Clinical Assessment of a Point-of-Care Serum Amyloid A Assay in Foals with Bronchopneumonia.

BACKGROUND: Despite the paucity of data available, stall-side serum amyloid (SAA) assays are commonly used to make diagnostic and treatment decisions in foals with bronchopneumonia. HYPOTHESIS: Measurement of SAA concentrations can accurately differentiate pneumonic from healthy foals. ANIMALS: Fifty-four pneumonic foals between 3 weeks and 5 months of age were compared to 44 healthy controls. In addition, 47 foals on a farm endemic for R. equi infections were studied. METHODS: Serum samples were collected from pneumonic foals at hospital admission. Foals were categorized as having pneumonia caused by R. equi or by other microorganisms based on culture of a tracheobronchial aspirate. In addition, serum samples were obtained at 2-week intervals from foals born at a farm endemic for R. equi. SAA concentrations were measured by a point-of-care assay. Diagnostic performance of SAA was assessed by use of receiver operating characteristic curves. RESULTS: Concentrations of SAA in foals with bronchopneumonia were significantly (P < 0.001) higher than those of healthy foals, but 15 of 54 pneumonic foals (28%) had SAA concentrations <5 µg/mL. There was no correlation between SAA concentrations and radiographic score in foals with R. equi pneumonia. The ability of SAA to predict development of R. equi pneumonia at the endemic farm was limited with a sensitivity of 64% and a specificity of 77%. CONCLUSION AND CLINICAL IMPORTANCE: Overall, SAA concentrations are significantly higher in pneumonic than in healthy foals. However, performance of SAA in detecting pneumonic foals is limited by the high proportion of false-positive and false-negative results.

Frequency of electrocardiogram testing among HIV-infected patients at risk for medication-induced QTc prolongation.

OBJECTIVES: HIV-infected patients are commonly prescribed several medications and are thus at risk for drug interactions that may result in QTc prolongation. We sought (1) to identify the frequency of electrocardiogram (ECG) monitoring (2), to determine the prevalence of drug interactions involving QTc-prolonging medications, and (3) to quantify the prevalence of QTc prolongation. METHODS: A cross-sectional study was conducted among HIV-infected adults. Demographics, medications, drug interactions and comorbidities were abstracted from patients' medical records. Abnormal QTc interval was defined per the UK Committee for Proprietary Medicinal Products. Clinical characteristics were compared among ECG recipients and nonrecipients. Among ECG recipients, the prevalence and predictors of QTc prolongation were assessed. RESULTS: Among the 454 patients included in the study, 80.8% were prescribed a medication associated with QTc prolongation and 39% had drug interactions expected to increase QTc prolongation risk. There were 138 patients (30.3%) who received ECG testing. Receipt of ECG monitoring was associated with increasing age, diabetes, increasing total number of medications and gastroesophageal reflux disease. Among ECG recipients, the prevalence of abnormal QTc interval was 27.5%. Chronic kidney disease [prevalence ratio (PR) 3.47; 95% confidence interval (CI) 1.37-8.83; P = 0.009], hepatitis C virus coinfection (PR 2.26; 95% CI 0.97-5.27; P = 0.06) and hypertension (PR 2.11; 95% CI 0.93-4.81; P = 0.07) were independently associated with an abnormal QTc interval. CONCLUSIONS: A low frequency of ECG testing was observed, despite a high use of medications associated with QTc prolongation. The risk of abnormal QTc interval was highest among patients with chronic kidney disease, hypertension and hepatitis C virus coinfection.

D-dimer threshold increase with pretest probability unlikely for pulmonary embolism to decrease unnecessary computerized tomographic pulmonary angiography.

