Clinical complications of urinary catheters caused by crystalline biofilms: something needs to be done.

This review is largely based on a previous paper published in the journal Spinal Cord. The care of many patients undergoing long-term bladder catheterization is complicated by encrustation and blockage of their Foley catheters. This problem stems from infection by urease-producing bacteria, particularly Proteus mirabilis. These organisms colonize the catheter forming an extensive biofilm; they also generate ammonia from urea, thus elevating the pH of urine. As the pH rises, crystals of calcium and magnesium phosphates precipitate in the urine and in the catheter biofilm. The continued development of this crystalline biofilm blocks the flow of urine through the catheter. Urine then either leaks along the outside of the catheter and the patient becomes incontinent or is retained causing painful distension of the bladder and reflux of urine to the kidneys. The process of crystal deposition can also initiate stone formation. Most patients suffering from recurrent catheter encrustation develop bladder stones. P. mirabilis establishes stable residence in these stones and is extremely difficult to eliminate from the catheterized urinary tract by antibiotic therapy. If blocked catheters are not identified and changed, serious symptomatic episodes of pyelonephritis, septicaemia and endotoxic shock can result. All types of Foley catheters including silver- or nitrofurazone-coated devices are vulnerable to this problem. In this review, the ways in which biofilm formation on Foley catheters is initiated by P. mirabilis will be described. The implications of understanding these mechanisms for the development of an encrustation-resistant catheter will be discussed. Finally, the way forward for the prevention and control of this problem will be considered.

Endstation for ultrafast magnetic scattering experiments at the free-electron laser in Hamburg.

An endstation for pump-probe small-angle X-ray scattering (SAXS) experiments at the free-electron laser in Hamburg (FLASH) is presented. The endstation houses a solid-state absorber, optical incoupling for pump-probe experiments, time zero measurement, sample chamber, and detection unit. It can be used at all FLASH beamlines in the whole photon energy range offered by FLASH. The capabilities of the setup are demonstrated by showing the results of resonant magnetic SAXS measurements on cobalt-platinum multilayer samples grown on freestanding Si(3)N(4) membranes and pump-laser-induced grid structures in multilayer samples.

Ultrafast optical demagnetization manipulates nanoscale spin structure in domain walls.

During ultrafast demagnetization of a magnetically ordered solid, angular momentum has to be transferred between the spins, electrons, and phonons in the system on femto- and picosecond timescales. Although the intrinsic spin-transfer mechanisms are intensely debated, additional extrinsic mechanisms arising due to nanoscale heterogeneity have only recently entered the discussion. Here we use femtosecond X-ray pulses from a free-electron laser to study thin film samples with magnetic domain patterns. We observe an infrared-pump-induced change of the spin structure within the domain walls on the sub-picosecond timescale. This domain-topography-dependent contribution connects the intrinsic demagnetization process in each domain with spin-transport processes across the domain walls, demonstrating the importance of spin-dependent electron transport between differently magnetized regions as an ultrafast demagnetization channel. This pathway exists independent from structural inhomogeneities such as chemical interfaces, and gives rise to an ultrafast spatially varying response to optical pump pulses.

Myasthenic syndrome caused by plectinopathy.

BACKGROUND: Plectin crosslinks intermediate filaments to their targets in different tissues. Defects in plectin cause epidermolysis bullosa simplex (EBS), muscular dystrophy (MD), and sometimes pyloric atresia. Association of EBS with a myasthenic syndrome (MyS) was documented in a single patient in 1999. OBJECTIVES: To analyze the clinical, structural, and genetic aspects of a second and fatal case of EBS associated with a MyS and search for the genetic basis of the disease in a previously reported patient with EBS-MD-MyS. METHODS: Clinical observations; histochemical, immunocytochemical, and electron microscopy studies of skeletal muscle and neuromuscular junction; and mutation analysis. RESULTS: An African American man had EBS since early infancy, and progressive muscle weakness, hyperCKemia, and myasthenic symptoms refractory to therapy since age 3 years. Eventually he became motionless and died at age 42 years. At age 15 years, he had a marked EMG decrement, and a reduced miniature endplate potential amplitude. The myopathy was associated with dislocated muscle fiber organelles, structurally abnormal nuclei, focal plasmalemmal defects, and focal calcium ingress into muscle fibers. The neuromuscular junctions showed destruction of the junctional folds, and remodeling. Mutation analysis demonstrated a known p.Arg2319X and a novel c.12043dupG mutation in PLEC1. The EBS-MD-MyS patient reported in 1999 also carried c.12043dupG and a novel p.Gln2057X mutation. The novel mutations were absent in 200 Caucasian and 100 African American subjects. CONCLUSIONS: The MyS in plectinopathy is attributed to destruction of the junctional folds and the myopathy to defective anchoring of muscle fiber organelles and defects in sarcolemmal integrity.

