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Biomedical subjects

J Parsonnet

Publications and source records attributed to J Parsonnet.

At least 55 records · Page 3Linked to original sources
PubMed1997

Risk for gastric lymphoma in persons with CagA+ and CagA- Helicobacter pylori infection.

Infection with Helicobacter pylori increases the risk for gastric non-Hodgkin's lymphoma (GNHL). Strains that express CagA protein are thought to be particularly virulent. It was determined whether CagA+ H. pylori infection increased the risk for GNHL more than CagA infection. Thirty-two cases and 130 controls previously tested for H. pylori antibodies were tested for CagA antibodies by ELISA. The risk for GNHL was compared among CagA+, CagA-, and uninfected persons by use of conditional logistic regression. CagA+ subjects had 8.2 times the risk for GNHL than uninfected persons (95% confidence interval [CI], 2.5-26.7). CagA- subjects had 4.4 times the risk for GNHL than uninfected persons (95% CI, 1.2-16.5). Among infected subjects only, CagA+ infection was not associated with significantly increased risk for GNHL when compared with CagA- infection (odds ratio, 2.1; 95% CI, 0.8-5.4). This study does not support a major role for CagA in lymphomagenesis.

Antibodies, Bacterial↗
PubMed1997

Seroprevalence of CagA-positive strains among Helicobacter pylori-infected, healthy young adults.

Helicobacter pylori is categorized into two phenotypes on the basis of the presence or absence of the CagA protein. CagA protein-positive H. pylori are more closely associated with peptic ulcer disease and cancer. Whether CagA-positive strains are similarly represented among racial or ethnic groups in northern California was investigated. Sera from 152 H. pylori-infected healthy young adults were tested by ELISA for IgG against CagA. CagA antibodies were detected in 79.4% of blacks, 63.8% of Hispanics, and 50% of whites. After adjusting for demographic factors, blacks had significantly more infections with CagA-positive H. pylori than did whites (odds ratio [OR] = 5.0; 95% confidence interval [CI] = 1.6-15.3) or Hispanics (OR = 5.5, 95% CI = 1.9-16.0). Also, there was a higher prevalence of CagA in persons born in developing countries than in persons born in industrialized nations (OR = 3.5, 95% CI = 1.3-9.4). This suggests either a genetic predisposition of racial or ethnic groups to infection with particular H. pylori phenotypes or transmission of H. pylori within relatively segregated population groups.

Adult↗
PubMed1997

Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection.

BACKGROUND AND AIMS: It is not known why some people with Helicobacter pylori infection develop gastric cancer whereas others do not. Whether the CagA phenotype of H pylori infection affected risk for cancer independently of other posited risk factors was evaluated. SUBJECTS: 242 persons who participated in a previous nested case-control study of gastric cancer. 179 (90 cases and 89 controls) were infected with H pylori as determined by enzyme linked immunosorbent assay (ELISA) in serum and 63 (13 cases and 50 controls) were uninfected. METHODS: Serum samples from cases and controls, obtained a mean of 14.2 years before diagnosis of cancer in the cases, were tested by ELISA for IgG antibodies against the CagA gene product of H pylori. They had previously been tested for pepsinogen I. Using logistic regression analysis, risk for cancer was compared among infected persons with CagA antibodies, infected persons without CagA antibodies, and uninfected persons. RESULTS: Subjects infected with H pylori who had CagA antibodies were 5.8-fold more likely than uninfected subjects to develop gastric cancer (95% confidence interval (95% CI) = 2.6-13.0). This was true for both intestinal (odds ratio (OR) 5.1, 95% CI = 2.1-12.2) and diffuse type (OR 10.1, 95% CI = 2.2-47.4) cancers. By contrast, H pylori infected subjects without CagA antibodies were only slightly, and not significantly, at increased risk for cancer (OR 2.2, 95% CI = 0.9-5.4) and any possible association was restricted to diffuse type carcinoma (OR 9.0, 95% CI = 1.2-65.8). Pepsinogen 1 < 50 ng/ml significantly increased risk for both cancer types in H pylori infected persons and lessened the magnitude of association between CagA and cancer. Educational attainment, cigarette smoking, and ABO blood group were not associated with malignancy. CONCLUSIONS: When compared with uninfected subjects, persons infected with CagA positive H pylori are at considerably increased risk of gastric cancer. CagA negative H pylori are less strongly linked to malignancy and may only be associated with diffuse type disease.

