A combined PET/CT scanner for clinical oncology.

UNLABELLED: The availability of accurately aligned, whole-body anatomical (CT) and functional (PET) images could have a significant impact on diagnosing and staging malignant disease and on identifying and localizing metastases. Computer algorithms to align CT and PET images acquired on different scanners are generally successful for the brain, whereas image alignment in other regions of the body is more problematic. METHODS: A combined PET/CT tomograph with the unique capability of acquiring accurately aligned functional and anatomical images for any part of the human body has been designed and built. The PET/CT scanner was developed as a combination of a Siemens Somatom AR.SP spiral CT and a partial-ring, rotating ECAT ART PET scanner. All components are mounted on a common rotational support within a single gantry. The PET and CT components can be operated either separately, or in combined mode. In combined mode, the CT images are used to correct the PET data for scatter and attenuation. Fully quantitative whole-body images are obtained for an axial extent of 100 cm in an imaging time of less than 1 h. When operated in PET mode alone, transmission scans are acquired with dual 137Cs sources. RESULTS: The scanner is fully operational and the combined device has been operated successfully in a clinical environment. Over 110 patients have been imaged, covering a range of different cancers, including lung, esophageal, head and neck, melanoma, lymphoma, pancreas, and renal cell. The aligned PET and CT images are used both for diagnosing and staging disease and for evaluating response to therapy. We report the first performance measurements from the scanner and present some illustrative clinical studies acquired in cancer patients. CONCLUSION: A combined PET and CT scanner is a practical and effective approach to acquiring co-registered anatomical and functional images in a single scanning session.

Association between condom use and HIV infection: a randomised study of self reported condom use measures.

STUDY OBJECTIVE: To compare the association between different measures of condom use and prevalent HIV infection. DESIGN: Randomised cross sectional study to assess association between HIV infection and different measures of self reported condom use. Female sex workers were randomised to one of five different face to face questionnaires on condom use. Three questionnaires used always to never scales to measure use but differed in the reference period for use; a fourth asked about use in the last 10 coital acts; and the fifth was a retrospective log of coital acts in the past two weeks. Use was assessed with new clients, repeat clients, and non-clients. SETTING: Yaoundé and Douala, Cameroon. PARTICIPANTS: 2266 female sex workers. MAIN RESULTS: The association between condom use and prevalent HIV infection varied for different measures of condom use. None of the five level measures showed a dose response protective effect of condom use. Measures aimed at reducing recall bias (measures based on the past 10 coital acts or a coital log) showed little or no association with prevalent infection. Measures based on the past month or six months had a stronger association with prevalent infection. Regardless of the type of measure or reference period, the strongest association between use and infection was for use with partners who were not clients. CONCLUSION: These findings underscore challenges described by others of measuring condom use and interpreting the association between use and prevalent infection.

A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases.

BACKGROUND: Nonoxynol 9 is a proved spermicide, but whether it is also a microbicide is uncertain. A truly effective vaginal microbicide would reduce the susceptibility of women to sexually transmitted diseases, including infection with the human immunodeficiency virus (HIV). METHODS: We enrolled 1292 HIV-negative female sex workers in Cameroon and enrolled them in a double-blind, placebo-controlled study in which the participants were randomly assigned to use either a film containing 70 mg of nonoxynol 9 or a placebo film, inserted into the vagina before intercourse. All of the women were provided with latex condoms and were instructed to have their male sexual partners use them. At monthly follow-up visits, we examined the women with a colposcope for genital lesions, tested endocervical specimens for gonorrhea and chlamydia infection with DNA probes, tested for HIV infection, and treated the women for curable sexually transmitted diseases. RESULTS: The rates of HIV infection (cases per 100 woman-years) were 6.7 in the nonoxynol 9 group and 6.6 in the placebo group (rate ratio, 1.0; 95 percent confidence interval, 0.7 to 1.5). The rates of genital lesions were 42.2 cases per 100 woman-years in the nonoxynol 9 group and 33.5 in the placebo group (rate ratio, 1.3; 95 percent confidence interval, 1.0 to 1.6). The rates of gonorrhea were 33.3 and 31.1 cases per 100 woman-years in the nonoxynol 9 and placebo groups, respectively (rate ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4). The corresponding rates of chlamydia infection in the nonoxynol 9 group and the placebo group were 20.6 and 22.2 per 100 woman-years (rate ratio, 0.9; 95 percent confidence interval, 0.7 to 1.3). The women reported that condoms were used during 90 percent of sexual acts. CONCLUSIONS: The use of a nonoxynol 9 vaginal film did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in this group of sex workers who used condoms and received treatment for sexually transmitted diseases.

