3 May 2019: Vaccines

Vaccines

by Nat Pernick, M.D.

I was happy to learn that my measles titer blood test (technically, Measles Antibody, IgG) was positive at 4.6 Elisa units (1). This means I have antibodies to the measles virus and do not need to get the MMR vaccine. With a record number of measles cases in the US, including in Southeast Michigan where I live, I wanted to ensure I was protected (2). However, I had been told by physicians in the past to NOT get the MMR vaccine due to my medical history, because it uses a live but weakened virus, which meant I might be in a similar situation to newborns that were unprotected but unable to be vaccinated (3).

In late 1983, while a first semester law student in Ann Arbor, I felt a large, rock hard mass in my abdomen. I was diagnosed with Hodgkin lymphoma and treated with radiotherapy. 

Hodgkin lymphoma is a relatively common cancer, typically of young adults (4), first described by Sir Thomas Hodgkin in 1832 (5). It previously was called Hodgkin’s disease because its cause was unknown. However, we now know that it is arises from post germinal center B lymphocytes (a type of white blood cell) with "crippling" mutations of the IgH variable region segment. B lymphocytes are a type of white blood cell that respond to microorganisms by producing a large variety and number of antibodies. After these cells are stimulated by exposure to microorganisms, they multiply and cluster in the region of lymph nodes known as the germinal center. Then, they multiply and mature into a plasma cell, which produces antibodies (6). Rarely, B lymphocytes acquire crippling mutations that prevent their maturation (7).

Antibodies have a heavy chain, referred to as IgH, with constant and variable regions, as well as a light chain. The diversity of the heavy and light chains creates millions of antibodies that can bind to different substances. B lymphocytes tend to be relatively unstable, which makes sense given their physiologic function of rapidly producing millions of “daughter” cells. To counter the inherent risk of B lymphocytes and other cells reproducing out of control, multicellular organisms have evolved a sophisticated process of “cell suicide,” also called apoptosis, that intentionally destroys these cells and recycles their contents. When apoptosis is hindered, cancer may occur.

Why Hodgkin lymphoma arises is unknown. In a paper I am finalizing on How Cancer Arises Based on Complexity Theory (8), I propose that Hodgkin lymphoma may be due to a “runaway” immune system, which couples the inherent instability of activated B lymphocytes with defects in apoptosis and other immune system control mechanisms, either congenital or acquired. The immune system has a delicate balance between activating and dampening forces, which I speculate occasionally undergoes major disruption by seemingly trivial events, based on features of complex systems.

In Hodgkin lymphoma, the tumor cells, called Hodgkin Reed-Sternberg cells after Dorothy Reed Mendenhall (9) and Carl Sternberg (10), constitute a very small amount of the tumor mass. These cells secrete cytokines (biologically active molecules) that recruit normal cells to the area and change their properties to produce a mass that destroys organs and may cause death. Remarkably, when the Hodgkin Reed-Sternberg cells are killed by radiotherapy or chemotherapy, the normal cells revert to normal (11). Today, Hodgkin lymphoma has a high (80-90%) cure rate, but this was not always true. One of my high school classmates had an older sister who died of this disease.

After my diagnosis, my oncologist told me that I was immunocompromised and should not get live vaccines. Thus, when working as a physician in a hospital that required the MMR (for protection against rubella, or German measles, which can cause congenital rubella syndrome (12)), I was given an exemption. However, at age 61, after living a lifetime with better health than almost anyone I know, I questioned if I was really immunocompromised and could safely get the vaccine. My internist did not have an opinion. So I had the measles test to help with the decision process (if positive, I would not need it). As it turns out, the current MMR recommendations are to avoid the vaccine only if “severely immunocompromised,” which clearly does not apply to me.

Last week, by coincidence, a Ukrainian pathologist sent me microscopic images of the appendix of his 40 year old patient with measles appendicitis (13). The measles virus induces the formation of Warthin-Finkeldey cells, which are multinucleated cells containing the measles virus, in the appendix and lymph nodes. They indicate the presence of measles virus, but have no other known significance.

This past week I also decided to get the Shingrix vaccine against shingles, which is recommended for healthy adults age 60 or older (14). Although in short supply, the vaccine was available at Maple Pharmacy in West Bloomfield. Amazingly, even with my high deductible HAP insurance, there was no charge, but the list price is about $200 per shot. A second dose is recommended after 2-6 months. Shingles is a very painful disease due to the chicken pox virus which features a prominent rash and can cause encephalitis (15).

