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PubMed2005

Population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam in patients with complicated intra-abdominal infection.

OBJECTIVES: We investigated the population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam in hospitalized patients. PATIENTS AND METHODS: A multicentre, randomized clinical trial was conducted in hospitalized patients with complicated intra-abdominal infection. Patients received piperacillin/tazobactam administered by either continuous infusion (13.5 g over 24 h, n = 130) or intermittent infusion (3.375 g every 6 h, n = 132). NONMEM was used to perform population pharmacokinetic analysis in a subset of patients (n = 56) who had serum samples obtained at steady-state for drug concentration analyses. Classification and regression tree analysis was used to identify the breakpoints of piperacillin PK-PD indexes in 94 patients with causative pathogen's MIC. RESULTS: A one-compartment model was applied to fit the data. Creatinine clearance and body weight were the most significant variables to explain patient variability in piperacillin and tazobactam clearance and volume of distribution. The infusion method had no influence on PK parameters. For patients (n = 30) receiving intermittent infusion in the pharmacokinetic study, mean Cmax and half-life were 122.22 mg/L and 1.17 h for piperacillin, and 15.74 mg/L and 1.81 h for tazobactam. For patients (n = 26) receiving continuous infusion in the pharmacokinetic study, mean steady-state concentration was 35.31 +/- 12.15 mg/L for piperacillin and 7.29 +/- 3.28 mg/L for tazobactam. As a result of a low rate of failures (<11%) observed in the trial and the low MICs for infecting pathogens, no association could be established between clinical/microbiological outcome and drug exposure. CONCLUSIONS: Intermittent infusion and continuous infusion of piperacillin and tazobactam provided sufficient drug exposure to treat those pathogens commonly implicated in intra-abdominal infections.

Abdomen↗
PubMed2000

Mitochondrial cytochrome b gene analysis of Aspergillus fumigatus and related species.

Nucleotide sequences of 426 bp from the mitochondrial (mt) cytochrome b genes of six anamorph species and two species of Neosartorya teleomophs of Aspergillus section Fumigati were determined. These sequences were used to build nucleotide- and amino acid-based trees for phylogenetic analysis. Thirteen strains of A. fumigatus including 10 clinical isolates of A. fumigatus, 1 type culture of A. fumigatus var. fumigatus, 1 type culture of A. fumigatus var. ellipticus, and 1 strain of A. fumigatus var. albus, had the same nucleotide sequences. One strain of A. fumisynnematus, two strains labeled A. neoellipticus, two strains of A. viridinutans, and one strain of A. duricaulis had distinct nucleotide and amino acid sequences. Two strains of A. brevipes were divided into two types. One produced a 1,500-bp fragment that included an intron. The nucleotide sequences of its two exons were similar to those of the A. fumigatus, and the derived amino acid sequence was the same as that for A. fumigatus. The other produced a 426-bp fragment and had the same nucleotide and amino acid sequences as A. unilateralis. Neosartorya fischeri var. fischeri and N. stramenia had nucleotide sequences that differed from that of A. fumigatus. These species possessed their own characteristic nucleotide sequences that differed from each other. In comparisons of homologous sequences from four other pathogenic species of Aspergillus, regions specific to section Fumigati were found. The mt cytochrome b gene analysis was valuable for the identification, classification, and phylogenetic analysis of isolates of section Fumigati.

Amino Acid Sequence↗
PubMed1998

The evolving contribution of renal pathology to understanding interstitial nephritis.

One hundred years of progress in the study of interstitial nephritis has expanded our diagnostic entities, resulted in identification of numerous pathogenic events, and defined the nature of the inflammatory infiltrate in ways that are useful both for general understanding and for diagnostic classification. We stand poised to enter the next hundred years with new techniques applicable to renal biopsies that detect specific biologic activities in situ in tissue sections. In the future, the information gained from these techniques is likely to result in refined and more accurate assessments of prognosis in patients with kidney disease, and to guide therapeutic interventions designed to interrupt specific sequences of active renal injury.

Biopsy↗
PubMedDate not supplied

Spectrum of autoimmune responses in systemic vasculitis.

