CHOLANGIO ANN INT MED 1977 LETTER

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LETTERS AND CORRECTIONS Letters submitted for publication must be typed double-spaced. Table 1. Summary of Results in Treatment of Renovascular Disease Text length must not exceed 500 words, and no more than five and Hypertension references may be used. Complete references must be furnished, as specified in "Information for Authors" (page I-6). Specific Patient Good Drug Operated Cured permission to publish should be appended as a postscript. Publi- Surgical Resistant On cation depends on availability of space: we give preference to Risk Surgery and Drug comment on recent content and to new information. Letters for Surgery + Drug Alone this section should be concise-the Editor reserves the right to Positive renin lateralization shorten them and make changes that accord with our style. 1 + + 2 + + Renovascular Disease and Saralasin Tests 3 + 4 + + + 5 + + + TO THE EDITOR: The excellent paper by Marks, Maxwell, and 6 + + + + Kaufman (Ann Intern Med 87:176-182, 1977) did not discuss 7 + + + their findings of a 100% cure rate after surgery in patients with 8 + + renovascular disease and hypertension. Even their five patients 9 + with nonlateralized renin had blood pressure control: three 10* were cured, two were improved. One of the former had a nega- 11 tive response to saralasin. Thus 40% of their operated patients 12 lacked renin criteria and yet had a successful outcome. Negative renin lateralization We also have had the opportunity to study 20 patients with Group I renovascular disease and hypertension from 1972-77 at the Los 13 + Angeles County-University of Southern California Medical 14 + + + Center and the White Memorial Medical Center (Table 1). 15 + + Twelve patients had positive renin lateralization, and of these 10 were operated on, with a resultant cure or marked improve- ment in nine. One patient with a positive saralasin response Group II 17 remained severely hypertensive after documented surgical cor- 18 + rection. Two patients had positive renin lateralized lesions 19 + thought to be difficult to repair technically; these patients are 20 normotensive on drug treatment. Eight patients with negative renin testing were separated into two groups: group I subjects * Positive and negative responses to saralasin. were drug resistant and good surgical risks; and group II sub- Chose drug therapy only. jects were either poor surgical risks or drug sensitive, or both. Three of the group I patients accepted surgery and were cured However, two points are puzzling to me: first, we are not or became normotensive with the addition of drugs. The fourth given the criteria for patient selection in the study. Because of patient chose drug therapy despite marked sedation. All group the large number of patients with renal artery stenosis, there II patients were well controlled on drug therapy. was obviously some selective inclusion of these cases. Second, Forty-five percent of our patients were drug sensitive. Opera- the authors comment, angiotensin blockade is a specific tive repair was attempted in three of five drug-sensitive patients test for the identification of renin-dependent forms of hyperten- with positive renin lateralization, and they were cured or im- sion. The widely used rapid sequence pyelogram and renal proved. Surgery was not done in the remaining four without scans are much less specific tests for the detection of renovascu- renin lateralization. The latter patients were controlled with lar hypertension. drug therapy. It seems to me that this statement, although it may be true, is Thus the findings of Marks, Maxwell, and Kaufman reinforce still unsupported by prospective double-blind studies in which our policy of providing renovascular intervention for patients the hypotensive response to saralasin is evaluated without who have good surgical risk, technically feasible repair, and knowledge of the patient's renovascular status, as determined resistance to drug therapy despite the results of renin or sarala- radiologically. sin testing. On the other hand, the latter tests may help deter- The key question is whether saralasin infusion will detect the mine which drug-sensitive patients should have surgical inter- 10% to 15% of patients with significant renal artery stenosis vention. Perhaps a good-risk, drug-sensitive patient with an ab- and normal intravenous pyelograms (2). Until such a study is normal intravenous pyelogram might not be subjected to angi- done, we, as clinicians, will continue to rely on the radiologists, ography unless the saralasin test was positive. Surgical repair not the pharmacologists (3). would then be attempted if the lesion were operable. NICHOLAS J. VOGELZANG, M.D. VINCENT DEQUATTRO, M.D. Luke's Medical Center Los Angeles County-University of Southern Chicago, IL 60612 California Medical Center Los Angeles, CA 90033 REFERENCES 1. BAER L, PARRA-CARRILLO JZ, RADICHEVICH I, WILLIAMS GS: Detec- tion of renovascular hypertension with angiotensin II blockade. Ann In- TO THE EDITOR: Baer and associates (1) reported a strikingly tern Med 86:257-260, 1977 high percentage of patients having saralasin-responsive or reno- 2. BOOKSTEIN, JJ, ABRAMS HL, BUENGER RE, LECKY FRANKLIN SS, vascular hypertension. The results show good correlation with REISS MD, BLEIFER KH, KLATTE EC, VARADY MAXWELL MH: renal abnormalities detected by radiologic studies or by selec- Radiologic aspects of renovascular hypertension. 2. The role of urogra- tive renal vein renins. phy in unilateral renovascular disease. JAMA 220:1225-1230, 1972 790 December 1977 Annals of Internal Medicine Volume 87 Number 63. MOSER M (Chairman): Report of the Joint National Committee on De- Quality-of-Care Assessment tection, and Treatment of High Blood Pressure. A coopera- tive study. JAMA 237:255-261, 1977 TO THE EDITOR: Recent medical literature abounds with new and more complex schemes for evaluating cost effectiveness and In comment: the quality of care we give our patients. The article "Quality-of- Care Assessment by Process and Outcome Scoring" by Ruben- The criteria for patient selection in our study were neither ran- stein, Mates, and Sidel (Ann Intern Med 86:617-625, 1977) and dom nor double-blind. In many cases drug-resistant hyperten- the editorial by Freeman in the same issue (pp. 647-648) detail a sion or hypertension in a young patient was the criterion for very sophisticated and innovative approach to the assessment of further diagnostic studies including angiotensin II blockade. patient care. I applaud their emphasis on assessment methods Our large medical center with its availability of special diagnos- that "reinforce appropriate decision-making rather than un- tic tests tends to attract a greater fraction of secondary forms of thinking adherence to a rigid checklist." hypertension. We do not imply that the high prevalence of renal The facts that the clinician must consider for effective deci- artery stenosis in our study reflects the true prevalence of this sion-making, even for problems such as uncomplicated urinary disease in the general population, estimated at 5% to 10% (1). tract infection, are often myriad. Algorithms have been devised The second issue raised in Dr. Vogelzang's letter concerns for effective care of several common illnesses including urinary the reliability of angiotensin II blockade in detecting "signifi- tract infections (1). Not only do these algorithms seem to rein- cant" renal artery stenosis despite normal intravenous pyelo- force unthinking adherence to a checklist, they are often de- grams. In our experience and that of others (2) the false-nega- vised by "experts" and are too expensive and time-consuming tive rate with saralasin infusion using the criteria of depressor to be of value in general medical practice. responses and concomitant renin stimulation is low. We also I recently reviewed 100 patient visits to a large family-medi- find that surgical cure correlates well with positive saralasin cine practice for symptoms suggestive of urinary tract infection. responses (3), and Wilson and associates have recently reported Although I did not use methods