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Immunomodulators that induce local endogenous interferon-alpha (IFN-alpha) production by plasmacytoid dendritic cells (pDCs) may offer new strategies for the treatment of patients chronically infected with the hepatitis C virus (HCV). However, such an approach may be compromised if reports are true that IFN-alpha production by pDCs from patients with chronic HCV (cHCV) is profoundly impaired. To address the question of pDC dysfunction in cHCV more definitively, in the present study a panel of four prototypic synthetic agonists of toll-like receptor 7 (TLR7) or TLR9 were administered in vitro to pDCs purified from cHCV patients and from normal uninfected donors and their responses compared in terms of not only IFN-alpha production but also the global expression of other cytokines and phenotypic maturation. Plasmacytoid DCs from uninfected donors produced substantial levels of IFN-alpha in response to three of the four agonists and yet only one TLR9 agonist, a class C CpG oligodeoxynucleotide (ODN), induced robust IFN-alpha production by pDCs from cHCV patients. Proinflammatory cytokine production and phenotypic maturation in response to all four agonists was equivalent in infected and uninfected pDCs. These data point to a profound but selective defect in IFN-alpha production by pDCs from cHCV donors. Nonetheless, a class C CpG ODN successfully induced robust IFN-alpha production, suggesting that this class of TLR9 agonist may have utility as a future immunotherapeutic for the treatment of chronic HCV infection.

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We have described previously an immunostimulant derived from Onchocerca volvulus, the helminth parasite that causes onchocerciasis. Recombinant O. volvulus activation-associated secreted protein-1 (rOv-ASP-1) was a potent adjuvant for antibody and cellular responses to protein, polypeptide and small peptide antigens. Our aims were to determine whether rOv-ASP-1 is immunostimulatory for human peripheral blood mononuclear cells (PBMC) and, if so, whether it could augment cellular responses against human pathogen antigens in vitro. Cytokines from rOv-ASP-1-stimulated human PBMC were measured by a fluorescence activated cell sorter-based multiplex assay. Recall responses of normal healthy donor (NHD) and chronic hepatitis C virus (c-HCV)-infected patient PBMC to tetanus toxoid (TT) or HCV core (HCVco) antigen, respectively, were measured by interferon-gamma enzyme-linked immunospot assays. Interferon-gamma was the predominant cytokine induced by rOv-ASP-1. 77.3% of NHD anti-TT and 88.9% of c-HCV anti-HCVco responses were enhanced by rOv-ASP-1. The immunostimulant effect was dependent upon contact between CD56+ and CD56- fractions of PBMC. We have described a helminth-derived protein that can act as an immunostimulant for human recall responses in vitro to TT and, perhaps more importantly, HCV antigens in patients with chronic HCV infection. Our longer-term goal would be to boost anti-viral responses in chronic infections such as HCV.

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Self incompatibility (SI) in Phalaris coerulescens is gametophytically determined by two unlinked multi allelic loci (S and Z). Neither the S nor Z genes have yet been cloned. As part of a map-based cloning strategy, high-resolution maps of the S and Z regions were generated from distorted segregating populations using RFLP probes from wheat, barley, oat, and Phalaris. The S locus was delimited to 0.26 cM with two boundary markers (Xwg811 and Xpsr168) and cosegregated with Xbm2 and Xbcd762. Xbcd266 was the closest marker linked to Z (0.9 cM). A high level of colinearity in the S and Z regions was found in both self-incompatible and -compatible species. The S locus was localized to the subcentromere region of chromosome 1 and the Z locus to the long arm end of chromosome 2. Several rice BAC clones orthologous to the S and Z locus regions were identified. This opens the possibility of using the rice genome sequence data to generate more closely linked markers and identify SI candidate genes. These results add further support to the conservation of gene order in the S and Z regions of the grass genomes.

