Peterli.Berczeller------------------------~
Laughing on the Outside, Crying on the Inside Von Recklinghausen, Chvostek, Addison, Master, and Cushing are just a very few of the names that have been associated with the original description of a disease entity, the development of a diagnostic test, or the landmark recognition of a crucial physical finding. In the 1950s and '60s, more "rational" and more descriptive terminology began to come into vogue. However, all was not lost. Happily, it was still possible to show off arcane eponymic skills, and in doing so gloss over gaps in personal basic science knowledge while at the same time wowing the natives with one's erudition. This was the jousting, and often the sport. of rounding. The names of the worthies enumerated above were, of course, not adequately obscure for the fray. To come off nobly in the tournament, not only did references to the literature have to be flung down like so many gauntlets, but mention of such war-horses as the Carvallo sign, Mendelson syndrome, the Albright syndrome, or Nelson syndrome was de rigueur. If, as a coup de grace, one could introduce Seabright Bantam syndrome into the conversation, in one glorious moment one would both impress those above and below in the pecking order and memorialize a strain of chickens. Times have changed. Now it is acronyms that are in fashion. GBD and CREST, HLA and SIADH are heard in our wards and corridors as the technology of the computer generation supersedes the historical nostalgia of its forebears. In a certain sense, however, this development is reassuring, for it suggests that, conversationally at least, a measure of irrationality remains with us. After all, acronyms, like eponyms, are not
self-explanatory. They are meant to be used as a kind of shorthand, and some knowledge of the entity to which they refer is necessary for deciphering. In other words, there may be hope for relief from the bland, noncontentious rounds that are the norm today, where the most extreme notion expressed is that someone will make copies of this or that article and bring them in one of these days. All of the above is either beside the point or an extended excuse, because to the plethora of acronyms available I should like to add a new one. Contrary to accepted scientific principles, I have not done a literature search, but I believe that the name is an original. On the other hand, the individual facets of the entity are well known to practitioners, especially in internal medicine, gynecology, and urology. With the potent therapeutic tools currently at our command, we are squarely in the age of diseases of medical progress. Graft-versus-host (GVH, if you prefer) disease, leukemia after treatment for myeloproliferative disorders, and severe infections associated with chemotherapy are just several examples of the dark flip side of laudable therapeutic intention. In contrast to these complications of therapy that tend to take on a life of their own, often as dreary as the original affliction, the complications arising from diagnostic procedures are usually (continues}
Dr. Berczeller Is Professor of Clinical Medicine, New York University School of Medicine.
Hospital Practice September 15. 1992
17
Peter H. Berczeller
(canttnuedJ---------------.
less grave, perhaps even somewhat prosaic. Not always. Certainly, we see anaphylactic shock or renal failure associated with the use of iodine dyes as well as accidental perforation of the colon with lower endoscopy and intra-abdominal bleeding after liver biopsy. In such cases, a heavy burden of proof rests on our shoulders. Was the procedure truly indicated? However, even if the indication is impeccable, there are few more distressing experiences in medicine than a critical event arising from a "test." This is where Diagnosis-Related Anxiety Syndrome (DRAS) comes in. Having coined a syndrome (and an acronym), I am constrained by training at least to su~est the incidence and offer some prognostic criteria. My data base is weak; I can only extrapolate from my own experience and state that the prevalence of this syndrome is high, especially in bigcity upper- and middle-class patients in North America. Before going further into a clinical description, let me narrow the definition of DRAS somewhat. The syndrome is related to screening procedures that may or may not tell the patient whether this or that disease is present. The problem is that because of the enhanced diagnostic capabilities we possess, we cannot trust our own bodies anymore! It used to be that if youfelt well and looked well, for all intents and purposes you were well. But nowadays, just because you are laughing on the outside, you cannot exclude the possibility that something is crying within you. In the not-distant past, it was possible to say unequivocally, "I am fine." At this juncture of our medical progress, however, one can only say: "I feel okay. But on the other hand, I don't know what my current PSA or CA-125 or mammography or prostatic ultrasound show, not to mention HIV serology. Mter all, I did have lunch with some-
one 10 years ago who later proved to have AIDS."
