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To determine the effect of daily acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 (HSV-2) in a randomised placebo-controlled trial among rural Zimbabwean sex workers.214 women were recruited and tested for HIV-1 and HSV-2 antibodies, HIV plasma viral load, CD4 lymphocyte count and genital swabs for qualitative detection of HIV-1 and HSV-2 genital shedding. Women were randomly assigned to acyclovir 400 mg twice a day for 12 weeks or matching placebo and were followed weekly to detect HIV-1 or HSV-2 genital shedding. Shedding analyses were only undertaken on 125 women co-infected with HSV-2 and HIV-1. Data were analysed using logistic regression, with random effects modelling used to account for repeated measurements on the same women.All women were randomly assigned to acyclovir or placebo; 125 of whom were co-infected with HIV-1 and HSV-2. 69 women were randomly assigned to acyclovir and 56 to placebo. Although twice daily acyclovir reduced rates of HSV-2 genital shedding, (adjusted odds ratio (AOR) 0.24; 95% CI 0.12 to 0.48; less than p0.001), it had no effect on the proportion of visits at which HIV-1 shedding was detected (AOR 1.08; 95% CI 0.48 to 2.42; p = 0.9). Adherence varied between participants but even when adherence was high (as determined by pill count and extent of HSV-2 suppression) HIV-1 shedding was not reduced.Among these HIV-1 and HSV-2-seropositive women, suppressive acyclovir therapy had no effect on the rate of HIV genital shedding despite a reduction in genital HSV-2. Treatment adherence and its measurement clearly affect the interpretation of these results.

We studied the association between herpes simplex virus type-2 (HSV-2) and HIV-1 viralload in plasma, semen, cervico-vaginal secretions and genital ulcers. Forty-seven (68%) men and 57 (80%) women were HSV-2 antibody positive, of whom 12 (26%, 95% confidence interval [CI] 20, 32) and five (8%, 95% CI 4, 12), respectively, had HSV-2 genital shedding detected by polymerase chain reaction. The mean HIV-1 seminal and cervico-vaginal viral loads did not differ significantly according to the presence of HSV-2 shedding. Eleven men and 15 women presented with genital ulcers; all ulcers were due to HSV-2. Ten men and nine women were followed up over six days: the mean (95% CI) HIV-1 log viral load copies/mL in the genital ulcers at baseline and final visits were 2.5 (2.3, 2.7) and 3.1 (2.0, 4.2) for men and 3.0 (2.6, 3.4) and 2.7 (2.3, 3.1) for women. These findings do not support the hypothesis that HSV-2 increases the HIV-1 viral load in genital secretions.

This study describes the differences in sexual behaviour in individuals with genital herpes (GH) during "symptomatic" and "asymptomatic" periods of the disease.A cross sectional questionnaire was undertaken by 1193 individuals attending clinics between 1998 and 2001. All participants in this analysis were in heterosexual, monogamous partnerships, self identified with a history of symptomatic GH and with confirmed HSV-2 infection.Sexual activity reported during asymptomatic v symptomatic periods of GH was 98% v 40% (p0.001), 76% v 29% (p0.001), and 25% v 11% (p0.001) for vaginal, oral, and anal intercourse, respectively, while "always" condom use during asymptomatic and symptomatic periods was 20% v 35% (p0.001), 2% v 7% (p0.001), and 10% v 15% (p = 0.131), respectively. The proportion of individuals who either abstained from vaginal intercourse or "always" used condoms was 21% v 74% (p0.001), for asymptomatic v symptomatic periods. Multivariable analyses indicated that factors associated with engaging in intercourse during symptomatic periods of GH included current intrauterine device use (adjusted odds ratio (aOR) = 2.96, 95% confidence interval (CI) = 1.46 to 6.02); living in Latin America (aOR = 2.16, CI = 1.19 to 3.91) or Europe (aOR = 1.67, CI = 1.21 to 2.28), compared with North America; previous sexually transmitted disease (aOR = 1.42, CI = 1.08 to 1.89); a higher number of sexual acts per month (aOR = 1.09, CI = 1.06 to 1.11); and a higher number of GH recurrences per year (aOR = 1.08, CI = 1.03 to 1.12).These data indicate that the majority of people with GH either abstained from intercourse or "always" used condoms during symptomatic periods of GH. However, condom use was relatively low during asymptomatic periods in comparison with symptomatic periods. These results highlight that further education on GH prevention is warranted, particularly for symptomatic periods.

Introduction: Herpes simplex virus type 2 (HSV-2) facilitates sexual acquisition of HIV-1 but data on transmission are less clear. In this study the interaction between genital shedding of HIV-1 and HSV-2 was explored among Zimbabwean sex workers. Methods: Women (n = 214) were interviewed about genital symptoms. Blood samples were analysed for HIV-1 and HSV-2 antibodies, HIV-1 plasma viral load (PVL) and CD4 lymphocyte count and genital swabs for detection of HIV-1 and HSV-2 genital shedding, Chlamydia trachomatis, Neisseria gonorroheae and Trichomonas vaginalis, and a cervico-vaginal lavage (CVL) for quantitative measurement of HIV-1 shedding. Shedding analyses were undertaken on women co-infected with HSV-2 and HIV-1. Results: A total of 124 women were co-infected with HIV-1 and HSV-2; 58 were infected with HSV-2 alone. Most HIV-1-infected women were co-infected with HSV-2 (95.4%). Genital HIV-1 shedding was detected in 84.3% of co-infected women and was associated with low CD4 cell count and high PVL but not with reported symptoms of genital herpes or genital shedding of HSV-2. There was no difference in HIV-1 shedding among women shedding HSV-2 (79.3%) and women not shedding HSV-2 (83.2%) (P = 0.64). The adjusted odds ratio for HIV-1 shedding between HSV-2 shedders and non-shedders was 0.8 [95% confidence interval (CI), 0.2-3.3]. HIV-1 PVL(log(10)) and CVL viral load(log(10)) were correlated (r = 0.38; 95% Cl, 0.2-0.5). After adjusting for PVL, genital symptoms and age, HSV-2 shedding had no effect on CVL viral load (P = 0.13). Conclusion: Rate and quantity of HIV-1 genital shedding do not appear to be altered by presence of HSV-2 genital shedding. (C) 2006 Lippincott Williams & Wilkins.

