Biomedical subjects

Hubert Lepidi

Publications and source records attributed to Hubert Lepidi.

At least 19 recordsLinked to original sources

PubMed2007

Vanin-1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection.

Q fever is caused by Coxiella burnetii, a bacterium that survives in MPhi. Vanin-1 is a membrane-anchored pantetheinase that controls tissue inflammation. Consequently, Vanin-1-deficient mice represent a unique mouse model in which stress-induced inflammation is limited by the reaction of resident tissue cells. To investigate the contribution of host tissues in the control of a bacterial infection, we infected Vanin-1-deficient mice with C. burnetii. Mortality and morbidity of mice were not affected. The lack of Vanin-1 had no effect on C. burnetii clearance but decreased the formation of granulomas in spleen and liver. Granuloma formation depends upon MPhi recruitment and activation in these tissues. Whereas the former was slightly impaired in mutant mice, the lack of Vanin-1 significantly affected the activation pattern of BM-derived MPhi stimulated by C. burnetii. While their microbicidal activity against C. burnetii was moderately impaired, they exhibited decreased inducible nitric oxide synthase (iNOS) and MCP-1 gene expression, and increased IL-10 and arginase expression. In liver from mutant mice, increased arginase expression and decreased expression of MCP-1 and iNOS were reminiscent of MPhi data. These results suggest a role of Vanin-1 in granuloma formation in response to C. burnetii by skewing MPhi activation toward an M2 program.

Amidohydrolases↗

PubMed2006

Pneumonia in mice inoculated experimentally with Acanthamoeba polyphaga mimivirus.

In an attempt to elucidate whether Acanthamoeba polyphaga mimivirus (APM) was pathogenic (i.e., induces histological evidence of inflammation or tissue destruction or both) in mammalian host, we inoculated adult BALB/c (n=6) and C57BL/6 (n=6) mice with APM via intracardiac route. C57BL/6 mice developed histopathological features of pneumonia by post-inoculation day (PID) 3 and BALB/c mice, by PID7. The histopathological features of pneumonia, characterized by the presence of thickened alveolar walls with cellular infiltrates comprising mononuclear leukocytes, macrophages and lymphocytes, diffuse alveolar damages with the formation of hyaline membrane and erythrocytes in the alveolar lumen, were most marked by PID 7. We conclude that APM is pathogenic in mice in experimental conditions.

Acanthamoeba↗

PubMed2006

Experimental model to evaluate the human body louse as a vector of plague.

Yersinia pestis has been found in human body lice during plague outbreaks. To evaluate the role that the human body louse plays as a vector of plague, we allowed lice to feed on rabbits made bacteremic by intravenous inoculation of 10(9) colony-forming units of 3 strains of Y. pestis. High mortality rates were observed in all lice 2 and 3 days after infection. The lice remained infected with the strains for their life span and excreted viable organisms in their feces from day 1, although they were unable to lay eggs. The lice infected with 2 virulent strains of Y. pestis transmitted the organisms during feeding to uninfected rabbits, which became septicemic and died of plague (with 1 exception) 1 day later. Infections were transmitted to naive lice that were fed on these rabbits, showing that lice can be vectors of Y. pestis in an experimental model.

Animals↗

PubMed2006

Bartonella quintana coinfection with Mycobacterium avium complex and CMV in an AIDS patient: case presentation.

BACKGROUND: As a greater number of HIV-infected patients survive despite profound immunodepression due to medical progress, we face complex infection with multiple agents in AIDS-patients. CASE PRESENTATION: We report the case of an AIDS patient with a primary clinical presentation suggestive of bacillary angiomatosis. We also found in cutaneous lesions Mycobacterium avium complex and cytomegalovirus. CONCLUSION: This clinical case illustrates the possibility of multiple coinfections in AIDS patients and the need to be exhaustive in evaluating infectious diseases in severely immunocompromised patients.

