Serologic markers anti-Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies with perinuclear staining (pANCA) have been proposed to study the immunopathogenesis of ...IBD. Their measurement may allow better phenotyping of the disease and the detection of subclinical disease.
To test the hypothesis that serological markers identify an immunologic trait related to disease susceptibility. We also wanted to test the hypothesis that ASCA is a marker related to abnormal tissue permeation by common antigens.
We studied the prevalence of pANCA and ASCA in a large cohort of sporadic and familial inflammatory bowel diseases and their unaffected relatives and spouses. Kinetics of ASCA was studied and the relationship between ASCA and 51Cr-EDTA intestinal permeation was investigated.
ASCA was associated with sporadic Crohn's disease (CD) (63%), with Crohn's patients belonging to pure CD families (62%) and also with their unaffected family members (21%). pANCA was associated with UC (58%). The prevalence of ASCA in CD patients belonging to mixed families was strikingly low (33%). ASCA was a stable marker throughout the disease and was not related to an increased small intestinal permeability.
ASCA is strongly associated with familial CD in Belgium, and 21% of healthy family members also display the marker. The association is much weaker in patients belonging to mixed families. ASCA is a stable marker and is not a secondary phenomenon due to increased intestinal permeability.
Objective To identify determinants of growth during infancy. Study design The sample included 424 twin pairs from the East Flanders Prospective Twin Survey. Multilevel regression analysis was ...performed and intrapair growth correlations were calculated. The main outcome measure was growth, measured in g/kg/d (0-1 month) or in change in weight z-score (0-6, 6-12 and 12-24 months). Results Growth during infancy was associated with birth weight and gestational age. One z-score increase in birth weight resulted in -1.77 g/kg/d less growth from 0-1 month ( P < .0001). The effect size decreased with age until -0.02 ( P = .70) z-scores less growth from 12 to 24 months. Corresponding numbers for one z-score increase in gestational age decreased from 0.78 ( P = .001) to 0.06 ( P = .40). From 12 to 24 months, paternal height had a significant positive effect. The difference in growth similarity within the twin pair between monozygotic and dizygotic twins increased from non-significant from 0 to 1 month ( P = .49) to a monozygotic:dizygotic ratio approximating 2:1 from 12 to 24 months ( P = .002). Conclusion From 0 to 1 month, environmental factors are most important for growth, whereas genetic factors become more important over time. This is a first step in identifying age windows for future counseling and interventions on the effects of accelerated growth.
Background: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and some related environmental contaminants are aryl hydrocarbon receptor (AhR) ligands that exert reproductive and developmental toxicity in ...laboratory animals. In humans, fertility-related effects are less documented. Objective: The aim of this study was to investigate the relationship between dioxin-like biological activity in serum and parameters of reproductive status in men from the general population 5 months after a polychlorinated biphenyl and dioxin food-contamination episode in Belgium. Design: In the framework of the cross-sectional Flemish Environment and Health Study (FLEHS), we recruited 101 men 20-40 years of age and evaluated sperm parameters, measured sex hormones, and gathered information on a number of lifestyle factors. In addition, we determined the AhR-mediated enzymatic response elicited by individual serum samples and expressed it as TCDD equivalent concentrations (CALUX-TEQs) using an established transactivation assay. Results: Age (p = 0.04) and the frequency of fish (p = 0.02) and egg (p = 0.001) consumption were independent positive determinants of serum dioxin-like activity. After correcting for possible confounders, we found that a 2-fold increase in CALUX-TEQ > 16 pg/L was associated with a 7.1% and 6.8% (both p = 0.04) decrease in total and free testosterone, respectively. We also observed a more pronounced drop in semen volume of 16.0% (p = 0.03), whereas sperm concentration rose by 25.2% (p = 0.07). No relationship was found with total sperm count or sperm morphology. Conclusions: These data suggest an interaction of dioxin-like compounds with the secretory function of the seminal vesicles or prostate, possibly indirectly through an effect on testosterone secretion, at levels not affecting spermatogenesis as such.
