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Secondary mycosis in surgery: treatment with fluconazole.

Together with the severity of the underlying disease, mycotic infections are assuming increasing significance in surgical patients under intensive care. 26 patients with severe internal mycotic infections were treated with fluconazole in an open clinical trial. The pathogens isolated were Candida albicans in 22 cases, Candida tropicalis in four, Torulopsis glabrata in three, Candida parapsilosis in two and Aspergillus fumigatus in one. Mixed infections were found in five cases. Most of this series of surgical patients had a severe, life-threatening post-operative condition. Their mean classification by the Apache score was 15.35. The most frequent risk factors were previous injuries to intraabdominal hollow organs and extensive antibiotic therapy; and the peritoneum was, therefore, the commonest site of infection. Antimycotic therapy was with fluconazole at a dose of 200-400 mg daily for at least ten days. The mycosis was cured in 22 of the 26 patients, one of these being a case of severe mycotic peritonitis. Nine patients died of the underlying disease within four weeks of the beginning of treatment. Fluconazole was effective and well tolerated in the treatment of severe life-threatening infections in surgical patients.

Adult↗

[Human intestinal spirochetosis].

Whenever biopsy material obtained from endoscopically normal colorectal mucosa reveals the blue haematoxyphilic line between the microvilli of the covering epithelium, the rare condition of intestinal spirochetosis is diagnosed. The classification of the bacteria detected with the aid of special stains (e.g. the Warthin Starry silver stain) and in the electron microscope, continues to be something of a problem. A further point of contention is the question whether this spirochetal infection is of pathological significance or not. A point mitigating against pathogenicity is the fact that no histological signs of an inflammatory reaction are to be seen. Also, the symptoms of patients with intestinal spirochetosis are such that they provide no basis for a pronouncement on whether the infection is of a pathological or a pathological nature. On the other hand, however, a number of studies do seem to indicate that the spirochetes might be the cause of such symptoms as diarrhoea, constipation and abdominal pain. A point that would appear to support this view is the fact that such symptoms may disappear after successful treatment with metronidazole. The histological diagnosis is easily established when, faced by an apparently normal histological appearance of the colorectal mucosa, the pathologist considers the possibility of spirochetosis, and undertakes a specific search for the blue haematoxyphilic line in the covering epithelium of the colorectal mucosa.

Anti-Bacterial Agents↗

Cryptococcosis.

In the past 2 decades, Cryptococcus has emerged in its clinical significance and as a model yeast for understanding molecular pathogenesis. C neoformans and C gattii are currently considered major primary and secondary pathogens in a wide array of hosts that are known to be immunocompromised or apparently immunocompetent. A recent outbreak of C gattii infections further underscores the clinical importance of the yeast through its epidemiology and pathogenicity features. With an enlarging immunosuppressed population caused by HIV infection, solid organ transplantation, and clinical use of potent immunosuppressives, such as cancer chemotherapy, monoclonal antibodies, and corticosteroids, this fungus has become a well-established infectious complication of modern medicine. This article examines current issues in cryptococcal infections, including new classification, epidemiology, pathogenesis, and specific clinical aspects.

Cryptococcosis↗

Biochemical identification and numerical taxonomy of Aeromonas spp. isolated from environmental and clinical samples in Spain.

AIMS: To study the phenotypic characteristics of Aeromonas spp. from environmental and clinical samples in Spain and to cluster these strains by numerical taxonomy. METHODS AND RESULTS: A collection of 202 Aeromonas strains isolated from bivalve molluscs, water and clinical samples was tested for 64 phenotypic properties; 91% of these isolates were identified at species level. Aeromonas caviae was predominant in bivalve molluscs and Aerom. bestiarum in freshwater samples. Cluster analyses revealed eight different phena: three containing more than one DNA-DNA hybridization group but including strains that belong to the same phenospecies complex (Aerom. hydrophila, Aerom. sobria and Aerom. caviae), Aerom. encheleia, Aerom. trota and three containing unidentified Aeromonas strains isolated from bivalve molluscs. CONCLUSIONS: Aeromonas spp. are widely distributed in environmental and clinical sources. A selection of 16 of the phenotypical tests chosen allowed the identification of most isolates (91%), although some strains remain unidentified, mainly isolates from bivalve molluscs, suggesting the presence of new Aeromonas species. Numerical taxonomy was not in total concordance with the identification of the studied strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Numerical taxonomy of Aeromonas strains isolated from different sources revealed the presence of potentially pathogenic Aeromonas spp., especially in bivalve molluscs, and phena with unidentified strains that suggest new Aeromonas species.

