Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial.

Importance: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain.

Objective: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy.

Design, Setting, And Participants: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours.

Covalent modification of primers improves PCR amplification specificity and yield.

We report a method for covalent modification of primers that enhances the specificity of PCR and increases the yield of specific amplification products at the end of PCR. The introduction of thermally stable covalent modifications, such as alkyl groups to the exocyclic amines of deoxyadenosine or cytosine residues at the 3'-ends of primers results in enhanced specificity of reactions. This higher specificity can result in greater sensitivity of detection by reducing competition with non-productive reactions.

Physiotherapy Models of Service Delivery, Staffing, and Caseloads: A Profile of Level I Trauma Centres across Canada.

Purpose: To examine and describe physiotherapy models of service delivery, staffing, and caseloads in Level I trauma centres across Canada.

Methods: A telephone questionnaire was administered to one experienced trauma physiotherapist at each of the 19 Level I trauma centres in Canada. Quantitative data were analyzed descriptively for national trends.

Comparison of the USCOM ultrasound cardiac output monitor with pulmonary artery catheter thermodilution in patients undergoing liver transplantation.

The aim of the study was to compare the standard technique of cardiac output determination by pulmonary artery catheter thermodilution (PAC-TD) with a noninvasive ultrasound Doppler monitor (USCOM Pty., Ltd., Coffs Harbour, Australia) in surgery for liver transplantation.

Influence of genotype, dose and sex on pruritogen-induced scratching behavior in the mouse.

Itch features considerable interindividual variability in humans, and initial studies using animal models have demonstrated a likely role of genetic factors in mediating such variability. In an attempt to systematically study genetic mediation of itch in the mouse such that gene identification by linkage mapping might be achieved, we examined scratching behavior induced by histamine and chloroquine in mice of 11 inbred mouse strains. Multiple chloroquine drug doses were used, revealing the existence of inverted-U dose-response relationships in every strain, allowing us to determine strain-dependent peak scratching behavior over the entire dose range.

Multicenter evaluation of a pathogenic mycobacterium screening probe.

The introduction of nucleic acid amplification assays into the clinical laboratory has reduced the time needed to diagnose diseases caused by members of the Mycobacterium tuberculosis complex (MTBC). However, several mycobacterial species other than those of the MTBC are known to cause disease, especially in immunocompromised individuals. A screening assay has been developed for the detection of the major pathogenic mycobacterial species.

Constraints on neutrino oscillations using 1258 days of Super-Kamiokande solar neutrino data.

We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.

Solar 8B and hep neutrino measurements from 1258 days of Super-Kamiokande data.

Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0-20.

Antagonistic interplay between antimitotic and G1-S arresting agents observed in experimental combination therapy.

Paclitaxel is a naturally occurring antimitotic agent that has been shown to stabilize microtubules, induce mitotic arrest, and ultimately induce apoptotic cell death. The favorable clinical activity of paclitaxel has prompted considerable interest in combining paclitaxel with numerous other antineoplastic agents. Our previous studies have suggested 5-fluorouracil (5-FU), an antineoplastic agent that usually arrests tumor cells at the G1-S phase of the cell cycle, in combination with paclitaxel significantly represses paclitaxel-induced mitotic arrest and apoptosis.

Development of calibrated viral load standards for group M subtypes of human immunodeficiency virus type 1 and performance of an improved AMPLICOR HIV-1 MONITOR test with isolates of diverse subtypes.

Accurate determination of plasma human immunodeficiency virus type 1 (HIV-1) RNA levels is critical for the effective management of HIV-1 disease. The AMPLICOR HIV-1 MONITOR Test, a reverse transcription-PCR-based test for quantification of HIV-1 RNA in plasma, was developed when little sequence information on HIV-1 isolates from outside North America was available. It has since become apparent that many non-subtype B isolates, particularly subtypes A and E, are detected inefficiently by the test.

Genus level identification of mycobacteria from clinical specimens by using an easy-to-handle Mycobacterium-specific PCR assay.

An easy-to-handle Mycobacterium-specific PCR assay for detection of the presence of a wide range of mycobacterial species in clinical samples was evaluated. The performance of the genus probe was compared with the performance of probes specific for Mycobacterium tuberculosis and Mycobacterium avium and with that of standard culture. In addition, the utility of an internal control in monitoring amplification inhibitors was studied.

