The Medical Detectives Volume I

by Berton Roueche

  Around the middle of November, Berry was seized with a new affliction. It hurt him to urinate. He endured this puzzling complaint for several uneasy days, and then went down to see the doctor. The doctor heard his symptoms with relief, and an examination, which disclosed an inflammation of the prostate gland, confirmed his first impression. Berry had prostatitis. The doctor then turned his attention to treatment. It consisted of a prostatic massage, a prescription for sulfisoxazole, and a warmly encouraging prognosis. He was hopeful that by the end of the week Berry would be greatly improved. It didn't turn out that way. The pain continued as before. A cystoscopic, or direct, examination of the urinary tract was made, and these findings, too, were inconclusive. The doctor saw no reason to alter his diagnosis. Or his treatment. He was convinced that periodic prostatic massage would eventually have a salutary effect.

  And so, before long, it apparently did. Berry's occasional abdominal cramps became increasingly occasional, and presently— early in 1960—they vanished altogether. This was followed by an encouraging change in his original urinary complaint. For a while, it seemed to Berry that his troubles might be almost over. But only for a while. The remissions, it soon became clear, were nothing more than remissions. In time, the pain always returned. Toward the end of 1960, Berry gave up any real hope of a cure and resigned himself to a life of chronic prostatitis.

  Berry's life as a chronic invalid lasted almost a year. It ended, with a jolt, one December evening in 1961, when he noticed a stain of blood in his urine. The next morning, it had noticeably deepened and darkened. Sick with dismay, he telephoned the family doctor. The doctor told him to come to the office at once. From there, on the doctor's referral, he went to see a urologist. The urologist asked some careful questions, and then led him into his surgery for another cystoscopic examination. At nine o'clock the following morning, Sunday, December 17, Berry was admitted to Memorial Hospital, in Manhattan, with a diagnosis of suspected cancer of the bladdci Berry spent six days in Memorial Hospital. On December 22, he was discharged in the care of Dr. Harry Most, chairman of the Department of Preventive Medicine at New York University Bellevue Medical Center, and an authority on tropical diseases The report of his stay read:

  Physical examination on admission revealed a WDWN [well- developed, well-nourished] white male with . . . prostate minimally enlarged and non-tender.

  Urine microscopically showed a few RBC [red blood cells] and few WBC [white blood cells]. Hgb. [hemoglobin] was 15 gms. Hct. [hematocrit] 42%. WBC [white blood count] 5.9 with 4% eosinophils on one differential and 20% eosinophiles on a second. Eosinophile count showed 98 eosinophiles per cc./mm. Blood sugar [was] within normal limits. Urinary cytologies were negative for malignant cells. ...

  Cystoscopy and biopsy were carried out. Bladder was of normal capacity and contour. Scattered throughout the bladder were numerous small, virtually punctate elevations of the bladder mucosa without any visible change in the normal lemon-yellow color of the bladder lining. These lesions appeared submucosal in location. High on the posterior wall of the bladder were irregular, partially confluent, reddened, raised areas with a surface midway in appearance between that of papillary neoplasm and bullous edema, but not characteristic of either. The latter areas totalled several sq. cm. but were resected completely transurethrally.

  Pathologic examination revealed unequivocal evidence of schistosomiasis.

