Dr. John Manzella's Microbial World

Dr. John Manzella

So, say you are in the seventh grade and the assignment is to write a book report on a famous person. And say this is the late 1950s.  And maybe your favorite uncle was a doctor.  And maybe your uncle miraculously cured your mother’s “quinsy” (a painful abscess next to the tonsil)  a few years ago.  And maybe you were bowled over by that.  Well, you go to the school library and you look for a biography that engages your interest.  If you are John Manzella you read about Louis Pasteur and you think, “This guy is really cool!”  

A Children's Book

The French microbiologist (1822-1895) was the first to blame micro-organisms for spoiling of beer, wine, and milk.  He found that he could prevent this, and the economic losses it was causing, by heating the liquids.  Hence...pasteurization.  

In 1859 (the year of Darwin’s “On the Origin of Species”) he proved the “germ theory” by showing that a heat-sterilized liquid without further exposure to the air remains sterile (that is, life only comes from life).  He created vaccines for prevention of rabies and anthrax.  When he claimed that microbes spread diseases among humans the scientific community was skeptical.

Dr. Manzella didn’t tell me what grade he got on his book report (we will assume it was an A+) but it had a lasting impact.  In high school he liked biology and in medical school he, in his words, “became totally smitten with microbiology."  He attended Canisius College (like his uncle) and went to the SUNY University at Buffalo medical school.  He moved away from snow and went to  the University of North Carolina for residency training in internal medicine (and for basketball).  Two of his most impressive attendings were infectious disease specialists.  The emotional and intellectual connection could not be ignored and he took a fellowship in infectious diseases.  

He joined the York Hospital staff in 1979 and enjoyed his practice as he diagnosed and treated acute infections.  Infection control including rigorous hand-washing was stressed, and all was well.  But then something happened.  

Dr. Manzella faced a frightening situation as young men, men close in age to him, were struck with infections that were not supposed to occur in formerly-healthy individuals. The appearance of AIDS in 1981 forever changed his practice.  Several very intense years ensued as patient after patient suffered and died without explanation.  But in 1984 Dr. Gallo with the NIH and Professor Luc Montagnier from the Pasteur Institute in France (there’s Louis again!) shared in identifying the HIV virus causing AIDS, and there was hope.

However, there was no treatment for the underlying immune deficiency until 1987 when AZT was taken off the shelf and repurposed.  Dr. Manzella was hugely gratified that “something” could now be done.  As he cared for individuals with a chronic viral infection the long-term relationships changed him.  This was, he noted, the most singular experience he had in his life in medicine.  

After highly-active antiretroviral therapy became available in 1995 HIV truly became a “manageable” illness.   But where had this threat to society come from?  

Drop in Deaths after HAART

HIV/AIDS is a zoonosis, an infectious disease caused by an organism that changed and made the leap from a non-human animal host to a human victim.  The HIV virus evolved from a virus infecting chimpanzees in West-Central Africa.   

Zoonotic diseases can be due to viruses, bacteria, fungi, protists, parasites, worms, or misfolded proteins called prions.  They include scary things like rabies, Ebola, Zika, SARS,  MERS, Mad Cow, West Nile, plague, and bird flu, but also common food-borne salmonella and certain E. coli infections.  Zoonoses are fostered by our close connections with the natural world, with other living creatures (as exhaustively reported in David Quammen's "Spillover").

"Spillover" 

Lyme disease is another zoonosis endemic in our area and many of us know someone touched by it (or the fear of it).

One early summer day about fifteen years ago my husband had a circular red rash above his belt-line; he recalled no tick bite but it was itchy.  He had not been in the woods or around deer and he didn’t feel sick, but I said (with absolutely no experience to back it up), "You have Lyme disease!"  

He looked at a photo of the typical bull‘s-eye rash in one of his medical books and thought it dis not quite match.

Bull's eye rash of acute Lyme infection

But by the third day he was not feeling so great and I made an appointment for him to see Dr. Manzella.  He resisted (of course) but he listened and he was immediately put on doxycycline for three weeks.  No blood testing was done since he was seen early, before the diagnostic (IgM) antibodies would appear.   