nearly as elaborate as weighted similar observations (4). I do not agree with Dr. Vogelzang that algorithmic assessment criteria as described by Rubenstein and we should rely on rapid sequence pyelograms and renal scans to co-workers, I was able to make some interesting observations. detect renovascular hypertension. Clinical criteria including In addition, after reviewing some recent literature, I have dis- age, rapid onset of hypertension, abdominal bruits, and severe covered that not only are some of their methods arbitrary, as or drug-refractory hypertension frequently point to the pres- Freeman points out in his editorial, but some facts that they ence of renal artery stenosis. The definitive diagnostic test to seem not to have considered could significantly alter the validi- exclude renovascular hypertension remains the renal arterio- ty of their observations. gram. Dr. Vogelzang's view of pharmacology may be proved Not surprisingly, in my brief review I found no consistent unduly pessimistic by further studies of angiotensin II blockade approach to symptoms suggestive of urinary tract infections by in hypertensive disorders. physicians in the practice. What was surprising was that in a LESLIE BAER, M.D. setting in which problem identification and long-term follow-up Columbia University College of Physicians and Surgeons are emphasized, effective accomplishment of these goals was New York, NY 10032 seldom achieved. Dysuria or urinary tract infection was infre- REFERENCES quently recorded on problem lists, and follow-up visits or diag- 1. HUNT JC, STRONG CG: Renovascular hypertension. mechanisms, natu- nostic procedures were conspicuously lacking. Lack of informa- ral history and treatment, in Hypertension Manual, edited by LARAGH tion recorded for history and physical examination, haphazard JH. New York, Yorke Medical Books, p. 509 use of laboratory procedures, and use of expensive antimicrobi- 2. STREETEN DHP, ANDERSON GH, FREIBERG JM, DALAKOS TG: Use of als when equally effective and much less expensive drugs were an angiotensin II antagonist (saralasin) in the recognition of "angiotensi- available I found distressingly common. nogenic" hypertension. N Engl J Med 1975 Symptoms suggestive of urinary tract infection are common 3. BUDA JA, BAER L, PARRA-CARRILLO JZ, KASHEF MM, MCALLISTER and frequently recurrent. About two thirds of women who see a FF, VOORHEES AB, JR, PIRANI CL: Predictability of surgical response in physician for these symptoms have significant bacteriuria, and renovascular hypertension. Arch Surg 111:1243-1248, 1976 4. WILSON WILSON JP, SLATON PE, FOSTER JH, LIDDLE GW, HOL- the other one third have what might be called "symptomatic LIFIELD JW: Saralasin infusion in the recognition of renovascular hyper- abacteriuria" (2). Several studies point out that distinction be- tension. Ann Intern Med 87:36, 1977 tween these two groups of women on clinical grounds alone is extremely difficult (2, 3). Whether antimicrobials are effective in treating symptomatic abacteriuria is not known; there is even Electrocardiography During Pericardiocentesis some evidence that antimicrobial therapy of uncomplicated documented urinary tract infection in nonpregnant women may TO THE EDITOR: The paper by Chandraratna and colleagues not make a difference over a period of several months (2). There (Ann Intern Med 87:199-200, 1977) nicely presents a useful seems to be general agreement that recurrent symptomatic in- technique for pericardiocentesis. I wish to take exception, how- fections are important mainly for the morbidity they produce, ever, to the statement that electrocardiographic monitoring of and unless there is a structural defect, obstruction, neurologic pericardial puncture is "routinely used." The authors mention deficit, or diabetes, renal parenchymal damage is infrequent (2, that ECG changes may not be evident when the exploring nee- 4). A vigorous effort should be made to identify persons with dle penetrates the myocardium, and indeed they penetrated the correctable problems, and the tip-off should be a history of re- right ventricle without any ST segment changes or extrasystoles currence. Also symptoms suggestive of urinary tract infection in the precordial lead (but of course extrasystole would be seen are frequently caused by other problems such as herpes genitalis in either a precordial lead or intrapericardial lead). Work on and monilial vaginitis. dogs showed this to be true also for the needle lead. In the These types of observations might be difficult to incorporate 1950s, I used the technique routinely. However, I found that into an already elaborate scheme of assessment as described by even light attachment of electrodes disturbed my sense of Rubenstein and colleagues. Although I appreciate the sophisti- "touch" and I also had the same experience the authors men- cation of their detailed study, with some of the above facts in tion; thus I stopped using it as a "routine" procedure. I even mind I am uncertain as to the value and validity of such a doubt if it is "routine"; at a meeting of "pericardiologists" in laborious investigation. I suspect that a few extra minutes of Lexington, Kentucky, in 1969, I polled the audience from the history-taking and physical appreciation of a few platform, and not one of the doctors present used the technique medical facts, and the ability to communicate will make the routinely. In fact, many did not use it at all. physician effective and the patient happy. DAVID H. SPODICK, M.D., D.SC. JOE OUSLANDER, M.D. Saint Vincent Hospital Case Western Reserve School of Medicine Worcester, MA 01604 Cleveland, OH 44106 Letters and Corrections 791REFERENCES was normal. Three months after hospital discharge she developed cough and 1. KUNIN C: Urinary tract infections. JAMA 1975 further weight loss. Her serum albumin level was 3.4 g/dl. New bibasilar 2. SANFORD JP: Urinary tract symptoms and infections. J Urol 113:585- infiltrates were present radiographically, and her tuberculin skin test had 594, 1975 become positive (15 mm). Sputum smear was negative for acid-fast bacilli, 3. FAIRLEY KF, GROUNDS AD, CARSON NE, LAIRD EC, GUTCH RC, but culture subsequently grew M. tuberculosis. She was begun on isoniazid, PHG, LEIGHTON P. SLEEMAN RL, O'KEEFE CM: Site of ethambutol, and streptomycin with improvement. infection in acute urinary-tract infection in general practice. Lancet 2:615-618, 1971 In addition to these cases, and others with intestinal bypass 4. BRANCH WT: Infections of the urinary tract. Med Times 105:92-107, surgery for obesity (3-5), two of 12 patients reported by Befeler 1977 and Baum (2) did not have gastrectomy. It therefore seems desirable to broaden the of the American Thoracic Society. All tuberculin-positive patients with upper In comment: gastrointestinal surgery associated with negative nitrogen bal- ance, not only those with gastrectomy, should be considered as We are grateful to Dr. Ouslander for his comments and sugges- candidates for preventative isoniazid therapy. Further, the im- tions on our study. Unfortunately, his letter does not distin- portance of preoperative screening and postoperative surveil- guish between protocols for treatment and criteria for quality- lance for active tuberculosis in this setting is apparent. of-care assessment, which was the subject of our paper. None- JEFFREY R. FISHER, M.D. theless, some of his suggestions, such as an appropriate history Phoenix Indian Medical Center and physical examination, are indeed included among our crite- Phoenix AZ 85016 ria; other suggestions, such as investigation for correctable causes, seem more relevant to follow-up care rather than care REFERENCES during the emergency room visit. 