The impact of MSAFP screening on genetic services, 1984–1986

The impact of maternal serum alpha-fetoprotein (MSAFP) screening on genetic centers was investigated by a questionnaire mailed to 220 genetic centers in the United States. Eighty-four (38%) of centers responded to the questionnaire; of these (34%) were adequate for analysis. About 33% of the programs performed their own MSAFP testing. Approximately 70% of centers used 2.5 times the median (MoM) as a cutoff for MSAFP elevations and approximately 75% of centers used a sliding cutoff for low MSAFP based on both maternal age and the multiple of the median. Between 1984 and 1986, the total number of women screened by the reporting centers increased by about 4.7 fold. The percentage of women seen in their centers for prenatal counseling due to high or low MSAFP levels increased from 1.3% in 1984 to 13.1% in 1986. The percentage of prenatal diagnoses utilizing amniocentesis for high or low MSAFP increased from 3% in 1984 to 10% in 1986. During this period, 76 cases of Down syndrome were detected based on low MSAFP; this represents 1.7% of amniocenteses for low MSAFP. These data demonstrate a significant increase in the number of women seen for prenatal counseling and amniocentesis at the reporting genetic centers and is likely to represent a similar trend at all genetic centers. The impact of high MSAFP screeing for neural tube defects and low MSAFP screening for Down syndrome is likely to increase over the coming years and genetic programs should prepare for the increasing utilization of services necessary to handle women with high and low MSAFP levels.     

Molecular epidemiology of the 1984-1986 outbreak of diphtheria in Sweden

Despite mass vaccination against diphtheria, many people have antibody titers below the protective level of 0.01 IU per milliliter. A recent outbreak of diphtheria in Sweden caused 17 clinical cases of diphtheria in the city of G?teborg; three of the patients died. A satellite outbreak occurred in Stockholm after a few months' delay. Using a new genetic probe, we analyzed 36 strains of Corynebacterium diphtheriae isolated in Sweden and Denmark during the period 1976 to 1986. Although the 36 strains can be classified in 17 different groups of C. diphtheriae (several of them containing toxigenic strains), all the clinical and fatal cases of diphtheria were caused by isolates from the same group, strongly suggesting that the outbreak in Sweden was caused by a single strain that possibly had a virulence factor separate from toxigenicity. This strain may have been imported into Sweden from Denmark, since it was isolated for the first time in Copenhagen in 1983, before the outbreak in Sweden.     

The changing landscape of genetic testing and its impact on clinical and laboratory services and research in Europe

The arrival of new genetic technologies that allow efficient examination of the whole human genome (microarray, next-generation sequencing) will impact upon both laboratories (cytogenetic and molecular genetics in the first instance) and clinical/medical genetic services. The interpretation of analytical results in terms of their clinical relevance and the predicted health status poses a challenge to both laboratory and clinical geneticists, due to the wealth and complexity of the information obtained. There is a need to discuss how to best restructure the genetic services logistically and to determine the clinical utility of genetic testing so that patients can receive appropriate advice and genetic testing. To weigh up the questions and challenges of the new genetic technologies, the European Society of Human Genetics (ESHG) held a series of workshops on 10 June 2010 in Gothenburg. This was part of an ESHG satellite symposium on the 'Changing landscape of genetic testing', co-organized by the ESHG Genetic Services Quality and Public and Professional Policy Committees. The audience consisted of a mix of geneticists, ethicists, social scientists and lawyers. In this paper, we summarize the discussions during the workshops and present some of the identified ways forward to improve and adapt the genetic services so that patients receive accurate and relevant information. This paper covers ethics, clinical utility, primary care, genetic services and the blurring boundaries between healthcare and research.     

The comparative impact of video-consultation on neurosurgical health services

This study evaluated the impact of telemedicine technology on the provision of neurosurgical health services. We focused on the differences between the use of real time audio-visual teleconferencing and teleradiology versus conventional telephone consultations in the referral of neurosurgical patients from a large district general hospital. All patients requiring emergency neurosurgical consultation were included for randomization into telephone consultation only (Mode A), teleradiology and telephone consultation (Mode B) and video-consultation (Mode C). Measures of effectiveness included diagnostic accuracy and adverse events during the transfer and Glasgow Outcome Score. In a 10-month period, 327 patients were recruited and randomized into the study: the male/female ratio was 2:1 and the number of patients required to be transferred to the neurosurgical unit was 125 (38%). There was a trend towards a more favourable outcome in the video-consultation mode (44%, Mode C), versus teleradiology (31%, Mode B), versus telephone consultation (38%, Mode A). The interim data of this prospective randomized trial suggests that video-consultation may have a favourable impact on emergency neurosurgical consultations.     