PIP: The potential of nonoxynol-9 to reduce women's susceptibility to sexually transmitted diseases (STDs) was investigated in a double-blind, placebo-controlled trial conducted among 1170 HIV-negative sex workers in Cameroon. Participants were randomly assigned to receive either a film containing 70 mg of nonoxynol-9 (n = 595) or a placebo film (n = 575). Women in both groups were provided with latex condoms for their male partners. At monthly follow-up visits during the 12-month study period, colposcopy was used to examine women for genital lesions, endocervical smears were tested for gonorrhea and chlamydia, HIV testing was performed, and curable STDs were treated. Nonoxynol-9 film failed to confer any additional protection against infection with HIV, gonorrhea, or chlamydia beyond that provided by condoms alone and STD treatment. The rates of genital lesions were 42.2 cases per 100 woman-years in the nonoxynol-9 group and 33.5 in the placebo group (rate ratio (RR), 1.3; 95% confidence interval (CI), 1.0-1.6). The majority of genital lesions in the nonoxynol-9 group were external. The rates of gonorrhea were 33.3 and 31.1 cases per 100 woman-years in the nonoxynol-9 and placebo groups, respectively (RR, 1.1; 95% CI, 0.8-1.4), while those of chlamydia were 20.6 and 22.2 cases per 100 woman-years, respectively (RR, 0.9; 95% CI, 0.7-1.3). Finally, there were 6.7 cases of HIV infection per 100 woman-years in the nonoxynol-9 group and 6.6 in the placebo group (RR, 1.0; 95% CI, 0.7-1.5). Condoms were used during 90% of sexual acts.

Measuring condom use: asking "do you or don't you" isn't enough.

This article compares cross-sectional measures of condom use among 2,269 female sex workers in Cameroon randomly assigned to receive one of five different questionnaires measuring condom use. We found that the level of reported condom use varied depending on the type of survey questions used. Measures based on 2-week coital logs or the past 10 acts categorized more women as "100%" or "0%" users than always-to-never scales categorized women as "always" or "never" users. Consistency of use also varied by type of partner. Internal consistency of responses was high. Future studies should assess differences in prospective measures of condom use and the level of association between various measures and infection with sexually transmitted disease.

PIP: Three methods of measuring condom use among a cross-sectional sample of 2269 female sex workers in Cameroon are compared with regard to the differences in the distribution of use. The methods compared are: 1) reported frequency of use, employing questions with always-to-never response scales; 2) calculated percentage of use based on questions asking for the number of acts protected by condoms during the last act, the last 5 acts, and the last 10 acts; and 3) percentage of coital acts protected by condoms as reported in a retrospective coital act log. The findings showed that the type of survey questions used to obtain the data influenced the levels of reported condom use. Measures based on 2-week coital logs or the past 10 acts categorized women as "100%" or "0%" users more frequently than always-to-never scales categorized women as "always" or "never" users. The type of partner also affected the data on consistency of use. Internal consistency of responses was high. Comparison of the differences in prospective measures of condom use should be taken up in future studies. The association between various measures and infection with sexually transmitted diseases should also be evaluated.

Prevalence and prediction of sexually transmitted diseases among sex workers in Cameroon.