The encrustation and blockage of long-term indwelling bladder catheters: a way forward in prevention and control.

OBJECTIVES: To review the literature showing that understanding how Foley catheters become encrusted and blocked by crystalline bacterial biofilms has led to strategies for the control of this complication in the care of patients undergoing long-term indwelling bladder catheterization. METHODS: A comprehensive PubMed search of the literature published between 1980 and December 2009 was made for relevant articles using the Medical Subject Heading terms 'biofilms', 'urinary catheterization', 'catheter-associated urinary tract infection' and 'urolithiasis'. Papers on catheter-associated urinary tract infections and bacterial biofilms collected during 40 years of working in the field were also reviewed. RESULTS: There is strong experimental and epidemiological evidence that infection by Proteus mirabilis is the main cause of the crystalline biofilms that encrust and block Foley catheters. The ability of P. mirabilis to generate alkaline urine and to colonize all available types of indwelling catheters allows it to take up stable residence in the catheterized tract in bladder stones and cause recurrent catheter blockage. CONCLUSION: The elimination of P. mirabilis by antibiotic therapy as soon as it appears in the catheterized urinary tract could improve the quality of life for many patients and reduce the current expenditure of resources when managing the complications of catheter encrustation and blockage. For patients who are already chronic blockers and stone formers, antibiotic treatment is unlikely to be effective owing to the resistance of cells in the crystalline biofilms. Strategies such as increasing fluid intake with citrated drinks could control the problem until bladder stone removal can be organized.

Imaging the in-plane magnetization in a Co microstructure by Fourier transform holography.

We report on experiments using Fourier transform holography to image the in-plane magnetization of a magnetic microstructure. Magnetic sensitivity is achieved via the x-ray magnetic circular dichroism effect by recording holograms in transmission at off-normal incidence. The reference beam is defined by a narrow hole milled at an inclined angle into the opaque mask. We present magnetic domain images of an in-plane magnetized cobalt element with a size of 2 µm × 2 µm× 20 nm. The domain pattern shows a multi-vortex state that deviates from the simple Landau ground state.

Magnetic ground state of single and coupled permalloy rectangles.

We have studied the magnetic domain structure in Permalloy rectangles that reveal flux-closure domain configurations. Arrays with varying spacing between the rectangles are investigated by scanning electron microscopy with polarization analysis as well as by micromagnetic simulation. In contrast to general expectation, rectangles in the flux-closure Landau state show significant coupling and form a magnetic pattern of common chirality. The coupling is due to the stray field that originates from small changes of the magnetization alignment, which is sensitive to the exact shape and the separation of the rectangles.

Coherent-pulse 2D crystallography using a free-electron laser x-ray source.

Coherent diffractive imaging for the reconstruction of a two-dimensional (2D) finite crystal structure with a single pulse train of free-electron laser radiation at 7.97 nm wavelength is demonstrated. This measurement shows an advance on traditional coherent imaging techniques by applying it to a periodic structure. It is also significant that this approach paves the way for the imaging of the class of specimens which readily form 2D, but not three-dimensional crystals. We show that the structure is reconstructed to the detected resolution, given an adequate signal-to-noise ratio.

Observations on the development of the crystalline bacterial biofilms that encrust and block Foley catheters.

