AIR IN THE BRAIN

 

 

         When looking for tumors, abscesses, and other lesions of the brain, physicians today turn to CT and MRI scans. That was not always the case. In the nineteenth century, a careful history and neurologic examination provided the only means available to diagnose and to localize such lesions. Since only the rare surgeon ventured into the cranial cavity without more concrete information, it was the autopsy, not surgery, that confirmed the clinical findings. 

         The discovery of X-rays in 1895 brought hopes of easier diagnosis, but the hopes foundered when tumors, brain tissue, and fluids all appeared gray, lacked contrast, and were indistinguishable. One surgeon lamented that the brain was still “a dark continent.” A possible solution was to introduce an agent that provided enough contrast on X-ray to demarcate a lesion. At Johns Hopkins Hospital, a rising neurosurgeon, Walter Dandy, tried several contrast agents that urologists used to visualize the bladder and ureters on X-ray, but in animal trials they were all too toxic to brain tissue. It was

Walter Dandy (Wikipedia)

common knowledge, though, that air appeared darker than soft tissue on X-rays. Why not introduce air into the ventricular system to provide the contrast?

         To accomplish this, a knowledge of the circulation of spinal fluid, the clear fluid that fills the ventricles and circulates over the entire brain, was necessary. Fortunately, Dandy had recently worked out the fluid dynamics in animal studies done in the Hunterian Laboratory at Hopkins. (The original name for the laboratory was the Magendie Laboratory but, after vociferous demonstrations by antivivisection activists, “Hunterian” replaced it.)  

Dandy began with children, primarily ones with hydrocephalus, injecting air directly into the ventricles through the still open space between fontanelles on top of the cranium. He needed to withdraw an equal amount of fluid to avoid changes in pressure, a tricky balancing act. His first paper on pneumoencephalography (PEG), as it came to be called, was in 1918. Soon after, he tried introducing air by lumbar puncture into the fluid-filled space around the spinal cord and published satisfactory results. This technique required rotating the patient in various ways, not all comfortable, to allow the air to move up the spine into the desired areas of the brain. He did not pursue the spinal approach, however.

Dandy's first X-rays using air to visualize the ventricles.
Here, the contrast is reversed, the air a lighter shade. (Hathi Trust)

         A year or two later, in Braunschweig, Germany, Adolf Bingel, chief of Internal Medicine at the Braunschweig Hospital, aware of work in Norway (and unaware of Dandy’s publications) using air
through the spinal route to see spinal tumors, adopted the lumbar approach. He noticed by chance that a patient, X-rayed the day after air was introduced spinally, showed air in the cranium. Trials on cadavers confirmed this route to the brain. Like Dandy, he showed that the air could outline the ventricles and provide contrast over the brain surface. His main concern about the spinal approach was that if the fluid pressure above grossly exceeded that from below, the stem of the brain could be squeezed, a life-threatening possibility. To avoid this, Bingel devised an apparatus to ensure that the spinal fluid pressure remained stable during the procedure, an important step (see illustration). He became aware of Dandy’s work with the lumbar approach only after his own first publication. Meanwhile, Dandy had returned to the ventricular approach, allegedly fearing potentially dangerous pressure differentials. Bingel, on the other hand, feared the direct ventricular injection approach, having lost two patients after using it. 

Frontal view of ventricles from paper by Bingel (Hathi Trust)

         Adolf Bingel appears to be an underappreciated innovator. Born in 1879 in Koblenz to a coal-and-wine-merchant father and the daughter of the famous guidebook publisher Karl Baedecker, he studied medicine at the University of Tübingen. He worked in academia in various places and was finally appointed chief of the medical service at the Braunschweig Hospital, a teaching hospital. He had already done research on blood pressure measurement and renin physiology and took up research on leukemia, syphilis therapy, pernicious anemia, neurologic problems, and more. He was a pioneer in needle biopsy of the liver as early as the 1920s. Over a period of 30 years, he conducted three blinded controlled trials of diphtheria antitoxin vs horse serum and found them equivalent, a controversial conclusion. It was at the Braunschweig Hospital, in the chaotic years after WWI, that Bingel began pneumoencephalography. He remained there through WWII, dying in 1953.

         In early days physicians removed most of the spinal fluid, replacing it with air. This produced severe headache and nausea, sometimes requiring anesthesia, and there were occasional fatalities. Understandably, pneumoencephalography was not widely accepted. In the 1930s the radiologist Cornelius Dyke and the neurosurgeon Leo Davidoff, at the Neurological Institute affiliated with Columbia-Presbyterian Hospital in New York, found that smaller amounts of air provided equally satisfactory imaging results. Fewer side effects and improved safety led more physicians to adopt the procedure, though it was still not risk-free.

