R. Grillo

Elevated Levels of C-Reactive Protein at Discharge in Patients With Unstable Angina Predict Recurrent Instability

BACKGROUND In a group of patients admitted for unstable angina, we investigated whether C-reactive protein (CRP) plasma levels remain elevated at discharge and whether persistent elevation is associated with recurrence of instability. METHODS AND RESULTS We measured plasma levels of CRP, serum amyloid A protein (SAA), fibrinogen, total cholesterol, and Helicobacter pylori and Chlamydia pneumoniae antibody titers in 53 patients admitted to our coronary care unit for Braunwald class IIIB unstable angina. Blood samples were taken on admission, at discharge, and after 3 months. Patients were followed for 1 year. At discharge, CRP was elevated (>3 mg/L) in 49% of patients; of these, 42% had elevated levels on admission and at 3 months. Only 15% of patients with discharge levels of CRP <3 mg/L but 69% of those with elevated CRP (P<0.001) were readmitted because of recurrence of instability or new myocardial infarction. New phases of instability occurred in 13% of patients in the lower tertile of CRP (</=2.5 mg/L), in 42% of those in the intermediate tertile (2.6 to 8.6 mg/L), and in 67% of those in the upper tertile (>/=8.7 mg/L, P<0.001). The prognostic value of SAA was similar to that of CRP; that of fibrinogen was not significant. Chlamydia pneumoniae but not Helicobacter pylori antibody titers significantly correlated with CRP plasma levels. CONCLUSIONS In unstable angina, CRP may remain elevated for at >/=3 months after the waning of symptoms and is associated with recurrent instability. Elevation of acute-phase reactants in unstable angina could represent a hallmark of subclinical persistent instability or of susceptibility to recurrent instability and, at least in some patients, could be related to chronic Chlamydia pneumoniae infection.

Association of Virulent Helicobacter pylori Strains With Ischemic Heart Disease

BACKGROUND Previous studies have reported an association between chronic Helicobacter pylori infection and ischemic heart disease. However, it is not clear whether this association is really due to the virulence of the bacterium or is merely the result of confounding factors (in particular, age and social class). METHODS AND RESULTS We assessed the prevalence of infection by Helicobacter pylori and by strains bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, in 88 patients with ischemic heart disease (age, 57+/-8 years; 74 men) and in 88 age- and sex-matched controls (age, 57+/-8 years; 74 men) with similar social background. Prevalence of Helicobacter infection was significantly higher in patients than in controls (62% versus 40%; P=.004), with an odds ratio of 2.8 (95% CI, 1.3 to 7.4; P<.001) adjusted for age, sex, main cardiovascular risk factors, and social class. Patients with ischemic heart disease also had a higher prevalence of CagA-positive strains (43% versus 17%; P=.0002), with an adjusted odds ratio of 3.8 (95% CI, 1.6 to 9.1; P<.001). Conversely, prevalence of CagA-negative strains was similar in patients and controls (19% versus 23%), with an adjusted odds ratio of 0.8 (95% CI, 0.4 to 1.4). CONCLUSIONS The association between Helicobacter pylori and ischemic heart disease seems to be due to a higher prevalence of more virulent Helicobacter strains in patients. These results support the hypothesis that Helicobacter pylori may influence atherogenesis through low-grade, persistent inflammatory stimulation.

Incremental prognostic value of serum levels of troponin T and C-reactive protein on admission in patients with unstable angina pectoris

