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Biomedical subjects

N Keiding

Publications and source records attributed to N Keiding.

At least 109 records · Page 6Linked to original sources

Size distribution of neurosecretory granules in the supraoptic nucleus and the neurohypophysis of water-loaded, normal and water-deprived rats.

The profiles of the neurosecretory granules were measured in the supraoptic nucleus and in axons, swellings and endings in the neurohypophysis. This was performed after the secretion of vasopressin had been fully suppressed by water load for 1.5, 2.5 and 24 h, after the secretion had been stimulated by water deprival for 72 h and in normal rats with water ad libitum. A finite-difference algorithm was used for unfolding the size distribution of neurosecretory granules from the observed profiles, and showed a clear grouping of the neurosecretory granules into 3 size groups: small, medium-sized and large granules. Estimates of the relative volumes of the granules from these 3 groups were combined with previous results. In the supraoptic nucleus, water deprival increased the total volumes of the small and medium-sized granules, and water load decreased the volumes of the medium-sized and especially the large granules. However, in the neurohypophysis, water deprival decreased and water load increased the volume densities of the small and medium-sized, but did not influence that of the large granules. The results indicate that the medium-sized granules are vasopressinergic and the large oxytocinergic. Moreover, the results are consistent with the hypothesis that the small contain another peptide.

Animals↗

Prognostic value of steroid hormone receptors: multivariate analysis of systemically untreated patients with node negative primary breast cancer.

The value of estrogen and progesterone receptor (ER and PgR, respectively) determinations in predicting the recurrence-free survival (RFS) has been evaluated in a group of 807 node negative breast cancer patients. All of these patients are enrolled in the Danish Breast Cancer Cooperative Group (DBCG) 77-1a and 82-a protocols for low risk patients, and none of them have received systemic adjuvant therapy. At a median observation time of 50 months and in an evaluation of the total patient population as an entity, ER+ patients had only a marginally significant (P = 0.07) longer RFS than ER- patients while PgR+ patients experienced a significant advantage (P = 0.02). Among patients subgrouped according to menopausal status, both ER and PgR statuses were found to be significant prognostic factors for predicting RFS in the premenopausal women (less than 50 years) but not in peri- or postmenopausal women. Using Cox's multivariate analysis, nuclear pleomorphy was found to be the only significant prognostic variable, while the value of PgR status as a prognostic factor approached significance (P = 0.065). Although knowledge of ER status did not significantly improve distinction between patients with good and poor prognoses in the relatively small subgroup of premenopausal patients (n = 120) when PgR status was known, ER+PgR- patients have a lower risk of recurrence or death than ER-PgR- patients. Using a log-likelihood model, significant and distinct cut-off limits for the definition of receptor positivity were found for premenopausal patients: these were 5 fmol/mg cytosol protein for ER and 10 fmol/mg cytosol protein for PgR. These cut-off levels may reflect the ability of the ligand binding assay method used to discriminate between tissues with and without receptor proteins. Qualitative assessment of receptor status was as valuable as quantitative expression of receptor concentrations in predicting the RFS of the natural course of the disease among node negative premenopausal patients.

Adult↗

Unemployment and mortality in Denmark, 1970-80.

Relative mortality in the period 1970-80 was studied among Danish men and women who were unemployed and employed on the day of the 1970 census. The study population consisted of the total labour force in the age range 20-64 on 9 November 1970--that is, about 2 million employed and 22,000 unemployed people. Relative mortality was analysed by a multiplicative hazard regression model (as a natural extension of the standardised mortality ratio) and a multiplicative regression model with extra-Poisson variation. A significantly increased death rate (40-50%) was found among the unemployed after adjusting for occupation, housing category, geographical region, and marital state. Analysis of five main causes of death showed increased mortality from all causes, but especially from suicide or accidents. In areas where the local unemployment rate was comparatively high the relative mortality among the unemployed was lower. The increased mortality among the unemployed was interpreted as a consequence of health related selection as well as increased susceptibility associated with the psychosocial stress of unemployment.

Adult↗

Histologic malignancy grading of invasive ductal breast carcinoma. A regression analysis of prognostic factors in low-risk carcinomas from a multicenter trial.