1. AMERICAN THORACIC SOCIETY: Preventive therapy of tuberculous infec- Although we certainly agree that "a few extra minutes of tion. Am Rev Respir Dis 110:371-374, 1974 history-taking and physical examination" may be useful in the 2. BEFELER B, BAUM GL: Active pulmonary tuberculosis after upper gas- emergency room care of many patients, determining with whom trointestinal surgery. Am Rev Respir Dis 96:977-980, 1967 and how to spend those few minutes most effectively may re- 3. PICKLEMAN JR, EVANS LS, KANE JM, AND FREEARK RJ: Tuberculosis quire sophisticated and detailed studies of process and outcome. after jejunoileal bypass for obesity. JAMA 234:744, 1975 While the "appreciation of a few medical facts" and the "ability 4. BATTERSHILL JH: Tuberculosis after intestinal bypass surgery for obesity (letter). Chest 70:318, 1976 to communicate" are of course extremely important, how to 5. HARRIS JO, WASSON KR: Tuberculosis after intestinal bypass operation choose the relevant facts and strengthen the ability to commu- for obesity. Ann Intern Med 86:115-116, 1977 nicate are issues that in our view require considerably more work. In short, complex and laborious investigations may be needed to learn which simple things are effective and which are Tuberculosis Chemoprophylaxis not. LISA RUBENSTEIN, M.D. University of California Medical Center TO THE EDITOR: Dr. Byrd and associates (Ann Intern Med Los Angeles, CA 90024 86:799-802, 1977) have called attention to several important SUSAN MATES, M.D. issues in the modern-day therapy of pulmonary tuberculosis. Of Columbia Presbyterian Hospital particular importance is the prevalence of isoniazid resistance New York, NY 10032 in patients contracting disease in Southeast Asia, and the need for alternate therapy under these circumstances. VICTOR W. SIDEL, M.D. However, a critical and yet unanswered problem is how to Montefiore Hospital and Medical Center approach the patient whose tuberculin skin test conversion oc- Bronx, NY 10467 curs in Southeast Asia. Although isoniazid prophylaxis is advo- cated in certain well-defined groups by current standards, these standards do not take into account possible isoniazid resistance Tuberculosis After Gastrointestinal Surgery of the infecting tubercle bacillus (1). Alternate drugs such as rifampin, while effective therapeutically against isoniazid-resist- TO THE EDITOR: Gastrectomy is one of several conditions asso- ant strains in combination with another agent (2), are exceed- ciated with an increased risk of developing tuberculosis. The ingly expensive and have not been proved effective in a chemo- American Thoracic Society currently recommends isoniazid prophylactic setting. Thus we must consider alternative regi- prophylaxis for persons with positive tuberculin skin tests who mens and ask whether they will reduce the risk of developing have had gastrectomy (1). The evidence supporting this recom- tuberculosis, what duration of protection will be achieved, and mendation has been reviewed elsewhere (2). More recently, tu- what the overall cost-risk benefit of chemoprophylaxis in this berculosis has been reported after jejunoileal bypass surgery for group of patients with possible isoniazid-resistant infection will obesity (3-5). During the past year, we have seen two patients be. Since drug compliance with isoniazid is known to be highly who developed tuberculosis after upper gastrointestinal surgery variable (3), the now recognized light-chain proteinuria, renal without gastrectomy or jejunoileal bypass. Neither patient had failure, and hematologic problems associated with intermittent contact with a known active case. rifampin therapy (4) have considerable impact on the decision of chemoprophylaxis with this agent. A 57-year-old diabetic man with a positive tuberculin reaction (12 mm) Several courses of action seem open: [a] isoniazid alone; [b] underwent a fundoplication for hiatal hernia and reflex esophagitis. The vagus nerve was inadvertantly severed, resulting in gastric atony and reten- isoniazid plus rifampin or an alternate agent; [c] rifampin or an tion. Seven months later a pyloroplasty was done to facilitate gastric empty- alternate agent alone; or [d] no chemoprophylaxis. Arguments ing. Preoperative chest radiographs were normal. Between operations the for and against each regimen are easily made, but data from patient lost 9.1 kg of body weight, and his serum albumin level fell from 4.1 appropriately controlled trials with long-term follow-up are ul- to 3.3 g/dl. Despite improved appetite, weight loss continued after the sec- timately needed. Unaware of any such studies, I would appreci- ond operation. Four months later he was admitted to the hospital with ate the authors' comments. cough and fever. Chest radiograph showed bilateral apical infiltrates with WILLIAM W. MCGUIRE, M.D. moderate numbers of acid-fast bacilli on sputum smear. Subsequent culture grew Mycobacterium tuberculosis. The patient was begun on isoniazid and University of Texas Health Science Center at San Antonio ethambutol with clinical and radiographic improvement. San Antonio, TX 78284 A 16-year old girl with a negative tuberculin reaction had a duodenojeju- nostomy performed for a superior mesenteric artery syndrome. Postopera- REFERENCES tively she gained weight slowly, requiring prolonged hospitalization for total 1. AMERICAN THORACIC SOCIETY: Treatment of mycobacterial disease. parenteral nutrition and physical therapy. Preoperative chest radiograph Am Rev Respir Dis 115:185-187, 1977 792 December 1977 Annals of Internal Medicine Volume 87 Number 62. VALL-SPINOSA A, LESTER W, MOULDING T, DAVIDSON PT, dium and some were incubated in an at- JK: Rifampin in the treatment of drug-resistant Mycobac- mosphere with added In general, however, their isolation terium tuberculosis infections. N Engl J Med 283:616-621, 1970 from blood has seemed not to be difficult or to require special 3. SBARBARO JA: Tuberculosis: the new challenge to the practicing clini- measures or additives. cian. Chest 68 (suppl):436-443, 1975 Nutritionally variant streptococci are usually recognized be- 4. SANDERS WE JR: Rifampin. Ann Intern Med 85:82-86, 1976 cause they produce flocculent or turbid growth in broth cul- tures, resemble streptococci microscopically in Gram-stained In comment: smears, but fail to grow when subcultured onto ordinary media The question proposed by Dr. McGuire on what medication to that are incubated aerobically or anaerobically. At this point use for chemoprophylaxis in the person who has converted his there is a definite risk that the discouraged technologist may skin test in Asia is indeed a difficult one for which there are no presume that these organisms represent nonviable residues of easy answers. In approaching the problem one must first accept the medium's original sterilization process and regard them as the fact that isoniazid used in the skin test convertor infected insignificant. Therefore it is important for laboratory personnel with isoniazid-resistant organisms will likely be ineffective as a to be alert to the existence of nutritional variants and to carry chemoprophylactic agent, as shown by a recent study (1). One out a few tests to confirm their presence. The first and simplest must also recognize that up to 50% of those with Asian-ac- procedure is based on the observation that all of these variants quired tuberculosis may have isoniazid drug-resistant disease have been symbiotic, that is, they have grown as satellite colo- (2). Therefore if one decides to use isoniazid chemoprophylaxis, nies around other bacteria such as Staphylococcus aureus, as he must assume a risk of failure of therapy in a significant illustrated by McCarthy and Bottone (5). Ancillary procedures number of those treated. include subcultures to media supplemented with 0.05% to Rifampin used as a chemoprophylactic agent would appear 0.1% L-cysteine or 0.001% pyridoxal hydrochloride. Suscepti- to be the most obvious alternative drug in this situation. Since bility testing may be, but is not always, possible in media sup- rifampin, like isoniazid, is bacteriocidal against tuberculosis, it plemented with these compounds. In our case (6), no supple- should be a good chemoprophylactic drug. However, Dr. mental growth factor could be identified that would permit its McGuire is correct in pointing out that no controlled study has growth for purposes of further classification and susceptibility been done to show that rifampin chemoprophylaxis is effective. testing. Obviously a study on the effectiveness and incidence of side JOHN A. WASHINGTON II, M.D. effects of rifampin when used as a