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Biomedical subjects

E D Renner

Publications and source records attributed to E D Renner.

At least 19 recordsLinked to original sources

Classification of non-bacterial osteitis: retrospective study of clinical, immunological and genetic aspects in 89 patients.

OBJECTIVE: To define non-bacterial osteitis (NBO) as a clinical entity possibly associated with autoimmune manifestations. Patients with sterile osteitis were analysed to develop diagnostic criteria. METHODS: A total of 89 patients with non-bacterial inflammatory bone lesions were observed for a median of 49 months. History, diagnostic imaging, laboratory and histological data were obtained. Mutation analysis in the genes PSTPIP1 and PSTPIP2 was performed. RESULTS: Patients had an onset of disease at a median age of 10 yrs [interquartile range (IQR) 7.5-12] and suffered a median period of 21 (IQR 9-52) months with a median of three foci per patient. Twenty percent of all the patients demonstrated associated autoimmune disorders, particularly of the skin and bowel. The majority of bone lesions were located in the vertebrae and metaphyses. Slight-to-moderate elevation of inflammation values were found in all the patients and antinuclear antibodies were elevated in 30%. Non-steroidal anti-inflammatory drugs (NSAIDs) were effective in 85% of the patients. HLA-B27 and Human Leukocyte Antigen-DR (HLA-DR)-classification did not differ from the general population. Autoimmune diseases in 40% of all the families, multiply affected family members, linkage to 18q21 and mouse models strongly indicate a genetic basis for NBO. We observed three different courses of disease regarding the duration of complaints, rate of complications and associated autoimmune manifestations leading to a new classification of NBO. CONCLUSIONS: Clinical analysis of our cohort leads us to define NBO as a distinct disease entity with three clinical presentations: acute NBO, chronic recurrent multifocal osteomyelitis or persistent chronic NBO. Diagnostic criteria were proposed to differentiate NBO from diseases with similar clinical presentation.

Adaptor Proteins, Signal Transducing↗

No indication for a defect in toll-like receptor signaling in patients with hyper-IgE syndrome.

Hyper-IgE syndrome is a rare primary immunodeficiency of unknown etiology characterized by recurrent infections of the skin and respiratory system, chronic eczema, elevated total serum IgE, and a variety of associated skeletal symptoms. Recent reports about susceptibility to pyogenic bacterial infections and high IgE levels in patients and animals with defects in toll-like receptor (TLR) signaling pathways prompted us to search for TLR signaling defects as an underlying cause of hyper-IgE syndrome. Blood samples from six patients with hyper-IgE syndrome were analyzed for serum cytokine levels, intracellular cytokine production in T cells after stimulation with PMA/ionomycin, and cytokine production from peripheral blood mononuclear cells stimulated by TLR ligands and bacterial products including LPS (TLR4), peptidoglycan (TLR2), PolyIC (TLR3), R848 (TLR7/8), CpG-A, and CpG-B (TLR9), zymosan and heat killed Listeria monocytogenes. All results were compared to data from healthy controls. A reduction in IFN-gamma, IL-2, and TNF-alpha producing T cells after PMA stimulation suggested a reduced inflammatory T cell response in patients with hyper-IgE syndrome. Increased serum levels of IL-5 indicated a concomitant Th2 shift. However, normal production of cytokines (TNF-alpha, IL-6, IL-10, IFN-alpha, IP-10) and upregulation of CD86 on B cells and monocytes after TLR stimulation made a defect in TLR signaling pathways highly unlikely. In summary, our data confirmed an imbalance in T cell responses of patients with hyper-IgE syndrome as previously described but showed no indication for an underlying defect in toll-like receptor signaling.

Adolescent↗

Genetic linkage of hyper-IgE syndrome to chromosome 4.

The hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated levels of serum IgE. HIES is now recognized as a multisystem disorder, with nonimmunologic abnormalities of the dentition, bones, and connective tissue. HIES can be transmitted as an autosomal dominant trait with variable expressivity. Nineteen kindreds with multiple cases of HIES were scored for clinical and laboratory findings and were genotyped with polymorphic markers in a candidate region on human chromosome 4. Linkage analysis showed a maximum two-point LOD score of 3.61 at recombination fraction of 0 with marker D4S428. Multipoint analysis and simulation testing confirmed that the proximal 4q region contains a disease locus for HIES.

Chromosome Deletion↗

Development and clinical evaluation of an amplified flow cytometric fluoroimmunoassay for Clostridium difficile toxin A.