In a prospective adjuvant trial including patients with primary operable breast cancer, invasive carcinomas of ductal type were subjected to histological malignancy grading. The parameters investigated were tubule formation, number of mitoses and cell pleomorphism. A Cox regression model for survival data was applied to evaluate the impact of the histological parameters on prognosis in 1809 patients with low-risk carcinomas. Cell pleomorphism proved superior to the other histologic tumor characteristics. It was found that low-risk invasive ductal carcinomas with severe cell pleomorphism had an excess recurrence intensity of 209% relative to carcinomas with no pleomorphism. It is therefore suggested that polymorphous invasive ductal breast carcinomas, other things being equal, should be regarded as high-risk tumors in future clinical trials. Finally it was found that the tripartite malignancy grading 1, 2 and 3 characterizing each of the histological parameters was not equidistant. Consequently, the traditional tripartite histologic scoring needs reconsideration.

Adult↗

Confirmatory analysis of survival data using left truncation of the life times of primary survivors.

In survival analysis, as in other branches of applied statistics, confirmatory analysis is often requested before an initial finding can be cleared of suspicion of being due just to mass significance. This paper points out that the special temporal structure of the classical clinical trial with staggered entry allows re-use of the initial survivors by left-truncating their remaining survival times. This procedure can often save a considerable amount of calendar time. The procedure is illustrated by data from the Danish Breast Cancer Cooperative Group.

Breast Neoplasms↗

Estimation of fetal weight in the third trimester by ultrasound.

A method to estimate the intrauterine fetal weight by use of ultrasound measurements of the fetal biparietal diameter (BPD) and the abdominal diameter (AD) is presented. From a consecutive series of single pregnancies the 238 pregnancies (3% of the hospital population) with ultrasound measurements obtained within 4 days before delivery were used in the estimation of birth weight. In addition, the estimated formula was applied on a test material consisting of 100 similarly selected pregnancies from the same hospital. To evaluate the expected selection effects, the birth weight for gestational age in the study group was compared with birth weight for gestational age in the total population. The weight could be estimated as 0.0351 X AD1.65 X BPD0.69 X exp(0.00196 X gestational age). Thus, the actual birth weight was within 83-120% of the estimated weight (95% prediction limits), with a residual coefficient of variation of about 9%. The gestational age could be omitted without major influence on the weight prediction. When applying the formula on the test material, 70% of the actual weights deviated less than 10% from the estimated fetal weight, but a tendency towards a slight overestimation of the weight for light for gestational age infants was found.

Birth Weight↗

Growth retardation in preterm infants.

This paper combines earlier results on the relation between birthweight and gestational age, and the relation between fetal weight and ultrasound measurements of the fetal biparietal diameter (BPD) and mean abdominal diameter (AD) to investigate whether preterm infants (viewed as a group) are smaller than unborn fetuses of the same gestational age. The birthweight distribution for each sex at 223 and 258 days gestation was derived from the birthweight-for-gestational age charts based on 3888 newborn infants. The sex-specific intrauterine weight distribution was estimated from ultrasound measurement of the fetal BPD and AD performed on randomly selected fetuses of gestational age 223 and 258 days. The birthweights were lower than the intrauterine weights, especially early in pregnancy and for female infants. Thus, the 10th birthweight centile for girls at day 223 corresponds to the 4th centile of the 'true' intrauterine weight, and the 'true' intrauterine 10th centile corresponds to the 25th centile birthweight at day 223.

Birth Weight↗

On the evaluation of routine ultrasound screening in the third trimester for detection of light for gestational age (LGA) infants.

Based upon 2194 consecutive pregnancies with known gestational age, formulas for weight deviation predicted in the 32nd and 37th gestational week were estimated by multiple linear regression on the measurements of the abdominal diameter (AD) and the biparietal diameter (BPD) of the first 64% of the pregnancies. The usefulness of the screening was evaluated on the remaining 36%. An attempt to diagnose light for gestational age (LGA) infants resulted in either a low sensitivity or a low predictive value of a positive test. The late third trimester screening was more sensitive than the early, indicating LGA as a late phenomenon in pregnancy. Knowing the result from the late scanning, the result from the early scanning contributed almost no further information about whether the infant would be LGA at birth. Basic epidemiological characteristics of other comparable investigations on high-risk pregnancies and non selected pregnancies are presented.

Birth Weight↗

The method of expected number of deaths, 1786-1886-1986.

