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Biomedical subjects

Maria Kalmanti

Publications and source records attributed to Maria Kalmanti.

At least 19 recordsLinked to original sources

T-cell acute lymphoblastic leukemia relapsing as acute myelogenous leukemia.

We present the unusual case of a 16-year-old girl with T-cell acute lymphoblastic leukemia (ALL) with an early thymocyte immunophenotype without myeloid markers, who after 13 months of complete hematological remission relapsed as acute myelogenous leukemia (AML) with minimal differentiation and died of her disease. Whether the AML represented a relapse with lineage switch of the original immature T-cell clone or a new secondary malignancy, could not be proven due to the absence of molecular or clonal markers. This report suggests that a subset of CD7+ T-cell leukemias without mature T-cell antigens (CD4-, CD8-) are minimally differentiated and can relapse as AML.

Acute Disease↗

Urine interleukin-8 as a marker of vesicoureteral reflux in infants.

OBJECTIVE: Vesicoureteral reflux (VUR) is a common finding in children presenting with urinary tract infection (UTI) and prenatally diagnosed urinary tract dilatation and in relatives of index patients. Children with VUR are at risk for ongoing renal damage with subsequent infections. Detecting VUR and renal scarring currently depends on imaging modalities with associated problems of radiation, invasiveness, and expense. Noninvasive methods would greatly facilitate diagnosis and would also help in identifying relatives of index cases who should be screened. Interleukin-8 (IL-8) is produced by epithelial cells of the renal tract in response to inflammatory stimuli and has been shown to increase during acute UTI. The objective of this study was to assess the urine levels of IL-8 as a noninvasive marker of VUR in infants in the absence of a recent UTI episode. METHODS: We evaluated urine concentrations of IL-8 in 59 infants aged 1 month to 2 years. All infants were free of UTI for a minimum of 3 weeks before IL-8 evaluation. Infants were divided into 3 groups: group A, subjects with proven VUR (24 infants aged 0.15-1.95 years, median 0.43); group B, subjects with a history of UTI but negative investigation for VUR (14 infants aged 0.32-1.95 years, median 0.57); and group C, subjects without any history of acute or chronic condition that might impair renal function (21 infants aged 0.08-1.92 years, median 0.33). IL-8 concentrations were determined by a commercially available quantitative enzyme-linked immunosorbent assay. To avoid dilution effects, urinary levels of IL-8 were expressed as the ratio of cytokine-to-urinary creatinine. RESULTS: Results were presented as medians and ranges. The Kruskal-Wallis test, the Mann-Whitney rank sum U test, and the Spearman rank order correlation test were performed for the univariate analysis. Two-tailed P values were calculated and the conventional level of significance P < .05 was applied in all cases. Infants in groups A and B had been free of UTI for a period of 3 to 52 weeks (median, 5.0 weeks) and 3 to 78 weeks (median, 4.5 weeks), respectively, before IL-8 determination. No significant difference was noted in the length of the UTI-free period between groups A and B (P = .469). Urine creatinine concentrations did not differ among groups A, B, and C (medians 1.15, 2.25, and 1.15 micromol/mL, respectively; P = .080). The median urine IL-8/creatinine concentrations (pg/micromol) were 40.5 (range, 2.04-3874) in group A, 1.91 (range, 0.001-386) in group B, and 2.47 (range, 0.002-55.6) in group C. Urine IL-8/creatinine concentrations were significantly higher in group A than both in group B (P = .0003) and in group C (P < .0001). No significant difference was observed between groups B and C (P = .749). In group A, no significant correlation was shown between IL-8/creatinine concentrations and the presence of renal parenchymal damage (P = .506), reflux grade (P = .770), or time from UTI (P = .155). A receiver-operator characteristic curve was constructed by plotting the sensitivity versus the specificity for different cutoff concentrations of IL-8/creatinine. With a cutoff concentration of urinary IL-8/creatinine at 5 pg/micromol, the sensitivity of this marker in diagnosing VUR was 88%, the specificity 69%, the positive prognostic value 66%, and the negative prognostic value 89%. In higher cutoff concentrations, specificity of the marker increased but sensitivity rapidly decreased. CONCLUSIONS: We present evidence that urine IL-8 concentrations remain elevated in infants with VUR even in the absence of UTI and that a cutoff of 5 pg/micromol IL-8/creatinine is of high sensitivity and adequate specificity for diagnosing VUR. Elevated urine IL-8 levels in VUR and renal scarring have already been reported; however, the present study is, to our knowledge, the first to confirm significant differences between infants with VUR and infants with a history of UTI alone and healthy controls, and to suggest a reliable cutoff concentration for diagnosing VUR. Our findings additionally suggest that inflammatory process in VUR is ongoing even after UTI has resolved, pointing against the currently held belief that sterile reflux cannot harm kidneys. The chronic inflammatory cell infiltrate associated with reflux nephropathy rather than VUR itself might offer an explanation for the secretion of IL-8, which may well be independent of reflux grade. Using urine IL-8 for diagnosing VUR is not free of limitations, because IL-8 may be elevated as a result of urinary tract manipulation or undetected UTI. In addition, this study focused on infants and not in older children with longstanding VUR. Increased urine IL-8 concentrations after UTI has resolved is a promising noninvasive marker for an initial screening for VUR in infancy with high sensitivity and adequate specificity.

