Increased activity of lysosomal enzymes in the peritoneal fluid of patients with gynecologic cancers and pelvic inflammatory disease.

PURPOSE: To investigate whether the activity of lysosomal enzymes is increased in the peritoneal fluid of patients with gynecologic cancers compared to activity in the peritoneal fluid from normal subjects and those with pelvic inflammatory disease, and fluid from benign ovarian cysts. PATIENTS AND METHODS: beta-glucuronidase, beta-galactosidase, and alpha-mannosidase activity was measured in the peritoneal fluid from patients with gynecologic cancer, pelvic inflammatory disease, and normal subjects, and fluid from benign ovarian cysts. RESULTS: The mean+/-SD of beta-glucuronidase, beta-galactosidase, and alpha-mannosidase activity in the gynecologic cancers was 120+/-50 nmol, 203+/-86 nmol, and 240+/-119 nmol 4-methylumbelliferone/ml/h, respectively; in the normal control subjects it was 22+/-9 nmol, 46+/-10 nmol, and 80+/-23 nmol, respectively (P=0.00003, 0.0001, and 0.0001, respectively). The activity was increased even in cases without malignant cells in the peritoneal fluid. In pelvic inflammatory disease it was 148+/-82 nmol, 278+/-112 nmol, and 291+/-140 nmol, respectively. The activity in the fluid of the ovarian cysts was similar to that of the normal peritoneal fluid. There was a significant positive correlation between enzyme activity and stage of cancer, that was stronger for beta-glucuronidase (r=0.889, P=0.003). CONCLUSION: The increased lysosomal enzyme activity in gynecologic cancers, without overlapping between patients and normal subjects or benign ovarian cyst fluid, indicates that such measurements might be applied for diagnostic purposes.

The effects of recombinant human erythropoietin given immediately after delivery to women with anaemia.

OBJECTIVE: Anaemia is a common problem during pregnancy and the puerperium. This study was designed to determine the efficacy and safety of giving recombinant human erythropoietin (EPO) to anaemic women during the puerperium. METHOD: Thirty-seven women received a single dose of EPO (20 000 IU intravenously) immediately after delivery. A control population (n = 37) matched according to age and haemoglobin concentration was evaluated. All women received oral iron supplementation for 40 days after delivery. Haemoglobin concentrations were measured 4 and 40 days after delivery. Blood transfusions were given depending on clinical condition and haemoglobin level. RESULTS: Patients treated with EPO had a significantly higher mean haemoglobin concentration than control patients at days 4 and 40. No women in the EPO group required a transfusion, compared with six in the control group. No side-effects and fewer anaemia-related symptoms were observed during EPO treatment. CONCLUSION: EPO given at delivery is effective in decreasing the need for blood transfusion and the incidence of problems associated with anaemia during the puerperium.

Clinical experience with Norplant subdermal implant system as long-term contraception during adolescence.

OBJECTIVE: This study was undertaken to assess the efficacy, acceptability and side-effects of the Norplant (Leiras) contraceptive system during adolescence. METHODS: A total of 13 adolescents were implanted with Norplant immediately after menstruation. Adolescents were advised to present for follow-up visits at 3 days after implantation, at 3, 6 and 12 months and every 1 year thereafter. Blood pressure, menstrual disorders, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, glucose and side-effects were recorded at every visit. RESULTS: The follow-up period was 24 months with a continuation rate of 100% (13/13) for the first 6 months, 92.5% (12/13) for 12 months and 53.8% (7/13) for the whole period. No pregnancies were observed. No infections at the implant site or expulsions were observed. Menorrhagia was observed in 4/13 (30.76%) adolescents in the third month. Thereafter all adolescents were treated with tenoxicam (prostaglandin synthetase inhibitor), so that by the end of the sixth month of treatment menorrhagia was not present in any of the 13 adolescents. No increase of blood pressure was observed. A statistically significant increase (p < 0.01) of triglycerides at 6 months after implantation was found; however, no difference was observed in the values of serum glucose, total cholesterol, HDL and LDL. CONCLUSIONS: This preliminary study has shown that Norplant is acceptable as a contraceptive method among adolescents in Greece and can be prescribed safely.

Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

Anticardiolipin antibodies levels in healthy pregnant and non-pregnant woman.

To determine the prevalence of anticardiolipin antibodies in healthy non pregnant women and during normal pregnancy, 110 healthy women of mean age 25 years old and 53 healthy pregnant females of mean age 24.5 years old, who no one suffered from any autoimmune disease, were studied. In all women the anticardiolipin antibodies were measured in duplicate by the Enzyme Linked Immunosorbent Assay (ELISA). There was no difference in the percentage of the positive anticardiolipin antibodies between non pregnant and pregnant healthy women (9.1% and 5.6% respectively). Also, there was no difference in the antibodies levels during normal pregnancy, as well as, during an equal time of observation in non pregnant women. The positive anticardiolipin antibodies levels were low.

Investigation of kinetic of lead during pregnancy and lactation.

Lead concentration was estimated in peripheral blood, milk as well as in cord blood in 47 women and their infants, using atomic absorption spectrophotometry. Mean maternal blood lead concentration was 14.9 +/- 4.1 microg/dl, while in milk a mean level of 2.0 +/- 0. 5 microg/dl was estimated. Mean lead concentration in cord blood was 13.1 +/- 3.7 microg/dl. Analysis of these data showed a statistically significant correlation between lead maternal and cord blood concentration (r = 0.413, p = 0.01) or maternal blood and milk (r = 0.543, p < 0.01). The difference between maternal and cord blood might be indicative of a small filtering effect of placental tissue on lead transfer to the fetus. Placenta can determine 57.4% of the level of lead transferred to the fetus in a dynamic modus, while 42.6% depends on the pollution's level of mothers.

Tenoxicam versus lynestrenol-ethinyl estradiol treatment of dysfunctional uterine bleeding cases during adolescence.

BACKGROUND: The purpose of this study was to compare the effectiveness of tenoxicam versus lynestrenol-ethinyl estradiol (L-EE) in the treatment of severe cases of dysfunctional uterine bleeding (DUB) during adolescence. METHODS: Forty-eight patients with objective DUB completed a randomized comparative trial of treatment with tenoxicam (20 mg daily, n = 23) or L-EE (1 tablet containing 0.05 mg + 2.5 mg, respectively, 3 times daily, n = 25). Treatment was given during menorrhagia until bleeding ceased. Mean age of the patients was 13.74 +/- 2.1 years (range, 11-18 years). RESULTS: A significantly higher level of hematocrit (35.9% v 32.6%, t = 2.1, P = 0.0217) and hemoglobin (11.5 v 10.4 g%, t = 1.7, P = 0.0495), and significantly less hospitalization (5.75 v 8.33 days, t = 2.45, P = 0.0106) was seen in the tenoxicam group in comparison to L-EE group after completion of the treatment. Three patients were submitted to curettage and seven to transfusion in the group receiving L-EE, but no patients in the tenoxicam group required these procedures. CONCLUSIONS: Tenoxicam is considered an effective medication for the management of DUB during adolescence.

Gynecologic cancer and surgical infectious morbidity.

The purpose of this study was to evaluate retrospectively the surgical infectious morbidity in gynecologic cancer. We examined 1,180 gynecologic oncology patients: 608 women had carcinoma of the endometrium, 510 cancer of the cervix, 48 ovarian cancer and 14 vulvar cancer. Thirty-five (6%), 92 (18%), 7 (15%) and 2 (14%) were complicated by infection in carcinoma of the endometrium, cancer of the cervix, ovarian cancer and vulvar cancer, respectively. Our conclusion is that the highest surgical infectious morbidity occurs in patients with cervical cancer and the lowest in patients with carcinoma of the endometrium.

Treatment of recurrent genital herpes with interferon alpha-2alpha.