This concept of the unknowability ofbiologtc phenomena, of forces beyond human control secretly conspiring within one's own body, is a very frightening one. It threatens any joie de vivre that we have left after the disagreeable encounters of our day-to-day lives. As a further constraint on its definition, let me note that DRAS is limited to people who have no evident illness or abnormal findings for which regular follow-up is indicated. The anxiety (and, frequently, depression) associated with definite pathology is another matter altogether and outside the scope of this essay. The obvious question that comes up, of course, is the following: Is early diagnosis worth it? Is the emotional cost-benefit ratio favorable, so that the psychic trauma sustained during repeated evaluation for as-yet-undiagnosed disease is countered by the shining hope of cure if only the "pickup" of the offending lesion is effected early enough? As a general internist, I have done thousands of complete evaluations of patients during my 32 years of practice. I urge my female patients of appropriate age or risk stratification to have regular mammograms. For male patients, I order prostate-specific antigen testing when appropriate. In other words, I try to do for my patients what is right, gtven the status of our knowledge of preventive medicine. But I remain unsure that the possibility of early diagnosis justifies the terrible anxiety that some patients suffer as they go from diagnostic procedure to diagnostic procedure, like pilgrims attending the stations of the cross. For some patients, six months or a year is defined as the amount of time that elapses between, for example, routine mam(conttnues)
Hospital Practice September 15. 1992
21
Peter H. Berczeller
(continued)
Ideal Therapy For:
!ifsmokers litj:Iderly Patients [!(Maintenance Patients
mograms. This is life at its lowest common denominator: going from fear to fear on a train that never reaches its destination. But to quote the late, currently unlamented V. I. Lenin, "What is to be done?" Certainly, doctors cannot leave diagnostic stones unturned as we cautiously subscribe to the belief that, in some tumors at least, early diagnosis favorably affects the ultimate outcome. But what we can do is explain and individualize screening so that it provokes less anxiety. And we should see to it that patients are kept waiting for a minimum of time before they get the results of screening examinations, so that intra- or extraoffice bureaucracy does not add further to the burden of fear.
Professooal U5e lnformatron
BRIEF SUMMARY CONTRAINOICATIONS T'lere are no known contramdiCa!IOns to the use of sutralfate
PRECAUTIONS Duodenal ulcer rs a chrome, recurrent drsease Whrle shorHerm treatment wrth sucralfate can result rn complete healing of the ulcer. a successful course of treat,ent wrth sucrallate should not be expected to alter the pcsthealrng Ire
quency or seventy of duodenal ulceratiOn Special Populations: Chronic Renal Failure and Oialysrs Patients. When sucralfate rs admmrs!ered orally. small amounts of alummum are absorbed from the gastromtestrnal tract Concomitant use of. sucrallate wrth other products that contam alummum. such as alummum-cantammg antacrds. may lfltrease the total
Beyond that, faced with a patient who suffers from DRAS, we should be flexible enough to let routine be swayed by judgment. For example, if a woman with a negative famUy history who is not on estrogens and who has no lumps in the breast would rather have manunography every 18 rather than every 12 months, I do not feel that it is reckless on my part to act in accordance with her wishes. We doctors, as is so frequently the case, are torn and conflicted. We want to do the "right" thing but are not always sure what that is. We must be true to our training, and, ever guiltprone, we are ashamed if we do not make a diagnosis at the earliest possible moment. Yet the emotional lives of some patients are severely disturbed by the uncertainty engendered by repeated survey procedures.
