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Mein et al • Special communications JAOA • Vol 101 • No 8 • August 2001 • 441 Manual medicine covers a broad spectrum of techniques, including soft tissue treatment and high-velocity low-amplitude (HVLA) thrusting. In osteopathic terminology, these and many other manual medicine techniques as a whole are commonly referred to as osteo-pathic manipulative treatment (OMT).1 Although many osteopathic physicians take the variety of techniques for granted because of the rich heritage of their pro-fession, there remains ignorance of man-ual medicine diversity in the healthcare community at large, and this has led to serious shortcomings in current research methodology with regard to manipula-tion. Consequently, the role of manual medicine in the emerging medical paradigm is uncertain. Healthcare services that use manual medicine include osteopathic medicine, chiropractic, physical therapy, and mas-sage therapy. Specific types of practi-tioners often rely more often on certain techniques or sets of techniques than do other practitioners (for example, long-lever techniques with osteopathic physi-cians, HVLA adjustments with chiro-practors), but there remains considerable diversity within manual medicine–ori-ented professions and significant overlap between them. However, the research lit-erature often fails to reflect this diversity. For example, one recent study of treat-ments for low back pain refers simply to “chiropractic” in the abstract and throughout most of the article, as if a general set of modalities were being applied (the article only noted briefly that side-posture, HVLA adjustments were the only chiropractic modality used).2 Early osteopathic physicians used a variety of articular and nonarticular approaches to achieve their goal of nor-malizing blood flow. They used general mobilizations (the osteopathic “general treatment”), long- and short-lever manip-ulations of the entire musculoskeletal sys-tem, strain-counterstrain, and specific pressures (“stimulation” and “inhibi-tion”) to influence and regulate sympa-thetic nervous system functions. Also, drainage techniques were part of com-monly accepted practice.3 Early chiropractors, with the goal of normalizing nerve function by reducing the vertebral subluxation, were some-what more limited in their approach, rely-ing primarily on HVLA thrusts. As time has passed, chiropractors have added con-siderably to their body of therapeutic applications, broadening their range of manual articular techniques; adding man-ual reflex and muscle relaxation tech-niques; and incorporating nonmanual therapeutic modalities, such as electrical and thermal modes of therapy, bracing, casts, support, traction, and nutritional counseling—all of which have been ben-eficial. However, in their research approach to demonstrate the validity of manual medicine, chiropractors have focused almost entirely on the HVLA spinal adjustment, ignoring the diversity of other manual techniques with claims of effectiveness.4 Problematic research methodology Two well-publicized studies reported in leading medical journals illustrate the potential methodologic problems associ- Dr Mein is medical director at Meridian Institute, Virginia Beach, Virginia, where Mr McMillin is program director, Dr Richards is director of research, and Dr Nelson is a clinical researcher. Dr Greenman is professor emer-itus at Michigan State University College of Osteopathic Medicine, East Lansing, Mich. Correspondence to Eric A. Mein, MD, Meridian Institute, 1853 Old Donation Park-way, Suite 1, Virginia Beach, VA 23454. E-mail: meridian@meridianinstitute.com Manual medicine diversity: research pitfalls and the emerging medical paradigm ERIC A. MEIN, MD; PHILIP E. GREENMAN, DO; DAVID L. MCMILLIN, MA; DOUGLAS G. RICHARDS, PhD; CARL D. NELSON, DC Special communications Recent studies published in leading medical journals have concluded that chiropractic treatment is not particularly helpful for relieving asthma and migraine symptoms because even though study participants showed notable improvement in symptoms, those subjects who received sham manual medicine treatments also showed improvement. Yet the sham treatment received by control groups in these studies is reminiscent in many ways of traditional osteopathic manipulation. This seems to represent not only a failure to recognize the value of many manual medicine tech-niques but also an ignorance of the broad spectrum of manual medicine tech-niques used by various practitioners, from osteopathic physicians to chiropractors to physical therapists. Such blind spots compromise research methodology with regard to manual medicine studies, which could, in turn, diminish the role of manual medicine in clinical practice. Osteopathic manipulative treatment pro-vides an excellent model for recognizing and integrating the full range of manual medicine techniques into research and clinical applications because of the wide range of techniques employed. The potential exists for these techniques to