Biomedical subjects

H M Surcel

Publications and source records attributed to H M Surcel.

At least 19 recordsLinked to original sources

PubMed2001

Admission neopterin and interleukin 12 concentrations in identifying infections in adult cancer patients.

Differential diagnosis between infections and neoplastic fever is a common diagnostic problem. The utility of admission serum concentrations of neopterin and interleukin 12 (IL-12) was prospectively evaluated in this respect. The infection group (n=56) had a higher median neopterin value (12.8 nmol/l vs 4.0 nmol/l, P<0.001) and neopterin-to-IL-12 ratio (1.74 vs 0.11, P<0.001) than the non-infection group (n=36); the median IL-12 values were higher in the latter group (10.6 pg/ml vs 71.6 pg/ml, P=0.007). According to the area under the operating characteristics curves (AUC), especially neopterin (0.90), but also the neopterin-to-IL-12 ratio (0.79), was good at identifying bacteremia. However, in differentiating infections in general from neoplastic fever (n=10), the neopterin-to-IL-12 ratio was less powerful (0.64), though still better than neopterin (0.58) and clearly better than IL-12 (0.42). The present results show that the neopterin-to-IL-12 ratio, which reflects simultaneously both the ongoing infection and the tumour load, may have promising clinical implications for differential diagnosis between infections and neoplastic fever.

Adult↗

PubMed2001

C-reactive protein and erythrocyte sedimentation rate in differential diagnosis between infections and neoplastic fever in patients with solid tumours and lymphomas.

The goals of our work were to study prospectively the possibility of differentiating between infections and neoplastic fever in adult cancer patients on admission, by means of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) or of follow-up CRP values. Patients and methods were as follows: the final infection group consisted of 56 patients and the noninfection group of 10 patients with neoplastic fever; CRP was measured on days 0, 3 and 5 and ESR at entry. The main results showed that the median CRP did not differ between the groups (91 mg/l vs 102 mg/l) on entry, while the ESR level was higher in the neoplastic fever group (50 mm/H vs 89 mm/H, P = 0.023). On admission, both markers had low area under receiver operating characteristic curves for the demonstration of infection (CRP 0.42; ESR 0.27). The CRP level dropped significantly in the infection group within 5 days (P = 0.009). We conclude that neither of the markers was useful in differentiating between infections and neoplastic fever on admission, but that the follow-up CRP values were advantageous in this respect.

Bacterial Infections↗

PubMed2001

Balance between interleukin-10 and interleukin-12 in adult cancer patients with or without infections.

Reliable markers for identifying infections in cancer patients on admission are lacking. The utility of the balance between interleukin (IL)-10 and IL-12 was analysed in this respect. The infection group (n=56) had higher median serum levels of IL-10 (3.8 pg/ml; interquartile range (IQR) 1.7-11.4 pg/ml versus 1.8 pg/ml; IQR 0.6-4.6 pg/ml; P=0.005) and IL-10 to IL-12 ratio (0.4; IQR 0.06-4.23pg/ml versus 0.05; IQR 0.02-0.31pg/ml; P<0.001) than the non-infection group (n=36). IL-10 and the ratio had the following figures of sensitivity (79%; 95% confidence interval (CI) 66-88 versus 39%; 95% CI 27-53), specificity (40%; 95% CI 12-74 versus 90%; 95% CI 56-100) and positive predictive value (88%; 95% CI 76-96 versus 96%; 95% CI 78-100) for identifying infections (56 cases with infection and 10 with neoplastic fever), and the corresponding area under curve (AUC) values for IL-10 and the ratio in identifying infections in general were 0.58; 95% CI 0.39-0.78 versus 0.64; 95% CI 0.46-0.82 and in bacteraemia 0.71; 95% CI 0.50-0.92 versus 0.75; 95% CI 0.58-0.93, respectively. Thus, IL-10 can be used as a screening method for identifying infections in cancer patients and the ratio of IL-10 to IL-12 for confirming the diagnosis.

Area Under Curve↗

PubMed2001

Activation of cell-mediated immunity following immunization with pneumococcal conjugate or polysaccharide vaccine.

