Administration to humans of ORG 21465, a water soluble steroid i.v. anaesthetic agent

Ten male volunteers received a 1-min i.v. infusion of a new water soluble steroid anaesthetic agent, ORG 21465. Individuals received doses ranging from 0.8 to 1.8 mg kg-1. All subjects experienced venous pain at the site of injection; those receiving 1.0 mg kg-1 or more became anaesthetized. There was no evidence of histamine release and apnoea did not occur. Excitatory phenomena were observed in all subjects and were dose related; no spikes were seen on the EEG. Pharmacokinetic analysis supported a three-compartment (non-weight- related) model with compartmental volumes V1, V2 and V3 of 4.31, 14.2 and 89.4 litre, respectively. Clearance from the central compartment V1 was 1.55 litre min-1. Inter-compartmental clearances Q1 and Q2 were 2.54 and 1.79 litre min-1. We found that ORG 21465 was an effective anaesthetic in humans. The relationship between sedation, anaesthesia and excitation requires further exploration.      

RETROPERITONEAL SCHWANNOMA: A CASE SERIES AND REVIEW

Schwannomas account for only a small percentage of retroperitoneal tumours. Presentation is typically varied and non-specific and pre-operative diagnosis is difficult. Herein are described five cases of retroperitoneal schwannoma. Presentation was varied, ranging from abdominal pain, abdominal mass, obstructed labour or an incidental finding. All patients had either an abdominal computed tomography scan and/or ultrasound performed. Pre-operative biopsy either by fine needle aspiration (in one patient) or core biopsy in two patients was unhelpful. In four patients with smaller tumours, complete excision was possible with no apparent long-term morbidity and no clinical evidence of recurrent tumour with follow up from 3.5 months to 11 years. For the largest tumour, complete surgical excision was not attempted as it would have entailed significant morbidity.     

Circadian variation in the frequency of onset of chest pain in elderly patients with acute myocardial infarction.

This study reports the time of onset of chest pain in 792 consecutive elderly patients admitted to a coronary care unit with myocardial infarction during a 10-year period. Statistical analysis demonstrated a bimodal frequency distribution with peaks in the time of onset of chest pain between 23 h 30 and 00 h 30 and between 06 h 30 and 08 h 30.     

A review of the clinical applications of the pattern electroretinogram

The pattern electroretinogram (PERG) has recently been introduced as a clinical procedure. It has been thought by many to represent activity of the retinal ganglion cells, although this is still a matter of contention. The exciting prospect of a selective test of ganglion cell function led to the application of the PERG in a variety of ophthalmological conditions. In the course of these investigations the PERG was found to be diminished in cases of maculopathy, optic atrophy, optic neuritis, toxic optic neuropathy, neurotransmitter disorders, glaucoma and ocular hypertension and in retinal vascular disorders such as diabetes. It was also affected in some cases of amblyopia. This paper briefly describes the techniques used to record the PERG and reviews current literature pertaining to its clinical application.     

Organization of subcortical pathways for sensory projections to the limbic cortex. II. Afferent projections to the thalamic lateral dorsal nucleus in the rat

Afferent projections to the thalamic lateral dorsal nucleus were examined in the rat by the use of retrograde axonal transport techniques. Small iontophoretic injections of horseradish peroxidase were placed at various locations within the lateral dorsal nucleus, and the location and morphology of cells of origin of afferent projections were identified by retrograde labeling. For all cases examined, subcortical retrogradely labeled neurons were most prominent in the pretectal complex, the intermediate layers of the superior colliculus, and the ventral lateral geniculate nucleus. Labeled cells were also seen in the thalamic reticular nucleus and the zona incerta. Within the cerebral cortex, labeled cells were prominent in the retrosplenial areas (areas 29b, 29c, and 29d) and the presubiculum. Labeled cells were also seen in areas 17 and 18 of occipital cortex. Peroxidase injections in the dorsal lateral part of the lateral dorsal nucleus result in labeled neurons in all of the ipsilateral pretectal nuclei, but especially those that receive direct retinal afferents. Labeled cells were also seen in the ventral lateral geniculate nucleus and the rostral tip of laminae IV-VI of the superior colliculus. In contrast, peroxidase injections in ventral medial portions of the lateral dorsal nucleus result in fewer labeled pretectal cells, and these labeled cells are found exclusively in the pretectal nuclei that do not receive retinal afferents. Other labeled cells following injections in the rostral and medial portions of the lateral dorsal nucleus are seen contralaterally in the medial pretectal region and nucleus of the posterior commissure, and bilaterally in the rostral tips of laminae IV and V of the superior colliculus. Camera lucida drawings of HRP labeled cells reveal that projecting cells in each pretectal nucleus have a characteristic soma size and dendritic branching pattern. These results are discussed with regard to the type of sensory information that may reach the lateral dorsal nucleus and then be relayed on to the medial limbic cortex.     

