AbstractIn ninety-three cases of newly diagnosed acute myeloid leukaemia (AML) we investigated the importance to short- and long term clinical outcome of the in vitro short term leukaemia cell survival as measured by a 4-day MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide)-assay. In 67 patients treated by intravenous remission induction therapy we found that patients who after the first induction cycle or after induction therapy overall achieved a complete remission (CR) had leukaemia cells with significantly lower in vitro cell survival ability than cells of non-responders (p=0.02 and 0.06, respectively). These relations remained statistically significant in subsequent multivariate analyses. Likewise, a favourable effect of low in vitro leukaemia cell survival on overall survival of the patients was detected in the (largest) subgroup of adult patients treated uniformly by the same remission induction regimen as well as in all patients. However, in the 44 patients, who achieved CR, the in vitro leukaemia cell survival did not show significance to remission duration or time to first relapse. Furthermore, the leukaemia cell survival (MTT-assay) did not to correlate with the Bcl-2 expression level (quantitative flow cytometry) of the leukaemia cells (r=0.18, n=34, p=0.32). In addition, in a cell line model employing the growth factor dependent MO7 human AML cell line, growth factor withdrawal was associated with rapid onset of cellular apoptosis as evaluated by morphology, occurrence of a subGl peak in DNA histograms, and loss of cellular activity in the MTT-assay. In contrast, a more moderate decline in Bcl-2 expression and gradual loss of ability to exclude the trypan blue dye was seen in the leukaemia cells in response to growth factor withdrawal. We conclude, that the MTT-assay provides a simple and sensitive method for measuring in vitro cell survival. The differences in leukaemia cell survival seen in AML may well be clinically relevant and may help to provide a better understanding of clinical drug resistance.Key Words: MTT-assayleukaemia cell survivalapoptosisprognosis
ABSTRACT. Beta 2 ‐microglobulin (β 2 m) is synthesized particularly in lymphocytes. Its value for early detection of central nervous system (CNS) involvement in acute lymphoblastic leukemia in children was tested by serial determinations. Before 9 overt CNS relapses, the mean increase of the cerebrospinal fluid (CSF) β 2 m concentration was 588 μg/l/month (range: ‐50 to +2020), which was significantly higher than the steady levels during maintenance treatment. Although the absolute value of CSF β 2 m was increased to 1430 μg/l in the group with overt CNS relapse, individual variations in CSF β 2 m before a relapse were so great that no difference was seen between samples from CSF with or without lymphoblasts. The ratio between β 2 m in the CSF and in serum did not increase in serial samples prior to overt relapse, but the ratio was higher in patients with CNS relapse compared with a control group on maintenance therapy. In 9 children without CNS leukemia, the β 2 m concentration in CSF and serum decreased to a nadir 4 weeks after the start of induction treatment. The subsequent increase of CSF β 2 m was similar to the increase before a CNS relapse. Mean values of CSF β 2 m changes differed between groups of children with and without CNS leukemia early in the induction phase and during the maintenance treatment, but the wide range in individual values made serial β 2 m determinations unsuitable for detecting a CNS relapse.
Three siblings with Morquio’s syndrome are described. Cultured fibroblasts from the youngest sibling demonstrated a total absence of N‐acethylgalactosamine‐6‐sulphate‐sulphatase whereas β–galactocidase activity was normal, thus verifying the diagnosis of MPS‐IV A. Dental features such as pointed cusps, spade‐shaped incisors, thin enamel and pitted buccal surfaces were observed in all three children. Furthermore, in all three siblings the TMJ was affected with severe resorption of the head of the condyle. Histological examination of exfoliated primary molars showed a band of increased porosity following the striae of Retzius in the outer part of the enamel. These developmental disturbances were occasionally associated with minor localized defects in the enamel surface. The importance of close monitoring of dental development and regular dental care in order to prevent attrition of the teeth, loss of vertical face height and subsequent risk of TMJ dysfunction is emphasized.
Abstract Background We evaluated the inter-rater agreement between self-assessed Tanner staging and clinical examination and the intra-individual agreement of self-assessed information on various puberty markers in late adolescents from the longitudinal nationwide Puberty Cohort, a sub-cohort of the Danish National Birth Cohort (DNBC). Methods We invited 715 children from the ongoing Puberty Cohort between June 2016 and January 2017. In total, 366 children (51%) returned an add-on questionnaire identical to the questionnaire used to collect information on puberty markers, including Tanner staging, in the Puberty Cohort. Of these, 197 (54%) also participated in a clinical examination with Tanner staging. We used percentage agreement and weighted kappa statistics to evaluate the inter-rater and intra-individual agreement. Results Due to late entry, more than 75% of children were Tanner stage 4 or above at clinical examination. In girls, the inter-rater agreement for pubic hair and breast staging was 54% and 52%, respectively, yielding weighted kappas of fair strength. In boys, pubic hair and genital staging agreed in 55% and 33%, respectively, corresponding to weighted kappas of fair to moderate strength. Boys tended to underestimate genitalia staging consistently. The intra-individual agreement on Tanner staging was 75–77% in girls and 69% in boys, whereas the intra-individual agreement on axillary hair and acne was above 92%. Conclusions Self-assessment of late stages of pubertal development may be misclassified, leading to random errors in studies of puberty timing. However, self-assessment continues to serve as an important time- and cost-saving tool in large prospective puberty cohorts.
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