An automated microcomputer-based system for determining canine paw pressure quantitatively in the dog synovitis model.

The automated system for measuring canine paw pressure is a very useful tool for the evaluation of nonsteroid antiinflammatory drugs such as indomethacin and ibuprofen in the dog synovitis model. The apparatus has been designed to give the operator control over the dog's posture while measuring hind-paw pressure. The stability of the measuring platform permits reproducible measurement of paw pressures. The software package performs direct data recording and data reduction and eliminates tedious manual calculations. Subsequently, the software produces a printout summarizing the experimental results in tabular and graphic form.

A method for chronically recording brain-stem and cortical auditory evoked potentials from unanesthetized mice.

Anesthetizing or sedating animals affords control over movement artifact during electrophysiological recording. However, the use of chemical restraint leads to unwanted side effects such as drug-induced hypothermia. Hypothermia is problematic because BAEP amplitudes and latencies are affected significantly by core temperature changes. Moreover, several recent studies have indicated that anesthetics and sedatives may significantly alter the BAEP and CAEP even in thermoregulated subjects. There is a need, therefore, to develop a practical technique for obtaining chronic BAEPs and CAEPs in restrained, unanesthetized animals. The present report describes a technique that permits the gathering of consistent, reliable evoked potential recordings over time in unanesthetized mice. The preparation is useful for studying the CNS effects of pharmacological agents, pathological conditions, aging and development in the mouse and could be adapted for use with other small animals as well.

Protection of mice by intraperitoneal vaccination against challenge in the foot pad with Mycobacterium marinum.

In a study of local infection of mice with Mycobacterium marinum, heat-killed M. marinum suspended either in Hanks' balanced salt solution or in Freund's incomplete adjuvant was administered i.p. to BALB/c mice. The mice were challenged in the hind foot pad 3, 7, or 14 days thereafter with 5 x 10(3) viable M. marinum. At every time interval, killed M. marinum in the saline medium conferred modest protection against the challenge infection, whereas the antigen suspended in adjuvant conferred protection only when the challenge was administered 14 days after vaccination. Freund's incomplete adjuvant appeared to enhance the infection and to minimize the immune response to the antigen.

Viability of Mycobacterium leprae after multiplication in mice.

To measure the rate at which Mycobacterium leprae are killed in the course of the mouse footpad infection after the maximum of multiplication has been achieved, M. leprae were harvested shortly before and at intervals after multiplication had reached the level of 10(6) organisms per footpad, serially diluted, and inoculated into the footpads of passage mice. Beginning 1 year later, foot-by-foot harvests of M. leprae were performed from passage mice, and the proportion of viable organisms in the passage inocula was calculated by means of a most-probable-number calculation. In addition, the proportion of solidly staining M. leprae was measured in the passage inocula. The proportion of viable M. leprae in the passage inocula was found to decrease with the time after multiplication to 10(6) organisms per footpad of donor mice; the half-time of loss of viable M. leprae was 25 days. The proportion of solidly staining organisms appeared to be directly related to the proportion of viable organisms, as measured by mouse passage, and inversely proportional to the time after multiplication to 10(6) organisms per footpad.

Survival of BALB/c mice after intraperitoneal infection with Mycobacterium lepraemurium.

In an attempt to develop a single, quantitative method of studying the disease that follows infection of susceptible mice with Mycobacterium lepraemurium, survival of BALB/c mice was measured as a function of time following i.p. inoculation with the organisms. Survival was found to be inversely related to the challenge dose of M. lepraemurium and unrelated to the organ-source of the organisms; survival was prolonged by treatment with isoniazid. Mice infected with M. lepraemurium were protected against i.v. challenge with M. marinum administered early in the disease, whereas they demonstrated enhanced susceptibility to the same challenge administered later. Conversely, prior M. marinum infection of mice in the hindfoot pad conferred protection against subsequent challenge with M. lepraemurium.

Survival of BALB/c mice after intravenous infection with Mycobacterium marinum.

In a search for a simple technique by which to study the disease of mice that follows infection with Mycobacterium marinum, survival of BALB/c mice after i.v. inoculation of M. marinum was measured. Length of survival was inversely proportional to the number of viable organisms in the inoculum, and was greater in weanling than in yearling mice. Prior infection with M. marinum in a hindfoot pad at least two weeks before i.v. challenge with the same organism conferred protection against the challenge.

Treatment of Bechçet's syndrome with transfer factor.

Six patients with Behçet's syndrome were treated with transfer factor (TF) from randomly selected donors. Mucocutaneous symptoms and signs were predominant at the time that TF injections were started. Three patients showed great improvement, one moderate improvement, and one was unresponsive to multiple injections of TF from different donors. One case was uninterpretable because of concomitant administration of high doses of prednisone and chlorambucil and brief treatment with TF. These results indicate that TF therapy may be beneficial in some patients with Behçet's syndrome and that a trial of TF is warranted at least in the absence of severe ocular or neurologic manifestations.

The presence of systemic and local activated macrophages in mice infected in the foot pad with Mycobacterium leprae and M. marinum.

A highly sensitive assay for quantitating the presence of activated macrophages was employed to show that foot pad infection of mice with neither M. leprae nor M. marinum induced a population of activated peritoneal macrophages. In vitro attempts to demonstrate local activated macrophages in the foot pads of M. leprae infected mice failed, but, because of the technical problems encountered, do not preclude their presence. Additional studies are being carried out.