~ Archive for Uncategorized ~

Russian support for Vladimir Putin and freedom of expression


Growing up in the 1970s I was told by American media that Russia was to blame for everything that wasn’t going well here in the U.S. This is apparently still true today. A one-day (May 16) sample from Facebook:

  • “Trump Revealed Highly Classified Intelligence to Russia” (nytimes; referenced by a concerned Facebook friend)
  • The guy under investigation for illegal ties to Russia leaks classified material to the…Russians! Yes, but she used email
  • Another Russian Connected To Trump Has Turned Up Dead – That’s 8 So Far
  • Trump’s business network reached alleged Russian mobsters
  • “Top Senate Democrat Calls on White House to Release Trump-Russia Meeting Transcripts” (nytimes)

Our media portrays Russians as living under a cruel dictatorship. Vladimir Putin and his friends are stealing all of their money. Our go-to “look how they abuse their women” slam against enemies doesn’t work with Russians (since women obtained an equal role in their society 100 years ago) so we decry the cruel oppression of gay and transgender people by a heteronormative government.

What was it like on the ground? I visited Moscow, which I was told was the part of Russia least likely to support Putin. Nonetheless, I met Putin supporters and Russians of all political persuasions agreed that Putin would win 65-70 percent of the vote in a completely free election. Putin is credited with eliminating corruption and chaos at local and intermediate levels of government. Although Russians might be happy to live in an English- or German-style parliamentary democracy, they don’t see this as the alternative to Putin. Instead they envision pervasive corruption, violence, and looting. What about the fact that Putin and people close to the government seem to have become richer than typical civil servants? [Though let’s keep in mind that these folks haven’t made anywhere near as much money, in the aggregate, as cronies of the U.S. government! Consider the $182 billion A.I.G. bailout, for example, and all of the Wall Streeters protected from their own incompetence thereby.] “I look at Putin as a hedge fund manager,” said one Russian. “We have about $500 billion in foreign currency reserves and Putin should get a fee for managing that. At least he hasn’t buried us in debt the way that Bush and Obama buried the Americans.” (A Boston-based emerging markets bond fund manager confirmed Putin’s basic fiscal prudence: “When oil prices went up, Russia paid off a lot of its debt early. Compare that to Venezuela where they spent it on social programs and making Hugo Chavez’s daughter a billionaire.”)

Russia has a flat 13-percent individual income tax, a flat 20-percent corporate income tax, and a European-style value-added tax of 10-18 percent (PWC). They are suffering from more or less permanent “austerity” because the government spends only about what it takes in via revenue. I.e., they don’t have deficit spending.

Tyler Cowen said that the stagnation of the U.S. economy shouldn’t make us weep because we now have the option of same-sex marriage (and, fortunately for litigators, divorce). Russians certainly don’t have this option. Is the oppression of gays as bad as portrayed in the American media? “You can be as gay as you like here,” said one expat. From the Lonely Planet Moscow:

Moscow is the most cosmopolitan of Russian cities, and the active gay and lesbian scene reflects this attitude. Newspapers such as The Moscow Times feature articles about gay and lesbian issues, as well as listings of gay and lesbian clubs. Visit Gay.ru (http:// english.gay.ru) for up-to-date information, good links and a resource for putting you in touch with personal guides.

Students at the university that I visited had a much more diverse set of opinions regarding social and political issues than their American counterparts. On the issue of gay rights, for example, students at the same cafeteria table might range from someone actively interested in promoting LBGTQ issues (maybe not the Transgender part, though; I didn’t hear anyone mention gender ID) to someone who would openly say “It doesn’t bother me if people want to have sex in their apartments, but I don’t want to hear about it.” They could all go back to eating after discovering these differences, instead of one group trying to enforce political orthodoxy on the other! What do university students who don’t put energy into enforcing conformity do with all of their leftover time and energy? I met economics masters students who not only knew the names of a bunch of (Russian-language) poets, but actually had poems memorized!

As in Soviet times, though there is probably more freedom of expression in social and work situations than we have here in the Boston area (e.g., you can express your opposition to race-based hiring preferences at your employer, but you won’t have a job a day later!), running a mass-market TV network with 24/7 anti-government stories wouldn’t work. People thought that Putin would still win in totally free elections in a country with totally free media, so restrictions on media may not have any practical effect on the government.

What about something that corresponds to our obsession with Russians controlling important events here in the U.S.? Are there Russian stories about how various officials are being manipulated by Americans or the American government? There don’t seem to be. Government-influenced Russian media do seem to enjoy pointing out American hypocrisy and of course we give them plenty to choose from. The Land of Liberty (TM) has the world’s highest incarceration rate. The Land of Opportunity (TM) has a massive underclass. From those two contradictions alone the Russians can fill all of the pages that they want with stories that make us look ridiculous.

Medical School 2020, Year 1, Week 28


From our anonymous insider…

Exam Week: physiology (including pharmacology), anatomy, and clinical (x2).  

