What are the conclusions that one can draw from this study in the absence of a placebo arm? The study clearly shows, using a number of well-established standard measures, that the group receiving exenatide improved over fourteen months and that the patients not receiving the drug declined. This could be due to an acute treatment effect or, as discussed above, a placebo effect (16). However, the very mild symptomatic decline during the washout period speaks more in favor of a disease-modifying effect. In short, this study demonstrated that a drug in clinical use for another medical condition can successfully be tested for its disease-modifying effects in patients with PD using standard clinical measures, without biomarkers and without a placebo-controlled arm, in a relatively inexpensive way. Obviously, any results can only be seen as providing a signal of possible efficacy that is worth pursuing further. As with any experiment, replication is the first step in proving that a result is true, and a double-blind, placebo-controlled trial will ultimately be required.
Perhaps the most important feature of this study is that it has adopted a pragmatic approach to the problems of taking established drugs to new areas of therapy in a neurodegenerative disorder and done so with a study design that is informative and affordable. This is critical in an environment in which costs for drug trials have escalated and have become a significant hurdle. The authors are to be congratulated for their efforts, although establishing whether this agent truly can modify the progression in PD will require further work.
A.Hailey The Final Diagnosis One
At midmorning of a broiling summer day the life of Three Counties Hospital ebbed and flowed like tide currents around an offshore island. Outside the hospital the citizens of Burlington, Pennsylvania, perspired under a ninety-degree shade temperature with 78 per cent humidity. Down by the steel mills and the rail yards, where there was little shade and no thermometers, the reading—if anyone had bothered to take it—would have been a good deal higher. Within the hospital it was cooler than outside, but not much. Among patients and staff only the fortunate or influential escaped the worst of the heat in air-conditioned rooms.
There was no air conditioning in the admitting department on the main floor, and Madge Reynolds, reaching into her desk for her fifteenth Kleenex that morning, dabbed her face and decided it was time she slipped out to make another application of deodorant. Miss Reynolds, at thirty-eight, was chief clerk in Admitting and also an assiduous reader of feminine-hygiene advertising. As a result she had acquired a horror of being less than completely sanitary and in hot weather maintained a shuttle service between her desk and the women’s toilet down the corridor. First, though, she decided, she must locate four patients for admission that afternoon.
A few minutes earlier the day’s discharge slips had come down from the wards, showing that twenty-six patients were being sent home instead of the twenty-four Miss Reynolds had expected. That, added to two deaths which had occurred during the night, meant that four new names could be plucked from the hospital’s long waiting list for immediate admission. Somewhere, in four homes in and around Burlington, a quartet of patients who had been waiting for this call either hopefully or in fear would now pack a few essential belongings and put their trust in medicine as practiced at Three Counties. Holding now her sixteenth Kleenex, Miss Reynolds opened a file folder, picked up the telephone on her desk, and began to dial.
More fortunate than the Admitting clerks in the heat were those awaiting treatment in the outpatient clinics, now in full session over in the opposite wing of the main floor. They at least would enjoy air conditioning when their turn came to enter one of the six offices leading off the general waiting room. Within the offices six specialists were making their exclusive talents available free to those who couldn’t, or wouldn’t, afford the private-patient fees charged on the specialists’ home ground in the Medical Arts Building downtown.
Old Rudy Hermant, who worked periodically at laboring when his family bullied him into it, sat back and relaxed in cool comfort as Dr. McEwan, the ear, nose, and throat specialist, probed in search of the cause of Rudy’s growing deafness. Actually Rudy didn’t mind the deafness too much; at times, when foremen wanted him to do something else or work faster, he found it an advantage. But Rudy’s eldest son had decided the old man should get his ears looked at, and here he was.
Dr. McEwan fretted irritably as he withdrew the otoscope from old Rudy’s ear. “It might help a little if you washed some of the dirt out,” he remarked acidly.
Such ill humor was unusual in McEwan. This morning, however, his wife had carried to the breakfast table a running fight about household expenses which they had started the night before, causing him, afterward, to back his new Olds out of the garage in such a temper that he had crumpled the right rear fender.
