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PubMed2026

Expert consensus on the reporting and clinical follow up of individuals with incidentally discovered germline RET variants in the UK.

Incidentally discovered pathogenic germline genetic variants refer to the finding of a pathogenic variant in a gene that is unrelated to the reason for the initial test and is not actively sought. Our clinical understanding of the risk of developing a particular medical condition and the required clinical action for a specific pathogenic gene variant is predominantly based on knowledge and information acquired from cases ascertained through a 'phenotype-first approach' rather than in clinically unselected individuals. Therefore, a modified approach is required for incidentally discovered gene variants. Data from large UK and US population-based cohorts have demonstrated that RET variants classified as moderate-risk RET variants as per the American Thyroid Association (ATA) classification have a low penetrance for medullary thyroid cancer and other RET-related conditions (e.g. phaeochromocytoma) and are not associated with excess mortality when identified incidentally in clinically unselected adult individuals. Here, we provide guidance based on multidisciplinary expert consensus opinion for the reporting and subsequent clinical surveillance and management of patients with incidentally discovered RET gene variants in the UK.

Humans↗
PubMedDate not supplied

[The scavenger receptor and its importance in amyloid processes].

The scavenger receptor (SRA or RPA) belongs to a wide family of receptor proteins. The classification is based on sequence homologies and structural similarities; nevertheless, it has been useful to group them on the basis of ligand specificity. The SRA was first identified as a receptor for modified low-density lipoproteins, where such modification permits to regulate the uptake of modified LDL by macrophages leading to a massive cholesterol accumulation. Moreover, SRA facilitates the clearance by phagocytic cells of microbial pathogens and senescent cells. SRA is a transmembrane glycoprotein that exists as a trimer comprised of a cystein-linker dimer and a non-covalently bound monomer. SRA has an a-helical coiled coil domain, which is essential for both trimer formation and acid-dependent ligand dissociation. It also contains a collagenous domain, essential for ligand binding. The majority of these ligands are polyanionic molecules, such as the A beta-peptide, important in the development of Alzheimer's disease. Present findings including our own consider that binding of these peptides to SRA activates an inflammatory response with the production of oxidative stress.

Alzheimer Disease↗
PubMedDate not supplied

Coinfection of specific-pathogen-free chickens with Marek's disease virus (MDV) and chicken infectious anemia virus: effect of MDV pathotype.

Both Marek's disease virus (MDV) and chicken infectious anemia virus (CIAV) infections are prevalent in chickens throughout the world. In the past decade, MDV strains with increased virulence (very virulent plus MDV pathotype [vv+MDV]) have been isolated. The purpose of this experiment was to determine the effects of coinfection of chickens with CIAV and a vv+MDV isolate. Specific-pathogen-free chickens were inoculated at 1 day posthatch with RB1B (very virulent MDV pathotype [vvMDV]) only, 584A (vv+MDV) only, CIAV only, RB1B + CIAV, 584A + CIAV, or nothing. Samples of spleen, thymus, and bursa of Fabricius were collected at 4, 7, 10, and 13 days postinoculation (DPI). Thymic and bursal atrophy at 13 DPI and final mortality at 30 DPI were significantly greater in chickens inoculated with 584A with or without added CIAV, or with RB1B plus CIAV, compared with birds inoculated with RB1B alone. Both amounts of virus reisolated and levels of virus detected by quantitative-competitive polymerase chain reaction were greater at 4 DPI in 584A inoculates compared with RB1B inoculates. To monitor the early cytolytic infection, northern analysis was done with a probe for the MDV immediate early gene ICP4 (infected cell protein 4). In the absence of CIAV, ICP4 expression was more apparent in chickens inoculated with 584A than in those inoculated with RB1B. CIAV coinfection increased ICP4 expression in the spleens of chickens infected with RB1B. These results indicated that inoculation of chickens with the 584A isolate caused a more robust early cytolytic infection compared with inoculation with RB1B alone and support the classification of 584A as a vv+MDV strain. Coinfection with CIAV exacerbated vvMDV strain RB1B infection. The extent of this exacerbation was less evident when birds were coinfected with 584A and CIAV.

