Effectiveness of Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) Compared to Fluoride Products in an In-Vitro Demineralization Model

The goal of this study was to evaluate the effectiveness of the toothpaste Tooth Mousse compared to conventional fluoride-based versions in the prevention of enamel and dentin demineralization. Human enamel and dentin samples (n = 120 each) were exposed to artificial demineralization at pH 4.92. During the demineralization process, the samples in the test groups were periodically treated with Tooth Mousse (TM) containing casein-phosphopeptide -amorphous-calcium-phosphate (CPP-ACP) and Tooth Mousse Plus (TMP) containing amorphous-calcium-fluoride-phosphate (CPP-ACPF) to evaluate their protective properties. Fluoride toothpastes containing 1400 ppm amine fluoride (AmF) and 1450 ppm sodium fluoride (NaF) were applied in the positive control groups. Treatment with distilled water (group C-W) or demineralization without treatment (group C-D) served as negative controls. After the demineralization and treatment process, all samples were cut longitudinally and lesion depths were determined at six locations using polarized light microscopy. In TM/TMP groups (enamel: 80/86 µm, dentin: 153/156 µm) lesion depths were significantly smaller compared to the negative control groups C-W/C-D (enamel: 99/111 µm, dentin: 163/166 µm). However, TM and TMP compared to the positive controls AmF/NaF (enamel: 58/63 µm, dentin: 87/109 µm) showed higher lesion depths. The application of TM/TMP (89%/78%) during demineralization led to a reduced number of severe lesions compared to the negative controls C-W/C-D (100%/95%). In this study we demonstrate that Tooth Mousse is less effective regarding prevention of enamel and dentin demineralization compared to fluoride containing toothpastes.     

Oral condition in children treated with bone marrow transplantation

Oral health was studied in 49 children below 12 years of age treated with bone marrow transplantation (BMT). Dental treatment prior to BMT was required in 41% of the children. Ulceration of the mucous membranes in the mouth was observed in 37% of the patients during treatment. Those given methotrexate as prophylaxis against graft-versus-host disease (GVHD) exhibited oral ulcerations more frequently (p less than 0.05) than those given cyclosporin. One year after BMT all patients with a clinical chronic GVHD exhibited changes in the oral mucosa. During the first year after BMT 31% of the children developed carious lesions. Children treated with 10 Gy total body irradiation (TBI) had a significantly (p less than 0.05) reduced salivary secretion rate. Dental development was severely affected in children treated with TBI. These disturbances consisted of arrested root development, enamel hypoplasias and microdontia.     

Oropharyngeal mucositis complicating bone marrow transplantation: prognostic factors and the effect of chlorhexidine mouth rinse

Oral mucosal ulceration complicating bone marrow transplantation interferes with patients' comfort, nutrition and may lead to systemic infection derived from the mouth. The mucosal injury results from epithelial damage due to the cytotoxic effects of chemotherapy and radiation conditioning as well as from superficial oropharyngeal infection. Because chlorhexidine gluconate is a broad spectrum topical antimicrobial which has been demonstrably effective in preventing oral infection and gingivitis, we performed a randomized, placebo controlled, double-blind trial of chlorhexidine as a mouth rinse in BMT recipients to study the severity of oral mucositis and both oral and systemic infectious complications. One hundred patients were randomly assigned to receive either chlorhexidine gluconate 0.12% mouth rinse or placebo three times daily from the initiation (day -8) of chemoradiotherapy conditioning until day +35 post-BMT. Chlorhexidine use resulted in a trend toward improved oral hygiene index (reduced dental plaque) (p = 0.06) but did not modify the oral mucositis. Patients using chlorhexidine developed a maximum ulceration of 18 +/- 22% of their oral mucosa, while placebo patients ulcerated 25 +/- 31% of the mouth. Ulcerative mucositis was significantly worse in adults compared with children, in individuals who received methotrexate for graft-versus-host disease prophylaxis, and was most prominent on non-keratinized epithelium. Overall, there was no clinically demonstrable additional therapeutic advantage to the use of chlorhexidine in either reducing the mucositis, controlling oral pain, facilitating oral nutrition, shortening hospital stay, or reducing oral infection with herpes simplex virus. There was a trend toward diminished oral candidiasis in chlorhexidine users (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)     