Now Rudy looked up blandly. “What was that?” he inquired.
“I said it might help . . . oh, never mind.” McEwan was debating whether the old man’s condition might be due to senility or a small tumor. It was an intriguing case, and already his professional interest was outweighing his irritability.
“I didn’t hear you,” the old man was saying again.
McEwan raised his voice. “It was nothing! I said forget it!” At this moment he was glad of old Rudy’s deafness and slightly ashamed of his own outburst.
In the general medical clinic fat Dr. Toynbee, an internist, lighting a fresh cigarette from the stub of the last, looked over at the patient on the other side of his desk. As he considered the case he felt a slight biliousness and decided he’d have to lay off Chinese food for a week or two; anyway, with two dinner parties coming off this week, and the Gourmet’s Club next Tuesday, it shouldn’t be too hard to endure. Deciding his diagnosis, he fixed his eye on the patient and said sternly, “You’re overweight and I’m going to put you on a diet. You’d better cut out smoking too.”
A hundred yards or so from where the specialists held court Miss Mildred, senior records clerk at Three Counties, perspired profusely as she hurried along a busy main-floor corridor. But, ignoring the discomfort, she moved even faster after a quarry she had just seen disappear around the next corner.
“Dr. Pearson! Dr. Pearson!”
As she caught up with him the hospital’s elderly staff pathologist paused. He moved the big cigar he was smoking over to the corner of his mouth. Then he said irritably, “What is it? What is it?”
Little Miss Mildred, fifty-two, spinsterish, and five foot nothing in her highest heels, quailed before Dr. Pearson’s scowl. But records, forms, files were her life. She summoned up courage. “These autopsy protocols have to be signed, Dr. Pearson. The Health Board has asked for extra copies.”
“Some other time. I’m in a hurry.” Joe Pearson was at his imperious worst.
Miss Mildred stood her ground. “Please, Doctor. It’ll only take a moment. I’ve been trying to get you for three days.”
Grudgingly Pearson gave in. Taking the forms and the ballpoint pen Miss Mildred offered him, he moved over to a desk, grumbling as he scribbled signatures. “I don’t know what I’m signing. What is it?”
“It’s the Howden case, Dr. Pearson.”
Pearson was fretting still. “There are so many cases. I don’t remember.”
Patiently Miss Mildred reminded him. “It’s the workman who was killed when he fell from a high catwalk. If you remember, the employers said the fall must have been caused by a heart attack because otherwise their safety precautions would have prevented it.”
Pearson grunted. “Yeah.”
As he went on signing Miss Mildred continued her summation. When she started something she liked to finish it and leave it tidy. “The autopsy, however, showed that the man had a healthy heart and no other physical condition which might have caused him to fall.”
“I know all that.” Pearson cut her short.
“I’m sorry, Doctor. I thought . . .”
“It was an accident. They’ll have to give the widow a pension.” Pearson tossed out the observation, then adjusted his cigar and scrawled another signature, half shredding the paper. He has rather more egg than usual on his tie, Miss Mildred thought, and she wondered how many days it was since the pathologist had brushed his gray, unruly hair. Joe Pearson’s personal appearance verged somewhere between a joke and a scandal at Three Counties Hospital. Since his wife had died some ten years earlier and he had begun to live alone, his dress had got progressively worse. Now, at sixty-six, his appearance sometimes suggested a vagrant rather than the head of a major hospital department. Under the white lab coat Miss Mildred could see a knitted woolen vest with frayed buttonholes and two other holes which were probably acid burns. And gray, uncreased slacks drooped over scuffed shoes that sadly needed shining.
Joe Pearson signed the last paper and thrust the batch, almost savagely, at little Miss Mildred. “Maybe I can get on with some real work now, eh?” His cigar bobbed up and down, discharging ash partly on himself, partly on the polished linoleum floor. Pearson had been at Three Counties long enough to get away with rudeness that would never be tolerated in a younger man and also to ignore the “No Smoking” signs posted conspicuously at intervals in the hospital corridors.
“Thank you, Doctor. Thank you very much.”
