Chemokines and pro-inflammatory cytokines in Down's syndrome: an early marker for Alzheimer-type dementia?

BACKGROUND: People with Down's syndrome (DS) show early Alzheimer-like dementia. It has been suggested that the pro-inflammatory cytokine class plays a role in Alzheimer's disease (AD). The study aims at verifying whether pro-inflammatory cytokines in DS are correlated with age, affective symptoms and intellectual decline to a different degree than in subjects with non-DS learning disabilities. METHODS: Cases: 19 subjects with DS; controls: sex- and age-matched individuals with learning disabilities caused by perinatal ischaemic damage. The level of mental retardation was assessed according to DSM-IV; psychopathological symptoms were measured by the Assessment and Information Rating Profile. Serum levels of cytokines were determined with ELISA. RESULTS: DS patients showed higher levels of cytokines and chemokines, with the exception of RANTES; but the only significant difference detected was for MIP-1alpha. A correlation between the degree of mental retardation and IL-6, and between MIP-lalpha and age was found in patients with DS, but not in controls. CONCLUSIONS: The data obtained suggest a possible involvement of chemokines in the inflammatory and degenerative processes similar to AD in DS. Further longitudinal research is required to confirm these findings.     

Informed consent documents for BRCA1 and BRCA2 screening: how large is the readability gap?

The decision to undergo testing for the BRCA1 and BRCA2 mutations, which are associated with an increased risk of breast and ovarian cancer, can have long-term consequences on women's lives. Women who decide to undergo such testing are required to sign informed consent documents, which indicate that they understand the test and its risks and benefits. These documents are generally written for advanced-level readers. However, the reading abilities of many women are substantially lower than the level of the consent forms, resulting in a 'readability gap'. This disparity suggests that women may not fully understand the documents they are asked to sign. The 'readability gap' poses the serious issues about informed consent, raising questions about institutional review boards and the effectiveness of the documents that are currently in use.     

Molecular pathologic diagnosis in solid tumors. What is clinically relevant?

There are only a few clinically relevant applications of molecular pathology assays in solid tumors. Among the findings which may influence therapy decisions are the amplification of Her-2/new in breast cancer and specific translocations in sarcomas. Mutation analyses of p53 may be helpful for only a very few cases, e.g. for confirming high grade dysplasia in the upper gastrointestinal tract or for diagnosing malignant soft tissue tumors in isolated cases. Microsatellite analyses are important for HNPCC screening or distinguishing tissue specimens of questionable identity. Other applications of molecular pathology assays such as detection of minimal residual disease or tumor cell dissemination and FISH analysis of urine and effusion specimens, may be increasingly applied in the future.     

Hepatitis C: is there a case for universal screening in pregnancy?

Hepatitis C (HCV) is not routinely screened for antenatally in all maternity hospitals. Most hospitals adopt a policy of targeted screening. The policy in the Coombe Women and Infants University Hospital in Dublin changed from targeted screening in 2006 to universal screening in 2007. We audited the two consecutive years. The prevalence of HCV in our antenatal population was 1.4% for 2006 (67/4666) when targeted screening applied and in 2007--0.71% (66/9222) when universal screening came into affect. One woman in 2007 would not have been detected by targeted screening--1.49% (1/67). Fifty five percent (37/67) of women were HCV-RNA positive in 2006 and 57.5% (38/66) were positive in 2007. We conclude that there were similar detection rates for HCV in 2006 and 2007 and that universal screening is not required if inclusive criteria for selective screening are employed but is of use in research context.     

What next for preimplantation genetic screening?

Preimplantation genetic diagnosis for aneuploidy screening (preimplantationgenetic screening—PGS) has been used to detect chromosomallynormal embryos from subfertile patients. The main indicationsare advanced maternal age (AMA), repeated implantation failure,repeated miscarriages and severe male factor infertility. Manynon-randomized PGS studies have been published and report anincrease in implantation rate, and/or a decrease in miscarriagerate. Recently, two randomized controlled trials have been conductedon patients with AMA as the only indication. Neither study showeda benefit in performing PGS using live birth rate as the measureof success. The debate on the usefulness of PGS is ongoing;the only effective way to resolve the debate is to perform morewell-designed and well-executed randomized clinical trials.     

