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N Keiding

Publications and source records attributed to N Keiding.

At least 73 records · Page 4Linked to original sources
PubMed1995

Declining semen quality and increasing incidence of testicular cancer: is there a common cause?

Male reproduction has been given little attention in science and in medical practice. However, a recent metaanalysis on semen quality, which clearly pointed to a decrease over the past 50 years, has been repeatedly quoted. Three recent reports have found that semen quality has declined among candidate semen donors during the past 20 years. The evidence of decline in the quality of semen is not the only indicator that the human testis is at risk. During the past 50 years, cancer of the testis has also become more common. This is a disorder of young men, and it is associated with a high rate of other abnormalities of the testis including undescended testis and poor semen quality. Furthermore, the incidence of both hypospadias and undescended testis has been reported to be rising in the general population. We believe that the evidence of declining semen quality should be seen in the light of these trends in other reproductive disorders of men. However, the etiology is unknown. A recent hypothesis that links the trends in the health of the male reproductive system to xenoestrogens in the environment is discussed.

Adult↗
PubMed1995

Do environmental estrogens contribute to the decline in male reproductive health?

Several observations suggest that male reproductive health has been declining since World War II in many countries. The incidence of testicular cancer, hypospadias, and cryptorchidism has been increasing and semen quality has been decreasing, and these may have a common etiology. Treatment of several million pregnant women with the synthetic estrogen diethylstilbestrol led to an increase in these conditions among the sons of these women. These abnormalities probably arise during fetal development. The similarity between these effects and the adverse change in male reproductive development and function raised the question of whether the adverse changes are attributable to altered exposures to estrogenic and other endocrine-disrupting agents during fetal development. We speculate that alteration in exposure to estrogen in the past half-century may have caused the changes in male reproductive health.

Cryptorchidism↗
PubMed1994

[The significance of prognostic factors on the occurrence of metastases from breast cancer to various localizations].

The aim of the study was to identify and compare risk factors for development of metastases from breast cancer at specific anatomical sites. The sites were grouped into ten categories, simultaneous occurrences at several sites being common. The influence of various risk factors for recurrence at one specific site can be modelled by well-established survival analysis techniques such as the Cox regression model. Recently, a generalization has been proposed that allows for joint occurrences at more than one site. The prognostic influences of various risk factors on recurrence at different sites may be compared using these models. Both methods were applied to data from the Danish Breast Cancer Cooperative Group on recurrence after breast cancer; the risk factors examined were degree of anaplasia, number of positive lymph nodes, site of primary tumour, skin or deep fascial invasion, age of the patient and adjuvant treatment regimens. Adjuvant therapy had the same effect on recurrence at all sites. For chemotherapy, this effect was marginally significantly positive. The number of positive lymph nodes was associated with an increased risk of metastases at all sites except the brain, where an opposing trend was found. The degree of anaplasia was associated with a somewhat increased risk of metastases at all sites, again the brain was an exception, here the effect of degree of anaplasia was significantly more pronounced. Application of the new types of models resulted in fewer differences between the relative influence of the prognostic factors than are implied by the use of the traditional regression models.

Adult↗
PubMed1994

The prognosis of patients with alcoholic liver disease. An international randomized, placebo-controlled trial on the effect of malotilate on survival.

The aim of this study was to examine the effect of malotilate on survival in patients with alcoholic liver disease and to determine prognostic variables for survival. Four hundred and seven patients with alcoholic liver diseases, from seven European liver units, entered a randomized placebo-controlled, double-blind trial: 140 patients received malotilate 1500 mg/day, 133 patients received 750 mg/day, and 134 patients received placebo. The patients were included in the study over a period of 3 1/2 years, and the study was closed 1 year after the entry of the last patient. Eighty-four patients died (35, 19, 30 patients in groups 1500 mg/day, 750 mg/day, and placebo, respectively). Survival was slightly better in the 750 mg/day group than in the two other treatment groups, when tested by conventional log-rank tests (p = 0.06). However, a treatment effect was supported by a highly significant (p = 0.006) non-proportionality of the death intensity in patients receiving 750 mg/day against those receiving either 1500 mg/day or placebo. Prognostic variables for survival were evaluated using the multiple Cox regression analysis of clinical and laboratory variables and with or without liver histology variables, as determined at entry into the study. The analysis was stratified for the three treatment regimens. In the analysis including liver histology variables, independent significant prognostic variables were: years of high alcohol intake, prothrombin index, alkaline phosphatases, creatinine, immunoglobulin M, white blood cell count, and liver cell steatosis. In the analysis without liver histology variables, prognostic variables were: years of high alcohol intake, prothrombin index, alkaline phosphatases, creatinine, and immunoglobulin M.

