[In vitro evaluation of bactericidal activity of an over-heated saturated dry atomized steam electro-medical device on inert contaminated surfaces]. / Valutazione in vitro dell'efficacia battericida di un'apparec- chiatura elettro-medicale con erogazione di vapore saturo secco surriscaldato ad alta temperatura applicata a superfici contaminate.

Surface disinfection together with cleaning practises and aseptic procedures are established measures for effective prevention of infectious diseases reducing infection risks. In this study, we evaluated the bactericidal effectiveness in vitro of the electro-medical device Sani System, an over-heated saturated dry-steam disinfection system, against predetermined bacterial load dried on inert surfaces. In particular we have tested different materials, representative of operating rooms furnishing and walls commonly used in healthcare setting, with Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii. As a result of treatment, the mean bacterial load on all the test surfaces was reduced by a factor of 102 in the contact plate experimental study and by a factor of 10 in the total bioburden experimental study. The Sani System Polti proved to be efficacious in killing 100% of the bacteria in all experimental conditions, therefore it could help to reduce the risk of spreading nosocomial infections in healthcare facilities.

Comparison between different cell kinetic variables in human breast cancer.

Cell kinetics holds a prominent role among biological factors in predicting clinical outcome and response to treatment in neoplastic patients. Different cell kinetic variables are often considered as valid alternatives to each other, but the limited size of case series analysed in several studies and the lack of simultaneous determinations of all the variables on the same tumours do not justify this conclusion. In the present study, the correlation between [3H]thymidine labelling index ([3H]dT LI), flow cytometric S phase cell fraction (FCM-S) and Ki-67 immunoreactivity (Ki-67/MIB-1) was verified and the type of correlation with the most important clinical, pathological and biological patient and tumour characteristics was investigated in a very large series of breast cancer patients. Ki-67/MIB-1, FCM-S and [3H]dT LI were determined in 609, 526 and 485 patients, respectively, and all three cell proliferation indices were evaluated in parallel on the same tumour in a series of 330 breast cancer patients. All the cell kinetic determinations were performed within the context of National Quality Control Programmes. Very poor correlation coefficients (ranging from 0.37 to 0.18) were observed between the different cell kinetic variables determined in parallel on the same series of breast cancers. Moreover, Ki-67/MIB-1 and FCM-S showed a significant relationship with histological type, grade and tumour size, whereas statistically significant correlations were not observed for [3H]dT LI. In conclusion, the results show that the different cell kinetic variables provide different biological information and cannot be considered as alternatives to each other.

Epidermal growth factor receptor expression and endometrial cancer histotypes.

Epidermal growth factor receptor (EGF-R) has been implicated in the growth of endometrial cancer. In the present study, immunostaining of EGF-R was investigated in different endometrial cancer histotypes. For this purpose 34 surgical samples of primary endometrial carcinoma were studied using monoclonal anti-EGF-R antibody. The endometrial carcinomas were classified according to the International Society of Gynaecological Pathology (I.S.G.P.). EGF-R expression was observed in: 1 of 5 classical endometrioid adenocarcinomas (AE), in 8 of 9 endometrial adenocarcinomas with benign squamous metaplasia (AA), and in 3 of 14 adenosquamous adenocarcinomas (AS). In mucinous (M) and serous papillary adenocarcinoma (SP) EGF-R immunostaining was not observed. The EGF-R positivity was observed in endometrial cancer with squamous (SQ) differentiation, especially in those with benign SQ metaplasia. These results suggest that EGF-R immunostaining is related to the endometrial cancer histotype regardless of the tumor grade or extent of miometrial invasion.

The effect of progestin on factors influencing growth and invasion of endometrial carcinoma.

Progesterone (P) and progestins play an important role in the control of endometrial growth. We have investigated P and progestin effects on endometrial estrogen extraction, on basement membrane (BM) synthesis and on the presence of the epidermal growth factor receptor (EGFr) in normal and pathologic endometrium. E2 uptake, evaluated in human isolated perfused uteri is significantly decreased by P. BMs investigated using immunohistochemistry, with antisera to collagen IV and laminin, were found around stromal cells only in the luteal phase or during P or progestin administration. Glandular BM, discontinuous in hyperplastic and carcinomatous endometria, were restored to integrity only in typical hyperplasia after therapy with progestin. Endometrial EGFr is modified by P: revelation of this antigen is increased in proliferative phase and decreased in secretory phase. Similarly this molecule was present in hyperplastic and carcinomatous endometria. Only in benign hyperplasia did we observe no staining for the same antigen after progestinic therapy. These data suggest that P or progestins may also have an indirect influence through mechanisms such as estrogen uptake and tissue factor activity with important differences between normal and pathologic endometrium.