contribute much to medical research and clinical practice—provided that osteopathic physicians and other manual medicine practitioners work to alleviate ignorance about the effica-cy of various forms of manipulation. (Key words: osteopathic manipulative treatment, chiropractic, research design, alternative medicine) ated with manual medicine diversity. One such example is a study that compared “active” and “simulated” chiropractic manipulation as adjunctive treatment for childhood asthma, conducted by Balon and others.5 The active treatment consisted of “manual contact with spinal or pelvic joints followed by high-velocity low-amplitude directional push often associ-ated with joint opening, creating a cavi-tation, or ‘pop.’” This treatment is a standard HVLA technique used by a wide variety of practitioners, such as osteo-pathic physicians, chiropractors, and phys-ical therapists. The simulated treatment involved the following parameters: (1) providing “soft-tissue massage and gentle palpation” to the spine, paraspinal muscles, and shoul-ders; (2) “turning the subject’s head from one side to the other”; (3) providing “a nondirectional push, or impulse” to the gluteal area with the subject lying on one side and then the other; (4) placing the subject in a prone position so that “a similar impulse was applied bilaterally to the scapulae”; (5) putting the subject in a supine position “with the head rotated slightly to each side, and an impulse applied to the external occipital protu-berance”; and (6) applying low-ampli-tude, low-velocity impulses “in all these nontherapeutic contacts, with adequate joint slack so that no joint opening or cavitation occurred.” Jongeward6 and Rossner7 have ques-tioned the appropriateness of such simu-lated treatment, noting that standard chi-ropractic practice can include soft tissue work. Another problem is that the simu-lated treatment bears a marked similari-ty to a traditional general osteopathic treatment.8,9,10(pp85-86) Balon and colleagues5 summarized the simulated treatment by stating, “Hence, the comparison of treatments was between active spinal manipulation as routinely performed by chiropractors and hands-on procedures without adjustments or manipulation.” Based on the conclu-sions of the researchers, it would seem they were unaware of the early osteo-pathic works addressing asthma8-10 and the more recent literature on OMT for respiratory conditions, particularly by Kuchera and Kuchera.11 The method-ologic limitations of the study by Balon and others with regard to manual medicine diversity have been noted.12 Balon and coworkers responded that they were unconvinced by the evidence sup-porting the efficacy of their “simulated treatment.”13 The results as reported by the re-searchers were “Symptoms of asthma and use of -agonists decreased and the quality of life increased in both groups, with no significant differences between the groups.” The conclusion was that “the addition of chiropractic spinal manipulation to usual medical care pro-vided no benefit.”5 Thus, the conclusion suggests an apparent failure of chiropractic to address systemic dysfunction, such as asthma. Although technically this conclusion is limited to HVLA spinal adjustments, the fallout will, for all practical purpose, prob-ably affect attitudes toward all types of manual medicine and manual medicine practitioners. The problem is that while the study is widely perceived as indicating a failure of manual medicine for the treat-ment of systemic dysfunction, it may instead be indicative that the subjects in both groups benefited—but from two distinct forms of manual medicine. Igno-rance (whether by lack of knowledge or by the choice to ignore the available infor-mation) has severely distorted the findings of this widely publicized study. This study is not the only example of such confusion. A similar study14 demon-strates a comparable ignorance of manual medicine diversity, duplicating the methodologic flaws, favorable outcomes, and unfounded conclusions of the study by Balon and others. The researchers in this study compared two forms of man-ual therapy for the treatment of tension headache. The experimental treatment consisted of standard HVLA chiropractic treatment and deep friction massage, plus trigger point therapy if indicated. The subjects receiving this intervention were designated as the “manipulation” group. The control group received deep friction massage plus low-power laser light (con-sidered not to be efficacious for tension headache). Thus, essentially, one form of manual medicine is again compared to another. The researchers observed that “by week 7, each group experienced sig-nificant reductions in mean daily headache hours...and mean number of analgesics per day.”14 Because both groups bene-fited equally, the authors concluded that “As an isolated intervention, spinal manipulation does not seem to have a positive effect on episodic tension-type headaches.”14 Both studies were reported in the mass media with the simplistic conclusion that chiropractic