Search

Background: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients. Subsequent small studies failed to substantiate these spectacular claims, but controversy on the efficacy of this treatment persisted., Methods: We studied 559 adult Ugandan patients with WHO stage 2-4 HIV infection and a Karnofsky performance score of more than 50, who had not received any drugs with antiretroviral activity in the previous 3 months. The patients were randomly assigned in a double blind fashion either to 150 IU oral nHuIFN-alpha/day or placebo. The duration of treatment was extended from 28 weeks to 60 weeks 9 months after enrollment had started. At that time 112 subjects had already received 28 weeks of treatment and been discontinued from the study., Results: Both study groups were comparable with respect to all baseline characteristics studied, except that the nHuIFN-alpha group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 x 10(6)/l) than the placebo group (median 85.3 x 10(6)/l) (p = 0.033). Therefore, all analyses were adjusted for CD4+ lymphocyte counts at entry. In both treatment groups there was relentless progression of HIV disease. Subjects treated with nHuIFN-alpha and placebo had similar mortality, disease progression rates, decline of CD4+ lymphocyte counts and Karnofsky performance scores, and prevalence of symptoms. No patient reverted to HIV-1 seronegative antibody status. Serious adverse events were not seen. Quality control of the study medication documented that the active drug indeed contained IFN-alpha activity., Conclusions: The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-alpha/day in a population of African patients with symptomatic HIV infection.

Menstrual histories recorded by more than 1000 healthy, untreated women have been analyzed using the reference period method. Results were obtained for each year of age from 15 to 49. Between menarche and age 19, the most important feature of menstrual patterns is their variability. Within-woman mean segment (cycle) length then decreases slowly but steadily, from 29.0 days at age 20 to 26. 7 days at age 40. The range of segment lengths over a year also falls, to a minimum of 7 days at age 38. During the 40s, mean segment length rises to 29 days at age 49, and there is a sharp increase in the range, to 28 days. The length and variability of bleeding episodes, however, changes little between the ages of 19 and 49. Modifications to the World Health Organization definitions of 'clinically important' bleeding patterns are proposed.

A placebo-controlled randomized clinical trial was conducted in six centres to compare the effects of a 14 day treatment with either 50 micrograms ethinyl oestradiol daily or 2.5 mg oestrone sulphate daily, on depot medroxyprogesterone acetate (DMPA)-induced prolonged bleeding. Out of 1035 women admitted to the study, 278 requested treatment and were given ethinyl oestradiol (n = 90), oestrone sulphate (n = 91) or placebo (n = 97). Ethinyl oestradiol was successful in stopping the bleeding episode in 93% of cases, compared with oestrone sulphate and placebo which had success rates of 76 and 74% respectively. However, the relative advantage of ethinyl oestradiol was marginal, with an average reduction of 1 bleeding day and 3 spotting days compared with the other two groups. Immediately after treatment, women given ethinyl oestradiol had less bleeding but a more unpredictable pattern than the other two groups. In the long term, there were no differences between the bleeding patterns or the discontinuation rates for any reason in the three groups, and the most important single reason for discontinuation in those groups remained 'menstrual problems'. In summary, the study showed that treatment of DMPA-induced prolonged bleeding with ethinyl oestradiol had a limited short-term effect but no beneficial effect on the acceptability of DMPA as a contraceptive method. Treatment with oestrone sulphate was no different from placebo.

Objectives: To determine the sensitivity of HIV-antibody assays for detecting low levels of HIV antibody using seroconversion and other panels containing plasma of varying titres., Methods: Eight HIV-antibody assays, available under the World Health Organization bulk-procurement agreement, were evaluated on sets of sequential plasma samples derived from 11 individuals who had recently become HIV-infected (seroconversion panels). In addition, two non-seroconversion panels, consisting of low performance (titre) and mixed titre samples were used to further define the sensitivity of the assays. The eight assays included two rapid tests, one simple test, and five enzyme-linked immunosorbent assays (ELISA)., Results: On average, the eight assays detected antibody 0.5-4.8 days later than the reference test (Abbott HIV-1/HIV-2 3rd generation ELISA); these differences were statistically significant for six of the eight tests. All tests performed well on the low performance and mixed titre panels. All eight assays also had comparable sensitivity to that of the reference test on a large panel of known positive plasma. The additional risk of missing an infectious unit of blood during seroconversion by using the least sensitive rather than the reference test was estimated to be 1 in 7600 and 1 in 76 million at annual HIV incidence rates of 1 and 0.0001%, respectively. The cost of eliminating this additional risk by using the reference test is between US$ 15,150 and 151 million per unit detected at the above incidence rates., Conclusions: Although there are differences in sensitivity between the assays when used to test blood from individuals during the course of seroconversion, the differences are small, and all eight tests are appropriate for use as screening tests.

