Pyruvate-modified perfadex improves lung function after long-term hypothermic storage.

BACKGROUND: Lungs harvested for transplantation are stored while inflated with oxygen, which can serve to support oxidative metabolism. However, strategies aimed at increasing graft metabolism during storage have received little attention. In this study, we added pyruvate to the preservation solution Perfadex and measured the effects on oxidative metabolism and reperfusion lung function. METHODS: Rat lungs were stored for 6 and 24 hours in low-potassium dextran solution at 10 degrees C containing either 5 mmol/liter uniformly carbon-13 (U-(13)C) labeled glucose (Perfadex), 32 mmol/liter 3-(13)C pyruvate (pyruvate), or both (combined). Oxidation of exogenous substrates was measured as the incorporation of (13)C into tricarboxylic acid cycle intermediates by magnetic resonance spectroscopy. Additional groups of lungs with each substrate modification were preserved for 6 or 24 hours and then reperfused. RESULTS: Enrichment of tricarboxylic acid cycle intermediates was low in the Perfadex group (9% at 6 hours and 32% at 24 hours of storage, respectively). In contrast, enrichment was significantly increased in both the pyruvate group (50% and 59%, respectively) and combined group (39% and 54%, respectively) compared with the Perfadex group (p<0.01). Graft function was excellent after 6-hour storage in all groups. All lungs stored for 24 hours exhibited inferior lung function, but oxygenation, pulmonary artery pressures, and airway pressures in the combined group were significantly improved compared with the Perfadex group (p<0.05). CONCLUSIONS: Preservation solution substrate composition influences graft metabolism during storage. The addition of pyruvate to Perfadex increases metabolism during storage and improves reperfusion lung function.     

Three-dimensional magnetic resonance myocardial motion tracking from a single image plane.

Three-dimensional imaging for the quantification of myocardial motion is a key step in the evaluation of cardiac disease. A tagged magnetic resonance imaging method that automatically tracks myocardial displacement in three dimensions is presented. Unlike other techniques, this method tracks both in-plane and through-plane motion from a single image plane without affecting the duration of image acquisition. A small z-encoding gradient is subsequently added to the refocusing lobe of the slice-selection gradient pulse in a slice following CSPAMM acquisition. An opposite polarity z-encoding gradient is added to the orthogonal tag direction. The additional z-gradients encode the instantaneous through plane position of the slice. The vertical and horizontal tags are used to resolve in-plane motion, while the added z-gradients is used to resolve through-plane motion. Postprocessing automatically decodes the acquired data and tracks the three-dimensional displacement of every material point within the image plane for each cine frame. Experiments include both a phantom and in vivo human validation. These studies demonstrate that the simultaneous extraction of both in-plane and through-plane displacements and pathlines from tagged images is achievable. This capability should open up new avenues for the automatic quantification of cardiac motion and strain for scientific and clinical purposes.     

Small-animal PET of tumor angiogenesis using a (76)Br-labeled human recombinant antibody fragment to the ED-B domain of fibronectin.

The aim of this study was to image the extra domain B (ED-B) of fibronectin, an angiogenesis-related target, in solid tumors using small-animal PET. Toward this aim, an ED-B fibronectin-binding human antibody derivative (L19-SIP) was labeled with (76)Br via an enzymatic approach. Biodistribution and imaging studies were performed in human teratoma-bearing mice for up to 48 h after injection. METHODS: L19-SIP was labeled with (76)Br using bromoperoxidase/H(2)O(2). The stability of the labeled antibody was tested both in vitro and in vivo. Biodistribution and small-animal imaging studies (PET and CT) were performed in F9-bearing 129/sv mice (n = 3 or 4). RESULTS: The enzymatic radiobromination approach afforded the labeled antibody in high yield (>55%) under mild reaction conditions. (76)Br-L19-SIP stability in mouse serum proved to be similar to that of the (125)I-labeled analog (>80% of intact material at 48 h after injection). Fast and specific in vivo targeting was obtained in tumors and other organs expressing ED-B fibronectin (i.e., ovaries and uterus). However, slow renal clearance and persistent activity predominately in blood and stomach suggests partial (76)Br-L19-SIP debromination in vivo. This debromination was confirmed in a metabolism study in normal mice. The F9 tumors were clearly imaged by small-animal PET at each considered time point, starting at 5 h up to 48 h after injection. CONCLUSION: (76)Br-L19-SIP specifically accumulated at the target site, enabling detailed small-animal PET of tumor neovasculature. Therefore, targeting the angiogenesis-associated expression of ED-B fibronectin can be a valuable tool for tumor detection using molecular imaging with PET.     