The aim of the study was to determine the prevalence of sexually transmitted diseases (STDs), describe the frequency of genitourinary symptoms and signs, and to assess the accuracy of clinical diagnoses of STD in a cohort of Cameroonian sex workers. Physical examinations were conducted on 1233 sex workers in Yaoundé and Douala, Cameroon. Symptoms experienced within the 14 days prior to examination were collected. Women were tested for gonorrhoea, chlamydia infection, and trichomoniasis. Doctors' clinical impressions were compared with laboratory tests. Prevalence of cervical infection and trichomoniasis was 20%. A high percentage of abnormal signs and symptoms was found in this cohort. Clinical diagnosis for cervicitis and trichomoniasis had low sensitivities (<50%) while specificity remained high (>65%). In conclusion STDs are common among sex workers in Cameroon. Clinical diagnosis was not an accurate predictor of infection at the individual level in this population at risk of STD.

PIP: The prevalence of sexually transmitted diseases (STDs) and the frequency of genitourinary symptoms and signs were assessed in 1233 female prostitutes aged 18-45 years, of mean age 26, in Yaounde and Douala. Researchers recorded the physical signs and symptoms experienced by the study subjects within 14 days prior to the physical examination provided as part of the study. The women were tested for gonorrhea, chlamydia infection, and trichomoniasis, with doctors' clinical impressions compared to laboratory test findings. 20% had cervicitis; gonorrhea (11%), chlamydia (12%), or both (3%). 20% had a positive wet mount test for trichomoniasis; 10 subjects were diagnosed with gonorrhea, chlamydia, and trichomoniasis; 65.1% reported abnormal vaginal discharge; and 44.7% reported pelvic pain. Clinical diagnosis for cervicitis and trichomoniasis in this study had sensitivities of less than 50% and specificities of greater than 65%. STDs are therefore common among prostitutes in Cameroon and clinical diagnosis was not an accurate predictor of infection at the individual level.

A randomized controlled trial comparing nonoxynol-9 lubricated condoms with silicone lubricated condoms for prophylaxis.

OBJECTIVE: We tested the effect of nonoxynol-9 (N-9) in condom lubrication on the risk of acquiring STD and genital discomfort. METHODS: The study was a triple masked, randomised controlled trial comparing N-9 lubricated condoms with plain silicone lubricated condoms among Dominican female sex workers. RESULTS: Randomisation provided two groups (313 for N-9 and 322 for plain) similar in baseline characteristics, but extensive loss to follow up occurred (56 women in each group completed the 24 week follow up). Most vaginal acts with clients were protected with condoms (99% of vaginal sex) but fewer acts with non-clients were protected (43% of vaginal sex). No significant differences occurred in rates of cervical infections (N-9 = 3.4 per 100 person months v plain = 2.8), trichomoniasis (N-9 = 2.8 v plain = 3.6), or discomfort rates (N-9 = 0.82 v plain = 0.92). CONCLUSIONS: Plain silicone lubricated condoms are as effective as N-9 lubricated condoms, cost less, have longer expected shelf life, and therefore may be the better condom to provide.

Characteristics associated with prevalent HIV infection among a cohort of sex workers in Cameroon.

OBJECTIVE: To determine prevalence of HIV infection in a cohort of female sex workers in Cameroon, and to describe characteristics associated with HIV infection in this population. METHODS: In a cross sectional study, 2260 female sex workers in Cameroon were interviewed and screened for HIV serostatus. A standardised questionnaire was used to collect information on sociodemographic characteristics and sexual and health behaviours. RESULTS: Seropositive participants (18%) were more likely to be over age 25, have four or more children, live in Yaoundé or Douala for 5 years or less, solicit clients in their homes or on the street, have a low educational level, earn a weekly income of less than $24, and have no other occupation outside of sex work. A logistic regression model of selected sociodemographic characteristics indicated that women at particularly high odds of HIV infection were older, poorer, and new immigrants to their city of residence. CONCLUSION: This seroprevalence study found a lower HIV prevalence than had been previously reported. Although our results are different, this group is still at much higher risk of HIV infection than the population as a whole.

Microbicides, meta-analysis, and the N-9 question. Where's the research?

