Acute lymphoblastic leukemia in children: correlation of musculoskeletal manifestations and immunophenotypes

Purpose Studies on musculoskeletal manifestations (MSM) of childhood acute lymphoblastic leukemia (ALL) have yielded variable findings with regard to their clinical impact. We investigated the significance for differential diagnosis, treatment and outcome of musculoskeletal complaints as presenting symptoms of ALL, and their correlation with leukemia immunophenotypes, for which data is lacking. Methods Data on 783 children in the national study for childhood ALL between 1984 and 2003 were reviewed retrospectively. Statistical analysis examined possible relationships between MSM at the time of diagnosis and demographic and clinical data, biological features of leukemia (peripheral blood counts, immunophenotype and main cytogenetic aberration), response to initial prednisone treatment, and outcome. Results Of 765 children with data on orthopaedic complaints, 240 presented with MSM (31.4%). Among these children, B cell precursor (BCP) was much more common (209/576, 36.3%) than T cell ALL (25/176, 14.2%). Patients with MSM had lower white blood cell counts (WBC) (median of 9 vs. 20 × 10⁹/L, P < 0.001) and percentage of blast cells in the peripheral blood at diagnosis compared to those without (median of 27 vs. 53%, P < 0.001). Hepatomegaly and splenomegaly were less common in MSM group (67 vs. 53% <3 cm, P < 0.001, and 63 vs. 50% <3 cm, P < 0.001, respectively). Poor response to initial treatment with prednisone was recorded in 7.1% of patients with MSM versus 11.5% of those without (P = 0.086). The analysis revealed no independent effect of MSM on event-free survival (EFS), after correcting for differences in EFS related to immunophenotype or initial WBC. Conclusions MSM occur mostly in children with BCP ALL who present with less involvement of extramedullary organs, low peripheral blood blasts and white blood cells counts. These findings highlight the importance of including ALL in the differential diagnosis of MSM even in the presence of an apparently normal peripheral blood count. Our study also suggests that MSM are caused by leukemic cells with enhanced biological propensity to remain relatively confined within the intramedullary bone-marrow space.     

Deficits in spatial coding and feature binding following damage to spatiotopic maps in the human pulvinar.

We report a patient with unilateral damage to the rostral part of the pulvinar who was impaired in localizing stimuli in the inferior visual field contralateral to the lesion and who made errors in the binding of shape and color in that quadrant. The findings demonstrate the importance of the pulvinar in spatial coding and provide support for the function of the thalamus in binding of features. They also provide evidence for a homology between the visual field maps of the inferior and lateral subdivisions of the pulvinar in monkeys and in humans, such that the inferior visual field is represented in the rostral part of the nucleus.     

Role of transrectal ultrasonography in the evaluation of azoospermic men with low-volume ejaculate.

OBJECTIVE: The purpose of this prospective study was to evaluate the incidence of distal ejaculatory system defects with transrectal ultrasonography (TRUS) among patients evaluated for azoospermia. METHODS: Forty-two patients with low-volume ejaculate and azoospermia were evaluated by physical examination, serum follicle-stimulating hormone and luteinizing hormone level determination, karyotyping, selective screening for cystic fibrosis mutations, and TRUS. RESULTS: On physical examination, in 29 patients (69%), either 1 (12 patients) or both (17 patients) of the vasa deferentia could not be palpated. In the group of 17 patients with bilateral involvement of the vasa deferentia, the ultrasonographic imaging universally showed bilateral absence or hypoplasia of the seminal vesicles with bilateral agenesis of the vasa deferentia and nonvisualization of both ejaculatory ducts. In the patients with a unilateral abnormality on physical examination, the ultrasonographic imaging showed absence of the ipsilateral seminal vesicle in 7 patients and the hypoplastic seminal vesicle in 5. In the group of 13 patients with normal physical examination findings, a variety of obstructive causes were diagnosed by TRUS examination. CONCLUSIONS: According to this study, TRUS appears to be a sensitive method for evaluating the anatomy of the distal ejaculatory system. Its safety and low costs make it a good alternative to the other invasive and expensive methods.     

Prognostic significance of caspase-3 expression in primary resected esophageal squamous cell carcinoma.