He nodded curtly, then made for the main lobby, intending to take an elevator to the basement. But both elevators were on floors above. With an exclamation of annoyance he ducked down the stairway which led to his own department.
On the surgical floor three stories above the atmosphere was more relaxed. With temperature and humidity carefully controlled throughout the whole operating section, staff surgeons, interns, and nurses, stripped down to their underwear beneath green scrub suits, could work in comfort. Some of the surgeons had completed their first cases of the morning and were drifting into the staff room for coffee before going on to subsequent ones. From the operating rooms which lined the corridor, aseptically sealed off from the rest of the hospital, nurses were beginning to wheel patients still under anesthesia into one of the two recovery rooms. There the patients would remain under observation until well enough to go back to their assigned hospital beds.
Between sips of scalding coffee Lucy Grainger, an orthopedic surgeon, was defending the purchase of a Volkswagen she had made the day before.
“I’m sorry, Lucy,” Dr. Bartlett was saying. “I’m afraid I may have stepped on it in the parking lot.”
“Never mind, Gil,” she told him. “You need the exercise you get just walking around that Detroit monster of yours.”
Gil Bartlett, one of the hospital’s general surgeons, was noted for possession of a cream Cadillac which was seldom seen other than in gleaming spotlessness. It reflected, in fact, the dapperness of its owner, invariably one of the best dressed among the Three Counties attending physicians. Bartlett was also the only member of staff to sport a beard—a Van Dyke, always neatly trimmed—which bobbed up and down when he talked, a process Lucy found fascinating to watch.
Kent O’Donnell strolled over to join them. O’Donnell was chief of surgery and also president of the hospital’s medical board. Bartlett hailed him.
“Kent, I’ve been looking for you. I’m lecturing the nurses next week on adult tonsillectomies. Do you have some Kodachromes showing aspiration tracheitis and pneumonia?”
O’Donnell ran his mind over some of the color photographs in his teaching collection. He knew what Bartlett was referring to—it was one of the lesser known effects which sometimes followed removal of tonsils from an adult. Like most surgeons, O’Donnell was aware that even with extreme operative care a tiny portion of tonsil sometimes escaped the surgeon’s forceps and was drawn into the lung where it formed an abscess. Now he recalled a group of pictures he had of the trachea and lung, portraying this condition; they had been taken during an autopsy. He told Bartlett, “I think so. I’ll look them out tonight.”
Lucy Grainger said, “If you don’t have one of the trachea, give him the rectum. He’ll never know the difference.” A laugh ran round the surgeons’ room.
O’Donnell smiled too. He and Lucy were old friends; in fact, he sometimes wondered if, given more time and opportunity, they might not become something more. He liked her for many things, not least the way she could hold her own in what was sometimes thought of as a man’s world. At the same time, though, she never lost her essential femininity. The scrub suit she was wearing now made her shapeless, almost anonymous, like the rest of them. But he knew that beneath was a trim, slim figure, usually dressed conservatively but in fashion.
His thoughts were interrupted by a nurse who had knocked, then entered discreetly.
“Dr. O’Donnell, your patient’s family are outside.”
“Tell them I’ll be right out.” He moved into the locker room and began to slip out of his scrub suit. With only one operation scheduled for the day he was through with surgery now. When he had reassured the family outside—he had just operated successfully for removal of gallstones—his next call would be in the administrator’s office.
One floor above surgical, in private patient’s room 48, George Andrew Dunton had lost the capacity to be affected by heat or coolness and was fifteen seconds away from death. As Dr. MacMahon held his patient’s wrist, waiting for the pulse to stop, Nurse Penfield turned the window fan to “high” because the presence of the family had made the room uncomfortably stuffy. This was a good family, she reflected—the wife, grown son, and younger daughter. The wife was crying softly, the daughter silent but with tears coursing down her cheeks. The son had turned away but his shoulders were shaking. When I die, Elaine Penfield thought, I hope someone has tears for me; it’s the best obituary there is.
Now Dr. MacMahon lowered the wrist and looked across at the others. No words were needed, and methodically Nurse Penfield noted the time of death as 10:52 a.m.
