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.     

Familial thyroglossal duct cyst

Thyroglossal duct cysts are common congenital abnormalities or developmental field defects, usually detected in early childhood. Despite their frequent occurrence, familial patterns are rare. We report on two new families with thyroglossal duct cysts. In the first family three siblings were involved, while in the second one, father and son were affected. This trait may be autosomal recessive or possibly multifactorial, as the first family would indicate, and also autosomal dominant, as the second family would suggest.     

Systemic inflammatory mediators and cystic fibrosis genotype

Abstract. Morbidity and mortality in cystic fibrosis patients is mainly attributed to pulmonary infection and inflammation. Chemokines play a pivotal role in the inflammatory process. Although genotype-phenotype correlation in cystic fibrosis patients has been defined, a clear relationship between the defect in the cystic fibrosis transmembrane regulator (CFTR) gene and pulmonary inflammation has not been established. The aim of this study was to assess whether serum chemokines levels in cystic fibrosis patients correlate with genotype and pulmonary function tests, as well as with other clinical characteristics. Serum levels of interleukin-8, RANTES, and monocyte chemoattractant protein-1 were measured in 36 cystic fibrosis patients grouped according to their genotype. Group A included 25 patients who carried two mutations associated with a pathological sweat test and pancreatic insufficiency (F508, W1282X, G542X, N1303K, S549R). Group B included 11 compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat test and pancreatic sufficiency (3849+10kb C to T, 5T). Associations between chemokine levels, genotype, pulmonary function, Pseudomonas aeruginosa colonization, age, sweat chloride level, and pancreatic and nutritional status were examined. Mean interleukin-8 and monocyte chemoattractant protein-1 levels were significantly higher in group A than group B (11.4±2.1 pg/ml vs. 5±0.9 pg/ml and 157±16 pg/ml vs. 88.8±16.4 pg/ml, respectively) (P<0.01). No difference in RANTES levels were found between groups. interleukin-8 levels were inversely related to forced expiratory volume in 1 s (r=-0.37, P<0.02), while there was no association between the latter and RANTES and monocyte chemoattractant protein-1 levels. The Pseudomonas colonization rate was higher among group A patients than group B (88% vs. 40%, P<0.01). No relationship was found between measured chemokines and age, sweat chloride levels, and pancreatic and nutritional status. Our study demonstrates an association between interleukin- 8, forced expiratory volume, and cystic fibrosis genotype. Hence, elevated interleukin-8 serum levels could serve as an indicator of an early inflammatory process and encourage the initiation of anti-inflammatory treatment.     

Comparison of NK activity in mouse spleen and peripheral blood lymphocytes

Natural killer (NK) cells originating in mouse peripheral blood were studied with regard to their lytic activity against YAC-1 target cells and to their expression of asialo-GM1 marker on their surface. In Balb/c, CBA/LAK and A/J mice, PBL were found to be approximately twice as effective as splenocytes. Splenic and peripheral NK cells were shown by flow cytometry to have similar lytic potential per cell; the difference in NK activity found in the spleen and in PBL was solely due to the differences in the size of the NK cell population found in the two sites. Strain distribution of NK activity in PBL followed the same pattern observed in splenocytes. The difference in NK activity between CBA and Balb/c mice was shown to be due to the fact that the lytic potential per NK cell was approximately twice as high in the former.