Adenovirus infection among pediatric patients with cancer and in pediatric recipients of hematopoietic stem cell: A multicenter nationwide study.

The aim was to evaluate the incidence, clinical course, and outcome of adenoviral infection (AdVI) in pediatric patients diagnosed and treated due to cancer and in pediatric recipients of hematopoietic stem cell. Over a 72-month period, all-in 5599 children with cancer: 2441 patients with hematological malignancy (HM) and 3158 with solid tumors (ST), and 971 patients after transplantation: 741 after allogeneic (allo-HSCT) and 230 after autologous (auto-HSCT) were enrolled into the study. Among cancer patients, 67 episodes of AdVI appeared in 63 (1.1%) children, including 45 (1.8%) with HM and 18 (0.6%; P < .001) with ST. Within transplanted patients, AdVIs were responsible for 88 episodes in 81 (8.3%) children (P < .001), including 78 (10.5%) patients after allo-HSCT and 3 (1.3%) after auto-HSCT. Time to develop AdVI was short, especially after allo-HSCT. The most common clinical manifestation in cancer patients was enteritis diagnosed in 63 (94.0%) cases, while among HSCT recipient asymptomatic adenoviremia was found in 36 (40.9%) cases and the most common clinical manifestation was urinary tract infection. Cancer patients with disseminated disease, as well as HSCT recipients with either asymptomatic viremia or disseminated disease, received antiviral treatment. The most commonly used first-line therapy was cidofovir. None of the cancer patients died due to AdVI, while within HSCT recipients three patients developed disseminated adenoviral disease and died despite antiviral treatment. In cancer patients, AdVIs are rare and associated with very good prognosis even without specific treatment. However, in allo-HSCT recipients, disseminated disease with fatal outcome is more likely to occur.

Hematopoietic stem cell transplantation does not increase the risk of infection-related complications for pediatric patients with Hodgkin and non-Hodgkin lymphomas: A multicenter nationwide study.

BACKGROUND: Hodgkin (HL) and non-Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens; however, 15%-30% of lymphoma patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second-line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications (IC), remain unclear. OBJECTIVE: The aim of this population-based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL. PATIENTS AND METHODS: We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A), patients with rel/ref lymphoma treated with second-line chemotherapy (group B), and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center, and the data were analyzed centrally. RESULTS: Within 637 patients with primary lymphoma, at least one IC was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed, and in transplanted group, 28 (57.1%) out of 49 children were diagnosed with IC (P = .151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC were diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram-positives were predominant. The rate of multidrug-resistant bacteria was high, especially for Gram-negatives (41.1% in group A, 62.5% in group B, and 84.6% in group C). The infection-related mortality was comparable for each group. CONCLUSIONS: The incidence of IC was comparable during first- and second-line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy.

Incidence, course, and outcome of Clostridium difficile infection in children with hematological malignancies or undergoing hematopoietic stem cell transplantation.

Clostridium difficile infection (CDI) is one of the most common causes of nosocomial infectious diarrhea in children during anticancer therapy or undergoing hematopoietic stem cell transplantation (HSCT) in Europe. Immunosuppression in these patients is a risk factor for CDI. Malignant diseases, age, acute graft-versus-host disease (aGVHD), HLA mismatch, or use of total body irradiation may play an important role in CDI course. The aim of this study was to evaluate the incidence, course, and outcome of CDI in children treated for malignancy or undergoing HSCT. Between 2012 and 2015, a total number of 1846 patients were treated for malignancy in Polish pediatric oncological centers (PHO group) and 342 underwent transplantation (HSCT group). In PHO group, episodes of CDI occurred in 210 patients (14%). The incidence of CDI was higher in patients with hematological malignancies in comparison to that with solid tumors. Patients with acute myeloblastic leukemia had shorter time to episode of CDI than those with acute lymphoblastic leukemia. Patients over 5 years and treated for acute leukemia had more severe clinical course of disease in PHO group. In HSCT group, CDI occurred in 29 (8%) patients. The incidence of CDI was higher in patients transplanted for acute leukemia. The recurrence rate was 14.7% in PHO and 20.7% in HSCT patients. CDI incidence was highest in patients with hematological malignancies. Most of patients experienced mild CDI. Age < 5 years and diagnosis other than acute leukemia were the positive prognostic factors influencing clinical CDI course.

First-line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

The progressive reduction in the ovarian reserve in young women after anticancer treatment.

