Re: The relationship of sperm counts to birth rates: a population based study.
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Biomedical subjects
Publications and source records attributed to N Keiding.
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Valid generalizations of results from population-based epidemiological surveys requires knowledge about how representative the sample is. The Copenhagen Center for Prospective Population Studies have assessed mortality on the basis of pooled data from three research programmes in the region of Copenhagen. In two of the studies, subjects were randomly selected, using the Danish Central Population Registry, within certain age groups and area-restricted sectors of the Greater Copenhagen. In the third study, men employed in 14 companies participated. Participation rates were between 78% and 87% in the three programmes. Standardized mortality rates (SMR) were calculated in relation to mortality rates in the municipality of Copenhagen and in the whole country in three age groups and the two genders. SMR values in the whole sample including non-participants were similar to rates for Copenhagen in the Copenhagen City Heart Study, whereas mortality rates in the Glostrup Population Studies were similar to rates for the whole country. The mortality rates among participants were lower than in the whole sample, and differences existed in relation to region and selection criteria of the cohorts. The Copenhagen Male Study, where only employed men were included, showed the lowest mortality rates, and higher rates were found in the study from the central part of the City (the Copenhagen City Heart Study) compared to the study from the suburbs (the Glostrup Population Studies). The difference between mortality rates in the cohorts and in Copenhagen City decreased with increasing age. The SMR converged towards 1.00 with increasing observation time. In conclusion, high participation rates were found in all three studies, resulting in SMR values for participants only slightly lower than in the source population in the two randomly selected samples, but 30% lower values in the sample of employed men. As mortality rates in the total samples including non-participants were markedly higher than among the participants, generalizations of results for participants to the whole population should be made with caution, especially during the first years of observation.
Cells from 7 patients operated on for thyroid cancer were investigated. Samples of cells from the carcinoma and from the normal thyroid tissue were cultured with and without TSH stimulation. For light microscopy, serial sections of cells were cut and the size of nucleoli was measured and the number of nucleoli per cell counted. At the electron microscopic level the number and the volume of the fibrillar centres (FC) were estimated taking the Swiss cheese effect into account. The areal densities of FC, the fibrillar and granular component in nucleoli were determined by point counting. The results indicate that the malignant transformation has no influence on the size of the FC, but the observed numbers as well as the total area of FC are larger in cancer cells than in the normal thyroid epithelial cells. The nucleolar density of the fibrillar component is larger and that of the granular component is smaller in thyroid carcinoma cells than in non-malignant thyroid epithelial cells (p = 0.0001). Thus simple morphometry at the electron microscopic level might be helpful to discriminate between thyroid epithelial cells and thyroid carcinoma cells in culture.
OBJECTIVES: Several reports indicate a secular decline of human sperm counts. It is still not known if these findings are artifacts related to shortcomings in the data and applied methodologies. Even less is known about possible mechanisms, but it has been proposed that potential changes may be related to disruption of the hormonal regulation of testicular development in prenatal life. The objective of this study was to examine whether sperm count was related to year of birth. METHODS: An analysis was made of the sperm count of 1196 men participating in 10 cross-sectional occupational sperm studies in 3 regions of Denmark from 1986 through 1995. RESULTS: The median sperm concentration was 63 million per milliliter for men born in 1937-1949 and 52 million per milliliter for men born in 1970 or later, and the median total sperm was 206 million and 117 million, respectively. The inverse relationship between sperm concentration and year of birth was statistically significant even after adjustment for duration of sexual abstinence, season of the year, and study population. However, bias because of differential participation related to age and fertility or lack of comparability across the populations cannot be ruled out. CONCLUSIONS: The apparent decline of sperm count with increasing year of birth is compatible with the hypothesis of a common risk factor for male reproductive health operating in prenatal life or early childhood, but the evidence is circumstantial. Age-related selection bias is an alternative and perhaps not a less likely explanation.
BACKGROUND: Several cohort studies have shown the feasibility of early amniocentesis (between 11 and 13 weeks of gestation) as an alternative to chorionic villus sampling (CVS) for karyotyping, but the only completed randomised study of fetal safety showed a significant fetal-loss risk related to first-trimester amniocentesis. We assessed fetal safety in early amniocentesis and CVS. METHODS: We assessed early amniocentesis at 11-13 weeks gestational age compared with the fetal risk associated with CVS at 10-12 weeks. 1160 pregnant women were randomly assigned one procedure (581 early amniocentesis, 579 CVS) after a baseline ultrasound examination at 10 weeks' gestation and were followed up until birth. Total fetal loss and neonatal morbidity were the primary outcome measures. Sampling success and pregnancy complications were secondary outcomes. We used a filter to increase the cell yield in the early amniotic-fluid samples. CVS was transabdominal. FINDINGS: We found a significantly increased occurrence of talipes equinovarus in the early amniocentesis group (p < 0.01), the risk of which was associated with sampling at the earliest gestational ages and with temporary leakage of amniotic fluid after sampling. Therefore, the trial was stopped early, which reduced the power of the safety study. 4.8% (27) of fetuses in the CVS group and 5.4% (30) in the early amniocentesis group were lost after randomisation (p = 0.66). More detailed survival analysis did not show any significant differences in fetal loss rates. Leakage of amniotic fluid after sampling occurred significantly more frequently after early amniocentesis than after CVS (p < 0.001), but we found no other major differences in pregnancy complications. Significantly more CVS than early amniocentesis procedures were repeated or failed to produce a karyotype (p < 0.01). INTERPRETATION: Even though the numbers were small, we found an association between early amniocentesis and talipes equinovarus. We believe this association to be true, since it supports a trend in a similar randomised study. Our results show that early amniocentesis, when done with the filter technique, is associated with an abortion risk similar to CVS, although the limited size of our study population reduced the strength of this conclusion.
