PubMed Health⌕ Search

Biomedical subjects

E T Hille

Publications and source records attributed to E T Hille.

9 recordsLinked to original sources
PubMed2001

Behavioural problems in children who weigh 1000 g or less at birth in four countries.

BACKGROUND: The increased survival chances of extremely low-birthweight (ELBW) infants (weighing <1000 g at birth) has led to concern about their behavioural outcome in childhood. In reports from several countries with different assessments at various ages, investigators have noted a higher frequency of behavioural problems in such infants, but cross-cultural comparisons are lacking. Our aim was to compare behavioural problems in ELBW children of similar ages from four countries. METHODS: We prospectively studied 408 ELBW children aged 8-10 years, whose parents completed the child behaviour checklist. The children came from the Netherlands, Germany, Canada, and USA. The checklist provides a total problem score consisting of eight narrow-band scales. Of these, two (aggressive and delinquent behaviour) give a broad-band externalising score, three (anxious, somatic, and withdrawn behaviour) give a broad-band internalising score, and three (social, thought, and attention problems) indicate difficulties fitting neither broad-band dimension. For each cohort we analysed scores in ELBW children and those in normal- birthweight controls (two cohorts) or national normative controls (two cohorts). Across countries, we assessed deviations of the ELBW children from normative or control groups. FINDINGS: ELBW children had higher total problem scores than normative or control children, but this increase was only significant in European countries. Narrow-band scores were raised only for the social, thought, and attention difficulty scales, which were 0.5-1.2 SD higher in ELBW children than in others. Except for the increase in internalising scores recorded for one cohort, ELBW children did not differ from normative or control children on internalising or externalising scales. INTERPRETATION: Despite cultural differences, types of behavioural problems seen in ELBW children were very similar in the four countries. This finding suggests that biological mechanisms contribute to behavioural problems of ELBW children.

Canada↗
PubMed2000

Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden).

Familial atypical multiple mole melanoma (FAMMM) is an autosomal dominant disease characterized by the familial occurrence of malignant melanoma of the skin and multiple atypical precursor lesions. Germline mutations in the p16 (CDKN2A) gene have been reported in at least a quarter of such families. An association has been reported between p16 mutations and pancreatic cancer. The aim of this study was to assess the risk of developing pancreatic and other cancers in Dutch FAMMM families with a 19 bp deletion in exon 2 of the p16 gene (p16-Leiden). Mutation analysis was performed in 27 families suspected of FAMMM. Clinical and pathological data were collected from all relatives affected with cancer. A p16-Leiden mutation was identified in 19 families. These families included 86 patients with melanoma. The second most frequent cancer was pancreatic cancer, which was observed in 15 patients from 7 families. The mean age at diagnosis of pancreatic cancer was 58 years (range 38-77 years). The estimated cumulative risk of developing pancreatic cancer in putative mutation carriers by age 75 years was 17%. In 8 p16-Leiden-negative families, no cases of pancreatic cancer occurred. p16 mutation carriers have a considerable risk of developing pancreatic cancer. Further studies should evaluate the value of surveillance of the pancreas in these high-risk families.

Adult↗
PubMed1999

Risk of cutaneous malignant melanoma in patients with nonfamilial atypical nevi from a pigmented lesions clinic.

BACKGROUND: Atypical nevi (AN) are regarded as a major risk factor for occurrence of malignant melanoma. Few studies report an increase in relative risk for melanoma in patients with nonfamilial AN. OBJECTIVE: We measured the risk of melanoma in 195 patients with nonfamilial AN. METHODS: In a retrospective follow-up study the number of newly diagnosed melanomas during follow-up were inventoried. Included patients were invited for skin screening and nevus count. RESULTS: On the basis of our calculations, the relative risk for invasive melanoma in patients with nonfamilial AN, including those patients with a history of melanoma, is 41. For individuals with AN without a previously diagnosed melanoma, the relative risk was 37. Multivariate analysis did not reveal a specific risk factor for the occurrence of melanoma (including number of AN) because of small numbers. Invasive melanomas occurred in persons having 1, 5, 12, and 172 AN, respectively. CONCLUSION: An increased risk for invasive cutaneous malignant melanoma in patients with nonfamilial AN was established.

Adolescent↗
PubMed1999

A locus linked to p16 modifies melanoma risk in Dutch familial atypical multiple mole melanoma (FAMMM) syndrome families.

The CDKN2A gene that encodes the cell cycle inhibitor p16 shows mutations in many but not all 9p21-linked melanoma families. Most Dutch melanoma families segregate for a unique founder mutation (p16-Leiden), encoding a truncated nonfunctional p16 protein. The highly variable risk for p16-Leiden carriers to develop melanoma suggests a role for other genetic and/or environmental factors. We hypothesized that a 9p21 gene other than CDKN2A may be relevant in the remaining 9p21-linked melanoma families without p16 mutations but may also act as a risk modifier in p16-Leiden carriers. Haplotype analysis for 9p21 was performed using microsatellite markers in six p16-Leiden families originating from a founder population. p16-Leiden carriers in two families shared an unexpectedly large founder haplotype ( approximately 20-cM) around CDKN2A, mostly in proximal direction. Melanoma-positive p16-Leiden carriers from these families showed this extensive proximal haplotype compared with melanoma-negative p16-Leiden carriers from the same families. Additional p16-Leiden families less heavily affected with melanoma showed shorter haplotypes sharing, excluding the region proximally of CDKN2A. The presence of a gene involved in melanoma susceptibility proximal of CDKN2A is corroborated by somatic deletions of 9p in tumors, which frequently do not include CDKN2A but a more proximal chromosomal area instead. Our results provide a candidate region for further gene mapping in p16-negative 9p21-linked melanoma families and guide the search for risk modifiers in melanoma development.