Anticancer treatment can disturb gonadal function and deplete the primordial follicle pool, leading to premature menopause. We made a prospective analysis of serum hormone levels in young female cancer survivors who had been treated during childhood and adolescence. Serum anti-Müllerian hormone (AMH) as a marker of ovarian reserve, FSH, LH, and estradiol were measured in 33 women treated previously (6-11 years earlier) for Hodgkin Lymphoma, solid tumours, and after bone marrow transplantation, and in 34 healthy controls. The group of survivors was divided according to the risk of gonadotoxicity into the low risk and median risk group (LR+MR), and into the high risk (HR) group. The measurements were repeated after 5 years. In the HR group, AMH levels were significantly lower than in controls (p=0.001) and in the LR+MR group (p=0.006) at the time of the first examination fell progressively after 5 years (p=0.03), whereas elevated FSH values (p=0.053) increased (p=0.001). Unchanged LH values in the first measurement rose in the second one (p=0.001). In the LR+MR group, the levels of AMH and FSH were normal (compared to the control) at baseline, but after 5 years serum AMH decreased (p=0.027) and FSH increased (p=0.008). Our findings indicate that anticancer treatment during childhood and adolescence is associated with a serious, progressive risk of ovarian failure. It is necessary to inform female cancer survivors, especially the high risk patients, about the risk of premature menopause.

Cerebrospinal fluid IL-6, TNF-α and MCP-1 in children with acute lymphoblastic leukaemia during chemotherapy.

The aim of the study was to investigate the levels of cerebrospinal fluid (CSF) cytokines during chemotherapy of acute lymphoblastic leukaemia (ALL). Examination of 12 ALL child (6 boys and 6 girls) patients evidenced significant increases in interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) after induction treatment and significant increases in IL-6, tumour necrosis factor-α (TNF-α) and MCP-1 levels during the consolidation phase, as compared to their values at the time of diagnosis. There were no significant differences in CSF IL-6, TNF-α and MCP-1 concentrations after therapy. Our data suggest that standard ALL treatment may cause a subclinical inflammation and neurotoxicity.

Cerebrospinal fluid changes in the excitatory amino acids concentration caused by the standard treatment of acute lymphoblastic leukaemia in children do not correlate with their later cognitive functioning.

The aim of this study was to ascertain whether changes in the concentrations of cerebrospinal fluid excitatory amino acids (EAAs) contribute to neurotoxicity of the standard acute lymphoblastic leukaemia (ALL) treatment protocols. We found a statistically significant increase in glutamate and aspartate in 12 ALL patients during their treatment. Cognitive functioning was examined in all patients at an average of 3.7 years after the disease diagnosis. Importantly, the levels of EAAs during the therapy were not correlated with the results of the cognitive test. This study suggests that standard ALL treatment-induced neurotoxicity may not lead to persistent neurocognitive deficits.

Acute lymphoblastic leukemia-derived dendritic cells express tumor associated antigens: PNPT1, PMPCB, RHAMM, BSG and ERCC1.

In all types of leukemia both in children and adults there is a need for novel therapies that could reduce the risk of relapse after standard treatment. Acute lymphoblastic leukemia (ALL) cells are ineffective antigen presenting cells, but as shown by many authors including results from our laboratory, stimulation with CD40L restores their antigen expressing capacity. The development of T-cell therapies for leukemic patients can be based on discovery of leukemia-associated antigens (LAA) which could be recognized by the host immune system. The aim of our present study was to test the hypothesis that leukemia-derived dendritic cells maintain the expression of tumor associated antigens. Twenty five children with B-cell precursor ALL were prospectively enrolled into the study. The mononuclear cells from peripheral blood or bone marrow were cultured and stimulated (or not) with CD40L and IL-4. The assessment of costimulatory/adhesion molecules with the use of flow cytometry and real-time RT PCR were used to confirm the possibility of turning ALL cells into dendritic-like cells. Additionally 22 tumor associated antigens mRNA levels were determined by real-time PCR technique with the TaqMan chemistry using ready-to-use Low Density Arrays for Gene Expression. The results of the study showed maintained expression and even up-regulation of some (PNPT1, PMPCB, HMMR/RHAMM, BSG and ERCC1) tumor associated antigens in CD40-activated leukemic cells. CD40L stimulation leading to the differentiation of leukemic cells into DCs which combine both antigen presenting function and expression of tumor associated antigens represents an interesting approach in cancer immunotherapy.

