A randomized, placebo-controlled study to evaluate the role of salmeterol in the in-hospital management of asthma.

STUDY OBJECTIVES: To assess the safety and efficacy of salmeterol xinafoate as an adjunct to conventional therapy for the in-hospital management of acute asthma. DESIGN: A prospective, double-blind, randomized placebo-controlled trial. SETTING: Medical wards of a large university-based hospital. PATIENTS: Forty-three patients admitted for an acute exacerbation of asthma. INTERVENTIONS: Salmeterol (42 microg) or two puffs of placebo every 12 h in addition to standard therapy (short-acting beta-agonists, corticosteroids, and anticholinergic agents). RESULTS: No clinically adverse effects were seen with the addition of salmeterol to conventional therapy. After salmeterol, there was no difference in pulse, respiratory rate, oxygen saturation by pulse oximetry, severity of symptoms, or dyspnea score. Patients receiving salmeterol had greater FEV(1) percent improvements than the placebo group at 12, 24, 36, and 48 h. These findings were not statistically significant. By paired Student's t tests, there were significant improvements in FEV(1) (p = 0.03) and FVC (p = 0.03) in the salmeterol group after 48 h of treatment with no comparable improvement in the placebo group. In a subgroup analysis of patients with an initial FEV(1) < or = 1.5 L, the absolute FEV(1) percent improvement for salmeterol vs placebo was 51% vs 16% at 24 h and 54% vs 40% at 48 h. The relative FEV(1) percent improvement for salmeterol vs placebo was 17% vs 8% at 24 h and 18% vs 14% at 48 h. CONCLUSION: The addition of salmeterol to conventional therapy is safe and may benefit hospitalized patients with asthma. Further studies are needed to clarify its role in the treatment of acute exacerbation of asthma.

Point mutations identify a conserved region of the saccharomyces cerevisiae AFR1 gene that is essential for both the pheromone signaling and morphogenesis functions.

Mating pheromone receptors activate a G protein signal pathway that leads to the conjugation of the yeast Saccharomyces cerevisiae. This pathway also induces the production of Afr1p, a protein that negatively regulates pheromone receptor signaling and is required to form pointed projections of new growth that become the site of cell fusion during mating. Afr1p lacks strong similarity to any well-characterized proteins to help predict how it acts. Therefore, we investigated the relationship between the different functions of Afr1p by isolating and characterizing seven mutants that were defective in regulating pheromone signaling. The AFR1 mutants were also defective when expressed as fusions to STE2, the alpha-factor receptor, indicating that the mutant Afr1 proteins are defective in function and not in co-localizing with receptors. The mutant genes contained four distinct point mutations that all occurred between codons 254 and 263, identifying a region that is critical for AFR1 function. Consistent with this, we found that the corresponding region is very highly conserved in the Afr1p homologs from the yeasts S. uvarum and S. douglasii. In contrast, there were no detectable effects on pheromone signaling caused by deletion or overexpression of YER158c, an open reading frame with overall sequence similarity to Afr1p that lacks this essential region. Interestingly, all of the AFR1 mutants showed a defect in their ability to form mating projections that was proportional to their defect in regulating pheromone signaling. This suggests that both functions may be due to the same action of Afr1p. Thus, these studies identify a specific region of Afr1p that is critical for its function in both signaling and morphogenesis.

Inflammatory mediators induce sequestration of VE-cadherin in cultured human endothelial cells.

The mechanisms through which inflammatory mediators modify endothelial junctional structure are not well understood. Endothelial cells exposed to 1 mM H2O2, 0.1 mM histamine or 4 mM EDTA displayed decreased amounts of VE-cadherin on the cell surface in a time-dependent manner. H2O2 and EDTA-treated cells showed a sustained reduction in surface VE-cadherin, but histamine (0.1 mM) decreased cell surface VE-cadherin only at 5 and 15 min, not at 30 and 60 min. Sequestering of VE-cadherin could also be visualized as a decrease in immunofluorescent labeling of endothelial junctions in fixed, non-extracted monolayers. However, junctional staining was observed in these cells after membrane extraction. This decreased surface expression of VE-cadherin was actin-filament, but not PKC/MAP kinase dependent. VE-cadherin binding to the cytoskeleton was decreased by EDTA, but was not diminished by histamine or H2O2. Therefore, by promoting sequestration of junctional cadherins, inflammatory mediators may decrease adhesive bonds between apposed endothelial cells and increase solute permeability.

Phytophotodermatitis: the other "lime" disease.

Phytophotodermatitis is a skin eruption that occurs after contact with photosensitizing compounds in plants and exposure to UV light. There are two common presentations of phytophotodermatitis. Acutely, erythema and vesiculation similar to a severe sunburn are noted. After resolution of the inflammation, the involved skin has marked hyperpigmentation. Many plants have been identified that contain furocoumarins (psoralens), including limes, lemons, and celery. We present a patient with an acute phototoxic eruption and hyperpigmentation after contact with limes during a beach vacation.

Successful treatment of valproic acid overdose with hemodialysis.

A 43-year-old woman took a large amount of depakote (divalproex, a slow-release form of valproate), became comatose, and developed severe hypotension refractory to fluid resuscitation and high-dose vasopressors. The serum valproic acid (VPA) concentration on admission was 1,380 microgram/mL (therapeutic range, 50 to 100 microgram/mL). She also had metabolic acidosis, thrombocytopenia, and normal renal and liver functions. Hemodialysis was initiated 4 hours after presentation. After 6 hours of hemodialysis with a high-flux dialyzer, her serum VPA concentration decreased from 940 microgram/mL to 164 microgram/mL, coincident with improvement in clinical status. The half-life of VPA was reduced to 2.4 hours with hemodialysis, whereas it was 7.2 hours before the procedure. Hemodialysis could be a valuable therapeutic intervention in VPA toxicity.

Expression of zonula occludens and adherens junctional proteins in human venous and arterial endothelial cells: role of occludin in endothelial solute barriers.

OBJECTIVE: The purpose of this study was to correlate the expression of occludin and VE-cadherin with the solute barrier properties of arterial and venous endothelial monolayers. METHODS: Immunofluorescent confocal and traditional microscopy were used to determine junctional protein localization in endothelium in vivo and in vitro respectively, and western and northern analysis used to determine protein and gene expression levels. Permeability of endothelial monolayers was examined under normal, low calcium, and cytochalasin-D treatment conditions. Antisense oligonucleotide experiments for occludin were performed to determine the contribution of occludin to solute barrier. RESULTS: Occludin protein in endothelial monolayers is more concentrated in arterial junctions than in venous junctions both in vivo and in vitro. Arterial endothelial cells express 18-fold more occludin protein and nine times more occludin mRNA compared to venous endothelial cells. In vivo, both endothelial cells demonstrate VE-cadherin staining; and in vitro, only venous endothelial cells express VE-cadherin protein and mRNA. Occludin antisense experiments suggest that both arterial and venous barrier properties are due to these different amounts of occludin expression. Venous barrier was remarkably sensitive to low extracellular calcium, while arterial barrier was more sensitive to cytochalasin-D. CONCLUSIONS: These findings suggest strongly that arterial and venous endothelial barrier reflects the level of expression of different adhesion molecules and that modulation of these proteins, especially occludin, may regulate the level of endothelial solute barrier.

Diagnostic impact of four postprocessing techniques in evaluating contrast-enhanced three-dimensional MR angiography.