Treatment of hirsutism by an association of oral cyproterone acetate and transdermal 17 beta-estradiol.

Twenty-four hirsute women were treated with an inversal sequential scheme of cyproterone acetate, 50 mg/d by oral route from the 1st to the 15th day of the menstrual cycle, along with 100 micrograms/24 h of 17 beta-estradiol transdermally administered from days 1 to 21, for nine cycles at weekly intervals. The acne and seborrhea as well as hirsutism showed a significant improvement in all subjects studied. The plasma testosterone and dehydroepiandrosterone sulfate decrease from 1.5 +/- 1.3 ng/mL and 6.9 +/- 1.3 micrograms/mL to 0.5 +/- 0.03 ng/mL and 2.7 +/- 1.7 micrograms/mL, respectively. Similar values were observed in subjects with idiopathic hirsutism during the treatment. The metabolic parameters, as well as the plasma levels of sex hormone-binding globulin, appeared unaffected by the therapy. Furthermore, the luteinizing hormone and follicle-stimulating hormone secretion was strongly inhibited from the first cycle of treatment. In conclusion, considering the good clinical results and the avoidance of any hepatic effect, this association should be taken into account in the treatment of hirsutism, especially in case of oral estrogen intolerance.

Epidermal growth factor receptor (EGF-R) and transforming growth factor alpha (TGFA) expression in different endometrial cancers.

The role of epidermal growth factor receptor (EGF-R) and transforming growth factor alpha (TGFA) in endometrial cancer is still controversial. In this study the immunostaining of EGF-R and TGFA, investigated in 44 cases, proved to be related to endometrial cancer histotype regardless of the tumor grade or the extent of myometrial invasion. In fact, EGF-R expression was observed in 12.5% (1/8) of cases with classical endometrioid adenocarcinoma, in 91% (10/11) with endometrial adenocarcinoma and benign squamous metaplasia, and in 35% (6/17) with adenosquamous carcinoma. TGFA expression was concomitant with EGF-R in the first two histotypes, and was present in about 50% (9/17) of the latter. Conversely, in mucinous and serous papillary adenocarcinoma, EGF-R and TGFA immunostaining was not observed. In conclusion, EGF-R positivity was observed in endometrial cancer with squamous differentiation, especially in those cases with benign squamous metaplasia. EGF-R and TGFA coexpression appeared as a constant feature of benign squamous metaplasia.

Comparative metabolism of oestrone sulphate after oral and intravenous administration in post-menopausal women.

Oestrone sulphate (E1S) is currently used in hormone replacement therapy in post-menopausal women. While isotope studies have demonstrated that E1S is metabolised in a similar way after administration by either the oral or intravenous route, pharmacokinetic studies point to its efficient extraction and metabolism by the liver. E1S was accordingly administered orally and intravenously at pharmacological dosages in a group of post-menopausal women and its conversion to oestrone (E1) and oestradiol (E2) was determined. We were able to demonstrate that E1S may cross the splanchnic area unaltered, since its conversion to E1 and E2 was similar after administration by each of the routes investigated.

Biological and endocrine aspects of transdermal 17 beta-oestradiol administration in post-menopausal women.

The plasma protein distribution of oestradiol (E2) and oestrone (E1) during transdermal E2 administration (100 micrograms/24 hr) was studied in 12 post-menopausal women. The E2 and E1 levels observed were 43-83 pg/ml and 37-73 pg/ml, respectively. The levels of the free, albumin-bound and sex-hormone-binding globulin (SHBG) bound fractions were in the ranges 1.4-1.9%, 60-65% and 35-45%, respectively, in the case of E2, and 2.8-3.0%, 80-89% and 15-20%, respectively, in that of E1. The SHBG levels also remained unaltered. It was concluded that transdermal administration of E2 at the dosage employed produces a physiological plasma protein distribution of E2 and E1 and does not affect liver protein production.

Feasibility of a cell kinetic-based adjuvant chemotherapy trial in axillary node-negative breast cancer.

