Measuring pressure-derived fractional flow reserve through four French diagnostic catheters

Measurement of fractional flow reserve (FFR) with a pressure wire is used to discriminate between patients with and without functionally significant lesions. FFR can be assessed through a conventional 4Fr diagnostic catheter, which is a more convenient method of assessment. The aim of this study was to assess the feasibility, safety, repeatability, and reliability of routine FFR measurements through 4Fr diagnostic catheters. From a single-center prospective registry, results of FFR assessment through a 4Fr catheter were used to determine: (1) feasibility and safety, by the procedural success rate and immediate and 30-day clinical outcome; (2) repeatability, by the intraclass correlation coefficient and comparison of the difference (means +/- 2 SDs); and (3) reliability, by comparison of results obtained using 4Fr versus 7Fr guiding catheters. During the study period, FFR was measured in 190 patients, in 122 using a diagnostic 4Fr catheter (study population) and in 68 using a 7Fr guiding catheter. Measurement of FFR wa successful in 115 of 122 patients (94%). No complications related to the use of the 4Fr catheter occurred. Repeatability was determined from 108 repeated measurements: the intraclass correlation coefficient was 0.942 and the mean difference between repeated FFR measurements was -0.001 +/- 0.038. Reliability was determined from 15 unselected patients; there was no systematic error and only 1 value was out of the range of 2 SDs of the mean difference. Using a threshold value of 0.75, the Kappa coefficient for the qualitative agreement was 0.84. Thus, pressure-derived FFR assessment can safely be performed through 4Fr diagnostic catheters, with similar repeatability and reliability as 7Fr guiding catheters, resulting in a simplification of the measurement procedure.     

Cardiac valves in patients with Whipple endocarditis: microbiological, molecular, quantitative histologic, and immunohistochemical studies of 5 patients

The pathological features of Whipple endocarditis, which is caused by Tropheryma whipplei, were histologically evaluated in cardiac valves from 5 patients. We used quantitative image analysis to compare the valvular fibrosis, calcifications, vegetations, inflammation, and vascularization due to Whipple endocarditis with those due to non-Whipple endocarditis and degenerative valves. We also studied the presence of T. whipplei in valves by immunohistochemical analysis, culture, and polymerase chain reaction (PCR). In histologic analysis, Whipple endocarditis was characterized by significant fibrosis, a lack of calcifications, slight inflammation and vascularization, and vegetations of intermediate size. Inflammatory infiltrates consisted mainly of foamy macrophages and lymphocytes. We found that the detection of T. whipplei in cardiac valves, by immunohistochemical analysis, was correlated with the detection of the bacterium by culture and PCR. We report, for the first time, the immunodetection of T. whipplei in a surgically removed arterial embolus. Pathological and immunohistologic analyses may contribute to the diagnosis of Whipple endocarditis.     

Management of Demented Patients with Urinary Incontinence: A Case Study

Objective: To assess whether a demented patient with urinary incontinence (UI) could learn to use an adapted version of timed voiding (i.e., instead of being led by a caregiver, the patient learns to perform timed voiding by herself). Indeed, UI affects a large number of patients with dementia and creates a substantial burden to the caregiver. UI is the most common complaint at the time of institutionalization and it is often the cause of premature institutionalization. Timed voiding is a promising intervention, but one whose effectiveness remains to be demonstrated. Additionally, timed voiding has the disadvantage of being constraining for caregivers, requiring them to be present to stimulate the patient to urinate at each of the scheduled occasions. Method: The present intervention required the patient to learn (1) to associate an auditory signal from a timer to the action of urination, (2) to reprogram the timer, using the spaced retrieval technique. An ABAB paradigm was used to assess the effectiveness of this program to eliminate urinary accidents. Results: The results of the intervention showed that the use of the timer was effective in helping the patient to reduce her urinary leaks from 1.5 diurnal accidents per week to zero during four months. Conclusion: UI in patients with dementia seems treatable. Such intervention could contribute to delay institutionalization of patients with dementia through maintaining their autonomy and reducing the burden of caregivers.     

