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Biomedical subjects

V M Kosma

Publications and source records attributed to V M Kosma.

At least 145 records · Page 8Linked to original sources
PubMed1991

Hormone receptors as prognostic factors in female breast cancer.

The oestrogen (ER) and progesterone receptor (PR) status in a series of 281 women with breast cancer (followed up for a mean of 8.5 years) was correlated with eight histological variables, seven nuclear morphometric factors and two mitotic indices. Sex steroid receptor status was not significantly related to tumour size, axillary lymph node status or tumour recurrence. Sex steroid receptors were related to histological grade (P less than 0.0001), nuclear grade (P less than 0.0001), tumour necrosis (P = 0.0003), tumour circumscription (P = 0.0027), inflammatory cell reaction (P = 0.007), intraductal growth pattern (P = 0.0378), and tubule formation (P = 0.0432). Receptor status was also significantly related to nuclear morphometric variables (P less than 0.001) and mitotic indexes (P less than 0.001). In univariate analysis, ER (P = 0.2) and PR (P = 0.1) negatively predicted the recurrence free survival. Cancer related survival was predicted by ER (P = 0.0068) and PR (P = 0.0027). In small (diameter less than or equal to 2 mm) axillary lymph node negative tumours, ER (P = 0.09) and PR (P = 0.1) had some value in predicting the survival. The survival advantage of steroid receptor positive tumours was not due to adjuvant hormone therapy. Sex steroid receptors had independent predictive value in multivariate survival analysis and also in small (diameter less than or equal to 20 mm) tumours. The results indicate that sex steroid receptor negativity is related to several malignant histological features in breast cancer and hormone receptors have prognostic value. Their prognostic influence seems to be mediated through the different proliferation rates in receptor positive and negative breast carcinomas.

Breast Neoplasms↗
PubMed1990

Verrucous carcinoma of the anus containing human papillomavirus type 16 DNA detected by in situ hybridisation: a case report.

Verrucous carcinoma of the anus is a distinct and rare variant of well-differentiated squamous cell carcinoma. A case of anal verrucous carcinoma in a 35 year old man was studied by light microscopy and in situ DNA hybridization. Human papillomavirus (HPV) type 16 DNA sequences were demonstrated in the tumour cells, as well as in cells showing koilocytotic and dyskeratotic changes. The possible viral (HPV) aetiology of verrucous carcinoma is considered with a review of the previous literature.

Adult↗
PubMed1990

Potential of nuclear morphometry and volume-corrected mitotic index in grading transitional cell carcinoma of the urinary bladder.

The potential of nuclear morphometry and volume-corrected mitotic index (M/V index) in grading cases of transitional cell carcinoma of the urinary bladder was studied. 30 cases of bladder cancer including all three WHO grades were evaluated. Four investigators selected independently the most atypical field from paraffin sections, and one investigator measured the nuclear areas from these fields using the IBAS 1&2 image analyzer system. Following the same sampling rule, four investigators counted the mitotic figures per area of neoplastic tissue in the microscopic image at an objective magnification of X40. The mean nuclear areas covered values from 28.1 to 139.0 microns 2 (mean +/- SD 57.2 +/- 18.9). The total variance of measurements was 359.1 and the mean variance between corresponding fields 110.2 (about 30% of the total variation). The efficiency was evaluated by estimating the fraction of falsely classified cases. Instrumental morphometry of nuclear area in a three-grade system gave an efficiency of 79% and of 90%, in a two-grade system. The M/V index varied from 0 to 54 (mean +/- SD 12.3 +/- 10.9). The total variance was 119.8 and the methodological variance 15.5 (about 13% of total variance). In a three-grade system this would correspond to an efficiency of about 75%; in a two-grade system the efficiency would be 88%. The results suggest that nuclear area and M/V index estimates constitute efficient grading systems in bladder carcinoma.

Carcinoma, Transitional Cell↗
PubMed1989

Morphometric study of human myocardium in acquired valvular diseases.

