An Australian twin study of the genetic basis of preeclampsia and eclampsia

OBJECTIVE: We investigated maternal versus fetal genetic causes of preeclampsia and eclampsia by assessing concordance between monozygotic and dizygotic female co-twins, between female partners of male monozygotic and dizygotic twin pairs, and between female twins and partners of their male co-twins in dizygotic opposite-sex pairs. STUDY DESIGN: Two large birth cohorts of volunteer Australian female twin pairs (N = 1504 pairs and N = 858 pairs) were screened and interviewed, and available medical and hospital records were obtained and reviewed where indicated, with diagnoses assigned according to predetermined criteria. RESULTS: With strict diagnostic criteria used for preeclampsia and eclampsia, no concordant female twin pairs were found. Collapsing diagnoses of definite, probable, or possible preeclampsia or eclampsia resulted in very low genetic recurrence risk estimates. CONCLUSION: Results from these two cohorts of female twin pairs do not support clear, solely maternal genetic influences on preeclampsia and eclampsia. Numbers of parous female partners of male twins were too low for conclusions to be drawn regarding paternal transmission.

Variation in Alcohol Pharmacokinetics as a Risk Factor for Alcohol Dependence

Background: The significant association between alcohol dehydrogenase (ADH)-2 genotype and alcohol-dependence risk, demonstrated in both Asian and non-Asian populations, suggests a link between the metabolism of alcohol (ethanol) and individual differences in susceptibility to dependence. Methods: We tested this hypothesis by following up on subjects who took part in the Alcohol Challenge Twin Study conducted in 1979-1981 and comparing the blood and breath alcohol results in that study between subjects who subsequently did or did not meet diagnostic criteria for lifetime alcohol dependence in 1992-1993. Results: Subjects who met DSM-III-R criteria for lifetime alcohol dependence at follow-up had higher blood and breath alcohol values after alcohol challenge than never-dependent subjects. Multivariate analysis showed independent effects of susceptibility to alcohol dependence and smoking status on blood alcohol concentrations, whereas habitual alcohol intake at the time of the initial study had marginally significant effects. The risk of alcohol dependence was 2-fold higher in men and 3-fold higher in women with blood or breath alcohol concentrations in the highest quartile than in the lowest quartile. Conclusions: In view of this association and the known genetic influences on both alcohol pharmacokinetics and alcohol dependence, it is probable that part of the heritability of dependence is mediated by genes (other than the known ADH2 and ADH3 polymorphisms) affecting alcohol metabolism.

Using postoperative cardiac troponin-I (cTi) levels to detect myocardial ischaemia in patients undergoing vascular surgery

Background, Cardiac complications occur commonly in vascular surgery patients. Diagnosis of cardiac complications is difficult because of the inaccuracies associated with traditional cardiac enzyme measurements. CTi, a highly sensitive and specific marker of myocardial injury, may be able to detect cardiac complications with greater ease and accuracy. Methods. The study prospectively examined 100 consecutive patients who underwent major vascular surgery between 6/7/98 and 31/12/98 at the Royal Brisbane Hospital. Daily measurements of cTi, creatine kinase (CK), creatine kinase MB (CKMB), CKMB index, renal function and haemoglobin were taken for three postoperative days. One postoperative electrocardiograph (ECC) was taken. An extensive cardiac history was taken. Intraoperative and postoperative events were recorded. Findings. There were 100 patients, 18 patients (18%) had a cTi elevation. On the basis of classical diagnostic criteria, 15 patients (15%) suffered one or more cardiac complication (either myocardial infarction, congestive cardiac failure, unstable angina or atrial fibrillation), One patient (1%) who had a cTi elevation died. CTI elevation occurred in five patients (5%) who were not diagnosed with cardiac complications based on traditional criteria. Despite not meeting specific diagnostic criteria for cardiac complications, all patients showed signs and symptoms that could be attributed to myocardial ischaemia, Every patient who developed congestive cardiac failure or atrial fibrillation had a cTi elevation. A Chi-square analysis revealed a significant association between cTi elevation and postoperative cardiac complications. Four variables contributed small but significant amounts of unique variance to the prediction of peak cTi on linear regression analysis. These were peak CKMB index, postoperative congestive cardiac failure, postoperative chest pain and postoperative cardiac complications. Conclusions. Routine cTi monitoring of postoperative vascular patients would be an effective and inexpensive way to detect patients with cardiac complications. The relationship between postoperative cTi elevation and significant coronary artery disease remains to be shown, (C) 2001 The international Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved.