The purpose of the present study was to evaluate the efficacy and safety of parenteral administration of interferon alpha-2alpha in the treatment of recurrent herpes genitalis. A total of 97 patients (66 males, 31 females, mean age 34.86 +/-16.74 years), who had at least five recurrences of genital herpes during the previous 12 months, participated in a prospective open study on the effects of treatment with interferon alpha-2alpha (Roferon-A; Roche). The patients were treated with interferon alpha-2alpha (3 x 10(6) IU) by subcutaneous injection, three times weekly for 4 weeks, and the same schedule was repeated after 3 and 6 months. All patients were asymptomatic at the start of the study. After initiation of treatment, all patients reported to the clinic every 3 months for 2 years (the males were submitted to peoscopy and the females to Pap test and colposcopy) at the time of their recurrences. Comparison was made of the number of recurrences, duration of lesions, duration and severity of pain, and itching and burning. Prophylactic administration of interferon alpha-2alpha prevented recurrences of genital herpes virus infection in 51 patients (20 males and 31 females). Interferon administration shortened the healing time from 8.5 days before treatment to 2.5 days after treatment (p < 0.001). There was a significant reduction in the number of recurrences during the study period, from 7.46 before treatment to 2.64 after treatment (p < 0.001). On the basis of the overall efficacy and adverse effects, this regimen may be of value in the routine treatment of recurrent herpes.

Treatment of penile intraepithelial neoplasia (PIN) with interferon alpha-2a, CO2 laser (vaporization) and 5-fluorouracil 5% (5-FU).

This study was undertaken to assess the effectiveness of CO2 laser (vaporization), 5-FU topical application and Interferon (IFN alpha-2a) parenterally in the therapy of penile intraepithelial neoplasia (PIN). From March 1986 to September 1991, 1,372 men, sexual partners of women with condylomata accuminata or flat or cervical intraepithelial neoplasia (CIN), were submitted to peoscopy, of 1,019 men who presented with various lesions caused by human papillomavirus (HPV)-confirmed histologically-208 were treated for PIN. The best treatment modalities irrespective of grade of lesion were found to be the combination of 5-FU plus CO2 laser vaporisation plus IFN alpha-2a (high dose) (96.15%), the combination of 5-FU plus CO2 laser vaporization (87.09%) and the combination of CO2 laser vaporization plus IFN alpha-2a (high dose) (80%). It is concluded that IFN alpha-2a (low dose) can be used as first line treatment in combination with 5-FU in patients with PIN II and as an adjuvant treatment (high dose) in patients with recurrent PIN I and PIN III.

Postmenopausal uterine bleeding.

The purpose of this study was to evaluate the incidence of the etiologic factors of postmenopausal uterine bleeding and the recurrence rate of uterine bleeding before total hysterectomy. Six hundred and twenty-eight patients (mean age 52.2) with postmenopausal uterine bleeding were studied. Atrophic endometrium was found in 522 cases (83.1%), carcinoma of the endometrium in 70 cases (11.1%), proliferative endometrium in 29 cases (4.6%) and secretory endometrium in 7 cases (1.1%). The recurrence rate of uterine bleeding was very high in carcinoma of the endometrium, moderate in proliferative endometrium and low in secretory and atrophic endometrium.

Peoscopic diagnosis of flat condyloma and penile intraepithelial neoplasia. Clinical manifestation.

Peoscopy was performed in order to assess penile lesions in the male sexual partners of 326 women with cervical intraepithelial neoplasia (CIN) or flat condyloma (FC). Each patient was submitted to a careful naked-eye inspection, peoscopy and biopsy of any suspicious lesion which was confirmed histologically and immunohistochemically. A brush cytologic examination of the distal portion of the urethra was also performed. The distribution of penile lesions was as follows: (1) 8 patients with herpes virus infection; (2) 37 patients with condyloma accuminata (CA); (3) 89 patients with FC; (4) 51 patients with FC and CA; (5) 18 patients with penile intraepithelial neoplasia grade 1 (PIN-I); (6) 2 patients with PIN-II; (7) 17 patients with PIN-III; (8) 92 patients with no penile lesions; (9) 7 patients with human papilloma virus infection of papillae coronae glandis, and (10) 5 patients with FC of the distal portion of the urethra. Naked-eye inspection revealed the presence of penile lesions in 39 of 233 patients (16.73%). Peoscopic examination revealed the presence of penile lesions in 233 of 326 patients (71.48%). In 135 of 155 patients the peoscopic findings were in accordance with the histologic diagnosis (87.09%). Immunohistochemical (by indirect peroxidase-antiperoxidase method) detection of virus antigens was positive in 16 of 34 patients (47.03%). It is concluded that peoscopy of the male sexual partners of women with CIN or FC should be performed to better assess the treatment used in the couple.

