Immunomodulation of Delayed Hypersensitivity to Methylated Bovine Serum Albumin (MBSA) in Mice Using Subliminal and Normal Sensitization Procedures

Delayed hypersensitivity (DH) was induced in the footpads of mice sensitized to methylated bovine serum albumin (MBSA). The magnitude of this DH response increased with increasing sensitizing concentration of MBSA. Levamisole administered 1 hr prior to MBSA challenge stimulated the DH response and this was optimal using subliminal sensitizing concentrations of antigen. A number of antirheumatic agents, immunomodulators mediator antagonists and antiallergies were subsequently examined using the subliminal sensitizing concentration of MBSA. The same drugs were also evaluated using a normal sensitizing procedure. These studies indicate that the sensitizing concentration of antigen is critical in establishing whether a drug will stimulate or suppress a DH response.     

Cardiac arrhythmogenic action of benzo(a)pyrene in the rabbit

Rabbits treated with benzo(a)pyrene developed cardiac arrhythmias when exposed by inhalation to 8100 ppm trichloroethylene or 15000 ppm halothane to a greater extent and at lower doses of epinephrine challenge than did controls. Benzo(a)pyrene and 3-methylcholanthrene both increased the metabolism of trichloroethylene, but 3-methylcholanthrene did not increase its cardiotoxic effect. The basis of the arrythmogenic action of benzo(a)pyrene appears to be unrelated to its ability to induce xenobiotic metabolism.     

Electrophysiologic target localization in posteroventral pallidotomy

Summary The current interest in stereotactic posteroventral pallidotomy (PVP) for treating Parkinson's disease and the variability of published results have raised questions regarding techniques for target localization. In our technique the probe is guided to the optimum target at the most ventral pallidum and ansa lenticularis by macroelectrode stimulation of the internal capsule and optic tract from within the globus pallidus, with the thresholds providing a relative measure of the electrode proximity to these structures. We have characterized these localizing macroelectrode stimulation parameters in 57 posteroventral pallidotomies with consistent anatomic lesion placement, excellent outcome, and no complications.Using a 1.8 × 2.0 mm radiofrequency electrode for macroelectrode stimulation (RFG-3C, Radionics Inc.), minimum voltages (thresholds) to activate motor (at a frequency of 2 Hz) or visual (at a frequency of 100 Hz) responses as well as impedance measurements were obtained at the final target (Tf) and at distances proximal to Tf along the electrode trajectory. The visual and motor threshold voltages at Tf via our standard approach angles (50 ° above base plane, 20 ° from the sagittal plane), had a range of 1.0 to 1.5 V, and 2.0 to 3.5 V respectively. We also found that as the probe approaches Tf there is a significant decrease in voltage thresholds for motor (P<.0001) and visual (P<.0001) responses in an individual patient indicating that the probe is converging on these structures. Increases in impedance between Tf, 2–3 mm, and 4–5 mm proximal to Tf were also statistically significant (P<.0001). Microelectrode recording of electrophysiological neuronal activity at various points along the trajectory towards the target showed distinct firing patters providing identification of the globus pallidus externus and internus, ansa lenticularis, and optic tract.Macroelectrode electrophysiological stimulation within the target volume, inducing threshold responses in the internal capsule and optic tract, provides for accurate localization of the most effective PVP target in the ansa lenticularis. In unresponsive patients, the utilization of microelectrode recording for the identification of the pallidal borders and the optic tract improves safety.     

Asymptomatic HIV infection does not cause EEG abnormalities: results from the Multicenter AIDS Cohort Study (MACS)

We conducted EEG testing in 200 asymptomatic homosexual men, half of whom were HIV seropositive. We chose to include half of the subjects because they were rated as impaired on a neuropsychological screening test. We used both traditional visual EEG interpretation and quantitative EEG analysis. Abnormal EEGs and borderline degrees of EEG slowing occurred in 32% of these men. These EEG changes were not related to HIV serostatus. EEG changes did correlate with the impaired neuropsychological test performance. Clinicians faced with abnormal EEG results or borderline EEG slowing in an asymptomatic HIV-seropositive patient should not attribute the EEG change to effects of the serostatus itself but should look for other causes.     

