From our anonymous insider…
Two weeks before exams and the small library is packed in the evening. We have to review every topic since August while simultaneously being introduced to the complex biochemistry of the urea cycle, the process our body uses to eliminate ammonia freed from normal recycling and breakdown of protein and DNA. Free ammonia is normally turned into urea by the liver for excretion in urine.
Our patient this week was a 20-year-old woman suffering from a Urea Cycle Disorder (UCD) since birth. She had the cognitive function of a toddler. A few of my classmates were left speechless after seeing the patient and hearing from the mother about her round-the-clock caregiver role. She described struggling against the adult strength of her daughter during basic tasks such as bathing and feeding. UCDs are typically caused by a genetic mutation to an enzyme that catalyzes an intermediate product in the conversion from ammonia to urea. If not detected early, excess blood ammonia (hyperammonemia) can alter blood pH enough to cause irreversible effect on the nervous system or death. Most states’ newborn screening programs now test for several UCDs. Treatment typically is a combination of strict dietary restrictions and nitrogen scavenger drugs.
We heard from a hospital Institutional Review Board (IRB) administrator in charge of approving clinical trial requests and access to patient data. The IRB does not evaluate the value of the proposed research; instead, the IRB evaluates if the project can be conducted in a reasonable manner to benefit and to protect the research participants. This process is historically a huge pain for physicians who want to conduct research. The board can take months to review a simple clinical trial proposal or data analysis project of patient data. She did not deny that the IRB process is cumbersome, but used the 1999 example of Jesse Gelsinger to explain why these protocols are followed. Gelsinger was a functioning teenager with a UCD that was so mild he should not have qualified for the trial to begin with. Scientists attempted to use adenovirus (influenza) modified with a functioning form of the mutated urea cycle enzyme to cure the patient. Potential dangers of the trial were not disclosed to the patient and his family. A principal investigator for this NIH trial had relationships with the pharmaceutical company providing the adenovirus vector. Gelsinger died from a massive immune response and liver failure. This tragedy triggered review of clinical trial procedures and halted many ongoing and future gene therapy trials.
After the 1.5-hour IRB presentation, an Emergency Room Physician talked about his experience with the IRB for a pain medication clinical trial. He clearly was frustrated with the IRB, but diplomatically limited his criticisms to “there is plenty of room for improvement.”
Anatomy lab continued with the previous week’s dissection of the shoulder joint from the anterior side. We saw the actions of the four rotator cuff muscles and observed the massive vessels and nerves near the clavicle. Between the clavicle and the joint capsule lies a fascinating mesh of nerve fibers called the brachial plexus, by far the most complex nervous feature we’ve seen so far. We learned how upper extremity range of motion is a function of three joints: sternoclavicular (SC), acromioclavicular (AC) and glenohumeral (shoulder blade-humerus). I never realized we have movement in the SC, the single point of contact between our upper extremity and our axial skeleton, when we raise or rotate an arm. When orthopedic surgeons came in to demonstrate shoulder exam techniques, nearly 20 percent of our young class had bad enough shoulders to line up for a free exam.
Statistics for the week… Study: 16 hours; Sleep: 6 hours/night; Fun: 2 nights out. Example Fun: Friday after-class soccer tradition followed by bowling night, in which we learned that one of our classmates is a former competitive bowler.
The Whole Book: http://tinyurl.com/MedicalSchool2020