References: 

1. ELISA stands for Enzyme Linked ImmunoSorbent Assay. This laboratory method detects a “target” molecule by attaching a sample that may contain the target to a solid substance, then adding an antibody to the target which is linked to an enzyme. In this case, the target is the measles antibody, so the method uses an antibody to an antibody. Then the antibody-enzyme is washed away, but it persists if it has bound to the target, which, in this case, means the measles antibody is present. Finally, the presence of the enzyme (and thus the target) is detected by adding a substance which typically changes color in the presence of the enzyme, see https://en.wikipedia.org/wiki/ELISA 

2. https://www.washingtonpost.com/health/2019/04/16/how-patient-zero-spread-measles-across-state-lines-infected-people

3. https://www.cdc.gov/vaccines/vpd/mmr/public/index.html, https://www.nytimes.com/2019/05/02/us/measles-babies-vaccine.html

4. http://www.pathologyoutlines.com/topic/lymphomanonBhodgkins.html 

5. https://www.ncbi.nlm.nih.gov/pubmed/16252028/ 

6. https://en.wikipedia.org/wiki/File:B_cell_activation.png 

7. https://www.ncbi.nlm.nih.gov/pubmed/16076866

8. http://www.natpernick.com/HowCancerArises.pdf 

9. https://en.wikipedia.org/wiki/Dorothy_Reed_Mendenhall

10. https://en.wikipedia.org/wiki/Carl_Sternberg

11. This is one mechanism in which dysfunctional cells influence normal cells. They can also confer toxic properties on normal cells that are not reversed by removal of the original cells, as described by prion proteins (https://www.cdc.gov/prions/index.html).

12. https://www.cdc.gov/vaccines/pubs/surv-manual/chpt15-crs.html

13. https://www.pathologyoutlines.com/topic/appendixmeasles.html

14. https://www.cdc.gov/vaccines/vpd/shingles/public/index.html 

15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693903/figure/F1 

26 February 2019: Suicide prevention

I had an experience with someone I know that I want to share. I’ll call this person “Pat” and use male pronouns. I have changed many details to protect Pat’s privacy. My take home points are: (1) make sure you know the physical address of people you care about, particularly if they are having significant problems, (2) if you are worried about someone and cannot physically visit them, call the local police to have them check. That is why you need the physical address. The police may not be excited about trying to track someone down from their cell phone number. Pat had been declining for years due to losing a job, relationship issues and health problems. Some time ago, he called me to tell me that “this was the end”, and he was going to harm himself. He had the number of a suicide center but would not call. I had no idea what to do – I didn’t know any of his friends or family who might help. I wondered if he had any other close friends. His significant other appeared to have left him. A physician friend of mine suggested I call the local police, but I didn’t know exactly where he lived. I made my best guess, and spent a fair amount of time getting transferred around and explaining what I knew, which was not that much. Since I was not sure this police department was going to do anything, I called Pat again, and surprisingly he gave me his address. I called the correct police department, who was at his place in 2 minutes. The police asked some questions, and ultimately took Pat to a hospital with a psychiatric department. Within a day, Pat was released home and to the significant other, who was now back in Pat’s life to some extent. I have called Pat several times since. He was mad at me at first. Didn’t I know he wasn’t serious? But eventually he “forgave” me for calling the police. I actually thought it would be much worse. There is no great ending. Pat is not suicidal, but still seems pretty miserable. His significant other is back, at least for now. I am a little more grateful for my life, which seems pretty good in comparison. I also feel a stronger obligation to help those whose life is not so good.

17 February 2019: Living without a car in Detroit's suburbs - an update

Living without a car in Detroit’s suburbs, an update

17Feb19

It has now been almost 2 years since I gave up driving (technically I just gave my car to one of my kids; I can drive if I want). There were several reasons: to reduce my carbon footprint (i.e. take action against climate change), to get more exercise and to see what it would be like. I was also worried about driving after a stressful day. I had no accidents, but was not as attentive as I thought I should be.

After two years, I can confidently proclaim that I am not going back.

