Comparative efficacy of postpartum sterilisation with the titanium clip versus partial salpingectomy: a randomised controlled trial.

A multicentre trial was conducted to compare efficacy of postpartum sterilisation with clip and partial salpingectomy. Life-table estimates of pregnancy probabilities were compared through 2 years of follow up. A significantly different risk of pregnancy between the clip and partial salpingectomy groups was observed. Nine pregnancies were observed in the clip group versus two in the partial salpingectomy group. Cumulative probability of pregnancy through 2 years was 0.017 with the clip and 0.004 [correction added after online publication 25 September 2012; 0.044 has been replaced with 0.004] for partial salpingectomy (P < 0.04). Equivalent efficacy of the clip compared with partial salpingectomy has not been demonstrated in postpartum women.

Geographic and temporal stability of HIV seroprevalence among pregnant women in Bujumbura, Burundi.

OBJECTIVE: To establish whether HIV seroprevalence in Bujumbura is stable or continuing to increase. METHODS: HIV seroprevalence data among pregnant women from 1986 were compared with comparable data from 1991-1992. RESULTS: HIV seroprevalence among antenatal clinic attendees at three sites was 10.5, 28.0 and 11.9% in 1986, compared with 7.7, 25.6 and 12.4%, respectively, in 1991-1992. A weighted least squares analysis showed significant differences in HIV seroprevalence between the different sites (chi 2, 71.71; P > 0.0001), but no evidence of any differences between the 1986 and the 1991-1992 prevalence levels (chi 2, 0.51; P = 0.6). CONCLUSIONS: Bujumbura appears to be in the endemic phase of the spread of HIV. The stable geographic variation among clinic populations in Bujumbura suggests the need for focused interventions, and a general need for surveillance data to be gathered from numerous sites so to identify those with the highest incidence of HIV infection.

PIP: The authors compared HIV seroprevalence data among pregnant women from 1986 with comparable data from 1991-92 to establish whether HIV seroprevalence in Bujumbura is stable or continuing to increase. They found HIV seroprevalence among antenatal clinic attendees at 3 sites to be 10.5%, 28.9%, and 11.9% in 1986, compared with 7.7%, 25.6%, and 12.4%, respectively, in 1991-92. Significant differences were found between the different sites in HIV seroprevalence, but not between the 1986 and 1991-92 prevalence levels. HIV therefore appears to be endemic in Bujumbura. The stable geographic variation among clinic populations suggests the need for and appropriateness of focused interventions, as well as a general need for surveillance data to be gathered from numerous sites in order to identify those with the highest incidence of HIV infection.

AVERT: a user-friendly model to estimate the impact of HIV/sexually transmitted disease prevention interventions on HIV transmission.

OBJECTIVE: To introduce the newly developed AVERT model by describing the purpose, logic, advantages and limitations of the model, to validate the model's estimates against seroconversion data from a large randomized controlled trial, and to provide practical examples of its applications. DESIGN: Static, deterministic spreadsheet-type model based on per sex act HIV-1 transmission probabilities. METHODS: Data from a recently completed trial carried out in Cameroon were used to validate the estimated number of new HIV infections generated by the AVERT model. A relatively limited set of biological and behavioral parameters was used to estimate the impact of a targeted HIV/sexually transmitted disease (STD) prevention intervention in a South African mining community. RESULTS: The comparison of AVERT estimates with actual seroincidence data from the Cameroon trial not only confirmed the validity of the model's outputs but also illustrated its potential to provide additional options in data analysis. Modeling the pre-and post-intervention scenarios for the South African mining community with AVERT provided estimates of the number of HIV infections averted due to targeted periodic presumptive STD treatment and community-based peer education. CONCLUSIONS: With a small number of accessible input variables, AVERT can provide plausible and defendable impact estimates of intervention effects on the reduction of HIV transmission. The AVERT model may be a helpful tool for decision-makers and planners in setting appropriate program priorities and analysing the cost-effectiveness of different intervention packages.

The effects of GABA(B) receptor activation on spontaneous and evoked activity in the dentate gyrus of kainic acid-treated rats.

