Autoimmunization induced by interferon alpha therapy in chronic hepatitis C

We report the case of a 56 year-old woman with post-transfusion chronic hepatitis C who presented with a severe ALT flare up associated with a rapid progression of liver fibrosis during interferon alpha 2b therapy. Several hypotheses were considered to explain the etiology of this ALT flare: there was no viral super infection by other hepatotropic viruses, no toxic hepatitis, no metabolic disease, and no other specific liver diseases could be identified. HLA typing showed a specific profile A1 B8 DR3 (risk factor of auto-immunization during interferon alpha therapy) with antinuclear antibodies and anti smooth muscle antibodies. This case suggests that auto-immunization induced by interferon alpha should be investigated in case of ALT flare that is not followed by an HCV breakthrough.     

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.     

A temporal/nasal asymmetry for blindsight in a localisation task: evidence for extrageniculate mediation

Some patients with hemianopia due to striate cortex lesions show above chance ability in reporting visual stimuli presented in the blind visual field, a phenomenon commonly known as blindsight. Here we report a patient with a dense right hemianopia whose blindsight shows a temporal/nasal asymmetry. MP was tested in a two-alternative forced-choice localisation task, with either the right eye or the left eye patched in separate blocks. When targets appeared in the contralesional temporal hemifield, MP's localisation performance was extremely accurate, whilst she performed at chance with targets in the contralesional nasal hemifield. This is the first demonstration of a temporal/nasal asymmetry for blindsight in a forced-choice paradigm, and is consistent with blindsight in MP's hemianopic field being mediated by a subcortical, extrageniculate route.     

Effect of variation in diacylglycerol kinase eta (DGKH) gene on brain function in a cohort at familial risk of bipolar disorder

Several lines of evidence indicate that the diacylglycerol kinase eta (DGKH) gene is implicated in the etiology of bipolar disorder (BD). However, the functional neural mechanisms of DGKH's risk association remain unknown. Therefore, we examined the effects of three haplotype-tagging risk variants in DGKH (single nucleotide polymorphisms rs9315885, rs1012053, and rs1170191) on brain activation using a verbal fluency functional magnetic resonance imaging task. The subject groups consisted of young individuals at high familial risk of BD (n=81) and a comparison group of healthy controls (n=75). Individuals were grouped based on risk haplotypes described in previous studies. There was a significant risk haplotype*group interaction in the left medial frontal gyrus (BA10, involving anterior cingulate BA32), left precuneus, and right parahippocampal gyrus. All regions demonstrated greater activation during the baseline condition than sentence completion. Individuals at high familial risk for BD homozygous for the DGKH risk haplotype demonstrated relatively greater activation (poor suppression) of these regions during the task vs the low-risk haplotype subjects. The reverse pattern was seen for the control subjects. These findings suggest that there are differential effects of the DGKH gene in healthy controls vs the bipolar high-risk group, which manifests as a failure to disengage default-mode regions in those at familial risk carrying the risk haplotype.