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Biomedical subjects

N Keiding

Publications and source records attributed to N Keiding.

At least 127 records · Page 7Linked to original sources
PubMed1985

A Cox regression model for the relative mortality and its application to diabetes mellitus survival data.

A Cox-type regression model for the ratio between the mortality in a cohort and that in a reference population is introduced. By means of the model it is possible to include in the survival analysis both individual (possibly time-dependent) characteristics for the study cohort and changing trends in the mortality in the reference population. This is particularly relevant in long-term follow-up studies where there may be considerable changes in the mortality in the reference population. Estimation procedures in the model are discussed and large-sample properties of the estimators are outlined. The model is applied to the analysis of two sets of data concerning the survival among insulin-dependent diabetics in Denmark.

Adolescent↗
PubMed1984

Circadian-stage dependence of methotrexate in a keratinized epithelium. An in-vivo study using flow cytometry on the hamster cheek pouch epithelium.

The partially synchronized cell system of the hamster cheek pouch epithelium shows a characteristic diurnal rhythm of cell proliferation. Bolus injections of methotrexate (Mtx) in both lethal (10 g/m2) and non-lethal (2 g/m2) doses were found to inhibit cell-cycle progression primarily by impairing the G1/S transition. The results were obtained by flow cytometric DNA analysis. The inhibitory effect of Mtx manifested itself as a relative decrease of the S fraction (drug-effector phase), and was found to be dependent both on the dose and on the time of the day it was given. A bolus injection of Mtx was given either at 1200 hr (when a minimal number of cells are in S phase) or at 0200 hr (when a maximum number of cells are in S phase). The greatest cumulative decrease in S fraction was seen when the injection was given at 1200 hr. The time between injection and the effect (seen as a decrease in S fraction) was independent of the time of the Mtx injection, but seemed instead to be related to the natural diurnal period of increasing flux from G1 to S phase (at the onset of the dark period). The main effect (the relative decrease in S fraction) was repeated during the following 24-hr period, pointing to a protracted effect of Mtx on G1 cells. G1 cells affected by the initial high Mtx plasma concentration seem to be responsible for the reduced influx into S phase in both the first and second 24-hr period. In earlier toxicological studies, the survival rate of hamsters was dependent on the time of injection and was highest after injection at 1200 hr. Thus maximum cytokinetic effect on epithelial cells was found at the time of the day when there was a minimum lethal effect on the animal.

Animals↗
PubMed1984

Effect of methotrexate on cells in a keratinized epithelium with an active thymidine salvage pathway assessed by autoradiography.

In the partially synchronized cell system of the hamster cheek pouch epithelium, the inhibitory effect of a bolus injection of methotrexate (Mtx) (2 g/m2, injected at 1200 hr) was analysed by means of both autoradiography and flow cytometry (FCM) in a 21-hr experiment. For autoradiography [3H]TdR and [3H]UdR were used as tracers for salvage and de novo pathways of thymidylate (TMP) synthesis, respectively. For FCM no tracers were injected. The autoradiographic studies demonstrated an active TdR salvage pathway for DNA synthesis, not affected by the impaired de novo TMP synthesis. The blocked de novo TMP synthesis was partially released 7 hr after Mtx injection, but it had not totally recovered at the end of the experiment. The decrease in the fraction of S-phase cells detected about 10 hr after Mtx injection by autoradiographic labelling with [3H]TdR and by FCM was found to be caused by a decrease in the number of cells entering S phase. However, Mtx did not influence the salvage TMP synthesis rate of cells entering S phase.

Animals↗
PubMed1983

Long-term storage of samples for flow cytometric DNA analysis.

A simple procedure for long-term storage of cells for flow cytometric DNA analysis was developed and tested. The cells were stored as single cells or fine-needle aspirates suspended in a citrate buffer with dimethylsulfoxide (DMSO), or as small blocks of tissue from solid tumors. The cells were stored for up to one year by freezing at -80 degrees C. Statistical analysis of the results showed no change in the fractions of cells in the cell cycle phases as determined by deconvolution of the DNA-histograms. It was found that in addition to the intrinsic sample variation from the parameter estimation by deconvolution, there was significant intraday and interday variation. Hence the most accurate results are obtained if different aliquots of a sample are measured on different days rather than on the same day. Use of the storage method thus has the potential of increasing the accuracy of the analysis. The storage method makes sample collection independent of immediate subsequent analysis. This has enabled us to perform large internally controlled experiments, involving more samples than can be analyzed in one day, to examine tumor samples from different hospitals and to utilize fully the capacity of our flow cytometer. The method was a prerequisite for developing an accurate standardization procedure for DNA content determination.

Analysis of Variance↗
PubMed1982

DNA flow cytometry on human epidermis. The effect of serial biopsy sampling at various times.

The effect of serial biopsy sampling on S- and G2 + M-fractions in lower abdominal skin from leg ulcer patients was studied by single-nuclei DNA flow cytometry. Significant differences in both measurements were found in four biopsies taken at equal intervals within 24 h, but not in four biopsies taken at noon on four consecutive days. The variation in S-fractions was closely related to the injury from previous biopsy sampling(s) while the G3 + M-fraction variation tended to follow the time of the day. The study indicated local as well as systemic effects from previous biopsy sampling.