To ease the distribution of air into the ventricles and over the brain surface, moveable chairs were devised that could move the patients into almost any position. They bore the interesting name of “somersault chairs,” and indeed, using a side arm, tilted the strapped-in patient into bizarre positions, maneuvers that made some radiologists nervous. Headache and vomiting were still common.

         The 1950s brought change with the introduction of angiography, followed by CT scanning in the 1970s, then MRI scanning. Compared to the new scanning techniques PEG seemed quite primitive and the difficult and potentially dangerous technique quickly passed into the realm of interesting historical curiosities and medical history blogs. 

 

SOURCES:

 

Marmaduke, M E, et al, Walter Dandy: The Personal Side of a Premier Neurosurgeon, 2002; Lippincott Williams & Wilkins.

 

Dandy, W E, “Ventriculography Following the Injection of Air into the Cerebral Ventricles.” Ann Surg 1918; 63 (1): 5-11.

 

Müller, J, et al, “Adolf Bingel, the Second Inventor of Lumbar Pneumoencephalography.” Amer J Neuroradiol 1995; 16: 487-90.

 

Kieffer, S A, “Cornelius G Dyke and the Neurological Institute of New York: The Foundations of American Neuroradiology.” Amer J Neuroradiol 1997; 18: 801-9.

 

Hoeffner, E G, et al, “Neuroradiology Back to the Future: Brain Imaging,” Amer J Neuroradiol2012; 33: 5-11. 

 

Trohler, U, “Adolf Bingel's Blinded, Controlled Comparison of Different Anti-diphtheritic Sera in 1918,” J Roy Soc Med 2011; 104 (7): 302-5.

 

 

        

 

 

 Theodor Bilharz and Egypt’s

Ancient Disease

 

         The American parasitologist Norman Stoll, in 1946, delivered an address to an assembly of parasitologists entitled “This Wormy World,” in which he recounted the hundreds of millions of people infested with helminths globally.

Thus, it is not surprising that, in 1851 a young German physician, Theodor Bilharz, bending over an autopsy table in Cairo, Egypt, found in the corpse’s portal vein (that carries blood from the intestines to the liver) a worm, the first ever seen within a blood

Theodor Bilharz (Wikipedia)

vessel. Further autopsies revealed eggs with a spine at one end that produced irritation and bleeding in the bladder wall and passed out in the urine. The worm eventually received the designation Schistosoma hematobium and the disease resulting from its presence became known as schistosomiasis. An alternate name is bilharzia, named after the discoverer of the worm.

         Why was Bilharz in Cairo? A European presence in Egypt began with Napoleon’s invasion in 1798. The general’s entourage of highly skilled scientists, linguists, and scholars made it clear that progress in medicine and the sciences was virtually nonexistent. A

Muhammed Ali Pasha (Wikipedia)

subsequent ruler, Mohammed Ali Pasha, undertook the task of modernizing the country. This ruthless and visionary ruler first attempted to build an army along European lines, but disease outbreaks kept decimating the troops, highlighting the need for sanitary reforms. Ali, through an emissary, invited Antoine Bertelemy Clot, a physician practicing in Marseilles, to intercede. Ali put Clot in charge of a military hospital in Abu Zaabal, northeast of Cairo, to cope with the smallpox, plague, and cholera that crippled his army. Looking to the future, Ali also asked Clot to organize a medical school. The first students knew no French and lectures required

Antoine Clot "Bey" in Arab dress
(Wikipedia)

 translators, though eventually French texts appeared in Arabic and students learned French. Dissections, fiercely opposed by conservative clergy, were introduced slowly, starting with dogs (only from Christian or Jewish owners), progressing to autopsies on deceased slaves, and finally to dissection/autopsy on others. For safety, guards were posted around the pathology quarters. Ali sent promising students to Europe for advanced study. Ten years after the school opened, 420 students had taken the Hippocratic oath on receiving their medical diplomas.

Clot Bey teaching anatomy, Cairo, 1829, unknown artist (Wikipedia)

In 1837, the hospital and school moved into a 15^th century palace along the Nile, in Cairo, and was renamed the Kasr el Ainy Hospital after the builder of the palace. The school flourished and Cairo’s first printing press, purchased in Milan by Ali, turned out more and more texts. Smallpox vaccination was introduced and epidemics subsided. Muhammed Ali awarded the honorific “Bey” to Clot for his service.

 In 1848 Ali retired, succeeded in a year by Abbas I, who disliked the French. Clot Bey and the faculty left, and the school and hospital deteriorated. To save the medical service, Abbas turned to Germany, where Wilhelm Griesinger, a professor of pathology in

Wilhelm Griesinger (Wikipedia)

Kiel, accepted Abbas’ call to step in as director of the hospital and medical school. Griesinger had known Bilharz as a former student who was interested in helminths and invited him to Cairo as professor of pathology. Griesinger, on a two-year contract, returned to Germany 1852, later to pioneer in neuropsychiatry, while Bilharz stayed on, entranced by his exotic surroundings.