Animals↗
PubMed2003

Acute pyelonephritis in adults: prediction of mortality and failure of treatment.

BACKGROUND: To formulate a classification tool for early recognition of patients admitted with acute pyelonephritis (AP) who are at high risk for failure of treatment or for death. METHODS: A retrospective chart review of 225 patients (102 men) admitted with AP. We considered 13 potential risk factors in a multivariate analysis. RESULTS: Recent hospitalization, previous use of antibiotics, and immunosuppression were found to be independent correlates of the prevalence of resistant pathogens in both sexes. Additional predictors included nephrolithiasis in women and a history of recurrent AP in men. Prolonged hospitalization should be expected for a man with diabetes and long-term catheterization who is older than 65 years or for a woman of any age with the same characteristics, when the initial treatment was changed according to the results of urine culture. For mortality prediction, we derived an integer-based scoring system with 6 points for shock, 4 for bedridden status, 4 for age greater than 65 years, and 3 for previous antibiotic treatment for men and 6 points for shock, 4 for bedridden status, 4 for age greater than 65 years, and 3 for immunosuppression for women. Among patients with at least 11 points, the risk for in-hospital death was 100% for men and 91% for women. CONCLUSIONS: Simple variables available at presentation can be used for risk stratification of patients with AP. The additional identification of certain risk factors by means of a carefully obtained history could contribute to early recognition of patients infected by resistant bacteria and optimize the selection of antimicrobial agents.

Adult↗
PubMed2006

Risk of infection and tracking of work-related infectious diseases in the funeral industry.

This review demonstrates that funeral service professionals (FSPs) have a risk of exposure to bacterial and viral pathogens as well as to prion-mediated diseases. It reveals a lack of published studies focusing on the implementation and effectiveness of infection control policies for this occupational group as well as the difficulty involved in determining actual infection rates related to workplace exposure events. Possible reasons for this lack of data include the categorization of these workers by the Bureau of Labor Statistics Standard Occupational Classification System as service providers rather than health care professionals.

Bacterial Infections↗
PubMed2001

Glomerular crescents in renal amyloidosis: an epiphenomenon or distinct pathology?

There have been several reports of cases of renal amyloidosis with glomerular crescents. However, it is not clear whether the association is fortuitous or pathogenic related. The present study analyzed 105 cases of renal amyloidosis (61 autopsy cases and 44 biopsy cases) and found glomerular crescents in 14 (13.3%) cases. Among the 14 cases with crescents, a female predominance was noted (male: female, 3: 11) and rheumatoid arthritis was the most common primary disease of amyloidosis. Immunohistochemical analysis demonstrated amyloid protein of AA type in 12 cases. According to the histologic classification, there were 11 cases of mesangial nodular type, which was almost exclusively accompanied by AA amyloid deposition. Of note, the incidence of crescents neither correlated with the extent of amyloid deposition nor the presence of nephrotic syndrome. By contrast, localization of amyloid deposition was closely related to crescent formation. Moreover, electron microscopic observation displayed rupture of the glomerular basement membrane at the site of amyloid deposition. Our results indicated that glomerular crescents were more frequently associated with renal amyloidosis than previously appreciated. Rupture of the fragile glomerular basement membrane by amyloid deposition, as revealed by immunostaining and electron microscopy, may be the mechanism of crescent formation. We suggest that glomerular crescents are a distinct pathology associated with renal amyloidosis, not fortuitous conditions.

Adult↗
PubMed2005

The Microbial Rosetta Stone database: A common structure for microbial biosecurity threat agents.

