Serum antibodies to benzo(a)pyrene diol epoxide-DNA adducts in the general population: effects of air pollution, tobacco smoking, and family history of lung diseases

Polycyclic aromatic hydrocarbons (PAHs) are almost ubiquitous pollutants that may interact with metabolic systems in human tissues and eventually cause cancer. PAH-adducted DNA becomes antigenic and antibodies anti-benzo(a)pyrene diol epoxide (BPDE)-DNA may be found in serum of PAH-exposed subjects. The presence of serum antibodies anti-BPDE-DNA adduct was investigated in 1345 individuals from family clusters of the general population of a small area in central Italy in whom information about smoking habits, site of residence, and personal and family history of lung diseases, including cancer, were obtained. Anti-BPDE-DNA antibodies in the sera were detected with a direct ELISA and the association of anti-BPDE-DNA antibodies with subjects' data from a standardized respiratory questionnaire including age, occupation, tobacco smoking habits, respiratory symptoms, and family history of respiratory diseases was subsequently tested by multivariate logistic regression analysis. The overall prevalence of subjects with anti-BPDE-DNA antibodies was 21.0% (n=283), with no differences between males and females. Anti-BPDE-DNA positivity was associated with living in the urban area [odds ratio (OR), 1.49; 95% confidence interval (CI), 1.16-1.92], with active tobacco smoking (OR, 1.25; 95% CI, 1.06-1.48), and with family history of lung cancer (OR, 1.30; 95% CI, 0.90-1.88), and positivity increased with the number of members in the family cluster positive to anti-BPDE-DNA antibodies (OR, 1.30; 95% CI, 1.03-1.65). This study on a large general population sample indicates that serum anti-BPDE-DNA antibodies may be considered as biomarkers of exposure to environmental carcinogens and of DNA damage. The genetic and familial components of their association with tobacco smoking lend further support to the argument about the familial predisposition to lung cancer.     

Cloning and characterization of a putative testis-specific pyruvate dehydrogenase beta subunit from the parasitic nematode, Ascaris suum

We enrolled five hundred twenty-one patients with atrophic gastritis and 769 controls in a case-control study of atrophic gastritis and Helicobacter pylori infection and lifestyle factors. The participants had no history of upper gastrointestinal surgery. They were selected from 1,395 adult (35 years or older) residents of a rural town in Kyoto prefecture who participated in an annual health examination in 1987. Atrophic gastritis was diagnosed on the basis of serum pepsinogen levels: pepsinogen I levels (< or = 70 ng/ml) and pepsinogen I/pepsinogen II ratios (< or = 3.0). The presence of immunoglobulin G antibodies to H. pylori indicated H. pylori infection. At the time of the health examination, participants were interviewed about daily lifestyle habits such as use of cigarettes and alcoholic beverages and consumption of green-yellow vegetables. Unconditional logistic regression analysis indicated that H. pylori infection was associated with a significantly increased risk for atrophic gastritis for all participants (odds ratio, 8.17; 95% confidence interval, 5.63-11.84); for men (odds ratio, 10.91; 95% CI, 5.25-22.67); and for women (odds ratio, 7.28; 95% CI, 4.72-11.22). We found no statistically significant relations between lifestyle factors and atrophic gastritis.     

Patterns of symptoms in functional dyspepsia: role of Helicobacter pylori infection and delayed gastric emptying

OBJECTIVE: Functional dyspepsia (FD) is a syndrome in which several causes are probably involved. Our aim was to investigate the association between specific dyspeptic symptoms and Helicobacter pylori infection or delayed gastric emptying. METHODS: Nine hundred thirty-five consecutive outpatients with unexplained dyspepsia were studied. After appropriate investigation, 304 patients were diagnosed as affected by chronic FD and were tested for H. pylori infection and gastric emptying of solids by means of 13C-urea and 13C-octanoic acid breath tests. Four dyspeptic symptoms (epigastric pain or burning, postprandial fullness, nausea, and vomiting) were scored as absent, mild, moderate, or severe (0-3) according to their influence on the patients' activities. Symptoms of irritable bowel syndrome and gastroesophageal reflux disease were also assessed. On the basis of symptom scores, three groups were identified: "prevalent pain" (10.5%), "prevalent discomfort" (32.6 %), and "unclassifiable" dyspepsia (56.9%). RESULTS: Of the 304 patients with FD, 208 (68.4 %) were H. pylori-positive on urea breath test. Gastric emptying was delayed in 99 subjects (32.6%). Patients with "prevalent pain" were infected significantly more often (81.2% vs 59.6%; p = 0.026) and less frequently had delayed gastric emptying (6.2% vs 40.4%; p = 0.0001) than those with "prevalent discomfort." H. pylori infection was independently associated with age > or =40 yr and epigastric pain or burning > or =2 (odds ratio [OR] and 95% confidence interval [CI] 4.09 [2.39-7.00] and 1.70 [1.04-2.77], respectively). Delayed gastric emptying was independently associated with a cumulative score > or =6 for postprandial fullness, nausea, and vomiting (OR [95% CI]: 3.13 [1.06-9.18]). H. pylori status had no influence on gastric emptying. Logistic regression analysis showed that delayed gastric emptying, female sex, and concomitant symptoms of inflammatory bowel syndrome were independently associated with a cumulative score > or =6 for postprandial fullness, nausea, and vomiting (p = 0.0281, p = 0.0387, and p = 0.0316, respectively). Moreover, concomitant symptoms of gastroesophageal reflux disease, female sex, and H. pylori infection were independently associated with epigastric pain or burning > or =2 (p = 0.002, p = 0.0001, and p = 0.0875, respectively). CONCLUSIONS: Two subsets of FD patients have been identified on the basis of symptoms. One subgroup is mainly characterized by "prevalent pain," H. pylori infection, and normal gastric emptying; the other one demonstrates "prevalent discomfort" and delayed gastric emptying. These findings shed some light on possible etiopathogenetic mechanisms of FD.     