Bilharz was perhaps as much a biologist as a doctor and was fascinated with the variety of flora and fauna before his eyes. He discovered two other intestinal parasites and did research on electric eels. He moved to a non-European part of Cairo to mix with locals and took an interest in the language and local customs. He corresponded regularly with naturalists in Germany. In 1858, tragically, he joined an exploratory expedition to the Red Sea under Duke Ernst von Coburg-Gotha, serving as physician to the

Grave of Bilharz in Cairo (Wikipedia)

duchess. Though the duchess remained well, Bilharz, succumbed to either typhus or typhoid fever, it is not clear which. He was 37 years old. His grave is still preserved in Cairo. 

     Bilharz had recognized only one of the three species of Schistosoma. The one other species found in Egypt, Schistosoma mansoni, was not identified until 1902 when Patrick Manson (the “father of tropical medicine”), in London, distinguished it from Bilharz’s worm. The entire life cycle was worked out in 1915 by Robert Leiper, a British parasitologist called to Egypt at the outbreak of WWI to advise on how to keep British troops free of schistosomiasis. There he identified the intermediate snail host, solving the puzzle.

Published drawings made by Bilharz. Figs 11-14 are of S hematobium (Hathi Trust, click on image 
to enlarge)

Schistosomiasis is an old Egyptian disease. Ancient mummies show remnants of the parasite and Arabic texts, including those of Avicenna, describe bloody urine. Wading or swimming in infested water allows the microscopic early stage of the parasite to penetrate the skin and develop into adult worms. Their eggs produce damaging effects on the urinary and intestinal tracts and the liver. The Aswan dam, by enhancing irrigation, resulted in greater exposure of the farmers as they worked barelegged in augmented irrigation channels. The prevalence of the infection rose to over 70% of the population in some areas and was a drain on the economy. Fortunately, in recent years a combination of public health measures and the administration of easy to take, oral medication (praziquantel) has greatly reduced the impact of this formerly widespread and debilitating disease.

The influence of Bilharz was lasting, and he was fondly remembered. With the cooperation of the West German government, the Egyptian government constructed the Theodor Bilharz Research Institute, opened in 1977. Its mission is the control of endemic diseases. And the Kasr El Ainy Hospital is now a major medical center in Cairo. 

Kasr Al Ainy Hospital today (Wikipedia)

SOURCES:

Lotfy, W M, “Human Schistosomiasis in Egypt: Historical Review, Assessment of the Current Picture, and Prediction of the Future Trends.” J of the Medical Research Institute 2009; 30 (1): 1-7.

 

El-Dib, N A, “Theodor Bilharz and a Life Trip to Egypt.” Parasitologists United Journal 2019; 12 (1): 3-7.

 

Mahfouz, N B, The History of Medical Education in Egypt, 1935; Government Press, Bulaq, Cairo.

 

Stanisch, F W, “Wilhelm Griesinger (1817-1869)” 2007; Dictionary of Medical Biography London, Greenwood, 2007, v.2, 582-3.

 

Kloos, H and David, R, “The Paleoepidemiology of Schistosomiasis in Ancient Egypt.” 2002; 9 (1): 14-25.

 DINNER AT EIGHT WITH 

         ENGLAND’S FIRST UROLOGIST

 

 

         One of the most painful medical conditions is a bladder stone. Less common today, bladder stones at one time plagued young and old alike, from kings to paupers. Until the early nineteenth century, sufferers had a choice between enduring the pains or resorting to an operation that involved cutting directly into the bladder, usually from below, without anesthesia, to remove the stone. Understandably, the surgeon had to be lightning-fast and precise at the same time. William Cheselden was the leading practitioner of this operation in 18^th century England, accomplishing it within 24 to 60 seconds.

         In the early 1800s a French doctor, Jean Civiale, developed a snare that could be passed through the urethra and grab the stone.

Jean Civiale (Wikipedia)

Another probe, a slender drill, was then threaded through the first instrument. Drilling a few holes in the ensnared stone would usually crumble it enough to allow flow to the outside. Civiale founded probably the world’s first urology service at the Hospital Necker in Paris, relieving many sufferers without surgery. His fame and his practice grew rapidly.

         One of Civiale’s students was a young Englishman named Henry Thompson. Born in 1820, Thompson worked at first in his father’s tallow business, then decided to study medicine. He earned early recognition with a prize essay on urethral stricture and soon thereafter published a book on prostate diseases.