The immunogenicity of pneumococcal polysaccharide (PS) vaccines can be improved by conjugating PS to a polypeptide carrier that alters the immune response from T-cell independent to T-cell dependent. In order to study the influence of PS or protein antigens as inducers of cell-mediated responses, 30 adults were immunized with a 23-valent pneumococcal PS vaccine (PS-group) or an 11-valent, tetanus and diphtheria mixed carrier conjugate vaccine with (adjuvant group) or without aluminium adjuvant (nonadjuvant group). Cell-mediated responses were analyzed on days 0, 14 and 28 after vaccination by measuring lymphocyte proliferation and production of interferon (IFN)-gamma (Th1 marker) or interleukin (IL)-4 and IL-5 (Th2 markers) cytokines after in vitro stimulation with the PS and protein components of the vaccines. Tetanus and diphtheria proteins were the main inducers of lymphocyte proliferative and cytokine responses. Conjugate vaccines induced increased proliferative responses to the tetanus or diphtheria protein, but not to the PS components. In the PS-group, a lymphocyte proliferative response to protein antigens was not observed. The number of antigen-specific and nonspecific IFN-gamma-secreting cells detected by ELISPOT tended to increase in all three groups in response to protein or to PS antigen. No major differences were detected in the number of IL-4-secreting cells measured 14 and 28 days after vaccination. The conjugate vaccine with adjuvant was associated with Th2 type of activation indicated by an enhanced IL-5 secretion in response to the tetanus and diphtheria protein antigens.

Adjuvants, Immunologic↗

PubMed2001

Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: Eradication of Chlamydia pneumoniae infection and inhibition of elastolytic matrix metalloproteinases with doxycycline have been suggested to reduce the growth rates of small abdominal aortic aneurysms (AAA). We designed a study to investigate the efficacy of doxycycline in reducing the expansion of small AAAs. SUBJECTS AND METHODS: This was a prospective, double-blind, randomized, placebo-controlled study that was set in a university referral hospital. The study group consisted of 32 of 34 initially eligible patients who had an AAA diameter perpendicular to the aortic axis of 30 mm or more in size or a ratio of infrarenal to suprarenal aortic diameter of 1.2 or more and a diameter less than 55 mm. Patients were randomly assigned to receive either doxycycline (150 mg daily) or placebo during a 3-month period and underwent ultrasound surveillance during an 18-month period. Outcome measures included aneurysm expansion rates, the number of patients who had AAA rupture or repair, C pneumoniae antibody titers, and serum concentrations of C-reactive protein. RESULTS: The aneurysm expansion rate in the doxycycline group was significantly lower than that in the placebo group during the 6- to 12-month (P = .01) and the 12- to 18-month periods (P =.01). Five patients (41%) in the placebo group and 1 patient (7%) in the doxycycline group had an overall expansion of the aneurysm of 5 mm or more during the 18-month follow-up. Among the placebo group patients, a higher expansion rate was observed in those with enhanced C pneumoniae immunoglobulin G antibody titers (> 128) than in those with lower titers (P = .03). Doxycycline treatment had no clear effect on antibody titers. However, at 6-month follow-up, C-reactive protein levels in the doxycycline group were significantly lower than the baseline levels (P = .01). CONCLUSIONS: The results of this small pilot study suggest that doxycycline may favorably alter the outcome of patients with small AAA. However, because of the small size of this randomized study and of the potentially confounding effect of pretreatment risk factors, doxycycline-based treatment cannot be justified only on the ground of the current results. Because of the high prevalence of this disorder and its clinical, social, and economic relevance, a multicenter study should be performed to further investigate whether there is any place for medical treatment of small AAAs.

Aged↗

PubMed2000

C-reactive protein, procalcitonin and interleukin-8 in the primary diagnosis of infections in cancer patients.