Dyspepsia in relation to Helicobacter pylori infection and psychosocial work stress in white collar employees

OBJECTIVE: We undertook an investigation of the relationship between psychosocial work stress and Helicobacter pylori (H. pylori) infection with dyspepsia. METHODS: We conducted a cross-sectional study among 189 employees of a health insurance company in the city of Ulm, Germany. RESULTS: A clear association between work-related psychosocial factors and the occurrence of dyspeptic symptoms during the past 3 months was evident. Persons who were considered to have a critical style of coping with work demands suffered more often from dyspeptic symptoms. Current infection with H. pylori was not associated with prevalence of dyspeptic symptoms. These results were also confirmed by adjustment for age, gender, smoking status, education, and use of antiinflammatory drugs within the past 3 months, by means of multivariate analysis. The odds ratio (OR) for having a dyspepsia symptom score in the upper tertile versus the 1st or 2nd was 3.22 (95% confidence interval [CI], 1.56-6.65), given that the employee was considered to have a critical style of coping with work demands. The OR for having a dyspepsia symptom score in the upper tertile given H. pylori infection was 1.23 (95% CI, 0.44-3.46), indicating no association of current H. pylori infection with dyspeptic symptoms. CONCLUSIONS: A critical style of coping with work demands may be an important determinant for dyspepsia-like symptoms. Therefore, in the absence of an underlying disease, specific intervention programs should be targeted at the behavior of the affected individual (e.g., stress-reduction programs) rather than on the treatment of specific symptoms or infection with H. pylori.     

A case-control study of dietary intake and other lifestyle risk factors for hyperplastic polyps

BACKGROUND & AIMS: Despite the high prevalence of the hyperplastic polyp, little is known about its etiology. The aim of this study was to assess the relationship between diet and other lifestyle factors and the presence of colorectal hyperplastic polyps. METHODS: Information on diet and other known or suspected risk factors for colorectal cancer or adenoma was collected among 81 subjects with hyperplastic polyps and 480 controls. RESULTS: The multivariate-adjusted odds ratio (OR) for hyperplastic polyps for individuals in the upper vs. the lower quartile was 0.30 (95% confidence interval [CI], 0.10-0.88) for dietary fiber, 0.32 (95% CI, 0.11-0.96) for dietary calcium, 0.90 (95% CI, 0.27-2.95) for total fat, and 2.02 (95% CI, 1.05-3.91) for alcohol consumption. Compared with individuals in the lower category, those in the upper category of body mass index had a higher risk for hyperplastic polyps (OR, 4.50; 95% CI, 1.84-10.97). Cigarette smoking was associated with a higher risk (OR, 1.97; 95% CI, 1.02-3.81 for > 20 pack-years vs. never), whereas an inverse association was seen for use of aspirin and other nonsteroidal anti-inflammatory drugs (OR, 0.29; 95% CI, 0.12-0.67 for once per day or more vs. never). CONCLUSIONS: Hyperplastic polyps share common lifestyle risk factors with colorectal adenomas and carcinomas.     

