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Biomedical subjects

Y Collan

Publications and source records attributed to Y Collan.

At least 109 records · Page 6Linked to original sources

Representativity of endomyocardial biopsies: a theoretical approach based on quantitative light microscopy.

To create a model for studying the regional variation in the histologic structure of left ventricular myocardium and the representativity of samples from endomyocardium in predicting the state of myocardium as a whole, 12 human hearts (3 normal and 9 pathological) were investigated with histoquantitative methods. Ten small endomyocardial areas representing biopsy sites (mean area on section 0.94 mm2) were delineated from each heart. The volume fractions of myocardial fibers (VVMY), interstitial space (VVINT) and connective tissue (VVCT) were determined with a point counting method on these areas. Also the mean fiber diameter was measured. The results were compared with the results from three full thickness samples (mean area 3 cm2) from each heart. The values for fiber diameter estimates were almost identical in endomyocardial samples and full thickness samples. On the other hand, VVCT was significantly higher and VVMY lower in endomyocardial samples. The coefficient of variation (10 endomyocardial areas) was 8.3% for fiber diameter, 17.8% for VVMY and 77.5% for VVCT. When estimates of the regional variation within the heart area are available, it is possible to create a model for the prediction of the number of endomyocardial biopsies needed to reach a given accuracy and probability of measurements. The representativity and clinical value of endomyocardial biopsies are discussed on the basis of this statistical approach.

Adult↗

Frozen section diagnosis of breast cancer.

In Savonlinna Central Hospital, Southeastern Finland, 371 frozen section examinations were made from September 1981 to December 1986 to detect breast cancer. There was one false positive diagnosis (0.7%) among the 147 lesions interpreted as carcinoma. Among the 224 biopsies, which were benign on frozen section investigation, four showed carcinoma in paraffin sections (1.8%). Thus, the diagnostic sensitivity of frozen section method was 97.3% (146/150) and the clinical diagnostic specificity 99.5% (220/221) when the diagnosis in the paraffin sections was used as reference. In the four false negative cases the tumour was small and limited to the breast without any evidence of metastases. Two of them were ductal carcinomas, one was microinvasive lobular carcinoma, and one intraductal non-invasive papillary carcinoma. The false positive case had benign intraductal papillomatosis. Our results suggest that the probability of a false diagnosis in frozen section examination increases with diminishing size of the lesion. We suggest that small lesions (less than 1 cm in diameter, or non-palpable) should not be subjected to frozen section examination to avoid unnecessary loss of neoplastic tissue during the preparation process. Instead surgically radical lumpectomy and careful investigation of paraffin-embedded tissue are recommended.

Adult↗

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↗

Interactive morphometry: the influence of magnification.

The influence of magnification on light microscopic morphometry was studied. Morphometry was performed on 34 hepatocytes by using a digitizer plate with micrographs of the nuclei, and with digitized image of the nuclei on a separate monitor. Intraobserver variation was smallest at objective magnifications of 40 and 100 X (CV of form factor, maximum diameter and nuclear perimeter under 1%, of nuclear area under 2%, when measured from the monitor). The results show that more reproducible measurements are possible with higher magnifications. The authors recommend objective magnifications of 40 and 100 X for morphometric measurements on nuclei. The results also suggest that morphometric grading should apply an intermediate third grade in dichotomous grading scales.

Animals↗

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↗

Transmural differences in ischaemic heart disease: a quantitative histologic study.

To evaluate the possible transmural differences in the structure of left ventricular myocardium in patients with ischaemic heart disease, 45 human hearts were examined with morphometric methods. There were 10 control hearts, 10 hearts with coronary atherosclerosis but without myocardial infarction, 11 hearts with acute subendocardial infarction and 14 hearts with acute transmural infarction. The following histoquantitative parameters were separately estimated for both subendocardium and subepicardium in each heart: the volume fraction of diffuse connective tissue, the mean fiber diameter and the numerical density of arterioles. Diffuse myocardial fibrosis was more severe in subendocardium in all groups, the highest values were found in hearts with acute subendocardial infarction. In all groups the numerical density of arterioles was higher in subendocardium. The numerical density of arterioles was increased in respect to the controls in both subendocardium and subepicardium in hearts with coronary atherosclerosis without evidence of myocardial infarction and in hearts with acute subendocardial infarction. The possible pathophysiological implications for ischaemic heart disease are discussed on the basis of these results. The results suggest different pathophysiological mechanisms in subendocardial and transmural myocardial infarction. They also suggest that transmural differences should be considered when the findings of endomyocardial biopsies are evaluated.