AIMS AND BACKGROUND: Accumulated information on biologic prognostic indicators and predictors of response to different types of treatment in patients with different tumor characteristics has made it possible to design clinical protocols on biologic bases. Among cell proliferation indices, the thymidine labelling index (TLI) has proved to be an independent and consistent prognostic indicator over time. Moreover, experimental and retrospective analyses of clinical studies have revealed a direct relation between TLI and response to chemotherapy. On the basis of the results, a prospective clinical protocol on axillary node-negative breast cancer was activated in Italy in 1989. METHODS: Patients with low TLI tumors were treated with local-regional therapy alone, whereas patients with high TLI tumors were randomized to receive local-regional therapy followed or not by adjuvant chemotherapy consisting of 6 cycles of CMF. RESULTS AND CONCLUSIONS: The present paper reports on the feasibility of a prospective clinical protocol based on a subgroup of patients with specific pathologic (node negative) and biologic (rapidly proliferating) breast cancers. However, patient eligibility was only 11%.

[Controlled clinical study of cyclopyroxolamine in vaginal candidiasis]. / Studio clinico controllato della ciclopiroxolamina nelle candidosi vaginali.

The clinical and microbiological results of the treatment of vulvovaginal candidiasis with cyclopyroxolamine or miconazole in thirty-eight patients are discussed. Cyclopyroxolamine treatment was demonstrated to be an effective and well-tolerated compound for the treatment of this kind of infection.

[Hypothalamic phospholipid liposomes in the treatment of the climacteric syndrome]. / I liposomi di fosfolipidi ipotalamici nel trattamento della sindrome climaterica.

Phospholipid liposomes have a dopaminergic effect on the human brain. Changes in prolactin and growth hormone secretion have been observed in humans given phospholipid liposomes. The authors have investigated the therapeutic efficacy of hypothalamic phospholipids in the menopausal syndrome. The study was an open trial on 37 outpatients treated with 1 and 2 ampoules i.m. of a preparation of phospholipids (in the form of unilamellar liposomes) for a period of six months. The therapeutic effects were assessed by means of the Hamilton rating scale, MMPI (Minnesota multiphasic inventory test), and a list of psychosomatic symptoms (LSP). In the patients no change in FSH, LH, PRL, or E2 secretion was observed, whereas the neurotic symptomatology appeared remarkably reduced.

[Cell-block immunocytochemical characterization of effusions. Use of antibody panel: calretinin, Ber-EP4, keratin and CD68]. / Caratterizzazione immunocitochimica dei versamenti su citoincluso. Applicazione del pannello anticorpale: calretinina, Ber-EP4, cheratina e CD68.

An anticorpal panel formed by Calretinin, Ber-EP4, Keratin and CD 68 has been applied to differentiate mesothelial hyperplasia/mesothelioma from metastastic carcinoma in cavity effusions. The study was performed in 86 cases in which paraffinated cell-blocks were obtained. All cases positive for malignancy had histological confirmation. The series included 2 malignant mesothelioma, 54 reactive mesothelial hyperplasia, and 30 metastatic carcinoma. All cases of reactive mesothelial showed strong cytoplasmatic positivity for Calretinin, and hyperplasia negativity for Ber-EP4. The 2 cases of mesothelioma were positive for Calretinin and negative for Ber-EP4. In contrast, all cases of metastatic carcinoma had membrane or cytoplasmatic positivity for Ber-EP4. The sensitivity (100%) and specificity (100%) of reactivity for Calretinin and Ber-EP4 showed that the immunocytochemical results on paraffin embedded material from cavity effusions are very reliable, so that the tested immunocytochemical panel can be useful in cytological differential diagnosis between reactive mesothelial hyperplasia/mesothelioma and metastatic carcinoma.

Reduced conversion of dehydroepiandrosterone into estrogens in premenarchal girls.

The purpose of this study was to evaluate the increases in plasma levels of E1, E1S and E2 during constant infusion of dehydroepiandrosterone (D) in premenarchal girls (PG) and in normal menstruating women (AW). Unlabelled D was infused for 48 h in 10 premenarchal girls and in 10 normal menstruating women. Plasma levels of D, estrone (E1), estrone sulfate (E1S) and estradiol (E2) were measured before and during 48 h infusion. Metabolic clearance rates of D (MCRD), production rates of D (PRD), and increases in plasma concentration of E1, E1S and E2, relative to the corresponding increase in plasma concentration of D, were determined. The baseline plasma levels of D were found significantly lower in premenarchal girls than in normal menstruating women. MCRD was found significantly higher in premenarchal girls than in normal menstruating women (2565 +/- 467 L/day versus 1317 +/- 242 L/day, p less than 0.01). Administration of D increased the plasma levels of E1 and E1S in the group of normal menstruating women but not in the premenarchal girls. Considering all subjects studied, the increases in plasma levels of E1 and E1S during the infusion of D were significantly correlated with body weight (p less than 0.01 and p less than 0.001, respectively). From these results, we conclude that in premenarchal+ girls there is: a reduced peripheral contribution of D to E1 and E1S, and/or a higher MCRE1 and MCRE1S than in normal menstruating women.

