Medical School 2020, Year 1, Week 21


From our anonymous insider…

Goodbye gastrointestinal system; hello renal system. I was only two-thirds of the way through the GI textbook chapter.

Lectures introduced how the kidneys regulate body fluid “compartments.” The body contains about 42 liters of water: 28 liters intracellular (within cell membranes) and 14 liters extracellular (outside cell membranes). The extracellular fluid includes 11 liters of interstitial fluid (between cells) and 3 liters of blood plasma. These compartments are constantly changing their equilibrium with excretion of urine and intake of food with varying osmolarities (concentration of solution). Western diets high in salt increase the osmolarity of blood, causing a net increase in blood volume and increase in blood pressure for a given vascular tone, also known as volume-loading hypertension.

In Anatomy we continued dissection of the abdomen, removing the liver, spleen and kidneys. Liver removal required five scalpel cuts, each of which took about five minutes to prevent damage to surrounding tissue. The liver is anchored in the body by several strong ligaments: hepatogastric, hepatoduodenal, hepatodiaphragmatic and falciform. The falciform ligament connects the liver to the anterior abdominal wall including the belly button. Ligamentum teres, the remnant of the umbilical vein, runs through the falciform.

There are five regular Anatomy instructors, three of whom are surgeons and two are veterinary anatomists(!). However, our school also brings in three or four working surgeons. This week my favorite trauma surgeon noted how in some conditions the umbilical vein remnant can reopen! Two groups were scolded for ripping the hepatoduodenal ligament without dissecting the portal triad (portal vein, common bile duct and hepatic artery). Our cadaver had no gallbladder, so we worked with other groups to understand that region.

Next we removed the kidneys, slicing each into anterior and posterior sections. Most kidneys had large renal cysts, one the size of a golf ball embedded in the cortex (outer region), and some included stones ranging in size from sand grains that one could feel up to two centimeters in diameter.

Every day we bombard our body with a variety of food and water with different concentrations. It is up to our kidneys, the interface between the vascular system and the urinary tract, to maintain electrolyte and volume homeostasis (equilibrium).The urinary tract is a continuous, branching tubular network that extends from the urethra to the bladder to each kidney’s ureter. The ureter branches into microscopic collecting ducts. Each collecting duct connects to hundreds of nephrons (specialized tubule segment). The nephron tubule segment ends at Bowman’s capsule, a spherical bulge in the tubule and the glomerulus (specialized capillary network). Each kidney has about 1-1.5 million nephrons.

It is here at the glomerulus that blood plasma spills into the tubule system becoming filtrate. Under normal physiological conditions, the kidneys receive 20 percent of the cardiac output. Every day 180 liters of plasma is filtered by the tubule system. However, normal urine output is about 1.5 liters per day. That is an immense amount of reabsorption of solutes and water!

The glomerulus is the first step in deciding what becomes urine. The glomerulus supports the beautiful “foot processes” of podocytes, amazingly specialized epithelial cells (see the details in this Nature article).  During kidney development, the distal (far) end of the nephron tubule, which becomes Bowman’s capsule, is penetrated by blood vessels, which become the glomerular capillaries. The glomerular endothelial cells begin to loosen their connection with each other to form fenestrated (“fenetre” meaning windows) capillaries. The tubule epithelial cells interacting with the capillary endothelial cells become these specialized podocytes. The cell body of a podocyte sends thousands of “foot processes” to wrap around the capillary cylinder. Proteins on the podocytes’ cell membrane bring these foot processes together to create slit diaphragms, the final filter pore of 10-20 nanometers in diameter. For blood plasma to reach the urinary tract, it traverses through the fenestrated glomerular capillaries, a dense extracellular basement membrane and and the podocytes’ slit diaphragms. This multi-layered biological nanofilter filter prevents large particles and negatively charged proteins from entering the tubule.

The plasma that is filtered becomes filtrate. Unlike the epithelial cells of the more distal urinary tract, the epithelial cells of the nephron are highly specialized in transport processes. Along the way the epithelial cells of the tubule reabsorb filtered solutes (e.g, sodium, glucose and amino acids), secrete waste products (e.g., protons and urea) and determine how much water should be reclaimed back into the vascular system. The kidney is under sensitive hormonal and nervous control to regulate plasma osmolarity and plasma volume. If blood volume decreases, baroreceptors in the carotid bodies signal the kidney to increase isosmotic absorption via aldosterone. If blood osmolarity is too high, the hypothalamus (part of the brain) signals the pituitary gland to release Antidiuretic Hormone thereby increasing free water reabsorption (urine concentration).

