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We report a prospective pilot study which evaluated the feasibility of combined ultrasonographically guided drainage and laparoscopic excision after pre-operative administration of a gonadotrophin-releasing hormone analogue for 3 months in the management of ovarian endometriotic cysts >5 cm. Ten patients with an ultrasonographic diagnosis of large unilateral or bilateral ovarian endometriotic cysts received an intramuscular injection of leuprorelinum acetate 3.75 every 4 weeks for 12 weeks. After 4 weeks of medical treatment, the endometrioma was carefully drained transabdominally under ultrasonographic control. Within 8 weeks since the last injection, the patients were submitted to a second ultrasonography, and laparoscopy-guided stripping of the endometrioma was performed. A videotape review was undertaken to evaluate duration and complexity of the different phases of surgery. Stripping of endometriomas with preservation of residual ovarian parenchymas was obtained in all cases; adhesiolysis was complete in 6 cases. There were neither intra-operative complications nor conversions in laparotomy. In conclusion, gonadotrophin-releasing hormone analogue and cyst drainage seem to permit an easy laparoscopic approach of large endometriomas; the findings of our pilot phase seem to justify a randomized trial to better define the effectiveness of this approach with respect to standard procedures.

Objective: This study was designed to: (i) evaluate the effect of amnioinfusion on the latency period in patients with oligohydramnios for preterm premature rupture of membranes, and (ii) to investigate the relationship between changes in the amniotic fluid index and fetal heart rate short-term variability by computerized Hewlett-Packard cardiotocography, longitudinally estimated before and after prophylactic amnioinfusion., Materials and Methods: All singleton pregnancies with prolonged premature rupture of membranes after 25 weeks of gestation and seen at the Institute of Obstetrics and Gynecology, University of Ancona (Italy), between January 1994 and June 1995 were included in the study. Transabdominal amnioinfusion with 150-350 ml warmed normal saline (25-50 ml/min) was performed at weekly intervals. Amniotic fluid volume was assessed ultrasonographically by means of the four-quadrant technique on a weekly basis before and after each amnioinfusion, as well as the short-term variability by a Hewlett-Packard computerized cardiotocographic system., Results: 18 women were enrolled and underwent prophylactic transabdominal amnioinfusion at weekly intervals until delivery. Eighteen controls, who did not undergo prophylactic amnioinfusion, were recruited from our 1992-1993 series and included in the study. The median interval between premature rupture of membranes and delivery was 3.0 weeks (range 1-8 weeks), with an average delivery age of 33.0 weeks (range 27-36 weeks). The latency period was significantly longer in patients who underwent prophylactic amnioinfusion (mean +/- SD, 4.1 +/- 1.7 weeks) than in controls(1.7 +/- 1.0 weeks; p < 0.001). An increase in both the weekly amniotic fluid index (linear regression analysis r = 0.8, p = 0.03) and the weekly short-term variability (linear regression analysis r = 0.82, p = 0.02) was observed among patients who underwent prophylactic amnioinfusion. A direct relationship was observed between the amniotic fluid index and short-term variability (linear regression analysis r = 0.54, p = 0.04). The mean values of fetal movements recorded by computerized tomography during the 20 min of observation significantly increased after amnioinfusion in comparison with those before it (2.6 +/- 0.9 and 0.9 +/- 0.7 respectively; p = 0.001)., Conclusion: The present study has shown a positive effect of prophylactic transabdominal amnioinfusion on the latency period in patients with preterm premature rupture of membranes and oligohydramnios. Among the patients who underwent amnioinfusion, an interesting improvement in fetal heart rate short-term variability was associated with the progressive increase in amniotic fluid volume, as an expression of fetal well-being.

