Mathematical modelling of species formation
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Journal Article↗
Biomedical subjects
K Christensen
Publications and source records attributed to K Christensen.
Heritability of death from respiratory diseases: an analysis of Danish twin survival data using a correlated frailty model.
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Cause of Death↗
[Why do we age so differently?].
One of the most intriguing aspects of ageing is how different the ageing process is from person to person: some maintain their physical and cognitive abilities throughout a long life while others lose these abilities rather early in adult life. The basis for this variation is largely an enigma. In this review some of the most prominent ageing theories are described and compared with results from Danish genetic-epidemiological aging research.
Adult↗
Recurrence risk of congenital anomalies--the impact of paternal, social, and environmental factors: a population-based study in Denmark.
The authors investigated the recurrence risk of congenital anomalies as a function of changes in genetic and environmental factors in single births following the birth of a child with an anomaly. The study is a population-based historical follow-up using the Danish Medical Birth registry, hospital discharge diagnoses, and Statistic Denmark's Fertility Database. The investigators identified 8,671 women who gave birth to a child with a diagnosed malformation between 1980 and 1992 and had a subsequent birth. Following the birth of an affected infant, 474 (5.5%) women gave birth to another child with a malformation, 155 of which (1.8%) were similar to the malformation of the older sib or half sib. When the father changed between the two births, the risk of a similar anomaly was significantly reduced (odds ratio (OR) = 0.26, 95% confidence interval (CI) 0.11, 0.65). Higher social status at enrollment was associated with a lower recurrence risk (OR = 0.67, 95% CI 0.45, 0.99, for the middle status group and OR = 0.49, 95% CI 0.30, 0.81, for the highest status group), independently of partner change. A rise in social status between the two births was marginally associated with a decline in the recurrence risk. No variation in the recurrence risk associated with change of municipality or occupation was seen.
Cohort Studies↗
Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood.
To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and flow cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.
Adolescent↗
[Why do we age so differently?].
One of the most intriguing aspects of ageing is how different the ageing process is from person to person: some maintain their physical and cognitive abilities throughout a long life while others lose these abilities rather early in adult life. The basis for this variation is largely an enigma. In this review some of the most prominent ageing theories are described and compared with results from Danish genetic-epidemiological aging research.
Adult↗
Oral clefts, transforming growth factor alpha gene variants, and maternal smoking: a population-based case-control study in Denmark, 1991-1994.
Studies in the United States have indicated that maternal first trimester smoking and infant transforming growth factor alpha (TGFA) locus mutations are associated with non-syndromic cleft lip and/or palate (CLP) and that a synergistic effect of these two risk factors occurs. Based on a Danish case-control study of CLP, the authors studied the effects of smoking and TGFA alleles in an ethnically homogeneous setting. Interview information was obtained for mothers of 302 CLP cases (96% of eligible) and for 567 mothers of nonmalformed children (94% of eligible). Multivariate logistic regression analyses revealed that smoking was associated with a moderately increased risk of cleft lip +/- cleft palate (CL(P)) (odds ratio = 1.40, 95% confidence interval 0.99-2.00). No association between smoking and isolated cleft palate (CP) was observed. TGFA genotype was not associated with either CL(P) or CP, and no synergistic effect with smoking was observed. The "rare" TGFA allele occurred in 25% of both cases and controls compared with an average of 14% in other white control groups. Furthermore, the frequency of CLP in Scandinavia is among the highest in the world. Hence, it is possible that the previously reported association between TGFA and CLP to some degree can be attributable to confounding by ethnicity.
Adult↗
Randomized clinical trial of laparoscopic versus open inguinal hernia repair.
BACKGROUND: Several studies have suggested that better results are obtained after laparoscopic repair of inguinal hernia than after conventional operation. This is most obvious for bilateral and recurrent hernias but less accepted for primary unilateral hernias. METHODS: This was a randomized clinical trial comparing transabdominal preperitoneal laparoscopic repair with the Shouldice technique in patients with primary unilateral hernia. Some 138 patients were randomized to laparoscopic hernia repair and 130 to open surgical repair. RESULTS: The complication rates in the two groups were similar. In the laparoscopic group the patients returned to work more rapidly with a median time of 13 versus 18 days (P < 0.005) and had a shorter period of analgesia intake with a median time of 2.1 versus 2.7 days (P < 0.02). The follow-up was 97.8 per cent complete. At a median of 12 months, four recurrences (2.9 per cent) were detected in the laparoscopic group and three (2.3 per cent) in the open group. CONCLUSION: This study shows that in patients with a primary unilateral hernia laparoscopic repair results in less postoperative pain and a quicker recovery than open repair.