chemoprophylactic agent Mayo Clinic needs to be done. In the interim it would seem logical to indi- Rochester, MN 55901 vidualize the approach to therapy. For those with increased risk factors or who have extensive contact with children, we believe REFERENCES it is reasonable to use rifampin despite the limitations discussed, 1. CAREY RB, GROSS KC, ROBERTS RB: Vitamin Streptococ- while otherwise healthy young adults could logically be given cus mitior (mitis) isolated from patients with systemic infections. J Infect isoniazid, recognizing that at least half of them will have isonia- Dis 131:722-726, 1975 zid-sensitive organisms and thus be susceptible to effective ther- 2. GEORGE RH: The isolation of symbiotic streptococci. J Med Microbiol 7:77-83, 1974 apy. However, there should be close follow-up for several years 3. FRENKEL A, HIRSCH W: Spontaneous development of L forms of strep- in those treated with isoniazid because some will likely develop tococci requiring secretions of other bacteria or sulphydryl compounds isoniazid-resistant active disease. for normal growth. Nature 191:728-730, 1961 COL. RICHARD B. BYRD, USAF, MC 4. CAYEUX P. ACAR JF, CHABBERT YA: Bacterial persistence in strepto- USAF Medical Center Scott coccal endocarditis due to thiol-requiring mutants. J Infect Dis 124:247- Scott AFB, IL 62225 254, 1971 5. MCCARTHY LR, BOTTONE EJ: Bacteremia and endocarditis caused by satelliting streptococci. Am J Clin Pathol 61:585-591, 1974 REFERENCES 6. SHERMAN SP, WASHINGTON JA II: Pyridoxine inhibition of a symbiotic 1. FAIRSHTER RD, RANDAZZO GP, GARLIN J, WILSON AF: Failure of streptococcus. Am J Clin Pathol, in press isoniazid prophylaxis after exposure to isoniazid-resistant tuberculosis. Am Rev Respir Dis 112:37-42, 1975 TO THE EDITOR: The recent article by Carey, Brause, and Rob- 2. WILDER NJ, GERACE JE, BYRD RB, NELSON RA: Patterns of drug erts (Ann Intern Med 87:150-154, 1977) on the nutritionally resistance in the tuberculous oriental immigrant (abstract). Am Rev Re- fastidious streptococci makes more widely known the occasion- spir Dis 115 (suppl):410, 1977 al importance of these organisms as a cause of infective endo- carditis. A simple laboratory technique can detect the satellitism of Nutritionally Variant Streptococci these fastidious organisms and has diagnostic value, as in the following case report. TO THE EDITOR: Carey, Brause, and Roberts (Ann Intern Med A 50-year-old white woman with mitral insufficiency, secondary to rheu- 87:150-154, 1977, and Reference 1) have emphasized the impor- matic heart disease, was transferred to the University Hospital, Morgan- tance of nutritionally variant streptococci as a cause of endocar- town, West Virginia, in July 1976 with a 5-week history of fever, chills, night ditis. In addition to the pyridoxine (vitamin strains sweats, and anorexia. In April 1976, she had had two dental extractions for reported by them and earlier by George (2), streptococci have which she had been given oral tetracycline prophylaxis. Nine blood cultures been identified with requirements for D-alanine and thiol groups drawn at the referring hospital had yielded no pathogenic organism. On (2-5). To complicate matters further, we have isolated from the admission the patient was pale, febrile, had a tachycardia, and was in mild congestive heart failure. A holosystolic murmur grade IV/VI was audible blood of a patient with endocarditis a pyridoxine-sensitive viri- throughout the precordium but loudest at the apex. There was no splenome- dans streptococcus (6). galy or evidence of peripheral embolisation. A clinical diagnosis of infective Fifteen of 23 streptococci included in these reports (Frenkel endocarditis was made. Three blood cultures were drawn using brucella and Hirsch [3] stated the sources of their strains but not the broth (Pfizer Laboratories, New York, New York) and thioglycollate medi- numbers) were from blood, perhaps reflecting the greater care um (Pfizer). All failed to grow organisms on routine subculturing to sheep and prolonged incubation given to cultures of this material. blood agar at 24 and 48 h. However, at 96 h the thioglycollate bottles were Although no information is given in George's report about ini- slightly cloudy and showed Gram-positive cocci, which again failed to grow tial isolation procedures for the pyridoxine-deficient strains, all on subculture. After a Staphylococcus aureus was streaked across the agar of the other nutritional variants were initially detected in a vari- plate, previously inoculated from the thioglycollate bottles, satelliting a-he- molytic streptococci grew during overnight incubation in 10% CO₂. The ety of liquid media including brain-heart infusion, soybean-ca- suspicion that this was a thiol-dependent strain was confirmed by the Center sein digest, Columbia, and thioglycollate broths. Some of these for Disease who designated it a Streptococcus morbillorium. The media were supplemented with cysteine, carbohydrates, and so- minimum inhibitory concentration to penicillin in thioglycollate broth was Letters and Corrections 7930.006 mg/ml. The patient responded to 4 weeks of intravenous penicillin G Drug Treatment of Asthma with no relapse on follow-up. George (1) stressed the value of using Staphylococcus aureus TO THE EDITOR: The article "Drug Therapy in the Manage- to detect these fastidious and occasionally slow-growing satellit- ment of Asthma" by VanArsdel and Paul (Ann Intern Med ing strains of Streptococcus viridans. Many other bacteria in- 87:68-74, 1977) is an excellent review. A few points should be cluding Staphylococcus epidermidis, Escherichia coli, Entero- clarified regarding aminophylline therapy. In patients not re- bacter species, Klebsiella pneumoniae, and Candida albicans (2) sponding to usual doses, the authors recommend that the dose have also been found able to support streptococcal satellitism, of aminophylline be increased to the point of toxicity (that is, but none as consistently as S. aureus. Diagnostic bacteriology nausea, abdominal pain, nervousness, headache, and tachycar- laboratories could easily check for satellitism whenever subcul- dia) and then reduced slightly. However, several recent articles turing blood cultures from patients with suspected infective en- (1-4) do not recommend this practice. docarditis, thus facilitating a diagnosis. Hendeles and colleagues (1) reported that nausea and vomit- The minimum inhibitory concentration of our strain was de- ing occurred in less than 50% of patients who developed life- termined in thioglycollate medium, without supplementation, threatening toxicity from aminophylline. In addition, in a study and appeared very sensitive to penicillin. This was reflected in by Zwillich and co-workers (4), only one of eight patients with the good response to therapy. From an increased awareness of aminophylline-induced seizures complained of previous nausea these nutritionally exacting streptococci, further information or other minor side effects. These findings show that VanArsdel should arise in terms of their prevalence, pathogenicity, and and Paul's assumption that the previously noted side effects can susceptibility to antibacterial agents. be used to establish adequate dosage is in error. There is also some confusion in the article on intravenous ROGER G. FINCH, M.B., M.R.C.P. (UK) dosing of aminophylline in hospitalized patients. The 9 mg/kg RICHARD E. PICCIRILLO, M.D. loading dose of aminophylline suggested by the authors to give West Virginia University Medical Center serum levels from 10 to 20 µg/ml may produce toxic serum Morgantown, WV 26506 levels of theophylline if previous drug therapy is not considered. Weinberger and colleagues (3) have noted initial serum levels of aminophylline from 0 to 37.5 µg/ml in 17 of 19 patients. Ten of REFERENCES these patients were not given a loading dose because initial se- 1. GEORGE RH: The isolation of symbiotic streptococci. J Med Microbiol rum levels were > 9 µg/ml. In addition, the article recom- 1974 mends a 1 mg/kg h continuous intravenous drip to maintain 2. LR, BOTTONE EJ: Bacteremia and endocarditis caused by good blood levels. Kordash, Van Dellen, and McCall (2) how- satelliting streptococci. Am J Clin Pathol 61:585-591, 1974 ever, have reported that 34% of the patients given this regimen had serum levels of greater than 20 µg/ml. In conclusion, empiric dosing of aminophylline by body Addenda to Drug Guidelines weight should be cautioned against without aid of serum levels. The recent nomogram by Jusko and co-workers (5) may be of value for initial therapy to clinicians because it incorporates TO THE EDITOR: I am writing to you on our article, "Guidelines dosage reductions for elderly patients with liver and cardiac for Drug Therapy in Renal Failure" published in the June issue disease who may be more susceptible to toxicity. (Ann Intern Med 86:754-783, 1977). In looking over the tables L.J. DAVIS I have discovered that the drug tobramycin was inadvertently Virginia Commonwealth University School of Pharmacy omitted under the category of aminoglycoside antibiotics in Ta- Richmond, VA 23298 ble 1. Because this drug is widely used, perhaps the recommen- dations for this drug should be published in the "Letters" sec- REFERENCES tion. The pertinent information follows. Tobramycin has a major route of excretion (renal). The half- 1. HENDELES L, et al: Frequent toxicity from IV aminophylline infusions in critically ill patients. Drug Intell Clin Pharm 11:12-18, 1977 life, under normal circumstances, is 2 h and with end-stage 2. KORDASH TR, VAN DELLEN RG, JT: Theophylline concentra- renal disease is extended to 24 to 48 h. Normal dosage interval tions in asthmatic patients after administration of aminophylline. JAMA is every 8 h with 0 to 20% protein binding taking place under 238:139-141, 1977 normal circumstances. There are two major ways to adjust dos- 3. WEINBERGER MW, MATTHAY RA, GINCHANSKY EJ, CHIDSEY CA, age-by dosage reduction or interval extension. With glomeru- PETTY TL: Intravenous aminophylline dosage. Use of serum theophyl- lar filtration rates (GFRs) greater than 50 ml/minute, 75% to line measurement for guidance. JAMA 1976 100% of the usual dose should be given; with GFRs between 10 4. ZWILLICH CW, SUTTON FD JR, NEFF TA, COHN WM, MATTHAY RA, and 50 ml/minute, 50% to 75% of the usual dose should be WEINBERGER MM: Theophylline-induced seizures in adults. Correlation with serum concentrations. Ann Intern Med 82:784-787, 1975 given; and with GFRs less than 10 ml/minute, 25% to 50% of 5. JUSKO WJ, KOUP JR, VANCE JW, SCHENTAG JJ, KURITZKY P: Intrave- the usual dose should be given. Interval extension is accom- nous theophylline therapy: nomogram guidelines. Ann Intern Med plished by extending the interval to 8 to 12 h with GFRs great- 86:400-404, 1977 er than 50 ml/minute, 12 to 24 h in the range of 10 to 50 ml/ minute, and 24 to 48 h in the range of less than 10 ml/minute. TO THE EDITOR: Drs. VanArsdel and Paul have perpetuated a The drug is removed by both hemodialysis and peritoneal dialy- frequent misconception regarding oxygen administration by na- sis and has the same "Remarks and Toxicities" that apply to sal prongs (or cannulae). Contrary to their statement, it is not the remainder of the aminoglycoside antibiotics in Table 1. Two references to the use of metronidazole were excluded. If necessary to use an oxygen mask to achieve adequate oxygena- tion in a patient who breathes through his mouth. With oxygen these references could be provided to your readers, I think they delivered by nasal cannulae, Kory and associates (1) showed might be useful. that the levels of alveolar oxygen (by end-expiratory samples) INGHAM HR, RICH GE, SELKON JB: Treatment with metronidazole of three were no less when the subject breathed through his mouth than patients with serious infections due to Bacteroides fragilis. J Antimicrob when he breathed through his nose. Kory noted only one inves- Chemother 1:235-242, 1975 tigation, by Poulton and Adams (2), supporting the thesis that SPECK WT, STEIN AB, ROSENKRANZ HS: Metronidazole bioassay. Antimi- oxygen concentrations were somewhat higher with nasal crob Agents Chemother 9:260-261, 1976 breathing than with mouth breathing, whereas "the studies of WILLIAM M. BENNETT, M.D. Wineland and Waters (3) and of Marriott and Robson (4) with University of Oregon Health Sciences Center the nasal catheter, however, showed no such difference in oxy- Portland, OR 97201 gen concentration, whether the subject breathed through his 794 December 1977 Annals of Internal Medicine Volume 87 Number 6mouth or nose." The air flow in the oropharynx creates a Ber- Aspirin and Hemophilia noulli effect in the nasopharynx, drawing the oxygen adminis- tered by the nasal cannulae through the nose even when the subject breathes through his mouth. Patients with nasal ob- TO THE EDITOR: The review of acetaminophen by Ameer and struction are an exception to this generalization. Greenblatt (1) contains what appears to be a typographical er- ror, the implication of which is seriously misleading. The au- PAUL A. KVALE, M.D. thors state on p. 205, "Hemophilic patients receiving aspirin KENT CHRISTOPHER, M.D. (my italics) or multiple doses of acetaminophen showed no sig- PATRICK DROSTE, M.S.R.R.T. nificant changes in bleeding time." The reference given for that Henry Ford Hospital statement, in fact, is quite clear in stating that acetaminophen Detroit, MI 48202 only was given to hemophiliac persons, not aspirin (2). Al- though the use of aspirin might not cause significant changes in REFERENCES the bleeding time of patients with mild bleeding disorders, in 1. KORY RC, BERGMANN JC, SWEET RD, SMITH JR: Comparative evalua- severe hemophilia the results of its administration could be very tion of oxygen therapy techniques. JAMA 179:767-772, 1962 serious (3). It should be avoided in hemophiliac persons, if pos- 2. POULTON EP, ADAMS TW: Oxygen tents and nasal catheters. Br Med J sible (4). 1:567-571, 1936 3. WINELAND AJ, WATERS RM: Oxygen therapy. Arch Surg 22:67-71, HARRY M. BAUER, M.D. 1931 Martin Luther King, Jr., General Hospital 4. MARRIOTT HL, ROBSON K: Oxygen administration by nasal catheter. Br Los Angeles, CA 90059 Med J 1:154-157, 1936 REFERENCES 1. AMEER B, GREENBLATT DJ: Acetaminophen. Ann Intern Med 87:202- TO THE EDITOR: The excellent review by Drs. VanArsdel and 209, 1977 Paul does great disservice to patients with asthma by complete- 2. MIELKE CH, BRITTEN AFH: Use of aspirin or acetaminophen in hemo- ly ignoring the fact that specific allergy injection therapy cou- philia (letter). N Engl J Med 282:1270, 1970 pled with elimination of specific allergens is the most effective 3. KANESHIRO MM, MIELKE CH, KASPER CK, RAPAPORT SI: Bleeding and reliable treatment for this chronic condition. The clinical time after aspirin in disorders of intrinsic clotting. N Engl J Med 1969 allergist who relies on specific therapy has, in my opinion, kept his patients out of hospitals more effectively than the chest spe- 4. RAPAPORT SI: Introduction to Hematology. New York, Harper and Row, 1971, p. 352 cialist who relies on the drugs reported and not infrequently overmedicates with them. Unfortunately, there is as yet no reli- In comment: able objective assessment of injection therapy, but this should not prevent acknowledgement of its value. We are grateful to Dr. Bauer for pointing out the typographical error in our article. The sentence to which he refers should RALPH BOOKMAN, M.D., F.A.C.P. read: "Hemophiliac patients receiving single (60) or multiple University of Southern California School of Medicine doses (58) of acetaminophen showed no significant changes in Los Angeles, CA 90033 bleeding time." BARBARA AMEER, R.PH. In comment: DAVID J. GREENBLATT, M.D. Massachusetts General Hospital In the last 4 years, an extraordinary number of papers have Boston, MA 02114 been published with variations on the theme of theophylline therapy in asthma. Space limitations in our review made a full discussion impossible. The letter from Mr. Davis is helpful in allowing further discussion. We did not recommend that the Percutaneous Transhepatic Cholangiography dose of aminophylline be raised to the point of toxicity. Our TO THE EDITOR: We, too, are impressed with the diagnostic intent was to point out that in the occasional patient with an yield and low