Along the corridor in the other wards and private patients’ rooms this was one of the quieter times of day. Morning medications had been given; rounds were over, and there was a lull until lunch time would bring the cycle of activity to a peak once more. Some of the nurses had slipped down to the cafeteria for coffee; others who remained were writing their case notes. “Complains of continued abdominal pains,” Nurse Wilding had written on a woman patient’s chart and was about to add another line when she paused.
For the second time that morning Wilding, gray-haired and at fifty-six one of the older nurses on staff, reached into her uniform and took out the letter she had read twice already since it had been delivered to her desk along with the patients’ mail. A snapshot of a young naval lieutenant, j.g., with a pretty girl on his arm, fell out as she opened it, and for a moment she gazed down at the picture before reading the letter again. “Dear Mother,” it started. “This will come as a surprise to you, but I have met a girl here in San Francisco and we were married yesterday. I know in some ways this will be a big disappointment since you always said you wanted to be at my wedding, but I’m sure you’ll understand when I tell you . . .”
Nurse Wilding let her eyes wander from the letter and thought of the boy she remembered and of whom she had seen so little. After the divorce she had taken care of Adam until college; then there had been Annapolis, a few weekends and brief holidays, after that the Navy, and now he was a man, belonging to someone else. Later on today she must send them a telegram of love and good wishes. Years ago she had always said that as soon as Adam was on his own and self-supporting she would quit nursing, but she never had, and now retirement would come soon enough without hastening it. She put the letter and photograph back in her uniform pocket and reached for the pen she had laid down. Then in careful script she added to the chart: “Slight vomiting with diarrhea. Dr. Reubens notified.”
In Obstetrics, on the fourth floor, there was never any time of day which could be predictably quiet. Babies, Dr. Charles Dornberger thought, as he scrubbed alongside two other obstetricians, had an annoying habit of coming in batches. There would be hours, even days, when things would be orderly, quiet, and babies could be delivered in tidy succession. Then suddenly all hell would break loose, with half a dozen waiting to be born at once. This was one of those moments.
His own patient, a buxom, perpetually cheerful Negress, was about to deliver her tenth child. Because she had arrived at the hospital late, and already advanced in labor, she had been brought up on a stretcher from Emergency. While he was still scrubbing Dornberger could hear part of her duologue outside with the intern who had escorted her to Obstetrics.
Apparently, as was normal for an urgent case, the intern had cleared the passenger elevator down below on the main floor.
“All them nice peopl’ movin’ out of th’ elevator fo’ me,” she was saying. “Why, ah nevah felt so important befo’ in all mah life.” At this point Dornberger heard the intern tell the patient to relax and the answer came back, “Relax, sonny? Ah am relaxed. Ah always relaxes when ah has a baby. That th’ only time there’s no dishes, no washin’, no cookin’. Why, ah look forward to comin’ in here. This just a holiday fo’ me.” She paused as pain gripped her. Then, partly through clenched teeth, she muttered, “Nine children ah’ve got, and this’ll be the tenth. Th’ oldest one’s as big as you, sonny. Now you be lookin’ fo’ me a year from now. Ah tell you, ah’ll be back.” Dornberger heard her chuckling as her voice faded, the delivery room nurses taking over, while the intern went back to his post in Emergency.
Now Dornberger, scrubbed, gowned, sterile, and sweating from the heat, followed his patient into the delivery room.
In the hospital kitchens, where the heat was less of a problem because people who worked there were used to it, Hilda Straughan, the chief dietitian, nibbled a piece of raisin pie and nodded approvingly at the senior pastry cook. She suspected that the calories, along with others, would be reflected on her bathroom scales a week from now but quelled her conscience by telling herself it was a dietitian’s duty to sample as much as possible of the hospital fare. Besides, it was somewhat late now for Mrs. Straughan to be fretting on the subject of calories and weight. The accumulated result of many earlier samplings caused her nowadays to turn the scales around two hundred pounds, a good deal of which was in her magnificent breasts—twin Gibraltars, famed through the hospital, and which made her progress not unlike the majesty of an aircraft carrier preceded by an escort of twin battleships.