AIDS-Related Opportunistic Infections↗

PubMed2006

Autoimmunohistochemistry: a new method for the histologic diagnosis of infective endocarditis.

BACKGROUND: Although the pathologic examination of cardiac valves remains the reference standard for the diagnosis of infective endocarditis, the detection of microorganisms often poses a challenge for pathologists. This can be done by use of nonspecific histochemical stains or by immunohistochemical analysis, but specific antibodies are often not available. We describe a novel method for the detection of microorganisms in valve specimens from patients with infective endocarditis. METHODS: Detection of microorganisms was performed in valve specimens from patients with endocarditis caused by gram-positive cocci (25 specimens), blood culture-negative endocarditis (15 specimens: 6 cases caused by Coxiella burnetii, 5 caused by Tropheryma whipplei, and 4 caused by Bartonella species), or noninfective degenerative damage (30 specimens, used as negative controls), using the patients' own serum. This technique, called "autoimmunohistochemistry," is an immunohistochemical peroxidase-based method that we compared with results of culture and polymerase chain reaction (PCR) assay. RESULTS: Bacteria were detected by autoimmunohistochemistry in 20 (80%) specimens from patients with endocarditis caused by gram-positive cocci and in 15 (100%) specimens from patients with blood culture-negative endocarditis but in no control specimens. The rate of detection of bacteria by autoimmunohistochemistry was significantly higher than that by culture but was similar to that by PCR. CONCLUSIONS: Autoimmunohistochemistry may be useful for the detection of microorganisms in samples of valves from patients with infective endocarditis. This new diagnostic tool may be particularly useful in cases of blood culture-negative endocarditis.

Actinomycetales↗

PubMed2006

Endocarditis after acute Q fever in patients with previously undiagnosed valvulopathies.

We describe 3 cases of endocarditis after acute Q fever in 3 patients with clinically silent, undiagnosed valvulopathies, including mitral valve prolapse, minimal valvular leak, and biscuspid aortic valve. We conclude that, to prevent endocarditis, these minor valvulopathies must be actively searched for with echocardiography after diagnosis of acute Q fever.

Aortic Valve↗

PubMed2006

Quantitative histological examination of bioprosthetic heart valves.

BACKGROUND: The histological features that characterize infective endocarditis in bioprosthetic valves are not accurately defined. Moreover, bioprosthetic valves may have a noninfective, degenerative evolution associated with calcifications, vegetation-like lesions, and inflammatory infiltrates. Such histological findings may be misdiagnosed as infective endocarditis. METHODS: Pathologic analysis of inflamed bioprosthetic valve tissues was conducted retrospectively for 21 patients who underwent surgical removal of a bioprosthetic valve because of suspected infective endocarditis and for 67 patients who underwent surgical removal of a bioprosthetic valve because of noninfective dysfunction. To better define the histological criteria for infective endocarditis, we used quantitative image analysis to compare these 2 groups of patients with respect to vegetations, calcifications, and patterns of inflammation. RESULTS: Histologically, infective endocarditis in patients with bioprostheses was characterized by demonstration of microorganisms, vegetations, and neutrophil-rich, inflammatory infiltrates. Valve tissue specimens from patients whose bioprosthetic valves were removed because of noninfective complications showed, in 30% of cases, inflammatory infiltrates mainly composed of macrophages and lymphocytes. Inflammatory adherent thrombi that can occur to the surface of noninfective degenerative bioprostheses are differentiated because their vegetations have macrophage-rich content. A neutrophil surface area with a cutoff value of > or =1.5% of the total valve tissue surface area is highly specific (94%) for infective endocarditis. CONCLUSIONS: When no microorganisms are detected and vegetations are not found in bioprosthetic valve tissues during the histological examination, a neutrophil-rich inflammation might better define the term "active endocarditis" in the Duke criteria and would allow differentiation between infective endocarditis and inflammatory, noninfective valve processes in patients with bioprosthetic valves.