Adolescent↗
Edta chelation therapy: an ethical problem.
The randomized, double-blind study is generally regarded as the ideal standard of clinical drug trials, but uncritical blinding in clinical studies should be questioned (1,2). Most often, the method of randomization is not sufficiently described. There are examples of researchers having used opaque envelopes or opened several envelopes or X-rayed the envelopes. Violation of the randomization is unfortunately common (3). New guidelines for structured reporting of clinical trials with focus on the randomization method have been worked out (4). However, other methods of violation of the randomization have not been covered in the new guidelines. In a claimed double-blind multi-center study, isotonic Na2 ethylenediaminetetraacetic acid (edta) solution as verum and isotonic saline as placebo was used without any problem with the blinding. In the multi-center study, only nine incidents of burning at the infusion site were registered out of a total of more than 1000 Na2edta infusions (5). In our study, a total of 10 persons were given exactly the same kind of infusions and nine out of 10 receiving Na2edta infusions reacted with burning at the infusion site, thus proving it impossible to use Na2edta versus saline and maintain the blinding in a study of double-blind design. The difference in painful reactions between the Na2edta group and the saline group at the infusion site is statistically significant (P<0.001).
Adult↗
Male factors and socioeconomic indicators correlate with the risk of spontaneous abortion.
No less than 10% of clinically recognised pregnancies end as spontaneous abortions and the recurrence risk is high. Due to lack of data and appropriate study design only little is known about preventable causes of miscarriage. The aim of this study was to estimate the effect of paternal and environmental factors by studying reproductive histories in population based cohorts. We based the study upon two cohorts. The 'abortion cohort' consisted of 55 259 women who had a hospitalised spontaneous abortion in Denmark between 1980 and 1992 and who had a subsequent non-terminated pregnancy. The 'birth cohort'was based upon a 5% random sample of all women who in the same time period gave birth and subsequently had a non-terminated pregnancy (11 269 women). Data on change of partner, residence, mother's social status or occupation between the two pregnancies were linked to these two cohorts using the personal identification numbers and information stored in several population registers. Change of partner reduced the recurrence risk of spontaneous abortion substantially (OR = 0.59; 95 CI 0.52-0.67), but also changes in social status or job reduced the recurrence risk significantly. Changing the municipality of residence to a low risk area (based upon the geographical distribution of spontaneous abortions) reduced the risk of spontaneous abortion in both cohorts. A paternal effect on the recurrence risk of spontaneous abortion cannot be ruled out but environmental factors also play a role.
Journal Article↗
Declining physical abilities with age: a cross-sectional study of older twins and centenarians in Denmark.
OBJECTIVE: To evaluate whether physical disability reaches a plateau in the oldest age groups. DESIGN: Cross-sectional survey. PARTICIPANTS: A total of 3351 individuals, which included all those living in Denmark who celebrated their 100th anniversary during the period from 1 April 1995 to 31 May 1996 (276 subjects) and all Danish twins aged 75-94 registered in the Danish Twin Register (3075 subjects). MAIN OUTCOME MEASURES: The ability to perform selected items of basic activities of daily living independently. RESULTS: The prevalence of independence in each of six selected activities of daily living was significantly lower in both men and women centenarians compared with octo- and septuagenarians. The sex difference in independence in all six selected activities of daily living was larger for each advancing age group, with women being most disabled (P < 0.001). In centenarians 20% of women and 44% of men were able to perform all selected activities of daily living independently. CONCLUSION: Compared with individuals aged 75-79 years, physical abilities of men and women gradually diminished in age groups 80-84, 85-90 and 90-94, with the lowest levels among 100-year-olds. Although women have lower mortality, they are more disabled than men, and this difference is more marked with advancing age.