Arachidonic acid metabolites produced by primary cultures of human endometrial cells derived from biopsies obtained before and after exposure to 20 micrograms/day levonorgestrel for 84 +/- 1 days were analysed by reverse phase HPLC. This revealed a significant increase in PGF1 alpha and an epoxide metabolite upon levonorgestrel stimulation. The proportion of epoxide metabolite, PGF1 alpha and PGE2 were positively correlated with serum levonorgestrel levels while HETES, PGE2 and epoxide were similarly correlated with serum oestradiol. The extent of intermenstrual bleeding during exposure to levonorgestrel was correlated with the proportion of epoxide and HETES products in vitro which is discussed in relation to their physiological function.

The effects of vaginal devices releasing levonorgestrel (LNG) at a constant rate of approximately 20 micrograms/24 hrs on the human endometrium were studied in a group of 69 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn three times weekly starting at day 10 of a pretreatment (control) cycle and then three times weekly from day 60 to 90 of the treatment period. The levels of LNG, estradiol, progesterone and sex hormone binding globulin (SHBG) were analyzed by radioimmunoassay techniques. Endometrial biopsies were obtained in the luteal phase of the pretreatment cycle and on day 84-87 of the treatment period. Increased bleeding occurred in most subjects exposed to the LNG-releasing device; the mean number of bleeding and spotting days was 26.4 +/- 8.9 S.D. which exceeded that found in their control cycle. Morphometric analyses of the endometrial biopsies using 9 quantitative indices, revealed highly significant changes in glands and stroma following the use of the LNG-releasing vaginal device. Irrespective of the circulating steroid levels, the administration of LNG significantly diminished the glandular diameter (p less than 0.001), reduced the volume density of the glands (p less than 0.001) and of the glandular epithelium (p less than 0.001). and modified the ratio glandular epithelium: glands (p less than 0.001). It is concluded that levonorgestrel released at a rate of 20 micrograms/24 hrs, induces characteristic changes in the histologic structure of the human endometrium. Although no simple correlation has been found between any of the endometrial indices and the numbers of bleeding/spotting days or bleeding days, the changes as such may represent biochemical alterations which could be predisposing factors for intermenstrual bleeding and spotting. To prove a causal relationship between morphological and biochemical changes and changes in bleeding patterns, further in-depth studies may be required.

The activities of four lysosomal enzymes, i.e. N-acetyl-beta-hexosaminidase, acid phosphatase, alpha-D-mannosidase and alpha-L-fucosidase have been measured in extracts of endometrial biopsies from untreated and levonorgestrel-treated women of fertile age. Values were compared with protein and DNA content, as well as with lactate dehydrogenase activity, used as reference constituents. In parallel, organ cultures were established from the same endometrial specimens and the release of lysosomal enzymes into the medium was followed. The human endometrium possesses a rich lysosomal equipment, comparable to that found in the human liver. In the untreated cycles, the activities of lysosomal enzymes show a coordinate response to the hormonal changes, decreasing by about 40% from the proliferative to the mid-late secretory phase. Long-term levonorgestrel treatment causes a marked cytoplasmic atrophy, as shown by decreased protein content and lactate dehydrogenase activity, whereas DNA content remains unchanged. In contrast, N-acetyl-beta-hexosaminidase, one of the most active lysosomal enzymes studied, shows a higher specific activity upon levonorgestrel. In both untreated and treated endometria, the organ cultures provide biochemical evidence for a higher release of N-acetyl-beta-hexosaminidase than of lactate dehydrogenase, indicating active secretion of the lysosomal enzyme. During levonorgestrel treatment, there was no correlation between clinically recognized spotting-bleeding patterns and lysosomal enzyme content in, or release from, the endometrium.

