Mast Cells Might Have a Protective Role against the Development of Calcification and Hyalinisation in Severe Aortic Valve Stenosis.

Aortic valve stenosis is characterized by inflammation and extracellular matrix remodelling. The aim of this study was to analyse the impact of mast cells on the occurrence of histopathological changes of aortic valves in patients with severe grade, non-rheumatic degenerative aortic valve stenosis. Valve specimens were obtained from 38 patients undergoing valve replacement. The role of mast cells was analysed by dividing the specimens into two groups, characterized by the presence (group A, N = 13) or absence of mast cells (group B, N = 25). There were no significant differences in clinical data between the two groups. In group A, T cells and macrophages were present in all aortic valves, as compared to a significantly lower proportion of valves with T cells and macrophages in group B. Valves in group A were less often calcified and hyaline-degenerated than valves in group B. There were no changes in fibrosis between the two groups. We found a positive correlation between the presence of mast cells and macrophages/T cells, a negative correlation between the presence of mast cells and calcification/ hyaline degeneration, and no correlation between the presence of mast cells and fibrosis. There was also a negative correlation between the presence of macrophages/T cells and calcification. The linear regression model identified only the presence of mast cells as an independent negative prediction value for calcification. In conclusion, mast cells might have a protective role against the development of calcification and hyaline degeneration in severe grade, non-rheumatic aortic valve stenosis.

Inflammatory changes in small blood vessels in the endomyocardium of cardiac syndrome X in female patients with increased C-reactive protein.

The pathogenesis and pathohistological changes of CSX, a syndrome characterized by anginal chest pain and normal coronary arteries on coronary angiography, is poorly understood. The purpose of this study was to analyse morphological changes in small blood vessels of the CSX patients with increased CRP levels (above 5 mg/l). EMB was performed for diagnostic purposes in 31 female patients with CSX, and EMB specimens were histologically and immunohistochemically analysed. Increased CRP was found in 18 (58.1%) female patients with CSX. Signs of inflammation in the walls of small blood vessels were demonstrated in 13 (76%) and TUNEL-positive endothelial cells in 3 (17%) women with increased CRP. Morphological analysis of small blood vessels in EMB in CSX female patients with increased CRP levels revealed signs of inflammation and apoptosis of endothelial cells, indicating the role of inflammation in the pathogenesis of CSX.

Colon mucosal cells after combined radiotherapy and chemotherapy.

The aim of this study was to investigate early histological and stereological changes in enterocytes, lymphocytes, mast cells, serotonin- and somatostatin-secreting cells in colon mucosa the first day after the end of combined radiotherapy and chemotherapy. For experimental model 20 Beagle dogs were used. Ten dogs were given platinol every 5 days over 20 days and they were irradiated 20 days with 32 Gy (every second day with a fractional dose of 3.2 Gy) onto the whole pelvis and tail. Another 10 dogs represented a control group. For detection of apoptosis the TUNEL technique was used, whereas immunohistochemical methods were performed for detection of somatostatin- and serotonin-secreting cells, and for proliferating cell nuclear antigen in epithelial cells. The volume density of enterocytes in apoptosis was increased, and Vv of paracrine cells (mast cells, somatostatin and serotonin positive cells) was significantly increased in the treated group compared to the control group. In the treated group a significantly lower Vv of lymphocytes and PCNA-positive enterocytes was shown compared to the control group. The results of our experiments showed that combined radiotherapy and chemotherapy caused loss of enterocytes and lymphocytes early after the therapy. It was associated with an increased volume density of paracrine cells. These morphological changes in the colon mucosa might be the earliest changes leading to disruption of the mucosal barrier, malabsoption syndrome, stenosis, inflammation and other complications resulting from the radiotherapy and chemotherapy.

Colon mucosal cells after high-dose fractional irradiation.

The aim of this study was to investigate histological and stereological changes in cryptal enterocytes, mucosal lymphocytes and mast cells 10 days after irradiation. For experimental model, 24 Beagle dogs 1-2 years old were used. Twelve dogs were irradiated 20 days with 32 Gy over the whole pelvis and tail. Another 12 dogs represented a control group. For the detection of apoptosis, the TUNEL technique was used. Histological and stereological analyses were performed using a Wild sampling microscope M 1000. In the irradiated group, volume density (P < 0.01), numerical density (P < 0.05) and average volume of lymphocytes (P < 0.001) were significantly lower than in the nonirradiated group. Numerical areal density of mast cells in the irradiated group was also significantly lower (P < 0.05). Volume density (P < 0.001) and average volume of mast cells (P < 0.001) were significantly higher in the irradiated group. The results of our experiments show that irradiation causes injury and loss of lymphocytes and mast cells in the colon mucosa. Apoptosis was detected in enterocytes and lymphocytes in the irradiated group and in nonirradiated group in equal numbers (2.5+/-0.3 vs. 2.3+/-0.3; ns.), suggesting that 10 days after high-dose irradiation, the cell loss is not due to apoptosis.

An unusual complication after percutaneous drainage of a pancreatic pseudocyst into the stomach.