Classmates are nervous about physiology due to range of systems covered in this block: endocrinology, reproductive, kidney, and gastrointestinal. From our class GroupMe chat: “I cannot believe they could not put one of these systems into the next block.” (We can believe anything about the next block because we haven’t experienced it!); “FML,” [F… My Life] liked by 26 classmates.

Anatomy questions were easier than on the previous two exams. Every question was first order (e.g., What is this structure?), instead of a more challenging clinical scenario or applied reasoning (e.g., Which of the following structures would be used to access the posterior aspect of the stomach?). The most difficult question asked us to identify two arteries in the abdomen on a CT image slice. Classmates speculated that standards were lowered in response to complaints during the last block regarding the anatomy curriculum. I wasn’t among the dissatisfied; if I get a well thought-out question wrong I tend to remember the material.

I spoke with an M4 (fourth-year medical student) after the anatomy exam. The school apparently used to conduct the anatomy exam in the lab on your individual cadaver. They stopped this because some students felt under too much pressure from being “pimped” by instructors and “it did not look good for the LCME [Liaison Committee on Medical Education].” I asked, “What does pimping mean?” The term refers to an attending bombarding a resident or medical student with questions. The M4 chuckled, “Hospitals have not succumbed to these restrictions so be prepared on your rotations. A good attending won’t let his or her resident leave the day without feeling humbled or inadequate, depending on how you take the experience.”

After exams we completed a Web-browser-based anonymous evaluation for every instructor. The “Learning Environment” section requires a response to “Were you required to perform any personal services?” and “Did you feel you were denied opportunities for training or subjected to offensive remarks because of gender, ethnicity, or sexual orientation?” We were informed via mass email to be careful with this section because every “yes” response causes an email marked “urgent” to be sent to each dean. Accidental “yes” responses at the end of the last block caused a bit of an inbox meltdown among the academic administrators.

The good news about “offensive remarks” is that LCME requires they be recorded, along with the rest of each lecture, on video. This way students who can’t be bothered to attend still have access and anyone who enjoys being offended can repeat the experience. Over half the class uses this feature and our large IT staff are frequently called to help with issues. Before the weekend, a student asked a beloved instructor, “What is your favorite beer?” He responded, “The video is recording, I’ll tell you afterwards.”

Statistics for the week… Study: 25 hours. Sleep: 8 hours/night (I once again get more sleep during exam week?); Fun: 1 night. Example fun: Final exams ended at 12:00pm. Ten of us went to classmate’s apartment for beer and mimosas, followed by an early happy hour excursion downtown and late night dancing. Jane and I slept until noon the next day.

More: http://fifthchance.com/MedicalSchool2020

Why are whales whale-sized?


“Why Did The Biggest Whales Get So Big?” (Atlantic) is popular science at its most fun. Is this profound or obvious? Argument for obvious: If you want to cross an ocean you need a bigger ship than for crossing a pond, so of course ocean-crossing animals are bigger than pond-crossing animals. Argument for profound: Arctic terns are small and yet they migrate across continents.

[The writer quotes a biologist (not a planetary physicist, but that’s okay because any American who didn’t major in Gender Studies or Folklore is now a climate prophet!) who seems confident that the Earth’s oceans will be completely different in 100 years and won’t support big whales. Is it time to invest in a whale museum? Or will there still be some cold nutrient-rich waters closer to the poles?]

Medical School 2020, Year 1, Week 27


From our anonymous insider…

“Lactation: Use it, or lose it” is our theme for two days. A family physician brought in one of her patients, a 30-year-old mother of two. When four-month-old “Nora” got hungry, she whipped her breasts out in front of the whole class. The physician explained that the breasts are made of 4-18 glandular ducts with suspensory connective tissue and fat. The baby needs to be rotated using different positions (e.g., the football hold) to ensure each duct is used.

Two hormones are important for lactation. Prolactin, secreted by the anterior pituitary gland, signals the glandular ducts to produce milk. If the ducts begin to build up in pressure, prolactin secretion will be inhibited. Once this cascade has begun, it is almost impossible to reverse the spiral, which is why breastfeeding in the first days after delivery is critical. Although prolactin produces milk, oxytocin (the love hormone) causes the release of milk. When a baby is on the nipple, the ducts contract, producing a let down. Other signals, such as a baby crying,can cause oxytocin release. We were fortunate enough to see a let down: Milk shot out of the nipple for several inches and sprayed all over the baby’s face and clothes. Nora was loving it.

“Breastfeeding should last for at least six months and up to one year plus/minus two months.” The physician continued, “A child will let you know when he or she is ready to wean. The child will start grabbing solid foods and teething on the nipple.” Current conventional wisdom, confirmed by the most heavily cited studies, is that breastfeeding for at least six months (1) builds mother-child bonds with oxytocin release, (2) decreases the child’s risk of obesity, increases IQ, improves immune system function and improves social skills, and (3) decreases the mother’s risk of breast and ovarian cancer.

The family physician noted that her specialty, increasingly rare in American cities, is the only one that follows both mother and child during pregnancy, labor, and after birth. “This allows a whole different perspective that used to be the norm. In most big city hospitals, the moment after delivery, the infant is whisked away by the pediatrician, while the mother is followed up by the Ob/Gyn. Family medicine bridges this patient divide by caring for both mother and child and sometimes grandmother too.”