A study of endometrial vasculature, mast cell numbers and tissue levels of tissue plasminogen activator (tPA) prior to and following exposure to levonorgestrel (20 micrograms/day) administered via a vaginal ring was undertaken. Following exposure to levonorgestrel, significantly fewer arterioles were present in the endometrium. During the early secretory phase of the control cycle, a positive correlation was found between mast cell numbers and progesterone levels. Levonorgestrel-exposed biopsies had significantly higher numbers of vessels with endothelial gaps and haemostatic plugs when compared with early secretory endometrium and significantly higher numbers of haemostatic plugs when compared with mid-late secretory endometrium. During the early secretory phase, the numbers of vessels possessing haemostatic plugs positively correlated with the peripheral blood levels of oestradiol and the number of contracted endothelial cells showed a positive correlation with progesterone levels. In mid-late secretory biopsies, the numbers of vessels with contracted endothelial cells were found to correlate negatively with oestradiol levels and the difference in the levels of contracted endothelial cells between the mid-late secretory endometrium and levonorgestrel-exposed endometrium correlated positively with progesterone levels of post-treatment cycles.

The disturbance in menstrual bleeding induced by many methods of contraception is an important factor in their acceptability, and women participating in clinical trials of new methods are usually asked to keep a calendar record of the occurrence of bleeding. A recent WHO report recommends that, for analysis and presentation, each menstrual diary should be divided into successive periods, and the woman's bleeding pattern in each period summarized in ten indices. These indices are simple to calculate and easily understood by clinicians, but comparison of several groups is problematic because of the large number of summary statistics generated. Principal components analysis was therefore used to determine whether the indices could be reduced to a smaller number of measures. The analyses showed that three of the indices--the range and maximum value of bleeding/spotting episode lengths and the minimum bleeding-free interval--rarely measure their intended dimension of the bleeding pattern. Most of the essential information about a woman's bleeding pattern is contained in only four of the ten indices: the number of bleeding/spotting episodes, the mean lengths of episodes and intervals, and the range of bleeding-free interval lengths. Together, these indices describe the most important dimensions of a pattern: the amount, frequency and variability of the bleeding.

In a retrospective study of 2581 microbiologically confirmed female cases of gonorrhoea seen in STD clinics in England and Wales 96% of infections were detected by the first set of Gram-stained smears and cultures. A comparison of the outcome of the two tests between clinics according to their size and location showed considerable variation. The reasons for these disparities are analysed and physicians advised to re-examine their present methods in the light of these findings and newer techniques.

Menstrual diary records were obtained from women using either a natural method of contraception, a combined or progestogen-only oral contraceptive, a vaginal ring, or a long-acting injectable (DMPA). Within each method group, multiple regression analysis was used to examine the relationships between the subjects' bleeding patterns and their age, age at menarche, ponderal index, obstetric and contraceptive history and ethnic origin. The influence of ethnic origin was described in the preceding paper. Among combined pill users, increasing age was associated with more frequent spotting episodes. In both the untreated and combined pill groups, women with a higher ponderal index had less variable bleeding-free intervals; in the vaginal ring and DMPA groups, the more obese women had shorter bleeding/spotting episodes and longer bleeding-free intervals. Among combined oral contraceptive users, the most influential variable was the time since the end of the woman's last pregnancy: subjects who had been more recently pregnant had longer, less predictable episodes and shorter intervals. Previous oral contraceptive use was associated with more predictable bleeding patterns among women currently using either type of oral pill. In the vaginal ring and DMPA groups, subjects whose last pregnancy had ended in abortion had more bleeding/spotting days and episodes than those who had had a live birth. As reported previously, bleeding patterns were more closely related to the woman's geographical region of residence than to any other factor. The associations found with other individual characteristics were often inconsistent or difficult to interpret. A number of variables which could potentially influence menstrual bleeding patterns, such as nutritional status, were not measured and therefore could not be included in the analysis. However, contraceptive method and ethnic origin may be predominant influences, overriding any other factor.

In a study to quantify epidemiological treatment given to female contracts for gonorrhoea and non-specific genital infection in STD clinics in England and Wales two-thirds of women treated for gonorrhoea during 1978 were named contacts, a quarter of whom received epidemiological treatment. Only 35% of cases treated in this way were subsequently confirmed microbiologically, but nearly 1000 unconfirmed cases were returned as if they were true cases of gonorrhoea. In view of modern culture techniques and the low default rates found in this study, there seems to be little justification for the use of epidemiological treatment for gonorrhoea. Of women who gave a history of exposure to non-specific urethritis, 86% received epidemiological treatment. The variation in diagnostic and notification criteria for non-specific genital infection results in virtually worthless statistics for female cases treated.