OBJECTIVE: The purpose of this study was to determine the added diagnostic value of various three-dimensional (3D) data viewing techniques when analyzing contrast-enhanced 3D MR angiography. MATERIALS AND METHODS: Twenty patients (mean age, 62 years) with symptomatic peripheral vascular disease were assessed with breath-hold, contrast-enhanced 3D MR angiography and catheter angiography, which served as the standard of reference. After an initial interpretation of the 3D MR angiographic data sets based only on standardized maximum intensity projections (MIP), the diagnostic gain of the stepwise addition of interactive multiplanar reformations, shaded-surface displays (SSD), and virtual intraarterial endoscopy (VIE) images was calculated. Time required for each step of postprocessing was measured. RESULTS: Pathologic changes were revealed by catheter angiography in 60 vascular segments (50 severe stenoses, seven aneurysms, and three occlusions). The average postprocessing times were MIP, 8 min (range, 5-12 min); multiplanar reformations, 9 min (range, 3-11 min); SSD, 15 min (range, 8-25 min); and VIE, 40 min (range, 18-63 min). Addition of multiplanar reformations to MIPs resulted in the greatest gain of diagnostic accuracy, from 92% to 96%, and diagnostic confidence. When analysis was based on all four techniques, receiver operating characteristic curve analysis revealed only minimal improvements in diagnostic confidence, whereas diagnostic accuracy remained unchanged at 96%. CONCLUSION: Accurate and time-effective analysis of contrast-enhanced 3D MR angiography should be based on MIP algorithms and multiplanar reformations. Additional evaluation with VIE or SSD techniques is time-consuming and provides little diagnostic gain.

Postprocessing techniques for gadolinium-enhanced three-dimensional MR angiography.

Contrast material-enhanced three-dimensional (3D) magnetic resonance (MR) angiography is rapidly gaining acceptance as a versatile noninvasive alternative to conventional angiography. The technique has proved useful in the visualization and assessment of complex pathologic entities in the thoracic and abdominal aorta, renal arteries, pelvic arterial system, and pulmonary arteries. Several postprocessing techniques are available for reformation of the imaging data, including maximum intensity projection (MIP), surface rendering, and virtual intraluminal endoscopy (VIE). MIP and subvolume MIP reconstructions can be produced quickly and are useful for demonstration and archiving purposes. Because of its unique ability to display vessels without overlap, surface rendering is especially useful in depicting diseases that influence either the outer shape of the vessels or their topographic arrangement. VIE allows assessment of the inside of the vascular wall and is helpful in detecting wall-bound thrombus and evaluating the degree of stenosis. Most clinically relevant questions (eg, presence of pulmonary embolism, aortic aneurysm, renal artery stenosis) can be fully answered if analysis is based on MIP and thin multiplanar reformations of contrast-enhanced 3D MR angiograms. In some cases, the use of additional postprocessing techniques enhances diagnostic confidence.

New approach to patency and flow assessment after left internal thoracic artery hypoperfusion syndrome with additional saphenous vein graft to the left anterior descending artery with phase-contrast magnetic resonance angiography.

OBJECTIVE: Perioperative and early postoperative flow reduction of a left internal thoracic artery conduit is a rare complication of myocardial revascularization and may lead to the potentially fatal left internal thoracic artery hypoperfusion syndrome. It has been advocated that an additional vein graft be placed to the distal left anterior descending artery to provide sufficient myocardial perfusion. Some evidence exists, however, that this high-flow vein might lead to competing or even backward flow through the internal thoracic artery. METHODS: In the past 2 years, 21 patients received an additional vein graft to the distal left anterior descending artery for left internal thoracic artery hypoperfusion syndrome. Nineteen of these patients were available for magnetic resonance imaging. Early (< 6 months) and late (> 12 months) postoperative flow measurements, both in the left internal thoracic artery and in the saphenous vein grafts, were performed by means of conventional and a segmented k-space phase-contrast magnetic resonance angiography technique. RESULTS: Early magnetic resonance examinations indicated that all conduits had adapted to the coronary flow type with predominant diastolic perfusion. Patency rate both at the early and at the late study was 100%. No concurrent flow, flow reversal, or steal phenomena were observed. Mean flow rates were 49.2 ml/min for the left internal thoracic artery and 72.6 ml/min for the saphenous vein graft. CONCLUSION: On the basis of the flow data obtained with magnetic resonance angiography, the use of an additional saphenous vein graft as the treatment of choice in left internal thoracic artery hypoperfusion syndrome does not lead to occlusion of the artery. Conduit flow adaptation to the diastolic predominance occurs in the first 6 months after operation.

MR angiography of patients with peripheral arterial disease before and after transluminal angioplasty.

OBJECTIVE: This study was performed to evaluate the feasibility of using MR angiography for following up patients who have undergone interventional therapy of the infrapopliteal vascular bed. SUBJECTS AND METHODS: Fourteen patients with peripheral vascular disease underwent MR imaging before and after percutaneous transluminal angioplasty (PTA) using a two-dimensional time-of-flight technique (TR/TE, 33/3.9; section thickness, 2.9 mm). As the gold standard, selective digital subtraction angiography was obtained for all evaluated extremities before and after PTA. For data analysis, the distal peripheral arterial system was divided into 11 segments: the popliteal artery; the tibioperoneal trunk; and the proximal, mid, and distal portions of the three trifurcation vessels. Each segment was characterized as normal, mildly diseased, moderately diseased, severely diseased, or occluded. RESULTS: We found overall agreement between the two techniques in 110 segments (71%) and 123 segments (80%) on data obtained before and after PTA, respectively. Before PTA, our interpretation of MR angiograms overestimated 14 lesions (9%). After PTA, we overestimated five lesions (3%) on MR angiograms. We underestimated lesion severity in 30 cases (19%). The high incidence of agreement between the two techniques was reflected by the high Kendall's tau-beta values of .83 and .87 for data obtained before and after PTA, respectively. CONCLUSION: The excellent depiction of the PTA-induced morphologic changes suggests great potential for the use of MR angiograms during interventional follow-up.

Coronary flow and coronary flow reserve measurements in humans with breath-held magnetic resonance phase contrast velocity mapping.

Objective evidence for coronary lesion significance can be obtained with ischemic stress testing. Since flow-limiting stenoses have already undergone compensatory vasodilatation to maintain flow, the response to vasoactive stimulation is dampened. The degree of response limitation is reflected by the coronary flow reserve (CFR). Absolute volume flow rates can be accurately and noninvasively measured with MRI techniques. The purpose was to assess the ability to measure coronary volume flow rate noninvasively, and characterize the effect of pharmacologic stress on coronary flow quantitatively by using ultrafast, breath-held segmented k-space phase-contrast-MR imaging (PC-MRI). Ten healthy volunteers were examined by using ultrafast breath-held PC-MRI. Coronary volume flow rates were measured in the anterior descending coronary artery (LAD) at rest and following intravenous administration of dipyridamole. CFR was determined based on these data. Mean LAD volume flow rates increased from 38 +/- 11 ml/min before application of dipyridamole to 169 +/- 42 ml/min. The mean CFR amounted to 5.0 +/- 2.6 (median = 4.15). This study demonstrates the feasibility of breath-held PC-MRI to noninvasively quantify coronary volume flow rates over the cardiac cycle. Pharmacologically induced changes in volume flow rate and thus CFR can be quantitated.

[Virtual intravascular endoscopy in the renal arteries: a new way of observing 3-D-MIR angiography data sets]. / Virtuelle intravasale Endoskopie in den Nierenarterien: Eine neuartige Betrachtungsform von 3-D-MRA-Datensätzen.

PURPOSE: To determine the potentials and limitations of a recently developed algorithm for virtual intravascular endoscopy (VIE) based on 3-dimensional (3-D) magnetic resonance (MR) data sets. METHOD: The data from 6 patients derived from gadolinium-enhanced MR angiography of the renal arteries were reviewed. All patients had unilateral or bilateral renal arterial pathologies (stenoses n = 2, aneurysms n = 4). Imaging was performed on a 1.5-T scanner using a 3-D gradient-echo MR sequence. The imaging parameters were as follows: TR/TE/flip angle 3.9/1.9/40 degrees, matrix 256 x 192, slice thickness 1.5 to 2 mm, FOV 32 cm, and 48 slices. Image acquisition time was 28 seconds under apnoeia conditions. A total of 60 ml 0.5 molar Gd-DTPA was injected during the scan. RESULTS: 3-D data sets could be obtained in all patients and postprocessed for VIE. The intraluminal vessel wall was depicted with high clarity in all cases. All pathologies that were not intraparenchymal could be easily seen. Limitations to the technique include the image quality of the original data set, use of the ideal threshold to minimise intraluminal artifacts, and a complicated prescription sequence. CONCLUSIONS: We have shown that VIE can be consistently performed in the renal arteries using MR data sets acquired with a contrast enhanced 3-D gradient-echo technique. It provides a hitherto unused approach to viewing 3-D vascular MR data sets.