Management of unstable angina is largely determined by symptoms, yet some symptomatic patients stabilize, whereas others develop myocardial infarction after waning of symptoms. Therefore, markers of short-term risk, available on admission, are needed. The value of 4 prognostic indicators available on admission (pain in the last 24 hours, electrocardiogram [ECG], troponin T, and C-reactive protein [CRP]), and of Holter monitoring available during the subsequent 24 hours was analyzed in 102 patients with Braunwald class IIIB unstable angina hospitalized in 4 centers. The patients were divided into 3 groups: group 1, 27 with pain during the last 24 hours and ischemic electrocardiographic changes; group 2, 45 with pain or electrocardiographic changes; group 3, 30 with neither pain nor electrocardiographic changes. Troponin T, CRP, ECG on admission, and Holter monitoring were analyzed blindly in the core laboratory. Fifteen patients developed myocardial infarction: 22% in group 1, 13% in group 2, and 10% in group 3. Twenty-eight patients underwent revascularization: 37% in group 1, 35% in group 2, and 7% in group 2 (p <0.01 between groups 1 or 2 vs group 3). Myocardial infarction was more frequent in patients with elevated troponin T (50% vs 9%, p=0.001) and elevated CRP (24% vs 4%, p= 0.01). Positive troponin T or CRP identified all myocardial infarctions in group 3. Only 1 of 46 patients with negative troponin T and CRP developed myocardial infarction. Among the indicators available on admission, multivariate analysis showed that troponin T (p=0.02) and CRP (p=0.04) were independently associated with myocardial infarction. Troponin T had the highest specificity (92%), and CRP the highest sensitivity (87%). Positive results on Holter monitoring were also associated with myocardial infarction (p=0.003), but when added to troponin T and CRP, increased specificity and positive predictive value by only 3%. Thus, in patients with class IIIB unstable angina, among data potentially available on admission, serum levels of troponin T and CRP have a significantly greater prognostic accuracy than symptoms and ECGs. Holter monitoring, available 24 hours later, adds no significant information.

C-reactive protein is increased in patients with degenerative aortic valvular stenosis

OBJECTIVES The goal of this study was to assess the presence of systemic inflammation in degenerative aortic valvular stenosis. BACKGROUND Local inflammatory changes, resembling those observed in atherosclerosis, have been recently reported in degenerative aortic valvular stenosis. It is presently unknown whether systemic signs of inflammation, similar to those observed in atherosclerosis, may be present in this disorder. METHODS C-reactive protein (CRP) was measured by enzyme immunoassay in 141 subjects: 62 with trileaflet degenerative valvular aortic stenosis and 79 volunteers with similar demographic and clinical characteristics. IgG antibodies against Helicobacter pylori (enzyme-linked immunosorbant assay) and Chlamydia pneumoniae (microimmunofluorescence assay) were also measured. RESULTS C-reactive protein levels (mg/dl, mean +/- SD) were 0.848 +/- 1.42 in patients and 0.394 +/- 0.50 in controls (p = 0.0001, Mann-Whitney U test). Seroprevalence of H. pylori was 68.7% in patients and 79.7% in controls (p = NS), whereas seroprevalence of C. pneumoniae infection was higher in patients than it was in controls (59.7% vs. 33%, p = 0.003; chi-square test). After adjustment for various covariates in multiple logistic regression, the odds ratio for degenerative aortic stenosis was 3.41 for C. pneumoniae infection (95% confidence intervals [CI]: 1.60 to 7.30) and 2.76 for CRP (95% CI: 1.08 to 7.05). There was no significant difference in patients or controls in CRP levels according to the serostatus for C. pneumoniae. CONCLUSIONS Systemic signs of inflammation, similar to those found in atherosclerosis, are present in patients with degenerative aortic valve stenosis. They do not seem to be linked to C. pneumoniae or H. pylori infection.

PCR detection of Toxoplasma gondii DNA in CSF for the differential diagnosis of AIDS-related focal brain lesions