Helicobacter pylori among preschool children and their parents: evidence of parent-child transmission

This study assessed the role of parental infection status in the transmission of Helicobacter pylori infection in a large population-based sample of preschool-aged children. The subjects, who lived in Ulm, Germany, and in two nearby communities, were screened for school fitness between January and July 1997. Their H. pylori infection status was determined by 13C-urea breath test. Of 1522 eligible children, 1221 (80.2%) participated in the study. Crude prevalence of H. pylori infection in children was 11.3% (95% confidence interval [CI], 9.5-13.3) and 36.4% in their parents (95% CI, 33.5-39.4). The crude odds ratio (OR) for H. pylori infection of children whose mothers were infected was 16.5 (95% CI, 8.9-30.8) and 7.9 after adjustment for potential confounders (95% CI, 4.0-15.7). The crude OR if the child's father was infected was 7.8 (95% CI, 2. 5-24.2) and 3.8 after adjustment for potential confounders (except maternal infection) (95% CI, 0.8-19.1). The results suggest that infected parents, especially infected mothers, may have a key role in transmission of H. pylori within families.     

The impact of Helicobacter pylori eradication on peptic ulcer healing

OBJECTIVE: Current literature was reviewed analyzing the outcome of peptic ulcer healing in relation to the results of the posttherapeutic Helicobacter pylori (HP) status. METHODS: Literature was reviewed along with an analysis of 60 studies, comprising a total of 4329 patients. RESULTS: Successful Helicobacter pylori eradication was found to induce a better response in peptic ulcer healing, regardless of diagnosis: gastric ulcer 88% vs 73% (odds ratio [OR] 2.7, p < 0.01), duodenal ulcer 95% vs 76% (OR 5.6, p < 0.0001), and peptic ulcer 95% vs 76% (OR 6.6, p < 0.0001), for patients having their HP infection successfully cured versus those remaining HP-positive, respectively (Fisher's exact test). For all evaluated time points (< or = 6, 7-8, and 10-12 wk after beginning treatment), HP-negative patients had higher healing rates than HP-positive patients (95% vs 82%, 94% vs 69%, and 96% vs 78% with corresponding OR of 4.2, 6.5, and 7.4, all p < 0.0001, Fisher's exact test). The use of concomitant acid suppression therapy during initial HP eradication provided a benefit on peptic ulcer healing only for patients with persistent HP infection (improved healing rates of 78% vs 67%; otherwise rates were 94-96%). Likewise, prolonged acid inhibition in HP treatment failures after the initial HP treatment phase resulted in 7-20% improved healing rates, whereas patients becoming HP-negative did not profit. CONCLUSION: Successful HP eradication therapy accelerates peptic ulcer healing even without concomitant acid suppression.     

Erosive duodenitis: prevalence of Helicobacter pylori infection and response to eradication therapy with omeprazole plus two antibiotics

OBJECTIVES: To study the prevalence of Helicobacter pylori infection in patients with erosive duodenitis (ED), the associated gastric histological lesions and their response to eradication therapy with omeprazole plus two antibiotics. METHODS: A prospective study was made of 57 patients with ED (mean age 46 +/- 16 years, 72% males). At endoscopy, biopsies from gastric antrum and body were obtained for histological study (haematoxylin and eosin). A 13C-urea breath test was also performed. Omeprazole 20 mg twice daily plus two antibiotics (amoxycillin 1 g twice daily, clarithromycin 500 mg twice daily, metronidazole 500 mg twice daily) were administered for 1 week. Endoscopy and breath test were repeated 1 month after completing therapy, and the breath test was performed again at 6 months. RESULTS: All patients were H. pylori positive. Overall eradication was achieved in 86% (95% CI 75-93%). Duodenal erosion healing was obtained in 45 patients (79%). Healing was achieved in 86% (CI 73-93%) of cases with successful eradication therapy, but only in 3/8 (37%; CI 8.5-75%) patients with therapy failure (P < 0.01). In the multivariate analysis, H. pylori eradication was the only variable which correlated with erosion healing (odds ratio 10; CI 2-51; P < 0.01). Histological improvement, in both the gastric antrum and body, was demonstrated when eradication was achieved (P < 0.001). Six months after diagnosis H. pylori absence was confirmed in all patients with initial therapy success (all of them asymptomatic), and infection was confirmed in the eight patients who were H. pylori positive after therapy (six of them symptomatic). At 6-month follow-up, endoscopy was normal in 6/7 H. pylori-negative patients with previously persistent ED, while erosions were still present in 4/5 H. pylori-positive patients with previously persistent ED. CONCLUSION: A high prevalence (100%) of H. pylori infection in patients with ED was observed. A 1-week twice daily therapy with omeprazole plus two antibiotics (clarithromycin plus amoxycillin or metronidazole) was very effective in H. pylori eradication, duodenal erosion healing, symptomatic improvement, and in disappearance of associated histological gastritis. These observations suggest that ED should be considered a variant form of duodenal ulcer disease and treated accordingly; that is, with H. pylori eradication therapy.     