In the period between September 1995 and June 1999, we performed percutaneous drainage into the stomach in 12 patients. There were no complications or pseudocyst recurrences on insertion or after endoscopic removal of the catheter, which was left in site for 1 year on average. After endoscopic removal of the drainage catheter, one of the patients presented with a cystic formation in the stomach wall, which caused stomach emptying disorder. Therefore, the patient had to be reoperated. The cyst wall was incised and a part of the cystic wall sampled for histological examination. The cyst was then drained into the isolated Roux loop of the jejunum. Histological findings of the cystic wall specimen showed the presence of granulation tissue and smooth muscle layers with ganglia cells of myenteric nerve plexus. Despite this complication, we believe that percutaneous endoscopically and ultrasonographically guided drainage of pancreatic pseudocyst into the stomach by means of a double pigtail catheter is a good method that yields encouraging results in sonographically selected cases. The position of the drainage catheter needs to be checked endoscopically, and the catheter should be removed only after 1 year.

[Carcinoma in situ of the testis in infertile men. Experience in a medically assisted reproduction program]. / Carcinome in situ du testicule des hommes infertiles. Expérience d'un service d'aide médicale à la reproduction.

Three cases of carcinoma in situ were found by testicular biopsy among a group of 85 infertile men, most with diagnosed azoospermia. It remains difficult and unclear how to manage such patients to achieve offspring and to assure the adequate oncological therapy.

Morphometrical and stereological analysis of myocardial mast cells in myocarditis and dilated cardiomyopathy.

Mast cells play a certain role in inflammation and immunological reactions. Cardiac mast cells, shown by sodium sulfate-alcian blue staining, were evaluated in endomyocardial biopsy specimens in patients with unexplained congestive heart failure. The results of histopathological analysis were consistent with active myocarditis according to the Dallas criteria in 10 patients (15%), borderline myocarditis in 9 (13.8%), and dilated cardiomyopathy in 25 patients (38.5%); these results were compared with a control group of 10 traffic accident victims. The highest numerical areal density of mast cells was found in active myocarditis (3.92 counts/mm2, SD = 1.84), followed by borderline myocarditis (2.76 counts/mm2, SD = 1.66), dilated cardiomyopathy (1.56 counts/mm2, SD = 0.45) and control group (0.77 counts/mm2, SD = 0.19). Degranulation involved 27% (SD = 3.6) of mast cells in active myocarditis, 18% (SD = 4.5) of mast cells in borderline myocarditis, 10.8% (SD = 3.12) of mast cells in dilated cardiomyopathy and 4% (SD = 2.0) of mast cells from autopsy tissue. The differences among the four groups were statistically significant (P <0.001). The increased number of mast cells and the higher degree of their degranulation in myocarditis compared to dilated cardiomyopathy and to control group indicate that they were activated. The mast cells could be involved in modulation of fibrous response, since they tended to be associated with areas of fibrosis. Likewise, numerical areal density and degree of degranulation of mast cells could also be used as additional diagnostic criteria for acute myocarditis, since a higher numerical areal density and degree of degranulation were present in myocarditis vs. dilated cardiomyopathy and control group.

The interdependence of the follicular, parafollicular, and mast cells in the mammalian thyroid gland: a review and a synthesis.

The aim of this paper is to summarize some of our quantitative descriptive and experimental studies, to discuss them in view of the literature data, and to present a synthesis of the topic. The results of stereological analysis of some tissue components of the rat thyroid gland have been compared with the results of topological studies on the parafollicular cells of various mammalian species. Localization of the parafollicular cells in the central regions of the thyroid gland lobes, where the follicular cell activity seems to be greater than in the periphery of the lobes, has led to the hypothesis that the parafollicular cells regulate (stimulate and/or suppress) the activity of the follicular cells. Long-term application and antithyroid drugs to mice and rats has shown that excessive concentrations of thyrotropin provoke hyperplasia of both the follicular cells and the intrathyroid mast cells and, transiently, of the parafollicular cells. This and some of the literature data are congruent with the hypothesis that the parafollicular and mast cells also stimulate the follicular cells by their paracrine secretions. Long-term application of antithyroid drugs to mice and rats has shown that excessive concentrations of cular cells but also probably stimulation of the follicular cells, as judged by the stereological measurements. The biological meaning of the spatial integration of follicular and parafollicular cells seems to be a functional coordination of both epithelial cell lines, supported by intrathyroid mast cells.

Mitral valve replacement for lupus valvulitis.

This paper describes a 47-years old patient with the history of lupus valvulitis for six and a half years, who had implantation of a Starr-Edwards prosthesis for a mitral insufficiency four years ago. This case represents the longest survival reported so far after mitral valve replacement for lupus valvulitis.

Carcinogenesis after sublethal ionizing irradiation and regular avoidance irritation.

