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Biomedical subjects

P H Kurver

Publications and source records attributed to P H Kurver.

At least 19 recordsLinked to original sources

Effects of maternal smoking on neonatal morbidity.

In this paper a prospective study of the association between maternal smoking and neonatal morbidity variables is presented. Caucasian nulliparous women (n = 115) were studied throughout pregnancy, childbirth and puerperal period. Birthweight(-centiles), Apgar scores, mode of delivery, umbilical arterial and venous blood gas analyses, admission incidence to the neonatal ward and the neurological examination according to Prechtl were considered to be representatives for the starting condition of the newborns. The babies of smokers were statistically significantly at a disadvantage compared to babies of non-smokers for birthweight(-centiles), pH of the umbilical vein (medians: smokers 7.29, non-smokers 7.30) and the score of the neurological examination (medians: smokers 57, non-smokers 58).

Apgar Score↗

Maternal characteristics and expected birth weight.

Fetal growth charts currently used aggregate birth weights of infants with various natural histories from 1931 until 1967. In order to modernize these charts, avoiding deviation from the natural history of fetal development, we report data from infants born after spontaneous onset of labour in 'normal' pregnancy from a gestational age of 267 to 295 days between 1972 and 1982 (n = 14,113). The relationship between birth weight and gestational age in days was studied by multiple regression analysis, containing dummy variables for parity and gender. The estimated proportion of the variance in the model, attributed to these characteristics, was 15%. This could be improved to 22% by supplementing the model with maternal characteristics such as age, height, mid-pregnancy weight and ethnic origin. According to this extended model, in the Dutch section of the population 511 (4.6%) babies had a birth weight below the 5th percentile, whereas 412 (3.7%) babies would be labeled as such according to the conventional birth weight tables. Moreover, 93 babies would be wrongly considered too small, corresponding with a sensitivity of 62.4%, and 192 babies would be wrongly considered normal, corresponding with a specificity of 99.3%. Integration of the four currently used tables into one, and adjustment for easily available maternal characteristics, could substantially improve classification methods.

Birth Weight↗

Regional differences in breast cancer survival are correlated with differences in differentiation and rate of proliferation.

Patients with invasive ductal breast cancer and with 5 to 12 years of follow-up, identified from two pathology laboratories serving hospitals in two distinct but fairly close regions, were studied for differences in length of survival. In the years when the cases were diagnosed, population screening was not performed, adjuvant systemic therapy was not administered, and surgical treatment and irradiation protocols were similar in the hospitals served by the two laboratories. There was a significant difference in length of survival between the two regional groups (N1 = 160, N2 = 111; P = .006). Survival rate at 10 years in the two regions was 48% and 69%. Distribution of age, tumor size, and lymph node status (as negative or positive as well as number of positive nodes) were similar, but quantitative and qualitative microscopic features differed. Patients from the region in which the prognosis was less favorable had the higher median values for the mitotic activity index (14 v 4; P less than .0001) and for nuclear area (59.2 v 38.2; P less than .0001). Nuclear and histologic grade distributions were also different between the regions. Logistic regression analysis confirmed that the regional survival differences are correlated with the microscopic features, even after adjustment for age, tumor size, and lymph node status. Comparison of breast cancers from the periods 1970 to 1974 and 1988 to 1989 in one of the two regions revealed that the clinical and microscopic proliferation features were similar over time. These results, apart from indicating regional variation in breast cancer survival rate correlated to differences in the microscopic characteristics of the disease between regions, provide additional support to previous reports that qualitative and, especially, quantitative microscopic differentiation and proliferation features have significant bearing on the prognosis of breast cancer patients.

Breast Neoplasms↗

Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the Multicenter Morphometric Mammary Carcinoma Project.

