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Evaluation of white-tailed deer (Odocoileus virginianus) as natural sentinels for Anaplasma phagocytophilum.

Anaplasma phagocytophilum, the causative agent of human granulocytotropic anaplasmosis, can infect white-tailed deer (WTD; Odocoileus virginianus), and this species is a crucial host for adult Ixodes scapularis, the primary vector of A. phagocytophilum. The goal of this study was to determine the geographic distribution of A. phagocytophilum among WTD across a 19 state region and to evaluate the utility of WTD as natural sentinels. Serologic testing using the indirect fluorescent antibody (IFA) assay was conducted on WTD serum samples and molecular and xenodiagnostic tests were performed to confirm serologic results. The surveillance system was assessed through examination of vital attributes including WTD age and gender associations with serologic status, sample size adequacy for accurate infection status classification, and presence of the vector, I. scapularis. Six hundred thirty-three of 2,666 (24%) WTD in 17 states tested positive for antibodies (>or=128) when tested by IFA assay. Testing for p44 and/or 16S rRNA gene targets identified 73 (16%) PCR positive WTD among 458 animals tested, all of which originated from seropositive populations. Attempts to culture A. phagocytophilum from WTD were unsuccessful; however, xenodiagnostic mice inoculated with blood from 3 WTD became infected. Seroprevalence did not differ by deer age or gender; however, WTD<or=0.75 years old had a higher prevalence of PCR positivity. Using seroprevalence data, a sample size of 6-9 animals per population was projected to be adequate for identifying seropositive populations. The presence of I. scapularis was significantly associated with A. phagocytophilum antibodies in WTD. Collectively, the results of this study demonstrate that WTD would be suitable natural sentinels for this emerging zoonotic pathogen.

Age Distribution↗

Interleukin 1beta and tumour necrosis factor alpha secreting cells are increased in the peripheral blood of patients with primary Sjögren's syndrome.

OBJECTIVE: To study systemic alterations of cytokine secreting peripheral blood mononuclear cells (PBMC) in primary Sjögren's syndrome (pSS) and their relation to common clinical and immunological manifestations of this disease. METHODS: PBMC spontaneously secreting tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), and interleukin 6 (IL6) were assessed by enzyme linked immunospot (ELISPOT) analysis in a cohort of 31 patients with pSS fulfilling the modified European classification criteria. Nineteen healthy volunteers served as controls. ELISPOT results were correlated with glandular and extraglandular manifestations and autoantibody titres-that is, rheumatoid factor (RF) isotypes, anti-Ro/SS-A, anti-La/SS-B as determined by an enzyme linked immunosorbent assay (ELISA) technique. RESULTS: The number of TNFalpha and IL1beta secreting cells was significantly higher in patients with pSS than in controls. No differences were detected in the number of IL6 secreting PBMC. Patients with recurrent parotid swelling (RPS) had a significantly increased number of IL1beta secreting PBMC. Moreover, the number of IL1beta secreting PBMC correlated with the disease duration (r(s)=0.479; p<0.01) and with the concentration of IgM RF (r(s)=0.63; p<0.01) and IgG RF (r(s)=0.42; p<0.05). Other autoantibodies did not correlate with cytokine secreting PBMC. CONCLUSION: The increased systemic secretion of IL1beta and TNFalpha in patients with pSS points to a pathogenic impact of these cytokines in this autoimmune disease. In particular the correlation of IL1beta secreting PBMC with RPS and RF production indicates that IL1beta is a crucial regulator in the development of local and systemic disease manifestations.

Adult↗

Actinobacilli in domestic fowl.

Reports on haemolytic rods from salpingitis in hens and from organs of died chicks may be found since the year 1950 (Kjos-Hanssen). Correct systematic classification on these microorganisms is still lacked because not all relations to the nearest pasteurellae were known as well as the clear differences in the Pasteurella-Actinobacillus group. The authors have isolated 34 suspected strains from 14 localities; 25 strains were from salpingitis or internal organs of died fowl inclusively chicks, and 9 strains from choanas of pullets clinically healthy. Bacteriological, serological, chemical and biological tests gave the results as follows: 1) All strains exhibit fundamental properties of Pasteurella-Actinobacillus group, and moreover, they show ability to grow on MacConkey agar with crystal violet (BioQuest) being a significant feature of the genus Actinobaccillus (Mráz, 1975). 2) From the nearest species Actinobacillus haemolyticus (Newsom and Cross, 1932) Mráz, 1969, they differ with expressive haemolysis on agar with sheep blood, single haemolytic zone on agar with lamb blood according to Smith (1962), structure of somatic antigen, with natural hosts (gallinaceous birds) and pathogenicity for 5-day-old chicks. The GC content in DNA was determined in the range 39,6-42,9% (mean value 41,5%). 3) The first who presumed an independent state of these microorganisms, was Kohlert (1968), from the work of which the epithet for correct name, i.e. Actinobacillus salpingitidis (Kohlert, 1968) comb. nov., was accepted.

