Screening for eating disorders and high-risk behavior: caution

OBJECTIVE: The current study reviews the state of eating disorder screens. METHODS: Screens were classified by their purported screening function: identification of cases with (a) anorexia nervosa only; (b) bulimia nervosa only; (c) eating disorders in general; (d) partial syndrome, eating disorder not otherwise specified (EDNOS), or subclinical; (e) not a-d but at high risk. Information is presented on development, psychometric properties, and external validation (e.g., sensitivity, specificity, positive predictive values, and negative predictive values). RESULTS: Screens differ widely with regard to objective, psychometric properties and the validation methodology used. Most screens that identify cases are not appropriate for the identification of at-risk behaviors. Little data on the external validity of screens are available. DISCUSSION: Screens should be used with caution. A sequential procedure, in which subjects identified as being at risk during the first stage is followed by more specific diagnostic tests during the second stage, might overcome some of the limitations of the one-stage screening approach.     

Preeclampsia in the parous woman: who is at risk?

OBJECTIVE: The purpose of this study was to identify risk factors for preeclampsia in second pregnancies and to determine whether gestational age at delivery in the first pregnancy increases the risk of recurrent preeclampsia. STUDY DESIGN: We conducted a population-based, case-control study using birth certificate data from the Missouri maternally linked cohort. Data from women delivered of their first 2 singleton pregnancies between 1989 and 1997 (2332 cases with preeclampsia in the second pregnancy and 2370 control cases) were analyzed with logistic regression. RESULTS: Significant risk factors for preeclampsia in a second pregnancy include longer birth interval, previous preterm delivery, previous small-for-gestational-age newborn, renal disease, chronic hypertension, diabetes mellitus, obesity, black race, and inadequate prenatal care. Smoking and same paternity are protective. A history of preeclampsia confers the highest risk for preeclampsia in the second pregnancy; the risk is inversely proportional to gestational age at delivery of the first pregnancy: adjusted odds ratio, 15.0; 95% CI, 6.3-35.4 for 20 to 33 weeks; adjusted odds ratio, 10.2; 95% CI, 6.2-17.0 for 33 to 36 weeks; and adjusted odds ratio, 7.9; 95% CI, 6.3-10.0 for 37 to 45 weeks. CONCLUSION: The relative risk of recurrent preeclampsia increases with earlier gestational age at delivery of the first pregnancy that was complicated by preeclampsia.     

No association between the lipoprotein lipase S447X polymorphism and Alzheimer's disease

Results from various genetic association studies of the lipoprotein lipase (LPL) S447X polymorphism and Alzheimer's disease (AD), range from a statistically significant negative association of clinically examined patients to a non-significant but consistent trend for under-representation of the X447 allele in neuropathologically confirmed subjects. In this report we have compared the distribution of the above polymorphism in an independent group of clinically diagnosed AD patients, including a subgroup where the disease was pathologically confirmed, and a spousal control group. No statistically significant differences emerged from this comparison. We conclude that LPL cannot be a major factor in pathogenesis of AD.     

Treatment of colon and breast carcinoma cells with 5-fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA-A(*)02.01 restricted,CEA-peptide-specific cytotoxic T cells in vitro

Cancer vaccines directed against tumor associate antigen (TAA) have produced encouraging results in preclinical models but not in cancer patients. A major limitation of this strategy is the relative degree of tolerance to these antigens and the low and heterogeneous tumor cell expression of TAA and major histocompatibility complex (MHC). Previous studies have shown that 5-fluorouracil (5-FU) can upregulate the expression of membrane-associated carcino-embryonic antigen (CEA), and MHC molecules in colon and breast carcinoma cell lines. We have investigated whether this drug can also enhance their sensitivity to the lytic effects of CEA-peptide specific Cytotoxic T cell lymphocytes (CTL). The CEA peptide-specific CTLs generated in our laboratory from normal HLA-A(*)02.01(+) donor PBMCs, were able to kill HLA-A(*)02.01(+)/CEA(+) breast (MCF-7-T103) and colon (HLA-A(*)02.01 gene-transfected HT-29 and C22.20) carcinoma cells in HLA-A(*)02.01 restricted manner. The treatment of target cells with 5-FU, enhanced their CEA expression and susceptibility to CTL-mediated lysis. Cold competition assays confirmed these results, thus supporting the hypothesis that immune target cell lysis and 5-FU mediated enhancement were dependent on CEA peptide presentation by cancer cells. 5-FU treatment of functionally "mature" CTL after in vitro expansion, did not reduce their cytolytic activity against MT-2 target cells but, when the anti-metabolite was added during the immune-sensitization phase, CTL generation was significantly inhibited. These results provide a rationale for investigating a possible new role of 5-FU as an immuno targeting amplifier agent in breast and colorectal cancer patients immunized with CEA-directed cancer vaccines.     