The care of many patients undergoing long-term bladder catheterisation is complicated when the flow of urine through the catheter is blocked by encrustation. The problem results from infection by urease-producing bacteria, especially Proteus mirabilis, and the subsequent formation of crystalline biofilms on the catheter. The aim of this study was to discover how P. mirabilis initiates the development of these crystalline biofilms. The early stages in the formation of the biofilms were observed on a range of Foley catheters in a laboratory model of the catheterised bladder. Scanning electron micrographs revealed that when all-silicone, silicone-coated latex, hydrogel-coated latex, hydrogel/silver-coated latex and nitrofurazone silicone catheters were inserted into bladder models containing P. mirabilis and alkaline urine, their surfaces were rapidly coated with a microcrystalline foundation layer. X-ray microanalysis showed that this material was composed of calcium phosphate. Bacterial colonisation of the foundation layer followed and by 18h the catheters were encrusted by densely populated crystalline P. mirabilis biofilms. These observations have important implications for the development of encrustation-resistant catheters. In the case of silver catheters for example, bacterial cells can attach to the crystalline foundation layer and continue to grow, protected from contact with the underlying silver. If antimicrobials are to be incorporated into catheters to prevent encrustation, it is important that they diffuse into the urine and prevent the rise in pH that triggers crystal formation.

Complicated catheter-associated urinary tract infections due to Escherichia coli and Proteus mirabilis.

Catheter-associated urinary tract infections (CAUTIs) represent the most common type of nosocomial infection and are a major health concern due to the complications and frequent recurrence. These infections are often caused by Escherichia coli and Proteus mirabilis. Gram-negative bacterial species that cause CAUTIs express a number of virulence factors associated with adhesion, motility, biofilm formation, immunoavoidance, and nutrient acquisition as well as factors that cause damage to the host. These infections can be reduced by limiting catheter usage and ensuring that health care professionals correctly use closed-system Foley catheters. A number of novel approaches such as condom and suprapubic catheters, intermittent catheterization, new surfaces, catheters with antimicrobial agents, and probiotics have thus far met with limited success. While the diagnosis of symptomatic versus asymptomatic CAUTIs may be a contentious issue, it is generally agreed that once a catheterized patient is believed to have a symptomatic urinary tract infection, the catheter is removed if possible due to the high rate of relapse. Research focusing on the pathogenesis of CAUTIs will lead to a better understanding of the disease process and will subsequently lead to the development of new diagnosis, prevention, and treatment options.

Some observations on the diffusion of antimicrobial agents through the retention balloons of foley catheters.

PURPOSE: We examined the ability of antimicrobial agents to diffuse through the retention balloons of urinary catheters and inhibit their encrustation by Proteus mirabilis. MATERIALS AND METHODS: An agar diffusion screening test was developed to detect agents capable of diffusing through catheter balloons and inhibiting the growth of P. mirabilis. The effect of inflating the balloons with antibacterials on the ability of P. mirabilis to encrust catheters was tested in laboratory models of the catheterized bladder. RESULTS: Of 18 antimicrobial agents active on P. mirabilis only mandelic acid, phenoxyethanol, nalidixic acid and triclosan diffused through all-silicone catheter balloons to produce zones of inhibition against P. mirabilis. Polyurethane balloons were permeable to gentamicin and fluoroquinolones. Experiments with silicone catheters showed that inflating balloons with mandelic acid (100 gm/l) or ciprofloxacin (10 gm/l) failed to extended the time at which catheters became blocked in models inoculated with P. mirabilis. However, nalidixic acid (50 gm/l) significantly extended the lifespan of catheters (p <0.05). Triclosan (10 gm/l) prevented the increase in urinary pH that induces crystal formation and inhibited the formation of crystalline biofilm, enabling the catheters to drain freely for the full 7-day experimental period. CONCLUSIONS: Inflation of silicone catheter retention balloons with solutions of nalidixic acid or triclosan rather than water should be considered as strategies to control catheter encrustation. Polyurethane balloons are more permeable than silicone balloons to gentamicin and the fluoroquinolones, and they should be investigated as an alternative to silicone or latex in catheter manufacture.

Sural neuropathy: etiologies and predisposing factors.

Isolated sural neuropathy is an uncommon diagnosis. We identified 36 patients with isolated sural neuropathy. Sixteen had various forms of ankle trauma, in three of whom the associated sural neuropathies developed following medical intervention. Three patients developed sural neuropathy associated with vasculitis, and there were single patients with schwannoma and ganglionic cyst. In patients without a history of trauma, structural causes, such as schwannoma or ganglionic cysts and vasculitis, should be considered and managed as appropriate.