Structural characterization of Campylobacter jejuni lipooligosaccharide outer cores associated with Guillain-Barre and Miller Fisher syndromes

Molecular mimicry between lipooligosaccharides (LOS) of Campylobacter jejuni and gangliosides in peripheral nerves plays a crucial role in the pathogenesis of C. jejuni-related Guillain-Barré syndrome (GBS). We have analyzed the LOS outer core structures of 26 C. jejuni strains associated with GBS and its variant, Miller Fisher syndrome (MFS), by capillary electrophoresis coupled with electrospray ionization mass spectrometry. Sixteen out of 22 (73%) GBS-associated and all 4 (100%) MFS-associated strains expressed LOS with ganglioside mimics. GM1a was the most prevalent ganglioside mimic in GBS-associated strains (10/22, 45%), and in eight of these strains, GM1a was found in combination with GD1a mimics. All seven strains isolated from patients with ophthalmoplegia (GBS or MFS) expressed disialylated (GD3 or GD1c) mimics. Three out of 22 GBS-associated strains (14%) did not express sialylated ganglioside mimics because their LOS locus lacked the genes necessary for sialylation. Three other strains (14%) did not express ganglioside mimics because of frameshift mutations in either the cstII sialyltransferase gene or the cgtB galactosyltransferase gene. It is not possible to determine if these mutations were already present during C. jejuni infection. This is the first report in which mass spectrometry combined with DNA sequence data were used to infer the LOS outer core structures of a large number of neuropathy-associated C. jejuni strains. We conclude that molecular mimicry between gangliosides and C. jejuni LOS is the presumable pathogenic mechanism in most cases of C. jejuni-related GBS. However, our findings suggest that in some cases, other mechanisms may play a role. Further examination of the disease etiology in these patients is mandatory.     

Barriers and facilitators of evidence-based practice perceived by behavioral science health professionals

Progress in implementing evidence-based behavioral practices has been slow. A qualitative study was performed to characterize the major facilitators and barriers to evidence-based practice (EBP) perceived by behavioral professionals. Members of professional e-mail listservs were queried and 84 barriers and 48 facilitators were nominated by 37 respondents. Thematic analysis revealed seven themes to describe both barriers and facilitators: (a) training, (b) attitudes, (c) consumer demand, (d) logistical considerations, (e) institutional support, (f) policy, and (g) evidence. Most frequently cited barriers included negative attitudes about EBP and lack of training. Barriers also reflected confusion between EBP and the products of EBP (i.e., empirically supported treatments [ESTs]). Main facilitators included a growing evidence base. Results suggest that uptake of EBP may be facilitated by education and training.     

Adapter protein SH2-Bbeta stimulates actin-based motility of Listeria monocytogenes in a vasodilator-stimulated phosphoprotein (VASP)-dependent fashion

SH2-Bbeta (Src homology 2 Bbeta) is an adapter protein that is required for maximal growth hormone-dependent actin reorganization in membrane ruffling and cell motility. Here we show that SH2-Bbeta is also required for maximal actin-based motility of Listeria monocytogenes. SH2-Bbeta localizes to Listeria-induced actin tails and increases the rate of bacterial propulsion in infected cells and in cell extracts. Furthermore, Listeria motility is decreased in mouse embryo fibroblasts from SH2-B(-/-) mice. Both recruitment of SH2-Bbeta to Listeria and SH2-Bbeta stimulation of actin-based propulsion require the vasodilator-stimulated phosphoprotein (VASP), which binds ActA at the surfaces of Listeria cells and enhances bacterial actin-based motility. SH2-Bbeta enhances actin-based movement of ActA-coated beads in a biomimetic actin-based motility assay, provided that VASP is present. In vitro binding assays show that SH2-Bbeta binds ActA but not VASP; however, binding to ActA is greater in the presence of VASP. Because VASP also plays an essential regulatory role in actin-based processes in eukaryotic cells, the present results provide mechanistic insight into the functions of both SH2-Bbeta and VASP in motility and also increase our understanding of the fundamental mechanism by which Listeria spreads.     