Adult↗

PubMed2006

Murine model of infection by Tropheryma whipplei.

We developed an animal model reproducing several aspects of Whipple's disease. Immunocompetent mice were persistently infected with Tropheryma whipplei, its etiological agent, and developed liver granulomas. SCID mice were infected similarly but did not develop tissue lesions. The delayed clearance of T. whipplei suggests a protective role for innate immunity.

Actinomycetales↗

PubMed2006

Role for the CD28 molecule in the control of Coxiella burnetii infection.

Q fever is an infectious disease caused by Coxiella burnetii, an obligate intracellular bacterium that replicates in macrophages. As cell-mediated immune response to microbial pathogens requires signals mediated by T-cell receptors and costimulatory molecules such as CD28, we wondered if CD28 is involved in protection against C. burnetii infection. CD28-deficient (CD28-/-) mice were inoculated with C. burnetii by intraperitoneal and intravenous routes. With both wild-type and CD28-/- mice, C. burnetii organisms were detected exclusively in spleen and liver. The antibody response against C. burnetii was impaired in CD28-/- animals, but, surprisingly, the lack of CD28 decreased C. burnetii burden in the infected tissues, whatever the manner of inoculation of bacteria. The CD28 deficiency had no effect on either granuloma formation, which reflects cell-mediated immunity against C. burnetii, or the production of gamma interferon and tumor necrosis factor, two cytokines known to be involved in granuloma formation. On the other hand, the production of interleukin-10 (IL-10) by peritoneal macrophages was highly impaired in CD28-/- mice. The results suggest that CD28 initiates a signal that favors C. burnetii replication through the modulation of the IL-10 pathway.

Animals↗

PubMed2006

"Candidatus Rickettsia kellyi," India.

We report the first laboratory-confirmed human infection due to a new rickettsial genotype in India, "Candidatus Rickettsia kellyi," in a 1-year-old boy with fever and maculopapular rash. The diagnosis was made by serologic testing, polymerase chain reaction detection, and immunohistochemical testing of the organism from a skin biopsy specimen.

Anti-Bacterial Agents↗

PubMed2006

Histologic features and immunodetection of African tick-bite fever eschar.

African tick-bite fever (ATBF) is a rickettsiosis caused by Rickettsia africae. We describe histologic features and immunodetection of R. africae in cutaneous inoculation eschars from 8 patients with ATBF, which was diagnosed by culture or association of positive PCR detection and positive serologic results. We used quantitative image analysis to compare the pattern of inflammation of these eschars with those from Mediterranean spotted fever. We evaluated the diagnostic value of immunohistochemical techniques by using a monoclonal antibody to R. africae. ATBF eschars were histologically characterized by inflammation of vessels composed mainly of significantly more polymorphonuclear leukocytes than are found in cases of Mediterranean spotted fever (p < 0.05). Small amounts R. africae antigens were demonstrated by immunohistochemical examination in 6 of 8 patients with ATBF. Neutrophils in ATBF are a notable component of the host reaction, perhaps because ATBF is a milder disease than the other rickettsioses. Immunohistochemical detection of rickettsial antigens may be useful in diagnosing ATBF.

Adult↗

PubMed2006

Lymph node biopsy specimens and diagnosis of cat-scratch disease.

We report microbiologic analysis of 786 lymph node biopsy specimens from patients with suspected cat-scratch disease (CSD). The specimens were examined by standard, cell culture, and molecular methods. Infectious agents were found in samples from 391 (49.7%) of 786 patients. The most commonly identified infectious agent was Bartonella henselae (245 patients, 31.2%), the agent of CSD. Mycobacteriosis was diagnosed in 54 patients (6.9%) by culture and retrospectively confirmed by using a specific real-time PCR assay. Neoplasm was diagnosed in 181 specimens suitable for histologic analysis (26.0%) from 47 patients. Moreover, 13 patients with confirmed Bartonella infections had concurrent mycobacteriosis (10 cases) or neoplasm (3 cases). A diagnosis of CSD does not eliminate a diagnosis of mycobacteriosis or neoplasm. Histologic analysis of lymph node biopsy specimens should be routinely performed because some patients might have a concurrent malignant disease or mycobacteriosis.

