Oral contraceptives and cervical carcinoma in situ in Chile.

A case-control study of cervical carcinoma in situ was conducted in Santiago, Chile, to determine whether risk of this condition is altered by use of oral contraceptives. Responses to a standardized questionnaire were compared in 133 hospitalized cases and 254 age-matched controls selected from the same screening program through which the cases were detected. After controlling for the possible confounding influence of a variety of indices of sexual behavior, socioeconomic status, and prior cytological smears, no increase in risk was found in women who ever used oral contraceptives. No trend of increasing or decreasing risk was seen in relation to duration of use, up to more than 6 years of exposure, or with the passage of time from either initial or most recent exposure. An observed increase in risk in current users of oral contraceptives was not considered likely to represent a causal relationship.

PIP: A case-control study of cervical carcinoma in situ was conducted in Santiago, Chile, to determine whether risk of this condition is altered by the use of oral contraceptives (OCs). Responses to a standardized questionnaire were compared in 133 hospitalized cases and 254 age-matched controls selected from the same screening program through which the cases were detected. After controlling for the possible confounding influence of a variety of indices of sexual behavior, socioeconomic status, and prior cytological smears, no increase in risk was found in women who had ever used OCs. No trend of increasing or decreasing risk was seen in relation to duration of use, up to more than 6 years of exposure. An observed increase in risk in current OC users was not considered likely to represent a causal relationship.

Ovulation induction: ovarian response to human gonadotropins and synthetic gonadotropin-releasing hormone.

Human ovarian responses to FSH- and LH-releasing hormone (FSH/LH-RH) were observed at laparotomy and studies by histologic and histochemical examination of ovarian biopsy specimens. The responses were compared to those induced by human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) singly and together. The subjects were healthy, fertile, young women rendered anovulatory by injections of depomedroxyprogesterone acetate (DMPA) or depochlormadinone acetate (CA). Supplementary studies included measurement of urinary pregnanediol, examination of the cervix and vagina for estrogenic and progestational responses, and endometrial biopsy, Both HMG and HCG induced follicular growth and proliferation of granulosa and theca cells, but neither, when given alone, induced ovulation or corpus luteum formation. When given in conjunction they induced single or multiple ovulations and corpora lutea in 11 of 18 women treated. FSH/LH-RH CONSISTENTLY STIMULATED FOLLICULAR DEVELOPMENT AND INDUCED OVULATION IN 2 OF 16 WOMEN TREATED. Preovulatory mature follicles were found in 3 more. FSH/LH-RH may prove to be useful in the treatment of some cases of anovulatory sterility of hypothalamic origin.

Prevalence and standardized incidence rates of preclinical cervical pathology among 1,061 women sterilized with transcervical quinacrine hydrochloride pellets.

OBJECTIVE: To determine whether the incidence of in situ cervical carcinoma was increased among a cohort of women who received transcervical insertions of quinacrine hydrochloride pellets into the uterine cavity as a method of nonsurgical sterilization. DESIGN: Retrospective review of Papanicolaou (Pap) test results, comparing incidence of high-grade lesions among quinacrine acceptors with a comparison population. SETTING: Outpatient clinics, Santiago, Chile. SUBJECTS: Women attending a family planning clinic (quinacrine acceptors) and a comparison population from another area of Santiago. MAIN OUTCOME MEASURE: Incidence of in situ cervical carcinoma. RESULTS: During 3,668 woman-years of follow-up, 8 women in the quinacrine group were found to have in situ carcinomas for an age-adjusted rate of 2.62 per 1,000 woman-years. The incidence in a comparison population was 1.62 per 1,000 woman-years, but the difference was not statistically different. CONCLUSIONS: The age-standardized incidence of in situ carcinoma among the quinacrine sterilized women was not significantly different from the rate in a comparison population of women in Santiago. However, the study has a number of limitations.

