The SIDS prevention campaign, now named Safe to Sleep, continues across the world. Dramatic decreases in the rates of SIDS have been achieved in countries where the educational campaign has been introduced, including the United States and including Native American lands within the U.S.
Maybe our miracle baby survived the night and beyond because the nurse and I turned him on his back to pull his ankle with the twine and reflex hammer. Maybe the miracle was that he was seen the day before for viral pneumonia, alerting his mother to a problem and prompting her to venture out on this rainy night when the baby “just didn’t look right.” Or maybe it was just all of our good fortunes to be there together, in the right place and just in time.
For more about SIDS and safe sleep for babies, see:
National Institutes of Health “Safe to Sleep” website: https://www.nichd.nih.gov/sts/Pages/default.aspx
Date of event: 1979
The Vitamin That Worked Wonders
Mortimer Poncz, MD
Baby Isadora came to our neonatal intensive care unit with massive diarrhea and in heart failure. She was the second child for these parents, immigrants from a small town in Europe. Their first child had died in infancy of unknown causes; it wasn’t long before we discovered the reason for that child’s death as well as for Isadora’s life-threatening problems.
I was in my fellowship training in hematology at the time, and we were asked to evaluate Isadora for severe megaloblastic anemia. Anemia means low red blood cell count, and megaloblastic means that the red blood cells she did have were much too large. The anemia contributed to her heart failure; having too few red cells, and ineffectively large ones at that, made the heart work much too hard to provide oxygen to the rest of the body. But she also had a poorly functioning heart even after transfusing her with healthy donor red cells.
When I first saw Isadora, she was terribly sick—wasting away from malnutrition due to her diarrhea, and bloated from her heart failure. We hurriedly did testing on her blood and her bone marrow (where the blood is made) and discovered her anemia was due to severe deficiency of a B vitamin called folic acid. Folic acid is essential for nutrition, for making normal cells (including blood cells), and for normal development of the nervous system. Normally, there is enough folic acid in a baby’s diet of milk to sustain her, but for some reason Isadora wasn’t absorbing the vitamin from her gastrointestinal tract, explaining her severe diarrhea. She was clearly dying in front of our eyes, and it was now apparent her sibling had previously died of the same condition.
At the time, there were a few cases described in the world’s medical liter-ature of newborn babies with failure to absorb folic acid. Disappointingly, most of these babies died, and the two or three who had survived were left with severe brain damage, calcifications in the brain, difficult-to-control sei-
zures, and mental retardation. Realizing Isadora’s intestines were not absorb-ing folic acid, we tried giving the vitamin to her with shots. But even if we could get enough vitamin into her by that route, we still had to determine if the folic acid was getting to her brain where it was critical for a normal neurological outcome. It was known that for folic acid to reach the brain it needed to cross the blood-brain barrier, a tight layer of cells in the smallest blood vessels of the brain that prevents certain substances from reaching the brain. So we did a spinal tap, a procedure to withdraw a small amount of cerebrospinal fluid (CSF), the fluid bathing the brain and spinal cord, to measure the levels of folic acid. We sent the specimen to a research laboratory in the Bronx, New York, which was the only lab in the country at the time testing CSF for folic acid levels. We discovered she had virtually no folic acid in her CSF—a situation which would lead to severe brain damage even if we were able to save her life by treating her anemia and heart failure with the injections.
At this point, I hypothesized that perhaps Isadora and others like her must have had two barriers to folic acid penetration—the one we knew about in her gastrointestinal tract, and another barrier blocking folic acid uptake into the brain. I needed to find a way to get folic acid into her brain (injections into the brain itself would be much too dangerous to give on a daily basis and local concentrated folic acid could itself cause seizures). Reviewing the chemistry of folic acid, I recalled that a related molecule called folinic acid had many of the properties of folic acid but also had a modification of its chemical structure that might allow it to bypass the blood-brain barrier. Folinic acid had been used (and is still used) in cancer therapy, but had never been tried in the very rare type of folic acid deficiency that was killing Isadora.
With her parents’ permission, I transferred Isadora to a special research unit at our hospital. There, with the approval of the hospital’s human experiment review committee and the consent of her parents, we administered folinic acid to her by shots, carefully monitoring her for side effects. I stayed overnight with her to do three spinal taps following the doses of folinic acid, and arranged with the same laboratory in the Bronx to measure the levels of folic acid in her spinal fluid. If the folinic acid was reaching her brain, the levels of folic acid in her CSF should rise—and they did! I was beyond ecstatic, truly feeling as if I had found a mechanism to not only save this little baby’s life, but to also give her the opportunity to grow up intellectually intact and have a full life.
We put Isadora on a regimen of once daily shots of folinic acid. Her diarrhea resolved, as did her anemia and heart failure. Most importantly, as she grew up, we anxiously had her tested and retested to follow her neurol-ogic development and quality of life. We published her case in the medical literature as well as two follow-up reports describing her excellent progress as she went to college and then went on to marry and have two children of her own.