BACKGROUND: Increasing the threshold to define a positive D-dimer could reduce unnecessary computed tomographic pulmonary angiography (CTPA) for a suspected pulmonary embolism (PE) but might increase rates of a missed PE and missed pneumonia, the most common non-thromboembolic diagnosis seen on CTPA. OBJECTIVE: Measure the effect of doubling the standard D-dimer threshold for 'PE unlikely' Revised Geneva (RGS) or Wells' scores on the exclusion rate, frequency and size of a missed PE and missed pneumonia. METHODS: Patients evaluated for a suspected PE with 64-channel CTPA were prospectively enrolled from emergency departments (EDs) and inpatient units of four hospitals. Pretest probability data were collected in real time and the D-dimer was measured in a central laboratory. Criterion standard was CPTA interpretation by two independent radiologists combined with clinical outcome at 30 days. RESULTS: Of 678 patients enrolled, 126 (19%) were PE+ and 93 (14%) had pneumonia. Use of either Wells' ≤ 4 or RGS ≤ 6 produced similar results. For example, with RGS ≤ 6 and standard threshold (< 500 ng mL(-1)), D-dimer was negative in 110/678 (16%), and 4/110 were PE+ (posterior probability 3.8%) and 9/110 (8.2%) had pneumonia. With RGS ≤ 6 and a threshold < 1000 ng mL(-1) , D-dimer was negative in 208/678 (31%) and 11/208 (5.3%) were PE+, but 10/11 missed PEs were subsegmental and none had concomitant DVT. Pneumonia was found in 12/208 (5.4%) with RGS ≤ 6 and D-dimer < 1000 ng mL(-1). CONCLUSIONS: Doubling the threshold for a positive D-dimer with a PE unlikely pretest probability could reduce CTPA scanning with a slightly increased risk of missed isolated subsegmental PE, and no increase in rate of missed pneumonia.

Rilpivirine: a new addition to the anti-HIV-1 armamentarium.

HIV has shifted from an acute illness to a chronic condition that can be successfully managed long-term with combination antiretroviral therapy. Rilpivirine (TMC-278) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that is positioned to become an importation therapy option for HIV-1-infected patients, particularly for those that are naive to therapy. In phase III studies this agent demonstrated similar virologic and immunologic efficacy compared to a current standard of care, efavirenz, while causing less adverse events. A higher proportion of rilpivirine-treated patients did experience virologic failure, however, and providers will need to weigh this risk with the improved tolerability of rilpivirine. In vitro studies have demonstrated that rilpivirine, as a diarylpyrimidine NNRTI with greater flexibility, has a higher genetic barrier to resistance when compared to first-generation NNRTI agents. Longer-term clinical data will be necessary to better understand rilpivirine's durability and activity against viral resistance in patients. Rilpivirine will be available as a stand-alone agent and will also be coformulated with tenofovir and emtricitabine to create a safe and effective antiretroviral regimen that can be administered as a single daily-dosed tablet.

Copper and cadmium: responses in Pseudomonas putida KT2440.

AIMS: To compare responses of a soil bacterium to Cu and Cd. METHODS AND RESULTS: In minimal medium, Cd caused a dose-dependent growth stasis of logarithmic phase cells of Pseudomonas putida, strain KT2440, whereas Cu did not compromise growth up to 10 mg l(-1). Proteomics showed changes in accumulation of both membrane and soluble proteins by 6 h of treatment; increased Krebs cycle enzymes were apparent. Transcript analysis showed Cd- and Cu-induced different genes. Cd-induced genes encoding the transcriptional regulator CzrR2; an outer membrane protein associated with lipopolysaccharide stability, H1; two oxidative stress protective proteins and the P-type ATPase, CadA2, associated with Cd(2+) efflux. The genes most responsive to Cu encoded the regulator CopR1 and the outer membrane resistance protein regulated by CopR1, CopB1; a putative porin, PorD and the Cu-binding protein, PacZ or CopZ, and CopA2. CONCLUSIONS: These findings support that a soil pseudomonad restricts internalization of the metals by using different sets of binding proteins and efflux pumps. Activation of mechanisms to protect against oxidative stress also was evident especially with Cd exposure. SIGNIFICANCE AND IMPACT OF THE STUDY: The differential cellular responses to Cd and Cu suggest that risk assessment for Cd and Cu should be different.

Predictors of high vancomycin MIC values among patients with methicillin-resistant Staphylococcus aureus bacteraemia.

