A population-based familial aggregation analysis indicates genetic contribution in a majority of renal cell carcinomas

The etiology of RCC is incompletely understood and the inherited genetic contribution uncertain. Although there are rare mendelian forms of RCC stemming from inherited mutations, most cases are thought to be sporadic. We sought to determine the extent of familial aggregation among Icelandic RCC patients in general. Medical and pathologic records for all patients diagnosed with RCC in Iceland between 1955 and 1999 were reviewed. This included a total of 1,078 RCC cases, 660 males and 418 females. With the use of an extensive computerized database containing genealogic information on 630,000 people in Iceland during the past 11 centuries, several analyses were conducted to determine whether the patients were more related to each other than members drawn at random from the population. Patients with RCC were significantly more related to each other than were subjects in matched groups of controls. This relatedness extended beyond the nuclear family. RRs were significantly greater than 1.0 for siblings, parents and cousins of probands. RRs were 2-3 for first-degree relatives and 1.6 for third-degree relatives. The risk of RCC is significantly higher for members of the extended family of an affected individual, as well as the nuclear family. Our results indicate that germline mutations are significantly involved in what has been defined as sporadic RCC.     

Reliability of ultrasonography for the cervical multifidus muscle in asymptomatic and symptomatic subjects

A test-retest and inter-tester study was designed to assess the reliability of ultrasonography to depict the size of the cervical multifidus muscle in asymptomatic and symptomatic subjects. Ten asymptomatic women (range 19-48 years) and 10 women with chronic whiplash associated disorder (WAD), grade II, (range 19-49 years), matched for height and weight participated. The women were imaged by ultrasonography on two separate occasions by two different testers. On each occasion the cross-sectional area (CSA), and the transverse versus the anterior-posterior dimensions (shape ratio) at the C4 level were measured. The repeated measurements of the CSA were plotted against their means to reveal the limit of agreement. Good agreement was found for the asymptomatic group measurements and the intra-tester agreement for the symptomatic group. The inter-tester agreement for the symptomatic group was questionable. The size of the multifidus muscle was significantly reduced in the symptomatic group ( P<0.05 ). The results indicate that loss of clarity of the fascial layer between the semispinalis cervicis muscle and the cervical multifidus muscle may be a diagnostic sign of muscle atrophy. Ultrasonography can be used to precisely measure the size of the cervical multifidus muscle at the C4-level in asymptomatic young female subjects; it is also reliable for symptomatic subjects if the same tester performs the measurements. Additional criteria are recommended to improve the inter-tester agreement for symptomatic subjects.     

Cognitive decline in high-functioning older adults: reserve or ascertainment bias?

The detection of mild cognitive impairment and dementia in high-functioning older adults can be difficult. It has also been observed that high-functioning persons show a lower prevalence of dementia than low-functioning persons. Three alternative explanations for this observation have been proposed in the literature: brain reserve capacity (BRC), cognitive reserve, and ascertainment bias. With data from a prospective, population-based study of incident dementia, the Canadian Study of Health and Aging (CSHA), we classified participants as being high- (HF) or low-functioning (LF) in three ways: educational and occupational attainment, and estimated premorbid IQ. We observed that fewer HF older adults were diagnosed with dementia after five years, which is in accordance with both the BRC and cognitive reserve models. Contrary to expectations, no difference on rate of memory deterioration was observed between those HF and LF persons who exhibited mild cognitive impairment at CSHA-1. However, HF persons who subsequently were diagnosed with dementia (CSHA-2) showed more rapid decline on five of the six memory measures over time than did LF persons diagnosed with dementia at CSHA-2. When performance on measures of memory functioning at CSHA-1 was examined for highly educated older adults, significantly more of those with dementia at CSHA-2 (n = 59) had scores falling within or below the average range in comparison to normative standards than those who continued to show no cognitive impairment (n = 145). Our findings suggest that the lower incidence of dementia for HF persons may be primarily the result of ascertainment bias, not underlying differences in brain or cognitive reserve.     