Adult↗
PubMed1982

Subclassification of cells in S phase in a partially synchronized cell system.

A circadian dependent delay in the incorporation of [3H]TdR into DNA, presumably due to variations in the intracellular pool of [3H]TdR derivatives, was found. It seems reasonable to relate this effect to a circadianally varying age distribution of cells in S phase. At any given time the S phase cells showed large variations in DNA synthesis rate, but it was still possible to identify a mean diurnal variation in the DNA synthesis rate. Differences in the ability of S phase cells to incorporate [3H]TdR are also discussed in relation to flow cytometrical measurements, and this contributes to the understanding of the commonly observed phenomenon that flow cytometry estimates of S-fractions are higher than those obtained with autoradiography.

Animals↗
PubMed1982

Circadian variations in influx and efflux of the S phase in a partially synchronized cell system. Double-labelling with [3H]thymidine in the epithelium of the hamster cheek pouch.

By means of a double-labelling experiment, circadian variations in the kinetic parameters of the S phase of the hamster cheek pouch epithelium were studied. The evaluation of the experiment included a recently developed correction for deviations from the strict pulse interpretation of the labelling technique. Pronounced circadian variations were found in S phase influx and efflux; the diurnal mean of both was estimated as 0.5%/hr, when based on measurements of all nucleated epithelial cells. Variations in S phase influx seem mainly responsible for the diurnal variation in cell proliferation, although diurnal variation in DNA synthesis rate, and thus in mean transit time, was also found. The increases in LI and influx were closely correlated and related to the beginning of the dark period. A circadian variation in cell number was also observed.

Animals↗
PubMed1980

Precision of histological grading of malignancy.

The precision of a grading system based upon average score of 8 items for histological evaluation of malignancy of epidermoid carcinomas of the larynx was studied by letting 6 pathologists examine biopsies from 22 new cases. Exploratory statistical tools as well as a statistical framework (variance component models) for separating and evaluating the noise components are suggested. The order of magnitude of the resulting overall measurement uncertainty allowed discrimination between patients, though if a patient is graded by only one pathologist, only results as the extremes of the scale of malignancy should be trusted as possible therapeutical guidance. Based upon an analysis of the basic structure of the grading system the single noise components making up the measurement uncertainty were determined. Of greatest importance was noice created by disagreement between the pathologists in their ranking of the patients on the scale of malignancy. Furthermore the pathologist used the individual items differently, and certain items seemed to conform little to the scoring system. An attempt to minimize these two last components was performed; however neither calibration of the pathologists nor omission of the deviating items improved the precision significantly.

Carcinoma, Squamous Cell↗
PubMed1975

A morphometric study of normal human liver cell nuclei.

Using the projecting method, measurements were made of the size of nuclei of liver cells in liver biopsies taken from ten patients with normal liver histology and normal liver function tests and from two patients with acromegaly. For the statistical analysis a parametric model of the distributions of the nuclear radii, the chi distributions, was used, making an estimation of the frequencies of di-, tetra- and octaploid nuclei possible. The distribution of the lengths of the nuclear radii was consistent with normal distributions corresponding to the different ploidy classes. Diploid nuclei constituted 84 to 99 per cent of the liver cell nuclei, and the frequency of polyploid nuclei increased with increasing age. Samples of nuclei within the same biopsy revealed significant differences in the mean radius of diploid nuclei and in the frequency of polyploid nuclei. This biological variation must be taken into account in the interpretation of karyometric data. One of the patients with acromegaly had a higher frequency of polyploid nuclei than seen in normal patients, and in both patients with acromegaly the size of diploid nuclei was large compared with normals. The frequency of binuclear nuclei was unrelated to age and frequency of polyploid nuclei, but males were found to have more binuclear liver cells than females.

Acromegaly↗
PubMed1975

Karyometry of liver biopsies in virus hepatitis.

Liver biopsies from ten patients with clinically mild or moderate acute virus hepatitis, taken in the acute phase of the disease and in the recovery phase or later, were assessed for the size of liver cell nuclei and the number of binuclear nuclei. A parametric model of the distributions of the nuclear radii was used to estimate the mean nuclear radius of diploid nuclei and the frequencies of di-, tetra- and octaploid nuclei. During the acute phase of virus hepatitis the liver cell nuclei were often larger, with greater variation in size, than in the recovery phase. This pleomorphism was not only due to pyknotic and necrotic nuclei as these were not measured. It is assumed that the enlargment of the nuclei was due to increased metabolic activity of the nuclei. The frequencies of polyploid nuclei and binuclear liver cells were higher in the first biopsies, probably reflecting regenerative activity. No correlation was found between the severity of the disease as judged by liver histology or routine liver tests and the degree of nuclear changes with respect to size and frequency of polyploid or binuclear liver cells.

Acute Disease↗