ABO Blood-Group System↗
PubMed1997

Urinary phytoestrogen levels in young women from a multiethnic population.

Phytoestrogens include several classes of chemical compounds (i.e., isoflavones, coumestans, and lignans) which are structurally similar to endogenous estrogens. In biological systems, they have both estrogenic and antiestrogenic effects and may reduce the risk of developing certain types of hormonally related diseases. However, little information is available on population differences in exposure to phytoestrogens. To examine racial/ethnic differences in urinary phytoestrogen levels, 50 young women (ages 20-40 years) were randomly selected from participants in a previous epidemiological study in which 24-h urine specimens and a dietary assessment were obtained. Subjects were members of the Kaiser Permanente Medical Care Program of northern California. Selection was stratified on race/ethnicity. Urinary levels of seven phytoestrogens were measured using high-performance liquid chromatography-mass spectrometry. Substantial variation in phytoestrogen levels was observed and racial/ethnic differences are described. The highest levels of coumestrol and the lignans were observed in white women and the lowest levels in Latina and African American women. Genistein levels, however, were highest in Latina women; other isoflavone levels did not differ significantly by race/ethnicity.

Adult↗
PubMed1996

Modelling cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer: a mandate for clinical trials.

BACKGROUND: It is unknown whether eradication of Helicobacter pylori infection prevents development of gastric adenocarcinoma. To determine whether screening and treatment trials are warranted, we conducted a cost-effectiveness analysis to estimate the costs and benefits associated with screening for H pylori at age 50 and treating those individuals infected with antibiotics. METHODS: We compared two interventions: (1) screen for H pylori and treat those with a positive test, and (2) do not screen and do not treat. Estimates of risks and costs were obtained by review of published reports. Since the efficacy of H pylori therapy in cancer prevention is unknown, we did sensitivity analyses, varying this estimate widely. In our base-case analysis, we assumed that H pylori treatment prevented 30% of attributable gastric cancers. FINDINGS: In the base-case analysis, 11,646,000 persons in the US would be screened and 4,658,400 treated, at a cost of $996 million. Cost-effectiveness was $25,000 per year of life saved. Cost-effectiveness was sensitive to the efficacy of the cancer prevention strategy. At low efficacy rates (< 10%), the screening programme was more expensive (> $75,000 per year of life saved). In a high-risk group such as Japanese-Americans, however, screening and treatment required less than $50,000 per year of life saved, even at 5% treatment efficacy. INTERPRETATION: Screening and treatment for H pylori infection is potentially cost-effective in the prevention of gastric cancer, particularly in high-risk populations. Cancer prevention trials are strongly recommended.

Adenocarcinoma↗
PubMed1996

Increased risk of Helicobacter pylori associated with birth in wartime and post-war Japan.

BACKGROUND: Helicobacter pylori infection is now widely recognized as a cause of stomach cancer. We assessed trends in H. pylori infection in Japan, a population with high rates of gastric malignancy. METHODS: Using an enzyme-linked immunosorbent assay (ELISA), we tested sera collected between 1980 and 1993 from Tokyo University Hospital patients for anti-H. pylori IgG. Patients ranged in age from 0 to 94 years. Helicobacter pylori prevalence was then assessed for age and/or birth cohort effects. RESULTS: Of 1207 sera, 470 (38.9%) were positive for H. pylori IgG. By univariate analysis, both older age and birth in an earlier decade were associated with an increased risk of infection. Age-specific prevalence of H. pylori by birth cohort suggested increases in infection during the decades from 1900 to 1959, and age-specific decreases since 1960. In multivariate analysis, H. pylori infection increased with age and was most prevalent among those born in the 1940s and 1950s. CONCLUSION: Relative to other birth cohorts, people born in the 1940s and 1950s have a higher prevalence of H. pylori. This increased prevalence of infection among those born in wartime Japan likely attests to the impact of compromised living conditions on acquisition of H. pylori, and may portend continued high rates of gastric cancer in forthcoming years.

