthritis (JRA) and systemic lupus erythematosus (SLE) in different phases of the diseases. The study comprised 34 patients with rheumatic disease, 24 with JRA and 10 with SLE, and 64 healthy controls. The tADA activity and its isoenzymes were measured in serum and PBLs of all patients by the method of Giusti and by the presence or absence of EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine) during the active phase of the disease (before treatment), as well as during remission and relapse. Our data show that increased tADA activity in the serum and PBLs of patients with JRA and SLE is correlated mainly to increased levels of ADA2 activity in serum and ADA1 activity in PBLs. It also closely correlates with clinical disease activity and relapse. The cause of this increased tADA/ADA2 activity in serum and tADA/ADA1 activity in PBLs in JRA and SLE remains to be elucidated. Nevertheless, it may be noted that the measurement of tADA activity, together with ADA2 activity in serum and tADA with ADA1 activity in PBLs, could offer a biochemical approach to the assessment of the pathophysiology of JRA and SLE. Also, tADA and its isoenzymes could be used as alternative parameters representing disease activity.

Circulating soluble adhesion molecule levels in children with acute lymphoblastic leukaemia.

UNLABELLED: The aim of this study was to evaluate levels of serum soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) as parameters of disease activity and to monitor the response to treatment in children with acute lymphoblastic leukaemia (ALL). The above soluble adhesion molecules were determined in the serum of 35 children with ALL and 30 healthy children (control group) of the same age range. The samples were obtained before treatment, 6 months after the beginning of the treatment (remission of the disease), 6 months after the end of the treatment and during relapse of the disease. The mean levels of sICAM-1, sVCAM-1 and sE-selectin at the onset of the disease were 646.6 +/- 80.9 ng/ml, 1786 +/- 151.8 ng/ml and 140.5 +/- 17.3 ng/ml, respectively. These values were significantly higher (P < 0.001) than those of the control group, which were, 245.8 +/- 25.7 ng/ml, 798.6 +/- 78.9 ng/ml and 44.7 +/- 18.2 ng/ml respectively. During remission, the mean levels did not differ significantly from those of the control group. After the end of the treatment the mean levels again did not show any significant differences compared to the control group. During relapse the soluble adhesion molecule mean levels (923.9 +/- 110.1 ng/ml, 2945.7 +/- 349.9 ng/ml and 258.2 +/- 5.1 ng/ml) were significantly higher (P < 0.001) than those of the control group and also than those obtained during remission and after the end of the treatment (P < 0.001). Pearson's correlation coefficient r was computed in order to detect possible linear correlations between: (1) sICAM-1 and sVCAM-1 (r = 0.632); (2) sICAM-1 and sE-selectin (r = 0.788) and (3) sVCAM-1 and sE-selectin (r = 0.752). All three cases correspond to P < 0.001, thus indicating strong linear correlations. CONCLUSIONS: The levels of soluble circulating adhesion molecule levels can be utilized for monitoring disease activity of ALL and its response to treatment, as well as for early detection of relapse. Strong linear correlations between the three soluble adhesion molecules tested suggest that each of them may be sufficient as an indicator.

Prognostic significance of adenosine deaminase in children with malignancies.

In 33 children, 23 with acute lymphoblastic leukemia (ALL) and 10 with solid tumors, the phenotype of the enzyme adenosine deaminase (ADA) was detected in the erythrocytes by electrophoresis in cellulose acetate. In all children the ADA enzyme activity was also determined in the plasma by spectrophotometry at the onset of the disease, during remission, at the end of the therapy, and during relapse. The phenotype in all children was ADA1-1. There was a difference in enzyme activity between the mean values of children with ALI and those with solid tumors. There were also differences among the subtypes of ALL and also among the stages of ALL and the stages of solid tumors. In 23 children with ALL the mean value (MV) and the corresponding standard error (SEM) of enzyme activity at the onset of the disease were MV +/- SEM = 60.2 +/- 6.2 IU/L. This was higher than that of the control group (control group: MV +/- SEM = 27.8 +/- 3.3 IU/L). During remission the enzyme activity was lower than that of the control group (MV +/- SEM = 19.6 +/- 1.7 IU/L); at the end of the therapy it was MV +/- SEM = 24.0 +/- 1.3 IU/L, which is close to that of the control group; and during relapse it was much higher compared with the control group (MV +/- SEM = 73.1 +/- 4.6 IU/L). These values are discussed in connection to the leukaemic subtypes. In 10 children with solid tumors the mean value of enzyme activity at the onset of the disease was MV +/- SEM = 48.8 +/- 2.4 IU/L. During therapy it was MV +/- SEM = 32.4 +/- 1.9 IU/L and at the end of therapy MV +/- SEM = 22.1 +/- 2.5 IU/L. The aim of this work is to study the qualitative isoenzyme abnormalities to better understand the biological nature of the malignancies, to distinguish main groups and subsets of ALL and solid tumors on an enzymatic basis, and to identify possible sensitive key enzymes as targets for chemotherapy.

Response of blood and bone marrow neutrophils to the nitroblue-tetrazolium test in children.

The ability of blood and bone marrow neutrophils to reduce nitroblue-tetrazolium both before and after stimulation with Escherichia coli endotoxin was investigated. The polymorphonuclear cells of the bone marrow are less able to reduce the dye than blood cells. This difference is maintained after stimulation by endotoxin. Early forms of neutrophils (myelocytes and metamyelocytes) have some reducing ability but this is more marked after stimulation with endotoxin.