PIP: To determine whether transcervical quinacrine hydrochloride sterilization increases the risk of in situ cervical cancer, Papanicolaou smear data from 1061 women who underwent this procedure in Santiago, Chile, in 1977-90 were compared to those from a similar group of nonsterilized Santiago women. The average length of follow-up was 3.5 years in the quinacrine group and 2.4 years among controls. The 3285 woman-years of exposure recorded in the quinacrine group yielded 8 cases of in situ cervical carcinoma; among controls, there were 22 cases in 12,355 woman-years of observation. The crude incidence rates of high-grade cervical pathology were 2.18/1000 woman-years in the quinacrine group and 1.78/1000 among controls, for a crude rate ratio of 1.37 (95% confidence interval, 0.61-3.07). The age-standardized rates were 8.62/3285 or 2.62/1000 woman-years and 19.96/12.355 or 1.62/1000 woman-years, respectively, yielding a nonsignificant rate ratio of 1.62 (95% confidence interval, 0.73-3.61). Although this study suggests that quinacrine sterilization is not associated with an increased risk of cervical carcinoma, the analysis was limited by differences in the length of follow-up between the two groups, the non-uniformity of recruitment and follow-up procedures, and an absence of data on other risk factors for cervical cancer. Additional research on the toxicity of quinacrine is planned to better assess its possible carcinogenicity.

Cancer risk among women sterilized with transcervical quinacrine in Chile: an update through 1996.

OBJECTIVE: To determine whether further follow-up of a cohort of Chilean women would demonstrate an increased risk of invasive cancer associated with quinacrine sterilization. DESIGN: Cohort study. Cancer cases were evaluated using cohort analyses. SETTING: Santiago and Valdivia, Chile. SUBJECT(S): Fourteen hundred ninety-two women who received transcervical quinacrine pellets for contraceptive sterilization between 1977 and 1989. METHOD(S): Interviews and reviews of medical records. MAIN OUTCOME MEASURE(S): Age- and site-specific incidence of invasive cancers. RESULT(S): During 13,444 person-years of follow-up, 25 invasive cancers were identified, including 8 new cases. This compares with 21.9 expected cancers, based on age-specific rates from the Cali, Colombia, cancer registry. Eight cases of cervical cancer were observed, compared with the 6.3 expected. Since the initial study's confirmation of a single case of leiomyosarcoma, no other noncervical uterine cancers have been diagnosed. The number of observed person-years gives an expectation of 0.62 noncervical uterine cancers. One case of ovarian cancer was diagnosed, compared with the 0.99 expected. CONCLUSION(S): Rates of cancer among women exposed to intrauterine quinacrine are not significantly different from population-based rates.

Quinacrine and copper, compounds with anticonceptive and antineoplastic activity.

Changes in the evolution of a malignant transplantable tumor in mice to whom quinacrine, copper and zinc were supplied in drinking water are reported. Male AJ mice were inoculated in the right thigh with 1,000,000 TA3 or TA3 MTXR tumoral cells. Three experiments were designed with different types of tumors and different schedules of quinacrine and cations administered in drinking water. The animals that received quinacrine or quinacrine plus copper in drinking water had significantly smaller tumors, and some groups had a high rate of complete tumor regression (up to 60%). Quinacrine and copper have synergistic antineoplastic activity. Zinc salts do not improve the antitumoral effect of quinacrine. The relevant fact of this experiment lies in the fact that a large number of women using IUDs with copper could occasionally be treated with quinacrine.

Quinacrine: sclerosing agent of the utero-tubal junction in women, with anticarcinogenic actions in transplanted tumors in mice.

Quinacrine, an acridine derivative that was in widespread use as an anti-malarial, has been shown to have both sclerosant and anticarcinogenic actions. The sclerosant action of quinacrine has been used to produce occlusion of Fallopian tube in both experimental animals and women, and several clinical studies are reviewed. Both actions of quinacrine are potentiated by steroidal and non-steroidal antiprostaglandins as well as by ionic copper. Combinations of quinacrine with antiprostaglandin drugs, and also with copper, improved the efficacy of quinacrine when used for female sterilization and reduced side effects. A review of the experimental and epidemiological evidence suggests that quinacrine has no carcinogenic effects.

Contraceptive efficacy of two different metals using a modified seven vector.

Early studies with copper suggested that few improvements in overall IUD performance could be obtained with the use of more than 200 mm2 of copper. Thus, the use of other metals paired with copper has been investigated. This report of two studies of the small Copper-7, one with zinc and the other with copper alone, suggests that the addition of zinc in the superior position of the small Cu-7 decreases the incidence of pregnancy and that the small Cu-7 may be associated with higher retention rates than the standard Cu-7.

