Late magnetic resonance imaging features of leukoencephalopathy in children with central nervous system tumours following high-dose methotrexate and neuraxis radiation therapy

High-dose methotrexate (HDMTX) is used increasingly to treat children with central nervous system (CNS) tumours. Although the neuro-imaging features of leukoencephalopathy associated with systemic or intrathecal methotrexate administered after cranial radiation have been well described, the extent to which the sequencing of HDMTX prior to cranial radiation in infants and children predisposes to late neuroradiological features of leukoencephalopathy is unknown. This report describes the National Cancer Institute (NCI) toxicity grade of leukoencephalopathy based on magnetic resonance imaging (MRI) findings in all patients who survived 4 or more years after treatment on an earlier phase II study. These patients, with newly diagnosed CNS embryonal tumours, were in the age range 3.5-14.2 years (median 6.9 years) at diagnosis, and received four courses of pre-irradiation combination chemotherapy, including HDMTX 8 g/m(2). Following completion of the 'up-front' phase II study, all patients received conventionally fractionated whole brain doses of 36-50.4 Gy. The radiation dose and treatment volumes were determined individually according to the primary tumour location and results of extent of disease evaluations. The most recent MRI brain scans, obtained 4.0-10.5 years (median 6.5 years) after radiation therapy and comprising a minimum of T1, T1 following gadolinium and T2 sequences, were reviewed centrally to assess the neuroradiological grade of leukoencephalopathy, based on the NCI Common Terminology Criteria for Adverse Events, v3.0. Grade I changes (mild increase in subarachnoid space, and/or mild ventriculomegaly, and/or small/focal T2 hyperintensities) were evident in 8 of the 12 patients and grade II changes (moderate increase in subarachnoid space and/or moderate ventriculomegaly, and/or focal T2 hyperintensities extending to the centrum ovale) were found in the remaining 4. In conclusion, treatment with multiple courses of HDMTX prior to 36-50.4 Gy cranial radiation did not result in moderate to severe MRI features of leukoencephalopathy. Future studies in paediatric neuro-oncology patients, involving HDMTX combined with prospective neuropsychological evaluations appear justified.     

Influence of weight and weight change on bone loss in perimenopausal and early postmenopausal Scottish women

Weight is recognized as an important factor in determining an individuals risk of osteoporosis. However, little is known about whether weight or weight change influences bone loss around the time of the menopause, and the relationship with energy intake and physical activity level remains largely undefined. Healthy premenopausal women (1,064 selected from a random population of 5,119 women aged 45–54 years at baseline) each had bone mineral density (BMD), weight and height measurements, and completed a food frequency and physical activity questionnaire. Of the original participants, 907 women (85.2%) returned 6.3 ± 0.6 years later for repeat BMD measurements, and 896 women completed the questionnaires. Bone loss at the hip (FN) and spine (LS) occurred before the menopause. Weight change rather than weight was associated with FN BMD loss (r=0.102, p=0.002), but weight at follow-up was associated with LS BMD change (r=0.105, p=0.002). Although an increase in physical activity level (PAL) appeared to be beneficial for FN BMD in women who were heavy weight gainers, PAL was associated with increased LS BMD loss in women who lost weight. For current HRT users, neither weight nor weight change was associated with change in BMD. Postmenopausal women not taking HRT should be made aware that low body weight or losing weight during this particularly vulnerable period may worsen bone loss.     

Nuclear magnetic resonance (NMR) imaging of tumors in the posterior fossa

Nuclear magnetic resonance (NMR) images were obtained in 12 patients with mass lesions in the posterior fossa and the results compared with X-ray computed tomography (CT). Inversion recovery T1-weighted images demonstrated abnormalities in six of six intrinsic lesions and three of six extrinsic lesions. Spin echo T2-weighted images demonstrated abnormalities in two of two intrinsic lesions and four of five extrinsic lesions. Saturation recovery T1-weighted images were normal in two of two intrinsic lesions and two of four extrinsic lesions. Overall, NMR detected 11 of 12 lesions. Two intrinsic tumors detected by NMR were not detected by CT evaluation. Two small extrinsic tumors required CT gas cisternography for detection.     

Computed tomography of the orbit with special emphasis on coronal sections: Part I. Normal anatomy

Computed tomography (CT) of the orbit is capable of demonstrating soft tissue structures not visualized yet by any other radiological modality. The possibility of obtaining direct coronal slices has added a new dimension to the study. Direct enlargement viewing on the display console reveals many anatomical details. For better evaluation of pathological findings, an accurate anatomical knowledge is required. The purpose of this study is to report on the normal anatomy of the orbital soft tissues made visible by CT, with emphasis on the coronal views.     

