Prediction of psychosis onset in Alzheimer disease: The role of cognitive impairment, depressive symptoms, and further evidence for psychosis subtypes.

BACKGROUND: Psychotic symptoms in Alzheimer disease (AD+P) identify a heritable phenotype associated with more rapid cognitive decline. The authors have proposed that AD+P is itself a composite of a misidentification and a paranoid subtype with increased cognitive impairment restricted to the misidentification type. Most prior studies of the clinical correlates of AD+P have been limited, however, by the inclusion of prevalent cases. METHODS: Subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis at study entry were assessed at the time of initial presentation and then annually. Psychotic symptoms were assessed using the CERAD Behavioral Rating Scale. Survival analyses used Cox proportional hazard models with time-dependent covariates to examine the predictors of psychosis onset. RESULTS: A total of 288 subjects completed at least one follow-up examination. Mean duration of follow-up was 22.1 months. The incidence of psychosis was 0.19 per person-year. Cognitive impairment was associated with onset of psychosis, largely as a result of its association with onset of the misidentification, but not the paranoid, subtype. Including psychotropic medication use in the model revealed an association of antidepressant use with the onset of psychosis. This latter association appeared to arise from an underlying association between depression and the risk of psychosis onset rather than from antidepressant treatment. CONCLUSION: These findings are consistent with the hypothesis that the misidentification and the paranoid subtypes each define a more biologically homogeneous group than AD+P as a whole. Further exploration of the relationship between depressive symptoms and psychosis in patients with AD is warranted.     

Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumour of the skin, with an estimated incidence of 0.8 to five cases per 1 million people per year. OBJECTIVE: To study epidemiological, immunohistochemical and clinical features, delay in diagnosis, type of treatment and outcome of DFSP from 1982 to 2002. METHODS: Using data from the population-based cancer registry, 66 patients with pathologically proved DFSP were included (fibrosarcomatous DFSP were excluded). Each patient lived in one of the four departments of Franche-Comté (overall population of 1 million people) at the time of diagnosis. The main data sources came from public and private pathology laboratories and medical records. The rules of the International Agency for Research on Cancer were applied. RESULTS: The estimated incidence of DFSP in Franche-Comté was about three new cases per 1 million people per year. Male patients were affected 1.2 times as often as female patients were. The trunk (45%) followed by the proximal extremities (38%) were the most frequent locations. DFSP occurred mainly in young adults between 20 and 39 years of age. Mean age at diagnosis was 43 years, and the mean delay in diagnosis was 10.08 years. Our 66 patients initially underwent a radical local excision. Among them, 27% experienced one or more local recurrences during 9.6 years of follow-up. There was one regional lymph node recurrence without visceral metastases. These recurrences were significantly related to the initial peripheral resection margins. We observed a local recurrence rate of 47% for margins less than 3 cm, vs. only 7% for margins ranging from 3 to 5 cm [P=0.004; OR=0.229 (95%, CI=0.103-0.510)]. The mean time to a first local recurrence was 2.65 years. Nevertheless, there was no death due to the DFSP course at the end of the follow-up, and the final outcome was favourable. CONCLUSION: Our study emphasizes the importance of wide local excision with margins of at least 3 cm in order to prevent local recurrence. However, the recent development of inhibitors of signal transduction by the PDGFB pathway should soon modify the surgical strategy, which is often too mutilating.     

Development of the New Lung Allocation System in the United States

This article reviews the development of the new U.S. lung allocation system that took effect in spring 2005. In 1998, the Health Resources and Services Administration of the U.S. Department of Health and Human Services published the Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule, which became effective in 2000, the OPTN had to demonstrate that existing allocation policies met certain conditions or change the policies to meet a range of criteria, including broader geographic sharing of organs, reducing the use of waiting time as an allocation criterion and creating equitable organ allocation systems using objective medical criteria and medical urgency to allocate donor organs for transplant. This mandate resulted in reviews of all organ allocation policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN Thoracic Organ Transplantation Committee. This paper reviews the deliberations of the Subcommittee in identifying priorities for a new lung allocation system, the analyses undertaken by the OPTN and the Scientific Registry for Transplant Recipients and the evolution of a new lung allocation system that ranks candidates for lungs based on a Lung Allocation Score, incorporating waiting list and posttransplant survival probabilities.     

Entrapment of the C2 root and ganglion by the atlanto-epistrophic ligament: clinical syndrome and surgical anatomy

Two cases of progressive, occipital lancinating pain and dysesthesias associated with a sensory deficit of the C2 dermatome are presented. Symptoms were relieved, and C2 sensory function restored by releasing a hypertrophied atlanto-epistrophic ligament entrapping the C2 root and ganglion. The normal anatomy and abnormal surgical findings are described. C2 entrapment by the atlanto-epistrophic ligament is discussed in reference to other C2 lesions causing occipital pain. We conclude that some patients whose progressive occipital pain is accompanied by a C2 sensory deficit are suffering from entrapment of the C2 root and ganglion amenable to surgical decompression.     

The impact of poverty on educational outcomes for children

Over the past decade, the unfortunate reality is that the income gap has widened between Canadian families. Educational outcomes are one of the key areas influenced by family incomes. Children from low-income families often start school already behind their peers who come from more affluent families, as shown in measures of school readiness. The incidence, depth, duration and timing of poverty all influence a child’s educational attainment, along with community characteristics and social networks. However, both Canadian and international interventions have shown that the effects of poverty can be reduced using sustainable interventions. Paediatricians and family doctors have many opportunities to influence readiness for school and educational success in primary care settings.     

Naphthalimido derivatives as antifolate thymidylate synthase inhibitors

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds.