Uptake of interventions to reduce mother-to-child transmission of HIV in the United Kingdom and Ireland.

OBJECTIVES: To describe the uptake of interventions to reduce mother-to-child transmission of HIV infection. DESIGN: Voluntary confidential reporting of HIV infection in pregnancy and childhood; telephone interview with key professionals in all London maternity units. SUBJECTS AND SETTING: HIV-infected pregnant women and children in the United Kingdom and Ireland. MAIN OUTCOME MEASURES: Trends in breastfeeding, use of zidovudine, mode of delivery and terminations of pregnancy. RESULTS: Between 1990 and 1995, 14 (4%) out of 314 women diagnosed with HIV infection before delivery breastfed compared with 109 (77%) out of 142 diagnosed after delivery. Since 1994, zidovudine use has increased in each 6-month period (14, 39, 67, and 75%; chi 2 = 17.5, P < 0.001), although in 1995 it was the policy of only 48% of London maternity units to offer zidovudine to HIV-infected women. During 1995, 44% of HIV-infected women were delivered by elective Cesarean section. Since 1990, 20% of women first diagnosed in pregnancy were reported to have their pregnancy terminated. CONCLUSIONS: Although detection of previously undiagnosed HIV infection in pregnancy remains low in the United Kingdom, and particularly in London, HIV-infected pregnant women who are aware of their status are increasingly active in taking up interventions to reduce transmission to their infants. If all HIV-infected women attending for antenatal care in London consented to testing and took up interventions and termination of pregnancy at the rates observed in this study, the number of vertically infected babies born in London each year could be reduced from an estimated 41 to 13.

Synchronous 5-fluorouracil, mitomycin-C and radiation therapy in the treatment of locally advanced carcinoma of the cervix.

Locally advanced carcinoma of the cervix has a poor prognosis with a high incidence of persistent or recurrent local disease contributing to distressing symptoms and poor survival. This has remained unaltered over the past 30 years in spite of the addition of other therapeutic modalities. Between 1983 and January 1986, 38 patients with locally advanced carcinoma of the cervix were treated with synchronous 5-fluorouracil, mitomycin-C, and radiotherapy. The results of this pilot study indicate both an improvement in pelvic control and in 3-year survival rate for the chemosensitized therapy compared to conventional radiotherapy alone (55% v 28%) using historical controls. Improved survival was only significant for bulky FIGO Stage IIb tumors. The toxicity of this combination was predominantly gastro-intestinal and led to modification of both radiation dose and technique with subsequent improvement in the incidence of side effects. The results suggest that the combination of synchronous chemotherapy with radiotherapy is an improved method of treatment for locally advanced carcinoma of the cervix and that a prospective randomized trial is now justified.

The purification and development of a radioimmunoassay for beta-core fragment of human chorionic gonadotrophin in urine: application as a marker of gynaecological cancer in premenopausal and postmenopausal women.

The beta-core fragment of human chorionic gonadotrophin (hCG) is a major part of the immunoreactive hCG-like material found in the urine of normal pregnant women. Patients with non-trophoblastic gynaecological malignancies have been found to have raised levels of urinary beta-core. We describe the purification of beta-core, the preparation of a polyclonal sheep antiserum and the development of radioimmunoassay. The minimum detection limit of this assay was 0.025 micrograms beta-core/l. There was no significant cross-reaction with the free alpha-subunit, hLH, hFSH and hTSH (less than 0.7%), and only partial cross-reaction with intact hCG and free beta-subunit of hCG (6.9 and 18%). Within-assay variability ranged from 2.03 to 12.5% and between-assay variability from 2.25 to 13.4%. The assay was applied to urine samples from 92 normal non-pregnant premenopausal women, 54 normal postmenopausal women and 65 women with active gynaecological disease (47 postmenopausal and 18 premenopausal). In normal premenopausal women the values ranged from less than 0.025 to 0.62 micrograms beta-core/l (median 0.043 micrograms beta-core/l). The values for normal postmenopausal women ranged from less than 0.025 to 0.64 micrograms beta-core/l (median 0.26 micrograms beta-core/l). Postmenopausal women with gynaecological malignancy had values which ranged from less than 0.025 to 4.0 micrograms/beta-core/l (median 0.31 micrograms beta-core/l); premenopausal women in this group had values which ranged from less than 0.025 to 1.15 micrograms beta-core/l (median 0.12 micrograms beta-core/l). On molecular sieve chromatography, the material found in the urine of normal postmenopausal women showed the physicochemical characteristics of authentic beta-core.(ABSTRACT TRUNCATED AT 250 WORDS)

Multivariate analyses of DNA index, p62c-myc, and clinicopathological status of patients with ovarian cancer.

