Metformin improves endothelial function in normoinsulinemic PCOS patients: a new prospective.

BACKGROUND: Metformin was reported to improve the alterations of endothelial reactivity in normal-weight subjects with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the mechanisms of action of this drug on the vascular function of this population. METHODS: Thirteen normal-weight, normoinsulinemic and normolipemic PCOS women were studied before and after 6 months of metformin treatment (1000 mg/day). The endothelial function was assessed by evaluating the flow-mediated dilatation (FMD) of the brachial artery. We correlated this parameter with the endocrine-metabolic features of the patients. RESULTS: Metformin significantly reduced testosterone (1.56 +/- 0.52 after 6 months versus 2.98 +/- 1.00 at baseline) and 17-hydroxyprogesterone (0.03 +/- 0.01 versus 0.06 +/- 0.02 nmol/ml) levels, without affecting gluco-insulinemic parameters. Concomitantly, the basal vessel diameter and the FMD significantly increased (4.12 +/- 0.68 versus 3.2 +/- 0.41 and 5.2 +/- 0.6 versus 3.76 +/- 0.5 mm, respectively), thus documenting an improved endothelial function. CONCLUSIONS: Our data confirm the positive effects of metformin on the altered vascular reactivity, a precocious marker of cardiovascular risk, in normoinsulinemic PCOS subjects. This improvement seems to be mediated through hormonal changes, thus highlighting the detrimental role of hyperandrogenemia on the endothelial function, even beyond the metabolic factors. However, a direct effect of metformin on the endothelium should not be excluded.

Low-molecular weight heparin induces in vitro trophoblast invasiveness: role of matrix metalloproteinases and tissue inhibitors.

Heparin is used widely for the prevention of pregnancy loss in pregnant women with thrombophilia. However, it is still unknown if heparin may be able to affect trophoblast functions. Therefore, we investigated the hypothesis that low-molecular weight heparin (LMWH) might regulate in vitro trophoblast invasiveness and placental production of matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs). In the first-trimester placental tissue, the MMP-9 expression was observed in both villous and extravillous cytotrophoblast cells, and MMP-2 mainly in villous cytotrophoblast. In human choriocarcinoma cells (JAR), MMP-2 was the dominant form. Heparin significantly enhanced both pro-MMPs and the active forms, and increased Matrigel invasiveness of extravillous trophoblast and choriocarcinoma cells. In choriocarcinoma cells the heparin effect was also indirect, inducing a significant decrease in TIMP-1 and TIMP-2 protein expressions and mRNAs. The present data suggest that the increase in trophoblast invasion by heparin is due to a specific protein playing a role in placental invasion. These observations may help in understanding the effects of heparin treatment during pregnancy.

[Ethics and rights in biomedical research: documents by the Council of Europe and UNESCO]. / Etica e diritto nella ricerca biomedica: i documenti del Consiglio d'Europa e dell'UNESCO.

After having indicated, in brief, the international documents of major interest for the safeguard of the human being subject to biomedical experiment, the author dwells upon two recent initiatives: "Convention for the safeguard of the human rights and the dignity of the human being with regard to the applications of biology and medicine: agreement on humans rights and biomedicine" by the Council of Europe and "Draft of declaration on human genome" issued by UNESCO. Of both documents he explains the genesis and the main objectives that are aimed to be reached. In particular, he dwells upon the contents of those articles that concern scientific research. Finally, he positively evaluates the promotional effort of the human being rights that the two initiatives pursue, highlighting however that there are some limits under a strictly bioethical profile.

Squamous cervical cancer at stage IB and II: a ten years experience, analysis of 231 cases.

The authors have reviewed their experience on treatment of carcinoma of the uterine cervix at stage I and II, with a special regard for prognostic factors. The best survival results at 7 years for patients at stage I B and II A were obtained with integrated treatments, while for stage II B patient no treatment proved to be really effective. Lymphnodal infiltration, increasing with the stage, was the most important prognostic factor, but stage must always be taken into account, especially in N- patients. Some considerations are then made on the importance of prognostic factors such as lymphnode status and tumour volume, in order to improve the survival results.

Endometrial carcinoma: 128 cases at stages I and II.

The authors have re-examined 146 patients with stage I and II endometrial carcinoma according to pathological findings. An understaging of FIGO classification of 9.8% and 14.2% in stages I and II, respectively, was found. Also evaluated was the influence of some risk factors (histologic grade, myometrial infiltration) on survival rates which was highly significant for both stages I and II. Surgery was the main form of treatment with an operability rate higher than 90%. The bilateral salpingo-oophorectomy appeared to improve the survival at stage I, 85.8% versus 63.6%, while postoperative external radiotherapy (ERT) seemed to be ineffective.

Early hemostatic disorders in patients with gynecologic tumors.