Clinical, hormonal and cytogenetic evaluation of 46,XX males and review of the literature

The main factor influencing the sex determination of an embryo is the genetic sex determined by the presence or absence of the Y chromosome. However, some individuals carry a Y chromosome but are phenotypically female (46,XY females) or have a female karyotype but are phenotypically male (46,XX males). 46,XX maleness is a rare sex reversal syndrome affecting 1 in 20,000 newborn males. Molecular analysis of sex-reversed patients led to the discovery of the SRY gene (sex-determining region on Y). The presence of SRY causes the bipotential gonad to develop into a testis. The majority of 46, SRY-positive XX males have normal genitalia; in contrast SRY-negative XX males usually have genital ambiguity. A small number of SRY-positive XX males also present with ambiguous genitalia. Phenotypic variability observed in 46,XX sex reversed patients cannot be explained only by the presence or absence of SRY despite the fact that SRY is considered to be the major regulatory factor for testis determination. There must be some other genes either in the Y or other autosomal chromosomes involved in the definition of phenotype. In this article, we evaluate four patients with 46,XX male syndrome with various phenotypes. Two of these cases are among the first reported to be diagnosed prenatally.     

Pregnancy outcomes in women with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency

OBJECTIVE: Despite earlier detection, treatment, and surgical advances, fertility prognosis in women with classical 21-hydroxylase deficiency (21-OHD) is still low, especially in the salt-wasting (SW) form. PATIENTS AND METHODS: We analysed the course and outcome of four pregnancies in two simple virilizing (SV) and one SW patient. RESULTS: The evaluation of carrier status indicated that all three fathers had two normal CYP21 genes. During the pregnancy, the dose of prednisolone was increased in one of the SV patients and the SW patient. In the SW patient who developed pre-eclampsia, the dose of fludrocortisone was also increased. Three patients gave birth to a total of four healthy girls who were heterozygotes for 21-OHD with normal genitalia (one by vaginal delivery and three by Caesarean section). Family studies revealed that the mother of the SW patient has nonclassical 21-OHD. CONCLUSION: Improving a low birth rate in females with SW 21-OHD remains a problem and new approaches are required. If the mother has 21-OHD (even nonclassical 21-OHD), pre-conception counselling and paternal genotyping are advisable and prenatal dexamethasone therapy should be considered.     

Caspofungin for invasive fungal infections: combination treatment with liposomal amphotericin B in children undergoing hemopoietic stem cell transplantation

Abstract:  Invasive fungal infections often prove difficult to eradicate especially in the stem cell transplant setting. Amphotericin has been the mainstay of treatment for years but has significant toxicity. Newer antifungal agents, such as caspofungin, have shown promising results in adults, particularly when used in combination with amphotericin as both drugs differ in their mode of action. However, there are few data from children and no previous published information about the use of Caspofungin after paediatric stem cell transplantation. We report our experience in children with proven invasive fungal infections after stem cell transplantation. This combination was non-toxic, and two of three patients survived their infections.     

Brain serotonin transporter distribution in subjects with impulsive aggressivity: a positron emission study with [11C]McN 5652

OBJECTIVE: The serotonin system is believed to play a role in modulating impulsivity and violence. Previous imaging studies have implicated the anterior cingulate and orbitofrontal cortex in impulsive aggression. This study evaluated regional serotonin transporter distribution in the brain of individuals with impulsive aggression by using positron emission tomography (PET) with the serotonin transporter PET radiotracer [(11)C]McN 5652. METHOD: Ten individuals with impulsive aggression and 10 age- and sex-matched healthy comparison subjects underwent [(11)C]McN 5652 PET. All individuals were medication free at the time of scanning. Regional total distribution volumes were derived by using a one-tissue compartment kinetic model with arterial input function. Outcome measures of serotonin transporter availability included the binding potential and the specific-to-nonspecific partition coefficient (V(3)'). RESULTS: Serotonin transporter availability was significantly reduced in the anterior cingulate cortex of individuals with impulsive aggression compared with healthy subjects, as noted by differences in both binding potential (mean=3.1 ml/g [SD=1.9] versus 5.0 ml/g [SD=2.0], respectively) and V(3)' (mean=0.15 [SD=0.09] versus 0.26 [SD=0.09]). In other regions examined, serotonin transporter density was nonsignificantly lower in individuals with impulsive aggression compared with healthy subjects. CONCLUSIONS: Pathological impulsive aggressivity might be associated with lower serotonergic innervation in the anterior cingulate cortex, a region that plays an important role in affective regulation.