Heterogeneity of immunoglobulin G response to Helicobacter pylori measured by the unweighted pair group method with averages.

The heterogeneity of the immune response to Helicobacter pylori has always been noticed but has never been evaluated by obtaining a quantitative measure. For this purpose, sera were tested by enzyme-linked immunosorbent assay, and 207 positive serum specimens were subsequently tested by immunoblotting. The presence or absence of six specific bands was noted. The homology of the different profiles of bands was measured by calculating the Dice coefficient, and a dendrogram was constructed. Thirty-four profiles were found, with each profile containing from 1 to 43 serum specimens. At a level of 72% similarity, 115 of the serum specimens studied fell into eight profiles. At a level of 48% similarity, 186 of the serum specimens studied fell into 22 profiles. The difference in immunoblot profiles was probably linked to the host immune response, but infection with strains carrying different antigens cannot be ruled out.

Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C.

BACKGROUND: Hepatitis A virus (HAV) infection rarely causes fulminant hepatic failure in people with no underlying liver disease. There are limited data on the course of this infection in patients with chronic hepatitis B and chronic hepatitis C. METHODS: We prospectively followed, from June 1990 to July 1997, 595 adults with biochemical and histologic evidence of chronic hepatitis B (163 patients) or chronic hepatitis C (432 patients) who were seronegative for HAV antibodies. All were tested every four months for serum IgM and IgG antibodies to HAV. RESULTS: Twenty-seven patients acquired HAV superinfection, 10 of whom had chronic hepatitis B and 17 of whom had chronic hepatitis C. One of the patients with chronic hepatitis B, who also had cirrhosis, had marked cholestasis (peak serum bilirubin level, 28 mg per deciliter [479 micromol per liter]); the other nine had uncomplicated courses of hepatitis A. Fulminant hepatic failure developed in seven of the patients with chronic hepatitis C, all but one of whom died. The other 10 patients with chronic hepatitis C had uncomplicated courses of hepatitis A. CONCLUSIONS: Although most patients with chronic hepatitis B who acquired HAV infection had an uncomplicated course, patients with chronic hepatitis C had a substantial risk of fulminant hepatitis and death associated with HAV superinfection. Our data suggest that patients with chronic hepatitis C should be vaccinated against hepatitis A.

Population-based survey of hepatitis A virus infection in the Republic of San Marino.

In 1990-1991, the prevalence of antibodies to hepatitis A virus infection (anti-HAV) was assayed by the ELISA method among 1528 apparently healthy subjects, 20-85 years old in the Republic of San Marino. Subjects were selected from the list of residents by a random stratified sampling procedure with a proportional allocation by age, sex and district of residence. The overall anti-HAV prevalence was 64.7%; it increased from 28.6% in subjects 20-30 years old to 97% in those > 60 years (p < 0.01). No gender difference was observed. At the multivariate analysis age > 40 years (OR: 39.5; 95% CI: 12.4-126) and lowest level of schooling (OR: 1.8; 95% CI: 1.1-2.9), which is a good indirect indicator of socio-economic status, resulted both independent predictors of anti-HAV seropositivity. These findings reflect the improved sanitation standards in this area and indicate that the proportion of non-immune adults is increasing with a higher risk of symptomatic infection in the near future.

The smaller size of the 'coeliac iceberg' in adults.

BACKGROUND: Since it has been ascertained that the prevalence of coeliac disease in the general paediatric population is 3.3 per 1000, we decided to evaluate this prevalence in the general adult population. METHODS: Two thousand two hundred and thirty-seven adult subjects aged 20-87 years, representative of a population with sociodemographic characteristics typical of Western European countries with regard to sex and age, were studied. In all serum IgA antiendomysial antibodies (EMA) were searched for, and all patients who turned out to be positive underwent intestinal biopsy. RESULTS: Four symptomless subjects aged between 20 and 39 years proved positive at the IgA EMA screening. This intestinal biopsy confirmed coeliac disease in all of them. The prevalence in our study group was, therefore, 1.8 per 1000. CONCLUSIONS: This study shows that the size of the submerged part of the 'coeliac iceberg' is perhaps smaller in the adult population and suggests a linear trend towards a lower coeliac disease prevalence as age increases.

Seroprevalence of hepatitis A virus and Helicobacter pylori infections in the general population of a developed European country (the San Marino study): evidence for similar pattern of spread.

OBJECTIVE: To evaluate the role of faecal-oral transmission in the spread of Helicobacter pylori. DESIGN: A cross-sectional comparison of the patterns of hepatitis A and H. pylori seropositivity. METHODS: At interview, blood samples and questionnaire data were collected from a random sample of 1528 healthy subjects aged 20-85 years from the Republic of San Marino. Serum samples from each subject were then tested for anti-H. pylori and anti-hepatitis A antibodies. RESULTS: Overall, 529 of 670 H. pylori-seropositive subjects (78.9%) and 460 of 858 H. pylori-seronegative subjects (53.6%) were hepatitis A seropositive (P<0.01; odds ratio=3.2; confidence interval 95%=2.6-4.1). This association remained after adjustment by a multiple logistic regression analysis for the confounding effect of age and length of schooling, as surrogate for socio-economic status (OR=2.0; CI 95%=1.3-3.3). The age-specific prevalence curves for H. pylori and hepatitis A infections showed a parallel increase by age, although to a lesser extent for H. pylori. CONCLUSION: These findings provide evidence that in the community studied H. pylori may have spread in a manner similar to that of hepatitis A.