I never realized how much stress was connected with driving - I just assumed it was part of life. But when I listen to other people, I now realize how much easier and less stressful my life is because I don’t drive. This is what I don’t worry about - moving cars around in the garage or driveway, shoveling the driveway, warming up the car in the morning, flat tires, cars that don’t start, dodging cars when leaving my house, driving in bad weather, driving when tired or sick, slow traffic, bad drivers, getting lost, parking, car maintenance, car insurance, car payments, tickets, accidents, getting a tow, getting a rental car and buying / leasing a replacement car.

There are problems with not driving, but they seem minor. In the warm weather I bike, and sometimes I get caught in the rain or get a flat tire. It’s annoying, but not that bad. Rarely I fall, but at least to date, I have only had some bruises. Sometimes I take the SMART bus, which involves some waiting. Once the bus hit a car and went “off line” until a supervisor came. I got a ride from someone else, rather than wait. If I am worried that the bus is not showing up, I can use Uber / Lyft as a backup.

In the cold weather, I use Uber and Lyft. For the past 2-3 weeks, in the morning, Uber does not seem to work for me. No cars are available, although once I tried the “upgrade” of Uber XL, which did work, but cost an extra $5. Fortunately, Lyft cars have been available. I use both and check the best price - often there is a dramatic difference. The drivers are typically interesting and pleasant. I like talking to most of them about their lives. Some are not the friendliest, but none are hostile or threatening, unlike the taxi drivers in my past.

My life is now simpler. I don’t spend the weekend running around doing errands. I bundle trips, shop online, and avoid doing things that really are not important. If I am meeting someone and there is a supermarket nearby, I will try to go there afterwards. This also introduces me to different places to shop.

What about the cost? I estimate that ride sharing costs me more in the winter than car ownership, but less in the warm weather when I bike. Even if it does cost more overall, it is worth it to me to have my own personal driver, so that I can work or sleep or socialize with the driver, instead of anxiously watching the road. In addition, I get dropped off and picked up right at the door of my office or wherever I am going. The down side is waiting, typically 5-20 minutes, for the driver to arrive, but I just read or use the computer. Every once in a while I have to go back and forth between the Uber and Lyft apps for a few minutes until I get a decent rate.

Living without a car works for me, but I am not preaching - everyone has to figure out how to optimize their own life. But you should know that not having a car is a possibility, even for someone with an active life.

Prior articles about living without a car:

4Apr18 - http://natpernickhealth.blogspot.com/2018/04/4-april-2018-living-without-car-in.html

18Jun17 - http://natpernickhealth.blogspot.com/2017/06/18-june-2017-life-in-detroit-suburbs.html

12 January 2019: The decline of mental inhibition

The New York Times recently published an article about the acclaimed scientist, James Watson, co-discoverer of DNA, and his bizarre thoughts about differences in IQ between ethnic groups, click here. The article can best be summed up by the statement of Dr. Michael Wigler, a scientist at Cold Spring Harbor Laboratory in New York, which revoked some of the honors it had bestowed upon Dr. Watson:

It is not news when a ninety year old man who has lost cognitive inhibition, and has drifted that way for decades as he aged, speaks from his present mind,” Dr. Wigler wrote in an email. “It is not a moment for reflection. It is merely a peek into a corner of this nation’s subconscious, and a strong whiff of its not-well-shrouded past secrets.”

Detroiters may recall a similar situation when veteran White House reporter Helen Thomas started spouting anti-Semitic views, click here. Wayne State University ultimately revoked an award in her name, click here.

I suggest that family and friends of public figures need to protect their legacy by keeping them away from situations that will be harmful. All of us have evil thoughts, but our intact intellect keeps us from making them public. But when we lose that inhibition under the influence of  alcohol or when suffering from dementia or other mental decline, it is not surprising that we will say terrible things. Of course, this is true for those who are not public figures, but their friends and family know their true nature, and that this is part of their condition.

In addition, I suggest that the awards should not be revoked. These individuals did great things, and their statements, although terrible, were made when their minds were damaged. We should not hold that against them.

x

16 October 2018: Kosher / vegetarian Detroit

What kosher or vegetarian restaurants are in the Metro Detroit area? I have compiled a list, updated regularly, at http://www.myjewishdetroit.com. New vegetarian restaurants include: Chili Mustard Onions (vegan), 3411 Brush Street, (313) 649-2759, https://www.facebook.com/chilimustardonions Neehee's Indian Vegetarian Street Food (vegetarian), 45656 Ford Road, Canton, 734-737-9777; 4924 Rochester Road, Troy, 248-250-6335, http://www.neehees.com The Garden Asian Vegetarian Cuisine (vegetarian), 2156 Wyandotte Street West, Windsor, Ontario (Canada), (519) 915-5566, http://www.thegardenwindsor.com Let me know of any updates at NatPernick@gmail.com.