does not work for such con-ditions as childhood asthma and tension headache. The design and outcome of the studies do not allow us to draw such conclusions, however. Perhaps a more accurate conclusion should have been that we do not know if HVLA adjust-ments are specifically helpful or not. Although the favorable outcomes could have resulted from chance or placebo effects, a reasonable person might also justifiably conclude that various forms of manual medicine can be helpful for these conditions. Kuchera15 recently dis-cussed in detail the mechanisms by which OMT could be used in treatment of headaches of various types. Ignorance of the diversity and validity of the full spec-trum of manual therapy applications con-founds the issue. More research is des-perately needed—research which seriously considers the full spectrum of manual medicine options from a variety of health-care professions. Developing an appropriate research methodology is a challenge. Consideration must be given not only to the diversity of potentially effective manual techniques, but to the difficulty of identifying a sim-ulated treatment with no physical effects. Even light stroking of the skin may have significant effects on physiology.16 In con-trast to randomized clinical trials of drugs, double-blind methodology is not possible with manual medicine research; the ther-apist is always aware of the technique being applied. Even blinding patients is problematic, particularly if they have pre-vious exposure to manual techniques. Rather than a treatment/placebo com-parison, perhaps the only possible com- 442 • JAOA • Vol 101 • No 8 • August 2001 Mein et al • Special communications parison will be between active treatment methods. This then raises the problem of individualization of treatment; even the study by Balon and others5 acknowledges that the therapists tailored their treat-ments to the needs of the individual patients. A wider discussion of the methodologic issues inherent in the study of manual therapy is necessary to counter the application of overly simplistic and inappropriate methodologies in studies of manual medicine and in the media coverage of such studies. Manual medicine and the emerging medical paradigm So what does this have to do with osteo-pathic medicine? It would seem that chi-ropractors and many members of the medical establishment involved in report-ing these studies are simply ignorant of the osteopathic medical perspective. While this type of misunderstanding is neither new nor surprising, it has tremendous implications for the future. We are in the midst of a medical rev-olution, and in this revolution, many questions are being asked about manual medicine and other techniques that are sometimes referred to as “alternative” medicine. What is the role of manual medicine in the emerging medical paradigm? Will manual medicine be lim-ited to relieving musculoskeletal pain? Will osteopathic manipulative treatment remain a self-contained system of healing? Is there a legitimate role for the full spec-trum of manipulative techniques in the treatment of systemic dysfunction? Osteopathic medicine has a great deal to offer. Because of its rich heritage of philosophy, research, and clinical tech-niques, the profession can influence the direction of healthcare in a positive man-ner. Osteopathic medicine has integrated the diversity of manual medicine tech-niques into its own system in the form of OMT. Thus, osteopathic medicine is the single best representative of manual medicine diversity currently available to researchers and clinicians. Another primary factor driving the current changes in healthcare is eco-nomics. Not only must treatment options be safe and efficacious, they must be cost-effective. The diversity of manual medicine techniques provides a variety of approach-es that could have significant cost-saving potential. This is particularly true for sim-ple regulatory techniques, as contrasted with corrective techniques. For example, inhibitive pressure and thoracic lymphatic pump applications can be easily adapted for application by lay persons and thera-pists. In a study on labor pain during con-tractions of gravid uterus at term, lumbar inhibitory pressure was shown to be effec-tive in reducing pain in a group of 175 women. This simple technique was applied by husbands and other family members, as well as by nurses and physi-cians. “Since back pressure in a high per-centage of cases was administered by the husband, this suggests that training of husbands in the proper technique would minimize staff time required in labor and delivery, as well as the need for medica-tion.” 17 Also, thoracic lymphatic pumping (TLP) has been shown to be at least as effective as incentive spirometry in pre-venting atelectasis in patients who have undergone cholecystectomy. In addition to its treatment efficacy, the authors noted that TLP costs were lower than those for incentive spirometry and that “the TLP treatment costs could be further reduced by training a respiratory therapist to administer