Sir Henry Thompson, photo by Walery 

(Wellcome Library)
       During an educational trip to the continent, he learned the lithotrity technique from Civiale and, seeing a niche, opened a urologic practice in London, the first in England to specialize in urology. He improved the transurethral device making it easier and faster to crush stones. Anesthesia had just been introduced, allowing patients to undergo the transurethral procedure without pain. He published further works on lithotrity, prostate disease, and other topics, wrote numerous articles, gave lectures, traveled to the continent for consultations, and devised new surgical approaches to bladder problems. He earned a knighthood and attracted prominent patients, including Queen Victoria’s physician, Sir James Clark.

         The queen’s uncle, Leopold I, King of Belgium, was a victim of bladder stones and, during a visit to England, consulted Thompson. Thompson referred him to his former teacher, Civiale, but after several tries Civiale was unable to remove the stones. Another surgeon tried and failed, and Thompson, under Sir James Clark’s urging, nervously took on the case. Fortunately, he was able to crush and remove the royal stones, writing to his wife that “no one knows how anxious [I was] but those who are placed in like circumstances.” The grateful king awarded him the equivalent of about $300,000 in today’s money, with an extra bonus on a follow-up visit. 

    Nine years later he treated the Emperor Napoleon III, nephew of Bonaparte, and now exiled in England after losing the Franco-Prussian War. The former emperor had refused treatment for six painful months, passing blood and pus in the urine, but finally

Napoleon III, 1872, a year before death
 (Wikipedia)

allowed Thompson to proceed. Thompson found a stone the size of a date, crushed what he could, and removed some gravel. That evening, Napoleon developed chills, pus and blood in the urine, and passed away two days later. An autopsy showed the remains of the stone and both kidneys nearly destroyed by longstanding obstruction and infection. Thompson accepted only one half of the £2000 fee. Despite this incident, his reputation continued to rise. Over the years, he collected nearly 1000 stones, which he gave to the Royal College of Surgeons. Sadly, the WWII bombing of London obliterated the collection.

         Thompson had boundless energy. As his income grew, he practiced urology only nine months a year and devoted three months to other activities. His wife was the daughter of an artist. Thompson studied art with the help of artist friends and became accomplished enough to exhibit in the Royal Academy and the Paris Salon. He collected Chinese porcelain, studied astronomy and had expensive telescopes made (later donated to the Royal Observatory), ventured into poultry breeding, and later in life wrote two novels, both

Book on Cremation (Wellcome
Library)

popular enough to warrant several reprintings, and he wrote on food and diet. 

        The crusader Edwin Chadwick had reported on the deleterious health effects of overwhelming numbers of burials, often using shallow graves, that were a consequence of overpopulated English cities. To relieve the problem, Thompson  and others founded the Cremation Society of England, organized in 1874 and Thompson served as president for several years. After a long struggle, a Cremation Law was eventually passed legalizing the process.

Thompson loved gourmet food and good company. He instituted the famous “Octaves,” dinners for eight guests (men only), at eight o’clock, serving eight courses and eight wines. A guest of honor might be an extra. His guests included, among others, Conan Doyle, Robert Browning, Dickens, Thackery, the Prince of Wales, Stanley the explorer, and distinguished medical men. An invitation to the renowned dinners was seldom refused. Thompson’s gracious humor and keen intellect rendered the dinners unique experiences. At work, however, he was described as irritable and impatient, as might be expected of someone with his schedule.

Painting of an "Octave" dinner by Solomon J Solomon

Clockwise from the centre background (right of mantelpiece): Ernest Abraham Hart, editor of the British Medical Journal 1866-1898; Sir Thomas Spencer Wells, gynaecological surgeon; Sir Joseph Fayrer, Surgeon-general, Indian medical service; Newman, butler to Sir Henry Thompson; Sir Thomas Lauder Brunton, physician and teacher of pharmacology and therapeutics; Sir William Henry Broadbent, physician; Sir George Anderson Critchett, ophthalmic surgeon; Sir Victor Horsley, surgeon, pathologist and physiologist; Sir Richard Quain, physician; Sir James Paget, surgeon and pathologist; Sir Henry Thompson, urological surgeon, host of the Octaves (behind and slightly to right of left table lamp).

 (Courtesy Wellcome Library)

In later years he became interested in automobiles and bought a Daimler at age 80. Four years later he passed away and, as you might suppose, ordered his body to be cremated. 

He is remembered today for his significant contributions to urologic practice and for his energy, intelligence, and multifaceted talents. A Renaissance man clothed in Victorian garments. 

SOURCES:

Gordetsky, J and Rabinowitz, R, “Sir Henry Thompson: Royal Stones,” Urology 2014; 84: 737-9.

Cope, V Z, “Master Surgeons in Urology: Sir Henry Thompson,” Brit J Urol 1950; 3-5.

Broos, P, “The Death of Napoleon III: Medical Errors at the Sickbed of an Emperor,” Acta Chir Belg, 2007; 107: 588-94.