Enhancement of GABAergic inhibition is central to the treatment of epilepsy. The role of the GABA(B) receptor, however, is poorly understood. The current study investigates the effects of r-baclofen (a GABA(B) receptor agonist) on spontaneous and evoked electrophysiological activity in the dentate gyrus of normal and epileptic rats in vivo. Administration of kainic acid (KA), which causes similar pathology to that seen in human temporal lobe epilepsy, was used to prepare chronically epileptic rats. Bursts of spontaneous high-amplitude field potentials (spiking) were observed in isoflurane-anaesthetised control and KA-treated rats in vivo; however, this activity was significantly more frequent in KA-treated rats (223+/-26.1 spikes min(-1)) than in control rats (124+/-17.4 spikes min(-1)). Feedback inhibition, measured using paired-pulsed stimulation, was also greater in KA-treated rats; 50% inhibition of the second response was observed at 43.05+/-4.46 ms in KA-treated animals, as opposed to 26.27+/-2.39 ms in control animals. r-Baclofen (10 mg kg(-1) i.v.) abolished spontaneous spiking and also reduced feedback inhibition in both control and KA-treated rats. These effects of r-baclofen may be due to inhibition of GABA release, through activation of pre-synaptic GABA(B) receptors on terminals of interneurones in the inhibitory feedback pathway. These results suggest a link between feedback inhibition and spontaneous spiking, and provide support for the hypothesis that mechanisms of synchronisation may give rise to seizure activity in human temporal lobe epilepsy.

Multi-neuronal recordings reveal a differential effect of thapsigargin on bicuculline- or gabazine-induced epileptiform excitability in rat hippocampal neuronal networks.

The present study was performed to investigate the effects of depleting intracellular Ca(2+) stores on bicuculline- or gabazine-induced epileptiform excitability. Studies were performed on monolayer rat hippocampal neuronal networks utilising a system that allowed simultaneous multiple extracellular single-unit recordings of neuronal activity. Hippocampal neuronal networks were prepared from enzymatically dissociated hippocampi from 18-day-old fetal Wistar rats. The cells were cultured in Neurobasal medium with B27 serum-free supplements directly onto the surface of planar multiple microelectrode arrays with a central recording array of 64 (4 x 16) indium-tin thin-film recording electrodes. All cells recorded at 21 days-in-vitro exhibited spontaneous discharge activity with firing rates between 0.3-30.7 Hz. gamma-aminobutyric acid (GABA) produced a concentration-dependent decrease in firing (EC(50)=9.1 microM) which could be blocked by pre-application of bicuculline methobromide (10 microM). Addition of the GABA(A)-receptor antagonists gabazine (10 microM) or bicuculline (10 microM) resulted in the rapid generation of synchronised bursting within all the cells recorded. Bicuculline exhibited heterogeneity of action on firing rate, whereas gabazine always increased firing. Pre-incubation with thapsigargin, which depletes intracellular calcium stores, resulted in a decrease in the amount of neuronal excitation produced by bicuculline, but not by gabazine, suggesting that bicuculline-induced neuronal excitation requires release of Ca(2+) from intracellular stores.

Intraplantar injection of anandamide inhibits mechanically-evoked responses of spinal neurones via activation of CB2 receptors in anaesthetised rats.

Anti-nociceptive effects of the endocannabinoid anandamide are well established. Anandamide has, however, also been shown to activate pro-nociceptive vanilloid 1 (VR1) receptors present on primary afferent nociceptors. The aim of the present study was to determine the effect of intraplantar injection of anandamide on dorsal spinal neuronal responses in control rats and rats with hindpaw carrageenan-induced inflammation. Effects of intraplantar administration of anandamide (50 microg in 50 microl) on peripheral mechanically-evoked responses of spinal neurones were studied in halothane-anaesthetised rats in vivo. Responses of spinal neurones to mechanical punctate stimulation (von Frey filaments, 8-80 g) of the peripheral receptive field were similar in non-inflamed rats and rats with hindpaw carrageenan-induced inflammation. Intraplantar injection of anandamide, but not vehicle, significantly (P<0.05) inhibited innocuous and noxious mechanically-evoked responses of spinal neurones in rats with hindpaw inflammation, but not in non-inflamed rats. Co-administration of the cannabinoid (2) (CB(2)) receptor antagonist, SR144528 (10 microg in 50 microl), but not the cannabinoid (1) (CB(1)) receptor antagonist, SR141716A (10 microg in 50 microl), significantly blocked inhibitory effects of anandamide on peripheral evoked neuronal responses in rats with hindpaw inflammation. This study demonstrates inhibitory effects of exogenous anandamide on mechanically-evoked responses under inflammatory conditions in vivo, which are mediated by peripheral CB(2) receptors.