Infectious microorganisms are important to multiple communities engaged in biodefense and biosecurity, including the agencies responsible for health, defense, law enforcement, agriculture, and drug and food safety. Many agencies have created lists of high priority infectious microorganisms to prioritize research efforts or to formally control the possession and distribution of specific organisms or toxins. However, the biological classification of infectious microorganisms is often complex and ambiguous, leading to uncertainty and confusion for scientists involved in biosecurity work. To address this problem, we created a database, known as the Microbial Rosetta Stone, which resolves many of these ambiguities and includes links to additional information on the microbes, such as gene sequence data and scientific literature. Here we discuss the efforts to coordinate organism names from pathogen lists from various governmental agencies according to biological relatedness and show the overlap of high-priority organisms from multiple agencies. To our knowledge, this is the first comprehensive coordination of pathogens, synonyms, and correct taxonomic names. The organized tables and visual aids are freely available at http://www.microbialrosettastone.com. This website provides a single location where access to information on a broad range of disease-causing organisms and toxins is available to members of the biosecurity community.

Access to Information↗
PubMed2005

Listeria monocytogenes in the Chinese food system: strain characterization through partial actA sequencing and tissue-culture pathogenicity assays.

Human listeriosis is generally caused by consumption of ready-to-eat (RTE) foods that are stored for extended periods of time at refrigeration temperatures and that permit the growth of the causative agent, Listeria monocytogenes. Food-consumption patterns in China are undergoing rapid changes and more regular consumption of refrigerated-storage RTE foods may increase the risk of human listeriosis. In total, 40 L. monocytogenes isolates were obtained from food (n=32) and sewage (n=6) samples and from two human listeriosis cases that occurred in China. All isolates were characterized into molecular subtypes by DNA sequencing of the 597 bp 3'-terminal region of the virulence gene actA. Sequence data were used to classify the 40 Chinese L. monocytogenes isolates into sequence types and phylogenetic lineages, and to compare the sequence types of the Chinese isolates with those of isolates from the USA. Phylogenetic analyses showed that the Chinese isolates could be separated into two genetic lineages, with 14 and 26 isolates belonging to lineages I and II, respectively. Lineage II could be subdivided further into two clusters, IIA and IIB. Lineages I and II were identical to the two lineages described previously among US L. monocytogenes isolates. In total, 14 actA sequence types could be differentiated among the 40 Chinese L. monocytogenes isolates; two specific actA sequence types were found among both Chinese and US isolates. Isolates belonging to lineage II showed a significantly lower ability to invade and multiply within human intestinal epithelial Caco-2 cells than lineage I isolates. It was concluded that DNA sequencing of the 3'-terminal region of actA appears to be an effective method for rapid subtype and lineage classification of L. monocytogenes. As strains belonging to lineages I and II have previously been found among isolates from Europe and North America, these results show that L. monocytogenes clonal groups found in China are very similar to those found in the USA. Many L. monocytogenes strains may thus represent globally distributed clonal types. Together with the first description of two human listeriosis cases in China, these data indicate that changes in food-distribution and -consumption patterns in China and other countries will probably lead to the emergence of human listeriosis as a food-safety issue, as virulent strains of this pathogen appear to be present in the Chinese food supply.

Adult↗
PubMed1999

Prevalence and risk factors for nosocomial infections in four university hospitals in Switzerland.

OBJECTIVE: To determine the prevalence and risk factors for nosocomial infections (NIs) in four Swiss university hospitals. DESIGN AND SETTING: A 1-week period-prevalence survey conducted in May 1996 in medical, surgical, and intensive-care wards of four Swiss university hospitals (900-1,500 beds). Centers for Disease Control and Prevention definitions were used, except that asymptomatic bacteriuria was not categorized as NI. Study variables included patient demographics, primary diagnosis, comorbidities, exposure to medical and surgical risk factors, and use of antimicrobials. Risk factors for NIs were determined using logistic regression with adjustment for length of hospital stay, study center, device use, and patients' comorbidities. RESULTS: 176 NI were recorded in 156 of 1,349 screened patients (11.6%; interhospital range, 9.8%-13.5%). The most frequent NI was surgical-site infection (53; 30%), followed by urinary tract infection (39; 22%), lower respiratory tract infection (27; 15%), and bloodstream infection (23; 13%). Prevalence of NI was higher in critical-care units (25%) than in medical (9%) and surgical wards (12%). Overall, 65% of NIs were culture-proven; the leading pathogens were Enterobacteriaceae (44; 28%), Staphylococcus aureus (20; 13%), Pseudomonas aeruginosa (17; 11%), and Candida species (16; 10%). Independent risk factors for NI were central venous catheter (CVC) use (odds ratio [OR], 3.35; 95% confidence interval [CI95], 2.91-3.80), admission to intensive care (OR, 1.75; CI95, 1.30-2.21), emergency admission (OR, 1.57; CI95, 1.15-2.00), impaired functional status (Karnofsky index 1-4: OR, 2.56; CI95, 1.953.17), and McCabe classification of ultimately fatal (OR, 2.50; CI95, 2.04-2.96) or rapidly fatal (OR, 2.25; CI95, 1.52-2.98) underlying condition. CONCLUSIONS: According to the results of this survey, NIs are frequent in Swiss university hospitals. This investigation confirms the importance of CVCs as a major risk factor for NI. Patient comorbidities must be taken into account to adjust for case mix in any study comparing interhospital or intrahospital infection rates.

