Rapid Intravenous Injection Research Articles

Evaluation of solitary and scattered esophageal varices according to infrared endoscopy and endoscopic ultrasonography

The aim of this study was to clarify the etiology and clinical significance of solitary and scattered esophageal varices by evaluating their hemodynamics and other characteristics using infrared endoscopy and endoscopic ultrasonography. The study group comprised 44 lesions of these two related types detected in 28 patients by visible-light endoscopy. Infrared endoscopy was used to characterize blue-black coloration before and after rapid intravenous injection of indocyanine green (2 mg/kg). During endoscopic ultrasonography, depth within the esophagus and echo patterns of these varices were characterized. Diameters of these varices were significantly smaller in lesions more strongly staining by infrared endoscopy. Lesion diameter was significantly smaller in varices showing homogeneous low echogenicity than in those showing mixed echogenicity. Lesions showing homogeneous high echogenicity stained most weakly followed in turn by lesions with mixed echogenicity and finally those showing homogeneous low echogenicity. Indocyanine green injection was useful for infrared observation of the hemodynamics of solitary and scattered esophageal varices, as was endoscopic ultrasonography in defining the location and morphology of these lesions. Varices with larger diameters stained more persistently when hemodynamics were evaluated by infrared endoscopy, and often showed a mixture of low and high echogenicity by endoscopic ultrasonography. These observations suggest that blood flow in the varices is slowed, and that the risk of hemorrhage increases with increased diameter especially with uniform enhancement and uniform echogenicity.

MR imaging and proton spectroscopy of the breast: how to select the images useful to convey the diagnostic message

The purpose of this study was to propose a short way to summarise a breast magnetic resonance (MR) examination including a precontrast and contrast-enhanced dynamic study and proton spectroscopy (1H-MRS) in order to convey the diagnostic message. At the Department of Radiology of the Policlinico San Donato (University of Milan), breast MR is routinely performed at 1.5 T as follows: 36-slice axial 2D short-time inversion-recovery (STIR) sequence; 128-partition 3D gradient-echo coronal sequence (1-mm3 siotropic voxel) before and after rapid automatic intravenous injection of 0.1 mmol/kg of Gd-DOTA (one precontrast and four postcontrast phases). Postprocessing includes temporal subtraction (postcontrast minus precontrast), maximum intensity projections (MIPs), percent enhancement-to-time curves for small regions of interest, and axial and/or sagittal multiplanar reconstructions. Single-voxel 1H-MRS is acquired to characterise focal lesions. Applying this protocol, more than 1,200 images are generated for each examination. We select only four MIPs of an early subtracted dynamic phase: one axial similar to craniocaudal x-ray mammographic views, one coronal, and two lateral similar to lateral 90 degrees x-ray mammographic views. For each lesion described in the report, we select five items, including three images, one graph, and one table: STIR image, precontrast and subtracted postcontrast images (morphology), percent enhancement-to-time curves and a table of raw data generating the curves (dynamics). If 1H-MRS has been performed, we add other five items: two postprocessed spectra (metabolism) and three images localising the volume of interest. Only the selected items are printed on films and attached to the report. The selected items range usually from four (no detected lesion) to 14 (one lesion, studied also with 1H-MRS), to 44 (five lesions, one of them studied also with 1H-MRS). The percentage of items presented with the report if compared with the total number of generated images is equal to 0.33% (4/1,200), 1.17% (14/1,200), and 2.83% (34/1,200), respectively. Breast MR imaging and 1H-MRS can be effectively summarised presenting only a minimal fraction of all generated images.

The administration of naked plasmid DNA into the liver induces antitumor innate immunity in a murine liver metastasis model

Gene therapy is a promising strategy against advanced cancer; however, the safety of viral vectors and the effectiveness of non-viral vectors have not yet been established. Recently, a hydrodynamics-based procedure was reported to be an effective and safe method to deliver and transduce DNA into the liver. Herein, we propose a strategy for liver metastasis by a hydrodynamics-based procedure to deliver naked non-coding plasmid DNA (pDNA) into the liver as an immunocompetent organ. Mice received a rapid intravenous (i.v.) injection of naked pDNA in a large volume of saline (0.1 ml/g body weight). The single administration of a naked non-coding pDNA by the hydrodynamics-based procedure before tumor cell inoculation strongly suppressed liver metastasis formation. However, the usual i.v. injection (200 microl/body) of the same dose of naked pDNA could not suppress liver metastasis formation. Following the methylation of CpG sequences within the pDNA using CpG methylase, injection of the methylated pDNA by the hydrodynamics-based procedure could not suppress liver metastasis formation. Gadolinium chloride pretreatment did not interfere with this antitumor effect, but anti-asialo GM1 antiserum treatment did. These findings indicated that natural killer (NK) cells, not Kupffer cells, were involved in this antitumor effect. The NK cytotoxic activities of liver mononuclear cells were strongly enhanced after receiving a naked pDNA by the hydrodynamics-based procedure. These observations suggest that unmethylated CpG motifs in pDNA stimulated immune cells, resulting in the activation of NK cells in the liver to suppress liver metastases in a murine model.

