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Biomedical subjects

C A Fux

Publications and source records attributed to C A Fux.

6 recordsLinked to original sources

Biofilm-related infections of cerebrospinal fluid shunts.

Cerebrospinal fluid (CSF) shunts carry a high risk of complications. Infections represent a major cause of shunt failure. Diagnosis and therapy of such infections are complicated by the formation of bacterial biofilms attached to shunt surfaces. This study correlated the pathophysiology and clinical course of biofilm infections with microscopical findings on the respective shunts. Surface irregularities, an important risk-factor for shunt colonisation with bacteria, were found to increase over time because of silicone degradation. Scanning electron-microscopy (SEM) documented residual biological material (dead biofilm), which can further promote extant bacterial adhesion, on newly manufactured shunts. Clinical course and SEM both documented bacterial dissemination against CSF flow and the monodirectional valve. In all cases, biofilms grew on both the inner and outer surfaces of the shunts. Microscopy and conventional culture detected all bacterial shunt infections. Analyses of 16S rDNA sequences using conserved primers identified bacteria in only one of three cases, probably because of previous formalin fixation of the samples.

Adolescent↗

Can laboratory reference strains mirror "real-world" pathogenesis?

The extraordinary plasticity of bacterial genomes raises concerns about the adequacy of laboratory-adapted reference strains for the study of "real-world" pathogenesis. Some laboratory strains have been sub-cultured for decades since their first isolation and might have lost important pathophysiological characteristics. Evidence is presented that bacteria rapidly adapt to in vitro conditions. Genomic differences between laboratory reference strains and corresponding low-passage clinical isolates are reviewed. It appears that no bacterial strain can truly represent its species. For DNA microarray and proteomic studies, this limitation might be overcome by the summation of individual genomes to produce a species-specific virtual supragenome.

Escherichia coli K12↗

Survival strategies of infectious biofilms.

Modern medicine is facing the spread of biofilm-related infections. Bacterial biofilms are difficult to detect in routine diagnostics and are inherently tolerant to host defenses and antibiotic therapies. In addition, biofilms facilitate the spread of antibiotic resistance by promoting horizontal gene transfer. We review current concepts of biofilm tolerance with special emphasis on the role of the biofilm matrix and the physiology of biofilm-embedded cells. The heterogeneity in metabolic and reproductive activity within a biofilm correlates with a non-uniform susceptibility of enclosed bacteria. Recent studies have documented similar heterogeneity in planktonic cultures. Nutritional starvation and high cell density, two key characteristics of biofilm physiology, also mediate antimicrobial tolerance in stationary-phase planktonic cultures. Advances in characterizing the role of stress response genes, quorum sensing and phase variation in stationary-phase planktonic cultures have shed new light on tolerance mechanisms within biofilm communities.

Adaptation, Physiological↗

Detachment characteristics and oxacillin resistance of Staphyloccocus aureus biofilm emboli in an in vitro catheter infection model.

Catheter-related bloodstream infections due to Staphylococcus aureus are of increasing clinical importance. The pathophysiological steps leading to colonization and infection, however, are still incompletely defined. We observed growth and detachment of S. aureus biofilms in an in vitro catheter-infection model by using time-lapse microscopy. Biofilm emboli were characterized by their size and their susceptibility for oxacillin. Biofilm dispersal was found to be a dynamic process in which clumps of a wide range of diameters detach. Large detached clumps were highly tolerant to oxacillin compared with exponential-phase planktonic cultures. Interestingly, the degree of antibiotic tolerance in stationary-phase planktonic cultures was equal to that in the large clumps. The mechanical disruption of large clumps reduced the minimal bactericidal concentration (MBC) by more than 1,000 times. The MBC for whole biofilm effluent, consisting of particles with an average number of 20 bacteria was 3.5 times higher than the MBC for planktonic cultures. We conclude that the antibiotic resistance of detached biofilm particles depends on the embolus size and could be attributed to nutrient-limited stationary-phase physiology of cells within the clumps. We hypothesize that the detachment of multicellular clumps may explain the high rate of symptomatic metastatic infections seen with S. aureus.

Anti-Bacterial Agents↗

Cytomegalovirus-associated acute transverse myelitis in immunocompetent adults.

We report a case of transverse myelitis as a complication of acute cytomegalovirus (CMV) infection in immunocompetent patients; and review the literature on the entity. Primary CMV infection was documented by CMV antigenemia and high serum titers of CMV IgM and IgG antibodies. Cerebrospinal fluid (CSF) pleocytosis indicated central nervous system inflammation; CSF polymerase chain reaction (PCR) for CMV, however, was negative. The results of magnetic resonance imaging of the myelon were normal. Although CMV-associated transverse myelitis has been well described in HIV-positive individuals, but is very rare in immunocompetent individuals. It remains unclear whether the neuronal damage is immune mediated or due to a cytotoxic effect of viral infection. The outcome is mainly favorable.

Adult↗

Haemodialysis activates phospholipase A2 enzyme.

BACKGROUND: Clinical and experimental evidence suggest that haemodialysis (HD) procedure is an inflammatory process. For the production of proinflammatory lipid mediators in many inflammatory reactions, the release of arachidonic acid by phospholipase A2 (PLA2) enzyme is a prerequisite. Therefore, the purpose of the present investigation was to establish whether the activity of PLA2 increases during HD and whether the increase depends on the type of dialyser used. METHODS: We performed dialysis in eight chronic HD patients. Blood samples entering and leaving the dialyser were obtained before and at 15, 60, 120 and 180 min after the dialysis was started, on one occasion using a cuprophane and on another occasion a cellulose triacetate dialyser. PLA2 activity was assessed in crude plasma and in plasma extract. RESULTS: PLA2 activity in plasma extract exhibited similar biochemical properties to that of inflammatory human synovial fluid PLA2 enzyme which is of group II PLA2. PLA2 activity in crude plasma represents a type of PLA2 other than the synovial type. In HD patients, baseline PLA2 activities in a crude plasma and plasma extract were significantly increased when compared to normal subjects. An increase in PLA2 activity was observed in crude plasma with a peak appearing at 15 min when the patients were dialysed with cuprophane and cellulose triacetate membranes. This increase was observed in both arterial and venous blood samples and was more pronounced when the patients were dialysed with cuprophane than with cellulose triacetate membranes. When PLA2 was assessed in plasma extract, the activity increased only with cuprophane but not with cellulose triacetate membranes. CONCLUSION: PLA2 activity in plasma is increased in HD patients and increases during the dialysis procedure to a greater extent with a less biocompatible membrane. Continuous activation of PLA2 might be relevant for long-term deleterious consequences of HD.

Adult↗