Genetic and Environmental Influences on Migraine: A Twin Study Across Six Countries

Migraine is a common neurovascular brain disorder that is manifested in recurrent episodes of disabling headache. The aim of the present study was to compare the prevalence and heritability of migraine across six of the countries that participate in GenomEutwin project including a total number of 29,717 twin pairs. Migraine was assessed by questionnaires that differed between most countries. It was most prevalent in Danish and Dutch females (32% and 34%, respectively), whereas the lowest prevalence was found in the younger and older Finnish cohorts (13% and 10%, respectively). The estimated genetic variance (heritability) was significant and the same between sexes in all countries. Heritability ranged from 34% to 57%, with lowest estimates in Australia, and highest estimates in the older cohort of Finland, the Netherlands, and Denmark. There was some indication that part of the genetic variance was non-additive, but this was significant in Sweden only. In addition to genetic factors, environmental effects that are non-shared between members of a twin pair contributed to the liability of migraine. After migraine definitions are homogenized among the participating countries, the GenomEUtwin project will provide a powerful resource to identify the genes involved in migraine.

ASD explained for peers, parents, and professionals

Can the parent of a child with autism or Asperger Syndrome ever really comprehend the experiences of their child? As a greater number of cases are identified and more is understood about these conditions, autism and Asperger Syndrome seem to be increasingly commonly understood terms. Despite the clear definitions provided by diagnostic criteria for the conditions (e.g., American Psychiatric Association [APA], 1994), it often remains difficult for professionals, parents and other carers, particularly those who are newcomers to this field, to truly understand the complexities of these conditions with respect to the day-to-day influences upon the affected individual.

Searching for schizophrenia in ancient Greek and Roman literature: A systematic review

Objective: The aim of this study was to systematically examine ancient Roman and Greek texts to identify descriptions of schizophrenia and related disorders. Method: Material from Greek and Roman literature dating from the 5th Century BC to the beginning of the 2nd Century AD was systematically reviewed for symptoms of mental illness. DSM IV criteria were applied in order to identify material related to schizophrenia and related disorders. Results: The general public had an awareness of psychotic disorders, because the symptoms were described in works of fiction and in historical accounts of malingering. There were isolated instances of text related to psychotic symptoms in the residents of ancient Rome and Greece, but no written material describing a condition that would meet modern diagnostic criteria for schizophrenia. Conclusion: In contrast to many other psychiatric disorders that are represented in ancient Greek and Roman literature, there were no descriptions of individuals with schizophrenia in the material assessed in this review.

A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia

Based on the epidemiological finding that individuals with schizophrenia tend to be born in winter/spring when compared to the general population, we examined (1) the strength and timing of this effect in Northern Hemisphere sites, and (2) the correlation between the season of birth effect size and latitude. Studies were located via electronic data sources, published citations, and letters to authors. Inclusion criteria were that studies specify the diagnostic criteria used, that studies specify the counts of schizophrenia and general population births for each month, and that subjects and the general population be drawn from the same birth years and catchment area. We extracted data from eight studies based on 126,196 patients with schizophrenia and 86,605,807 general population births and drawn from 27 Northern Hemisphere sites. Comparing winter/spring versus summer/autumn births, we found a significant excess for winter/spring births (pooled odds ratio = 1.07; 95% confidence interval 1.05, 1.08; population attributable risk = 3.3%). There was a small but significant positive correlation between the odds ratios for the season of birth comparison and latitude (r = 0.271, p < 0.005). Furthermore, the shape of the seasonality in schizophrenia births varied by latitude band. These variations may encourage researchers to generate candidate seasonally fluctuating exposures.