body burden or alum1num Pat1ents w1th normal renal lunct1on rece1v1ng the recommended doses of sucralfate and alummum-contam1ng products adeQuately excrete alummum 1n the ur1ne Patients with chron1c renal fa1lure or those rece1vmg 01alys1s have 1mpa1red excretiOn of absorbed alummum In add1t1on. alum1num does not cross d1alyS1S membranes because 11 IS bound to album1n and transferrm plasma protems Alummum accumulatiOn and tOXICity 1a1um1num osteodystrophy, osteomalacia. encephalopathy) have been descnbed 1n pat1ents w1th renal 1mpa1rment Sucralfate should be used w1th caut1on 1n patients w1th chror1c renal failure Drug Interactions: Some stud1es have shown that Simultaneous sucrallate adm1nistrat1on 1n healthy volunteers reduced the extent ol absorp11on (bloavaJiabilltyl ol s1ngle doses ol the followu"'Q drugs Clmelldrne. C1profloxac1n. d1go~m. norllo~acm. phenytom. ranl!idme. tetracycl1ne. and theophylline The mec11an1sm of these mteract1ons appears to be nonsystemrc m nature. presumably resulling from sucralfate b1nding to theconcormtantagent m the gastromtestmal tract In all cases stud1ed to date(c1melldme. Clprolloxacm. d1gox1n. and ramt1dme). dosmg the concom11ant medication 2 hours before sucralfate eliml· nated the mteracliOn Because of the potent1al of CARAFATE to alter the absorptiOn of some drugs. CARAFATE should be admm1stered separately !rom other drugs when alterat1ons m b10availabi11ty are felt to be cntJcal In these cases. pat1ents should be monitored appropnately Carcinogenesis, Mutagenesis, Impairment of Fertility: Chrome oral tOXICity studieS ol 24 months' durat1on were conducted 1n m1ce and rats at doses up to 1 gm/kg (12 t1mes the human case) There was no ev1dence ol drug-related tumO'JgenJCJty A reproductiOn study m ra~~ at doses up to 38 t1mes the human dose d1d not reveal any md1Cali0n of fertli1ty 1mpa1rment MutageniCity stud1es were not conducted Pregnancy: TeratogeniC effects Pregnancy Category B Teratogemc11y stud1es have been performed m m1ce. rats. and rabbits at doses up to 50 11mes the human dose and have revealed no ev1dence of harm to the fetus due to sucrallate There are. however, no adeQuate and well-controlled stud1es m pregnant women Because an1mal reproduct1on stud1es are not always pred1ct1ve of human response. th1s drug should be used durmg pregnancy only 1f clearly needed Nursmg Mothers It IS not known whether this drug IS excreted m human milk Because many drugs are excreted m human milk, caut1on should be exerCISed when sucrallate 1s admm1stered to a nursing woman Pediatric Use: Safety and effectiveness in children have not been established
ADVERSE REACTIONS Adverse reactions to sucraltate 1n clin1cal trials were mmor and only rarely led to dJscon!lnuatiOn of the drug In stud1es mvolvmg over 2700 pat1ents treated w1th sucra'fate tablets. adverse effects were reponed 1n 129 !4 7%1 Const1pat10n was the most freQuent complamt !2~el Ott'er adverse effects reponed 1n less than 0 5% ol the pa11ents are listed below by body system Gastromtestinal: d1arrhea. nausea. vom1!1nQ. gastnc d1scomlon md1ges110n. flatulence. dry mouth Dermatological: pru111us. rash Nervous system: dimness. sleepmess. ver11go Other: back pam. headache Postmarketmg reports of hypersensitiVIty react1ons. mcludng url1Ca11a !h1vesl. angmedema. resp1ratory d11f1culty. and rhm1t1s have been rece1ved However. a causal relat1onsh1p has not been establiShed
The old dictum "do neither too much nor too little" should guide those of us who understand that recurrent severe anxiety is in many ways as catastrophic as is severe organic illness. Yes, early diagnosis is the only game in town, but I would feel a lot better if I were more sure that the game is unequivocally and invariably loaded in the patient's favor.
