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Biomedical subjects

E Pesonen

Publications and source records attributed to E Pesonen.

At least 91 records · Page 5Linked to original sources

Elucidation of the natural history of ventricular septal defects by serial Doppler color flow mapping studies.

Two-dimensional echocardiography has provided information to aid in the diagnosis and management of infants with ventricular septal defect, but its inability to resolve very small ventricular septal defects and problems with defining ventricular septal defect orifice size (because of overlying muscle or tricuspid tissue) have made it unsuitable as a standard for defining the natural history of ventricular septal defect. In this study, 114 serial two-dimensional Doppler color flow mapping studies were performed to define ventricular septal defect anatomy, location and color flow diameter as an indicator of shunt size in 66 patients (over a 40 month period). Twenty-five patients first studied at 6 months of age (mean age at most recent study 15.9 months) had congestive heart failure and 41 (mean age 45 months) did not. In the congestive heart failure group, there were 24 perimembranous and 1 muscular ventricular septal defect and aneurysm formation was present in 17. Mean (+/- SD) color flow diameter was 8.2 +/- 1.9 mm and color flow diameter/aortic root diameter ratio was 0.63. In the 30 patients who underwent cardiac catheterization, color flow diameter bore a close relation to angiographic diameter (r = 0.96) and pulmonary/systemic flow ratio (Qp/Qs) (r = 0.88). In the patients with congestive heart failure, 4 of the 25 ventricular septal defects, all with aneurysm present or positioned adjacent to the tricuspid valve, became smaller but none closed. Of the 41 patients without congestive heart failure, 21 had a perimembranous defect (15 with aneurysm), 18 had a muscular ventricular septal defect and 2 had a supracristal ventricular septal defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Volume corrected mitotic index (M/V-INDEX). The standard of mitotic activity in neoplasms.

Estimation of mitotic activity by counting the number of mitotic figures per high power fields is subject to many sources of error. The microscope fields vary in size in different microscopes, which makes comparisons arbitrary. Also the areas covered by neoplastic and non-neoplastic tissue in the microscope image vary in different tumors. We found that each microscope could easily be characterized in terms of the size of the microscope field at 40x objective magnification (usually at ocular magnification of 10x). We also found that the number of mitotic figures can be related to the area covered by neoplastic tissue in the microscope field. The resulting index, the volume corrected mitotic index (M/V-index) will express the mitotic activity as the number of mitotic figures per square millimeter of neoplastic tissue in the microscope fields. The M/V-index will not be subject to the variation in volume fractions of neoplastic tissue between different neoplasms. With the M/V-index the mitotic activity as measured in different microscopes can be compared reliably. The value of the method is demonstrated in a series of ovarian tumors.

Adenocarcinoma↗

Sources and nature of variation in DNA analysis of follicular thyroid adenoma.

We investigated the sources and nature of variation that may occur in the DNA analysis of thyroid adenomas from cytological and histological samples. Imprints and smears gave identical results. However, the nuclear area was higher in smears where the optical density of the nuclei was lower. In measuring imprints, the interactive selection of nuclei was preferred to the automatic, because the risk of measuring nuclear fragments or undesired objects was thus avoided. The reproducibility and the variation of the DNA measurements depended on the degree of observer training in quantitative pathology, the method of field selection, and the type of instrumentation. Biological variation in the spatial distribution of nuclei with different ploidy values in some adenomas seemed to hide the influence of section thickness on measurements. Our data seem to suggest that it is best to apply a constant section thickness and 5 micron sections seem acceptable.

Adenoma↗

Potential of morphometry in grading transitional cell carcinoma of the urinary bladder.

The potential of morphometry in grading cases of transitional cell carcinoma of the urinary bladder was evaluated. Thirty cases of bladder cancer including all three WHO grades were studied. Three investigators measured the nuclear areas using the IBAS 1&2 image analyser system. The means, the standard deviations and the variances of the measurements were calculated. The nuclear areas covered values from 25.1 to 107.4 square micrometers, the mean +/- SD being 52.6 +/- 17.5. The total variance of measurements, including biological and methodological variation, was 304.6, and the methodological variance 10.4 (about 3.5% of the total variation). In a 3-grade grading system this would correspond to an efficiency of about 92%, and in a 2-grade system of about 96%, which are the percentages correctly graded by the grading system.

Carcinoma, Transitional Cell↗

The flow-cytometric analysis of DNA content and S-phase fraction (SPF) of human breast cancer.