Anterior and posterior marginal fracture-dislocations of the distal radius. An analysis of the results of treatment

Anterior and posterior marginal fractures of the distal end of the radius associated with dislocation of the carpus are rare injuries. The results of 20 patients with 12 anterior and eight posterior marginal fracture-dislocations of the distal radius were reviewed. Eleven patients had closed reduction and plaster cast immobilization, including three with external fixation, while nine patients required surgery and internal fixation. At a mean of 3.2 years, 40% were rated as excellent, 45% as good, 5% as fair, and 10% as poor. There was roentgenographic evidence of posttraumatic arthritis in 13 patients (65%). Major factors affecting the clinical results were accurate articular realignment and the presence of ipsilateral carpal injuries. There were no significant differences in results between anterior and posterior marginal fractures or between closed or operative methods of treatment when the radiocarpal articular surface was restored to less than 1 mm residual displacement. Restoration of articular congruency is the primary goal of management of these fractures.     

Characteristic modifications of the breathing pattern of mice to evaluate the effects of airborne chemicals on the respiratory tract

A system was developed for exposure of unanesthetized mice to airborne chemicals and for continuous measurement of their breathing pattern prior to, during and following exposure. By measuring inspiratory and expiratory airflows (VI and VE), and integration with time to yield tidal volume (VT), we obtained characteristic modifications to the normal breathing pattern. These permitted recognition that a specific portion of the respiratory tract was affected by the selected airborne chemicals. Following recognition, we also quantitated the degree of effect using one specific measurement in each case. An effect on the upper respiratory tract, induced by the sensory irritant, 2-chlorobenzylchloride, was quantitated by measuring a decrease in respiratory frequency. An effect on the conducting airways, induced by the airway constrictor, carbamylcholine, was quantitated by a decrease in VE at the mid-point of VT. An effect at the alveolar level, induced either by the vagal nerve ending stimulant, propranolol, or by the pulmonary irritant, machining fluid G, was quantitated by an increase in the length of a pause induced at the end of expiration. The system is easy to construct and operate and can be used to rapidly evaluate the effects of airborne chemicals on the respiratory tract.     

A method for repair of aortic dissection originating in the transverse arch using two sutureless intraluminal prostheses

We present a method for repair of ascending aortic dissections that originate in the transverse aortic arch. The technique utilizes two sutureless intraluminal prostheses, which are joined together and inserted during hypothermic circulatory arrest. A diamond-shaped opening between the two grafts is anastomosed about the orifices of the brachiocephalic arteries. This method affords the advantage of excluding the intimal tear, thereby preventing further propagation of the dissection. Additionally, the method offers the time-saving advantage of the sutureless prosthetic rings for the proximal and distal anastomoses.     

Immunogenic and Antigenic Epitopes of Immunoglobulins Binding of Human Monoclonal Anti-D Antibodies to FcRI on the Monocyte-Like U937 Cell Line

Seventeen human monoclonal IgG1- or IgG3 anti-D-secreting clones have been examined for their ability to sensitise O+ red cells for Fc-receptor-mediated rosette formation with U937 cells. IgG3 but not IgG1 anti-D antibodies were able to mediate stable rosette formation with unstimulated U937 cells via interaction with the FcRI receptor. Decreasing FcRI density by incubating U937 cells with di-butyryl cAMP almost completely abolished rosette formation, whilst increasing FcRI density by incubating U937 cells with interferon-gamma increased the percentage of cells forming rosettes with IgG3- and IgG1-sensitised red cells. These data suggest that rosette formation between IgG anti-D-sensitised red cells and FcRI-expressing cells is dependent upon the density of IgG3 on the red cell surface, the density of FcRI on the effector cell, multiple FcRI/IgG interactions are required for stable rosette formation and that more FcRI/IgG1 than FcRI/IgG3 interactions are required.