Adolescent↗
PubMed2001

[The importance of different pig diseases in the Netherlands].

As part of the project 'Clean pigs', IPG Institute for Pig Genetics BV made an inventory of the impact of different diseases on the Dutch pig industry. An expert panel assessed the importance of the different diseases with regard to public health, farm economy, the pig sector and export sales. The possibilities for the diagnosis of the different pathogens were listed and the goal for the next years, was set. Diseases were classified into three categories, according to their importance for the Dutch pig industry (Table 2). The diseases that can be eradicated are Salmonella (only specific strains), Pasteurella multocida DNT + PAR), Actinobacillus pleuropneumoniae, Haematopinus suis (lice) and Sarcoptes scabei (var. suis) (mange). National introduction of list A en most list B diseases of the OIE classification must be prevented.

Actinobacillus Infections↗
PubMed2001

[Identification and epidemiologic investigation of bacteria by the Riboprinter Microbial Characterization System, the automated ribotyping system].

An automated ribotyping system, RiboPrinter Microbial Characterization System(Qualicon), was evaluated as a typing tool. Strains used in this study is as follows; 40 strains of methicillin-resistant Staphylococcus aureus (MRSA) with 40 distinct PFGE patterns, 20 MRSA from two hospital ward with suspicion of outbreaks, 53 strains of Escherichia coli including 43 strains of pathogenic E. coli, and 50 strains of Streptococcus pyogenes including 31 strains from patients with severe streptococcal disease. Typeability was 100%. Excellent result was obtained in identificating E. coli including Enterohemorrhagic E. coli O157, but poor in two species of gram positive cocci. Concerning discriminatory power, the RiboPrinter was generally less sensitive than PFGE in identifying different strains, but good correlation with strain relatedness by PFGE and antigenic classification. RiboPrinter surpassed PFGE at handling, result interpretation, and rapidity, therefore, hierarchical approach with the first pass through the RiboPrinter followed by PFGE as the occasion demands can be very useful to save labor. The RiboPrinter has the potential to be a widely useful tool in molecular epidemiology.

Automation↗
PubMed2002

Chlamydia pneumoniae infection and its role in asthma and chronic obstructive pulmonary disease.

Chlamydia pneumoniae (CP) is a common cause of respiratory tract infections, and several studies have asked whether it may play a pathogenic role in connection with bronchial asthma and chronic obstructive pulmonary disease (COPD). Evidence that CP infection is associated with these diseases is a cardinal item. However, evaluation of CP infection is hampered by difficulties in obtaining agreement on the definition of a gold standard. In the literature, serology is based on different cutoff points of antibody titres, which complicates the definition of CP seropositive findings and the classification of acute infection, chronic and past infection. In connection with acute and chronic infection, it is important to demonstrate the presence of CP by culture or polymerase chain reaction (PCR) in the respiratory tract, especially in the lower airways. Often, the results of serology is not associated with the findings by culture or PCR testing, which may involve the risk of inconclusive evidence. Evaluation of a possible presence of CP by clinical improvement after treatment with antibiotics is difficult since uncontrolled studies have been used and other microorganisms are also affected by antibiotics. Furthermore, many patients improve without antibiotics, and improvement has also been observed in patients remaining culture positive after treatment with antibiotics. It should also be noted that the antiinflammatory effects of antibiotics may improve the clinical status of patients. Despite these obstacles, studies point to the possibility that in some patients acute CP infections may lead to acute exacerbations of bronchial asthma. Whether a persistent CP infection contributes to chronic asthma or severe COPD, or whether it incites the diseases in previously healthy individuals is a question for further studies. Whether a causal relationship exists between CP infection and obstructive pulmonary disease or whether these patients are more susceptible to CP infection is unknown. Nevertheless, a cooperative role of CP in the proinflammatory mechanisms involved in these diseases remains to be examined since cellular studies show that CP stimulates the production and expression of cytokines, chemokines and adhesion molecules, actions that may amplify and prolong the inflammation.