Jellinek, E H, “Sarcophilia, Cremation, and Sir Henry Thompson,” J Med Biography, 2009; 17: 202-5.

Urquhart-Hay, D, “Sir Henry Thompson BT, the First English Urologist, Brit J Urol 1994; 73: 345-51.

Coues, W P “Jean Civiale – Pioneer French Urologist,” Lancet 1927; Jan 13, 70-71.

 

         

         

                                                      THE PAP SMEAR 

 

         The number of lives saved by the routine use of the “Pap smear” over the last sixty to seventy years probably runs into the millions. The simple and relatively low-tech procedure has had an enormous impact on public health. Behind it is an interesting story.

         George Nikolas Papanicolaou was born in 1883 in the charming Greek town of Kymi on the island of Euboea. His father was a physician and mayor of the town. After a liberal arts education, George attended medical school, served in the military, earned a PhD in biology in Germany, and decided on a life of

Papanicolaou as young man (Wikipedia)

research rather than the practice of medicine. On return to Greece from Germany, George met and married Andromache Mavroyeni. After a short stint on an oceanographic research vessel, George served medically in the Balkan War of 1912 against the Ottomans, during which he met Greek-American volunteers who encouraged him to go to America to seek a scientific career. He decided to take their advice.

         He and “Mache” arrived in New York the next year with no job, no contacts, no knowledge of English, and $250. George worked at Gimbel’s department store selling rugs and, being a good violinist, earned extra cash playing at restaurants. He eventually contacted Thomas Hunt Morgan, the famous geneticist at Columbia University, who helped him obtain a position as a technician in the anatomy department at Cornell Medical College, with Andromache as his assistant. George investigated the role of the X and Y chromosomes in determining sex, a problem still under exploration at the time. Studying guinea pigs, George needed to obtain ovarian eggs at the precise time of ovulation. He examined samples of guinea pig vaginal discharge daily and discovered that the smears could accurately determine the day of ovulation. To see if similar changes occurred in humans, he turned to his wife, who became the first person to have a “Pap smear”, and he enrolled volunteer workers at the New York Women’s Hospital. The results demonstrated a similar human sexual cycle. 

         By chance, a smear from one of the volunteers revealed malignant cells. This generated a study of women with known cancers of the cervix and uterus, showing that the technique might prove valuable in detecting early stages. The findings were first presented at, of all places, the Third Race Betterment Conference in Battle Creek, Michigan, in 1928, a meeting of the eugenics

Cancer cells shown at Race Betterment Conference
(from report of 1928)

organization founded by John Harvey Kellogg, the inventor of breakfast cereals who worried about “race degeneracy.” The findings generated little interest, however. Papanicolaou, prodded by Cornell’s chief of anatomy and in conjunction with Cornell’s chief of gynecology, embarked on a study in 1939 to do a smear on all women admitted to the gynecological service of Cornell’s New York Hospital. The results made it clear that early cancers, with no symptoms, could be detected accurately, and established a milestone in cancer prevention. The following years were devoted to teaching the methods and refining the techniques for use on a mass scale. The “Pap smear” and an entirely new specialty, cytotechnology, were born.

         Papanicolaou was suddenly a famous man. He visited medical centers in Europe, was hosted by the royal family in Greece, received numerous awards and honorary degrees, and gazed at his portrait on postage stamps and Greek currency bills. National Cytotechnology Day, to recognize the value of the technicians who examine the smears, falls every year on his birthday, May 13. 

He was nominated five times for the Nobel Prize, though never received it. It is not clear why, but one possibility relates to near simultaneous reports of cancer cells in cervical scrapings by a Romanian, Dr. Aurel Babeș, published in the Proceedings of the Romanian Society of Gynecology of January and April of 1927 and again in April 1928 in Presse Medicale. Babeș was a highly

Cancer cells from cervical scraping by Aurel
Babeș, Presse Medicale 1928 (Hathi Trust)

regarded scientist in Romania, had his name on over 200 papers, and had published a major work on pellagra. The two sampling methods differed somewhat. Babeș used a platinum loop to scrape the cervix while Papanicolaou used a narrow pipette to obtain free cells and employed a more refined stain. Babeș did not pursue the study of vaginal smears but the presence of the Babeș reports may have caused hesitation by the Nobel committee. Additionally, Papanicolaou’s main supporter at the fifth nomination died just before the final voting. Babeș never contested Papanicolaou’s world recognition. 

 Incidentally, the uncle of Aurel Babeș, Victor Babeș, had discovered the parasite causing a disease named after him: babesiosis, and was a well-known bacteriologist. 

         George’s wife, Andromache, was instrumental in his success. She was the “special patient,” who underwent hundreds of vaginal

Andromache and George Papanicolaou
(from Exper Therap Med 18, 2019, Creative Commons License)

smears and was certainly the “most over-tested woman of all time” (Vilos). In addition, she was the breadwinner during the lean years after arrival in New York. She became an expert cytotechnologist and taught the skill to many others, while still finding time to prepare and serve Greek specialties to distinguished guests in their home.