morbidity of percutaneous transhepatic cholangi- extraordinary dose requirement, the therapeutic dose may need ography with the Chiba needle as described by Pereiras and to be determined on purely clinical grounds, if serum theophyl- colleagues (Ann Intern Med 86:562-568, 1977). However, their line levels are unavailable. This entails some toxicity risk. paper raises some important questions. The second point that Mr. Davis raised is particularly impor- tant. When planning intravenous theophylline therapy for a 1. The success rate of (95.6%) of entering nondilated systems newly hospitalised asthmatic patient, one can no longer assume is considerably greater than in previous reports (56% to 89%) (1-3). Assuming the same degree of competence existed, one that theophylline intake before admission has been negligible. wonders whether their increased success was due to excessive The loading dose, of course, should be reduced appropriately for the amount ingested during the previous 12 h. passes into the liver. They state that "if after seven passes the Mr. Davis concludes by emphasizing again the variation in biliary tree is not it is assumed that we are dealing with a nondilated duct system." What they fail to mention is dose requirements and the consequent need to monitor intrave- the maximum number of times they "stuck" patients who had nous therapy with serum theophylline levels. However, until serum levels are more generally available-and without several nondilated systems. Surely 15 or 25 passes is uncomfortable for the patient and creates an increased radiation hazard. Of their hours delay-empiric dosing, modified by clinical judgment, will still have its place. 45 nondilated systems, six had common duct stones. Might these surgery-requiring entities have been diagnosed with ultra- The letter from Dr. Kvale and associates needs little com- sound or retrograde cannulation? ment because we are in basic agreement with them. The contro- 2. The authors fail to mention the maximal number of sticks versy about oxygen for mouth breathers does seem to be resolv- performed to enter a dilated system. What is needed is a relative ing in favour of using the simpler nasal oxygen therapy. With regard to Dr. Bookman's letter, we had considered add- "stick limit" beyond which the chances of visualizing a dilated ing a section on allergy injection therapy but decided that to do system are small. This standard will probably require a statisti- cal analysis of a larger series of patients. There is as yet no it properly we would have ended up with a paper that was universal agreement as to when one should assume the cholan- unacceptably long. Further, allergenic extracts are generally giographer is aiming for a normal caliber biliary tree. considered biologicals rather than drugs, and this was a drug- spotlight article. 3. We have found that premedication with meperidine and hydroxyzine enhances patient cooperation, especially when nu- PAUL P. VANARSDEL, JR., M.D. merous passes into the liver are required. Cardiothoracic Institute 4. Because there is some doubt as to whether ampicillin London SW3 6HP, England reaches appreciable levels in the obstructed biliary tree (4), it Letters and Corrections 795has been suggested that gentamicin be added directly to the REFERENCES Renografin (E.R. Squibb & Sons, Inc., New Brunswick, New 1. FERUCCI JT JR, WITTENBERG J: Refinements in Chiba needle transhe- Jersey) when an obstructed system is encountered (GALAMBOS patic cholangiography. Am J Roentgenol 129:11, 1977 J: Personal communication). 2. GREENWALD RA, PEREIRAS R JR, MORRIS MJ, SCHIFF ER: Jaundice, STEVEN BROZINSKY, M.D. choledocholithiasis, and a non-dilated common duct. Submitted for pub- lication ELIAS PUROW, M.D. 3. KEIGHLEY MRB. DRYSDALE RB, QUORAISHI AH, BURDON DW, AL- SAUL J. GROSBERG, M.D. EXANDER-WILLIAMS J: Antibiotics in biliary disease: the relative impor- Brooklyn Veterans Administration Hospital tance of antibiotic concentrations in the bile and serum. Gut 17:495-500, Brooklyn, NY 11203 1976 REFERENCES Phenformin and Pancreatitis 1. BURCHARTH F, NIELBO N: Percutaneous transhepatic cholangiography with selective catheterization of the common bile duct. Am J Roentgenol 127:409-412, 1976 TO THE EDITOR: We wish to report our experience with a pa- 2. REDEKER AG, KARVOUNTZIS GG, RICHMAN RH, HORISAWA M: Per- tient who developed pancreatitis while using phenformin. Be- cutaneous transhepatic cholangiography. An improved technique. JAMA cause hemorrhagic pancreatitis was proved at autopsy, this case 231:386-387, 1975 complements that of Chase and Mogan (1). The pancreatitis 3. PEREIRAS R JR, WHITE P. DUSOL M JR, IRWIN G III, HUTSON D, LIEBERMAN B, SCHIFF ER: Percutaneous transhepatic cholangiography was complicated by lactic acidosis and hypothermia; dissemi- utilizing the Chiba University needle. Radiology 121:219-221, 1976 nated intravascular coagulation and elevated phenformin levels 4. RABB R: The use of antibiotics in biliary tract disease. Am J Gastroenter- were seen. (Phenformin assays performed by Geigy Pharmaceu- ol 63:37-39, 1975 ticals. Therapeutic levels in serum have not been delineated. In comment: Known overdoses have had serum levels of 300 ng/ml and higher.) We thank Drs. Brozinsky, Purow, and Grosberg for their com- ments. Let us respond to the issues raised on a point-by-point A 50-year-old white woman was admitted to Milwaukee County General basis. Hospital because of sudden loss of consciousness. She was diabetic and had 1. To achieve the high success rate for entering nondilated been an alcoholic, but she had had no recent alcohol intake and no history of ducts, multiple passes may indeed be needed. On occasion 15 to biliary tract disease. She took phenformin, 50 mg twice daily. She had a rectal temperature of 32.5 °C; blood pressure, 60 mm Hg by 20 passes have been required, although usually the examination palpation; pulse, mental status, comatose; abdomen, no guard- is accomplished with fewer than this number. At times this does ing or bowel sounds, absent. prove uncomfortable to the patient. However, we have found, Her acidosis was corrected with alkali, but shock, coagulo- as Drs. Ferruci and Wittenberg recently reported (1), that this pathy, and anuria persisted. Peritoneal dialysis was done to correct sodium can be accomplished without excessive risk. Radiation is not a overload caused by excessive sodium bicarbonate administration. Two litres significant factor. Angiography and other special radiographic of peritoneal dialysate contained 24 ng/ml of phenformin, and later hemo- procedures require far more fluoroscopy time than skinny nee- dialysis reduced blood phenformin levels from 300 ng/ml in arterial blood dle cholangiography. Skinny needle cholangiography is not the entering the dialysis coil to 109 ng/ml in blood returning to the patient. The patient died after a 30-h hospitalization, and autopsy revealed acute hemor- only diagnostic approach to be used. Certainly ultrasound can rhagic pancreatitis without other biliary tract disease. give valuable information about the biliary tree and is not inva- sive. Endoscopic retrograde cholangiopancreatography is also Our patient had a syndrome similar to that reported by Chase and Mogan (1), although possibly surreptitious alcohol very valuable. We do not believe the procedures are mutually exclusive, but they should be used depending on availability and consumption or hypothermia (2) rather than phenformin pre- the clinical situation. Because of its ease and relative safety, we cipitated pancreatitis. Modestly elevated serum phenformin lev- els would support the latter as a causative agent. Phenformin believe that skinny needle cholangiography is the procedure of appeared to be dialyzable by two routes, but peritoneal perme- choice if extrahepatic obstruction is strongly suspected. One ability may have been enhanced by inflammation, and hemo- approach is to "screen" with ultrasound. If dilated ducts are dialysis clearance data could not be obtained due to the slow found, one proceeds to skinny needle cholangiography. If no and erratic flow rates caused by her hypotension. Once estab- dilated ducts are seen, endoscopic retrograde cholangiopancrea- lished, pancreatitis (3), acidosis (4), or hypothermia (5) are all tography may be the procedure of choice. If either procedure separately or synergistically able to initiate disseminated intra- fails, the other may be attempted. It should be emphasized that a nondilated biliary tree may be associated with a surgically vascular coagulation. Since pancreatitis can present as painless shock (5), we believe that in evaluating coma in a diabetic who remedial condition, for example, stones in the common duct, appears to have phenformin-induced lactic acidosis, pancreatitis and it is therefore important to persevere in an attempt to visu- should be considered as a treatable concomitant or etiologic alize the ductal system (2). 