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UNLABELLED: In July, 1998 a fire occurred in an operating room (OR) at the University Medical Center in Tucson, AZ. A patient was burned on the face, neck, and shoulders by the fire, which started during cranial burr-hole placement under monitored anesthesia care. This paper describes the actual case in some detail. The incident was simulated as accurately as possible in a laboratory experiment, in an attempt to determine specific risk factors for this event. The experiment found that a specific combination of factors was required to produce a fire similar in appearance to the one in the OR. The risk factors determined in these experiments are discussed in the context of previous reports of OR fires. Although other reports demonstrate some common characteristics of these events, the fire at the University Medical Center appears to be unique within the literature regarding the specific chain of events that led up to it. IMPLICATIONS: A patient was seriously burned in a fire that occurred during surgery. We performed laboratory experiments to re-create the fire, and found some of the key factors that led to this event.

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UNLABELLED: This article examines recent trends in the management of academic physician practice groups, and in particular the allocation of revenues and expenses to anesthesiology departments. The history of academic group practice is traced, beginning with the "corporate model," in which each department functioned in financial independence from the others. This evolved gradually into the "feudal system," in which departments were ostensibly independent, but paid variable and often large "assessments" to the central group. The final stage in this evolution is the "big bag," in which all clinical revenue is pooled by the central practice group, and then distributed by the group to departments or individuals according to some compensation plan formula. The advantages and disadvantages of each of these systems are discussed as they apply to anesthesiology departments. A productivity-based compensation plan formula under the big bag system is calculated for a typical anesthesiology department. This calculation shows that if the compensation formula is truly based on measured clinical productivity, anesthesiology departments may actually fare better under the big bag than under the feudal system. Finally, options for survival in the academic practice groups of the future are discussed. IMPLICATIONS: The history, current status, and trends of finances in academic anesthesiology departments are reviewed. Knowledge of these issues will help departments develop funds allocation methods to ensure that they receive an appropriate share of their faculty practice group's clinical income.

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BACKGROUND: Inhaled beta-agonist therapy is central to the management of acute asthma. The use of intravenous beta-agonist agents may also be beneficial in this setting. OBJECTIVES: To determine the benefit of intravenous (IV) beta2-agonists for severe acute asthma treated in the emergency department. SEARCH STRATEGY: Randomised controlled trials (RCT) were identified using the Cochrane Airways Group Register which is a compilation of systematic searches of MEDLINE, EMBASE, CINAHL, and CENTRAL as well as hand searching of 20 respiratory journals. Bibliographies from included studies and known reviews were also searched. Primary authors and content experts were contacted to identify eligible studies. SELECTION CRITERIA: Only RCTs were considered for inclusion. Studies were included if patients presented to the emergency department with acute asthma and were treated with IV selective or nonselective beta2-agonists versus placebo, inhaled beta2-agonists, or other standard of care. Pulmonary function, vital signs, arterial gasses, adverse effects, and/or clinical success could be reported as outcome measures. Two reviewers independently selected potentially relevant articles and selected articles for inclusion. Methodological quality was independently assessed using two scoring systems and two reviewers. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers, and confirmed with corresponding authors. Missing data were obtained from authors or calculated from data present in the papers. Trials were combined using a random effects model for odds ratios (OR) or weighted mean differences (WMD) and reported with 95% confidence intervals (95% CI). MAIN RESULTS: From 746 identified references, 55 potentially relevant articles were identified and 15 were included. The trials included 584 patients. Overall, selective IV beta2-agonist use conferred no advantage over the comparator regimes. For example, it was associated with a lower PEFR after 60 mins compared to inhaled beta2-agonist, although the difference was not statistically significant (-24.7 l/min; 95%CI 2.9, -52.3). There was no difference in heart rate (4.5 bpm; 95% CI -4.9, 14.0). In the well performed blinded studies there was no difference in autonomic side effects between treatments (Odds Ratio 2.2 (95%CI 0.9, 5.7). REVIEWER'S CONCLUSIONS: There is no evidence to support the use of IV beta2-agonists in patients with severe acute asthma. These drugs should be given by inhalation. No subgroups were identified in which the IV route should be considered.