Within 24 hours the spirochetes responsible for the sickness were being killed off and he developed fever, chills, shaking, and muscle pain of the so-called Jarisch-Herxheimer reaction, confirming Dr. Manzella’s clinical diagnosis.  We were relieved.  But my husband was still achy and tired for about two months.  Adequate treatment, we are told, almost always eradicates the disease, but it took time to feel better.  What if the rash is missed and treatment is delayed?  What then?  

I asked Dr. Manzella.  With early widespread infection, there may be nervous system involvement with headache, stiff neck, and facial paralysis.  There may be a heart arrhythmia, or acute arthritis (usually of the knee).  The neurologic and cardiac problems resolve with the standard treatment of two to four weeks of antibiotics.  But the joint symptoms may remain troublesome for a few years despite therapy, even though bacteria are no longer found in the joint.  Why do people then talk of chronic Lyme?     

Dr. Allen Steere (who was the first to identify Lyme disease in 1976) in a recent review notes that “In about 10% of patients with erythema migrans (the rash), and perhaps a higher percentage of patients with neurologic Lyme, fatigue, cognitive complaints, and musculoskeletal pain can persist for more than six months, or even years, after antibiotic therapy.”  He notes that placebo-controlled, randomized treatment trials of antibiotics (the gold standard) in patients with this syndrome have not demonstrated clinical benefit, and that evidence for the persistence of infection has not (to date) been found (Steere 2017).  

Dr. Manzella said that he is in agreement with these thoughts, conclusions also supported by the Infectious Disease Society of America.  He warns that prolonged antibiotic therapy has substantial risks including the development of resistant organisms, the nasty C. diff diarrheal syndrome, and indwelling catheter-related infections.  As Dr. Steere says, “Additional studies are needed to better understand the pathogenesis of persistent symptoms and to determine the best approaches for symptomatic relief.”  We don’t have all of the answers, and we need to be careful while we are looking for them.

(For example, a pending legal suit against the CDC argues that it suppressed a DNA test for Lyme that is many times more sensitive than the ELISA and Western Blot tests that are

currently used. The scientific community is still grappling with the limits of the technique and we need to be patient as we wait for the answer.)

So how did my husband get his Lyme?  In the garden.  We “knew” of "deer ticks" and the local deer problem, but it turns out that it was the black-legged tick carried by white-footed mice that transmitted the bug.  The busy housing construction in our neighborhood disturbed their natural habitats and they ended up invading our property.  Or did we invade theirs?  

Where will the next zoonosis come from? And will we be able to manage it? And who will be there to help us? 

Maybe somebody who is busily writing and stressing over a middle-school book report.  

By Anita Cherry 1/27/18

Addendum for those of us worried about ticks and acute Lyme disease (having weathered the expected zoonotic pandemic), the Infectious Disease Society of America, the American College of Rheumatology, and the American Academy of Neurology note:

We recommend that prophylactic antibiotic therapy be given only to adults and children within 72 hours of removal of an identified high-risk tick bite, but not for bites that are equivocal risk or low risk (strong recommendation, high-quality evidence). Comment: If a tick bite cannot be classified with a high level of certainty as a high-risk bite, a wait-and-watch approach is recommended. A tick bite is considered to be high-risk only if it meets the following three criteria: the tick bite was from (a) an identified Ixodes spp. vector species, (b) it occurred in a highly endemic area, and (c) the tick was attached for ≥36 hours. 

From: AAN/ACR/IDSA 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. Clinical Infectious Diseases, Volume 72, Issue 1, 1 January 2021, Pages e1-e48. (A reliable and complete reference,)

AC and SC 4/12/24

Polly Rost, PhD:On The Other Side Of The Couch

Since the older parts of our minds evolved long before the late appearance of consciousness their “automatic” work is not accessible to awareness.   The function of our “adaptive unconscious” (as Dr. Timothy Wilson in “Strangers to Ourselves” calls it) is completely hidden from view.  

"Strangers to Ourselves"

Through talk therapy our fears, phobias, and traumas that reside deep in the ancient parts of our brain can be brought to awareness so that they can be understood, and inhibited.  It falls to the skilled psychotherapist to help us understand how to rebalance the system and alleviate distress.  It is sad that we often have to feel our hurt intensely before we look carefully into what makes us who we are.

