Cardiopulmonary exercise testing: arm crank vs cycle ergometry.

This pilot study compared oxygen consumption during arm crank and cycle ergometer tests in 15 women. The mean (SD) peak oxygen consumption was less with arm cranking (25 (5) ml.kg(-1) .min(-1)) than with cycling (40 (7) ml.kg(-1) .min(-1)), p < 0.0001. The mean (SD) anaerobic threshold was less with arm cranking (13 (2) ml.kg(-1) .min(-1)) than with cycling (20 (4) ml.kg(-1) .min(-1)), p < 0.0001. There was moderate correlation, r(2) = 0.60, between the anaerobic thresholds determined by arm and leg exercise, p = 0.0007. This study suggests that arm crank cardiopulmonary exercise testing could be used for pre-operative assessment in those unable to cycle.

Comparison of the toxicity profiles of ISIS 1082 and ISIS 2105, phosphorothioate oligonucleotides, following subacute intradermal administration in Sprague-Dawley rats.

The systemic toxicity of two phosphorothioate oligonucleotides specific for herpes simplex viruses (ISIS 1082) and human papiloma virus (ISIS 2105) were evaluated following repeated intradermal injections of vehicle control, 0.33, 2.17, or 21.7 mg/kg daily to Sprague-Dawley rats (10/sex/group) for 14 days. Animals were sacrificed 1 day after the last dose, except for a portion of the ISIS 1082-treated animals (5/sex/group) which were maintained for an additional 14-day recovery period. The profile of alterations noted for both compounds was very similar. Other than local signs of irritation at the site of injection, there were no clinical signs of toxicity or treatment-related mortality, but there was a slight decrease in body weight gain for the 21.7 mg/kg dose groups. Alterations in hematology parameters included dose-dependent thrombocytopenia and anemia. Alterations in serum chemistry parameters were suggestive of mild alterations in hepatic metabolism, with increases in liver transaminases and bilirubin, along with decreases in albumin and cholesterol. Both spleen and liver weights were significantly elevated in a dose-dependent fashion. Histopathological alterations noted in liver, kidney, lung, injection site skin, and spleen were characterized as perivascular and interstitial infiltrates of macrophages and monocytes. Additional microscopic alterations in the spleen included mild lymphoid hyperplasia (seen in lymph nodes as well), and extramedullary hematopoiesis. Treatment-related cytopenias were likely related to mild, focal hypocellularity in the bone marrow. Alterations in ISIS 1082-treated animals were only partially reversed following the 14-day treatment-free period. In conclusion, repeated intradermal administration of ISIS 1082 and ISIS 2105 produced a similar spectrum of toxicities, with liver, kidney, spleen, and bone marrow being identified as target tissues.

Chronically indwelling venous cannula and automatic blood sampling system for use with nonhuman primates exposed to 60 Hz electric and magnetic fields.

An automated blood sampling system was developed for use with tethered baboons (Papio cynocephalus) during concurrent exposure to 60 Hz 30 kV/m electric fields and 0.1 mT (1.0 G) magnetic fields. The system was controlled by a FORTH-based microcomputer, which operated a pump, a fraction collector, and two pinch valves. A swivel mechanism at the end of the tether allowed the baboons to move freely in their cages. The hardware and software were designed for fail-safe operation. Heparinized saline was infused at a rate of 0.5 mL/min until a sample cycle was initiated. Then, blood was drawn from the animal into a storage tube at a rate of 12.5 mL/min, a sample of undiluted blood was taken from the end of the storage tube near the baboon, and the blood remaining in the storage tube was then flushed back into the animal. Use of the storage tube prevented the peristaltic pump rollers from pressing on tubing containing blood, and return of the blood diluted with saline limited the blood wasted per sample to less than 0.5 mL. The system functioned reliably in three experiments, collecting samples as scheduled 97% of the time. Although it was initially designed for and used successfully with primates in an electric and magnetic field environment, this type of system could be employed in many areas of biomedical research or medical treatment.

Regularly scheduled, day-time, slow-onset 60 Hz electric and magnetic field exposure does not depress serum melatonin concentration in nonhuman primates.