AIM: To determine if either DNA index or p62c-myc is an independent prognostic variable in ovarian cancer. METHODS: Multivariate and univariate analyses of the relation between DNA index, p62c-myc, FIGO stage, histological type, tumour grade, completeness of surgery, and patient survival in ovarian cancer were examined. RESULTS: Multivariate analysis showed significant association of survival only with stage and grade. There was no relation between survival and DNA index. CONCLUSIONS: DNA index is not an independent prognostic variable in ovarian cancer.

Serum placental-type alkaline phosphatase activity in women with squamous and glandular malignancies of the reproductive tract.

AIM: To investigate serum placental-type alkaline phosphatase (PLAP-type) activities in women with squamous and glandular malignancies of the reproductive tract using an immunoradiometric assay. METHODS: PLAP-type immunoreactivity was measured in 180 women with non-ovarian malignancies of the reproductive tract and the values were compared with those from 334 controls. The cases comprised 18 vulval, nine vaginal, 103 cervical, 46 endometrial, and five fallopian tube cancers. RESULTS: Serum PLAP-type activities were no different from controls in patients with squamous cell tumours. Women with adenocarcinoma of the cervix, endometrium, and fallopian tube had increased values: women with endometrial cancer had a median value nearly four times greater than that of controls. There was no direct correlation between PLAP-type activities and stage of disease in patients with endometrial cancer, but values reverted to normal after treatment. CONCLUSIONS: Serum PLAP-type measurements are of no value in the management of patients with squamous cell tumours of the female reproductive tract. Raised activities can, however, be found in glandular tumours, in particular endometrial cancer where serum PLAP-type measurements may be of value in predicting remission.

Early vulval cancer: the place of conservative management.

There is a trend towards conservative surgery for early vulval cancer, which is increasingly being diagnosed in younger women. In this series there were 21 patients who had lesions which had invaded to a depth of 3 mm or less. Nine patients were treated by wide local excision without any form of lymphadenectomy, and eight patients had wide local excision with ipsilateral groin dissection. In the remaining four patients, radical surgery was carried out, consisting of radical vulvectomy and bilateral lymphadenectomy. None of the 12 patients who had some form of lymphadenectomy was shown to have nodal involvement. None of the patients suffered from local recurrence or recurrence in the groin nodes. No patient died from vulval cancer, and all but one of the patients are still alive with a mean follow-up period of 54.8 months. Though there is as yet no universal agreement on the criteria for early vulval cancer, with superficial invasion there is a place for individualized treatment, when patients will benefit from less than radical surgery.

The effect of storage time and molybdate on steroid receptors in gynaecological tissues.

Human female reproductive tract tissues were analysed for estrogen and progestogen receptor content in the presence or absence of sodium molybdate immediately after removal at surgery. Other fractions of the tissue were stored in liquid nitrogen and similarly analysed after 2, 4, 6 and 8 weeks storage. The results showed that at all times the apparent receptor content for both steroids was significantly higher (P less than 0.001) and Kd values were significantly lower (P less than 0.02) in assays carried out with 10 mM molybdate added to the buffer systems. Furthermore, as soon as either whole tissue or tissue cytosol was frozen for storage, receptors were "lost" with values decreasing by approximately 30% for both steroid receptors. However, once frozen in liquid nitrogen tissue receptor content remained stable over the eight weeks of study. It is recommended that laboratories standardize techniques to allow valid comparisons of results.

Performance of antenatal HIV screening strategies in the United Kingdom.