The aim of the present study was critically to review how intentional weight loss in overweight and obesity influences mortality. No randomized weight loss intervention trial has included mortality as an end-point. However, even minor weight loss causes beneficial changes in risk factors for cardiovascular disease, whereas the vast majority of observational studies have linked weight loss to excess mortality. Most observational studies do not have information on intentionality of weight loss and suffer from other methodological limitations making inferences from these studies difficult. Given the available observational evidence, the possibility that intended weight loss may cause some increased mortality cannot be excluded. However, considering the totality of the evidence on effects of intended weight loss among overweight and obese subjects, there may be other benefits, such as: psycho-social and physical well-being, risk factor improvement, decreased morbidity, and in certain high-risk subgroups decreased mortality. Treatment of obesity is therefore recommended, particularly in the presence of risk factors or complications.
Some recent studies have indicated that sperm concentration has decreased during the last 50 years. However, comparisons between laboratories have revealed that geographical differences seem to exist and that any decrease may not be global. One point of criticism concerning comparison of results from different laboratories has been that some of the discrepancies detected could reflect the lack of standardized methods used in the different laboratories. Four teams, each consisting of one physician and one technician from groups which have recently published data on semen quality, met in order to evaluate the variability between their laboratories on semen analysis. Twenty-six fresh semen samples from unselected men were analysed. The groups analysed the samples according to the normal practice in their laboratories, using their own equipment. The variation between laboratories was estimated through a random effects model. For sperm concentration and semen volume assessment a remarkable consistency between laboratories was detected, in contrast to the very considerable inter-individual variation. For sperm motility and morphology assessments interlaboratory consistency was much poorer. In conclusion, evaluation of sperm motility and morphology characteristics requires further standardization in order to achieve comparable data from different laboratories. However, semen volume and sperm concentration are characteristics which can be compared reliably between laboratories, when similar methodologies are used.
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The study was undertaken to identify determinants of health services' utilization related to organizational characteristics of the health services, social characteristics of the community, and health and socio-demographic characteristics of the population. We used a follow-up design involving a time dimension of 12 months. A cohort of 3000 50-year old males and females were randomly selected from an urban county near Copenhagen and a rural county in Western Jutland and 65% agreed to participate. Data were collected through: 1) mailed questionnaires to the participants every three months, 2) a mailed questionnaire to all general practitioners in the counties, and 3) the Health Insurance Register. Data were analyzed by multivariate logistic regression analysis. Utilization of health services was found to be strongly associated with gender and health characteristics, especially with respect to functional status and chronic diseases. Health service characteristics, demographic and psycho-social factors had very little impact on utilization patterns. The utilization of publicly financed health services was found to be determined by health needs rather than by social, psychological and organizational factors, indicating geographical and social equity in the access to the Danish health services.
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The nonparametric maximum likelihood estimator for current-status data has been known for at least 40 years, but only recently have the mathematical-statistical properties been clarified. This note provides a case study in the important and often studied context of estimating age-specific immunization intensities from a seroprevalence survey. Fully parametric and spline-based alternatives (also based on continuous-time models) are given. The basic reproduction number R0 exemplifies estimation of a functional. The limitations implied by the necessarily rather restrictive epidemiological assumptions are briefly discussed.
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The microbiota associated with ligature-induced marginal inflammation around osseointegrated dental implants, ankylosed teeth, and normal control teeth was investigated in 8 cynomolgus monkeys (Macaca fascicularis). Submucosal/subgingival plaque was sampled with paper points on the day of literature placement and after 7 weeks. The samples were evaluated by phase-contrast microscopy and by cultivation on enriched non-selective and various solid media. The submucosal/subgingival flora was changed 7 weeks after ligation. The total number of cultivable bacteria and the proportions of motile rods, anaerobic Gram-negative rods, black-pigmented rods, Porphyromonas gingivalis, and Prevotella intermedia increased significantly around implants, ankylosed teeth, and normal control teeth. Except for a significantly higher proportion of anaerobic Gram-positive cocci around implants compared to ankylosed teeth and normal control teeth at the end of the study, no significant microbiological differences were observed between implants, ankylosed teeth, and normal control teeth neither at baseline nor at the end of the study. Consequently, the microbiota associated with marginal inflammation around implants, ankylosed teeth, and normal control teeth appears to be rather similar in cynomolgus monkeys.
Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.
Recursive graphical models allow description of the simultaneous development of several (discrete) characteristics such as are recorded in a panel study. Irreversible events (death, irreversible disease occurrence) between exams are naturally included. This paper reviews these models and gives a detailed discussion of an example consisting of 49-50 year old males from the Framingham Heart study. The program DIGRAM is used throughout and the present paper may also serve as an introduction to this software.
Comparison of observed mortality with 'known,' 'background,' or 'standard' rates has taken place for several hundred years. With the developments of regression models for survival data, an increasing interest has arisen in individualizing the standardisation using covariates of each individual. Also, account sometimes needs to be taken of random variation in the standard group. Emphasizing uses of the Cox regression model, this paper surveys a number of critical choices and pitfalls in this area. The methods are illustrated by comparing survival of liver patients after transplantation with survival after conservative treatment.