the treatment.”18 There is historical precedent for involv-ing lay persons and therapists in the less technical manual therapy applications. The early osteopathic physicians recog-nized a hierarchy of expertise with regard to technique. One early osteopathic text-book was specifically written with the lower end of this hierarchy in mind. In the preface to the second edition of his book, Eduard Goetz acknowledged the accessi-bility of simple manual medicine appli-cations when he wrote, “The mere read-ing of the book cannot possibly result in one’s becoming a full fledged osteopath. The intention is simply to impart sufficient knowledge of the mode of procedure to enable the careful reader to apply the treatment in his home in case of emer-gency and until such a time as a regular practicing osteopath can be called in should that be found necessary.”10 (For those interested in the work of Goetz and other early osteopathic physicians, some of their texts are now available on the Early American Manual Therapy Web site at www.meridianinstitute.com.) When considering the relatively low level of expertise required to perform deep friction massage and soft-tissue tech-niques, such as those used as control treat-ments in the previously discussed asth-ma and tension headache studies, one wonders if there might be a role for fam-ily members or massage therapists in treat-ing conditions like asthma and headache. Theoretically, the physician could become an educator, trainer, and supervisor of the treatment regimen for certain condi-tions. With the increased emphasis on home health and cost-effectiveness, this could be a workable model in the new medical paradigm—so long as issues of training and safety are addressed. Osteopathic medicine is now pre-sented with the opportunity to contribute to the broader emerging medical paradigm with regard to research into manual medicine and clinical applica-tions of manual techniques. Osteopath-ic physicians are in an excellent position to shape the new paradigm, but they also face the danger of sitting quietly on the sidelines while others determine the role of manual medicine in the evolving health-care system. References 1. Glossary of Osteopathic Terminology. Kirksville, Mo: Kirksville College of Osteopath-ic Medicine; 1990. 2. Cherkin DC, Deyo RA, Battie M, Street J, Barlow W. A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low-back pain. N Engl J Med 1998;339:1021-1029. 3. Mein EA, Richards DG, McMillin DL, McPart-land JM, Nelson CD. Physiologic regulation through manual therapy. Phys Med Rehab 2000;14:27-42. 4. Nelson CD, McMillin DL, Richards DG, Mein EA, Redwood D. Manual healing diversity and other challenges to chiropractic integration. J Manipulative Physiol Ther 2000;23:202-207. Mein et al • Special communications JAOA • Vol 101 • No 8 • August 2001 • 443 5. Balon J, Aker PD, Crowther ER, Danielson C, Cox PG, O’Shaughnessy D, et al. A com-parison of active and simulated chiropractic manipulation as adjunctive treatment for child-hood asthma. N Engl J Med 1998;339:1013- 1020. 6. Jongeward BV. Chiropractic manipulation for childhood asthma. N Engl J Med 1999; 340: 391-392. 7. Rossner A. Scratching where it itches: core issues in chiropractic research. Dynamic Chi-ropractic 1999;17:16,22. 8. Hazzard C. The Practice and Applied Ther-apeutics of Osteopathy. 3rd ed. Kirksville, Mo: Journal Printing Company; 1905: 75-80. 9. Barber ED. Osteopathy Complete. 4th ed. Kansas City, Mo: Hudson-Kimberly Publish-ing Co; 1898:60-68. 10. Goetz EW. A Manual of Osteopathy. 2nd ed. Cincinnati, Ohio: Nature’s Cure Co; 1909: 85-86. 11. Kuchera M, Kuchera WA. Osteopathic Considerations in Systemic Dysfunction. Kirksville, Mo: Kirksville College of Osteopath-ic Medicine; 1991. 12. Richards DG, Mein EA, Nelson CD. Chi-ropractic manipulation for childhood asthma. N Engl J Med 1999;340:391-392. 13. Balon J, Crowther ER, Sears MR. Chiro-practic manipulation for childhood asthma. N Engl J Med 1999;340:392. 14. Bove G, Nilsson N. Spinal manipulation in the treatment of episodic tension-type headache. JAMA 1998;280:1576-1579. 15. Kuchera ML. Osteopathic principles and practice/osteopathic manipulative treatment considerations in cephalgia. JAOA 1998;98(suppl):514-519. 16. Kurz I. Textbook of Dr. Vodder’s Manual Lymph Drainage. Vol 2. Brussels, Belgium: Haug International; 1986. 17. Guthrie RA. Lumbar inhibitory pressure for lumbar myalgia during contractions of the gravid uterus at term. JAOA 1980;80:264-266. 18. Sleszynski SL, Kelso AF. Comparison of thoracic manipulation with incentive spirometry in preventing postoperative atelectasis. JAOA 1993;93:834-845. 