Despite the longer gestation of girls, their birthweight is less than that of boys. Because unlike-sex twins provide a natural situation in which to investigate the influence of sex on gestation, we ...compared birthweight and gestation of 1929 same-sex and unlike-sex dizygotic pairs. Length of gestation in unllke-sex pairs was similar to that of female same-sex pairs, and significantly (0·4 weeks; p=0·02) longer than that of male same-sex pairs. Birthweight of girls from unlike-sex pairs was similar to that of girls from same-sex pairs, but boys from unlike-sex pairs weighed 78 g more than boys from same-sex pairs (p=0·001). These data show that in unlike-sex pairs it is the girl that prolongs gestation for her brother, resulting in a higher birthweight than that of same-sex boys.
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The sensitivity of the foreskin and its importance in erogenous sensitivity is widely debated and controversial. This is part of the actual ...public debate on circumcision for non-medical reason. Today some studies on the effect of circumcision on sexual function are available. However they vary widely in outcome. The present study shows in a large cohort of men, based on self-assessment, that the foreskin has erogenous sensitivity. It is shown that the foreskin is more sensitive than the uncircumcised glans mucosa, which means that after circumcision genital sensitivity is lost. In the debate on clitoral surgery the proven loss of sensitivity has been the strongest argument to change medical practice. In the present study there is strong evidence on the erogenous sensitivity of the foreskin. This knowledge hopefully can help doctors and patients in their decision on circumcision for non-medical reason.
To test the hypothesis that sensitivity of the foreskin is a substantial part of male penile sensitivity. To determine the effects of male circumcision on penile sensitivity in a large sample.
The study aimed at a sample size of ≈1000 men. Given the intimate nature of the questions and the intended large sample size, the authors decided to create an online survey. Respondents were recruited by means of leaflets and advertising.
The analysis sample consisted of 1059 uncircumcised and 310 circumcised men. For the glans penis, circumcised men reported decreased sexual pleasure and lower orgasm intensity. They also stated more effort was required to achieve orgasm, and a higher percentage of them experienced unusual sensations (burning, prickling, itching, or tingling and numbness of the glans penis). For the penile shaft a higher percentage of circumcised men described discomfort and pain, numbness and unusual sensations. In comparison to men circumcised before puberty, men circumcised during adolescence or later indicated less sexual pleasure at the glans penis, and a higher percentage of them reported discomfort or pain and unusual sensations at the penile shaft.
This study confirms the importance of the foreskin for penile sensitivity, overall sexual satisfaction, and penile functioning. Furthermore, this study shows that a higher percentage of circumcised men experience discomfort or pain and unusual sensations as compared with the uncircumcised population. Before circumcision without medical indication, adult men, and parents considering circumcision of their sons, should be informed of the importance of the foreskin in male sexuality.
To examine, using a cross-twin cross-trait design, the hypotheses 1) that the genetic and environmental susceptibility to depression is expressed, in part, as alterations in cortisol day curves and ...2) that cortisol abnormalities are not merely the consequence of depressive states or the stressors associated with its onset. Alteration of diurnal secretion of cortisol is a possible endophenotype of depression, as depressed patients show alterations in cortisol dynamics over the day.
Salivary cortisol measurements were obtained in a sample of 279 twin pairs at 10 random times a day for 5 days. A structured clinical interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) axis I mood disorder (SCID) was administered. Using multilevel regression analysis, the moderating influence of a lifetime diagnosis of depression in the co-twin on the association between time of day and cortisol concentrations in the proband twin was examined.
Diurnal variation in cortisol in the proband twin differed as a function of lifetime diagnosis of depression in the co-twin. In addition, this moderating effect was significantly stronger for dizygotic than for monozygotic twins.
Probands of co-twins with lifetime depression have a different diurnal cortisol profile than those without, suggesting that altered hypothalamic-pituitary-adrenal axis functioning is an indicator of depression susceptibility.
The intrauterine environment may be a critical period for the development of hypertension in later life. In the present study, we applied the twin approach to estimate the contribution of genetic and ...environmental causes that may underlie the birth weight-adult blood pressure association.