Issued 3/91
© 1991, Marion Merrell Dow Inc. All rights reserved. CAFAF422/A1141
0532P1
24
Laughing on the Outside, Crying on the Inside Von Recklinghausen, Chvostek, Addison, Master, and Cushing are just a very few of the names that have been associated with the original description of a disease entity, the development of a diagnostic test, or the landmark recognition of a crucial physical finding. In the 1950s and '60s, more "rational" and more descriptive terminology began to come into vogue. However, all was not lost. Happily, it was still possible to show off arcane eponymic skills, and in doing so gloss over gaps in personal basic science knowledge while at the same time wowing the natives with one's erudition. This was the jousting, and often the sport. of rounding. The names of the worthies enumerated above were, of course, not adequately obscure for the fray. To come off nobly in the tournament, not only did references to the literature have to be flung down like so many gauntlets, but mention of such war-horses as the Carvallo sign, Mendelson syndrome, the Albright syndrome, or Nelson syndrome was de rigueur. If, as a coup de grace, one could introduce Seabright Bantam syndrome into the conversation, in one glorious moment one would both impress those above and below in the pecking order and memorialize a strain of chickens. Times have changed. Now it is acronyms that are in fashion. GBD and CREST, HLA and SIADH are heard in our wards and corridors as the technology of the computer generation supersedes the historical nostalgia of its forebears. In a certain sense, however, this development is reassuring, for it suggests that, conversationally at least, a measure of irrationality remains with us. After all, acronyms, like eponyms, are not
self-explanatory. They are meant to be used as a kind of shorthand, and some knowledge of the entity to which they refer is necessary for deciphering. In other words, there may be hope for relief from the bland, noncontentious rounds that are the norm today, where the most extreme notion expressed is that someone will make copies of this or that article and bring them in one of these days. All of the above is either beside the point or an extended excuse, because to the plethora of acronyms available I should like to add a new one. Contrary to accepted scientific principles, I have not done a literature search, but I believe that the name is an original. On the other hand, the individual facets of the entity are well known to practitioners, especially in internal medicine, gynecology, and urology. With the potent therapeutic tools currently at our command, we are squarely in the age of diseases of medical progress. Graft-versus-host (GVH, if you prefer) disease, leukemia after treatment for myeloproliferative disorders, and severe infections associated with chemotherapy are just several examples of the dark flip side of laudable therapeutic intention. In contrast to these complications of therapy that tend to take on a life of their own, often as dreary as the original affliction, the complications arising from diagnostic procedures are usually (continues}
Dr. Berczeller Is Professor of Clinical Medicine, New York University School of Medicine.
Hospital Practice September 15. 1992
17
Peter H. Berczeller
(canttnuedJ---------------.
less grave, perhaps even somewhat prosaic. Not always. Certainly, we see anaphylactic shock or renal failure associated with the use of iodine dyes as well as accidental perforation of the colon with lower endoscopy and intra-abdominal bleeding after liver biopsy. In such cases, a heavy burden of proof rests on our shoulders. Was the procedure truly indicated? However, even if the indication is impeccable, there are few more distressing experiences in medicine than a critical event arising from a "test." This is where Diagnosis-Related Anxiety Syndrome (DRAS) comes in. Having coined a syndrome (and an acronym), I am constrained by training at least to su~est the incidence and offer some prognostic criteria. My data base is weak; I can only extrapolate from my own experience and state that the prevalence of this syndrome is high, especially in bigcity upper- and middle-class patients in North America. Before going further into a clinical description, let me narrow the definition of DRAS somewhat. The syndrome is related to screening procedures that may or may not tell the patient whether this or that disease is present. The problem is that because of the enhanced diagnostic capabilities we possess, we cannot trust our own bodies anymore! It used to be that if youfelt well and looked well, for all intents and purposes you were well. But nowadays, just because you are laughing on the outside, you cannot exclude the possibility that something is crying within you. In the not-distant past, it was possible to say unequivocally, "I am fine." At this juncture of our medical progress, however, one can only say: "I feel okay. But on the other hand, I don't know what my current PSA or CA-125 or mammography or prostatic ultrasound show, not to mention HIV serology. Mter all, I did have lunch with some-
one 10 years ago who later proved to have AIDS."