Relation of Helicobacter pylori infection to 13-year mortality and incident ischemic heart disease in the caerphilly prospective heart disease study

BACKGROUND: Associations have been suggested between Helicobacter pylori seropositivity, cardiovascular risk factors, and ischemic heart disease (IHD). The effect of this common infection on mortality is uncertain. METHODS AND RESULTS: Plasma specimens collected during 1979 to 1983 from 1796 men in Caerphilly, South Wales, were analyzed for IgG antibodies to H pylori. Cause of death and occurrence of incident IHD events were ascertained over an average of 13.7 years from death certificates, hospital records, and ECG changes at 5-yearly follow-up examinations. Seventy percent of men were seropositive. The prevalence of IHD at entry was similar in men with and without H pylori antibodies (odds ratio [OR], 1.10; 95% CI, 0.87 to 1.40). Seropositivity was significantly (P<0.05) associated with poorer socioeconomic status currently and in childhood, shorter stature, and poorer ventilatory function at entry but not with age, smoking, body mass index, blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol, fibrinogen, plasma viscosity, or heat shock protein antibodies. Thirteen-year incidence of IHD was not significantly associated with H pylori (OR, 1.05; 95% CI, 0.80 to 1.39), but there was a stronger relationship with all-cause mortality (OR, 1.46; 95% CI, 1.12 to 1.92) and fatal IHD (OR, 1.54; 95% CI, 1.03 to 2.30). After adjustment for cardiovascular risk factors and both adult and childhood socioeconomic status, ORs were slightly reduced and lost statistical significance (OR=1.32 [95% CI, 0.99 to 1.78] for all-cause mortality and OR=1.52 [95% CI, 0.99 to 2.34] for fatal IHD). CONCLUSIONS: H pylori infection is unlikely to be as strong a risk factor for IHD as some previous studies have suggested, but its relationship to mortality, including fatal IHD, deserves further investigation. The mechanism underlying these associations is unlikely to involve hypertension, circulating lipid profile, fibrinogen, or cross-reacting antibodies to bacterial heat shock proteins.     

Prevalence of risk factors in spontaneous intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage

OBJECTIVE: To evaluate whether differences exist in the occurrence of modifiable risk factors between aneurysmal subarachnoid hemorrhage and spontaneous intracerebral hemorrhage, since these stroke subtypes have frequently been combined in epidemiological studies and labeled hemorrhagic stroke. DESIGN: Cross-sectional survey. SETTING: Helsinki University Central Hospital in Helsinki, Finland. PATIENTS: One hundred fifty-six consecutive patients with spontaneous intracerebral hemorrhage aged 16 to 60 years (96 males and 60 females) and 281 patients with aneurysmal subarachnoid hemorrhage (145 males and 136 females) who were admitted to an emergency department. MAIN OUTCOME MEASURES: Prevalence of several health habits, previous diseases, and medication of patients with spontaneous intracerebral hemorrhage were compared with that of patients with subarachnoid hemorrhage using multiple logistic regression. RESULTS: Hypertension (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.6-4.3), diabetes mellitus (OR, 26.4; 95% CI, 3.1-221.6), alcohol intake within the preceding week (for 1-150 g of alcohol: OR, 2.0; 95% CI, 1.1-3.6; for 151-300 g of alcohol: OR, 1.7; 95% CI, 0.8-3.8; and for > 300 g of alcohol: OR, 4.4; 95% CI, 2.1-9.1), and anticoagulant treatment (OR, 21.8; 95% CI, 2.3-207.3) were all significantly more common, but current cigarette smoking (OR, 0.3; 95% CI, 0.2-0.5) was less common in patients with intracerebral hemorrhage than in those with subarachnoid hemorrhage simultaneously after adjustment for sex, age, and body mass index. In males, hypertension (OR, 2.3; 95% CI, 1.1-4.5) and alcohol intake (for > 300 g/wk: OR, 5.8; 95% CI, 2.2-15.7) were more common, but current smoking (OR, 0.2; 95% CI, 0.1-0.4) was less common in patients with intracerebral hemorrhage than in those with subarachnoid hemorrhage after adjustment for age, body mass index, and diabetes mellitus. In females, hypertension (OR, 2.9; 95% CI, 1.4-5.8) and anticoagulant treatment (OR, 10.0; 95% CI, 1.0-100.2) were more common in patients with intracerebral hemorrhage after adjustment for age and body mass index. In univariate statistics, patients with intracerebral hemorrhage were also older, more often had previous symptoms of cerebral ischemia, and had higher values for body mass index and gamma-glutamyltransferase than did those with subarachnoid hemorrhage. CONCLUSIONS: Hypertension, diabetes mellitus, anticoagulant treatment, and amount of alcohol taken within 1 week seem more commonly to be associated with intracerebral hemorrhage than with subarachnoid hemorrhage, which is, however, associated more frequently with cigarette smoking.     

