Digital slide and virtual microscopy based routine and telepathology evaluation of routine gastrointestinal biopsy specimens.

AIMS: To evaluate a recently developed digital slide and virtual microscope system, and to compare this method with optical microscopy on routine gastrointestinal biopsy specimens in both local and remote access modes. METHODS: A fully computer controlled commercial microscope was used. The scanning program included object detection, autofocus, and image compression algorithms. The overall hard disk space for a gastric biopsy was between 30 and 50 MB and the scanning time was between 20 and 40 minutes. Haematoxylin and eosin stained routine gastric (61) and colon (42) biopsy specimens were selected, scanned, and evaluated by two specialists on an optical (OM) and virtual microscope (VM). RESULTS: The overall concordance of VM and OM with the consensus diagnosis was 95.1% and 97%, respectively. Clinically important concordance was 96.1% and 98% for VM and OM, respectively. The two methods showed concordance in 92% of cases and clinically important concordance in 94.1% of cases. The reasons for discordance were image quality (one case), interpretation difference (three cases), and insufficient clinical information (three cases). Remote evaluation of the digital slides through the Internet has the advantages of the previously used static and dynamic telepathology methods. CONCLUSIONS: Diagnostic concordance was found between OM and VM. The digital slide and the virtual microscope can be alternative techniques in the computerisation of the histology laboratory and in teleconsultation services after further evaluation of time and storage constraints.

Endocrine mechanisms of suppressive effect of low dose estrogen-antiandrogen treatment on androgen-dependent organs of male rats.

The effects of low doses of hexestrol (Hex) (2-40 micrograms/kg bw) and flutamide (FI) (10 mg/kg bw) on some endocrine mechanisms in mature intact male rats are described in the present paper. It has been shown that each preparation, administered separately for 10 days, induced a moderate decrease in the weight of the ventral prostate (VP), anterior prostate lobe or coagulating gland (CG) and seminal vesicles (SV), in the DNA content and number of cells in the VP. 5 alpha-reductase activity was also decreased; the epithelium secretory activity of the VP was suppressed. After combined FI (10 mg/kg bw) and Hex (40 micrograms/kg bw) the following castration-like effects were observed: an abrupt fall in the weight of the accessory sexual glands, a decrease of DNA level and cell number in the VP as well as a suppression of the production of 5 alpha-reductase metabolites in this structure. Histologically, a marked degenerative changes in the VP secretory epithelium was observed; on the contrary an hyperplasia of connective and smooth muscle cells was evident. When FI alone was administered to rat, the above-mentioned changes were accompanied by a pronounced elevation of plasma bio-LH and testosterone (T) levels, also an increase of testicular delta 5-3 beta-hydroxysteroid dehydrogenase activity was observed. On the contrary, when Hex was administered alone or in combination with FI, bio-LH and T levels and enzyme activity decreased. We conclude that Hex administration in low doses, in combination with FI, could be an alternative method for a complete androgen blockade of the accessory sexual glands.

[Recovery of various parameters of the functional state of the reproductive system in thymectomized rats as affected by thymic membrane factor]. / Vosstanovlenie nekotorykh pokazatelei funktsional'nogo sostoianiia reproduktivnoi sistemy u timéktomirovannykh krys pod vliianiem membrannogo faktora timusa.

Ten-month-old male rats thymectomized in early post-puberty were ascertained to have lower plasma luteinizing and testicular hormones and higher testicular steroid dehydrogenase activity. Following 24 hours of administration of a thymocyte membrane structural agent, pituitary gonadotropic and gonadal androgenic functions became normal. There was no agreement between the hormonal parameters and the levels of nucleic acids in the testes and prostate.

[The correlation of the hormonal and clinical effects in patients with prostatic cancer undergoing niftolid treatment in combination with low doses of synestrol]. / Koreliatsiia hormonal'nykh ta klinichnykh efektiv u khvorykh na rak peredmikhurovoï zalozy pry likuvanni niftolidom u poiednanni z malymy dozamy synestrolu.