Convulsions caused by endrin poisoning in Pakistan.

From July through September 1984, acute convulsions caused by endrin poisoning occurred in the subdistrict of Talagang, Attock District, Punjab province, Pakistan. Eighteen of the 21 affected villages were surveyed; 70% of the cases for which ages were known (106 of 152) were in children 1 to 9 years of age; 9.8% of all affected persons (19 of 194) died. The outbreak occurred in villages on the main roads of the subdistrict and peaked in early September. Endrin was detected in the blood of 12 of 18 patients with a history of convulsions but was not found in the blood of four hospitalized control patients. One composite sugar sample taken from the homes of three persons had an endrin level of 0.04 ppm. Because of the high toxicity, repeated association with large-scale outbreaks of neurologic illness, and the difficulties of monitoring distribution, endrin should not be used for agricultural purposes.

Spinal GABA(B)-receptor antagonism increases nociceptive transmission in vivo.

GABA(B) receptors modulate primary afferent fibre evoked responses of spinal neurones. Here effects of the selective GABA(B) receptor antagonist, CGP-35348, on electrically-evoked responses of spinal neurones in control and carrageenan-inflamed rats were studied. Spinal CGP-35348 (0.1-10 microg/50 microl) did not alter Abeta- or Adelta-fibre evoked neuronal responses in control rats, although C-fibre evoked responses and post discharge responses of spinal neurones were significantly facilitated by 3.0 and 10.0 microg/50 microl CGP-35348 (p < 0.05). In carrageenan-treated animals, spinal CGP-35348 did not alter electrically evoked responses of spinal neurones at any dose. Our data suggest that following acute peripheral inflammation there is loss of endogenous GABA(B) receptor mediated inhibition of C-fibre transmission at the level of the spinal cord.

Comparative effects of quinacrine and erythromycin in adult female rats: a nonsurgical sterilization study.

OBJECTIVE: To compare the efficacies of erythromycin and quinacrine for nonsurgical sterilization in rats. Quinacrine used for nonsurgical sterilization in women is mutagenic, and most clinical regimens have had a higher failure rate than surgical sterilization. DESIGN: This acute mammal study included five groups of rats assigned randomly and evaluated at two times after treatment. ANIMAL(S): Adult female Sprague-Dawley rats. INTERVENTION(S): Five groups of female Sprague-Dawley rats (20 per group) were given 70 or 280 mg/kg of erythromycin lactobionate, 350 mg/kg of quinacrine hydrochloride, or vehicle control administered transcervically. Rats were mated 21 days later. Additional groups (n = 4 per group) were treated and killed 21 days later without mating. MAIN OUTCOME MEASURE(S): Fourteen days after mating, numbers of ovarian corpora lutea, total uterine implants, and embryos were evaluated. For unmated animals, uterine sections were examined for fibrosis and lumen closure. RESULT(S): Neither drug altered numbers of corpora lutea. Erythromycin decreased pregnancy rate and number of implantations (increased preimplantation loss) in a dose-related fashion. Quinacrine increased resorptions. Uterine pathology was more extensive and frequent in erythromycin-treated animals, with extent and severity increasing from 21 to 35+ days. CONCLUSION(S): Erythromycin was more effective than quinacrine in preventing pregnancy.

Two randomized controlled trials comparing the tubal ring and filshie clip for tubal sterilization.

OBJECTIVE: To compare the effectiveness and safety of the Filshie Clip and Tubal Ring systems when applied via minilaparotomy and laparoscopy. DESIGN: Prospective, multicenter randomized controlled clinical trial, with postoperative evaluation by a physician who was masked to the operative technique. SETTING: Healthy volunteers in a variety of hospital settings. PATIENT(S): 2746 women (915 in the minilaparotomy study and 1831 in the laparoscopy study) who had requested permanent surgical sterilization. INTERVENTION(S): Surgical tubal ligation, using either Filshie Clips or Tubal Rings. A physician other than the surgeon evaluated the patients after the operation and again at 1, 6, and 12 months after surgery. MAIN OUTCOME MEASURE(S): Pregnancy rates and safety-related events. RESULT(S): During the 12 months after surgery, two women who received the Filshie Clip and two women who received the Tubal Ring became pregnant, giving a 12-month life-table pregnancy probability of 1.7 per 1000 women in both groups. The Tubal Ring was more difficult to apply and had higher rates of tubal or mesosalpingeal injuries at surgery. The Filshie Clip group had three cases of spontaneous clip expulsion during the follow-up period. CONCLUSION(S): Both the Filshie Clip and Tubal Ring are effective and safe for use in tubal occlusion.

