Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects. A prospective investigation

We performed magnetic resonance imaging on sixty-seven individuals who had never had low-back pain, sciatica, or neurogenic claudication. The scans were interpreted independently by three neuro-radiologists who had no knowledge about the presence or absence of clinical symptoms in the subjects. About one-third of the subjects were found to have a substantial abnormality. Of those who were less than sixty years old, 20 per cent had a herniated nucleus pulposus and one had spinal stenosis. In the group that was sixty years old or older, the findings were abnormal on about 57 per cent of the scans: 36 per cent of the subjects had a herniated nucleus pulposus and 21 per cent had spinal stenosis. There was degeneration or bulging of a disc at at least one lumbar level in 35 per cent of the subjects between twenty and thirty-nine years old and in all but one of the sixty to eighty-year-old subjects. In view of these findings in asymptomatic subjects, we concluded that abnormalities on magnetic resonance images must be strictly correlated with age and any clinical signs and symptoms before operative treatment is contemplated.     

Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti-cancer drug treatment.

Therapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport. It is with anti-cancer drugs that major progress has been made in the study of partition between the largest cellular blood compartment, i.e., erythrocytes, and the plasma compartment. The aim of the present review is to detail the progress made in predicting what a drug does in the body, i.e., pharmacodynamics including toxicity and plasma and/or red blood cell concentration monitoring. Furthermore, techniques generally used in anti-cancer drug monitoring are highlighted. Data for complex Bayesian statistical approaches and population kinetics studies are beyond the scope of this review, since this is generally limited to the plasma compartment only.     

Syntheses of Novel Pyridazinomorphinans by Inverse Electron Demand Cycloaddition and their Binding to μ and κ Receptors

A number of novel pyridazinomorphinans have been synthesized by the inverse electron demand Diels-Alder reaction of various 3,6-disubstituted 1,2,4,5-tetrazines with enamines derived from dihydrocodeinone and with codeinone. Reduction of some of the pyridazinomorphinans did not furnish the expected pyrroloepoxymorphinans; in all cases investigated reductive cleavage of the epoxybridge was observed to yield dihydropyridazino- or pyrrolomorphinans. The structures of all new compounds were assigned by the spectral data, that of the cycloadduct of codeinone was additionally verified by X-ray crystallography. Compounds 5a, 8, 11a , and 16 have been evaluated for their affinity at μ and κ opioid receptors in radioligand binding assays. Their ability to inhibit [³H]DAMGO binding at μ and [³H]U 69.593 binding at κ receptors, respectively as compared to codeine has been found to be lower.     

The HemoCue®, a point of care B-hemoglobin photometer, measures hemoglobin concentrations accurately when mixedin vitro with canine plasma and three hemoglobin-based oxygen carriers (HBOC)

PURPOSE: Accuracy of measurement of low hemoglobin concentrations using the HemoCue, a B-hemoglobin photometer (HemoCue AB, Angelholm, Sweden) may exhibit significant variability. Infusion of hemoglobin-based oxygen carriers (HBOC) results in low concentrations of plasma hemoglobin. Our study assessed B-hemoglobin photometer measurement accuracy of three HBOC: (hemoglobin glutamer-200 (bovine; Oxyglobin, Biopure Corp., Cambridge, MA, USA); hemoglobin glutamer-250 (bovine; Hemopure, Biopure Corp, Cambridge, MA, USA), and hemoglobin-raffimer, (human; Hemolink, Hemosol, Inc., Toronto, Ontario, Canada). METHODS: In the laboratory, 45 split canine plasma samples were mixed with hemoglobin glutamer-200 (8.13, 16.25, 32.5 g x L(-1) concentrations), 45 samples were mixed with hemoglobin glutamer-250 (8.13, 16.25, 32.5 g x L(-1) concentrations), 45 with hemoglobin-raffimer (12.5, 25.0, 50.0 g x L(-1) concentrations), and measured. Plasma samples without HBOC served as control. Hemoglobin concentration was determined by a laboratory analyzer (Coulter Corporation, Hiafeah, FL, USA) and B-hemoglobin photometer (HemoCue, Angelholm, Sweden). Two independent technicians performed blinded sample measurements and randomly tested each sample five times. Results were analyzed according to Bland and Altman analysis. RESULTS: B-hemoglobin photometer demonstrated high repeatability for all three HBOCs. Repeatability coefficients were 0.37 g x L(-1) and 0.48 g x L(-1) for hemoglobin glutamer-200, 0.39 g x L(-1) and 0.4 g x L(-1) for hemoglobin glutamer-250 and 1.07 g x L(-1) and 0.85 g x L(-1) for hemoglobin-raffimer. An acceptable agreement was found between the B-hemoglobin photometer and the laboratory analyzer for all three HBOCs tested. CONCLUSION: The B-hemoglobin photometer accurately determined the concentration of three HBOC solutions dissolved in canine plasma.     

The internal anatomy of the median nerve in the region of the elbow.

The internal anatomy of the median nerve in the region of the elbow has been studied by microdissection in 20 cadavers. Gross branching patterns were studied in an additional 14 cadavers. There are four major branches or branch groups: I to pronator teres, II to flexor carpi radialis, flexor digitorum superficialis, and palmaris longus; III to the anterior interosseous nerve; and IV to flexor digitorum superficialis. Three of these could be traced proximally within the main trunk of the median nerve, the average being I-10 cm; III-7.5 cm; IV-2 cm. This information should have clinical applications in repair and grafting of the median nerve near the elbow and in understanding clinical nerve compression sydromes.     

Azulene als Dienophile in der [4+2]-Cycloaddition mit inversem Elektronenbedarf,eine Ergänzung

Azulenes as Dienophiles in the [4+2]-Cycloaddition with Inverse Electron Demand, a Supplement [4+2] Cycloadditions of azulene ( 2 ) und 1-Nitroazulene ( 14 ) with the extremely electron-deficient, s-cis-fixed diazadiene system of 3,6-bis(trifluoromethyl)-1,2,4,5-tetrazine ( 1 ) are described. In addition to earlier findings 1 reacts with 2 probably in a two step [4+2] cycloaddition via 8 and 10 to yield the benzo[f]phthalazine 5a , via 8 and 9 to furnish the azuleno[d]pyridazine 3 and the azine 4 . The reaction of 1 with 1-Nitroazulene ( 14 ) leads to the azuleno[d]pyridazines 3 and 19 in low yield.