Countries in the the Asia-Pacific region and Africa tend to have the highest prevalence of hepatitis B infection worldwide. Hepatitis B infection progresses from an asymptomatic persistently infected status to chronic hepatitis B, cirrhosis, decompensated liver disease and/or hepatocellular carcinoma. The aim of this review was to summarize rates and risk factors for progression between disease states in the Asia-Pacific region and Africa. A literature search was conducted employing MEDLINE and EMBASE (1975-2003) using the following key words: hepatitis B, natural history, disease progression, cirrhosis, hepatocellular carcinoma, mortality, Africa and the Asia-Pacific region. Bibliographies of articles reviewed were also searched. Ranges for annual progression rates were: (i) asymptomatic persistent infection to chronic hepatitis B, 0.84-2.7%; (ii) chronic hepatitis B to cirrhosis, 1.0-2.4%; and (iii) cirrhosis to hepatocellular carcinoma, 3.0-6.6%. Patients with asymptomatic persistent infection and chronic hepatitis B had relatively low 5-year mortality rates ( 50%) were much higher in patients with decompensated liver disease and hepatocellular carcinoma. No data were found for progression rates in African populations. Hepatitis B e antigen was a risk factor for chronic hepatitis B, and bridging hepatic necrosis in chronic hepatitis B increased the risk of cirrhosis. Risk factors for hepatocellular carcinoma included cirrhosis, co-infection with hepatitis C virus, and genetic and environmental factors. In this review, wide ranges of disease progression estimates are documented, emphasizing the need for further studies, particularly in Africa, where progression rates are largely not available. Summarizing information on factors associated with disease progression should assist in focusing efforts to arrest the disease process in those at most risk.

Objectives: There have been few recent population-based herpes simplex virus type 2 (HSV-2) seroprevalence studies in England, but reports from the United States have indicated a 30% rise in HSV-2 seroprevalence between 1976 and 1994. This study aimed to ascertain trends in HSV-2 infection in England between 1991 and 2000. Study Design: Anonymized serum residues collected through public health laboratories across England from individuals aged 16 to 64 years seeking health care through the National Health Service in 1991 (n = 2259) and 2000 (n = 3646) were tested for anti-HSV-2 IgG using the HerpeSelect 2 enzyme-linked immunosorbent assay IgG (Focus). Results: In 9 sites across England, the age- and sex-standardized HSV-2 seroprevalence was 9.7% (95% confidence interval, 8.4-11.0%). Data from 4 sites common to both study years indicated no change in HSV-2 seroprevalence between 1991 and 2000. Conclusions: After adjustment for age, sex, and geographic location, there was no evidence of a change in seroprevalence between 1991 and 2000.

Several studies, notably from rural areas, have shown an association between mobility and HIV infection. However, reasons for this association are poorly documented. In this study, we examined the relationship between mobility, sexual behavior, and HIV infection in an urban population of Cameroon. A representative sample of 896 men and 1017 women were interviewed and tested for HIV infection and other sexually transmitted infections in Yaounde in 1997. Mobile and nonmobile people were compared with respect to sociodemographic attributes, risk exposure, condom use, and prevalence of HIV infection, using descriptive statistics and multivariate logistic regression. Seventy-three percent of men and 68% of women reported at least 1 trip outside of Yaounde in the preceding 12 months. Among men, the prevalence of HIV infection increased with time away from town. Men who declared no absence were 5 times less likely to be infected than were those away for >31 days (1.4% vs. 7.6%, respectively; adjusted odds ratio, 0.23; 95% confidence interval, 0.07-0.82). Furthermore, mobile men reported more risky sexual behaviors (ie, more partners and more one-off contacts). For women, the pattern was less clear: differences in the prevalence of HIV infection were less marked for nonmobile than for mobile women (6.9% vs. 9.8%, respectively; P > 0.1). This study suggests that characteristics of male mobility may be an important feature of the HIV epidemic in Cameroon.

Background and Aims: The present study aimed to describe the disease progression of chronic hepatitis B patients without or with compensated cirrhosis at baseline, to estimate the risk of progression to decompensated cirrhosis, hepatocellular carcinoma and death, and to determine prognostic factors of disease progression in patients in Shanghai, China. Methods: Stored medical records from 322 biopsy-confirmed chronic hepatitis B cases diagnosed between 1981 and 1993 were selected, and the status of patients was tracked in 1999–2000. Among consenting patients, ultrasound examination and laboratory tests were conducted. Person-year incidence rates, Kaplan–Meier analysis, log-rank tests, and Cox regression analysis were conducted. Results: Among chronic hepatitis B patients without compensated cirrhosis, the incidence rates of decompensated cirrhosis, hepatocellular carcinoma, and death were 6.3, 2.8, and 7.6 per 1000 person-years, respectively, while for patients with compensated cirrhosis, the rates were 35.6, 8.2, and 35.2 per 1000 person-years, respectively. The 15-year survival rate was 88% for patients without compensated cirrhosis, compared with 56% for patients with compensated cirrhosis (P

This study estimated the regional and age- and gender-specific seroprevalences of herpes simplex virus type 1 (HSV-1) and HSV-2 in Ontario, Canada. Stored serum specimens from subjects aged 15 to 44 years, including men ( n = 979), women not under prenatal care ( n = 638), and women under prenatal care ( n = 701) submitted for routine viral serology were randomly selected according to regional population size from public health laboratories. HSV-1 and HSV-2 testing was done with the MRL enzyme immunoassay (EIA) (Focus Technologies), and HSV-2 was also tested by the Gull/Meridian EIA. Specimens discordant for HSV-2 antibodies between the two EIAs were resolved by a recombinant immunoblot assay (Focus Technologies). The overall age- and gender-standardized seroprevalences of HSV-1 and HSV-2 were 51.1% (95% confidence interval [CI], 50.1 to 52.1) and 9.1% (95% CI, 8.6 to 9.7), respectively. The seroprevalence of HSV-1 antibodies increased from 26.9 to 54.7% in men between 15 to 16 and 40 to 44 years of age, from 32.0 to 88.7% in women not under prenatal care, and from 55.2 to 69.2% in women under prenatal care. The seroprevalence of HSV-2 increased from 3.8 to 21.3% in men between 15 to 16 and 40 to 44 years of age, from 0 to 18.9% in women not under prenatal care, and from 3.4 to 23.1% in women under prenatal care. HSV-2 results were discordant for 3.3% (76 of 2,318) of specimens. Both types of HSV antibodies appeared to be acquired earlier among women under prenatal care than among men and women not under prenatal care. Antibodies were more prevalent among people in northern Ontario (72.9% of subjects [range, 68.4 to 77.4%] for HSV-1 and 13.7% of subjects [95% CI, 10.2 to 17.2%] for HSV-2) than elsewhere.