Sound complicated and failure-prone? It is. Most hypertension and other nominally vascular disorders start with dysregulation or degradation of the kidney. Our nephrologist professor: “The kidney allows terrestrial life.”

Our patient case: “James,” an 18-year-old freshman at the local community college. James presented to his primary care physician with fatigue, general weakness, and hepatosplenomegaly (enlarged spleen and liver). Lab tests revealed a low platelet and white blood cell count. He was prescribed antibiotics and referred to a hematologist: earliest appointment in two weeks.

His symptoms worsened with swelling in his feet and periorbital (around the eye) region. His mother took him to the ED, where a physician, suspecting a reaction to the antibiotics, swapped the antibiotics for an antihistamine to combat the inflammation. At the appointment the next day, the hematologist suspected mononucleosis (the kissing disease “Mono”) but the test came back negative. He was referred to a nephrologist: earliest appointment in three weeks.

“The appointment made me put the symptoms to the back of my mind. I would deal with it at the appointment.” James gained twenty pounds in water weight with swelling extending to his lower extremity and scrotum. The nephrologist ran tests that showed extremely low albumin levels in his blood plasma. Albumin is the most abundant plasma protein. Without this oncotic  (protein solute) pressure, there was a net movement of water out of James’s plasma into the interstitial fluid. Why was his albumin so low? The nephrologist said, “You are either peeing out an unbelievable amount of albumin, or your liver is not able to produce it.” He suspected Hepatitis C or HIV.

What would peeing gobs of albumin out look like? The nephrologist told James that it would look like frothy urine: “Imagine whisking egg whites with water.” James responded, “I always thought frothy urine was normal. It’s all I have known.” He was sent straight to the ED.

James’s kidneys were shutting down. While in the hospital, blood pressure spiked from 150/90 to 250/150. Doctors thought he might not make it. He underwent plasmapheresis (filtering of plasma through a machine) and plasma transfusions for two straight days. “I was really drugged up but I do remember seeing my blood being pumped through these tubes out of my body. That was the first time I was scared.”

James stayed in the hospital for nine days.  “I did not sleep for two days straight. Every two hours a nurse would come in to check my blood pressure and take blood.” He was most frustrated that he was not allowed to shave or shower: “My platelet count was so low they thought I might bleed to death if I cut myself.” A kidney biopsy revealed inflammatory vascular deposits in his glomerular capillaries. He was diagnosed with Systemic Lupus Erythematosus, an autoimmune disease that causes destruction of various organs including the kidneys. He was put on short-term immune suppressors and glucocorticoids, which are anti-immune steroid hormones.

James’s recovery was long and painful. He had 45 lbs of excess water weight. He would urinate clear fluid every 30 minutes. Water seeped out of a cut on his left leg. Three months after discharge he resumed classes. “I wrapped a washcloth around the cut to soak up the water that still seeped out.” My legs were so swollen I could not bend them to walk up stairs. The severity of his disease did not hit him until after the critical episode.

The mother was thankful for his post-diagnosis medical care, but angry about the three-week wait between the hematologist and nephrologist. James’s nephrologist said that if the appointment had been even one day later, James would have not recovered normal kidney function, if he even survived the severe electrolyte imbalance and hypertension.

James is now considered cured, though he remains on immune suppressors. His kidney function has returned to normal. James hopes to become a biochemist developing new drugs.

Later that day, the head of the ED introduced emergency medicine, the art of triaging undifferentiated patients and sending diagnosed patients to specialists for care. Straight out of a three-year residency, EM physicians make an average salary of more than $310,000. Salaries at academic institutions are lower, while salaries tend to be higher for more rural institutions. EM physicians work 30-32 hours a week with regular shifts. “Once I am off, I am off. I don’t carry a pager. I do not have any patients once I am off my shift.” A more rural and less busy ED will have 12- or 24-hour shifts; a busy urban ED will have 8-10 hour shifts. He loves going rock-climbing and skiing on weekdays: “The slopes are clear at 11:00 am on a Tuesday. Internists and surgeons claim they have hobbies, but if you ask them how long it has been since they did that activity, it is usually months. Ask an EM physician and the answer is ‘Last week’.”

