Polymerase chain reaction amplification of Guthrie card deoxyribonucleic acid: extraction of nucleic acid from filter matrices

BACKGROUND: This study was designed to test the association of Chlamydia pneumoniae infection with asthma in a multi-racial population, after adjustments for several potential confounding variables. METHODS: Antibodies to C pneumoniae were measured by microimmunofluorescence in 123 patients with acute asthma, 1518 control subjects admitted to the same hospital with various non-cardiovascular, non-pulmonary disorders, and 46 patients with severe chronic asthma, including some with "brittle" asthma. Acute infection or reinfection was defined by titres of IgG of > or = 512 or IgM > or = 8 or a fourfold rise in IgG, and previous infection by IgG 64-256 or IgA > or = 8. Logistic regression was used to control for likely confounders, including ethnic origin, age, sex, smoking habit, steroid medication, diabetes mellitus and social deprivation, on antibody levels. RESULTS: Antibody titres consistent with acute C pneumoniae infection were found in 5.7% of patients with acute asthma and 5.7% of control patients, while 14.6% of patients with acute asthma and 12.7% of control patients had titres suggesting previous infection. These two groups did not differ significantly. However, titres suggesting previous infection were found in 34.8% of patients with severe chronic asthma: the difference between this group and the control group was statistically significant with an adjusted odds ratio of 3.99 (95% confidence interval 1.60 to 9.97). CONCLUSIONS: These data raise important questions about the previously demonstrated association of C pneumoniae infection with asthma, and suggest that future studies of this association should give particular attention to the presence or absence of a history of severe chronic asthma.     

Association of Chlamydia pneumoniae IgA antibodies with recently symptomatic asthma

To determine whether recently diagnosed adult-onset asthma is associated with serologic evidence of chronic Chlamydia pneumoniae infection, we performed a case-control study in a primary care clinic of cases with asthma (25 adults reporting first symptoms of asthma within 2 years of enrollment) and 45 concurrently enrolled sex and age (+/- 10 years) matched non-asthmatic controls with normal pulmonary function. C. pneumoniae-specific IgA, IgG and IgG4 antibodies, and circulating immune complexes (CIC) were measured by microimmunofluorescence testing. Results showed that frequencies of IgG titres > or = 16 (92%), IgG4 titres > or = 16 (20%) and CIC > or = 4 (60%) in asthma patients were not significantly different from those of controls. However, asthmatics had a significantly higher prevalence of C. pneumoniae-specific IgA titres > or = 10 (72% of cases vs 44% of controls, P < 0.05). After adjustment for the effects of age, sex and smoking, the odds ratio for an association of IgA and asthma was 3.7 (95% confidence interval 1.2-11.5). We conclude that recently symptomatic reversible airway obstruction in adults is associated with the presence of C. pneumoniae-specific IgA antibodies, a proposed indicator of chronic respiratory C. pneumoniae infection.     

The prevalence of chronic Chlamydia pneumoniae infection as detected by polymerase chain reaction in pharyngeal samples from patients with ischaemic heart disease