Akzeptanz und Nutzung öffentlicher Automaten durch Ältere: Ergebnisse einer europäischen Untersuchung

This article examines the use and acceptance of ticket machines, automatic teller machines (ATMs) and telephone cards by the elderly in four European regions. The analyses are based on data from an international project entitled "Keeping the Elderly Mobile", collected in Mannheim (former West Germany; N = 404 home-dwelling respondents), Chemnitz (former East Germany; N = 400), Ancona (Italy; N = 600), and Jyv?skyl? (Finland; N = 618). The random sample was stratified by age and gender in each country. Two generations of men and women (aged 55-74 and 75+ years, respectively) participated in the study. Results show that respondents generally made little use of the three technologies under investigation: in fact, the majority of respondents does not use them at all. The most frequently used devices were ATMs in Chemnitz and ticket machines and telephone cards in Mannheim. On the basis of logistic regression analysis, age was the most important explanatory factor for the three technologies and for all four regions, i.e., the users were mostly the "young-old." Education was a more important variable than gender. In all four regions, the majority of the respondents who used the technologies assessed felt that each of them made life easier; nevertheless, ticket machines make life more difficult to almost every third user in Mannheim. Interesting differences and similarities among the towns were also found. The present study exhibits preliminary results regarding elderly and technology which future research should investigate in greater depth.     

Design, synthesis, and preliminary pharmacological evaluation of 1, 4-diazabicyclo[4.3.0]nonan-9-ones as a new class of highly potent nootropic agents

Several 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones have been synthesized and tested in vivo on mouse passive avoidance test, to evaluate their nootropic activity. The results show that they represent a new class of nootropic drugs with a pharmacological profile very similar to that of piracetam, showing much higher potency with respect to the reference. Among the compounds studied, 7 (DM 232) shows outstanding potency, being active at the dose of 0. 001 mg kg(-1) sc.     

The genetic basis of non-syndromic intellectual disability: a review

Intellectual disability (ID), also referred to as mental retardation (MR), is frequently the result of genetic mutation. Where ID is present together with additional clinical symptoms or physical anomalies, there is often sufficient information available for the diagnosing physician to identify a known syndrome, which may then educe the identification of the causative defect. However, where co-morbid features are absent, narrowing down a specific gene can only be done by 'brute force' using the latest molecular genetic techniques. Here we attempt to provide a systematic review of genetic causes of cases of ID where no other symptoms or co-morbid features are present, or non-syndromic ID. We attempt to summarize commonalities between the genes and the molecular pathways of their encoded proteins. Since ID is a common feature of autism, and conversely autistic features are frequently present in individuals with ID, we also look at possible overlaps in genetic etiology with non-syndromic ID.     

Neuroinflammation and astrocytic reaction in the course of Phoneutria nigriventer (armed-spider) blood–brain barrier (BBB) opening

Phoneutria nigriventer spider venom (PNV) causes uneven BBB permeability throughout different cerebral regions. Little is known about cellular and molecular responses which course with the PNV-induced BBB opening. We investigate by immunohistochemistry (IHC) and Western blotting (WB), the GFAP, S100, IFN-γ and TNF-α proteins expression in hippocampus and cerebellum after different time-points from venom or saline intravenous injection. All proteins variably altered its expression temporally and regionally. WB showed increased GFAP content at 15–45 min followed by a shift below the control level which was less pronounced in hippocampus. IHC showed reactive gliosis during all the trial period. In cerebellum, GFAP was mostly immunodetected in astrocytes of the molecular layer (Bergmann glia), as was S100 protein. The maximum S100 immunolabeling was achieved at 5 h. IFN-γ and TNF-α, expressed mostly by hippocampal neurons, increased along the trial period, suggesting a role in BBB permeability. In envenomed animals, closer contacts astrocyte–astrocyte, granule cells–granule cells and astrocytes-Purkinje cells were observed in cerebellum. Closer contacts between neurons–neurons–astrocytes–astrocytes were also seen in hippocampus. PNV contains serotonin, histamine, Ca²⁺ channels-blocking toxins, some of which affect glutamate release. The hypothesis that such substances plus the cytokines generated, could have a role in BBB permeability, and that calcium homeostasis loss and disturbance of glutamate release are associated with the marked GFAP/S100 reaction in Bergmann glia is discussed. The existence of a CNS mechanism of defense modulated differentially for fast synthesis and turnover of GFAP, S100, IFN-γ and TNF-α proteins was evident. A clear explanation for this differential modulation is unclear, but likely result from regional differences in astrocytic/neuronal populations, BBB tightness, and/or extent/distribution of microvasculature and/or ion channels density/distribution. Such differences would respond for transient characteristics of BBB disruption. This in vivo model is useful for studies on drug delivery throughout the CNS and experimental manipulation of the BBB.