Extraction of estrogens by human perfused uterus. Effects of membrane permeability and binding by serum proteins on differential influx into endometrium and myometrium.

The present study was undertaken to examine the extractions of estradiol, estrone, and estrone sulfate from the circulation of the human perfused uterus. The differential permeability of endometrial and myometrial vascular beds to estrogens was evaluated in uteri samples obtained during the proliferative and secretive phases of the menstrual cycle. The effects of binding by human serum proteins on estrogen influx into the endometrium and myometrium were also determined by the use of double-isotope, single-injection, timed tissue sampling techniques adapted to the extracorporeal perfusion of human uterus. Tritiated test estrogen was injected into the uterine artery as a mixture with 14C-butanol, a free diffusible reference substance. The influx of 14C-dextran (a membrane-impermeable compound) was used to test the aspecific influx from vasculature to extravascular space. Results show that in the human perfused uterus: (1) membrane permeability plays different roles in estrogen influxes between the endometrium and myometrium; (2) during the proliferative and secretive phase of the menstrual cycle the uterine microvessels are differently permeable to the free plus protein-bound estrogens; and (3) plasma proteins decrease the endometrial and myometrial uptakes of estrogens.

Four-chromosomes complex translocations in acute promyelocytic leukemia: description of two cases.

Two cases of acute promyelocytic leukemia with variant translocation involving 4 chromosomes are described. The karyotypes were 47,XX, +8,t(13;15;17;20)(q22;q22;q12;q13) and 46,XY,t(5;15;16;17)(q22;q22;p13;q12), respectively. Variant translocations in APL apparently do not follow any preferential routes since no recurrent breakpoint additional to those of chromosomes 15 and 17 has been found in any of the cases reported in the literature and in those described here. Moreover, it seems that the translocation of the RAR alpha gene from chromosome 17 to chromosome 15 is directly involved in the pathogenesis of the disease, while the reciprocal one is not, as demonstrated by variant translocations where 15q migrates to chromosomes other than 17.

Treatment of endometrial hyperplasia with cyproterone acetate histological and hormonal aspects.

A regime of cyproterone acetate (CPA) (300 mg/day by the oral route for 30 days) has been used in 10 post-menopausal women with endometrial hyperplasia (8 atypical and 2 adenomatous). Androstenedione (A), estrone (E1), testosterone (T) and estradiol (E2) plasma levels were determined before and at the end of treatment. The regression of endometrial hyperplasia was ascertained histologically in all patients after 30 days of therapy. All steroids showed a significant decrease (p less than 0.05) as compared with their corresponding basal values. Moreover, the E1/A ratio was significantly lowered (p less than 0.01) following CPA administration (5.9 + 2.9% to 2.5 + 0.6%). From these data it is evident that CPA can not only act as a progestin, but may also reduce the endogenous estrogen production, lowering either the adrenal production of A (the most important estrogen precursor in the post-menopause) or the A to E1 peripheral conversion.

Preliminary report on postmenopausal endometrial hyperplasia treatment with Danazol: histological and endocrinological aspects.

The synthetic steroid Danazol is commonly used in the hormonal treatment of endometriosis; however, little is known about its effects on human endometrium. This study was performed to verify the efficacy of Danazol on the treatment of endometrial hyperplasia in postmenopausal patients. Ten patients with histologically proven endometrial hyperplasia were treated with Danazol at a dosage of 600 mg/day for 30 days. The E1S and E1 plasma levels were also determined before and at the end of therapy. In all patients the regression of endometrial hyperplasia was observed in the endometrial biopsy specimens obtained after the treatment. Furthermore, the increased E1S/E1 ratio as compared to the basal values suggests an impairment of the peripheral sulfatase activity. The inhibition of the conversion of E1S to active unconjugated estrogens appears to be one of the mechanisms by which Danazol may act on the endometrium.