AIMS: Cross-sectional serological studies have suggested an association between ischaemic heart disease and infections from Chlamydia pneumoniae and Helicobacter pylori. We therefore sought to find out if patients with ischaemic heart disease had an increased prevalence of C. pneumoniae in the pharynx. As the course of the C. pneumoniae infection remains unclear, both acute and follow-up samples were taken and compared with antibody levels. METHODS AND RESULTS: We studied 282 patients with ischaemic heart disease. One hundred and two subjects without history or symptoms of ischaemic heart disease served as controls. Pharyngeal specimens for polymerase chain reaction detection of C. pneumoniae, and blood samples for C. pneumoniae and H. pylori antibody detection, were collected. In patients with positive polymerase chain reaction or C. pneumoniae IgA titres > or = 32, indicating current infection, convalescent samples were taken at least 6 weeks later. An immunofluorescent antigen detection test was used to confirm the presence of C. pneumoniae elementary bodies in specimens found to be polymerase chain reaction positive. The prevalence of positive polymerase chain reaction tests was 36% among patients and 22% among controls (P<0.05). Forty-seven percent of patients with positive polymerase chain reaction remained positive in the convalescent test. Elevated C. pneumoniae IgG titres > or = 512 were found in 39% of patients and 26% of the controls (P<0.05). IgA titres > or = 32 were found in 46% of the patients and 44% of the controls (ns). Antibody titres remained largely unchanged at convalescent testing. Two patients and none of the controls had IgM titres > 16. There was no link between positive H. pylori serology and positive C. pneumoniae polymerase chain reaction tests. CONCLUSIONS: The high prevalence and persistence of positive pharyngeal C. pneumoniae polymerase chain reaction and elevated antibody titres in patients with ischaemic heart disease indicate a chronic infection. The pharyngeal presence of C. pneumoniae might contribute to a low grade inflammatory activation or be a source for further spread of the bacteria to atherosclerotic vessels.     

Chlamydia pneumoniae infection is frequent but not associated with coronary arteriosclerosis in cardiac transplant recipients

We sought to explore the relation between Chlamydia pneumoniae, cytomegalovirus (CMV), and cardiac transplant-associated arteriosclerosis. Serologic evidence of past Chlamydia pneumoniae infection was investigated in 3 patient groups at the time of cardiac catheterization: cardiac transplant recipients (n=49), patients having coronary artery bypass grafting (CABG) (n=39), and a control group free of angiographic coronary artery disease (n=21). High Chlamydia pneumoniae immunoglobulin G titers (> or =1:160) were more frequently observed in cardiac transplant recipients (odds ratio[OR] 13.7; 95% confidence intervals [CI] 1.6 to 117.4, p <0.05) and CABG patients (OR 21.7; 95% CI 1.6 to 287.0, p <0.05) than in controls. However, high Chlamydia pneumoniae titers did not distinguish between cardiac transplant recipients with or without angiographic transplant-associated arteriosclerosis or CABG patients with or without bypass vein graft disease. Furthermore, there was no significant relation between elevated Chlamydia pneumoniae titers and the presence or progression of transplant-associated arteriosclerosis in the subgroup of patients who were also CMV positive. Yet, analysis of the same angiograms demonstrated an association between CMV infection and the recent progression of transplant-associated arteriosclerosis. Thus, patients with cardiac transplantation have evidence of past Chlamydia pneumoniae and CMV infection but Chlamydia pneumoniae does not appear to have an independent role or synergistic relation to CMV in the development of transplant-associated arteriosclerosis.     

Association of chronic infection of Chlamydia pneumoniae and coronary heart disease in the Japanese

The association of Chlamydia pneumoniae with atherosclerosis of coronary and carotid arteries and the aorta has been demonstrated by seroepidemiology and by detection of the organism in atheromata. We investigated the frequency of C. pneumoniae seropositivity in patients with acute myocardial infarction (AMI). C. pneumoniae-specific antibodies were measured by the microimmunofluorescence test in 160 AMI patients and 160 control subjects matched for age and gender. The odds ratios (ORs) were 2.2 (95% confidence interval (CI), 1.2 to 3.9) for immunoglobulin (Ig)G and 2.7 (95% CI, 1.7 to 4.3) for IgA. After adjustment for other cardiovascular risk factors of age, gender, hypertension, diabetes, cigarette smoking and serum cholesterol, the ORs were essentially unchanged. This study confirmed that the observations of an association between antibody against C. pneumoniae and coronary heart disease in Western nations is also present in Japan. Our results are comparable to the previous seroepidemiological studies reporting ORs of 2.0 or greater.     

