Granulocyte transfusion: Stimulation of low dose granulocyte colony-stimulating factor in donors for leukapheresis

In order to assess the clinical utility of granulocyte transfusions (GT), the stimulating effects of donor granulopoiesis for GT therapy were examined using either low dose recombinant human granulocyte colony-stimulating factor (rhG-CSF) or dexamethasone (DEX). The increment of leukocytes, polymorphonuclear cells (PMN) and monocytes in the subjects stimulated with rhG-CSF (0.7 μg/kg SC) surpassed each increment in those with DEX alone (1 mg PO). The lymphocyte counts after DEX stimulation decreased in contrast to those after G-CSF stimulation. This dose of G-CSF did not enhance the priming effects on the superoxide release from PMN. The serum levels of lysozyme, but not of lactate dehydrogenase, in G-CSF stimulated donors were higher than those in DEX-treated donors. The serum macrophage/monocyte-colony stimulating factor (M-CSF) levels in DEX stimulation were lower than in either G-CSF stimulation or no stimulation. The net yield of the PMN in GT on G-CSF stimulation was practically larger than that on DEX stimulation. One of the two patients who received GT collected by DEX stimulation died of aspergillosis. Two of the five patients who received PMN mobilized by G-CSF died of fungal infections or necrotizing fasciitis, although two of the remaining patients overcame severe bacterial infections. These results suggest that low dose G-CSF effectively and safely mobilizes a sufficient quantity of PMN from GT-donors without excessive superoxide generation from the transfused cells. This low dose G-CSF stimulation may be substituted for conventional DEX stimulation for GT.     

Alloimmune Neonatal Neutropenia in Monozygous Twins: High-dose Intravenous Gammaglobulin Therapy

ABSTRACT. An indirect immunofluorescence test using a flow cytometer (FACS420) was useful for detection of antineutrophil antibodies (anti-NA2 antibodies) in a case of monozygous twins with alloimmune neonatal neutropenia. When high-dose intravenous gammaglobulin (300 mg/kg for five consecutive days) was given to one twin, the increase in neutrophils was not obvious. Although neutropenia persisted for about three months, no infections were observed in either of the twins.     

Unidirectional Atrio-Atrial Conduction after Surgical Isolation of the Posterior Part of the Left Atrium and Pulmonary Veins for Atrial Fibrillation:

A 66-year-old woman underwent mitral valve replacement and surgical isolation of the posterior part of the left atrium for persistent AF. During sinus rhythm an isolated atrial rhythm was recorded from the isolated posterior left atrium using an esophageal electrode catheter. After the intravenous administration of adenosine triphosphate sinus rhythm was suppressed and 1:1 conduction from the posterior left atrium to the rest of the atrium was recorded. Unidirectional atrio-atrial conduction was revealed by a simple electrophysiological evaluation.(PACE 2004; 27[Pt. I]:812–814)     

Influence of Mobile Magnetic Resonance Imaging on Implanted Pacemakers

KISHI, R., et al.: Influence of Mobile Magnetic Resonance Imaging on Implanted Pacemakers. Purpose: Mobile magnetic resonance imaging (MRI) systems will be widely used in Japan. When traveling, mobile MRI generate alternating electromagnetic waves which may cause electromagnetic interference (EMI). This study was designed to determine whether this may influence the function of implanted pacemakers (PM). Methods and Results: The influence of the static magnetic fields was tested in the first method using a PM-human model (Phantom). Magnetic force was simultaneously measured. The PM was switched to the magnet mode within 90 cm from the vehicle, where the magnetic force was = 2 mT. In the second method, six phantoms were placed on the side of the road, facing in three different directions in X-Y-Z axis orientations, at 1.3 m and 2.0 m above the ground. The mobile MRI passed by at a distance of 1 m from the phantoms at the speed of 20 or 40 km/h. In these experiments, magnet mode switch of the PM was observed for 2 seconds when the vehicle passed close to the phantoms, though no electrical noise was recorded. Conclusion: Mobile MRI vehicles can switch a PM to magnet mode when the distance between patient and vehicle is <90 cm, regardless of whether the vehicle is moving or at a stop. Patients with implanted PM should not approach within <1 m of a mobile MRI. No other EMI-induced PM dysfunction was detected. (PACE 2003; 26[Pt. II]:527–529)     

Simultaneous Mapping in the Left Sinus of Valsalva and Coronary Venous System Predicts Successful Catheter Ablation from the Left Sinus of Valsalva