Growing evidence supports the inclusion of primary forms of systemic vasculitis within the category of autoimmune diseases. Thus their association with a family of autoantibodies, related to their specificity or neutrophil cytoplasm antigens, has been identified and the role these autoantibodies play in pathogenesis is now being explored. Different members of the autoantibody family have now been characterised in terms of their molecular specificity and the isotype of immunoglobulin of which they are composed. These properties may be a useful adjunct in the classification of systemic vasculitis (see table I). It is the purpose of this review to put a perspective on the specificity and pathogenicity of autoantibodies found in patients with systemic vasculitis and to outline new strategies for the treatment of these conditions, based on the involvement of autoimmune mechanisms in the development of these disorders.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1990

[Etiology, diagnosis and therapy of soft tissue infections].

Soft tissue infections are caused by a multitude of bacteria. Their pathogenicity depends on the ability to adhere to surfaces, certain characteristics of the cell wall, exoenzymes or exotoxins, and endotoxins. Because etiologic classification of soft tissue infections is not satisfactory, we propose a clinical classification. 1. Abscesses are caused by staphylococci (carbuncle or suppurative hydroadenitis) or by polymicrobial infections (most subcutaneous abscesses). They are treated by incision and drainage and primary closure of the skin after drainage and curettage is often successful. Only in special cases are antibiotics indicated. 2. Cellulitis mostly caused by streptococci responds well to antibiotic therapy without surgery. 3. Ulcerative lesions i.e. pseudomonal gangrene and Meleney's gangrene need specific antibiotic therapy and complete excision with delayed grafting.

Abscess↗
PubMed1982

Studies on the etiology and symptomatology of root and storage rot disease of cocoyam in Nigeria.

The losses caused by root and storage rot of cocoyam in Nigeria are estimated as 40 to 45%. Field symptoms of the disease include inhibited growth, leaf chlorosis followed by necrosis and shrivelling of affected parts, and finally premature death of the aerial portions of the plant. A large proportion of the roots are destroyed. Poor production of cormels and reduced corm size are other field symptoms of the disease, differing according to the type of causal agent. Botryodiplodia theobromae, Fusarium solani, F. moniliforme, and Sclerotium rolfsii were isolated from diseased corms, occurring single or in mixed infection. All isolated fungi proved pathogenous on Xantbosoma spec. as well as on Colocasia spec., with Colocasia exhibiting greater damages. Three types of rot are suggested for classification of cocoyam rot in Nigeria: black rot, Fusarium rot, Sclerotium rot.

Fusarium↗
PubMedDate not supplied

[isolation and identification of Yersinia enterocolitica (author's transl)].

The classification of the Yersinia enterocolitica group into the true Yersinia enterocolitica and the Yersinia enterocolitica-like types based on DNA structure, pathogenicity, host-adaptation and ecology, tables III and IV, is now so well established that relatively few biochemical tests, table I, easily differentiate the true Yersinia enterocolitica from the Yersinia enterocolitica-like types, and further differentiate the 6 biotypes, table II. The isolation technique is described in details and in a flow diagram, table V. The use of a selective enrichment- and subcultivation-technique separate the human-pathogenic serotypes from the environmental, saprophytic types.

Antigens, Bacterial↗
PubMed1990

Safety aspects in biotechnology. Classifications and safety precautions for handling of biological agents.

The term "biotechnology" is today used much more widely than 10 years ago. According to the modern definition, biotechnology represents the "conveyor belt" which brings advances in the fields of molecular biology, cell biology, molecular genetics, microbiology, biochemistry and process engineering, etc., into the areas of application. It is attempted to indicate the development of safety standards concerning biotechnology. This development is in a state of flux, and the finding that the risks in handling r-DNA organisms are not larger than those arising when handling the known pathogens is becoming more accepted. Accordingly, these r-DNA organisms can also be classified into the known risk groups I-IV and handled under the corresponding safety conditions according to this classification: In the laboratory under the laboratory safety measures L1-L4 described in the BMFT-Guidelines or guidelines for occupational health and hygiene (UVV Biotechnologie) and on a process scale under the process safety measures described in the OECD report. The discussion of aspects on waste disposal, education/training and public perception in the field of biological safety completes the report.