The physician said that emergency medicine is the youngest speciality. In the 1940s, a critically ill patient would be brought to the family physician. Formal recognition of emergency medicine as a specialty came in the early 1970s.

Any downsides to the specialty? “Other specialists have no respect for EM physicians. We are a jack-of-all-trades, master of none.” EM physicians are required by federal law to see all patients. “We do not get to pick our patients.” EM physicians also get no appreciation from patients. “The patient sends the fruit basket to his cardiologist after a heart attack, even though it was the EM physician that saved his life. Instead, we get lawsuits. Patients don’t sue their internist they have been seeing for a decade when their condition deteriorates into a heart attack. They sue the ED.”

Our school’s full-time chief diversity officer, a Ph.D. in psychology, hosted a lunchtime diversity discussion with catered Indian and Thai food. Sadly I was forced to miss this event due to shadowing a physician in the hospital. Classmates said the main topic was diversity in the classroom. Fortunately this was not my last chance. The chief diversity officer’s assistant sent an email this week inviting students to a self-defense class:

Students who identify as female: Learn maneuvers to help you evade uncomfortable and/or dangerous situations. … Students who identify as male: Learn tips on how to engage in a situation and diffuse it without escalating it.

Statistics for the week… Study: 15 hours. Sleep: 8 hours/night; Fun: 1 night. Example fun: Medical school formal, also known as “MedProm” at a downtown ballroom. The medical school deans and instructors left around 10:00 pm, perhaps because the social chairs hired a DJ specializing in electronica and hip-hop. We danced to Lil Jon’s “Get Low” and the pop hit “Closer“. One of my favorite classmates and his wife brought hip flasks of liquor to spice up the cash bar concoctions.


Don’t let your kids grow up to be engineers, Part 3


If you wondered about the practical value of academic computer science, here’s a Google PhD Summit attendee in the Everglades (90+ degrees in the shade) wearing long black pants:



Medical School 2020, Year 1, Week 20


From our anonymous insider…

Lectures detailed the absorption mechanisms of the gastrointestinal system. The sodium-potassium ATPase pump creates the electrochemical gradient that energizes transport of glucose and amino acids. (See next week for how the kidneys use almost the exact same proteins to get rid of waste.)

Stretch and presence of food causes G-cells in the Antrum of the stomach to secrete the peptide hormone gastrin. Gastrin acts directly on parietal cells to secrete hydrochloric acid into the stomach lumen. In case those cells don’t respond adequately, gastrin also acts via intermediary enterochromaffin-like (ECL) cells that release histamine, which in turns activates parietal acid secretions. Eating complex macromolecules, rather than simple refined sugars, may activate more levels of regulation for processing.

Every day before anatomy lab, Jane and I watch the corresponding Acland videos, fascinating dissections by Robert Acland, the late surgeon and clinical anatomist who developed important microsurgery techniques. We get so enthralled by these that we have to stop ourselves from watching too far beyond the upcoming dissection.

This week we opened the peritoneal cavity, revealing the stomach, intestines, liver, pancreas, and spleen. Several cadavers, including mine, had appendectomies. My group’s liver felt rock solid due to cirrhosis.  One cadaver had sigmoid colon volvulus: her sigmoid colon had twisted around itself, causing pressure to build up and stretching the typical 1.5-foot section to three times the normal diameter and twice the length. It looked like a massive caterpillar. One student stepped out due to nausea as her group accidentally sliced the colon, causing feces to ooze out. That’s something we didn’t see Robert Acland do.

A pediatric surgeon joined my anatomy group. She was was wonderfully helpful with a story to go along with every structure. She commented that our cadaver had been good for GI surgeons, with at least three abdominal surgeries: appendectomy, hysterectomy, bariatric surgery (stomach stapling). Darwin was interested in the origin of species; GI surgeons look at the “origin of appendixes.” Surgeons look for an odd triangular fat fold at the ileocecal fold to locate the appendix during appendectomies.