  The cause of schistosomiasis is a small but readily visible endoparasitic worm of the genus Schistosoma that has an essential environmental predilection for human blood. Its name derives from the Greek schistos, meaning "cleft," and soma, meaning "body," and refers to a deep longitudinal crevice in the body of the male worm in which the female more or less permanently resides. The schistosomes, though humbly placed in the evolutionary scale, lead highly complicated lives. They reach maturity only after three total metamorphoses in three distinctly different settings. The organism first manifests itself as a newly hatched larva in a pond or lake or river. If all goes well, the larva soon finds and enters the body of a suitable species of fresh-water snail. It is there transformed into an aggregation of reproductive spores, and these, after several weeks of ceaseless proliferation, emerge from the snail as a multitude of tadpole-like wrigglers. The wrigglers must promptly find a suitable animal host, and one host to which they have irrevocably adapted themselves is man. Wrigglers fortunate enough to come upon the necessary host attach themselves to the skin, discard their tails, and (with the help of a tissue-dissolving enzyme) burrow through the epidermal barrier. Penetration usually takes about twenty-four hours and is unperceived by the host. Once through the skin, the wrigglers launch themselves in the current of the peripheral blood vessels and are carried along to the veins and through the heart and into the systemic circulation. The survivors of this intricate voyage (which may take several days) then gather in the richly nutritious blood that flows from the gastro-intestinal tract to the liver and beyond. There they grow to maturity (about an inch in length for the females, and less than half that for the males), and mate. They then retire to the comfort of a tiny backwater vein, where the female, still enclosed in the male's embrace, deposits—for incubation and eventual excretion with the body's wastes—the first of an almost infinite number of eggs. It is not unheard of for a female schistosome to live and breed for thirty years.

  The site that a schistosome chooses for its eggs is not a haphazard choice. It is predetermined by the species of worm. There are three species to which man is warmly hospitable—Schistosoma haematobium, Schistosoma mansoni, and Schistosoma japonicum. Gravid 5. haematobium worms are drawn to the urinary bladder. Those of the other species prefer the bowels, S. japonicum lodging in the small intestine, and S. mansoni in the large intestine. The species differ in other respects as well. They have different intermediate hosts, different geographical ranges, and different rates of growth. Each schistosome species has so evolved that it can pass from the larval to the wriggler stage in the body of only certain species of snail, and the snails accept able to one are unacceptable to either of the others. It is thus this snail that determines the distribution of the worm. The distribution of S. japonicum is largely confined to coastal China and the Yangtze Valley, parts of Japan, and the Philippines. S. hac matobium, though probably indigenous to the Nile Valley (its calcified eggs have been found in Egyptian mummies of the twelfth pre-Christian century), occurs throughout most of humid Africa, in much of the Middle East, and at the southern tip of Portugal. The range of S. mansoni extends from the Mid die East (Arabia and Yemen), through much of Africa (the Nile Delta, the southeast coast, and the rain forests of the Congo), to Brazil, Venezuela, and the Caribbean islands. Its extension to the Western Hemisphere is generally attributed to the slave-trade, but there is more to the matter than that, for the African slaves were infested with S. haematobium as well. The decisive factor was the presence here of a species of snail (Australorbi glabratus) to which S. mansoni could adapt. Just why the different species have different rates of growth is yet to be satisfactorily explained. The only certainty is that 5. japonicum matures in four or five weeks, S. mansoni in six or seven, and S. haematobium in ten or twelve.

  For all their several differences, the schistosomes are essentially much alike. So are the varieties of schistosomiasis they produce. A schistosome is not a toxic organism in the usual sense. Except for certain allergic reactions (of the sort that any foreign protein may excite), its impact is largely mechanical. The eggs of a schistosome are equipped with clawlike spines to hold them in their venous incubator against the constant pull of the circulating blood, and it is from this constant tugging and tearing that the chief discomfort of schistosomiasis stems. For reasons not entirely clear, schistosomiasis japonica (as an infestation of S. japonicum is called) tends to be the most destructive of the three forms, but all are serious diseases—always unpleasant, often debilitating, and not infrequently fatal—and the symptoms of their presence are fundamentally the same. They typ
ically in elude, as in the case of Vernon Berry, an outbreak of hives, an elevated eosinophile count, and internal (gastro-intestinal or genitourinary) bleeding.

  Merry's referral to still another physician was unusual but in no sense exceptional. It was arranged, with the enthusiastic approval of the Jersey City urologist, by the head of the urological service at Memorial Hospital, and was made for the best of reasons. Dr. Most is not just another physician. He is one of the law physicians in the New York metropolitan area with a particular knowledge of schistosomiasis, and one of even fewer experienced in its sometimes tricky treatment.