Incidence of benign and malignant breast disorders in women taking hormones (contraceptive pill or hormonal replacement therapy).

The incidence of breast disorders, in a series of 142 women of reproductive age who received combined oral contraception (OC) for birth control and in 98 postmenopausal women who received hormone replacement therapy (HRT) with estrogens and progestins, for seven years, was compared with control groups. A lower incidence of benign breast diseases was observed among OC users (p < 0.001) and HRT recipients (p < 0.001). No differences were observed in the incidence of breast cancer among the groups studied. OC use and HRT do not increase the risk for breast cancer and decrease the incidence of benign breast diseases.

PIP: To assess the association between benign and malignant breast disease and hormone use, the incidence of such disorders was compared in 142 women (mean age, 29.9 years) who took combined oral contraceptives (OCs) for birth control and 98 postmenopausal women (mean age, 59.4 years) receiving hormone replacement therapy (HRT). The duration of use in both groups was 7 years. Women with a family history of breast cancer were excluded. Controls for OC users included 975 recruited from a family planning clinic; 323 women attending a menopause clinic served as controls for the HRT group. Participants received both mammography and/or breast ultrasound at baseline and at regular age-appropriate intervals. A statistically significant (p 0.001) difference between hormone users and controls was observed in the incidence of benign breast disease. There were 45 cases (31.69%) of benign breast disease among OC users compared with 536 (54.97%) among their controls and 19 such cases (19.88%) among HRT users compared with 121 (37.46%) among their controls. There was no observed breast cancer among women in either the OC or HRT group. These findings support the hypothesis that hormonal treatment has a beneficial effect on breast tissue and does not increase the risk of breast cancer.

Treatment of men with flat (FC) or acuminata (CA) condylomata with interferon alpha-2a.

This study was undertaken to assess the effect of CO2 laser vaporization, 5-fluorouracil 5% (5-FU) topical application and Interferon alpha-2a (IFA alpha-2a) in the treatment of C.A. or F.C. of the male genital tract. From March 1986 to September 1991, 1372 men, sexual partners of women with F.C. or C.A. or cervical intraepithelial neoplasia, were submitted to peoscopy. One thousand and nineteen (74.27%) men presented with various penile lesions caused by HPV (histologically confirmed); of these 505 were treated for C.A. or F.C. or a combination of F.C. and C.A. The best treatment modalities, irrespective of the kind of lesion, were found to be the combination of 5-FU plus IFN alpha-2a (high dose) (98.27%), the combination of CO2 laser vaporization plus 5-FU plus IFN alpha-2a (high dose) (93.93%) and the combination of CO2 laser vaporization plus 5-FU (87.23%). In conclusion we believe that IFN alpha-2a can be used with excellent results as first line treatment in combination with CO2 laser vaporization or/plus 5-FU in patients with C.A. or F.C. or combined condylomata.

Comparative study of systemic interferon alfa-2a with oral isotretinoin and oral isotretinoin alone in the treatment of recurrent condylomata accuminata.

OBJECTIVES: We attempted to test the hypothesis that the combination of systemic interferon alfa-2a and oral isotretinoin is more effective than isotretinoin alone in the treatment of recurrent condylomata accuminata. STUDY DESIGN: Fifty seven women with recurrent condylomata accuminata were randomly assigned in two groups. Group A (n = 24) received isotretinoin alone (Roaccutan, Roche) 1 mg/kgr orally daily for 3 months or until a remission was achieved; Group B (n = 33) received Interferon alfa-2a (Roferon-A, Roche) 3 million units subcutaneously three times for 8 weeks plus isotretinoin 1 mg/Kg orally for 3 months or until a remission was achieved. RESULTS: There was no statistically significance in remission rates between the two groups (18/24 vs 28/33, p > 0.1). However the duration of treatment was statistically significantly shorter in Group B (1.9 vs 2.5 months, p < 0.01). Side effects were minimal.