I stayed late with the surgeon to dissect the vessels near the pancreas, which is nestled in among the stomach, spleen, and transverse colon. “Never touch the pancreas,” she explained. “In surgery, all those pancreatic digestive enzymes can leak out and start digesting organs.” I cut the pancreas to reveal the deep structures behind. I saw how the splenic artery runs with the pancreas to the spleen. The splenic vein then travels across the pancreas to fuse with the inferior and superior mesenteric veins to form the massive portal vein. Working in the cramped space gave me an appreciation for why pancreatic cancer is so difficult to remove surgically.

Our patient case: “George,” a 55-year-old combat veteran with a history of alcohol abuse, pancreatitis (inflammation of the pancreas), and liver cirrhosis. He presented with jaundice, clay stool bowel movements and dark orange urine. These symptoms pointed to issues with the liver and pancreas for our differential diagnosis. Blood work showed vitamin deficiency and anemia. An x-ray revealed a pancreatic tumor mass obstructing the Ampulla of Vater. This prevented pancreatic enzymes and bile from being secreted into the duodenum of the small intestine. In a healthy person, bilirubin, the toxic product formed from recycling red blood cells’ hemoglobin, is transferred into the duodenum with bile from the liver. Gut bacteria convert this into stercobilin which is excreted in feces giving it its characteristic dark color. George’s obstruction caused a buildup of bilirubin in extracellular tissue, blood and urine. The tumor was inoperable and he was referred to hospice care, where he passed away after eight months.

George’s wife came in to discuss her experience along with a nurse and a social worker who had managed George’s “home-care hospice” case. The nurse manages 10-15 patients and makes up to 5 home visits per day. Many of these visits are pain management emergencies. A student asked if there was ever an issue with opioid abuse? She responded, “We err on the side of the patient. If the patient tells us there is an issue we listen. The prescriptions are for two-week periods.” She explained that prescription is typically methadone, a slow-release opioid which has less addiction potential, but in the last year the hospice facility has tried to tighten control of opioids. “I dealt with one case this year where the family was stealing pain pills from granny.”

“You are the gateway to hospice care,” continued the nurse. “Saying there is nothing more I can do as a physician for a patient that you may have been caring for decades is heartbreaking. The patient transitioning from aggressive care with hope to comfort care is similarly heartbreaking for the family.”

George’s wife described how helpful hospice care was for her family. She described being crushed by the immense requirements for medical appointments and medications during chemotherapy. “We had no time to think about what comes next. We had no chance to enjoy the time he had left.” George was able to live at home for his last eight months. The case manager described how hospice care allows families to plan and come together: “When the white flag goes up people have time to adjust. An estranged brother or daughter will travel to reconnect with the family.” The nurse added, “People think someone in hospice care is going to die within a week. That is simply not the case. Most are there for several months to even one-and-a-half years.”

The case manager added that hospice centers have coordinated care with other facilities to meet a patient’s needs. “If a patient’s last wish is to go to the beach, we’ll coordinate care with a local facility.” The team will typically attend a patient’s funeral.

One student asked about assisted suicide. Although illegal in this state, the nurse believed it should be a terminally ill patient’s choice. Some do ask about getting transported to Michigan or other states where it is legal. The nurse commented how one Huntington’s patient made the decision to starve to death. George’s wife commented how George considered assisted suicide. “He would never take his own life but he did ask about assisted suicide. If it wasn’t for me and his son, I believe he would have done it.” The panel concluded by stressing the need to have end-of-life discussions with patients early, before terminal disease states, and promoting patients to have an advanced directive (or living will).

At lunch our class discussed the cost and quality of end-of-life care. More than 80 percent of patients living with a chronic disease claim they want to avoid hospitalization and intensive care during the terminal portion of their illness. However, in 2005 the CDC estimates that only 25 percent of deceased died in their own home. In 2008, Medicare spent $55 billion for the last two months of patients’ lives (CBS). One-quarter of Medicare expenditures are for care in a beneficiary’s last year of life, an unchanged ratio from twenty years ago.

The next day, the state’s chief medical examiner gave a lecture on opioid abuse. “Sherry” is a trained pathologist who conducts autopsies on suspect deaths and public health crises (at a much lower salary than if she were practicing).

According to Sherry, heroin use became widespread in the 1960s when addicted Vietnam veterans returned home. Poppies were cultivated in Vietnam. The 1980s cocaine boom caused a decline in heroin. “We have Kurt Cobain to thank for bringing back heroin with 90s Grunge.”