To evaluate whether the detection of Toxoplasma gondii DNA in CSF could contribute to the differential diagnosis of AIDS-related focal brain lesions, CSF samples from 88 HIV-infected patients (56 with focal brain lesions and 32 without) were tested prospectively by a nested PCR for the B1 gene of T. gondii. The assay had a detection limit of 10 trophozoite equivalents. Six of 18 patients with toxoplasmic encephalitis, but none of the 70 patients with other disorders, were PCR-positive (33.3% sensitivity and 100% specificity). Considering only those patients with cerebral toxoplasmosis from whom CSF was collected before or during the first week of antitoxoplasmic therapy, sensitivity rose to 50%. This was higher than the sensitivity in patients whose CSF was collected after the first week of treatment (odds ratio (OR) of 7.0; 95% CI: 0.46-218.2). The administration of antitoxoplasmic prophylaxis did not affect the PCR results. Patients with a poor response to therapy had a higher probability of detectable T. gondii DNA in their CSF (OR of 5.0; 95% CI: 0.37-86.6). All patients with other central nervous system disorders were PCR-negative. Despite the moderate sensitivity, the high specificity and positive predictive value (100%) make this assay a useful tool in the differential diagnosis of AIDS-related focal brain lesions as part of a series of CSF and neuroradiological examinations.

Serodiagnosis and follow up of patients with pulmonary tuberculosis by enzyme-linked immunosorbent assay

A new ELISA assay based on antigen A60 from M. bovis BCG was used to quantitate specific anti-mycobacterial antibodies in 250 sera from 133 subjects: 90 tubercolosis cases and 43 controls. Controls were all negative, suggesting the specificty of this assay. In subjects with secondary pulmonary tuberculosis, a correlation was observed between the anti-mycobacterial antibody titer and culture positivity. In fact, positive ELISA assays were found in 88.8% of patients with positive cultures for M. tuberculosis and in 45% of culture-negative tuberculosis patients under therapy.According to our results the A60 ELISA assay is useful in monitoring the efficacy of antimycobacterial drugs. In pulmonary tuberculosis cases with positive cultures for M. tuberculosis higher levels of specific anti-mycobacterial lgGs were found after therapy.

Sporadic HEV hepatitis in Italy

Editor,—We read with great interest the paper of McCrudden et al concerning acute hepatitis E (HEV) in the UK ( (2000) Gut 46:732–3; [OpenUrl][1][PubMed][2][Web of Science][3] ). We agree wholeheartedly with the authors that this form of hepatitis is on the increase in industrialised countries. In Italy, the reported prevalence of anti-HEV IgG positivity ranges from 0.74% to 1.94%,1 although a recent study found a prevalence of 2.6% in one small town in central Italy.2 A value of 1.5% has been reported for the general adult population of the Republic of San Marino.3 We have recently observed two cases of acute hepatitis E with no evidence of any known risk factors. Case 1 . In September 1997, a 45 year old Italian woman (not pregnant) was … [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2Bmedical%2Bvirology%26rft.stitle%253DJ%2BMed%2BVirol%26rft.aulast%253DZanetti%26rft.auinit1%253DA.%2BR.%26rft.volume%253D42%26rft.issue%253D3%26rft.spage%253D318%26rft.epage%253D320%26rft.atitle%253DHepatitis%2Btype%2BE%2Bin%2BItaly%253A%2Ba%2Bseroepidemiological%2Bsurvey.%2BStudy%2BGroup%2Bof%2BHepatitis%2BE.%26rft_id%253Dinfo%253Apmid%252F8006645%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=8006645&link_type=MED&atom=%2Fgutjnl%2F48%2F4%2F580.1.atom [3]: /lookup/external-ref?access_num=A1994MY34600020&link_type=ISI

Bacteriophages induced from weakly beta-haemolytic human intestinal spirochaetes by mitomycin C

A comparative electron microscopic analysis of weakly beta‐haemolytic spirochaetes related to human and animal intestinal spirochaetosis was done in order to search for the presence of inducible bacteriophages associated with these spirochaetes. Bacteriophages were detected at the electron microscope after experimental induction with mitomycin C in 4 strains of weakly beta‐haemolytic spirochaetes related to human intestinal spirochaetosis, in Serpulina pilosicoli strain P43/6/78, the causative agent of swine intestinal spirochaetosis, in a spirochaetal strain related to avian intestinal spirochaetosis, and in Serpulina hyodysenteriae, strain P18A, the causative agent of swine dysentery, which was comparatively analysed as control. All phage‐particles observed in both human and animal intestinal spirochaetes were morphologically similar with an isometric head of 45 nm diameter and a tail 63–70 nm long and 7–12 nm width. The presence of morphologically similar phages in all the haemolytic intestinal spirochaetes of human and animal origin analysed in this study opens some important questions, about the genetic relationship of phages present in pathogenic intestinal spiro‐chaetes, their host range, and the possibility of natural gene transfer among pathogenic haemolytic intestinal spirochaetes of human and animal origin.