Biotechnology↗
PubMed2003

Classification of B-cells according to their differentiation status, their micro-anatomical localisation and their developmental lineage.

B-lymphocytes or B-cells form a diverse and flexible repertoire of immune cells that are reactive to almost all potential pathogens by means of the production of antigen-specific immunoglobulins. They can be divided into different populations or subsets, characterised by a distinct combination of properties. These subsets are identified on the base of their differentiation status (precursor B-cells, peripheral B-cells), their localisation in the micro-anatomical compartments of the B-cell follicle (marginal zone B-cells, lymphocytic corona B-cells, follicle centre B-cells), and the developmental lineage to which they belong (B-1 cells, and B-2 or conventional B-cells). The latter classification of B-cells into B-1 cells and B-2 cells is commonly followed by immunologists, mainly in the study of mice models, while pathologists and haematologists tend to use a terminology for B-cells which refers to their localisation in the micro-anatomical compartments of the B-cell follicle and/or differentiation status. In this review, we will discuss the various subsets of B-cells and point to the similarities between the various classification systems in use.

Animals↗
PubMed2006

Identification of Vibrio isolates by a multiplex PCR assay and rpoB sequence determination.

Vibrio, a diverse genus of aquatic bacteria, currently includes 72 species, 12 of which occur in human clinical samples. Of these 12, three species--Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus-account for the majority of Vibrio infections in humans. Rapid and accurate identification of Vibrio species has been problematic because phenotypic characteristics are variable within species and biochemical identification requires 2 or more days to complete. To facilitate the identification of human-pathogenic species, we developed a multiplex PCR that uses species-specific primers to amplify gene regions in four species (V. cholerae, V. parahaemolyticus, V. vulnificus, and V. mimicus). The assay was tested on a sample of 309 Vibrio isolates representing 26 named species (including 12 human pathogens) that had been characterized by biochemical methods. A total of 190 isolates that had been identified as one of the four target species all yielded results consistent with the previous classification. The assay identified an additional four V. parahaemolyticus isolates among the other 119 isolates. Sequence analysis based on rpoB was used to validate the multiplex results for these four isolates, and all clustered with other V. parahaemolyticus sequences. The rpoB sequences for 12 of 15 previously unidentified isolates clustered with other Vibrio species in a phylogenetic analysis, and three isolates appeared to represent unnamed Vibrio species. The PCR assay provides a simple, rapid, and reliable tool for identification of the major Vibrio pathogens in clinical samples, and rpoB sequencing provides an additional identification tool for other species in the genus Vibrio.

Bacterial Typing Techniques↗
PubMed1988

[Multiple autoimmune syndromes].

The possibility of three or more autoimmune diseases occurring in the same patient cannot be fortuitous and suggests a pathogenic relationship between each of them. In the light of 4 personal cases, the authors have recorded 87 reports of such associations in the literature, an analysis of which leads them to propose a classification of three types of multiple autoimmune syndrome. The grouping of these syndromes under a single heading should make the research and analysis of these morbid associations easier. Moreover, the classification adopted by the authors allows a more precise definition of patients with at least two autoimmune diseases and so helps to recognize the onset of a third autoimmune disease at a later date. Multiple autoimmune syndromes can be classified in 3 groups according to the prevalence of their associations one with another. Type I comprises myasthenia, thymoma, polymyositis and giant cell myocarditis, this association having a single pathogenic mechanism. Type II includes the Sjögren's syndrome, rhumatoid arthritis, primary biliary cirrhosis, scleroderma and autoimmune thyroid disorders. Type III groups together 10 autoimmune diseases (autoimmune thyroid disease, myasthenia and/or thymoma, Sjögren's syndrome, pernicious anaemia, idiopathic thrombocytopaenic purpura, Addison's disease, insulin-dependent diabetes, vitiligo, autoimmune haemolytic anaemia, systemic lupus erythematosus) for which a genetic predisposition (phenotype HLA B8 and/or DR3 or DR5) seems to be an important factor.

