Susceptibility of multidrug resistant clinical pathogens to a chlorhexidine formulation.

Multidrug resistant pathogens are a widespread problem in the hospital setting especially on intensive care units (ICU). This study evaluated the susceptibility of clinical isolates of gramnegative extensively drug resistant organisms (XDR), methicillinresistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) to a proprietary chlorhexidine digluconate (CHG) formulation used in one brand of CHG-impregnated cloths. Ten isolates each of XDR Pseudomonas aeruginosa, XDR Acinetobacter baumannii, XDR Klebsiella pneumoniae, XDR Escherichia coli, MRSA, and vancomycin-resistant Enterococcus faecium from our hospital were tested. All isolates were susceptible to the proprietary CHG formulation (0.5%, 1%, 2%), with 99% to 100% suppression of growth at the earliest time point in time kill assays (1 minute for gram-positive and 15 seconds for gram-negative organisms). Minimum inhibitory concentrations ranged from 1 : 4096 to 1 : 65536 for MRSA, 1 : 1024 to 1 : 2048 for VRE, 1 : 2048 to 1 : 4096 for XDR E. coli, 1 : 512 to 1 : 2048 for XDR A. baumannii, 1 : 512 to 1 : 1024 for XDR P. aeruginosa, and 1 : 512 to 1 : 1024 for XDR K. pneumoniae. Cloths impregnated with this CHG formulation provide effective protection against colonization and infection by many pathogens. This study provides in vitro evidence that the proprietary CHG formulation used in one brand of CHG-impregnated cloths is effective against XDR gram-negative organisms, MRSA, and VRE.

Detection of marijuana use by oral fluid and urine analysis following single-dose administration of smoked and oral marijuana.

We compared oral fluid testing to urine testing in subjects who were administered single doses of marijuana by smoked and oral routes. Oral fluid specimens were collected with the Intercept DOA Oral Specimen Collection Device, screened for THC with the Cannabinoids Intercept MICRO-PLATE Enzyme Immunoassay (EIA) utilizing a 1.0-ng/mL cutoff concentration, and confirmed for THC by gas chromatography-tandem mass spectrometry (GC-MS-MS) with a 0.5-ng/mL cutoff concentration. Urine specimens were screened for 11-nor-carboxy-delta9-tetrahydrocannabinol (THCCOOH) by immunoassay utilizing a 50-ng/mL cutoff concentration and confirmed for THCCOOH by GC-MS with a 15-ng/mL cutoff concentration. Oral fluid specimens tested positive following smoked marijuana (N = 10) consecutively for average periods (+/-SEM; range) of 15 (+/-2; 1-24) and 13 h (+/-3; 1-24) by EIA and GC-MS-MS, respectively. The average THC detection times of the last oral fluid positive specimen following smoked marijuana by EIA and GC-MS-MS were 31 (+/-9; 1-72) and 34 h (+/-11; 1-72), respectively. In comparison to oral fluid, urine specimens generally tested negative for THCCOOH immediately after marijuana use. The average times to detection of the first urine specimen positive for THCCOOH by EIA and GC-MS were 6 (+/-2; 1-16) and 4 h (+/-1; 2-8), respectively. Urine specimens tested positive consecutively for average periods of 26 (+/-9; 2-72) and 33 h (+/-10; 4-72) for EIA and GC-MS, respectively. The average THCCOOH detection times of the last specimen by EIA and GC-MS were 42 (+/-10; 2-72) and 58 h (+/-6; 16-72), respectively. Considering the noninvasive nature of oral fluid collection and improved detection of recent marijuana use compared to urine testing, it was concluded that oral fluid testing for THC offers specific advantages over other means of marijuana testing when used in safety-sensitive testing programs.

Sensory gating deficit expressed by a disturbed suppression of the P50 event-related potential in patients with Alzheimer's disease.

OBJECTIVE: Disturbed sensory gating has been related to attention deficit and greater distractibility in patients with schizophrenia, and dysfunction of the alpha-7 subunit of the cholinergic nicotinic receptor has been discussed as its biological basis. Alzheimer's disease is characterized by a cholinergic deficit, and postmortem studies have reported alpha-7 receptor loss in patients with Alzheimer's disease. In this study, the authors tested whether sensory gating is disturbed in patients with Alzheimer's disease. METHOD: Suppression of the P50 event-related potential following the second click of a double-click paradigm, a measure of sensory gating, was assessed in 17 Alzheimer's disease patients and 17 comparison subjects. RESULTS: Alzheimer's disease patients showed less P50 suppression following the second click relative to the comparison subjects. CONCLUSIONS: Disturbed sensory gating might result from cholinergic dysfunction and possibly from alpha-7 nicotinic receptor loss in patients with Alzheimer's disease. Prospective studies should investigate the relationship between sensory gating deficit and behavioral disturbances in Alzheimer's disease patients.