Five-year follow-up of cognitive impairment with no dementia

CONTEXT: The importance of early identification of dementia has prompted numerous investigations of mild cognitive impairment and the preclinical stages of progressive degenerative disorders. To date, there is limited information from large-scale studies regarding outcomes of persons specifically identified with cognitive impairment but no dementia (CIND). OBJECTIVES: To investigate outcomes for persons with no cognitive impairment (NCI) or CIND, focusing on its etiologic subcategories, from the Canadian Study of Health and Aging (CSHA) and to examine the predictive validity of a set of core features thought to be early manifestations of subsequent dementia. DESIGN: Five-year, longitudinal follow-up of all persons without dementia examined during the first phase of the CSHA in 1991. SETTING: Community and institutional settings. PARTICIPANTS: Population-based sample of 883 persons with NCI and 801 persons with CIND at the first phase of the CSHA. At follow-up, 517 persons with NCI (59%) and 327 persons with CIND (41%) were alive and received clinical diagnoses. MAIN OUTCOME MEASURES: Mortality, institutionalization, and clinical diagnoses using the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria for dementia. RESULTS: Persons with CIND were more likely than those with NCI to die (49% vs 30%), to be admitted to facility care (29% vs 14%), or to receive diagnoses of dementia (47% vs 15%) at follow-up. Those subsequently diagnosed as having dementia were more likely to have had impaired memory, informant-reported change in memory, and functional impairment at baseline. CONCLUSIONS: Persons with CIND were more likely to have a negative outcome than persons with NCI during a 5-year interval. This was true across etiologic subcategories and suggests that the use of specific diagnostic criteria sets does not improve our identification of those who develop dementia compared with a broader, more inclusive approach. More factors contributed to the prediction of all forms of dementia than to AD, but the most accurate prediction was for those who remained dementia free.     

Social correlates of cigarette smoking among Icelandic adolescents: A population-based cross-sectional study

Background  

Previous research has shown that between 80 and 90 percent of adult smokers report having started smoking before 18 years of age. Several studies have revealed that multiple social factors influence the likelihood of smoking during adolescence, the period during which the onset of smoking usually occurs. To better understand the social mechanisms that influence adolescent smoking, we analyzed the relationship and relative importance of a broad spectrum of social variables in adolescent smoking in Iceland, a Nordic country with high per-capita income.     

Trends in prevalence of substance use among Icelandic adolescents, 1995–2006

Background  

Adolescent substance use continues to be of great global public health concern in many countries with advanced economies. Previous research has shown that substance use among 15–16 year-old-youth has increased in many European countries in recent years. The aim of this study was to examine trends in prevalence of daily smoking, alcohol intoxication, and illicit substance use among Icelandic adolescents.     

Niemann-Pick-like liver disease and reduced cholesterol esterification in fibroblasts of two male infants

Niemann-Pick disease type C (NPC) presents in about half of the cases in the newborn period with jaundice, hepato-splenomegaly, and a clinical pattern similar to neonatal hepatitis. The definitive diagnosis can in most instances be made by the appropriate biochemical testing of lipoprotein stimulated cholesteryl ester synthesis and cholesterol accumulation in cultured patient fibroblasts. We report two infants who by liver biopsy had classical findings of NPC and a cholesteryl ester synthesis level about 50% of the normal lower limit. On the other hand neither of these patients' fibroblasts showed any evidence of low density lipoprotein-induced cholesterol accumulation, precluding the possibility of a definitive diagnosis. These cases demonstrate the importance of the appropriate biochemical testing before final counseling is carried out. The possibility of our patients representing allelic or nonallelic variants of NPC are discussed.     

A syndrome of progressive pancytopenia with microcephaly, cerebellar hypoplasia and growth failure

A male infant with congenital thrombocytopenia, progressing to pancytopenia in the second year of life is presented. Other findings included microcephaly with cerebellar hypoplasia, growth failure of prenatal onset and severe psychomotor retardation. He died at 23 months of age from candida albicans septicemia. Laboratory studies and a postmortem examination failed to reveal any known etiology for his disorder, but parental consanguinity suggests a genetic basis with an autosomal recessive mode of inheritance. H?yeraal et al. have previously reported two brothers with similar clinical and laboratory findings. It is proposed that the condition of these three patients should be considered as a separate syndrome of congenital pancytopenia, distinguished from other congenital myeloid dysplasias by the extramedullary findings.