B-cell chronic lymphocytic leukemia-derived dendritic cells stimulate allogeneic T-cell response and express chemokines involved in T-cell migration.

UNLABELLED: Despite discovery of new therapeutic agents, including nucleoside analogs and monoclonal antibodies, the B-cell chronic lymphocytic leukemia (B-CLL) remains incurable. In recent years, some effort has been made in developing T-cell specific immunity against neoplasmatic cells. Reconstitution of effective costimulation and immunological response of host T-cells against CLL cells could be a potential approach in immunotherapeutic trials. CD40/CD40L system is involved in the survival and proliferation of normal and neoplasmatic B-cells. Some preclinical studies have shown that CD40 stimulation can differentiate leukemic cells into dendritic cells (DCs) and result in host response. In this study, we sought to determine whether B-CLL cells could be turned into efficient and functional antigen presenting cells, as well as to assess the type of allogeneic T-cell response against B-CLL - derived DCs. MATERIAL AND METHODS: B-CLL cells from 25 patients were cultured with or without the presence of CD40L and IL-4 for 96 hours and then cultured in mixed lymphocyte reaction with allogeneic T-cells. RESULTS: 1) after CD40 stimulation B-CLL cells achieved phenotypical and functional characterization of DCs (i.e. upregulated co-stimulatory and adhesion molecules at mRNA and protein level) 2) leukemia-derived DCs expressed higher amount of mRNA for chemokines involved in T-cell migration (MDC, TARC and CCR7) 3) the proliferating response of Tcells against leukemia-derived DCs consisted of CD4 and CD8 cells (upregulation of HLA-DR and OX40). CONCLUSIONS: our experiment confirm that B-CLL cells can be turned into dendritic-like cells, additionally, these cells express chemokines involved in T-cell migration and stimulate allogeneic response.

Low expression of costimulatory molecules and mRNA for cytokines are important mechanisms of immunosuppression in acute lymphoblastic leukemia in children?

UNLABELLED: Mechanisms leading blasts of acute lymphoblastic leukemia to escape from immune surveillance are still unknown. Only few reports showed that ALL cells are inefficient antigen presenting cells. The aim of the study was to assess expression of critical costimulatory/adhesion molecules and mRNA for main pro- and anti-inflammatory cytokines in ALL cells. Children with B-cell precursor ALL (n=20) were prospectively enrolled into the study. Expression of costimulatory/adhesion molecules (CD1a, CD11c, CD40, CD54, CD80, CD83, CD86, CD123, HLA class I and II) was assessed by flow cytometry and mRNA for cytokines (IFN-gamma, IL-10, IL-4, TGF-beta) - with real-time PCR. RESULTS: 1) high expression was observed for HLA I and II class, moderate for CD40, CD83, CD86 and low or no expression for CD80, CD54, CD1a, CD11c and CD123; 2) we found expression of mRNA for IFN-gamma, IL-10, IL-4 and TGF-beta in blasts cells (but not in all specimens). We noted relatively lower expression of all assessed cytokines comparing to T-cells obtained from healthy donors but interestingly expression for IL-10 was higher in normal B-cells than in blast cells, and IFN-gamma and IL-4 were not found in normal B-cells. In summary we suggest that ALL-blasts present low expression of costimulatory/adhesion molecules and mRNA for cytokines and this probably contribute to the absence of host T- cells stimulation to immune response.

Increased risk of infections and infection-related mortality in children undergoing haematopoietic stem cell transplantation compared to conventional anticancer therapy: a multicentre nationwide study.

This nationwide multicentre study analysed the epidemiology of bacterial, viral and fungal infections in paediatric haematopoietic stem cell transplantation (HSCT) and paediatric haematology and oncology (PHO) patients over a period of 24 consecutive months, including incidence, hazard risk and outcome of infections as well as occurrence of multidrug-resistant bacteria. During this period, 308 HSCTs were performed and 1768 children were newly diagnosed for malignancy. Compared to PHO, the risk in HSCT patients was significantly higher for all infections (hazard ratio (HR) 2.7), bacterial (HR 1.4), fungal (HR 3.5) and viral (HR 15.7) infections. The risk was higher in allo- than auto-HSCT for bacterial (HR 1.4), fungal (HR 3.2) and viral (HR 17.7) infections. The incidence of resistant bacteria was higher in HSCT than in PHO patients for both G-negative (72.5% vs. 59.2%) and G-positive (41.4% vs. 20.5%) strains. Cumulative incidence of bacterial, fungal and viral infections in HSCT patients was 33.9, 22.8 and 38.3%, respectively. Cumulative incidence of viral infections in allo-HSCT was 28.0% for cytomegalovirus, 18.5% for BK virus, 15.5% for Epstein-Barr virus, 9.5% for adenovirus, 2.6% for varicella zoster virus, 0.9% for influenza, 0.9% for human herpesvirus 6 and 0.3% for hepatitis B virus. Survival rates from infections were lower in HSCT than in PHO patients in bacterial (96.0 vs. 98.2%), fungal (75.5 vs. 94.6%) and most viral infections. In conclusion, the risk of any infections and the occurrence of resistant bacterial strains in allo-HSCT patients were higher than in auto-HSCT and PHO patients, while the outcome of infections was better in the PHO setting.