Major DNA fragmentation is a late event in apoptosis.

Apoptosis, the terminal morphological and biochemical events of programmed cell death, is characterized by specific changes in cell surface and nuclear morphology. In addition, DNA fragmentation in an internucleosomal pattern is detectable in mass cultures of apoptotic cells. However, DNA fragmentation and nuclear morphological changes may not necessarily be associated events.

Rapid detection of Mycoplasma pneumoniae by an assay based on PCR and probe hybridization in a nonradioactive microwell plate format.

A new molecular assay, based on a rapid DNA extraction protocol, PCR, and hybridization to a specific probe in a nonradioactive microwell plate format was used to detect Mycoplasma pneumoniae in bronchoalveolar fluid specimens. The sensitivity of the assay was determined to be 10 to 100 organisms with M. pneumoniae reference strains.

Detection of Mycobacterium tuberculosis by PCR amplification with pan-Mycobacterium primers and hybridization to an M. tuberculosis-specific probe.

Nucleic acid amplification techniques such as the PCR are very useful in the rapid diagnosis of infections by Mycobacterium tuberculosis. However, recent studies have shown that the accuracy of results can vary widely when tests are performed with nonstandardized reagents. We have developed a PCR assay for the detection of M.

Fatal acute hepatorenal failure following potassium permanganate ingestion.

Potassium permanganate (KMnO4), a powerful oxidizing agent, is readily available without prescription. Tissue contact produces coagulation necrosis and the lethal consequences of oral ingestion are well described, with most deaths because of airway oedema and obstruction or circulatory collapse. Whilst systemic toxicity is reported, its mechanism is unclear.

Detection of hepatitis C virus RNA by a combined reverse transcription PCR assay: comparison with nested amplification and antibody testing.

Many of the current reverse transcription (RT)-PCR assays for the detection of hepatitis C virus (HCV) RNA are multistep processes which use multiple enzymes and buffers. The assays are also often suboptimal, requiring nested amplification to achieve the desired levels of sensitivity. As a result, these assays are cumbersome and prone to false-positive results.

Midazolam and flumazenil pharmacokinetics and pharmacodynamics following simultaneous administration to human volunteers.

Resedation after antagonism of midazolam sedation with flumazenil may occur because some individuals have rapid elimination of flumazenil but slow elimination of midazolam. To determine whether there are parallel or divergent rates of elimination of the two drugs between individuals, the pharmacokinetic profiles of midazolam and flumazenil were studied simultaneously in 12 adult male volunteers. Free drug concentration data for the two drugs were incorporated into a receptor occupancy model and psychomotor testing was performed and correlated with receptor occupancy.

Detection of hepatitis C virus RNA by a combined reverse transcription-polymerase chain reaction assay.

Amplification of RNA by the polymerase chain reaction (PCR) is normally a two-step process requiring separate enzymes and buffer conditions. We describe a combined reverse transcription-PCR (RT-PCR) assay for hepatitis C virus (HCV) RNA amplification in which a single enzyme and buffer condition are used. In this assay, both the RT and PCR steps are carried out with the thermoactive DNA polymerase of Thermus thermophilus.

Significance of human T-lymphotropic virus type I indeterminant serological findings among healthy individuals.

Follow-up studies on 67 blood donors with indeterminant serological findings for human T-lymphotropic virus (HTLV) type I by standard immunoassays showed no evidence of infection by polymerase chain reaction analysis for HTLV-I or HTLV-II nucleic acids or by antibody reactivity to a unique HTLV-I recombinant envelope protein, MTA-4. Among HTLV-I- or -II-infected individuals, a history of blood transfusion, past residence in established HTLV-I endemic areas or some association with intravenous drug use were common. In contrast, 85% of indeterminant cases had none of these risk factors.

Detection of HIV DNA in peripheral blood by the polymerase chain reaction: a study of clinical applicability and performance.

We evaluated the applicability and performance of the polymerase chain reaction (PCR) in a clinical setting in two independent studies. In a study of its applicability, the specificity and sensitivity of PCR for detection of HIV DNA were 100% (225 out of 225 seronegative, low-risk individuals tested negative) and 94% (67 out of 71 seropositive individuals tested positive), respectively. In a second study evaluating the performance of PCR, seven out of 474 (1.