To begin, Cushing monitored the caliber and color of cortical vessels by fitting a glass window into the skull of the dog. Intracranial pressure was raised by filling an intracranial, soft, rubber bag with mercury. Cushing recorded the intracranial pressure along with blood pressure, pulse rate, and respiratory rate simultaneously. This three part effect is commonly referred to as Cushings triad. In later experiments performed by Mosso, intracranial pressure was induced by injecting physiological saline into the subarachnoid space rather than increasing mercury content of an intracranial bag.This research clearly displayed the cause and effect relationship between intracranial pressure and cerebral compression. Cushing noted this relationship in his subsequent publications. He also noted that there must exist a specific regulatory mechanism that increased blood pressure to a high enough point such that it did not create anemic conditions. Cushings publications contain his observations and no statistical analysis. The sample size of the experiment is also not known. Other researchers
Several notable figures in the medical field, including Ernst von Bergmann, Henri Duret, Friedrich Jolly, and others experimented with intracranial pressure similarly to Cushing. Some of these researchers published similar findings concerning the relationship of intracranial pressure to arterial blood pressure before Cushing had begun experimenting. Cushing studied this relationship more carefully and offered an improved explanation of the relationship.Some controversy concerning plagiarism does surround some of Cushings research.
The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia. Ammonia is especially damaging to the nervous system, so argininosuccinic aciduria causes neurological problems as well as eventual damage to the liver.This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder. Diagnosis
Diagnosis is based mainly on clinical findings and laboratory test results. Plasma concentrations of ammonia (>150 μmol/L) and citrulline (200-300 μmol/L) are elevated. Elevated levels of argininosuccinic acid (5-110 μmol/L) in the plasma or urine are diagnostic. Molecular genetic testing confirms diagnosis. Newborn screening for ASA is available in the U.S. and parts of Australia, and is considered in several European countries

Treatment
During an acute hyperammonemic episode, oral proteins must be avoided and intravenous (I.V.) lipids, glucose and insulin (if needed) should be given to promote anabolism. I.V. nitrogen scavenging therapy (with sodium benzoate and/or sodium phenylacetate) should normalize ammonia levels, but if unsuccessful, hemodialysis is recommended. Long-term management involves dietary protein restriction as well as arginine supplementation. In those with frequent episodes of metabolic decompensation or with hyperammonemia even when following a protein-restricted diet, daily oral nitrogen scavenging therapy may be successful. Orthotopic liver transplantation offers long-term relief of hyperammonemia but does not seem to sufficiently correct neurological complications.