PIP: The development and marketing of effective topical microbicides would provide women with a way to protect themselves against sexually transmitted diseases (STDs). However, the strong desire among researchers to secure such a method could cause people to accept encouraging results from less than optimal studies. Not all randomized controlled trials (RCT) are well done, and studies of lower quality have been found to exaggerate estimates of treatment effect. Recent data and problems inherent to the process of meta-analysis indicate the need for caution about endorsing the use of nonoxynol-9 (N-9) for STD protection. The 3 better-quality RCTs have compared 3 different N-9 products: a gel, the sponge, and the film. Taken together in a common graphic, the studies have shown N-9 reduces the risks of both gonorrhea and chlamydial infection at relatively low levels of protection. Questions also exist upon how to factor in results from observational studies and which level of protection will induce women to use microbicides. Moreover, studies of barrier methods of contraception or STD prophylaxis are especially susceptible to compliance bias.^ieng

Nonoxynol-9 use, genital ulcers, and HIV infection in a cohort of sex workers.

OBJECTIVES: To measure the associations between use of nonoxynol-9 (N-9) and incidence of genital ulcers, and incident ulcers and HIV seroconversion. METHODS: In a study of barrier contraceptive use and HIV infection, 273 female sex workers used condoms and 100 mg N-9 suppositories, and recorded sexual activity on coital logs. Genital ulcers were diagnosed clinically at monthly clinic visits. HIV infection was diagnosed by ELISA and Western blot. We calculated ulcer incidence rates by level of N-9 use. A nested matched case-control analysis assessed the effect of ulcers on HIV acquisition. RESULTS: More frequent N-9 use was not associated with genital ulcers and may have been protective against the lesions. Ulceration was not a strong risk factor for HIV acquisition in this study (odds ratio 1.1; 95% confidence interval 0.3-3.5). CONCLUSIONS: Frequent use of N-9 can cause genital irritation and ulceration. Ulcers, in turn, may be risk factors for HIV acquisition. This study, however, did not find an association between N-9 use and ulcers, nor between ulcers and HIV. There is probably a threshold of N-9 use frequency or dose below which the risk of ulceration is minimal. Ulcers due to infectious causes may have been prevented by N-9 use in this cohort.

PIP: To determine whether nonoxynol-9 produces disruption of the genital epithelium and, in turn, places users of this spermicide at increased risk of human immunodeficiency virus (HIV), 273 seronegative female commercial sex workers in Cameroon were enrolled in a 12-month cohort study. Subjects were instructed to use condoms and 100 mg nonoxynol-9 suppositories at each act of intercourse and to maintain coital logs. The presence or absence of vaginal and cervical ulcers was recorded at monthly gynecologic examinations; HIV testing was performed every three months. Included in the final analysis were the 191 women with no cervical ulcers at baseline. Of these, 77 (40%) were classified as frequent (15 times/month) nonoxynol-9 users, 84 (44%) as intermediate (11-15 times/month) users, and 30 (16%) as infrequent (10 or fewer times/month) users. 40 women had evidence of cervical ulceration during the observation period and 18 developed vaginal ulcerations. Unexpectedly, nonoxynol-9 use was not associated with an increased risk of ulceration. The incidence rates for cervical and vaginal ulcers, respectively, were 2.7% and 0.6% among frequent users, 2.2% and 0.8% among intermediate users, and 9.0% and 3.0% among infrequent users. Of the 17 women who became infected with HIV during the study, 29% had experienced ulceration compared to a rate of 28% for matched controls (odds ratio, 1.1; 95% confidence interval, 0.3-3.5). It is speculated that nonoxynol-9 provides sufficient lubrication during intercourse to prevent epithelial trauma. It is further plausible that any ulcers caused by nonoxynol-9--as opposed to those of infectious etiology--lack the immunologic cell responses required to increase susceptibility to HIV.

The effectiveness of barrier methods of contraception in preventing the spread of HIV.