Biomarkers↗

The impact of mode of delivery and gestational age on cord blood hematopoietic stem/progenitor cells.

Human cord blood has been successfully used as an alternative source of hematopoietic stem cells suitable for transplantation. The aim of this study was to assess the impact of gestational age and the mode of delivery on cord blood hematopoietic stem/progenitor cell characteristics. The mode of delivery does not seem to affect either the replating capacity of hematopoietic progenitors colony-forming unit-granulocyte-macrophage or the cord blood content in CD34(+) cells. The higher percentage of CD34(+) cells in cord blood from preterm deliveries compared to full-term ones indicates that hematopoietic progenitors from preterm cord blood may be suitable for transplantation. These findings should be taken into consideration when selection of cord blood units is required for potential use in transplantation.

Antigens, CD34↗

Clarithromycin treatment and QT prolongation in childhood.

UNLABELLED: The effect of clarithromycin on the QT interval was studied in a group of 28 children treated for respiratory tract infections. QTc was measured before and following 24 h of treatment. A modest (average 22 ms, 95% CI 14-30 ms) but significant QTc prolongation (p<0.001) was observed, with seven cases having a QTc >440 ms during treatment (including a single case with QTc >460 ms). CONCLUSION: Serial QTc measurements are necessary for early detection of children at risk for drug-induced arrhythmias.

Adolescent↗

Insulin-induced oedema in children and adolescents.

Oedema is an uncommon complication of insulin therapy, which has only rarely been reported in childhood. We describe a case of a 12-year-old girl with newly diagnosed type 1 diabetes, who presented with oedema of the lower extremities and periorbitally, one day after the initiation of insulin treatment. Other causes of oedema were excluded. Following administration of frusemide, oedema resolved within ten days. An extended review of the literature revealed only nine cases of insulin-induced oedema in children and adolescents aged </=16 years. In conclusion, insulin-induced oedema should be considered during the introduction of insulin therapy in children and adolescents with newly diagnosed type 1 diabetes. Loop diuretics and ephedrine may be beneficial when spontaneous resolution does not occur.

Adolescent↗

Childhood encephalitis in Crete, Greece.

This study included all 18 cases of children hospitalized for encephalitis in the referral university hospital of Heraklion, Crete, Greece, during the 5-year period from 2000 to 2004. Encephalitis was attributed to viral infection (echovirus, herpes simplex virus 1, varicella-zoster virus, cytomegalovirus, and influenza A) in eight children and to bacteria (Mycoplasma pneumoniae, group A beta-hemolytic streptococcus, and Rickettsia typhi) in a further five cases. Multiple hyperintense brain lesions on magnetic resonance imaging (MRI) were associated with a severe clinical presentation but not with a guarded long-term outcome. Five children still presented with mild to moderate sequelae after 1.5 to 5.3 (median 4.0) years. Our findings confirm the elimination of measles, mumps, and rubella-associated encephalitis in the postvaccine era. MRI appeared to be of great diagnostic value. Although no fatalities were observed, deficits did persist in several patients.