OBJECTIVES: To compare the epidemiology of gonorrhoea, chlamydial infection and syphilis in four cities in sub-Saharan Africa; two with a high prevalence of HIV infection (Kisumu, Kenya and Ndola, Zambia), and two with a relatively low HIV prevalence (Cotonou, Benin and Yaounde, Cameroon). DESIGN: Cross-sectional study, using standardized methods, including a standardized questionnaire and standardized laboratory tests, in four cities in sub-Saharan Africa. METHODS: In each city, a random sample of about 2000 adults aged 15-49 years was taken. Consenting men and women were interviewed about their socio-demographic characteristics and their sexual behaviour, and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection, and (women only) Trichomonas vaginalis infection. Risk factor analyses were carried out for chlamydial infection and syphilis seroreactivity. RESULTS: The prevalence of gonorrhoea ranged between 0% in men in Kisumu and 2.7% in women in Yaounde. Men and women in Yaounde had the highest prevalence of chlamydial infection (5.9 and 9.4%, respectively). In the other cities, the prevalence of chlamydial infection ranged between 1.3% in women in Cotonou and 4.5% in women in Kisumu. In Ndola, the prevalence of syphilis seroreactivity was over 10% in both men and women; it was around 6% in Yaounde, 3-4% in Kisumu, and 1-2% in Cotonou. Chlamydial infection was associated with rate of partner change for both men and women, and with young age for women. At the population level, the prevalence of chlamydial infection correlated well with reported rates of partner change. Positive syphilis serology was associated with rate of partner change and with HSV-2 infection. The latter association could be due to biological interaction between syphilis and HSV-2 or to residual confounding by sexual behaviour. At the population level, there was no correlation between prevalence of syphilis seroreactivity and reported rates of partner change. CONCLUSION: Differences in prevalence of chlamydial infection could be explained by differences in reported sexual behaviour, but the variations in prevalence of syphilis seroreactivity remained unexplained. More research is needed to better understand the epidemiology of sexually transmitted infections in Africa.

OBJECTIVE: To identify factors that could explain differences in rate of spread of HIV between different regions in sub-Saharan Africa. DESIGN: Cross-sectional study. METHODS: The study took place in two cities with a relatively low HIV prevalence (Cotonou, Benin and Yaounde, Cameroon), and two cities with a high HIV prevalence (Kisumu, Kenya and Ndola, Zambia). In each of these cities, a representative sample was taken of about 1000 men and 1000 women aged 15-49 years. Consenting men and women were interviewed about their socio-demographic background and sexual behaviour; and were tested for HIV, herpes simplex virus type 2 (HSV-2), syphilis, Chlamydia trachomatis and Neisseria gonorrhoea infection, and (women only) Trichomonas vaginalis. Analysis of risk factors for HIV infection was carried out for each city and each sex separately. Adjusted odds ratios (aOR) were obtained by multivariate logistic regression. RESULTS: The prevalence of HIV infection in sexually active men was 3.9% in Cotonou, 4.4% in Yaounde, 21.1% in Kisumu, and 25.4% in Ndola. For women, the corresponding figures were 4.0, 8.4, 31.6 and 35.1%. High-risk sexual behaviour was not more common in the high HIV prevalence cities than in the low HIV prevalence cities, but HSV-2 infection and lack of circumcision were consistently more prevalent in the high HIV prevalence cities than in the low HIV prevalence cities. In multivariate analysis, the association between HIV infection and sexual behavioural factors was variable across the four cities. Syphilis was associated with HIV infection in Ndola in men [aOR = 2.7, 95% confidence interval (CI) = 1.5-4.91 and in women (aOR = 1.7, 95% CI = 1.1-2.6). HSV-2 infection was strongly associated with HIV infection in all four cities and in both sexes (aOR ranging between 4.4 and 8.0). Circumcision had a strong protective effect against the acquisition of HIV by men in Kisumu (aOR = 0.25, 95% CI = 0.12-0.52). In Ndola, no association was found between circumcision and HIV infection but sample sizes were too small to fully adjust for confounding. CONCLUSION: The strong association between HIV and HSV-2 and male circumcision, and the distribution of the risk factors, led us to conclude that differences in efficiency of HIV transmission as mediated by biological factors outweigh differences in sexual behaviour in explaining the variation in rate of spread of HIV between the four cities.

The objective was to estimate the likely percentage of HIV infections that may be attributable to one-off partnerships (such as those between female sex workers and their clients) and longer-term partnerships in rural Uganda. This was addressed by the application of a microsimulation model (SimulAIDS) of the transmission dynamics of HIV infection, drawing on data from a population cohort of 10,000 in rural Uganda. For a scenario reproducing documented characteristics of the study population in 1990, when adult HIV prevalence was 9%, and during subsequent follow up (1990-1994), when adult HIV incidence was 8 per 1000 person-years, the percentage of HIV infections in men (women) attributed to one-off partnerships decreased from 96% (26%) during 1980 to 67% (8%) in 1989 and 22% (5%) in 1994. Reducing HIV transmission between one-off partners early in an HIV epidemic may substantially limit the potential for the spread of HIV infection. At a later phase, prevention must also focus on control of transmission between longer-term HIV-discordant partners.This paper presents results of a study using a simulation model in estimating the likely percentage of HIV infections that may be attributable to one-off partnerships (e.g., female sex workers and their clients) and longer-term partnerships among the rural population of Uganda. The study adopted SimulAIDS, an age-structured microsimulation model of the HIV infection dynamics along with ulcerative and non-ulcerative sexually transmitted diseases. Data obtained from the 10,000 cohort population reflected a decline in the incidence of HIV in adults between 1990 and 1994, a result which could be attributed to one-off sexual partnerships in 1980, 1984, 1989, 1994, and 1999. The study supports that minimizing transmission of HIV from short-term sexual partnerships during early stage of the disease could have a strong impact on the reduction in the spread of HIV infection.

This article reviews scientific and other literature during the 1990s that links migration and mobility with the spread of sexually transmitted diseases (STDs), including HIV/AIDS. The focus is on key population groups linked to the spread of HIV and STDs in West and Central Africa: migrant laborers, truck drivers, itinerant traders, commercial sex workers (CSWs), and refugees. Countries with high emigration and immigration tend to have high levels of HIV infection, with the exception of Senegal. The main destination of immigrants are Senegal, Nigeria, and Cote d'Ivoire in West Africa and Cameroon, Congo, Gabon, and Congo in Central Africa. The risk of infection and the spread of HIV is variable among migrants. There is little in the literature that substantiates hypotheses about the strong association between migration and HIV-positive status. Information is needed on the duration, frequency of return visits, living conditions, sexual activities with multiple partners, and information before departure, along the routes, at final destination, and at the time of returns. Action-based research in five West African countries (Burkina Faso, Cote d'Ivoire, Mali, Niger, and Senegal) should produce results in late 1998. Comparable studies in Central Africa are unknown. Regional studies should be complemented by local studies. Prevention would benefit from studies on the relative size of these five population groups by geographic location.