This Month in Anesthesiology

This Month in Anesthesiology

Fluorescence Dilution Technique for Measurement of Cardiac Output and Circulating Blood Volume in Healthy Human Subjects

The authors previously validated in an animal model a new indicator dilution technique for measuring cardiac output and circulating blood volume by recording transcutaneously the fluorescence of circulating indocyanine green with an optical probe placed on the skin surface. The current study compared fluorescence dilution recordings recorded from several locations on the human face in terms of signal intensity and stability and estimated the subjects' cardiac output and circulating blood volume from the recordings. Fluorescence dilution traces were recorded transcutaneously in six healthy human volunteers after rapid intravenous injection of 1 mg indocyanine green. Three placements of the optical probe were tested: the nose ala, the ear lobe, and the temple area. In three subjects, the recordings were calibrated in terms of circulating indocyanine green concentration to estimate cardiac output and circulating blood volume. Fluorescence dilution traces had the same duration for the three locations, but the recordings obtained from the nose ala and the ear lobe were twice as intense as those from the temple. The fluorescence intensity at each site was linearly related to the local laser Doppler perfusion index. The coefficient of variation for the area under the first pass curve (inversely proportional to cardiac output) was approximately 6% for triplicate measurements at the same location. Cardiac output and circulating blood volume derived from the fluorescence recordings were in the normal range. The study demonstrates that intense and reproducible fluorescence dilution signals can be measured transcutaneously in healthy humans and could potentially be used to measure cardiac output and circulating blood volume minimally invasively.

Hydrodynamic Limb Vein Delivery of a Xenogeneic DNA Cancer Vaccine Effectively Induces Antitumor Immunity

Tumor-associated antigens (TAA) are typically poorly immunogenic "self" antigens. An effective strategy to break tolerance and induce antitumor immunity is by genetic vaccination, employing the orthologous TAA-sequence from a different species. We recently developed a clinically relevant approach for intravascular hydrodynamic limb vein (HLV) delivery of nucleic acids to skeletal muscle. Using the human gp100 xenogeneic TAA in the murine B16 melanoma model, we show that genetic vaccination of mice by HLV plasmid DNA delivery was highly effective at breaking tolerance against the homologous murine gp100 (mgp100) TAA and induced prophylactic antitumor protection. HLV vaccination resulted in an anti-hgp100 humoral and cellular response, with 4-5% of CD8(+) T cells being gp100(25-33)-epitope-specific. Vaccinated animals demonstrated in vivo cytolytic activity against human and mgp100(25-33) peptide-pulsed targets. Antitumor immunity could be adoptively transferred by splenocytes from human gp100-vaccinated animals. Furthermore, a durable antitumor memory response was established as approximately 3% of CD8(+) T cells were gp100(25-33) antigen-specific in mice 6 months after vaccination. Following a single HLV human gp100 DNA boost, this level increased to approximately 17% and protected animals from subsequent B16 tumor rechallenge. Our results warrant further consideration of HLV as a clinically relevant method for cancer gene therapy.

Diuretic effect of injecting furosemide into low hydraulic resistance point Shuifen along the conception meridian in pigs with acute edema