I had met Dr. Polly Rost many years ago, and I decided to ask her for an interview.  She enthusiastically said yes.  She is a York native, and she received her Ph.D. at Temple.  She started her practice of clinical

Dr. Polly Rost

psychology in 1986 from a small rented office on South George Street.  She said that she had “no grand plan or vision” and  that the growth of her practice was solely “due to the growing needs of the community."  The practice has thrived, and her 14 therapists help meet the needs of our town inside a stately Victorian home a bit further north on the same street in the city where she began.  

I opened the weathered front door and sat in the small sun room on the side of the house and waited for Dr. Rost.  I remembered coming here years ago in pain. Wouldn’t it be easier, I thought, to hook ourselves up to Dr. Wilson’s “Inner-Self Detector”?  After attaching electrodes to our scalp and adjusting a few dials we could ask it questions such as, “What am I really doing here today?”  And the machine would display the answer... just like that!

Anyway, Dr. Rost greeted me and I followed her into her therapy room.  Gordon, her lazy gray cat, was lying on his back displaying his belly.  Sinking into the well-worn cozy wing chairs we sat across from each other.  The stray cat and Dr. Rost had found each other years ago behind the house.  I thought, “What makes him different than the others in the house who come and go?”  Why, he lives here, he stays here, and is protected.

I asked Dr. Rost how she came to be a therapist.  She quickly said, "I love science and people.  I was delighted, even in high school, by being sought after by peers.  I was known as being a problem-solver.  And I learned in college that I was helpful to those around me too.

Before Insurance Coverage for Mental Health

 I realized, on some level, that just being available and helping people figure things out was good in and of itself."  And that is what she has done for the past three decades.  I was curious to know how her practice has changed.

Without hesitating for a second she got up from her chair and walked over to a bookshelf.  She handed me the second version of the “Diagnostic and Statistical Manual of Mental Disorders” (so-called DSM); it was about 40 pages.  She then produced the 2013  “DSM-5.”  It ran for  947 pages, more than 20 times as long!   I was struck by the difference; here was evidence of great work in understanding and treating mental illness.  

Tattered DSM II, 1968

I flipped through the tiny book and my mind wandered to what it was like in the early 1980’s when I faced cancer myself.  I was given exactly three short once-over visits with an oncologist-psychiatrist, visits to be used over two years.  No “tools” were provided to deal with the emotional trauma of a cancer diagnosis, and I was not exactly sure what these sessions were supposed to do for me.  Maybe there was no appropriate DSM code back then for young patients such as me.  No-one saw that my coat of armour was missing a few laces.

We now do better.  Just the other day (11/20/17) the BBC reported a Malaysian study in which 20% of cancer patients had full-blown post-traumatic stress disorder six months after their cancer diagnosis, and that nearly 6% still had debilitating PTSD four years later. The hopeful finding was that, compared with other cancer patients, women with breast cancer were three times less likely to have developed PTSD. The difference seemed to be due to the early counseling these patients received. Patients with serious life-threatening illness like cancer no longer have to carry the hidden burden alone. Caring and empathic doctors like Dr. Rost and her staff can help them navigate through, and come to understand, the early anxiety and fear of trauma to be able to prevent problems later.

"The Neuroscience of
Psychotherapy"

She is pleased that there is more ready access to therapy, and that our culture is more willing to include improved psychological along with physical functioning as a goal.  She feels that there is more  respect for the power of psychology now, especially seeing that as a culture we have come to value the quality of life; our personal lives, our relationships with others, the all-important parent-child bond.  She is glad that the medical community and the schools recognize that a multidisciplinary approach to psychological stress “can make all the difference.”  

Dr. Rost is an optimist, noting that our understanding of biochemistry and the brain's workings has enhanced our ability to relieve suffering, and she predicts that “one day there will be a blending of psychology and neurology.”  

Who are your most difficult patients?" I asked.  She paused, and said that after she sees patients at the hospital for "group" and she leaves the third floor Psychiatry Unit someone may see her stumble and ask, “Are you okay, Polly?"  Her quick response is to say that she’s fine.  She said that she never leaves these moving sessions without being deeply touched by the depth of the pain experienced by the hurting patients.   

She wishes that “others could somehow appreciate how dark it can be at times” for those who suffer.   And she works “very hard to bring sunshine to them.”   Her patients know that she will never give up on them, and that they will somehow work things through together.

Feeling her own emotion surface as she spoke, I asked if she is spiritual.