Objective: The aim of the present study was to evaluate the dynamic changes in serially obtained amniotic fluid index values and to determine any association with intrapartum fetal distress in a term population., Materials and Methods: All patients, > or = 40 weeks of gestational age, evaluated at the Institute of Obstetrics and Gynecology, 'G. Salesi' Hospital, University of Ancona, between January 1, 1994, and December 31, 1995, participated in this longitudinal study. Women with an amniotic fluid index of > 50 mm, who also demonstrated a reactive nonstress test, underwent semiweekly amniotic fluid assessment until spontaneous labor. After 42 gestational weeks, the patients underwent an elective induction of labor. All patients were managed with continuous electronic fetal heart rate monitoring throughout labor. The incidence of intrapartum fetal distress, and meconium staining of amniotic fluid were evaluated with respect to the amniotic fluid index., Results: Of the 117 patients that were evaluated by ultrasound, 83 women had multiple amniotic fluid index measurements and were enrolled in the study. A serial decrease in amniotic fluid index was documented in 54 women; the mean decrease per week was 20.7 +/- 15.4%. An increase in amniotic fluid index was noted in 17, while 11 women showed no change in amniotic fluid index over time. The 14 patients who underwent cesarean section for fetal distress had a significantly lower amniotic fluid index (p < 0.001) at the last sonographic examination than the normal outcome group. Significant differences were also observed for a serial decrease in the amniotic fluid index within a week (p < 0.001). The sensitivity and specificity of the 30% serial decrease in the amniotic fluid index cutoff point, with respect to intrapartum fetal distress were 86 and 93%, respectively., Conclusion: Longitudinal measurement of the amniotic fluid index seems to be an effective method in predicting intrapartum fetal distress in a term population.

Objective: MIB 1 is a new monoclonal antibody which recognizes nuclei of proliferating cells throughout the cell cycle except during the G0 and early G1 phases. In the present study we analyzed the MIB 1 immunostaining as an index of cellular proliferation in cervical intraepithelial neoplasia (CIN) and microinvasive carcinoma, with the aim to identify a relationship with the degree of dysplastic lesion and the risk of neoplastic progression. A correlation between the MIB 1 index and human papillomavirus (HPV) DNA presence was also investigated, Methods: Cervical bioptic samples were consecutively obtained from 86 women who attended our Colposcopic Service from January 1993 to June 1994, because of abnormal pap smears suspicious for cervical dysplasia and/or HPV infection. On histologic evaluation, 41 women had CIN, 23 cervical condyloma, and 22 squamous metaplasia. Ten patients with microinvasive squamous cervical carcinoma, matched for age and demographic characteristics, were selected from our series of cervical carcinomas and immunohistochemically analyzed. The expression of primary tumor cellular proliferation was immunohistochemically evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on microwave oven-processed formalin-fixed paraffin-embedded tissue. Positive staining was expressed as the percentage of positive cells per 10(3) counted dysplastic cells for each case., Results: A progressive significant increase in positive MIB 1 immunostaining was observed from squamous metaplasia to microinvasive carcinoma throughout the CIN lesions (p < 0.001). Considering only CINs, the MIB 1 index showed a significant increase with respect to CIN degrees (p < 0.001); no correlation was found between MIB 1 immunostaining and HPV infection, and lesion size. By analyzing the MIB 1 index with respect to CIN outcome in mild and moderate dysplasias, regressive lesions had lower values of MIB 1 immunostaining, while persistent and progressive lesions presented significantly higher positivity (p < 0.001)., Conclusions: Our data demonstrated: (1) that positive MIB 1 immunostaining increased progressively from squamous metaplasia to CIN and microinvasive carcinoma, suggesting that neoplastic transformation is associated with a dysfunctional proliferation of cervical epithelium; (2) that there was a significant correlation between the MIB 1 index and CIN degree but not with respect to HPV DNA presence, and (3) that MIB 1 immunostaining might be useful for a clinical evaluation of mild and moderate dysplastic lesions. However, a much larger study needs to be done over a longer period of time to truly determine the value of the technique in prognostically predicting which lesions might or might not regress.