Inhaled corticosteroid has been shown to be effective in the management of asthma. However, there is a lack of studies that assess the effect of cessation after long-term treatment with inhaled corticosteroid. This question was addressed in 28 children with stable asthma, aged 11 to 18 yr of age, who had completed 28 to 36 months of treatment with inhaled corticosteroid (budesonide 200 µg 3 times/day) and inhaled β-2-agonist (salbutamol 200 µg 3 times/day). The children were randomized in a 1:2 ratio in a double-blind study either to continue budesonide (n = 8) during a period of 6 months or to decrease the dose of budesonide (n = 20) within 2 months, followed by placebo for 4 months. Treatment with salbutamol 600 µg daily was continued in both groups. Eight children from the tapering-off group withdrew, mainly due to symptoms of asthma, compared with none in the continuous treatment group. Five patients in the tapering-off group experienced exacerbations for which prednisolone was given, compared with no...

Background. The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy. Methods. In a multicenter trial we compared three inhalation regimens in which a β2-agonist (terbutaline, 2000 μg daily) was combined with a corticosteroid (beclomethasone, 800 μg daily), an anticholinergic bronchodilator (ipratropium bromide, 160 μg daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years. Results. Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per mil...

Purpose To estimate the incidence of cataracts in an adult idiopathic thrombocytopenic purpura (ITP) and in a comparable non-ITP population, stratified by age, gender and medication use in order to determine whether the risk of cataracts is greater in ITP patients. Methods Retrospective cohort of 745 newly diagnosed ITP patients and 3725 non-ITP subjects who were 18 years of age or older. The study population included patients registered on the General Practice Research Database (GPRD) during the period 1992–2005. ITP patients, identified using Read/Oxmis codes, were matched to five non-ITP patients. The exposure of interest was oral systemic steroid use and the primary outcome was cataracts. Results The overall incidence rate of cataracts in males was 11.8 per 1000 PY (95%CI: 6.3–20.2) and in females 9.0 per 1000 PY (95%CI: 5.2–14.4). In the non-ITP population these rates were 14.0 per 1000 PY (95%CI: 11.0–17.4) and 8.1 per 1000 PY (95%CI: 6.4–10.1), respectively. In the ITP population, users of oral steroids (OS) had a cataract incidence rate of 14.0 per 1000 PY (95%CI: 8.7–21.4) and non-users 6.0 per 1000 PY (95%CI: 2.8–11.4). In the non-ITP population, these rates were 16.9 per 1000 PY (95%CI: 11.9–23.3) and 9.2 per 1000 PY (95%CI: 7.6–11.0), respectively. OS were associated with an increased risk for cataracts. Conclusions The rates of cataract in an adult ITP population are comparable to that in a non-ITP population. Copyright © 2009 John Wiley & Sons, Ltd.

A person experiencing more than one medical condition may have ambiguous clinical presentation. ITP is a serious autoimmune disease with little epidemiological evidence on its burden, risk factors, and comorbidities. Using the United Kingdom general practice research database, we conducted a 14 years population-based case control-type study to explore medical conditions more likely to cooccur with ITP and their temporal relationship in association with ITP. ITP patients were matched to non-ITP on practice, age, gender, and follow-up period. Potential comorbidities were represented by patients’ medical information at the preferred term level of the MedDRA international classification. As well as death (OR=60.0; 95% CI [4.47–806.0]) and known clinical signs and symptoms of ITP, ITP is associated with considerable number of medical conditions. The association between ITP and some of these conditions is apparent both before and after ITP diagnosis. Specific targeted studies can now be setup to reexamine observed associations.

The objective of this study was to evaluate risk factors for herpes simplex virus type 2 (HSV-2) infection among men whose female partners have genital herpes (GH).Between 1998 and 2001, 717 men in heterosexual monogamous relationships, without a history of GH, completed a cross-sectional questionnaire on demographic, behavioral, and knowledge factors for GH. Their female partners were symptomatic and HSV-2-seropositive. Risk factors for HSV-2 seropositivity were assessed using logistic regression.On laboratory confirmation, 25% of the men were HSV-2-seropositive. Factors significantly (P0.01) associated with HSV-2 infection included: never using condoms (adjusted odds ratio [aOR], 1.84; 95% confidence interval [CI], 1.15-2.95), prior sexually transmitted disease (STD) (aOR, 1.80; CI, 1.27-2.58), vaginal intercourse during symptomatic episodes (aOR, 1.77; CI, 1.19-2.62), longer partnership (for each additional year aOR, 1.07; CI, 1.03-1.09), and lower knowledge of GH (aOR, 1.14; CI, 1.05-1.23).Potentially modifiable risk factors for HSV-2 infection included engaging in vaginal sex during symptomatic episodes, never using condoms, and lower knowledge of GH.

Biological strategies for interrupting transmission of human immunodeficiency virus (HIV) type 1 should be directed at reducing infectiousness of and susceptibility to HIV-1. Potential antiretroviral interventions include reducing the likelihood of transmission of HIV-1 by reducing HIV-1 load in the blood and genital tract of HIV-1--infected person, prophylaxis after high-risk exposure, and pre-exposure prophylaxis for very high risk populations. Antiviral treatment of herpes simplex virus (HSV) type 2, the most common cause of genital ulcers, should be evaluated as a strategy for HIV-1 infection prevention by reducing infectiousness of and susceptibility to HIV-1, on the basis of biological and epidemiological data indicating that HSV-2 facilitates transmission and acquisition of HIV-1. The rationale for antiretroviral and HSV-2-specific interventions and studies to test these strategies are described.

