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.

Role of the hypothalamus in the aging woman.

Relationships between the hypothalamus and the pituitary in the aging woman are discussed under the following subheadings: synthesis and release of follicle-stimulating and luteinizing hormones, estrogen receptors, other releasing factors, neurotransmitters, and the mechanisms of hot flushes and migrainoid headaches. The hypothalamus is the main regulator of pituitary function. In the female the hypothalamic-pituitary axis appears to remain functionally intact well into old age.

Danazol treatment of endometriosis: long-term follow-up.

Forty-nine women diagnosed as having pelvic endometriosis were treated with 800 mg of danazol/day for a mean duration of 6 months. The average length of the follow-up period was 78 months. Side effects were minimal, and regular ovulatory menses returned within 25 to 90 days (average 42 days). Forty-two (85.7% of these women had associated infertility. Recurrence of symptoms was reported in 33% but in no patient were the symptoms worse than before entering the study. Of 30 patients desirous of pregnancy, 20 were potentially fertile; of these, 10 conceived within 6 months of discontinuing therapy, for a conception rate of 50%. Nine of the remaining ten patients required additional therapeutic procedures (surgery and/or danazol), and four of these conceived within 12 months. These results compare favorably with those of other investigations, since most of our patients were referred to us after being subjected to a variety of regimens, both hormonal and surgical.

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.

Sequential chemo-immunotherapy treatment of metastatic malignant melanoma.

Twelve patients with recurring metastatic inoperable malignant melanoma (performance status ECOG 0-1), received the following chemotherapy: tamoxifen p.o., carmustine i.v., dacarbazine i.v., and cisplatin i.v., followed by immunotherapy: interleukin-2 s.c. and interferon-alpha s.c. The treatment cycle was repeated every 6 weeks. Total response rate was 66.6%, with 25% (3 patients) achieving complete cure that has persisted for a period of 17.75 months (mean). In addition, different responses to treatment were observed between the local recurrence lesions and the metastatic lesions. Medium to severe side effects were observed, all but one of them being reversible (neurotoxicity), such as fever, anemia, leukopenia: nephrotoxicity, neurotoxicity, and dyspnea.

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.

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.

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.

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.

The fate of a large bolus of exogenous estrogen administered to postmenopausal women.

Seventeen postmenopausal women were given a bolus of conjugated estrogens (USP, Premarin), 17 beta-estradiol and estriol orally, intravenously or by pellet implantation, and circulating levels of estrone, estradiol and/or estriol were measured by radioimmunoassay at various intervals during a 48--72-h period. Oral administration resulted in a marked rise in serum estrone; parenteral administration resulted in a marked increased in serum estradiol. There was no significant fall in serum gonadotropins during this period. Following estriol administration orally, there was a decided elevation in estriol levels but minimal change in estrone and estradiol.

Short-term verus long-term prophylactic tocolysis in patients with preterm premature rupture of membranes.

A randomised prospective clinical trial was conducted over a 7-year period (1987-1993) in the Department of Obstetrics and Gynaecology, University of Patras. The purpose of this study was to compare two management protocols of Preterm Premature Rupture of Membranes (PPROM). Two-hundred forty-one women entered the study and were assigned randomly to one of two groups. Group A consisted of 105 subjects who were managed expectantly (tocolysis used for 48 h only, if necessary, to permit full course of steroid therapy), while Group B consisted of 136 subjects, in whom aggressive tocolysis was utilised. The differences in the latency period (time from rupture of membranes to the onset of labour) were not statistically significant between the two groups. On the contrary, statistically significant differences in the incidence of chorioamnionitis and postpartum endomyometritis were found between the two groups (higher in Group B). Twelve subjects in Group A (12/105, 11.4%) and 40 in Group B (40/136, 29.4%) had chorioamnionitis. The relative risk (RR) was 2.47 (95% C.I. 1.42-4.66, P < 0.001). Endomyometritis was diagnosed in 20 subjects in Group A (20/105, 19%) and in 45 in Group B (45/136, 33.3%). The RR was 1.74 (95% C.I. 1.10-2.75, P < 0.05). These data suggest that long term prophylactic tocolytic therapy in patients with PPROM, while without demonstrated benefit, may result in an increased risk of maternal infectious morbidity, and raise the cost of treatment.

Subcutaneous hormone replacement therapy.