On the advice of yesterday’s physicians, Americans abandoned breastfeeding in favor of formula. On the advice of today’s physicians, Breastfeeding rates are back up to roughly 50 percent and are tracked by the CDC. The mother explained how difficult breastfeeding was for her first child. “If it was not for my physician, I would have quit after one month.” She developed a severe case of mastitis (inflammation of the glandular ducts caused by an infection or obstruction). “Every time I breastfed, I would cry in pain.” The worst thing to do for mastitis is to stop feeding. Instead, you should feed or pump in short pulses. The physician noted, “A big misconception about breastfeeding is that it should not hurt. It will hurt. A lot.” In addition to the biting, oxytocin release in the first few weeks can cause painful uterine contractions similar to the experience of labor. The physician continued to explain the difficult decisions her patient’s face without extended maternity leave. “They ask themselves, ‘should I quit my job to breastfeed, pump, or switch to formula?’ Each presents challenges especially if the pump is not covered by insurance, or if the family gets insurance through their job.” (This seemed to support Ivanka Trump’s observation that motherhood has become the primary obstacle to women’s professional advancement, but Anita still isn’t in a positive mood about any Trump family member.)

The physician noted how there exists a black market for milk, especially for colostrum. Colostrum is the milk produced in late pregnancy that is rich in antibodies and protein. Our modern range of reproductive technologies, including surrogacy, has produced the largest number of families in which an infant is present and yet no adult is capable of lactation. “Colostrum is worth more than gold!”

That evening I attended an optional workshop on women’s health led by three female physicians, one of them an OB/GYN specialist. Fifteen students, including five men, from different years showed up. We practiced inserting different intrauterine devices (IUDs) in dummies. IUDs are shaped like a “T” with arms that spring out when deployed, thus anchoring the device in the uterine horns. The IUD is connected to two strings that exit the uterus through the cervix. A physician can pull on the strings to remove the IUD. The strings are trimmed during insertion so that they end just outside the cervix, which enables women with IUDs to check the strings every month to ensure the device has not been displaced. None of my classmates with IUDs knew that they were supposed to do this.

The first IUD marketed was Teva’s Paragard. “Paragard is the most cost-effective contraceptive ever created,” noted the gynecologist. Paragard uses copper to kill sperm before they can reach the egg for fertilization. It is is effective for ten years. Most women are choosing Skyla and Mirena, a progesterone IUD. These are more expensive but women like it because of the decreased bleeding. One family physician with experience with adolescents noted, “Paragard has this unfortunate misnomer that it causes heavy bleeding. It’s just a woman’s normal cycle. The progesterone IUDs give lighter bleeding. Some women on Skyla or Mirana stop having periods altogether.” I asked if older or younger women are more receptive to IUDs versus normal birth control methods. She responded, “Younger women (under 25) are by far more resistant to IUDs. They don’t want anything in their body but they want to have plenty of sex. I have to beg them to use some form of contraceptive.”

A pediatric gynecologist gave two lectures on puberty. My favorite fact: fifty percent of healthy adult weight is added during puberty. Females begin puberty, on average, at age nine with the growth spurt, followed by thelarche (breast development) at age 10 and finally menarche at age 12.5. These ages are delayed in larger families, higher altitudes, and rural settings. Males begin puberty, on average, at age 11 with an increase in testicular volume. This is followed by pubic hair, the all-important growth spurt, voice changes, axillary hair, the ability to ejaculate, and fertility. The class chuckled when he commented, “Males are shooting blanks for a bit. Males can ejaculate before fertility.”

In his practice, he evaluates “precocious puberty”. He deems puberty premature if the child reaches a stage three or more years before normal. The most severe cases are generally due to a hormone-secreting pituitary adenoma. Some of his patients undergo the growth spurt and menarche at age six. Black children typically undergo puberty 1-1.5 years before risk-adjusted white children. “My colleagues in other countries have it easier. Race cohorts are not as meaningful in the US because of genetic and ethnic mixing. Other countries these ‘normal’ numbers are more relevant.”

A week before exams and the library once again is crowded. Students stare at laptops (with peeks at an open Facebook window) or textbooks. The librarian brings her 12-cup coffee machine out for students to use during exam week. About half of us bring mugs while the rest walk across the street for Starbucks.

Pharmacology is a huge part of this exam and memorizing drug names is one of our toughest challenges to date. A friend’s mother advises companies on drug names, which may reflect millions of dollars of analysis. Names that “flow” are easily remembered: gliflozin is a typical suffix for drugs that make glucose flow in the urine (SGLT2 inhibitor); glutides keep the GLT1 incretin tide coming on. Classmates say that they are enjoying TV drug ads a lot more than they used to.

Statistics for the week… Study: 20 hours. Sleep: 7 hours/night; Fun: 1 day. Example fun: Jane and I ran a 5k trail run.