OBJECTIVES: To describe the epidemiology of Trichomonas vaginalis infection and its association with HIV infection, in women in four African cities with different levels of HIV infection. DESIGN: Cross-sectional study, using standardized methods, including a standardized questionnaire and standardized laboratory tests, in four cities in sub-Saharan Africa: two with a high prevalence of HIV infection (Kisumu, Kenya and Ndola, Zambia), and two with a relatively low prevalence of HIV (Cotonou, Benin and Yaounde, Cameroon). METHODS: In each city, a random sample of about 2000 adults aged 15-49 years was taken. Consenting men and women were interviewed about their socio-demographic characteristics and their sexual behaviour, and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection, and (women only) T. vaginalis infection. Risk factor analyses were carried out for trichomoniasis for each city separately. Multivariate analysis, however, was only possible for Yaounde, Kisumu and Ndola. RESULTS: The prevalence of trichomoniasis was significantly higher in the high HIV prevalence cities (29.3% in Kisumu and 34.3% in Ndola) than in Cotonou (3.2%) and Yaounde (17.6%). Risk of trichomoniasis was increased in women who reported more lifetime sex partners. HIV infection was an independent risk factor for trichomonas infection in Yaounde [adjusted odds ratio (OR) = 1.8, 95% confidence interval (CI) = 0.9-3.7] and Kisumu (adjusted OR = 1.7, 95% CI = 1.1-2.7), but not in Ndola. A striking finding was the high prevalence (40%) of trichomonas infection in women in Ndola who denied that they had ever had sex. CONCLUSION: Trichomoniasis may have played a role in the spread of HIV in sub-Saharan Africa and may be one of the factors explaining the differences in levels of HIV infection between different regions in Africa. The differences in prevalence of trichomoniasis between the four cities remain unexplained, but we lack data on the epidemiology of trichomoniasis in men. More research is required on the interaction between trichomoniasis and HIV infection, the epidemiology of trichomoniasis in men, and trichomonas infections in women who deny sexual activity.

OBJECTIVES: To estimate age- and sex-specific herpes simplex virus type-2 (HSV-2) prevalence in urban African adult populations and to identify factors associated with infection. DESIGN AND METHODS: Cross-sectional, population-based samples of about 2000 adults interviewed in each of the following cities: Cotonou, Benin; Yaounde, Cameroon; Kisumu, Kenya and Ndola, Zambia. Consenting study participants were tested for HIV, HSV-2 and other sexually transmitted infections. RESULTS: HSV-2 prevalence was over 50% among women and over 25% among men in Yaounde, Kisumu and Ndola, with notably high rates of infection among young women in Kisumu and Ndola (39% and 23%, respectively, among women aged 15-19 years). The prevalence in Cotonou was lower (30% in women and 12% in men). Multivariate analysis showed that HSV-2 prevalence was significantly associated with older age, ever being married, and number of lifetime sexual partners, in almost all cities and both sexes. There was also a strong, consistent association with HIV infection. Among women, the adjusted odds ratios for the association between HSV-2 and HIV infections ranged from 4.0 [95% confidence interval (CI) = 2.0-8.0] in Kisumu to 5.5 (95% CI = 1.7-18) in Yaounde, and those among men ranged from 4.6 (95% CI = 2.7-7.7) in Ndola to 7.9 (95% CI = 4.1-15) in Kisumu. CONCLUSIONS: HSV-2 infection is highly prevalent in these populations, even at young ages, and is strongly associated with HIV at an individual level. At a population level, HSV-2 prevalence was highest in Kisumu and Ndola, the cities with the highest HIV rates, although rates were also high among women in Yaounde, where there are high rates of partner change but relatively little HIV infection. The high prevalence of both infections among young people underlines the need for education and counselling among adolescents.

OBJECTIVE: The objective of this study was to explore whether the differences in rate of spread of HIV in different regions in sub-Saharan Africa could be explained by differences in sexual behaviour and/or factors influencing the probability of HIV transmission during sexual intercourse. METHODS: A cross-sectional, population-based study was conducted in two cities with a high HIV prevalence (Kisumu in Kenya and Ndola in Zambia) and two cities with a relatively low HIV prevalence (Cotonou in Benin and Yaounde in Cameroon). In each of these cities, approximately 1000 men and 1000 women, aged 15-49 years, were randomly selected from the general population. Consenting men and women were interviewed and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection and trichomoniasis (the latter for women only). In addition, a survey was conducted on a random sample of 300 sex workers in each city. The research instruments, including the questionnaires and the laboratory procedures, were standardized to permit comparison of results. RESULTS: The numbers of men interviewed were 1021 in Cotonou, 973 in Yaounde, 829 in Kisumu, and 720 in Ndola. The corresponding figures for women were 1095, 1116, 1060 and 1130. In Yaounde, Kisumu and Ndola, the response rates for men were lower than for women due to failure to make contact with eligible men. The proportion of eligible women who were interviewed was 86% in Yaounde, and 89% in Kisumu and Ndola. In Yaounde, 76% of eligible men were interviewed, along with 82% in Kisumu and 75% in Ndola. The prevalence of HIV infection in men was 3.3% in Cotonou, 4.1% in Yaounde, 19.8% in Kisumu and 23.2% in Ndola. For women, the respective figures were 3.4, 7.8, 30.1 and 31.9%. The prevalence of HIV infection among women aged 15-19 years was 23.0% in Kisumu and 15.4% in Ndola. Among women in Kisumu who had their sexual debut 5 years before the interview, the prevalence of HIV infection was 46%; in Ndola, it was 59%. Among sex workers, the prevalence of HIV infection was 57.5% in Cotonou, 34.4% in Yaounde, 74.7% in Kisumu and 68.7% in Ndola. CONCLUSIONS: The HIV prevalence rates in the general population confirmed our preliminary assessment of the level of HIV infection in the four cities, which was based on estimates of HIV prevalence from sentinel surveillance among pregnant women. The very high prevalence of HIV infection among young women in Kisumu and Ndola calls for urgent intervention.

In all regions of sub-Saharan Africa the predominant mode of transmission of HIV is through heterosexual intercourse however there are large variations in the rate and extent of the spread of HIV in different populations. This study was conducted to identify the factors that influence the rapid spread of HIV in four African cities namely Cotonou (Benin) Yaounde (Cameroon) Kisumu (Kenya) and Ndola (Zambia). Results demonstrated that high rates of partner change and being married are risk factors for HIV infection in men in at least one city but are risk factors for women in all four cities. In addition condom use among sex workers did not show a difference between the low and high prevalence cities. Furthermore no evidence of changes towards safer sexual behavior was identified in the high HIV prevalence cities. The only factors that were more common in the two high HIV prevalence cities than in the two low HIV prevalence cities were young age at first intercourse for women young age at first marriage and large age difference between the spouses. It was also noted that the high levels of HIV infection among young people especially among female adolescents in Kisumu and Ndola highlight the importance of interventions targeted at young people and their partners.