To what extent do decision aids for prenatal screening and diagnosis address involvement of partners in decision-making? - An environmental scan

ObjectiveNumerous decision aids (DAs) have been developed to inform pregnant people about prenatal screening as the decision whether or not to accept the prenatal screening offer may be difficult. Currently, little is known about the role of the decisional partner of the pregnant people in this decision-making process and to what extent DAs involve and engage the partner.MethodsA broad search was conducted to identify publicly available DAs in English and/or Dutch regarding prenatal screening and diagnosis. These DAs were analysed on aspects of partner involvement.ResultsTen of the 19 identified DAs (52.6%) contained at least one aspect of partner involvement. Several DAs acknowledged that both partners should be involved in the decision (n = 7). The content that was least likely to contain aspects of partner involvement in the DA was value clarification content (n = 2) and only one DA contained content with plural addressing.ConclusionJust over half of the included DAs included some aspect(s) of partner involvement.Practical implicationsMore research is needed to determine to what extent, and how, the partner should be involved in the decision-making process as expectant people consider the input of their partner as important.     

Balanced information about Down syndrome: What is essential?

The purpose of this study was to explore the perspectives of genetic counselors and parents of children with Down syndrome to define essential information for the initial discussion of a new diagnosis. We compared information given in both prenatal and postnatal settings, and also aimed to distinguish differences between the informational needs of parents and the information genetic counselors provide. Online surveys were distributed to members of the National Down Syndrome Congress, National Down Syndrome Society, and National Society of Genetic Counselors. Participants included 993 parents of children with Down syndrome and 389 genetic counselors. Participants rated 100 informational features about Down syndrome as Essential, Important, or Not Too Important for inclusion in the first discussion of the diagnosis. Responses identified 34 essential informational items for the initial discussion of Down syndrome, including clinical features, developmental abilities, a range of prognostications, and informational resources. Healthcare providers should consider incorporating these items in their initial discussion of a diagnosis in both prenatal and postnatal settings. Statistically significant differences between parent and genetic counselor responses illustrate that information is valued differently and that parents appreciate information about the abilities and potential of people with Down syndrome, as opposed to clinical details. Balancing clinical information with other aspects of the condition, as well as a better understanding of the information parents consider most important, may enable healthcare professionals to more effectively satisfy families' informational needs following a new diagnosis of Down syndrome.     

What is the most relevant standard of success in assisted reproduction?: challenges in measuring and reporting success rates for assisted reproductive technology treatments: what is optimal?

For assisted reproductive technology (ART) treatments, measures of success that move beyond traditional measures of pregnancy and live birth and narrow the numerator to infant outcomes with an optimal short- and long-term prognosis are needed. Hence, presentation of singleton live birth delivery rates is warranted. Twins have greatly increased risks for morbidity and mortality in comparison with singletons. Success rates based on singleton live births will more completely inform patients evaluating which ART treatment options will maximize their chance for a healthy infant. Additionally, providers who limit embryos transferred can feel they are on an even playing field in reporting their success rates. Measures of success that narrow the numerator further to exclude preterm or low birth weight singleton births might also be informative. However, the utility of such measures is less clear because the aetiologies of preterm birth and low birth weight among singletons are probably multifactorial. While it may be desirable to consider adverse outcomes such as congenital anomalies in defining treatment success, it is unfeasible to collect complete and accurate data on anomalies in current ART registries. As ART use increases, continual re-examination and critique of the manner in which success is defined and presented to the public is critical.     

What is the point: will screening mammography save my life?

Background  

We analyzed the claim "mammography saves lives" by calculating the life-saving absolute benefit of screening mammography in reducing breast cancer mortality in women ages 40 to 65.     

Carrier screening panels for Ashkenazi Jews: is more better?