Amplitude reduction of the mismatch negativity in first-degree relatives of patients with schizophrenia.

First-degree relatives of schizophrenic patients display alterations in various cognitive domains and their electrophysiological counterparts similar to schizophrenic subjects. The mismatch negativity (MMN) is an event-related potential that reflects sensory memory in the pre-attentive stage of auditory processing. An amplitude reduction of the MMN has been reported in schizophrenia. The present study investigated the MMN in patients with schizophrenia, first-degree relatives and control subjects. The MMN amplitude was reduced in relatives compared to controls. The MMN amplitude reduction in schizophrenic patients compared to controls, however, did not reach significance in the present study. These results provide first evidence for disturbed sensory memory in relatives of patients with schizophrenia.

Electrophysiologic endpoint measures in a multicenter ALS drug trial.

We report the analysis of a battery of secondary electrophysiologic measurements to assess the progression of amyotrophic lateral sclerosis (ALS) in a two center, six month, double-blind, three arm trial comparing branched chain amino acids to L-threonine with pyridoxal 5-phosphate to placebo. The endpoint measurements were chosen to separately assess the effects of lower motor neuron loss and collateral reinnervation. For tests of inter-center reliability, we found no differences that could not be readily explained by variations in electrophysiologic testing techniques. Since the drug study was negative for the primary endpoint measure (muscle strength), we combined data from both centers and the three treatment arms. For measures of progression, all measures changed in the expected direction during the 6 months of the trial. We conclude that a battery of electrophysiologic measures can be used in a multicenter ALS drug trial to provide information on changes in lower motor neuron numbers and the effects of collateral reinnervation.

Immunoassay for detection of cocaine/metabolites in oral fluids.

There is growing interest in the use of alternate biological fluids for drug testing. An advantage of oral fluids is that collection can be made from individuals under direct observation without undue embarrassment or invasion of privacy. This study evaluated the STC Cocaine Metabolite MICRO-PLATE EIA for use in detection of cocaine and metabolites in oral fluids. Intra- and interassay precision of the EIA was < 10%. The EIA was cross-reactive to benzoylecgonine (100%), cocaine (> 12.9%), and cocaethylene (13.8%), but did not demonstrate detectable cross-reactivity with other commonly encountered medicants. Evaluation of a series of potential adulterants of oral fluids indicated that common household chemicals and foodstuffs did not alter the outcome of EIA testing for cocaine metabolite. Analysis by EIA and by gas chromatography-mass spectrometry (GC-MS) of oral fluids and urine specimens collected from current drug users in treatment programs and subjects participating in research studies involving controlled dosing of cocaine provided assessment of the clinical sensitivity and specificity of the STC Cocaine Metabolite EIA. Analysis of the data by means of receiver operating characteristic (ROC) plot indicated that the optimal cutoff concentration for the oral fluids EIA was 10 ng/mL. In comparison to GC-MS (10-ng/mL combined cutoff concentration for cocaine and benzoyleogonine), the EIA (10-ng/mL cutoff concentration) demonstrated a sensitivity, specificity, and accuracy of 95%, 82%, and 88%, respectively. The oral fluids EIA was slightly less sensitive than the urine EIA (300-ng/mL cutoff concentration) for the detection of cocaine metabolite with a sensitivity, specificity, and accuracy of 73%, 85%, and 88%, respectively. Overall, testing of oral fluids for cocaine metabolite with the STC Cocaine Metabolite MICRO-PLATE EIA appears to offer a viable alternative to urine for detection of recent cocaine use.

Chronic inflammatory demyelinating polyradiculoneuropathy: a study of proposed electrodiagnostic and histologic criteria.