Activities of Daily Living↗
Low birthweight and prematurity in relation to paternal factors: a study of recurrence.
BACKGROUND: The importance of paternal determinants in the occurrence of low birthweight and prematurity is not well known. We investigated these outcomes in siblings and paternal half siblings as a function of changes in putative external determinants between two births in fathers who had experienced the birth of a premature and/or low birthweight (PTB/LBW) infant. METHODS: All fathers who, between 1980 and 1992, had an infant born before 37 completed weeks' gestation or weighing <2500 g and a following child were studied. We identified 14 147 pairs of siblings from Danish national registers. The recurrence risk was studied in three sub-cohorts defined by the outcome in the index child (PTB only, PTB/LBW, LBW only). We estimated the recurrence risk in the younger sibling according to changes of female partner, municipality type, occupation, and father's social status. RESULTS: The overall recurrence risk was 16.7% for preterm delivery and 16.8% for LBW. Changing female partner was, as expected, associated with a reduction in the recurrence risk for both outcomes (RR = 0.40; 95% CI: 0.27-0.60 for preterm delivery and RR = 0.38; 95% CI : 0.26-0.56 for LBW). None of the other studied factors was associated with changes in the recurrence risk. Fathers who changed partner had offspring with similar birthweight and gestational length between the three sub-cohorts, while a difference was evident in offspring to fathers whose female partner was unchanged. CONCLUSIONS: We did not identify any paternal factor of importance in the occurrence of LBW and preterm delivery.
Adult↗
Study of environmental, social, and paternal factors in preterm delivery using sibs and half sibs. A population-based study in Denmark.
OBJECTIVE: The aim of this study was to evaluate the influence on preterm delivery of changes in putative genetic and environmental risk factors between two consecutive births. Low social status is a suspected risk indicator of preterm delivery, but the impact of social mobility has not been studied before. PARTICIPANTS: The study uses national cohorts in which women act as their own controls. Subjects were identified by means of registries: 10,455 women who gave birth to a preterm child and had a subsequent live birth between 1980 and 1992 and 9849 women who gave birth to a child after 37 completed weeks of gestation and had a subsequent live born child in the same time period formed the cohorts. METHODS: The risk of having a premature infant in the subsequent pregnancy was analysed in each cohort as a function of changes in male partner, residency, occupation, and social status between the two pregnancies. RESULTS: There was a strong tendency to repeat a preterm delivery (18% v 6% in the general population). Social decline was associated with a moderate increase in the recurrence risk (OR: 1.22; 95% CI: 1.02, 1.47). In the reference cohort the risk of preterm delivery associated with changing from a rural to an urban municipality was 2.03 (95% CI: 1.14, 3.64). CONCLUSIONS: Social decline and moving to an urban municipality may be associated with preterm delivery.
Adolescent↗
A Danish population-based twin study on general health in the elderly.
OBJECTIVES: To study the relative influence of genetic and environmental factors on self-rated health and hospitalization patterns in the elderly. METHODS: A survey among all 3,099 Danish twins ages 75 years and older identified in the Danish Twin Registry. An interview was conducted with 77% of the twins. The number of hospitalizations in the previous 18 years was obtained through register linkage, thereby obtaining health information on 96% of the study population, including all nonresponders. RESULTS: Structural equation modeling suggested that approximately a quarter of the variation in the liability to self-reported health and the number of hospitalizations could be attributed to genetic factors. The remaining variation was most likely due to nonfamilial environment. Analyses of the hospitalization patterns of proxy responders and nonresponders suggest that the estimates of the genetic influence on health outcomes in the study are conservative. DISCUSSION: The present study indicates that variation in general health among the elderly is partly explained by genetic factors.
Aged↗
Genetic and environmental influence on asthma: a population-based study of 11,688 Danish twin pairs.