Isadora represented the first cure of this severe form of folic acid deficiency, the first patient to not only survive but with no brain damage. Just as importantly, she hopefully represents the last child who will ever suffer from this rare disorder. Occasionally cases of this type of severe folic acid deficiency still occur. Since our report of this case, it has become standard to treat all such cases as we did for Baby Isadora. And, as with Isadora, the outcomes have been excellent.
Her disease is genetic (inherited), but it requires both parents to be carriers of this very rare defective gene. Isadora’s parents were obviously both carriers, but Isadora’s husband was not and their children are entirely normal. The defective gene responsible for this disorder has also been identified in part because of our studies of Isadora. It is called the “proton-coupled folate transporter gene.”
The care of this baby, who is now, amazingly, a young lady, has contributed greatly to science and to the understanding of how this B vitamin, folic acid, works in the body.
It clearly works wonders.
The original report of this baby’s treatment, as published in the medical literature, can be found here:
Poncz M, Colman N, Herbert V, Schwartz E, Cohen AR. Therapy of congenital folate malabsorption. 1981 J Pediatr. Jan;98(1):76–9.
The follow-up reports and identification of the responsible gene can be found here:
Poncz M, Cohen. Long-term treatment of congenital folate malabsorption. A. J Pediatr. 1996 Dec; 129(6): 948.
Min SH, Oh SY, Karp GI, Poncz M, Zhao R, Goldman ID. The clinical course and genetic defect in the PCFT gene in a 27-year-old woman with hereditary folate malabsorption. J Pediatr. 2008 Sep; 153(3): 435–7.
Date of event: 1980s–2010s
The Thirty-Year Miracle
Kenneth G. Adams, MD
I am not a big believer in miracles, but please indulge me in some philosophical rambling about the term. Is there really such a thing as a “miracle”? Moses crossing the Red Sea might be explained by his knowledge of weather patterns. The “burning bush” due to a spontaneous brush fire. The “miracle of flight” by the Wright brothers occurred after much studying, obse
rvation, and numerous flight trials. I line up more on the side of Thomas Edison, who famously stated that genius is “One percent inspiration and 99 percent perspiration.” In the medical field, we all “perspire” a lot. And, sometimes, miracles are the result.
Years ago I consulted on a patient in a local hospital’s intensive care unit. He was in a prolonged coma from complications of heart disease. His family was very astute medically and understood the limited chance he had for any recovery whatsoever. For weeks I advised the family to be very pessimistic about recovery. Then he somehow regained consciousness for a few days, talked with me and his family—only to spiral down again.
I have no explanation for how this all happened. Surely his family thought it a miracle that they were able to spend quality time with him before his death, time they never thought they’d have. But the intensive care treatments we were able to provide in terms of blood pressure and breathing support—the “perspiration”—had to have helped, right? Exactly how and why they helped so dramatically for a few days just before his death, and not at all before that or after that, well, I can’t really say.
Then there’s “broken heart syndrome.” We all know stories of someone who passed away a short time after their spouse of many years died. My wife’s grandparents died within a week of each other after more than fifty years of marriage. They were reliant upon each other. After all these years of perspiration— expert doctors and scientists trying to figure out what happens in these cases—there was finally some inspiration from specialists in Japan. This syndrome now has a name and an explanation. It’s called takotsubo cardiomyopathy. It occurs in situations of great stress. One of my patients entered her home, found her husband dead and proceeded to develop takotsubo cardiomyopathy. It has all the markings of a heart attack but is different. There is usually no evidence of blockage in the coronary (heart) arteries the way there is for typical heart attacks. And the hearts in these “broken-hearted” patients are, for lack of a better term, broken. More precisely, they have the characteristic shape of a takotsubo, the Japanese word meaning octopus pot (a type of trap used to catch octopuses; the octopus crawls into the pot and can’t get out, with only a part of the creature protruding from the opening of the pot). There is ballooning (protruding) of the entire left ventricle (the main pumping chamber of the heart), except for the base (the “pot”). On imaging studies, it looks like an octopus pot. Takotsubo cardiomyopathy seems to be stress-induced. No one understands how the heart muscle weakens under stress, but the real miracle here is that most patients recover fully within months. How does the muscle strengthen again? My patient, the one who found her deceased husband, fully recovered her heart strength and function. If only we could harness this miracle of heart muscle recovery and use it in other situations.
Those cases, and the hundreds of other heart patients I’ve cared for since my training as a cardiologist—much perspiration, indeed—leads me to describe what I call the thirty-year miracle. We have witnessed an amazing trajectory in the treatment of coronary artery disease over the past three decades.
* * *
It was 1980 and I was a medical intern (physician-in-training) standing at the bedside of one of my patients in the intensive care unit. He was in the midst of a heart attack with severe chest pain, with significant changes on his cardiogram test, predictive of impending severe damage. I’ve got nothing to offer except pain medicine and nitroglycerin. Just that week my supervising resident physician had given me a new article from the medical literature about the use of long-acting nitrates like nitroglycerin in coronary artery disease. That’s where we were. I was watching a man have a heart attack. I was perspiring but not because I was doing much.