AIMS: The present study retrospectively examines the expression of caspase-3 in primary resected esophageal squamous cell carcinoma (ESCC) and the correlation between the outcome of patients and the expression of proteins. METHODS: Immunohistochemistry and Western blot analyses were used to analyse the expression of caspase-3 in 40 archival specimens of patients with primary resected ESCC. RESULTS: According to our cut-off point of the staining for caspase-3, 24 (60%) cases were positive and 16 (40%) negative. Caspase-3 expression correlated with a significant favorable prognosis in primary resected ESCC (P=0.02). A multivariate analysis of clinical and biological factors indicated that stage, tumor differentiation, and caspase-3 expression were independent prognostic factors. CONCLUSIONS: Caspase-3 expression might be a good and new prognostic indicator for primary resected ESCC.     

Development of a highly sensitive quantitative competitive PCR assay for the detection of murine cytomegalovirus DNA

Viral persistence and molecular latency are characteristic of infection by the human cytomegalovirus (HCMV). Using the murine cytomegalovirus (MCMV) as a model for human infection, a quantitative-competitive polymerase chain reaction (QC-PCR) assay was developed to detect and quantify MCMV-DNA in the salivary glands of infected mice. The QC-PCR detected high numbers of MCMV DNA copies in the absence of infectious virus. By comparing the DNA content and the results obtained from a standard semiquantitative plaque assay, it is concluded that 1 plaque-forming unit (pfu) is the equivalent of approximately 1500 viral genomes. By day 42-post infection (pi) 4x10(3) copies of DNA/1 mg tissue were sufficient to reactivate infectious virions after cyclophosphamide immunosupression. By day 90 pi, however, when the DNA load was decreased to <1.2x10(2), reactivation was not observed. These results indicate that viral reactivation will occur when the number of infectious DNA copies is equivalent about 2-3 pfu. This quantitative test may therefore help to detect CMV and the risk of reactivation in immunosupressed patients.     

Switching yeast from meiosis to mitosis: double-strand break repair, recombination and synaptonemal complex

Background:

When Saccharomyces cerevisiae cells that have begun meiosis are transferred to mitotic growth conditions (‘return-to-growth’, RTG), they can complete recombination at high meiotic frequencies, but undergo mitotic cell division and remain diploid. It was not known how meiotic recombination intermediates are repaired following RTG. Using molecular and cytological methods, we investigated whether the usual meiotic apparatus could repair meiotically induced DSBs during RTG, or whether other mechanisms are invoked when the developmental context changes.

Results:

Upon RTG, the rapid disappearance of meiotic features—double-strand breaks in DNA (DSBs), synaptonemal complex (SC), and SC related structures—was striking. In wild-type diploids, the repair of meiotic DSBs during RTG was quick and efficient, resulting in homologous recombination. Kinetic analysis of double-strand breakage and recombination indicated that meiotic DSB formation precedes the commitment to meiotic levels of recombination. DSBs were repaired in RTG in dmc1, but not rad51 mutants, hence repair did not occur by the usual meiotic mechanism which requires the Dmc1 gene product. In haploids, DSBs were also repaired quickly and efficiently upon RTG, showing that DSB repair did not require the presence of a homologous chromosome. In all strains examined, SC and related structures were not required for DSB repair or recombination following RTG.

Conclusions:

At least two pathways of DSB repair, which differ from the primary meiotic pathway(s), can occur during RTG: One involving interhomologue recombination, and another involving sister-chromatid exchange. DSB formation precedes commitment to recombination. SC elements appear to prevent sister chromatid exchange in meiosis.

     

The antiatherogenic effect of allicin: possible mode of action.

OBJECTIVE: Garlic (Allium sativum) has been suggested to affect several cardiovascular risk factors. Its antiatherosclerotic properties are mainly attributed to allicin that is produced upon crushing of the garlic clove. Most previous studies used various garlic preparations in which allicin levels were not well defined. In the present study, we evaluated the effects of pure allicin on atherogenesis in experimental mouse models. METHODS AND RESULTS: Daily dietary supplement of allicin, 9 mg/kg body weight, reduced the atherosclerotic plaque area by 68.9 and 56.8% in apolipoprotein E-deficient and low-density lipoprotein (LDL) receptor knockout mice, respectively, as compared with control mice. LDL isolated from allicin-treated groups was more resistant to CuSO(4)-induced oxidation ex vivo than LDL isolated from control mice. Incubation of mouse plasma with (3)H-labeled allicin showed binding of allicin to lipoproteins. By using electron spin resonance, we demonstrated reduced Cu(2+) binding to LDL following allicin treatment. LDL treatment with allicin significantly inhibited both native LDL and oxidized LDL degradation by isolated mouse macrophages. CONCLUSIONS: By using a pure allicin preparation, we were able to show that allicin may affect atherosclerosis not only by acting as an antioxidant, but also by other mechanisms, such as lipoprotein modification and inhibition of LDL uptake and degradation by macrophages.