The Multicenter Morphometric Mammary Carcinoma Project is a prospective study on the reproducibility and prognostic value of routine quantitative assessments, especially the mitotic activity index (MAI), the multivariate prognostic index (MPI; a combination of MAI, tumor size, and lymph node status), the mean nuclear area, and DNA ploidy assessments in patients with invasive breast cancer. Fourteen pathology laboratories providing routine services to 35 hospitals throughout The Netherlands are participating in this project. In this article, the reproducibility of MAI and MPI assessments is described. Assessment of the MAI was, according to a strict protocol, first performed in the participating laboratories; thereafter, slides were transferred to the coordination center in Amsterdam for quality control. Analysis of the reproducibility of the assessments in 2,469 patients showed correlation coefficients between 0.81 and 0.96 (mean, 0.91) for the MAI and between 0.91 and 0.97 (mean, 0.96) for the MPI. The reproducibility was fairly constant in time, although it showed a slight drop in the middle of the 2-year intake period. A prognostically relevant discrepancy in MPI (caused by differences in MAI) between the original and quality control assessments was found in only 7.2% of the cases. When analyzing the reasons for these discrepancies, a plausible explanation could be found in all cases: bad tissue processing and ignorance of or negligence in following the protocol guidelines for selection of the counting area or in the process of counting were the most important flaws. Since these errors are largely controllable, an even lower discrepancy rate is theoretically achievable. In conclusion, in a routine setting it can be learned, within a reasonable time, to perform mitosis counting in a highly reproducible way if a strict protocol is carefully followed. This opens the way for a wider application of the MAI and MPI in breast cancer patients. Motivation is, however, an important factor to obtain reproducible results, and ongoing quality control is essential to guarantee the reproducibility of the assessments.

Breast Neoplasms↗

Assessment of tobacco-exposure during pregnancy; behavioural and biochemical changes.

Smoking-behavior during pregnancy and the reliability of an interview were prospectively investigated. The tobacco-exposure was assessed a) by an intake interview b) by a smoking diary and c) by maternal thiocyanate and carboxy-hemoglobin concentrations. Of the 115 nulliparous women, 66 smoked (57.4%). Seventeen women (25.8%) quit and 39 women (59.1%) reduced smoking. Directly after intake, in the first week of the diary, significantly more cigarettes were smoked than stated during the intake interview. According to the diaries, the number of cigarettes increased during the first half of pregnancy. In the 24th week significantly more cigarettes were smoked than in the first week after intake. Also a significant increase of thiocyanate between the measurements at intake and in the 24th of amenorrhea was found. The maternal carboxy-hemoglobin levels did not significantly change during pregnancy. Investigators should be aware of changes in smoking behavior during pregnancy and the potential bias of self reported smoking behavior at the beginning of pregnancy. The tobacco-exposure should be assessed (anamnestic or biochemical) several times during pregnancy, anyway it should include the second half of pregnancy.

Adult↗

[Are earlier birth weights different from current ones?].

A sample was taken from non-pathological Caucasian births in Amsterdam from 1972 until 1982. The methods replicated as closely as possible those applied by Kloosterman to births from 1931 until 1967 for the Amsterdam Growth Curves. Birth weight percentiles and confidence intervals were determined non-parametrically in groups distinguished by sex, order of birth and duration of pregnancy. The correlations among the weekly means and the extreme percentiles were tested from the 36th to the 43th pregnancy week. We found a strong correlation (r = 0.983) between our sample and the Amsterdam Growth Curves. The means in the latter sample exceeded ours by 48.5 grammes which equals the estimated clerical error of the birth weights of 50 grammes. There is no strong evidence that the birth weights have changed much in the Caucasian part of the Amsterdam population.

Birth Order↗

Prognostic value of quantitative pathologic features and DNA content in individual patients with stage I endometrial adenocarcinoma.

The prognostic value of clinical features, qualitative and quantitative pathologic characteristics and steroid receptor incidence was evaluated in 50 patients with Stage I endometrial adenocarcinoma. It turned out that many of these features were prognostically important. Estrogen receptor content was not significantly associated with prognosis in our material, but patients with progesterone receptor positive lesions had a better survival than those in which the tumors were progesterone receptor negative. Multivariate analysis also clarified that only three features in combination had independent significance: mean shortest nuclear axis, DNA index, and depth of myometrial invasion (in sequence of decreasing importance). The prognostic rule consisting of these features overshadowed the value of all other features investigated. The overriding prognostic value of this highly reproducible rule was clear from the complete separation of 27 survivors and six nonsurvivors in the learning set of 33 patients. In an independent test set, all three nonsurvivors and 13 of the 14 survivors were correctly classified, thus confirming the accuracy and reliability of the developed rule to predict the outcome of future patients with Stage I endometrial adenocarcinoma.