To study the effect of various valvular heart diseases on the quantitative histology of myocardium, 38 human hearts with valvular lesions were examined (11 aortic stenoses, nine mitral stenoses, nine mitral incompetence and nine combined aortic and mitral valve lesions). The control group consisted of ten hearts without any valvular lesions. With morphometrical methods the volume fractions of myocardial components (myocardial fibres, interstitial space and diffuse connective tissue), the numerical density of arterioles and the mean fibre diameter were estimated. Myocardial fibrosis was more severe in hearts with valvular lesions than in the controls (5.4% vs 3.3%, P less than 0.01), but did not correlate with the anatomical severity of the valvular lesions. The most severe myocardial fibrosis was found in hearts with mitral incompetence (6.7%). Fibre hypertrophy was most severe in hearts with aortic stenosis and in hearts with mitral incompetence (22 microns and 23 microns, respectively). In hearts with severe valvular lesions the mean fibre diameter was 23 microns and in hearts with mild to moderate lesions 19 microns (P less than 0.01). Good correlation was observed between the mean fibre diameter and the weight of the left ventricle (r = 0.81, P less than 0.01). The volume fractions of connective tissue and interstitial space were significantly higher and the volume fraction of myocardial fibres was correspondingly lower in the subendocardium than in the subepicardium in hearts with either pressure overload (aortic stenosis) or volume overload (mitral incompetence). In conclusion, myocardial fibrosis occurs in patients with various valvular lesions, but the severity of the fibrosis does not correlate with the anatomical severity of valvular lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Comparative liver toxicity of various erythromycin derivatives in animals.

The hepatotoxicity of a new erythromycin derivative, erythromycin acistrate (EA, 2'-acetyl erythromycin stearate), was compared with that of erythromycin stearate (ES), erythromycin estolate (EE) and erythromycin-11,12 cyclic carbonate (EC) in 4-5-day, 28-day and 6-month oral toxicity studies in rats and dogs. In the 4-day rat study, EC caused fatty metamorphosis in the liver. ES caused similar, but milder changes at a dose nearly five times higher. The 5-day dog study revealed markedly increased serum alanine aminotransferase (S-ALAT), serum aspartate aminotransferase (S-ASAT), serum alkaline phosphatase (S-APHOS) and serum gamma-glutamyl transpeptidase (S-gamma-GT) values in the EC- and EE-groups, and slightly elevated S-ALAT values also in the EA- and ES-groups. Microscopy revealed cholangitis, pericholangitis and phlebitis in the portal areas in the EC-group at all doses. Epithelial hyperplasia was observed also in the bile ducts. EE caused similar but milder changes. The changes in the EA-group were small, but mildly atypical bile duct epithelium was seen in female dogs receiving 2 x 200 mg/kg of EA. The ES-group was practically without changes and very much like the EA-group. Thus the dog proved to be a more sensitive model for assessing the hepatotoxicity of erythromycin derivatives. In the 28-day studies, only EA and ES were investigated. In the rat study, slightly elevated serum enzyme levels within the normal range were measured in the high-dose regimens of both drugs. In the dog study, 300 mg/kg of EA caused slightly elevated S-ALAT in males, but the values returned to normal after a 2-week off-dose period. Only EA was studied in the 6-month study. In male rats, 400 mg/kg of EA caused slightly elevated enzyme levels and neutral fat droplets in centrilobular hepatocytes. In male dogs given 150 mg/kg of EA, S-ALAT, S-APHOS, and S-gamma-GT values were elevated after four weeks of treatment but returned to normal thereafter. No severe changes were seen in the liver histopathology. In conclusion, EC and EE were clearly hepatotoxic in dogs, and EC also in rats. EA, and to a somewhat lesser extent ES, showed signs of mild hepatotoxicity only at high doses. This evidently reversible effect was considered a common characteristic of erythromycins.

Animals↗
PubMed1987

Decreased somatostatin-like immunoreactivity in cerebral cortex and cerebrospinal fluid in Alzheimer's disease.