In vitro sensitivity of leukemic cells to nucleoside derivatives in childhood acute leukemias: good activity in leukemic relapses.

Nucleoside analogues such as fludarabine and cladribine are used in therapy of indolent lymphomas and leukemias in adults, while cytarabine is used mainly in protocols for acute leukemias. Mechanisms of their activity is based on inhibition of enzymes involved in DNA, RNA and protein synthesis. The objective of the study was the analysis of in vitro cellular drug sensitivity in childhood acute lymphoblastic (ALL) and myeloid (AML) leukemia. Isolated leukemic cells obtained from 264 patients, including 152 initial ALL, 45 relapsed ALL, 54 initial AML and 13 relapsed AML were tested for cytotoxicity for fludarabine, cladribine, and cytarabine by the MTT assay. Drug concentration lethal to 50% of tested cells was regarded as a value of drug resistance. Three tested nucleoside analogues showed highest cytotoxicity against initial ALL samples. Samples of relapsed ALL and initial AML were more resistant than ALL de novo ones. Unexpectedly, no differences were observed between initial and relapsed AML samples for all tested drugs, what suggests that nucleoside analogues are active drugs in relapsed AML, which is commonly regarded as a resistant disease. All tested drugs presented significant cross-resistance in each of analyzed subgroups. In summary, tested nucleoside analogues presented relatively good activity against childhood leukemias at relapse stage.

[Usefulness of antioxidant vitamin supplementation in children and adolescents with newly diagnosed diabetes mellitus type I]. / Przydatnosc zastosowania witamin antyoksydacyjnych u dzieci i mlodziezy z nowo rozpoznana cukrzyca insulinozalezna.

BACKGROUND: Diabetes type I is caused by immune-mediated destruction of the b-cells. During the immune response macrophages release free oxygen radicals and cytokines which damage DNA. Ascorbic acid, b-carotene, a-tocopherol and nicotinamide act as antioxidants (free radical scavengers). OBJECTIVES: Comparative analysis of diabetes mellitus clinical course in the first year after diagnosis with and without antioxidative vitamin supplementation. MATERIAL AND METHODS: 40 children and adolescents with newly-diagnosed diabetes type I treated with: group A (n=13) n insulin + diet, group B (n=14) n additional vitamins A+E, C, group C (n=13) n additional vitamins A+E, C, PP. RESULTS: The remission was observed in n=13 (92.8%) children in group B, in n=6 (46.1%) in group C and only in 2 (15.4%) in group A after 3-4 months. After 6-7 months the remission was obtained in 10 patients (71.5%) in group B, in 6 (46.1%) - in group C and in 4 (30.8%) - in group A. After one year observation 6 (42.5%) patients in group B had remission, 4 (30.7%) in group C and 2 (15.4%) - in group A. Daily insulin demand was similar after diagnosis, after 3-4 months it was more reduced in group B (x - 0.28 u./kg/d, SD n 0.23) vs. x - 0.40 u./kg/d SD n 0.24 (group C) and vs., x - 0.5 u./kg/d - (group A). The insulin demand was augmented in the following months but all the time it was lower in the group supplemented by vitamins A, E, C. The glycaemic control and the values of lipids, thiobarbituric and reactive substances, group-SH of glutathione and vitamin C were similar in analysed groups in simultaneous periods. CONCLUSIONS: Supplementation with antioxidant vitamins in newly diagnosed diabetes mellitus type I leads to more frequent remissions and reduced insulin demand, particularly in the first months of diabetes duration.