癌基因MDM2mRNA在儿童急性淋巴细胞白血病的过度表达（附32例报告）

应用逆转录聚合酶链反应方法检测32例急性淋巴细胞白血病（ALL）患儿的外周血单个核细胞MDM2mRNA表达,以β-actin为内参照,对结果进行半定量。结果 MDM2mRNA在儿童ALL中过度表达率明显高于正常对照组;在不良预后组、高白细胞性白血病组中的表达分别高于一般预后组、非高白细胞白血病组。认为MDM2过度表达在儿童ALL发病中起有重要作用,并与儿童ALL的不良预后、高白细胞性有显著相关性。     

Oral health in adult patients with congenital coagulation disorders – a case control study

Summary. Inflammatory disorders of the periodontium, gingivitis and periodontitis are among the most prevalent diseases worldwide. A few studies have found poorer oral health in patients with congenital coagulation disorders (CCD) like haemophilia and von Willebrand’s disease compared with non‐affected controls. The aim of this study was to investigate the effect of congenital coagulation disorders on oral health and periodontal (alveolar) bone loss. This is a case control study comparing oral health and periodontal bone loss of patient with congenital coagulation disorders with matched healthy subjects. The examination included dental status (DMF‐T), assessment of oral hygiene (modified Quigley‐Hein‐Index: QHI) and a dental panoramic X‐ray for assessment of alveolar bone loss caused by periodontal disease. A total of 15 patients with CCD (Haemophilia A: n = 8, von Willebrand’s disease: n = 7) were matched with 31 non‐affected controls. We observed no clinical relevant difference of oral health (DMF‐T, QHI) between patients with CCD and controls despite better oral hygiene (QHI) of patients with CCD. Moreover, there was a statistically significant difference in periodontal bone loss, but the observed difference is not clinically meaningful. Unlike previous studies carried out mainly in children we found no evidence that oral health or periodontal status in adult patients with CCD is worse than that in healthy subjects. However, larger studies and longitudinal studies in adults are needed to confirm our results.     

Increased risk for invasive pneumococcal diseases in children with acute lymphoblastic leukaemia

Asplenia and other conditions of immunodeficiency are established risk factors for invasive pneumococcal disease (IPD). There are no current data available on the risk of IPD in children with acute lymphoblastic leukaemia (ALL), the most common type of childhood malignancy. This study combined data from a nation-wide surveillance for IPD and the German childhood cancer registry, and showed that children with ALL carry a more than 10-fold higher risk for IPD than the general paediatric population. As a substantial proportion of IPD occurs during maintenance chemotherapy, children with ALL may represent candidates for the evaluation of prophylactic interventions including vaccination.     

Purine metabolism enzyme pattern, cytochemical characteristics and clinicopathologic features of CD10-positive childhood T-cell leukemia.

Purine metabolism enzyme pattern, cytochemical markers and clinicopathologic features of common acute lymphoblastic leukemia antigen (cALLA; CD10)-positive, CD10-negative T acute lymphoblastic leukemia (ALL), and cALLA-positive non-T, non-B ALL (common ALL; C ALL) of children were compared. The results of immunophenotyping of blast cells in 61 children with ALL who were treated and followed during the last 7 years at the Second Pediatric Clinic in Bratislava are presented. The aim of our study was to determine the correlation of CD10 marker expression with purine enzyme activities and clinical course in ALL of children. Immunologic phenotype performed by a panel of monoclonal antibodies in indirect immunofluorescence assay revealed 3 main ALL groups: Common ALL (C ALL), T ALL and CD10+ T ALL (C + T ALL). An additional exact cytochemical marker analysis was performed in these three ALL immunologic subtypes. Two enzymes of purine metabolism, i.e. adenosine deaminase (ADA) and purine nucleosidephosphorylase (PNP) were investigated in blast cells by paper radiochromatography. Life-table analysis revealed significant prognostic differences with regard to event-free survival and overall survival in followed groups of ALL patients. Our results showed a rather high frequency of mixed (C + T) ALL phenotype. The characteristic T ALL enzyme pattern (high ADA, low PNP) was present not only in T, but also in CD10+ T ALL blast cells. The T cell marker showed to be dominant in the determination of clinical course and prognostic significance in children with ALL; children with T and CD10+ T ALL phenotype, in contrast to C ALL phenotype, experienced more frequent relapses and a shorter event-free survival.     