“Yes,” she replied, “I am one of the few people that can be sitting still and sweating at the same time that all of my being is (invested) in the patient in front of me.  There are times when I hear it, but I am not sure how to get things across to the patient.  I say a quiet little prayer,  ‘Please help me put this in a fashion that can be tolerated and is useful,’ and then something magically comes.” That is good, in and of itself.  

The Couch (Freud's, not Dr. Rost's!)

When Your Doctor is Your Friend ("Insights from Dr. Sanstead and 35 Years of Practice in York")

Jack Sanstead, M.D.

We have an absolute need to live with other people.  As Rabbi Jonathan Sacks has noted, “We reproduce as individuals, but we survive as members of a group.“  This is how we are still here.  Dr. John Sanstead recently retired from his practice of medicine  and he frequently reminded me that we are “big social animals.”

When the brain is finished with the task at hand it lapses into a default network.  That is, what it does when it has nothing pressing.  Matthew Lieberman (in “Social: Why Our Brains Are Wired to Connect”) has studied this and concludes that the "default network" is there to help us do our most important job as humans, to learn how to cooperate and share with others.  Thousands of hours of brain activity go into making sense of the people around us and of our role in the group.

There may be a limit to the size of such groups. According to the anthropologist Robin Dunbar this relates to brain size.  Our large brain allows us to have stable relationships with 150 people, casual friends.   These are “relationships in which an individual knows who each person is and how each person relates to every other person.”  Fifty is the number of our close friends.  Fifteen is the number of people we confide in and sympathize with, but are not true intimates.  Five is our closest support group, our best friends or family members.  On the other end of the scale, we may be able to put a name to a face for 1,500 people.  The composition of groups changes through time.

The number of our closest supports

When I was 23 a member of my close group, my family doctor and neighbor, died two weeks after he diagnosed his own pancreatic cancer.  At his funeral those that gave eulogies felt deeply that they were his friends.  So did the other shocked mourners in the audience.  We all felt the same connection.

More than 40 years later my general internist who cared for and counseled me though several difficult problems retired, and I again had a sense of loss.  Though he could no longer address my health he did agree to an interview.  I wanted to know what he had seen in more than 35 years of practice in York and what his concerns were for the future.  We sat in his cozy living room with the soothing “tick-tock” of a grandfather clock to keep us company.

I put my iphone on the coffee table between us and tried to turn on the recording app but the little “working” thing went round and round so I resorted to pen and paper. 

Why did he decide to become a doctor?  At Dartmouth he majored in Chemistry and minored in Religion.   He considered basic research, but he realized he preferred the socialness of listening to people, that this is where he would fit in.  In the late 1960’s youthful idealism and the reality of  a deeply unpopular war permeated college campuses and shaped his view of a world that was not black and white.

Vietnam War protest at Harvard in the 1960s

How would he contribute?  He turned to medicine.  He got his degree from Jefferson Medical College and did Residency training at Duke and the University of Pennsylvania.  He settled in York for his practice of medicine and geriatrics.   He had mastered science and learned textbook medicine in training but had brought the ability to feel what others feel with him.

Dr. Sanstead joined a practice and taught residents.  He greatly enjoyed being needed and found that he could know his patients through active listening.  After establishing a diagnosis guiding the patient  through (sometimes difficult) treatment or (imperfect) management  was rewarding.  But he always remained careful when recommending action. He took time to know the patient and their family dynamics; time to befriend them.  He accepted them just as they were, hoping this would allow them to accept themselves.  He always saw the good.  And as a friend, he needed to protect. 

Among the problems confronting those with illness, problems that may be physical, emotional, psychological, or  financial, one that particularly worried Dr. Sanstead was the overuse of prescription medicines.  While medicines for hypertension, for example, have been spectacularly effective in preventing heart failure, kidney failure, and strokes, others he saw as of dubious benefit and of unproven long-term safety.