13 October 2018: How Lung Cancer Arises based on Complexity Theory

I am presenting a paper at the College of American Pathologists Annual Meeting, How Cancer Arises Based on Complexity Theory. Useful links - Abstract, table, Poster, All abstracts - see Session 400, Poster No. 36 

20 May 2018: What Do Scientists Do?

Progress Report
20 May 2018

What do scientists do? With many questioning the value of scientists regarding climate change, vaccinations and other matters, I thought it might be worthwhile to document my scientific life. Before I entered medical school, I had limited exposure to scientists in a social setting, and even now, talk to few people outside of my professional life who write papers or do research to advance scientific understanding.

Alas, I am not a typical scientist. I graduated medical school (University of Michigan 1983) and did a residency and fellowship in pathology (Wayne State University 2000). Most scientists work for a university or research institute, but I do not. I own a business which publishes a free online pathology textbook and am currently its Editor, although I recently hired a Deputy Editor who is much smarter than me and more attuned to the academic world.

Here are the projects / papers I am working on:

1. The Laws of Complexity and Self-organization: A Framework for Understanding Neoplasia (see natpernick.com/TheLawsJune2017.pdf).

This was my first complexity and cancer paper, initially published in 2011 and updated in 2017. I submitted it to several pathology conferences but it was repeatedly rejected. In fairness, it did not fit any of the categories for papers at the conferences, which logically suggests that the paper will not be well received.

This paper was accepted for presentation at the International Conference on Complex Systems in Boston in July 2018 (see http://www.necsi.edu/events/iccs2018/). I had to shrink the abstract (summary) to 250 words. I am starting my preparation for a 12 minute talk, which will be followed by 3 minutes of questions. The purpose of the talk is to get feedback, leading to new insights, corrections of errors and possibly new directions to study. The questions often are impossible to answer in that setting other than “I don’t know, I will follow up”. Sometimes, the questioner is really giving a speech about his/her own work.

I also submitted my complete paper for their published proceedings. Using their very wide margins my paper was 18 pages, which I have chopped to their limit of 10 pages.

2. How Cancer Arises Based on Complexity Theory (see natpernick.com/HowCancerArises.pdf)

A revised abstract of this paper (currently 37 pages) will be submitted to the 2019 ASCO conference (American Society of Clinical Oncology) in May 2019. I tried in 2018 but the hurdles were (a) I had to find an ASCO member to sponsor me and (b) I had previously posted the paper on my personal website and prior publication was prohibited. But I eventually found a sponsor and will revise the paper for 2019 based on the findings in the other papers I am working on, as described below. I will also try to find a medical center (Wayne State, University of Michigan, Oakland University) where I can give a talk about it, to get feedback.

3. How lung cancer arises based on complexity theory
I am writing papers on the  top 20 leading causes of cancer death in the US, beginning with lung cancer, applying the knowledge / theory derived from my first 2 cancer and complexity papers. This paper has been through many drafts, and is now complete. I submitted an abstract for this paper to a pathology conference for presentation, and they should accept or reject it this month for an October 2018 conference.

4. How colon cancer arises based on complexity theory (under development)
I am working on the first draft of this paper. The plan is to finish this paper by September 30, 2018, completing one paper every 3 months. At this rate, it will take 5 years to write papers on the top 20 causes of cancer death.

5. Preinvasive neoplasia
I published a Letter to the Editor (see http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2017-0581-LE) about how complexity theory suggests that tumors such as glioblastoma, which currently do not have a known premalignant condition, likely do have one. I suggested that although we have not identified microscopic features of premalignancy, there probably are molecular patterns.

This was my first Letter to the Editor of a scientific journal in many years. It is a quite complicated task compared to preparing a Facebook post. There is much back and forth with the editor over formatting and references. Sometimes their copy editor changes the text to make it more “readable”, although in my case they completely changed the meaning. Fortunately they corrected it.

That’s it for now.