The recent introduction of a vaccine against hepatitis B has raised the questions of who should be offered it and what the cost would be of a vaccination programme. An analysis was performed of the financial costs and benefits of such a programme designed to prevent acute hepatitis B in male homosexuals in the United Kingdom. Under various assumptions the total costs of screening and vaccination ranged from 2.2m pounds to 3m pounds for a five year programme and from 3.3m pounds to 4.8m pounds for a 10 year programme. The benefits over the same two periods for the programme, depending on two different assumptions of mortality prevented, ranged 3.9m pounds to 13.7m pounds and from 7m pounds to 24.4m pounds. Thus considerable savings may be made to the national economy by offering vaccination to homosexuals. These savings are obtained after consideration of only the acute aspects of hepatitis B. Had it been possible to determine the costs of the chronic sequelae of this disease the savings, compared with the costs, would have been greatly increased.

Four areas of neonatal behaviour have been assessed at delivery and during the following six weeks in a group of infants whose mothers were given epidural bupivacaine during labour. The influence on such a behaviour of the total maternal dose of bupivacaine and umbilical cord blood concentration of the drug has been examined with the confounding effects of other maternal and obstetric variables controlled. Significant and consistent effects of bupivacaine throughout the assessment period can be demonstrated. Immediately after delivery, infants with greater exposure to bupivacaine in utero were more likely to be cyanotic and unresponsive to their surroundings. Visual skills and alertness decreased significantly with increases in the cord blood concentration of bupivacaine, particularly on the first day of life by also throughout the next six weeks. Adverse effects of bupivacaine levels on the infant's motor organisation, his ability to control his own state of consciousness and his physiological response to stress were also observed. Muscle tone alone appeared to improve with increases in the values of the drug variables. These results show that the neonate differs from the adult in respect of both the nature of effects of the drug and sensitivity to it.

Records of the occurrence of vaginal bleeding were obtained from women using either a natural method of contraception or one of four types of hormonal contraceptive. The relationships between their bleeding patterns and a number of demographic variables were examined, with the aim of identifying subgroups of women who, if they used a particular hormonal method of contraception, would be likely to suffer more or less disruption to their bleeding pattern than the 'norm'. Within contraceptive method, bleeding patterns were more closely related to the women's geographical region of residence than to any other factor. Some of the differences between regions were consistent across contraceptive methods. European women tended to have more bleeding/spotting days than women in other regions; Latin American women had relatively short episodes and long bleeding-free intervals, whether they were using the ovulation method, combined pills or a vaginal ring. Other differences were method-specific. Women using combined pills in India or Pakistan had fewer spotting episodes than women using the same method elsewhere; those using progestogen-only pills had more. Regional variations in bleeding patterns were particularly marked among women using DMPA, and increased over time: by their fourth injection interval, 25% of European women had amenorrhea, as compared with 72% of subjects in North Africa. These findings need to be confirmed by carefully controlled studies of menstrual bleeding patterns and their acceptability in various ethnic groups. The results would be valuable in counselling new contraceptive acceptors, and could eventually guide the choice of methods for introduction into national family planning programmes.

A study was carried out to determine whether the diagnosis of non-specific urethritis was affected by differences in the microscopical interpretation of urethral smears between individual observers (interobserver variation) and the same observer on separate occasions (intraobserver variation). A marked degree of both intraobserver and interobserver variation was found which--depending on the diagnostic criteria adopted--could affect both the diagnosis and treatment of many patients attending a clinic of genitourinary medicine.