[The prevalence of autoimmunological diseases in families of children with type I diabetes]. / Wystepowanie chorób o podlozu autoimmunoagresji w rodzinach dzieci chorych na cukrzyce typu I.

BACKGROUND: type I diabetes mellitus is considered as an autoimmune disease and is often associated with other diseases of that etiology. The genetic susceptibility to autoimmune disorders causes type I diabetes to occur more frequently in relatives of the diabetic patients. OBJECTIVE: To evaluate the prevalence of type I diabetes and other autoimmune diseases in families of the children with type I diabetes. MATERIAL AND METHODS: The prevalence of type I diabetes mellitus and other autoimmune endocrinopathies was evaluated in I, II and III degree relatives of 155 children with type I diabetes mellitus and 90 control children. RESULTS: It was observed that: 1) diabetes mellitus occurred more often in relatives of diabetic children (in 22 families - 14.2%) in comparison with the control group (in 2 families - 2.2%); 2) other autoimmune diseases occurred frequently in families of diabetic children and they affected 2 or more members of one family more often than in the control group (18 families vs 4); 3) rheumatoid arthritis occurred more frequently in families of diabetic children. CONCLUSIONS: The familial prevalence of type I diabetes mellitus and the tendency to more frequent prevalence of other autoimmune diseases in families of diabetic children was confirmed.

[Lipid metabolism in children and adolescents with insulin dependent diabetes. II. Evaluation of changes in lipoprotein A-I in children and adolescents with insulin dependent diabetes]. / Stan gospodarki tluszczowej u dzieci i mlodziezy z cukrzyca insulinozalezna Czesc II. Ocena zachowania sie czasteczek LP A-I u dzieci i mlodziezy z cukrzyca insulinozalezna.

The levels of lipoprotein A-I (LP A-I) containing apolipoprotein A-I (apo A-I) and devoid of apolipoprotein A-II (apo A-II) have been determined in a group of 86 children and adolescents with insulin-dependent diabetes of age between 1.3 and 22 years. The duration of diabetes in the studied group ranged between 0.25 and 15 years. The patients studied were further divided into subgroups taking into account the duration of diabetes as well as the occurrence of complications of diabetes, obesity and predisposition to early development of atherosclerosis in family history. The analysis of the results took into account the relations between the levels of LP A-I and other parameters of lipid metabolism like cholesterol, triglycerides, HDL-cholesterol, apo A-I and apo A-II concentrations as well as the effectiveness of metabolic control of diabetes. LP A-I concentration was the lowest in group of children with diabetes lasting up to one year. This parameter was correlated positively with the levels of HDL-cholesterol and apo A-I, and negatively with HbA1c. It was not related to the coexisting complications, obesity or predisposition to atherosclerosis in family history. The above results indicate that the state of metabolic control of diabetes significantly influences the level of LP A-I. Considering the importance of LP A-I in preventing atherosclerosis it should be stressed that a decrease in its level during the period of prolonged hypoglycemia constitutes still another risk factor for development of atherosclerosis in diabetic children and adolescents.

[Lipid metabolism in patients with insulin dependent diabetes. III. Effect of metabolic control of diabetes on the concentration of some blood serum lipid constituents in patients with insulin dependent diabetes]. / Stan gospodarki tluszczowej u chorych na cukrzyce insulinozalezna. Czesc III. Wplyw wyrównania metabolicznego ustroju na wartosc wybranychparametrów gospodarki lipidowej w surowicy krwi u chorych na cukrzyce insulinozalezna.

The levels of the following blood serum lipid constituents: total cholesterol, triglycerides, phospholipids, HDL-cholesterol, lipoprotein fractions, as well as apolipoproteins AI, AII and B, have been determined in patients with insulin-dependent diabetes lasting from 3 months to 15 years in relation to the degree of metabolic control characterized by the levels of fructosamine and glycosylated hemoglobin HbA1c. The group of patients having the level of HbA1c exceeding 10% was characterized by significantly higher levels of cholesterol, triglycerides and Apo-B, and lower content of alpha-lipoprotein as compared to the group with HbA1c level beneath 10%. When fructosamine concentration was considered as an index of metabolic control of diabetes, it was found that the levels of cholesterol, phospholipids and apolipoproteins apo-A and apo-AI are highest in the group with the poor metabolic control and differ significantly from the respective values found in patients with mediocre and good metabolic control. Considering biological role of the individual lipids and lipoproteins, it should be stressed that the proper control of glycaemia is important for preventing the development of atherosclerosis in patients with insulin-dependent diabetes.