Asthma↗
PubMedDate not supplied

[Morphopathological study of 101 hearts with interventricular septal defect].

The various terms and classifications of ventricular septal defects (VSD) stimulated us to perform the present study with the purpose of adopting a common terminology and classification in which morphologic, topographic and surgical criteria concur. One hundred and one VSD where studied by means of the sequential segmental approach from the pathologic collection of the Instituto Nacional de Cardiología "Ignacio Chávez". The ventricular septum (VS) was divided in four areas, three muscular (inlet, trabecular and outlet) and one perimembranous. The VSD where described and cathegorized according to their tissue borders, localization and relationship with the cardiac valves and the conduction tissue. The results were: Perimembranous type (77 = 77.23%), with the subtypes according to the muscular extensions: inlet (31 = 39.75%), inlet and trabecular (25 = 32.05%), with three extensions (17 = 21.80%), inlet and outlet (2 = 2.56%), outlet (1 = 1.28%), trabecular (1 = 1.28%), trabecular and outlet (1 = 1.28%); trabecular (9 = 8.91%), outlet (7 = 6.93%), inlet (3 = 3.97%) and mixed types (4 = 3.96%). The topographic-structural classification permits the localization of VSD, as well as to specify their border's tissue and their relationship with the cardiac valves and conduction system. Knowledge of the surgical anatomy of VSD is useful to the surgeon, and constitutes the basis to interpret with precision the diagnostic imaging studies. Delay in the development of the embryonic primordia of the VS and the absence of septal consolidation are the pathogenic mechanisms involved.

Heart Septal Defects, Ventricular↗
PubMed2006

Backfilling missing microbial concentrations in a riverine database using artificial neural networks.

Predicting peak pathogen loadings can provide a basis for watershed and water treatment plant management decisions that can minimize microbial risk to the public from contact or ingestion. Artificial neural network models (ANN) have been successfully applied to the complex problem of predicting peak pathogen loadings in surface waters. However, these data-driven models require substantial, multiparameter databases upon which to train, and missing input values for pathogen indicators must often be estimated. In this study, ANN models were evaluated for backfilling values for individual observations of indicator bacterial concentrations in a river from 44 other related physical, chemical, and bacteriological data contained in a multi-year database. The ANN modeling approach provided slightly superior predictions of actual microbial concentrations when compared to conventional imputation and multiple linear regression models. The ANN model provided excellent classification of 300 randomly selected, individual data observations into two defined ranges for fecal coliform concentrations with 97% overall accuracy. The application of the relative strength effect (RSE) concept for selection of input variables for ANN modeling and an approach for identifying anomalous data observations utilizing cross validation with ANN model are also presented.

Bacteria↗
PubMed1980

Numerical and DNA: DNA reassociation analyses of Erwinia rubrifaciens and other members of the Enterobacteriaceae.