The DNA ploidy of breast cancer tissue from paraffin blocks was measured by flow cytometry in 122 patients. In this material there was a difference in lymph node involvement and in the presence of distant metastases between diploid and aneuploid tumors. Diploid tumors were smaller than aneuploid tumors. Aneuploid tumors were more common in postmenopausal than in premenopausal women. Near tetraploid tumors were found in older patients rather than tumors with other ploidy patterns. The ploidy pattern was not associated with survival during the mean follow-up of 4.1 years. We specially studied the S-phase fraction (SPF) which was distinctly higher in aneuploid tumors than in diploid tumors. Also near tetraploid, hypertetraploid and multiploid tumors showed higher SPF than diploid tumors. The median of SPF in our material was 8.5%. Positive axillary lymph nodes were found in 32% of the patients who had tumors with an SPF below the median and in 46% of those with tumors above the median (SPF greater than 8.5%). The difference, however, was not statistically significant. In our material the SPF of the tumor did not show a significant association with survival. However, longer follow up time is needed for firm conclusions on the predictive value of cell DNA on survival.

Breast Neoplasms↗

Prognosis of ovarian carcinomas: prediction by histoquantitative methods.

Prediction of prognosis of ovarian carcinomas by morphometric, histopathological and clinical indices was estimated in 105 tumours. Morphometric parameters included mitotic activity index, volume-corrected mitotic index (M/V index), volume fraction of neoplastic epithelium, nuclear area, nuclear perimeter, shortest and longest nuclear axis and form factor of nucleus. Cox's multivariate regression model showed that the clinical stage was the best predictor of prognosis followed by the M/V index, which expresses the mitotic activity as the number of mitotic figures per square millimeter of neoplastic epithelium in the microscope field. In all tumour subgroups studied the M/V index was the best prognostic factor and for stage I tumours it was the only parameter selected by the Cox's model as a significant and independent prognostic predictor. We conclude that the M/V index can be used as a significant prognostic factor in ovarian carcinomas.

Carcinoma↗

Closure of the ductus arteriosus and mechanics of breathing in preterm infants after surfactant replacement therapy.

Treatment of premature infants with exogenous surfactant is thought to increase the incidence of the patent ductus arteriosus (PDA) due to improved mechanics of breathing and the resultant reduced pulmonary vascular resistance. As part of a prospective, blinded, controlled study of human amniotic fluid-derived surfactant, we assessed the time of closure of the PDA, defined by Doppler echocardiographic studies, performed at 6-h intervals, and the mechanics of breathing at 6, 18, and 30 h of age in 61 infants (gestational age, 25-29 wk, and birth wt, 450-1580 g). All infants had respiratory distress syndrome as confirmed by immature surfactant phospholipid profiles determined on either amniotic fluid and/or tracheal aspirate analysis, and chest radiograph, and all had a PDA at 6 h of age. Surfactant treatment was associated with more frequent clinically determined need for treatment of the PDA, but did not prolong the patency of the ductus in infants with spontaneous closure or in those requiring treatment with indomethacin. Infants with spontaneous closure of the PDA had significantly higher dynamic lung compliances and lower oxygen requirements and were treated with lower mean airway pressures than those requiring PDA treatment, although their arterial blood gas status was the same. The dynamic lung compliance of infants with right to left ductal shunting was significantly lower than those with left to right shunting at 6 and 18 h but was not different thereafter. This study suggests that the maturity of the ductus arteriosus, reflected by its tendency to close spontaneously, parallels the maturity of the lungs, reflected by their mechanical stability, and that ductal closing is not significantly altered by surfactant therapy.

Clinical Trials as Topic↗

Cardiac function, substrate utilization, and myocardial energy metabolism studied with 31-P NMR spectroscopy during acute hypoglycemia and hyperketonemia.

Whether severe hypoglycemia alone or in combination with hyperketonemia might cause deterioration of cardiac function has been controversial. Therefore, the influence of acute hypoglycemia (mean 33 mg/dL) with and without hyperketonemia (mean 1.3 and 3.3 mM) on cardiac function, substrate utilization, and myocardial high energy phosphate levels was studied in 10 mongrel dogs. After 45 min of hypoglycemia, mean aortic pressure, total peripheral resistance, and myocardial oxygen consumption had increased significantly, but other hemodynamic parameters and regional myocardial function had not changed. Additional infusion of 3-hydroxybutyrate did not affect hemodynamic variables significantly. During both metabolic interventions in vivo phosphorus-31 nuclear magnetic resonance spectroscopy showed stable levels of myocardial phosphocreatinine, ATP, as well as the phosphocreatinine/ATP (3.0-3.2) ratio. Biochemical measurements revealed that hyperketonemia led to significant alterations in arterial concentrations and arteriocoronary venous differences of selected citric acid cycle intermediates, thus confirming previous reports which suggested a blockade of the 2-oxoglutarate-dehydrogenase reaction induced by ketone body oxidation. However, despite this blockade, the energy supply to the heart was not impaired as shown by normal nuclear magnetic resonance spectroscopy and cardiac performance. It is speculated, that the blockade might be due to an enhanced NADH/NAD ratio.