Chlamydia pneumoniae infection and cardiac ischemic syndromes

The aim of this study was to assess the presence of Chlamydia pneumoniae antibodies in patients with angiographically verified atherosclerotic coronary artery disease. A total of 114 consecutive patients were investigated between April 1995 and June 1996. Patients were divided into two groups: 72 patients with acute myocardial infarction (AMI; 53 men, 19 women, mean age 62.27 +/- 10.1 years), and 42 patients with chronic ischemic heart disease (CAD; 37 men, 5 women, mean age 62.75 +/- 9.2 years). A control group of 50 normal subjects matched for age (mean 62 +/- 9 years), sex, social status and geographical area was used. Identification of Chlamydia pneumoniae was carried out with the microimmunofluorescence method, on two serum samples taken from patients on admission and after 15 days. The IgM, IgG and IgA anti-Chlamydia pneumoniae titers were assessed, values > or = 1:16, > or = 1:32 and > or = 1:8 being respectively considered positive. Acute (IgM > or = 16 or four fold rise of IgG titer) and chronic (IgG > or = 128 e IgA > or = 32 or only elevated IgA titer) infections were analyzed. IgM antibodies were not found in AMI, CAD and control groups. IgG positivity (IgG > or = 32) was found in 38% of the control group, in 58.3% of the AMI group (p < 0.05) and 42.8% of the CAD group (p < 0.01). IgA positivity > or = 8) was found in 22% of the control group, in 31.9% of the AMI group (NS) and in 33.3% of the CAD group (p < or = 0.05). Acute infection was observed in 5.5% of AMI patients and in 12% of CAD patients (NS), whereas no subject of the control group showed these values. Chronic infection was observed in 9.7% of AMI patients and in 16.6% of CAD patients (NS) whereas nobody of the control group showed these values. In conclusion, our results suggest that Chlamydia pneumoniae infection is present only in the AMI and CAD groups. It is possible to suppose that this infection may be linked to atherosclerosis through an endothelial damage or a systemic endogenous procoagulant and inflammatory activity.     

Dynamin undergoes a GTP-dependent conformational change causing vesiculation

BACKGROUND: We assessed the value of dobutamine stress echocardiography (DSE) in predicting cardiac events in patients with acute or chronic myocardial infarction (MI), and we studied the association between DSE and these events. METHODS AND RESULTS: Two hundred sixty-six patients (mean [+/-SD] age 65.3 +/- 11.4 years) with acute (n = 139) or chronic (n = 127) MI were recruited from March 1995 through April 1997. Both groups underwent DSE and were followed up for an average of 14.1 +/- 8.0 months. DSE was positive in 111 (79.9%) patients with acute MI and 65 (51.2%) patients with chronic MI (P <.0001 ). Positive DSE results were associated with a higher rate of all cardiac events (cardiac mortality rate, reinfarction, and unstable angina) than negative DSE results in both patients with acute MI and patients with chronic MI (44 in 111 patients vs 6 in 28 patients, P =.052, and 31 in 65 patients vs 10 in 62 patients, P <.0001, respectively). Among patients with acute MI, the positive and negative predictive values of DSE for all cardiac events were 39.6% (95% confidence interval [CI] 30.5% to 48. 7%) and 78.6% (95% CI 63.4% to 93.8%), respectively. In chronic MI, the positive and negative predictive values were 47.7% (95% CI 35.5% to 59.8%) and 83.9% (95% CI 74.7% to 93.0%), respectively. In both acute (P =.03) and chronic (P <.0001 ) MI, positive DSE findings were independent predictors of all cardiac events. CONCLUSIONS: DSE is useful for predicting cardiac events. A positive finding on DSE is an independent predictor of cardiac events after both acute and chronic MI, whereas a negative DSE result predicts a low likelihood of subsequent cardiac events.     

Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport

Since the 1950s the U.S. military has used intramuscular injections of benzathine penicillin G (BPG) to control outbreaks of respiratory disease. In an effort to find an alternative prophylaxis, a randomized field trial was conducted among 1,016 male U.S. Marine trainee volunteers at high risk for respiratory disease. Participants were evaluated for evidence of acute respiratory infection by serological tests on pretraining and posttraining sera (63 days apart). Oral azithromycin prophylaxis (500 mg/w) outperformed BPG, preventing infection from Streptococcus pyogenes (Efficacy [E] = 84%; 95% confidence interval [CI], 63%-93%), Streptococcus pneumoniae (E = 80%; 95% CI, 50%-92%), Mycoplasma pneumoniae (E = 64%; 95% CI, 25%-83%), and Chlamydia pneumoniae (E = 58%; 95% CI, 15%-79%) in comparison with results in a no-treatment group. Azithromycin group subjects reported few side effects and less respiratory symptoms than the BPG and no-treatment groups. According to serological tests, oral azithromycin is an effective alternative prophylaxis to BPG for military populations.     

Chlamydia pneumoniae and Helicobacter pylori infections in Sámi and Finnish reindeer herders

The Sámi people in northernmost Finland have lower mortality from cardiovascular diseases than the main population of Finland. Chronic infections caused by Chlamydia pneumoniae and Helicobacter pylori, both quite recently discovered gram-negative bacteria, have been associated with atherosclerosis. We studied the prevalence of these infections in Sámi and Finnish men by analysing the C. pneumoniae and H. pylori specific serum IgG and IgA antibodies using microimmune fluorescence and enzyme linked immunosorbent assay methods, respectively. The frequency of C. pneumoniae IgG antibodies and the age adjusted geometric mean titres differed significantly between these groups. The Finns were more often sero-positive than the Sámi (76% vs. 67%, respectively), the age adjusted geometric mean titre being 71.6 in the Finns and 38.3 in the Sámi; p = 0.001. No significant difference was found in the H. pylori IgG and IgA antibody prevalences, nor in the geometric mean titres between these groups. The difference in cardiovascular mortality between the Sámi and Finns may be partly explained by the lower incidence of chlamydial infections in the Sámi.     

Confirmed previous infection with Chlamydia pneumoniae (TWAR) and its presence in early coronary atherosclerosis

BACKGROUND: Chlamydia pneumoniae has been identified in coronary atheroma, but concomitant serum antibody titers have been inconsistently positive and unavailable before the detection of early or advanced atherosclerotic lesions. METHODS AND RESULTS: This retrospective investigation was performed on premortem serum specimens and autopsy tissue from 60 indigenous Alaska Natives at low risk for coronary heart disease, selected by the potential availability of their stored specimens. Serum specimens were drawn a mean of 8.8 years (range, 0.7 to 26.2 years) before death, which occurred at a mean age of 34.1 years (range, 15 to 57 years), primarily from noncardiovascular causes (97%). Coronary artery tissues were independently examined histologically and, for C pneumoniae organism and DNA, by immunocytochemistry (ICC) and polymerase chain reaction (PCR) with species-specific monoclonal antibody and primers. Microimmunofluorescence detected species-specific IgG, IgA, and IgM antibody in stored serum. C pneumoniae, frequently within macrophage foam cells, was identified in coronary fibrolipid atheroma (raised lesions, Stary types II through V) in 15 subjects (25%) and early flat lesions in 7 (11%) either by PCR (14, 23%) or ICC (20, 33%). The OR for C pneumoniae in raised atheroma after a level of IgG antibody > or =1:256 >8 years earlier was 6.1 (95% CI, 1.1 to 36.6) and for all coronary tissues after adjustment for multiple potential confounding variables, including tobacco exposure, was 9.4 (95% CI, 2.6 to 33.8). CONCLUSIONS: Serological evidence for C pneumoniae infection frequently precedes both the earliest and more advanced lesions of coronary atherosclerosis that harbor this intracellular pathogen, suggesting a chronic infection and developmental role in coronary heart disease.     