An Australian comparison of specialist care of acute myocardial infarction

Objective. To determine whether patients hospitalized with acute myocardial infarction (AMI) in an Australian setting receive better pharmacological care if managed by cardiologists than by non-cardiologists. Design. Retrospective chart review of patients hospitalized between 1 January 1997 and 30 June 1998, undertaken by abstractors blind to study objectives. Setting. One tertiary and two community hospitals in south-east Queensland, Australia, in which all patients admitted with AMI were cared for by cardiologists and general physicians, respectively. Study participants. Two cohorts of consecutive patients satisfying diagnostic criteria for AMI: 184 in the tertiary hospital and 207 in the community hospitals. Main outcome measures. Frequency of use, in highly eligible patients, of thrombolysis, P-blockers, aspirin, angiotensin-converting enzyme (ACE) inhibitors, lipid-lowering agents, nitrates, and calcium antagonists. Cohorts were compared for differences in prognostic factors or illness severity. Results. In community hospital patients, there was greater use of thrombolysis [100% versus 83% in the tertiary hospital; difference 17%, 95% confidence interval (CI) 11-26%; P < 0.001] and of ACE inhibitors (84% versus 66%; difference 18%, 95% CI 3-34%; P = 0.02), and lower median length of stay (6.0 days versus 7.0 days; P = 0.001) compared with tertiary hospital patients. Frequency of use of other drugs, and adjusted rates of death and re-infarction were the same for both cohorts. Conclusions. With respect to pharmacological management of patients hospitalized with AMI, cardiologists and general physicians appear to provide care of similar quality and achieve equivalent outcomes. Further studies are required to confirm the generalizability of these results to Australian practice as a whole.

A simplified endogenous erythroid colony assay for the investigation of polycythaemia

The in vitro growth of erythroid colonies in the absence of erythropoietin, known as endogenous erythroid colonies (EEC) forms part of the diagnostic criteria for polycythaemia vera (PV). The availability of EEC culture in routine laboratory setting is limited as culture methods are technically demanding, difficult to standardize, expensive and laborious. In this study, we assessed the performance characteristics of a simplified method using ammonium chloride red cell lysis followed by culture on commercially available, batch-tested, methylcellulose media. Seventy-six patients were included; four were secondarily excluded on the basis of culture failure. Of the 14 patients with PV, 13 (93%) were positive for EEC on at least one occasion: 90% (nine of 10) of bone marrow and 67% (six of nine) of peripheral blood specimens were positive. All 30 patients with secondary polycythaemia (n = 12) or apparent polycythaemia (n = 18) were negative for EEC. The incidence of EEC in idiopathic erythrocytosis was 40% (eight of 28); 50% (five of 10) in those who met one of the minor criteria for PV and 17% (three of 18) in those who did not. We conclude that our EEC assay yield results comparable with that of more elaborate methods.

Latent class and genetic analysis does not support migraine with aura and migraine without aura as separate entities

Latent class and genetic analyses were used to identify subgroups of migraine sufferers in a community sample of 6,265 Australian twins (55% female) aged 25-36 who had completed an interview based on International Headache Society UHS) criteria. Consistent with prevalence rates from other population-based studies, 703 (20%) female and 250 (9%) male twins satisfied the IHS criteria for migraine without aura (MO), and of these, 432 (13%) female and 166 (6%) male twins satisfied the criteria for migraine with aura (MA) as indicated by visual symptoms. Latent class analysis (LCA) of IHS symptoms identified three major symptomatic classes, representing 1) a mild form of recurrent nonmigrainous headache, 2) a moderately severe form of migraine, typically without visual aura symptoms (although 40% of individuals in this class were positive for aura), and 3) a severe form of migraine typically with visual aura symptoms (although 24% of individuals were negative for aura). Using the LCA classification, many more individuals were considered affected to some degree than when using IHS criteria (35% vs. 13%). Furthermore, genetic model fitting indicated a greater genetic contribution to migraine using the LCA classification (heritability, h(2) =0.40; 95% CI, 0.29-0.46) compared with the IHS classification (h(2)=0.36; 95% CI, 0.22-0.42). Exploratory latent class modeling, fitting up to 10 classes, did not identify classes corresponding to either the IHS MO or MA classification. Our data indicate the existence of a continuum of severity, with MA more severe but not etiologically distinct from MO. In searching for predisposing genes, we should therefore expect to find some genes that may underlie all major recurrent headache subtypes, with modifying genetic or environmental factors that may lead to differential expression of the liability for migraine. (C) 2004 Wiley-Liss, Inc.

The jigsaw sign. A reliable indicator of congenital aetiology in os odontoideum

There is evidence in the literature for both a congenital and a post-traumatic aetiology for os odontoideum. In no series published to date has CT been used to aid in the diagnosis. This is a prospective study of the history of trauma and presence of diagnostic features on CT of 18 consecutive cases with os odontoideum. Our objective was to derive clinically useful radiological features enabling accurate differentiation between congenital and post-traumatic aetiologies. A mid-sagittal CT reconstruction of the atlanto-dens joint was obtained. Hypertrophy of the anterior arch of the atlas was quantified by measurement of the arch-peg-area ratio. The presence of dysplastic features (a positive jigsaw sign) of the atlanto-axial joint were noted. These included narrowing of the cartilage space and interdigitation of the two joint surfaces. A history of a potential traumatic aetiology was only obtained in one of the 18 (6%) in our series. A significant elevation of the arch-peg ratio was found when comparing this series to 85 controls. And a positive jigsaw sign was observed in 75% of cases. These features were not seen in paediatric cases of atlanto-axial instability, including odontoid non-union. In conclusion, an elevated arch-peg ratio and the presence of a jigsaw sign are sensitive and specific diagnostic criteria for os odontoideum. This series supports a congenital aetiology for this condition.