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Phosphate (P) is taken up by plants through high-affinity P transporter proteins embedded in the plasma membrane of certain cell types in plant roots. Expression of the genes that encode these transporters responds to the P status of the plants, and their transcription is normally tightly controlled. However, this tight control of P uptake is lost under Zn deficiency, leading to very high accumulation of P in plants. We examined the effect of plant Zn status on the expression of the genes encoding the HVPT1 and HVPT2 high-affinity P transporters in barley (Hordeum vulgare L. cv Weeah) roots. The results show that the expression of these genes is intimately linked to the Zn status of the plants. Zn deficiency induced the expression of genes encoding these P transporters in plants grown in either P-sufficient or -deficient conditions. Moreover, the role of Zn in the regulation of these genes is specific in that it cannot be replaced by manganese (a divalent cation similar to Zn). It appears that Zn plays a specific role in the signal transduction pathway responsible for the regulation of genes encoding high-affinity P transporters in plant roots. The significance of Zn involvement in the regulation of genes involved in P uptake is discussed.

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OBJECTIVE: To describe a new pulse oximetry technology and measurement paradigm developed by Masimo Corporation. INTRODUCTION: Patient motion, poor tissue perfusion, excessive ambient light, and electrosurgical unit interference reduce conventional pulse oximeter (CPO) measurement integrity. Patient motion frequently generates erroneous pulse oximetry values for saturation and pulse rate. Motion-induced measurement error is due in part to widespread implementation of a theoretical pulse oximetry model which assumes that arterial blood is the only light-absorbing pulsatile component in the optical path. METHODS: Masimo Signal Extraction Technology (SET) pulse oximetry begins with conventional red and infrared photoplethysmographic signals, and then employs a constellation of advanced techniques including radiofrequency and light-shielded optical sensors, digital signal processing, and adaptive filtration, to measure SpO2 accurately during challenging clinical conditions. In contrast to CPO which calculates O2 saturation from the ratio of transmitted pulsatile red and infrared light, Masimo SET pulse oximetry uses a new conceptual model of light absorption for pulse oximetry and employs the discrete saturation transform (DST) to isolate individual "saturation components" in the optical pathway. Typically, when the tissue under analysis is stationary, only the single saturation component produced by pulsatile arterial blood is present. In contrast, during patient motion, movement of non-arterial components (for example, venous blood) can be identified as additional saturation components (with a lower O2 saturation). When conditions of the Masimo model are met, the saturation component corresponding to the highest O2 saturation is reported by the instrument as SpO2. CONCLUSION: The technological strategies implemented in Masimo SET pulse oximetry effectively permit continuous monitoring of SpO2 during challenging clinical conditions of motion and poor tissue perfusion.

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A fully automated nucleic acid analysis system is described, which offers positive sample identification, improved sensitivity and reduced user interaction compared to conventional techniques. The system relies on the sequence-specific capture of DNA onto solid-phase particles, confirming product identity without the problems of interpretation and lack of sequence information inherent in gel-based analyses. The system can be used for sequence confirmation, mutation analysis and semiquantitative detection of PCR products.

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This paper reports the successful isolation and preliminary characterisation of a mutant of Lycopersicon esculentum Mill. with highly reduced vesicular-arbuscular (VA) mycorrhizal colonization. The mutation is recessive and has been designated rmc . Colonization by G. mosseae is characterised by poor development of external mycelium and a few abnormal appressoria. Vesicles were never formed by this fungus in association with the mutant. Gi. margarita formed large amounts of external mycelium, complex branched structures and occasional auxiliary cells. Small amounts of internal colonization also occurred. Laser scanning confocal microscopy (LSCM) gave a clear picture of the differences in development of G. intraradices and Gi. margarita in mutant and wild-type roots and confirmed that the fungus is restricted to the root surface of the mutants. The amenability of tomato for molecular genetic characterisation should enable us to map and clone the mutated gene, and thus identify one of the biochemical bases for inability to establish a normal mycorrhizal symbiosis. The mutant represents a key advance in molecular research on VA mycorrhizal symbiosis.