“You will quickly realize that today’s opioids are nothing like yesterday’s heroin when you go on your ED [emergency department] clinical rotation,” explained Sherry. “You’ll see several ODs in a given night.” In 2013, drug overdoses became the U.S.’s number one cause of unintentional death. Heroin is found in urban centers whereas pills are found in more rural and suburban areas.

“Street” heroin used to be cut to 6-7 percent purity, thus requiring intravenous injection to get high. This drove Hepatitis C infections, which Sherry said have declined due to access to clean insulin needles from Walmart and the increasing purity of heroin. Today’s 20-percent-pure heroin can be snorted: “Without the needles there is no social stigma.” Sherry said that students are trying heroin in the same way that older generations might have tried alcohol and marijuana. 1 in 13 high school students in our area admitted to using heroin.

“Do not touch any bag or foil you might find in the ED!” Sherry exclaimed. “If you touch it, you could overdose and die.” Synthetic opioids are now so powerful that some act through absorption through the skin. Pure heroin is about twice as potent an agonist (binds to mu-receptor producing “high” response) as morphine. Fentanyl, quite widespread now, is 100 times as potent as morphine. “The new rave is carfentanil. Addicts are quite excited about this one, 10,000 times as potent as morphine and used to put elephants down. Drug labs and health workers are petitioning for access to the opioid-blocker Narcan in case of skin contact with carfentanil.”

“Drug dealers are actually quite brilliant businessmen,” Sherry explained. “They realized the demand does not go away after the prescriptions are cut off. Police try to suppress the names of individuals who overdose because users will look for his or her dealer. The overdose means that the product must have been good.Some dealers purposefully overdose a client because it boosts sales.”

A student asked what she would recommend doing to prevent this epidemic. “Death penalty for heroin dealers,” she laughed and continued, “Loved ones see the signs of drug abuse but they do not realize how serious they are. With the potency and variability of drugs these days, you can overdose on the first high, or the hundredth high.” She also cautioned us that the gateway to addiction is frequently prescriptions from physicians. The individual who overdoses is on several prescriptions: antidepressants, anti-anxiety, sleep. “These are people connected to the healthcare system. These mental illnesses present as physical pain such as back pain. It takes one doctor to overlook the mental cause and prescribe painkillers for the physical pain.”

Sherry said that prescription opioid abuse has been reduced by prescription monitoring networks. “A few years ago, drug addicts were able to state-hop because these monitoring networks would not talk across state lines.”

Statistics for the week… Study: 18 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: drinks at classmate’s apartment with about 10 other students, followed by the downtown bar scene (everyone else) and home (me and Jane).


Laptop ban on airlines will lead to more support for the docked-phone idea?



Back in 2005 I suggested a dock for a mobile phone that would enable consumers to imagine that they were using the phone as a desktop computer. Twelve years later it still hasn’t happened on any large scale and there has been a convergence of CPU capability in the handheld and desktop worlds (which means that putting a CPU in the dock might have become a dumb idea, except for video editing).

In response to global jihad, the U.S. government is now talking about banning laptops on Transatlantic flights. Might it be time to defrost my old idea? United Airlines has given up on seatback screens in favor of the world’s most cumbersome download-an-app-and-register-before-boarding system. Why not beef up the seatback screen into a mobile phone dock with keyboard and mouse? Or does it make more sense to tell everyone who is going to fly Transatlantic “buy a monster-sized mobile phone”? Or do we just admit that flying time is TV-watching time for most “business” travelers who claim to be working?

I will be pondering this on my London to Boston flight today!

Don’t let your kids grow up to be engineers, Part 2


A Facebook post during our family sojourn in Ft. Lauderdale:

Amazon said that the four items I ordered had shipped, but that they were canceling my Prime membership…


Comment from MIT graduate from roughly my year (i.e., the last Ice Age): “Why would they cancel your membership??”

Medical School 2020, Year 1, Week 19


From our anonymous insider…

We’re back from our three-week Christmas and New Year’s break. Our previous block was exclusively on the cardiopulmonary system. This seven-week block will cover the gastrointestinal (GI), endocrine, reproductive and renal systems.