PURPOSE: To describe the characteristics of Ashkenazi Jewish carrier testing panels offered by US Laboratories, including what diseases are included, the labels used to describe the panels, and the prices of individual tests compared to the prices of panels for each laboratory. METHODS: GeneTests (http://www.genetests.org) was searched for laboratories that offered Tay-Sachs disease testing. Information was obtained from laboratory web sites, printed brochures, and telephone calls about tests/panels. RESULTS: Twenty-seven laboratories offered up to 10 tests. The tests included two diseases associated with death in childhood (Niemann-Pick type A and Tay-Sachs disease), five with moderate disability and a variably shortened life span (Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia, and mucolipidosis type IV), and two diseases that are not necessarily disabling or routinely shorten the lifespan (Gaucher disease type I and DFNB1 sensorineural hearing loss). Twenty laboratories offered a total of 27 panels of tests for three to nine diseases, ranging in price from $200 to $2082. Of these, 15 panels cost less than tests ordered individually. The panels were described by 24 different labels; eight included the phrase Ashkenazi Jewish Disease or disorder and six included the phrase Ashkenazi Jewish Carrier. CONCLUSION: There is considerable variability in the diseases, prices, and labels of panels. Policy guidance for establishing appropriate criteria for inclusion in panels may be useful to the Ashkenazi Jewish community, clinicians, and payers. Pricing strategies that offer financial incentives for the use of "more tests" should be reexamined.     

Familial aggregation in Rett syndrome: What is the evidence for clustering of other disorders in the families of affected girls?

Rett syndrome is a neurodevelopmental disorder of unknown cause which affects girls almost exclusively. Apparently normal development in the first year of life is usually followed by loss of skills and the development of stereotypic hand movements. This study has used genetic epidemiological methods including a case control design to examine the evidence for aggregation of other disorders in families of girls with Rett syndrome. In one family there were two sisters with a condition consistent with Rett syndrome. Intellectual disability was not reported more commonly in case families (P = 0.46). However, “learning problems” were slightly commoner (P = 0.05) especially in the parental generation (P = 0.02) and these findings warrant further investigation. Mental illness and seizures were not reported at an increased prevalence. However, we would recommend the use of other strategies to collect information about psychiatric illness. Spinal curvature was reported more commonly in case families (P = 0.07) but no mechanism for clinical verification of this was included in the study. There was an apparent increase in bowel problems in the parents (P = 0.04). The major weaknesses of our study were our inability to validate any diagnosis clinically and the lack of power (due to the comparative rarity of the outcomes). The strengths are that we have been able to collect pedigree data on the families of a substantial proportion of a total population of girls with Rett syndrome and to collect comparative data from a control population. Our reported findings warrant further investigation in a larger study. Am. J. Med. Genet. 82:228–234, 1999. © 1999 Wiley-Liss, Inc.     

Are elevated FSH concentrations in the pre-conceptional period a risk factor for Down's syndrome pregnancies?

Recent publications have reported a relation between a decreased ovarian reserve and Down's syndrome pregnancies. Using the data of a case-control study into risk factors for a Down's syndrome pregnancy, we estimated the usefulness of pre-conceptional basal follicle stimulating hormone (FSH) screening (detection rate, false positive rate, positive and negative likelihood ratio, as well as the loss rate of unaffected pregnancies) to identify Down's syndrome pregnancies. The optimal detection rate of pre-conceptional basal FSH screening for Down's syndrome pregnancies was 14%, corresponding to a false positive rate of 5% and a positive likelihood ratio of 2.8. Incorporation of basal FSH screening into the regimen of first trimester serum screening followed by nuchal translucency measurement would increase the detection rate from 85 to 87%. However, basal FSH screening alone or in combination with other screening methods would cause an unacceptably high loss rate of unaffected pregnancies compared with current screening protocols, indicating that routine pre-conception basal FSH screening would not be useful to identify women at risk for a Down's syndrome pregnancy. However, when elevated basal FSH concentrations are diagnosed during subfertility evaluation, an elevated risk for a Down's syndrome pregnancy could be discussed with women who become pregnant.