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.

Cancer risk among women sterilized with transcervical quinacrine hydrochloride pellets, 1977 to 1991.

OBJECTIVE: To determine whether a cluster of eight cancers among 572 women who had received transcervical quinacrine hydrochloride was a random occurrence or evidence of an increased risk of cancer. DESIGN: Retrospective cohort study using interviews and reviews of medical records. Cancer cases were evaluated using cohort analyses and space-time cluster methods. SETTING: Santiago and Valdivia, Chile. SUBJECTS: Fourteen hundred ninety-two women who received transcervical quinacrine pellets for sterilization between 1977 and 1989. MAIN OUTCOME MEASURE: Age- and site-specific incidence of invasive cancers. RESULTS: Eight hundred two women were interviewed. From 1 to 14 years of data were available on 600 of the noninterviewed women from clinic records. During 7,852 women-years of follow-up, 17 invasive cancers were identified, compared with 11.8 expected, based on age-specific rates from the Cali, Colombia cancer registry. Five cases of cervical cancer were observed, compared with 3.96 expected. Only one other uterine cancer was observed, a leiomyosarcoma, compared with 0.2 or 0.3 other uterine cancers expected. CONCLUSIONS: The occurrence of an unusual cluster was confirmed, but no evidence was found of excess cancer risk associated with quinacrine pellet sterilization. However there was a single provocative observation (the leiomyosarcoma), and surveillance of the cohort is continuing.

PIP: A long-term follow-up of 572 Chilean women who were sterilized by transcervical insertion of two or three 250 mg quinacrine hydrochloride pellets in 1977-81 revealed eight cases of cancer. To evaluate further the possible association between quinacrine and cancer risk, a retrospective cohort study of 1492 women from Santiago and Valdivia, Chile, who received this procedure in 1977-89 was undertaken by Family Health International (FHI). Study methods included clinic record review, interviews with traceable women or their families, hospital record review for cancer cases, and review of pathology slides for gynecologic cancers. 802 (54.6%) of cohort members were located; sufficient data were available from clinic records on another 600 women. This process revealed a total of 36 cancers; 7 were diagnosed before quinacrine sterilization, 17 were invasive carcinomas in situ of the cervix (excluded from cancer registry data), and 17 were invasive cancers diagnosed after sterilization. Of the third group of cancers--the focus of the analysis--9 were from Santiago and 8 were from Valdivia. Given the 7852 woman-years of follow-up available and the age-specific rates from the Cali cancer registry, 11.82 new cancer cases (9.15 in Santiago and 2.67 in Valdivia) would be expectable. Most common were breast and cervical cancers (5 cases each). The observed/expected ratio was 1.64 for breast cancer and 1.26 for cervical cancer; no temporal clustering was found for either cancer. Of greatest concern was the single case of uterine leiomyosarcoma; US cancer registries suggest that only 0.08-0.15 cases are expectable. Cluster analysis revealed an unusual occurrence of cancers in Valdivia in 1985-87. Although the present study lacked sufficient power or cases to determine whether transcervically administered quinacrine is or is not carcinogenic, further evaluation is warranted and FHI plans to conduct a similar study in Vietnam.

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.

Long-term follow-up after quinacrine sterilization in Vietnam. Part I: interim efficacy analysis.

OBJECTIVE: To determine the long-term efficacy of nonsurgical sterilization with quinacrine. DESIGN: Observational cohort study. SETTING: Rural provinces in northern Vietnam. PATIENT(S): Two thousand seven hundred and nine women who had quinacrine insertions between 1989 and 1993. INTERVENTION(S): Interviews in 1994, 1995, and 1996 and review of available medical records. Pregnancy rates were corrected for problems in detecting and confirming pregnancies. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): Over 90% of women were interviewed at least once. Uncorrected cumulative pregnancy rates were 12.9% at 5 y after two insertions and 27.3% after one insertion. Effectiveness varied by age group: the partially corrected pregnancy rates after two insertions were 6.8% in women 35 or older at the time of insertion and 13.0% in women under 35. A subgroup of women who received oral papaverine at the time of quinacrine insertion had lower pregnancy rates, with a cumulative uncorrected rate of 5.3% at 4 years among women of all ages. CONCLUSION(S): Efficacy of quinacrine appears reasonable for two insertions of quinacrine in women 35 and older. It may be possible to improve efficacy by the use of papaverine or the Hieu insertion technique.