Lectures introduced the components of the GI system, including the enteric nervous system (ENS), a network of 500 million neurons (as many as in the spinal cord!). In the 1900s anatomists dissected portions of the GI tract and tested responses to specific foods and distensions (see pioneering work by Bayliss and Starling, referred to as “The Law of the Gut”).  The ENS contains afferent (sensory) neurons that possess mechano- and chemo-receptors that sense the lumen of the gut. These afferent neurons send their information to interneurons that synapse (connect) with efferent (response) neurons. Efferent neurons control smooth muscle tone and secretory gland cells. Drugs that affect neural synapse communication can affect GI function: I saw a patient abusing opioids hospitalized because he had not defecated in over three months.

The autonomic nervous system integrates with the enteric nervous system, relaying information from the central nervous system, which includes the brain, but the ENS can function independently.

We learned the embryological origin of GI organs: the liver, pancreas, spleen and lungs are all outgrowths of the same tissue! Classmates had a lot of questions and after-class discussions about the fetal twisting of the gut tube that produces these organs.

Lectures also covered the basics, e.g., peristalsis: when a bolus of food enters the lumen of what doctors call the gut, a continuous tube from esophagus to stomach to intestine to rectum. Sensory information is integrated in the myenteric plexus, a region of dense nerve activity that travels between the smooth muscle layers. Efferent neurons contract circular smooth muscle about two centimeters proximal to the distension. Simultaneously, efferent neurons relax distal circular smooth muscle. This ring of contraction propagates and moves the food about five centimeters before being succeeded by the next wave.

Anatomy lab kicked off with the dissection of the abdominal wall. We saw the numerous fascial layers that separate the abdominal muscles and the peritoneum. Every cadaver had six-pack abs once we removed the fat covering the rectus abdominus. Rectus abdominus is a superficial muscle that runs from the lower sternal border and ribs to the pubic tubercle (bony prominence in the front of hip). The muscle alternates between a muscle sheath and three or four horizontal tendinous lines creating six-pack or eight-pack abs.

We were told to concentrate on understanding the inguinal ligament, the division of abdomen from the legs, and inguinal canal. There are two routes for vessels to enter a lower extremity: under the inguinal ligament to the anterior leg or through the pelvic cavity into the posterior leg. Groups with male cadavers showed classmates dissecting female cadavers how the vas deferens takes sperm through the inguinal canal into the abdominal wall and down into the pelvic cavity to connect to the urethra. Sperm travel right next to the peritoneum membrane which encloses the intestines. My favorite trauma surgeon commented that interns and residents are selected to determine the hernia type by feeling up the patient’s scrotum into the inguinal canal.

Three classmates and I stuck around through the lunch break to watch a GI surgeon attending dissect a “Fem-Fem”. The cadaver had an obstructed left femoral artery. A tube was inserted into the left femoral artery distal (farther away from the origin) of the blockage and connected to the perfused (supplied with blood) right femoral artery. It felt like a hard rubber tube, not what I imagined for a biologically compatible material. I asked if this tube would cause stenosis (hardening) of the attached arteries. He said, “Eventually, but this man’s comorbidities would likely kill him within two or three years, well before stenosis. This was a way for him to keep his leg for his last years.”

Our patient case: “Jenny,” a beautiful, intelligent 35-year-old female. After college she moved to start work at an advertising firm. She began to lose weight steadily despite a normal diet. She had regular diarrhea and terrible acne. “The acne was by far the most debilitating. It made me severely depressed,” explained Jenny. “And the dermatologist was worthless.” After the dermatologist’s suggestions did not work, she proposed putting Jenny on Accutane. She declined because of the potential for depression due to interactions with her anti-anxiety medications. She lived with the acne and diarrhea for five years.

Seemingly overnight, everything changed. Jenny lost thirty pounds in a month. Her hair fell out. She developed painful bruises on her legs. “My coworkers thought I was crazy. I thought I was dying.”

A new doctor tested her for celiac disease, and, after a positive result, referred Jenny to the Gastroenterologist who came to present her case. The physician, a woman in her 40s, explained, “Five years is quite typical for time until diagnosis following the onset of celiac symptoms. It wasn’t on physicians’ radar ten years ago.” Celiac disease is an autoimmune disease triggered by gluten, an abundant protein in wheat. Gluten survives the acidic environment of the stomach and is phagocytosed by macrophages in the small intestine. In normal individuals, this elicits a small inflammatory response. Individuals with MHC gene variants may experience an aggressive immune response that destroys the gut epithelial lining. Due to the damage to the lining of her intestines, Jenny was unable to absorb essential vitamins and nutrients, which caused malnutrition and anemia.

