Effects of ethanol on eye movements in the monkey

Ethanol (0.25-2.0 g/kg) was administered by remotely controlled intravenous infusion to monkeys engaged in performance of a short-term memory task which required attention to and retention of visual stimuli. Eye movements were monitored and measured by recording the electrooculogram with implanted periorbital Ag/AgCl electrodes. Ethanol induced the following dose-dependent changes of ocular motility: (a) diminution of the frequency of saccades; (b) prolongation of fixation (immobility) periods, though stimulus-elicited fixations became shorter; (c) increase in saccade excursion; (d) increase in saccade duration; and (e) decrease in saccade velocity (preceded at low doses by a transient increase). These changes were correlated with an impairment of behavioral performance. The results of eye movement analysis complement the results obtained on studies of human subjects by oral administration of ethanol. The findings of the present study in the nonhuman primate are interpreted as a reflection of the deleterious effects of alcohol on the cerebral substrate of visual attention.     

Persistence of herpes simplex virus DNA in rabbit corneal cells.

Corneal cell cultures were established from the corneas of rabbits killed during a period of latency 118 d after ocular infection with the RE strain of herpes simplex virus (HSV). DNA was isolated from frozen cell pellets of 42 cell cultures that did not develop viral cytopathic effects during 44 d in culture. Using the polymerase chain reaction (PCR) to amplify HSV thymidine kinase (TK) gene sequences, HSV-specific DNA was detected in 15 of 42 culture-negative cell cultures. Subsequent reamplification, using nested primers that were complementary to HSV TK sequences internal to the orginal primers, resulted in eight additional culture-negative samples showing positive hybridization for HSV TK DNA. Twenty three of the 42 virus culture-negative corneal cell cultures tested by PCR were found to contain HSV genetic material. Detailed examination of the clinical histories of the eyes from which the corneal cultures were obtained showed no correlation between increased frequency or severity of epithelial disease, stromal disease, or virus shedding and more frequent isolation of virus or detection of HSV-specific DNA. These studies document that HSV DNA residues in the corneas of HSV-infected rabbits up to 118 d post-infection. About 10% of the eyes contained virus that could be reactivated in culture, whereas an additional 55% of the eyes contained DNA sequences homologous to a portion of the HSV TK gene.     

The principal projection pathway between the olfactory bulb and the prepyriform cortex in the cat

The anatomy and neuroelectric properties of the lateral olfactory tract (LOT) were investigated in the cat. Electron micrographs were obtained from sampled areas across the rostro-caudal projection of the pathway. Fiber diameters were estimated and axon spectra were obtained from three regions corresponding to penduncle, mid-LOT, and caudal-LOT. The mean inside diameter for all measured axons was 1.13 ± 0.53 μm. The greatest number was found in the peduncle (approximately 600,000 axons). Mid-LOT and caudal-LOT each contained approximately 250,000 axons. Unmyelinated processes were estimated to be more numerous than the myelinated axons. Synaptic structures were also observed in the LOT. Crosssectional area measurements of the LOT were obtained from tissue repared for light microscopy. The area decreased from about 0.3 to 0.2 mm² across the projection from olfactory bulb to cortex. The anatomical data were used to predict the conduction properties of transmission over the LOT. The olfactory bulb mitral cells were stimulated electrically and conduction velocity and temporal dispersion were evaluated in the tract. The strength-duration and stimulus-response curves and the potential profile during stimulation were also obtained. The time constant for LOT axons was 0.3 msec. The stimulus-response curve was sigmoidal in shape for both presynaptic and postsynaptic responses. The relationship between input (the action potentials) and output (cortical postsynaptic potentials) was linear up to 90 times threshold. Action potentials were conducted at 20 m/sec across the pathway over the peduncle and decreased to about 10 m/sec in caudal aspects. The potential profile for action potentials decayed exponentially into the depths of the cortex whereas the synaptic potential was a surface negative dipole field. The axon spectra were convolved with the electrophysiological properties of the LOT Yto mathematically reconstruct action potentials. The empirically derived monoand biphasic curves fitted reasonably well with experimentally derived data under various stimulus conditions.     

Dosimeters of human exposure to carcinogens: polycyclic aromatic hydrocarbon-macromolecular adducts

The metabolic activation of polycyclic aromatic hydrocarbons (PAH), for example benzo[a]pyrene, leads to the formation of carcinogen-macromolecular adducts. Methods that make it possible to detect low levels of these adducts in human peripheral blood samples should be useful in the dosimetry of human exposure to carcinogens. We demonstrated previously the usefulness of enzyme immunoassays and of synchronous fluorescence spectroscopy (SFS) for detecting and characterizing low levels of PAH-macromolecular adducts present in synthetic adduct mixtures. These methods have now been refined and applied to the analysis of samples of peripheral blood collected from occupationally exposed individuals (coke-oven workers) and from people attending smoking cessation clinics. The results of both immunoassays and SFS show the presence of benzo[a]pyrene diol epoxide (BPDE)-DNA, BPDE-haemoglobin and other putative PAH-macromolecular adducts in peripheral blood samples from certain individuals.     

Benefit design and specialty drug use

In this paper we examine spending by privately insured patients with four conditions often treated with specialty drugs: cancer, kidney disease, rheumatoid arthritis, and multiple sclerosis. Despite having employer-sponsored health insurance, these patients face substantial risk for high out-of-pocket spending. In contrast to traditional pharmaceuticals, we find that specialty drug use is largely insensitive to cost sharing, with price elasticities ranging from 0.01 to 0.21. Given the expense of many specialty drugs, care management should focus on making sure that patients who will most benefit receive them. Once such patients are identified, it makes little economic sense to limit coverage.