To investigate changes in the somatostatinergic neurons of patients with Alzheimer's disease (AD), we determined the somatostatin-like immunoreactivity (SLI) in post-mortem brain tissue of histopathologically confirmed AD patients and in CSF of probable AD patients (according to DSM III). The CSF values were then correlated with psychological test scores. In 6 AD patients the SLI values were decreased 42% (P less than 0.005) in the frontal cortex, 28% (P less than 0.05) in the temporal cortex and 42% (P less than 0.01) in the parietal cortex but not in the thalamus and putamen compared to 11 control patients. In some brain areas there were statistical correlations between SLI values and cholinergic markers, choline acetyltransferase and acetylcholine esterase activities, suggesting a relationship between these two neurotransmitter systems. In the CSF among 75 AD patients SLI was 35% lower (P less than 0.001) than in controls. Severely demented power (P less than 0.001) than in controls. Severely demented patients showed lower SLI values than moderately demented individuals, but this difference was not significant. There was a weak but statistically significant correlation between SLI values in CSF and neuropsychological test scores. This study further confirms the involvement of somatostatinergic neurons in AD and suggests that this involvement may be related to the progression of dementia symptoms.

Acetylcholinesterase↗
PubMed1987

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↗
PubMed1987

Elimination and toxicity of perfluorooctanoic acid during subchronic administration in the Wistar rat.

Perfluorinated fatty acids have been used commercially as corrosion inhibitors, wetting agents, fire extinguishers and surface active agents. In an earlier study the male rats were more susceptible to the toxic effects of perfluorooctanoic acid (PFO) than females. PFO-concentrations in the plasma suggested that there was a sex related difference in the urinary elimination rate. Active tubular secretion was observed only in the female kidney. The aim of the present study was to compare the urinary elimination of PFO between the two sexes during subchronic administration to the Wistar rat. PFO was administered by gavage to 48 newly-weaned animals at 0 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg for 28 consecutive days. The urine was collected on the 7th and 28th day of the study. At the end of the study, blood was collected by cardiac puncture. At necropsy, tissue specimens for histopathologic examination were collected from the controls and from the group receiving 30 mg/kg of PFO daily. Unlike the female rats, on the 7th day of the study all three groups of male rats excreted significant less PFO than their daily dose of PFO, which suggested that the males had not reached a steady state by seven days. On the 28th day, the males excreted an amount of PFO equal to their daily dose. The PFO concentrations in the plasma of the male animals suggested that the binding sites of PFO may become saturated at the chronic daily dose level of 30 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Application of morphometry in tumor pathology.

The application of morphometry in tumor pathology is discussed, e.g., its use in studying the biology of tumors, in creating tumor classification(s), in creating methods for the identification of a tumor in the diagnostic context, and in characterizing diagnostic histopathology in absolute terms. In traditional subjective diagnostic histopathology, reproducibility can be defined satisfactorily, but the definition of accuracy is ambiguous; in morphometric histopathology, a satisfactory definition is found for both concepts but it may be difficult to separate them in practice. Morphometric histopathology can study parameters measured from sections or parameters derived from the primary measurements through calculations. In the histopathology of tumors, the following parameters have turned out to be specially valuable: densitometric measurements of nuclei, nuclear area, perimeter and form factors, nucleolar parameters, the number of mitotic cells per area, the cellularity, the volume fraction of the epithelium, and parameters associated with the fraction of tumor tissue in the sample. The standard deviation or other moments of the distribution of these measurements can be more relevant than the mean values of the results. This indicates that more attention should be given to sampling rules, which are important in defining the efficiency of the methods. For rational application of morphometric methods, it is very important to make a distinction between group morphometry and diagnostic morphometry. The latter engenders numerous sources of variation (variation in section thickness, variation in tissue processing, variation in the techniques of measurement, interobserver variation, interlaboratory variation, variation due to subjective interpretation, etc.), which are usually better controlled in group morphometry. The influence on morphometric parameters of variation in section thickness and tissue shrinkage during processing are discussed.

Animals↗
PubMed1987

Kinetics and toxic effects of repeated intravenous dosage of formic acid in rabbits.

Adult male rabbits were injected i.v. with 100 mg buffered formic acid per kg body weight daily for 5 days with 24 h between the doses. The fifth dose was labelled with 14C-formic acid. Rabbits were killed 1, 2 and 20 h after the last injection. The highest formic acid concentrations were found one hour after the fifth dose. Total formic acid concentrations were always higher than radiometrically measured. The maximum concentrations of formic acid in brain, heart, kidney and liver were roughly similar to the concentration which inhibits half of the cytochrome oxidase activity in vitro. Histological studies clearly demonstrated the histotoxic changes at cellular level. Calcium deposits were detected in all organs of the injected rabbits. They were absent in control animals. It seems that the formic acid metabolism is slow and that it may cause sufficient hypoxic acidosis to allow the calcium influx and cellular damage.