Helicobacter pylori infection: relation with cardiovascular risk factors, ischaemic heart disease, and social class

OBJECTIVE: To determine whether Helicobacter pylori infection is associated with the development of ischaemic heart disease and whether such infection can explain the social class inequality in ischaemic heart disease. DESIGN: Cardiovascular risk factor levels, prevalence of ischaemic heart disease (Rose questionnaire angina, and/or a history of myocardial infarction), and serum antibodies to H pylori (enzyme linked immunosorbent assay) were assessed in a cross sectional population based survey. SETTING: Belfast and surrounding districts, Northern Ireland. PARTICIPANTS: 1182 men and 1198 women aged 25-64 years randomly selected from the Central Services Agency's general practitioner lists. MAIN OUTCOME MEASURES: The relation of H pylori infection with cardiovascular risk factors and ischaemic heart disease. The association of social class with ischaemic heart disease. RESULTS: Systolic and diastolic blood pressure, plasma viscosity, and total cholesterol were not associated with H pylori infection. A weak negative association existed between H pylori infection and fibrinogen (mean (SE) difference in fibrinogen between infected and uninfected individuals -0.09 (0.04) g/l, P = 0.02) and between infection in women and high density lipoprotein (HDL) cholesterol (mean (SE) difference in HDL cholesterol between infected and uninfected individuals -0.06 (0.02) mmol/l, P = 0.006). A potentially important association was demonstrated between H pylori infection and ischaemic heart disease but this did not reach statistical significance (odds ratio (95% confidence interval (CI) 1.51 (0.93 to 2.45), P = 0.1). Social class was associated with ischaemic heart disease independently of cardiovascular risk factors and H pylori infection (odds ratio, manual v non-manual (95% CI) 1.82 (1.14 to 2.91), P = 0.01). CONCLUSION: H pylori may be independently associated with the development of ischaemic heart disease but if this is so the mechanism by which this effect is exerted is not through increased concentration of plasma fibrinogen. H pylori infection does not explain the social class inequality in ischaemic heart disease which exists independently of known cardiovascular risk factors.     

Animal model of human medulloblastoma: clinical, magnetic resonance imaging, and histopathological findings after intra-cisternal injection of MHH-MED-1 cells into nude rats

OBJECTIVES: It was our goal to evaluate the efficacy and safety and patient compliance with omeprazole-based dual and triple therapy for eradication of Helicobacter pylori in peptic ulcer disease. MATERIALS AND METHODS: One hundred seventy-five consecutive patients with H. pylori infection and associated active peptic ulcer were included. H. pylori infection was assessed by rapid urease test and histological analysis. Patients were randomized among three treatments: group 1 (56 patients): omeprazole, 20 mg bid, and amoxicillin, 1 gm bid, for 2 weeks; group 2 (61 patients): omeprazole, 20 mg bid, plus amoxicillin, 1 gm bid, and metronidazole, 500 mg bid, for 1 week; and group 3 (58 patients): omeprazole, 20 mg bid, plus amoxicillin, 1 gm bid, and clarithromycin, 500 mg bid, for 1 week. Ulcer healing and cure of infection were evaluated at 4 to 6 weeks after cessation of therapy. Eradication rate was calculated per-protocol and by an intention-to-treat analysis. RESULTS: At posttreatment endoscopy, duodenal ulcer was healed in 98.3% of patients. Eleven patients (6%) were lost to follow-up. H. pylori infection was treated successfully in 55% (95% confidence interval [CI] = 41%-69%) of patients of group 1; 86% (95% CI = 77%-95%) of group 2 (p < .001 vs. group 1); and 93% (95% CI = 85%-100%) of group 3 (p < .001 vs. group 1). On intention-to-treat analysis, eradication was 52%, 80%, and 86% in groups 1, 2, and 3, respectively. A good compliance was observed in more than 90% of patients of all groups. Side effects were reported by 7% of patients in group 1, 9% in group 2, and 11% in group 3. None of the patients stopped therapy because of side effects. CONCLUSIONS: Dual-therapy omeprazole-amoxicillin for 2 weeks is associated with significantly lower eradication rate than is 1-week omeprazole-based triple therapies. Triple therapy is well-tolerated and produces side effects similar to those of dual therapy. The highest cure rate of H. pylori infection was achieved with triple therapy of omeprazole, amoxicillin, and clarithromycin for 1 week.     