         In 1961 Dr. Papanicolaou accepted the directorship of a new Cancer Research Institute of Miami and early the next year the couple moved to Florida. Tragically, three months before the dedication ceremony of May 1962, George Papanicolaou was stricken with chest pain and succumbed rapidly to a failing heart. He was buried in Clinton, New Jersey, next to his niece. 

Though he missed the Nobel Prize, the gratitude of millions of women must have been a sufficient reward for the creator of the “Pap smear”.

 

SOURCES:

Vilos, G A, “The History of the Papanicolaou Smear and the Odyssey of George and Andromache Papanicolaou,” Obstet and Gynecol, 1998; 91(3): 479-83.

 

Elgert, P A and Gill, G W, “George N Papanicolaou, MD, PhD: Cytopathology.” Lab Medicine2009; 40(4): 245-6.

 

Papanicolaou, G, “New Cancer Diagnosis.” Proc Third Race Betterment Conference, Battle Creek, Mich., Jan. 2-6, 1928, pp 528-34.

 

Papanicolaou, G, traut, HF, “The Diagnostic Value of Vaginal Smears in Carcinoma of the Uterus.” Amer J Obstet Gynecol 1941; 42: 193-206.

Albert, P, “George Papanicolaou: Biography,” accessible at: https://library.weill.cornell.edu/george-papanicolaou-biography

Mammas, I N, et al, “Mache Papanicolaou (1890‐1982), the dedicated companion of the great benefactor: An interview with Dr Julie Kokkori, one of the only living relatives of Dr George N. Papanicolaou.” Exp Therap Med 2019; 18: 3248-51.

Tasca, L, et al, “History of Gynecological Pathology XII. Aurel Babeș.” Int J Gynecolog Pathol2002; 21: 198-202.

Naylor, B, et al, “In Romania It’s the Méthode Babeș-Papanicolaou.” Acta Cytologica 2002; 46(1): 1-12.

Diamantis, A, et al, “What’s in a Name? Evidence that Papanicolaou, not Babeș, Deserves Credit for the Pap Test.” Diagnostic Cytopathol 2009; 38(7): 473-6.

 

 

         

         

 

THE STRANGE CASE OF EVA PERON

 

         Here is a tale for students of medical ethics as applied to the rich and famous.

         Eva Perón, wife of Juan Perón when he was president of Argentina in the 1950s, arose from humble circumstances. She was born in 1919 to the mistress of a land manager in a small village in the Argentine “pampa” (flat, extensive plains). Her father departed to rejoin his wife about a year later, leaving the family of mother and five children in poverty. Eva left home at age 15 and headed for Buenos Aires where she worked as an actress and singer. Gradually attaining some reputation, she formed her own company. In 1944, she met Col. Juan Perón, Secretary of Labor at the time. They married in a small, semi-secret ceremony in 1945 when Peron became president. Eva, often called Evita, champion of the “descaminados” (the shirtless ones) and popular with the poor, organized the Eva Perón Foundation, a huge institution dispensing charity, and she was important in helping women obtain the right to vote. 

Eva and Juan Perón (Wikipedia)

         In 1950, the fourth year of the Perón presidency, Eva had a fainting spell, after which she had an appendectomy. One of her physicians later wrote that he had diagnosed uterine cancer and had advised a hysterectomy, but this story was not confirmed. Apparently recovered, she threw herself into her work, doling out charitable gifts in all directions. In time, she grew thinner, pale, and tired. Unknown to the public, she suffered vaginal bleeding and abdominal pain. Her doctors now made a diagnosis of cervical cancer and gave her radium implants preparatory to resectional surgery, but never told her she had cancer. Her brother and other relatives asked that Eva not be informed. Dr. Ricardo Finochietto, director of the Presidente Perón Hospital (built by Eva’s Foundation), was to do the abdominal surgery. 

Juan Perón, however, asked a local oncologist, Abel Canónico, about an outside expert, and was advised of George Pack, a renowned cancer surgeon at New York’s Memorial Hospital Sloan-Kettering Center. Pack was contacted secretly by the Argentine embassy in Washington and agreed to operate on Eva. Because of possible political ramifications, he worked in cooperation with the State Department and the ambassador to Argentina, Ellsworth Bunker, who also approved the contemplated surgery. Pack flew with Dr. Canónico to Buenos Aires, examined Eva under anesthesia without her knowledge, confirmed the diagnosis, and flew back to New York, all in complete secrecy. He returned to Argentina and performed a radical hysterectomy and lymph node dissection on November 6, 1951, again seeing Eva only under anesthesia. He left the operating room before Eva awakened and stayed in a hotel room until she had stabilized. Eva, and the public, never saw him or knew of his involvement in either encounter, believing that Finochietto had done the surgery. Dr. Pack suspected the tumor would recur, which it did. He declined to do further surgery and never sent a bill.