More: http://fifthchance.com/MedicalSchool2020

Medical School 2020, Year 1, Week 26


From our anonymous insider…

“This is for 3,000 years of patriarchy!” exclaimed a female classmate as she slices off the penis. Today we are dissecting the external genitalia. We noted the three main regions of the penis: left corpus cavernosum, right corpus cavernosum, and corpus spongiosum.

Lectures introduced the female reproductive cycle, also known as the hypothalamus-pituitary-ovarian (HPO) axis.

This topic requires us to learn the derivatives of cholesterol and the enzymes that catalyze these conversions (graphic). Cholesterol is a 27-carbon structure that gives rise to numerous signaling molecules such as androgens, estrogens, progesterone, aldosterone (isoosmotic antidiuretic) and cortisol. When discussing cholesterol signaling, there are two questions: What enzymes are found in what cell? How much access does the given cell have to low-density lipoproteins (LDL) in circulation?

Two-thirds of the class is memorizing the names and important enzymes in First-Aid that will be tested on Step I. For example, they memorize 17-alpha hydroxylase deficiency will lead to increased aldosterone and cortisol levels with decreased sex hormones and ambiguous genitalia. They aren’t trying to learn the structure of cholesterol. I am wishing them good luck in retaining that information for next year.

The cells of the body have an ability to make fine distinctions among these related cholesterol-derived compounds. For example, aldosterone is very similar in structure to glucocorticoids (e.g., cortisol). So similar that kidney cells’ aldosterone receptors have an affinity to cortisol. However, the aldosterone receptor is typically near an enzyme that degrades cortisol into cortisone which has a lower affinity. In this clever way, the aldosterone receptor can maintain its high sensitivity (percent true positive) to aldosterone while increasing the specificity (percent true negative). [After you enjoy a bag of licorice, it is possible to have transient psuedohyperaldosteronism, including hypertension and hypokalemia from cortisol activating the aldosterone receptor; licorice inhibits the activity of the enzyme that degrades cortisol into cortisone.]

The menstrual cycle is divided into the ovarian cycle (follicular and luteal phase) and the uterine cycle (proliferative and secretory phase). Different regions in the hypothalamus release pulses of Gonadotropin-Releasing Hormone (GnRH) into the pituitary portal system. GnRH activates gonadotroph cells in the pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH) into the systemic circulation. FSH and LH act on ovarian follicles.

Each follicle is surrounded by granulosa cells that nurture a single dormant egg. Outside the granulosa cells are connective tissue called theca cells. LH binding to theca cell receptors initiates a signaling cascade that increases cholesterol uptake into the cell and increases transcription of the enzymes required to convert cholesterol into androgens. These androgens diffuse out of the cell and suppress further development of the follicle.

FSH binding to granulosa cell receptors upregulate aromatase, the enzyme that converts androgens into estrogens. Granulosa cells do not have the enzymes to synthesize androgens (estrogen precursor) themselves. Follicles are selfish. Once FSH has selected a follicle it will suppress other follicles from maturing, thereby ensuring only one follicle ovulates each cycle.

As FSH increases aromatase activity in granulosa cells, estrogen levels rise throughout the follicular phase of the ovary. Estrogen has many effects including proliferation of the uterine lining (proliferative phase of the uterus). Estrogen also has negative feedback on the neurons in the hypothalamus controlling GnRH release and negative feedback on the gonadotropins in the pituitary. Every 26-32 days in a healthy female, estrogen levels reach such high levels that the negative feedback switches to positive feedback. (The mechanism of this about-face remains a mystery to medicine.) The positive feedback produces the LH surge, a massive release of LH and FSH from the pituitary, initiating ovulation.

Ovulation is the rupture of the follicle. The oocyte or egg is released into the peritoneal cavity (space between abdominal wall and visceral gut organs) where the fimbriae of the fallopian tube sweeps it into the fallopian tube. Fertilization typically occurs in the ampulla of the fallopian tube and is carried into the uterus for implantation. An ectopic pregnancy occurs when a fertilized egg implants anywhere outside the uterus, most commonly in the fallopian tube. However, our embryology professor mentioned it is possible to have implantation in the peritoneal cavity on the the connective tissue of the gut.

After ovulation, the follicle enters the luteal phase. The ruptured follicle becomes the corpus luteum, a highly vascularized endocrine structure. Before, only the theca cells had adequate access to cholesterol in the bloodstream. Now, the granulosa cells have abundant access to cholesterol from LDL in the blood. Granulosa cells lack the enzyme to convert cholesterol into androgens. They are able only to convert androgens into estrogens and cholesterol into an androgen precursor, progesterone. Thus, progesterone levels spike initiating the secretory phase of the uterus. The uterus is ready for implantation of a fertilized egg. If fertilization occurs, the placenta secretes HCG (a close analog of LH) which preserves the corpus luteum production of progesterone. If fertilization does not occur, the corpus luteum involutes (degrades) causing progesterone withdrawal. This sudden decrease in progesterone causes shedding of the uterine lining or menstruation. The decline in progesterone and estrogen disinhibits the GnRH pulsations initiating the whole cycle again.