Adolescent↗

PubMed2005

Whipple disease: intestinal infiltrating cells exhibit a transcriptional pattern of M2/alternatively activated macrophages.

Whipple disease (WD) is a rare systemic disease caused by Tropheryma whipplei and is characterized by the presence of foamy macrophages with periodic acid-Schiff-positive inclusions in tissues such as lamina propria. For the first time, we report the gene-expression profile of macrophages in intestinal lesions from a patient with WD. Microarray and real-time polymerase chain reaction revealed that genes encoding CCL18, cathepsins, scavenger receptor, interleukin-10, and lipid metabolites were up-regulated in intestinal lesions. This transcriptional pattern corresponds to that of M2/alternatively activated macrophages. Our results suggest that the T helper 2 response in the intestinal environment may account for the pathophysiological properties of WD.

Actinobacteria↗

PubMed2005

Risk of embolism and death in infective endocarditis: prognostic value of echocardiography: a prospective multicenter study.

BACKGROUND: The incidence of embolic events (EE) and death is still high in patients with infective endocarditis (IE), and data about predictors of these 2 major complications are conflicting. Moreover, the exact role of echocardiography in risk stratification is not well defined. METHODS AND RESULTS: In a multicenter prospective European study, including 384 consecutive patients (aged 57+/-17 years) with definite IE according to Duke University criteria, we tested clinical, microbiological, and echocardiographic data as potential predictors of EE and 1-year mortality. Transesophageal echocardiography was performed in all patients. Embolism occurred before or after IE diagnosis (total-EE) in 131 patients (34.1%) and after initiation of antibiotic therapy (new-EE) in 28 patients (7.3%). Staphylococcus aureus and Streptococcus bovis were independently associated with total-EE, whereas vegetation length >10 mm and severe vegetation mobility were predictors of new-EE, even after adjustment for S aureus and S bovis. One-year mortality was 20.6%. In multivariable analysis, independently of the other predictors of death (age, female sex, creatinine serum >2 mg/L, moderate or severe congestive heart failure, and S aureus) and comorbidity, vegetation length >15 mm was a predictor of 1-year mortality (adjusted relative risk=1.8; 95% CI, 1.10 to 2.82; P=0.02). CONCLUSIONS: In IE, vegetation length is a strong predictor of new-EE and mortality. In combination with clinical and microbiological findings, echocardiography may identify high-risk patients who will need a more aggressive therapeutic strategy.

Adult↗

PubMed2005

Experimental schistosomiasis, protective aspects of granulomatous reaction in the mouse liver.

We show two mechanisms of liver protection by the granulomatous reaction against Schistosoma mansoni eggs entrapped in the organ. First, eosinophil peroxidase and its substrate H(2)O(2) are released by inflammatory cells in the immediate vicinity of the parasite eggs. The efficiency of this process was demonstrated by administration of antioxidants to infected mice. The treatment, which reduces H(2)O(2) production, significantly improved the ability of parasite eggs to hatch after collection from the liver. Secondly, we labeled the released egg antigens in liver histological sections and we found that the lattice of collagen fibers which is built around eggs appears to create a barrier preventing released compounds from diffusing freely in surrounding tissues. Together, oxidative processes and antigen containment allow the parasitized liver to cope with the dual threat posed by parasite eggs, i.e. a highly resistant chitinous eggshell and the release of toxic substances.

Animals↗

PubMed2005

Quantitative histological examination of mechanical heart valves.

BACKGROUND: Histological demonstration of microorganisms, vegetations, or active endocarditis in cardiac valve tissue is included in the Duke criteria and is considered to be a criterion of confirmed infective endocarditis. However, the histological features that characterize infective endocarditis are not accurately defined at the qualitative and quantitative levels. METHODS: Pathologic analysis of tissue adjoining mechanical cardiac valves was undertaken retrospectively for 21 patients who underwent surgical removal of a mechanical valve because of suspected infective endocarditis and 69 patients who underwent surgical removal of a mechanical valve because of noninfectious dysfunction. To better define the histological criteria for infective endocarditis, we used quantitative image analysis to compare these 2 groups of patients with respect to valvular fibrosis, calcifications, vegetations, patterns of inflammation, and vascularization. RESULTS: Histologically, infective endocarditis in patients with mechanical valves was characterized by the demonstration of microorganisms, vegetations, and significant neutrophil-rich inflammatory infiltrates with extensive neovascularization. In contrast, valve tissue specimens from patients with mechanical valves that were removed because of noninfectious complications showed significant rates of extensive fibrosis and, when present, inflammatory infiltrates that were mainly composed of macrophages and lymphocytes. A neutrophil surface area with a cutoff value of > or =2% of the total valve tissue surface is highly predictive of (90%) and specific for (98%) infective endocarditis. CONCLUSIONS: When no microorganisms are detected and vegetations are lacking in tissue adjacent to a mechanical valve, neutrophil-rich inflammation and extensive neovascularization might better histologically define the term "active endocarditis" in the Duke criteria. This definition would allow differentiation between infective endocarditis and inflammatory noninfectious valve processes in patients with mechanical cardiac valves.

Acremonium↗

PubMed2005

Diagnosis of infectious endocarditis in patients undergoing valve surgery.

PURPOSE: Histologic examination of valve samples is considered as the gold standard for the diagnosis of infectious endocarditis. Molecular tools are also very promising for patients with negative-culture endocarditis. Thus, we studied the contribution of valvular histology, culture, and 16S rRNA PCR amplification plus sequencing to the diagnosis of infectious endocarditis in patients undergoing valve surgery. SUBJECTS AND METHODS: We performed culture, histological examination, and broad-range PCR amplification plus sequencing on valve samples taken from 127 patients with infectious endocarditis and from 118 patients without endocarditis. The sensitivity and specificity of these tests for the diagnosis of endocarditis in patients undergoing valve surgery were studied. RESULTS: The sensitivity of PCR was of 61% (64/105) whereas that of histological examination was of 63% (62/98) and that of valve culture was of only 13% (14/105). All 68 positive PCR results considered reliable according to an interpretation scheme were from patients with infectious endocarditis, resulting in a 100% (118/118) specificity of the interpreted molecular approach. The specificity of histology was also of 100% (118/118) when using stringent criteria (ie, presence of vegetation, microorganisms, and/or valvular inflammation with mainly polymorphonuclear cells). PCR identified an etiological agent in 38% (5/13) of definite blood culture-negative infectious endocarditis. CONCLUSION: We show that valvular histology with stringent criteria is the gold standard for the diagnosis of infectious endocarditis. Broad-range amplification of 16S rRNA gene is indicated for infectious endocarditis of unknown etiology, whereas valve culture is of limited sensitivity.

Adult↗

PubMed2005

Is pyogenic granuloma associated with Bartonella infection?

Lobular capillary hemangioma and bacillary angiomatosis due to Bartonella infection share several clinical and histopathologic characteristics. We sought to determine whether lobular capillary hemangioma is caused by the same agent as bacillary angiomatosis. Forty-five pathology specimens with a histologic diagnosis of lobular capillary hemangioma obtained from patients with the same clinical diagnosis were tested by immunohistochemistry and polymerase chain reaction for the presence of DNA elements of Bartonella spp. None of the 45 lobular capillary hemangioma specimens tested positive for Bartonella spp. We conclude that lobular capillary hemangioma is not associated with Bartonella spp infection. Further research is required to determine the etiologic agent.

Angiomatosis, Bacillary↗