We read with interest the paper by Segal and Powe [1] on the prevalence of immune thrombocytopenic purpura (ITP). ITP is a disease caused by inadequate platelet production, as well as increased platelet destruction, and is traditionally categorized into acute and chronic forms. For the latter, thrombocytopenia needs to be present for at least 6 months [2]. In this paper, Segal and Powe refer to ITP as immune (rather than idiopathic) thrombocytopenia purpura. There is relatively little epidemiological evidence on chronic ITP, and its prevalence in the US is poorly documented. The paper by Segal and Powe is one of the first population-based studies of prevalence of ITP in the US that provides an estimate of chronic ITP (albeit informal). However, as the authors noted, there were some limitations in their study. Most of these were related to the limitations in the data source. In the analysis presented here, we aimed to estimate the diagnosed prevalence of chronic ITP in the US in 2005, using a large US claims data base. In particular, our analysis overcomes some of the main limitations in Segal and Powes paper. (i) Segal and Powe used only one calendar year (2002) of data and identified potentially chronic ITP patients as those with at least two ITP ICD-9 codes (287.3), which were separated by at least 6 months. Therefore, a patient whose first ITP ICD-9 code occurred in the second half of 2002 had no chance of presenting a second code within the 2002 calendar year. Hence, as the authors pointed out, their estimation of the prevalence of chronic ITP in all people under 65 years (4.5 per 100 000) may be a considerable underestimate. (ii) Segal and Powe se stimation only includes patients under 65 years old. The increased risk of ITP with age is well documented [3–5] and excluding patients over 64 years of age would lead to an underestimate. We analyzed the Integrated Healthcare Information System (IHCIS) database, one of the largest US health care managed databases, fully de-identified, with over 70 million patients from more than 45 health plans. It covers 7 out of 10 census regions and contains patient demographics, age, gender and morbidity. Our patient population consisted of patients enrolled to one of the health plans before or any time between 2002 and 2006 with a continuous enrollment throughout the year 2004. Chronic ITP cases were defined as patients with at least two diagnoses (ICD-9 code 287.3) for primary thrombocytopenia separated by at least 6 months between 2002 and 2006. A patient sfi rst identified 287.3 ICD-9 code over the period 2002–2006 had to be in 2004 or earlier and the last one in 2004 or later. Prevalence rates of chronic ITP were calculated as the total number of identified chronic ITP cases divided by the total population with continuous enrollment in the data base in 2004 stratified by age group and gender. The total age- and gender-adjusted rate was estimated as the total number of expected ITP cases divided by the total 2005 US population (given the observed age- and gender-specific rates, and the structure of the 2005 US population). To assess chronic idiopathic thrombocytopenia rather than chronic immune thrombocytopenia, and following the Segal and Powe approach, we repeated the above estimates, excluding patients with a diagnosis of human immunodeficiency virus (HIV) infection, hematological malignancies or aplastic anemia, any time between 2002 and 2004.

Estimates of HIV prevalence in 1995 among all adults in Zimbabwe range between about 18% and 24%. The objective of this study was to estimate, for Zimbabwe, the impact of HIV infection on adult mortality, by age and gender, between 1995 and the year 2000.For this analysis, we used 1992 census data to estimate the number of non-HIV-related deaths, and a short-term projection model to estimate the number of deaths attributed to HIV infection in 1995 and the year 2000.It was estimated that between 52% and 60% of all adult deaths in 1995 were attributed to HIV infection, and between 69% and 76% in both males and females in the group between 20 and 39 years of age. The estimated adult mortality rate per 1000 increased from 9.8 in 1987 (based on census data) to between 20.6 and 24.3 in 1995. For the year 2000, it was projected that between 66% and 73% of all adult deaths would be attributed to HIV infection, and between 81% and 86% in those aged 20 to 39 years. The estimated adult mortality rate in the year 2000 increased to between 29.1/1000 and 36.6/1000. Even if all transmission was assumed to cease after 1995, it was projected that60% of adult deaths would be attributed to HIV in the year 2000. Adult population growth is projected to decrease to between 0.3% and 1.0% in the year 2000.Results suggest that the impact of HIV infection on mortality in Zimbabwe is already severe and will continue to increase. Efforts to reduce numbers of new HIV infections today will serve to reduce the future burden of mortality, particularly in the longer term.Sentinel surveillance surveys for HIV infection have been conducted in Zimbabwe since 1990. Between 1990 and 1995, HIV prevalence among antenatal clinic attendees was 7.7-43.9% in rural areas and 12.3-67.1% in urban areas, with even higher prevalence among STD clinic attendees. As of 1995, an estimated 18-24% of all adults in Zimbabwe were infected with HIV. The authors estimated the impact of HIV infection upon adult mortality in Zimbabwe, by age and gender, between 1995 and 2000. 1992 census data were used to estimate the number of non-HIV-related deaths, while a short-term projection model estimated the number of deaths attributed to HIV infection in 1995 and 2000. An estimated 52-60% of all adult deaths in 1995 were attributed to HIV infection, and 69-76% of all deaths among men and women aged 20-39 years. The estimated adult mortality rate per 1000 increased from 9.8 in 1987 to 20.6-24.3 in 1995. For the year 2000, 66-73% of all adult deaths are projected to be attributed to HIV infection, and 81-86% among people aged 20-39 years. The estimated adult mortality rate in 2000 increased to 29.1-36.6/1000. Even were it assumed that all HIV transmission would cease after 1995, it is projected that more than 60% of adult deaths will be attributed to HIV in 2000, as the rate of adult population growth in that year is projected to decrease to 0.3-1.0%. The already severe impact of HIV infection upon mortality in Zimbabwe will continue to increase.

Background: The institution of inhaled corticosteroids is generally advocated for effective treatment of patients with asthma. It is yet unknown what is the best time to start inhaled corticosteroid therapy and especially whether delayed introduction is harmful. Phase 1: In a previous study in patients with asthma and COPD, we found that 2.5 years of treatment with a beta(2)-agonist plus inhaled corticosteroid (BA+CS) was more effective in improving the FEV(1) and the provocative concentration of histamine causing a 20% reduction in FEV(1) (PC20) than treatment with a beta(2)-agonist plus anticholinergic (BA+AC) or placebo (BA+PL). Phase 2: We extended this study with 6 months to investigate whether delayed introduction of inhaled CS therapy (800 mu g beclomethasone dipropionate) in the groups previously not treated with inhaled CS (BA+/-AC) could also improve FEV(1) and PC20 to the same degree, A distinction was made between patients with predominantly asthma (high baseline reversibility, Delta FEV(1) greater than or equal to 9% of predicted), and predominantly COPD (low baseline reversibility, Delta FEV(1) Results: Improvement of FEV(1) percent predicted by inhaled CS was comparable both in the asthmatics between phase 1 (13.8% predicted) and phase 2 (8.5% predicted; p=0.13) as well as in the patients with COPD (2.5% and 1.5% predicted, respectively), PC20, however, increased significantly more in the asthmatics in phase 1 (1.77 doubling concentration [DC]) than in phase 2 (0.79 DC; p=0.03). Improvement of PC20 in the patients with COPD was not significantly higher in phase 1 (0.74 DC) than in phase 2 (0.00 DC; p=0.19). Conclusions: Our study indicates that although delayed introduction of inhaled CS in asthmatics leads to similar improvements in FEV(1), improvements in PC20 are significantly less. These findings in patients with longer-existing asthma concur with other findings in newly detected asthma. We suggest that institution of inhaled CS therapy should not be postponed in asthmatics with documented airways obstruction and reversibility.