"The method of expected number of deaths is an integral part of standardization of vital rates, which is one of the oldest statistical techniques. The expected number of deaths was calculated in 18th century actuarial mathematics...but the method seems to have been forgotten, and was reinvented in connection with 19th century studies of geographical and occupational variations of mortality.... It is noted that standardization of rates is intimately connected to the study of relative mortality, and a short description of very recent developments in the methodology of that area is included." (SUMMARY IN FRE)

Demography↗

Birthweight-for-gestational age charts based on early ultrasound estimation of gestational age.

Birthweight-for-gestational age charts were based on the analysis of 3888 consecutive births in which the gestational age was estimated by measuring the fetal biparietal diameter before the 20th week of gestation. The data showed, in contrast to previous studies, a linear relation between gestational age and birthweight without inflection after term. The regression parameters showed a strongly significant difference between girls and boys. Thus, boys were 1.5% heavier than girls at 190 days gestation and 3.6% heavier at 300 days gestation. The linearity in the birthweight-for-gestational age charts could be due to the more reliable gestational age based on early ultrasound.

Birth Weight↗

Onset of the release of spermatozoa (spermarche) in boys in relation to age, testicular growth, pubic hair, and height.

The onset of production of spermatozoa (spermarche) is the basis for achievement of reproductive capacity in men. We collected 24-h urine samples every 3 months in a 7-yr longitudinal study of 40 normal boys initially aged 8.6-11.7 yr. After centrifugation, the urine was analyzed for the presence of spermatozoa by microscopic examination, and spermarche was estimated on the basis of age at first observed spermaturia. The results were corrected for the intermittent occurrence of spermatozoa in the urine after first observed spermaturia and the fact that the urine samples were collected quarterly. In addition, physical examination, including determination of testicular size by orchidometer measurement, pubic hair distribution (Tanner stage), and height, was carried out every 6 months. Spermarche occurred at a median age of 13.4 yr (range, 11.7-15.3 yr), at a time when testicular size was 4.7-19.6 ml (median, 11.5 ml), and pubic hair distribution was 1-5 (median, 2.5). In most boys, spermarche preceded the age of peak height velocity (median, 13.8 yr; range, 12.2-15.2 yr); at the time of spermarche, median peak height growth velocity was 9.9 cm/yr (range, 7.5-13.4 cm/yr), and median height was 160.4 cm (range, 151.7-175.9 cm). We conclude that spermarche is an early pubertal event and that a wide variation in testicular size and secondary sex characteristics is found at that time. In particular, spermarche may occur when little or no pubic hair has developed, and the testes have grown only slightly.

Adolescent↗

Longitudinal study of testosterone and luteinizing hormone (LH) in relation to spermarche, pubic hair, height and sitting height in normal boys.

In a 7-year longitudinal study of 40 normal boys, initially aged 8.6-11.7 years, 24-h urine samples were collected every 3 months and analysed for LH and testosterone as well as for the presence of spermatozoa (spermaturia). Spermarche (onset of the release of spermatozoa) was estimated on the basis of age at the first observed spermaturia. Physical examination, including measurements of height and sitting height and staging of pubic hair (Tanner stage) was performed every 6 months. Spermarche occurred early in puberty when the median pubic hair stage was 2.5. Urinary testosterone did not reach maximum levels until approximately 2 years after spermarche. Peak height velocity occurred when urinary testosterone levels were low, 1-2 years before adult levels of testosterone were attained. Our results support the proposition that low levels of testosterone have a predominantly growth-promoting effect, whilst higher concentrations have an inhibitory effect on height spurt.

Body Height↗

Relative mortality of type 1 (insulin-dependent) diabetes in Denmark: 1933-1981.

The relative mortality of Type 1 (insulin-dependent) diabetes in Denmark during the period 1933-1981 was studied using a modification of Cox's regression model on the basis of two patient populations, ascertained in different ways and independently of each other. Initial analysis showed that the two groups could be combined completely into one common analysis. Relative mortality was the same for both sexes. The additional variables studied were age at diagnosis, current age, calendar year at diagnosis and calendar time during follow-up. All these interrelated variables were accounted for in the analysis. The analysis showed that relative mortality decreased with increasing age at diagnosis; increased from 1933 to a maximum in about 1965, after which it decreased; increased with increased duration of diabetes to a maximum at 15-25 years, after which it declined.

Adolescent↗

Meningeal involvement in non-Hodgkin's lymphoma: symptoms, incidence, risk factors and treatment.

