Plasma level studies on different brands of sodium diphenylhydantoin (DPH) and primidone.

Comparative plasma level studies on different brands of sodium diphenylhydantoin (DPH) and primidone are described. Steady state plasma levels of both drugs were measured in epileptic patients who were chronically maintained on this medication. Simultaneous measurements of phenobarbital, primidone and diphenylhydantoin were carried out by gas chromatography. Drug product equivalence and clinical significance of plasma levels of DPH and primidone are discussed.     

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.     

The initiation of parturition at term

This article discusses the initiation of parturition at term.     

Compulsive features in the eating disorders: a role for trauma?

There is considerable evidence of a link between reported childhood trauma and the current presence of impulsive behaviors in eating-disordered populations. However, there is no research testing the possibility of links with compulsive behaviors in this group, despite evidence that both impulsive and compulsive behaviors can serve to affect regulation functions. This study of 62 eating-disordered women examined potential links between different forms of reported childhood trauma (emotional, physical, sexual) and current compulsive behaviors (cleaning, checking). Each woman was interviewed to establish diagnosis, reported trauma history, and the presence of compulsive checking and cleaning behaviors. Chi-squared analyses demonstrated that there were no associations of either emotional or physical abuse with checking or cleaning behaviors. However, there was a significant association of reported childhood sexual abuse with the presence of cleaning behaviors. Although further research is needed to establish the generalizability of this conclusion across diagnostic group and measures, it implies that treatment of eating-disordered patients with comorbid compulsive cleaning behaviors might need to include a focus on the cognitive and affective consequences of childhood sexual abuse.     

PET imaging of the normal human auditory system: responses to speech in quiet and in background noise

The neural mechanisms involved in listening to sentences, and then detecting and verbalizing a specific word are poorly understood, but most likely involve complex neural networks. We used positron emission tomography to identify the areas of the human brain that are activated when young, normal hearing males and females were asked to listen to a sentence and repeat the last word from the Speech in Noise (SPIN) test. Listening conditions were (1) Quiet, (2) Speech, (3) Noise, and (4) SPIN with stimuli presented monaurally to either the left ear or the right ear. The least difficult listening task, Speech, resulted in bilateral activation of superior and middle temporal gyrus and pre-central gyrus. The Noise and SPIN conditions activated many of the same regions as Speech alone plus additional sites within the cerebellum, thalamus and superior/middle frontal gyri. Comparison of the SPIN condition versus Speech revealed additional activation in the right anterior lobe of the cerebellum and right medial frontal gyrus, near the cingulate. None of the left ear–right ear stimulus comparison revealed any significant differences except for the SPIN condition that showed greater activation in the left superior temporal gyrus for stimuli presented to the right ear. No gender differences were observed. These results demonstrate that repeating the last word in a sentence activates mainly auditory and motor areas of the brain when Speech is presented, whereas more difficult tasks, such as SPIN or multi-talker Noise, activate linguistic, attentional, cognitive, working memory, and motor planning areas.