[Lipid metabolism in patients with insulin dependent diabetes. IV. Effect of sex, age, excess body weight, duration of diabetes, insulin dosage and family history on lipid metabolism in patients with insulin dependent diabetes]. / Stan gospodarki tluszczowej u chorych na cukrzyce insulinozalezna Czesc IV. Wplyw plci, wieku pacjenta, nadmiaru masy ciala, czasu trwania cukrzycy, dawki insuliny oraz obciazen rodzinnych na stan gospodarki tluszczowej u chorych na cukrzyce insulinozalezna.

The levels of the following blood serum lipid constituents: total cholesterol, triglycerides, phospholipids, HDL-cholesterol, apolipoproteins AI, AII and B, and lipoprotein fractions have been determined in patients with insulin-dependent diabetes in relation to sex, age, duration of diabetes, coexistence of obesity, insulin dosage and history of genetic predispositions. The age of the patients was between 1.3 and 22 years and the duration of the disease ranged between 3 months and 15 years. The analysis of the results revealed that sex, age, daily insulin dose and the known genetic predispositions have no influence on the values of the parameters of lipid metabolism. However, an increase in the levels of cholesterol, HDL-cholesterol, triglycerides and apolipoproteins AI and B was observed along with the progressing duration of the disease. An increase in the levels of cholesterol, apolipoprotein B and beta-lipoprotein, and a decrease in the level of alpha-lipoprotein have been found in diabetic children with coexisting obesity. The above analysis indicates that besides metabolic control of diabetes its duration and accompanying obesity may negatively influence the course of the disease contributing to the precocious development of atherosclerosis.

[State of lipid metabolism in children and adolescents with insulin-dependent diabetes. I. Evaluation of lipoprotein (A) behavior in children and adolescents with insulin-dependent diabetes]. / Stan gospodarki tluszczowej u dzieci i mlodziezy z cukrzyca insulinozalezna. Czesc I: Ocena zachowania sie lipoproteiny (A) u dzieci i mlodziezy z cukrzyca insulinozalezna.

The level of lipoprotein Lp(a), one of the risk factors of atherosclerosis, was determined in 91 children and adolescents of age ranging from 3.3 to 22 years suffering from insulin-dependent diabetes. The changes in Lp(a) were analyzed in relation to the group of patients, the duration of diabetes, possible genetic factors, other factors predisposing to early onset of atherosclerosis, and occurrence of obesity in the analyzed group. The relation between the level of Lp(a) and other parameters of lipid metabolism (total cholesterol, triglycerides, phospholipids, HDL-cholesterol and apolipoprotein B) as well as a degree of metabolic normalization of diabetes (as assessed by the determination of glycosylated hemoglobin and fructosamine) was studied in addition. No relation between Lp(a) and the factors mentioned above, with exception of glycosylated hemoglobin and fructosamine concentrations, could be demonstrated. The elevated level of Lp(a) in children and adolescents during the period of poor metabolic control of diabetes may constitute an additional risk factor for early onset of atherogenic changes.

Intellectual functioning of childhood leukemia survivors--relation to Tau protein--a marker of white matter injury.

PURPOSE: Chemo- and radiotherapy used in acute lymphoblastic leukemia (ALL) can influence on brain functioning in the future. In a prospective study we analysed the cognitive functions of ALL survivors in relation to Tau protein as a marker of white matter injury. MATERIAL AND METHODS: Thirty-one survivors of childhood ALL (6.3 years after diagnosis); without the signs of CNS involvement, treated with chemotherapy alone, rested in first remission; underwent Intelligence tests- Wechsler Intelligence Scales (WISC-R, WAIS-R). Their results were analyzed in relation to the levels of Tau in cerebrospinal fluid (CSF) obtained during the treatment. RESULTS: The analysis showed that all survivors attained the average scores in intelligence tests. A negative correlation was found between methotrexate (MTX) doses and Freedom from Distractibility (FFD). Females had higher values of Performance Intelligence Quotient (PIQ) than males. A negative correlation was noted of Tau protein levels obtained from the last CSF with: Total and Verbal Intelligence Quotient, PIQ, Perceptual Organisation Index and FFD but not with Verbal Comprehension Index. CONCLUSION: Our results suggest the possibility of white matter injury during the treatment for ALL with chemotherapy alone. Elevated Tau protein level in CSF at the end of treatment might indicate future difficulties in neurocognitive functioning.