OBJECTIVE: To examine the sensitivity of the 3 proposed electrodiagnostic (EDX) criteria for demyelination, the sensitivity and specificity of the proposed Ad Hoc Subcommittee of the American Academy of Neurology AIDS [Acquired Immunodeficiency Syndrome] Task Force histologic criteria (AAN criteria), the degree of agreement among these criteria, and the diagnostic value of sural nerve histologic criteria in patients with idiopathic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). DESIGN AND METHODS: A retrospective analysis of 24 patients with idiopathic CIDP and 12 patients with diabetic polyneuropathy (DP) who underwent comparable testing of clinical, histologic, and EDX features. RESULTS: We found 42%, 50%, and 79% sensitivity of the proposed EDX, AAN teased fiber, and AAN electron microscopic (EM) criteria, respectively, for demyelination in CIDP. The specificity of the proposed AAN teased fiber and EM criteria for demyelination was greater than 80% when tested against patients with DP. There was lack of agreement between the EDX and histologic criteria. Almost two thirds of patients with CIDP who met the EM criteria but none of the EDX criteria for demyelination showed a favorable response to immunomodulatory therapy. CONCLUSIONS: Sural nerve histologic criteria offer unique sensitivity and acceptable specificity toward the diagnosis of CIDP. Sural nerve biopsy should be considered when a clinical suspicion of CIDP remains in patients who do not meet the proposed EDX criteria for demyelination.

Decreases in rat extracellular hippocampal glucose concentration associated with cognitive demand during a spatial task.

Using in vivo microdialysis, we measured hippocampal extracellular glucose concentrations in rats while they performed spontaneous alternation tests of spatial working memory in one of two mazes. Extracellular glucose levels in the hippocampus decreased by 32% below baseline during the test period on the more complex maze, but by a maximum of 11% on the less complex maze. Comparable decreases were not observed in samples taken from rats tested on the more complex maze but with probes located near but outside of the hippocampus. Systemic glucose fully blocked any decrease in extracellular glucose and enhanced alternation on the more complex maze. These findings suggest that cognitive activity can deplete extracellular glucose in the hippocampus and that exogenous glucose administration reverses the depletion while enhancing task performance.

Men's attitudes regarding genetic testing for hereditary prostate cancer risk.

OBJECTIVES: Little is known about the attitudes of men unselected for a family history for prostate cancer concerning genetic testing for prostate cancer risk or genetic testing for inherited cancer predisposition. To explore this, we examined the interest in molecular testing for hereditary prostate cancer (HPC) predisposition among a self-selected cohort of 342 men presenting for prostate cancer screening. METHODS: Participants were surveyed concerning their attitudes about DNA testing for HPC predisposition and knowledge of prostate cancer-associated risk factors, including heredity. RESULTS: Of the participants completing the survey, 92% expressed interest in learning about DNA testing, and 89% stated that they would undergo DNA analysis for HPC predisposition, if available. Twenty-eight percent of respondents failed to demonstrate an adequate understanding of the concept of "inherited tendency." The demonstrated level of understanding of this concept did not differ by the respondent's family history, although it varied by race. An interest in learning about or undergoing testing did not vary by race, family history, or demonstrated understanding of the concept of inherited risk. CONCLUSIONS: Among men presenting for routine prostate cancer screening, interest in learning about testing for HPC predisposition and in having such testing performed may be high. The data also provide evidence that, in a population of men unselected for family history, interest in molecular testing for this common, male-specific cancer may parallel the high interest level demonstrated among women in DNA testing for inherited breast and ovarian cancer risk.

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy.

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.

Surface roughness of orthodontic wires via atomic force microscopy, laser specular reflectance, and profilometry.

The surface roughness of orthodontic archwires is an essential factor that determines the effectiveness of arch-guided tooth movement. Using the non-destructive techniques of atomic force microscopy (AFM) and of laser specular reflectance, the surface roughness of 11 nickel-titanium orthodontic wires, a stainless steel and a beta-titanium wire was measured. The results were compared with those obtained using surface profilometry. The smoothest wire, stainless steel, had an optical roughness of 0.10 micron, compared with 0.09 micron from AFM and 0.06 from profilometry. The surface roughness for the beta-titanium wire measured by all three methods was approximately 0.21 micron, while that of the NiTi wires ranged from 0.10 to 1.30 microns. As the surface roughness not only affects the effectiveness of sliding mechanics, but also the corrosion behaviour and the aesthetics of orthodontic components, the manufacturers of orthodontic wires should make an effort to improve the surface quality of their products.