Adult↗

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↗

Oral cancer in children under 15 years of age. A clinicopathological and virological study.

11 malignant tumours of the oral region in children under 15 years of age were diagnosed in Finland during the 20-year period from 1961 to 1980; the age adjusted annual incidence rate being 0.31 per 1,000,000 children. 5 cases were intraoral cancer and 5 cases malignant tumours of the major salivary glands. The formalin-fixed tumours were studied using the in situ DNA hybridization technique for Adenovirus, group II, Epstein-Barr and human papillomavirus, type 16. For the first time, evidence was provided for the presence of Epstein-Barr virus in a malignant salivary gland tumour, implicating a possible etiological role for this virus in salivary gland neoplasms.

Adolescent↗

Reproducibility of mitotic counts and identification of mitotic figures in malignant glial tumors.

Quantitative pathology is a rapidly growing field of pathology. This field is developing methods allowing greater objectivity and better reproducibility in diagnostic decisions. The introduction of quantitative pathology as a teaching subject in medical education will help this field to become more widely and more correctly applied. Courses on quantitative pathology are organized yearly by the Department of Pathology at the University of Ancona. The 1986 course emphasized training of students in understanding basic problems such as variation caused by tissue processing, instrumentation, data handling and interpretation, and variation between observers. In this paper we describe experiments performed during the course on identification and quantitation of mitoses in malignant glial tumors. The participants, i.e. students of the postgraduate Pathology School, could identify mitoses with a 'substantial' reproducibility. However, when the observers were allowed freely to choose the fields to count, the reproducibility was 'slight'. The study suggests that sampling rules should be applied which secure reproducible application of morphometric method also on condition of free selection of fields. Because the application of such rules needs expertise in histopathology, it seems that morphometric method can best be applied by histopathologists themselves.

Glioma↗

Cancer-associated antigen CA 15-3 in the diagnostics of breast tumours.

The serum concentration of the new marker CA 15-3 was determined by a kit method, which is based on the use of two different monoclonal antibodies 115D8 and DF3, in a coated tube immunoradiometric technique. The mean CA 15-3 values in breast cancer patients (n = 40) were significantly higher than in patients with benign breast disease (n = 52, p less than 0.001) and in control subjects (n = 32, p less than 0.001). When we used the cut-off level 35 kU/l for CA 15-3, 0/32 of control subjects, 1/52 (2%) of patients with benign breast disease, 8/40 (20%) of all breast cancer patients, 6/19 (32%) of breast cancer patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were above this level. Among the same patients the CEA serum test was positive at a cut-off level of 5 micrograms/l in 7/40 (18%) cancer cases, and in 6/19 (32%) of cancer patients with nodal involvement. When we used the cut-off level 35 kU/l for CA 15-3 and 5 micrograms/l for CEA 1/52 (2%) of patients with benign breast disease, 10/40 (25%) of all breast cancer patients, 7/19 (37%) patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were positive in one or both of the tests. The serum CA 15-3 and CEA values were higher in patients with tumour size above 2 cm in diameter than in patients with smaller tumours (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intravascular bronchioloalveolar tumor.

A 17-year-old girl was operated for a solitary well-circumscribed pulmonary parenchymal tumor and reoperated ten times for multiple recurrent similar pulmonary tumors during 24 years. Histologic examination revealed the so-called intravascular bronchioloalveolar tumor (IVBAT) in all instances. The patient died from pneumonia superimposed on decreased respiratory function 24 years after the onset of disease. This is the longest survival so far reported in IVBAT. The treatment was surgical in all phases of the disease, and the patient did not receive radiotherapy or cytostatic drug therapy. Mediastinal and pleural tumor nodules were removed 17 years from the first pulmonary operation, and 24 years after the first operation a fibrous tumor was removed from the retroperitoneal space. Immunohistologically, the tumor cells were positive for vimentin-type of intermediate filaments, in line with their mesenchymal nature. Endothelial markers, Factor VIII-related antigen and Ulex europaeus I lectin binding, were not found in convincingly neoplastic cells, and Schwann cell, epithelial cell, muscle cell, and histiocytic markers were absent. Thus, IVBAT appears to be a low-grade malignant mesenchymal neoplasm, composed of poorly differentiated mesenchymal cells, whose exact nature remains undefined with the currently used cell-type markers.