To observe whether injection of medicine into low hydraulic resistance point along meridian brings about higher medicinal effect and to explore the efficacy of the theory that meridians are made up of channels featuring low hydraulic resistance by observing the diuretic effect of injecting furosemide or saline into the low hydraulic resistance point Shuifen (CV 9), vein and Zusanli (St 36) respectively. Acute edema was induced in pigs by rapid intravenous injection of 2 000 ml normal saline. The pigs were divided into four groups: Shuifen (CV 9) injection of half dose furosemide group (SFF group), intravenous injection of full dose furosemide group (VF group), Zusanli (St 36) injection of full dose furosemide group (ZSLF group), and Shuifen (CV 9) injection of half dose normal saline group (SFS group). The accumulated urine quantity and the urine quantity generated in every 15-minute period were measured in each group respectively, every 15 minutes after injection, and the measurement lasted for two hours at one experiment. Each group involved eight times of experiments with one pig used for one experiment, which means the whole observation involved 32 times of experiments. The accumulated urine quantities observed in both SFF group and VF group were higher than those in the ZSLF group and the SFS group all through the measurement, showing significant differences during the period from the 15th minute to the 45th minute (P<0.05). But no significant difference was observed between the SFF group and the VF group during the whole 2-hour measurement (P>0.05). Analysis of urine quantity generated in every 15-minute period showed that diuretic effect climaxed during the 15th minute to the 30th minute in both SFF group and VF group. By contrast, ZSLF group reached diuresis climax during the 45th minute to 60th minute and no diuresis climax was observed in the SFS group all through the measurement. Injection of medicine into low hydraulic resistance point along meridian generates faster and more powerful medicinal potency, and this is likely to be applied to clinical practice. The theory that meridians are channels featuring low hydraulic resistance is important to the elucidation of meridians.

Protective effects of atorvastatin in rat models of acute pulmonary embolism: Involvement of matrix metalloproteinase-9*

Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of acute pulmonary embolism (APE)-induced pulmonary hypertension. Here, we evaluate the effects of atorvastatin pretreatment on APE-induced pulmonary hypertension, 24-hr mortality rate, and changes in plasma and lung MMP-2 and MMP-9 activities. Controlled animal study. University research laboratory. Male Wistar rats. Rats received atorvastatin (30 mg/kg/day orally) or tap water for 2 wks. In study 1, we examined whether atorvastatin affected APE-induced pulmonary hypertension by using a rat isolated lung perfusion model of APE. In study 2, we examined whether atorvastatin affects the survival rate after APE, which was induced by rapid intravenous injection of 14 mg/kg of a suspension of microspheres (or saline) into the tail vein. Plasma nitrite/nitrate concentrations were measured by chemiluminescence. Pretreatment with atorvastatin was associated with 49% higher nitrite/nitrate levels compared with controls (p < .05). In study 1, whereas APE increased mean pulmonary artery pressure (MPAP) by 13.0 +/- 1.6 mm Hg in perfused lungs isolated from rats pretreated with water, pretreatment with atorvastatin attenuated by 27% the increases in MPAP after APE. In study 2, pretreatment with atorvastatin was associated with a significant increase in 24-hr survival rate after APE, which was 48% in embolized rats pretreated with water and 64% in rats pretreated with atorvastatin (p < .05). Gelatin zymography of lung and plasma MMP-2 and MMP-9 was performed. Lungs and plasma from embolized rats showed higher levels of both pro- and activated forms of MMP-9 compared with those from nonembolized animals (all p < .05). However, pretreatment with atorvastatin attenuated by 32% the increases in lung-activated MMP-9 levels after APE (p < .05). These results suggest that pretreatment with atorvastatin attenuates APE-induced pulmonary hypertension and increases 24-hr survival rate by mechanisms that result in attenuated increases in lung activated MMP-9 after APE.

Advances in the management of corticosteroid-induced osteoporosis with bisphosphonates

Corticosteroids are widely used as anti-inflammatory and immunosuppressive agents to treat a variety of chronic conditions. Long-term (>1 year) corticosteroid use can lead to bone loss, and therefore, osteopenia or osteoporosis. Corticosteroid-induced osteoporosis (CIO) leads to increased bone fragility and subsequently fractures, which, in turn, lead to a loss of physical, emotional and social health for the patient and increased costs for healthcare providers. A wealth of data exists demonstrating the efficacy of the oral bisphosphonates, etidronate, alendronate and risedronate in increasing bone mineral density in patients with CIO or preventing bone loss in patients commencing corticosteroid therapy. Data regarding fracture prevention are less clear, as statistically significant reductions in the incidence of fractures have only been reported for patient subgroups or meta-analyses. However, many treatment guidelines recommend the use of oral bisphosphonates for the prevention and treatment of CIO. These guidelines are, however, not reflected in prescribing practice, and the majority of patients do not receive adequate concomitant therapy. This review summarizes the available data for bisphosphonates in CIO. Therapeutic adherence with oral bisphosphonates is an issue, with approximately 50% of patients discontinuing therapy within the first year. The primary reasons for this are poor gastrointestinal tolerability and the frequency with which complex dosing requirements must be followed. The inconvenience of taking daily or weekly bisphosphonate therapy is of particular importance in patients with CIO who may be regularly taking several other medications. Data obtained in studies with ibandronate indicate that bisphosphonate administration by rapid intravenous injection provides an effective, well-tolerated and practical alternative to current oral regimens in the management of patients with CIO.