BACKGROUND: Recent evidence suggests that vancomycin demonstrates reduced activity against methicillin-resistant Staphylococcus aureus (MRSA) infections when vancomycin MIC values are at the high end of the susceptibility range (> or = 1.5 mg/L). However, scant research exists on factors predictive of high vancomycin MICs (> or = 1.5 mg/L) among MRSA bacteraemic patients. Empirical therapy decisions would greatly benefit from such information. OBJECTIVES: To identify the parameters predictive of high vancomycin MICs (> or = 1.5 mg/L) among MRSA bacteraemic patients and to develop an evidence-based clinical prediction tool. METHODS: This observational cohort study included adult patients with MRSA bloodstream infections between January 2005 and May 2007. Demographics, co-morbid conditions, and microbiology and antibiotic exposure data were collected. Vancomycin MICs were determined by Etest. Stepwise logistic regression was used to identify independent predictors of high vancomycin MICs. RESULTS: Of the 105 patients who met the inclusion criteria, 77 patients (73.3%) exhibited a high vancomycin MIC (> or = 1.5 mg/L). In the bivariate analysis, prior vancomycin exposure within 30 days of index culture collection [15 patients (19.5%) versus 1 patient (3.6%), P = 0.05] and residence in an intensive care unit (ICU) at the onset of infection [27 patients (35.1%) versus 3 patients (10.7%), P = 0.02] were both significantly associated with a high vancomycin MIC value and both were independent predictors of high MICs in the logistic regression. CONCLUSIONS: Patients with MRSA bloodstream infections in the ICU or with a history of vancomycin exposure should be considered at high risk of infection with strains for which vancomycin MICs are elevated. Appropriate and aggressive empirical therapy is required for these patients.

Initial risk stratification and presenting characteristics of patients with evolving myocardial infarctions.

OBJECTIVES: To describe the presenting characteristics and risk stratification of patients presenting to the emergency department with chest pain who have a normal initial troponin level followed by a raised troponin level within 12 h (evolving myocardial infarction (EMI)). METHODS: Data from the Internet Tracking Registry for Acute Coronary Syndromes (i*trACS), a registry of patients presenting with undifferentiated chest pain, were used. This analysis included patients without ST segment elevation with at least two troponin assay results < or = 12 h apart. Patients were stratified into three groups: EMI (initial troponin assay negative, second troponin assay positive), non-ST elevation myocardial infarction (NSTEMI) (initial troponin assay positive) and no MI (all troponin assays negative). RESULTS: Of 4136 eligible patients, 5% had EMI, 8% had NSTEMI and 87% had no MI. Patients with EMI were more similar to those with NSTEMI than those with no MI with respect to demographic characteristics, presentation, admission patterns and revascularisation. The initial ECG in patients with EMI was most commonly non-diagnostic (51%), but physicians' initial impressions commonly reflected MI, unstable angina or high-risk chest pain (76%). This risk assessment was followed by a high rate of critical care admissions (32%) and revascularisation (percutaneous coronary intervention 17%) among patients with EMI. CONCLUSION: Patients with EMI appear similar at presentation to those with NSTEMI. Patients with EMI are perceived as being at high risk, evidenced by similar diagnostic impressions, admission practices and revascularisation rates to patients with NSTEMI.

Optimizing the use of frozen-thawed equine semen.

This manuscript is a review of current protocols, advantages, and disadvantages of breeding mares with frozen-thawed equine semen. Issues affecting pregnancy rates are discussed, including proper mare selection, induction of ovulation, insemination dose, timing of insemination (single-dose versus multiple-dose insemination), methods of insemination (transrectal-guided deep-horn versus hysteroscopic insemination), and post-insemination mare management procedures. In a retrospective analysis of breeding records, a single-dose of frozen-thawed semen was inseminated within 6h post-ovulation; the pregnancy rate (14-16 days after AI) was 67 of 149 (45%). These results were comparable to those previously achieved under commercial conditions, as well as previous studies using multiple doses of frozen-thawed semen per estrous cycle. In conclusion, these data provided evidence that, with appropriate breeding management, an acceptable pregnancy rate can be achieved in mares with a single-dose of frozen-thawed semen (per-cycle) inseminated within 6h after ovulation.

Pyrene mineralization by Mycobacterium sp. strain KMS in a barley rhizosphere.