Two-thirds of the males had at best a fuzzy knowledge of the menstrual cycle. For example, how long is it? When do menses takes place in relation to ovulation? About half of the women did not know how their birth control works. Classmates argued about whether males should be given a handicap for the reproductive block: “You females have it easy. We’ve never seen this stuff before.”

Our patient case: Gina, 31-year-old overweight female presenting with amenorrhea (lack of periods) and hirsutism (hair growth on chin, armpits, etc.). A pregnancy test is negative. A hormone panel reveals high levels of estrogens, androgens and LH.

Gina suffers from Polycystic Ovarian Syndrome (PCOS). PCOS is named for the ultrasound appearance of small cysts in the ovary. Confusingly these fluid-filled sacs are not “ovarian cysts,” but simply mature follicles that are unable to ovulate. The elevated levels of androgens inhibit further maturation of follicles and ovulation and cause hair growth. The endocrinologist explained that hair growth, especially on the chin and neck, is what brings women to her office: “The amenorrhea is alarming but it is not what typically brings them in.”

PCOS affects about eight percent of reproductive age females, although there is not a standardized diagnostic criteria for PCOS and the causes are not fully understood. Diabetes and obesity are known risk factors: adipose (fat) tissue produces androgens, which interfere with follicle maturation. The inability to menstruate is serious. The uterus is stuck in proliferation mode, which vastly increases the risk of endometrial (lining of the uterus that regenerates every cycle) cancer.

How do we get Gina to ovulate? The endocrinologist explained how every woman’s HPO axis is different. “It’s really trial and error.” Gina, like many women with suspected PCOS or infertility issues, undergo a progesterone challenge. A high dose progesterone injection is given initiating the transition from the proliferative phase of the uterus (high estrogen, low progesterone) to the secretory phase of the uterus (high progesterone). Once progesterone is metabolised, progesterone withdrawal should initiate menses. This confirms that the problem is an inability to ovulate.

Gina is taking clomiphene, a drug also used to treat infertility. Clomiphene inhibits estrogen receptors in the hypothalamus to prevent estrogen negative feedback. Therefore, there continues to be release of GnRH and downstream release of FSH despite the presence of estrogen at levels which should cause negative-feedback . Clomiphene increases the risk of twins as multiple ovulations may occur. Gina also underwent what sounds like a barbaric procedure called ovarian drilling. A needle inserted laparoscopically destroys various follicles in a random array. Ovarian drilling is quite successful in decreasing androgen levels and inducing ovulation. Gina still is not on a normal cycle, but has been menstruating. She is trying to get pregnant with her husband.

[See also “Small-sample Behavioral Economics” for how clomiphene may be taken by women with normal fertility.]

Statistics for the week… Study: 20 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: One of our classmates recently moved in with two males in their 20s. Her new apartment is a bachelor pad equipped with a pool table, beer pong table, dart board and xbox. After two weeks of straight exam study, she was demonstrating her social skills by hosting a 26th birthday party for another classmate.

More: http://fifthchance.com/MedicalSchool2020

How do you spend $2.75 billion on signals for a subway system?


Buried in this article on $100 billion in capital spending on the New York City subway system is the following:

the capital plan invests $2.75 billion to upgrade signals

If there are already signalling cables along the tracks capable of supporting TCP/IP, how is it possible to spend $2.75 billion on a set of lights driven by a few microprocessors? That’s enough to build two of the world’s largest passenger ships (see Symphony of the Seas), complete with water park, skating rink, thousands of cabins, accommodations for 2,175 crew members, etc. I don’t think the answer is “stuff purchased by the government costs a lot” because, according to the same article, they are going to get 1,000 subway cars for almost the same price ($3.2 billion).

[Separately, the Moscow Metro system was amazing by American standards. It is huge and growing every year. Trains on every line run every minute on weekdays and every two minutes on weekends. A 23-year-old native said that the longest she’d ever waited for a train was 12 minutes. That was at 1:00 am and the delay excited a lot of discussion among customers. The artwork is justly famous. I loved the aviation emphasis of the ceiling mosaics, which are designed to show what you might see if you looked skyward (some photos that I took a few hours after staggering out of the Moscow airport).]

What would that $100 billion spent by New York City buy in China? The World Bank says it costs China roughly $20 million per km to build a high-speed rail system. So $100 billion would suffice for 5000 km of track, stations, and trains(?). That’s 3,100 miles, or Boston to San Francisco.


Medical School 2020, Year 1, Week 25


From our anonymous insider…

Five hour-long lectures over three days on calcium regulation to control neuronal activity, coagulation, heart function, and bone structure. One challenge is that calcium is a cation (positively charged ion) that can come out of solution. Too much calcium will cause calcium precipitation with various anions (negatively charged ions) potentially causing thrombosis of vessels, kidney stones, and coma. Too little calcium will cause hyperexcitability of neurons with the classic Trousseau sign.

Calcium in your body is governed by mass balance: What comes in must come out to maintain equilibrium levels (flux in = flux out). Calcium intake varies, so calcium efflux adapts accordingly. Two hormones, parathyroid hormone (PTH) and 1,25 dihydroxycholecalciferol (vitamin D) regulate calcium homeostasis through the gut, the kidney and the massive calcium reservoir of bones. (Calcitonin used to be thought to play an important role, but, at least in adulthood, appears secondary to PTH and vitamin D.)