Alleles↗
PubMed1999

Two centuries of mortality in ten large families with Huntington disease: a rising impact of gene carriership.

To estimate the impact of the Huntington gene on mortality, we studied ten families with Huntington disease, whose records started before 1800. We investigated mortality from 1800 to 1997 in 257 carriers of the Huntington gene and 474 potential carriers. Follow-up extended from age 20 years to the date of death or end-of-study date. The observed deaths were compared with those expected on the basis of the general population, adjusted for sex, age, and calendar time. To study the influence of the family and parental transmission, we calculated hazard ratios adjusted for sex, probability of carrying the gene, and year of birth. In 25,013 person-years, 420 deaths occurred, whereas 278 deaths were expected [standardized mortality ratio = 1.5; 95% confidence interval (CI) = 1.4-1.7]. Excess mortality was confined to ages 40-70 years (standardized mortality ratio = 2.2; 95% CI = 1.9-2.4). To study the evolution of mortality over time in this age group, we calculated absolute mortality rates per calendar period. From 1800 onward, mortality rates in the general population continuously declined, but among the families with Huntington disease this decline was absent. There were only small differences in risk between families, and the relative risk for paternal over maternal transmission was 1.2 (95% CI = 0.9-1.5). Our main finding is that persons who carry the Huntington gene and reach middle age have not benefited from advances in medical care and overall increase in life expectancy.

Adult↗
PubMed1998

Excess cancer mortality in six Dutch pedigrees with the familial atypical multiple mole-melanoma syndrome from 1830 to 1994.

An increased incidence of systemic cancers has been described in some reports of familial atypical multiple mole-melanoma kindreds. If the gene defect underlying the familial atypical multiple mole-melanoma syndrome is not only important for the development of melanoma of the skin, the impact of the defect on life expectancy may be much higher than previously thought. We investigated all-cause mortality from 1830 to the present and causes of death from 1941 to 1994 in proven, obligate, and potential CDKN2 mutation carriers to obtain an estimate of the impact of a hereditary defect of the CDKN2 gene on mortality. From 1830 to 1994 there were 65 deaths, although only 42 deaths were expected [standardized mortality ratio (SMR) 1.6, 95% confidence interval (CI) 1.2-2.0] and the SMR doubled with calendar time. Excess mortality was shown in most of the families, but was confined to ages 35-70 y (SMR 2.1, 95%CI 1.5-2.9). Excess mortality could be fully attributed to cancer mortality, especially to pancreatic carcinoma and melanoma of the skin. There appeared to be some heterogeneity among the families, especially due to the specific cancer pattern within a family. The impact of the defect of the CDKN2 gene is rising over calendar time, mainly because the mortality in the general population has been falling. Excess mortality was not only due to melanoma, but also to pancreatic carcinoma. Therefore, follow-up programs of affected family members should not be confined to a regular check of the atypical nevi.

Adult↗
PubMed1997

Mortality and causes of death in families with the factor V Leiden mutation (resistance to activated protein C).

To investigate whether resistance to activated protein C (APC resistance) because of a mutation in the factor V gene (factor V Leiden) leads to a decrease in life expectancy, we analyzed overall and cause-specific mortality in 171 parents whose offspring carried this mutation. Compared with the Dutch general population, and after adjustment for age, sex, and calendar period, we found no excess deaths in the parents (standardized mortality ratio [SMR], 1.0; 95% confidence interval [CI], 0.8 to 1.2). The cause-specific SMR for malignant neoplasms (1.0; 95% CI, 0.6 to 1.4), diseases of the circulatory system (1.0; 95% CI, 0.7 to 1.4), and cerebrovascular disease (1.0; 95% CI, 0.4 to 1.9) also did not differ from unity. The SMRs for diseases of the respiratory system (1.4; 95% CI, 0.6 to 2.6) and for ischemic heart diseases (1.1; 95% CI, 0.7 to 1.7) were slightly increased. Under the age of 45 years, there was a ninefold increase of dying from ischemic heart disease. Thromboembolic complications were mentioned only once (venous embolism or thrombosis) as an underlying ("primary") cause of death (SMR, 2.3; 95% CI, 0.1 to 13.0) and three times (pulmonary embolisms) as a contributing ("secondary") cause of death (SMR, 1.5; 95% CI, 0.3 to 4.4). We conclude that there is no major effect of APC resistance on life expectancy. Therefore, long-term anticoagulation in carriers of factor V Leiden, on the basis of the carrier state alone, is not indicated.

Adult↗
PubMed1994

School performance at nine years of age in very premature and very low birth weight infants: perinatal risk factors and predictors at five years of age. Collaborative Project on Preterm and Small for Gestational Age (POPS) Infants in The Netherlands.

To assess the impact of both perinatal disorders and developmental problems identified at preschool age on school performance, we followed a virtually complete birth cohort of very premature (< 32 completed weeks of gestation) and very low birth weight infants until they were 9 years of age. In 84% of the survivors (n = 813), data on school performance were available for analysis. At the age of 9 years, 19% of the children were in special education. Of the children in mainstream education, 32% were in a grade below the appropriate level for age and 38% had special assistance. After correction for other perinatal items, children of low socioeconomic status and boys had significantly higher adjusted odds ratios for special education. Logistic regression with a perinatal and a 5-year time category showed that the most predictive factors for special education were developmental delay, neuromotor and speech/language function, inattention and hyperactivity score, total problem score, and reported school results at the age of 5 years. When children with disabilities were left out of the analysis, the importance of neuromotor function and total problem score disappeared. Increased risks of any school failure in nondisabled children included mild or severe developmental delay and marginal or poor school performance at the age of 5 years. Long-term follow-up with specific attention to these predictors at 5 years of age, although time-consuming, is necessary.

Birth Weight↗