Actinobacillus↗

[Alignment of DNA sequences of ompL1 genes of insert fragment of recombinant plasmid, pDC38 of L. interrogans serovar lai and L. kirschneri].

In a previous study a genomic library of L. interrogans serovar lai was constructed by the present authors. Hybridization analysis (In situ, dot blot, Southern blot) with the DNA fragment containing OmpL1 (alpha-32P labeled) was performed. One of positive clones designated pDC38, was analyzed with 9 restriction enzymes (EcoRI, Bam HI, Hind III, Bgl, XbalI, ScaI, KpnI, PstI, Dra II). DNA hybridization was applied to analyze the homology of the recombinant fragment of ompL1 with the DNA of 18 strains of L. interrogans. The results showed that the homology of fragments of ompL1 were present in pathogenic Leptospira strains, but they were not in the non-pathogenic Leptospira biflexa strain Patoc I, Leptonema illini strain 3055. Therefore, Dr. David A. Haake performed the sequencing of pDC38. The results showed that pDC38 contained two inserts of 2.7 kb and 3.0 kb. The 3.0 insert contained a complete copy of the ompL1 gene. Dr. David A. Haake amplified the ompL1 gene using PCR primers specific for the ends of the gene and cloned the amplicon into pBluescript KS for sequencing. The alignment of complete DNA sequences of ompL1 of L. kirschneri and L. interrogans serovar lai showed the similarity of nucleotide sequences was 90%, variation was 10%. The derived amino acid sequence showed there was a high degree of amino acid sequence homology with ompL1 of L. kirschneri. These findings indicated that ompL1 gene was one of the important outer membrane protein genes in the L. interrogans serovar lai and using the probe pDC38 might provide a good tool for classification and identification of Leptospira.

Amino Acid Sequence↗

APPLICATION OF FLUORESCENT-ANTIBODY PROCEDURES TO THE STUDY OF PATHOGENIC DEMATIACEOUS FUNGI.II. SEROLOGICAL RELATIONSHIPS OF THE GENUS FONSECAEA.

Gordon, Morris A. (New York State Department of Health, Albany), and Yousef Al-Doory. Application of fluorescent-antibody procedures to the study of pathogenic dematiaceous fungi. II. Serological relationships of the genus Fonsecaea. J. Bacteriol. 89:551-556. 1965.-The staining spectra of fluorescein-labeled antiglobulins to Fonsecaea compactum, F. dermatitidis, and F. pedrosoi were determined with respect to 71 strains of morphologically related and 21 miscellaneous molds (including so-called "black yeasts"). All three conjugates showed considerable reaction with saprophytic Cladosporium spp. F. dermatitidis appeared to be most closely related serologically to the genus Cladosporium; F. compactum conjugate was fairly specific; and the few non-specific reactions of diluted F. pedrosoi reagent were almost unexceptionally with species of Fonsecaea and Cladosporium. Most strains of F. pedrosoi were unstained by F. compactum conjugate, and there was very little relationship shown between either of these species and Phialophora verrucosa. Conjugates of two strains of P. verrucosa failed to react with any of the three species of Fonsecaea. The possible significance of these results for classification of the "black yeasts" and other dematiaceous molds is discussed.

Ascomycota↗

[Human prion diseases].

Prion diseases are rare neurodegenerative transmissible fatal diseases affecting humans and mammals. The causative agent is a novel pathogen termed the prion. Unlike classical infectious agents such as bacteria or viruses, prions lack an independent genome and consist largely of an abnormal form of the host-encoded prion protein. Creutzfeldt-Jakob disease (CJD) is the main representative of human prion diseases that may be sporadic in most cases, hereditary, or acquired. Clinical examination yields only a suspected diagnosis with formal criteria for probable or possible. Definite diagnosis relies on autopsy and neuropathology findings. This is also true for the new variant CJD (vCJD), a previously unknown prion disease of humans that is connected with the same strain of prions as found in bovine spongiform encephalopathy (BSE). The autopsy and handling of laboratory material for histopathological examination requires specific precautionary measures and decontamination. For definite histopathological diagnosis of a human prion disease, immunohistochemical detection of the prion protein deposits is the gold standard. Furthermore, molecular and genetic investigations are necessary for classification because a close correlation could be established between distinct CJD phenotypes, codon 129 genotypes of the prion protein gene, and the prion protein type.