The diagnostic utility of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-8 (IL-8) were studied in 66 cancer patients with suspected infection (39 with definite foci of infection, 17 with antibiotic responses without foci and 10 with neoplastic fever without infection) and 26 patients scheduled for chemotherapy. The infection group (n=56) had higher median CRP (91 versus 19 mg/l, P<0. 001), PCT (0.28 versus 0.12 ng/ml, P<0.001) and IL-8 values (27.7 versus 16.9 pg/ml, P=0.032) than the non-infection group (n=36). In patients with suspected infection, only PCT was a good marker to discriminate bacteraemia with an area under the receiver operating characteristics curve of 0.92 (95% confidence interval (CI), 0.77-1. 0), but even PCT was less well able to differentiate between non-bacteraemic infections and neoplastic fever (0.56; 95% CI, 0. 35-0.77). In conclusion, PCT was a good indicator for bacteraemia, but none of the three markers were reliable indicators for minor infections in non-neutropenic cancer patients.

Bacteremia↗

PubMed2000

The resistance of human monocyte-derived macrophages to Chlamydia pneumoniae infection is enhanced by interferon-gamma.

Chlamydia pneumoniae is an intracellular bacterium which commonly causes respiratory infections. Chronic infections have been associated with atherosclerosis and the organism has been detected in macrophages in the disease lesions. Growth of chlamydiae in different epithelial cell lines is restricted by interferon-gamma (IFN-gamma), a monocyte activator produced by T cells. We have studied the influence of IFN-gamma on the growth and infectivity of C. pneumoniae in HL-cells and human monocyte-derived macrophages. Low concentrations of the cytokine significantly restricted the growth and productivity of C. pneumoniae in epithelial cells in vitro. In macrophages, however, no effect on the growth of the bacteria in infected cells was found, but high doses clearly restricted the production of infectious progeny. The results suggest that IFN-gamma participates in the resistance to C. pneumoniae. The bacterium is, however, still capable of infecting macrophages that are important in the pathogenesis of atherosclerosis and it may thus participate in the inflammatory process associated with the disease.

Cell Line↗

PubMed2000

Chlamydia trachomatis reactive T lymphocytes from upper genital tract tissue specimens.

Chlamydia trachomatis infection is associated with pelvic inflammatory disease (PID) and tubal factor infertility (TFI). We investigated the role of C. trachomatis as a target antigen of endometrial and salpingeal tissue lymphocytes derived from PID and TFI patients. Antigen specificity of the tissue originated T lymphocyte lines (TLL) was tested against C. trachomatis elementary bodies and chlamydial heat shock protein 60 (CHSP60). C. trachomatis antigen stimulated proliferation in two out of eight endometrial TLL derived from PID patients and three out of four TLL derived from TFI patients. All (n = 4) TLL derived from the salpingeal specimens responded to CHSP60 compared with only one out of 12 TLL derived from the endometrial specimens. In-vivo expression of interferon-gamma (IFN-gamma) mRNA revealed that it was present in nine of 13 specimens obtained from PID patients. The dominant activity of type-1 T lymphocytes was confirmed by the in-vitro production of IFN-gamma (median 1007 pg/ml) from all (n = 5) C. trachomatis specific TLL while IL-5 secretion was lower (median 779 pg/ml). In conclusion, C. trachomatis reactive TLL were established from in-vivo activated lymphocytes from the upper genital tract tissue of PID and TFI patients. The reactivity of the salpingeal TLL to CHSP60 provided further evidence that immunoreactivity to CHSP60 is a predominant response in patients with tubal damage.

Adolescent↗

PubMed2000

Cell-mediated immune response during primary Chlamydia pneumoniae infection.

The development of Chlamydia pneumoniae-specific cell-mediated immunity was studied during a primary C. pneumoniae infection. The immune response was detected as positive lymphocyte proliferation and secretion of interferon gamma. C. pneumoniae-induced activation of both CD4(+) and CD8(+) T cells was detected in the early phase of infection, but activation of only CD4(+) T cells was detected in the later stage.

Adolescent↗

PubMed2000

Detection of Chlamydia pneumoniae-reactive T lymphocytes in human atherosclerotic plaques of carotid artery.