Evaluation of proposed cytomorphologic criteria for the diagnosis of Chlamydia trachomatis in Papanicolaou smears.

To evaluate the proposed cytomorphologic criteria for the cervical cytologic diagnosis of Chlamydia trachomatis infection, a study was made of 171 endocervical smears. All cytomorphologic elements that could be ascribed to Chlamydia trachomatis infection were correlated with the diagnostic confirmation of this microorganism by monoclonal antibody (MAb) staining. The presence of Chlamydia trachomatis was detected in 21 samples (12.28%) by MAb staining. Comparing the cytomorphologic results with the MAb results, the sensitivities and specificities of the Papanicolaou smear diagnoses were 19% and 86% using the cytologic criteria proposed by Gupta and coworkers, 38% and 87% using the criteria proposed by Kiviat and coworkers and 23% and 91% using the criteria proposed by Shiina. In view of (1) its low sensitivity, (2) the subjective elements and individual variations in the proposed cytologic criteria, (3) the similarity with Trichomonas vaginalis-produced exudates and (4) the implications of a misdiagnosis of a sexually transmitted disease, it is concluded that cervical cytology is not useful for ascertaining the presence of Chlamydia trachomatis.

[Particpation of apoptosis in immunologic processes]. / Participación de la apoptosis en los procesos inmunológicos.

Apoptosis is a biological process that leads certain cells to die in a controlled fashion. Its biochemical manifestation is DNA fragmentation due to the action of an endonuclease and morphological consequence is the formation of apoptotic bodies, seen with light or electron microscopy. Apoptosis is universally important in embryogenesis and morphogenesis of all tissues. Lately, a fundamental role of apoptosis in the physiology and physiopathology of immunological events has been uncovered. This review details the role of apoptosis in the development of auto-tolerance, immunological memory and AIDS pathogenesis.

[Female non-surgical sterilization: use of endo-uterine quinacrine and betamethasone pellets. Review of the subject: experimental bases--pharmacology--toxicology--efficacy]. / Stérilisation féminine non chirurgicale: utilisation de pellets endo-utérins de quinacrine et bétaméthasone. Révision du sujet: bases expérimentales--pharmacologie--toxicologie--efficacité.

Quinacrine produces obstruction of the region of the uterine tube by its fibroblastic granulomatous action. Factors such as the Zn++ and Cu++ content of tubal tissue, as well as the use of anti-prostaglandins, potentialise this action. Two groups of patients were evaluated in this study: Group A--95 women. 180 mg of quinacrine +0.6 mg of betamethasone were inserted into the uterine cavity, on the basis of two insertions separated by a one month interval. Two pregnancies were found by the end of the 2nd year, the percentage failure rate being 2.2 and the Pearl index 0.58. Group B--129 women. 216 mg of quinacrine +1.2 mg of betamethasone were inserted into the uterine cavity, on the basis of two insertions separated by a one month interval. Two pregnancies were found by the end of the 1st year, the percentage failure rate being 0.59 and the Pearl index 0.54. Iatrogenic adverse reactions associated with quinacrine only were not seen in either of these two study groups. None of the pregnancies was ectopic.

[Oviductal physiological alterations and endosalpingiosis (author's transl)]. / Alteración de la fisiología de las trompas de falopio por la endosalpingiosis.

A study was made of the oviducts from 110 patients salpingectomized between 1943 and 1976, after endosalpingiosis had been diagnosed. All of the patients were infertile women in whom histopathology performed after surgery revealed diverticula located mainly in the isthmic and interstitial portions of the oviductal wall. By either continuity or invasion, these configurations spread the endosalpingeal epithelium into the peritoneum and/or the ovary. Endosalpingiosis affects the muscular layer of the oviduct, which becomes thickened and rigid, thus accounting for the severe alterations of tubal physiology. The clinical aspects and microscopy of endosalpingiosis are described, and their differences from those of adnexo-peritoneal endometriosis are discussed.

[Superficial invasive squamous carcinoma of the vulva]. / Carcinoma escamoso invasor superficial de la vulva.

