Interleukin-1 beta single-nucleotide polymorphism's C allele is associated with elevated risk of gastric cancer in Helicobacter pylori-infected Peruvians.

Particular alleles of the interleukin-1B (IL-1B) gene have been correlated with increased risk of atrophic gastritis and gastric cancer in the populations of East Asia and Europe. No such data exist from Peru, a developing country with a population genotypically different from others studied and with a high prevalence of Helicobacter pylori infection and gastric cancer. We conducted a case-control study comparing 334 hospitalized patients with atrophic gastritis or gastric cancer with 158 nonatrophic gastritis patients (controls). Conditional logistic regression analysis revealed that an increased risk of atrophic gastritis (odds ratio, 5.60) and gastric cancer (odds ratio, 2.36) was associated with the IL-1B-511 C allele. Our study is the first to establish this allele as a risk for these conditions. Given the high prevalence of H. pylori and recurrence rate after treatment, IL-1B-511 single-nucleotide polymorphism analysis may identify those individuals who would benefit most from robust H. pylori eradication efforts in Peru.

Susceptibility-guided vs. empiric retreatment of Helicobacter pylori infection after treatment failure.

Successful eradication of Helicobacter pylori after failure of standard triple therapy is difficult because of the higher resistance to metronidazole and clarithromycin. We evaluated the efficacy of susceptibility-guided vs. empiric retreatment for H. pylori after at least one treatment failure and determined the prevalence of posttreatment antibiotic resistance. Forty-nine patients in whom at least one treatment regimen for H. pylori eradication had failed underwent gastric biopsy and culture and were retreated according to the in vitro susceptibility results. Findings were compared with those for 49 control patients referred to our center for a (13)C-urea breath test. H. pylori eradication was assessed by urea breath test at least 6 weeks after retreatment in both groups. Susceptibility-guided retreatment was associated with better eradication rates than empiric treatment. The difference remained significant in stratified and multivariate analysis. Susceptibility-guided retreatment appears to be significantly more effective than empiric retreatment in eradicating H. pylori after at least one previous treatment failure.

Incidence of tuberculin skin test conversion among HIV-infected and -uninfected women: results of a 6-year study.

OBJECTIVE: To define the incidence of tuberculin skin test (TST) conversion and to evaluate the yield of annual testing in an era of declining tuberculosis incidence rate in the United States. METHODS: Annual TSTs were performed on initially TST-negative women (HIV infected, 995; uninfected, 260) from October 1995 through March 2002. RESULTS: A total of 4,622 repeat TSTs were performed during 5,530 person-years. The incidence of TST conversion was 0.8 case per 100 person-years for HIV-infected and 1.0 case per 100 person-years for uninfected women. Non-Hispanic blacks, women younger than 40 years of age, and HIV-infected women who had recently initiated active therapy were more likely to experience TST conversion. The incidence of conversion decreased over the course of the study from a peak of 21 cases per 937 tests in 1996 to 1 case per 179 tests in 2002 (P = 0.046 for trend). Twenty-one of 47 conversions occurred on the second TST, implying that boosting accounted for a number of conversions. CONCLUSIONS: The yield of annual skin testing diminished from 1996 to 2002. Our data suggest that repeating testing after initiation of HIV therapy, regardless of CD4 cell change, is warranted. If serial testing is undertaken, initial 2-step testing should be performed to allow for accurate interpretation of subsequent tests and earlier identification of persons with latent Mycobacterium tuberculosis infection.

The public health imperative for a neonatal herpes simplex virus infection surveillance system.

About 1 in 5 sexually active adults in the United States has serologic evidence of genital herpes caused by herpes simplex virus type-2. Neonatal herpes simplex virus infection is a serious consequence of genital herpes infection. Herpes infection in neonates causes significant morbidity and neurologic damage and generally has a case-fatality ratio untreated of 60%. It is estimated that 440 to 1,320 cases of neonatal herpes infections occur in the United States per year (11-33 cases occur per 100,000 live births). Given the challenges in surveillance for genital herpes due to the large number of asymptomatic infections and infrequent laboratory-based diagnosis, we recommend that to begin an effective national control program for herpes infections, a mandatory national surveillance system for neonatal herpes be implemented. Such a system would help assure appropriate therapy, help monitor trends and understand the burden of disease, identify risk determinants, and evaluate prevention efforts.