It is estimated that 75% of women are in an acute estrogen deficiency state within a few years after the onset of the menopause. Every woman inevitably reaches this phase except for a fortunate few who have some source of endogenous estrogens available to them. We believe it would be prudent to offer hormone replacement therapy to every woman with symptoms of the menopause, and to those in whom symptoms are not patently manifest, if an estrogen deficit is present as indicated by vaginal cytology. Certainly even in the absence of symptoms, the presence of osteoporosis is sufficient reason to initiate small doses of estrogens (along with increased calcium and protein uptake, and exercise) for the remainder of the woman's lifetime. Crystalline pellets of 17 beta-estradiol offer excellent relief of symptoms for those postmenopausal women who fare poorly on oral estrogens or intramuscular injections. Although somewhat more expensive than other modes of therapy, pellet use is convenient, highly effective and associated with few side effects.

Radiographic abnormalities in patients with Stein-Leventhal syndrome.

Radiographic abnormalities in 254 patients with Stein-Leventhal syndrome are presented in a retrospective study of the six-year period from 1972--1977. Twenty-two (8.7%) of the patients were found to have abnormal sella turcica x-rays, eight (3.2%) patients had abnormal hysterosalpingograms and five (2.0%) patients had abnormal intravenous pyelograms. In addition, three patients with an abnormal sella turcica had serum prolactin levels greater than 45 ng/ml, which should be regarded as evidence of a pituitary adenoma. These findings suggest that serum prolactin assays and skull x-rays with polytomography should be routinely performed on patients with Stein-Leventhal syndrome.

The significance of adrenal and ovarian catheterization in patients with polycystic ovary syndrome.

A previously unreported series of 15 anovulatory hirsute women with polycystic ovaries made up this study. Each underwent left adrenal and left ovarian vein catherization. Blood samples were obtained from the ovarian, adrenal and peripheral veins to test the levels of testosterone, delta 4 androstenedione (delta 4A), dehydroepiandrosterone (DHEA), estradiol and/or total estrogens, before and after administration of human chorionic gonadotropin (ten cases) and adrenocorticotropic hormone (ACTH) (five cases). Following intravenous human chorionic gonadotropin administration, the only response seen was a slight rise in ovarian levels of delta 4A and DHEA; after intravenous adrenocorticotropic hormone stimulation, the adrenal levels of delta 4A, testosterone and DHEA rose significantly. Peripheral concentrations of testosterone and delta 4A were in the high normal range and DHEA levels were high normal or slightly above normal range.

Insulin levels in the amniotic fluid and in maternal and fetal blood.

The effects of excessive maternal weight gain during pregnancy (five cases) and of glucose infusion in the mother (five cases) on insulin levels are compared with the insulin levels in a control group (19 normal pregnancies) by radioimmunologic determination of insulin levels in the amniotic fluid and in maternal and fetal blood. The mean values for insulin in the control group were as follows: mother, 23.9 +/- 2.23 muU per ml; fetus, 9.86 +/- 2.11 muU per ml; and amniotic fluid, 5.08 +/- 2.27 muU per ml. In patients with excessive weight gain during pregnancy, maternal insulin mean values were 38.45 +/- 4.16 muU per ml; fetal, 19.99 +/- 9.8 muU per ml; and amniotic fluid, 11.25 +/- 2.58 muU per ml. After an infusion of 25 mg of glucose in the mother, the mean maternal insulin values were 53.6 +/- 13.74 muU per ml; fetal, 24.7 +/- 6.67 muU per ml; and amniotic fluid, 14.3 +/- 5.52 muU per ml. Insulin concentrations in maternal blood (p less than 0.001), fetal blood (p less than 0.001) and amniotic fluid (p less than 0.001) were higher in pregnancies with excessive weight gain as compared to those in the control group, whereas the glucose infusion in the mother increased the concentration of insulin in the three components studied.

Treatment of benign breast disease with danazol: a follow-up report.

One hundred thirty-five women with benign breast disease (BBD) were treated with danazol, an impeded androgen. Their ages ranged from 19 to 60 years (mean age, 30). The dose varied from 100 to 800 mg per day for 90 to 180 days, depending upon the severity of the disorder. Overall relief of pain was observed in 97% and of tenderness in 90.5%. There was complete or marked improvement of nodosities in 73%. Seventy-eight patients were followed every six months for two to four years. The recurrent symptoms were pain in 6%, tenderness in 6% and nodosities in 10%. Incidentally, we found that 29.3% of infertile women with BBD conceived within 24 months after cessation of a course of therapy. The side effects, when present, were trivial.

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.

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.

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.