Long-term follow-up after quinacrine sterilization in Vietnam. Part II: interim safety analysis.

OBJECTIVE: To determine the long-term safety of nonsurgical sterilization with quinacrine. DESIGN: Observational cohort study. SETTING: Rural provinces in northern Vietnam. PATIENT(S): Two thousand eight hundred forty women who had had quinacrine insertions and an age-matched comparison group of 1,658 women who had an intrauterine device (IUD) insertion between 1989 and 1993. METHOD(S): Interviews in 1994, 1995, and 1996 and review of available medical records. This is a planned interim analysis. MAIN OUTCOME MEASURE(S): Ectopic pregnancies and the occurrence of other adverse health events. RESULT(S): Over 90% of women were interviewed at least once. Despite matching on age, the groups differed on baseline parity. The ectopic pregnancy rates were similar after either one or two insertions and were similar to the rate of ectopic pregnancies after surgical sterilization in the United States. The quinacrine group reported more gynecologic health problems than the IUD group. However, after correcting for information bias, there was no dose-response effect between the one- and two-insertion quinacrine groups, suggesting the possibility of recall bias or differing baseline health status. CONCLUSION(S): Ectopic pregnancies do not appear to be increased compared with U.S. surgical sterilization rates. The data on other adverse events are more difficult to interpret.

Phase I prehysterectomy studies of the transcervical administration of quinacrine pellets.

To determine the safety of transcervical administration of quinacrine pellets as a method of voluntary female sterilization, three noncomparative Phase I clinical trials of the administration of 250 mg quinacrine were carried out in 21 women who were scheduled to undergo hysterectomy 24 h or one month later. Detailed results are presented for one of the trials using 10-min pellets. Six of 10 women had minor transitory complaints during the postinsertion 24-h follow-up period. Five women reported pelvic/abdominal cramping, one experienced headache, and one experienced dizziness. Blood chemistry values were not adversely influenced by the quinacrine. The average plasma level of quinacrine peaked at 3 h, 36.1 ng/ml, slightly lower than the value observed 4 h after oral administration of 200 mg in a previous study. An average of 27% of the administered dose was recovered in tampons. Quinacrine was detected in the plasma of two women at the four/six-week visit. Selected results are presented from two other trials that were halted because of slow recruitment. The transcervical administration of 250 mg of 10-min quinacrine pellets was well tolerated. However, based on recent mutagenicity testing and meetings with regulatory officials, it appears unlikely that the use of quinacrine for nonsurgical sterilization could be approved in the United States or Europe.

Pregnancy rates among Chilean women who had non-surgical sterilization with quinacrine pellets between 1977 and 1989.

We describe cumulative pregnancy probabilities among women who underwent quinacrine pellet sterilization in Chile between 1977 and 1989 (N = 1492). We interviewed the women or relatives in 1991-93 and 1994-96, and reviewed hospital records. Mean follow-up was 9.6 years (median 9 years). We recorded 120 pregnancies, including 40 that went to term or near-term. There were nine adverse outcomes in eight infants: one fetal death at 18 weeks gestation; three infants born prematurely; one stillbirth (placental infarct); and four infants with birth defects. There was no clustering of any particular kind of birth defect. For two insertions, the 10-year cumulative pregnancy probability was 8.9 (95% confidence interval 3. 7, 14.1). For 3 insertions, the 10-year rate was 7.0 (4.4, 9.5). For women who were under 35 years at insertion, the 10-year rate was 10. 7 (7.4, 14.1). For women who were 35 or older at insertion, the 10-year rate was 3.1 (0.6, 5.7). The pregnancy rate varied little for 2 vs. three insertions, but the rate did vary significantly by age, with women who received quinacrine at 35 years or older 0.3 (0. 2, 0.5) times as likely to become pregnant as younger women. The 10-year cumulative ectopic pregnancy probabilities for women with two and three insertions of quinacrine were 0.9 (<0.1, 2.6) and 0.5 (<0.1, 1.2), respectively. Pregnancy rates after quinacrine insertion are higher than after surgical sterilization, but ectopic pregnancy rates appear similar.

A 5-year clinical evaluation of Norplant implants in Senegal.