The aim of this study was to estimate the relative influence of genetic and environmental factors on the aetiology of asthma. The classic twin study design was used to analyse data on self-reported asthma obtained by a questionnaire mailed to 34,076 individuals, aged 12-41 yrs and originating from the Danish Twin Register. The cumulative incidence of asthma was 6.2% in the pooled sample. The data showed a decreasing cumulative incidence with age for males, but no sex or zygosity difference was observed. Substantially higher concordance rates, odds ratios and correlations for asthma were estimated in the monozygotic than in the dizygotic twins. Using biometric modelling, a model including additive genetic and nonshared environmental effects provided the best overall fit to the data. According to this model, 73% of the variation in liability to asthma was explained by genetic factors. No sex difference or age-dependency in the magnitude of genetic effects was observed. The biometric analysis emphasized a major influence of genetic factors in the aetiology of asthma. However, a substantial part of the variation in liability to asthma is due to the impact of environmental factors specific to the individual. There is no evidence for a substantial impact of genetic dominance or the shared environment.
Adolescent↗
Isolation and characterization of MC3T3-E1 preosteoblast subclones with distinct in vitro and in vivo differentiation/mineralization potential.
A series of subclonal cell lines with high or low differentiation/mineralization potential after growth in the presence of ascorbic acid (AA) were derived from murine MC3T3-E1 cells. Subclones were characterized in terms of their ability to mineralize a collagenous extracellular matrix both in vitro and in vivo and express osteoblast-related genes. When compared with nonmineralizing cells, mineralizing subclones selectively expressed mRNAs for the osteoblast markers, bone sialoprotein (BSP), osteocalcin (OCN), and the parathyroid hormone (PTH)/parathyroid hormone-related protein (PTHrP) receptor. In contrast, alkaline phosphatase mRNA was present in certain nonmineralizing as well as mineralizing subclones, suggesting that its expression may be subject to different controls from other osteoblast markers. Only highly differentiating subclones exhibited strong AA-dependent induction of a transiently transfected OCN promoter-luciferase reporter gene, indicating that there was a good correlation between mRNA levels and transcriptional activity. Consistent with its postulated role in biomineralization, BSP as measured by Western blotting was only present in mineralizing subclones. After implantation into immunodeficient mice, highly differentiating subclones formed bone-like ossicles resembling woven bone, while poorly differentiating cells only produced fibrous tissue. Interestingly, subclones with both high and low differentiation potential produced similar amounts of collagen in culture and expressed comparable basal levels of mRNA encoding Osf2/Cbfa1, an osteoblast-related transcription factor. Although some strongly differentiating cells exhibited a modest AA-dependent up-regulation of Osf2/Cbfa1 mRNA, there was no clear relationship between levels of this message and induction of mRNAs for other differentiation markers. Thus, the mere presence of Osf2/Cbfa1 in a subclone was not sufficient for osteoblast differentiation. These subclones will be very useful for studying critical events in osteoblast differentiation and mineralization.
Animals↗
The 20th century Danish facial cleft population--epidemiological and genetic-epidemiological studies.
Since Dr. Fogh-Andersen's legendary 1942 thesis, the Danish facial cleft population has been one of the most extensively studied in terms of epidemiology and genetic-epidemiology. The etiology of cleft lip and/or palate (CLP) is still largely an enigma, and different results concerning environmental and genetic risk factors are obtained in different countries and regions. This may be due to etiological heterogeneity between settings. Therefore, an in-depth studied area with an ethnically homogeneous population, such as Denmark, has provided one of the best opportunities for progress in CLP etiological research. The present review summarizes epidemiological and genetic-epidemiological studies conducted in the 20th century Danish facial cleft population. Furthermore, analyses of sex differences, time trends and seasonality for more than 7000 CLP cases born in Denmark in the period 1936 to 1987 are presented. The review also points toward the excellent opportunities for continued etiological CLP research in Denmark in the 21st century using already established resources and an on-going prospective cohort study of 100,000 pregnant women.
Child, Preschool↗
A case of trisomy 22 in a live hereford calf.
A case of the rare genetic trisomy 22 in a live calf is described. The calf had low blood thyroxine level and low growth rate. It had several defects including brachygnathia superior, strabismus convergence, aortal cusp insufficiency and hypertrophy of clitoris. Chromosome analysis was performed on cultured blood lymphocytes and fibroblast cells. In all counted metaphases 61 chromosomes were present. The extra chromosome was identified as a chromosome 22 by R-banding. The defects of the calf have similarities with cases of partial trisomy 3p25-pter in human. This section of the human chromosome 3 corresponds to sections of cattle chromosome 22.
Animals↗