Acute lymphoblastic leukaemia in children with Down syndrome: an updated review

Down syndrome (DS) is the most common chromosomal abnormality in children and also carries a marked increased incidence of acute leukaemia. Current therapy for acute lymphoblastic leukaemia (ALL) in children with DS offers similar treatment outcome as compared to children without DS. However, in general, there is increased morbidity associated with chemotherapy in children with DS. In recent years, a better understanding of the biology of ALL has led to the elucidation of differences in DS ALL vs non-DS ALL. Further research in these differences may provide a more targeted therapy for DS ALL, with the hopes of continuing good therapeutic outcome while decreasing the toxicities seen in these patients. This review provides an update on the current treatment outcomes and the biological differences seen in DS ALL.     

Oral and dental health status in patients with primary antibody deficiencies

Primary antibody deficiencies (PAD) are a group of immune system disorders, associated with decreased levels of secretory and protective immunoglobulins. Because of the important role of immunoglobulins in the protection of oral cavity, patients with PADs are more susceptible to dental caries or oral manifestations. This study was performed to investigate the oral and dental manifestations of PADs patients. In this study, 33 patients with PADs (21 common variable immunodeficiency, 8 X-linked agammaglobulinemia and 4 hyper IgM syndrome) and 66 controls were examined; the number of decayed, missed and filled teeth (DMFT) were investigated. Aphthous was the most frequent manifestation in PADs patients (38.7%), which was significantly 16.7% higher than the controls (p=0.03). The patients with PADs showed significantly higher presentation of other oral and dental manifestations, including herpes sores, candidiasis tonsillitis, gingivitis, calculus, enamel hypoplasia and other ulcerations. The mean DMFT scores were 6.15±3.6 and 1.93±0.4 in PADs patients and controls, respectively (p<0.001). Although the patients with common variable immunodeficiency had higher means of DMFT in comparison with other groups of PADs, this difference was not statistically significant. This study showed significantly higher frequency of oral and dental manifestations in the patients with PADs compared to controls. Therefore, regular examination of oral cavity could be suggested in this group of immunodeficient patients.     

Motility of leukemic cells in collagen gel related to immunological phenotype in childhood acute lymphoblastic leukemia

Motility of leukemic cells was measured in a three-dimensional collagen matrix assay. Leukemic cells from 16 children with acute lymphoblastic leukemia (ALL) and normal peripheral blood lymphocytes (NPBL) from 6 healthy volunteers, were allowed to migrate into this collagen matrix for 48 h at 37 degrees C. NPBL migrated much further (300-600 micron) than leukemic cells (0-200 micron). Among the leukemic cases, only common ALL and one case of null ALL showed some migration (0-200 micron). T-All cells did not migrate at all under the circumstances of this experiment.     

Dental health indices and caries-related microflora in children with severe haemophilia

The purpose of this work was to investigate the prevalence of dental caries, bacterial dental plaque, gingivitis, enamel defects and caries- related microflora in children with severe haemophilia. Thirty-eight children with severe haemophilia (factor VIII and IX < 2 U dL(-1)) were recruited from Great Ormond Street Hospital for Children and matched for age, gender and ethnicity with healthy control children from the Eastman Dental Institute. Indices were recorded for decayed, missing, and filled teeth and surfaces in both the deciduous dentition (dmfs/dmft) and the permanent dentition (DMFS/DMFT). The plaque and gingivitis scores and developmental enamel defects were also recorded. The caries-related microflora was sampled and cultured for Streptococcus mutans, and Lactobacilli and Candida species. A significantly greater proportion of children with severe haemophilia were caries-free compared with the controls (36.7% vs. 13.3%; P=0.04). Both the DMFS and DMFT were significantly greater in the controls (3.6 and 2.8, respectively) compared with the haemophilia group, (0.8 and 0.7; P=0.007 and P=0.04). The plaque score for the permanent dentition only was significantly greater for the control children (24.2) compared with the haemophilia group, (10.2; P=0.04). The mean number of colony forming units of S. mutans was significantly greater in the control group compared with the haemophilia group (P=0.05). We conclude that children with severe haemophilia have a significantly lower prevalence of dental caries compared with matched, healthy controls.     