The parathyroid glands, four small tissue regions within the thyroid in the neck, release PTH in response to decreased extracellular calcium. PTH instructs the kidney to increase calcium reabsorption and decrease phosphate reabsorption. The decrease in phosphate is thought to prevent precipitation of calcium-phosphate crystals.  Further, PTH increases the kidney’s conversion of inactive 25-hydroxycholecalciferol reserves into active vitamin D. Vitamin D primarily acts on the intestines to increase calcium and phosphate absorption. Both PTH and vitamin D act on bone cells to fine-tune bone maintenance.

Bone is an organized mesh of specialized bone cells, blood vessels, extracellular proteins and mineral crystals (primarily hydroxyapatite). There are three main types of bone cells: osteoblasts (bone-building cells), osteocytes (imprisoned osteoblasts), and osteoclasts (bone-destroying cells). Osteoblasts secrete various proteins, primarily collagen, into the extracellular environment that form osteons (nucleation site for mineral deposition). As the osteons become mineralized, the osteoblasts, now termed osteocytes, become imprisoned in this mineral matrix. Osteocytes communicate to each other with cellular foot processes, forming the elaborate osteocytic membrane.

The osteocytic membrane forms a cellular interface that separates the mineral deposits from the vascular network: bone on one side, blood vessels on the other. Therefore, the osteocytes can regulate the “bone fluid” to determine net bone resorption or deposition. If osteocytes pump calcium and phosphate from the blood into the bone fluid, net bone deposition occurs in this microenvironment; if the osteocyte membrane pumps calcium and phosphate out of the bone fluid into the blood, net bone resorption occurs in this microenvironment. Activated osteoclasts secrete enzymes and acid that degrade the osteon proteins and the mineral deposits, respectively. Although overactive osteoclasts lead to weakened bones, transient osteoclast activity is needed to make stronger bone by making room for more densely packed osteons. Perhaps next year I will understand enough to relate osteocyte and osteoclast activity.

Bone development and maintenance require adequate calcium input (1200mg/day), steady levels of vitamin D (greater than 30 IU/mL), and mechanical stress signals. One of the most overlooked bone health tools is weight-being exercise, the mechanical stress of which is sensed by the imprisoned osteocytes, inducing bone formation.

Our patient case: Lucy, 60-year old female artist with a history of kidney stones presents to the ED for a femur fracture after a fall. In addition to having broken the largest bone in her leg, a CT showed microfractures in several additional bones. Blood work showed extremely elevated PTH despite hypercalcemia  (high calcium levels in the blood). Presence of a parathyroid adenoma, a benign tumor that secretes PTH, is suspected. Physicians recommend the removal of Lucy’s parathyroid glands, a parathyroidectomy.

Lucy suffered from several psychological diseases in childhood and had become a fervent believer in holistic medicine. Lucy’s internist explained, “It’s always a challenge to emphasize how these complementary approaches are complementary, not supplementary. The Internet has introduced patients to a lot of information. Some good, some bad.” The internist explained that Lucy is one of her favorite patients despite the extra time required for each visit. “She would bring me stacks of articles on supplements I had never heard about. We would dig to find the active ingredient. I’ve learned a great deal from her.” Lucy tried several herbal, yoga and acupuncture therapies for osteoporosis and joint pain. A student asked the internist, “When do you draw the line if a patient does not want to follow your recommendation?” She responded, “If a patient is not following my advice I don’t boot them out. I ask myself, ‘Would another physician have a better outcome?’ The only patients I have kicked out were ones that forged my signature on prescriptions.” After several months of holistic treatment, Lucy elected to get the parathyroidectomy. Her calcium levels have come down and osteoporosis, measured by bone mass density, has improved. Although this was a success for our healthcare system, Lucy was diagnosed with breast cancer six months ago.

Instead of dissection (anatomy lab), we went to a radiology workshop. My classmates describe radiologists as “antisocial people who sit in a dark reading room all day with $40,000 monitors.” The consensus among our class is that this profession is at risk of being replaced by image-recognition algorithms. Only one of our classmates, a quiet Asian-American gentleman, admits he would like to be a radiologist. Our lecturer is a father of two whose phone repeatedly buzzed with a toddler’s voice saying “dada” as the ringtone. “I teach one class a month, and this is the day imaging blows up,” exclaimed the radiologist. The radiologist was quirky, but sociable and self-deprecating. He did mention his monitors at least twice: “they cost as much as your tuition!”

Although the software that can replace a radiologist with 12 years of training is purportedly around the corner, our workshop was derailed when we were not able to log into the Picture Archiving and Communication System (PACS) due to a recent software upgrade being incompatible with the browser. After the school’s entire IT staff swarmed in to update the browser, we were up and running. I greatly enjoyed investigating abdominal and pelvic anatomy on de-identified patient CT and MRI scans.