The surgery and the concomitant maneuverings took place against the background of a violent campaign for a presidential election. Juan Perón felt that the survival of Eva was important to his reelection and her popularity was cetainly evident when a crowd of 20,000 gathered outside the hospital on the day of her surgery. Five days later, Eva cast her presidential vote from a hospital bed, helping her husband win the election. Then, fortified by large doses of pain medicine and a plaster frame, she stood next to him in an open automobile during the victory parade. She finally passed away on July 26, 1952, weighing less than 80 pounds.

A number of features of this case would not pass muster today. Regarding the diagnosis, Pap smears were uncommon in Argentina at the time and relatively new in the U.S. Though available in the late 1940s, the first time an Argentinian cancer organization advised Pap smears was in 1950. It received little public response and remained under-utilized. The dangers of vaginal bleeding were also not publicized. Furthermore, doctors were still wary of telling patients they had cancer, both in the U.S. and even more so in Argentina. In a survey of the staff of the Michael Reese Hospital in Chicago, published in 1961, fewer that 5% never told a patient of cancer but many couched the diagnosis in ambiguous terms, often leaving the patients confused. Even if Eva knew the diagnosis, she might have resisted further diagnostic measures, given her tendency to brush off illness. According to the priest who gave her last rites, she was never told the diagnosis.

More bizarre, the surgery was carried out secretly by a surgeon not known to the patient and without the patient’s knowledge or permission. In addition, the State Department and the U.S. ambassador to Argentina encouraged the plan, almost certainly to accommodate political considerations. The Assistant Secretary of State, Edward Miller, Jr., praised Pack for his skills “in such an important and critical situation.” Pack himself felt that he could render a service by performing an operation not well known in Argentina and he was flattered to be asked. He wanted to tell the story publicly one day but respected the privacy of the matter and died before the facts came out.

Medical care of the rich and famous, especially of political figures, can lead to compromises and unusual medical practices that would not meet today’s ethical standards. In addition to Eva’s surgery, the secret operation on President Cleveland and the care of the Shah of Iran raise similar questions.

 

SOURCES:

Lerner, Barron H, “The Illness and Death of Eva Perón: Cancer, Politics, and Secrecy,” Lancet 2000; 355: 1988-91. (Dr. Lerner is a bioethicist and Professor of Medicine at New York University)

 

Fraser, N and Navarro, M, Eva Perón. W.W. Norton, 1980.

 

Oken, Donald, “What to Tell Cancer Patients: A Study of Mental Attitudes.” JAMA 1961; 175(13): 1120-28.

 

Grant, Ronald M, “Never Say Die: A Personal tribute to George T. Pack, MD (1898-1969).” CA: A Cancer Journal for Clinicians, 2008; 19(3): 198-200.

 

De Gonzales, V, et al, “Argentina: Telling the Truth to Cancer Patients.” Bull NY Acad Science 1997; 809: 152-62.

 

Altman, Lawrence, “From the Life of Evita, a New Chapter on Medical Secrecy.” NY Times, June 6, 2000.

 

      

  

 

THE LIFE AND DEATH

OF CHLOROFORM

 

      Ether burst onto the medical stage in October of 1846 when a dentist, William Thomas Green Morton, administered the volatile compound to twenty-year-old Edward Abbott while the noted Boston surgeon, Dr. John Warren removed a neck tumor. Painless surgery had arrived.

         News of the dramatic effect of ether flew across the Atlantic. That December, Dr. James Simpson, Professor of Midwifery in

James Simpson (Wikipedia)

Edinburgh, traveled to London to witness its use in an operation by his old teacher, Robert Liston. Liston took 28 seconds (surgeons before anesthesia had to be quick) to amputate a leg without any complaint from the etherized patient. He announced after the procedure, “This Yankee dodge, gentlemen, beats mesmerism hollow.” Simpson eagerly took up ether anesthesia to ease the pains of labor as well as in surgeries. He ignored objections from clergy and other quarters that pain was natural in childbirth and should not be suppressed.

But difficulties administering and transporting ether led Simpson to assess many other agents. After trying somewhat indiscriminately, primarily on himself, various volatile compounds, a chemist friend suggested chloroform. On the evening of November 4, 1847, Simpson and two assistants sat at his dining room table and inhaled a small amount of the sweet-smelling substance. Simpson soon found himself on the floor along with his two semiconscious companions. The trio were so delighted with the result that they inhaled the substance several times more, finally heading home at 3 AM, determined to use it.

