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D C Sokal

Publications and source records attributed to D C Sokal.

At least 19 recordsLinked to original sources
PubMed2001

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.

Animals↗
PubMed2000

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.

Adult↗
PubMed2000

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.

Adult↗
PubMed1998

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.

Cameroon↗
PubMed1996

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.

Abdominal Pain↗
PubMed1995

Transcervical quinacrine sterilization: clinical experience.

OBJECTIVE: To review the use of quinacrine pellets for non-surgical female sterilization. BACKGROUND: The transcervical insertion of quinacrine pellets has been under study for over 15 years. It could potentially expand access to sterilization services, because it is relatively simple to administer, with the use of a modified IUD inserter, and is inexpensive. METHODS: Published and unpublished data are reviewed. RESULTS: The short-term safety of transcervical quinacrine appears to be better than surgical sterilization, but it is less effective, especially among women under 35, and there are virtually no data on its reversibility. Thus, it is probably most appropriate for older women, aged 35 and over, but it could be an option for others where access to surgical sterilization is limited. CONCLUSION: The use of quinacrine pellets for female sterilization needs to be reviewed by appropriate regulatory authorities, especially with regard to long-term safety issues, and additional clinical studies are needed to better define a standardized regimen.

Cervix Uteri↗
PubMed1995

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.

Adult↗
PubMed1995

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.

Adolescent↗
PubMed1994

Impact of Thailand's HIV-control programme as indicated by the decline of sexually transmitted diseases.

The Thai government began an HIV-control programme in 1989. The programme had the following parts: the government bought and distributed sufficient condoms to protect much of the commercial sex in the country; sanctions were brought against commercial sex establishments where condoms were not used consistently; and a media campaign bluntly advised men to use condoms with prostitutes. Between 1989 and 1993 the use of condoms in commercial sex in Thailand increased from 14 to 94%, according to surveys of prostitutes, and the number of cases of the five major sexually transmitted diseases declined by 79% in men. We estimate that sex acts with prostitutes where there was a risk of HIV transmission declined from about 2.6% in June, 1989, to about 1.6% in June, 1993. If condom use in commercial sex stays high, future cohorts of young men and women may experience lower HIV incidence rates than those of the recent past. However, although condom use is high, there are many more infected prostitutes than before and many infected men who will pass HIV to their wives.

Condoms↗
PubMed1994

Modeling the HIV/AIDS epidemic in the English-speaking Caribbean.

The study reported here examines the past and potential future impact of HIV/AIDS in 19 nations of the primarily English-speaking Caribbean. The authors use DemProj, a demographic projection model, to explore two different HIV scenarios. In the low scenario adult HIV prevalence stabilizes at 2% in the year 2000, and in the high scenario adult HIV prevalence stabilizes at 5%. By the year 2010, annual AIDS incidence exceeds 11,000 cases in the low scenario and 28,000 in the high scenario. In both scenarios, 70% of the cases are in young adults 20-45 years old and 12% are in children 0-15. Age-specific mortality is more than doubled in the 20-40 age range in the low scenario, and more than quadrupled in the high scenario. The impact on death rates is also severe among children 0-10. In assessing the economic impact, the authors estimate that the total annual costs of the epidemic will approach US$ 500 million (in constant 1989 US$) or 2% of GDP in the low scenario, and will exceed US$ 1,200 million or 5% of GDP in the high scenario.

Acquired Immunodeficiency Syndrome↗
PubMed1993

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.

Adolescent↗
PubMed1988

Mortality from neonatal tetanus in rural Côte d'Ivoire.

A 30-cluster survey was carried out in order to estimate the incidence of neonatal tetanus in rural Côte d'Ivoire. Births in the 19 months preceding the survey were enumerated by interviewers in house-to-house visits. If a child born in that period had died, the interviewer asked a series of questions to establish a presumptive diagnosis of neonatal tetanus. A total of 41 deaths from neonatal tetanus was found in the study area among 2324 live births that occurred from 1 January 1981 to 31 July 1982. This gives a neonatal tetanus mortality rate of about 2%. Most deliveries and almost all deaths occurred at home, and only about 2% of neonatal tetanus cases were reported through the routine health information system. Birth in a clinic and antiseptic care of the umbilical cord protected infants from neonatal tetanus. Tetanus immunization of all women of child-bearing age is recommended as a preventive measure.

Adult↗
PubMed1980

Prenatal chromosomal diagnosis. Racial and geographic variation for older women in Georgia.

In a study of Georgia women aged 40 years and older, 15% made use of prenatal chromosomal diagnosis. There was, however, substantial racial and geographic variation, ranging from a use ratio of 60% among whites in two large urban counties to 0.5% among blacks outside Augusta and Atlanta health districts. This simple population-based epidemiologic analysis suggests that future program planning for genetic services in Georgia should address ways to increase access by rural women, especially blacks. Similar analyses in other states could be used for planning genetic services.

Abortion, Therapeutic↗
PubMedDate not supplied

Cancer and birth defects near the Drake Superfund site, Pennsylvania.

The Drake Superfund site in Clinton County, Pennsylvania, has been contaminated with the carcinogens beta-naphthylamine, benzidene, and benzene. The authors reviewed county-wide, age-adjusted, sex-, race-, and site-specific cancer mortality rates for the years 1950-1959, 1960-1969, and 1970-1979, and type-specific birth defects incidence rates for 1973-1978. During the 1970s, a significantly increased number of bladder cancer deaths occurred among white males in Clinton County, and a significantly increased number of other cancer deaths occurred in the general population of Clinton and three surrounding counties. There were no statistically significant clusters of any specific birth defect or of all birth defects. County-wide data on cancer and birth defects can be used for initially screening counties with Superfund sites, but more definitive studies are needed to assess the actual health effects caused by these sites.

Age Factors↗