Adenocarcinoma↗

Data processing and analysis in the Multicenter Morphometric Mammary Carcinoma Project (MMMCP).

In the Multicenter Morphometric Mammary Carcinoma Project (MMMCP), the prognostic value and reproducibility of routinely assessed quantitative pathological parameters in breast cancer is prospectively studied in approximately 3000 patients. Considering the high number of patients and the fact that many laboratories and hospitals throughout the Netherlands participate in this project, data acquisition, processing and analysis is an important component of the project. The data collection scheme, the structure of the database and the processing of data are described.

Breast Neoplasms↗

Development and use of a rule-based pathology expert consultation system.

Since histologic sections of pathologically changed tissues (e.g., tumors and inflammations) are highly complex structures, their subjective diagnostic or prognostic interpretation may result in a lack of interobserver and intraobserver agreement. Rule-based expert systems have the advantages that they require precise representation of the problem and can be used quickly and efficiently, even if the user is not acquainted with the special field concerned. Because of these and other advantages, a rule-based "Pathology Expert Consultation System" (PECS) is under development for the assessment of different premalignancies, malignancies and noncancerous conditions. In addition to supporting diagnosis making, the expert system can infer stage, type and grade, can check for inconsistencies in the answers and can predict the prognosis of an individual patient. PECS permits total integration of information contained in database, worksheet and text files with the rules and other control structures inherent in the rule base. The consultation can be interrupted to display a graph; when the user dismisses the graph, the consultation will resume where it left off or will move to another part of the system (if desired). If the user asks why a question is raised, the system will answer with a textual, graphic or combined explanation. The construction and use of the PECS expert system is discussed. Its initial applications to tumors of the lung, breast and endometrium have shown it to have both educational and clinical significance.

Computer Systems↗

Smoking and low birth weight: absence of influence by carbon monoxide?

Fetal outcome in 77 uneventful pregnancies was examined and related to venous cord carboxyhaemoglobin (HbCO) levels. 30 women were smokers, 47 were non-smokers. Birth weight and birth weight centiles were found to be substantially reduced in children of mothers who smoked. HbCO levels were significantly elevated in venous cord blood of children of smokers compared with non-smokers. The role of fetal HbCO as a causal factor in reducing birth weight centiles of children of smoking mothers is discussed. It is concluded that carboxyhaemoglobin concentration in fetal venous cord blood did not account for fetal growth retardation in pregnant women who smoked.

Birth Weight↗

The value of morphometry to classic prognosticators in breast cancer.

In 271 breast cancer patients with adequate follow-up for at least 5.5 and maximally 12 years, the value of morphometry to classic prognosticators of breast cancer (tumor size and axillary lymph node status) was assessed. Previous studies had indicated the value of this quantitative microscopic technique. Apart from quantitative microscopic features, subjective qualitative features such as nuclear and histologic grade were assessed as well. Univariate life-table analysis showed the significance (p less than 0.001) of several features such as lymph node status, tumor size, nuclear and histologic grade, and several morphometric variables (mitotic activity index, mean and standard deviation of nuclear area). Cellularity index was also significant (p = 0.02). Survival analysis with Cox's regression model, using a stepwise selection as well as backwards elimination, pointed to three features: mitotic activity index, tumor size, and lymph node status. Mitotic activity was the most important prognostic feature, but the combination of these three features in a multivariate prognostic index had even more prognostic significance. Kaplan-Meier curves showed that the 5-year survival of lymph node-negative patients (n = 146) is 85%, versus 93% in patients with a "good prognosis index" (n = 150). For lymph node-positive patients (n = 125), 5-year survival was 55%, compared with 47% in the "high index" (poor prognosis) patients (n = 121). Logistic discriminant analysis with 5.5-year follow-up as a fixed endpoint (191 survivors and 80 nonsurvivors) essentially gave the same results. Application of two instead of one decision threshold (e.g., numerical classification probability 0.60 and 0.40) decrease the number of false-negative and false-positive outcomes, however, with a number of patients falling in the class "uncertain." Thus, in agreement with other studies, morphometry significantly adds to the prognosis prediction of lymph node status and tumor size. Mitotic activity index is the best single predictor of the prognosis. An additional index advantage is that the multivariate model results in a continuous index variable that can be subdivided in many classes with an increasing risk of recurrence, so that more refined clinical therapeutic decision making is possible in individual patient care. The morphometric techniques are inexpensive and fairly simple and therefore can be applied in most pathology laboratories.