Linkage between Chlamydia pneumoniae infection and atherosclerosis has been confirmed in several studies, but the precise role of this organism in the disease process is not known. We investigated the relation and reactivity of T lymphocytes of human carotid plaques to C pneumoniae antigens. Tissue specimens were obtained from 17 patients who underwent carotid endarterectomy. Immunohistological staining and/or in situ hybridization revealed the presence of C pneumoniae in 11 (64%) of the 17 of the cases. Inflammatory infiltration seen in the vessel walls consisted primarily of CD45RO+ T-memory lymphocytes (median 80%, range 50% to 90%), whereas CD20+ B cells and monocytes were in minor proportion. In vivo activated T lymphocytes were propagated from the specimens with interleukin-2, and the antigen specificity of the established T-cell lines (TLLs) was analyzed against C pneumoniae elementary body antigen. TLLs were established from all 17 carotid tissues but none from the control specimens of ascending aorta. C pneumoniae was recognized as a specific T-cell-stimulating antigen in 7 (41%) of 17 cases. Further analyses of the C pneumoniae-reactive TLLs showed that chlamydial 60-kDa heat-shock protein induced specific proliferation in 5 (71%) of 7 cases and revealed 2 haplotype (DRB1*1502 and DQB1*06) binding motifs in human 60-kDa heat-shock protein. C pneumoniae was identified as a specific microbial antigen recognized by 41% of TLLs propagated from in vivo activated plaque T cells. Our results suggests that cell-mediated immunity to C pneumoniae plays a role in the atherosclerotic process and that this response may involve autoimmunity.

Aged↗

PubMed1999

Chlamydia pneumoniae reactive T lymphocytes in the walls of abdominal aortic aneurysms.

BACKGROUND: The presence of Chlamydia pneumoniae in the walls of abdominal aortic aneurysms (AAAs) has been demonstrated recently, but its role in the cause and/or maintenance of aortic wall inflammation is not known. In the present study, we have investigated the possible relationship between C. pneumoniae and the antigen specificity of T lymphocytes mediating inflammation in AAA tissue. MATERIALS AND METHODS: Tissue specimens were obtained from 22 consecutive AAA patients undergoing elective surgery (mean age 67 +/- 1 year). Immunohistochemical analysis of the formalin-fixed tissue was performed using the streptavidin-biotin-peroxidase method. In vivo activated T lymphocytes were propagated from the specimens with interleukin (IL) 2, and antigen specificity of the established T-cell lines was analysed in the presence of autologous antigen-presenting cells using radioactive thymidine labelling. RESULTS: Immunohistological staining of AAA tissue showed the presence of C. pneumoniae antigen in 55% (6/11) of the samples studied. The inflammatory cell infiltrate of the AAA tissue contained 60-90% T (CD45RO) and 0-10% B (CD20) cells. When the tissue specimens were cultured without antigen in the presence of IL-2, lymphocyte propagation was achieved in 17 out of the 22 samples. Chlamydia pneumoniae antigen was found to induce a positive proliferative response in 8 of the 17 lines. CONCLUSIONS: The presence of C. pneumoniae specific T lymphocytes among in vivo activated cells from the AAA tissue specimens suggests that C. pneumoniae participates in the maintenance of the inflammatory response in the tissue and may thus be involved in the progression of the disease.

Aged↗

PubMed1999

Chlamydia pneumoniae infection in human monocytes.

Chlamydia pneumoniae infection has been associated with cardiovascular diseases in seroepidemiological studies and by demonstration of the pathogen in atherosclerotic lesions. It has the capacity to infect several cell types, including monocyte-derived macrophages, which play an essential role in the development of atherosclerosis. However, the persistence of C. pneumoniae in mononuclear cells is poorly understood. To study the morphology and biological characteristics of the infection, human peripheral blood monocytes were infected with C. pneumoniae. Freshly isolated monocytes resisted the development of infectious progeny, and confocal and transmission electron microscopy showed that the morphology of the inclusions and chlamydial particles was abnormal. Addition of tryptophan or antibodies against gamma interferon did not diminish the inhibition of C. pneumoniae, suggesting that other factors are involved in the chlamydiostatic activity of the monocytes. Chlamydial mRNA was expressed at least 3 days after infection, however, and a capability for infected monocytes to induce a positive lymphocyte proliferative response was detected for up to 7 days, indicating that C. pneumoniae remains metabolically active in the monocytes in vitro. These results are in accordance with the hypothesis that C. pneumoniae may participate in the maintenance of local immunological response and inflammation via infected monocytes and thus enhance atherosclerosis.