A phase II study of tamoxifen combined with cisplatin-interleukin 2 and alpha-interferon in metastatic melanoma.

Tamoxifen (TAM) has been reported to enhance cisplatin (CDDP) cytotoxicity in experimental and clinical melanoma studies. Based on our previous experience with sequential cisplatin-interleukin-2 (IL2)-interferon (IFN), we performed a phase II study of TAM combined with our original CDDP-IL2-IFN regimen in 22 pretreated metastatic melanoma patients. With a 41% response rate (95% CI, 21-61) we confirmed the interesting antitumor activity of CDDP-IL2-IFN combination; however, TAM enhanced neither the response rate nor the duration of response, but appeared to induce significantly more myelotoxicity, as compared to our previous results with CDDP-IL2-IFN alone. Whereas mechanisms by which TAM may modulate CDDP cytotoxicity in melanoma tumors remain unknown, the exact place of TAM, if any, and its safety in chemotherapeutic or chemoimmunotherapeutic combinations require further investigations.

A population based study of Helicobacter pylori infection in a European country: the San Marino Study. Relations with gastrointestinal diseases.

Helicobacter pylori is present worldwide but few large population studies exist on the epidemiology of the infection. A random cross sectional study was performed of H pylori infection in the adult population of San Marino, a European country with high gastric cancer rate, to assess its prevalence and to evaluate its relations with gastrointestinal disease. In 2237 subjects (77% of the initial sample) H pylori IgG antibodies were detected with enzyme linked immunosorbent assay (ELISA) and immunoblotting. A questionnaire including questions about occupation, place of birth, and smoking was given to all subjects. Dyspepsia, peptic ulcer, and gastric cancer in the subjects, relatives, and partners as well as use of drug, dental treatment/prostheses, and gastrointestinal endoscopies, were evaluated by multivariate analysis. H pylori prevalence was of 51%, increased with age from 23% (20-29 years) to 68% (> or = 70 years), and was higher among manual workers. H pylori was independently associated with ulcer (OR = 1.63, 95% confidence intervals (CI) = 1.16 to 2.27), H2 antagonists (OR = 1.94, 95% CI = 1.21 to 3.10), and benzodiazepines (OR = 1.57, 95% CI = 1.02 to 2.42), dental prostheses (OR = 1.25, 95% CI = 1.05 to 1.49), gastroscopy in the past five years (OR = 1.50, 95% CI = 1.05 to 2.14), peptic ulcer in siblings (OR = 1.52, 95% CI = 1.09 to 2.12), gastric cancer in father (OR = 1.61, 95% CI = 1.02 to 2.52). The association of seropositivity with history of ulcer, gastric cancer in family, gastroscopy, and H2 antagonists suggests that H pylori is an epidemiological key factor in the pathogenesis of gastroduodenal diseases in this area.

Gastric cancer in San Marinese and their first degree relatives in San Marino and the United States. Gastroscopic biopsy as an epidemiological tool.

The Republic of San Marino, a small, 23-square mile, independent country near the Adriatic Coast within Italy, has been noted to have a high incidence of gastric cancer in its 22,000 population (9% of all deaths from 1969-1983 with 33% of all cancer deaths attributed to gastric cancer). Gastroscopic biopsy studies on 284 first degree relatives of San Marinese gastric cancer patients in the Republic of San Marino and in Detroit, where 2,000-2,500 San Marinese reside, have allowed detection of six gastric malignancies. Intestinal metaplasia of gastric mucosa was found in 16 (52%) of 31 Detroit first degree relatives and 51 (36%) of 143 San Marino first degree relatives. Gastroscopy provides an important tool not only for the early detection of gastric cancer in populations of high risk (such as that of San Marino), but also for providing clues to the genetic and environmental factors in gastric neoplasia.

Observations on gastric cancer in San Marino. I. Familial factors.

The Republic of San Marino (RSM) is a 23-square mile independent country within Italy with a population of 20,000. A large percentage of deaths have been found to be due to gastic cancer (9.2% of all death certificate diagnoses for 1969 through 1973). The frequency of gastric cancer in the families of all 36 patients (78% male) who were born and died in RSM with this diagnosis for this period was compared with the frequency in relatives of age and sex-matched controls. Although 42--44% of both groups had relatives with death certificate diagnoses of stomach cancer, 25% of the patients had first degree relatives affected versus 5.6% of the controls. A high prevalence has also been reported in the area of Italy near RSM. San Marino's size and stability of population provide unique opportunities for elucidating genetic and environmental etiological factors in stomach cancer.