Animals↗

Integrative oral and gut microbiome profiling highlights microbial correlates of complications in type 1 diabetes: a cross-sectional analysis.

BACKGROUND/OBJECTIVE: Chronic vascular complications are the primary threat in long-standing type 1 diabetes (T1D) patients. We examined the associations between oral-gut microbiome dysbiosis and these complications, offering novel insights into therapeutic strategies and underlying mechanisms. METHODS: This cross-sectional study enrolled 75 T1D participants (disease duration&#x2009;&#x2265;&#x2009;10&#xa0;years) and 43 healthy controls who underwent comprehensive clinical assessment, including blood glucose, lipid profile, and complication-related examinations. Fecal and oral rinse samples were collected for shotgun metagenomic sequencing. T1D participants were stratified by the presence of microvascular (retinopathy, nephropathy, or neuropathy) or macrovascular complications separately. Microbial differences across groups were assessed. RESULTS: Significant differences in oral and gut microbiota compositions were observed between T1D participants with and without complications (both microvascular and macrovascular). A core set of 26 gut and 8 oral microbial species was specifically associated with vascular complications. Butyrate-producing gut bacteria (Blautia wexlerae, Anaerobutyricum hallii, Roseburia inulinivorans, A. soehngenii) and specific oral Neisseria species were enriched in T1D without complications individuals, suggesting protective effects against complications. Mediation analysis indicated associations consistent with partial mediation between certain microbial species and the relationships of glycemic control or insulin resistance (HbA1c, glucose risk index, estimated glucose disposal rate) with complication risk. Moreover, potential oral-gut microbiome interconnections were implicated in complication development. Finally, classification models integrating both oral and gut microbial features significantly outperformed models based on either site alone in distinguishing T1D patients with complications. CONCLUSIONS: Distinct oral and gut microbiome features are associated with chronic vascular complications in T1D. These findings highlight the potential of microbiome-targeted strategies for understanding and preventing T1D-related complications.

Humans↗

Simplified analysis of pathogenic leptospiral serovars by random amplified polymorphic DNA fingerprinting.

A rapid, simplified procedure combining random amplified polymorphic DNA (RAPD) fingerprinting of boiled cultures with high resolution agarose gel electrophoresis was used to compare strains from 46 pathogenic leptospiral serovars. The serovars were placed in eight groups on the basis of RAPD profile similarities. Groups 1-7 corresponded with the genome species Leptospira interrogans, L. borgpetersenii, L. santarosai, L. noguchii, L. weilii, L. kirschneri and L. meyeri. The eighth group did not correspond with a known genome species and may represent a new genome species. Primer choice determined the degree of discrimination possible between closely related serovars and genotypes. This procedure, unlike other procedures used for analysing taxonomic relationships between leptospiral serovars, does not require extensive DNA purification, polyacrylamide gel electrophoresis or autoradiography.

Classification↗

[Isolation, classification and antimicrobial activity of endophytic actinomycetes from plant leaves].

Leave samples of Paeonia lactiflora and Trifalium repens were collected from Sichuan Province and Beijing respectively to study their endophytic actinmycetes. After a well-established surface-sterilized procedure, the samples were plated on agar media of TWYE, HV, YECD, NA and WA, followed by incubation at 28 degrees C for 2 - 4 weeks. With the help of light microscope, 15 actinomycetes strains were isolated from the plates. Comparison of cultural features and fingerprinting analyses of BOX-PCR products were performed to cluster the isolates, with the result that all the strains were assigned to 12 different genotypes, half of them from Paeonia lactiflora and half from Trifalium repens. A combination of morphological and 16S rRNA gene sequence data showed that except strains C4 and C5, which belonged to Pseudonocardia, 13 of the isolates were streptomycetes. Most isolates share high 16S rRNA gene sequence similarities to known type strains. However, strain C12 shares low values, 96.6% in maximum, and strain C5 shares 97.9% in maximum; more assays are needed to ascertain their taxonomic positions. In the tests of antimicrobial activity against 7 bacteria, 3 fungi and 1 yeast, 11 isolates were positive in one or more tests, and 55% of the positive ones could inhibit the growth of Rhizoctonia solani, a significant pathogen of plants.