It has been shown that the antiprogestin RU 486 (mifepristone) increases the sensitivity of the early pregnant human uterus to the stimulatory action of synthetic prostaglandin E (PGE) analogues. To examine if RU 486 also increases uterine sensitivity to the naturally occurring PGE2 given orally, two investigative approaches were used in the present studies: (i) direct registration of uterine contractions before and after PGE2 administration in untreated and RU 486-treated early pregnant women; and (ii) a double-blind, randomized, controlled efficacy trial involving treatment of pregnant women (amenorrhoea of less than or equal to 49 days) with RU 486 (25 mg twice daily for 4 days) and PGE2 (1 mg once or twice) or placebo on the last day of RU 486 treatment. The results indicate that oral PGE2 at the doses employed had little or no stimulatory effect on uterine contractility and that it did not improve the rate of complete abortion achieved with RU 486 alone. Overall, 25 of 42 women (59%) had a complete abortion, 15 women (36%) did not abort and the remaining two had incomplete abortions. Women with complete abortions had significantly lower pretreatment levels of progesterone and a longer duration of induced bleeding than those who did not abort. Thus oral PGE2, when given in clinically acceptable doses, is not a suitable alternative to synthetic PGE analogues for use in combination with RU 486 for termination of early pregnancy.

A study was conducted to identify and estimate the proportion of patients suffering from gonorrhoea, trichomoniasis, and candidosis, both with and without symptoms, seeking care or failing to seek care at all. Samples women in a defined population were studied in antenatal, gynaecology, family planning, and sexually transmitted diseases clinics and in general practice. The incidence rates varied according to the conditions and to whether cases not proved microbiologically were included or excluded. The incidence rate may be less important than the prevalence rate since the former takes into account patients who have sought care whereas the latter is largely contributed by asymptomatic women who do not consult. The highest prevalence rates, in different agencies, were found for candidosis followed by trichomoniasis, with very low or zero rates for gonorrhoea. In view of these results general practitioners could treat women with genital symptoms empirically so long as accurate sexual histories are taken and follow-up were guaranteed. There is no place for wide-scale screening for gonorrhoea, but limited screening for trichomoniasis in antenatal, gynaecology, and hospital family planning clinics should be encouraged.

A follow-up study is reported of a consecutive series of 360 women who underwent termination of first trimester pregnancies by vacuum aspiration. Each patient received brief counselling before termination. Follow-up examinations were carried out by means of detailed, structured interviews at three months and between 15 months and two years (mean: 18 months) after termination. Outcome was assessed in terms of psychiatric symptoms, guilt feelings, and adjustment in marital and other interpersonal relationships, sexual responsiveness and work record. Compared with ratings of psychosocial adjustment before termination, significant improvement had occurred at follow-up in respect of psychiatric symptoms, guilt feelings and interpersonal and sexual adjustment; there was no significant change in marital adjustment. Adverse psychiatric and social sequelae were rare.

Increased menstrual blood loss (MBL) associated with intrauterine device (IUD) use may precipitate or aggravate iron deficiency anaemia, adversely affecting the health of women particularly those from developing countries. Studies were conducted to define the association of MBL and iron status in South American women; to determine the level of MBL induced by IUD use which would result in iron depletion, the length of time for this depletion to occur and, comparing various IUDS, to determine if any currently tested IUDs are suited to long-term use in South American women. A total of 395 women received one of 5 types of IUDs in Santiago, Chile, and Juiz de Fora, Brazil: Lippes Loop, Multiload-250 and Multiload-375 were used in both centres; in Santiago some subjects received the Copper-7 or ProgestasertR devices and in Juiz de Fora, the TCu 200 and the T-Chloroquin IUDs were also tested. MBL and haemoglobin (HGB) were measured for 3 menstrual cycles before insertion, and following insertion, at one, two, four, six, nine, twelve, eighteen and twenty-four months in the majority of cases. Serum ferritin was measured before insertion and at intervals of six months. Mean values of MBL prior to IUD insertion in both centres varied from 21-30 ml. As with previous publications, the use of the Lippes Loop was associated with the greatest increase in MBL which was sustained throughout the 24 months of observation. Women who had one of the two types of Multiload devices inserted also had increased MBL and reduced ferritin for at least 12 months of use. TCu 200 and Copper-7 IUD users had an initial increase in MBL of 1 to 17 ml in the first six months of observation returning to normal levels beyond six months. Serum ferritin levels were lower for one year and then returned to admission values. ProgestasertR users confirmed previous reports of a reduction of 40-50% in MBL and an increase in serum ferritin. Few significant changes in haemoglobin (HGB) concentrations were found. Serum ferritin levels on admission ranged from 7.1 to 16.4 ng/ml in Santiago and from 15.8 to 23.2 ng/ml in Juiz de Fora. Many women were in a marginal state of iron balance as evidenced by lower serum ferritin values. Changes in serum ferritin were very closely related to those in MBL.(ABSTRACT TRUNCATED AT 400 WORDS)