Effects were studied of niftolide in tablets, 0.25 g on a three-times daily basis in combination with low doses of sinestrol, 5 mg intramuscularly within 24 h, on tumor growth, blood plasma content of luteinizing hormone (LH), testosterone (T) and testosterone-estradiol-binding globulin (TEBG) in 46 patients with prostate gland carcinoma, including seven patients with metastases. After treatment for three months, plasma T level decreased by 63%, that of LH by 53% whereas TEBG increased twice as much. The treatments were administered for as long as 10 months, with estrogen therapy being tapered to a dose of 3 mg daily. The above treatment schedule resulted in stabilization or partial regression of tumor growth in as many as 94.9% cases; also deserving to be noticed was improvement in the outflow of urine and alleviation of the pain syndrome. The clinical effect is believed to be due to pharmacological blockade of androgenic receptors in the tumor and its metastases as well as to antigonadotropic activity of estrogen and striking lowering of blood plasma free T.

[Effect of 131I incorporation on the status of the reproductive system in male rats and the dose-dependent effect]. / Vliianie inkorporatsii 131I na sostoianie reproduktivnoi sistemy samtsov krys dozozavisimogo éffekta.

Radioactive 131I was injected in single doses 9.25, 37, and 92.5 kBq to prepubertal (30-day-old) male rats. Iodine incorporation in doses 37 and 92.5 kBq resulted in some functional changes in the reproductive system of mature rats: blood testosterone level increased, its hypothalamic aromatization intensified, and biologically active LH level in the blood dropped. Incorporation of 9.25 kBq of 131I had no effect on male reproductive system. A possibility of direct injury to rat testicles by 131I incorporation is suggested.

[The reproductive function of male rats in the late periods after x-ray irradiation]. / Reproduktivnaia funktsiia samtsov krys v otdalennye sroki posle rentgenovskogo oblucheniia.

Reproductive function in male rats was studied in 1, 3 and 6 months after X-ray irradiation of doses of 2 and 3 Gy. It has been established that long-term effects of irradiation at a dose of 3 Gy are manifested through decrease in spermatozoa content in the epididymis and reduction of nucleic acid and protein content in the testes. Fertility of male rats under study significantly lowered shortly after irradiation and full recovery of fecundating ability was observed 6 months later. The effect of irradiation with a dose of 2 Gy was less pronounced.

[Evaluation of the gonadoliberin and niftolid tests in the diagnosis of male hypogonadism]. / Otsenka prob s gonadoliberinom i niftolidom v diagnostike muzhskogo gipogonadizma.

Comparative analysis with an antiandrogen niftolid and synthetic GnRH was carried out in 22 normal subjects, 14 patients with primary and 20 ones with secondary hypogonadism, and in 5 patients with clinical signs of gonadal insufficiency and obscure diagnosis in order to elucidate the pituitary gonadotropin reserves. Blood plasma and daily urine gonadotropin levels were measured. Changed gonadotropin excretion under the effect of niftolid in health and hypogonadism was in line with changed gonadotropin level in the blood after RF administration, this indicating a similar informative value of both tests for the differential diagnosis of various hypogonadism forms. In the first case measurements of blood gonadotropin were more informative, in the second daily urine analysis. Niftolid test, noninvasive and readily available, is recommended as an alternative test with RF administration.

[The functional activity of the hypothalamo-hypophyseal-gonadal system in male rats in the late periods after x-ray irradiation]. / Funktsional'naia aktivnost' gipotalamo-gipofizarno-gonadnoi sistemy u samtsov krys v otdalennye sroki posle rentgenovskogo oblucheniia.

The hypothalamo-hypophysis-gonad system was studied in male rats 1, 3 and 6 months after external irradiation with doses of 2 and 3 Gy. Irradiation with a dose of 3 Gy was shown to cause a decrease in the level of LH and testosterone in blood plasma, impairment of steroidogenesis in the testes and diminution of their mass. All this was most pronounced 6 months after X irradiation. The morphofunctional status of prostate, inhibited by X radiation, was restored by that time.

[Androgen status in rabbits after long-term administration of non-steroid androgen antagonist niftolid]. / Androgennyi status u krolikov v usloviiakh prodolzhitel'nogo vvedeniia nesteroidnogo antiandrogena niftolida.

Niphtholid (25 mg/kg/dl for 60 days) significantly increases the LH and testosterone blood levels but has no marked effect on ++androstenedione and testosterone-estradiol-binding globulin levels in Chinchilla++ mature rabbits. The concentration of latter was elevated against a background of low testosterone and androstenedione and high LH levels in the castrated rabbits. The obtained results show that niphtholid exerts a continuous stimulating and pronounced effect on the rabbit pituitary-gonadal axis and simultaneously prevents the manifestation of suppressing androgen effect on testosterone-estradiol-binding globulin contents in the organism.

