Phenylbutyrate inhibits homologous recombination induced by camptothecin and methyl methanesulfonate.

Homologous recombination is accompanied by extensive changes to chromatin organization at the site of DNA damage. Some of these changes are mediated through acetylation/deacetylation of histones. Here, we show that recombinational repair of DNA damage induced by the anti-cancer drug camptothecin (CPT) and the alkylating agent methyl methanesulfonate (MMS) is blocked by sodium phenylbutyrate (PBA) in the budding yeast Saccharomyces cerevisiae.

Tonsillitis, tonsillectomy and Hodgkin's lymphoma.

It has been debated whether the reported increased risk of Hodgkin's lymphoma (HL) after tonsillectomy could be due to some underlying factor rather than the surgery itself. We studied whether not only tonsillectomy but also tonsillitis was associated with HL. This nationwide cohort study included all Danish residents during 1977-2001.

Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial.

Background: Parasitic helminth infections can protect against allergic airway inflammation in experimental models and have been associated with a reduced risk of atopy and a reduced course of asthma in some observational studies. Although no clinical evidence exists to support the use of helminth therapy for allergic disease, the helminth Trichuris suis has demonstrated efficacy in treatment of inflammatory bowel disease.

Objective: To determine efficacy of helminth therapy for allergic rhinitis.

Maternal and gestational risk factors for hypospadias.

Background: An increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown.

Objectives: Our goal was to assess the association between risk of hypospadias and indicators of placental function and endogenous hormone levels, exposure to exogenous hormones, maternal diet during pregnancy, and other environmental factors.

Methods: We conducted a case-control study in Sweden and Denmark from 2000 through 2005 using self-administered questionnaires completed by mothers of hypospadias cases and matched controls.

Familial aggregation of cryptorchidism--a nationwide cohort study.

Although cryptorchidism is the most common birth defect in boys affecting 4-9 percent of newborns and 1-2 percent of boys 1 year of age, the etiology remains largely unknown. The authors investigated the contribution of genetic and environmental factors to familial aggregation of cryptorchidism. Using Danish health registers, they identified 25,395 boys diagnosed with cryptorchidism in a cohort of 1,022,713 boys born in 1977-2005.

Testicular cancer risk in first- and second-generation immigrants to Denmark.

Background: Immigrant studies offer insights into the relative importance of environment and genes in disease etiology. There is considerable variation in testicular cancer incidence worldwide. We investigated testicular cancer risk in first- and second-generation immigrants to Denmark, a high-incidence country, to evaluate the relative influence of genes and environment and the potential timing of action of environmental factor(s).

Association between intussusception and tonsil disease in childhood.

Background: Intussusception is the most common cause of intestinal obstruction in infancy and early childhood, but its etiology remains unknown. The present study analyzes whether some children with intussusception subsequently have a higher risk of tonsil disease, suggesting an enhanced tendency to lymphoid hyperplasia.

Methods: This nationwide cohort study included all Danish children younger than age 15 years, who were born in 1977-2001 and diagnosed with intussusception at a hospital (n = 2018).

Incidence of tonsillectomy in Denmark, 1980 to 2001.

Background: Tonsillectomy is one of the most frequent operations performed on children and young adults, but little is known regarding its distribution by age, sex, and calendar period.

Methods: We designed a population-based cohort study including all Danish residents from 1980 to 2001 to describe national incidence figures for tonsillectomy. Persons undergoing tonsillectomy were identified in the Danish National Patient Registry and from the Danish Health Security System.

Familial aggregation of hypospadias: a cohort study.

Hypospadias is one of the most common birth defects. However, its etiology remains largely unknown. The authors investigated the contribution of genetic and environmental factors to familial aggregation of hypospadias.

Type 1 diabetes and multiple sclerosis: A Danish population-based cohort study.

Background: Type 1 diabetes mellitus (T1D) and multiple sclerosis (MS) contribute considerably to the burden of autoimmune diseases in young adults. Although HLA patterns of T1D and MS are considered mutually exclusive, individual and familial co-occurrence of the 2 diseases has been reported.

Objective: To assess the co-occurrence of T1D and MS by estimating the risk for MS in patients with T1D and the risk for T1D in first-degree relatives of patients with MS.

Maternal serum alpha-fetoprotein level during pregnancy and isolated cryptorchidism in male offspring.

Cryptorchidism is thought to result from a disruption of the androgen-estrogen balance in utero. Alpha-fetoprotein (AFP) interacts with and may modulate fetal responses to estrogens. Using a cohort of boys born to women participating in a Danish maternal serum AFP screening program between 1980 and 1994, the authors explored whether AFP levels (as reflected by maternal serum AFP levels in gestational weeks 14-22) were associated with the risk of isolated cryptorchidism in male offspring.

Sibship characteristics and risk of multiple sclerosis: a nationwide cohort study in Denmark.

It has been hypothesized that age at infection with a common microbial agent may be associated with the risk of multiple sclerosis (MS). The authors addressed this hypothesis by using number of older siblings and other sibship characteristics as an approximation of age at exposure to common infections. Data on family characteristics and vital status from the Danish Civil Registration System were used to establish a cohort of all Danes whose mothers had been born in Denmark since 1935.

Familial risk of multiple sclerosis: a nationwide cohort study.