Objective: In the present study we investigated the cytologic and colposcopic characteristics of a cohort of HIV-infected women, with the aim to determine a relationship between immunologic status and frequency and/or severity of cervical abnormalities., Materials and Methods: 21 women, who tested positive for the HIV antibody and who were admitted as outpatients because of various gynecologic complications or because of an HIV infection that was under regular clinical surveillance. A pelvic examination was performed and Papanicolaou smears were obtained from endocervix and ectocervix before colposcopic examination. Cytologic samples for human papillomavirus (HPV) detection by polymerase chain reaction were also collected. Results obtained in the group of HIV-infected women were compared with findings in a group of 473 seronegative women recruited consecutively from our outpatient population. Serum samples for T lymphocytes were drawn within 2 weeks of cytologic and colposcopic examination. CD4 and CD8 monoclonal antibodies were purchased from Becton Dickinson (Mountain View, Calif., USA)., Results: HIV-infected women had a significantly higher percentage of HPV DNA positivity with respect to the outpatient population (67 vs. 7%, respectively, p < 0.001). Analysis of cytologic specimens revealed 9 women (43%) with cytologic evidence of cervical dysplasia in the HIV-seropositive group vs. 23 (5%) of 473 in the outpatient population (p < 0.001). All the HIV-seropositive women with cervical dysplasia presented an associated HPV DNA positivity; in particular, the percentage of associated HPV DNA type 16 in cervical dysplasia was 78% (7/9 cases). In HIV-infected women, the evaluation of T lymphocyte subset distribution suggested a significant relationship between CD4+ cell decrease and severity of cytologic findings (p = 0.03)., Discussion: The HIV-infected women had a tenfold higher prevalence of both HPV infection and cervical dysplasia than the outpatient population; this increased risk seems to be limited mainly to those who also had genital HPV infection. The analysis of immunologic status confirmed previous observations that an impaired immune system results in increased cervical disease.

Objective: To analyze longitudinally the basal natural killer cell activity in patients with invasive cervical carcinoma, the natural cytotoxicity was related to the most important known prognostic factors, and evaluated with respect to the clinical outcome of cervical disease., Materials and Methods: Forty-six patients with histologically proven invasive cervical carcinoma treated and followed at the Institute of Gynecology and Obstetrics, Ancona University, Salesi Hospital, were consecutively recruited from 1989 to 1992 and included into the study. For immunologic investigation, natural killer cell activity and peripheral blood T-lymphocyte subsets were tested before primary treatment and during the follow-up period, every 6 months. Natural killer activity was determined by target cell retention of the fluorescent dye carboxyfluorescein diacetate; the K 562 cell line was used as target cells., Results: A significant inverse relationship was observed between natural killer activity and disease stage (p = 0.001); patients with stage IV disease had the lowest level of natural cytotoxicity. The reduction of natural cytotoxicity was not accompanied by any alteration of lymphocyte distribution. The longitudinal analysis showed an increase of natural killer activity after surgical removal of the tumor, persisting during the follow-up, but all the 9 patients who recurred showed, at the time of disease recurrence, a significant decrease of their natural cytotoxic potential., Conclusion: Natural killer cell activity seems to be a functional index of immune status, significantly related to the stage and the clinical outcome of disease.

The objective was to examine the prevalence of human papillomavirus (HPV) DNA infection in mild cervical dysplasia and to evaluate longitudinally the persistence of HPV DNA positivity in an observational study, aiming at identifying the role of peripheral blood lymphocyte natural killer activity in the natural history of dysplastic disease. Twenty-three patients with histologically proven mild cervical dysplasia were selected. The HPV DNA positivity, determined by polymerase chain reaction, and cervical dysplasia were monitored cytologically and colposcopically at the 3rd (time 1), 6th (time 2) and 12th months (time 3), and defined by biopsies for routine histology taken at times 2 and 3. For each patient included in the study, the immune reactivity was evaluated at the time of diagnosis and afterwards, longitudinally during the follow-up. The immune status analysis included T lymphocyte subsets (CD3, CD4, CD8, CD56, CD16 monoclonal antibodies by Beckton Dickinson, Mountain View, Calif., USA) and determinations of natural killer cell activity (against the sensitive cell line K 562). Eighteen out of the 23 women with mild cervical dysplasia (78.3%) were found positive for HPV DNA, with a significantly high representation of HPV DNA type 16 (55.6% of cases). At the end of the study, 12 out of 18 HPV-DNA-positive women became negative (defined by two or more negative tests) for the original HPV DNA type, with 66.7% of spontaneous HPV DNA negativization rate (p = 0.6).(ABSTRACT TRUNCATED AT 250 WORDS)