The impact of genetic factors on response to anaesthetics

In recent years, exceptional progress has been observed in pharmacogenetics, i.e. investigations of inherited conditioning of the organism's response to drugs or xenobiotics. On the other hand, modern molecular biology techniques have been implemented, making it possible to perform studies determining the involvement of genetic factors in differing responses to agents employed in general anaesthesia. Unexpected and incorrect response of the organism to the administration of specific anaesthetics is most commonly associated with a genetic defect of the metabolic pathway of a given agent or its receptor.The majority of agents used in anaesthesia are metabolised in the liver by the cytochrome P450 superfamily enzymes (CYPs) and phase II drug-metabolising enzymes: glutathione S-transferases (GSTs), sulphotransferases (SULTs), UDP-glucuronosyltransferases (UGTs) and NAD(P)H:quinone oxidoreductase (NQO1). Propofol is presently widely used for gastrointestinal (GI) and several other procedures. Among genes associated with metabolism of the most commonly applied anaesthetics such as propofol and sevoflurane, the following ones can be mentioned: CYP2E1, CYP2B6, CYP2C9, GSTP1, UGT1A9, SULT1A1 and NQO1. Moreover, the basic mechanism of propofol action involves its interaction with an ionotropic receptor GABAA inhibiting transfer of nerve impulses. Molecular studies have shown that polymorphic changes in GABRG2 receptor gene turn out to be important in the propofol anaesthesia.Planning of optimal anaesthesia can be considerably assisted by the determination of genetic factors of prognostic value taking advantage of genotyping and making it possible to select anaesthetics and reduce risk of side effects as well as undesirable actions.     

The impact of newborn screening on cystic fibrosis testing in Victoria, Australia.

Newborn screening for cystic fibrosis (CF) by examining the levels of immunoreactive trypsinogen was introduced in Victoria in 1989. This was modified by the addition of testing for the common CF gene mutation, delta F508, in 1990. Problems with the first newborn screening protocol were overcome with the addition of the DNA test as there was no need to contact the majority of families, there was a reduced number of sweat tests, and less anxiety was experienced by parents. The mode of diagnosis changed from failure to thrive, steatorrhoea, rectal prolapse, and family history to diagnosis through newborn screening. Newborn screening dramatically reduced the time of diagnosis of CF to approximately six weeks or less in the majority of cases. Since the introduction of newborn screening, the uptake of prenatal diagnosis in CF families has increased two and a quarter fold.     

The impact origin of genetic material.

It is proposed that high velocity asteroidal impacts with the Earth created polymeric nucleotide sequences out of monomeric nucleotides via direct compressive forces. The developed model describes the simultaneous formation of histone-equivalent proteins and RNA/DNA-equivalent template structures as a natural and expected consequence of bolide impactions with organic material accumulating on the crustal surface of the Earth approximately 3.8-3.5 billion years ago. It is shown that literally billions of different gene-equivalent nucleotide sequences, each one having a set of surface-complementary histone-equivalent proteins, might be created in such a manner. It is hypothesized that it is this process that gave rise to the chemical substrate upon which Darwinian selective forces have acted ever since.     

The impact of multiplex genetic testing on disease risk perceptions

This study assessed the effects of multiplex genetic testing on disease risk perceptions among 216 healthy adults. Participants, aged 25–40, were recruited through the Multiplex Initiative, which offered a genetic susceptibility test for eight common diseases. Participants completed baseline telephone and web‐based surveys prior to making the testing decision. Three months after the receipt of mailed test results, participants completed a follow‐up telephone survey. Risk perceptions for the eight diseases were measured at baseline and follow‐up, along with beliefs about genetic causation of those diseases. The main results were: (i) mean risk perceptions were considerably stable from baseline to follow‐up; (ii) the best predictors of follow‐up risk perceptions were the corresponding baseline perceptions and family history; and (iii) within‐individuals, most participants increased or decreased their risk perceptions for specific diseases in concordance with the number of risk markers they carry, their family history and their beliefs about genetic causality of diseases. In conclusion, participants presented a vigilant approach to the interpretation of genetic test results, which provides reassurance with regard to a potential inflation of risk perceptions in the population because of multiplex genetic testing.     