Because barrier methods provide protection against bacterial sexually transmitted diseases, these methods are valuable public health adjuncts irrespective of their effect on HIV. Male latex condoms offer substantial protection against HIV infection. Women at risk of sexual acquisition of HIV infection need one or more prophylactic methods that they can control. While the available spermicide products may serve this purpose, current data do not allow firm casual inferences. Large and well designed epidemiologic studies are required to examine the association between female use of barrier methods and HIV infection. These are difficult and costly to perform, however, and to date have yielded conflicting results. Finally, prospective studies in high-incidence cohorts are necessary, and the relationships between spermicide use, local irritation, the vaginal flora and HIV incidence rates must be clarified.

PIP: The effectiveness of barrier methods of contraception in preventing sexually transmitted diseases (STDs) such as human immunodeficiency virus (HIV) has been assessed in vitro studies and epidemiologic research. Both types of studies have indicated that consistent use of high-quality latex condoms confers substantial protection against HIV transmission. Less certain is the capability of nonoxynol-9 to inactivate HIV. Of concern are several studies indicating that 1-8% of female nonoxynol-9 users experience signs and symptoms of tissue irritation, which can facilitate HIV transmission. These findings may reflect overenrollment of women with a high incidence of STDs and above-average (more than one per day) spermicide doses. Meetings sponsored by the World Health Organization and the US Public Health Service during 1993-94 reached consensus on five ethical and methodological principles to govern studies investigating whether currently available nonoxynol-9 spermicides reduce the incidence of HIV infections: 1) a randomly allocated controlled trial in which all participants are given male condoms; 2) allocation of half the women to an active spermicidal product and the other half to a placebo product; 3) counseling participants to use both a condom and the vaginal product at every coital act; 4) sufficient study size to measure HIV rate ratios within frequency strata; and 5) inclusion of colposcopic examinations and regular appraisal of participant safety by a data and safety monitoring board. Studies of less irritating yet effective spermicidal compounds, the determinants of consistent use of barrier methods, and the impact of social marketing are also recommended.

Gonorrhea as a risk factor for HIV acquisition.

OBJECTIVE: The role of gonorrhea in facilitating acquisition of HIV infection has only recently been studied. A previous nested case-control analysis in a cohort of female sex workers in Zaïre found a strong association between HIV seroconversion and prior gonorrheal infection. The objective of this study was to replicate the Zaïre study analysis in a cohort of 273 Cameroonian sex workers to determine whether gonorrhea increased the risk of HIV acquisition, and if the crude association between gonorrheal infection and HIV acquisition was weakened when the level of unprotected coitus was more carefully controlled. METHODS: We conducted a nested case-control study of initially HIV-1-negative women (n = 273) followed prospectively (with monthly sexually transmitted disease check-ups and 3-monthly HIV-1 serology). As in Zaïre, cases (seroconverters, n = 17) were compared with controls (women who remained HIV-1-negative, n = 68) for incidence of gonorrhea and sexual exposure during the presumed period of HIV-1 acquisition. RESULTS: The association between gonorrheal infection and subsequent HIV acquisition was stronger in Zaïre than in Cameroon [crude odds ratios (OR), 6.3 versus 2.2]. In both the Zaïre and Cameroon data the crude OR were reduced (6.3 to 4.8, and 2.2 to 1.7, respectively) by controlling for risk factors including a dichotomous variable indicating irregular or no condom use. When this variable was replaced in the Cameroon data with a more precise continuous variable indicating the percentage of unprotected coital acts, the gonorrhea OR was further reduced to 1.4 (95% confidence interval, 0.4-4.9). CONCLUSION: These results suggest that in the Cameroon cohort, gonorrheal infection did not facilitate HIV acquisition, but that having gonorrhea was a marker for unprotected coitus that facilitated HIV acquisition. The data demonstrate how OR can be overestimated when imprecise dichotomous measures of unprotected coitus are used. Future studies should plan for better control of self-reported condom use.