99mTc-labelled red blood cell single-photon emission computed tomography for the diagnosis and follow-up of juvenile nasopharyngeal angiofibroma*

To confirm the usefulness of blood pool scintigraphy with Tc-labelled red blood cells ((99m)Tc-RBCs) in the diagnosis and follow-up of juvenile nasopharyngeal angiofibroma. A prospective study design was used. (99m)Tc-RBCs were prepared by a modified in-vivo method. After the rapid intravenous injection of 370-740 MBq of (99m)Tc-RBCs, dynamic imaging of 1-min duration was performed. After dynamic imaging, static acquisitions at 5 min (second phase: blood pool phase) and 2 h (third phase: static image) were obtained. In addition, single-photon emission computed tomography (SPECT) imaging was performed at 2 h. SPECT images were obtained using a rotating gamma camera (GE-Starcam 4000 XR/T). All patients showed no activity in the first phase and mild activity in the second phase (blood pool phase). All patients with juvenile nasopharyngeal angiofibroma showed a prominent increased activity in the third phase and in SPECT images. This study shows that blood pool scintigraphy with (99m)Tc-RBC SPECT is very accurate, easy to perform and a suitable alternative to pre-operative and post-operative imaging techniques, including computed tomography scan, magnetic resonance imaging (MRI) and MRI angiography, for the detection of juvenile nasopharyngeal angiofibroma.

Intravenous ibandronate injections in postmenopausal women with osteoporosis: One‐year results from the dosing intravenous administration study

Although oral bisphosphonates are effective treatments for postmenopausal women with osteoporosis, oral dosing may be unsuitable for some patients. An efficacious intravenously administered bisphosphonate could be beneficial for such patients. Ibandronate, a potent nitrogen-containing bisphosphonate, can be administered using extended dosing intervals, either orally or by rapid intravenous injection. The aim of this study was to identify the optimal intravenous dosing regimen for ibandronate in postmenopausal women with osteoporosis. In a randomized, double-blind, double-dummy, phase III, noninferiority study, we compared 2 regimens of intermittent intravenous injections of ibandronate (2 mg every 2 months and 3 mg every 3 months) with a regimen of 2.5 mg of oral ibandronate daily, the latter of which has proven antifracture efficacy. The study group comprised 1,395 women (ages 55-80 years) who were at least 5 years postmenopausal. All patients had osteoporosis (lumbar spine [L2-L4] bone mineral density [BMD] T score less than -2.5). Participants also received daily calcium (500 mg) and vitamin D (400 IU). The primary end point was change from baseline in lumbar spine BMD at 1 year. Changes in hip BMD and in the level of serum C-telopeptide of type I collagen (CTX) were also measured, as were safety and tolerability. At 1 year, mean lumbar spine BMD increases were as follows: 5.1% among 353 patients receiving 2 mg of ibandronate every 2 months, 4.8% among 365 patients receiving 3 mg of ibandronate every 3 months, and 3.8% among 377 patients receiving 2.5 mg of oral ibandronate daily. Both of the intravenous regimens not only were noninferior, but also were superior (P < 0.001) to the oral regimen. Hip BMD increases (at all sites) were also greater in the groups receiving medication intravenously than in the group receiving ibandronate orally. Robust decreases in the serum CTX level were observed in all arms of the study. Both of the intravenous regimens were well tolerated and did not compromise renal function. As assessed by BMD, intravenous injections of ibandronate (2 mg every 2 months or 3 mg every 3 months) are at least as effective as the regimen of 2.5 mg orally daily, which has proven antifracture efficacy, and are well tolerated.