Actuarial Analysis↗

Large cell lymphoma. II. Differential diagnosis of centroblastic and B-immunoblastic subtypes by morphometry on cytologic preparations.

Measurements were made, using semiautomatic electronic planimetry, of nuclear and nucleolar parameters of cytologic preparations from 18 cases of centroblastic and 9 cases of B-immunoblastic Non-Hodgkin's lymphomas, in order to determine whether these two subgroups of large cell lymphoma could be differentiated objectively by morphologic criteria. Statistically significant differences between centroblastic and B-immunoblastic lymphoma occurred in the mean and standard deviation of nucleolar area, the mean nuclear area, and the number of nucleoli per nucleus. The most useful discriminatory parameter was mean nucleolar area. The mean percentage of immunoblasts, defined as cells with nuclear area greater than 35 micron 2 and mean nucleolar area greater than 3 micron 2, was significantly different between the two groups of patients. The results suggest that although the groups of centroblastic and of immunoblastic lymphomas can be differentiated by measurable morphologic criteria, the individual cases form a spectrum from nodular centroblastic through diffuse centroblastic to immunoblastic, with polymorphic forms in between. A comparison with the results of a similar study on histologic sections from the same patients demonstrated that morphologic measurements on these two types of material are not interchangeable but, in general, the same conclusions were reached by morphometric study on histologic and cytologic specimens.

Adult↗

Is maternal whole blood viscosity a factor in fetal growth?

Many authors have correlated changes in maternal hemodynamics during pregnancy with fetal growth. Sufficient plasma volume expansion in pregnancy seems mandatory for an optimal reproductive result. A correlation between rheological characteristics (low-shear whole blood viscosity and yield shear stress) and birthweight centiles was found in 26 third-trimester pregnancies. The level of statistical significance (P less than 0.05) was reached in nulliparous pregnancies but not in parous pregnancies. Measurements of whole blood viscosity at low shear rate and yield shear stress seem to provide information on the efficacy of placental perfusion. There have been reports in the literature to support the assumption of the prevalence of low-shear circumstances in the intervillous space. The hypothesis is put forward that, during pregnancy, the changes in maternal hemodynamics influence fetal growth by their impact on the flow through the placenta.

Adult↗

Morphometric grading of bladder tumors in comparison with histologic grading by pathologists.

The authors describe the results of the grading of bladder tumors using morphometry and then compare these with results of histologic grading of the same tumors by different pathologists. Nuclear sizes of cells obtained from superficial and deep cell layers of each carcinoma and from giant cells were measured in 27 cases in which histologic tumor grading by different pathologists was unequivocal. In cells from all three areas, nuclear area increased with higher tumor grade. However, tumors of grades I and II showed significant differences in the size only of the large cells. It is concluded that morphometry is a valuable tool in the objective grading of bladder tumors, with the exception of carcinoma in situ lining the bladder lumen.

Carcinoma↗

Prognostic indicators in breast cancer--morphometric methods.

Morphometric methods were applied to predict the clinical course of individual patients with breast cancer. Measurement of tumour diameter, assessment of mitotic and cellular indices, and quantitative microscopy of nuclear features were assessed together with nuclear features and histological grades. Of the tumours from 78 patients investigated, 42 had died from metastases within 6.5 years ('non-survivors'), while the other 36 were alive and well without evidence of metastases at the end of the follow-up period (minimum 6.5 years) ('survivors'). If the tumours of the 42 non-survivors are compared with those of 36 survivors, there are many reproducible significant differences, the most important being cellularity index and mitotic activity index, followed by quantitative microscopical nuclear parameters and nuclear and histological grade. Discriminant analysis, of the quantitative microscopical data alone showed 82% of all patients to be correctly classified as survivor or non-survivor. By contrast with the axillary lymph node invasion status alone, or the tumour diameter and axillary lymph node status together, 59% and 64% of the patients were predicted correctly as survivor or non-survivor. With a more realistic statistical approach of discriminant analysis, 78% of the patients were classified correctly with quantitative microscopy, in place of 54% with the axillary lymph node status, 56% with the TNM-system and 64% with a combination of TNM system and nuclear and histological grade. Morphometry thus seems possible to predict the outcome of individual patients more accurately than with the usual staging/grading methods. This technique might therefore prove to be useful in the selection of patients for adjuvant chemotherapy.