This concept of the unknowability ofbiologtc phenomena, of forces beyond human control secretly conspiring within one's own body, is a very frightening one. It threatens any joie de vivre that we have left after the disagreeable encounters of our day-to-day lives. As a further constraint on its definition, let me note that DRAS is limited to people who have no evident illness or abnormal findings for which regular follow-up is indicated. The anxiety (and, frequently, depression) associated with definite pathology is another matter altogether and outside the scope of this essay. The obvious question that comes up, of course, is the following: Is early diagnosis worth it? Is the emotional cost-benefit ratio favorable, so that the psychic trauma sustained during repeated evaluation for as-yet-undiagnosed disease is countered by the shining hope of cure if only the "pickup" of the offending lesion is effected early enough? As a general internist, I have done thousands of complete evaluations of patients during my 32 years of practice. I urge my female patients of appropriate age or risk stratification to have regular mammograms. For male patients, I order prostate-specific antigen testing when appropriate. In other words, I try to do for my patients what is right, gtven the status of our knowledge of preventive medicine. But I remain unsure that the possibility of early diagnosis justifies the terrible anxiety that some patients suffer as they go from diagnostic procedure to diagnostic procedure, like pilgrims attending the stations of the cross. For some patients, six months or a year is defined as the amount of time that elapses between, for example, routine mam(conttnues)
Hospital Practice September 15. 1992
21
Peter H. Berczeller
(continued)
Ideal Therapy For:
!ifsmokers litj:Iderly Patients [!(Maintenance Patients
mograms. This is life at its lowest common denominator: going from fear to fear on a train that never reaches its destination. But to quote the late, currently unlamented V. I. Lenin, "What is to be done?" Certainly, doctors cannot leave diagnostic stones unturned as we cautiously subscribe to the belief that, in some tumors at least, early diagnosis favorably affects the ultimate outcome. But what we can do is explain and individualize screening so that it provokes less anxiety. And we should see to it that patients are kept waiting for a minimum of time before they get the results of screening examinations, so that intra- or extraoffice bureaucracy does not add further to the burden of fear.
Professooal U5e lnformatron
BRIEF SUMMARY CONTRAINOICATIONS T'lere are no known contramdiCa!IOns to the use of sutralfate
PRECAUTIONS Duodenal ulcer rs a chrome, recurrent drsease Whrle shorHerm treatment wrth sucralfate can result rn complete healing of the ulcer. a successful course of treat,ent wrth sucrallate should not be expected to alter the pcsthealrng Ire
quency or seventy of duodenal ulceratiOn Special Populations: Chronic Renal Failure and Oialysrs Patients. When sucralfate rs admmrs!ered orally. small amounts of alummum are absorbed from the gastromtestrnal tract Concomitant use of. sucrallate wrth other products that contam alummum. such as alummum-cantammg antacrds. may lfltrease the total
Beyond that, faced with a patient who suffers from DRAS, we should be flexible enough to let routine be swayed by judgment. For example, if a woman with a negative famUy history who is not on estrogens and who has no lumps in the breast would rather have manunography every 18 rather than every 12 months, I do not feel that it is reckless on my part to act in accordance with her wishes. We doctors, as is so frequently the case, are torn and conflicted. We want to do the "right" thing but are not always sure what that is. We must be true to our training, and, ever guiltprone, we are ashamed if we do not make a diagnosis at the earliest possible moment. Yet the emotional lives of some patients are severely disturbed by the uncertainty engendered by repeated survey procedures.
