Teaching practice recommendations: prevention and screening

The aim of this article is to provide guidance to family doctors on how to tutor students about effective screening and primary prevention. Family doctors know their patients and adapt national and international guidelines to their specific context, risk profile, sex and age as well as to the prevalence of the disorders under consideration. Three cases are presented to illustrate guideline use according to the level of evidence (for a 19-year-old man, a 60-year-old woman, and an 80-year-old man). A particular strength of family medicine is that doctors see their patients over the years. Thus they can progressively go through the various prevention strategies, screening, counselling and immunisation, accompanying their patients with precious advice for their health throughout their lifetime.

Inherited progressive cardiac conduction disorders.

PURPOSE OF REVIEW Progressive cardiac conduction disorder (PCCD) is an inherited cardiac disease that may present as a primary electrical disease or be associated with structural heart disease. In this brief review, we present recent clinical, genetic, and molecular findings relating to PCCD. RECENT FINDINGS Inherited PCCD in structurally normal hearts has been found to be linked to genetic variants in the ion channel genes SCN5A, SCN1B, SCN10A, TRPM4, and KCNK17, as well as in genes coding for cardiac connexin proteins. In addition, several SCN5A mutations lead to 'cardiac sodium channelopathy overlap syndrome'. Other genes coding for cardiac transcription factors, such as NKX2.5 and TBX5, are involved in the development of the cardiac conduction system and in the morphogenesis of the heart. Mutations in these two genes have been shown to cause cardiac conduction disorders associated with various congenital heart defects. SUMMARY PCCD is a hereditary syndrome, and genetic variants in multiple genes have been described to date. Genetic screening and identification of the causal mutation are crucial for risk stratification and family counselling.

Dysregulation of alternative splicing of coagulation factor V results in bleeding disorder, east Texas type and other disorders of hemostasis

The studies completed herein explore different phenotypes related to the genetic defects that predispose individuals to a disruption of normal hemostasis. In the first study, a novel autosomal dominant bleeding disorder, which is characterized by excessive bleeding with trauma or surgery and menorrhagia in affected women, was studied in a large family (16 affected individuals) from east Texas. Affected members had a prolongation of their PT and/or aPTT, but normal clinical coagulation studies. Previous linkage analysis by Kuang et. al. (2001) mapped the defective gene to 1g23-24 (LODmax 7.22), which contains the gene for coagulation factor V (FV). I identified an alteration (A2440G) in the FV gene in exon 13 that segregated with the disease and was not present in 62 controls. Interestingly, this alteration resulted in a 22-fold up-regulation of a novel alternative splicing variant in patients' RNA versus controls. This translated into a similar fold increase in a 250-kDa isoform of FV seen in patients' plasma versus controls. A recombinant of this splicing event exhibited an increased sensitivity to cleavage by activated protein C (APC) that was more striking in the presence of PS. In addition, this novel isoform had increased APC cofactor activity, thus increasing the degradation of FVIIIa. These data indicated that A2440G up-regulates an alternatively spliced transcript of FV, and increases a FV isoform that hinders coagulation as opposed to promoting it like its wild-type counterpart. ^ The second study reports the largest screening to date of African Americans in two independent cohorts for a rare prothrombin variant, C20209T, which is suspected to be associated with thrombotic disease. The Texas Medical Center Genetics Resource (TexGen) Stroke DNA repository revealed 1.67% (Fisher p=0.27) of African American stroke patients were heterozygous for the 20209*T allele. Screening of the Atherosclerosis Risk in Communities Study (ARIC) cohort (n=3470) for the 20209*T allele revealed a population prevalence of 0.58% in individuals of African American descent; however, all associations with thrombotic disease were negative. Analysis of these two independent cohorts revealed that, unlike its neighbor G20210A, the C20209T variant does not increase the risk of thrombotic events in the African American population. ^

Implementing universal newborn hearing screening programs : early identification of hearing loss.

Shipping list no.: 99-0282-P.

Newborn metabolic screening in Illinois, 2005 /

"This publication was supported in part by Grant/Cooperative Agreement Number U50/CCU523303-04 from the U.S. Centers for Disease Control and Prevention. ... "--p. ii.

Universal newborn hearing screening in Illinois, 2003-2004 /

"This publication was supported in part by Grant/Cooperative Agreement US50/CCU523303-04 and Early Hearing Detection and Intervention Award UR#CC1520048 from the U.S. Centers for Disease Control and Prevention. ..."--Leaf ii.