Idiopathic ventricular tachycardia originating from the left epicardium (Epi-VT) can be ablated from the left sinus of Valsalva (LSV) in selected patients. We hypothesized that the analysis of electrograms at the LSV and transitional zone from the great cardiac vein to the anterior interventricular vein (GCV-AIV) could predict the efficacy of radiofrequency catheter ablation (RFCA) from the LSV. Simultaneous mapping in the LSV and coronary venous system was performed in 25 patients (12 VTs and 13 premature ventricular contractions). The earliest ventricular activation (VA) during the arrhythmias was found at the LSV or GCV-AIV in all patients. RF applications from the LSV were successful in 17 patients success group (S-Gr) and failed in 8 failure group (F-Gr). The earliness of the VA recorded in the LSV (VA[LSV]) and in GCV-AIV (VA[GCV-AIV]) was compared between the two groups. (1) The VA[LSV] preceded the QRS onset by 28 ± 11 ms in S-Gr and 14 ± 10 ms in F-Gr (P < 0.01). (2) In S-Gr, the VA[GCV-AIV] was earlier than the VA[LSV] in 5 five patients (35%). However, in F-Gr, the VA[GCV-AIV] was earlier than the VA[LSV] in all patients. (3) In patients in whom the earliest VA was found at the LSV or GCV-AIV, a VA [GCV-AIV] preceding the VA[LSV] by less than 10 ms identified successful RFCA from the LSV with a sensitivity of 88 %, specificity of 100%, and high predictive value. With a detailed analysis of the electrograms recorded from the GCV-AIV and LSV, it was possible to identify the successful catheter ablation of Epi-VT from the LSV.     

Geranylgeranylacetone, an anti-ulcer drug, stimulates hexosamine production in a rat gastric mucosal cell line through binding to a specific cytosolic protein

An anti-ulcer drug, geranylgeranylacetone (GGA), stimulates hexosamine production in a rat gastric mucosal cell line (RGM-1). The aim of this study was to elucidate the mechanism of this action. The role of protein kinase A, inositol phospholipid turnover and tyrosine kinase in the stimulatory action of GGA on hexosamine production in RGM-1 was determined by observing cAMP production, [³H]-inositol phosphate turnover and western blotting of tyrosine phosphorylation, respectively. Any trophic effect of GGA on RGM-1 was also checked by [³H]-thymidine incorporation. Our experiments showed that GGA has no effect on cAMP production, inositol phospholipid turnover, tyrosine phosphorylation or DNA synthesis in RGM-1. Finally, a [¹⁴C]-GGA competitive receptor binding assay was performed on RGM-1 and we found that [¹⁴C]-GGA specifically bound to RGM-1 cytosolic protein. Although retinoic acid (RA), another polyisoprenoid compound significantly stimulated hexosamine production in RGM-1, we confirmed that the [¹⁴C]-GGA binding site in RGM-1 is different from the RA binding site. In summary, GGA stimulates hexosamine production in RGM-1 and this action is probably mediated through its binding to a specific cytosolic protein in RGM-1.     

Hepatocyte apoptosis and hepatic expression of transforming growth factor-β1 mRNA during involution of hyperplastic rat liver induced by hepatocyte growth factor

Hepatocyte apoptosis occurs during involution of hyperplastic liver induced by administration of xenobiotic compounds in rats. With this hyperplasia and involution, hepatic transforming growth factor (TGF)-β₁ is reported to be expressed to stimulate hepatocyte apoptosis. In regenerating liver after partial resection showing no hyperplasia, such expression of TGF-β₁ is also seen. However, no hepatocyte apoptosis develops despite the high levels of TGF-β₁. When rats received an intravenous injection of human hepatocyte growth factor at 12 h intervals for 14 days, the hepatic DNA content was increased 12 h after the last injection to 140% of control. This DNA content was significantly decreased at 108 and 180 h after discontinuation of treatment. At 60 h after the last injection, the number of apoptotic bodies positive for nick end-labelling of DNA in hepatocytes was significantly greater in treated rats than in control rats. Hepatocyte apoptosis was also identified electron micrographically. Hepatic TGF-β₁ mRNA levels in treated rats were significantly lower than in control rats at 12 h and then gradually increased towards control levels. We conclude that hyperplastic liver induced in normal rats by hepatocyte growth factor regresses with hepatocyte apoptosis and suppressed hepatic TGF-β₁ mRNA levels.