In order to go about attenuating his polio vaccine, he repeatedly passed the virus through monkeys. Using methods of production that were later described as "hair-raisingly amateurish, the therapeutic equivalent of bath-tub gin," Kolmer ground the spinal cords of his infected monkeys and soaked them in a salt solution. He then filtered the solution through mesh, treated it with ricinolate, and refrigerated the product for 14 days to ultimately create what would later be prominently critiqued as a "veritable witches brew".In keeping with the norms of the time, Kolmer completed a relatively small animal trial with 42 monkeys before proceeding to self experimentation in 1934. He tested his vaccine upon himself, his two children, and his assistant. He gave his vaccine to just 23 more children before declaring it safe and sending it out to doctors and health departments for a larger test of efficacy. By April 1935, he was able to report having tested the vaccine on 100 children without ill effect. Kolmers first formal presentation of results would not come about until November 1935 where he presented the results of 446 children and adults he had vaccinated with his attenuated vaccine. He also reported that together the Research Institute of Cutaneous Medicine and the Merrell Company of Cincinnati (the manufacturer who held the patent for his ricinoleating process) had distributed 12,000 doses of vaccine to some 700 physicians across the United States and Canada.
When attacks occur due to such precipitation, pain and flushing are often present in the area of attack precipitation, though symptoms may also be diffuse in nature.Other symptoms may include hypersalivation when attacks are localized in the mandibular region, or leg weakness after foot trauma. A prominent non-physical symptom are tonic non-epileptic seizures. Such seizures are more common in infancy and childhood than during adulthood. In older children, inconsolable screaming usually precedes such attack, followed by apnea, paleness, and stiffness. Such stiffness can last from seconds to a few minutes.Attack precipitants are usually physical in nature, such as defecation, eating, or taking medicine. Some less common precipitants are micturition, coitus, and painful stimuli. There are also non-physical precipitants, such as the thought or sight of food. In general attacks tend to occur in the precipitated area, though this is not always the case. While some individuals have described a build-up to attacks, in general they tend to be abrupt. The duration of these attacks can be from a few seconds to two hours.Patients are largely normal between attacks. The only notable interictal problem is constipation, likely due to apprehension of precipitating an attack. This symptom often decreases with age, likely due to coping mechanisms such as the use of stool softeners. Cause
The voltage-gated sodium channel NaV1.7 is expressed in nociceptive and sympathetic neurons, where it aids in action potential creation and regulation. The mutations in this gene that have received study all alter the channels ability to inactivate.