Actinobacteria↗

Human immune responses to oral microorganisms. II. Serum antibody responses to antigens from Actinobacillus actinomycetemcomitans and the correlation with localized juvenile periodontitis.

Human serum antibody responses to antigens from a suspected oral pathogen, Actinobacillus actinomycetemcomitans (Aa), were studied. IgG and IgM isotype antibodies to four antigen preparations, sonicate antigen (SA), leukotoxin (LT), group carbohydrate (LG), and lipopolysaccharide (LPS), were determined using an ELISA. An ELISA inhibition technique was developed to show that human serum antibodies reacting with the LT, LG, or LPS materials were binding to different antigenic moieties in each preparation. Cross-sectional studies of serum IgG antibodies showed that patients with localized juvenile periodontitis (LJP) had a greater frequency of occurrence and a higher level of antibodies to the SA (82%), LT (70%), and LG (62%) antigens compared to all other diseased (11-46%) or normal (4-13%) groups. Serum IgM antibodies to LPS were increased in LJP, generalized juvenile periodontitis, and adult periodontitis patients compared to all other groups. Therefore, while both IgG and IgM antibodies were found against various Aa antigens, the detection of IgG antibodies was most clearly associated with the specific disease classification of LJP. Blocking studies suggested that the human serum responses were specific for the Aa antigens and that the LT, LG, and LPS comprise major antigenic determinants on the organisms to which human serum antibody reacts.

Actinobacillus↗

Raman spectroscopic method for identification of clinically relevant microorganisms growing on solid culture medium.

Routine clinical microbiological identification of pathogenic microorganisms is largely based on nutritional and biochemical tests. In the case of severely ill patients, the unavoidable time delay associated with such identification procedures can be fatal. We present a novel identification method based on confocal Raman microspectroscopy. With this approach it is possible to obtain Raman spectra directly from microbial microcolonies on the solid culture medium, which have developed after only 6 h of culturing for the most commonly encountered organisms. Due to the limited thickness of microcolonies, some of the underlying culture medium is sampled together with the bacteria. Spectra measured at different depths in a microcolony contain different amounts of the medium signal. A mathematical routine, involving vector algebra, is described for the nonsubjective correction of spectra for variable signal contributions of the medium. To illustrate the possibilities of our approach for the identification of microorganisms, Raman spectra were collected from 6-h microcolonies of five bacterial strains on solid culture medium. The classification results show that confocal Raman microspectroscopy has great potential as a powerful new tool in clinical diagnostic microbiology.

Bacteriological Techniques↗

Appraisal of various random amplified polymorphic DNA-polymerase chain reaction primers for Leishmania identification.

Pathogenic Leishmania can cause a variety of symptoms ranging from asymptomatic or mild infections to severe mucocutaneous disease, partly according to the species of Leishmania involved. Genomic and kinetoplast-derived DNA probes as well as species complex-specific kinetoplast-derived polymerase chain reaction (PCR) primers have been successful for parasite identification in epidemiologic and taxonomic studies. However, the lack of a species DNA probe or PCR primer set, their relatively poor availability, and unknown comparative sensitivity and specificity have precluded their routine and widespread use as identification tools in many laboratories. This study addresses this problem for 28 different random amplified polymorphic DNA (RAPD)-PCR primers that have been assessed regarding their sensitivity, specificity, and reliability for distinguishing each of four closely related New World Leishmania species. The degree of relatedness between species was quantified and estimates were made of the accuracy and precision of the determinations. The results compared well with standard methods for Leishmania classification. The application of RAPD-PCR for screening isolates for possible interspecific hybrids is also demonstrated.

Animals↗

Differentiation between calcium- and cholesterol-dominated types of arteriosclerotic lesions: antiarteriosclerotic aspects of calcium antagonists.

