Ervin Adam

Epidemiology of Helicobacter pylori in an asymptomatic population in the United States: Effect of age, race, and socioeconomic status

A causative role is now accepted for Helicobacter (formerly Campylobacter) pylori in type B gastritis, and evidence is accumulating that H. pylori infection plays a major contributory role in peptic ulcer disease. Preliminary studies have reported that the prevalence of H. pylori infection increases with age, but detailed information on the prevalence of the bacteria in any defined population and on the factors that may influence the pattern of distribution remains scanty. In the present study, a sensitive enzyme-linked immunosorbent assay and a [13C] urea breath test were used to investigate the prevalence of H. pylori infection among 485 healthy asymptomatic volunteers between the ages of 15 and 80 residing in the Houston metropolitan area. H. pylori infection was present in 52%. The prevalence of H. pylori infection increased rapidly with age at 1%/yr for the overall population. The frequency of H. pylori infection was higher in blacks (70%) than whites (34%) (P less than 0.001); this difference remained after adjustments were made for age, gender, educational level, income, and use of tobacco or alcohol. H. pylori infection was independent of gender but was closely correlated with socioeconomic class. There were significant inverse correlations between age-adjusted frequency of H. pylori infection and income and between educational level and H. pylori infection. There was no association between H. pylori infection and consumption of alcohol or nonsteroidal antiinflammatory drug use or smoking. Having pets was associated with a lower frequency of H. pylori infection, but this was highly associated with higher socioeconomic status. The mode(s) of transmission of H. pylori is unknown, but the social patterns of H. pylori infection are consistent with fecal-oral transmission as one important pathway. Socioeconomic factors seem to determine the age of acquisition.

Seroepidemiology ofHelicobacter pylori infection in India

Helicobacter pylori (previouslyCampylobacter pylori) is now accepted as the major cause of type B gastritis and thus what is known about the epidemiology of type B gastritis can reasonably be transferred toH. pylori. We used a specific ELISA for anti-H. pylori IgG to study the prevalence ofH. pylori infection in a population of lower socioeconomic class from Hyderabad, India. The results from India were compared to studies from other parts of the world. Two hundred thirty-eight individuals ages 3 to 70 participated. The frequency ofH. pylori infection increased with age (P<0.01) and was >80% by age 20.H. pylori infection was present in 79% of the population studied; there was no gender-related difference in prevalence ofH. pylori infection. IgG antibody against hepatitis A (HAV) was rapidly acquired in Hyderabad; in a subset of 58 children between the ages of 3 and 21 tested, the frequency of anti-HAV was 98.2%. The prevalenc ofH. pylori infection increases with age in both developed and developing countries. The high age-specific prevalence ofH. pylori infection in developing countries is probably a reflection of the lower socioeconomic level of those areas.

Adverse Health Outcomes in Women Exposed In Utero to Diethylstilbestrol

BACKGROUND Before 1971, several million women were exposed in utero to diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood. METHODS We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls. We assessed the risks of 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero. RESULTS Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows: for infertility, 33.3% vs. 15.5% (hazard ratio, 2.37; 95% confidence interval [CI], 2.05 to 2.75); spontaneous abortion, 50.3% vs. 38.6% (hazard ratio, 1.64; 95% CI, 1.42 to 1.88); preterm delivery, 53.3% vs. 17.8% (hazard ratio, 4.68; 95% CI, 3.74 to 5.86); loss of second-trimester pregnancy, 16.4% vs. 1.7% (hazard ratio, 3.77; 95% CI, 2.56 to 5.54); ectopic pregnancy, 14.6% vs. 2.9% (hazard ratio, 3.72; 95% CI, 2.58 to 5.38); preeclampsia, 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI, 1.07 to 1.89); stillbirth, 8.9% vs. 2.6% (hazard ratio, 2.45; 95% CI, 1.33 to 4.54); early menopause, 5.1% vs. 1.7% (hazard ratio, 2.35; 95% CI, 1.67 to 3.31); grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4% (hazard ratio, 2.28; 95% CI, 1.59 to 3.27); and breast cancer at 40 years of age or older, 3.9% vs. 2.2% (hazard ratio, 1.82; 95% CI, 1.04 to 3.18). For most outcomes, the risks among exposed women were higher for those with vaginal epithelial changes than for those without such changes. CONCLUSIONS In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes. (Funded by the National Cancer Institute.).

Transmission of Helicobacter pylori Infection Studies in Families of Healthy Individuals

Helicobacter pylori is accepted as the commonest cause of type-B gastritis. Detailed information about the mode of transmission remains scanty. We investigated the frequency of H. pylori infection within families, defined as consisting of a husband and wife with at least one biologic child, all living in the same household. Inclusion criteria required that both the parents and the children had been born in the United States, had used no antibiotic or bismuth for the previous 2 months, had no recent major illness or surgical operation, and had no symptoms referable to the upper gastrointestinal tract. H. pylori infection was identified with a 13C-urea breath test and an enzyme-linked immunosorbent assay for anti-H. pylori IgG. Forty-one families (151 healthy individuals) were enrolled. Before the results of the H. pylori tests were known, one parent was selected as the index subject. H. pylori infection clustered; that is, 68% of spouses of H. pylori-infected index subjects were also H. pylori-infected, compared with 9% of spouses of H. pylori-negative index subjects (p less than 0.0001). The children of infected index parents were also more likely to be infected than children of uninfected index parents--40% versus 3%, respectively (p less than 0.0001)--and the results in the children were independent of whether the father or the mother was the index subject. Clustering of H. pylori infection within families suggests person-to-person transmission or common source exposure. The high frequency of H. pylori infection in spouses suggests that genetic factors are less important than living conditions for transmission of H. pylori infection.