Adolescent↗
PubMed1996

Effect of tampon composition on production of toxic shock syndrome toxin-1 by Staphylococcus aureus in vitro.

To determine whether tampons composed of cotton or rayon differ in their effects on production of TSST-1 in vitro, two methods of bacterial cultivation, with and without agitation, were used to study the effects of 16 commercially available and experimental tampons on production of TSST-1. Experiments were done in blinded fashion. TSST-1 was produced in medium alone in the absence of a tampon by both methods. Neither cotton nor rayon tampons consistently increased toxin production, nor were there significant differences between them in their effects on TSST-1. In contrast, a tampon composed of carboxymethylcellulose and polyester foam increased production of TSST-1 to a large degree in both culture systems. Thus, neither cotton nor rayon amplifies production of TSST-1 in vitro, and cotton tampons cannot be claimed to be inherently safer on the basis of such data.

Bacterial Toxins↗
PubMed1996

Epidemiology of gastric non-Hodgkin's lymphoma patients: parallels with Helicobacter pylori.

BACKGROUND: The incidence of gastric non-Hodgkin's lymphoma (NHL) is increasing in the United States. However, little is known about the etiology of the disease. Some studies have shown an association between gastric NHL and Helicobacter pylori. No study has specifically delineated demographic features that distinguish gastric NHL patients from nongastric NHL patients. MATERIALS AND METHODS: To obtain information about the differences between gastric and nongastric NHL patients, we conducted a hospital chart review study. We examined charts of all 25 cases of primary gastric NHL, as well as charts of 75 randomly selected nongastric NHL patients as controls. All patients were seen in the Division of Oncology at Stanford University Medical Center from 1972 to 1991. Demographic information was tabulated, and differences between the cases and controls were noted. The identified risk factors were determined by both univariate and logistic regression analyses. RESULTS: There was no difference between gastric NHL cases and nongastric controls with respect to age, gender, race, and family history of any cancer. However, in logistical regression, persons with gastric NHL were more likely than those with other forms of NHL to be born outside the United States (odds ratio = 12.8; 95% confidence interval = 2.9-56.0) and also to have a family history of stomach cancer (odds ratio = 18.4; 95% confidence interval 2.1-160.1). CONCLUSIONS: Gastric NHL is more likely than NHL at other sites to occur in persons with a family history of gastric cancer or in those born in developing countries. This epidemiological pattern supports the identified role of H. pylori in the development of gastric lymphoma.

Adult↗
PubMed1995

Biologic sex as a risk factor for Helicobacter pylori infection in healthy young adults.

Diseases associated with Helicobacter pylori infection, such as peptic ulcer disease and gastric cancer, afflict men more frequently than women. No study, however, has demonstrated any difference in sex-specific rates of H. pylori infection. In a healthy population undergoing multiphasic health evaluations in 1992-1993 as members of the Kaiser Permanente Medical Care Program of Northern California, adults aged 20-39 years were screened for antibodies to H. pylori infection using a serum enzyme-linked immunosorbent assay and were surveyed with regard to their demographic characteristics and health practices. Among 556 African-American, Hispanic, and white men and women, male sex was a significant risk factor for infection. Other risk factors included African-American race and Hispanic ethnicity, increasing age, living with children, birth in a developing country, and lower levels of income and education. Men consistently had a higher prevalence of antibodies across all strata of race/ethnicity, age, education, and income, and in multivariate analysis male sex remained significantly associated with infection (odds ratio = 2.0, 95% confidence interval 1.2-3.1). African-American race, Hispanic ethnicity, increasing age, lower levels of education, and birth in a developing country were also associated with infection in multivariate analysis. Data from previously reported seroprevalence studies support a tendency for men to have a higher risk of infection. The higher prevalence of infection among young males as observed in Northern California may account in part for the increased incidence of H. pylori-related diseases among men in later decades of life.

Adult↗
PubMed1995

Flagellar serotypes of Salmonella typhi in Indonesia: relationships among motility, invasiveness, and clinical illness.