Evaluation of status of tuberculin skin sensitivity test among medical students

BACKGROUND: The role of lipoproteins as markers of peripheral arterial disease (PAD) is not well defined. METHODS: We measured both lipid and non-lipid risk factors in 51 male patients with angiographically proven PAD and in 56 control subjects. The independent association of risk factors with PAD was evaluated by means of a multiple logistic regression analysis. RESULTS: The levels of cholesterol bound to high density lipoprotein (HDLc) and to its subfraction HDL2 were lower and triglycerides were higher in patients than in control subjects (1.0 +/- 0.3 vs 1.2 +/- 0.3, p < 0.003; 0.4 +/- 0.2 vs 0.5 +/- 0.3, p < 0.03; and 1.8 +/- 1.2 vs 1.3 +/- 0.7, p < 0.02, respectively). Total cholesterol and LDLc levels were similar in both groups. In the multiple logistic regression analysis that was done with lipid parameters, a statistically significant association of triglycerides (OR = 1.73; CI95% = 1.06-2.80) and HDLc (OR = 0.15; CI95% = 0.05-0.50) with PAD was observed, while HDL subfractions and apolipoproteins were not significantly associated. In the multiple logistic regression analysis that was done with non-lipid parameters, hypertension (OR = 5.35; CI95% = 1.86-15.4) and smoking (packs-year) (OR = 1.04; CI95% = 1.10-1.06) were the only significantly associated with PAD. When lipid and non-lipid parameters were included in the regression analysis, a statistically significant association between hypertension, smoking and HDLc with PAD was observed. CONCLUSIONS: Among lipid risk factors, a low HDLc and high triglycerides, and among non-lipid risk factors hypertension and smoking, are significantly and independently associated with lower limb arteriopathy.     

Helicobacter pylori infection and genetic polymorphisms for cancer-related genes in gastric carcinogenesis

The development of gastric cancer is a multistep process that is multi-factorial. An association with the Helicobacter pylori infections, gastric atrophy and gastric cancer has received recent attention. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiological techniques for genetic susceptibility, gastric atrophy and serum markers including H pylori infection. We used an age- and gender-matched case-control study, where patients with benign gastric lesions were the controls. Low serum pepsinogen I levels (cut-off < 50 ng/mL) and low pepsinogen I/pepsinogen II ratios (cut-off < 3.0) were significantly associated with the risk of gastric cancer (odds ratio [OR] = 3.53: 95% confidence interval [CI] = 2.46-5.09 and OR = 4.73: 3.26-6.88, respectively). However, seropositivity of serum immunoglobulin G (IgG) antibody against H pylori (OR = 1.09: 0.74-1.61) was not associated with gastric cancer, even when analyzed by age greater than or less then 50 years. Specific genotypes of the cytochrome p450 2E1 (CYP2E1) RsaI polymorphism and glutathione-S-transferase (GST) M1 gene deletion were determined but were not associated with gastric cancer; however, a Lmyc genetic polymorphism was associated with gastric cancer (OR = 1.55: 1.03-2.34). Therefore, in this Japanese study, atrophic mucosal change, indicated by serum pepsinogen levels, is a possible risk factor for gastric cancer.     

Risk factors for multiple intracranial aneurysms

OBJECTIVE: Risk factors that predispose to the formation of multiple intracranial aneurysms, which are present in up to 34% of patients with intracranial aneurysms, are not well defined. In this study, we examined the association between known risk factors for cerebrovascular disease and presence of multiple intracranial aneurysms. METHODS: We reviewed the medical records and results of conventional angiography in all patients with a diagnosis of intracranial aneurysms admitted to the Johns Hopkins University hospital between January 1990 and June 1997. We determined the independent association between various cerebrovascular risk factors and the presence of multiple aneurysms using logistic regression analysis. RESULTS: Of 419 patients admitted with intracranial aneurysms (298 ruptured and 121 unruptured), 127 (30%) had multiple intracranial aneurysms. In univariate analysis, female gender (odds ratio [OR] = 1.9; 95% confidence interval [CI], 1.1-3.3) and cigarette smoking at any time (OR = 1.8; 95% CI, 1.1-3.0) were significantly associated with presence of multiple aneurysms. In the multivariate analysis, cigarette smoking at any time (OR = 1.7; 95% CI, 1.1-2.8) and female gender (OR = 2.1; 95% CI 1.2-3.5) remained significantly associated with multiple aneurysms. Hypertension, diabetes mellitus, and alcohol and illicit drug use were not significantly associated with presence of multiple aneurysms. CONCLUSION: Cigarette smoking and female gender seem to increase the risk for multiple aneurysms in patients predisposed to intracranial aneurysm formation. Further studies are required to investigate the mechanism underlying the association between cigarette smoking and intracranial aneurysm formation.     