Brain↗

Correlation of plasma N-terminal pro-brain natriuretic peptide levels with left ventricle mass in children treated with anthracyclines.

BACKGROUND: The incidence of subclinical cardiotoxicity following anthracycline treatment for childhood cancer varies according to the method used for its detection. The aim of the study was to document the prevalence of left ventricular myocardial mass (LVM) reduction and its possible association with plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in asymptomatic children treated with anthracyclines. PATIENTS AND METHODS: Nineteen asymptomatic children who had received anthracyclines during their treatment for cancer were evaluated. They had received an equivalent of doxorubicin dose 240 mg/m2 (22-1200 mg/m2) on average 3.9 years (0.6-8.3) before (median age at diagnosis 3.8 years). The LVM was determined by M-Mode echocardiography and compared to the expected value, obtained from the regression equation of LVM on height of a group of 160 healthy children. Additionally the patients' plasma NT-pro BNP levels were determined. RESULTS: A high prevalence of reduced LVM associated with increased NT-proBNP levels was found. The average LVM value was -14.4% (+/-4.9) lower than expected whereas fourteen patients (73%) had a lower LVM than predicted. The NT-pro BNP levels in patients with reduced LVM were significantly higher than those measured in patients without LVM reduction (0.316+/-0.02 versus 0.17+/-0.01 pmol/ml respectively, p=0.009). A cut off NT-pro BNP level of 0.2 pmol/ml could differentiate patients with LVM reduction from those with normal or greater than expected LVM. CONCLUSION: The association of higher NT-proBNP levels with reduced LVM in asymptomatic children after anthracycline administration could be an early indication of subclinical cardiotoxicity.

Adolescent↗

Perception and knowledge of medicines of primary schoolchildren: the influence of age and socioeconomic status.

UNLABELLED: This study describes perception and knowledge of medicines and the degree of familiarity with them in a group of primary schoolchildren. Participants were 360 primary school children from three age groups (6-7, 8-9, 10-11 years) recruited from one private and two public schools in the area of Athens. The children were interviewed individually at school. Results indicate that most of the children believe strongly in the therapeutic power of medicines independent of age or socioeconomic status (SES). Only 31.9% could describe correctly the role of vaccines. Also the children of higher SES were more knowledgeable compared to those of lower SES. Children draw their information on medicines from the parents or the physician; however the children of lower SES used other sources, such as reading, more frequently. Of the sample, 50% stated having easy access to home medicines and the percentages were high even for the youngest. CONCLUSION: Children's strong belief in the curative power of medicines, their limited knowledge on prevention and the easy accessibility to household medicines raises serious concerns. Additionally socio-economic differences in knowledge of medicines underscore the need for planning community and school-based health education programmes, with special attention to medicine education.

Age Factors↗

Stroke following Glenn anastomosis in a child with inherited thrombophilia.

The optimal anticoagulation following Fontan operation and its modifications remain controversial and it is even less well defined as regards patients with inherited thrombophilia. We present a case of a child with bidirectional Glenn anastomosis for double inlet left ventricle that suffered a stroke despite aspirin prophylaxis; the patient was combined homozygous for prothrombin G20210A mutation and for methylenetetrahydrofolate reductase C677T mutation as well. The family history was positive for fetal loss and premature cardiovascular disease. Large-scale studies are needed to evaluate whether carriers of thrombophilia mutations need more intense thromboprophylaxis.

Anastomosis, Surgical↗

Hypermethylation of CpG islands in the promoter region of the p15INK4B gene in childhood acute leukaemia.