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STUDY OBJECTIVE: To compare the performance of five pulse oximeters during hypoperfusion, probe motion, and exposure to ambient light interference. DESIGN: Prospective study. SETTING: Laboratory facility at a university medical center. PATIENTS: 8 unanesthetized, ASA physical status I volunteers. INTERVENTIONS: We evaluated five common pulse oximeters with respect to three scenarios: (1) an operating room light was shone on oximeter probes, (2) a motion generator was used to generate 2 Hz and 4 Hz hand motion, and (3) a pneumatic compression device overlying the brachial artery was used to simulate hypoperfusion. Electrocardiographic (ECG) and arterial blood gas values were considered gold standards for heart rate (HR) and oxygen saturation (SpO2) respectively. SpO2 nondisplay and values greater than 4% from simultaneous arterial SaO2-oximeter values were defined as errors. Nondisplay of HR, or HR greater than 5% from ECG values, were also considered errors. MEASUREMENTS AND MAIN RESULTS: The Ohmeda and Nellcor N200 with finger probe had the highest total failure rates with respect to both SpO2 and HR due to ambient light interference (p < 0.05). The Nellcor N200 with finger probe and N200 with C lock were the most accurate with regard to SpO2 during 2 Hz and 4 Hz motion (p < 0.05). However, all oximeters failed dramatically during 4 Hz motion when measuring HR. In the hypoperfusion model, the Nellcor N200 with finger probe and the Nellcor C Lock oximeters performed significantly better than all others in terms of both HR and SpO2 (P < 0.05), while the Criticare oximeter failed 100% of the time. CONCLUSION: There are significant differences in the accuracy of commercially available pulse oximeters during nonideal circumstances, with failure rates varying from approximately 5% to 50% depending on the oximeter and source of interference. Furthermore, no single oximeter performed the best under all conditions.

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STUDY OBJECTIVE: To compare pulse oximeter performance during induced hypoxemia. DESIGN: Prospective investigation in human volunteers. SETTING: Laboratory facility at a university medical center. PATIENTS: 8 unanesthetized, healthy ASA physical status I volunteers. INTERVENTIONS: We evaluated the accuracy and response times of seven popular pulse oximeters during induced hypoxemia. Arterial blood fractional oxygen saturation (SaO2) measurements were performed simultaneously and considered a gold standard. MEASUREMENTS AND MAIN RESULTS: All oximeters were accurate (+/-2%) while subjects were breathing room air. During maximal hypoxemia (induced by breathing a FIO2 = 10% in nitrogen), large differences were noted between oxygen saturation as measured by pulse oximetry (SpO2) and SaO2 values, with pulse oximeters consistently underreporting SpO2 when actual SaO2 values were 75% or less. The Ohmeda 3740 (Ohmeda, Boulder, CO) using an ear probe was the first to detect desaturation (change in SpO2 > 3%) in 4 of 8 subjects (p < 0.05), and the Nellcor N200 reflectance oximeter (Nellcor, Inc., Pleasanton, CA) was first in 3 of 8 subjects (p < 0.05). During resaturation (after administering 100% oxygen), the Novametrix Oxypleth (Novametrix, Wallingford, CT) was significantly faster than other oximeters (p < 0.05) to return to baseline (SpO2 = 98%). CONCLUSION: Most models of oximeters tested performed well when hemoglobin oxygen saturation was high, but all were inaccurate when SaO2 was approximately 75%. During induced hypoxemia, there were significant differences in the response times of oximeters tested, with no model demonstrably superior to others in all measures of performance.