BACKGROUND: In 1996 only 13.5% of previously undiagnosed HIV infected women were detected in pregnancy. In this study, all 265 maternity units in the United Kingdom were surveyed to determine the relation between screening strategy, uptake of testing, and detection rate. METHODS: Data on HIV screening strategy and uptake of testing were collected in 1997 by postal questionnaire. The proportion of women with previously undiagnosed HIV infection identified during pregnancy (detection rate) was calculated using data from national obstetric HIV surveillance and unlinked anonymous seroprevalence studies. RESULTS: 239 (90%) units responded; 25 of these (10%) had a universal offer strategy, 89 (37%) a selective offer, and 125 (52%) tested only women who requested it. All selective units offered testing to injecting drug users, but only 26% to women who had lived abroad in high prevalence areas. Uptake was over 10% in only eight units, all with a universal strategy, and in 76% of selective units it was below 0.1%. The detection rate was 14.7% in universal units, 7.8% in selective units, and 7.7% in on request units. In universal units, detection increased by 6.3% (95% confidence interval 3.7% to 8.8%) for every 10% increase in uptake of testing. There was evidence of both selective presentation for testing and avoidance of testing among infected women. CONCLUSIONS: All current antenatal HIV testing strategies fail to identify most infected women. Universal offer strategies achieve a very low uptake and a poor detection rate. Units with selective strategies tend to test only a minority of women at high risk and do not target all the main high risk groups.

Use of anonymous newborn serosurveys to evaluate antenatal HIV screening programmes.

OBJECTIVE: To evaluate the extent to which antenatal HIV screening programmes identify HIV infected women who go to term. DESIGN: Comparison of results of two surveillance systems. An anonymous neonatal HIV serosurvey was used to estimate the numbers of HIV infected women giving birth; reporting by obstetricians was used to assess the proportion who had been identified. SETTING: Three Thames regions. RESULTS: 729,105 neonatal blood samples were tested, of which 484 were HIV seropositive. Newborn HIV seroprevalence is increasing, at different rates, in inner London, suburban London, and in non-metropolitan districts. During the past four years the proportion of infected women who have been identified before delivery is 16.9%, but less than half of these were diagnosed during pregnancy. In 1993 only five of the 128 (4%) previously undiagnosed infected women delivering babies were identified by antenatal screening. CONCLUSION: Despite increased emphasis on antenatal testing for HIV in areas of higher prevalence the number of undiagnosed women delivering babies continues to increase. Consideration should be given to alternative strategies for offering antenatal HIV testing. Antenatal screening programmes should be monitored continuously by comparing anonymous neonatal seroprevalence with clinical reports from obstetricians.

Treatment of advanced carcinoma of the vulva with chemoradiotherapy - can exenterative surgery be avoided?

Thirty-seven patients with advanced FIGO stage (17 stage III, 20 stage IV) carcinoma of the vulva whose extent of disease would have required extenterative surgery were treated with chemoradiotherapy (CRT). Radiotherapy was given as a split course (2500 cGy mid-plane dose in 10 daily fractions, repeated 1 month later) to the first seven patients. Subsequently radiotherapy was given as a continuous course (4500 cGy mid-plane dose in 20-25 daily fractions). Chemotherapy included mitomycin c as an intravenous bolus and 5 fluorouracil as a continuous intra-venous infusion over 4-5 days, with variations in timing and dose according to the type of radiotherapy course. Fifteen (47%) complete and 11 (34%) partial responses were seen at 3 months after completion of treatment. Of the 15 patients with complete response, 10 remained disease-free for a median of 24 months (range 6-36 months). The median sur-vival for complete and partial responding patients was 15 and 11 months, respectively (range 2-37 months). Acute toxicity included moist perineal desquamation, diarrhea and myelosupression. One death secondary to neutropaenic sepsis occurred in the split course group. WHO grade 3 radiation enteritis occurred in one patient (14%) in the split course and two patients (6%) in the continuous CRT groups. Using CRT, very high response rates have been obtained with relatively low toxicity. There is a useful role for CRT in the treatment of patients with locally advanced recurrent disease although its place in the management of extensive primary disease requires further evaluation.

Unsuspected sphincter damage following childbirth revealed by anal endosonography.