PIP: The objective was to replicate a Zaire study with a cohort of 273 Cameroonian sex workers to determine whether gonorrhea increased the risk of HIV acquisition, and whether the crude association between gonorrheal infection and HIV acquisition was weakened when unprotected coitus was more carefully controlled. 303 Cameroonian female sex workers were enrolled in Yaounde between 1989 and 1990. Eligibility criteria included age 18 years or older; no pregnancy during the previous 42 days; no history of adverse reaction to a spermicidal product; negative enzyme-linked immunosorbent assay (ELISA) HIV-antibody test; and monthly follow-up visits for 1 year. Women were asked to use condoms and suppositories containing N-9 at every sexual activity and coital logs were reviewed monthly. 17 women were identified as cases and 68 as controls. Unlike in Zaire, where 8% of the cases and controls reported never using condoms, none of the women reported unprotected coitus more than 50% of the time in Cameroon. Almost 30% of both cases and controls in Cameroon had evidence of genital ulcers, compared with less than 5% of the cases and controls in Zaire. The crude OR of HIV infection among those who had gonorrhea during the exposure period was much higher in Zaire than in Cameroon (6.3 vs. 2.2). In both the Zaire and Cameroon data the crude OR were reduced (6.3 to 4.8 and 2.2 to 1.7, respectively) by controlling for risk factors of young age, number of partners per week, trichomoniasis, genital ulcers, and a dichotomous variable indicating irregular or no condom use. In the 1st alternative model, the OR for gonorrhea was 2.0 when the dichotomous measure of unprotected coitus (i.e., more than 25% of coital acts were unprotected) was used. When a more precise continuous estimate of level of unprotected coitus was used (i.e., the percentage of acts where neither condoms nor N-9 was used) the OR for gonorrhea was reduced to 1.4.

The use of nonoxynol-9 for protection against cervical gonorrhea.

OBJECTIVES: Although condoms are the best defense against sexually transmitted disease, little is known about the effectiveness of female-controlled methods containing nonoxynol-9 as backup protection when condoms are not being used. METHODS: To assess the extent to which nonoxynol-9 protects women against gonorrhea, a cohort of 303 female sex workers (prostitutes) in Yaounde, Cameroon, were asked to use condoms and suppositories containing nonoxynol-9 at every sexual encounter and to record daily sexual activity and use of condoms and suppositories on coital logs that were reviewed monthly. Evidence of gonorrheal infection was based on a positive gonorrhea culture. Stratified analysis and proportional hazards regression were used to estimate rate ratios. RESULTS: Forty-one women enrolled in the study were excluded from the current analysis. The estimated incidence of gonorrhea was 6.2 infections per 100 person-months of observation. Incidence rate ratios estimated from proportional hazards regression models controlling for condom use showed that using nonoxynol-9 during acts not protected by condoms reduced the risk of infection. CONCLUSIONS: Although the protective effect of condoms against sexually transmitted disease is greater than that afforded by nonoxynol-9, using nonoxynol-9 when condoms are not used is a far better strategy in gonorrhea prevention than using no method at all.

A dosing study of nonoxynol-9 and genital irritation.

The objective of the study was to assess the symptoms and signs of genital irritation produced by different frequencies of nonoxynol-9 (N-9) use. Thirty-five women were randomized to each of 5 groups and used a vaginal suppository for 2 weeks. Group 1: N-9 once every other day; Group 2: N-9 once a day; Group 3: N-9 twice a day; Group 4: N-9 4 times a day; and Group 5: placebo 4 times a day. Study women were examined at admission, one week and 2 weeks with a colposcope for erythema and epithelial disruption, and were interviewed about vaginal itching and burning. The rates of reported symptoms for N-9 users were not significantly different from that of placebo users. The rate of epithelial disruption for women using N-9 every other day was essentially the same as that of women using placebo. The rates of epithelial disruption for women using N-9 1/day and 2/day were 2.5 times greater than that of placebo users. The rate of epithelial disruption for women using N-9 4/day was five times greater than that of placebo users. Genital irritation was located primarily on the vagina or cervix, and vulvitis was not a significant problem. Women who infrequently use N-9 products may not experience an increase in genital irritation. Women who choose to use N-9 frequently may experience an increase in epithelial disruption.

Use of nonoxynol-9 and reduction in rate of gonococcal and chlamydial cervical infections.