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BACKGROUND: Pulse oximetry is considered a standard of care in both the operating room and the postanesthetic care unit, and it is widely used in all critical care settings. Pulse oximeters may fail to provide valid SpO2 data in various situations that produce low signal-to-noise ratio. Motion artifact is a common cause of oximeter failure and loss of accuracy. This study compares the accuracy and data dropout rates of three current pulse oximeters during standardized motion in healthy volunteers. METHODS: Ten healthy volunteers were monitored by three different pulse oximeters: Nellcor N-200, Nellcor N-3000, and Masimo SET (prototype). Sensors were placed on digits 2, 3, and 4 of the test hand, which was strapped to a mechanical motion table. The opposite hand was used as a stationary control and was monitored with the same pulse oximeters and an arterial cannula. Arterial oxygen saturation was varied from 100% to 75% by changing the inspired oxygen concentration. While SpO2 was both constant and changing, the oximeter sensors were connected before and during motion. Oximeter errors and dropout rates were digitally recorded continuously during each experiment. RESULTS: If the oximeter was functioning before motion began, the following are the percentages of time when the instrument displayed an SpO2 value within 7% of control: N-200 = 76%, N-3000 = 87%, and Masimo = 99%. When the oximeter sensor was connected after the beginning of motion, the values were N-200 = 68%, N-3000 = 47%, and Masimo = 97%. If the alarm threshold was chosen SpO2 less than 90%, then the positive predictive values (true alarms/total alarms) are N-200 = 73%, N-3000 = 81%, and Masimo = 100%. In general, N-200 had the greatest SpO2 errors and N-3000 had the highest dropout rates. CONCLUSIONS: The mechanical motions used in this study significantly affected oximeter function, particularly when the sensors were connected during motion, which requires signal acquisition during motion. The error and dropout rate performance of the Masimo was superior to that of the other two instruments during all test conditions. Masimo uses a new paradigm for oximeter signal processing, which appears to represent a significant advance in low signal-to-noise performance.

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STUDY OBJECTIVE: To determine the incidence of new episodes of myocardial ischemia in patients undergoing transurethral resection of the prostate (TURP). DESIGN: Prospective, nonrandomized study. SETTING: Veterans Administration medical center. PATIENTS: 39 patients undergoing elective TURP. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Myocardial ischemia was detected with a 3-channel ambulatory ECG recorded. The ambulatory ECG recorder was applied preoperatively and removed when the patient left the recovery room. New myocardial ischemia was defined as a 1 mm or greater ST depression or a 2 mm or greater ST elevation from baseline, lasting for 1 minute or longer in at least one lead at the J point plus 60 msec unless this point fell within the T wave, in which case the J point 40 msec or greater was used. ST changes consistent with myocardial ischemia were confirmed by a cardiologist blinded to the patient's clinical course. Seven of 39 TURP patients (18%) had ST segment changes indicative of new myocardial ischemia. These seven patients had more prostate tissue resected and more blood loss than the 32 patients who did not have any myocardial ischemia (p < 0.05). CONCLUSIONS: Patients undergoing TURP have an 18% incidence of myocardial ischemia. Patients undergoing TURP with more prostate tissue resected and greater blood loss are at increased risk for perioperative myocardial ischemia.