While the H1-d flagellar serotype of Salmonella typhi has been found worldwide, the H1-j serotype occurs only in Indonesia. A cross-sectional survey in Indonesia compared epidemiologic, clinical, and pathogenetic characteristics of these two serotypes. S. typhi isolates were collected from patients with acute typhoid fever in four Indonesian cities. Flagellar serotype was determined by polymerase chain reaction amplification of the fliC locus of the flg gene. Of 321 isolates, 51 (15.9%) were H1-j. Patients with H1-j infection were older than those with H1-d (P < .001). Among 30 patients with known clinical outcomes, H1-j infection was associated with milder clinical illness than H1-d (P = .06). In vitro, H1-j isolates were both less motile on semi-solid agar plates (P = .004) and less invasive of HEp-2 cells (P = .002) than H1-d isolates. The association of decreased severity of illness with decreased motility and invasiveness suggests that flagellar properties are a component of S. typhi's virulence.

Base Sequence↗
PubMed1995

Recombinant endotoxin neutralizing protein improves survival from Escherichia coli sepsis in rats.

OBJECTIVE: A recombinant endotoxin neutralizing protein was evaluated for its ability to ameliorate the effects of Escherichia coli sepsis in rats. DESIGN: Prospective, controlled animal trial. SETTING: Hospital animal research laboratory. SUBJECTS: Wistar rats, treated with gentamicin 1 hr after challenge with intraperitoneal E. coli O18ac. INTERVENTIONS: The animals received a recombinant endotoxin neutralizing protein, in doses of 5, 25, or 50 mg/kg, either 30 or 60 mins after challenge; controls received saline. MEASUREMENTS AND MAIN RESULTS: Geometric mean serum endotoxin concentrations in endotoxin neutralizing protein-treated animals did not differ from control animals. Tumor necrosis factor concentrations in animals treated with endotoxin neutralizing protein 30 mins after challenge were significantly lower than controls. Animals treated with 25 or 50 mg/kg of endotoxin neutralizing protein 30 mins after E. coli challenge had significant improvements in survival compared with controls. Animals treated with 50 mg/kg of endotoxin neutralizing protein 60 mins after E. coli challenge had significant improvements in survival compared with controls. CONCLUSION: Endotoxin neutralizing protein significantly reduces mortality from Gram-negative sepsis in an antibiotic-treatment model of E. coli peritonitis and bacteremia in rats, mediated by a neutralization of the biological effects of endotoxin.

Animals↗
PubMed1995

Failure of prophylactic and therapeutic use of a murine anti-tumor necrosis factor monoclonal antibody in Escherichia coli sepsis in the rabbit.

OBJECTIVE: To determine the efficacy of a murine anti-tumor necrosis factor (TNF) monoclonal antibody in the treatment of Escherichia coli peritonitis and sepsis in the rabbit. DESIGN: Prospective, paired, randomized, blinded, controlled animal trial. SETTING: Animal research laboratory. SUBJECTS: Male New Zealand white rabbits. INTERVENTIONS: Anesthetized rabbits were cannulated with indwelling femoral arterial and venous catheters. Peritonitis and sepsis were induced by intraperitoneal challenge using live E. coli O18ac bacteria. All animals were treated with gentamicin and ceftriaxone 1 hr after challenge. One group (prophylaxis experiment) consisting of ten rabbit pairs (the prophylaxis group), was treated with either murine anti-TNF monoclonal antibody or an equivalent volume of 5% albumin 3 hrs before E. coli challenge. A second group (therapeutic experiment) of 17 rabbit pairs, the treatment group, was also treated with murine anti-TNF monoclonal antibody or albumin control 1 hr after E. coli challenge. MEASUREMENTS AND MAIN RESULTS: All animals were bacteremic 1 hr after challenge. Physiologic measures of sepsis (heart rate, mean arterial pressure, serum bicarbonate, and arterial pH) did not differ between control, prophylaxis, and treatment groups. Peak serum TNF concentration was significantly (p < .01) lower in animals receiving anti-TNF monoclonal antibody, in both the prophylaxis and treatment groups, than in control animals. The survival rate was not improved significantly in either the prophylaxis or treatment group. CONCLUSIONS: Prophylactic and therapeutic use of anti-TNF monoclonal antibody in a rabbit model of E. coli peritonitis and sepsis significantly lowers TNF concentrations but does not ameliorate the physiologic effects of sepsis and does not significantly improve survival.