A rapid (2 h) amplified flow cytometric fluoroimmunoassay (AFCF) for Clostridium difficile toxin A was developed and compared with the cytotoxin assay (CTA) and culture of the organism from stool specimens from patients with suspected C. difficile-associated gastrointestinal disease (CAD). For this assay polyclonal antitoxin A was attached to 10-microns diameter and monoclonal antitoxin A was attached to fluorescent 0.1 micron-diameter polystyrene microspheres. The microspheres and sample were reacted together as in a conventional double-antibody sandwich assay. However, laser flow cytometric measurement allowed the omission of separation and washing steps by gating on light scattered by the larger microspheres and measuring only the fluorescence associated with these particles. The amount of fluorescence from the attached 0.1 micron microspheres was dependent on the concentration of toxin A in the sample. The AFCF detected purified toxin A at levels of 1 pg/ml and was linear from 1 to 40 pg/ml. The AFCF was compared with the CTA and culture of C. difficile for clinical use by comparing results from 198 stool specimens from patients with suspected CAD. The AFCF was 85.7% sensitive and 95.8% specific relative to the CTA, and 85.2% sensitive and 98.3% specific compared to the culture assay. If the isolation of toxigenic C. difficile or the patients clinical course was considered indicative of CAD, the sensitivities of the AFCF, CTA, and culture assay were 77.4%, 67.7% and 96.8%, respectively. The AFCF demonstrated a specificity of 98.8%, while both CTA and culture had a specificity of 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fatal Legionnaires' disease coincident with initiation of immunosuppressive therapy.

A fatal relapse of legionnaires' disease occurred coincidental with the initiation of chemotherapy in a patient who had received previous parenteral erythromycin gluceptate therapy for 30 days. Sputum examinations utilizing the direct fluorescent antibody test for Legionella pneumophila suggested persistence of infection during the course of antibiotic therapy. This case suggests that administration of immunosuppressive agents should be delayed in patients whose sputum is positive on direct fluorescent antibody testing, regardless of previous antibiotic therapy.

Adenocarcinoma↗

A new staining method for Legionella pneumophila.

Most of the methods that have been described for the staining of bacteria in tissue sections have been found unsatisfactory for Legionella pneumophila. In this report, we describe a method that consistently stains L. pneumophila in tissue and has certain advantages over recommended methods currently in use.

Bacteriological Techniques↗

Coinfections of Mycoplasma pneumoniae and Legionella pneumophila with influenza A virus.

Serum samples from patients with documented influenza A virus infections were examined for antibodies to Legionella pneumophila and Mycoplasma pneumoniae to determine whether simultaneous or sequential infections with L. pneumophila and M. pneumoniae were complicating factors in influenza. When the frequency of copositivity of sera to influenza A virus and L. pneumophila was compared with the expected frequency for each infection alone, the difference was not statistically significant. However, when the frequency of copositivity of sera to influenza A virus and M. pneumoniae was compared with the expected frequency for each infection alone, there was a statistically significant (P less than 0.005) absence of coincident titers. Seasonal variations and differences in relative age frequencies for the two infections may partially explain the absence of coinfections. These data also suggest that in patients with either M. pneumoniae or influenza A virus infection, some type of protective mechanism which prevents coinfections with these organisms is present.

Humans↗

A survey of domestic animals to detect serological responses against Legionella spp. by indirect fluorescent antibody.

One hundred ninety-six (196) animal sera were examined for antibodies against heat-killed antigens of Legionella pneumophila serogroups 1 to 5, L. bozemanii, L. dumoffii, L. gormanii and L. micdadei by the indirect fluorescent antibody technique. Only two animals (1%), both sheep, reacted against L. pneumophila serogroups at a titer of 256. However, 29% of the horses and 24% of the sheep tested were reactive to at least one non-L. pneumophila Legionella spp. antigen at a titer of 256. At a titer of 128, 72% of the pigs, 56% of the sheep and 50% of the horses were reactive to at least one Legionella spp. antigen. Despite the presence of high antibody titers against Legionella antigens, conclusive evidence of infection by these agents in animals is dependent upon further studies.

Animals↗

Seroreactivity to Mycoplasma pneumoniae and Legionella pneumophila: lack of a statistically significant relationship.

We reviewed antibody titers to Mycoplasma pneumoniae and Legionella pneumophila serogroup I in sera from 1,060 cases of acute respiratory infection to determine whether there was an association in seroreactivity to these organisms. Of the 170 serum pairs with antibodies to L. pneumophila (35 seroconversions and 135 with presumptive titers), 32 (18.8%) demonstrated seroreactivity to M. pneumoniae (17 seroconversions and 15 with presumptive titers). This frequency was not significantly greater than the seroreactivity to M. pneumoniae observed in sera without antibodies to L. pneumophila (17.5%) (0.05 less than P less than 0.10), which included 111 seroconversions and 45 sera with presumptive titers.

Acute Disease↗

Sporadic Legionnaires' disease. A pathologic study of 23 fatal cases.

Twenty-three fatal sporadic cases of serogroup 1 Legionella pneumophila pneumonia have been analyzed. Bilateral consolidating fibrinopurulent pneumonia was evident in most cases. In four leukopenic immunosuppressed subjects, and acute fibrinoserous pneumonia with a remarkable lack on inflammation was present. The bacterium was found at extrathoracic sites in 27% of the cases. Involvement of the spleen (25%), bone marrow (13%), and kidneys (4.5%) suggests that hematogenous spread of the infection is not uncommon. Involvement of the hilar lymph nodes in 44% of the cases, and multiple peripheral lymph nodes in one case, suggest that lymphatic vessels may also be an important pathway of dissemination. We concluded that systemic spread of L pneumophila is not uncommon in seriously ill patients and we believe that some of the unusual extrathoracic manifestations of this disease may be related to bacteremia.

