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.     

Management of drug misusers in police custody.

Police surgeons are increasingly being asked by the police to assess whether drug misusers held in police custody are fit to be detained and fit for interview. There has been little published on how they manage these questions, furthermore the management appears to vary in different parts of the country. This study sets out to determine the attitudes and practise of police surgeons to the management of drug misusers in police custody. A questionnaire was sent to the full members of the Association of Police Surgeons of Great Britain (APSGB) in March 1993. It was found that police surgeons are very aware of the increasing drug problem, indeed 76% reported that they were seeing an increasing number of drug misusers. However, they exhibit significantly negative attitudes to drug misusers and there is no common practice for prescribing controlled drugs. Fifty-two per cent said that on average they notified no drug misusers each month. Seventy-six per cent of respondents said they had received a hepatitis B immunization. The majority of respondents called for more training on drug problems. Therefore, there is an urgent need for specific guidelines for police surgeons on the management of drug misusers in police custody to address the arbitrary nature of the current practice.     

Interpretation of functional series expansions

While much research has been devoted to the implementation and application of Volterra and Wiener functional series expansions in the identification and characterization of biological systems, little effort has been focused on the fundamental problem of interpreting the resulting kernels. This paper describes the application of the series to the components of a known model of the human pupil control system. As more complicated elements are put together, insight into kernel interpretation is built up incrementally until the total system is identified. Practical limitations and methods are also discussed.     

乳酸脱氢酶实验检测细胞新陈代谢的实验研究

目的 探索LDH实验检测细胞活力的可行性。方法 原代培养骨髓细胞和软骨细胞，用LDH实验测定上述两组细胞的活力，并与镜下活体观察到细胞的生长状况相比较。与目前比较成熟的测定细胞活力的MTS实验的测得的值相比较。结果 LDH实验对上述两组细胞的活力的测定结果与镜下活体观察到的结果相符合。与MTS实验的测得的结果经统计学处理无显著差异。结论 LDH实验可用于细胞活力的直接测定，而对活细胞的生存、繁殖无影响。     

Dynamic spin-echo MRI of liver cancer using Gadolinium-DTPA: animal investigation

An animal model of liver cancer was used to demonstrate that with a fast MRI technique, Gadolinium-DTPA increases tumor-liver contrast. A spin-echo pulse sequence with short repetition (TR) and echo-delay (TE) times (TR 250/TE 15/Excitations 1) has a scan time of 0.6 min, which allows early dynamic postcontrast infusion imaging. This is necessary to capture peak compartmental differences when an extracellular contrast agent such as Gadolinium-DTPA is used. This short TR/short TE pulse sequence also increases T1-dependent tissue contrast over the traditional (inversion recovery or spin echo) T1-weighted pulse sequences. Our studies suggest a significant potential for improved detection of liver metastases with Gadolinium-DTPA-enhanced liver MRI.     

Childhood Malignant Thymoma: Clinical, Therapeutic, and Immunohistochemical Considerations

Malignant thymomas are among the least common mediastinal tumors in the pediatric age group. Thymomas are considered malignant on the basis of macroscopic and microscopic invasiveness. As only 20 well-documented cases involving children have been reported in the literature, the pattern of responsiveness to therapy and the value of prognostic signs is obscure. Two cases of malignant pediatric thymomas are reported with pathognomonic histoimmunological features of aggressive thymoma. One was cured, with a follow-up of 70 months, and one died while on therapy. Analysis of the histological features and the immunoperoxidase staining displays the complexity of pediatric thymomas and the inability to prognosticate the outcome, respectively.     

Quantitation of T2′ anisotropic effects on magnetic resonance bone mineral density measurement

In this paper, the authors quantitate the anisotropy of susceptibility effects in an uniaxial trabecular bone model and show its relevance to clinical MR bone mineral density measurements. A physical model is described that quantitates the anisotropic MR behavior of uniaxial trabecular bone. To test the model, a phantom of parallel polyethylene filaments was scanned every 15° between 0° and 90° with respect to the system's main magnetic field (B₀). The distal radial metaphysis of a healthy female volunteer was scanned in orthogonal projections. The signal from each phantom image and each radial image was separated in a pixel-wise fashion into R₂ and R₂′ maps. As predicted, R₂′ relaxation showed anisotropic behavior and changed according to sin² (?), confirming that columnar structures parallel with B₀ will cause no MR susceptibility effects. Scans of the distal radius showed that R₂′ relaxation was twice as great with the forearm perpendicular to B₀ as when it was parallel to it, demonstrating different contributions from struts and columns. For both phantom and radial bone scans, R₂ relaxation was isotropic and did not change with object orientation.     

Time after excision and temperature alter ex vivo tissue relaxation time measurements

Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40°C, at room temperature (28°C), or in an ice bath (4°C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40°C (20-MHz spectrometer), the T1 of liver decreased from 280 msec ± 8 to 212 msec ± 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec ± 3 to 208 msec ± 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors.