The National ALS Registry: a recruitment tool for research.

INTRODUCTION: Subject recruitment is critical for understanding fatal diseases like ALS, however linking patients with researchers can be challenging. The U.S. population-based National ALS Registry allows recruitment of persons with ALS (PALS) for research opportunities. METHODS: The Registry's Research Notification Mechanism was used to recruit PALS aged ≥21 years; participants completed a Web-based epidemiologic survey. PALS (n = 2,232) were sent an email describing the study, and 268 surveys were completed. RESULTS: The mean age (± SD) of eligible participants was 57.7 ± 9.3 years for men and 61.5 ± 8.9 for women. Most were men (63%) and Caucasian (92%). Of 256 potentially eligible participants, 37.5% (n = 96) returned an authorization to disclose protected health information. ALS was confirmed for 94% (83/88) from physician responses. CONCLUSIONS: This analysis demonstrates the National ALS Registry's usefulness in recruiting PALS for research. This recruitment source can potentially foster the discovery of better treatment options and therapies, and of prevention strategies.

Biocide activity against urinary catheter pathogens.

Antimicrobial effects of essential oils against bacteria associated with urinary catheter infection was assessed. Tests were performed on 14 different bacterial species cultured either planktonically or as biofilms. Biofilms were found to be up to 8-fold more tolerant of the test agents. Higher antimicrobial tolerance was also evident in tests conducted in artificial urine. Eugenol exhibited higher antimicrobial effects against both planktonic cells and biofilms than did terpinen, tea tree oil, and cineole.

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy.

INTRODUCTION: Disease inclusion in the newborn screening (NBS) panel should consider the opinions of those most affected by the outcome of screening. We assessed the level and factors that affect parent attitudes regarding NBS panel inclusion of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and spinal muscular atrophy (SMA). METHODS: The attitudes toward NBS for DMD, BMD, and SMA were surveyed and compared for 2 categories of parents, those with children affected with DMD, BMD, or SMA and expectant parents unselected for known family medical history. RESULTS: The level of support for NBS for DMD, BMD, and SMA was 95.9% among parents of children with DMD, BMD, or SMA and 92.6% among expectant parents. CONCLUSIONS: There was strong support for NBS for DMD, BMD, and SMA in both groups of parents. Given advances in diagnostics and promising therapeutic approaches, discussion of inclusion in NBS should continue.

Environmental and occupational risk factors for amyotrophic lateral sclerosis: a case-control study.

BACKGROUND/AIMS: Environmental and occupational exposures are implicated as risk factors for amyotrophic lateral sclerosis (ALS), the etiology of which is largely unknown, although no causal relationships have been established. OBJECTIVE: The aim of the study was to evaluate the associations of personal risk factors and self-reported environmental and occupational exposures with risk of ALS. METHODS: The cases involved ALS patients (n = 66) identified from major neurological centers in Pittsburgh and Philadelphia, Pa., USA, from 2008 to 2010. The age-, race- and sex-matched controls included outpatient hospital and population-based controls (n = 66). A detailed questionnaire obtaining data on occupation, vocational and avocational exposure as well as personal lifestyle factors was administered. RESULTS: Occupational exposure to metals (odds ratio, OR = 3.65; 95% CI: 1.15, 11.60) and pesticides (OR = 6.50; 95% CI: 1.78, 23.77) was related to increased risk of ALS after controlling for smoking and education. No associations were found for occupational exposure to organic or aromatic solvents. CONCLUSION: Workers exposed to metals and pesticides may be at greater risk of ALS. Future research should involve more accurate exposure assessment through the use of job exposure matrices, confirmation of occupation and biomarkers.

Facial diplegia, pharyngeal paralysis, and ophthalmoplegia after a timber rattlesnake envenomation.

The timber rattlesnake, also known as Crotalus horridus, is well known to cause significant injury from toxins stored within its venom. During envenomation, toxic systemic effects immediately begin to cause damage to many organ systems including cardiovascular, hematologic, musculoskeletal, respiratory, and neurologic. One defining characteristic of the timber rattlesnake is a specific neurotoxin called crotoxin, or the "canebrake toxin," which is a potent ß-neurotoxin affecting presynaptic nerves that can cause paralysis by inhibiting appropriate neuromuscular transmission. We present an unusual case of an 8-year-old boy bitten twice on his calf by a timber rattlesnake, who presented with a life-threatening envenomation and suffered multisystem organ failure as well as a prominent presynaptic neurotoxicity resulting in facial diplegia, pharyngeal paralysis, and ophthalmoplegia.

Development of an "early warning" sensor for encrustation of urinary catheters following Proteus infection.

Biofilm formation in long-term urinary catheterized patients can lead to encrustation and blockage of urinary catheters with serious clinical complication. Catheter encrustation stems from infection with urease-producing bacteria, particularly Proteus mirabilis. Urease generates ammonia from urea, and the elevated pH of the urine results in crystallization of calcium and magnesium phosphates, which block the flow of urine. The aim of this research is to develop an "early warning" silicone sensor for catheter encrustation following bacterial infection of an in vitro bladder model system. The in vitro bladder model was infected with a range of urease positive and negative bacterial strains. Developed sensors enabled catheter blockage to be predicted ~17-24 h in advance of its occurrence. Signaling only occurred following infection with urease positive bacteria and only when catheter blockage followed. In summary, sensors were developed that could predict urinary catheter blockage in in vitro infection models. Translation of these sensors to a clinical environment will allow the timely and appropriate management of catheter blockage in long-term catheterized patients.

An indwelling urinary catheter for the 21st century.

What's known on the subject? and What does the study add? A vast literature has been published on the prevalence, morbidity and microbiology of catheter-associated urinary tract infections. Research and development in recent years has focused on producing antibacterial coatings for the indwelling Foley catheter with insufficient attention to its design. This article provides a critical examination of the design of the indwelling Foley catheter. Design specifications are outlined for a urine collection device that should reduce the vulnerability of catheterised urinary tract to infection. The indwelling urinary catheter is the most common cause of infections in hospitals and other healthcare facilities [1]. As long ago as 1958, Paul Beeson [2] warned '… the decision to use this instrument should be made with the knowledge that it involves the risk of producing a serious disease which is often difficult to treat'. Since then, scientific studies have progressed revealing a greater understanding of the bladder's defence mechanisms against infection and how they are undermined by the Foley catheter [3-5]. In addition, the complications caused by the development of bacterial biofilms on catheters have been recognised and the ways in which these bacterial communities develop on catheters have become clear [5,6]. It is now obvious that fundamental problems with the basic design of the catheter, which has changed little since it was introduced into urological practice by Dr Fredricc Foley in 1937 [7], induce susceptibility to infection. These issues need to be addressed urgently if we are to produce a device suitable for use in the 21st century.

Accuracy and usefulness of ICD-10 death certificate coding for the identification of patients with ALS: results from the South Carolina ALS Surveillance Pilot Project.

The purpose if this study was to investigate the positive predictive value and sensitivity of the ICD-10 code G12.2, which is used to identify patients who have possibly died from ALS. All patients with a motor neuron disease diagnosis code during the study period (2001-2005) were identified using administrative data. South Carolina death certificate data were used to assess the positive predictive value and sensitivity of the ICD-10 code G12.2. Two hundred and seventy known cases of ALS linked to the death certificate data file. G12.2 was coded as either the underlying or contributing cause of death for 229 cases, sensitivity = 85%. There were 318 deaths due to ALS identified by the G12.2 code where a medical record was available for review. Of those, 205 contained information supporting the diagnosis of ALS, positive predictive value = 65%. This evaluation raises questions concerning the validity of using mortality data in forming epidemiological conclusions in this patient population. However, it does appear that mortality data can be used in the development of case-finding algorithms to identify ALS patients through the use of administrative data sets.

Validity of hospital discharge data for identifying cases of amyotrophic lateral sclerosis.

Inpatient hospital encounters and emergency department visits were examined to identify cases of amyotrophic lateral sclerosis (ALS).The ninth edition of the International Classification of Disease, clinical modification (ICD-9-CM) for ALS was confirmed for ALS was confirmed in 93% of inpatient discharges and in 91% of emergency department visits by the diagnostic standard (chart review). Yearly prevalence rates ranged from 2.94 to 3.28 per 100,000 residents. The low calculated prevalence rates suggest that this method of case identification is inadequate and must be combined with other data sets to maximize confirmation of the clinical diagnosis.

Neurological deficits during treatment with tumor necrosis factor-alpha antagonists.

INTRODUCTION: Neurological deficits that occur during treatment with tumor necrosis factor (TNF)-α antagonists are rare, and their clinical features have not been fully elucidated. METHODS: Retrospective review of medical records of 9 patients who were given TNF-α antagonists, subsequently developed neurological deficits and were cared for at the Medical University of South Carolina between January 2002 and May 2010. Adverse drug reaction probability scale was used for the assessment of their causal connection. RESULTS: The underlying diseases for which TNF-α antagonists were administered included rheumatologic disorders (4), sarcoidosis (3), psoriasis (1) and Crohn's disease (1). Etanercept, infliximab or adalimumab was administered to these patients. Neurological complications included central or peripheral demyelination (5), antiphospholipid syndrome/central nervous system lupus (1), Epstein-Barr virus encephalitis (1), axonal sensory polyneuropathy (1) and small fiber polyneuropathy (1). TNF-α antagonists were discontinued in 8 patients and clinical improvement was seen in 3 of them. Additional therapies were given in 4 patients. An adverse drug reaction probability score suggested probable (3/9) and possible (6/9) causal relationships. CONCLUSIONS: Neurological deficits that develop during treatment with TNF-α antagonists are relatively rare but important potential complications of these drugs. Determining if the relationship between the neurological deficits and TNF-α antagonist therapy is causal can be challenging and can impact patient care.

Strategy to control catheter encrustation with citrated drinks: a randomized crossover study.

PURPOSE: Nucleation pH is the pH at which Ca and Mg come out of urine to form crystals. If the safety margin between voiding pH and nucleation pH could be increased, it would increase the possibility of an alternative to controlling the activity of urease producing bacteria as a strategy to control catheter encrustation. MATERIALS AND METHODS: We performed a 6-week randomized crossover study in 24 patients with catheter blockage who were randomly allocated to a specific sequence of 3 consecutive available treatments, including increased fluid intake, lemon juice and potassium citrate. Each patient received all available regimens. At the end of each week 24-hour urine samples were analyzed for voiding and nucleation pH, citrate, Ca and Mg. RESULTS: Mean +/- SD nucleation pH increased from 7.45 +/- 0.60 at baseline to 7.93 +/- 0.50, 7.68 +/- 0.64 and 7.96 +/- 0.37 in the lemon juice, increased fluid intake and potassium citrate groups, respectively (p <0.0001). Mean urinary citrate increased significantly (p <0.0001), in particular due to lemon juice and potassium citrate effects. The association between treatment and Ca was weak (p = 0.12) while that of Mg was negative due to lemon (p <0.001). Average increase in the safety margin (nucleation pH minus voiding pH) beyond baseline was 0.84 (95% CI 0.63-1.04), 0.57 (95% CI 0.37-0.78) and 0.41 (95% CI 0.20-0.61) for lemon juice, increased fluid intake and potassium citrate, respectively. A strong treatment effect on the safety margin was apparent even when controlling for study design (p <0.001). CONCLUSIONS: Increased fluid intake with lemon juice may be a simple, inexpensive, effective strategy to control catheter encrustation.

Voltage gated potassium channel antibodies in amyotrophic lateral sclerosis.

Although overlap exists between the clinical manifestations in patients with acquired peripheral nerve hyperexcitibility and amyotrophic lateral sclerosis (ALS), the presence of VGKC antibodies has not been associated with the development or clinical manifestations of motor neuron disease. We present the finding of elevated potassium channel antibodies in a cohort of patients with ALS and demonstrate a higher number of abnormal titer levels and higher mean titer levels in ALS patients compared to a cohort of patients with peripheral nervous system disorders. These results suggest the possibility of a subset of ALS patients where autoimmunity could play a role in disease development and progression.

Crystalline bacterial biofilm formation on urinary catheters by urease-producing urinary tract pathogens: a simple method of control.

The problem of catheter encrustation stems from infection by urease-producing bacteria. These organisms generate ammonia from urea, elevate the pH of urine and cause crystals of calcium and magnesium phosphates to form in the urine and the biofilm that develops on the catheter. In this study, a laboratory model was used to compare the ability of 12 urease-positive species of urinary tract pathogens to encrust and block catheters. Proteus mirabilis, Proteus vulgaris and Providencia rettgeri were able to raise the urinary pH above 8.3 and produce catheter-blocking crystalline biofilms within 40 h. Morganella morganii and Staphylococcus aureus elevated the pH of urine to 7.4 and 6.9, respectively, and caused some crystal deposition in the biofilms but did not block catheters in the 96 h experimental period. Isolates of Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Serratia marcescens, Pseudomonas aeruginosa and Providencia stuartii were only capable of raising the pH of urine to a maximum of 6.4 and failed to cause crystal deposition in the biofilm. The most effective way to prevent catheter encrustation was shown to be diluting urine and increasing its citrate concentration. This strategy raises the nucleation pH (pH(n)) at which calcium and magnesium phosphates crystallize from urine. Increasing the fluid intake of a healthy volunteer with citrated drinks resulted in urine with a pH(n) of >8.0 in which catheter encrustation was inhibited. It is suggested that this dietary strategy will be an effective means of controlling catheter encrustation, whichever bacterial species is causing the problem.

The effect of EDTA instillations on the rate of development of encrustation and biofilms in Foley catheters.

The aim of this research was to examine whether a daily instillation of tetra sodium ethylenediaminetetraacetic acid (EDTA) solution could reduce the rate at which encrustation by crystalline Proteus mirabilis biofilms blocks urinary catheters. Sets of three bladder models were fitted with size 14 all-silicone catheters. Tetra sodium EDTA solution was instilled into the catheter following biofilm development. Catheters were examined by digital photography and scanning electron microscopy for evidence of encrustation. The results showed that the mean time to blockage of the control catheters was 45 h for saline, 57 h for water and 67 h for those exposed to daily instillations of the EDTA solution. Statistical analysis confirmed that the mean encrustation rate on the EDTA-treated catheters was significantly lower than on the control-treated devices (P = 0.047). This in vitro study indicates that EDTA may have beneficial effects in reducing the complication of catheter encrustation and blockage by crystalline biofilms.

A study of the structure of the crystalline bacterial biofilms that can encrust and block silver Foley catheters.

The aim of this study was to examine the structure of the crystalline bacterial biofilms that encrust and block silver/hydrogel-coated latex catheters. Scanning electron microscopy was used to examine the crystalline deposits that were found encrusting catheters obtained from six patients undergoing long-term catheterization in a community setting. Large populations of bacilli and cocci were seen on all catheters developing on a basal foundation layer of crystalline material. These observations show that in patients prone to catheter encrustation, crystalline material formed in the urine can cover the surfaces of silver catheters. Extensive bacterial biofilms then develop on the crystals, shielded from the underlying silver. It is suggested that if antimicrobials are to be incorporated into catheters to prevent encrustation, they must diffuse out from the catheter surface and reduce the viable cell populations of the urease producing bacteria that elevate the urinary pH and trigger crystal formation.

Bacterial biofilms in patients with indwelling urinary catheters.