But, as well as food, Mrs. Straughan was in love with her job. Glancing around her with satisfaction, she took in her empire—the shining steel ovens and serving tables, the gleaming utensils, the sparkling white aprons of the cooks and their assistants. Her heart warmed at the sight of all of it.
This was a busy time in the kitchens—lunch was the heaviest meal of the day because, as well as patients, there was the full hospital staff to be fed in the cafeteria. In twenty minutes or so the diet trays would be going up to the wards, and for two hours afterward the service of food would continue. Then, while the kitchen help cleared and stacked dishes, the cooks would begin preparing the evening meal.
The thought of dishes caused Mrs. Straughan to frown thoughtfully, and she propelled herself into the back section of the kitchen where the two big automatic dishwashers were installed. This was a part of her domain less gleaming and modern than the other section, and the chief dietitian reflected, not for the first time, that she would be happy when the equipment here was modernized, as the rest of the kitchens had been. It was understandable, though, that everything could not be done at once, and she had to admit she had browbeaten the administration into a lot of expensive new equipment in the two years she had held her job at Three Counties. All the same, she decided as she moved on to check the steam tables in the cafeteria, she would have another talk with the administrator about those dishwashers soon.
The chief dietitian was not the only one in the hospital whose thoughts were on food. In Radiology, on the second floor, an outpatient—Mr. James Bladwick, vice-president of sales for one of Burlington’s big-three automobile dealerships—was, in his own words, “as hungry as hell.”
There was reason for this. On his physician’s instructions Jim Bladwick had fasted since midnight, and now he was in number one X-ray room, ready for a gastric series. The X-rays would confirm or deny the suspicion that flourishing in the Bladwick interior was a duodenal ulcer. Jim Bladwick hoped the suspicion was unfounded; in fact, he hoped desperately that neither an ulcer nor anything else would conspire to slow him down now that his drive and sacrifice of the past three years, his willingness to work harder and longer than anyone else on sales staff, were at last paying off.
Sure he worried; who wouldn’t when they had a dealer sales quota to meet every month. But it just couldn’t be an ulcer; it had to be something else—something trivial that could be fixed up quickly. He had been vice-president of sales only a matter of six weeks, but despite the high-sounding title he knew better than anyone that retention of it depended on a continued ability to produce. And to produce you had to be on the ball—tough, available, fit. No medical certificate would compensate for a declining sales graph.
Jim Bladwick had put this moment off for some time. It was probably two months ago that he had become aware of distress and a general aching in the stomach region, had noticed, too, he was burping a lot, sometimes at awkward moments with customers around. For a while he had tried to pretend it was nothing out of the ordinary, but finally he had sought medical advice, and this morning’s session was the outcome. He hoped, though, it was not going to take too long; that deal of Fowler’s for six panel trucks was getting hot, and they needed the sale badly. By God, he was hungry!
For Dr. Ralph Bell, the senior radiologist—“Ding Dong” to most of the hospital staff—this was just another G.I. series, no different from any of a hundred others. But, playing a mental game he sometimes indulged in, he decided to bet “yes” on this one. This patient looked the type for an ulcer. From behind his own thick-lensed, horn-rimmed glasses Bell had been watching the other man covertly. He looked a worrier, Bell decided; he was obviously stewing right now. The radiologist placed Bladwick in position behind the fluoroscope and handed him a tumbler of barium. “When I tell you,” he said, “drink this right down.”
When he was ready he ordered, “Now!” Bladwick drained the glass.
In the fluoroscope Bell watched the path of the barium as it coursed first through the esophagus, then into the stomach, and from there into the duodenum. Sharpened by the opaque liquid, the outline of each organ was clearly visible, and at various stages Bell thumbed a button recording the results on film. Now he palpated the patient’s abdomen to move the barium around. Then he could see it—a crater in the duodenum. An ulcer, clear and unmistakable. He reflected that he had won the bet with himself. Aloud he said, “That’s all, Mr. Bladwick, thank you.”
“Well, Doc, what’s the verdict? Am I going to live?”