Targeted stent use in clinical practice based on evidence from the Basel Stent Cost Effectiveness Trial (BASKET): reply

We thank Agostini Pierfranco and colleagues for their interestin our analysis of the     

CMSS-VEPs: Contrast modulated steady state visual evoked potentials: Its neuronal origin and clinical use

CMSS-VEPs are presented as a sensitive, non-invasive functional investigation technique of the visual function, applicable in clinical practice. New improvements of the technique are presented. The underlying neuronal mechanisms are discussed. The clinical use is illustrated in a case of optic neuritis.     

The effect of maximal doses of formoterol and salbutamol from a metered dose inhaler on pulse rates, ECG, and serum potassium concentrations

In a randomized, double-blind, crossover cumulative study, the individual maximal bronchodilator dosages for formoterol (F) and salbutamol (S) were assessed for their respective influence on ECG, pulse rate, and serum potassium levels in 13 patients with stable and reversible asthma. The following dosages were administered with an interval of 1 h: 12-24-48-(48)-(48) micrograms for F and 100-200-400-400-(400)-(400) micrograms for S. The study day was discontinued if pulse rate was above 140 beats min-1, a flattening of T wave on the ECG was recorded, or a maximal bronchodilation in FEV1 was observed (above 110 percent of the predicted value or an increase in FEV1 in the last two measurements below 5 percent). The maximal individual dose of F administered was 84 micrograms in six patients, 132 micrograms in three patients, 180 micrograms in three patients, and 228 micrograms in one patient. For S, the maximal individual dose was 400 micrograms in three patients, 2,200 micrograms in eight patients, 3,000 micrograms in one patient, and 3,800 micrograms in one patient. The mean maximal increase in FEV1 was 36.0 percent after F and 35.1 percent after S. Pulse rate increased from 73 to S3 beats.min-1 after F and from 75 to 84 beats.min-1 after S (both statistically significant). No pulse rate above 140 beats.min-1 was observed. In the high-therapeutic range (up to 36 micrograms of F and 6,090 micrograms of S), no changes in potassium level were observed. In still higher dosages, mean potassium level decreased from 4.16 to 3.78 mmol.L-1 after F and from 4.02 to 3.88 mmol.L-1 after S (not clinically relevant). The lowest individual potassium level recorded was 3.1 mmol.L-1. No clinically important changes in ECG were observed. In conclusion, very high doses of F and S administered from a metered dose inhaler proved to be safe for patients.     

Determinants of the public's preference for social distance from people with schizophrenia.

OBJECTIVE: To examine the extent to which the public's desire for social distance from people with schizophrenia is influenced by beliefs about the disorder and stereotypes about those suffering from it. METHODS: In spring 2001, we carried out a representative survey of individuals of German nationality aged 18 years and over (n = 5025). Each subject was given a fully structured interview that began with the presentation of a vignette. RESULTS: Both labelling and beliefs about the disorder's causes and prognosis, as well as the perception that those suffering from it are unpredictable and dangerous, had an impact on the public's desire for social distance. However, the latter proved to be more important. As expected, respondents who identified the disorder depicted in the vignette as mental illness, those who blamed the individual for its development, and those who anticipated a poor prognosis expressed a stronger desire for social distance. Endorsing biological factors as a cause was also associated with increased social distance. CONCLUSIONS: Our findings have important implications for interventions aimed at reducing stigma and discrimination related to schizophrenia. Targeting the stereotype of unpredictability and dangerousness appears to be particularly important.