Adenosine Triphosphate↗

Human surfactant in the treatment of respiratory distress syndrome. A spectrum of clinical responses.

Surfactant substitution is an incompletely studied, promising approach to treat respiratory distress syndrome (RDS). In this report we describe a spectrum of clinical responses following administration of human surfactant from amniotic fluid to 64 newborn infants. There was apparently no harm when surfactant was given to three infants with "mature" surfactant profile. Altogether 40% of the 42 "immature" small preterm infants (gestational age 26-29 weeks) required only a single dose, and 50% of them required two or three doses for successful treatment. In infants with persistent foetal circulation (6 cases) or hydrops (2 cases), there was only a transient or a small improvement of respiratory function. Most notably, the very small preterm infants (24-26 weeks, 15 cases) may require substantial increase in blood volume to prevent cardiac failure during the first neonatal day. We propose that the clinical response to exogenous surfactant can be improved by modifying the current management of very small preterm infants.

Amniotic Fluid↗

Preliminary and early stages of atherosclerosis in childhood.

According to the unified theory of atherosclerosis, endothelial cell injury and lipid infiltration play an important role in atherogenesis. Newborn babies may suffer endothelial cell damage, as may be detected by electron microscopy. Connective tissue elements are occasionally abundant already in newborns. Chondroitin sulfate A and C increase with age. The children may exhibit continuous accumulation of cholesterol esters in the intima of coronary arteries. Cholesteryl ester fatty acid composition, along with age, tends to approach that of serum low-density lipoproteins. Fatty streaks appear in coronary arteries in puberty, and fibrous plaques are recordable beyond the age of 20 years. The topography of myo-intimal thickenings, fatty streaks, and fibrous plaques is similar to complicated atherosclerotic lesions. Even newborn babies have obstructive myo-intimal thickenings in their coronary arteries. One fifth of all infants under one week of age suffer 20% stenosis, with percentile manifestation of stenosis in the arterial cross-section being established as ratio of intimal area to luminal area of a dilated coronary artery multiplied by 100. Occasionally, the intima is very thick, in our series initiating up to 57% of all narrowing. There are probably noxious factors which temporarily damage the endothelial cells and initiate a rapid, partially reversible thickening reaction. Some of this response of the intima to exogenous stimuli might be genetically determined. A thickened intima is susceptible to lipid deposition and atherosclerosis.

Adolescent↗

Principles of morphometric grading.

Grading of the severity of lesions has increased in importance in histopathology. The simplest grading system has 2 grades. If there is variation in the measuring system, the grading will not be perfect, and there are also misgraded samples. We estimated the fraction of falsely graded cases by applying th NAG (Numerical Algorithm Group) Fortran Library. If all possible measurement values are equally probable the grades based on measurements within +/- 1 SD around the division line are false in 31.6% of cases. The corresponding figures for regions +/- 2 SD, +/- 3 SD, 1 to 2 SD, 1 to 3 SD, and 2 to 3 SD are 19.6, 13.3, 7.5, 4.2, and 0.8%, respectively. Detailed calculations were made which allowed accurate determination of the probability of a grade being false in different positions of the measurement scale. The results suggest that for diagnostic grading a borderline region should be defined (e.g. +/- 2 SD or +/- 3 SD around the division line).

Diagnostic Errors↗

Reproducibility of DNA measurements in imprints of thyroid adenoma. Variation sources.

DNA measurement represents a type of quantitative analysis which allows us to gain prognostic information on malignant tumors and to study the natural history of the epithelial neoplasia. However, there are sources of variation in evaluating the DNA content. These include variation due to field selection, variation between observers (interobserver variation), and variation between laboratories (interlaboratory variation). The influence of various variation sources was studied in 4 experiments. When DNA measurements were made from the same microscopic fields, the results did not differ remarkably. However, observer training proved to be important. Intra- and interobserver variation was lower among experienced morphometrists than among inexpert observers. Different laboratories and image analyzers may give different results when the same case is measured. To overcome at least part of the potential variation sources, undergraduates and postgraduates at the Departments of Pathology of Ancona and Kuopio Universities are specially trained in the use and application of morphometry. Special sampling rules should be applied and observers encouraged to follow the rules as uniformly as possible.