A sensor to detect the early stages in the development of crystalline Proteus mirabilis biofilm on indwelling bladder catheters.

A simple sensor has been developed to detect the early stages of urinary catheter encrustation and avoid the clinical crises induced by catheter blockage. In laboratory models of colonization by Proteus mirabilis, the sensor signaled encrustation at an average time of 43 h before catheters were blocked with crystalline biofilm.

Observations on the adherence of Proteus mirabilis onto polymer surfaces.

AIMS: Infection of the catheterized urinary tract with Proteus mirabilis causes blockage of the catheter by crystalline bacterial biofilms. The aim of this work is to identify a surface-coating for catheters that is not vulnerable to colonization by Pr. mirabilis. METHODS AND RESULTS: A parallel-plate flow-cell and phase contrast microscopy were used to follow bacterial adhesion onto polymer films. Experiments with a urease-negative mutant of Pr. mirabilis suspended in buffer or urine, identified agarose as a polymer on which biofilm did not form. In tests with wild-type urease-producing cells in urine, no adhesion of cells onto agarose was observed for 3 h but then as the pH rose above 8.2, the surface rapidly became colonized by crystalline biofilm. CONCLUSIONS: In urine at pH below 8.0, Pr. mirabilis does not adhere to agarose-coated surfaces. When the pH rises above 8.2, however, aggregates of crystals and bacteria form in the urine and are deposited on such surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: Strategies to prevent the formation of crystalline biofilms on urinary catheters will need to consider both the properties of the surface-coatings and the requirement to prevent the alkaline conditions that induce crystal formation in urine.

Effect of triclosan on the development of bacterial biofilms by urinary tract pathogens on urinary catheters.

OBJECTIVES: To examine (i) the effect of triclosan on the formation of catheter biofilms by urinary tract pathogens and (ii) the diffusion of triclosan through the retention balloons of urinary catheters. METHODS: Models of the catheterized bladder were infected with eight different urinary tract pathogens and the effect of triclosan on biofilm formation was assessed by determining the numbers of viable cells colonizing the catheters and by scanning electron microscopy. HPLC was used to determine the triclosan concentration in urine draining from models that had been fitted with triclosan-inflated silicone catheters. RESULTS: When catheters were inflated with triclosan (10 g/L) the formation of catheter biofilm by Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Proteus mirabilis was prevented. The numbers of Enterococcus faecalis and Providencia stuartii cells colonizing catheters were also significantly reduced (P<0.05). Serratia marcescens, Morganella morganii and Pseudomonas aeruginosa, however, were able to produce extensive catheter biofilms in the presence of triclosan. Only P. mirabilis produced alkaline urine and encrusted the catheters. Concentrations of 0.02-0.16 mg/L of the biocide were detected in urine draining from the model over the 48 h experimental period. CONCLUSIONS: Triclosan diffused through silicone catheter balloons and produced urinary concentrations that prevented catheter encrustation by P. mirabilis and biofilm formation by several other common pathogens of the catheterized urinary tract. It had little effect on urease-producing P. aeruginosa, S. marcescens or M. morganii but these species did not produce alkaline urine or crystalline biofilms.

A strategy for the control of catheter blockage by crystalline Proteus mirabilis biofilm using the antibacterial agent triclosan.

OBJECTIVES: Catheter blockage by crystalline Proteus mirabilis biofilm is a common complication in patients undergoing long-term indwelling bladder catheterisation. Previously we have shown that inflating the retention balloons of all-silicone catheters with triclosan solutions prevents the encrustation process. The aim of the present work was to examine whether this strategy is effective in latex-based catheters. METHODS: Laboratory bladder models were fitted with catheters and the retention balloons inflated with water or various concentrations of triclosan. The urine was inoculated with Pr. mirabilis and the times catheters took to block recorded. RESULTS: Control catheters blocked in mean times ranging from 18 to 27 h. The pH of the urine rose from 6.1 to >8.6. In models with latex-based catheters inflated with 1-10 mg/ml triclosan, the urinary pH was controlled, the numbers of organisms in the urine was reduced and the catheters drained freely for the 7 day experimental period. Electron microscopy confirmed that crystalline biofilm was blocking control catheters. Little sign of encrustation was visible on the test catheters. CONCLUSION: Inflating the retention balloons with triclosan could have practical applications in controlling encrustation on both latex and silicone-based catheters.