In a series of animal studies we have clearly demonstrated since 1970 that calcium overload of the arterial wall is crucially involved in the pathogenesis of arteriosclerotic lesions. Following excessive calcium uptake, vascular stretch compliance and distensibility were lost together with structural integrity. Conversely, calcium antagonists that counteract abundant calcium uptake were found to prevent pathogenic mural calcium accumulation and damage. These effects were realized with light and electron microscopy as well as with measurements of calcium accumulation using atomic absorption spectrometry and radiocalcium. The experiments were carried out on rats exposed to various well-known risk factors such as nicotine, alloxan diabetes, high doses of vitamin D3, or dihydrotachysterol. Another particularly vasotoxic factor appeared to be hypertension, which develops in spontaneously hypertensive Okamoto rats (SHRs), in hypertensive NaCl-loaded salt-sensitive Dahl-S rats, and in rats with nephrogenic Goldblatt hypertension. Interestingly, aging arteries in animals and humans also exhibit, as a characteristic phenomenon, a steady increase in arterial calcium content. This natural age-dependent calcium accumulation is further enhanced in severe diabetics, heavy smokers, and hypertensive patients. However, the most excessive degree of toxic calcium overload, correlated with dramatic structural damage, occurred in human coronary artery plaques. Here, in "fatty streaks" (type I plaques according to World Health Organization classification), the mural calcium content exhibited a rise by 13 times above normal; in type II lesions (fibrous plaques), the increase in calcium was 24-fold; and in type III plaques, i.e., in "complicated lesions of stenosing character," calcium overload amounted to a value greater than 80 times above that found in healthy coronary segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Phylogenetic relationships among adenovirus serotypes.

Phylogenetic comparisons of adenovirus DNA sequences, including the recently completed genomic sequences of Ad40 and Ad12, have been performed in order to investigate the evolutionary relationships among the various serotypes. Phylogenetic trees were constructed from sequence data for the ITR, E1a, E1b, E2a, E3b, major late promoter, hexon, protease, and fiber regions of the genome using programs contained in the PHYLIP (Phylogeny Inference) package. In general the branching pattern of the human serotypes at each locus correlated well with the classification of the human serotypes into six subgenera (A-F). However, a close evolutionary relationship was inferred between Ad4 (the only member of subgenus E) and the subgenus B viruses Ad3, Ad7, and Ad35, and challenges the placement of Ad4 in a subgenus of its own. In addition, the human viruses of subgenera A (Ad12, Ad18, and Ad31) and F (Ad40 and Ad41), as well as the simian adenoviruses SAV16 (SA7) and SAV8 (SV30), all of which are associated with infections of the gastrointestinal tract, were found to cluster together. The results suggest that these viruses have followed a course of evolution distinct from those of the other subgenera which largely infect the respiratory tract. Analysis of genetic variability between the four complete genomic sequences (Ad2, Ad5, Ad12, and Ad40) identified three regions subject to more rapid change, corresponding to the hexon-, fiber- and E3a-coding regions. Genetic variability at the E3a locus is particularly striking and may relate to the pathogenicity of the various serotypes.

Adenoviridae↗

Survey and expression analysis of five new chitin synthase genes in the biotrophic rust fungus Puccinia graminis.

We have isolated and characterised the first set of chitin synthase genes from a rust fungus, a large group of economically highly important, obligately biotrophic plant pathogens. Puccinia graminis was used as a model organism for the rust fungi which are not well investigated on the molecular level today. One of the major structural components of most fungal cell walls is the chitin polymer which is synthesised by a family of enzymes called chitin synthases. In P. graminis, we have isolated five new chitin synthase genes from four different classes, chsII, chsIIIa, chsIIIb, chsIV, and chsV. The genes contain a high number of introns, unusual for other known fungal chitin synthases. The dinucleic stage of the fungus seems to contain two slightly different genes or alleles for four isoforms. One isoform, chsIIIa, seems to be expressed only in the youngest stages of fungal growth. Analysis of the derived proteins shows that together with other basidiomycete CHS, the pgtCHS form separate subgroups in the phylogenetic tree. This set of five rust chitin synthase genes, with some unusual features compared to known fungal chitin synthases, allows new insights into chitin synthase classification, and may help in the development of novel functional fungicides.

Basidiomycota↗

Revised definition of Actinobacillus sensu stricto isolated from animals. A review with special emphasis on diagnosis.

The taxonomy of the members of the genus Actinobacillus associated with animals has been reviewed with focus on classification and identification including molecular based characterization, typing and identification. Out of the 22 species or species like taxa reported as Actinobacillus, 19 are associated with animals. When classified on the basis of 16S rRNA sequence based phylogenetic analysis, DNA-DNA hybridizations and phenotypic analysis, Actinobacillus sensu stricto is restricted to include A. lignieresii, A. pleuropneumoniae, A. equuli subsp. equuli, A. equuli subsp. haemolyticus (taxon 11 of Bisgaard), A. hominis, A. suis, A. ureae, A. arthritidis (taxon 9 of Bisgaard), Actinobacillus genomospecies 1 and 2 and the taxa 8 and 26 of Bisgaard. The remaining 11 species of Actinobacillus are unrelated to A. sensu stricto and should consequently be grouped with other genera or be renamed as new genera depending on new data. Identification of members of Actinobacillus at species level is possible through phenotypic characterization combined with information on host of isolation. PCR tests are available for specific detection of A. pleuropneumoniae. Only A. pleuropneumoniae is presently considered as a primary pathogen. Based on different types of RTX genes it is possible to PCR type A. pleuropneumoniae to serotype level. PCR might also be used for the specific detection of A. equuli subsp. haemolyticus. Epidemiological investigations and surveillance have so far included serotyping, multilocus enzyme electrophoresis (MLEE), ribotyping and restriction fragment length profiling.

