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.     

Effect of intralipid on the phagocytic and microbicidal capacity of human monocytes in culture

We studied the effect of Intralipid (IL) in monocyte cultures based on the ability of the cultures to phagocytose and kill Candida albicans and produce the oxidative burst. The IL was taken up by monocytes in cultures, and these cells phagocytosed more Candida organisms than did the control cells [85 +/- 2.2% in the IL treated (1%) compared to 68 +/- 2.3% after 1 h in the control]. The percentage of killing of Candida albicans, which had been taken up by the IL-treated monocytes measured after 2 h in culture (48.3 +/- 6.0%), was no different when compared to control (47.0 +/- 5.8%). Following ingestion of IL, there was an increase in basal H2O2 production, however, the presence of the IL in the cells had no effect on the expected increase in H2O2 production following stimulation with either phorbol myristate acetate (PMA) or zymosan particles. Compared to untreated cells, a significant increase in the number of monocytes with positive nitroblue tetrazolium staining was observed in monocytes that had ingested IL (when they were stimulated with either PMA or Candida microorganisms). Similar results were obtained in monocyte-derived macrophages (i.e., monocytes in monolayer cultures for 10 days). These findings suggest that the essential monocyte functions of phagocytosis, microbicidal activity, and ability to elicit an oxidative burst are not directly altered by the conventional use of IL in clinical practice.     

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.     

Testicular testosterone biosynthesis in male Saanen goats with XX sex chromosomes

Testosterone biosynthesis was examined in three pairs of twin male Saanen goats. In each pair, one goat was a phenotypically normal male of XY chromosome constitution; the other showed testicular hypoplasia of the sort typically associated with homozygosity for the dominant gene for polledness in genetic females, and was of XX chromosome constitution.
The histological and hormonal situations in the hypoplastic male goats resembled those found in Kleinfelter and XX human males, both in their nature and in their variability. Histological examination of the testes of the hypoplastic XX males showed various degrees of degeneration. In one case a "sperm pocket" full of spermatozoa was observed, and in this case sperm cells with heads separated from tails were observed in the semen. In the other two cases semen was devoid of sperm cells. In two cases plasma testosterone levels of the hypoplastic goats were lower than those of their normal counterparts, in one of the cases much lower. When testicular microsomal fractions of these goats were tested for their in vitro ability to bring about the conversion of androstenedione to testosterone, it was observed that 17β-hydroxysteroid dehydrogenase activity was either absent or lower in the hypoplastic goats than in their normal twins. In the third pair of animals, plasma testosterone levels were similar in both normal and hypoplastic animals. In this case, however, the increase in testosterone levels following HCG administration was lower in the hypoplastic than in the normal goats. 3β-hydroxysteroid dehydrogenase was the same in normal and hypoplastic goats. The variable effects on testosterone biosynthesis support the notion that the sex chromosomes, while affecting steroid biosynthesis in the testis, do so indirectly.