Experiments conducted with laboratory rodents indicate that exposure to 60 Hz electric fields or magnetic fields can suppress nocturnal melatonin concentrations in pineal gland and blood. In three experiments employing three field-exposed and three sham-exposed nonhuman primates, each implanted with an indwelling venous cannula to allow repeated blood sampling, we studied the effects of either 6 kv/m and 50 microT (0.05 G) or 30 kV/m and 100 microT (1.0 G) on serum melatonin patterns. The fields were ramped on and off slowly, so that no transients occurred. Extensive quality control for the melatonin assay, computerized control and monitoring of field intensities, and consistent exposure protocols were used. No changes in nocturnal serum melatonin concentration resulted from 6 weeks of day-time exposure with slow field onset/offset and a highly regular exposure protocol. These results indicate that, under the conditions tested, day-time exposure to 60 Hz electric and magnetic fields in combination does not result in melatonin suppression in primates.

A 60 Hz electric and magnetic field exposure facility for nonhuman primates: design and operational data during experiments.

A unique exposure facility was designed and constructed to generate large-scale vertical electric fields (EF) of up to 65 kV/m and horizontal magnetic fields (MF) of up to 100 microT (1G), so that the behavioral and neuroendocrine effects of 60 Hz EF or combined electric and magnetic field (E/MF) exposure could be examined using nonhuman primates as subjects. Facility design and operational problems and their solutions are presented, and representative operational data from four sets of experiments are provided. A specially designed, optically isolated, 4 cm spherical-dipole EF probe and a commercially available MF probe were used to map the EF and MF within the fiberglass animal cages. In addition, amplifiers, signal conditioners, and A/D converters provided EF, MF, and transformer signals to a microcomputer at 15 min intervals. The apparatus produced homogeneous, stable E/MF at the desired intensities, and the fiberglass cages did not produce appreciable distortion or attenuation. Levels of recognized EF artifacts such as corona and ozone were negligible. The facility worked as intended, providing a well-characterized and artifact-controlled environment for experiments with baboons (Papio cynocephalus).

Detection thresholds for 60 Hz electric fields by nonhuman primates.

Because responses of animals to detection of the presence of an electric field (EF) are a possible mechanism for production of biological effects, it is important to know what EF intensities are detectable. Operant methods were used to train six baboons (Papio cynocephalus) to perform a psychophysical task involving detection of EF presence. During the response phase of a trial, a subject responded on one push button to report the presence of the EF and on a different push button to report the absence of the EF. Correct reports of EF presence of absence produced delivery of food rewards. The subjects became proficient at performing this psychophysical detection task; during 35 days of testing, false alarm rates averaged 9%. The average EF detection threshold was 12 kV/m; the range of means among subjects was 5-15 kV/m. Two special test procedures confirmed that the subjects were responding directly to EF presence of absence and not to artifacts that might be associated with EF generation. The EF detection threshold of nonhuman primates is similar to thresholds reported for rats and humans.

Initial exposure to 30 kV/m or 60 kV/m 60 Hz electric fields produces temporary cessation of operant behavior of nonhuman primates.

In two separate experiments, we examined the effects of a 60 Hz electric field (EF) on performance of an operant schedule consisting of two signaled components: fixed-ratio (FR30) and differential reinforcement of low-rate (DRL20). In each experiment, 12 naive baboons (Papio cynocephalus) were assigned randomly to either an EF-exposed experimental group or a sham-exposed control group. A homogeneous vertical EF of 30 kV/m was used in one experiment; 60 kV/m was used in the other. The experimental design for both experiments included 6 week preexposure, exposure, and postexposure periods. The planned analyses indicated no evidence of statistically significant (P < .05) effects of EF exposure. However, exploratory analyses comparing performance during the last week of preexposure and the first week of exposure revealed statistically significant acute effects (work stoppage): The mean response rates of the EF-exposed groups were greatly reduced on day 1 of exposure but were normal by the end of day 2 of EF exposure. We hypothesize that introduction of a highly unusual stimulus, the EF, temporarily interfered with normal operant behavior to produce a primary work stoppage. Supplementary cross-over experiments added at the end of each main experiment indicated that work stoppage occurred again when formerly EF-exposed subjects served as sham-exposed controls, while other subjects received their first EF exposure. Presumably, reoccurrence of other stimuli correlated with initial exposure to the EF became sufficient to subsequently cause secondary work stoppage in the absence of direct EF exposure. The primary and secondary work-stoppage effects were reproducible.