The spermicide nonoxynol-9 (N-9) has been used as a contraceptive for over 30 years, but the use of a vaginal spermicide and condoms for the prevention of sexually transmitted infections has not been examined in randomised studies. We report a single-blind randomised field trial to assess the effect of N-9 film on the rate of gonococcal and chlamydial cervical infection in women at high risk of these diseases. 343 women were randomly assigned to use either condoms and N-9 (186 women) or condoms and a placebo (157). Compliance with condom use was much the same in the two groups. Overall, N-9 reduced the rate of cervical infection by 25% (rate ratio [RR] 0.75, 95% confidence interval [Cl] 0.5-1.1); in women who used N-9 for more than 75% of their coital acts the infection rate was reduced by 40% (RR 95% Cl 0.3-1.0). The rate of yeast vulvovaginitis or genital ulcers was not higher in N-9 users than in placebo users, but the rate of symptomatic irritation was increased by 70% (RR 95% Cl 1.1-2.6) among N-9 users. Condom use was more protective against cervical infection than N-9 use. The rate of infection was 50% (RR 95% Cl 0.3-0.7) lower with 75% than with 0-50% condom compliance. The use of a vaginal N-9 spermicide with condoms whenever possible seems to be a better strategy than the use of condoms only for prevention of gonococcal and chlamydial cervical infection.

The effects of frequent nonoxynol-9 use on the vaginal and cervical mucosa.

The authors conducted a single-dose phase I local toxicity study of the effects of frequent insertion of nonoxynol-9 (N-9) on the lower genital tract to determine whether a phase II dose-ranging study is warranted. Fourteen women used 150 mg of N-9 cumulatively four times a day for 14 days. Epithelial disruption of the cervix and vagina, the main outcome of interest, occurred in 43% (95% CI, 18-71%) of women on this high-frequency use schedule. None of the women experienced symptoms that prompted them to discontinue the study. This preliminary study indicates that a phase II study to examine the local toxicity of different use schedules is needed to provide further safety information about the use of N-9.

PIP: A Phase I type clinical trial was conducted to study the local toxic effects of nonoxynol-9 (N-9) on the vaginal and cervical mucosa of women, to see whether a Phase II trial is needed, since women may use the spermicide frequently to prevent sexually transmitted diseases. 14 women inserted suppositories containing 150 mg N-9 every hour for 4 doses for 14 days. They were checked before the trail and for 2 or 3 weeks, with pelvic exam, smears for trichomonas and monilia, and colposcopy. 5 women inserted placebos to blind the trial. 43$ of the subjects had physical findings including sloughing of the cervical epithelium in 4, cervical erythema in 4, cervical bleeding in 1, vaginal erythema in 3, vaginal sloughing and bleeding in 1, vaginal dryness in 3, dryness in 2 and itching in 2. The cervical sloughing did not cross the transformation zone. 1 woman had edema and bleeding of the cervix resembling severe strawberry cervix. All symptoms resolved in 1 week. No effects were seen on the vulva, perineum or anus. The dose and frequency of use of N-9 in this trail are larger than women would normally be expected to use, but the data do justify a Phase II study.

Psychological consequences of the Enniskillen bombing.

Eleven people were killed and 60 injured in the Enniskillen bombing of November 1987. Survivors were psychologically appraised six months and one year later. At six months 50% had developed post-traumatic stress disorder (PTSD). This group comprised more females than males. However, all victims had high scores on the GHQ. We found no correlation between psychological injury (as measured by the GHQ) and physical injury (as measured by the ISS), calling into question previous assertions.

Post-traumatic stress disorder and civil violence in Northern Ireland.

The case records of 499 victims of civil and terrorist violence were examined, and the presence or absence of post-traumatic stress disorder (PTSD) and associated features recorded. The results support the face, and predictive, validities of PTSD. 'Acting as if the event were reoccurring' and 'survivor guilt' seemed not to be characteristic symptoms, and the homogeneity of the emotional state in PTSD was questionable. Only marital disharmony and suicidal behaviour were associated complications. PTSD seemed to be found in a wide range of stressors, but the danger in over-reliance on results from combat veterans is emphasised.