A prospective randomized trial comparing the use of omeprazole-based dual and triple therapy for eradication of Helicobacter pylori

BACKGROUND: Controversy surrounds the optimal composition, dosage, and duration of therapies for eradication of Helicobacter pylori. We prospectively compared omeprazole-based dual and triple therapies in the eradication of H. pylori in a randomized manner. METHODS: Between June 1995 and March 1997, 1000 consecutive patients with acid-peptic disease associated with H. pylori infection (duodenal ulcer, 388 patients, gastric ulcer, 179 patients; duodenitis, 173 patients; gastritis, 260 patients) were prospectively recruited. They were randomized to either a 2-wk (OA) course of omeprazole 20 mg and amoxicillin 1 g, both given twice daily, or treatment for 1 wk (OCM) with omeprazole 20 mg once daily, clarithromycin 500 mg twice daily, and metronidazole 400 mg twice daily. RESULTS: The age of these 1000 patients ranged from 16 to 90 yr, with a mean of 54.9 yr. Side effects occurred in 29.6% (95% confidence interval [CI] 25.6-33.8%) and 10.6% (95% CI 8.0-13.6%) of patients taking OCM and OA, respectively (p < 0.0001). Apart from taste disturbance, however, there were no significant differences in the incidences of side effects between the two groups. One patient in the OA group and four patients of the OCM group could not tolerate the medications, and therefore did not complete treatment (p = 0.37). Seven and 13 patients in the OA and OCM groups, respectively, refused a second endoscopy (p = 0.25). The remaining 975 patients underwent a second endoscopy. Positive endoscopic findings were significantly more common in the OA group (51/492; 10.4%; 95% CI 7.8-13.4%) than in the OCM group (25/483; 5.2%; 95% CI 3.4-7.5%) in the per-protocol (PP) analysis (p = 0.004). On intent-to-treat (ITT) analysis, the overall eradication rates in the OA and OCM groups were 73.6% (95% CI 69.5-77.4%) and 92% (95% CI 89.3-94.2%), respectively (p < 0.0001). On PP analysis, the corresponding rates were 74.8% (95% CI 70.7-78.6%) and 95.2% (95% CI 92.9-97.0%), respectively (p < 0.0001). CONCLUSIONS: A course of omeprazole, clarithromycin, and metronidazole for 1 wk is a safe, well-tolerated, efficacious, and cost-effective treatment for H. pylori infection.     

alpha-1-Microglobulin: epidemiological indicator for tubular dysfunction induced by cadmium?

OBJECTIVES: To evaluate the suitability of alpha-1-microglobulin as a marker for cadmium induced renal dysfunction. METHODS: alpha-1-Microglobulin was studied in a cross sectional survey in relation to the body burden of cadmium. Concentrations of alpha-1-microglobulin in 24 h urine of 831 people aged 2-87 years were analysed in association with urinary cadmium excretion, cadmium blood concentration, age, sex, occupational and smoking history, and estimated creatinine clearance. Participants came from a population residentially exposed to cadmium and from two control populations matched for socioeconomic status. RESULTS: The excretion of alpha-1-microglobulin/24 h ranged from 0.1 mg to 176.3 mg and 44.4% of samples showed concentrations near the detection limit. Ordinal logistic regression analysis of people of all ages identified a high risk only for males compared with females (odds ratio (OR) 2.14; 95% confidence interval (95% CI) 1.56 to 2.94), age group, and duration of living on contaminated soil (OR 1.03/year; 95% CI 1.02 to 1.04), but not urinary cadmium excretion (OR 1.30; 95% CI 0.96 to 1.77) as significant predictors. For people < or = 50 years of age a weaker effect of sex (OR 1.76; 95% CI 1.13 to 2.73) and age group and an effect of similar magnitude for the duration of soil exposure (OR 1.03; 95% CI 1.01 to 1.04) were found. Also, the urinary cadmium excretion (OR 2.26; 95% CI 1.38 to 3.70) and occupational exposure (OR 1.71; 95% CI 1.03 to 2.83) were found to be significant in this younger age group. The estimated creatinine clearance had no significant impact on the alpha-1-microglobulin excretion. CONCLUSION: alpha-1-Microglobulin is a suitable marker for early tubular changes only for people < or = 50 years. It may not be sufficiently specific for cadmium, and therefore not a suitable surrogate for cadmium exposure in epidemiological studies.     