The provision of the sexually transmitted disease clinic service in the regional health authorities of England and Wales has been compared by relating the opening hours of clinics to the size of the population served. Relatively low levels of service were provided in the West Midlands and South-west Thames regions and high levels in the North-east and North-west Thames regions. When the service in the Greater London area health authorities was examined in relation to both resident and day-time populations, provision was relatively high in both instances, particularly in certain central London areas. Valid conclusions, however, about the equality of the service in different areas can only be drawn if the needs of the population for that service are known.

The current methods of diagnosing and treating herpes genitalis in clinics for sexually transmitted diseases in England and Wales are reported. Virus cultures were used as a diagnostic test in some or all patients in nearly two-thirds of clinics. Darkground examinations were performed on all or selected patients in most clinics, but fewer than half the clinics performed them on three or more separate occasions. In over 80% of clinics attempts were made to see some or all contacts of patients with herpes. The treatments prescribed varied, the commonest being saline washes, idoxuridine, and oral antibiotics. Serological tests were repeated after the disappearance of the lesions in 90% of clinics, while in 60% of clinics women with herpes genitalis were advised to have cytological examination at regular intervals in future. The importance of excluding syphilis in patients presenting with genital ulceration, the most appropriate treatments for herpes, and the possible association between the disease and cervical carcinoma are discussed.

A survey of infant-feeding practices among 265 mothers of 12-week-old infants in a London borough showed that only 18 gave breast milk alone, 236 giving bottle feeds, and 197 solids. Serious mistakes in feed preparation were common, and only 51 mothers followed manufacturers' instructions exactly. Most mothers (239) had attended a well-baby clinic, but clinic staff gave conflicting advice on infant feeding. Health workers must pay greater attention to educating mothers on the details of infant feeding if the risks of hypernatraemia and obesity are to be reduced.

A multi-centre, randomized trial was conducted to compare the efficacy and side-effects of two combination regimens of the antiprogestin RU 486 and the intramuscular PGE2 analogue sulprostone for termination of early pregnancy (amenorrhoea up to 49 days). Women in the 3-day group (n = 125) received 25 mg RU 486 twice daily for 3 days plus a single injection of 0.25 mg sulprostone in the morning of the third day of antiprogestin treatment. In the 4-day group (n = 126), RU 486 was given for 4 days and the sulprostone injection in the morning of the fourth day. Treatment outcome in the two groups was similar. Overall, 88.8% had a complete abortion, 6.8% an incomplete abortion and 2.4% were treatment failures; in the remaining 2% treatment outcome could not be determined. Only three of the six women with treatment failure still had detectable fetal heart activity when the pregnancy was terminated by vacuum aspiration two weeks after the start of treatment. Five of the 17 interventions for incomplete abortion were carried out as emergency procedures because of heavy bleeding; two of these five women were given a blood transfusion. The majority of the curettages (10/17) were performed in one centre. If the data from this centre and the women with undetermined treatment outcome were excluded, the rates for complete abortion, incomplete abortion and treatment failure in the remaining six centres were 93.6, 3.7 and 2.7%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical and psychological characteristics of 18 women with pelvic pain but no demonstrable pathology have been compared with those of 17 women with a similar complaint but some form of pelvic pathology and a control group of 9 women with no gynecologic problems. The results suggest that pelvic pain can have a psychosomatic origin which is amenable to short-term psychotherapeutic measures.

A study was conducted to collect information from consultants about the facilities and diagnostic criteria used in clinics for sexually transmitted diseases in England and Wales. Most of the information was obtained by personal interview with a response rate of 92%. Half the clinics were open for 10 hours or less a week, the mean length of time for all clinics was 14 1/2 hours a week. Eighty per cent of clinics had a full or part-time contact-tracing service. All the clinics had microscopical and serological services and almost all (99%) had cultural facilities. The policy concerning the most efficient use of these facilities is discussed.