To determine whether the soil Mycobacterium isolate KMS would mineralize pyrene under rhizosphere conditions, a microcosm system was established to collect radioactive carbon dioxide released from the labeled polycyclic aromatic hydrocarbon. Microcosms were designed as sealed, flow-through systems that allowed the growth of plants. Experiments were conducted to evaluate mineralization of 14C-labeled pyrene in a sand amended with the polycyclic aromatic hydrocarbons degrading Mycobacterium isolate KMS, barley plants, or barley plants with roots colonized by isolate KMS. Mineralization was quantified by collecting the 14CO2 produced from 14C-labeled pyrene at intervals during the 10-d incubation period. Roots and foliar tissues were examined for 14C incorporation. Mass balances for microcosms were determined through combustion of sand samples and collection and quantification of 14CO2 evolved from radiolabeled pyrene. No pyrene mineralization was observed in the sterile control systems. Greater release of 14CO2 was observed in the system with barley colonized by KMS than in microcosms containing just the bacterium inoculum or sterile barley plants. These findings suggest that phytostimulation of polycyclic aromatic hydrocarbons mineralization could be applied in remediation schemes.

Diversity of soil mycobacterium isolates from three sites that degrade polycyclic aromatic hydrocarbons.

AIMS: This paper investigates the diversity of polycyclic aromatic hydrocarbon (PAH)-degrading mycobacterium isolates from three different sites within United States: Montana, Texas and Indiana. METHODS AND RESULTS: All five mycobacterium isolates differed in chromosomal restriction enzyme-fragmentation patterns; three isolates possessed linear plasmids. The DNA sequence between the murA and rRNA genes were divergent but the sequence upstream of nidBA genes, encoding a dioxygenase involved in pyrene oxidation, was more highly conserved. Long-chain fatty acid analysis showed most similarity between three isolates from the same Montana site. All isolates were sensitive to rifampicin and isoniazid, used in tuberculosis treatment, and to syringopeptins, produced by plant-associated pseudomonads. Biofilm growth was least for isolate MCS that grew on plate medium as rough-edged colonies. The patterns of substrate utilization in Biolog plates showed clustering of the Montana isolates compared with Mycobacterium vanbaalenii and Mycobacterium gilvum. CONCLUSION: The five PAH-degrading mycobacterium isolates studied differ in genetic and biochemical properties. SIGNIFICANCE AND IMPACT OF THE STUDY: Different properties with respect to antibiotic susceptibility, substrate utilization and biofilm formation could influence the survival in soil of the microbe and their suitability for use in bioaugmentation.

Polycyclic aromatic hydrocarbon-degrading Mycobacterium isolates: their association with plant roots.

Five environmental mycobacterium isolates that degrade polycyclic aromatic hydrocarbons (PAHs) were associated with barley root surfaces after growth of the seedlings from inoculated seed. Mycobacterium cells were detected along the total root length for four of these isolates. These PAH-degrading mycobacterium strains had hydrophilic cell surfaces, whereas one strain, MCS, that was hydrophobic had reduced association along the root length with no cells being detected from the root tips. The root-tip-competent strain, KMS, was competitive for its root association in the presence of the root-colonizing pseudomonad, Pseudomonas putida KT2440. All mycobacterium strains utilized simple sugars (fructose, glucose) and the trisaccharide 6-kestose, present in barley root washes, for planktonic growth, but they differed in their potential for biofilm formation under in vitro conditions. Mineralization of pyrene by the KMS strain occurred when the components in the barley root wash were amended with labeled pyrene suggesting to us that mineralization could occur in plant rhizospheres containing such mycobacterium strains.

Equilibrium nonaqueous phase liquid pool geometry in coarse soils with discrete textural interfaces.

This paper presents a model for the geometry of nonaqueous phase liquid (NAPL) pools and mounds in homogeneous soils and soils with discrete textural interfaces. It is shown that the concepts of capillary pressure-saturation curve hysteresis and entry pressures are integral to the complete conceptualization of pool and mound geometry. Unless hysteresis is included in the analysis, light NAPL (LNAPL) in homogeneous soils cannot exist in pools at all, and dense NAPL (DNAPL) will not mound on horizontal textural interfaces unless lateral confining boundaries are present. The proposed model also implies that remobilization of DNAPL pools will occur at lower hydraulic gradients than those predicted with previous models. Comparing predicted and experimental DNAPL and LNAPL pool thicknesses and the location of an LNAPL lens with respect to the top of the capillary fringe validate the model.