Benign symmetrical lipomatosis: Madelung''s disease

The relationship between smoking and bladder cancer risk was investigated using data from a case-control study conducted between January 1994 and July 1996 in Alexandria, Egypt. Cases were 151 males with incident, histologically confirmed invasive cancer of the bladder, and controls were 157 males admitted to hospital for acute, non-neoplastic, non-urinary tract, non-smoking-related conditions. With reference to never smokers, ex-smokers had a multivariate odds ratio (OR) of 4.4 [95% confidence interval (CI) 1.7-11.7] and current smokers of 6.6 (95% CI 3.1-13.9). The ORs were 5.4 for < 20 and 7.6 for > or = 20 cigarettes per day. After adjustment for cigarette smoking, the ORs were 0.8 for waterpipe and 0.4 for hashish smokers. The risk was significantly related to duration of smoking (OR of 16.5 for > 40 years), and inversely related to age at starting (OR of 8.8 for starting < 20 years), and inversely related to time since quitting smoking. Compared with never smokers who did not report a clinical history of schistosomiasis, the OR was 9.4 for smokers with a history of schistosomiasis, and 10.7 for smokers ever employed in high-risk occupations compared with non-smokers not reporting such a history. Thus, our results, while not giving indications of an increased bladder cancer risk with habits other than cigarette smoking, found a remarkably strong association with various measures of cigarette smoking that could explain 75% of bladder cancer cases among males from Alexandria. The prevalence of smoking was very low among women, and consequently tobacco was not a relevant risk factor for female bladder cancer.     

Biologic activity of interleukin 1 (IL-1) alpha in patients with refractory malignancies

To examine the effects of smoking and N-acetylation genetics on breast cancer risk, we analyzed data from an ongoing, population-based, case-control study of invasive breast cancer in North Carolina. The study population consisted of 498 cases and 473 controls, with approximately equal numbers of African-American and white women, and women under the age of 50 and age 50 years or older. Among premenopausal women, there was no association between current smoking [odds ratio (OR), 0.9; 95% confidence interval (CI), 0.5-1.5] or past smoking (OR, 1.0; 95% CI, 0.6-1.6) and breast cancer risk. Among postmenopausal women, there was also no association with current smoking (OR, 1.2; 95% CI, 0.7-2.0); however, a small increase in risk was observed for past smoking (OR, 1.5; 95% CI, 1.0-2.4). For postmenopausal women who smoked in the past, ORs and 95% CIs were 3.4 (1.4-8.1) for smoking within the past 3 years, 3.0 (1.3-6.7) for smoking 4-9 years ago, and 0.6 (0.3-1.4) for smoking 10-19 years ago. Neither N-acetyltransferase 1 (NAT1) nor N-acetyltransferase 2 (NAT2) genotype alone was associated with increased breast cancer risk. There was little evidence for modification of smoking effects according to genotype, except among postmenopausal women. Among postmenopausal women, ORs for smoking within the past 3 years were greater for women with the NAT1*10 genotype (OR, 9.0; 95% CI, 1.9-41.8) than NAT1-non*10 (OR, 2.5; 95% CI, 0.9-7.2) and greater for NAT2-rapid genotype (OR, 7.4; 95% CI, 1.6-32.6) than NAT2-slow (OR, 2.8; 95% CI, 0.4-8.0). Future studies of NAT genotypes and breast cancer should investigate the effects of environmental tobacco smoke, diet, and other exposures.     

Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection

BACKGROUND: Experimental models and analyses of human tumors suggest that oncogenic, sexually transmittable human papillomaviruses (HPVs) are etiologic factors in the development of oral squamous cell carcinoma (SCC). We conducted a population-based, case-control study to determine whether the risk of this cancer is related to HPV infection and sexual history factors. METHODS: Case subjects (n = 284) were 18-65-year-old residents of three counties in western Washington State who were newly diagnosed with oral SCC from 1990 through 1995. Control subjects (n = 477) similar in age and sex were selected from the general population. Serum samples were tested for HPV type 16 capsid antibodies. Exfoliated oral tissue collected from case and control subjects and tumor tissue from case subjects were tested for HPV DNA. Odds ratios (ORs) were calculated after adjusting for age, sex, cigarette smoking, and alcohol consumption. RESULTS: Among males only, oral SCC risk increased with self-reported decreasing age at first intercourse, increasing number of sex partners, and a history of genital warts. Approximately 26% of the tumors in case subjects contained HPV DNA; 16.5% of the tumors contained HPV type 16 DNA. The prevalence of oncogenic HPV types in exfoliated oral tissue was similar in case and control subjects. The ORs for HPV type 16 capsid seropositivity were 2.3 (95% confidence interval [CI] = 1.6-3.3) for all oral SCCs and 6.8 (95% CI = 3.0-15.2) for oral SCCs containing HPV type 16 DNA. The joint association of cigarette smoking and HPV type 16 capsid seropositivity with oral SCC (OR = 8.5; 95% CI = 5.1-14.4) was stronger than predicted from the sum of individual associations with current smoking (OR = 3.2; 95% CI = 2.0-5.2) and seropositivity (OR = 1.7; 95% CI = 1.1-2.6). CONCLUSIONS: HPV type 16 infection may contribute to the development of a small proportion of oral SCCs in this population, most likely in combination with cigarette smoking.