Airways hyperresponsiveness is a hallmark of asthma, and many patients with COPD also demonstrate hyperresponsiveness. Inhaled corticosteroids improve hyperresponsiveness, but the extent of improvement may vary considerably between patients. This study was designed to determine which patient characteristics predict these differences in response. Patients with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if PC20 less than or equal to 8 mg/ml and FEV(1)

To measure the prevalence of HIV and to describe established risk factors in female prostitutes.A cross sectional survey.A genitourinary medicine clinic, streets, and magistrates' courts in London.280 female prostitutes recruited between April 1989 and August 1991.Infection with HIV-1, reported risk behaviours, and prevalence of sexually transmitted infections.228 of the women had HIV tests, and two (0.9% (95% confidence interval 0% to 2.1%)) were infected with HIV-1. Reported use of condoms was high for commercial clients and low for non-paying partners: 98% (251/255) of women used condoms with all clients and 12% (25/207) with non-paying partners for vaginal intercourse. Twenty two women were current or past injecting drug users. Of the 193 women examined for sexually transmitted infections, 27 had an acute infection (gonorrhoea, chlamydia, trichomonas, or primary genital herpes) at the time of interview. Infection was associated with younger age and increasing numbers of non-paying sexual partners, but not with duration of prostitution, numbers of clients, or reports of condom failures. When age and numbers of non-paying partners were analysed by logistic regression they remained significantly associated with sexually transmitted infections.A large and diverse sample of prostitutes had a low prevalence of infection with HIV and high levels of use of condoms in commercial sex. There was a significant risk of other sexually transmitted infections associated with prostitutes' non-commercial sexual relationships, in which unprotected sex is common. Interventions to reduce the risk of sexually transmitted infections in prostitutes should address both commercial and non-commercial sexual partnerships.In a cross sectional survey, 280 female prostitutes were recruited between April 1989 and August 1991 by referral from health workers in the genitourinary medicine clinic at St. Mary;s Hospital, London, England, and referral from friends and colleagues of prostitutes, fieldwork (visiting streets, magistrates' courts, flats, agencies, and saunas), and telephone contacts. The objective was to measure the prevalence of HIV and to describe established risk factors in female prostitutes. 228 of the women had HIV tests, and 2 (09%) were infected with HIV-1. A high 98% (251/255) of women used condoms with all clients, while 12% (25/207) did with nonpaying partners for vaginal intercourse, 22 of the women had a history of blood transfusion; 22 women were current or past iv drug users; 53 reported use of injected drugs either by themselves or by their sexual partners; and 58 reported having sex with bisexual men and 4 with men known to be infected with HIV. Women recruited through fieldwork were more likely to report use of injected drugs than those interviewed at the clinic (11/87 (13%) vs. 11/193 (6%). 193 women were examined for sexually transmitted infections (STDs) on the day of their interview or within a week later, and 27 had one or more current, acute infections; 9 had gonorrhoea, 12 chlamydia, 7 trichomonas, and 4 primary genital herpes. Infection was related to younger age and increasing numbers of nonpaying sexual partners but not to duration of prostitution, numbers of clients, or reports of condom failures. The age and numbers of nonpaying partners remained significantly associated with STDs when analyzed by logistic regression. There was a significant risk of other sexually transmitted infections associated with the prostitutes frequently unprotected, noncommercial sexual relationships. Interventions should consider both commercial and noncommercial sexual partnerships in order to reduce the risk of sexually transmitted infections in prostitutes.

ITP is a disease caused by inadequate platelet production as well as increased platelet destruction. Oral systemic steroids are recommended as first-line treatment. Prolonged use of oral steroids in other disease populations has been associated with an approximately two-fold increase in the risk of developing a cataract. This study aimed to quantify the underlying risk of cataracts among ITP patients compared with non-ITP patients. Using the GPRD, a retrospective matched cohort study was conducted in which each ITP patient newly diagnosed between 1992 and 2005 and age 18 years or older was matched to 5 non-ITP patients on gender, age, practice and duration of follow-up. ITP patients and cataract events were identified using specific Read/Oxmis disease codes and validated by a clinical epidemiologist. The exposure of interest was oral steroid use and the primary outcome was cataracts (recorded as cataracts or cataract surgery). Patients with a history of cataracts were not excluded from the study. Potential covariates of interest were diabetes, schizophrenia, glaucoma, splenectomy and hypertension. The risk of cataracts was quantified using incidence rates and 95% confidence intervals (CI) and, the difference between groups was estimated using a rate ratio and 95% CI. All analyses were further stratified by age and gender. Adjusted rate ratios were estimated using the Cox proportional hazard model. Seven hundred sixty ITP patients were identified, 745 (98%) of whom had 5 matched controls. The entire sample had a mean age of 56.4 years and 60.1% were female. Among ITP patients, users of oral steroids had a cataract incidence rate of 14.0 per 1000 person-years (PY) (95% CI: 8.7 – 21.4) and non steroid users 6.1 per 1000 PY (95% CI: 2.7 – 11.4). In the non-ITP population, these figures were 16.9 per 1000 PY (95% CI: 11.9 – 23.3) and 9.2 per 1000 PY (95% CI: 7.6 – 11.0), respectively. The incidence of cataracts was observed to increase with age. Adjusting for steroid use and other factors, the risk of cataracts was similar in the ITP and non-ITP populations (adjusted rate ratio 0.8, 95% CI: 0.5 – 1.2) whereas, oral steroid use was associated with an increased risk of cataracts in both ITP and non ITP populations (adjusted rate ratio 1.6, 95% CI: 1.2 – 2.2). There was no evidence of increased risk with either inhaled steroids, or intranasal steroids. As expected, our study shows that the use of oral steroids is associated with an increased risk of cataracts in both ITP and non-ITP populations. However, we found no evidence of a difference in the risk of cataracts between an ITP and a matched non-ITP population.

