Superparamagnetic iron oxide: clinical application as a contrast agent for MR imaging of the liver

Superparamagnetic iron oxide (ferrite) particles were evaluated as a contrast agent for magnetic resonance (MR) imaging. In this pilot study, doses ranging from 10 to 50 mumol/kg were administered intravenously to 15 patients. Ferrite-enhanced images of the liver obtained with standard pulse sequence techniques significantly increased the number of hepatic lesions detected (P less than .01) and reduced the threshold size for detection to 3 mm (P less than .01). The improved clinical performance of ferrite-enhanced images correlated with significant increases in measured contrast-to-noise ratios (P less than .01). Degradation of superparamagnetic activity and/or clearance of ferrite from the liver was demonstrated as early as 12 hours after injection, suggesting that the lack of chronic toxicity observed in animal studies may be reproduced in humans. These initial clinical results appear to confirm extensive preclinical data indicating that ferrite administered at a dose of 20 mumol/kg has the potential to significantly improve the performance of abdominal MR imaging.     

Posturally induced vasoconstriction in diabetes mellitus

In healthy subjects, standing elicits a reduction in blood flow to the skin of the foot. In adults with insulin dependent diabetes this posturally induced response is deficient, resulting in capillary hypertension when the foot is in the dependent position (that is, below heart level). Such functional abnormalities of the microcirculation in diabetes may precede any evidence of clinically detectable microangiopathy. This study investigates the posturally induced change in blood flow to the skin of the foot in prepubertal and postpubertal patients with insulin dependent diabetes. Laser Doppler fluximetry was used to assess the postural change in blood flow at the pulp of the great toe. Postural vasoconstriction (dependent flux value/supine flux value x 100) was greater after puberty in normal subjects (median (range) 60.4 (7.0-164.9)% prepubertal v 20.5 (5.9-101.0)% postpubertal). Prepubertal children with diabetes did not differ from their healthy peers (69.8 (7.2-192.7)% with diabetes v 60.4 (7.0-164.9)% controls); however postpubertal children with diabetes had a significantly impaired postural vasoconstriction (40.6 (7.9-140.2)% with diabetes v 20.5 (5.9-101.7)% controls). Abnormalities in the normal reduction of blood flow on standing occurred in young postpubertal children with diabetes, most of whom were free of complications.     

A lower-lobe-seeking pulmonary artery catheter

The Grollman pulmonary artery catheter was modified by turning the pigtail downward to facilitate lower lobar catheterization with the femoral approach. The advantage of this tip configuration was obvious in the 30 cases in which it was attempted. The superiority of this catheter in traversing the tricuspid valve and in entering the right or left pulmonary artery with equal ease was also noted.     

Hepatic micrometastases in the rat: ferrite-enhanced MR imaging

A rat tumor model was used to evaluate the ability of ferrite-enhanced magnetic resonance (MR) imaging to demonstrate hepatic metastases smaller than 1 cm. Twenty-eight rat livers were inoculated with 5 X 10(5) mammary carcinoma cells and imaged with a 0.6-T MR system. Non-enhanced and ferrite-enhanced images were analyzed and correlated with autopsy findings for each rat. Lesion detection rates correlated closely with cancer-to-liver contrast-to-noise ratios. Ferrite-enhanced MR imaging demonstrated significantly more lesions than non-enhanced imaging (P less than .05) and decreased the threshold size for lesion detectability (less than 2 mm). Ferrite also enabled more accurate measurements of the lesions (r = .96).     

Effect of platelet-activating factor (PAF) on human platelets

The effect of pure synthetic PAF (1-0-alkyl-2-acetyl-sn-glycero-3- phosphorylcholine) was studied in human platelets. PAF (0.2--2.0 micrograms/ml) produced a dose-dependent aggregation in human platelet- rich plasma (PRP) or platelet suspension obtained by gel-filtration (GFP). In addition, PAF (0.8 microgram/ml) induced secretion of 14C- serotonin (45% +/- 10%; mean +/- SD, n = 9) and platelet factor 4 (PF4) (12.89 +/- 3.81 micrograms/10(9) platelets; n = 9) in PRP. Similar results were obtained in GFP. Aggregation and release of 14C-serotonin and PF4 were inhibited by the metabolic inhibitors 2-deoxyglucose (16.7 mM) and antimycin-A (8.3 micrograms/ml), by the membrane-active drugs mepacrine (10 microM) and chlorpromazine (0.025 mM), by PGI2 (5.34 nM), which elevates intracellular c-AMP, by indomethacin (10 microM) or aspirin (100 microM). The ADP scavengers, creatine phosphate and creatine phosphokinase (CP/CPK), inhibited the second wave of aggregation but not secretion. These data suggest that the major effect of PAF on human platelets is mediated through the cyclo-oxygenase pathway and not through a third pathway.