Adult↗
PubMed1994

Spermaturia in two normal boys without other signs of puberty.

We report spermaturia in two normal boys with testicular volumes of 3 ml and no other signs of puberty. This supports the hypothesis that spermatogenesis can begin before any other signs of puberty and indicates that the definition of start of puberty as testicular volumes of 4 ml or more may be too rigorous.

Child↗
PubMed1993

Plotting summary predictions in multistate survival models: probabilities of relapse and death in remission for bone marrow transplantation patients.

Multistate survival analysis usually involves a series of detailed regressional analyses describing transitions between various states. There is an often neglected need for the many estimates resulting from such an analysis to be re-synthesized into summary statements, such as prediction of various outcomes from specified patient histories. Arjas and Erola recently proposed a framework for dynamic probabilistic causality which has calculation of such prediction statements as a central tool. We illustrate these procedures on data from a multicentre bone marrow transplantation study, with death while in remission and relapse as terminal events and recovery of the patients's platelets to a normal level and the onset of acute graft-versus-host disease as intermediate events, using Cox regression models throughout. Among the features illustrated by the resulting plots is a strong effect on death while in remission if the platelets do not recover within the first three months.

Bone Marrow Transplantation↗
PubMed1993

[Decline in semen quality from 1930 to 1991].

It has been suspected for years that semen quality has declined. However, the issue is still controversial since previous studies were criticized for methodological errors. We therefore attempted to systematically review the complete international literature on semen quality since 1930 with rigorous selection criteria and statistical analysis. Based on a literature search using Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-august 1991), we identified 61 papers concerning sperm density in a total of 14,957 males without a history of infertility. A significant decline in mean sperm density from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in mean seminal volume from 3.40 ml to 2.75 ml (p = 0.027) was noted. The incidence of testis cancer and possibly also that of cryptorchidism and hypospadias has increased during the same relatively short time period. Such a remarkable deterioration in male genitourinary function is more likely to be due to environmental rather than genetic factors.

Global Health↗
PubMed1993

Epidemiology of renal involvement in newly-diagnosed middle-aged and elderly diabetic patients. Cross-sectional data from the population-based study "Diabetes Care in General Practice", Denmark.

We report on a study in which 487 Danish general practitioners participated with the purpose of including all newly-diagnosed diabetic patients aged 40 years or more from a well-defined catchment population during a well-defined time period. A total of 1267 diabetic patients with a median age of 65.3 years were included. Renal involvement was assessed from the albumin/creatinine ratio in a morning urine sample. Albumin/creatinine ratio was < 2/2- < 20/ > or = 20 mg/mmol in 59.8/33.6/6.6% of male and 66.6/28.8/4.6% of female patients. The level of albumin/creatinine ratio increased with age and the observed overall male predominance was almost confined to diabetic patients with an albumin/creatinine ratio of 5 mg/mmol or greater. By taking into account the confounding effect of age and sex, a positive association between smoking and albumin/creatinine ratio was disclosed. Moreover, high systolic blood pressure, hypertriglyceridaemia, hypercholesterolaemia (males only) and high HbA1c, but not body mass index or diastolic blood pressure were identified as correlates of elevated albumin/creatinine ratio. Glucosuria was positively correlated with albumin/creatinine ratio even when the influence of HbA1c, sex and age was taken into account. A positive correlation between serum creatinine and albumin/creatinine ratio was seen in males, but not in females. In addition, renal involvement was associated with the presence of peripheral angiopathy and diabetic retinopathy and with high resting heart rate. The cross-sectional data presented highlight the importance of reducing the overall burden of modifiable risk factors in newly-diagnosed Type 2 diabetic patients.

Adult↗
PubMed1993

Spermaturia and puberty.

The pattern of spermaturia in boys at different stages of puberty was investigated. Fractionated 24 hour urine was collected for nine consecutive days from eight boys aged 13-14 years and 10 boys aged 15-17 years. Spermatozoa were detected by microscopic examination of the sediment. Sex characteristics were recorded. Fifty five per cent of all urine samples were positive for sperm and all boys showed spermaturia. A large variation in spermaturia was found between and within boys at the same stage of puberty. Spermaturia was a more common and regular event during early and mid-puberty than in more mature subjects. This indicates that the mechanism of spermaturia in early and late puberty could be different. It is suggested that spermaturia in non-virilised boys could be a result of a spontaneous, continuous flow of spermatozoa to the urethra in contrast with the peristaltic flow during ejaculation occurring at a later stage of puberty.