For this he directed me to “An American Sickness” by Elisabeth Rosenthal who notes that in “1991 the FDA relaxed its rules for what constituted proof that a drug was effective…(as) drug makers no longer had to show that their product actually cured the (illness)...they could measure things like blood markers” (p.99-100).  He saw that this warped the pharmaceutical industry, as “pushing” of drugs for profit became the sole driving force, not the welfare of the patient . The cost  of medicines soared, and the benefits were inobvious.  This made him feel sad.  He protected his patients by refusing to be swayed by the lure of using the latest (and heavily advertised)  drugs without convincing data to support their use.  (Direct-to-consumer advertising is permitted only here,  in New Zealand, and in Hong Kong.)  He was also exceedingly cautious not to order  testing or recommend surgery when the benefit was questionable or marginal.

Dr. Sanstead loved seeing his patients out in the community, and feeling a part of it.  He  loved learning from patients and watching them grow, and said that he would have seen them for free (well, maybe not entirely for free).

Since leaving practice he has felt somewhat lost, he sorely misses the socialness of his life’s work.  His own Dunbar number used to be in the tens of thousands, now it is a whole lot lower.

Published in the York daily Record 11/12/17.

Reclaiming the Heart and Soul of Medicine Through Storytelling

Andre Lijoi, M.D.

We connect with others by telling a story. We tell stories about what has happened to us, how we feel about it, and what it means. We tell especially important stories to our doctors.  Some we tell repeatedly, some we prefer to forget, and some still hold mysteries. After a routine office visit, I was handed a printout listing my diagnoses without any accompanying narrative. This made me anxious. Where was my story?

I heard that the best person to talk to about narrative in medicine would be Andre F. Lijoi, M.D.  Dr. Lijoi is the Associate Program Director of the York Hospital Family Medicine Residency Program. Since February he has been running a series of seminars titled: "The Future of Healthcare is the Story." I asked I could interview him for the paper. He quickly agreed and said he could give me about half an hour. Great. It was four-thirty Saturday afternoon when we sat at my kitchen table. I placed my iPhone down to record the conversation.

Dr. Lijoi’s program is open to students, residents, nurses, practicing physicians, clergy, and administrators.  The focus is on enhancing empathy and compassion by teaching how to be better at understanding the patient's life story.  This was once the essential task in caring for patients, for how else to know what was happening without sophisticated blood work, radiographs, CT scans, MRIs, and genetic testing, among other technical marvels?  But this skill has lost importance.  This “sacred sharing” should be preserved, and he would tell me why he started the program.

I glanced down at my phone to make sure it was recording and when I looked up I had missed the first part of his careful answer and missed his body language.  Sitting up straighter in my chair I tuned in.  His reason was that “Someone had to do something.”  

He was first drawn to the subject by experiences several decades ago at his first job following a residency at the University of Maryland.  This was in the Public Health Service in eastern Kentucky and he discovered something he was (somewhat) prepared for through his interest in literature.  

Cancer deaths 2014 by county

Appalachia in the early 1980s was then (and still is) one of the absolute poorest parts of the country.  Coal and tobacco were responsible for much chronic illness.  People had devastating illnesses caused by their life’s work, illnesses often picked up too late.  He was moved by their colorful but ultimately heartbreaking yet stoic tales of their hard lives.  He began to know and to love his patients through these stories.  This element had been missing plowing through (a top-notch) medical school and his (excellent) residency.  He realized that listening to the narrative, the full story, was good for the patient, and good the physician.  He saw this gap in the training of young doctors and he sought a fix.  

I looked down at my phone again; everything was fine.

While the electronic health record is excellent for standardizing the history, for seeing what was done, for viewing test results, and for insurance coding, the non-scripted elements that may reveal the critical part of the patient’s story are often absent.   Asking the “unscripted” questions and listening emphatically are necessary to understand the person with the illness, not just the illness.

How to foster this?   By studying the “humanities.”  His group discusses an excerpt from a book, or an article, or a poem that touches on aspects of the patient encounter relevant to narrative.  Dr. Lijoi gently guides things.  In the short time the program has been running he has witnessed his residents grow emotionally and professionally.  He has heard them say, for example,"I finally feel human again" or, “This experience took me to places I don't normally go with patients."  It made me sad to hear this.  This is where great joy comes from in helping patients, and until then the residents didn't know that they were missing that connection.  