Dynamic helical CT mammography of breast cancer

The purpose of this study was to determine whether dynamic helical computed tomography (CT)-mammography could assist in selecting the most appropriate surgical method in women with breast cancer. Preoperative contrast-enhanced helical CT scanning of the breast was performed on 133 female patients with suspicion of breast cancer at the same time as clinical, mammographic, and/or ultrasonographic examinations. The patients were scanned in the prone position with a specially designed CT-compatible device. A helical scan was made with rapid intravenous bolus injection (3 ml/s) of 100 ml of iodine contrast material. Three-dimensional maximum intensity projection (MIP) images were reconstructed, and CT findings were correlated with surgical and histopathological findings. Histopathological analysis revealed 84 malignant lesions and seven benign lesions. The sensitivity, specificity, and accuracy levels of the CT scanning were 94.6%, 58.6%, and 78.9%. Helical scanning alone revealed additional contralateral carcinomas in three of four patients and additional ipsilateral carcinomas in three of five patients. However, the technique gave false-positive readings in 24 patients. The preoperative CT-mammogram altered the surgical method in six patients. Dynamic helical CT-mammography in the prone position may be one of the choices of adjunct imaging in patients with suspected breast cancer scheduled for surgery.

Stimulatory effect of polyethylene glycol (PEG) on gene expression in mouse liver following hydrodynamics‐based transfection

Rapid intravenous injection of a large volume of plasmid DNA (pDNA), i.e. a transfection procedure based on hydrodynamics, is known to be an efficient and liver-specific method of in vivo gene delivery. However, the gene expression is transient. We investigated the effect of addition of polyethylene glycol (PEG) to a solution of naked pDNA (luciferase) on the expression of the gene in mouse liver following transfection by the hydrodynamics-based technique. In addition, the mechanism leading to the enhancement of the gene expression was studied. The addition of 1% (w/v) PEG2000 to the pDNA solution enhanced the resulting gene expression in the liver. Increasing the PEG2000 concentration to more than 1 and up to 10% (w/v) rather diminished the gene expression level. By contrast, increasing the molecular weight of PEG to over 2000 up to 10 000 did not affect the level of gene expression. Histopathological and serum-chemistry examinations indicated that hydrostatic or osmotic pressure increased tissue and hepatocellular damage in a PEG-concentration-dependent manner, and resulted in a decrease in gene expression. Quantitative evaluation showed that the enhanced gene expression resulted from stabilization of the pDNA introduced into the hepatocytes and an enhancement of the transport of intact pDNA to the nucleus. For most gene therapy applications and gene function studies, sustained expression of the introduced gene(s) is necessary. This simple method to achieve enhanced gene expression in liver may have a great potential for a wide variety of laboratory studies in molecular and cellular biology as well as possibly for future clinical applications in humans.

Ethical Validity of Palliative Sedation Therapy: A Multicenter, Prospective, Observational Study Conducted on Specialized Palliative Care Units in Japan

Although palliative sedation therapy is often required in terminally ill cancer patients to achieve acceptable symptom relief, empirical data supporting the ethical validity of this approach are lacking. The primary aim of this study was to systematically investigate whether empirical evidence supports the ethical validity of sedation. This was a multicenter, prospective, observational study, which was conducted by 21 specialized palliative care units in Japan. One-hundred two consecutive adult cancer patients who received continuous deep sedation were enrolled. Continuous deep sedation was defined as the continuous use of sedative medications to relieve intolerable and refractory distress by achieving almost or complete unconsciousness until death. Prior to the study, we conceptualized the ethical validity of sedation from the viewpoints of physicians' intent, proportionality, and autonomy. Sedation was performed mainly with midazolam and phenobarbital. The initial doses of midazolam and phenobarbital were 1.5 mg/hour and 20 mg/hour, respectively. Main administration routes were continuous subcutaneous infusion and continuous intravenous infusion, and no rapid intravenous injection was reported. Of 59 patients who received artificial hydration or could intake adequate fluids/foods orally before sedation, 63% received artificial hydration therapy after sedation, and in the remaining patients, artificial hydration was withheld or withdrawn due to fluid retention symptoms and/or patient wishes. Of 66 patients who were able to verbally express themselves, 95% explicitly stated that symptoms were intolerable. The etiologies of the symptoms requiring sedation were primarily related to the progression of the underlying malignancy, such as cancer cachexia and organ failure, and standard palliative treatments had failed: steroids in 68% of patients with fatigue, opioids in 95% of patients with dyspnea, antisecretion medications in 75% of patients with bronchial secretion, antipsychotic medications in 74% of patients with delirium, and opioids in all patients with pain. On the basis of the Palliative Prognostic Index, 94% of the patients were predicted to die within 3 weeks. Before sedation, 67% of the patients expressed explicit wishes for sedation. In the remaining 34 patients, previous wishes for sedation were noted in 4 patients, and in the other 30 patients, the families were involved in the decision-making process. The chief reason for patient non-involvement in the decision making was cognitive impairment. These data indicate that palliative sedation therapy performed in specialized palliative care units in Japan generally followed the principles of double effect, proportionality, and autonomy.

The safety and efficacy of ferumoxytol therapy in anemic chronic kidney disease patients

Administration of safe and effective iron therapy in patients with chronic kidney disease is a time consuming process. This phase II clinical trial studied ferumoxytol, a semi-synthetic carbohydrate-coated iron oxide administered by rapid intravenous injection to anemic chronic kidney disease patients (predialysis or undergoing peritoneal dialysis). Inclusion criteria included hemoglobin < or =12.5 g/dL and transferrin saturation < or =35%. Twenty-one adult patients were randomized to receive ferumoxytol in a regimen of 4 doses of 255 mg iron in 2 weeks or 2 doses of 510 mg iron in 1 to 2 weeks. Ferumoxytol was administered at a rate of up to 30 mg iron/sec. The maximum hemoglobin response following ferumoxytol administration occurred at 6 weeks, increasing from a baseline of 10.4 +/- 1.3 g/dL to 11.4 +/- 1.2 g/dL (P < 0.05). Ferritin increased from a baseline of 232 +/- 216 ng/mL to a maximum of 931 +/- 361 ng/mL at 2 weeks (P < 0.05), while the baseline transferrin saturation increased from 21 +/- 10% to 37 +/- 22% at 1 week (P < 0.05). Seven adverse events in 5 patients during this trial were deemed possibly related to ferumoxytol, none serious. These events included constipation, chills, tingling, a gastrointestinal viral syndrome, delayed pruritic erythematous rash, and transient pain at the injection site. Although larger studies are required, this small study demonstrates that ferumoxytol can be safe and effective in increasing iron stores, is associated with an increased hemoglobin response, and is well tolerated at a rapid infusion rate.

Diagnosing Traumatic Arterial Injury in the Extremities with CT Angiography: Pearls and Pitfalls

Computed tomographic (CT) angiography is a reliable and convenient imaging modality for diagnosing arterial injuries after blunt and penetrating trauma to the extremities. It is a noninvasive modality that could replace conventional arteriography as the initial diagnostic study for arterial injuries after trauma to the extremities. The technique requires scanning with multidetector helical CT after rapid intravenous injection of iodinated contrast material. The CT angiographic signs of arterial injuries in the extremities are active extravasation of contrast material, pseudoaneurysm formation, abrupt narrowing of an artery, loss of opacification of a segment of artery, and arteriovenous fistula formation. Metallic streak artifact, motion artifact, and inadequate arterial opacification may render a CT angiogram nondiagnostic. Studies have shown the sensitivity of CT angiography to be 90%-95.1% and its specificity 98.7%-100% for detecting arterial injury to the extremities after trauma.

Perfusion Study of Hypervascular Hepatocellular Carcinoma with SPIO

We evaluated whether a perfusion study with Resovist is useful to assess blood flow in tumors in patients with hypervascular hepatocellular carcinoma (HCC). The subjects were 28 patients; the lesions consisted of 68 hypervascular HCC, 14 post-treatment nodules, and 7 hepatocellular hypovascular nodules. After rapid intravenous injection of Resovist, 7-phase imaging was performed using the single-shot echo-planar method. Diagnostic accuracy and tumor vascularity were evaluated by 3 radiologists using the alternative free response receiver operating characteristic method. Sensitivity, Az values, and positive predictive values were calculated. To assess interobserver variability, we evaluated the kappa static to measure the degree of agreement. The 3 observers indicated no significant difference in Az value related to the presence or absence of a perfusion study, and only one remarked a significant difference in sensitivity. However, kappa values were better in the presence than in the absence of a perfusion study. Blood flow assessment was poor in less than 1 cm. The 3 observers showed a positive predictive value of 90% or more. A perfusion study may facilitate the diagnosis of hypervascular HCC, improving the diagnostic accuracy.

Initial antipyrine disposition in man is altered by propranolol

Purpose β-Adrenergic antagonists decrease intravenous (IV) anesthetic dose requirements. The present study determined the effect of propranolol on antipyrine (AP) disposition from the moment of rapid IV injection using a recirculatory pharmacokinetic (PK) model. AP is a physiologic marker that distributes to a volume as large as total body water in a blood flow-dependent manner and is a surrogate for many lipophilic drugs, including IV anesthetics. Methods AP disposition was determined twice in 5 healthy adult males in this IRB-approved study, once during a propranolol infusion. After rapid AP injection, arterial blood samples were collected frequently for 2 min and less frequently thereafter. Plasma AP concentrations were measured by HPLC. AP disposition was characterized, using SAAM II, by a recirculatory PK model that describes drug disposition from the moment of injection. Parameters were compared using the paired t-test. Results The disposition of concomitantly administered indocyanine green (ICG) demonstrated that propranolol decreased cardiac output (C.O.) at the expense of the fast peripheral (nonsplanchnic) intravascular circuit. AP AUC was doubled for at least the first 3 min after rapid IV injection due to both decreased C.O. and maintenance of nondistributive blood flow at the expense of a two-thirds reduction of blood flow (intercompartmental clearance) to the rapidly equilibrating (fast, splanchnic) tissue volume. Conclusion The increase in AP AUC due to the propranolol-induced alteration of initial AP disposition could explain decreased IV anesthetic dose requirements in the presence of β-adrenergic blockade. Clinical Pharmacology & Therapeutics (2004) 75, P34–P34; doi: 10.1016/j.clpt.2003.11.128

Multiple enhancing lesions detected on dynamic helical computed tomography-mammography.

To review pathologic diagnoses of multiple enhancing lesions in a unilateral breast detected on dynamic helical computed tomography (CT)-mammography and to correlate imaging findings with pathologic results. From May 1998 to July 2001, preoperative contrast-enhanced helical CT scanning of the breast was performed in 200 female patients clinically diagnosed with breast cancer. The patients were scanned in the prone position in a specially designed CT-compatible device, with rapid intravenous bolus injection of 100 mL contrast material. Three-dimensional maximum intensity projection images were reconstructed. The cases with multiple enhancing lesions in a unilateral breast were retrospectively reviewed. The maximum diameter of the largest stain in each breast was measured, the patterns of multiple enhancing lesions were classified, and imaging findings were correlated with surgical and pathologic outcomes. Twenty-five of 200 (12.5%) patients (age range: 39-86 years, mean age: 56 years) showed multiple stains on CT-mammography. Two patients showed multiple stains in bilateral breasts. The maximum diameter of the largest stain in each breast ranged from 5 to 55 mm (average: 22 mm). Among cases with multiple stains, 21 (78%) were shown to be invasive ductal carcinoma with multiple satellite cancer nodules. Four cases were ductal carcinoma in situ with multiple satellite nodules. One case revealed multiple fibroadenomas, and another showed intraductal papilloma. Multiple enhancing lesions on CT-mammography in patients with breast cancer were relatively common, and most of them represented multiple cancer lesions. Dynamic CT-mammography is potentially useful in evaluating the spread of breast cancer.

Value of rapid beta-blocker injectionat peak dobutamine-atropine stressechocardiography for detection of coronary artery disease

ObjectivesWe studied the value of a rapid beta-blocker injection at peak dobutamine-atropine stress echocardiography (DASE) for the detection of coronary artery disease (CAD). BackgroundThe presence of tachycardia and hyperdynamic wall motion may make it difficult to recognize a new wall motion abnormality (NWMA) at peak stress. MethodsWe studied 101 patients (mean age 58.2 ± 9.8 years) who underwent effective DASE and coronary angiography. All patients received a rapid intravenous injection of metoprolol immediately after peak DASE image acquisition. Positivity in combined peak plus post-metoprolol images was defined when there was only peak NWMA, maintenance of peak NWMA, or NWMA detected only after metoprolol injection. Significant CAD was defined as ≥50% stenosis by quantitative angiography. ResultsThere were 37 patients without and 64 with CAD. The sensitivity, specificity, accuracy, and positive and negative predictive values for the detection of CAD at peak stress were 84%, 92%, 87%, 95%, and 77%, respectively. Five patients with CAD had negative peak images that became positive only after metoprolol. Extension of peak NWMA during metoprolol was observed in 14 patients, and multivessel CAD was detected in 10 of them. The sensitivity, specificity, accuracy, and positive and negative predictive values for peak plus metoprolol images were 92%, 89%, 91%, 94%, and 87%, respectively. ConclusionsThe use of metoprolol injected at peak of dobutamine infusion improved the detection of CAD by DASE.