Birth weights of 418 twin pairs were obtained prospectively, and resting and 24-hour ambulatory blood pressures were obtained at the age of 18 to 34 years. In women, resting systolic blood pressure decreased 4.27 mm Hg (P<0.001) and diastolic pressure decreased 2.18 mm Hg (P=0.02) per kilogram increase in birth weight. Similar associations were found for ambulatory measurements, although these were somewhat less pronounced. Pair-wise analysis confirmed these findings: twin pairs of whom both members had a low birth weight (<2500 g) had a higher systolic blood pressure compared with twins who both had a high birth weight (>/=2500 g). Systolic blood pressure of the lightest of a low-birth-weight pair was >/=4.7 mm Hg (P=0.02) higher and of the heaviest >/=2.4 mm Hg higher (P=0.2) than similar measurements in high-birth-weight pairs. Intrapair differences in blood pressure between the lightest and the heaviest at birth were only present in low-birth-weight pairs. The results were similar for monozygotic and dizygotic twin pairs. In men, no associations were found between birth weight and adult blood pressure.
These findings suggest that prenatal programming of adult blood pressure occurs at least in female twins. We suggest that particularly maternal influences, experienced by both twin members, may underlie the association between birth weight and blood pressure. The fetoplacental unit seems to influence blood pressure only when both fetuses had low birth weight.
Founder mutations among the Dutch ZEEGERS, Maurice P. A; VAN POPPEL, Frans; VLIETINCK, Robert ...
European journal of human genetics : EJHG,
07/2004, Volume:
12, Issue:
7
Journal Article
Peer reviewed
Open access
Many genetic disorders demonstrate mutations that can be traced to a founder, sometimes a person who can be identified. These founder mutations have generated considerable interest, because they ...facilitate studies of prevalence and penetrance and can be used to quantify the degree of homogeneity within a population. This paper reports on founder mutations among the Dutch and relates their occurrence to the history and demography of the Netherlands. International migration, regional and religious endogamy, and rapid population growth played key roles in shaping the Dutch population. In the first millenniums BC and AD, the Netherlands were invaded by Celts, Romans, Huns, and Germans. In more recent times, large numbers of Huguenots and Germans migrated into the Netherlands. Population growth within the Netherlands was slow until the 19th century, when a period of rapid population growth started. Today, the Dutch population numbers 16 million inhabitants. Several different classes of founder mutations have been identified among the Dutch. Some mutations occur among people who represent genetic isolates within this country. These include mutations for benign familial cholestasis, diabetes mellitus, type I, infantile neuronal ceroid lipofuscinosis, L-DOPA responsive dystonia, and triphalangeal thumb. Although not related to a specific isolate, other founder mutations were identified only within the Netherlands, including those predisposing for hereditary breast-ovarian cancer, familial hypercholesterolemia, frontotemporal dementia, hereditary paragangliomas, juvenile neuronal ceroid lipofuscinosis, malignant melanoma, protein C deficiency, and San Filippo disease. Many of these show a regional distribution, suggesting dissemination from a founder. Some mutations that occur among the Dutch are shared with other European populations and others have been transmitted by Dutch émigrés to their descendents in North America and South Africa. The occurrence of short chromosomal regions that have remained identical by descent has resulted in relatively limited genetic heterogeneity for many genetic conditions among the Dutch. These observations demonstrate the opportunity for gene discovery for other diseases and traits in the Netherlands.
Environmental factors are believed to trigger the onset of Crohn's disease (CD) in genetically susceptible individuals. The aim of this study was to assess environmental and familial factors that ...might be etiologically related to CD.
Twenty-one families with 3 or more affected first-degree relatives were studied, together with 10 matched control families. There were 74 patients with CD, 84 unaffected family members, and 59 controls. Family members were interviewed together at the parental home. A 176-item questionnaire delved into first symptoms, childhood vaccinations and diseases, food items, potable water supplies, social activities, travel, pets, and home and surrounding environment. Questions were directed specifically for 2 time-frames, childhood until age 20 and a 10-year epoch before the onset of first symptoms within a family. The possible factors linked to disease were evaluated using univariate and multivariate logistic regression.
There were significantly more smokers in the patients and their relatives than in controls. Patients had more appendicitis during adolescence, ate less oats, rye, and bran than controls, and consumed more unpasteurized cheese. Patients drank significantly less tap water and more well water than controls. Clustering of cases in time occurred in 13 of the 21 affected families.
The less frequent consumption of oats, rye, and bran and the more frequent eating of unpasteurized cheeses imitate potential dietary influences on gastrointestinal flora. More importantly, our data suggest that the drinking of well water represents an important risk factor for CD.
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