Migraine and risk of subarachnoid haemorrhage: a population-based case-control study

Objective. Evidence exists for an association between migraine and ischaemic stroke, but there is uncertainty about whether migraine is a risk factor for subarachnoid haemorrhage (SAH). Methods. A multi-centre, population-based, case-control study using cases of first-ever SAH during 1995-98 and matched controls in four study centres in Australia and New Zealand. Self- or proxy-reported history, frequency and characteristics of headaches, classified according to 1988 International Headache Society diagnostic criteria. Results. 206 of 432 (48%) cases and 236 of 473 (50%) controls had a history of headaches. The frequency and characteristics of headaches were similar between the two groups. No association was found in logistic regression analyses for history or frequency of headaches, or migraine headaches. Conclusions. No evidence was found for an association between recurrent headaches and SAH. Such information is important for counselling patients and families about the significance of past and ongoing headaches in relation to this illness. (c) 2005 Elsevier Ltd. All rights reserved.

Simulation of Brugada syndrome using cellular and three-dimensional whole-heart modeling approaches

Brugada syndrome (BS) is a genetic disease identified by an abnormal electrocardiogram ( ECG) ( mainly abnormal ECGs associated with right bundle branch block and ST-elevation in right precordial leads). BS can lead to increased risk of sudden cardiac death. Experimental studies on human ventricular myocardium with BS have been limited due to difficulties in obtaining data. Thus, the use of computer simulation is an important alternative. Most previous BS simulations were based on animal heart cell models. However, due to species differences, the use of human heart cell models, especially a model with three-dimensional whole-heart anatomical structure, is needed. In this study, we developed a model of the human ventricular action potential (AP) based on refining the ten Tusscher et al (2004 Am. J. Physiol. Heart Circ. Physiol. 286 H1573 - 89) model to incorporate newly available experimental data of some major ionic currents of human ventricular myocytes. These modified channels include the L-type calcium current (ICaL), fast sodium current (I-Na), transient outward potassium current (I-to), rapidly and slowly delayed rectifier potassium currents (I-Kr and I-Ks) and inward rectifier potassium current (I-Ki). Transmural heterogeneity of APs for epicardial, endocardial and mid-myocardial (M) cells was simulated by varying the maximum conductance of IKs and Ito. The modified AP models were then used to simulate the effects of BS on cellular AP and body surface potentials using a three-dimensional dynamic heart - torso model. Our main findings are as follows. (1) BS has little effect on the AP of endocardial or mid-myocardial cells, but has a large impact on the AP of epicardial cells. (2) A likely region of BS with abnormal cell AP is near the right ventricular outflow track, and the resulting ST-segment elevation is located in the median precordium area. These simulation results are consistent with experimental findings reported in the literature. The model can reproduce a variety of electrophysiological behaviors and provides a good basis for understanding the genesis of abnormal ECG under the condition of BS disease.

The empirical basis of substance use disorders diagnosis: research recommendations for the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V)

Aims This paper presents the recommendations, developed from a 3-year consultation process, for a program of research to underpin the development of diagnostic concepts and criteria in the Substance Use Disorders section of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and potentially the relevant section of the next revision of the International Classification of Diseases (ICD). Methods A preliminary list of research topics was developed at the DSM-V Launch Conference in 2004. This led to the presentation of articles on these topics at a specific Substance Use Disorders Conference in February 2005, at the end of which a preliminary list of research questions was developed. This was further refined through an iterative process involving conference participants over the following year. Results Research questions have been placed into four categories: (1) questions that could be addressed immediately through secondary analyses of existing data sets; (2) items likely to require position papers to propose criteria or more focused questions with a view to subsequent analyses of existing data sets; (3) issues that could be proposed for literature reviews, but with a lower probability that these might progress to a data analytic phase; and (4) suggestions or comments that might not require immediate action, but that could be considered by the DSM-V and ICD 11 revision committees as part of their deliberations. Conclusions A broadly based research agenda for the development of diagnostic concepts and criteria for substance use disorders is presented.