Aeromonas↗

Typing of heat-stable soluble Haemophilus parasuis antigen by means of agargel precipitation and the dot-blot procedure.

According to Morozumi's and Nicolet's (1986) investigations, a serological classification procedure for H. parasuis and to a certain extent, for H. parasuis-like strains was proposed on the basis of heat-stable cell antigens in the immunodiffusion test. It was possible to classify 72.8% of the investigated strains serologically using this procedure. 7 of 12 serotypes were described for the first time. 60.1% of the classified strains belonged to the already known serotypes SV 1 to SV 5, whereas the new serotypes SV Jena 6 to SV Jena 12 amounted to only 12.7% of the field isolates. The serotypes SV Jena 7 to 9 are represented by H. parasuis-like strains. Unencapsulated strains and isolates of serotype SV 5 dominate in animals with Glasser's disease. The serotypes SV 1, SV 5, Jena 6 and SV Jena 10 proved to be highly virulent in SPF pigs, SV 2 and SV 4 were of medium virulence. The other serotypes were non-virulent. The high specificity in AGPT was not reproducible in the more sensitive dot-blot procedure. This must be taken into account, if the dot-blot is to be used for the classification of serotypes of H. parasuis. The results point to a participation of nonimmunogenic polysaccharides in the detection reaction.

Animals↗

Headache and systemic lupus erythematosus.

Headache is a common feature in patients with systemic lupus erythematosus (SLE) and represents a significant source of patient discomfort. The exact prevalence of headache in SLE is unknown. The results of different studies widely vary, most likely due to the use of different classification for headache and the lack of controls in most studies. The relationship between headache and SLE is also unclear since it is difficult to determine which degree and type of headaches can be explained on the basis of chronic illness, or as part of the disease spectrum of SLE. No pathogenic mechanism has so far been described that can fully explain headache induced by SLE. The role of circulating cytokines, vascular injury, neuronal damage or antiphospholipid antibodies (aPL) in the development of headache in SLE patients is also a matter of debate. Other concomitant causes such as infection or hypertension should be excluded before assuming that headache is a feature of SLE activity. Therapeutic approach of headache SLE-related remains empirical and based on clinical experience.

Adrenal Cortex Hormones↗

The KEAP1-NFE2L2/NRF2 Axis in Non-Small Cell Lung Cancer Radioresistance: Redox Homeostasis and Emerging DNA Damage Response Mechanisms.

Radioresistance and local recurrence remain major barriers to effective radiotherapy in non-small cell lung cancer (NSCLC). Loss-of-function KEAP1 alterations or activating NFE2L2 alterations can stabilize NRF2, but do not alone establish sustained transcriptional activity or functional dependency. This focused narrative review evaluates clinical radiotherapy studies and mechanistically informative preclinical studies linking the KEAP1-NFE2L2/NRF2 axis to NSCLC radioresistance. We prioritized clinical studies reporting radiotherapy-specific outcomes and preclinical studies coupling NRF2-related molecular status or perturbation with radiation-response endpoints; contextual studies informed metabolic, DNA damage response (DDR), immune and normal-lung effects. Evidence most consistently supports NRF2-mediated redox protection through glutathione-dependent defense, cellular reducing capacity and antioxidant enzymes, limiting radiation-induced reactive oxygen species (ROS) accumulation and oxidative injury. Limited studies further suggest that NRF2 may affect DNA-damage signaling, checkpoint control and repair. The detailed RPA32-TOPBP1-ATR-CHK1 model is therefore considered proposed rather than established in NRF2-active NSCLC. Retrospective clinical studies associate pathogenic KEAP1/NFE2L2 alterations with impaired local control in some radiotherapy-treated cohorts, but do not justify treating genomic status, protein abundance, transcriptional activity and functional dependency as equivalent measures or demonstrate treatment-predictive value. NRF2-mediated normal-lung protection also constrains systemic inhibition. Prospective studies integrating molecular classification, radiation-response endpoints, local control and normal-tissue toxicity are required before biomarker-guided radiosensitization can be considered.