Adult↗
PubMed2001

Gene genealogies, cryptic species, and molecular evolution in the human pathogen Coccidioides immitis and relatives (Ascomycota, Onygenales).

Previous genealogical analyses of population structure in Coccidioides immitis revealed the presence of two cryptic and sexual species in this pathogenic fungus but did not clarify their origin and relationships with respect to other taxa. By combining the C. immitis data with those of two of its closest relatives, the free-living saprophytes Auxarthron zuffianum and Uncinocarpus reesii, we show that the C. immitis species complex is monophyletic, indicating a single origin of pathogenicity. Cryptic species also were found in both A. zuffianum and U. reesii, indicating that they can be found in both pathogenic and free-living fungi. Our study, together with a few others, indicates that the current list of known fungal species might be augmented by a factor of at least two. However, at least in the C. immitis, A. zuffianum, and U. reesii complexes, cryptic species represent subdivisions at the tips of deep monophyletic clades and thus well within the existing framework of generic classification. An analysis of silent and expressed divergence and polymorphism values between and within the taxa identified by genealogical concordance did not reveal faster evolution in C. immitis as a consequence of adaptation to the pathogenic habit, nor did it show positive Darwinian evolution in a region of a dioxygenase gene (tcrP gene coding for 4-HPPD) known to cause antigenic responses in humans. Instead, the data suggested relative stasis, indicative of purifying selection against mostly deleterious mutations. Two introns in the same gene fragment were considerably more divergent than exons and were unalignable between species complexes but had very low polymorphism within taxa.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed1998

Serum concentrations of soluble human leukocyte class I antigens and of the soluble intercellular adhesion molecule-1 in endometriosis: relationship with stage and non-pigmented peritoneal lesions.

Serum concentrations of soluble human leukocyte class I antigens (sHLA-I) and of the intercellular adhesion molecule-1 (sICAM-1) are increased in the early inflammatory stages of several immune-related diseases. These soluble molecules also exert immunomodulatory activity, including regulation of natural killer (NK) cell cytotoxicity. The aim of this study was to verify whether sHLA-I and sICAM-1 serum concentrations are related to the various stages of pelvic endometriosis, which is an immune-related disorder associated with impaired in-vitro NK cell activity. Serum sHLA-I and sICAM-1 concentrations were similar in patients and in healthy donors. However, when evaluated according to disease stage, sHLA-I and sICAM-1 concentrations were higher in patients with endometriosis stage I-II (revised American Fertility Society classification), or with non-pigmented peritoneal lesions. In conclusion, studies on sHLA-I and sICAM-1 may help to clarify the pathogenic mechanisms of endometriosis, and their serum concentrations may serve as additional markers for the early detection of recurrence of the disease during the monitoring of treatment outcome.

Adult↗
PubMed2003

Hypospadias in California: trends and descriptive epidemiology.

BACKGROUND: The occurrence of hypospadias has been reported to be increasing. The objectives of this study were to extend the literature on the descriptive epidemiology of hypospadias and to determine whether its birth prevalence increased in California in recent years. We used actively ascertained, population-based data for which detailed clinical descriptions permitted careful phenotypic classifications. METHODS: We examined registry data on 5838 male live births and stillbirths that occurred in California from 1984 through 1997. To reduce pathogenic heterogeneity, cases were classified as mild, severe, or not otherwise specified based on the anatomic position of the urethral opening. We also classified cases as isolated or nonisolated based on the presence and type of accompanying malformations. We used multivariable Poisson regression analysis to examine time trends and risk factors. RESULTS: There was no evidence for an increase in prevalence of any of the case groups between 1989 and 1997. The adjusted relative risk (RR) for change in prevalence per year of isolated severe cases was 0.99 (95% confidence interval = 0.96-1.03). Adjusted RRs indicated increased risks for specific types of hypospadias with maternal non-Hispanic white race-ethnicity, higher education, older age, and nulliparity. Delivery before 37 weeks and multiple births tended either not to be associated with risk or to be associated with reduced risk. Lower birthweight was associated with increased risk for all case groups. CONCLUSIONS: This study suggests that hypospadias prevalence has not been increasing in California in recent years. Differences by phenotype suggest that examining certain phenotypes separately could help to understand hypospadias etiology.