Helicobacter pylori infection in patients with Hashimoto's thyroiditis

Recent studies have suggested a role for some infectious agents, including Cytotoxin-associated gene A (CagA)-positive strains of H. pylori, in the pathogenesis of Hashimoto’s thyroiditis (HT), an autoimmune disorder of the thyroid gland defined by the detection of antibodies against thyroglobulin (anti-Tg) and thyroperoxidase (anti-TPO) [1–5]. To verify the possible role of H. pylori in HT we have designed a pilot study with two complementary aims: 1, to compare the prevalence of H. pylori infection (with Cag-positive and -negative strains) in patients with HT and in subject with no evidence of thyroid disease; and 2, to explore the possibility of a molecular mimicry between either anti-Tg or anti-TPO antibodies and any antigenic constituent of H. pylori. Sixteen patients (two men and 14 women, mean age 43.6 ± 11 years) with HT were evaluated for H. pylori infection by 13C urea breath test. Sera from all patients were tested for specific anti-CagA immunoglobulin G (IgG) using a commercial enzyme-linked immunosorbent assay (ELISA) (Radim, Pomezia, Italy). A control group of 20 blood donors (two men and 18 women, mean age 44.2 ± 12 years) without HT was also evaluated. Levels of anti-Tg and antiTPO antibodies in equal amounts of serum were evaluated through immunofluorescence either at enrollment or after absorption [6] with CagA-positive and CagA-negative H. pylori strains as well as with other Gram-negative bacteria, such as Campylobacter jejuni, Pseudomonas aeruginosa, Klebsiella spp. and Escherichia coli. Overall, 37.5% of the patients (six of 16; five women and one man; mean age 47 ± 12 years) with HT had H. pylori infection, compared to 35% of the controls (p > .05). Among infected subjects, 50% of the patients and 45% of the controls were infected by CagA-positive strains (p > .05). None of the absorbance tests with any of the bacteria induced significant changes in the levels of either anti-Tg or anti-TPO antibodies in the sera of patients with HT. The similar prevalence of H. pylori-infection (with and without CagA-positive strains) in patients and controls, as well as the lack of effect of the in vitro absorbance test on the relevant serum antibody titers, indicates that, in contrast to previous observations, an association between H. pylori infection and HT is unlikely. To further explore this relationship, we are currently conducting a clinical trial based on the evaluation of anti-Tg and anti-TPO antibody titers before and after eradication of H. pylori. Another area that may deserve further investigation is the possible cross-reactivity between anti-CagA antibodies and thyroid antigens other than TPO and Tg.

SEARCH FOR BACTERIOPHAGES SPONTANEOUSLY OCCURRING IN CULTURES OF HAEMOLYTIC INTESTINAL SPIROCHAETES OF HUMAN AND ANIMAL ORIGIN

An electron microscopic survey of the occurrence of bacteriophages which appear spontaneously in cultures of haemolytic intestinal spirochaetes of human and animal origin was made. Excluding one isometric tailed phage particle which was observed in the form of free particle in proximity to a spirochaete of the wβHIS strain HRM18, bacteriophages were never observed while examining cells of 21 weakly beta‐haemolytic human intestinal spirochaetes (wβHIS), swine Serpulina pilosicoli strain P43/6/78, and the avian strain 1380, although 50–100 cells of each spirochaetal strain were analysed. Isometric tailed bacteriophages were found associated with only three out of the 100 cells of strongly beta‐haemolytic swine Serpulina hyodysenteriae strain P18A comparatively analysed. According to our results and previous published reports, the occurrence of bacteriophages which appear spontaneously in cultures of intestinal spirochaetes is a rare event.