Role of MTHFR genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia

The central role of methylenetetrahydrofolate reductase (MTHFR) in the folate metabolism renders MTHFR gene polymorphisms (C677T and A1298C) potential modulators of a variety of disorders whose development depends on folate/homocysteine imbalance. Here, we provide additional evidence on the protective role of these polymorphisms in acute lymphoblastic leukemia (ALL), the most common pediatric cancer. A case-control study was conducted in 270 ALL patients and 300 healthy controls of French-Canadian origin. The TT677/AA1298 and CC677/CC1298 individuals were associated with reduced risk of ALL (crude odds ratio [OR] = 0.4; 95% confidence interval [CI], 0.2-0.9; and OR = 0.3; 95% CI, 0.1-0.6; respectively). Further stratification in patients born before and after January 1996 (approximate time of Health Canada recommendation for folic acid supplement in pregnancy) revealed that the protective effect of MTHFR variants is accentuated and present only in children born before 1996. Similar results were obtained when a transmission disequilibrium test was performed on a subset of children (n = 95) in a family-based study. This finding suggests gene-environment interaction and its role in the susceptibility to childhood ALL, which is consistent with previous findings associating either folate deficiency or MTHFR polymorphisms with risk of leukemia.     

Total body irradiation, fludarabine, melphalan, and allogeneic hematopoietic stem cell transplantation for advanced pediatric hematologic malignancies

We evaluated the efficacy and toxicity of adding 9 Gy of total body irradiation (TBI), in three single daily fractions of 3 Gy, to the reduced intensity regimen of fludarabine 30 mg/m2 i.v. x 4 days and melphalan 140 mg/m2 i.v. x 1 day in advanced pediatric hematologic malignancies. Twenty-two acute lymphoblastic leukemia (ALL), six acute myeloid leukemia (AML), and one non-Hodgkin lymphoma patients were transplanted. Of these, 13 were beyond second remission, and five had prior hematopoietic stem cell transplant (HSCT). Twenty-one donors were unrelated, of which 19 were from cord blood (CB) units. Three of the eight related donors were genotypically disparate. Oral mucositis and diarrhea were the most common toxicities. Twenty-seven patients achieved neutrophil engraftment (median 16 days), and 23 had platelet engraftment (median 42 days). One patient had primary graft failure. Seven patients died of non-relapse causes in the first 100 days. With a median follow-up of 52 months, seven of 22 ALL, five of six AML, and one of one lymphoma patients are alive and in remission. The regimen of TBI, fludarabine, and melphalan allows the engraftment of allogeneic hematopoietic stem cells (including mismatched CB). It was fairly well tolerated in pediatric patients, even for second transplants. Its efficacy requires further evaluation.     

Expression and production of aberrant PAX5 with deletion of exon 8 in B-lineage acute lymphoblastic leukaemia of children

Summary We investigated PAX5 expression in childhood B-lineage acute lymphoblastic leukaemia (ALL). Seven of 21 children with B-lineage ALL had multiple PAX5 variants, while 14 children and healthy controls showed full-length (FL) and one variant PAX5. By Western blotting, healthy controls displayed Pax5-FL, while one short Pax5, derived from the deletion of exon 8 (Pax5-DeltaE8) was produced in 90% of ALL samples, as well as in ALL cell lines. PAX5-DeltaE8 lacked more than 50% of the transactivation domain, indicating that aberrant Pax5 production might lead to the arrest of B-cell differentiation, contributing to the pathogenesis of B-lineage ALL.     

Methotrexate-induced mucositis in acute leukemia patients is not associated with the MTHFR 677T allele in Mexico

Methylenetetrahydrofolate reductase (MTHFR) has two common variants with reduced activity due to polymorphisms at nucleotides 677 and 1298. Both affect folate metabolism and thus remethylation of homocysteine, but are also thought to affect nucleotide synthesis and DNA methylation. Methotrexate (MTX), which interrupts folate metabolism, is used in the treatment of a variety of diseases including acute lymphoblastic leukemia (ALL), but exerts in some patients toxic effects on fast dividing tissues such as mucosal epithelia. The enhanced toxicity may be due to cooperative effects between MTX and MTHFR variants. Accordingly, it has been reported that carrying the 677T allele of the MTHFR is a risk factor for MTX-associated mucositis. As in the Mexican population, which is characterized by a high prevalence of the 677T MTHFR variant, several of its commonly associated defects have not been observed, we investigated the relationship between MTX toxicity and the 677T allele. Out of 28 patients with ALL (CC: 2, CT: 10, TT: 16), 16 had episodes of MTX-associated mucositis (CC: 0, CT: 6, TT: 10). Neither at the gene level nor at the genotype level was a significant association with mucositis found. It may be postulated that the risk of higher MTX toxicity in patients with decreased MTHFR activity could be neutralized by the normally folate rich diet in Mexico.     