Acidosis↗
PubMed1986

Toxicity of richterite in hemolysis test and macrophage cultures.

Richterite is a fibrous mineral associated with apatite deposits in eastern Finland. Fibre size features suggest potential toxicity but no data is available of fibrogenic effects on human lungs. The toxicity of richterite in a hemolysis test and in lung macrophage cultures was studied. In the hemolysis test richterite-rich samples showed the same degree of hemolysis as titanium dioxide whereas anthophyllite, crocidolite, chrysotile, wollastonite and quartz samples had distinctly higher degree of hemolysis. In the macrophage toxicity assay the percentage of dead cells was counted, and LDH, ASAT and acid phosphatase were determined from the culture medium. In this assay richterite showed lower toxicity than anthophyllite, crocidolite, chrysotile or quartz but gave higher values than titanium dioxide. Wollastonite showed similar level of toxicity. Differences were statistically highly significant. The results suggest that richterite (with wollastonite) belongs to a group of fibrous minerals which have distinctly smaller biological effect than traditional asbestos minerals.

Animals↗
PubMed1986

Ethylenethiourea and nabam induced alterations of function and morphology of thyroid gland in rats.

Male Wistar rats were given 0-200 mg/l of nabam and 0-300 mg/l of ethylenethiourea (ETU) in drinking water ad libitum for 28 d to study their effect on thyroid gland function and morphology. Blood samples for RIA hormone assays (T3, T4, TSH) were taken and thyroids of each rat were dissected out for routine light and electron microscopic analysis after sacrifice performed under CO2 anesthesia. Nabam (8.4-30.5 mg/kg bw/d) inhibited dose-dependently T4-secretion and increased T3-secretion, but had no effect on basal TSH-secretion. ETU (10.6-23.4 mg/kg bw/d) inhibited dose-dependently T4- and T3-secretion. ETU also increased basal TSH-secretion tenfold, obviously due to the lack of negative feedback by T4 and T3. Light microscopic analysis revealed neither nabam nor ETU induced morphological alterations in thyroids. Both but especially ETU induced, ultrastructural changes, namely increased number of myelin bodies, dilatation of the rough endoplasmic reticulum, and increased vacuolization in the epithelial cells of thyroid follicles. The functional alterations are obviously connected with, and preceed slight ultrastructural degenerative changes in thyroid follicle epithelial cells even at low doses of nabam, and ETU, after a short-term oral administration.

Animals↗
PubMed1986

Histopathological and morphometrical analysis applied to skin changes in NMRI mice induced by dithranol (anthranil) and its acyl analogs.

Histology and morphometric changes in skin lesions of NMRI mice caused by dithranol and its acyl analogs, with and without pretreatment with dimethylbenzanthracene (DMBA) are described. The course of neoplastic progression seems to have three distinct phases (normal skin, hyperplasia, papilloma), each characterized by typical architectural and cellular changes. The parameters reflecting the nuclear size increased in the above order and the differences between the groups were highly significant. Nuclear shape changes did not take place, as shown by the almost constant form factor. The study demonstrates the value of the morphometric methodology in characterizing quantitative nuclear changes in mouse skin models.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Toxicity and kinetics of perfluoro-octanoic acid in the Wistar rat.

