Brevetoxins bind to multiple classes of sites in rat brain synaptosomes.

The brevetoxins (PbTx series), neurotoxins produced by the marine dinoflagellate Ptychodiscus brevis, cause dose-dependent activation of the voltage-sensitive sodium channel (VSSC). Saturation binding studies employing adult rat brain synaptosomes suggest the existence of a high affinity/low capacity (HA/LC) and a second, lower affinity/higher capacity (LA/HC) class of binding site. LIGAND analysis of saxitoxin and brevetoxin saturation binding data yields a statistically identical Bmax for the brevetoxin high affinity/low capacity (HA/LC) site (1.9 +/- 0.98 pmol/mg protein) and for saxitoxin (1.72 +/- 0.78 pmol/mg protein; P less than 0.001). The stoichiometry of HA/LC brevetoxin binding and saxitoxin binding approaches 1:1. Covalent modification of synaptosomes with a brevetoxin photoaffinity probe preferentially blocks the HA/LC binding site. Hill plots of saturation binding data yield a coefficient of 1.0 +/- 0.02, demonstrating a lack of cooperativity between brevetoxin binding site classes. Kd and Bmax for toxin binding are independent of membrane polarity, intimating that the observed low affinity/high capacity (LA/HC) binding characteristics are not due to modification of the HA/LC site, and strongly argue for the presence of multiple brevetoxin binding site classes. Half-maximal binding at the LA/HC site, and strongly argue for the presence of multiple brevetoxin binding site classes. Half-maximal binding at the LA/HC site occurs at concentration ranges for which the brevetoxins allosterically modulate binding of other natural toxins to their specific sites.     

Electrocardiographic findings in children with Lyme disease.

The incidence of cardiac involvement in Lyme disease (LD) has been estimated to be 4 to 10% in adults, with conduction and rhythm disturbances noted most frequently. To assess the frequency of electrocardiographic abnormalities in children with LD, we prospectively performed 12-lead electrocardiograms in 32 randomly selected children presenting with LD between May and September 1989. No patient had symptoms of cardiac involvement. Using defined diagnostic criteria, combining symptoms, signs, serology, and residence in or travel to an endemic area, 14 patients were classified as having definite LD and 10 were categorized as probable. The incidence of electrocardiographic abnormalities in the definite group was 29% (4/14), including two patients with 1 degree atrioventricular block, one with left axis deviation, and one with ventricular ectopy. Thirty percent (3/10) of the probable group had abnormal ECGs, including one with ST-T wave abnormalities, one with prominent sinus arrhythmia, sinus bradycardia, and wandering atrial pacemaker, and one with ectopic atrial bradycardia. No patient required cardiac therapy. The incidence of abnormal ECG findings in this group of children with either probable or definite LD was thus 29%, with 1 degree atrioventricular block noted most frequently. When the diagnosis of LD is highly suspected, an electrocardiogram may be a useful screening test for cardiac involvement.     

Oxygen consumption following trauma: a reappraisal in severely injured patients requiring mechanical ventilation

Oxygen consumption (VO2) immediately following major injury in man has been said to be reduced. The evidence for this is poor. We have therefore measured VO2 soon after major injury in 16 patients. VO2 was reduced in only two patients, within the normal range in four and increased in ten. VO2 was maintained by increased oxygen extraction in six patients leading to low levels of mixed venous oxygen saturation. There is no evidence for an 'ebb phase' response in man.     

Postoperative radial nerve paralysis caused by fracture callus.

This is a case of late-onset (6 weeks) radial nerve paralysis following open reduction and internal fixation of a comminuted distal humerus fracture. A transected radial nerve within the callus was found at reoperation. The mechanism of transection was thought to be repetitive motion of the nerve across an edge of new bone. The nerve was repaired and tendon transfers done subsequently with less than full functional recovery at 16 months. No such case has been previously reported.     

CLINICAL ASSESSMENT OF AN ENZYME IMMUNOASSAY (EMIT) FOR MEASUREMENT OF SERUM SALICYLATE

Salicylic acid concentrations in serum were compared using a homogenous enzyme immunoassay (EMIT) and an automated colorimetric analysis (ACA) technique. Analysis of samples showed similar within-day and day-to-day coefficients of variation (CV): 1.3% and 4.6% by EMIT and 1.0% and 2.6% by ACA, respectively. Quantification of serum containing added salicylate and serum from patients receiving salicylate therapy showed a slight positive bias towards the ACA method over the range of 0-600 mg/l. No significant difference in reliability was found between the two methods. The EMIT assay showed no interference from other antiflammatory drugs being taken by patients who were not taking salicylates. If decisions to alter salicylate dosage are made with due regard to the drug's saturation kinetics, measurements using either EMIT or ACA should allow the clinician to titrate patients' serum concentrations accurately within the narrow therapeutic range.     

Prognostic implications of the proliferative potential of low-grade astrocytomas

The proliferative potential of low-grade astrocytomas was estimated in 47 patients. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, at the time of craniotomy to label cells in deoxyribonucleic acid (DNA) synthesis; the percentage of S-phase cells, or BUdR labeling index (LI), of each tumor was determined immunohistochemically. In 29 patients (60%), the tumors had BUdR LI's of less than 1%, indicating a slow growth rate; only three (10%) of these patients died of recurrent tumor during a follow-up period of up to 3 1/2 years. In contrast, of the 18 patients (40%) whose tumors had BUdR LI's of 1% or more, 12 (67%) had a recurrence and nine died during the same follow-up period. These results show that the proliferative potential, as reflected by the BUdR LI, is an important prognostic factor that separates low-grade astrocytomas into two groups and provides a more scientific rationale for selecting treatment for individual patients.