Immunological phenotype related to acid alpha-naphthyl acetate esterase and acid phosphatase in childhood acute lymphoblastic leukaemia

In 83 children with acute lymphoblastic leukaemia (ALL) the immunological phenotype of the lymphoblasts was determined using E rosetting, monoclonal anti-T cell sera, surface immunoglobulin staining and common ALL antiserum. The data were compared with acid alpha-naphthyl acetate esterase (ANAE) and acid phosphatase (AP) cytochemical data. The vast majority of T-ALL cells proved to be ANAE-negative (30/31) and AP-positive (29/31). Null-ALL was always AP-negative (12/12), the ANAE reaction was sometimes positive (4/12). In common ALL, findings ranged from negative to positive for both enzymes. Two cases of B-ALL were ANAE-negative and AP-negative. Enzyme cytochemical determinations gave thus preferential patterns, especially for T-ALL and null-ALL. In common ALL, considerable heterogeneity was found, which may be a reflection of differences in maturation between different cases of common ALL.     

Acute tumour lysis syndrome following a single-dose corticosteroid in children with acute lymphoblastic leukaemia

Acute tumour lysis syndrome (ATLS) is a well recognised complication of treatment of a variety of malignant disorders. It commonly occurs in patients with non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukaemia (ALL) with the administration of combined cytotoxic chemotherapy. It is rarely reported after single-agent corticosteroid therapy. We present two children with acute lymphoblastic leukaemia of T-cell lineage who developed acute tumour lysis syndrome after a single dose of prednisolone, and methylprednisolone at the beginning of the induction chemotherapy. In the first case (an 11-yr-old) ATLS had occurred after an oral dose of prednisolone as small as 12 mg and within 18 h. The second case was a 14-yr-old boy with ALL who developed ATLS following a single dose of methylprednisolone. A few similar cases in the English literature are summarised in the report. These cases indicate that acute tumour lysis syndrome may occur after a single dose of corticosteroids. One should be aware of this potentially life-threatening complication especially while prescribing corticosteroids to patients with NHL and leukaemia.     

Local hemostasis after tooth extraction in patients with abnormal hemostatic function. Use of human fibrinogen concentrate

Tooth extraction was carried out in 405 patients with various hemostatic disorders due to thrombocytopenia, chronic liver disease, hemophilia A and B, von Willebrand's disease and oral anticoagulants. Human fibrinogen concentrate was used as local hemostatic agent. Prophylactic replacement therapy (platelets or plasma concentrates) and antifibrinolytic agents were not administered. Oral anticoagulants were not discontinued. Minor postextraction bleeding occurred only in severe hemophilia A and occasionally in the oral anticoagulant group.     

Suppressed neutrophil function in children with acute lymphoblastic leukemia

Infection is a major obstacle in cancer chemotherapy. Neutropenia has been considered to be the most important risk factor for severe infection; however, other factors, such as impaired neutrophil function, may be involved in susceptibility to infection in patients undergoing chemotherapy. In this study, we analyzed neutrophil function in children with acute lymphoblastic leukemia (ALL). Whole blood samples were obtained from 16 children with ALL at diagnosis, after induction chemotherapy, and after consolidation chemotherapy. Oxidative burst and phagocytic activity of neutrophils were analyzed by flow cytometry. Oxidative burst of neutrophils was impaired in ALL patients. The percentage of neutrophils with normal oxidative burst after PMA stimulation was 59.0 ± 13.2 or 70.0 ± 21.0% at diagnosis or after induction chemotherapy, respectively, which was significantly lower compared with 93.8 ± 6.1% in healthy control subjects (P = 0.00004, or 0.002, respectively); however, this value was normal after consolidation chemotherapy. No significant differences were noted in phagocytic activity in children with ALL compared with healthy control subjects. Impaired oxidative burst of neutrophils may be one risk factor for infections in children with ALL, especially in the initial periods of treatment.