Cartoon of Simpson's home trial of chloroform (Wellcome Library)

Chloroform, like ether, had been around for a while before its anesthetic potential was realized. Credit for the first synthesis goes to an American, Samuel Guthrie. Trained as a physician, Guthrie became more interested in business and set up a gunpowder plant and other enterprises near the shore of Lake Ontario. Interested in chemistry, he read in writings of the Yale University chemist,

Samuel Guthrie (Wikipedia)

Benjamin Silliman, about a compound named “chloric ether,” whose sweet aroma might have uses in medicine. Dr. Guthrie devised a simpler method, in 1831, of making it by combining “best whisky” with chloride of lime and distilling the result. What he actually made was an alcoholic solution of chloroform. Sippers of this solution became pleasantly tipsy, sometimes drunk. Silliman chemically removed the alcohol, producing pure chloroform, but the mild alcoholic solution was used by American doctors for its pleasant and seemingly beneficial effects. Its anesthetic properties remained unknown.

Just over one year following Dr. Warren’s first use of ether and five days after Simpson’s chloroform experiment at home, a young woman in Edinburgh, Scotland, entered her second labor. She had previously endured an agonizing three-day labor resulting in a dead child. Simpson was her accoucheur, as he was called, and, anxious to avoid a second tortuous labor, he anesthetized her with chloroform – its first use in a patient. The young lady delivered a healthy child after a three-hour, painless labor. Within a few weeks Simpson helped over 50 women avoid labor pains and surgeons quickly adopted it for operations. His successful experience made him an enthusiast of the new agent and he publicized it relentlessly. It was cheap, easy to administer, acted rapidly, had a pleasant smell, lacked the irritating qualities of ether, and was not flammable. 

In London, when ether was first in use, the highly educated but relatively obscure practitioner, John Snow (later of cholera fame), took an interest. He had worked on respiratory physiology and

John Snow (Wikipedia)

surmised that the varying results with ether might be due to varying dosage. He measured the amount of ether in air at varying temperatures, devised a breathing apparatus that produced a predictable amount for administration, and characterized five levels of anesthesia. Later, responding to the enthusiasm for chloroform, Snow devised a similar breathing apparatus to administer an exact dose. He helped Queen Victoria through two labors with the new agent, though without the apparatus since she was lightly dosed. Most practitioners, in fact, continued to pour chloroform onto a sponge or cloth-covered cone. During the American Civil War and the Crimean War chloroform was the chief anesthetic employed. The agent also made headlines as an instrument in kidnappings, rapes, and other crimes, though much of this was exaggerated.

Before long, reports of sudden death during chloroform anesthesia appeared, often during induction, that were unrelated to dose or underlying medical problems. The Lancet criticized Snow for using it on Queen Victoria, citing reports of unexpected deaths. Not until 1911 did Goodman Levy show that ventricular fibrillation occurred in cats under chloroform, suggesting a mechanism. He later published data showing that over two decades chloroform use constituted between 72 and 90 percent of all anesthetic deaths in Britain. In these cases British doctors were obliged to testify at a coroner’s inquest, but none were charged with anesthetic

Henry J. Bigelow (Wikipedia)

malpractice throughout the nineteenth century. In the northern United states, however, doctors were sued for anesthetic deaths and, additionally, Henry J. Bigelow, Professor of Surgery at Harvard, used his influence to champion the use of ether as the safer choice. Chloroform usage died quickly in the north, though in the southern states its use continued for some time. 

Levy’s publications were persuasive and eventually the mortality statistics could not be ignored on either side of the Atlantic. Chloroform usage declined everywhere, replaced by ether and eventually newer agents.

Pierre Louis in Paris pioneered the use of statistical methods in the early 1800s to question the value of bloodletting as treatment for pneumonia. His methods, after over half a century, finally convinced chloroform users to choose another anesthetic.

 

SOURCES:

Stratmann, Linda, Chloroform: The Quest for Oblivion, Sutton Publishing, 2003

 

Johansen, Peter V, et al, Cholera, Chloroform, and the Science of Medicine: A Life of John Snow, Oxford University Press, 2003.

 

Shepherd, John A, Simpson and Syme of Edinburgh, E&S Livingston, 1969.

 

Snow, Stephanie J, Blessed Days of Anaesthesia: How Anaesthetics Changed the World, Oxford University Press, 2008.

 

Levy, A. Goodman, Chloroform Anesthesia, William Wood & Co. 1922

 

Bigelow, Henry J, “Death by Chloroform and Alleged Death by Ether,” Boston Med Surg Journal, 1872; 86: 277-9.

 

Holmes, Oliver Wendell, “Henry Jacob Bigelow,” Proc Amer Acad Arts Sci 1891; 

26; 339-51.

 

Thomas, K B, “The Early Use of Chloroform,” Anesthesia” 26(3): 348-62, 1971.