  "I was very glad to have Berry commended to my care," Dr. Most says. "Nothing could have interested me more. I thought I could help him, and I was eager to try. That, of course, was the first consideration, but it wasn't the only one. I was eager to talk to him—to learn everything I could about the case. Because I knew enough already to know that it signified something important. It seemed to confirm the development of a new and potentially rather ominous trend. I'll tell you what I mean. Schistosomiasis has always been among the rarest of rare diseases in this country. It doesn't exist here, and in the absence of a suitable species of snail to serve as intermediate host it can't. The only cases that are ever seen in the United States are importations. A lot of American soldiers came home from the Philippines after the Second World War with schistosomiasis japonica, and a certain number of Puerto Rican immigrants with schistosomiasis mansions turn up in the Eastern-seaboard cities every year, and that's been about the story. Until recently. It seems to be taking a new twist now. A new kind of victim has appeared. It isn't a soldier stationed in an endemic area and it isn't a native exposed from earliest childhood. It's a tourist—someone just passing through.

  "Berry was the fourth of these to come to my attention in less than two years. The others were a physician and his wife and a spinster friend of theirs who took a three-week Caribbean cruise in the winter of 1960. Their exposure occurred—it could only have occurred—in a fresh-water pool on St. Lucia, one of the Windward Islands. The physician was the first to become sick. He thought for several days that he had the flu. Then he was hospitalized, and a colleague took over. A high eosinophile count indicated a parasitic infection, and the attending physician sent an account of the clinical findings to the health officers of the various islands visited and asked for diagnostic suggestions. The replies he got came out most strongly for typhoid fever, hookworm, ascariasis, amoebic dysentery, and strongyloidiasis. The possibility of schistosomiasis was never even considered until I came into the picture. I was consulted because of my interest in tropical medicine. Schistosomiasis was suggested to me by a careful review of the itinerary, and a series of tests confirmed my hunch. A rectal biopsy identified the variety as schistosomiasis mansoni. That was exactly two weeks after onset. In the circumstances—classic clinical manifestations, a known recent visit to an endemic area, and first-rate hospital facilities—I think one might say that it could have been diagnosed a bit sooner. The two other cases were fairly mild at onset, and the symptoms were not particularly pronounced. If there hadn't been that obvious link with the sick physician, they might have gone undetected indefinitely. As Berry practically did. And yet the essential clues—a visit to an endemic area and eosinophilia—were there in his case, too. All that was needed was an awareness of the possibility.

  "The trouble is that the possibility of schistosomiasis just doesn't enter an American physician's mind. That's understandable enough—or, rather, it used to be. In my opinion, it isn't anymore. Berry and the physician and his wife and their friend may be merely isolated cases, but I don't think so. I think more likely there are others that I haven't heard about. That nobody has. And I think there are many more to come. I'll tell you why. The American tourist has changed in the past few years. There's a whole new breed. Our tourists are no longer mainly the rich or the well-to-do from a few big cities. They're everybody, and they come from everywhere. The reason, of course, is cheaper and faster air travel. There are more tourists now, and they do more traveling, and they visit more distant places. Including, increasingly, the tropics. And every year the chances are greater that some of them will be exposed to a serious tropical disease. Schistosomiasis is only one such disease, and it is far from being the worst. I'm not thinking of plague and cholera and that sort of thing. I mean bizarre diseases, like kala-azar and African trypanosomiasis, or sleeping sickness, and malignant tertian malaria. Malignant tertian malaria is an extremely serious disease with a high mortality rate, and the others can also be fatal, but they have their redeeming features. They are all amenable to treatment. They can be successfully treated and cured. They can, that is, if they are diagnosed correctly and in time. But first they have to be suspected. They have to be brought to mind. Brian Maegraith, of the Liverpool School of Tropical Medicine, has proposed an up-to-date addition to the routine interrogation of a patient. He suggests that at some point the doctor ask, 'Where have you been?' I second the motion.