160 mice of the BALB/C strain of both sexes, aged 3 months, were divided into four equal groups out of which two were regularly irritated by a combination of an optical signal and electrical stroke. After one month of irritation one nonirritated and one irritated group were whole body irradiated with a single dose of 6.65 Gy (1.83 Gy/min), the other two groups were sham irradiated. The mice lived until their spontaneous death or one year after irradiation, respectively, when the rest of the animals were sacrificed. The appearance of malignant tumors was noted. Irradiation shortened the survival time while the irritation had an appeasing, compensatory effect, more expressed in the males than in the females. After irradiation the number and assortment of the tumors increased and the latent period essentially shortened. In the irritated animals the number and assortment of the malignant tumors were reduced and a tendency for lengthening of the latent time period was seen; these differences, however, were not statistically significant. In spite of some differences the response in both sexes to irradiation and irritation or their combination was similar.

Stress and radiation carcinogenesis in mice.

In the present experiment irritation consisting of a combination of an optic signal followed by a mild electroshock administered at regular intervals was started in 2 groups of animals at the age of 3 months. At 4 months of age, one of the irritated and one of the nonirritated groups were exposed to whole-body gamma irradiation at 20 daily doses of 0.5 Gy (50 rad(, 1.4 Gy/min (140 rad/min), while the other 2 groups were sham-irradiated. The animals were autopsied and the specimens were microscopically studied for the presence of malignant tumors. Malignant tumors involving particularly the testes and lungs and leukosis were found in 29% of males, whereas in females the tumor incidence with mammary, pulmonary and ovarian involvement and leukosis was 39%. The irradiation decreased the minimum latency time in the irritated males and both female groups. In males, the irritation lowered the cumulative prevalence of malignant tumors, a significant decrease being noted at the age of 15 months. In females, it was increased, with a significant rise observed to occur at the end of the experiment. The opposite effects of irritation on the radiation carcinogenesis in males and females can be attributed to the irradiation-induced specific alterations of the gonads in females and, in part, to a longer survival time observed in the irradiated females.

Stress and Ehrlich ascites tumor in mouse.

The aim of the study was to investigate the interaction of the psychosomatic stress and the Ehrlich ascites tumor (EAT) growth in mice. The stressor consisted of combination of a light signal followed by a mild electric shock. The first experiment was performed on CBA mice irritated for 0, 2 and 4 weeks respectively, prior to intraperitoneal transplantation of the EAT. In the second study, mice of BALBc strain were used. Stress was applied 4 weeks before the tumor transplantation and continued throught the experiment. Both the irritated and the nonirritated animals were subjected to either intraperitoneal or subcutaneous inoculation of the EAT. In both experiments, mice were left to live until their spontaneous death. In the first experiment, after a 2-week irritation the experimental animals showed a significantly longer survival time as compared to the controls. Longer or shorter duration of the irritation had no significant effect on the results obtained. Results yielded by the second experiment showed no significant difference in the time of survival of the irritated and nonirritated animals after the i. p. transplantation, whereas after the s. c. inoculation of the EAT, the irritation significantly increased the survival period. The EAT in irritated mice was observed to have invaded the vitals later and less frequently than in the nonirritated animals. Quantitative histological analysis of some endocrine and lymphatic organs revealed signs of stress in the experimental animals. The EAT transplant, per se, had a stressogenic effect too.

Intravenous chemotherapy with syndronization in advanced cancer of oral cavity and oropharynx.

Sixty-one patients with locally advanced squamous cell carcinomas of oral cavity and oropharynx were treated with chemotherapy, intravenously applied, in addition to radiation and/or surgery. An attempt was made to synchronize the tumor cell population by application of low doses of Vinblastine and the subsequent chemotherapy was based on the uptake of 99m-Tc --labelled Bleomycin in the tumor as an indication of synchronization. Increased number of mitoses in aspiration biopsy specimens and shift in the DNA distribution pattern on DNA histograms were taken as indicative of synchronization. A 50--100% regression of the tumor was achieved in 19 out of 38 patients with residual or recurrent tumors. The results were better in those patients, who received chemotherapy based on individual Tc-Bleomycin uptake curves. In 23 patients with previously untreated T3 tumors of oral cavity and oropharynx the results were somewhat better, but there was not statistically significant improvement on attempts with synchronization in this small series. There were no serious complications connected with chemotherapy.

"Genital dyscrinism" as a cause of subfertility in mice of the CBA strain.

Following four generations of inbred mating (brother-sister) in three direct lineages of CBA strain mice, sterility appeared which from that generation forward became more frequent. The genital organs in animals of both sexes were altered. There was a noticeable occurrence of cysts in the ovaries of female animals already following the third month; in mice approximately one year of age this condition was followed by cystic glandular hyperplasia of the endometrium, sometimes complicated by disturbances in blood circulation, inflammation or even malignancy. In some female animals, manifesting, due to cysts, completely degenerated ovaries, the rest of the genital system was severely atrophic. Male animals frequently showed severe atrophy of the seminiferous epithelium along with preserved interstitial cells and hypertrophic seminal vesicles. These pathological changes represent an independent nosologic unit, for which the label "genital dyscrinism" has been proposed. The authors have considered an endocrine mechanism as the possible cause of these pathological changes which are presumed to be genetically conditioned.