The principal objective of this 5-year clinical study of Norplant implants was to introduce these implants into the family planning program in Senegal and to determine their overall acceptability and safety in Senegalese acceptors. A total of 300 subjects were enrolled into the trial from August 1986 to July 1991. All the women were followed-up for 5 years or until the implants were removed. The pooled cumulative discontinuation rate was 40.8 +/- 2.91 per 100 women resulting in a continuation rate of 59.2 +/- 2.91 per 100 women. Thirteen subjects (4.3%) were lost during the follow-up. Seven pregnancies were reported throughout the 5 years leading to a cumulative pregnancy rate of 3.3 +/- 1.25 per 100 women. Menstrual problems were the reason most often given for early removal during the first 2 years. After year 2, desire for another pregnancy was the main reason for implant removal. The results presented in this study show that the Norplant implant system is a safe, effective, and acceptable method that meets the needs of the Senegalese family planning program.

PIP: A 5-year prospective, noncomparative clinical evaluation of Norplant implants was conducted to introduce these implants into the family planning program and to determine the acceptability among women users in Senegal from August 1986 to July 1991. Findings showed that the pooled discontinuation rate was 40.8 +or- 2.91 per 100 women, resulting in a continuation rate of 59.2 +or- 2.91 per 100 women. During follow-up, 13 (4.3%) subjects were lost. Throughout the 5 years, 7 pregnancies were reported leading to a cumulative pregnancy rate of 3.3 +or- 1.25 per 100 women. The most common reason for early removal during the first 2 years was menstrual problems, while the main reason for removal in the second year was the desire to have a child. Overall, the Norplant implant system is a safe, effective, and acceptable method that is suitable for the Senegalese family planning program.

Re-evaluation of the mutagenic potential of quinacrine dihydrochloride dihydrate.

Quinacrine has been used for voluntary female non-surgical sterilization for its ability to produce tubal occlusion. Safety issues regarding quinacrine have been raised because it has been shown to intercalate with DNA. Therefore, safety issues need to be resolved by appropriate toxicology studies to support a review for human transcervical use. Such toxicology studies include mutagenicity assays. Here we report an evaluation of the genotoxicity of quinacrine dihydrochloride dihydrate (QH) using a battery of assays. In the bacterial mutagenicity assay, QH was strongly positive in Salmonella typhimurium tester strain TA1537 with and without S9-activation and in S. typhimurium tester strain TA98 with S9-activation; QH was also strongly positive in Escherichia coli WP2 uvrA without S9-activation. QH was not mutagenic in S. typhimurium tester strains TA100 and TA1535 with and without S9-activation. QH was mutagenic in the mouse lymphoma assay in the absence of S9-activation. QH was clastogenic in Chinese hamster ovary (CHO) cells, with and without S9-activation. QH was negative for polyploidy in the same chromosome aberration test. Using a triple intraperitoneal injection treatment protocol in both male and female mice, QH was negative in the in vivo mouse micronucleated erythrocyte (micronucleus) assay. These results confirm that QH is mutagenic and clastogenic in vitro and suggest a potential risk to human health due to QH exposure after intrauterine exposure.

Two randomized controlled trials comparing the Hulka and Filshie Clips for tubal sterilization.

To compare the effectiveness and safety of the Filshie Clip System and Hulka Clip System when applied via minilaparotomy and laparoscopy, we conducted 2 multicenter randomized controlled trials of 2126 women (878 in the minilaparotomy study and 1248 in the laparoscopy study) who received either the Filshie or Hulka Clip. A physician other than the operator evaluated patients postoperatively and again at 1, 6, and 12 months after surgery. We compared the cumulative incidence of pregnancy and the frequency of safety related events for the device groups. Twenty-four month follow-up was planned for a subset of 599 women in the laparoscopy study. One woman who received the Filshie Clip and 6 women who received the Hulka Clip became pregnant within one year. The 12-month life-table pregnancy probability was 1.1 per 1000 women in the Filshie Clip group and 6.9 per 1000 women in the Hulka Clip group. The difference in the risk of pregnancy through 12 months between device groups neared statistical significance (p = 0.06). Among the extended follow-up subset, the 12- and 24-month cumulative pregnancy probabilities were 3.9 and 9.7 per 1000 women for the Filshie Clip group and 11.7 and 28.1 per 1000 women for the Hulka Clip group (p = 0.16 for comparison through 24 months). Both the Filshie and Hulka Clips are effective and safe for use in tubal occlusion.