Isolation and characterization of polycyclic aromatic hydrocarbon-degrading Mycobacterium isolates from soil.

Bioremediation of soils contaminated with wood preservatives containing polycyclic aromatic hydrocarbons (PAHs) is desired because of their toxic, mutagenic, and carcinogenic properties. Creosote wood preservative-contaminated soils at the Champion International Superfund Site in Libby, Montana currently undergo bioremediation in a prepared-bed land treatment unit (LTU) process. Microbes isolated from these LTU soils rapidly mineralized the (14)C-labeled PAH pyrene in the LTU soil. Gram staining, electron microscopy, and 16S rDNA-sequencing revealed that three of these bacteria, JLS, KMS, and MCS, were Mycobacterium strains. The phylogeny of the 16S rDNA showed that they were distinct from other Mycobacterium isolates with PAH-degrading activities. Catalase and superoxide dismutase (SOD) isozyme profiles confirmed that each isolate was distinct from each other and from the PAH-degrading mycobacterium, Mycobacterium vanbaalenii sp. nov, isolated from a petroleum-contaminated soil. We find that dioxygenase genes nidA and nidB are present in each of the Libby Mycobacterium isolates and are adjacent to each other in the sequence nidB-nidA, an order that is unique to the PAH-degrading mycobacteria.

Distinguishing dural sinus thrombosis from benign intracranial hypertension.

Dural sinus thrombosis (DST) is a life threatening illness and is often overlooked but it must be considered in the differential diagnosis of a patient presenting with a significant headache. DST presents similarly to benign intracranial hypertension (BIH) with intracranial hypertension and headache. A case of a 23 year old woman with DST is described that was initially diagnosed as BIH. A Medline search to determine the examination of a patient with suspected BIH or DST yielded several articles on this topic but only two brief case reports in the emergency medicine literature. Any patient with suspected DST or BIH must have a confirmatory magnetic resonance imaging and magnetic resonance venography study. Treatment of DST seems to be effective, considerably different from BIH, and lack of treatment may lead to increased morbidity and mortality.

Insulin-like growth factor-I and insulin-like growth factor binding protein-2 and -5 in equine seminal plasma: association with sperm characteristics and fertility.

The objectives of this study were 1) to determine whether insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were present in seminal plasma of stallions; 2) to compare semen parameters (IGF proteins, sperm numbers, morphology, and motility) from stallions at sexual rest (SR) and when sexually active (SA); 3) to compare semen parameters between stallions with high and low seminal plasma IGF-I concentrations; and 4) to examine the relationship between seminal plasma IGF-I concentrations and fertility parameters of stallions. Ejaculates were collected from stallions at SR (n = 51) and SA (n = 46). Concentrations of IGF-I and IGFBP-2 in seminal plasma samples were determined by radioimmunoassay. Presence of IGFBPs in equine seminal plasma was verified using immunoprecipitation and Western ligand blot procedures. IGF-I, IGFBP-2, and IGFBP-5 were present in equine seminal plasma. Concentrations of IGF-I, IGF-I/protein, total IGF-I, IGFBP-2, IGFBP-2/protein, and total IGFBP-2 were not significantly different (P > or = 0.13) in seminal plasma between stallions at either SR or SA. At SR, stallions with higher seminal plasma IGF-I had more total IGFBP-2 per ejaculate (P < 0.01), more morphologically normal sperm (P = 0.05), and higher first-cycle pregnancy rates (P = 0.02). At SA, stallions with higher seminal plasma IGF-I had fewer cycles per pregnancy (P = 0.02). An association of seminal plasma IGF-I concentration with sperm motility, sperm morphology, and pregnancy rates in bred mares suggests that IGF-I may play a role in sperm function.

Effect of the addition of ketamine to morphine in patient-controlled analgesia.