Plasma Lp(a), apolipoprotein(a) isoforms and acute myocardial infarction in men and women: a case-control study in the Jerusalem population

The relationship of Lp(a) with manifestations of coronary heart disease (CHD) has not been studied extensively in women. There is little information as to the association of the unique Lp(a) apolipoprotein moiety (apo(a)) with CHD in either men or women. We therefore assessed the association of the apo(a) polymorphism and of Lp(a) with first acute myocardial infarction (MI) in a population-based case-control study in Jewish residents of Jerusalem between the ages of 25 and 64. The patients consisted of 238 men and 47 women hospitalized for a first acute MI in the 4 hospitals of Jerusalem serving the population (70% response rate among all first MI patients). The control subjects comprised 318 men and 159 women sampled from the national population registry and who were free of CHD (75% response). Lp(a) and apo(a) were measured in plasma stored at -20 degrees C for 6-24 months. Among men, plasma Lp(a) concentrations were higher in cases than controls in both univariate and multivariate analyses. The elevated risk was limited to the upper fifth of the Lp(a) distribution (unadjusted odds ratio = 1.65, P < 0.01 vs. the lower four quintiles, multivariable odds ratio = 1.82, P < 0.01). Among women, Lp(a) was not elevated in acute MI patients. Apo(a) isoforms with a B, S1 or S2 band (associated with higher Lp(a) values and having lower molecular weights) were more prevalent in female MI cases than controls (unadjusted odds ratio = 2.5, P = 0.016). This association could not be attributed to the higher Lp(a) concentrations associated with these isoforms and was not seen in men. In conclusion, our study points to an association of the apo(a) isoforms with acute MI in women, not evident in this population sample in men. Previously described associations of elevated Lp(a) with acute MI were confirmed in men but not in women. While the role of chance and inadequate statistical power cannot be excluded, the suggestion of a sex difference in the strength of these associations deserves further investigation, as does the question of whether apo(a) phenotype contributes to risk independently of Lp(a) level.     

Detection of serum antibodies against Chlamydia pneumoniae by ELISA

Chlamydia pneumoniae causes pneumonia and other respiratory infections in children, adolescents and adults. We tried to evaluate the diagnostic value of detection of serum antibodies by ELISA for C. pneumoniae infections in Japanese children. Serum IgG, IgA and IgM antibodies to C. pneumoniae were determined by the microimmunofluorescence (MIF) test. Serum IgG and IgA antibodies were also determined by ELISA test kits. Results obtained by ELISA were compared with those obtained by MIF test. IgG antibody to C. pneumoniae was detected in 135 (39.5%) by ELISA and in 125 (36.5%) by MIF out of 342 sera from Japanese infants and children without respiratory infections (aged from 2 months old to 15 years old). IgA antibody to C. pneumoniae was detected in 129 (37.7%) by ELISA and in 117 (34.2%) by MIF out of 342 sera tested. Of 342 specimens 113 were IgG-positive by ELISA and MIF (sensitivity: 90.4%, specificity: 89.9%, r = 0.853). Of 342 sera 28 had IgG antibody titers of 1:256 and none had titers 1:512 or higher by MIF. Of 28 infants and children a total of nine were less than 4 years of age. On the other hand, of 342 specimens 99 were IgA-positive by ELISA and MIF (sensitivity: 84.6%, specificity: 86.7%, r = 0.769). Of 342 sera 16 had IgA antibody titers of 1:256 or higher by MIF. Of 16 infants and children, ten were less than 4 years of age. ELISA had excellent sensitivity and specificity relative to MIF test for detection of IgC and IgA antibodies to C. pneumoniae. It was suggested that C. pneumoniae infection in Japanese infants and children under 4 years of age was not infrequent.     

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.     