Treatment of cervical intraepithelial neoplasia (CIN) with interferon alpha-2a, CO2 laser (vaporization, cone) and 5-fluorouracil.

This study was undertaken to assess the effect of CO2 laser (vaporization, conization), 5-FU topical application and interferon alpha-2a parenterally in the therapy of GIN. Three hundred and forty-seven (347) women with CIN were treated with CO2 laser (vaporization, conization), 5-FU topical application and interferon alpha-2a parenterally. The cure rates in the various treatment groups were analysed by the chi(2) test. The most effective treatment used for CIN I was the combination of CO2 laser vaporization plus 5-FU (p<0.05). The most effective treatment used for CIN II was the combination of CO2 laser vaporization plus 5-FU (p<0.001). The treatment modalities used for patients with CIN III achieved the same therapeutic results (p>0.1). The addition of interferon does not achieve better cure rates in patients with CIN.

Treatment of flat or accuminata condylomata of female genital tract.

This prospective study was undertaken to test the hypothesis that if the male partners of women with condylomata accuminata or flat are treated, the treatment failure rate, of women, decreases. From March 1986 to October 1992, 246 women with condylomata accuminata or flat were presented. The women were assigned into 4 groups. Group A (n=64) women whose partners were submitted to peoscopy and then treated if appropriate; moreover condom use was prescribed for one year. Group B (n=79) women whose partners were not submitted to peoscopy and not treated but they used condoms for one year. Group C (n=40) women whose partners were submitted to peoscopy and then treated if appropriate but without the use of condoms. Group D (n=63) women whose partners were not submitted to peoscopy, not treated and without the use of condoms. The treatment failure rate of women of group A (peoscopy, treatment, condom) was 29.68% and was independent upon the treatment of male sexual partners because of the use of condom (chi(2)=2.32, p>0.1). The treatment failure rate of group B (no peoscopy, no treatment, condom) was 32.91%. The treatment failure rate of group C (peoscopy, treatment, no condom) was 47.5% and was dependent upon the treatment of male sexual partners (chi(2)=14.71, p<0.001). The treatment failure rate of group D (no peoscopy, no treatment, no condom) was 69.84%. The results of this study supports the hypothesis that the treatment failure rate of women with flat or accuminata condylomata decreases if their male sexual partners are also treated.

Peoscopic diagnosis of flat condyloma and penile intraepithelial neoplasia V scrotal reservoir.

The aim of the present study was to evaluate prospectively male sexual partners of women with flat condyloma (FC) or accuminata (CA) or cervical intraepithelial neoplasia (CIN) and to determine the incidence of scrotal involvement by HPV. Of the 218 patients, 20 (9.17%) revealed areas of acetowhite epithelium involving the anterior lateral and superior aspects of the scrotum. Eight patients (40%) also presented concomitant small telangiectatic lesions measuring 1-3 mm of the scrotum in the acetowhite areas, and one patient presented scrotal intraepithelial neoplasia grade I (SIN I). The new combination treatment schedule (cream 5-fluorouracil 5% + Interferon alpha-2 alpha) resulted in a 100% cure rate, with no recurrences for the follow-up period (11.52 months). Concluding, the scrotum appears to be an important and presently overlooked area in the evaluation of male patients, and interferon in combination with 5-FU cream seems to be a promising treatment for HPV infection.

Treatment of flat or accuminata condylomata of the female genital tract with interferon alpha-2 alpha.

This study was undertaken to assess the effectiveness of Interferon administered parenterally in the treatment of flat or accuminata condylomata of the female genital tract. One hundred and forty-three women with condylomata were treated with CO2 laser vaporization, 5-FU topical application and interferon alpha-2 alpha (IFN alpha-2 alpha) parenterally. The cure rates in the various treatment groups were analysed by the chi-square test. The cure rates of the treatments used in the patients with condylomata accuminata were similar (p>0.1). The best cure rate for flat condylomata was achieved with the combination of CO2 laser vaporization plus 5-FU plus IFN alpha-2 alpha (high dose) (p<0.01). In conclusion, Interferon can be used as adjuvant treatment in patients with recalcitrant condylomata accuminata and as first line treatment in combination with 5-FU and CO2 laser vaporization in patients with flat condylomata.