  "Maegraith assumes that the doctor will hear and heed the answer. That, of course, is quite as important as the question. It could have made all the difference in Berry's case. I realize there were complicating factors there. The early allergic manifestations of schistosomiasis were confused with the even earlier penicillin reaction, and certainly that intestinal parasite was a most unfortunate coincidence. However, since the doctors concerned were fully aware from the very beginning that Berry had just returned from a rugged trip through some of the world's least hygienic countries, one can hardly say that his case was handled with much sophistication. Or so it seems to me after talking and working with Berry.

  "I saw Berry for the first time about a month after his discharge from Memorial Hospital. Sooner would have been better, but that couldn't be helped. I wanted to be sure just what I was treating before I started treatment. The treatment of schistosomiasis depends to some extent on the type. Or types. I knew that Berry had made a trip around the world, so it was possible that he had more than one type. He might even have all three. First, I wanted to see the slides from which the hospital diagnosis had been made, and there was some delay in getting them down to my office. Then I wanted to examine some stool and urine samples for the microscopic eggs that would identify the type, or types, and that meant another delay. We finally got started on January 29. I had the results of the sample tests by then, and they held no ugly surprises They simply confirmed the original bladder-biopsy findings. Berry had schistosomiasis haematobium, and only haematobium. Where he got it is a little hard to say. He visited half a dozen different places in the endemic areas in Egypt and the Middle East, and most of the washing and bathing he did there was in tubs or basins filled by hand with water from some possibly contaminated source. It's my guess, though, that he picked it up in Egypt—at Luxor, when he went swimming in the Nile.

  "The treatment of schistosomiasis involves some form of antimony. Potassium antimony tartrate, the most potent tolerable form, is generally used for schistosomiasis japonica. Its administration is intravenous, and is an exceedingly delicate process. A slip can cause real trouble. Moreover, there have been some serious, and even fatal, toxic reactions to the drug. A less powerful form containing sodium antimony and called stibophen is effective in both schistosomiasis haematobium and schistosomiasis man- soni, and it can be given intramuscularly. It isn't as bad as the other, but it can cause its share of trouble. January 29 was a Monday. I gave Berry a stibophen injection of five cc's that afternoon, and the same amount each afternoon for the next four days. We skipped the weekend to give him a breather, and then did the same the following week. He stood it pretty well. We got through seventeen injections—or a total of eighty-five cc.s of the drug— before he had any important toxic reaction. On February 22, the day of the seventeenth injection, he had a wave of nausea and vomited. Eighty-five cc.s was enough to do the job, so I stopped. He wasn't cured, but he was well on the way. Tests during the course of treatment showed his u
rine increasingly clear, and by the end of the course it contained no schistosome eggs and only a few microscopic traces of blood. His eosinophilia also showed a healthy change. At the beginning of treatment, he had an eosinophile reading of fifteen per cent. When I withdrew the drug, it was down to ten. A month later, when he came in for a checkup, it was down to four, and in the next few months it continued that encouraging decline. Another cystoscopy was performed on August 22. It showed no evidence of acute inflammation, and in general the look of the bladder was compatible with the other signs of improvement. Seven months later, on March 13, 1963, a final cystoscopy was done, and this time there was no doubt about it. We could safely say he was cured."

  [1964 ]

  CHAPTER 9

  The Orange Man

  Around eleven-thirty on the morning of December 15, 1960, Dr. Richard L. Wooten, an internist and an assistant professor of internal medicine at the University of Tennessee College of Medicine, in Memphis, was informed by the receptionist in the office he shares with several associates that a patient named (I'll say) Elmo Turner was waiting to see him. Dr. Wooten remembered Turner, but not much about him. He asked the receptionist to fetch him Turner's folder, and then, when she had done so, to send Turner right on in. The folder refreshed his memory. Turner was fifty-three years old, married, and a plumber by trade, and over the past ten years Dr. Wooten had seen him through an attack of pneumonia and referred him along for treatment of a variety of troubles, including a fractured wrist and a hip-joint condition. There were footsteps in the hall. Dr. Wooten closed the folder. The door opened, and Turner—a short, thick, muscular man— came in. Dr. Wooten had risen to greet him, but for a moment he could only stand and stare. Turner's face was orange—a golden, pumpkin orange. So were both his hands.