[Characteristics of the long-term effects of niphtholide on the functional state of the testes in animals]. / Osobennosti prodolzhitel'nogo vozdeistviia niftolidom na funktsional'noe sostoianie semennikov zhivotnykh.

Long-term application of non-steroid antiandrogen niphtholid (10 or 25 mg/kg daily for 8-9 months) exerts a stimulating effect on the functional state of testicles. This effect is more pronounced in rats, than in dogs and guinea pigs. In all these animals the drug antiandrogenic effect caused a decrease of the prostatic mass, while in rats--an increase of the adenohypophysis mass. The peculiarities of the niphtholid effect in various animals should be taken into account when evaluating and interpreting investigation results.

[Specific binding of androgens by the skin in hirsutism of ovarian genesis]. / Spetsificheskoe sviazyvanie androgenov kozhei pri girsutizme ovarial'nogo geneza.

The role of raised skin sensitivity to circulating androgens in the pathogenesis of hirsutism, determined by the syndrome of polycystic ovaries, was studied. A two-fold increase in the specific binding of 3H-methyltrienolone++ was noted in the cytosol fraction of the public skin of women suffering from hirsutism as compared to healthy women using saturation analysis. The specific binding of androgens indicated an increase in the content of androgen receptors of the skin in hirsutism.

[Problems of pathogenesis of ovarian and idiopathic hirsutism]. / Voprosy patogeneza ovarial'nogo i idiopaticheskogo girsutizma.

The content of total testosterone (T), dehydrotestosterone (DHT), androstenedione (A), estradiol (E2), luteotropin (LH) and follicle-stimulating hormone (FSH) was studied in patients with ovarian and idiopathic hirsutism by a radioimmunoassay. The level of T-E-binding globulin (TEBG) was determined by 3H-DHT binding. Concentrations of free and TEBG-unbound T, DHT and E2 were calculated on the basis of the mass action law. The level of free and TEBG-unbound T and DHT was found to be the most reliable marker of the excessive production of androgens in hirsutism. The level of total T and DHT was raised in 50-60% of patients with hirsutism. Patients with hirsutism of ovarian genesis were characterized by considerable blood elevation of LH and FSH with still greater values in patients with menstrual disturbance, and by a rise of an A level. Difference found in hormonal indices can be used in differential diagnosis of ovarian and idiopathic hirsutism.

[Diethylstilbestrol potentiation of the antiandrogenic effects of niftolide in the prostate]. / Potentsirovanie diétilstil'béstrolom antiandrogennykh éffektov niftolida v predstatel'noi zheleze.

In experiments on intact mature male Wistar rats it was shown that a combined administration of niftolide (2.5, 5 and 10 mg/kg) and diethylstilbestrol (10 and 50 mg/kg) produced a more pronounced antiprostatic effect than their separate administration.

[Antiandrogenic effects of hydroxyniftolide in male rats]. / Antiandrogennye éffekty gidroksiniftolida u samtsov krys.

Experiments on intact mature male Wistar rats showed the ability of hydroxyniftolide (4'-nitro-3'-trifluoromethyl-2-hydroxy-2-methylpropionylanilide), a hydroxylated antiandrogen derivative of niftolide, to inhibit the effects of male sex hormones in androgen target organs. At doses of 10 mg/kg and upwards administered intravenously or intramuscularly for 10 days, it stimulated the hypothalamohypophy-seogonadal system expressed in an increase in the activity of delta 5-steroid-3 beta-ol-dehydrogenase in the testicles and blood plasma testosterone concentration. Comparative studies on antiandrogenic properties of niftolide and hydroxyniftolide made it possible to show that the effect of the first agent was more noticeable with relation to the hypothalamic centers of gonadotropin secretion regulation whereas the effect of the second one was more noticeable in the accessory sex glands.

[Interrelation of sex hormone-binding globulin and the androgen-estrogen balance in patients with hypercorticism]. / Vzaimosviaz' globulina, sviazyvaiushchego polovye gormony, i angrogeno-éstrogennogo balansa u bol'nykh s giperkortitsizmom.

