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Biomedical subjects

N Keiding

Publications and source records attributed to N Keiding.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Epidemiology of myasthenia gravis in Denmark. A longitudinal and comprehensive population survey.

The incidence of myasthenia gravis (MG) was found to be constant in calendar time. The mean annual incidence rate was 4.4 per million population. Age- and sex-specific incidence rates disclosed a bimodal appearance for both sexes, with a peak age at onset located in the early-onset group and another peak for late onset of MG. Early onset of MG appeared 10 years later for male individuals than for female individuals, whereas the peak for late onset of MG was located at the same age for both sexes. It is suggested that the separation between early onset and late onset of MG should be at the age of 50 years for both sexes, rather than at 35 to 40 years as accepted in most studies. The prevalence of MG has increased in time. On January 1, 1988, the point prevalence rate was 77 per million population (female subjects, 96, and male subjects, 57). This reflects an improvement in prognosis despite the fact that life expectancy was found to be significantly lower for MG patients than that of the sex- and age-matched population. The factors causing increased mortality were found to be operative throughout the duration of the disease. Maximum severity of disease was reached within 2 years from onset in 78% of the cases, and more than 50% of all MG-related deaths occurred during the same period. In the course of MG, 70% of all patients experience generalized muscular weakness, and 30% to 40% also suffer from respiratory problems.

Denmark↗
PubMed1991

Assessing the influence of reversible disease indicators on survival.

In a randomized clinical trial of the effect of prednisone versus placebo on survival in patients with liver cirrhosis, follow-up visits were scheduled after 3, 6 and 12 months of treatment and thereafter once a year. At each follow-up the prothrombin index, a measure of liver function, was recorded and scored as either low or normal. The interaction between treatment and prothrombin index was analysed using a three-state illness-death model with recovery. The continuous-time Markov process model with constant or piecewise constant intensities suggested by Kay allows inference to proceed even though the status of the disease indicator, here the prothrombin index, is only known at the time of each visit and not between visits. We compare the analysis with the theoretically incorrect, but practically rather common approximation, where the status of the disease indicator is assumed to remain constant from one visit until just before the next. Under this approximation both standard parametric methods and non-parametric approaches developed by Aalen and Johansen are available.

Clinical Trials as Topic↗
PubMed1991

Excess mortality in giant cell arteritis.

A 13-year departmental sample of 34 patients with definite (biopsy-verified) giant cell arteritis (GCA) was reviewed. The mortality of this material was compared to sex-, age- and time-specific death rates in the Danish population. The standardized mortality ratio (SMR) was 1.8 (95% confidence limits, 1.1-2.8). During the same period 146 patients with probable (not biopsied, but clinically diagnosed in the department) GCA and 85 cases of possible (diagnosed and treated before admission) GCA had been admitted to the department. Those two groups did not differ from the biopsy-verified group with respect to SMR, sex distribution or age. In the group of patients with department-diagnosed GCA (definite + probable = 180 patients), the 95% confidence interval for the SMR of the women included 1.0. In all other subgroups there was a significant excess mortality. Excess mortality has been found in two of seven previous studies on survival in GCA. The prevailing opinion that steroid-treated GCA does not affect the life expectancy of patients is probably not correct.

Adult↗
PubMed1991

Estimation of spermarche from longitudinal spermaturia data.

A number of studies have dealt with determination of the age at onset of sperm emission (spermarche), based on observations of first occurrence of spermatozoa in urine. A major problem in this connection is the intermittent occurrence of sperm-negative urine samples after the achievement of spermarche. We have here considered an empirical Bayes approach for handling the probability of a sperm-positive urine sample after spermarche. The investigation was inspired by a concrete longitudinal study concerning 40 Scottish boys, which is used for illustration throughout. In this study, the urine was tested for spermatozoa from well before spermarche and every 3 months thereafter for at most 7 years. Some of the boys left the study earlier and techniques for handling such censoring were also developed.

Adolescent↗
PubMed1990

Hereditary ataxias: epidemiological aspects.

Hereditary ataxias, hereditary spastic paraplegia and Charcot-Marie-Tooth syndrome (HA) are chronic progressive neurological diseases. Epidemiologic studies of these disorders are few. In a geographically well-defined Danish population, we present incidence rates, cumulated incidence rates and prevalence for patients with HA based on modern continuous-time survival analysis techniques. From these, prevalence has been estimated to be 6.06 per 10(5) in the 10 to 50-year-old population. Combined risk of HA was found to be 0.16% for women and 0.20% for men up to their 51st birthday.

Adolescent↗
PubMed1990

Size of the fibrillar centres of the nucleoli in the supraoptic nucleus of the rat taking the Swiss cheese effect into account.

The size of the fibrillar centres (FC) in nucleoli was investigated taking the Swiss cheese effect into account. Electron microscopy was performed on the neurons of the rat supraoptic nucleus after the secretion of vasopressin had been fully suppressed by water load, after the secretion had been stimulated by water deprival and in normal rats with water ad libitum. When the secretory activity was suppressed from a normal level to approximately no activity, the size of the individual FC was doubled. Moreover, with increasing secretory activity the number of FC per cell increased.