Validity of serum pepsinogen levels and quininium resin test combined for gastric cancer screening.

BACKGROUND: To investigate the feasibility of combining several serum markers into a valid serum screening tool for gastric cancer, we performed a study evaluating the association between gastric cancer and precancerous conditions and a blood test for gastric acidity (the blood quininium resin test [QRT]) combined with serum pepsinogen levels. METHODS: We performed immunoradiometric assays of serum pepsinogen I (PG I), II (PG II) levels, and QRT's in 10 endoscopically normal subjects, in 20 patients with chronic atrophic gastritis, and in 13 patients with biopsy-confirmed gastric adenocarcinoma. RESULTS: Serum PG I, II levels, I/II ratio were significantly different among normal, gastritis, and cancer patients. Serum PG I/II ratios were much lower in cancer patients. Serum quinine levels by QRT were correlated with PG I/II ratio (rs=0.39, p<0.01). Age was negatively correlated both with PG I/II ratio (rs=-0.58, p<0.01) and serum quinine level (rs=-0.45, p<0.01). The screening using serum PG levels was more valid (sensitivity of 69%, specificity of 77%) than that using QRT alone. The combination of serum PG levels and QRT increased specificity for detecting gastric cancer to 87% without altering sensitivity. CONCLUSION: Although blood QRT is a useful addition to other serum screening tests for gastric cancer, these tests alone are not sufficiently accurate as screening tools for gastric cancer.

Outcome after negative colposcopy among human immunodeficiency virus-infected women with borderline cytologic abnormalities.

OBJECTIVE: To estimate the risk of and risk factors for progression among human immunodeficiency virus (HIV)-seropositive women with abnormal cervical cytology but negative colposcopy. METHODS: In a prospective cohort study, 391 HIV-seropositive and 103 seronegative women with cervical cytology read as atypical squamous cells (ASC) or low-grade squamous intraepithelial lesion (LSIL) but negative colposcopy were followed up for a mean of 4.0 years with cytology at 6-month intervals. Colposcopy was prescribed for any epithelial abnormality. RESULTS: Progression to CIN2, CIN3, high-grade SIL/severe dysplasia, or cancer occurred in 47 (12%) HIV-seropositive women and 4 (4%) HIV-seronegative women (P = .02). Progression to CIN1 was seen in an additional 12 HIV-seropositive women and 1 seronegative woman. In multivariate analysis, high-risk but not low-risk HPV detection (hazard ratio [HR] 2.46-95% confidence interval [CI] 1.18-5.12, P = .02 for high risk, HR 1.41, 95% CI 0.62-3.21, P = .42 for low risk), satisfactory colposcopy (HR 2.01, 95% CI 1.11-3.65, P = .02), and non-Hispanic African-American ethnicity (HR 5.08, 95% CI 1.72-14.98, P = .003) were the only factors associated with progression, while HIV serostatus was marginally significant (HR 2.53, 95% CI 0.85-7.50, P = .09). CONCLUSION: Human immunodeficiency virus-seropositive women with negative colposcopy after borderline cytology face a higher risk of progression than seronegative women, but the absolute risk is low and becomes nonsignificant after controlling for HPV risk type, ethnicity, and colposcopic findings. Observation is appropriate. LEVEL OF EVIDENCE: II-2.

A potential decline in life expectancy in the United States in the 21st century.

Forecasts of life expectancy are an important component of public policy that influence age-based entitlement programs such as Social Security and Medicare. Although the Social Security Administration recently raised its estimates of how long Americans are going to live in the 21st century, current trends in obesity in the United States suggest that these estimates may not be accurate. From our analysis of the effect of obesity on longevity, we conclude that the steady rise in life expectancy during the past two centuries may soon come to an end.

Association of CagA+ Helicobacter pylori infection with aortic atheroma.