Multiple sclerosis (MS) is known to accumulate within families. The magnitude of the familial risk, however, remains uncertain. Using a nationwide MS register and other national registers, the authors estimated relative and absolute risks of MS in a population-based cohort that included 19,615 first-degree relatives of 8,205 Danish MS patients followed from 1968 to 1997.

A comparison of risk factors for wheeze and recurrent cough in preschool children.

In a study of 2,978 Danish children aged 5 years from two suburban counties of Copenhagen, carried out in 1998, the authors compared risk factor profiles for wheeze and recurrent cough without wheeze by using polytomous logistic regression to clarify whether the two conditions are likely to have the same etiology. Data were obtained 1) by a mailed parental questionnaire (International Study of Asthma and Allergies in Childhood questions and supplementary questions on cough, sociodemography, perinatal factors, and environmental exposure); 2) through general practitioners (familial allergic disease); and 3) from the National Medical Birth Register (birth weight). Wheeze (WH) was defined as more than one episode of wheeze within the last 12 months (irrespective of cough status) and recurrent cough without WH (RC) as cough occurring outside colds and usually lasting for periods of more than 1 week in children with no more than one attack of wheeze within the last 12 months.

Sibship characteristics and risk of allergic rhinitis and asthma.

Studying associations between sibship characteristics and allergic diseases in detail may contribute clues to their etiology. The authors studied associations between sibship characteristics and risk of self-reported allergic rhinitis and asthma among 31,145 pregnant women participating in a nationwide study in Denmark during 1997-2000. Increasing sibship size was associated with a decreased risk of allergic rhinitis and asthma with allergic rhinitis but not with asthma without allergic rhinitis.

Reproductive factors and extreme levels of maternal serum alpha-fetoprotein: a population-based study.

Background: Levels of maternal alpha-fetoprotein (AFP) are increased during multiple gestations and preeclampsia but little is known regarding AFP levels in relation to other reproductive factors. Consequently, the objective of this work was to describe the possible relationship between AFP levels during pregnancy and maternal age at birth, maternal age at first birth, parity, time since previous birth and gender of the offspring.

Methods: Based on national registries we obtained the reproductive history on a population-based cohort of 44 227 women who had serum AFP levels determined in gestational weeks 14-21 and whose present and previous pregnancies resulted in live-born singletons.

Birth weight and risk for childhood leukemia in Denmark, Sweden, Norway, and Iceland.

Background: Compelling evidence suggests that childhood leukemia often originates in utero. Birth weight is one of the few pregnancy-related risk factors that has been associated with leukemia risk, but the association has remained poorly characterized. We conducted a population-based case-control study in Denmark, Sweden, Norway, and Iceland to investigate the association between birth weight (and other birth characteristics) and the risk of childhood leukemia.

Childhood infections and risk of multiple sclerosis.

Multiple sclerosis has been hypothesized to be the result from an aberrant immune response possibly triggered by delayed exposure to a common childhood infection. Because the vast majority of previous studies testing this hypothesis have been based on a history of childhood infections recalled years to decades later in adulthood, we investigated whether age at six common childhood infections was associated with risk of multiple sclerosis, using information recalled in the childhood of a historical cohort of school children in Denmark. Cases included all individuals with multiple sclerosis in the country born between 1940 and 1975, who had attended school in the capital, Copenhagen.

Breastfeeding and risk of atopic dermatitis, by parental history of allergy, during the first 18 months of life.

The role of breastfeeding in allergic diseases remains controversial. The authors studied the association between breastfeeding and development of atopic dermatitis during the first 18 months of life among children with and without a parental history of allergy. A cohort study of 15,430 mother-child pairs enrolled in The Danish National Birth Cohort was carried out between 1998 and 2000.

Birth weight as a risk factor for childhood leukemia: a meta-analysis of 18 epidemiologic studies.

Evidence has emerged that childhood leukemia is initiated in utero. High birth weight is one of the few birth-related factors that has been associated with childhood leukemia, albeit not consistently. The authors conducted a meta-analysis of studies of the association between birth weight and childhood leukemia risk.

Smallpox vaccination and risk of allergy and asthma.

Background: It has been proposed that childhood vaccinations may influence the development of allergy. Atopy and allergic diseases have increased after routine smallpox vaccination was stopped in the 1970s.

Objective: We examined whether administration of smallpox vaccination during childhood was associated with a decreased risk of atopy, allergic rhinitis, and asthma.

Does pregnancy induce the shedding of premalignant ovarian cells?

Background: High parity is associated with reduced risk of ovarian cancer. One hypothesis is that pregnancy is associated with clearance of a fraction of the genetically modified (premalignant) cells from the ovaries.

Methods: We evaluated this hypothesis using a model that estimates the cell clearance fraction at first and second pregnancy according to age at pregnancy.

Mode of delivery and risk of allergic rhinitis and asthma.

Background: It has been hypothesized that cesarean section might increase the risk of developing allergic disease by depriving the fetus and newborn of exposure to maternal microflora. Furthermore, it has been suggested that complicated modes of delivery might be associated with an increased risk of asthma.

Objective: The purpose of this investigation was to study whether cesarean section and other complicated modes of delivery are associated with an increased risk of allergic rhinitis or asthma.