Nonhuman primates will not respond to turn off strong 60 Hz electric fields.

Using a set of six baboons (Papio cynocephalus), we conducted a series of seven experiments designed to evaluate the potentially aversive character of a 60 Hz electric field (EF). Initially, the subjects were trained, using food rewards as the reinforcer, to respond only when a cue light was illuminated. Next, an EF was presented along with the cue light; responses produced delivery of a food pellet and turned off both the cue light and the EF. Then, stimulus and reward conditions were varied. We determined that 1) presence of a strong EF does not affect operant responding for food rewards, 2) subjects will not respond at normal rates when the only reinforcer is termination of a strong EF, 3) presence of a strong EF can serve as a discriminative stimulus, 4) presence of a strong EF does not affect extinction of an appetite-motivated task, and 5) presentation of an EF can become a secondary reinforcer. The pattern of results was consistent across all experiments, suggesting that an EF of as much 65 kV/m is not aversive to nonhuman primates. Separately, we demonstrated that the average EF detection threshold for baboons in 12 kV/m. Thus, EF exposure at intensities well above the detection threshold and at species-scaled EF strengths greater than those found environmentally does not appear to be aversive.

Exposure of baboons to combined 60 Hz electric and magnetic fields does not produce work stoppage or affect operant performance on a match-to-sample task.

We examined the effects of combined 60 Hz electric and magnetic field (EMF) exposure on performance of delayed match-to-sample (MTS) procedure involving the flash rate of a light as the stimulus. Six baboons (Papio cynocephalus) fully acquired the task; four others functioned accurately only when cued. All ten subjects were assigned to EMF-exposed or sham-exposed groups of five and were used to test for a work-stoppage effect that was previously observed with initial exposure to electric fields (EF) of 30 or 60 kV/m. Here, we report the results of two experiments, each consisting of 6 week preexposure, exposure, and postexposure periods. We found no evidence of work stoppage with fields of 6 kV/m and 50 microT (0.5 G) or with 30 kV/m and 100 microT (1.0 G). In neither experiment was there evidence of an adverse effect of 60 Hz EMF exposure on MTS performance.

Impairment in auditory and visual function follows perinatal viral infection in the rat.

Acoustic startle reflexes are elicited by intense tone bursts but inhibited if weak bursts precede reflex elicitation. Rats were infected by intracerebral inoculation with lymphocytic choriomeningitis virus (LCMV) at birth. Compared to control animals, infected animals had higher elicitation and inhibition thresholds and showed recruitment at intense stimulus levels. Histopathology revealed both cochlear and retinal degeneration. Like some infectious agents in humans, perinatal exposure to LCMV in the rat yields a severe polysensory neuropathy.

Behavioral system and apparatus for tone-detection and choice reaction times in the cat.

An efficacious operant-conditioning procedure for psychophysical experiments with cats is described. The system features (a) restraint of the cat and the use of the liquid reinforcement delivery cup to control orientation with respect to the stimuli, (b) a minimum of apparatus between the cat and a free-field sound source, (c) two response pedals so that separate "Yes" and "No" responses are defined, (d) a discrete trial procedure with reaction time (RT) defined as the time from the onset of a trial until the occurrence of a response, and (e) an effective liquid reinforcer and simple delivery system. Operation of the system was demonstrated with the method of constant stimuli. Detectability was directly related, and median RT for correct "Yes" responses inversely related, to tone sound pressure.

Mitochondria with impaired phosphate transport: 32P uptake studies.

Rat liver mitochondria which have been exposed to 0.15 M NaC1 at 35 degrees C for 15 min subsequently take up 32Pi from an external medium only to about 5% of the extent of uptake by control mitochondria. The volume into which 32Pi distributes in a pellet of such "aged" mitochondia is less than that available to 3H2O but is greater than that available to [3H]sucrose. Mitochondria treated in this manner cannot therefore accumulate Pi although limited penetration of the inner membrane can occur. These results confirm earlier findings by indirect methods (Williams, G. R. & Orr, J. L.: Dynamics of energy-transducing membranes (Ernster, L., Estabrook, R. W. & Slater, E. C., eds), Elsevier Scientific Publishing Company, Amsterdam, Netherlands, pp. 497-508 (1974).