Menstrual diary records were obtained from a total of 5257 women using nine different methods of contraception, one natural and eight hormonal. This paper presents a comparative analysis of their vaginal bleeding patterns. The analytic procedures follow the recommendations of a recent WHO workshop on bleeding pattern analysis, which involve dividing each subject's diary into successive 90-day reference periods, calculating ten indices for each period, and classifying women according to whether they have "clinically important" bleeding disturbances. In general, the findings of this analysis confirm those of previous studies. Women using the natural method, who were deliberately selected for the regularity of their menstrual cycles, averaged three bleeding/spotting episodes of length 5 days in each 90-day period, with very little variability within or between women. Subjects given a combined oral contraceptive had more regular patterns than any other treated group, with short (4-day) episodes and 23-24 day bleeding-free intervals. Progestogen-only pill users had more frequent, longer episodes and shorter, less predictable intervals than combined pill users. Contrary to widely-held beliefs, the progestogen-only pills produced fewer spotting days than the combined pills, and almost no spotting episodes at all. Nearly half of vaginal ring users experienced some menstrual disturbance in each period; their most common problems were irregular, infrequent or prolonged bleeding. Women using the long-acting injectable, depot medroxyprogesterone acetate, had totally unpredictable patterns, with infrequent but prolonged bleeding/spotting episodes. The incidence of amenorrhea rose from just under 10% in their first injection interval to over 40% in their fourth. The methods of analysis recommended by WHO in 1985 still require substantial refinement. Nevertheless, they are more sensitive than those used previously for WHO trials and produce an easily understood, clinically meaningful characterization of bleeding patterns.

Patterns of vaginal bleeding are an important factor in the acceptability of contraceptive methods. The analysis of data obtained from daily menstrual diary records is a major methodological problem to which no satisfactory solution exists. This review describes approaches to the analysis of bleeding patterns among contracepting and non-contracepting women and reviews the difficulties involved. The reference period method, introduced to avoid the arbitrary rules and definitions required for an analysis based on the concept of a menstrual cycle, is discussed and its limitations presented. The review draws on reports of meetings convened by the World Health Organization and the University of Exeter Family Planning Unit to discuss issues in the analysis. Previously unpublished methods are summarized and areas of controversy and topics for further research are identified.

A study was carried out to quantify and describe patients seen in sexually transmitted diseases clinics in England and Wales during 1978. Nine per cent of male patients were homosexual and 58% of female patients were under 25 years compared with only 42% of heterosexual men. Homosexual men had a higher mean number of cases per patient during the year than heterosexual men or women, largely because thay were more likely to have multiple episodes of disease. Female patients also had a higher mean number of cases than heterosexual men, because they often had several concurrent infections. There were 100,000 fewer patients than cases (322,000 compared with 432,000); 41% were seen in clinics in London. These findings show that current statistics for STDs are inadequate. Some quantification and categorisation of patients treated would be useful in analysing the trends in the incidences of the STDs.

Data previously collected on the facilities and diagnostic criteria used in clinics for sexually transmitted diseases in England and Wales were reanalysed to established how different consultant policies affected the management of individual cases. Several discrepancies were found between conclusions based on percentages of clinics and those based on numbers of cases. Full-time facilities for contact tracing were available to more cases than previously suggested and rectal sampling in women was more widespread. Laboratory facilities were limited and cultural facilities lacking in small clinics, which thus affected only a small number of cases. Previous indications that diagnostic criteria were fairly standardised in the diagnosis of non-specific urethritis were found to be invalid. Variation in the management of individual cases was found to lead to inconsistencies in the notification of STDs to the Department of Health and Social Security.

A study of diagnostic patterns in patients attending sexually transmitted disease clinics in England and Wales during 1978 showed that homosexuals contributed 10% of all male cases but 15% of gonococcal infections. In heterosexual and homosexual men only 6% of disease episodes included more than one positive diagnosis compared with 16% in women. One or more diseases occurred concurrently in over 30% of cases of gonorrhoea, trichomoniasis, candidosis, genital herpes, and genital warts in women. Men with multiple episodes of disease contributed a disproportionate number of gonococcal infections but were less likely to have candidosis or genital herpes than patients with only one disease episode. Thus, counting cases treated appears to be an inadequate way of measuring the problems caused by STDS. To enable more rapid identification of the diseases which are the most difficult to control, STD statistics should include the sexual orientation of male patients and differentiate between genuine "new" attenders at clinics and those previously seen.