Prospective study of herpes simplex virus, cytomegalovirus, and the risk of future myocardial infarction and stroke

BACKGROUND: It has been hypothesized that infection with either herpes simplex virus (HSV) or cytomegalovirus (CMV) is associated with atherogenesis. However, prospective data relating evidence of prior exposure to these agents with risks of future myocardial infarction (MI) and stroke are sparse. METHODS AND RESULTS: In a prospective, nested case-control study of apparently healthy men, the baseline prevalence of antibodies directed against HSV or CMV was similar among 643 men who subsequently developed a first MI or thromboembolic stroke and among 643 age- and smoking-matched men who remained free of reported vascular disease over a 12-year follow-up period. Specifically, the relative risks for future MI and stroke were 0.94 (95% CI, 0.7 to 1.2) for HSV seropositivity and 0.72 (95% CI, 0.6 to 0.9) for CMV seropositivity, after adjustment for other cardiovascular risk factors. These findings were not materially altered in comparisons of early versus late events or in analyses stratified by smoking status. There was no evidence of association between HSV or CMV antibodies and plasma concentration of C-reactive protein, a marker of inflammation that predicts vascular risk in this cohort. CONCLUSIONS: Among apparently healthy middle-aged men, IgG antibodies directed against HSV or CMV do not appear to be a marker for increased atherothrombotic risk. The observed possible inverse relationship of CMV with MI and stroke was unexpected and may well be due to chance, because the direction of association is not compatible with the a priori hypothesis based on proposed biological mechanisms or previous cross-sectional and retrospective data.     

Young Malaysian children with lower respiratory tract infections show low incidence of chlamydial infection

OBJECTIVE: The incidence of Chlamydia pneumoniae and Chlamydia trachomatis infection was studied among infants and young children admitted to hospital for the management of lower respiratory tract infections, over a 12 month period. METHODOLOGY: Respiratory secretions were examined for chlamydiae by cell culture, enzyme-linked immunosorbent assay and polymerase chain reaction-enzyme immunoassay. Sera were tested by micro-immunofluorescence for chlamydial IgG, IgM and IgA. Other bacterial and viral pathogens were also looked for by standard cultural and serological methods. RESULTS: Of 87 patients aged 2 months-3 years, an aetiologic diagnosis was made in 41 (47.1%). C. pneumoniae and C. trachomatis were each detected in 1 (1.2%) of the patients. Among common bacterial pathogens, Haemophilus influenzae (13.8%) and Streptococcus pneumoniae (8.1%) were the most frequently identified. Respiratory viruses and elevated Mycoplasma pneumoniae antibodies were found in 10.3% and 9.1% of patients, respectively. CONCLUSION: Chlamydiae are infrequent causes of community-acquired acute lower respiratory tract infections in infants and very young children in Malaysia.     

Value of acute rest sestamibi perfusion imaging for evaluation of patients admitted to the emergency department with chest pain

OBJECTIVES: This study sought to determine the ability of early perfusion imaging using technetium-99m sestamibi to predict adverse cardiac outcomes in patients who present to the emergency department with possible cardiac ischemia and nondiagnostic electrocardiograms (ECGs). BACKGROUND: Evaluation of patients presenting to the emergency department with possible acute coronary syndromes and nondiagnostic ECGs is problematic. Accurate risk stratification is necessary to prevent serious adverse outcomes. Initial results suggest that early perfusion imaging using technetium-99m sestamibi enables reliable risk stratification. METHODS: Patients presenting to the emergency department with a low to moderate probability of acute coronary syndromes underwent rapid sestamibi injection with gated single-photon emission computed tomographic imaging. Studies showing perfusion defects with associated wall motion abnormalities were considered positive. RESULTS: A total of 532 consecutive patients underwent serial myocardial marker analysis and rest perfusion imaging. Of these patients, perfusion imaging was positive in 171 (32%). Positive perfusion imaging was the only multivariate predictor of myocardial infarction (MI) (p < 0.0001, odds ratio [OR] 33, 95% confidence interval [CI] 7.7 to 141) and was the most important independent predictor of MI or revascularization (p < 0.0001, OR 14, 95% CI 7.3 to 25), followed by diabetes (p < 0.01, OR 2.8, 95% CI 1.5 to 5.1), typical angina (p = 0.01, OR 2.1, 95% CI 1.2 to 3.7) and male gender (p = 0.03, OR 1.9, 95% CI 1.1 to 3.5). The sensitivity of positive perfusion imaging for MI was 93% (95% CI 77% to 98%), and for MI or revascularization it was 81% (95% CI 71% to 88%), with negative predictive values of 99% (95% CI 98% to 100%) and 95% (95% CI 92% to 97%), respectively. CONCLUSIONS: Positive rest perfusion imaging accurately identified patients at high risk for adverse cardiac outcomes, whereas negative perfusion imaging identified a low risk patient group. Early perfusion imaging allows for rapid and accurate risk stratification of emergency department patients with possible cardiac ischemia and nondiagnostic ECGs.     