Phenetic data on 75 strains of Erwinia and other representative genera of the Enterobacteriaceae were collected and analysed using two numerical taxonomic methods. In both methods the same subclusters were recovered. The subclusters, however, were defined at different similarity levels and were classified into clusters of different composition. Erwinia rubrifaciens strains formed a very tight, homogeneous subcluster, completely distinct and readily distinguishable from other Erwinia and enterobacteria species studied. DNA: DNA hybridization between E. rubrifaciens and Erwinia and Shigella species were analysed to corroborate the numerical classifications. A good correlation between the numerical and DNA: DNA hybridization analyses was found and provided sufficient evidence for not supporting the previously proposed subspecific taxonomic position of E. rubrifaciens. The data clearly showed that E. rubrifaciens is a separate species in its own right. Based on the existence of very high genetic relatedness and high similarities in phenetic characters among E. rubrifaciens strains and the confinement of the pathogen to the state of California, the hypothesis is offered that E. rubrifaciens originated from a single source.

DNA, Bacterial↗
PubMed1992

Membrane properties of a plant-pathogenic mycoplasmalike organism.

In terms of biosystematics, the plant-pathogenic mycoplasmalike organisms (MLOs) have been tentatively placed into the class Mollicutes. Certain physiological tests have been used to distinguish families within this class: the sterol-nonrequiring Acholeplasmataceae differ from the sterol-requiring Mycoplasmataceae in that the former are more resistant to lysis by digitonin and more sensitive to lysis in hypotonic salt solutions. To test MLOs for these membrane properties and thus assist in their definitive classification, a dot-blot microassay procedure was used to detect nucleic acids released from lysed cells. The results show that MLOs resemble acholeplasmas grown in the absence of sterols in that they are resistant to digitonin and sensitive to hypotonic salt solutions. The MLOs can be differentiated from acholeplasmas grown without sterols by their greater resistance to lysis in hypotonic sucrose solutions.

Acholeplasma laidlawii↗
PubMed2002

The mouse as a model for investigation of human granulocytic ehrlichiosis: current knowledge and future directions.

The use of laboratory mice to investigate correlates of infectious disease, including infection kinetics, cellular alterations, cytokine profiles, and immune response in the context of an intact host has expanded exponentially in the last decade. A marked increase in the availability of transgenic mice and research tools developed specifically for the mouse parallels and enhances this research. Human granulocytic ehrlichiosis (HGE) is an emerging, zoonotic disease caused by tick-borne bacteria. The HGE agent (Anaplasma phagocytophila) is one of two recognized pathogens to cause human granulocytic ehrlichiosis (HGE). The mouse model of HGE complements in vitro tissue culture studies, limited in vivo large animal studies, and ex vivo studies of human and ruminant neutrophils, and promises new avenues to approach mechanisms of disease. In the overview reported here, we focus principally on current research into HGE pathogenesis using the mouse model. Included is a discussion of current changes in ehrlichial classification and nomenclature, a review of ehrlichial biology and ecology, and highlights of clinical disease in animals and people.

Anaplasma phagocytophilum↗
PubMed1995

Postoperative wound infections: risk factors and role of Staphylococcus aureus nasal carriage.

In the United States the rate of postoperative wound infection varies from one to nine per cent, depending on the surgical procedure. Each postoperative wound infection increases the length of stay in hospital, the cost of the procedure and is associated with significant morbidity. Staphylococcus aureus is the causative agent in 15 to 20% of these infections, although the pathogen isolated varies according to the surgical site. Risk factors for acquiring an infection can be divided into the following categories: host factors, surgical and environmental factors, and microbial characteristics. Host factors which may contribute to an increased risk of infection include: age, prolonged pre-operative length of stay, and concurrent infection at another body site. Increased infection risk may result from an extended surgical procedure, the wound classification, the use of a razor for hair removal before surgery and may also be dependent on the surgeon's technical skill. Microbial factors related to the risk of developing an infection postoperatively are less well defined, however, many outbreaks of surgical wound infections have been linked to personnel carrying an organism which is then transmitted to the patient. Furthermore, patients who carry intranasal S. aureus have a two-to ten-fold increased likelihood of developing a postoperative wound infection due to S. aureus. Identification of patients most at risk of developing an infection is the ultimate goal, however, risk indices must be highly sensitive, specific and accurate. To summarize, the epidemiology of postoperative wound infections remains poorly studied, however, since wound infections contribute significantly to morbidity, mortality and cost, future research is warranted.

Humans↗