Animals↗
PubMed1990

Health workers and AIDS: knowledge, attitudes and experiences as determinants of anxiety.

The objective of the study was to measure the level of HIV/AIDS related anxiety among health care workers and identify its determinants. Data were obtained by means of a mailed, anonymous, self-administered questionnaire distributed to 2561 Danish medical doctors, nurses and nursing aides drawn randomly from the lists of members of the respective national associations. The data were analysed on the basis of a pre-study model including 12 variables hypothesizing a hierarchy of causal dependencies with anxiety at the top. 44% of the participants expressed HIV/AIDS related anxiety--hospital workers more than primary care workers, the older less than the younger. Anxiety was significantly associated with negative/restrictive attitudes towards HIV positives and gay men and with low levels of knowledge about HIV transmission and less education about HIV/AIDS. Negative/restrictive attitudes towards HIV positives were associated both with less knowledge regarding HIV transmission and fewer contacts with HIV positives. Similar associations were found regarding gay men. It is suggested that new kinds of training programmes be established which focus much more on attitudes and norms concerning HIV/AIDS--especially among health care workers with only occasional contact with HIV patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Survival after liver transplantation of patients with primary biliary cirrhosis in the Nordic countries. Comparison with expected survival in another series of transplantations and in an international trial of medical treatment.

Until December 1988, 38 patients with primary biliary cirrhosis (PBC) had been transplanted in the Nordic countries. The observed survival probability in accordance with Kaplan-Meier analysis was around 75% 2-3 months after surgery, with few deaths during the next 3 years. The observed survival curve was compared with the expected survival calculated from the experience of a recent English PBC transplant series; the patterns are very similar. Secondly, the observed survival was compared with the expected survival curve, calculated from the survival experience of an international trial of medical treatment--that is, the expected survival had the patients not been transplanted; after the first 2-3 months the observed survival stayed better than the expected survival. Finally, the merits of transplantation for each particular patient was evaluated by means of the ratio of probability of survival when transplanted to probability of survival when medically treated 3, 6, and 8 months after surgery. The ratio increased with time, indicating a relative increase in the benefit of transplantation with time after surgery.

Denmark↗
PubMed1990

Graft-versus-leukaemia activity associated with CMV-seropositive donor, post-transplant CMV infection, young donor age and chronic graft-versus-host disease in bone marrow allograft recipients. The Nordic Bone Marrow Transplantation Group.

Risk factors for post-transplant relapse were analysed retrospectively in 163 patients treated with allogenic bone marrow transplantation for acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma in first to fourth remission or during relapse. Multifactorial analysis was performed according to Cox with fixed pretransplant covariates and post-transplant cytomegalovirus (CMV) infection and graft-versus-host (GVHD) as time-dependent covariates. Advanced stage of leukemia at the time of transplantation was an important risk factor for subsequent relapse. Furthermore, the study confirmed a graft-versus-leukaemia (GVL) activity associated with chronic GVHD, including de novo chronic GVHD (intensity factor 0.08, p = 0.004). In a model excluding chronic GVHD, female donor-to-male recipient (a risk factor for GVHD), was associated with decreased post-transplant relapse risk (intensity factor 0.3, p = 0.008), suggesting that an allo-reaction against a minor transplantation antigen (Hy) may mediate antileukaemic activity. A decrease of the relapse risk by a factor 0.18 was observed in recipients with AML as well as ALL when the donor was CMV seropositive (p = 0.0002). This effect was restricted to patients who had laboratory evidence of post-transplant CMV infection. When CMV infection occurred and donor was seropositive the relapse risk was reduced by a factor 0.035. The effect was not mediated through an increased occurrence of grade 2-4 acute or chronic GVHD and could not be explained by a statistical bias due to censoring of patients who died in remission. Rather, donor CMV immunity was associated with GVHD independent GVL activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Retrospective estimation of diabetes incidence from information in a prevalent population and historical mortality.

If the distribution of onset age of disease in a well-defined prevalent (cross-sectional) population of patients is known, disease incidence rates specific for age and calendar time period may be estimated, assuming known mortality rates and a closed population. This paper develops a method of estimation, illustrates this method on Danish diabetes data, and discusses its general applicability. The prevalent population of diabetic subjects in Fyn County on July 1, 1973 was ascertained from prescriptions, and information on disease onset was obtained from the patients' medical records. In this study only patients with onset of disease before or at age 30 years were studied. The mortality of diabetic subjects in Denmark was estimated from retrospective hospital data covering the period since 1933, and historical age-specific population sizes of Fyn County were obtained from census data. The incidence of diabetes increases with calendar time and with age for most cohorts. The variation with age for a fixed calendar year is more complicated, however, usually displaying a local maximum at about the age of puberty and a higher incidence at the upper end of the studied age range.

Adolescent↗