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BACKGROUND: Pulse oximetry is considered a standard of care in both the operating room and the postanesthetic care unit, and it is widely used in all critical care settings. Pulse oximeters may fail to provide valid pulse oximetry data in various situations that produce low signal-to-noise ratio. Motion artifact is a common cause of oximeter failure and loss of accuracy. This study compares the accuracy and data dropout rates of three current pulse oximeters during standardized motion in healthy volunteers. METHODS: Ten healthy volunteers were monitored by three different pulse oximeters: Nellcor N-200, Nellcor N-3000, and Masimo SET (prototype). Sensors were placed on digits 2, 3, and 4 of the test hand, which was strapped to a mechanical motion table. The opposite hand was used as a stationary control and was monitored with the same pulse oximeters and an arterial cannula. Arterial oxygen saturation rate varied from 100% to 75% by changing the inspired oxygen concentration. While pulse oximetry was both constant and changing, the oximeter sensors were connected before and during motion. Oximeter errors and dropout rates were digitally recorded continuously during each experiment. RESULTS: If the oximeter was functioning before motion began, the following are the percentages of time when the instrument displayed a pulse oximetry value within 7% of control: N-200 = 76%, N-3000 = 87%, and Masimo = 99%. When the oximeter sensor was connected after the beginning of motion, the values were N-200 = 68%, N-3000 = 47%, and Masimo = 97%. If the alarm threshold was chosen as pulse oximetry less than 90%, then the positive predictive values (true alarms/ total alarms) are N-200 = 73%, N-3000 = 81%, and Masimo = 100%. In general, N-200 had the greatest pulse oximetry errors and N-3000 had the highest dropout rates. CONCLUSIONS: The mechanical motions used in this study significantly affected oximeter function, particularly when the sensors were connected during motion, which requires signal acquisition during motion. The error and dropout rate performance of the Masimo was superior to that of the other two instruments during all test conditions. Masimo uses a new paradigm for oximeter signal processing, which appears to represent a significant advance in low signal-to-noise performance.

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OBJECTIVE: The pulmonary elimination of the volume of CO2 per breath (VCO2/br, integration of product of airway flow (V) and PCO2 over a single breath) is a sensitive monitor of cardio-pulmonary function and tissue metabolism. Negligible inspired PCO2 results when the capnometry sampling site (SS) is positioned at the entry of the inspiratory limb to the airway circuit. In this study, we test the hypothesis that moving SS lungward will result in significant inspired CO2 (VCO2[I]), that needs to be excluded from VCO2/br. METHODS: We ventilated a mechanical lung simulator with tidal volume (VT) of 800 mL at 10 breaths/min. CO2 production, generated by burning butane in a separate chamber, was delivered to the lung. Airway V and PCO2 were measured (Capnomac Ultima, Datex), digitized (100 Hz for 60 s), and stored by microcomputer. Then, computer algorithms corrected for phase differences between V and PCO2 and calculated expired and inspired VCO2 (VCO2[E] and VCO2[I]) for each breath, whose difference equalled overall VCO2/br. The lung and Y-adapter (where the inspiratory and expiratory limbs of the circuit joined) were connected by the SS and a connecting tube in varying order. RESULTS: During ventilation of the lung model (VT = 800 ml) with SS adjacent to the inspiratory limb, VCO2[E] was 16.8 +/- 0.4 ml and VCO2[I] was 1.1 +/- 0.1 ml, resulting in overall VCO2/br (VCO2[E] - VCO2[I]) of 15.7 +/- 0.4 ml. If VCO2[I] was ignored in the determination of VCO2/br, then the %error that VCO2[E] overestimated VCO2/br was 7.2 +/- 0.3%. This %error significantly increased (p < 0.05, Student's t-test) when VT was decreased to 500 mL (%error = 12.4 +/- 0.8%) or when SS was moved to the lungward side of a 60 mL connecting tube (VCO2[I] = 2.8 +/- 0.2, %error = 18.2 +/- 1.6) or a 140 mL tube (VCO2[I] = 5.9 +/- 0.3 mL, %error = 37.5 +/- 3.3). CONCLUSIONS: When the SS was moved lungward from the inspiratory limb, instrumental dead space (VDINSTR) increased and, at end-expiration, contained exhaled CO2 from the previous breath. During the next inspiration, this CO2 was rebreathed relative to SS (i.e. VCO2[I]), and contributed to VCO2[E]. Thus, VCO2[E] overestimated VCO2/br (%error) by the amount of rebreathing, which was exacerbated by larger VDINSTR (increased VCO2[I]) or smaller VT (increased VCO2[I]-to-VCO2/br ratio).

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