BACKGROUND: To investigate possible association between infection with CagA(+) strains of Helicobacter pylori and aortic atheroma diagnosed by transesophageal echocardiography. METHODS AND RESULTS: One hundred and eighty-eight consecutive subjects prospectively examined for presence of aortic atheroma (localized intimal thickening of >/=3mm) by transesophageal echocardiography were tested for serum IgG antibodies against H. pylori (enzyme-linked immunosorbent assay) and CagA protein (Western blot assay). The association between infection with H. pylori, CagA status of the infecting H. pylori strains, and aortic atherosclerosis was evaluated after adjusting for coronary artery disease risk factors. There was a linear trend for presence of atheroma in subjects with CagA-positive H. pylori infection (51/81, 63%) compared to subjects with CagA-negative H. pylori infection (21/45, 46.7%) and uninfected subjects (18/62, 29%) (p=0.003). H. pylori seropositivity was not associated with aortic atheroma (OR 2.9; 95% CI, 0.8-10.3; p=0.11) when CagA status is not taken into account. On multivariate analysis, parameters associated with risk of aortic atheroma were CagA-positive H. pylori seropositivity (OR 4.4; 95% CI, 1.4-14.7; p=0.01), older age (OR 1.2; 95% CI, 0.9-14.7; p=0.01), having ever smoked cigarettes (OR 3.6; 95% CI, 1.3-10.0; p<0.001), and elevated serum triglyceride level (OR 3.4; 95% CI, 1.3-9.4; p=0.02). CONCLUSIONS: After controlling for H. pylori infection and coronary artery disease risk factors, infection with a CagA-positive strain of H. pylori was independently associated with aortic atherosclerosis. This study suggests a gradient of atherosclerosis between uninfected individuals and patients with CagA-positive H. pylori infection and should prompt research into the role of CagA-positive H. pylori infection in the inflammatory atherosclerotic process.

Peering into the future of American longevity.

Extract: The trend in the life expectancy of humans during the past thousand years has been generally characterized by a slow, steady increase -- though this pattern is frequently punctuated by volatility in death rates caused by epidemic and pandemic infectious diseases, famines, and war. This volatility was dramatically curtailed in the mid-19th century as infectious agents swiftly succumbed to improved living conditions, advances in public health, and medical interventions. During the past 30 years in the United States, the rise in life expectancy at birth has decelerated relative to this historic pattern, and gains in life expectancy at older ages are now much smaller than they were in previous decades. How much higher can life expectancy rise? This is not just an academic question. The answer formulated today will have substantial influence on the rate at which taxes are levied and the potential solvency of age-entitlement programs. Some researchers predict that life expectancy will rise dramatically in this century, leading public policy makers to raise their estimates of how long Americans will live. It is predicted that historical trends in rising life expectancy will continue throughout this century, fueled primarily by anticipated but yet-to-exist advances in biomedical technology. Some have even predicted that aging itself will soon be mastered by science, enabling people to live well beyond 100 years.

Natural history of grade 1 cervical intraepithelial neoplasia in women with human immunodeficiency virus.

OBJECTIVE: We sought to estimate rates of progression and regression of grade 1 cervical intraepithelial neoplasia (CIN 1) among women with human immunodeficiency virus (HIV). METHODS: In a multicenter prospective cohort study, HIV-seropositive and HIV-seronegative women were evaluated colposcopically after receiving an abnormal cytology test result between November 1994 and September 2002. Women with CIN 1 were included, except those who had undergone hysterectomy, cervical therapy, or had CIN 2-3 or cervical cancer. Those women who were included were followed cytologically twice yearly, with colposcopy repeated for atypia or worse. RESULTS: We followed 223 women with CIN 1 (202 HIV seropositive and 21 HIV seronegative) for a mean of 3.3 person-years. Progression occurred in 8 HIV-seropositive women (incidence density, 1.2/100 person-years; 95% confidence interval [CI] 0.5-2.4/100 person-years) and in no HIV seronegative women. Regression occurred in 66 (33%) HIV-seropositive women (13/100 person-years, 95% CI 10-16/100 person-years) versus 14 (67%) seronegative women (32/100 person-years, relative risk 0.40, 95% CI 0.25-0.66; P < .001). In multivariate analysis, regression was associated with human papillomavirus (HPV) detection (hazard ratio [HR] for low risk 0.28, 95% CI 0.13-0.61, P = .001; and for high-risk 0.34, 95% CI 0.20-0.55, P < .001 versus no HPV detected) and Hispanic ethnicity (HR 0.48, 95% CI 0.230.98; P = .04); HIV serostatus was only marginally linked to regression (HR 0.52, 95% CI 0.27-1.03; P = .06), but seropositive women were less likely to regress when analysis was limited to 146 women with HPV detected at CIN 1 diagnosis (HR 0.18, 95% CI 0.05-0.62; P = .006). CONCLUSION: Grade 1 cervical intraepithelial neoplasia infrequently progresses in women with HIV. Thus, observation appears safe absent other indications for treatment. LEVEL OF EVIDENCE: II-1.