The radiologist showed a CT angiogram (CT with contrast agent injected into arteries) of “nutcracker” syndrome, in which the left renal artery is compressed by the superior mesenteric artery and aorta due to a lack of retroperitoneal fat. It turns out too little fat can be a bad thing! Nutcracker syndrome is diagnosed by radiologists and fixed by surgeons. He spent ten minutes examining different imaging planes to convey the complex anatomical relationships.

Statistics for the week… Study: 16 hours. Sleep: 8 hours/night; Fun: 1 night. Early bedtime for Jane and me. We competed in a 5k. We both got first place in our age group, perhaps because the competitive runners elected to do the 10k. Drinks with our favorite couple (classmate and his PA-student wife) that evening.

More: http://fifthchance.com/MedicalSchool2020

Verizon Wireless in Russia


Verizon has a $10/day “travel pass” program that lets you use your U.S. plan minutes and data in most European countries. With both my old iPhone 6 Plus and now my iPhone 7 Plus, this has proved to result in 3G service in both London and Paris, so it isn’t practical for much besides text messaging and maps.

The situation in Russia is better from a technical point of view: you get LTE data rates. It is worse from a contract point of view, however. There is a $40/month option for which you must sign up explicitly in advance. This provides only 100 minutes of voice and 100 MB of mobile data. Public WiFi is fairly common in Moscow, but sometimes you need a Russian cell phone number to activate it.

Facebook is a huge background cellular data hog, so consider deleting it from your phone altogether. I went into the “cellular” settings and shut off access to cellular data for most apps except Uber (a great service in Moscow, though the Metro and buses will get you almost anywhere), Google Maps, and Phone (iMessage uses this one? There is no separate Messages app control). I also turned off the big “Background App Refresh” switch under “General” settings. (Facebook ended up displaying some alerts, which I don’t see how it could have generated unless it was somehow still able to access cellular data.) Maybe if Apple stops concentrating on its Social Justice War it can develop a decent user interface to settings, e.g., a “minimize cellular data” wizard that asks what you really need to accomplish with the device.

The iPhone disagrees with Verizon regarding the quantity of data used. Verizon sent a text message regarding a $25 additional charge for another 100 MB data block when the phone showed only 88 MB having been used (I was careful to reset this when getting off the plane in Moscow). So I paid $65 for a week of limited usage in Moscow. My Russian friend said that he is paying $8/month for a comprehensive voice, text, and LTE data plan. So one week of roaming cost as much as eight months of domestic service. How do we get in on this business?

Medical School 2020, Year 1, Week 24


From our anonymous insider…

Reproductive lectures start this week. “Males will finally understand how much harder females have it,” joked a female classmate.

There are three main parts of the reproductive system: the internal genitals, external genitals and gonads (testis or ovary). A quick theme that emerges is female development is the default: unless some signal overrides this process, female parts will emerge.

Gonad (testes; ovaries): Primordial germ cells (PGCs) are some of the first cells that are formed after fertilization. PGCs have the potential to become any cell in the body including sperm and eggs. These cells end their migration at the genital ridge, a paired region in the right and left lower abdomen. Here, the PGCs interact with surrounding cells to form the gonad.

In females, each PGC differentiates into an oocyte (egg) that cannot replicate. The surrounding cells nurture each egg in a single follicle. These eggs lie dormant until puberty.

In males, the presence of a functional Y chromosome overrides ovary development. The SRY gene on the Y chromosome signals for the surrounding cells to form interweaving tubes of Leydig and Sertoli cells. Have you ever thought about why the testes are outside the body? Evidently, spermatogenesis (production of sperm) requires a lower temperature than body temperature. Thus production of testosterone by Leydig cells leads to the descent of the testes. My favorite embryology professor instructed, “Boys, don’t drive with the seat warmer on for a long trip. It’ll kill your sperm!” The testes are pulled out of the abdominal cavity through the inguinal canal (see prior chapter). This descent is typically complete a few weeks before birth, but may take as long as one year after birth. [At birth this canal is not sealed completely, which can cause an indirect hernia. Structures, typically small intestine, can squeeze through the inguinal canal and potentially into the scrotum! Infants are routinely checked for this disorder.]

Internal Genitalia (epididymis, vas deferens and prostate; uterus and fallopian tube): In females, an embryological remnant of the kidney forms the fallopian tubes, uterus and proximal (to cervix) vagina. These tubes must fuse together and the septum must be removed to form a normal uterus. Failure to remove the septum is not uncommon (~3%). A more serious defect is if the tubes fail to fuse completely resulting in a bicornuate uterus with two distinct cavities connected at the cervix. Both are still able to become pregnant but have a much higher risk for complications and miscarriages.

In males, a similar tube forms the epididymis, vas deferens and prostate. The vas deferens transports mature sperm from the testis through the inguinal canal into the abdomen. The vas deferens then descends into the pelvis to form an ejaculatory duct. The ejaculatory ducts open into the prostatic urethra (urethra section with the prostate surrounding it).