Cells, Cultured↗

PubMed1999

Detection of Chlamydia pneumoniae by colorimetric in situ hybridization.

Chlamydia pneumoniae causes chronic infections, which have been associated with cardiovascular diseases. The antigenic structures of the organism have been detected in atherosclerotic lesions by immunohistochemistry. We wanted to further evaluate the presence and localization of C. pneumoniae in different tissues by in situ hybridization. We established a new colorimetric in situ hybridization method using a digoxigenin-labelled probe and studied the localization of C. pneumoniae in formalin-fixed, paraffin-embedded lungs of infected mice. We also used the method to study its presence in 12 abdominal aortic aneurysms. In C. pneumoniae-infected mice, the organism was first detected in bronchial epithelial cells, and later in pneumocytes and endothelial cells. C. pneumoniae was also present in five of eight abdominal aortic aneurysms previously shown to be positive by immunohistochemistry. The findings are in accordance with the invasive nature of C. pneumoniae, and confirm its presence in abdominal aortic aneurysms.

Animals↗

PubMed1998

Chlamydia pneumoniae-specific cell-mediated and humoral immunity in healthy people.

In this work, cell-mediated immunity to Chlamydia pneumoniae was studied in 157 healthy individuals using lymphoproliferative assay and serum antibodies were analysed by microimmunofluorescence techniques. The C. pneumoniae-specific IgG antibodies were elevated more frequently and the geometric mean titres for IgG (67.5 versus 44.1; P = 0.05) and IgA (14.9 versus 11.3; P = 0.025) antibodies were significantly higher in males than in females. However, no gender-dependent differences were observed in cellular reactivity to C. pneumoniae, since the median cellular responses were similar (stimulation indices 7.5) in men and women. Although the cell-mediated and humoral responses to C. pneumoniae did not correlate clearly, elevated IgG antibodies were associated with slightly higher lymphocyte proliferation in comparison to all subjects (15.5 versus 7.5) and significantly stronger in comparison to those with persistently elevated IgA (> 80) antibodies (15.5 versus 3.5; P = 0.023). Further studies are needed to evaluate a possible role of reduced cellular reactivity in the cause of chronic C. pneumoniae infection.

Adult↗

PubMed1998

IgG subclass-specific antibodies in Chlamydia pneumoniae infections.

IgG subclass-specific antibodies to Chlamydia pneumoniae and chlamydial lipopolysaccharide (LPS) were analysed in paired sera obtained from 15 patients with primary C. pneumoniae pneumonia and from 16 pneumonia patients with reinfection, as well as in single sera of 40 subjects with possible chronic C. pneumoniae infection and 40 healthy controls. The microimmunofluorescence (MIF) method was used to measure total IgG, IgM and IgG subclass-specific antibodies to C. pneumoniae protein antigens and enzyme immunoassay (EIA) to measure antibodies against the LPS antigen. By MIF, IgG1 antibodies to C. pneumoniae were demonstrated in all individuals of the 3 patient groups and also in all healthy controls. IgG2 subclass antibodies were not found by MIF. IgG3 antibodies were detected in 40% of patients with primary infection, in 31% of patients with reinfection, in 25% of those with chronic infection and in 8% of the controls. IgG4 antibodies were associated with acute C. pneumoniae infection and were found in 13% of primary infections and 31% of reinfections. The subclass pattern of LPS antibodies resembled that of protein antibodies measured by MIF: IgG1 was the most common subclass among the antibodies to LPS.

Acute Disease↗

PubMed1998

Immune responses to Chlamydia pneumoniae in twins in relation to gender and smoking.

This study investigated whether gender or smoking has an impact on immune responses to Chlamydia pneumoniae in generally healthy adults. A total of 129 twins (46 twin pairs and 37 single twins) from the Finnish Twin Cohort who had previously reported the highest discordance for smoking with their co-twins participated. C. pneumoniae-specific serum IgA and IgG antibody levels were measured by the micro-immunofluorescence test (micro-IF) at admission and 3 months later if the IgA level in the first sample was elevated. Cell-mediated immune (CMI) responses to C. pneumoniae and control antigens from heparinised blood samples were assessed by the lymphoproliferation (LP) assay. When all the subjects were pooled and analysed by gender and smoking status, marked differences in the humoral immune response between the genders were observed, irrespective of smoking status. When twin pairs solely were analysed, significantly elevated IgA antibody levels suggestive of persistent infection were found among the currently or formerly smoking men compared to their non-smoking co-twins. The CMI response showed a reciprocal trend with respect to humoral immunity. In conclusion, specific antibody levels were found to be higher in men than in women irrespective of smoking status, although smoking may further enhance the humoral response and depress the CMI response in men.