Neurophysiological investigation of effects of the D-1 agonist SKF 38393 on tonic activity of substantia nigra dopamine neurons

The effects of the D-1 agonist SKF 38393 on tonic activity of rat substantia nigra pars compacta dopamine neurons were studied using extracellular, single-unit recording techniques. Unlike nonselective D-1/D-2 dopamine agonists or the D-2 agonist quinpirole, SKF 38393 did not inhibit dopamine neuronal activity when applied iontophoretically or when administered intravenously in doses up to 20 mg/kg to chloral hydrate-anesthetized rats. Moreover, pretreatment with SKF 38393 did not alter the inhibitory response of these neurons to apomorphine or the D-2 agonist quinpirole. However, in locally anesthetized, gallamine-treated, artificially respired rats, dopamine cell activity was significantly altered by i.v. administration of SKF 38393; firing rate increases and decreases were observed. Administration of the inactive enantiomer of SKF 38393, S-SKF 38393, did not induce similar changes in parallel experiments. These results support the idea that unlike D-2 autoreceptor stimulation, D-1 receptor stimulation does not exert a direct local effect on dopamine neurons in the substantia nigra pars compacta and suggest that D-1 receptor stimulation at sites postsynaptic to the dopamine cells may indirectly affect the activity of some dopamine neurons through long-loop feedback mechanisms.     

An electron microscopic study of local anesthetic-induced skeletal muscle fiber degeneration and regeneration in the monkey

An electron microscopic study was done on abductor pollicis brevis muscles of 18 Rhesus monkeys after intramuscular injections of 0.75% bupivacaine, 2% mepivacaine, or 2% lidocaine + epinephrine. The muscles were examined for from 2 h to 28 days. Severe muscle fiber damage, consisting of breakdown of sarcolemma and myofibrils, was seen as early as 2 h. Phagocyte mediated fragmentation of the degenerating muscle fibers was at its peak during the third and fourth days. Myoblasts were abundant during the fourth day. Early myotubes appeared on the fifth and sixth days, and they matured during the second week. Satellite cells appeared alongside mature myotubes. Overall, the local anesthetic-induced breakdown and regeneration of skeletal muscle fibers in the monkey followed a course quite similar to that seen in the rat.     

Reduction of Mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by Combined Treatment with Clofibrate and Nicotinic Acid

Consecutive survivors of a myocardial infarction from the Southern Hospital, below 70 years of age, were randomized into a Control group (n=276) and a Treatment group (n=279). The latter was openly prescribed the combination of clofibrate and nicotinic acid for serum lipid lowering. Each patient should remain in the study for 5 years and be seen regularly every 4 months at a special IHD outpatient clinic within the hospital. The concentration of serum cholesterol and triglyceride was lowered by 13% and 19%, respectively, in the Treatment group compared to the Control group. Total mortality was 82 cases in the Control group and 61 in the Treatment group, a 26% reduction (p<0.05). For patients above 60 years of age in the Treatment group the reduction in mortality was 28% (p<0.05). IHD mortality was reduced by 36% (p<0.01)in the Treatment group compared to the Control group. The beneficial effect of the serum lipid lowering treatment was related to the serum triglyceride concentration in two ways. First, it only occurred in patients with a triglyceride level >1.5 mmol/l (n=216). Secondly, it was most pronounced in the 44% of the treated patients who had a lowering of the serum triglyceride concentration by 30% or more, and in this subgroup the reduction of IHD mortality was 60% (p<0.01). For serum cholesterol there were no such relations. The difference between serum triglycerides and cholesterol concerning these relations to the treatment outcome may be due to the fact that hypertriglyceridaemia was the most common hyperlipidaemia among our patients, occurring in 50%, while hypercholesterolaemia only occurred in 13 %. Caution should be exercised in the interpretation of the results as the trial was not blind. However, the fact that the decrease in IHD deaths was directly related to the degree of serum triglyceride lowering indicates that it was the drug effect on serum lipids that was reponsible for the beneficial effect of the treatment.