California↗
PubMed2005

Current status and future directions for Laribacter hongkongensis, a novel bacterium associated with gastroenteritis and traveller's diarrhoea.

PURPOSE OF REVIEW: Despite extensive investigations, a microbiological cause cannot be found in about half of the patients with infectious disease. Throughout the years, scientists have spent tremendous efforts in looking for microorganisms associated with these "unexplained infectious disease syndromes". Recently, a novel bacterium, Laribacter hongkongensis, was discovered and shown to be associated with gastroenteritis and traveller's diarrhoea. This review summarizes the current status, and shares with the readers the authors' experience in the microbiology, classification, epidemiology, clinical disease, laboratory diagnosis, antibiotic resistance and treatment of L. hongkongensis. It also discusses the importance and perspective of describing novel pathogenic bacterial species. RECENT FINDINGS: L. hongkongensis was shown to be associated with gastroenteritis and traveller's diarrhoea. Consumption of fish was associated with recovery of L. hongkongensis. Freshwater fish was a reservoir of L. hongkongensis. Genotypic typing revealed the possibility of virulent clones of L. hongkongensis. The class C beta-lactamase of L. hongkongensis has been cloned and characterized. SUMMARY: In 2001, L. hongkongensis, a novel genus and species, was first discovered in Hong Kong from the blood and empyema pus of a patient with alcoholic cirrhosis. Subsequently, it was isolated from patients in other parts of the world. Recently, this bacterium was found to be associated with community-acquired gastroenteritis and traveller's diarrhoea using cefoperazone MacConkey agar as the selective medium. Further studies, including setting up of animal and tissue culture models and characterization of virulence factors, should be performed. For pathogenic microbes, even one strain of a novel species should be described, so that global concerted efforts can be drawn to look for more cases associated with such a pathogen.

Diarrhea↗
PubMed1982

The evaluation of autofluorescence emission spectra derived from neuronal lipopigment.

A method for measuring the emission spectra from regions of neuronal lipopigment in tissue sections is described and illustrated. Each emission spectrum was derived from the means of six sets of readings, from either six regions of lipopigment from six neurones which were presumed to be from a homogeneous cell population, or from one region of one neurone. Characteristics of the emission spectra from lipopigment in various forms of neuronal ceroid-lipofusinoses (NCLs) and in brains without evidence of NCL are presented and discussed. The results indicate that the classification of lipopigments should not be restricted to the two categories of 'lipofuscin' and 'ceroid'. This method may aid the identification of various pathogenic mechanisms in neurones, and provide another means of investigating the effects of certain drugs on cerebral function.

Aged↗
PubMed2003

[Antiphospholipid antibodies].

The concept of antiphospholipid syndrome(APS) has been widely accepted. Antiphospholipid antibodies originally included anticardiolipin antibodies and lupus anticoagulants as serological marker of APS. However, recent advances have shown that most pathogenic antiphospholipid antibodies are directed to phospholipid binding proteins such as beta 2-glycoprotein I and prothrombin as well as phospholipids. The preliminary classification criteria for definite APS have been advocated as the "Sapporo criteria". Further prospective investigations are required to re-evaluate the clinical significance of so-called antiphospholipid antibodies.

Antibodies, Antiphospholipid↗
PubMed1991

[Occupational risk factors in the biotechnology industry and workers' health status].

The mechanisms of the pathogenic effect of microbial cultures used in biotechnological industry and the products of their vital activity on the workers were investigated. A unique classification of the components of the disease incidence with temporary disability is described. The necessity of detecting prepathological conditions and initial occupational affections in the workers for preventing severe consequences of occupational diseases is indicated. On the basis of complex investigations of disease incidence in the workers, revision of the present sanitary and hygienic regulations may be of need.

Biotechnology↗