External genitalia (penis; vagina, labia minora, labia majora, clitoris, etc.): At six weeks post-fertilization, the undifferentiated external genitalia appear, namely the genital tubercle and genital swellings.  There is no way to differentiate male from female at this stage, just that normal development is occurring.This transformation all takes place in the perineum (square region formed from the pubis, ischial tuberosity (bone you sit on) and coccyx (pointy ). We quickly appreciate how crowded this area is — the rectum, bladder and, in females, vagina/uterus all lie in this small volume. Initially, the urinary tract and anus share a common lumen. A septum forms to separate these into the anus and the urogenital openings.

My classmates and I learn this dense region differently. I have found focusing on embryology helps me. Each component of the undifferentiated external genitalia gives rise to the respective female and male reproductive parts (see Netter’s, page 364). Therefore, each part has a homologue (typically with similar function) in the opposite sex. For example, the prostate in males which wraps around the urethra is analogous to the Gland of Skene in females (thought to be involved in female ejactulation). The genital tubercle will form into the glans of the penis or the glans of the clitoris. The glans is supported by erectile tissue and vascular tissue that engorges during sexual arousal.

Males fold each of these parts together as evidenced by the raphe, or ridge, noted on the ventral side of the penis all the way to the anus. Classmates laughed on learning that the anatomical terms for parts of the penis make sense only when the penis is erect: the ventral penis is the underside with the urethra; the dorsal penis faces up.

Looking at the above in real life: Anatomy lab was short. Most students left within an hour. We investigated the external structures of the male and female cadaver. One group found an undescended testicle that got stuck in the inguinal canal. It was far smaller than the descended testicle. The trauma surgeon did not notice any evidence of testicular cancer. She said, “He and his doctors most likely knew he only had one testicle. Today we would remove the undescended testicle at an early age.

In lecture, an internist introduced the male genitourinary (GU) exam before we practiced on dummies. He joked, “I still remember my introductory lecture on the GU exam. I remember the pictures. I was scarred by the pictures.” He continued this tradition by showing us images of foreskin infections and noted that “the most common reason 20-year olds come in to the office is for penis problems.”

The internist described a common reproductive defect: hypospadias is where the urethral meatus (opening of the urethra) in not at the tip of penis but along the shaft or even in the scrotum. He amplified on what we had seen in anatomy lab with 10 minutes on cryptorchidism, the failure of a testicle to descend into the scrotum at birth. An undescended testicle is infertile due to the higher temperature and carries an elevated risk of testicular cancer. If a testicle is not descended by age 1, the current standard of care is to remove it. The physician then asked the class, “What is the number one type of cancer in 20-year-old males?” Despite having been prompted by the lecture topic, nobody in the class was able to come up with the correct answer: testicular cancer.

We discussed 5-alpha reductase deficiency (5-ARD), a rare genetic disorder commonly referred to as güevedoce. The phallus of the penis forms under stimulation of 5-alpha dihydrotestosterone (DHT), a more activated form of testosterone (same compound that causes male baldness). DHT initiates enlargement of the paired vascular tissue (corpus cavernosum, crus of the penis) and the erectile tissue (bulb of the penis, corpus spongiosum). Females have analogous parts, just they have not folded onto each other, nor enlarged. 5-alpha reductase is the enzyme that converts testosterone into DHT. This prevents the enlargement of the phallus in utero. Las Salinas, Dominican Republic, is known for having a high prevalence of 5-ARD: 1 in 90 XY males are born with ambiguous genitals and raised as females. However, during puberty 5-ARD individuals have such high testosterone levels that the ambiguous clitoris enlarges into a penis. Hence güevedoce or “eggs at twelve”. The community holds coming-of-age parties for these chosen individuals. 5-ARD individuals can be fertile propagating this genetic defect through generations in the isolated village. On the bright side, these individuals do not worry about male baldness.

The most dreaded part of the male GU exam for physician and patient is the digital rectal exam. The prostate can be palpated by pushing on the anterior rectum with two digits. Enlargement or masses can be felt. However, the internist emphasized that only the lower third of the prostate can be felt. “The digital rectal exam cannot rule much out.” An ultrasound exam of the prostate can see much more without associated distress.

One student asked what the medical consensus is on circumcision. The internist replied, “There is no medical reason to get or not to get circumcision. The main medical argument is the increased risk of foreskin infection with poor hygiene. However, with good hygiene, there is no increased risk of infection.” He ended by asking, “Why do doctors ask patients to turn their head and cough?” The cough increases intraabdominal pressure that accentuates any inguinal hernia. “We ask patients to turn their head cause we don’t want to be coughed on…”
Statistics for the week… Study: 20 hours. Sleep: 8 hours/night; Fun: 1 night. Example fun: watched college basketball at the house of an M2 (second-year medical student). She is married to an engineer and they’re debating when to have kids. The current plan is for her to give birth during the third year of medical school so that she isn’t pregnant during residency.

More: http://fifthchance.com/MedicalSchool2020

Post Office sets brain on fire


Here’s a stamp design that I didn’t expect to see from an enterprise that gets revenue from selling stamps: “Repeal of the Stamp Act, 1766”

(Of course, if Vladimir Putin selects me as dictator to replace the Trumpenfuhrer, I will make it illegal to mail letters unless an Elvis Presley stamp is affixed.)

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