“You’ll live.” Most of them wanted to know what he saw in the fluoroscope. Magic mirror on the wall, who is healthiest of all? It wasn’t his job to tell though. “Your own physician will get these films tomorrow. I imagine he’ll be talking to you.” Hard luck, my friend, he thought. I hope you like lots of rest and a diet of milk and poached eggs.
Two hundred yards away from the main hospital block, in a run-down building that had once been a furniture factory and now did duty as a nurses’ home, Student Nurse Vivian Loburton was having trouble with a zipper that refused to zip.
“Damn and hellfire!” She addressed the zipper with an expression much favored by her father, who had made a comfortable fortune felling tall trees and saw no reason to have one language for the woods and another at home.
Vivian, at nineteen, sometimes provided an interesting contrast between her father’s robustness and her mother’s innate New England delicacy which close contact with Oregon lumbering had never changed. Now, in her fourth month of training as a nurse, Vivian had already found something of the traits of both parents in her own reaction to the hospital and nursing. At one and the same time she was awed and fascinated, repulsed and disgusted. She supposed that close contact with sickness and disease was always a shock for anyone new. But knowing that did not help much when your stomach was ready to do flip-flops and it took all the will you possessed not to turn and run away.
It was after moments like this that she felt the need for a change of scene, a cleansing antidote; and to some extent she had found it in an old love—music. Surprisingly, for a city of its size, Burlington had an excellent symphony, and, discovering this, Vivian had become one of its supporters. She found the switch in tempo, the balm of good music, helped to steady and reassure her. She had been sorry when concerts had ended for the summer, and there had been moments recently when she had felt the need of something to replace them.
There was no time now, though, for odd, stray thoughts; the gap between morning classes and reporting to a ward for duty had been short enough. Now this zipper! . . . She tugged again, and suddenly the teeth meshed, the zipper closed. Relieved, she ran for the door, then paused to mop her face. Jeepers, it was hot! And all that effort had made her sweat like crazy.
So it went—that morning as all mornings—through the hospital. In the clinics, the nurseries, laboratories, operating rooms; in Neurology, Psychiatry, Pediatrics, Dermatology; in Orthopedics, Ophthalmology, Gynecology, Urology; in the charity wards and the private patients’ pavilion; in the service departments—administration, accounting, purchasing, housekeeping; in the waiting rooms, corridors, halls, elevators; throughout the five floors, basement, and sub-basement of Three Counties Hospital the tides and currents of humanity and medicine ebbed and flowed.
It was eleven, o’clock on the fifteenth of July.
Two blocks from Three Counties Hospital the clock-tower bell of the Church of the Redeemer was chiming the hour as Kent O’Donnell made his way from the surgical floor down to Administration. The sound of the bell, off-key as always from a flaw in its long-ago casting, drifted in through an open stairway window. Automatically O’Donnell checked his wrist watch, then moved aside as a group of interns passed him hurriedly on the staff stairway, their feet sounding noisily on the metal treads. The interns quietened a little when they saw the medical-board president and offered a respectful “Good morning, Doctor,” as each went by. On the second floor O’Donnell halted to let a nurse with a wheel chair pass. In it was a girl of about ten with a bandage over one eye, a woman, plainly the mother, hovering protectively alongside.
The nurse, whom he smiled at but failed to recognize, appraised him covertly. In his early forties, O’Donnell still rated second glances from women. He had retained the build which had made him an outstanding quarterback in his college years—a tall, erect figure with big, broad shoulders and muscular arms. Even nowadays he had a trick of squaring his shoulders when ready to do something difficult or make a decision—as if readying instinctively to stop the charge of a red-dogging tackle. Yet despite his bulk—mostly bone and muscle with less than a pound of overweight—he still moved lightly; and regular sport—tennis in summer, skiing in winter—had kept him robust and lithe.
O’Donnell had never been handsome in the Adonic sense, but he had a rugged, creased irregularity of face (his nose still carried the scar of an old football injury) which women so often, and perversely, find attractive in men. Only his hair showed the real trace of years; not so long ago jet black, now it was graying swiftly as if the color pigments had suddenly surrendered and were marching out.
Now, from behind, O’Donnell heard his name called. He stopped and saw the caller was Bill Rufus, one of the seniors on surgical staff.