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[NNadir]

15. I don't know if you've ever had occasion to New York to the MOMA and see the Modigliani...

...Reclining Nude.

I've seen it many times myself.

There's a nice, cute, fluffy movie that I rather enjoyed watching with my wife on a lazy afternoon as a diversion, called "Like Sunday, Like Rain." It's about a super precocious boy/man who takes his "Nanny" on an intellectual tour of New York to avoid being sent by his absent mother to a Summer Camp.

There's a scene where they sit before Reclining Nude that's in the movie's trailer (1:50):

"He died in penury and squalor in 1920 at the age of 35."

We have other Modigliani's locally in the Princeton/NY/Philadelphia area, and no matter what else is in the room, you are compelled to spend time with any Modigliani you find there.

I definitely feel for your suffering; it sounds like you've been going through medical hell, as Modigliani did throughout his short life.

For many years, they had Picasso's "Guernica" at the Modern, and I saw it many times there - I've also seen it (where it's out of reach way up high) in Madrid. It's one of the most overwhelming paintings I have ever seen, it's clear that I have nothing against the highly successful and very wealthy and much rewarded Picasso. Picasso was Modigliani's contemporary, the two men met. Like Van Gogh, Modigliani's fame was posthumous; his art gave him no fame or money while he was alive.

And so when one looks at a Modigliani, one is struck more than anything by how it is that someone managed so much beauty in the context of so much pain.

I just thought, as an admirer of your work, that I might mention that.

As you mention having already have had health conditions including high blood pressure in 2005, you may be my contemporary; I'm an old man. Struggling as I am with old age, I am amused to find myself as at least one old man, (me), two possibly (you) sitting around talking about our meds.

Many years back, before my high blood pressure was diagnosed, I worked to support the development of a drug (primarily in a commercial sense, with some input, communication rather than experience, on synthetic considerations in a critical reagent in its synthesis) called Omapatrilat. It was expected to be a blockbuster, and billions of dollars were spent developing it - a tiny portion of which went to the company for which I worked - because it successfully treated a rather large class of patients, reportedly roughly 30% at that time, dominated by African Americans, who did not respond to blood pressure medications. In analyzing the clinical data, however, as I recall it, it was found that a subset of patients, suffered from pulmonary edema, with a few nearly fatal episodes being observed.

The application was withdrawn. I have always wondered to myself what the ratio of people saved from strokes - those with recalcitrant high blood pressure - and those who might have died from a pulmonary edema event might have been.

I say this only as an observer, and not one trained in or involved in drug approval processes, in which I only participate peripherally.

Today, with at least the potential for "personalized medicine" based on genetic mapping, it's quite possible it may have proved possible to approve that drug and save lives that otherwise might not be saved but lost to high blood pressure.

It appears that you may have been recalcitrant. Beta blockers are an old strategy, and from my limited knowledge, the reason there are other classes, is that they are not particularly effective at controlling high blood pressure. (My wife takes propranolol for arrhythmia; others take it as a sedative.)

My first blood pressure medication was lisinopril, and when I took it, I coughed like hell; I couldn't stop coughing. Like omapatrilat, it is a peptidomimetic designed to work on the ACE enzyme; omapatrilat also worked by another mechanism in addition to ACE inhibition, "NEP" inhibition.

My doctor switched me to one of the sartans, Valsartan, which has controlled my blood pressure perfectly for many years.

Those of us who cough with lisinopril and related drugs like captropril and enlanopril in the modified peptide class almost certainly have polymorphisms (mutations) in our ACE2 enzymes.

(Angiotensin-Converting Enzyme (ACE) Gene Insertion/Deletion Polymorphism and ACE Inhibitor-Related Cough: A Meta-Analysis)

This knowledge led me to be insufferable around the house during the early days of Covid, since I told my wife that I was a mutant and Sars-CoV-2 viruses would not be able to deal with my "superior" ACE2 for binding. (This was pure speculative nonsense, which my wife knew quite well; like everyone else, I was powerfully concerned that I might get Covid.) Nonetheless, I had fun telling my sons that I hoped they'd gotten my mutant genes rather than their mother's inferior (non-super) ACE2 genes. (Fortunately she's gentle and has a sense of humor, so I didn't risk getting hit over the head with a frying pan.)

Angioedemas are, or course, involved in TIAs, but with most drugs, we have to balance risks, which is not always an easy call, and one which often must be made blindly.

There was a shortage of Valsartan recently with the discovery of nitrosamines as a side product of a what I regard as a very wise and environmentally sound but sloppily monitored, and evaluated decision, to recycle a solvent. For a short time, I was switched to losartan, which worked but was later to be found to be subject to the same risk.

I have Barrett's esophagus, a precancerous condition for the cancer that killed my father and uncle, esophageal cancer. This cancer is driven by tobacco related nitrosamines, but other nitrosamines work very similarly to induce cancers, via alkylation of particular residues in a nucleic acid sequence that causes a substitution, a single nucleotide polymorphism, in a protein that suppresses cancer.

I recently gave a lecture on this topic at an international symposium and participated in the "expert panel," despite not actually being "an expert" on the level of the other experts on the panel. So I know all about the risk, but at the end of the day, I wanted my sartans. I'll take the risk of cancer over the risk of strokes. I cannot live in a risk free world.

Anyway, to return to Modigliani, formally he died just over a century ago, but his art is very much alive.

We all wish you recovery and a pain free existence - I'm sorry you, like my late mother-in-law, are a collateral casualty in the "war on drugs" - but inevitably what we leave in the world, should anything remain of us, is our works. I do hope at least when you take your ASA, it give you some relief. (It works great for me.) I would suggest though that your work is more important than your body. It can live when you cannot.

You have made great art, and led an interesting life. While deploring your pain, I celebrate the totality of what you have brought to us.

Be well.