Biomedical subjects

C P Davis

Publications and source records attributed to C P Davis.

At least 19 recordsLinked to original sources

PubMed2000

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.

Antigens, CD↗

PubMed2000

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.

Amino Acid Sequence↗

PubMed2000

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.

Acute Disease↗

PubMed1999

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.

Adult↗

PubMed1998

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.

Adult↗

PubMed1998

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.

Antigens, CD↗

PubMed1997

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.

Adult↗

PubMed1997

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.

Coronary Vessels↗

PubMed1997

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.

Aged↗

PubMed1996

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.

Humans↗

PubMed1996

[Virtual intravascular endoscopy in the renal arteries: a new way of observing 3-D-MIR angiography data sets].

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.

Adolescent↗

PubMed1996

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.

Adolescent↗

PubMed1996

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.

Adult↗

PubMed1996

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.

Adolescent↗

PubMed1995

[MRI venous angiography of the abdomen].

The assessment of abdominal vessels by conventional methods is invasive and frequently does not yield an accurate diagnosis, particularly in evaluation of the portal venous system. MR angiography is non-invasive and is well suited to the examination of abdominal veins. Both vessel morphology and intravascular flow patterns can be characterized with this method. Clinical indications include portal hypertension, portal vein thrombosis, portosystemic shunts as well as assessment of congenital anomalies, thrombus and tumor propagation into the inferior vena cava and the renal veins. In the future MR angiography is likely to evolve into the modality of choice for non-invasive evaluation of abdominal venous structures.

Abdomen↗

PubMed1995

Kidney transplantation in diabetic patients using cyclosporine. Five-year follow-up.

OBJECTIVE: To review our center's experience with kidney transplantation in diabetic recipients; specifically, to compare long-term (5-year) patient and graft survival rates between diabetic and nondiabetic recipients overall and according to donor source using cyclosporine-based immunosuppression. DESIGN: A retrospective review of all kidney transplants performed over the 7-year period from 1987 to 1993. SETTING: A large urban tertiary care referral center with a long history of kidney transplantation and care of the diabetic patient. PATIENTS: All patients receiving a kidney transplant, either alone or simultaneously with a pancreas transplant, were reviewed. MAIN OUTCOME MEASURES: Actuarial patient and graft survival, serum creatinine levels, and causes of late graft loss. RESULTS: There was no significant difference in actuarial 5-year patient or kidney graft survival between diabetic and nondiabetic recipients overall or when analyzed by donor source. There was no significant difference in mean serum creatinine levels at 5 years between diabetic and nondiabetic recipients overall or between diabetic and nondiabetic cadaveric recipients. While chronic rejection was the major cause of late graft loss in nondiabetic recipients, death with a functioning graft, principally due to cardiovascular disease, was the major cause of graft loss in diabetic recipients. CONCLUSIONS: With cyclosporine-based immunosuppression, diabetic kidney transplant recipients have 5-year patient and graft survival rates and allograft function comparable to nondiabetic recipients. Given the high mortality of diabetic patients receiving dialysis, kidney transplantation is the treatment of choice for end-stage diabetic renal disease.

Actuarial Analysis↗

PubMed1995

Evaluation of ultrafast phase-contrast imaging in the thoracic aorta.

PURPOSE: Two ultrafast phase-contrast (PC) data acquisition strategies, multishot echo-planar imaging (EPI)-PC and segmented k-space fast gradient-echo PC (FASTCARD-PC) were evaluated with regard to their measurement accuracy. MATERIALS AND METHOD: Flow measurements of the ascending and descending aorta were acquired in 10 healthy volunteers with an electrocardiogram (ECG)-triggered eight-shot EPI-PC sequence (TR/TE/flip 16/7.4/45 degrees, 32-ms flow-phase interval, 2 x 2 mm in plane resolution), and FASTCARD-PC (six k-lines per band, TR/TE/flip 11/6.1/45 degrees, 132-ms flow-phase interval, 2 x 1 mm in plane resolution). These were compared to flow-volume data acquired with conventional cine-PC (TR/TE/flip 24/7/45 degrees, 48-ms flow-phase interval, 2 x 1 mm in plane resolution). Using cine-PC as a gold standard, the measurement accuracy of FASTCARD-PC and EPI-PC were determined. RESULTS: Both EPI-PC and FASTCARD-PC significantly reduced data acquisition times compared to cine PC. EPI-PC flow measurements correlated well with aortic cine-PC flow-volume determinations (r = 0.98). Reflecting poorer temporal resolution, FASTCARD-PC measurements were less accurate (p < 0.05), evidenced by poor correlation with cine-PC data (r = 0.62). CONCLUSION: Ultrafast PC measurements are possible. In contrast to the segmented k-space PC technique, which is limited in temporal resolution, multishot EPI-PC provides high measurement accuracy in pulsatile vessles while keeping the image acquisition interval short enough for a comfortable breath-hold.

Adult↗

PubMed1995

Ketorolac versus meperidine-plus-promethazine treatment of migraine headache: evaluations by patients.

This study was designed to compare and contrast the speed and efficacy of meperidine (75 mg)/promethazine (25 mg) intramuscularly to ketorolac (60 mg) intramuscularly, in a double-blind study in reducing the symptoms of migraine headache. Forty-two patients who presented to the emergency department between July 1992 and February 1993, with previous diagnoses of migraine headache, were considered for this study. Patients subjectively evaluated parameters of their migraine headaches (eg, pain and nausea) using a numeric scale and were later asked to reevaluate these same parameters at 30, 60, and 360 minutes after a single intramuscular injection of either ketorolac (60 mg) or meperidine (75 mg)/promethazine (25 mg). Sixty-eight percent of patients given meperidine/promethazine responded whereas 55% of patients given ketorolac responded. The responder group showed a statistically significant reduction in headache within 30 minutes with both drug regimens. There was no statistically significant difference between the number of responders in either group. The responders from both groups had relief that lasted 6 hours after injection. In the nonresponder groups, most of the patients withdrew within 1 hour after treatment. As determined by patient response to treatment of their migraine headaches, there was no statistically significant difference between the ketorolac and the meperidine/promethazine groups.

Adult↗