Actinobacillus↗

[Perinatal differences in asphyxic full-term newborns in relation to the presence of hypoxic-ischemic encephalopathy].

OBJECTIVE: To study the perinatal differences of full-term newborn infants with perinatal asphyxia in relation to their neurologic manifestations (postasphyctic encephalopathy). MATERIAL AND METHODS: Prospective epidemiologic study over perinatal asphyxia in full-term infants born in our hospital between november 1991-february 1995. Perinatal asphyxia was graded as non-severe (first minute Apgar score < or = 6 and/or umbilical artery pH < 7.20, with abnormal fetal heart rate patterns and/or meconium stained amniotic fluid, and the need for immediate neonatal resuscitation) and severe (first minute Apgar score < or = 3 and umbilical artery pH < 7.10). Hypoxic-ischemic encephalopathy was graded as mild, moderate and severe based on classification of Levene and Sarnat & Sarnat. The perinatal variables were graded as prenatal (gestationals and obstetrics), neonatal (resuscitation, general data of the newborn, and organic manifestations of asphyxia) and postneonatal (neurologic sequelae at follow-up). RESULTS: During the study period there were 3,342 full-term, live births. Perinatal asphyxia developed in 156 (31 severe and 125 non-severe). Neurologic manifestations were present in 25.6% of asphyxiated newborns: 40 cases of hypoxic-ischemic encephalopathy (mild in 30, moderate in 5 and severe in 5). The main differences between asphyxiated newborns with and without hypoxic-ischemic encephalopathy were: chronic maternal diseases, pathologic obstetric antecedents, distocic deliveries, neonatal resuscitation, severity of perinatal asphyxia, sex and weight of newborns, days and origin of admission, birth injury, extraneurologic manifestations (mainly pulmonary, digestive, haemodynamic and cardiologic) during neonatal period, and neurologic sequelae at follow-up. CONCLUSIONS: The main perinatal differences in relation to postasphyctic encephalopathy are important in the knowledgement of their pathogenic mechanism (interrelation between neurologic and extraneurologic manifestations) and their follow-up (hypoxic-ischemic encephalopathy is the most important prognostic factor of neurologic sequelae in the full-term asphyctic newborn).

Apgar Score↗

Pathophysiological classification of chronic rhinosinusitis.

BACKGROUND: Recent consensus statements demonstrate the breadth of the chronic rhinosinusitis (CRS) differential diagnosis. However, the classification and mechanisms of different CRS phenotypes remains problematic. METHOD: Statistical patterns of subjective and objective findings were assessed by retrospective chart review. RESULTS: CRS patients were readily divided into those with (50/99) and without (49/99) polyposis. Aspirin sensitivity was limited to 17/50 polyp subjects. They had peripheral blood eosinophilia and small airways obstruction. Allergy skin tests were positive in 71% of the remaining polyp subjects. IgE was<10 IU/ml in 8/38 polyp and 20/45 nonpolyp subjects (p = 0.015, Fisher's Exact test). CT scans of the CRS without polyp group showed sinus mucosal thickening (probable glandular hypertrophy) in 28/49, and nasal osteomeatal disease in 21/49. Immunoglobulin isotype deficiencies were more prevalent in nonpolyp than polyp subjects (p < 0.05). CONCLUSION: CRS subjects were retrospectively classified in to 4 categories using the algorithm of (1) polyp vs. nonpolyp disease, (2) aspirin sensitivity in polyposis, and (3) sinus mucosal thickening vs. nasal osteomeatal disease (CT scan extent of disease) for nonpolypoid subjects. We propose that the pathogenic mechanisms responsible for polyposis, aspirin sensitivity, humoral immunodeficiency, glandular hypertrophy, eosinophilia and atopy are primary mechanisms underlying these CRS phenotypes. The influence of microbial disease and other factors remain to be examined in this framework. We predict that future clinical studies and treatment decisions will be more logical when these interactive disease mechanisms are used to stratify CRS patients.

Adult↗