Axilla↗

Computer-aided application of quantitative microscopy in diagnostic pathology.

The quantitative analysis of microscopic images gives objective, consistently reproducible results. The number of applications of such analysis in diagnostic pathology is increasing rapidly. In this chapter, two examples have been given of the development and application of a quantitative microscopic classification rule. Both examples involve admittedly difficult areas of diagnostic pathology, in which considerable disagreement may not only exist among pathologists, but may affect the same pathologist judging the same specimen at different times. These areas are: (1) the discrimination of endometrial hyperplasia from carcinoma, and the grading of endometrial carcinomas; and (2) the preoperative distinction of follicular adenoma from carcinoma of the thyroid in cytologic specimens. With routine use of the classification rule in 148 cases of endometrial hyperplasia or carcinoma received in our laboratory in 1980, with each case judged by one of eight pathologists, there was mild or absolute disagreement in 7.4 percent and 4.7 percent of the cases, respectively (total: 12.1 percent). However, with blind review of one of us (J.B.), there were no absolute and only 3.3 percent mild disagreement. In this series, the quantitative microscopically assigned grades of carcinomas correlated significantly with the depth of invasion in the myometrial wall, whereas the grade routinely indicated by eight pathologists did not. These two facts strongly support the quality and utility of the developed quantitative microscopic rule for classifying endometrial lesions in a diagnostic setting. The rule can also be used to objectively define such endometrial lesions in order to evaluate more accurately their clinical outcome in a prospective study. In the thyroid adenoma cases discussed in the chapter, material from follicular tumors was subjected to quantitative analysis in 1980, again using a classification rule developed in our laboratory. All 10 cases of adenoma were correctly classified, whereas frozen-section diagnosis often gave erroneous or inconclusive results. The quantitative microscopic techniques that we have used are simple, inexpensive, and can be applied in most pathology laboratories. The classification rules can also be used in cases submitted for consultation. The pathologist must use his or her full diagnostic knowledge when applying these techniques. In doing so, he or she will learn that quantitative microscopy has an educative function, automatically results in an increase in the quality of histopathologic work, and supports and sometimes corrects the diagnosis in an objective, consistent way.

Adenocarcinoma↗

Discrimination of hyperplasia and carcinoma of the endometrium by quantitative microscopy--a feasibility study.

Endometrial hyperplasias and carcinomas have been investigated by quantitative microscopical methods. The aim of this study was to develop an objective method of histopathological diagnosis because of the great subjective variability of these endometrial conditions. A total of 79 cases were studied. Only those were included, which, after re-examination of the material by different pathologists, were regarded as mild atypical hyperplasia (38 cases), marked atypical (adenomatous) hyperplasia (11 cases), well and moderately differentiated adenocarcinoma (19 and 11 cases, respectively). There are many significant differences between these four groups. Stereological features contained the most important information, whilst nuclear features were less successful discriminators. The volume percentage of the epithelium and of the glands and the inner surface density of the glands showed the most significant differences between adenomatous hyperplasia and well differentiated carcinoma. On the basis of these findings, a quantitative model is suggested which might give more insight into the development of these abnormalities, assuming a gradual transition from one to another. The great advantage of the quantitative analysis of data over subjective impressions, it that is is objective, and provides consistently reproducible results. The present results may be especially useful when histopathological diagnosis is in doubt. It is concluded that application of quantitative microscopy in the discrimination of endometrial hyperplasia and carcinoma in histopathology is feasible.

Adenocarcinoma↗