Adenoma↗

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs. Part II. Lipid and glycosaminoglycan analysis of intima and inner media.

We compared the effects of mild hypercholesterolemia and repeated endotoxin infusions on the biochemical composition of aortic intima and inner media of 24 piglets divided into 4 groups 5 days after weaning: controls on normal diet (group I); normal diet and endotoxin (group II); fat-supplemented diet (group III); and fat-supplemented diet and endotoxin (group IV). It was found that mild hypercholesterolemia increased the concentration of arterial esterified cholesterol and the relative amount of the fraction containing chondroitin sulphates A and C in total glycosaminoglycans. Endotoxin infusions partly prevented the increase of serum cholesterol caused by the fat-supplemented diet but had no independent effect on the arterial biochemical composition; nor did they affect the biochemical changes caused by hypercholesterolemia. When the results of all groups were combined, chondroitin sulphates A and C showed a significant positive correlation with the concentration of arterial esterified cholesterol and the percentage of linoleic acid in arterial cholesteryl esters. Serum total cholesterol did not correlate with arterial cholesterol fractions, but the ratio of high density lipoprotein-cholesterol to total serum cholesterol showed a negative association with arterial esterified cholesterol. The present findings indicate that (1) mild hypercholesterolemia is atherogenic in young piglets, and (2) changes in arterial glycosaminoglycan composition might be one of the earliest biochemical alterations in atherogenesis.

Animals↗

Atrial natriuretic peptide and atrial pressures in newborns with transposition of the great arteries.

The relation of atrial pressure to atrial plasma concentration of atrial natriuretic peptide (ANP) was studied in four newborns undergoing catheterization because of transposition of the great arteries. In three patients, mean left atrial pressure clearly exceeded right atrial pressure (12 +/- 7 vs. 2 +/- 3 mmHg; mean +/- SD). In one patient mean atrial pressures were identical (4 mmHg). In all patients the ANP concentration in the left atrium exceeded that of the right (833 +/- 464 vs. 415 +/- 366 pg/ml; mean +/- SD). There was a significant (r = 0.97; p less than 0.01) correlation between pressure and ANP concentration in the left atria. In the right atria, no linear correlation existed between pressure and ANP concentration. ANP concentration in the left atrium decreased after a lowering of the left atrial pressure by atrial septostomy. In these patients, the left atrium seems to be the main source of circulating ANP.

Atrial Natriuretic Factor↗

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs. Part 1. Scanning and transmission electron microscopic study.

Endothelial cell damage is considered to be the primary event in atherogenesis. In this study we compared the effects of mild hypercholesterolemia and repeated E. coli endotoxin infusions on the endothelial cells of the coronary arteries of the pig. We divided 24 pigs into 4 groups: I: controls on normal diet; II: normal diet and endotoxin treatment; III: fat-supplemented diet; IV: fat-supplemented diet and endotoxin treatment. The animals on a fat-supplemented diet showed the most frequent and most severe endothelial cell damage. The damage was less when this diet was combined with endotoxin treatment. Endotoxin reduced the serum total cholesterol level (P less than 0.01). The cholesterol level correlated very significantly (P less than 0.001) with endothelial damage of the coronary arteries. Mild hypercholesterolemia (s-cholesterol 5.68 mmol/l, controls 2.28 mmol/l) was thus associated with toxic effects in the endothelial cells. The E. coli endotoxin infusions did not have any cumulative effect on the lesions.

Animals↗

Sampling in diagnostic morphometry: the influence of variation sources.

The variation sources relevant to a diagnostic morphometric study were analysed. The influence of each source was estimated in two experiments, performed in systems applying computer assisted interactive morphometry. In the first experiment one observer measured the areas of a large number of nuclei in a section from a grade II transitional cell carcinoma of the bladder. In the second experiment two groups of researchers, from Ancona and Kuopio, measured one field from five different samples of transitional cell tumours (including the case of grade II carcinoma). It turned out that pure interobserver variation was responsible for about a half of the total variation present in the diagnostic system. When the variation characteristics of the diagnostic system had been determined, the number of nuclei that had to be measured to reach a defined level of accuracy could be estimated. Such an estimate was also dependent on the predefined expectancy probability of reaching a correct estimate. The study showed that group morphometry (statistical, investigative morphometry) and diagnostic morphometry must be understood as two different approaches in histopathology. By applying group morphometry, good research results can be gathered with cruder measurements than in diagnostic morphometry. Because investigations in group morphometry are more standardized than in diagnostic morphometry, a larger number of structures has to be measured in diagnostic histopathology for the same level of accuracy.

Analysis of Variance↗