Malignant peripheral nerve sheath tumour of the cervical vagus nerve in a neurofibromatosis type 1 patient.

One serious complication of neurofibromatosis type 1 (NF1) is the development of malignant peripheral nerve sheath tumours (MPNSTs). These malignancies often develop within pre-existing plexiform neurofibromas and their development is now thought to be associated with both tumour suppressor gene mutations and dysregulated growth factor signalling. Recent work demonstrates that the lifetime risk of malignant transformation is significantly greater than previously thought. Ionising radiation, a long-standing disease, particularly the presence of a large number of plexiform neurofibromas from an early age, are suggested risk factors. We present an NF1 patient who developed an MPNST of the cervical vagus nerve which was successfully treated with surgery. Close monitoring of patients with NF and a high level of suspicion towards rapidly enlarging and painful swellings is merited as these features may signify malignant transformation. Whether a positive history of MPNST in other affected family members predisposes the individual to a higher risk of malignant transformation is unclear.     

Negative chronotropic but no antiarrhythmic effect of (+)- and (-)-naloxone in rats and guinea pigs

STUDY OBJECTIVE--The aim was to investigate the antiarrhythmic effects of (+)- and (-)-naloxone in various arrhythmia models in vivo. DESIGN--Naloxone (1-40 mg.kg-1), naltrexone (20-40 mg.kg-1), or standard antiarrhythmic drugs (quinidine, lignocaine, phenytoin, (+)-sotalol) were injected intravenously. Ventricular extrasystoles were then elicited by infusion of either ouabain (guinea pigs) or aconitine (rats), or by electrical stimulation (guinea pigs). EXPERIMENTAL MATERIAL--Male Wistar rats and guinea pigs (n = 6-10) were used. Arterial blood pressure and ECG were recorded continuously. MEASUREMENTS AND MAIN RESULTS--Naloxone and naltrexone decreased the heart rate. The effect of naloxone was not stereospecific and is apparently not mediated by opioid receptors. Naloxone had no influence on ouabain induced arrhythmias or fibrillation threshold in guinea pigs. The appearance of aconitine induced extrasystoles was accelerated by 20 mg.kg-1 (-)-naloxone but delayed by 40 mg.kg-1. No effects were seen with (+)-naloxone or (-)-naltrexone. CONCLUSIONS--The results show that naloxone does not possess prominent antiarrhythmic properties.     

AUR Memorial Award 1991. Immunogenicity of gadolinium-based contrast agents for magnetic resonance imaging. Induction and characterization of antibodies in animals.

To evaluate the immunogenic potential of gadolinium-based magnetic resonance imaging (MRI) contrast agents, Sprague-Dawley rats were sensitized with gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) dimeglumine and with Gd-DTPA covalently linked to either human serum albumin, dextran, or polylysine. IgG antibodies directed against Gd-DTPA were detected in immune sera by an enzyme-linked immunosorbent assay (ELISA), and were confirmed by competitive inhibition of antibody binding using free Gd-DTPA dimeglumine. Antiserum induced by immunization with human serum albumin-(Gd-DTPA) was characterized by a monophasic competition curve with 50% inhibition (IC50) = 5.5 x 10(-4) M when Gd-DTPA dimeglumine was used as both the well-coating and the displacing agent in a competition ELISA. Antiserum induced by Gd-DTPA dimeglumine alone was characterized by a biphasic competition curve with IC50 = 6.5 x 10(-7) M and 7.9 x 10(-4) M. Antisera obtained after exposure to either dextran-(Gd-DTPA) or polylysine-(Gd-DTPA) were of insufficient titer for characterization. The detection of antibodies specific for Gd-DTPA suggests in vivo protein binding with formation of hapten-carrier conjugates. This hypothesis is supported by increased relaxivity values observed when Gd-DTPA dimeglumine is incubated in serum rather than in water. Gd-DTPA dimeglumine and albumin-(Gd-DTPA) are immunogenic in rats under idealized experimental conditions. Additional studies will be necessary to determine the potential for immunologic response in humans to gadolinium chelates under conditions of exposure inherent in clinical use.