Neonatal behaviour in a group of infants whose mothers received pethidine during labour was assessed at delivery and during the first six weeks of life by means of the Brazelton Neonatal Behavioural Assessment Scale. The influence of the total maternal dose of pethidine and umbilical cord blood concentration of the drug on such behaviour has been examined with the confounding effects of all other variables controlled. Higher cord blood levels of pethidine were associated with babies who were more prone to respiratory difficulties, drowsy and unresponsive immediately after delivery. Throughout the six weeks in which the assessments were made, depressed attention and social responsiveness were found in infants with high drug levels. At three and six weeks, the infant whose exposure ao pethidine had been high tended to change state more frequently, to cry during the test and to be less capable of quieting himself. These findings suggest that the newborn infant responds to pethidine in the same way as the adult, but the changes observed were relatively subtle, and comparison of these infants with a control groups whose mothers had received no drugs revealed no between-group differences in behaviour.

Contraceptive methods often induce disturbances in vaginal bleeding patterns which are the main reason for women to discontinue method use. Knowledge of these changes is essential for effective counselling and product development and necessitates adequate methods of collection and analysis of vaginal bleeding data. These issues were reviewed by clinicians, medical statisticians and computer analysts during several consultations organized by the World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction and their discussions are summarized in this paper. Recommendations are made on the use of menstrual diary cards for data collection. It is suggested that the analysis of menstrual patterns be based on the reference period method developed by Rodriguez et al. in 1976 to which several modifications in terminology and choice of summary statistics are proposed. While these are presented as the minimum required for the comparability of studies, other points of analysis are identified which need further study, in an attempt to stimulate research in this field by other investigators.

A selection of psychological and social factors present in 360 women who underwent legal termination of pregnancy are related to their contraceptive practice. One-third of the group were ignorant about contraceptive methods, ignorance being more common in women from social classes IV and V and in those under the age of 19. Nearly half of those who had some knowledge of contraceptive practice became pregnant after knowingly taking a risk. A total of 41% had been using some form of contraception immediately before conception. The reliability of contraceptive methods used was found to be inversely related to neuroticism scores obtained from the Eysenck Personality Inventory, neuroticism being highest in women who had not used any form of contraception.Of 91% of the group seen three months after their termination 86% were using reliable contraceptive methods. A follow-up study one or two years after termination has shown that 81% of the 215 women contacted so far are using a reliable method of contraception; two unwanted pregnancies have occurred but both were due to contraceptive failure. This satisfactory outcome has been ascribed to the system of counselling all women before and after termination.

This paper describes the relationship between menstrual bleeding patterns recorded and reasons for discontinuing method use given by women using one of four types of hormonal contraception: combined oral pills, progestogen-only oral pills, a vaginal ring or depot-medroxyprogesterone acetate (DMPA). The women were recruited to five clinical trials, each of which lasted at least 48 weeks. The subject's reason for discontinuation was recorded if she stopped contraceptive use before the scheduled time. Overall, the reason expressed for discontinuing method use was a close reflection of the subject's experience. Among women using either type of oral contraceptive or a vaginal ring, subjects who discontinued for a non-menstrual reason or were lost to follow-up had bleeding patterns which did not differ markedly from those of women who continued method use. Only in the DMPA group was there any evidence that women who complained of non-menstrual side effects or were lost to follow-up might have ceased method use because they were unwilling or unable to tolerate their bleeding patterns. Subjects who discontinued because of amenorrhea had few bleeding/spotting days and at least one prolonged bleeding-free interval; women who complained of longer bleeding had long episodes and short intervals. Women who reported heavier bleeding had patterns which were similar to, but less extreme, than those of subjects who reported longer bleeding. The complaint of irregular bleeding, however, did not concur with the bleeding patterns recorded, regardless of contraceptive method. The predominant menstrual disturbance in this group of women was frequency of bleeding. They had no special difficulty in predicting either the time of onset or the length of their bleeding episodes. There were marked differences between individuals in terms of their acceptance of bleeding disturbances. Nevertheless, the results of this study confirm the importance of counselling. Women using DMPA tolerated far greater menstrual disruption than subjects using any other method. Subjects using an oral contraceptive were unlikely to have been warned of potential bleeding problems; when they encountered any, they tended to cease method use. In contrast, subjects using DMPA would have been advised to expect irregular patterns and possibly amenorrhea; prepared for such disturbances, their perseverance was remarkable.