One hundred and seventeen female subjects were studied: 23 patients with cervical carcinoma; 25 with endometrial carcinoma; 29 with benign uterine diseases; 14 with ovarian carcinoma; 26 patients with benign ovarian tumors. These patients, together with 25 healthy female control subjects, underwent several coagulation tests including Beta-Thromboglobulin (Beta-TG) and Platelet Factor 4 (PF4) plasma levels. Among all Beta-TG and PF4 exhibited the most interesting results. They were increased in four groups of patients: those with malignant 92.2% (13/14) and benign 50% (13/26) ovarian tumors and those with endometrial 64% (16/25) and cervical carcinoma 69.5% (16/23). Our study showed a high incidence of abnormalities of Beta-TG and PF4, early signs of hemostatic disorders, in gynecological malignancies especially in ovarian carcinoma. These data suggest a possible value of these tests as tumor-markers and in order to detect the patients who develop thrombo-embolic accidents.

Evaluation of circulating immune complexes (C.I.C.) in endometrial cancer.

We evaluated the presence of CIC in 32 patients with histological proven cancer of endometrium: 23 stage IA or IB (i.e. localized disease), 9 in stage II or III (i.e. advanced disease). The determination of CIC was done at the time of the diagnosis before the patients underwent any surgical or medical therapy. The presence of CIC was demonstrated in 17% (4/23) of the patients with localized disease and in 56% (9/9) of the patients with more advanced disease. Our findings indicate that the presence of CIC is higher in patients with advanced endometrial carcinoma (stage II, III), than in those suffering of a more limited disease (stage IA, IB) and this seems could be consistent with a possible role in modulating the immune response against tumour itself.

Pelvic exenteration in gynaecologic oncology: analysis of 44 cases.

The Authors review 44 cases of pelvic exenteration performed at the Department of Obstetrics and Gynaecology of the Università Cattolica del S. Cuore - Rome, from 1967 to 1981, in patients affected by advanced or relapsed gynaecological malignancies. Operative mortality, medical and surgical complications and survival are analysed. Some characteristics of the disease are outlined as the most important criteria for patient selection, and the possible curative role of this operation is stressed.

[Electromyography of the perineum. Demonstration of the method]. / Elettromiografia del perineo. Messa a punto del metodo.

The Authors, by means of surface E.M.G. have investigated the perineal potentials. The choice of surface E.M.G. is due to the good acceptance of the method by the patients, as it does not interfere with muscular activity and mental concentration, which are fundamental for a good application of R.A.T.

[Results of electromyography of the perineum of women in labor prepared and unprepared by the respiratory autogenic training method]. / Risultati elettromiografici del comportamento del perineo in travaglio di parto in donne preparate e non preparate con il metodo R.A.T.

The Authors, by means of surface E.M.G. of perineum, have analyzed statistically the potentials registered in two groups of pregnant women in labor, the first prepared according to the R.A.T. method, the second utilized as a control group. The complete automatization of the analysis was allowed to exclude any bias. The differences of the perineal potentials registered in the groups were statistically significant.

Urinary diversion by ileal conduit in gynecologic oncology.

In the decade 1967-1977, 663 patients with different gynecologic neoplasms were admitted and treated at our Department. Because of the involvement of the urinary tract, urinary diversion was required in 41 cases. Ileal conduit was performed in 25 patients (20 affected by carcinoma of uterine cervix, 4 by adenocarcinoma of endometrium, 1 by carcinoma of vulva). In 19 patients such procedure was performed immediately after radical surgical therapy; in 6 patients ileal conduit was indicated because of post irradiation fistulas. Few complications were observed and all of them successfully cured. Authors conclude that Bricker operation is still an effective procedure in gynecologic oncology, both as a complement to radical surgery (in selected patients), and as a complementary treatment of recurrences and complications of radiation therapy.

The treatment of 48 patients affected by ovarian carcinoma at stages III and IV F.I.G.O.

The Authors analyzed the treatment of 28 patients in stage III (FIGO) and 20 patients in stage IV affected by epithelial ovarian cancer. In these cases, surgery was based on the criterion of cytoreduction and, where possible, maximum radicality. Within a month from surgery, all patients underwent a program of combined chemotherapy (VCR + 5 FU + CTX) envisaging successive cycles, every four weeks. Minimal side effects were generally observed. 13/28 (46.4%) responses were recorded in stage III and 4/14 (28.6%) in stage IV. The highest percentage of responses, 80%, was obtained in patients with a residual tumor less than 2 cm, all belonging to stage III. Stage III and stage IV patients with a residual tumor greater than 2 cm responded in 45% and 33% of the cases respectively. Patients who underwent explorative laparotomy showed negligible responses. There was a statistically significant difference survival between stage III and stage IV patients (p less than 0.001), among patients with a similar residual tumor greater than 2 cm, but in different stages (p less than 0.05), and among stage III patients who responded or not to chemotherapy (p less than 0.001).

[Research on the socioeconomic risk factors in pregnancy and delivery]. / Ricerca sui fattori socio-economici di rischio nella gravidanza e nel parto

PIP: The effects of various socioeconomic factors on the outcome of pregnancy and delivery in Italy are investigated. Variables considered include marital status, area of residence, educational level, occupation, income, and attitude toward pregnancy. Methods for accurate evaluation of risk factors are discussed. The need for physicians to consider the social and psychological aspects of pregnancy and delivery is emphasized. Data are for women interviewed at the Obstetrical and Gynaecological Clinic of the Catholic University of the Sacred Heart in Rome.^ieng