Anal endosonography was performed in 62 consecutive patients with incontinence of flatus or faeces following obstetric trauma, and in 18 parous controls. Of the incontinent group, 90% had defects in the external sphincter, 65% in the internal sphincter and 44% disruption of the perineal body, compared with none of the controls. This triad of lesions is pathognomonic of obstetric trauma. Anal endosonography revealed a higher prevalence of sphincter damage than expected from anorectal physiology tests, and therefore has a role in screening patients following complicated or difficult deliveries.

Anal sphincter trauma during instrumental delivery.

OBJECTIVES: To determine the incidence of defecatory symptoms, pudendal nerve damage and mechanical trauma to the anal sphincters during vacuum and forceps delivery. METHODS: Anal endosonography, manometry, pudendal nerve terminal motor latency (PNTML) measurements and perineometry were performed in 43 primiparae who had an instrumental delivery (17 vacuum and 26 forceps) and in 47 who had a normal vaginal delivery (controls). RESULTS: Defecatory symptoms developed in 10 (38%) women following a forceps delivery compared with 2 (4%) in the control group (P = 0.0003), and 2 (12%) following a vacuum extraction (P = NS). Anal sphincter defects occurred in 21 (81%) forceps deliveries compared with 17 (36%) controls (P = 0.0005) and 4 (21%) vacuum extractions (P = NS). Anal pressures were lower in those who developed a sphincter defect (P < 0.00001). PNTML was not significantly altered by the mode of delivery. CONCLUSIONS: Compared with vacuum extraction, forceps delivery is associated with significantly more damage to the anal sphincters and hence an increased incidence of defecatory symptoms.

FIGO Save the Mothers Initiative: the Pakistan-UK collaboration.

The pilot study in Punjab, Pakistan was one of the five paired demonstration projects sponsored by FIGO in the "Save the Mothers" maternal mortality project. The goal of the project was to bring basic and comprehensive emergency obstetric care (EmOC) to a semiurban and rural area some 30 km from Lahore, where effectively there was none. The aim was to achieve this by using the existing facilities within the rural health system without the deployment of extra specialist staff other than as initial facilitators. This report shows trebling of some performance indicators and an improvement in met need. There is coincidentally a similar increase in the uptake of general medical services. Reducing maternal mortality requires building local capacity for EmOC; the essential components being the premises, trained personnel, equipment, and availability of drugs and blood. Availability and provision of EmOC coupled with changes in the attitude of the population resulted in marked improvement of process indicators.

E-rosette forming cells and cell mediated immunity in ovarian cancer.

Parameters of cell mediated immunity were examined in 50 women with ovarian cancer, and included E-Rosette formation lymphocyte number, and lymphocyte blastogenesis to PPD. Alterations in these parameters were also determined following surgery and during chemotherapy. Relapse patients demonstrated significantly decreased numbers of "active" and "total" E-Rosette forming cells, as well as a significantly decreased spontaneous incorporation of 125Iododeoxyuridine into unstimulated lymphocytes; PPD responses and total lymphocyte counts were not significantly different from the control group. Analysis of T-cell subpopulations in relapse patients suggested that these cells were suppressed in the unseparated lymphocyte state. Chemotherapy led to an expected decrease in lymphocytes but an unexpected increase in the numbers of E-Rosette forming cells initially. It was postulated that serum factors accounted for the decreased values of these cells in relapse patients rather than a true depletion.

Victor Bonney Lecture, 1980. Ovarian cancer--a gynaecological disorder?

Ovarian cancer is a disease of great complexity. The diagnosis is commonly delayed and the condition may present in a number of specialties other than gynaecology. Inappropriate primary treatment may seriously compromise the subsequent course. Modern surgical management involves extension beyond the traditional total hysterectomy and bilateral salpingo-oöphorectomy and 'under treatment' by both gynaecologists and general surgeons is common. A multimodal approach is highly desirable, both radiotherapy and chemotherapy having a defined role in management which is largely determined by the histopathology. In spite of modern diagnostic aids the diagnosis is all too frequently only achieved at laparotomy. A plea is made for the transfer of such patients to a gynaecological oncologist for definitive therapy if the primary physician or surgeon is unfamiliar with the full ramifications of the disease or with the range of therapeutic measures, including radical surgery if suitable.

An audit of surgical treatment of ovarian cancer in a metropolitan health region. Association of Obstetricians and Gynaecologists of the North East Thames Region.