Breath-hold, contrast-enhanced, three-dimensional MR angiography.

Breath-hold gadolinium-enhanced three-dimensional magnetic resonance (MR) angiography was performed with a high-performance gradient MR imaging system in 10 volunteers with no history of vascular abnormalities (breath-hold interval, 28 seconds; repetition time, 4.0 msec; echo time, 1.9 msec; 0.4 mmol gadoterate meglumin per kilogram of body weight). High-resolution three-dimensional time-of-flight angiograms of the aorta, renal arteries, pulmonary arteries, pelvic arteries, and portal venous system were successfully acquired in all cases.

Serial myoglobin levels for patients with possible myocardial infarction.

OBJECTIVES: To determine the sensitivity and specificity of a new myoglobin assay for acute myocardial infarction (AMI), considering both the total amount of serum myoglobin and its percentage change over 2 hours. METHODS: A prospective, observational test performance study for the recognition of AMI was done using serial myoglobin assays of 42 admitted chest pain patients at a large, urban teaching hospital ED. Myoglobin testing was performed at presentation (time 0) and at 1 and 2 hours after arrival. A myoglobin level > 100 micrograms/L (ng/mL) or a change > or = 50% from baseline (increase or decrease) any time during the 2-hour period was considered positive. Patients and their physicians were blinded to the myoglobin results. The managing clinician's final diagnosis of the presenting event was used as the diagnostic criterion standard. RESULTS: The sensitivity of the myoglobin technique for detection of AMI in the first hours in the ED was 13/14 (93%; 95% CI: 66-100%). The 1 patient who had a false-negative test had evidence of AMI on the ECG and an initially abnormal creatine kinase-MB (CK-MB) assay. The specificity was 22/28 (79%; 59-92%). However, of the 6 patients who had "false-positive" myoglobin tests, all had serious illness: significant cardiac disease (n = 4), in-hospital death (n = 1), or deep venous thrombosis (n = 1). CONCLUSION: Myoglobin level determinations are sensitive tests to detect AMI during the first 2 hours of a patient's stay in the ED and may complement current clinical tools.

Human aorta: preliminary results with virtual endoscopy based on three-dimensional MR imaging data sets.

PURPOSE: To determine the feasibility of use of magnetic resonance (MR) imaging data sets to perform virtual intraarterial endoscopy (VIE). MATERIALS AND METHODS: Seven female and 14 male patients (aged 9-86 years [mean, 42 years]) with various pathologic aortic conditions underwent three-dimensional gadolinium-enhanced spoiled gradient-echo MR imaging. With prototype software, VIE postprocessing algorithms (based on ray casting) were applied to the imaging data sets. Findings at conventional angiography were used as the standards of reference. RESULTS: The vessel wall was seen from the inside in each case, and the following pathologic conditions were depicted clearly: the two lumina in a congenial double aortic arch and the single lumen after correction, vessel narrowing in coarctations, characteristics of Leriche syndrome, stenoses, occlusions, and the true and false lumina of dissections. CONCLUSIONS: Limitations of VIE include the image quality of the original data set, the threshold chosen to minimize intraluminal artifacts, and the inherent smoothing of vessel walls.

Ultra-high-speed MR imaging.

Conventional magnetic resonance imaging (MRI) has been shown to provide excellent morphological images of the body organs, particularly structures undergoing little physiologic motion. Nevertheless, the clinical usefulness of MRI has been hampered by long acquisition times, high cost of scanning because of limited patient throughput, and image artifacts due to patient motion. With recent technical developments, several ultrafast scanning techniques capable of acquiring images in a breath-hold now find their introduction into clinical use. The system improvements are potentially useful for a vast range of applications hitherto not accessible to MR imaging. Among these are functional brain imaging, realtime imaging of cardiac motion and perfusion, fast abdominal imaging, improved MR angiography, and potentially real-time monitoring of interventional procedures. Whereas some ultrafast techniques can be performed on conventional scanners, echo-planar imaging, the fastest currently available data acquisition strategy, requires specially designed hardware. This article provides an overview of the technical advances in ultrafast MRI and discusses potential applications and the possible future impact on body scanning.

[Fast and ultra-fast MRI imaging of the heart]. / Schnelle und ultraschnelle MR-Bildgebung des Herzens.

Conventional magnetic resonance imaging (MRI) is capable of providing satisfactory morphological images of the heart and the surrounding structures. It has further evolved into a well accepted modality for functional cardiac studies such as flow quantification and volumetry. MRI has, however, been hampered by long image acquisition times. This combined with its non-real-time nature and the limited spatial resolution hs made it difficult to extend MRT to the study of small cardiac structures. Recent technical improvements have made breath-held or real-time MRI feasible and thus laid the foundations for further applications in the field of cardiovascular imaging, notably MR coronary angiography, imaging of cardiac valve leaflets, as well as first-pass perfusion studies. Moreover ultrafast MR techniques may eventually replace conventional data acquisition strategies and thus drastically increase patient throughput by shortening acquisition time. This article provides an overview of the technical advances in MRI and their application to the cardiovascular system and discusses possibilities of combined ultrafast and interventional strategies.

In vivo reduction of bacterial populations in the urinary tract of catheterized sheep by iontophoresis.

PURPOSE: Iontophoresis kills microbes in vitro and, therefore, may be a useful method for eliminating microbial populations associated with catheter-induced urinary tract infections in vivo. MATERIALS AND METHODS: Catheters were modified to deliver current to platinum electrodes in the catheter tip. Female sheep were catheterized with this iontophoretic catheter and left ambulatory. In 5 sheep (experimental group) 400 microA was applied to the catheter and withheld in 4 sheep (control group) for 20 to 21 days. The animals were then sacrificed. During the study, types and concentrations of bacteria, and physical and chemical characteristics of the urine samples were determined. RESULTS: Throughout the study, bacteria levels were reduced in urinary tracts of the experimental group (10(3) to 10(4) microbes per ml.) compared with the control group (10(7) microbes per ml.), without extensive alterations to urine chemistry or the sheep urinary tract. CONCLUSIONS: Since iontophoresis safely reduced bacterial populations in catheterized sheep, this technology may reduce or eliminate nosocomial, catheter-induced urinary tract infections in humans.

Real-time biplanar needle tracking for interventional MR imaging procedures.

PURPOSE: To evaluate real-time biplanar tracking of a specially designed needle with magnetic resonance (MR) imaging guidance. MATERIALS AND METHODS: The needle is made of polyetheretherketone and has a miniature radio-frequency coil incorporated into the tip. Tracking software on two workstations is used to compute three-dimensional coordinates of the coil and to display the position as a moving symbol in two imaging planes. Validation of needle tracking was performed in a harvested human liver. T2-weighted fast spin-echo images were used to target a 1-cm cyst. Success of needle placement was confirmed with aspiration and with updated gradient-recalled-echo images. RESULTS: The cyst was successfully targeted from different approaches. Tracking procedures were monitored in real time simultaneously on two separate images. CONCLUSION: Real-time biplanar needle tracking may prove to be useful for both diagnostic and therapeutic interventional MR imaging procedures.

Mycoplasma pneumoniae and Mycoplasma genitalium mixture in synovial fluid isolate.

A mycoplasma cultured from synovial fluid specimens from a patient with pneumonia and subsequent polyarthritis was identified initially as Mycoplasma pneumoniae. In retrospective studies, the culture was shown also to contain Mycoplasma genitalium. In this paper, the laboratory techniques employed in the identification and separation of the two species are presented, and evidence to implicate postinfectious autoimmunity is provided. An increasing number of reports of M. genitalium in human tissue sites and difficulties in isolation and identification of the organism in the clinical laboratory suggest the need for more extensive application of rapid and specific detection systems for both M. genitalium and M. pneumoniae in the clinical laboratory.