Adolescent↗
PubMed1993

Evidence for increasing incidence of abnormalities of the human testis: a review.

Recent reports have suggested that the incidence of genitourinary abnormalities in human males has increased during the past 50 years, including congenital abnormalities such as cryptorchidism and hypospadia, which seem to be occurring more commonly. Also, the incidence of testicular cancer has increased 3- to 4-fold since the 1940s. This increase seems to be worldwide including countries with a very high frequency of testicular neoplasia as well as those in which this cancer is rather uncommon. It has also been postulated that semen quality has been decreasing for the last half century. A recent study showed that the average sperm density has decreased significantly from 113 million/mL in 1940 to 66 million/mL in 1990. The mean seminal volume has also declined, indicating that the decrease in the total sperm count is even more pronounced than the fall in sperm density would indicate. The remarkable increase in frequency of testicular abnormalities over a relatively short period of time may be due to environmental rather than genetic factors. There is an epidemiological link between the occurrence of different testicular abnormalities. Therefore, common prenatally acting etiological factors with adverse effects on the fetal male gonad might be suspected. However, postnatal influences may also have a deleterious effect on male fertility. From the reproductive point of view, an increased impact on the human male gonad is of concern.

Cryptorchidism↗
PubMed1992

Evidence for decreasing quality of semen during past 50 years.

OBJECTIVE: To investigate whether semen quality has changed during the past 50 years. DESIGN: Review of publications on semen quality in men without a history of infertility selected by means of Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991). SUBJECTS: 14,947 men included in a total of 61 papers published between 1938 and 1991. MAIN OUTCOME MEASURES: Mean sperm density and mean seminal volume. RESULTS: Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density. CONCLUSIONS: There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.

Humans↗
PubMed1992

Differential influence of prognostic factors on the occurrence of metastases at various anatomical sites in human breast cancer.

The present study was initiated by data on the anatomical occurrence of metastases from breast cancer. Metastases may occur at various organs, here grouped into ten categories, and simultaneous occurrences at several sites are common. Our aim was to identify and compare risk factors for development of metastases at each site. The influence of the various risk factors for recurrence at one specific site can be modelled as a standard competing risk problem, using well-established survival analysis techniques such as the Cox regression model. Recently a generalization to joint occurrences at more than one site has been proposed. The more general models allow comparison of the differential prognostic influence of various risk factors on recurrence at different sites. We applied these methods to data from the Danish Breast Cancer Cooperative Group on recurrence after breast cancer, and examined the effect of degree of anaplasia, number of positive lymph nodes, size of primary tumour, skin or deep fascial invasion, age of the patient and adjuvant treatment regimen, as possible risk factors. There were no differential effects of type of therapy on recurrence in different sites. However, chemotherapy had a marginally significant positive effect at all sites. Moreover the number of positive lymph nodes was associated with an increased risk of metastases, homogenous across sites, except for brain where an opposing trend was found. Similarly the degree of anaplasia was associated with a somewhat increased risk of metastases, homogenous except for brain. For brain metastases a significantly more pronounced effect of degree of anaplasia was found. Comparison of the results obtained from the two types of models reveals that the new more general models confirm fewer differences between the influence of the prognostic factors than the traditional regression models suggest.

Adult↗
PubMed1992

Estimation of the size distribution of fibrillar centres in nucleoli--an example of the "Swiss cheese" problem in stereology.

The "Swiss cheese" problem in stereology is that variant of the classical corpuscle problem where the size distribution of randomly distributed spherical "holes" in an opaque medium is to be inferred from the size distribution of the circular holes observed in sections. In our electron microscopical studies of the neurons of the rat supraoptic nucleus, we encountered a Swiss cheese problem in connection with the size distribution of the fibrillar centres of the nucleoli. We found no practical examples in the literature, and attempts to obtain a Wicksell-type algorithm met with severe numerical instability problems. The present paper shows that the chi-distributions of Keiding, Jensen, and Ranek (1972, Biometrics 28, 813-829) may be used as the basis for a parametric maximum likelihood solution for the Swiss cheese problem. The concept of a capping angle (nonobservability of spheres cut at too acute an angle), also introduced by Keiding et al., carries over as well. The methods are illustrated on data from the mentioned experiment.

Algorithms↗