The objective was to evaluate natural cytotoxicity of peripheral blood during interferon treatment in cervical intraepithelial neoplasia grade 2 (CIN2), as index of interferon activity. Twenty-one patients with CIN2, histologically proven, were treated with interferon alpha 2b (Intron A, Sheering-Plough Corp.), in a dose of 3,000,000 units three times per week for 8 weeks self-administered by intramuscular injection. The rate of remission to the interferon treatment was 38.1%. Eight healthy patients had a significant increase in natural killer activity during and after the treatment (p < 0.001), whereas the 13 nonresponder patients remained with low values of natural killer activity. By analyzing the basal natural killer activity before the treatment, the patients with clinicopathologic remission had a significantly higher mean value than nonresponder patients (p = 0.007). Notwithstanding the specimen exiguity, the individual basal natural killer activity seems to be a predictive parameter of interferon treatment response in patients with CIN2.

The objective of this study was to assess the human papillomavirus DNA presence in vaginal papillary lesions, with particular regard to micropapillomatosis to better define their clinical significance. Prospective study: the study population was composed of 62 women who were recruited consecutively from the Colposcopy Centre of the Ancona University, Department of Obstetrics and Gynecology, on the grounds of vaginal papillomatosis or/and typical acuminata warts. Biopsies for routine histology, and for human papillomavirus (HPV) DNA detection by means of in situ hybridization and polymerase chain reaction (PCR) were taken from the papillary lesions and from 24 healthy women, who were selected as controls. Macroscopically, vaginal micropapillomatosis was ascertained in 51 cases (82.3%), while in 11 cases (17.7%) the colposcopic diagnosis was condyloma acuminatum. During in situ hybridization, HPV DNA positivity was observed in 8 (9.4%) out of 85 samples of squamous papillae and in 11 (64.7%) out of 17 samples of condylomata; in control specimens, HPV DNA was detected in 2 (8.3%) out of 24 bioptic samples. The correspondence between in situ hybridization and PCR was 96.1%, with 17.4% more diagnosis obtained by PCR. Vaginal micropapillomatosis may be regarded as a variation in the normal anatomy of the lower genital tract without any significant relationship with HPV infection, and as a lesion easily distinguishable from condylomata acuminata by clinical examination alone.

A longitudinal evaluation of the natural killer (NK) cell activity of peripheral blood lymphocytes was performed in 17 patients with advanced ovarian cancer (treated surgically and with subsequent multiagent chemotherapy) for a median follow-up period of 32 months. At the time of primary treatment, the mean value of NK cell activity was significantly lower in patients who then had disease progression (p < 0.05) than in patients with progression-free survival. During the follow-up period, no significant modifications of the NK cell activity were observed; only at the time of clinical disease progression did the NK cell activity show a significant reduction. We conclude that the NK cell activity is a potentially important prognostic factor.

Basal natural killer (NK) cell activity in peripheral blood lymphocytes (PBLs) of 29 patients with gynecologic malignancy and 10 healthy controls was performed using K 562 cell line. A significant decrease of NK cell activity was observed in patients with gynecologic malignancy (p = 0.003). The NK cell activity of patients with poorly differentiated tumor or with stage IV of disease was significantly reduced with respect to patients at any other lower grade or earlier stage. We conclude that in patients with gynecologic malignancies there is a decrease of basal NK cell activity of PBLs, which is more significant in cases of distant tumor dissemination or poorly differentiated tumor (p less than 0.001).

We have studied the systemic T-lymphocyte subset and, in particular, the natural-killer (NK) activity in 23 patients with cervical intra-epithelial neoplasia (CIN), and 11 controls (a history of normal cervical PAP smears and colposcopy patterns). The lymphocyte phenotypes were studied using a panel of monoclonal antibodies, and NK activity was evaluated as the percentage lysis of K 562 target cells. In patients with CIN we found a significant decrease in NK activity (p = 0.002) which was directly correlated with the grade of CIN, with no alterations in the absolute number of NK cells.

Direct administration of isoxsuprine to the rat fetus increases placental transfer of 35S-methionine and this increase is statistically significant on day 17 as compared with intraperitoneal administration and controls (p less than 0.01; p less than 0.05). In contrast, no statistically significant differences were found between the groups on day 16.