Use of short-acting beta2-agonists during pregnancy and the risk of pregnancy-induced hypertension

BACKGROUND: The effect of inhaled short-acting beta(2)-agonists (SABAs) on pregnancy outcome, especially hypertensive complications, is not well documented. After the finding of a possible protective association of inhaled SABAs with pregnancy-induced hypertension (PIH) in a previous study, we decided to further investigate their effect on this condition. OBJECTIVE: We sought to determine the effect of inhaled SABA use during pregnancy on the risk of PIH (gestational hypertension, preeclampsia, or eclampsia) in asthmatic women. METHODS: Three of Quebec's administrative databases were linked to constitute a cohort of asthmatic women who had at least 1 delivery between 1990 and 2000. A nested case-control study was performed using up to 10 control subjects matched to each case patient for the year of conception and gestational age. Statistical analyses considered 22 confounders. RESULTS: The cohort was composed of 3505 asthmatic women who had a total of 4593 pregnancies. Three hundred two patients with PIH and 3013 control subjects were identified. Compared with nonuse, inhaled SABA use during pregnancy was significantly associated with a reduced risk of PIH (adjusted rate ratios: >0-3 doses/week, 0.62 (95% CI, 0.44-0.87); > 3-10 doses/week, 0.51 (95% CI, 0.34-0.79); and >10 doses/week, 0.48 (95% CI, 0.30-0.75)). CONCLUSIONS: To our knowledge, this is the first study reporting that inhaled SABA use during pregnancy is associated with a reduced risk of PIH. Potential explanations include pharmacologic and physiological effects or residual confounding. CLINICAL IMPLICATIONS: These results increase the evidence about the safety of inhaled SABAs in this population, although they should not undervalue the importance of maintaining good control of asthma symptoms.     

Wide geographic spread of diverse acquired AmpC beta-lactamases among Escherichia coli and Klebsiella spp. in the UK and Ireland

OBJECTIVES: To determine the distribution of acquired AmpC beta-lactamases in 173 isolates of Escherichia coli and Klebsiella spp. submitted to the UK's national reference laboratory for antibiotic resistance. METHODS: MICs were determined and interpreted according to BSAC guidelines. Candidate isolates were those resistant to cefotaxime and/or ceftazidime, irrespective of addition of clavulanic acid. Genes encoding six phylogenetic groups of acquired AmpC enzymes were sought by PCR. Selected isolates were compared by pulsed-field gel electrophoresis (PFGE), and one bla(AmpC) amplicon was sequenced. RESULTS: Genes encoding acquired AmpC enzymes were detected in 67 (49%) candidate E. coli and 21 (55%) Klebsiella spp. Sixty isolates produced CIT-type enzymes, 14 had ACC types, 11 had FOX types and 3 had DHA enzymes. The low-level cephalosporin resistance of the remaining isolates (n = 85; 49%) was inferred to result from reduced permeability or, in E. coli, from hyperexpression of chromosomal ampC. Twenty-four E. coli isolates from one hospital produced a CIT-type enzyme, with 20 of these additionally producing a group 1 CTX-M extended-spectrum beta-lactamase. PFGE indicated that these isolates belonged to UK epidemic strain A, which normally produces CTX-M-15, but no acquired AmpC. Sequencing a representative bla(AmpC) amplicon indicated that in one centre this strain had acquired a novel CMY-2 variant, designated CMY-23. CONCLUSIONS: Diverse acquired AmpC enzymes occur in E. coli and Klebsiella spp. isolates in the UK and Ireland, with CIT types the most common. Producers are geographically scattered, but with some local outbreaks. Acquisition of a CMY-2-like enzyme by E. coli epidemic strain A suggests that these enzymes may be poised to become an important public health issue.