2. We have no definite "stick" limit for entering a dilated factor. Serum amylase and amylase to creatinine clearance ra- duct. In our series almost all dilated ducts were entered on the tios would be particularly appropriate in the presence of hy- pothermia or coagulopathy. first three passes. One patient required seven "sticks." 3. We have found that most patients tolerate the procedure LAWRENCE M. RYAN, M.D. with local anesthesia. On the unusual occasions where pain PAUL HANKWITZ, M.D. medication is required, we give alphaprodine hydrochloride. MICHAEL BANASIAK, M.D. Many of our patients have significant liver disease, and we have Medical College of Wisconsin avoided the routine use of meperidine or diazepam to prevent Milwaukee, WI 53226 precipitating encephalopathy or aspiration. REFERENCES 4. Probably the level of antibiotic in the blood is more impor- tant than that in the biliary tree in treating cholangitis (3). 1. CHASE HS JR, MOGAN GR: Phenformin-associated pancreatitis. Ann Intern Med 87:314-315, 1977 Although we add gentamicin to the Renografin for endoscopic 2. DUGUID H, SIMPSON RG, STOWERS JM: Accidental hypothermia. Lan- retrograde cholangiopancreatography, we have not used it for cet 2:1213-1219, 1961 transhepatic cholangiography. 3. KWAAN HC, ANDERSON MC, GRAMATICA LN: A study of pancreatic RAUL PEREIRAS, JR., M.D. enzymes as a factor in the pathogenesis of disseminated intravascular ROBERTO O. CHIPRUT, M.D. coagulation during acute pancreatitis. Surgery 69:663-672, 1971 RICHARD A. GREENWALD, M.D. 4. BROERSMA RJ, BULLEMER GD, MAMMEN EF: Acidosis-induced dis- seminated intravascular microthrombosis and its dissolution by streptoki- EUGENE R. SCHIFF, M.D. nase. Thromb Diath Haemorrh 1970 Veterans Administration Hospital 5. TOFFLER AH, SPIRO HM: Shock or coma as the predominant manifesta- Miami, FL 33125 tion of painless acute pancreatitis. Ann Intern Med 57:655-659, 1962 796 December 1977 Annals of Internal Medicine Volume 87 Number 6Sternocostoclavicular Hyperostosis Klinikum der Johannes Gutenberg-Universität D 65 Mainz, Germany TO THE EDITOR: In their recent report on sternocostoclavicular REFERENCES hyperostosis, Köhler and colleagues (Ann Intern Med 87:192- 1. KÖHLER H, UEHLINGER E, KUTZNER WEIHRAUCH TR, WILBERT L, 194, 1977) have introduced American internists to a curious SCHUSTER R: Hyperostose, ein bisher nicht bes- and distinctive syndrome. Like any new report, though, their chriebenes Krankheitsbild. Dtsch. Med Wochenschr 100:1519-1523, article raises several questions of practical and theoretical im- 1975 portance. There are two specific areas in which information 2. KÖHLER H, UEHLINGER E, KUTZNER J, WEST TB: Sternocostoclavicu- would aid in the understanding of their case reports. lar hyperostosis: painful swelling of the sternum, clavicles, and upper First, the authors make several allusions to an "inflammatory ribs. Report of two new cases. Ann Intern Med 87:192-194, 1977 process." Indeed, the very high erythrocyte sedimentation rates and the increased uptake on bone scans are consistent with inflammation. Yet, the histologic reports give no evidence of Therapy such a process. Perhaps the authors have further data that re- solve this apparent discrepancy. TO THE EDITOR: We wish to comment on the paper by McDou- Second, there are a large number of similarities between the gall and Greig pertaining to therapy for Graves' disease (1). sternocostoclavicular hyperostosis syndrome and classic anky- This group had previously reported on 257 patients (2). Three losing spondylitis (1). These include elevated erythrocyte sedi- other groups have also studied a total of 189 patients, with mentation rate, involvement of the axial skeleton, ossifying per- varying follow-up periods (3-5). We recently reported our expe- iostitis, bony ankylosis of cartilaginous joints, response to in- rience with in 20 cases of Graves' disease and compared the domethacin, and response to radiotherapy. short-term follow-up with that of a similar group given be- I wonder, therefore, whether the authors have information tween 1972-75 (6). Twenty patients (10 women) were given 32 pertinent to this point, such as roentgenographic or scintigraph- treatments with (mean dose, 5.9 mCi; range, 3 to 8 mCi) ic evidence of sacroiliitis and spondylitis. Even more interesting based only on clinical severity and gland size. A similar group would be the histocompatibility typing in these patients, partic- of 69 patients (56 women) who had 88 treatments with dur- ularly in view of the association between HLA-B27 and a tend- ing the same 4-year period were given a mean dose of 5.7 mCi ency for excessive periosteal new bone formation (2). (range, 1.6 to 15.0 mCi), calculated from radioactive iodine up- MICHAEL SILVERMAN, M.D. take and thyroid size (planimetry) to deliver 70 µCi/g of thy- University of Colorado Medical Center roid. The two groups differed only in sex ratio. Denver, CO 80220 Of the 20 patients given 10 are euthyroid (mean follow-up 24 months, the shortest being 7 months). Eight patients failed REFERENCES to respond and required antithyroid medication or propranolol. 1. BOYLE JA, BUCHANAN WW: Clinical Rheumatology. Oxford, Blackwell Only one patient became hypothyroid, and she had received Scientific Publications, 1971, p. 282 two treatments. Thirty-four patients (50%) given became 2. SHAPIRO RF, UTSINGER PD, WIESNER KB, RESNICK D, BRYAN BL, hypothyroid, 30 of these within 1 year after treatment. Twenty- CASTLES JJ: The association of HLA-B27 with Forestier's disease (verte- seven patients (40%) are euthyroid (mean follow-up 22 months, bral ankylosing hyperostosis). J Rheumatol 3:4-8, 1976 the shortest being 5 months). Seven patients (10%) are persist- In reply: ently hyperthyroid (mean follow-up, 11 months). Our experience with is that short-term hypothyroid- Due to the limited space available we had shortened the report ism is uncommon, but this is accomplished with a some- on the histopathology of sternocostoclavicular hyperostosis, what unsatisfactory delay in reaching euthyroidism. Ten which had been described earlier in detail (1). A typical feature cases have required more than one treatment. We have is a slowly progressive, relapsing course over a period of years. no obvious explanation for the high incidence of early The varying clinical course of the disease seems to have a paral- hypothyroidism noted with the relatively low doses of lel in the histologic features. Repeated sternum, clavicle, and rib Since 1975, we have increased the amount of given to 15 biopsies obtained from the patients at various times showed patients (mean, 6.6 mCi; range, 4.5 to 10 mCi) to deter- comparable lesions but varied in details according to the activi- mine if this will result in more satisfactory control of ty of the disease process. The histologic findings included florid hyperthyroidism, without excessive hypothyroidism. ossifying periostitis with lymphocytic and plasmacellular infil- Among the 15 new cases of Graves' disease, no patient trations and ossifying periostitis with "remaniement pagétoid." has yet developed hypothyroidism, but the follow-up is However, quiescent osteosclerosis and spongy hyperostosis short. We disagree that is the isotope of choice for the without inflammatory signs were found (1, 2). Thus the disease routine treatment of Graves' disease, but it may be best can only partially be characterized as an