This randomised, double-blind, prospective study compared morphine (1 mg x m(-1)) with the combination of morphine (1 mg x m(-1)) and ketamine (0.75 mg x m(-1)) via a patient-controlled analgesia system (PCAS) for postoperative pain control. A total of 42 female patients, ASA grade I and II, undergoing elective total abdominal hysterectomy was studied. During a standardised anaesthetic, a loading dose from the PCA syringe of 10 ml x m(-2) of body surface area was given. A PCAS with a background infusion was commenced postoperatively. Pain and side-effects were assessed using numerical scoring systems and cardiovascular and respiratory parameters were recorded. There was no statistically significant difference between the groups in total morphine consumption or pain scoring. Side-effect profiles and time to mobilisation were similar. This study concludes that the addition of ketamine to morphine, in this dosage regimen, administered via PCAS for postoperative pain control, does not confer benefit following total abdominal hysterectomy.

Both solar UVA and UVB radiation impair conidial culturability and delay germination in the entomopathogenic fungus Metarhizium anisopliae.

The entomopathogenic hyphomycete Metarhizium anisopliae has been used in programs of agricultural pest and disease vector control in several countries. Exposure to simulated solar radiation for a few hours can completely inactivate the conidia of the fungus. In the present study we determined the effect of exposures to full-spectrum sunlight and to solar ultraviolet A radiation at 320-400 nm (UVA) on the conidial culturability and germination of three M. anisopliae strains. The exposures were performed in July and August 2000 in Logan, UT. The strains showed wide variation in tolerance when exposed to full-spectrum sunlight as well as to UVA sunlight. Four-hour exposures to full-spectrum sunlight reduced the relative culturability by approximately 30% for strain ARSEF 324 and by 100% for strains ARSEF 23 and 2575. The relative UV sensitivity of the two more sensitive strains was different under solar UV from that under ultraviolet B radiation at 280-320 nm (UVB) in the laboratory. Four-hour exposures to solar UVA reduced the relative culturability by 10% for strain ARSEF 324, 40% for strain ARSEF 23 and 60% for strain ARSEF 2575. Exposures to both full-spectrum sunlight and UVA sunlight delayed the germination of the surviving conidia of all three strains. These results, in addition to confirming the deleterious effects of UVB, clearly demonstrate the negative effects of UVA sunlight on the survival and germination of M. anisopliae conidia under natural conditions. The negative effects of UVA in sunlight also emphasize that the biological spectral weighting functions for this fungus must not neglect the UVA wavelengths.

The rpoS gene in Pseudomonas syringae is important in surviving exposure to the near-UV in sunlight.

The near-UV component of sunlight decreased culturability of the leaf epiphyte and plant pathogen Pseudomonas syringae. Exposure of the wild-type cells for 4 h to UV-A and UV-B in sunlight was ten fold more detrimental than exposure to sunlight with just UV-A. Sensitivity to UV-A especially increased in a mutant of P. syringae lacking the global regulatory sigma factor, RpoS. No RpoS-mutant cells were culturable after 4 h of exposure to near-UV sunlight. These findings suggest that both UV-A and UV-B wavelengths cause damage to the bacterial cell and that the RpoS protein regulates protective measures for the leaf-associated pseudomonad.

Clinical inertia.

Medicine has traditionally focused on relieving patient symptoms. However, in developed countries, maintaining good health increasingly involves management of such problems as hypertension, dyslipidemia, and diabetes, which often have no symptoms. Moreover, abnormal blood pressure, lipid, and glucose values are generally sufficient to warrant treatment without further diagnostic maneuvers. Limitations in managing such problems are often due to clinical inertia-failure of health care providers to initiate or intensify therapy when indicated. Clinical inertia is due to at least three problems: overestimation of care provided; use of "soft" reasons to avoid intensification of therapy; and lack of education, training, and practice organization aimed at achieving therapeutic goals. Strategies to overcome clinical inertia must focus on medical students, residents, and practicing physicians. Revised education programs should lead to assimilation of three concepts: the benefits of treating to therapeutic targets, the practical complexity of treating to target for different disorders, and the need to structure routine practice to facilitate effective management of disorders for which resolution of patient symptoms is not sufficient to guide care. Physicians will need to build into their practice a system of reminders and performance feedback to ensure necessary care.