* * *
Now take a time-lapse journey with me ahead through the subsequent thirty years. New medicines (beta blockers and calcium channel blockers) were added to our armamentarium to protect the heart in the midst of a heart attack. Then a new study was published in a prestigious medical journal about plaques (deposits of cholesterol, fat, and calcium on artery walls) rupturing inside the coronary arteries and forming clots when a heart attack occurs. This was the inspiration we needed. This led to the era of clot-busting therapy and debates about the best way to break apart clots in the coronary arteries before permanent damage to heart muscle occurs—lots of perspiration trying to figure that out.
The whole thing was messy since this therapy affected the whole body—what breaks up dangerous clots in the heart arteries can cause dangerous bleeding elsewhere. That led to the question of whether we should try to deliver the clot-busting drugs directly into the heart arteries (rather than to the whole body) by catheterization (where a tube is inserted through a vein in the groin and threaded up into the heart) while the patient was in the midst of a heart attack. More perspiration that ultimately led us to conclude catheterization and squirting clot-busting medicines directly into the heart arteries is a good thing.
And then we had coronary stents. Stents are small pieces of mesh that are threaded into the arteries of the heart and used to stretch the narrowed or blocked arteries. Not great at first because of the high rate of clotting in the stents, causing the arteries to become blocked again. And it could take hours to deliver the stent into the artery. The technology was early, and better guidewires and steering devices were yet to come. Medicated stents to prevent re-blockage were the next big thing. They were much better and by now easier to deliver into the artery. There were still problems but lots of perspiration and bursts of technological inspiration led to better stents and anti-clotting treatments that reduced the re-blockage rate to a low level.
Which brings us to the twenty-first century. Dr. Eugene Braunwald has been at the forefront of cardiology for the past fifty years, providing much of the inspiration. He showed us that “Time is muscle.” The faster we act, the less damage occurs to heart muscle during a heart attack. What can we do in the midst of a heart attack to help? We now know there is clot in the heart artery, and we have great stents to open blocked arteries, and we have better anti-clotting regimens to prevent re-blockage, and we know quick action is better. So we now take patients with certain types of heart attacks immediately to the catheterization room to get to the culprit artery as quickly as we can and put a stent in it. This process has been working so well that it is now done in local community hospitals without surgical backup. I wish I knew then what I know now. My patient back in 1980, having the heart attack while I could do little more than watch, would have called it a miracle.
It seems like it was medieval times when we were treating heart attacks thirty years ago. We may have done as much good by throwing a few leeches on (actually leeches might have led to some clot-busting, but that’s another story entirely). What will the next thirty years bring—or for that matter, the next thirty months, or thirty days? Our continued perspiration, with bursts of inspiration, is already leading us to improve stents further (making them biodegradable, for example), and trying to identify the vulnerable plaque that might rupture in a coronary artery before it happens.
An evolution over thirty years may not be what people generally refer to as a miracle, unless of course you are on the receiving end of an extraordinarily effective stent at the time of a heart attack and end up with no permanent damage to your heart. As I look back, as I suppose many of us do at this time in our careers, and see the transformation in what we can do and what might be coming down the road, it is nothing short of miraculous.
Date of event: 1996
A Miracle in Its Day, and Then Another
Mark F. Cotton, MMed (Paed), PhD
The setting is Cape Town, South Africa, in early 1996. Although we were seeing increasing numbers of cases of babies born with AIDS, there were no public programs in place yet for treating or preventing the infection in babies. Today, of course, we have effective medicines for both mothers and babies with the infection, but twenty years ago there were no medicin
es available in the public sector (the few wealthy patients with AIDS could purchase medicines privately). Today we have effective programs to prevent transmission of HIV from infected mothers to their babies—then we had no such programs. Today we have special clinics for HIV-infected adults, children, and babies—there were essentially none in 1996, and at the time we didn’t even realize the extent of the problem. We hadn’t started documenting the cases yet because they were difficult to recognize and the tests to make the diagnosis were either not widely available or of little utility—it did no good to know about an infection we could do nothing about.
So babies came to our clinic or were admitted to our hospital with the ravages of AIDS, and there was nothing to offer them. These are the stories of two babies with AIDS, very early in the South African epidemic of the disease, when we were happy to take any small miracles we could get.
Case One
A nine-month-old boy was admitted to our hospital with severe blockage of his upper airway. This means that he was not able to adequately move air from his nose and throat into his lungs. The cause of his obstruction was extreme enlargement of his tonsils and adenoids, and swollen lymph nodes protruding into the back of his throat. We initially treated him with medicines to relieve his symptoms, such as decongestants, and a spray of steroids into his nose to reduce the inflammation. We gave him continuous oxygen through a tube that went from his nose to the back of his throat. Because of several other worrisome findings on his physical examination, such as a yeast infection in his mouth (thrush), an enlarged liver and spleen, and severe weight loss, we tested him for AIDS. Not surprisingly, he was positive. He had his tonsils and adenoids taken out and his breathing improved enough to go home. Recall from my comments earlier, we were not yet treating kids with AIDS medicines in South Africa.
Miracles We Have Seen Page 25
