HNA antibody-mediated neutrophil aggregation is dependent on serine protease activity.

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is often caused by antibodies against human neutrophil alloantigen-2 (HNA-2) and HNA-3a. Neutrophil aggregation is considered as a major cause of TRALI, but little is known about how HNA antibodies initiate this process. We explored mechanisms involved in neutrophil aggregation induced by HNA-2 and HNA-3a antibodies. MATERIALS AND METHODS: Isolated neutrophils were pretreated with broad-spectrum or specific inhibitors against different cell functions or proteases. Granulocyte agglutination test (GAT) was performed with serially diluted anti-HNA-2 and anti-HNA-3a plasmas or control plasma, and reactivity was evaluated microscopically. Reactive oxygen species (ROS) production in neutrophils was investigated using a lucigenin-based chemiluminescence assay. RESULTS: HNA-2 and HNA-3a antibody-mediated neutrophil aggregation was inhibited by pretreatment with formaldehyde, iodoacetamide and the serine protease inhibitors Pefabloc-SC, N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and Nα-tosyl-L-lysine chloromethyl ketone hydrochloride (TLCK). In contrast, inhibition of actin polymerization, respiratory burst, cysteine proteases, metalloproteases or aspartic proteases did not affect neutrophil aggregation. Furthermore, HNA-3a antibodies did not directly cause ROS production in neutrophils. CONCLUSION: Aggregation of neutrophils induced by HNA-2 and HNA-3a antibodies is an active process and depends on trypsin- or chymotrypsin-like serine proteases but is not dependent on the production of ROS. These findings may open new prospects for the pharmacologic prevention of neutrophil-associated acute lung injury.

Exposure to pulse-modulated radio frequency electromagnetic fields affects regional cerebral blood flow.

We investigated the effects of radio frequency electromagnetic fields (RF EMF) similar to those emitted by mobile phones on waking regional cerebral blood flow (rCBF) in 12 healthy young men. Two types of RF EMF exposure were applied: a 'base-station-like' and a 'handset-like' signal. Positron emission tomography scans were taken after 30 min unilateral head exposure to pulse-modulated 900 MHz RF EMF (10 g tissue-averaged spatial peak-specific absorption rate of 1 W/kg for both conditions) and sham control. We observed an increase in relative rCBF in the dorsolateral prefrontal cortex on the side of exposure. The effect depended on the spectral power in the amplitude modulation of the RF carrier such that only 'handset-like' RF EMF exposure with its stronger low-frequency components but not the 'base-station-like' RF EMF exposure affected rCBF. This finding supports our previous observation that pulse modulation of RF EMF is necessary to induce changes in the waking and sleep EEG, and substantiates the notion that pulse modulation is crucial for RF EMF-induced alterations in brain physiology.

Electromagnetic fields, such as those from mobile phones, alter regional cerebral blood flow and sleep and waking EEG.

Usage of mobile phones is rapidly increasing, but there is limited data on the possible effects of electromagnetic field (EMF) exposure on brain physiology. We investigated the effect of EMF vs. sham control exposure on waking regional cerebral blood flow (rCBF) and on waking and sleep electroencephalogram (EEG) in humans. In Experiment 1, positron emission tomography (PET) scans were taken after unilateral head exposure to 30-min pulse-modulated 900 MHz electromagnetic field (pm-EMF). In Experiment 2, night-time sleep was polysomnographically recorded after EMF exposure. Pulse-modulated EMF exposure increased relative rCBF in the dorsolateral prefrontal cortex ipsilateral to exposure. Also, pm-EMF exposure enhanced EEG power in the alpha frequency range prior to sleep onset and in the spindle frequency range during stage 2 sleep. Exposure to EMF without pulse modulation did not enhance power in the waking or sleep EEG. We previously observed EMF effects on the sleep EEG (A. A. Borbély, R. Huber, T. Graf, B. Fuchs, E. Gallmann and P. Achermann. Neurosci. Lett., 1999, 275: 207-210; R. Huber, T. Graf, K. A. Cote, L. Wittmann, E. Gallmann, D. Matter, J. Schuderer, N. Kuster, A. A. Borbély, and P. Achermann. Neuroreport, 2000, 11: 3321-3325), but the basis for these effects was unknown. The present results show for the first time that (1) pm-EMF alters waking rCBF and (2) pulse modulation of EMF is necessary to induce waking and sleep EEG changes. Pulse-modulated EMF exposure may provide a new, non-invasive method for modifying brain function for experimental, diagnostic and therapeutic purposes.

Radiation exposure to sonographers from fluorine-18-FDG PET patients.

OBJECTIVE: We estimated the amount of radiation exposure to sonographers from patients who were injected with 18F-fluorodeoxyglucose (FDG) at 2 and 3 h postinjection. METHODS: We studied 8 patients who were given between 380-420 MBq 18F-FDG. The patients were measured with a RADOS RDS-120 dosimeter between 2 and 3 h after FDG injection. The dosimetry measurement was taken at a distance of 0.5 m from the injected patient, a distance used by a sonographer to perform an abdominal ultrasound. Measurements were taken at the levels of the sonographer's shoulder, abdomen, and gonads. RESULTS: At the first measurement at 2 h, the mean exposures to the shoulder, abdomen, and gonads of the sonographer in pSv/h were 31.9+/-11.3, 37.1+/-9.5, and 32.8+/-11.8, respectively. At 3 h, the mean exposures to the shoulder, abdomen, and gonads were 21.5+/-4.2, 20.2+/-5.8, and 19.6+/-4.9, respectively. CONCLUSION: The amount of radiation exposure to a sonographer is minimal. Radiation exposure risks should be considered, however, if the sonographer comes into daily, repeated contact with patients who have been given 18F-FDG.

Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling.

PURPOSE: To prospectively compare the accuracy of positron emission tomography (PET) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) with that of computed tomography (CT) in the nodal staging of non-small cell lung cancer. MATERIALS AND METHODS: PET and contrast material-enhanced CT were performed in 47 patients suspected of having or with newly diagnosed non-small cell lung cancer. Each imaging study was evaluated separately, and nodal stations were localized according to the American Thoracic Society mapping system. Extensive lymph node sampling (599 nodes from 191 nodal stations) of the ipsi- and contralateral tracheobronchial and mediastinal nodal stations was performed at thoracotomy and/or mediastinoscopy. Imaging findings were correlated with histopathologic staging results. RESULTS: The sensitivity of PET and CT was 89% and 57%, respectively, for the staging of N2 or N3 disease in mediastinal nodes; specificity was 99% and 94%, respectively; positive predictive value was 96% and 76%, respectively; negative predictive value was 97% and 87%, respectively; and accuracy was 96% and 85%, respectively. In assigning the correct N stage, PET was correct in 96% and CT in 79% of cases. CONCLUSION: PET with FDG appears to be superior to CT for nodal staging of non-small cell lung cancer.

Whole-body PET: physiological and artifactual fluorodeoxyglucose accumulations.

UNLABELLED: The purpose of this study was to semiquantitatively identify artifactual and physiological soft-tissue accumulations in whole-body FDG-PET scans with the aim of defining their frequency and anatomic distribution. METHODS: Fifty whole-body FDG-PET scans performed for the staging of malignant melanoma were obtained from transaxial scans and reconstructed without absorption correction by filtered backprojection in the form of coronal and sagittal sections. The patients were asked to stay n.p.o. for at least 4 hr and interrogated about their physical activity prior to injection and until scanning. Classification of FDG organ accumulations was done using grades 0-6. Means and standard deviations on this scale were then calculated for multiple organs and muscle groups and tabulated. RESULTS: On this grading scale, viscera showed uptake grades between 1.7 +/- 0.5 and 2.05 +/- 1.0. Except for the intestines, the activity in these organs was homogeneously distributed. Relatively high average uptake values of 2.0-4.2 (s.d. > or = 2.3) were found in various muscle groups, especially the orbital musculature. Myocardial uptake was visible in 90% of the scans. Reconstruction artifacts were seen around the renal collecting system and the bladder. CONCLUSION: Most of the "normal" accumulations of FDG in nonattenuation corrected whole-body PET are readily recognized and distinct from the usually focal FDG accumulation associated with metastatic disease, but the diagnostician must be familiar with them. Muscular FDG uptake is related to physical activity prior and immediately following injection and can be minimized by proper patient instructions and positioning.

Malignant melanoma: staging with whole-body positron emission tomography and 2-[F-18]-fluoro-2-deoxy-D-glucose.

PURPOSE: To evaluate whole-body positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in the detection of metastasis from melanoma. MATERIALS AND METHODS: Whole-body PET was performed in 33 patients with either known metastatic or newly diagnosed melanoma. Patients with suspected metastases also underwent computed tomography, magnetic resonance imaging, or both. Diagnoses were confirmed with histologic examination or with at least one imaging modality in addition to PET. Blinded interpretations of PET scans were performed. RESULTS: Forty of 53 lesions evaluated proved to be melanoma metastases. Whole-body PET correctly depicted 37 sites of metastases. Three cutaneous metastases (< 3 mm) were missed. PET correctly excluded malignancy in 10 cases where suspicious lesions were found with conventional cross-sectional imaging modalities but later ruled out with fine-needle biopsy. In six patients, PET depicted new metastases. The sensitivity for the detection of malignant lesions was 92%; the specificity for reading the PET images without clinical information was 77% and with clinical information was 100%. CONCLUSIONS: These results suggest that whole-body FDG PET is an effective imaging modality to screen for metastases from malignant melanoma.

Staging of metastatic melanoma by whole-body positron emission tomography using 2-fluorine-18-fluoro-2-deoxy-D-glucose.

Metastatic melanoma was staged in 15 patients using whole-body positron emission tomography (PET) and the radiopharmaceutical 2-fluorine-18-fluoro-2-deoxy-D-glucose (FDG). PET correctly demonstrated 30 metastases in lung, brain, pancreas, nasal cavity, skin and subcutaneous tissue, and lymph nodes. It detected 97% of all metastases exceeding its spatial resolution (> 5 mm). Two cutaneous metastases (approximately 3 mm) did not show increased FDG uptake; the overall detection sensitivity was 91%. Two false-positive lesions in one patient were due to severe wound infection. PET correctly excluded malignancy in four cases where suspicious lesions were found with conventional cross-sectional imaging modalities but later ruled out by fine-needle biopsy. PET therefore proved to be an excellent method for staging of metastatic melanoma. Due to its high sensitivity for malignant lesions and the possibility of covering the whole body in one examination, it can replace staging techniques employing multiple imaging modalities: chest X-ray, ultrasonography and computed tomography. Furthermore, it provides information on the malignant potential of the detected lesion.