The concentration of testosterone and estradiol in the blood plasma and the binding capacity of testosterone-estradiol binding globulin (TEBG) were studied in 30 women and 6 men with Icenko-Cushing's disease in the active phase and in 24 women with hormonally active adrenal tumors. In hypercorticism against a background of unchanged of lowered concentration of plasma estradiol there was a decrease in the concentration of testosterone and an increase in the testosterone-estradiol binding capacity (TEBC) in men and an increase in the concentration of testosterone and a decrease in TEBC in women. The authors have assumed that the testosterone/TEBC ratio reflects more accurately change in the dynamics of androgens than isolated concentrations of testosterone and TEBG, and recommended its determination for the assessment of the body androgenic saturation in disturbed function of the adrenal or sex glands.

[Biochemical bases of the antifertility action of the nonsteroidal antiandrogen niphtolid]. / Biokhimicheskie osnovy antifertil'nogo deistviia nesteroidnogo antiandrogena niftolida.

The study was made of biosynthesis and levels of nucleic acids and proteins in the head of epididymis as well as of the fertility of intact mature male rats under antiandrogenic exposure to nonsteroid antiandrogenic compound niphtolid. Niphtolid given per os in a dose of 25 micrograms/kg during 8 or 30 days decreased the mass of the organ and its concentrations of DNA, RNA and proteins. The above mentioned alterations seemed to be caused by inhibited inclusion of labeled precursors into biopolymers. A long-term intake of antiandrogen (10 micrograms/kg of body mass daily for a six-months period) was followed by developing transient infertility. The possibility to use niphtolid-like compounds both alone and in combination with antigonadotrophic drugs for fertility regulation is assumed.

[Use of the antiandrogen niftolide for studying reserves of the hypothalamo-hypophyseal system in patients with male hypogonadism]. / Primenenie antiandrogena niftolida dlia issledovaniia rezervov gipotalamo-gipofizarnoi sistemy u bol'nykh muzhskim gipogonadizmom.

A study was made of a possibility to use a test with the administration of the nonsteroid antiandrogen flutamide to male patients with testicular hypogonadism to evaluate the gonadotropic reserves in this pathology and differential diagnosis of the pathogenetically different forms of this diseases in male patients aged 12 to 33. Flutamide was prescribed for internal use, 10 mg/kg a day for 5 days. Functional reserves of the hypothalamo-hypophyseal-gonadal system were estimated by the change of LH secretion with morning and daily urine after 3 and 5 days as well as by the LH, FSH and T content in the blood plasma. A significant rise of LH excretion with morning and daily urine was noted in patients with primary hypogonadism receiving flutamide. On the contrary, no significant changes in LH secretion under the influence of flutamide were detected in secondary hypogonadism. It is suggestive of the preservation of the gonadotropic reserves in primary hypogonadism and their absence in secondary hypogonadism. The test is proposed for differential diagnosis in diagnostic difficulties. The most accurate results are obtained by using LH in the urine collected for 3 days of flutamide intake.

[New functional test using the antiandrogen niftolid for studying the gonadotropic reserves of the hypothalamo-hypophyseal system]. / Novaia funktsional'naia proba s primeneniem antiandrogena niftolida dlia issledovaniia gonadotropnykh rezervov gipotalamo-gipofizarnoi sistemy.

A study was made of a possibility to use a nonsteroidal antiandrogen flutamide to investigate the gonadotropic reserves of the hypothalamo-hypophysial system. In healthy males aged 12 to 36, the intake of flutamide tablets at a dose of 10 mg/kg bw for 3 or 5 days was accompanied by an increase in the LH excretion and general gonadotropic activity in the daily urine by 1.5-2 times and more. An elevation of the gonadotrophin level in morning urine portions was less noticeable. The LH level in the blood plasma did not change, that of FSH and testosterone increased but in certain age groups. For purposes of functional diagnosis it was suggested that the gonadotrophin level in the daily urine should be studied prior to and after 3- or 5-day of flutamide intake.

[In vitro models for research on cell differentiation and malignant degeneration in the human prostate]. / Modeli in vitro dlia izucheniia differentisirovki i malignizatsii kletok predstatel'noi zhelezy cheloveka.

The methods are reviewed for obtaining monolayer epithelium cultures both in normal and hyperplastic or malignant prostate glands. Preparation of pure epithelial tissue cultures is dealt with in detail. The major prostate cell lines are described. Special attention is paid to the markers of differentiation and sensitivity to hormones in normal and tumour prostatic cells in vitro. Prospects for the use of prostatic cell cultures as models in oncology are outlined.