Dyspepsia symptoms and Helicobacter pylori infection, Nakuru, Kenya.

The prevalence of Helicobacter pylori infection was studied in 138 patients with dyspepsia in a hospital in Nakuru, Kenya, and in 138 asymptomatic sex- and age-matched controls from the same population. Anti-H. pylori immunoglobulin (Ig) G was more prevalent in dyspeptic than asymptomatic persons (71% vs. 51%), particularly those <30 years old (71% vs. 38%). H. pylori seropositivity was associated with dyspepsia after adjusting for age, sex, and residence (urban or rural). Among adults, the association between H. pylori infection and dyspepsia remained after adjusting for the above factors and for educational attainment, family size, and manual occupation. H. pylori infection in asymptomatic residents of Nakuru, Kenya, was more prevalent in older persons, with a rate of 68%, than in those 31-40 years of age. However, young persons with dyspepsia had an unexpectedly high prevalence of H. pylori infection. H. pylori test-and-treat strategy should be considered in Kenyan patients with dyspepsia, particularly in persons <30 years of age.

Growth slowing after acute Helicobacter pylori infection is age-dependent.

OBJECTIVE: Most infections occur during childhood, but the health effects of childhood infection are poorly understood. We investigated whether growth decreases in the 2 months after acute seroconversion. METHODS: We performed a nested case-control study among children 6 months to 12 years of age in a community on the outskirts of Lima, Peru. Health interviews were completed daily. Anthropometric measurements were taken monthly. Sera were collected every 4 months and tested for immunoglobulin G. Two-month height and weight gains of seroconverters were compared with gains of sex, age, and size-matched seronegative controls. RESULTS: In the 2 months after infection, 26 seroconverters gained a median of 24% less weight than 26 matched controls (interquartile range, 63% less to 21% more). In multivariate analysis, infection attenuated weight gain only among children aged 2 years or older. This decrease was not explained by increased diarrhea. CONCLUSIONS: seroconversion is associated with a slowing of weight gain in children aged 2 years or older. Reasons for this finding merit additional study.

Helicobacter pylori: consensus and controversy.

Helicobacter pylori is uniquely adapted to colonize the human stomach. Infection leads to a range of subclinical and clinical outcomes that depend on properties of the infecting strain, the host, and the environment. Eradication therapy is indicated for infected persons who develop peptic ulcer disease or gastric lymphoma or who are beginning long-term treatment with nonsteroidal anti-inflammatory drugs. However, treatment may worsen gastroesophageal reflux disease and increase the risk of esophageal cancer. H. pylori infections can be diagnosed noninvasively and can be eradicated with approximately 85% success by a variety of multidrug, 7-14-day regimens. Unfortunately, antibiotic resistance is affecting treatment effectiveness in the United States and abroad. A more complete understanding of the variation in H. pylori pathogenesis should lead to clearer recommendations about treatment for infected persons who have neither peptic ulcer disease nor gastric lymphoma.

Resistance of Helicobacter pylori isolated in Israel to metronidazole, clarithromycin, tetracycline, amoxicillin and cefixime.

The resistance of Helicobacter pylori isolated in Israel to metronidazole, clarithromycin, tetracycline, amoxicillin and cefixime was tested in 138 isolates, including 28 from treatment failures. No resistance to tetracycline was detected. Resistance to amoxicillin was found in one isolate (MIC = 1.5 mg/L) from an untreated patient, and resistance to cefixime in two isolates from each group (P = 0.18). Resistance to metronidazole and clarithromycin was much higher in the isolates from treated than from untreated patients: 60.7% and 38.2% for metronidazole (MIC >or= 8 mg/L) (P = 0.03); 46.4% and 8.2% for clarithromycin (MIC >or= 2 mg/L) (P < 0.001). Therapeutic outcome would benefit from susceptibility testing, especially after treatment failure.