It has been reported that the cyclin-dependent kinase inhibitor (CDKI) gene p15INK4B is frequently inactivated by genetic alterations and may be responsible for various malignant tumours. Another way of inactivation of this CDKI is by hypermethylation of 5'CpG islands in the promoter region of the p15INK4B gene and this inactivation seems to be a frequent event in various haematological malignancies. In the present study, we investigated the methylation status of the p151NK4B gene to clarify its role in the pathogenesis of childhood acute myeloid (AML) and acute lymphoblastic leukaemia (ALL). The study included 23 cases of B-cell origin ALL, 13 cases of T-cell origin ALL, 32 cases of AML, and 10 apparently healthy controls. Hypermethylation was studied by methylation-specific polymerase chain reaction. Hypermethylation of the p15INK4B gene was more frequent in cases with T-cell origin ALL (46.2%), but similar among children with B-cell origin ALL (13.0%) and AML (18.8%). Hypermethylation of p15INK4B may be involved in the pathogenesis of T-cell origin ALL, but not in that of AML or B-cell origin ALL.

Child↗

Prevalence of Factor V Leiden and other thrombophilic traits among Cretan children with malignancy.

BACKGROUND: The prevalence of thrombophilic traits, which might further enhance the risk of thrombotic complications in children treated for cancer, varies significantly among different populations. OBJECTIVE: To evaluate the prevalence of common thrombophilic traits of the East Mediterranean Region, among native Cretan children treated for malignancy. METHODS: Blood samples were consecutively collected from 31 native Cretan children treated for acute lymphoblastic leukaemia (n = 19) or other malignancies (n = 12) over 3 years. A molecular diagnosis based on the presence of Factor V Leiden (FVL), as well as on PT G20210A and MTHFR C677T mutation (in 14 patients) using PCR was applied. Patients who had central venous catheters (n = 29) were treated with an intensified thromboprophylaxis protocol that had been previously established in our institution. RESULTS: The prevalence of the FVL mutation was 19.4% (95% CI = 5-32). The allele frequency is estimated at 11.3% (95% CI: 3.5-19.1) which is higher than that reported for the population of the mainland of Greece. The prevalence of the PT G20210A and MTHFR C677T mutation was 14.3 and 71.4%, respectively (corresponding allele frequencies 7.1 and 50%, respectively). Only one patient developed thrombosis, having although no thrombophilic trait. CONCLUSIONS: Thrombophilic traits were relatively common in this group of native Cretan children treated for malignancy. Thromboprophylaxis should be considered in Cretan children in the presence of known acquired risk factors for thrombosis, but a larger prospective to study is first needed.

Adolescent↗

Qualitative versus quantitative blood cultures in the diagnosis of catheter-related bloodstream infections in children with malignancy.

BACKGROUND: Paired quantitative and qualitative blood cultures have been introduced for the diagnosis of catheter-related bloodstream infections (CRBI) with the catheter in situ. The aim of the study was to compare the diagnostic performance and the prognostic value of the two methods in the evaluation of febrile episodes without an apparent source in children with cancer. PROCEDURE: During a 4-year period, in every febrile episode without an apparent focus, blood was drawn simultaneously from the catheter lumen and a peripheral vein in order to perform paired quantitative (Isolator) as well as qualitative (BacT/Alert) blood cultures. The diagnosis of a CRBI was defined as either a case of greater (at least 10 fold) or earlier (differential time to positivity >2 h) bacterial growth from the catheter compared to the peripheral blood sample, respectively. RESULTS: Nineteen febrile episodes manifested in 16 children (total period of observation 11,150 catheter-days) were evaluated with both methods. A concordant diagnosis of CRBI was stated with both methods in six episodes; one episode was diagnosed as CRBI only with qualitative culture criteria. Treatment failure resulted in catheter removal in five out of the seven episodes defined as CRBI with either method. Episodes where a CRBI was ruled out with both methods had a favorable outcome. CONCLUSIONS: In this study the two methods showed comparable results in the diagnosis of CRBI and both were of prognostic significance, regarding the outcome of the treatment. However, large scale studies are required in order to evaluate the clinical relevance and the cost effectiveness of performing routinely paired blood cultures with either method.

Bacteremia↗

Cancer chemotherapy reduces plasma total antioxidant capacity in children with malignancies.