Adolescent↗

Squamous cell carcinoma of the tongue in children.

Only 14 case reports of squamous cell carcinoma of the tongue in children under 15 years of age had been published until 1980. One was reported in Finland as a second tumor in a patient with retinoblastoma. According to the Finnish Cancer Registry, which covers the whole population, three cases of squamous cell carcinoma of the tongue in children under 15 years of age have been diagnosed in Finland during the 20 years from 1961 to 1980; the age-adjusted annual incidence rate being 0.13 per 1,000,000 children per year. According to the available material, the prognosis of squamous cell carcinoma of the tongue in children is poor. The treatment has followed the guidelines for adults.

Adolescent↗

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↗

Effect of testosterone and anabolic steroids on the size of sebaceous glands in power athletes.

The effect of testosterone and anabolic steroids on the size of sebaceous glands was studied by means of interactive morphometry in skin biopsies of power athletes. The subjects used self-administered high doses of testosterone and anabolic steroids during a 4-week strength training period. After 4 weeks' use of hormones, the area of sectioned sebaceous glands enlarged significantly by a factor of 89.2% (p less than 0.005). The number of cells in the so-called differentiating cell pool (DCP) and in the undifferentiated cell pool (UCP) also increased significantly (p less than 0.025, p less than 0.05, respectively). The size of the area occupied by UCP cells increased significantly (p less than 0.05). The study suggests that high doses of testosterone and anabolic steroids lead to an enlargement of sebaceous glands in male power athletes.

Adult↗

Human papillomavirus DNA in squamous cell carcinomas of the larynx demonstrated by in situ DNA hybridization.

A series of 116 consecutive laryngeal squamous cell carcinomas were analyzed using an in situ DNA hybridization technique with 35S-labelled human papillomavirus (HPV) DNA probes to demonstrate the DNA of HPV types 6, 11, 16 and 30, in routinely processed, paraffin-embedded biopsies. The lesions were also assessed on light microscopy for HPV-suggestive morphological features, and by indirect immunoperoxidase (IP-PAP) technique to demonstrate the expression of HPV structural proteins (viral antigens). A total of 15/116 (12.9%) of the tumors were shown to contain the DNA of at least one HPV type. HPV 11 was the most frequent DNA type, found in 9/116 (7.8%) of the lesions, followed by HPV 16 (5.2%), and HPV 6 (4.3%). Noteworthy is the failure to disclose the recently described HPV type 30 DNA (suggested to be specific for laryngeal carcinomas) in any of the 116 carcinomas studied. Double infections (more than one HPV type) were disclosed in 5 (33.3% of the HPV DNA-positive) carcinomas: HPV 6 and 11, 1 case; HPV 6 and 16, 2 cases, and HPV 11 and 16, 2 cases. Light microscopic morphology was HPV-suggestive in 6 (40%) of the 15 HPV DNA-positive lesions, but HPV antigen expression could be demonstrated in one of these tumors only (6.7%). The present findings provide support to the concept on HPV as an etiological agent in laryngeal squamous cell carcinoma, most probably acting synergistically with chemical carcinogens. In addition to the 'high risk' HPV 16, a risk to develop a laryngeal malignancy may be associated with the 'low risk' types HPV 6 and 11 as well, previously demonstrated in benign laryngeal papillomas only.

Biopsy↗

Artifacts in ultrastructure of respiratory cilia caused by various fixation procedures and different types of handling.

The ciliary ultrastructure with different fixatives and buffer combinations and artifacts caused by handling the specimens was studied in samples from respiratory mucosa. After different standard fixatives the ciliary ultrastructure did not vary much. Glutaraldehyde in cacodylate gave the best result; the contrast was good and the cell membrane did not show undulation and so many blebs as with other fixatives. With old 4% formaldehyde + 1% glutaraldehyde inphosphate the cytoplasm was darker and the contrast was not as good as with a fresh fixative. Mechanical damage caused rupture of the cell membrane and sometimes changes in axonemal architecture. These findings are similar to those often seen in human samples. The axonemal architecture was always intact if the cell membrane was intact.

Animals↗