The varied application of surgery to the initial treatment of 908 cases of primary ovarian cancer is analysed. In patients with advanced disease (FIGO Stages IIb, III and IV) 256 (46%) of 555 women achieved minimal residual disease status by primary surgery and this proportion fell to 24% when only stages III and IV were considered; of these cases 7% underwent adjunctive intestinal resection or urinary tract surgery. Although not in a clinical trial situation the women achieving minimal residual disease status before chemotherapy survived better in the short term, although long-term survival remained disappointing. In early disease 3% of young women have been subjected to hysterectomy and removal of both ovaries. By contrast, in 16% of women over the age of 40 years with early ovarian cancer bilateral oophorectomy was not carried out.

Paraneoplastic syndromes in patients with ovarian neoplasia.

The prevalence of several paraneoplastic syndromes associated with ovarian cancer was determined from a clinicopathological study of 908 patients with primary ovarian malignancy in the North East Thames Region. The diversity and rarity of these manifestations are great and the explanation for them is difficult. Circumstantial evidence suggests that in some cases an autoimmune phenomenon is the most plausible cause.

Risk factors for HIV infection overlooked in routine antenatal care.

We have ascertained the extent to which risk factors for HIV infection may escape detection by standard history-taking procedures in an antenatal clinic. This study was based on 1264 women from a multi-ethnic population in an inner London health district (City and Hackney). All had agreed to undergo attributable HIV testing and a detailed personal interview. Thirty-nine per cent (494 of 1264 women) reported risk factors contributed personally or by a partner. Most of these risk factors had not been earlier disclosed by routine history taking. In most cases the risk was residence and risk activity in a World Health Organization (WHO) Pattern 2 country. [HIV spread WHO categories: Pattern 1--principally homosexual/bisexual males and i.v. drug use (areas = North America, Western Europe, Australasia, parts of South America) with male to female ratio 10/1; Pattern 2--Heterosexual (areas = Sub Saharan Africa, Caribbean and part South America) with male to female 1/1.] Thirty-one subjects (2.4%) were aware that their partners had participated in bisexual activity. Only six subjects perceived themselves at risk through their own or partner's drug injecting activity. The frequency of risk factors was substantially greater than that ascertained by the routine history. The findings highlight the potential risk of heterosexual spread resulting from travel to or residence in high prevalence territories. The contribution by male partners is significant and is particularly difficult to detect during a routine interview. These data support the recommendation that voluntary HIV serum testing should be universal rather than a selective offer based on risk factors determined at a routine history.

Audit of compliance with antenatal protocols.

OBJECTIVE: To assess the implementation of action protocols dictated by antenatal risk factors noted at the initial (booking) antenatal visit. DESIGN: Retrospective study of 2000 women delivered between 1 March 1990 and 29 March 1991. SETTING: Maternity department of a district general hospital supporting a multiethnic population in inner London. MAIN OUTCOME MEASURES: Comparison of clinical actions performed against those dictated by the department's protocols. Analysis according to clinical importance, gestation at booking, maternal age, parity, birth order, ethnic origin, and certainty of gestational age. RESULTS: Interobserver agreement between the two auditors was good (kappa statistic for risk factors detected, 0.78; for actions generated, 0.80). Of the 15,658 actions dictated by department protocols, 3673 (23.5%) were actually performed by the clinicians. The 63 combinations of risk factors and actions believed by consultants to be of particular clinical importance had an action rate of 28.3% compared with 18.6% for those considered less important (p < 0.001). Mothers who first visited the hospital antenatal clinic at or before 24 weeks' gestation had 25.2% of relevant protocols fulfilled (p < 0.001). Compliance was significantly improved in women aged 36 or over (32.4%), black women (24.9%), and cases of uncertain gestation (24.5%). Parity and birth order were not associated with an altered action rate. Ethnic origin deemed as "other" (than white, black, Asian, or oriental) or "unknown" was associated with poor compliance (19.3%). CONCLUSIONS: Compliance to a set of agreed protocols was poor even though a computer system was available and a protocol manual had been distributed. Protocols were more likely to be implemented in women who booked early and in some groups of women deemed at high risk including older mothers, black women, and those denoted as having uncertain gestational age.