DNA damage response↗

[Comparison of genomes of new gigantic Pseudomonas aeruginosa phages from native populations from different regions].

To study the genome diversity of bacteriophages from geographically distant natural populations, new giant phi KZ-like Pseudomonas aeruginosa phages isolated in two different regions were compared with earlier known phages of three species (phi KZ, Lin68, EL). A broad spectrum of lytic activity was demonstrated for all phi KZ-like phages. Phages of the phi KZ species proved to be common in natural populations of various regions, while IL- and Lin68-related phages were extremely rare. Most phi KZ-related phages had unique DNA restriction patterns, but the differences between these were only minor, and the genomes did not contain nonhomologous fragments. The spectrum of capsid polypeptides proved to be conserved in each species, and was proposed as a character necessary and sufficient for express classification of phages with an accuracy of species. Phages isolated in different geographical regions showed no substantial difference. Some phages only slightly differing in DNA restriction pattern from phi KZ may be used to study the origin of phi KZ genes coding for orthologs of proteins of unrelated species (other phages, pathogenic bacteria, eukaryotes).

Blotting, Western↗

Epidermolysis bullosa.

The disorders known as epidermolysis bullosa constitute a group of genetic diseases of the skin which in the mildest form are debilitating throughout life and in the most severe forms result in death at an early age. The profound morbidity associated with all forms of the disease results not only in the loss of an economically productive life but also, in many cases, in the need for continuing medical care throughout life. Inroads are being made into potential pathogenic mechanisms in certain forms of EB. The current state of knowledge can best be characterized as a number of potentially significant disparate observations from various disciplines. The ultimate goals of research in EB are not only to understand the disease but also to provide the biochemical tools for reliable genetic classification, for antenatal diagnosis, and for rational modes of therapy.

Epidermolysis Bullosa↗

Microbial classification of seawaters. The case against arbitrary health standards.

Various microbial health standards for recreational bathing waters obtain in many parts of the world, including Europe and America. These criteria appear to be a product of water laboratory scientists and legislators, bypassing the person most concerned--the local medical officer with his experience and knowledge of parochial epidemiology. In Natal we have a sophisticated and stringent system of grading bathing beaches which includes pathogenic microorganisms. The system functions as a measuring device for assessing changes in water quality, not as an arbitrary health standard. It is hoped that the practice of setting capricious so-called health standards for marine recreational waters does not spread to this country.

Escherichia coli↗

Health benefits of non-digestible oligosaccharides.

Non-digestible oligosaccharides are complex carbohydrates of the non-a-glucan type which, because of the configuration of their osidic bonds, resist hydrolysis by salivary and intestinal digestive enzymes. In the colon they are fermented by anaerobic bacteria. Among the non-digestible oligosaccharides, the chicory fructooligosaccharides occupy a key position and, in most european countries, they are recognised as natural food ingredients. The other major products are the short chain fructooligosaccharides and galactooligosaccharides obtained by enzymatic synthesis using sucrose and lactose as substrates respectively, the soybean oligosaccharides, the xylooligosaccharides produced by partial hydrolysis of xylans and polydextrose or pyrodextrins prepared by a chemical treatment of carbohydrates. The most well known effect of most non-digestible oligosaccharides, and in particular of the fructooligosaccharides, is the selective stimulation of the growth of Bifidobacteria thus modifying significantly the composition of the colonic microbiota. Such a modification, which has clearly been demonstrated in human volunteers, is meant to be benificial in part because it is accompanied by a significant reduction in the number of bacteria reported to have pathogenic potential. Within the framework of research and development of "functional foods", such an effect justifies a "functional claim" for fructooligosaccharides namely "bifidogenesis". They are also typical "prebiotics". Besides their bifidogenic effect, the chicory fructooligosaccharides have additional nutritional properties on digestive physiological parameters like colonic pH and stool bulking which justify their classification as dietary fibers. Moreover, in experimental models, it has also been reported that they improve the bioavailability of essentiel minerals and that they reduce serum triglyceridemia by lowering hepatic lipogenesis. Such effects demonstrate interactions between the chicory fructooligosaccharides and key functions in the body but their significance for humans still need to be proven before being used to justify additional claims.