(What’s with this storytelling business anyway?  We are hardwired to search for meaning.   Jonathan Gottschall (in “The Storytelling Animal”) says that we have a Sherlock Holmes in our brains.  This “homunculus” (the “little man”) reasons backward from what we observe now to show what series of events led to this moment.  The storytelling module in the left frontal lobe permits us to experience our lives in a meaningful way.  But don't be fooled.  The “interpreter” (of Dr. Michael Gazzaniga who studied split brains) is not perfect.  This little person sitting above and behind your left eye can be a fibber.  If she doesn't encounter enough information she will force a meaningful pattern anyway and you won’t even guess it.   So we may not tell the real story after all! What’s a parent to do? )

Don Quixote and  Sancho Panza on their quest

So, why does Dr. Lijoi feel strongly about fostering empathy and compassion by using the humanities? Because this effort makes one a finer physician (and a finer person).  He quotes William Osler, "It is a safe rule to have no teaching without a patient for a text, and the best teaching is taught by the patient himself."  Dr. Lijoi hopes that for his students the practice of medicine thereby becomes one of their “Dulcineas in life; (the) elegant sweetness for which one (in the manner of Don Quixote) fights relentlessly.

The cooly digitized medical record needs an analog component to provide warmth, and that component is the story.  Let’s be sure we take the time to get the story right as we work on it together.

(Thank you, Dr. Lijoi, for the three-hour interview.)

Anita Cherry

Published in the York Daily Record 10/29/17

Open Letter to Sen. John McCain ("Sen. McCain should think of the people as he fights his tumor")

Dear John McCain;

Once again, you feel the weight of a shocking diagnosis as you, once again, face your mortality and, once again, enter into patient-hood, and all that comes with it.  It is different for everyone, and every time.  Responding to a disease where the body has mistakenly turned against itself can make you feel betrayed by what you took for granted, namely, that your body would always work in your best interest.  You feel ambushed.  You are changed.  Who will you decide to be now?  

John McCain after surgery for glioblastoma

You are saddled with a new project; your old self is left behind, as “becoming” is once again your mission.  It has taken a long time to be yourself, and suddenly it is not enough, there’s more to be done.

While you might think the goal is to quietly slide back into the land of the well there are frightful decisions to be made.  Nothing happens without emotion, and the emotions here are especially potent. We are members of the only species that can imagine the future.  While imagining your response to, and hoped-for escape from, this disease many decisions have to be made.    These decisions require constant monitoring of information with clear perception.  This information is fluid and it needs an open mind that can adapt quickly when things change.   

Sometimes the choice of what to do next is difficult because what we know is simply not enough. But we have to decide and when we finally do we can move forward and we usually find that we cope better.

As we try to imagine the future it may be more helpful to actually see the future.  How?  By hearing from people who have already been there.  As you are thinking about treatment for your glioblastoma you may look to those who have made decisions already and use them as surrogates.  For example, this procedure worked, that did not, this medicine was easy to tolerate, that was not.   Such information is exceedingly useful to avoid going down the wrong path.  

But, and this is key, since you are a member of the U.S. Senate looking yet again to repeal the Affordable Care Act, at the same time as you are deciding for yourself you are also making decisions for all of us.  Fateful decisions about the shape of healthcare for all Americans.   

You see,  the question before you, that is, how to ensure that all have access to timely and affordable medical care, has been settled by nearly every other industrialized country on Earth, and the decision has been to provide universal coverage from cradle to grave.   

There was repeated resistance to the Social Security Act that was finally passed by Congress in 1935 and the bills for Medicare and Medicaid that were eventually signed into law in 1965.  If we could have polled the people of the future then about these programs we would have seen that they prevented much anxiety and human suffering.    

The diagnosis of an aggressive glioblastoma used to mean a certain and relatively quick death but there has been progress recently and there are now more than 80 experimental therapies being studied.   These are costly, but you are fortunate to have good insurance and connections and I know they will be offered to you and that you will be able to afford them. The term “clinical equipoise” means that there is uncertainty in the expert medical community about whether a treatment will be beneficial, as is unfortunately so with the newest targeted treatments for your brain tumor.  The term “equipoise” by itself means living in balance,  as one must learn to do when facing the uncertainty of serious illness.  

Perhaps I’m a dreamer, but maybe in this state of mindful balance you will see clearly into the future and be able to tell your colleagues what it was like when everybody had what they needed.

Sincerely,

Anita Cherry

Published in the "York Daily Record" 10/08/17

(John McCain's treatment was stopped and he died peacefully on 8/25/18.)