Animals↗
PubMed1995

Bacterial infection as a cause of cancer.

Bacterial infections traditionally have not been considered major causes of cancer. Recently, however, bacteria have been linked to cancer by two mechanisms: induction of chronic inflammation and production of carcinogenic bacterial metabolites. The most specific example of the inflammatory mechanism of carcinogenesis is Helicobacter pylori infection. H. pylori has been epidemiologically linked to adenocarcinoma of the distal stomach by its propensity to cause lifelong inflammation. This inflammation is in turn thought to cause cancer by inducing cell proliferation and production of mutagenic free radicals and N-nitroso compounds. H. pylori is the first bacterium to be termed a definite cause of cancer in humans by the International Agency for Research on Cancer. Mutagenic bacterial metabolites are also suspected to increase risk for cancer. This model is best exemplified in colon cancer. Bile salt metabolites increase colonic cell proliferation. Exogenous compounds such as rutin may be metabolized into mutagens by resident colonic flora. Moreover, Bacteroides species can produce fecapentaenes, potent in vitro mutagens, in relatively high concentrations. In vivo data on human carcinogenesis by bacterial metabolites, however, are inconsistent. Local bacterial infections may also predispose to nonnodal lymphomas, although the mechanisms for this are unknown. Gastric lymphomas and immunoproliferative small intestinal disease have been most strongly linked to underlying bacterial infection. Because bacterial infections can be cured with antibiotics, identification of bacterial causes of malignancy could have important implications for cancer prevention.

Bacterial Infections↗
PubMed1995

The incidence of Helicobacter pylori infection.

Acute Helicobacter pylori infection invariably passes undetected. Consequently, the incidence of infection has been determined indirectly from epidemiological studies. In adults of industrialized countries, an estimated 0.5% of the susceptible population becomes infected each year. This incidence has been decreasing over time. Thus, adults who currently harbour the organism are more likely to have been infected in childhood than adulthood. The incidence of H. pylori infection continues to be high (between 3% and 10% per year) in developing countries. Throughout the world, incidence of H. pylori infection appears to be higher in children than in adults, possibly due to lower standards of personal hygiene in younger populations.

Adult↗
PubMed1994

The epidemiology of tuberculosis in San Francisco. A population-based study using conventional and molecular methods.

BACKGROUND: The epidemiology of tuberculosis in urban populations is changing. Combining conventional epidemiologic techniques with DNA fingerprinting of Mycobacterium tuberculosis can improve the understanding of how tuberculosis is transmitted. METHODS: We used restriction-fragment-length polymorphism (RFLP) analysis to study M. tuberculosis isolates from all patients reported to the tuberculosis registry in San Francisco during 1991 and 1992. These results were interpreted along with clinical, demographic, and epidemiologic data. Patients infected with the same strains were identified according to their RFLP patterns, and patients with identical patterns were grouped in clusters. Risk factors for being in a cluster were analyzed. RESULTS: Of 473 patients studied, 191 appeared to have active tuberculosis as a result of recent infection. Tracing of patients' contacts with the use of conventional methods identified links among only 10 percent of these patients. DNA fingerprinting, however, identified 44 clusters, 20 of which consisted of only 2 persons and the largest of which consisted of 30 persons. In patients under 60 years of age, Hispanic ethnicity (odds ratio, 3.3; P = 0.02), black race (odds ratio, 2.3; P = 0.02), birth in the United States (odds ratio, 5.8; P < 0.001), and a diagnosis of the acquired immunodeficiency syndrome (odds ratio, 1.8; P = 0.04) were independently associated with being in a cluster. Further study of patients in clusters confirmed that poorly compliant patients with infectious tuberculosis have a substantial adverse effect on the control of this disease. CONCLUSIONS: Despite an efficient tuberculosis-control program, nearly a third of new cases of tuberculosis in San Francisco are the result of recent infection. Few of these instances of transmission are identified by conventional contact tracing.

AIDS-Related Opportunistic Infections↗