body burden or alum1num Pat1ents w1th normal renal lunct1on rece1v1ng the recommended doses of sucralfate and alummum-contam1ng products adeQuately excrete alummum 1n the ur1ne Patients with chron1c renal fa1lure or those rece1vmg 01alys1s have 1mpa1red excretiOn of absorbed alummum In add1t1on. alum1num does not cross d1alyS1S membranes because 11 IS bound to album1n and transferrm plasma protems Alummum accumulatiOn and tOXICity 1a1um1num osteodystrophy, osteomalacia. encephalopathy) have been descnbed 1n pat1ents w1th renal 1mpa1rment Sucralfate should be used w1th caut1on 1n patients w1th chror1c renal failure Drug Interactions: Some stud1es have shown that Simultaneous sucrallate adm1nistrat1on 1n healthy volunteers reduced the extent ol absorp11on (bloavaJiabilltyl ol s1ngle doses ol the followu"'Q drugs Clmelldrne. C1profloxac1n. d1go~m. norllo~acm. phenytom. ranl!idme. tetracycl1ne. and theophylline The mec11an1sm of these mteract1ons appears to be nonsystemrc m nature. presumably resulling from sucralfate b1nding to theconcormtantagent m the gastromtestmal tract In all cases stud1ed to date(c1melldme. Clprolloxacm. d1gox1n. and ramt1dme). dosmg the concom11ant medication 2 hours before sucralfate eliml· nated the mteracliOn Because of the potent1al of CARAFATE to alter the absorptiOn of some drugs. CARAFATE should be admm1stered separately !rom other drugs when alterat1ons m b10availabi11ty are felt to be cntJcal In these cases. pat1ents should be monitored appropnately Carcinogenesis, Mutagenesis, Impairment of Fertility: Chrome oral tOXICity studieS ol 24 months' durat1on were conducted 1n m1ce and rats at doses up to 1 gm/kg (12 t1mes the human case) There was no ev1dence ol drug-related tumO'JgenJCJty A reproductiOn study m ra~~ at doses up to 38 t1mes the human dose d1d not reveal any md1Cali0n of fertli1ty 1mpa1rment MutageniCity stud1es were not conducted Pregnancy: TeratogeniC effects Pregnancy Category B Teratogemc11y stud1es have been performed m m1ce. rats. and rabbits at doses up to 50 11mes the human dose and have revealed no ev1dence of harm to the fetus due to sucrallate There are. however, no adeQuate and well-controlled stud1es m pregnant women Because an1mal reproduct1on stud1es are not always pred1ct1ve of human response. th1s drug should be used durmg pregnancy only 1f clearly needed Nursmg Mothers It IS not known whether this drug IS excreted m human milk Because many drugs are excreted m human milk, caut1on should be exerCISed when sucrallate 1s admm1stered to a nursing woman Pediatric Use: Safety and effectiveness in children have not been established
ADVERSE REACTIONS Adverse reactions to sucraltate 1n clin1cal trials were mmor and only rarely led to dJscon!lnuatiOn of the drug In stud1es mvolvmg over 2700 pat1ents treated w1th sucra'fate tablets. adverse effects were reponed 1n 129 !4 7%1 Const1pat10n was the most freQuent complamt !2~el Ott'er adverse effects reponed 1n less than 0 5% ol the pa11ents are listed below by body system Gastromtestinal: d1arrhea. nausea. vom1!1nQ. gastnc d1scomlon md1ges110n. flatulence. dry mouth Dermatological: pru111us. rash Nervous system: dimness. sleepmess. ver11go Other: back pam. headache Postmarketmg reports of hypersensitiVIty react1ons. mcludng url1Ca11a !h1vesl. angmedema. resp1ratory d11f1culty. and rhm1t1s have been rece1ved However. a causal relat1onsh1p has not been establiShed
The old dictum "do neither too much nor too little" should guide those of us who understand that recurrent severe anxiety is in many ways as catastrophic as is severe organic illness. Yes, early diagnosis is the only game in town, but I would feel a lot better if I were more sure that the game is unequivocally and invariably loaded in the patient's favor.
Issued 3/91
© 1991, Marion Merrell Dow Inc. All rights reserved. CAFAF422/A1141
0532P1
24