inflammatory process, for cases where complete ablation is intentional, or for even though several clinical signs and unspecific laboratory other forms of thyrotoxicosis. findings such as occasional increase in body temperature and E.C. M.D. increase in a- and and erythrocyte sedimentation R. MARTIN, M.D. rate, could be in favour of an inflammatory process. Camp Hill Hospital Histocompatibility-typing in these patients could indeed pro- Halifax, NS B3H 3G2, Canada vide some interesting information and will be obtained. Dr. Sil- verman mentioned some similarities between sternocostoclavi- REFERENCES cular hyperostosis and ankylosing spondylitis. Typically, ster- 1. IR, GREIG WR: Therapy in Graves' disease. Long- nocostoclavicular hyperostosis presents with characteristic, re- term results in 355 patients. Ann Intern Med 85:720-723, 1976 stricted location. Radiographic and scintigraphic studies in all 2. BREMNER WF, SPENCER CA, RATCLIFFE WA, GREIG WR, RATCLIFFE patients did not reveal any signs of ankylosing spondylitis. The JG: The assessment of treatment of thyrotoxicosis. Clin Endocrinol long duration of symptoms observed for up to 34 years may also (Oxf) 5:225-234, 1976 rule out that this disease represents an early stage of ankylosing 3. LEWITUS Z, LUBIN E, RECHNIC J, BEN-PORATH M, FEIGE Y: Treat- ment of thyrotoxicosis with and Semin Nucl Med 1:411-421, 1971 spondylitis. The abnormal laboratory findings in both diseases 4. WEIDINGER JOHNSON PM, WERNER SC: Five years' experience with are rather nonspecific inflammatory signs. Finally, histologic iodine-125 therapy of Graves' disease. Lancet 2:74-77, 1974 findings of sternocostoclavicular hyperostosis are quite distinc- 5. SIEMSEN JK, WALLACK MS, MARTIN RB, NICOLOFF JT: Early results tive from those observed in ankylosing spondylitis (1). There- of therapy of thyrotoxic Graves' disease. J Nucl Med 15:257-260, fore, the similarities between this disease and ankylosing spon- 1974 dylitis appear rather superficial. 6. ABBOTT EC, SCHLOSSBERG AH, MARTIN R, HICKEY J: Short-term out- H. KÖHLER, M.D. come of and therapy in Graves' disease (abstract). Ann R Coll Physicians Surg Can 10:48, 1977 Letters and Corrections 797Psychiatric Jargon aitch' spelling from the title of an English translation of the tales of Münchhausen." However, the reference to the English translation is not accurate, and in fact the reverse is true. TO THE EDITOR: In the review article by Leigh and Reiser (Ann The tales were originally written in English by R. E. Raspe Intern Med 87:233-239, 1977) is the following passage: "As (1737-1794), who was a German refugee living in England. Lipowski pointed out in 1974, the essence of consultation-liai- They were first published in Oxford in 1785 under the title son psychiatry today is a holistic approach to the total patient, Baron Munchausen's Narrative of his Marvellous Travels and in his biologic, psychologic, and social dimensions. This ap- Campaigns in Russia. Raspe merely based his tales on the real proach is obviously inimical to the simple reductionistic ones, Baron von Münchhausen who lived in Germany (1720-1795) whether to unconscious conflicts or twisted molecules." I as- and had a local reputation as a narrator of unlikely stories. It sume the first sentence could equally well read, "Psychiatrists was 11 years later, in 1796, after the original English publica- (behavioral medicine specialists?) when doing consultations tion had proved a great success, that the taies were translated should consider the whole patient." I cannot but wonder how into German by the poet Bürger and published in Göttingen one can have a holistic approach to a less than total patient? under the title Wundersame Reisen zu Wasser und zu Lande, Next, surely the "total patient" includes all dimensions-bio- Feldzüge und lustige Abenteur der Freyherrn Münchhausen. logical, psychologic, and so forth. This statement is just a trifle The original English stories were at first published anonymous- too tautological! The second sentence presumably means, "This ly, and it was only when the biography of Bürger appeared in approach conflicts with that of the usual subspecialist, which is 1824 (well after the real Baron's death) that the true author was limited to a particular body part or function." Perhaps the au- revealed to be Raspe. The real Baron did not have anything to thors have a message; if so, they do themselves and their readers do with the writing or publication of the tales, and he was a disservice with their obscurities and jargon. If they wish to unhappy in his later years when he became a figure of notoriety converse with their colleagues in other specialties, they had bet- and ridicule. ter learn a common language. It was, I believe, Seneca who Thus, it was the original author of the tales, R. E. Raspe, said, "What cannot be said simply is not worth saying." who decided to use the name Munchausen rather than the real W. KEITH C. MORGAN, M.D. Münchhausen. In all the numerous English editions that have West Virginia University Medical Center appeared in the past two centuries, the Munchausen spelling Morgantown, WV 26506 has been the rule, and correctly so, whereas in the German translation, Münchhausen has been used. It would be as well therefore to continue to use Münchhausen when referring to the More on Munchausen real Baron, and Munchausen for the fictional character. When Richard Asher described his syndrome, he referred to the Cres- TO THE EDITOR: The history of Baron Munchausen and his set Press 1948 English edition of the tales. He was therefore "syndrome" continues to be intriguing. The recent erudite re- correct in naming the condition Munchausen syndrome with marks of Dr. Taegtmeyer (1) on the correct spelling of Mun- "one-aitch." chausen need some amplification. The controversial single or A fuller account of this subject will be dealt with in my forth- double "aitch" issue was discussed in the third edition of The coming lecture, "Munchausen: Fact and Fiction" to be given at Adventures of Baron Munchausen (2). In the introduction, T. the Section of History of Medicine at the Royal Society of Med- Teignmouth Shore considers the question and states, I can- icine, London, and in a paper to be published shortly in the not find, in even the oldest English edition, that there has been Journal of the Royal College of Physicians of London. any variation from the familiar I am ALEX SAKULA, M.D., F.R.C.P. fortunate enough to possess a portrait of the Baron, which bears Redhill General Hospital date 1792, and which must have appeared in one of the earliest Surrey, England editions of the book, and the name under it is spelt with the single h-Munchausen. This, I think, sets at rest the question of the correct spelling of the name, for, as I shall presently show, Correction: Reprints of Sarcoidosis Review the Travels were, in their connected form at all events, original- ly published in English." No doubt the Baron, amused by this ongoing debate, might TO THE EDITOR: Concerning "Neurologic Manifestations in have provided us with a much more complex "explanation"! Sarcoidosis," (Ann Intern Med 87:336-345, 1977), reprints are RICHARD L. GOLDEN, M.D. available at the following address: Neurology Service, Reynolds State University of New York at Stony Brook Army Hospital, Lawton, OK 73503 PEYTON DELANEY, M.D. Stony Brook, NY 11790 Reynolds Army Hospital REFERENCES Lawton, OK 73503 1. TAEGTMEYER H: Munchausen to Münchhausen. Ann Intern Med 87:379-380, 1977 2. SHORE TT: The Adventures of Baron Munchausen, 3rd ed. New Cassell, Petter and Galpin, 1862 Correction: Misspelled Name TO THE EDITOR: In your editorial comment on the letter by Because of an error in the editorial office, Dr. Andrew P. Brugsch on Munchausen syndrome (Ann Intern Med 86:833- Somlyo's name was spelled incorrectly in "Arthritis Associated 834, 1977) you quote Leiber and Olbrich's Die Klinischen Syn- with Apatite Crystals" in the October 1977 issue (Ann Intern drome (1966): "Richard Asher carried forward the 'one- Med 87:411-416, 1977). We apologize for the error. 798 December 1977 Annals of Internal Medicine Volume 87 Number 6Copyright © 2002 EBSCO Publishing