ITP is a disease caused by inadequate platelet production as well as increased platelet destruction. Literature on the epidemiology of ITP is currently sparse and the disease remains poorly described. Based on previous reviews, the overall incidence of ITP among adults ranges from 1.6 to 3.0 per 100,000 person years of observation (PYO); prevalence estimates range from 2.1 to approximately 36.4 per 100,000 persons (Neylon AJ et al., Br J Haematol. 2003; Satia J et al., Eur Hematol Assoc. [poster presentation] 2006; Deitz AC et al., Blood. 2006). In this study, the objective was to estimate the prevalence of adult chronic ITP (in 2005) stratified by age and gender using a large US claims database (Integrated Healthcare Information Services, IHCIS). IHCIS comprises over 70 million patients from 45 health plans. Adult chronic ITP cases were defined as patients with at least two diagnoses (ICD-9 code 287.3) for primary thrombocytopenia separated by at least 6 months between 2002 and 2006, and age 18 or older in 2004. Although ICD-9 code 287.3 is not exclusive to ITP, its sensitivity and specificity are likely to be high (Segal et al., Am J Hem. 2004). A patient’s first identified 287.3 ICD-9 code over the period 2002–2006 had to be in 2004 or earlier and the last one in 2004 or later. Patients had to have continuous enrollment throughout the year 2004. We estimated the 2004 prevalence as the total number of identified chronic ITP cases divided by the total population in the database in 2004 stratified by age group and gender. Estimates of adult cases for the US population were obtained by multiplying the 2004 prevalence estimates by the 2005 adult US census population estimates. The estimated adult prevalence was 23.6 [95% CI 23.4 – 23.8] per 100,000 persons, translating to approximately 52,700 (95% CI 52,200 – 53,100) adult chronic ITP cases in the US. Females had higher prevalence than males (28.1 vs 18.8 per 100,000). In addition, prevalence increased with age (from 17.0 in the age group 18–49 to 36.2 in the age group 65 and older). These results are broadly similar to previously published data and help to better understand the epidemiology of chronic ITP. While the tight CIs predominantly reflect the large data set rather than the precision of the estimates, we believe these data are among the most robust estimates of ITP prevalence and are the first to specifically estimate adult chronic ITP prevalence by age and gender in the US.

We wanted to compare the efficacy and safety of fluticasone propionate, a new topically active inhaled corticosteroid, to that of high dose beclomethasone dipropionate, in severe adult asthma. Patients currently receiving between 1.5-2.0 mg.day-1 of an inhaled corticosteroid were treated for six weeks in a double-blind, randomized, parallel group study with 1 mg.day-1 fluticasone propionate (n=82), or 2 mg.day-1 beclomethasone dipropionate (n=72). Mean morning peak expiratory flow rates (PEFR) increased from 303 to 321 l.min-1 with fluticasone propionate, and from 294 to 319 1.min-1 with beclomethasone dipropionate. There was an increase in evening PEFR, asthma symptoms improved, and rescue beta2-agonist use decreased for both treatment groups. None of these differences between treatments were statistically significant However, diurnal variation was significantly reduced with fluticasone propionate, when compared with beclomethasone dipropionate (difference = 7 l.min-1; p=0.038). Clinic lung function also improved with both treatments and, apart from % predicted PEFR, which showed no difference after beclomethasone dipropionate but increased from 73 to 78 % with fluticasone propionate, there were no differences between treatments. Forced expiratory volume in one second (FEV1) increased with both treatments. The geometric mean plasma cortisol concentration rose after treatment with fluticasone propionate (from 293 to 309 nmol.l-1) and fell after beclomethasone dipropionate (from 256 to 224 nmol.l-1); the difference between treatments was significant. The incidence of adverse events was low in both treatment groups. In conclusion, 1 mg-day-1 fluticasone propionate was as effective as 2 mg-day-1 beclomethasone dipropionate in the control of severe asthma. However, adrenal function was affected less by fluticasone propionate, which gives it a better overall safety profile. This study, therefore, demonstrates the increased therapeutic potential of fluticasone propionate over beclomethasone dipropionate in severe asthma.

Background. The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy. Methods. In a multicenter trial we compared three inhalation regimens in which a beta2-agonist (terbutaline, 2000 mug daily) was combined with a corticosteroid (beclomethasone, 800 mug daily), an anticholinergic bronchodilator (ipratropium bromide, 160 mug daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years. Results. Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P Conclusions. The addition of an inhaled corticosteroid - but not an inhaled anticholinergic agent - to maintenance treatment with a beta2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease.

The majority of the cellular cadmium (less than 80%) in cadmium resistant Datura innoxia cells is bound to a small, metal induced peptide which is not metallothionein. This peptide consists of glutamate, cysteine and glycine in a ratio between 2:2:1 and 3:3:1 and has an apparent molecular weight of 776, under denaturing conditions. It is heat stable and complexes with cadmium to produce multimeric forms which are separable by gel filtration. Chemical analyses suggest that some amino acids are not joined by classical peptide linkages. This indicates that the synthesis of the peptide may not be directed by mRNA and that induction of its synthesis may not involve increased transcription from a putative gene corresponding directly to this peptide. A smaller proportion (greater than 15%) of the cellular cadmium is bound to a larger compound which is also heat stable and binds copper more readily than cadmium in vivo. This larger compound has an amino acid composition similar, in some respects, to metallothioneins.

Inhaled corticosteroid has been shown to be effective in the management of asthma. However, there is a lack of studies that assess the effect of cessation after long-term treatment with inhaled corticosteroid. This question was addressed in 28 children with stable asthma, aged 11 to 18 yr of age, who had completed 28 to 36 months of treatment with inhaled corticosteroid (budesonide 200 mu g 3 times/day) and inhaled beta-2-agonist (salbutamol 200 mu g 3 times/day). The children were randomized in a 1:2 ratio in a double-blind study either to continue budesonide (n = 8) during a period of 6 months or to decrease the dose of budesonide (n = 20) within 2 months, followed by placebo for 4 months. Treatment with salbutamol 600 mu g daily was continued in both groups. Eight children from the tapering-off group withdrew, mainly due to symptoms of asthma, compared with none in the continuous treatment group. Five patients in the tapering-off group experienced exacerbations for which prednisolone was given, compared with none in the continuous treatment group. After tapering-off, symptoms of asthma and additional bronchodilator use increased, and both FEV(1)% predicted and PD20 histamine (provocation dose of histamine causing a 20% fall in FEV(1)) decreased, whereas these all remained unchanged in the group that continued treatment with inhaled corticosteroid. We conclude that in this study long-term treatment with 600 mu g budesonide daily suppressed underlying mechanisms of asthma, but did not cure the disease.