score of 1 in 17 percent (1/6) of subjects given 60 mg of PB; a score of 1 or 2 in 83 percent (5/6) of subjects given 120 mg of PB; and a score of 2 or 3 in 100 percent (6/6) of subjects given 180 mg of PB.

There was general agreement among authors of studies reviewed on several issues: PB is safe and effective when used as a diagnostic test to augment GH responses to GHRH; the test is perhaps the best means of identifying GH deficiency in adults and children; and PB is safe to use in patients with a wide variety of physical and mental disorders. Symptoms were always noted to be brief and tolerable, without requiring medical intervention, and by implication did not require long-term follow-up.

Thus, the main strength of these studies is the careful documentation of acute hormonal responses to PB in normal volunteers of all ages, including children, and in a variety of disease states. Although there is no evidence that PB causes long-term problems when used as a diagnostic test, this point has not been studied. The available studies uniformly show a relatively mild side-effect profile for PB; however, a major weakness is that none were specifically designed to test for adverse effects of PB and many simply ignored this aspect of the drug. Moreover, all of the observations were done over several hours, although several studies administered PB to normal volunteers or patients daily for 2 to 3 days. Nonetheless it is clear that patients with a variety of disease states—many causing severe stress such as thyrotoxicosis or Cushing’s disease—had relatively mild acute and transient side effects from PB, and no study reported major clinical problems or obvious acute CNS symptoms after PB administration.

Clinical Studies of PB and Myasthenia Gravis

Myasthenia gravis is an autoimmune disorder characterized by antibody blockade of the ACh receptor of the neuromuscular junction. This immune disturbance results in impaired transmission across the neuromuscular junction and fluctuating weakness in patients with the disease. Myasthenia gravis can affect individuals of all ages with variable and unpredictable severity.

Patients with mild cases may exhibit symptoms of blurred or double vision, while patients with more severe cases may exhibit generalized paralysis and respiratory failure. Some patients with myasthenia gravis also have been shown to have subtle changes in cognitive function related to ACh antibodies binding to ACh receptors in the central nervous system (Iwasaki et al., 1990). These changes may be reversed by treatments for myasthenia gravis, including plasmapheresis (Iwasaki et al., 1990), or with anticholinesterases (e.g., physostigmine) that easily cross the blood–brain barrier and enhance ACh activity (Tucker et al., 1998). Thus, the possible reversal of cognitive dysfunction with anticholinesterases in myasthenics may be an argument against adverse effects of PB on cognition in normal individuals unless there is a difference in the CNS effects of PB in these two populations.



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