Jenny worked to adjust her diet in the pre-gluten-free label age: “I called up every manufacturer and asked if the food contained gluten. Brand-loyalty was key.” Adhering to a gluten-free diet, she is now the healthy mother of a healthy boy. “It is what it is. It is much easier now with labeling and I find my whole family eats healthier.” A student asked the doctor, “What is the difference between celiac disease and gluten-sensitivity?” The doctor chuckled. “I have many patients who tell me they feel better when they do not eat gluten. I tell them good for you. It is not because of an immune response from gluten. It is probably because they just eat healthier food.” Jenny chimed in, “I do not understand people who eat gluten-free foods that are 100-percent carbohydrates. How is that healthier?”

In lecture, a neurobiologist introduced the role of glial cells in regulating cerebral blood flow. Glial cells are the non-neuronal support network for neurons. Astrocytes, a type of glial cells, surround 98% of the surface area of the brain’s capillary network forming the blood-brain barrier. They decide what gets in and out. We learned about current trends in astrocyte pathology. Glioblastoma, cancer of glial cells, is one of the most aggressive forms of cancer. The cancer cells migrate along blood vessels to expand to other areas of the brain making It incurable by surgery. While migrating, the cancer cells scrape off the adherent astrocytes giving the voracious cancer cells direct access to the leaky capillary and its nutrients. As it migrates along the vessel, astrocytes are unable to re-adhere to the vessel causing fluid to leak into the brain’s microenvironment. This is theorized to be the cause of seizures in patients with glioblastoma.

Alzheimer’s is another area he believes involves dysregulation of astrocytes. Unlike most tissues, brain blood flow is regulated both at arteriole and capillary levels. Evidence shows astrocytes are able to constrict capillary networks, but amyloid plaques lead to stiffening of the capillary, which interferes with this control mechanism.

I asked him about a recent 60 Minutes episode, “The Alzheimer’s Laboratory”, about families in Colombia with genetic early-onset Alzheimer’s, based on church records going back to the 1800s. Children of an affected parent have a fifty percent chance of losing memory and independence in their thirties or forties. However, from this tragedy comes opportunity for researchers and future Alzheimer’s patients. There is currently no effective treatment for Alzheimer’s, which has thus become America’s most expensive disease, about $240 billion in 2016 and set to grow as Americans age.

“This represents a critical juncture in Alzheimer’s research,” he explained. “Although amyloids are the only target of all drugs in the research pipeline, there is no evidence that amyloid plaques actually cause Alzheimer’s. Some cases have tons of amyloid plaques, some none. Some people have tons of amyloid with no Alzheimer’s.” The 60 Minutes show described a clinical trial investigating whether a monoclonal antibody against amyloid can delay early-onset Alzheimer’s. I was reminded of another neuroscientist’s comment: “If a clinical trial fails they first blame the patient cohort, second the timing of therapy, and only then the science.”

Statistics for the week… Study: 18 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: Dinner with Jane’s visiting family before a Saturday morning 10K through 4 inches of snow.

30 classmates rented a ski lodge a two-hour drive away. Most did not go skiing but they still managed to have a grand-ole time, perhaps because they’d packed two car trunks full of peppermint schnapps.


Don’t let your kids grow up to be engineers, Part 1


A Facebook during our family sojourn in Ft. Lauderdale:

I have officially had it with Hertz. The minivan that I reserved was “not available” and this yellow car that they gave us as a substitute is definitely not “stroller-friendly” like the agent said.


At least a few engineers later asked me about Hertz, driving the “yellow car” (a Lamborghini, I think), etc.

Medical School 2020, Year 1, Week 18


From our anonymous insider…

Exam week covered cardiopulmonary physiology, anatomy and clinical skills. Pharmacology remains the most dreaded topic. Despite this universal struggle, two-thirds of the class appear comfortable with the pace. We know what to expect. We realize that the exams are meant as a stop-safe. If one of us fails the exam, typically a score less than 60%, it is a wake-up call that we are not on-track for the final judgement: Step 1.