Bifidobacterium↗

A corpus of GA4GH phenopackets: Case-level phenotyping for genomic diagnostics and discovery.

The Global Alliance for Genomics and Health (GA4GH) Phenopacket Schema was released in 2022 and approved by ISO as a standard for sharing clinical and genomic information about an individual, including phenotypic descriptions, numerical measurements, genetic information, diagnoses, and treatments. A phenopacket can be used as an input file for software that supports phenotype-driven genomic diagnostics and for algorithms that facilitate patient classification and stratification for identifying new diseases and treatments. There has been a great need for a collection of phenopackets to test software pipelines and algorithms. Here, we present Phenopacket Store. Phenopacket Store v.0.1.19 includes 6,668 phenopackets representing 475 Mendelian and chromosomal diseases associated with 423 genes and 3,834 unique pathogenic alleles curated from 959 different publications. This represents the first large-scale collection of case-level, standardized phenotypic information derived from case reports in the literature with detailed descriptions of the clinical data and will be useful for many purposes, including the development and testing of software for prioritizing genes and diseases in diagnostic genomics, machine learning analysis of clinical phenotype data, patient stratification, and genotype-phenotype correlations. This corpus also provides best-practice examples for curating literature-derived data using the GA4GH Phenopacket Schema.

Humans↗

Ecology and significance of Pasteurellaceae in man--an update.

Within the last decade new knowledge has emerged concerning the significance of Pasteurellaceae in man; the classification has undergone some changes, and new taxa were described. Haemophilus influenzae serotype b was shown to have a clonal distribution that is related to demographic patterns of the human host. Brazilian purpuric fever is caused by a special clone of Haemophilus aegyptius. H. influenzae biotype IV seems to be a genital pathogen, and may deserve species rank. New Pasteurella species have been described, that occur in well known pathological foci in man, e.g. bite wounds. Toxigenic P. multocida may occur in man also; the significance of toxigenicity in man is not known. The real actinobacilli of man, A. ureae and A. hominis are still very rarely reported. In order to avoid wrong epidemiological conclusions, correct diagnosis is emphasized.

Actinobacillus↗

Hospitalizations associated with rotavirus diarrhea in the United States, 1993 through 1995: surveillance based on the new ICD-9-CM rotavirus-specific diagnostic code.

The introduction of a specific International Classification of Diseases code for rotavirus diarrhea in 1992 prompted examination of the National Hospital Discharge Survey (NHDS) for trends in rotavirus-associated hospitalizations among US children aged 1 month through 4 years. During 1993-1995, 13.5% of hospitalizations were associated with diarrhea (n = 162,478/year). Rotavirus was the most common pathogen identified, coded in 16.5% of diarrhea cases (n = 26,798/year), and increased from 13.3% in 1993 to 18.9% in 1995. The age distribution and seasonality of hospitalizations of presumed noninfectious and viral etiology resembled those associated with rotavirus. Rotavirus was reported as a cause of diarrhea more frequently by hospitals that were large (> or =100 beds), proprietary-owned, or in the West/Midwest. Although these findings suggest incomplete detection of rotavirus diarrhea cases, the large number of rotavirus-associated hospitalizations underscores the need for vaccines and indicates that NHDS data could be used to monitor the impact of a US rotavirus immunization program.

Age Factors↗

Rapid bacterial identification using evanescent-waveguide oligonucleotide microarray classification.