Bacteria have a basic survival strategy: to colonize surfaces and grow as biofilm communities embedded in a gel-like polysaccharide matrix. The catheterized urinary tract provides ideal conditions for the development of enormous biofilm populations. Many bacterial species colonize indwelling catheters as biofilms, inducing complications in patients' care. The most troublesome complications are the crystalline biofilms that can occlude the catheter lumen and trigger episodes of pyelonephritis and septicemia. The crystalline biofilms result from infection by urease-producing bacteria, particularly Proteus mirabilis. Urease raises the urinary pH and drives the formation of calcium phosphate and magnesium phosphate crystals in the biofilm. All types of catheter are vulnerable to encrustation by these biofilms, and clinical prevention strategies are clearly needed, as bacteria growing in the biofilm mode are resistant to antibiotics. Evidence indicates that treatment of symptomatic, catheter-associated urinary tract infection is more effective if biofilm-laden catheters are changed before antibiotic treatment is initiated. Infection with P. mirabilis exposes the many faults of currently available catheters, and plenty of scope exists for improvement in both their design and production; manufacturers should take up the challenge to improve patient outcomes.

Effect of triclosan on the formation of crystalline biofilms by mixed communities of urinary tract pathogens on urinary catheters.

The crystalline bacterial biofilms that encrust Foley catheters compromise the care of many elderly and disabled patients. The aim of this study was to examine whether the biocide triclosan can prevent encrustation by the mixed flora of uropathogens that commonly infect patients undergoing long-term catheterization. Models of the catheterized bladder were inoculated with communities of organisms isolated from patients who were experiencing catheter blockage. The catheter retention balloons were inflated with water or triclosan (3 g triclosan l(-1) in 0.1 M sodium carbonate) and urine was supplied to the models for up to 7 days. The effect of triclosan was recorded on the viable cell populations, the pH of the residual urine and the times that catheters took to block. The extent of encrustation of the catheters was visualized by scanning electron microscopy. In models inoculated with communities containing Proteus mirabilis, triclosan prevented the rise in urinary pH that drives crystalline biofilm formation and catheter blockage. The biocide had no effect on populations of Enterococcus faecalis and Pseudomonas aeruginosa, but Proteus mirabilis, Escherichia coli and Klebsiella pneumoniae were eliminated from the residual urine and the catheters drained freely for the 7-day experimental period. In models inoculated with a mixed community containing Providencia rettgeri, catheters inflated with triclosan continued to block rapidly. Although K. pneumoniae and Proteus vulgaris were eliminated from the residual urine, there was no effect on the viability of Providencia rettgeri. The results indicate that the triclosan strategy should be limited to the treatment of patients who are infected with Proteus mirabilis.

Some observations on the migration of Proteus mirabilis and other urinary tract pathogens over foley catheters.

The ability of uropathogens to migrate along external surfaces of silicone Foley catheters was examined. Proteus mirabilis and Pseudomonas aeruginosa were the most motile organisms. P. aeruginosa migrated over both triclosan-impregnated and nitrofurazone-impregnated catheters, but these antibacterials inhibited the migration of P. mirabilis.

Reduced Susceptibility of Proteus mirabilis to triclosan.

Clinical isolates of Proteus mirabilis causing catheter encrustation and blockage are susceptible to the biocide triclosan (MICs of 0.2 mg/liter). Studies with laboratory models of the bladder have demonstrated that the inflation of catheter retention balloons with triclosan solutions rather than water results in the diffusion of triclosan from the balloons into the surrounding urine and the inhibition of catheter encrustation by P. mirabilis. The aim of this study was to test whether the exposure of P. mirabilis to triclosan under laboratory conditions resulted in the selection of strains with reduced susceptibilities to this biocide. Exposure to triclosan in agar was shown to select mutants with MICs elevated from 0.2 mg/liter up to 80 mg/liter. In a selection of 14 of these strains, the decreased susceptibility was found to be stable and not associated with increased resistance to antibiotics. Experiments with the laboratory models demonstrated that inflation of the catheter balloons with triclosan (10 mg/ml) prevented encrustation and blockage by the parent strain P. mirabilis B2 (MIC, 0.2 mg/liter) and the mutant strain M48 (MIC, 2.0 mg/liter) but had no effect on crystalline biofilm formation by strain M55 (MIC, 40 mg/liter). These results suggest that, in any clinical trial or subsequent clinical use of the strategy, it will be important to monitor the urinary flora of the catheterized patients for P. mirabilis strains with reduced susceptibility to triclosan. The emergence of these strains could undermine the ability of the triclosan strategy to control catheter encrustation.