Adult↗

PubMed1997

Detection of Chlamydia pneumoniae in human nonrheumatic stenotic aortic valves.

OBJECTIVES: We sought to study the possible presence of Chlamydia pneumoniae in aortic valve stenosis (AVS). BACKGROUND: Inflammation and immune mechanisms are considered important for the pathogenesis of nonrheumatic AVS. All chlamydial species are able to cause heart infections, and seroepidemiologic studies have indicated an association between chronic C. pneumoniae infection and coronary artery disease. Furthermore, the organism has been demonstrated in atherosclerotic lesions. METHODS: Aortic valve specimens with varying degrees of macroscopic disease were obtained from 35 subjects--17 consecutive patients undergoing aortic valve replacement for treatment of nonrheumatic AVS and 18 age-matched subjects at autopsy. The possible presence of C. pneumoniae in aortic valves was studied by immunohistochemical analysis, polymerase chain reaction or transmission electron microscopy, or a combination of these. RESULTS: Positive immunohistochemical staining with C. pneumoniae specific antibody was found in 9 (53%) of 17 patients with advanced aortic valve disease requiring surgical treatment (group A), 8 (80%) of 10 cadavers with clearly macroscopic aortic valve pathology (group B) and 1 (12%) of 8 grossly normal cadaver control subjects (group C). Statistical significance with regard to the presence of C. pneumoniae was found when combined diseased subjects (groups A and B: total 17 of 27 subjects) were compared with group C (p = 0.018). However, when group A was compared with group C, there was only marginal statistical significance (p = 0.088). Finally, there was a strong statistical significance (p = 0.015) when groups B and C were compared. Chlamydia pneumoniae DNA was also found in three stenotic valves, and in two of the three tested valve specimens chlamydia-like particles were seen by electron microscopy. CONCLUSIONS: Chlamydia pneumoniae is frequently present in nonrheumatic AVS. Similarly, the high number of C. pneumoniae infections detected in the early lesions of "degenerative" AVS suggest that this pathogen may play an etiologic role in the development of this disease. The validity of this relation requires additional study.

Aged↗

PubMed1997

Demonstration of Chlamydia pneumoniae in the walls of abdominal aortic aneurysms.

BACKGROUND: Seroepidemiologic studies have indicated an association between chronic Chlamydia pneumoniae infection and coronary heart disease. The organism, which is a common respiratory pathogen, has been demonstrated in atherosclerotic lesions of the aorta and coronary arteries. Abdominal aortic aneurysms are frequently associated with atherosclerosis, and inflammation may actually be an important factor in aneurysmal dilatation. Hence it could be assumed that C. pneumoniae may play a role in maintaining an inflammation and triggering the development of aortic aneurysms. METHODS AND RESULTS: Specimens from abdominal aortic aneurysm were examined for the presence of C. pneumoniae by immunohistochemical analysis, the polymerase chain reaction amplifying omp 1 gene, transmission electron microscopy, and culture methods with histologically atherosclerosis-negative human aortic tissues used as a control group. Chlamydial lipopolysaccharide and C. pneumoniae specific antigens were found by immunohistochemistry in 12 and 8 of 12 aneurysm specimens, respectively, and C. pneumoniae DNA could be demonstrated in 6 of 6 aneurysm specimens studied. Furthermore electron microscopy revealed the presence of Chlamydia-like elementary bodies in three of four aneurysm specimens tested. None of the control samples gave positive reaction in the polymerase chain reaction, and C. pneumoniae antigens were not detected in any of them. CONCLUSIONS: C. pneumoniae is frequently found in the vessel wall of abdominal aortic aneurysm. The potential etiopathogenetic role of C. pneumoniae in the development of these aneurysms remains to be studied.

Aged↗