The other third of my classmates are nervous wrecks. They are so concerned about what they need to know that they forget about learning. Four percent of the class failed and will have to retake the exam next week. Most of these individuals had adhered to Anita’s strategy of focusing on “High Yield” material, defined as material frequently included on the Step 1 exam and therefore in McGraw Hill’s First Aid for the USMLE Step 1. The First Aid summary figures are worth reviewing the day before the exam, but it seems that “High Yield”-minded individuals quickly forget a substantial amount of the information. These individuals go blank during discussion of some aspect of the patient case that was in the previous block, for example, an enzyme involved in a urea cycle disorder.

As soon as the exams were done, classmates were able to reflect on their experience. We agree that the tested block was much more enjoyable than our first block, which was devoted to clinical applications of molecular pathways, many of which students were exposed to in pre-med required courses and MCAT studying. The tested block was our first foray into predominantly “clinical” material: physiology and pathophysiology. We also got to use our stethoscopes!

After my second exams, a few things I wished I knew on day one:

  • find a good textbook
  • learning begins after lecture
  • study early, study consistently, repeat

Most of the class reads the suggested Costanzo’s Physiology (“I have a date with Costanzo tonight,” is a common inside joke), but I preferred the more in-depth Medical Physiology (Boron and Boulpaep).

Twenty percent of the class no longer goes to lectures because they find it less efficient than independent study. I continue to go to hear the clinical vignettes. Some lecturers are down to an attendance rate of less than 30 percent. Maybe medical school costs could be cut considerably; Jane and and I agree that we could learn everything besides anatomy and clinical exam skills using Web-based and library resources.

The job of a medical student is to study. Many of us got through undergraduate exams by cramming the night before. This purge-in, purge-out mentality does not work in medical school. Curiosity becomes the most valuable asset in medical school. The depth and breadth of information requires constant dedication to translate understanding into retention. My search for immediate answers to questions is challenging for classmates because I don’t have a smartphone right now. Jane suffers the most with my endless questions: “My ankle evertor muscles are sore. What muscles are those?” (Fibularis brevis and fibularis longus)

Statistics for the week… Study: 35 hours. The library was still packed when I left at 10:00 pm most nights this week. Sleep: 8 hours/night; Fun: Learning on Saturday that I’d passed!


Stocks for the long run: GE since 2001


Boston Magazine has an article on GE CEO Jeff Immelt. They note that the stock price has gone down from $40 per share to $29 during the 16 years that he has run the company. Adjusted for inflation, that’s nearly a 50-percent decline ($40 in 2001 is equivalent to about $55 today).

A Google Finance chart of GE versus the S&P 500 confirms the dismal performance of this stock.

What do readers think? Was GE just so crazily overvalued, even after the Crash of 2000, that the stock had nowhere to go but sideways? Revenue in 2001 was $126 billion and earnings per share were $1.41 (annual report). The 2016 annual report shows  $113 billion in “industrial segment revenues” and $1 in “continuing EPS” (GAAP measures) and $103 billion in revenue and $1.49 using non-GAAP techniques. So the company’s performance has become incomprehensible to laypeople in the intervening years, but revenue and profits do seem to have stagnated. How can this be in a world that is ever-more-friendly to the biggest companies?

[Not everyone is suffering. Boston Magazine notes that shareholders paid Immelt $21 million last year. He spent a full four months of salary on a modest dwelling: a $7.5 million Back Bay townhouse.]


  • 2003 Slate article on GE executives underperforming
  • Stocks for the Long Run, the investment classic that my money expert friend says can lead to infinite wealth. If you are in fact sure that stocks will outperform bonds over the next 10 years, for example, you can work with options and futures to pick up guaranteed risk-free cash. (This is in case you don’t want to get infinitely rich by starting a company with a 100-percent female workforce, which Hillary Clinton and Elizabeth Warren say will do the same work at much lower cost than what your stupid competitors are paying their workers who identify as male.)

Car and Driver is more convincing than Thomas Piketty


Thomas Piketty presented 704 pages about how rich the world’s rich bastards are and therefore it was time for the pitchforks (see Book review: Piketty’s Capital). We have a household member who, despite being 13 years shy of being able to drive, is fond of Car and Driver magazine in hardcopy. From the June 2017 issue, in a review of the $3 million Bugatti Chiron:

Bugatti by the numbers:

42: number of cars  owned by the average Bugatti driver

870: number of miles the average Veyron [previous version of the car] accumulates in a year

(This is in an inset box that is missing from the online version.)

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