Bacterial identification relies primarily on culture-based methodologies and requires 48-72 h to deliver results. We developed and used i) a bioinformatics strategy to select oligonucleotide signature probes, ii) a rapid procedure for RNA labelling and hybridization, iii) an evanescent-waveguide oligoarray with exquisite signal/noise performance, and iv) informatics methods for microarray data analysis. Unique 19-mer signature oligonucleotides were selected in the 5'-end of 16s rDNA genes of human pathogenic bacteria. Oligonucleotides spotted onto a Ta(2)O(5)-coated microarray surface were incubated with chemically labelled total bacterial RNA. Rapid hybridization and stringent washings were performed before scanning and analyzing the slide. In the present paper, the eight most abundant bacterial pathogens representing >54% of positive blood cultures were selected. Hierarchical clustering analysis of hybridization data revealed characteristic patterns, even for closely related species. We then evaluated artificial intelligence-based approaches that outperformed conventional threshold-based identification schemes on cognate probes. At this stage, the complete procedure applied to spiked blood cultures was completed in less than 6 h. In conclusion, when coupled to optimal signal detection strategy, microarrays provide bacterial identification within a few hours post-sampling, allowing targeted antimicrobial prescription.

Bacteremia↗

Determination of taxonomic status of pathogenic and nonpathogenic Entamoeba histolytica zymodemes using isoenzyme analysis.

Entamoeba histolytica infection results in either asymptomatic colonization or invasion of host tissues leading generally to clinical symptoms. Zymodemes studies have demonstrated a correlation between isoenzyme profiles and clinical presentation. Thus, strains have been attributed to pathogenic or nonpathogenic groups according to their zymodeme. To determine the taxonomic relationship of these two groups, the isoenzyme profiles of 14 loci of 38 E. histolytica strains (pathogenic and nonpathogenic) and seven strains of other species of the same genus were analyzed. Genetic distance analysis clearly demonstrates the existence of two separate groups within the species E. histolytica.

Animals↗

Neuropathotyping: a new system to classify Marek's disease virus.

A statistical approach was used to establish a new classification system of Marek's disease virus (MDV) on the basis of neurologic responses. To develop the system, neurologic response data from 15x7 chickens inoculated with 30 strains of serotype 1 MDV were statistically analyzed by a cluster analysis. The goal was to identify a statistical system that would verify if three neurovirulence groups correlated with the three pathotypes previously described. The system was also validated in two additional strains of specific-pathogen-free (SPF) chickens, SPAFAS and line SC (Hy-Vac). The proposed system is based on analysis of three variables: 1) frequency of birds showing transient paralysis between 9 and 11 days postinoculation (dpi), (2) mortality before 15 dpi, and (3) frequency of birds showing persistent neurologic disease between 21 and 23 dpi. By use of this system, a MDV may be classified in one of three groups, designated neuropathotypes A, B, and C, which roughly correspond to the virulent, very virulent, and very virulent plus pathotypes, respectively. However, correlation between neuropathotype and pathotype was not absolute, and neuropathotyping is more a complement to the current pathotyping system than a replacement for it. Our results showed that neuropathotyping studies can be conducted in two types of commercial SPF chickens by the use of the same variables, although the system would first have to be standardized by the use of prototype viruses. Neuropathotypes can also be estimated with our statistical analysis with reasonable accuracy. By use of this analysis, we established that MDV strains within the very virulent pathotype may be subdivided into neuropathotypes B and C, thus establishing a previously unrecognized pathotypic classification. This finding illustrates how neuropathotyping may extend important information not identified by conventional pathotyping.

Animals↗

The biochemistry and medical significance of the flavonoids.

Flavonoids are plant pigments that are synthesised from phenylalanine, generally display marvelous colors known from flower petals, mostly emit brilliant fluorescence when they are excited by UV light, and are ubiquitous to green plant cells. The flavonoids are used by botanists for taxonomical classification. They regulate plant growth by inhibition of the exocytosis of the auxin indolyl acetic acid, as well as by induction of gene expression, and they influence other biological cells in numerous ways. Flavonoids inhibit or kill many bacterial strains, inhibit important viral enzymes, such as reverse transcriptase and protease, and destroy some pathogenic protozoans. Yet, their toxicity to animal cells is low. Flavonoids are major functional components of many herbal and insect preparations for medical use, e.g., propolis (bee's glue) and honey, which have been used since ancient times. The daily intake of flavonoids with normal food, especially fruit and vegetables, is 1-2 g. Modern authorised physicians are increasing their use of pure flavonoids to treat many important common diseases, due to their proven ability to inhibit specific enzymes, to simulate some hormones and neurotransmitters, and to scavenge free radicals.

Animals↗