Telepaediatrics and diabetic retinopathy screening of young people with diabetes in Queensland

We have examined the feasibility of a telemedicine-enabled screening service for children and adolescents with diabetes in Queensland. There are approximately 1400 young people with diabetes in Queensland and only about two-thirds of them are screened in accordance with international guidelines. A regional retinal screening service was established using a non-mydriatic digital retinal camera. Seven centres volunteered to participate in the study. During a five-month pilot trial, 83 of the young people with diabetes who attend these centres underwent digital retinal screening (3.7%). Retinal images were sent via email to a paediatric ophthalmologist for review and results were returned via email. A copy of each participant's results was forwarded by mail to the referring diabetes doctor and the participant and family. The majority of the image files (96%) were rated as excellent or good. Only one participant was identified as having an abnormal result. Participants and their families expressed satisfaction with the digital retinal screening process.

Genetic screening for susceptibility to depression: can we and should we?

Objective: To summarize current knowledge about genetic susceptibility to mood disorders and examine ethical and policy issues that will need to be addressed if robustly replicated susceptibility alleles lead to proposals to screen and intervene with persons at increased genetic risk of developing mood disorders. Method: Empirical studies and reviews of the genetics of unipolar and bipolar depression were collected via MEDLINE and psycINFO database searches. Results: A number of candidate genes for depression have been identified, each of which increases the risk of mood disorders two- or threefold. None of the associations between these alleles and mood disorders have been consistently reported to date. Conclusions: Screening the population for genetic susceptibility to mood disorders is unlikely to be a practically useful policy (given plausible assumptions). Until there are effective treatments for persons at increased risk, screening is arguably unethical. Screening within affected families to advise on risks of developing depression would entail screening children and adolescents, raising potentially serious ethical issues of consent and stigmatization. Genetic research on depression should continue under appropriate ethical guidelines that protect the interests of research participants.

The relationship between personality and drinking restraint in an alcohol dependent sample

Consistent relationships have been demonstrated between problem drinking and certain personality characteristics. A contemporary cognitive model of alcohol misuse, drinking restraint, has recently shown promise in furthering our understanding of problematic drinking. This study examined the potential association between drinking restraint and personality characteristics in 168 alcohol dependent inpatients. Subjects completed the short-scale Revised Eysenck Personality Scales (EPS-R; Eysenck, Eysenck, & Barrett, 1985), Temptation and Restraint Inventory (TRI; Collins & Lapp, 1992), Alcohol Dependence Scale (ADS; Skinner & Allen, 1982) and drinking measures including quantity, frequency and weekly drinking total. Results indicated that although there was some conceptual overlap between drinking restraint and personality factors, the TRI had a unique relationship with indices of problem drinking once personality factors were taken into account. This indicates that restrained drinking and personality, although related, are discrete constructs. While restrained drinking may aid in the understanding of current drinking behavior, personality characteristics appear to contribute to the etiology and maintenance of drinking problems. (c) 2005 Elsevier Ltd. All rights reserved.

Employment restrictions among persons with ICD-10 anxiety disorders: characteristics from a population survey

Disability, employment, and employment restrictions among persons with ICD-10 anxiety disorders were investigated at a population level in comparison to persons without disability or long-term health conditions. Data were provided by the Australian Bureau of Statistics (ABS) collected in a 1998 national survey. Multistage sampling obtained a probability sample of 37,580 individuals in the household component of the survey. Trained lay interviewers using ICD-10 computer-assisted interviews identified household residents with anxiety disorders. Details of employment restrictions are reported and discussed. The four most commonly reported restrictions were: restricted in the type of job (24.0%); need for a support person (23.3%); difficulty changing jobs (18.6%); and restricted in the number of hours (15.4%). The nature and extent of employment restrictions characterizing persons with anxiety disorders indicates a need for strengthened disability and health condition screening at application for Government income support and at gateways to public funded vocational assistance. (c) 2004 Elsevier Inc. All rights reserved.

A yellow fluorescent protein-based assay for high-throughput screening of glycine and GABA(A) receptor chloride channels

There is a significant clinical need to identify novel ligands with high selectivity and potency for GABA(A), GABA(C) and glycine receptor Cl- channels. Two recently developed, yellow fluorescent protein variants (YFP-I152L and YFP-V163S) are highly sensitive to quench by small anions and are thus suited to reporting anionic influx into cells. The aim of this study was to establish the optimal conditions for using these constructs for high-throughput screening of GABA(A), GABA(C) and glycine receptors transiently expressed in HEK293 cells. We found that a 70% fluorescence reduction was achieved by quenching YFP-I152L with a 10 s influx of I- ions, driven by an extemal I- concentration of at least 50 mM. The fluorescence quench was rapid, with a mean time constant of 3 s. These responses were similar for all anion receptor types studied. We also show the assay is sufficiently sensitive to measure agonist and antagonist concentration-responses using either imaging- or photomultiplier-based detection systems. The robustness, sensitivity and low cost of this assay render it suited for high-throughput screening of transiently expressed anionic ligand-gated channels. (c) 2005 Elsevier Ireland Ltd. All rights reserved.