Perfluoro-octanoic acid [PFO; CF3 (CF2)6 COOH] is a single chain fatty acid with surfactant properties. Thus far the kinetics and toxicity of PFO has not been studied thoroughly. PFO was administered orally 3 mg/kg, 10 mg/kg, and 30 mg/kg to 36 Wistar rats daily for 28 consecutive days. Another 12 animals received 0.5 ml/100 g saline each day. Animal behaviour, body weight, as well as, water and food consumption were observed regularly. Blood, urine, and some viscera were collected for the analysis of PFO and histopathology. Food consumption decreased with increasing dose of PFO. Serum PFO concentrations were 6-19 times higher in the males than in the females (range 48.6-83.0 micrograms/ml males, and 2.4-11.2 micrograms/ml females) (p less than 0.001). On the 7th day the mean PFO excretion in the low dose group for the males was 157 +/- 63 micrograms/24 (SD) h and 255 +/- 27 micrograms/24 h for females (p less than 0.05). In the high dose group the corresponding figures were 2476 +/- 665 micrograms/24 h (males) and 2917 +/- 493 micrograms/24 h (females). On the 28th day the PFO excretion for the low dose males was 609 +/- 87 micrograms/24 h, 671 +/- 65 micrograms/24 h for the females. In the high dose group the figures were 4619 +/- 2886 micrograms/24 h (males) and 4379 +/- 692 micrograms/24 h (females).

Animals↗
PubMed1986

A 6-month dermal toxicity test with dithranol and butantrone in miniature swine.

Continuous topical administration of dithranol and butantrone for 6 months caused different irritation profiles in miniature swine. In paraffin wax sticks in white petrolatum, butantrone gave rise to much less initial irritation than dithranol, but after 2-3 weeks the situation had equalized. In gel formulations, butantrone was initially more irritant than dithranol. The vehicles themselves induced significant irritation. Signs of skin hyperplasia (parakeratosis and acanthosis) and inflammation were frequent histopathological findings at the end of the study, but no malignant changes were found. Dithranol and butantrone did not produce any chemical, hematological or serious histological abnormalities during the treatment, suggesting a lack of systemic toxicity. No evidence of systemic absorption was found. This long-term study did not predict delayed irritation of butantrone observed in about 1/3 of the psoriatic patients after treatment for 1-2 months.

Administration, Topical↗
PubMed1986

Quantitation of staining for amyloid in histological sections: sources of variation, correlation analysis, and interstain reproducibility.

Five pathologists estimated with point counting the amount of amyloid in heart muscle autopsy samples from 19 patients who suffered from amyloidosis. The serial sections had been stained with 5 different methods. The different variation sources involved in a quantitative study on amyloid and the interstain reproducibility between the results given by these 5 stains were analyzed. The volume fractions of amyloid after different stains were subjected to correlation analysis. In our test system about a third (34%) of the variation was due to the point counting method. Sirius red had the lowest and Congo red the highest variation due to point counting, since Sirius red gave the most intense staining and highest volume fractions for amyloid. The volume fractions were lowest in Congo red. About 40% of the total variation was composed of the field variation. This variation includes the variation due to variation between fields, field selection and subjective intraobserver variation. Sirius red showed the smallest field variation in respect to the total variation. Congo red, on the other hand, had the highest variation. The variation caused by pure interobserver variation is presented by the difference between total variation and the calculated field variation. This was largest with Sirius red and smallest with Congo red. The pure interobserver variation accounted for about 26% of the total variation. The high reproducibility with Sirius stain is most probably due to the high volume fractions of positively stained material after this stain, not to low interobserver variation. Congo red seems to have low interobserver variation. The senior pathologists were more reliable in measuring the amyloid deposits than the junior pathologists as suggested by interstain reproducibility and variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1986

Observer variation in interactive computerized morphometry.

The validity of a test system in morphometric histopathology depends on the variation sources involved. Biological variation is one of the variation sources, but is also the object to be studied with morphometry. We studied the variation sources in interactive computerized morphometry in two test systems involving two different commercially available image analyzers. The measurements were made on nuclei in a microscopic field of 5 transitional cell tumors (papilloma and WHO grade I-III carcinomas) of the urinary bladder. It turned out that different observers selected a variable number of nuclei for measurements, the coefficient of variation (CV) in the number of nuclei being 11-11.5%. Mean CV in nuclear perimeter measurements was 4.4-4.8%, and in nuclear area measurements 8.2-8.6%. The variation in measurements by 1 observer was smaller, the CV values being 2.8% for the number of nuclei, 1.2% for nuclear perimeter, and 2.4% for nuclear area. The results showed that interobserver variation can be considerable in these systems. It is suggested that special sampling rules should be tested with the idea of finding the relevant approach with the smallest interobserver variation.

Carcinoma, Transitional Cell↗