Sensitivity of boreal forest carbon balance to soil thaw

We used eddy covariance; gas-exchange chambers; radiocarbon analysis; wood, moss, and soil inventories; and laboratory incubations to measure the carbon balance of a 120-year-old black spruce forest in Manitoba, Canada. The site lost 0.3 +/- 0.5 metric ton of carbon per hectare per year (ton C ha-1 year-1) from 1994 to 1997, with a gain of 0.6 +/- 0.2 ton C ha-1 year-1 in moss and wood offset by a loss of 0.8 +/- 0.5 ton C ha-1 year-1 from the soil. The soil remained frozen most of the year, and the decomposition of organic matter in the soil increased 10-fold upon thawing. The stability of the soil carbon pool ( approximately 150 tons C ha-1) appears sensitive to the depth and duration of thaw, and climatic changes that promote thaw are likely to cause a net efflux of carbon dioxide from the site.

A controlled trial of amino acid therapy in amyotrophic lateral sclerosis: I. Clinical, functional, and maximum isometric torque data.

We conducted a two center, double-blind, placebo-controlled treatment trial with oral branched chain amino acids (BCAA) (L-leucine 12 g, L-isoleucine 8 g, and L-valine 6.4 g daily) or L-threonine (4 g daily) with pyridoxal phosphate (160 mg daily) for six months in patients with amyotrophic lateral sclerosis (ALS). The effect of treatment on disease progression was estimated every two months by recording clinical muscle strength, maximum isometric muscle torque in selected muscles, forced vital capacity (FVC), activities of daily living pertaining to the upper and lower limbs, and timed tasks. Ninety-five patients were randomized to receive BCAA (n = 31), L-threonine (n = 32), or placebo (n = 32), of whom 77 (81%) completed the trial. Mean weight loss in the placebo group was 1.1 kg and in the L-threonine group was 3.2 kg; the BCAA group gained 0.2 kg (p = 0.04). The estimated decline in FVC was about 2.5 times greater in the BCAA and L-threonine groups as compared to placebo (p = 0.03). Otherwise, no significant differences were found in the changes observed in clinical, functional, timed, or maximum torque measures among treatment groups. The amino acids were well tolerated. The results of our study failed to show a beneficial effect of BCAA or L-threonine treatment for six months on the disease course in ALS. The higher rate of loss of pulmonary function in patients treated with BCAA or L-threonine may have been due to chance, but an adverse effect of these amino acids cannot be ruled out.

Evidence for locus heterogeneity in the Bethlem myopathy and linkage to 2q37.

The Bethlem myopathy, a childhood onset autosomal dominant myopathy with joint contractures, has recently been localized to 21q in a series of Dutch families and the alpha 1 and alpha 2 subunits of type VI collagen (COL6A1 and COL6A2) have been postulated as candidate genes. We investigate a large family of French Canadian descent (family 1489) in which the Bethlem myopathy is segregating. Family 1489 is unlinked to the region of interest on 21q, thus demonstrating locus heterogeneity within the Bethlem myopathy classification. In view of the localization of the genes coding the alpha 1 and alpha 2 subunits of type VI collagen on chromosome 21q, we carried out linkage analysis on chromosome 2q where the alpha 3 subunit of type VI collagen has been localized. We demonstrate linkage to markers in this region, define the region of disease gene localization, and confirm by FISH analysis that COL6A3 is located within the interval of interest making COL6A3 a feasible candidate gene for the Bethlem myopathy.

Surface structure and roughness of Nickel-Titanium wires.

Nickel-Titanium wires not only show the well known shape memory effect, but also pseudoelastic behaviour. This means, as the material is bent in a wide range of tension, the stress in the material stays constant. This special behaviour allows the improvement of orthodontic devices. The investigation of wires for this application reveals great differences in the surface roughness of the wires from various suppliers. The roughness causes a loss of spring energy for the orthodontic wire by frictional effects. The investigation of the mechanical behaviour of these materials leeds to differences compared with the ideal behaviour expected for the stress/strain curve. Obviously these differences are caused by surface effects of the wires. To evaluate these questions intensive roughness measurements with profilometry, laser spectroscopy and scanning force microscopy have been performed. Further more defined bending and tensile experiments have been carried out and corresponding roughness and structure analysis with the scanning force microscope has been taken into account. By etching the wires significant surface effects could be found.

Lumbosacral radiculoplexopathy as a manifestation of Epstein-Barr virus infection.

We report the clinical features of five patients with lumbosacral radiculoplexopathy (LSRP) and one patient with a femoral neuropathy, all of whom had serologic evidence of a recent Epstein-Barr virus (EBV) infection. After a thorough investigation, no other etiology was apparent. Pain was a prominent feature in all cases, and the prognosis was generally good, with recovery in weeks to months. We conclude that LSRP may occur as a postinfectious process following recent EBV infection.