Search for intracranial aneurysm susceptibility gene(s) using Finnish families

Background

Cerebrovascular disease is the third leading cause of death in the United States, and about one-fourth of cerebrovascular deaths are attributed to ruptured intracranial aneurysms (IA). Epidemiological evidence suggests that IAs cluster in families, and are therefore probably genetic. Identification of individuals at risk for developing IAs by genetic tests will allow concentration of diagnostic imaging on high-risk individuals. We used model-free linkage analysis based on allele sharing with a two-stage design for a genome-wide scan to identify chromosomal regions that may harbor IA loci.

Methods

We previously estimated sibling relative risk in the Finnish population at between 9 and 16, and proceeded with a genome-wide scan for loci predisposing to IA. In 85 Finnish families with two or more affected members, 48 affected sibling pairs (ASPs) were available for our genetic study. Power calculations indicated that 48 ASPs were adequate to identify chromosomal regions likely to harbor predisposing genes and that a liberal stage I lod score threshold of 0.8 provided a reasonable balance between detection of false positive regions and failure to detect real loci with moderate effect.

Results

Seven chromosomal regions exceeded the stage I lod score threshold of 0.8 and five exceeded 1.0. The most significant region, on chromosome 19q, had a maximum multipoint lod score (MLS) of 2.6.

Conclusions

Our study provides evidence for the locations of genes predisposing to IA. Further studies are necessary to elucidate the genes and their role in the pathophysiology of IA, and to design genetic tests.     

Familial subarachnoid hemorrhage. Outcome study

BACKGROUND AND PURPOSE: The aim of our study was to compare outcome and its determinants in familial subarachnoid hemorrhage and in sporadic subarachnoid hemorrhage in a large and well-documented patient population. METHODS: Patients with aneurysmal subarachnoid hemorrhage (SAH) treated at the Department of Neurosurgery, Kuopio University Hospital, from 1977 to 1995 were included. Patients with polycystic kidney disease were excluded. The Glasgow Outcome Scale (GOS) score at 12 months was studied. RESULTS: There were 120 patients (97 first-, 15 second-, and 8 third-degree family connections) in 96 different families with familial SAH and 1237 patients with sporadic SAH. Age, gender, and admission grade on the Hunt and Hess scale did not differ between these 2 groups. In both groups >80% of patients were in relatively good condition at admission. The outcome was good (GOS score of 1 to 2) in 87 patients (73%) with familial SAH and in 874 patients (71%) with sporadic SAH. Analysis of 20 variables, including presence of coexisting diseases, aneurysm site and size, amount of blood shown on CT scan, intraventricular bleeding, preoperative intracerebral hematoma and hydrocephalus, as well as postoperative bleeding and vasospasm, revealed no significant differences between study groups. The degree of family connection (first-, second-, and third-degree) did not have any statistically important effect on outcome in the familial group in the Finnish study population. In multivariate analysis the knowledge of familial SAH was not an independent prognostic factor. CONCLUSIONS: Admission status, postoperative course, and outcome were similar in the familial and sporadic SAH groups in this Finnish population, in contrast to previous results. Familial SAH may not be a significant risk factor for poor outcome.     

High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: a Kalixanda study report

OBJECTIVE: Gastroesophageal reflux disease has been reported to be a common burden on health-care resources in the Western world, but its manifestations in the general population are as yet unclear. The aim of this study was to estimate the prevalence of, and to identify the risk factors for gastroesophageal reflux symptoms (GERS) and erosive esophagitis (EE) in the adult population of two Swedish municipalities. MATERIAL AND METHODS: A random sample (n =3000) of the adult population (20-81 years of age) of two Swedish municipalities (n =21,610) was surveyed using a validated postal questionnaire assessing gastrointestinal symptoms. The response rate was 74%. A subsample (n = 1000) of the responders was subsequently invited, in random order, for esophago-gastro-duodenoscopy with evaluation of GERS, risk factors and tests for Helicobacter pylori. RESULTS: GERS were reported by 40.0% and EE was found in 15.5% of the population that had undergone endoscopy. Of those with GERS, 24.5% had EE while 36.8% of those with EE reported no GERS. Hiatus hernia and obesity remained significant risk factors for GERS and/or EE, with or without symptoms in a main effect model (OR up to 14 at EE). Those with active H. pylori infection had a higher risk of GERS without EE than those without H. pylori infection (OR = 1.71 (1.23 2.38)). CONCLUSIONS: GERS and EE (of which one-third is asymptomatic) are highly prevalent in the Swedish adult population. H. pylori infection seems to play a role in the manifestations of gastroesophageal reflux.     

Validation of the translation and cross-cultural adaptation into Finnish of the Abdominal Symptom Questionnaire, the Hospital Anxiety and Depression Scale and the Complaint Score Questionnaire

BACKGROUND: Epidemiological surveys require questionnaires to be validated in the native language of the participants. The aim of this study was to validate the Finnish translations of the Abdominal Symptom Questionnaire (ASQ), the Hospital Anxiety and Depression Scale (HAD) and the Complaint Score Questionnaire (CSQ). METHODS: A random sample of adults (n = 3000) in a northern Swedish bilingual district was surveyed using a mailed ASQ offered in both SwedIsh and Finnish, and 2122 responded (239 in Finnish). A random subsample of the responders (n = 1001, 123 preferring Finish) was then surveyed once more using the ASQ, the HAD and the CSQ. The first 50 responders of the latter survey were then given the three questionnaires again within two weeks. The Finnish versions had been put through a comprehensive translation procedure RESULTS: A factor analysis comparison between the responders using either language in the mailed survey gave a comparable factor construction, and this was also comparable with an earlier analysis of the Swedish version. The Finnish responses to the second survey were further evaluated by testing internal consistency reliability, convergent validity towards previously validated relevant instruments (ShortForm-36 and the Gastrointestinal Symptom Rating Scale) and the test/re-test accuracy of the three questionnaires. These were found to be reliable, as was the correlation between the ASQ and the CSQ, for relevant domains. CONCLUSION: The Finnish translations of the ASQ, HAD and CSQ questionnaires all seem to be robust and usable for population-based surveys among Finnish adults.