Comparison of serological tests for the detection of antibodies against Chlamydia trachomatis and Chlamydia pneumoniae in rheumatological patients

In cases of reactive arthritis, a suspected Chlamydia trachomatis infection is often detected by serological methods. However, mostly tests with genus-specific antigens are used, neglecting the fact that antibodies against Chlamydia pneumoniae are highly prevalent in the adult population. Therefore we tested sera of 129 patients with various rheumatological disorders and of 18 healthy persons in parallel with a genus-specific test (IPAZYME) and with the species-specific microimmunofluorescence test for C. trachomatis and C. pneumoniae antibodies. The data showed that 55% of the 64 IPA-positive results were caused by antibodies (IgG) against Chlamydia pneumoniae, only 6% by anti-Chlamydia trachomatis IgG and 20% by both specificities. For IgA antibodies, the percentages were 44%, 12.5% and 12.5% respectively. In 12 IPA-positive cases, the MIF showed no reaction. 58% of all 147 sera tested with MIF had IgG antibodies against C. pneumoniae, 5% had anti-C. trachomatis IgG and 8% IgG against both species. The percentages for IgA were 29%, 2% and 2%, respectively. IgM positivity in MIF disappeared after absorption with rheumatoid factor absorbent. No significant differences were found between the various groups of patients. The data suggest that due to the high prevalence of anti-C. pneumoniae antibody, genus-species tests cannot be used as screening tests for the serological diagnosis of C. trachomatis infections.     

Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study

CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. OBJECTIVE: To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinics in Texas. PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION: Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. RESULTS: After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. CONCLUSIONS: Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.     

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 urethritis in heterosexual men. The role of fellatio and other sexual practices

BACKGROUND: Nonchlamydial nongonococcal urethritis (NGU) is a common sexually transmitted disease (STD) in heterosexual men. Prior studies have suggested that NGU may be acquired by insertive oral sex. GOAL: To assess the association of oral sex and other sexual practices with nonchlamydial NGU in heterosexual men in order to better understand this syndrome and to guide its prevention and treatment. Risk factors for urethral gonorrhea and chlamydial infection were explored to contrast with NGU. STUDY DESIGN: A retrospective case-control study was conducted among heterosexual men attending as STD clinic during 1993 and 1994. The study included 4,848 men who were sexually active within the prior 2 months and had urethral specimens obtained for Gram's stain, culture for Neisseria gonorrhoeae, and culture for Chlamydia trachomatis. RESULTS: Insertive oral sex was not shown to be an independent risk factor for NGU. Independent predictors of nonchlamydial NGU by multivariate analysis included African-American race (odds ratio [OR] 3.71, 95% confidence interval [95% CI] 3.06 to 4.50) and having > or = two sex partners in the prior 2 months (OR 1.45, 95% CI 1.20 to 1.75). History of using condoms "always" was negatively associated with NGU (OR 0.59, 95% CI 0.43 to 0.79), gonorrhea (OR 0.31, 95% CI 0.17 to 0.56), and chlamydial infection (OR 0.67, 95% CI 0.44 to 1.03). CONCLUSIONS: This study supports the sexually transmitted nature of nonchlamydial NGU but did not confirm an association with oral sex. However, the analysis was compromised by the rarity of insertive oral sex as patients' only sexual exposure. Consistent condom use protects against all causes of sexually acquired urethritis.