Assuring clinical genetic services for newborns identified through U.S. newborn screening programs

PurposeThe study purpose was to determine whether U.S. newborn screening and/or genetics programs systematically document whether newborns and their families, identified with genetic disorders through newborn dried blood spot screening, receive clinical genetic services.MethodsNineteen state genetic plans were reviewed and a 30-question survey was administered to 53 respondents, including state newborn screening program coordinators and state genetics program coordinators in 36 states and principal investigators of 5 Health Resources and Services Administration-designated regional genetic and newborn screening collaboratives.ResultsSurvey findings indicate that none of the state newborn screening and/or state genetics programs routinely tracked patient-level data on clinical genetic services for newborns identified with all of the genetic and congenital conditions for which their programs screened. Few programs could provide information systematically on whether patients were referred for, or received, genetic counseling.ConclusionsSystematic tracking of clinical genetic services for newborns identified by newborn screening programs is desirable and manageable. Recent national guidelines recommend tracking genetic counseling in newborn screening follow-up. The communications processes that state programs currently use to obtain follow-up reports from subspecialists could be augmented with clinical genetic service questions. Programs should be encouraged and supported in the efforts to track genetic services for the benefit of newborns and their families.     

Newborn blood spot screening and genetic services: a survey of Minnesota primary care physicians.

PURPOSE: To (1) obtain guidance on the preferred content and format of quick reference newborn blood spot screening information from the Minnesota Department of Health; (2) determine primary care physicians' perceptions of the benefits of genetic services; and (3) determine primary care physicians' satisfaction with genetic counseling services. METHODS: A written survey was mailed to family physicians and pediatricians in Minnesota (n = 300). RESULTS: Eighty physicians responded (28% response rate). Whereas 70% of respondents felt previous information received from the newborn screening program was adequate, 83% were interested in quick reference information. The majority of physicians preferred this information as a laminated sheet (63%). Physician procedure for an abnormal screen, newborn screening program protocol for an abnormal screen, and disease treatment and follow-up information were recommended for inclusion on quick reference. Over half of physicians agreed with the following benefits of genetic services: provide testing options (88%); evaluate family members (88%); reduce parental anxiety (87%); provide resources (83%); provide diagnostic information (76%); determine medical needs (67%); and determine emotional needs (51%). Ninety-nine percent of physicians were satisfied with genetic counseling services. CONCLUSIONS: Physicians indicated that reference material for primary care physicians should include a quick reference card with specific categories of information. Newborn screening programs should attempt to increase physician awareness of genetic services, including the subsequent medical and psychosocial benefits for their patients.     

The causative organisms of bacterial meningitis in Korean children, 1986-1995.

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood. Epidemiologic investigations have shown variability in disease risks among different populations and races. In Korea, however, basic epidemiologic information on bacterial meningitis in children is limited. The main purpose of this study was to analyze bacteriologically proven meningitis cases in terms of the relative frequency of causative organisms, mortality rate, and age distribution beyond the neonatal period. Data was obtained from the hospital records who had been diagnosed with bacterial meningitis at 13 general or university hospitals from 1986 through 1995. The patients had at least one positive CSF culture for bacteria. Of 140 cases of CSF culture-proven bacterial meningitis, 46.4% was < or =1 year, 62.1% was < or =2 years, 81.4% was < or =5 years cumulatively. Streptococcus pneumoniae was the most common bacteria responsible for 48 (35.0%) of all cases regardless of age, followed by Haemophilus influenzae for 48 (34.3%) and Neisseria meningitidis for 8 (6.4%) patients. The case fatality rate was 20.0%, 17.1%, and 16.7% for N. meningitidis, S. pneumoniae, and H. influenzae, respectively. In conclusion, the most common organisms of culture-proven bacterial meningitis in the last 10 years have been S. pneumoniae, H. influenzae, and N. meningitidis in order of frequency. Further study should be extended to nation-wide epidemiologic evaluation to show the incidence of bacterial meningitis caused by these three important organisms.     

Features, objects, action: The cognitive neuropsychology of visual object processing, 1984-2004

We review evidence on the cognitive neuropsychology of visual object processing, from 1984-2004, dividing the work according to whether it deals with the analysis of visual features, objects, or the relations between object processing and action. Research across this period has led to (1) a more detailed analysis of disorders of feature processing and feature binding, (2) a finer-grained understanding of disorders of object recognition, how these disorders can change over time, and their relations to visual imagery, and (3) new accounts of the relations between vision and action. Cognitive neuropsychological studies have played a key part in furthering our understanding of the functional nature of object processing in the brain.