We present our experience at University of Chile Clinical Hospital, about superficial scamous vulvar carcinoma, during January, 1967 and april, 1992. We studied eight patients, mean age 57.1 years. Diagnostic was histopathologic in all cases. Three patients were submitted to simple total vulvectomy; other three were treated by total vulvectomy and bilateral inguinal lymphadenectomy (classic form of treatment). The other two cases, were submitted to simple in one case and partial vulvectomy in other, with lymphadenectomy by separate bilateral inguinal incisions. Histopathological study proved in situ scamous carcinoma near invasive focus at 50% of all cases. Follow up was between 2 and 25 years, mean 10.5 years. In one patient, carcinoma in situ relapsed at 2 years and 8 months after treatment, and then, at 8 years after primitive treatment. In other patient, and anal carcinoma was demonstrated 20 years after vulvectomy.

[Intraepithelial squamous cell carcinoma of the vulva, 1972-1989]. / Carcinoma escamoso intraepitelial de la vulva, 1972-1989.

We report our experience about intraepithelial squamous carcinoma of the vulva, consisting of 20 cases with clinical and histopathological diagnosis, at the University of Chile Clinical Hospital. Between december 1972 and october 1989. The age of patients was between 30 and 78 years old, median age 57.6 years old. Clinical HPV infection was detected in three cases (15%) 17 patients were submitted to simple total, vulvectomy (94.5%) without operatory mortality. The follow-up was between 3 months and 11 years (mean follow-up 6.5 years). Recurrence was observed in 2 patients (11.1%) of the 18 submitted to treatment.

[Analysis of the association between previous contraceptive use and the incidence of cervico-uterine cancer in women from the northern and eastern area of Santiago]. / Análisis de la asociación entre uso previo de anticonceptivos e incidencia de cáncer cervicouterino en mujeres del area norte y oriente de Santiago.

PIP: The case-control method was used to analyze records of 85 women with cervical cancer detected by screening in the northern area of Santiago, Chile, to assess a possible relationship of oral contraceptive (OC) use and cervical cancer. Epidemiologic methods used to assess the association between OCs and cervical cancer were 1st described. Several of the cohort studies failed to provide adequate controls or to take into account the factor of sexual promiscuity. Most of the case control studies found no risk or a slight increase in risk; the study finding the greatest relative risk had inadequate controls. In the present study, 4 controls were sought for each case matched by age, parity, year of examination, and number of previous cytological examinations. The average age was 45.18 for the 85 cases and 44.28 for the 268 controls. The average parity was 3.73 for cases and 3.72 for controls. The average number of previous examinations was 3.46 for cases and 5.79 for controls. At the time of the examinations, 6 cases and 14 controls used OCs, no cases and 1 control used injectables, 24 cases and 118 controls used IUDs, 5 cases and 13 controls used other methods, and 51 cases and 117 controls used no method. No increase in the relative risk of developing cervical cancer was detected among OC users.^ieng

Opposing effects of quinacrine and chloroquine on the development of TA3 transplanted tumors in mice.

Both quinacrine and chloroquine had been used as antimalarial agents. Furthermore, antineoplastic and antiviral effects have been described for quinacrine, while chloroquine has been described to induce viral replication and promote tumor growth. To search for differences in the growing rate of transplanted tumors, chloroquine or quinacrine were administered orally to AJ mice from 30 days previous to the inoculation of TA3 transplantable tumor cells, treatment being continued up to the end of the experiment. A control group, transplanted with tumor cells received tap drinking water. Marked differences between the three groups were found. Quinacrine had antitumoral effect, while chloroquine promoted a faster tumoral growth than controls. (p < 0.01). Results suggest caution in the use of chloroquine, because it might have a similar promoting effect on human neoplasia.

Endometrial findings in postmenopausal women receiving long-term estrogen therapy.

An histological study of the endometrium of 43 postmenopausal women under the chronic effect of cyclically administered conjugated estrogens was performed. Four atypical hyperplasias and one adenocarcinoma in situ were found. The frequency of these findings is similar to the one found in a sample of the population consulting the gynecologic clinic of our Hospital that never received estrogen therapy.

[Standardized rates of incidence and prevalence of cervical preclinical pathology in 1,061 women sterilized with intrauterine quinacrine]. / Tasas estandarizadas de incidencia y prevalencia de patologia cervical preclínica en 1061 mujeres esterilizadas con quinacrina intrauterina.

The use of intrauterine quinacrine, as a esterilization method in women during the period of fertility age, demonstrated no relation whatsoever with increase in cervical cancer comparative with the rest of the population. This study was done in 1061 patients.