Meningeal involvement (MI) by non-Hodgkin's lymphoma (NHL) was seen in 38/602 patients (6.3%). In relation to histologic subtype the frequency of MI was: Follicular small cleaved and mixed cell 2/128 (1.6%), small lymphocytic and diffuse small cleaved cell 2/83 (2.4%), large cell and immunoblastic 13/295 (4.5%), small noncleaved cell 6/31 (19%), lymphoblastic 15/66 (23%). Risk factors that predict for MI were, besides histologic subtype, age under 40 yr, clinical stage IV, site of involvement (bone marrow, bone, skin gastrointestinal tract), and a poor response to initial therapy. In a Cox multivariate model encompassing the intermediate and high grade malignancy groups of the Working Formulation (WF), the 3 most important risk factors were histology, age, and stage. The estimated 1-yr probability of MI for combinations of the 3 risk factors was: 3 risk factors (61%), 2 risk factors (15-28%), 1 risk factor (4-8%), 0 risk factor (1.5%). At the diagnosis of MI, 84% of the patients had evidence of advanced systemic NHL, and the median survival after MI was 10 wk. CNS prophylaxis with whole-brain irradiation and intrathecal chemotherapy can only be recommended in patients with 2 or 3 risk factors. Improvement of the systemic chemotherapy might be the most important factor for prevention of MI in NHL.

Adult↗

Risk of acute nonlymphocytic leukemia and preleukemia in patients treated with cyclophosphamide for non-Hodgkin's lymphomas. Comparison with results obtained in patients treated for Hodgkin's disease and ovarian carcinoma with other alkylating agents.

Of 602 patients treated for non-Hodgkin's lymphomas, 9 developed overt acute nonlymphocytic leukemia or preleukemia with refractory cytopenia and cytogenetic abnormalities of the bone marrow. A Kaplan-Meier estimate of the cumulative probability of leukemic complications was 6.3 +/- 2.6% (mean +/- SE) 7 years after start of treatment. All 9 patients with leukemic complications belong to a major subgroup of 498 patients treated with alkylating agents, predominantly cyclophosphamide. The risk of leukemic complications in this subgroup was compared with the risk in 312 patients treated with other alkylating agents for Hodgkin's disease, and with the risk in 553 patients treated with dihydroxybusulfan for ovarian carcinoma. Cumulative 9-year risks were 8.0 +/- 3.3%, 12.8 +/- 3.5%, and 7.1 +/- 1.9%, respectively. The general risk of secondary leukemia after long-term treatment with alkylating agents ranges from 1% to 1.5% per year from 2 to at least 9 years after start of treatment.

Acute Disease↗

Circadian variation in mitotic influx in a keratinized epithelium. The stathmokinetic technique used in vivo on the hamster cheek pouch epithelium and analyzed by periodic regression analysis.

An in vivo study of the hamster cheek pouch epithelium using the stathmokinetic technique (Colcemid) demonstrated a circadian variation in mitotic influx. Based on measurements of all nucleated epithelial cells the diurnal mean was estimated in two separate experiments as 0.34%/h +/- 0.02 (SE) and 0.27%/h +/- 0.02 (SE) respectively. 3HTdR was injected in the latter study (a double labelling experiment). The significant difference between the two experiments is, however, probably due to biological variations. The maximal values for the mitotic rate were found during the light (resting) period, as were the maximal values for the mitotic index. The mean mitotic influx for the 'light period' was estimated as 0.5-0.4%/h, and for the 'dark period' as 0.2%/h. Independent analyses demonstrated the necessity of a circadian-dependent correction of the 1 and 4 h values of accumulated metaphases. The 1 h value was significantly too high during the light as well as the dark period. The 4 h value was found to be too low, but only significantly so during the dark period. Basing the estimation of mitotic rate on the 3 h accumulation value produced only very similar results to those found by using all four accumulation periods. The use of overlapping experiments proved that only cells entering mitosis after Colcemid application were arrested, so that when arrested metaphases were counted the accumulation line was correctly drawn through the origin. In the latter study (the double labelling experiment) both S- (Møller and Keiding 1982) and mitotic influx were estimated, the estimates being 0.55%/h +/- 0.03 (SE) and 0.27%/h +/- 0.02 (SE) respectively. Even considering possible methodological problems, the discrepancy between the S efflux and the mitotic influx indicates cell death and/or differentiation from G2.

Anaphase↗