The sum of endogenous and food-derived antioxidants provides an estimate of the total antioxidant capacity (TAC) of the extracellular fluids, while corrected TAC (cTAC) is an estimation of the exogenously provided antioxidants. Similar values for TAC and cTAC were observed between cancer free children and children with malignancy at diagnosis. Antineoplastic treatment induced a significant decrease of TAC and cTAC during chemotherapy. Additionally to the dietary factors, this might be attributed to the antineoplastic drugs as shown by the significant increase of ROS after administration of chemotherapeutic agents both in vitro and in vivo. According to our preliminary results TAC and cTAC returned to normal after the end of therapy.

Antineoplastic Agents↗

Life-threatening hypercalcemia complicated by pancreatitis in a child with acute lymphoblastic leukemia.

The authors describe a 9-year-old girl with precursor-B acute lymphoblastic leukemia (ALL) who presented with dehydration and severe hypercalcemia. She had received oral vitamin D and calcium supplementation for 4 days, the last dose 48 hours prior to admission, and required pediatric intensive care unit (PICU) hospitalization for management of the hypercalcemia and safe initiation of induction chemotherapy. Her clinical course was complicated by pancreatitis, disseminated intravascular coagulation, pleural effusion, and focal seizures. Although the exact mechanism of hypercalcemia was not elucidated, it was likely related to the underlying ALL, without dismissing the prior vitamin D and calcium supplementation as a possible contributing factor. The hypercalcemia resolved with specific antileukemic therapy along with supportive care and administration of calcitonin. Hypercalcemia is an uncommon metabolic abnormality in children with ALL, but it can be life-threatening. Children with ALL should be referred to tertiary-care institutions with PICU and subspecialty support because serious metabolic and other complications can occur before or after the administration of chemotherapy.

Acute Disease↗

Fulminant hepatitis due to varicella zoster virus in a girl with acute lymphoblastic leukemia in remission: report of a case and review.

The authors describe a 4-year-old girl with acute lymphoblastic leukemia in remission who developed fulminant hepatic failure due to varicella-zoster virus (VZV). Diagnosing VZV visceral infection in immunocompromised patients is often difficult due to atypical clinical presentation with few or no skin lesions and severe abdominal or back pain. Prompt initiation of empirical treatment with acyclovir and VZV immunoglobulin pending results of the serum polymerase chain reaction for VZV is warranted in this clinical setting.

Antineoplastic Combined Chemotherapy Protocols↗

Assessment of megakaryopoiesis in children with acute lymphoblastic leukemia.

The effect of the underlying disease and chemotherapy on megakaryopoiesis has not been extensively studied in children with acute lymphoblastic leukemia (ALL) during and at the end of therapy. Using a serum-free assay, we assessed the megakaryocyte (Mk) colony formation in vitro from bone marrow mononuclear cells of 25 children with ALL during chemotherapy and shortly after the cessation of it. Twelve children with solid tumors without bone marrow involvement and cord blood from 10 full-term normal vaginal deliveries were used as controls. A significant reduction in the number of Mk colonies was observed at diagnosis of ALL, and Mk colony formation remained lower than controls throughout the different phases of leukemia treatment. Our study suggests that defects in megakaryopoiesis of children with ALL in long-term remission may persist during chemotherapy and at least shortly after the end of it.

Child↗

Rituximab for refractory Evans syndrome and other immune-mediated hematologic diseases.

The authors describe a 21-year-old man with long-lasting Evans syndrome refractory to corticosteroids and immunosuppressive agents; the patient responded to four weekly infusions of rituximab. The patient relapsed with thrombocytopenia 7 months post-therapy and was successfully re-treated with two weekly doses of the same monoclonal antibody. He remains in remission for 7-plus months after the second treatment. Therapy was well tolerated, and no infectious complications occurred, despite avoiding administration of prophylactic gammaglobulin. Rituximab appears safe and modestly effective in a variety of immune-mediated hematologic diseases, including autoimmune hemolytic anemia, chronic immune thrombocytopenia, Evans syndrome, pure red cell aplasia, mixed type II cryoglobulinemia, cold agglutinin disease, and Waldenstrom's macroglobulinemia. However, as most of the published literature consists of case reports and small case series, international collaboration is essential in order to better define the efficacy and safety of this agent in children and adults with hematologic diseases.

Adult↗