Adult↗

Legionnaires' disease.

Described here is a unique case of Legionnaires' disease in a previously healthy 46 year old man in whom disseminated disease was demonstrated in the kidneys, bone marrow, spleen and multiple peripheral lymph nodes at autopsy. The pathologic distribution of the lesions suggests that dissemination occurred by both hematogenous and lymphatic pathways. Pancytopenia associated with bone marrow destruction and fibrosis suggests that substances toxic to hematopoietic cells were present. It is likely that many of the unusual systemic manifestations of this disease are related to dissemination of the bacterium. The findings presented extend the spectrum of the clinical and pathologic manifestations of Legionnaires' disease from a mild and self-limited illness to a severe and fatal disseminated form of the disease.

Bone Marrow↗

Background prevalence of microagglutination antibodies to Legionella pneumophila serogroups 1, 2, 3, and 4.

The background prevalence of microagglutination antibodies to Legionella pneumophila was determined by testing the sera of 517 individuals who lived or worked in a small Iowa town. In this population, the upper limit of normal microagglutination titer for serogroups 1, 3, and 4 was 1:16, and that for serogroup 2 was 1:8. The prevalence of microagglutination titers of greater than or equal to 1:32 against any serogroup of L. pneumophila was only 7.4% and did not vary significantly with age or sex.

Antibodies, Bacterial↗

Indirect immunofluorescence antibodies to Legionella pneumophila: frequency in a rural community.

The background prevalence of indirect immunofluorescence antibody to Legionella pneumophila in a rural community was determined by testing sera from 517 volunteers. The upper limit of normal antibody titer was found to be 1:64 with L. pneumophila serogroup 1 (Philadelphia 1) used as antigen. High titers (greater than or equal to 1:128) were found in 13.2% of the sera and occurred with similar frequencies in males and females. In individuals 40 years of age and older, however, high titers were 2.7 times as prevalent in males as females.

Adolescent↗

An agar--gel immunodiffusion test for detection of Brucella antibodies in human serum.

A comparison was made of results obtained with a Brucella agar--gel immunodiffusion (AGID) test and the standard tube-agglutination test on 612 human sera. Agreement between the tests was 97% when the titer was 1:160 or higher. Of 448 sera that showed no agglutination titer, 447 were negative with the AGID test. Results of the AGID test were also compared to those obtained with the 2-mercaptoethanol (2-ME) agglutination test on 148 sera that demonstrated a standard tube-agglutination titer of 1:20 or higher. All sera with a 2-ME-agglutination titer of 1:40 or higher were positive with the AGID test. Of 123 sera that showed no 2-ME-agglutination titer, 21 were positive with the AGID test. Two of these 21 sera were obtained from patients with bacteriologically proven brucellosis, and eight were from abattoir employees with suspected but not bacteriologically proven brucellosis.

Agglutination Tests↗

Comparative features of pneumococcal, mycoplasmal, and Legionnaires' disease pneumonias.

Retrospectively, we clinically compared community-acquired cases of Legionnaires' disease, pneumococcal, and mycoplasmal pneumonias. Relative to pneumococcal and mycoplasmal pneumonias, patients with Legionnaires' disease were significantly more likely to present with unexplained encephalopathy, hematuria, and elevation of serum glutamic-oxalacetic transaminase than were those with pneumococcal and mycoplasmal pneumonias. We found upper respiratory symptoms infrequently in patients with Legionnaires' disease, and progression of pulmonary infiltrates occurred commonly. Differentiation of Legionnaires' disease pneumonia without encephalopathy from pneumococcal and mycoplasmal pneumonias may be difficult because of demographic, clinical, laboratory, and radiographic similarities.

Adult↗

Legionnaires' disease in pneumonia patients in Iowa. A retrospective seroepidemiologic study, 1972-1977.

The frequency of Legionnaires' disease among 586 cases of pneumonia that occurred in Iowa between fiscal years 1972 and 1977 was studied retrospectively on the basis of paired sera. The frequency of confirmed Legionnaires' disease was 4.1% and of presumptive Legionnaires' disease was 11.4%. Infections with the Legionnaires' disease (LD) bacterium were most frequent in the summer. Of the 22% of pneumonias for which a cause could be defined, Legionnaires' disease was third in frequency behind Mycoplasma pneumoniae and influenza A virus infections. Infections with the LD bacterium occurred in association with pneumonias in most age groups. The youngest patient with LD infection was a 5-year-old boy with pneumonia. The disease occurred 3.2 times more often in males than in females. In males, the frequency of confirmed and presumptive Legionnaires' disease increased steadily to plateau after the fourth decade at about 12% and 28%, respectively. In females the frequency of presumptive Legionnaires' disease was 7% to 16%, relatively evenly distributed over all age groups. Pneumonias associated with LD bacterium infection should be considered in the differential diagnosis of community-acquired pneumonias in most age groups.

Adolescent↗