Upper genital tract changes and pregnancy outcome in offspring exposed in utero to diethylstilbestrol

Hysterosalpingography (HSG) was performed on 267 diethylstilbestrol (DES)-exposed women. One hundred eighty-five (69%) of these women demonstrated an abnormality and 82 women had normal findings. A relationship between abnormal x-ray findings and structural abnormalities of the cervix and vaginal epithelial changes was noted. Ninety-three women on whom roentgenography was performed had a total of 144 pregnancies. The pregnancy outcome in this group of women was significantly worse than that found in a control population of 87 women who had 147 pregnancies. In addition, women with abnormal x-ray films were found to have a poorer pregnancy outcome than the group of women with normal findings. The women with abnormal x-ray films had more ectopic pregnancies, spontaneous abortions, and premature deliveries than women with normal x-ray films although these differences were not statistically significant. Significantly fewer women with abnormal findings than women with normal x-rays were delivered of term infants.

Continued follow-up of Pregnancy outcomes in diethylstilbestrol-exposed offspring

Objective To evaluate long-term pregnancy experiences of women exposed to diethylstilbestrol (DES) in utero compared with unexposed women. Methods This study was based on diethylstilbestrol-exposed daughters, the National Collaborative Diethylstylbistrol Adenosis cohort and the Chicago cohort, and their respective nonexposed comparison groups. Subjects who could be traced were sent a detailed questionnaire in 1994 that contained questions on health history, including information on pregnancies and their outcomes. We reviewed 3373 questionnaires from exposed daughters and 1036 questionnaires from unexposed women. Results The response rate was 88% among exposed and unexposed women. Diethylstilbestrol-exposed women were less likely than unexposed women to have had full-term live births and more likely to have had premature births, spontaneous pregnancy losses, or ectopic pregnancies. Full-term infants were delivered in the first pregnancies of 84.5% of unexposed women compared with 64.1% of exposed women identified by record review (relative risk [RR] 0.76, confidence interval [CI] 0.72, 0.80). Preterm delivery of first births occurred in 4.1% of unexposed compared with 11.5% of exposed women, and ectopic pregnancies in 0.77% of unexposed compared with 4.2% of exposed women. Spontaneous abortion was reported in 19.2% of DES-exposed women compared with 10.3% in control women (RR 2.00, CI 1.54, 2.60). According to complete pregnancy histories (many women had more than one pregnancy), preterm births were more common in DES-exposed women (19.4% exposed versus 7.5% unexposed (RR 2.93 CI 2.23, 3.86). Second-trimester spontaneous pregnancy losses were more common in DES-exposed women (6.3% versus 1.6%; RR 4.25, CI 2.36, 7.66). More first-trimester spontaneous abortions occurred in DES-exposed women than in controls (RR 1.31, CI 1.13, 1.53), and DES-exposed women had at least one ectopic pregnancy more often than unexposed women (RR 3.84, CI 2.26, 6.54). Conclusion Pregnancy outcomes in DES-exposed women were worse than those in unexposed women.

Antibodies to Herpesvirus Nonvirion Antigens in Squamous Carcinomas

Serums from tumor-bearing patients, cured patients, and normal subjects were examined for antibodies to the separated complement-fixing reactive components of nonvirion antigens of herpesvirus type 1 and type 2. The occurrence of antibodies to the antigens was similar in serums from tumor-bearing patients and cured patients. Antibodies to the antigens were observed among 21 of 24 (87 percent) cervical cancer cases, 44 of 49 (90 percent) laryngeal cancer cases, 15 of 24 (62 percent) cases of squamous cell carcinomas of the head and neck excluding the larynx, 2 of 24 (8 percent) nonsquamous cell cancer cases, and 3 of 51 (6 percent) normal subjects. By contrast, no differences were found in the titers of neutralizing antibodies to the virus in serums from laryngeal cancer patients and controls. The observations support an etiologic role of herpesviruses in cervical cancer and in laryngeal cancer, and possibly other squamous cell cancers of the head and neck.

Design and preliminary observations of National Cooperative Diethylstilbestrol Adenosis (DESAD) Project.

The National Cooperative Diethylstilbestrol Adenosis (DESAD) Project has completed the major portion of its enrollment phase with the examination of more than 3000 daughters of women taking synthetic nonsteroidal estrogens (denoted DES) during pregnancies occurring from the early 1940s to the mid-1960s. The aims of the Project are to fill urgent needs for information on the prevalence and incidence of structural and epithelial abnormalities or neoplastic changes and their complications in these young women. Participants are grouped by mode of entry as identified by prenatal record review (40.1%), documented as DES-exposed but walking in (25.1%), or referred (22.8%) to the DESAD Project for examination, and not documented as exposed but having gynecologic abnormalities typical of those associated with DES exposure (12.0%). This study cohort, in part having paired controls, will be examined annually for at least 5 years. Details of the design and selected preliminary findings are reported.

Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States)

AbstractObjectives: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES. Methods: A cohort comprising 3899 DES-exposed and 1374 unexposed daughters was followed for 13 years (1982–1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates. Results: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2–3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4–5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis. Conclusions: The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.

Evidence of SV40 infections in hospitalized children

Simian virus 40 (SV40) is known to have contaminated poliovirus vaccines used between 1955 and 1963. Accumulating reports have described the presence of SV40 DNA in human tumors and normal tissues, although the significance of human infections by SV40 is unknown. We investigated whether unselected hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent. Serum samples were examined for SV40 neutralizing antibody using a specific plaque reduction test; of 337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the antibody-positive patients. This study, using 2 independent assays, shows the presence of SV40 infections in children born after 1980. We conclude that SV40 causes natural infections in humans.