Role of swarming in the formation of crystalline Proteus mirabilis biofilms on urinary catheters.

The care of many patients undergoing long-term bladder catheterization is frequently complicated by infection with Proteus mirabilis. These organisms colonize the catheter, forming surface biofilm communities, and their urease activity generates alkaline conditions under which crystals of magnesium ammonium phosphate and calcium phosphate are formed and become trapped in the biofilm. As the biofilm develops it obstructs the flow of urine through the catheter, causing either incontinence due to leakage of urine around the catheter or retention of urine in the bladder. The aim of this study was to investigate the role of the surface-associated swarming motility of P. mirabilis in the initiation and development of these crystalline catheter biofilms. A set of stable transposon mutants with a range of swimming and swarming abilities were tested for their ability to colonize silicone surfaces in a parallel-plate flow cell. A laboratory model of the catheterized bladder was then used to examine their ability to form crystalline, catheter-blocking biofilms. The results showed that neither swarming nor swimming motility was required for the attachment of P. mirabilis to silicone. Mutants deficient in swarming and swimming were also capable of forming crystalline biofilms and blocking catheters more rapidly than the wild-type strain.

MuSK-antibody positive myasthenia gravis: clinical and electrodiagnostic patterns.

OBJECTIVE: To examine the clinical manifestations and patterns of electromyographic abnormalities in MuSK-Ab positive myasthenia gravis. METHODS: The clinical evaluations and electrodiagnostic testing results of 20 MuSK-Ab positive myasthenia gravis patients were retrospectively reviewed and compared with matched AChR-Ab positive (N = 72) and MuSK-Ab negative/AChR-Ab negative (N = 24) patients. RESULTS: MuSK-Ab positive patients were younger and more frequently female and African-American, and compared to the AChR-Ab positive patients, were more likely to present with respiratory symptoms or neck extension weakness. MuSK-Ab positive patients were less likely to have abnormal jitter in a limb muscle: only 59% had abnormal jitter in the extensor digitorum communis muscle, compared to 80% of the AChR-Ab negative/MuSK-negative patients and 91% of the AChR-Ab positive patients. CONCLUSIONS: Our MuSK-Ab positive patients not only differ demographically from our MuSK-Ab negative cohort, but they also appear to have a more limited distribution of SFEMG abnormalities. SIGNIFICANCE: The possibility that electrophysiologic abnormalities may not be widely distributed should be considered during electrodiagnostic evaluation of suspected MuSK-Ab positive MG and in selecting muscles for molecular, morphologic, or microphysiologic studies in this condition.

Factors modulating the pH at which calcium and magnesium phosphates precipitate from human urine.

The factors controlling the rate at which crystalline bacterial biofilms develop on indwelling bladder catheters are poorly understood. It is known that normally the pH of voided urine (pHv) is lower than the pH at which calcium and magnesium phosphates come out of urine solution (pHn). In patients who develop infections with urease producing bacteria, however, the pHv rises above the pHn and precipitation of the phosphates occurs in the urine and the biofilm. The aim of this study was to examine ways of manipulating the pHn of urine so that more of its calcium and magnesium remain in solution under alkaline conditions. The experimental data show that pHn can be elevated by decreasing the calcium, magnesium and phosphate concentrations. Increasing the fluid intake of a human subject so that the urinary calcium fell from 120 mg/l to 25 mg/l, for example, resulted in the pHn increasing from 6.48 to 8.22. The addition of citrate to urine also produced a rise in the pHn. The daily consumption of 500 ml of fresh orange juice increased urinary citrate concentrations from 0.35 to around 1.21 mg/ml and the pHn rose from 7.24 to 8.2. The pHn of urine is thus a highly variable parameter. It can be manipulated by controlling the urinary concentrations of magnesium, calcium, phosphate and citrate ions. We suggest that increasing fluid intake with citrate containing drinks would reduce the extent of encrustation on catheters in patients infected with urease producing bacteria.