444 • JAOA • Vol 101 • No 8 • August 2001 Mein et al • Special communications/Scheinost • Case report Use of herbs as dietary supplements has become common in the United States. According to a 1997 survey, 12.1% of the households interviewed were using herbal medicines.1 The out-of-pocket expense for these medicines was estimated at $5.1 billion. Unfortunately, many people do not know the possible side effects of these treatments. Too often, patients perceive that because herbal med-ications are “natural,” they are therefore safe to take without fear of side effects. This case presents an otherwise healthy young female who was taking an herbal supplement for emotional stress. She came to the emergency department because of chest pain, and subsequently became bradycardic and hypotensive. The patient was then found to have an elevated digox-in level. Report of case A 26-year-old woman presented to the emergency department via ambulance with chest pain of approximately 7 hours’ duration. The patient was a topless dancer who started having the chest pain while at work. The pain was described as a shooting pain that was “in her ribs” on the left side. She went home after work and continued to have pain, and it even-tually became severe enough that she decided to visit the hospital. She had no known drug allergies. The patient’s only medication was birth con-trol pills. Her past medical history was negative, and her past surgical history was negative. The social history was sig-nificant in that the patient reported tobac-co use (1 pack/day) and reported that she had ingested four alcoholic drinks over the course of her shift at work. The patient denied use of illicit drugs. Review of sys-tems was noncontributory. Physical examination was significant only for chest pain, which was repro-ducible to palpation over the left chest, superior to the breast, and approaching the left sternal border. The patient’s heart exhibited regular rate and rhythm with-out murmur. Her lungs were clear to aus-cultation. Vital signs included tempera-ture, 98.6 F; respirations, 16 breaths/min; heart rate, 76 beats/min; and blood pres-sure, 112/59 mm Hg. The rest of the examination was unremarkable. In the emergency department, the patient was given oxygen via nasal can-nula, and she was placed on a cardiac monitor—according to standard chest pain protocol. During the course of mon-itoring, her heart rate dropped to 39 beats/min and her blood pressure dropped Dr Scheinost is in private practice in Hender-son, Kentucky. Correspondence to Michael E. Scheinost, DO, PhD, Family Health Center, 110 Third Street, Suite 370, Henderson, KY 42420. E-mail: mikescheinost@pol.net Digoxin toxicity in a 26-year-old woman taking a herbal dietary supplement MICHAEL E. SCHEINOST, DO, PhD Case report Herbal dietary supplements are often considered by patients to be safe and free from side effects. The case described here shows digoxin toxicity in a patient taking a dietary supplement not normally considered to contain digoxin. In addition to highlighting the risks of herbal supplements, this case also demonstrates the con-cept that digoxin equivalents are not picked up by the standard digoxin assay. (Key words: digoxin, dietary supplements) to 59/36 mm Hg. The monitor showed an absence of P waves (Figure 1). The patient was placed in Trendelenburg’s position and infused with normal saline. Before a 12-lead EKG could be obtained, the patient’s heart rate and blood pressure returned to original baseline. Cardiac lab-oratory results and urine drug screen results were normal with the exception of a digoxin level of 0.9 ng/mL (normal ther-apeutic range, 0.5 to 2.0 ng/mL). Further discussion with the patient revealed that she had been under a great deal of stress recently and that she had been taking an herbal dietary supplement that contained skullcap herb (Scutellaria lateriflora), wood betony herb (Pedicularis canadensis), black cohosh root (Cimi-cifuga racemosa), hops flowers (Humulus lupulus), valerian root (Valeriana offici-nalis), and cayenne pepper fruit (Cap-sicum annuum). She denied taking any more than the indicated dosage of one to two capsules three times a day. Poison control center personnel suggested that the herbs in the patient’s supplement could cause bradycardia and hypotension. The recommendation was to observe the patient, provide supportive care, and to instruct her to stop taking the medica-tion. The patient was admitted to teleme-try for 24-hour observation. She was dis-charged in normal sinus rhythm and was lost to subsequent follow-up after this time. Comments Use of herbal dietary supplements in the United States has become a multibillion dollar industry.1 Because many of these products are listed as dietary supplements, no US Food and Drug Administration controls are exerted over the quality or quantity of herbs in any given product. Patients tend to see such products as harmless supplements and therefore rarely inform their physicians of herbal supple-ment use, unless specifically asked about such use. In this case, the patient was tak-ing an herbal supplement to help relieve her stress—as the product name suggest-ed the supplement would do. The only warning on the product label was one Scheinost • Case report JAOA • Vol 101 • No 8 • August 2001 • 445 Table Digoxin-like “Factors” in Selected Herbs g Digoxin equivalents per 200 mL cup of tea Herb NKA* RIA† Cayenne 4.85 0.004 Hops 2.51 0.013 Skullcap 1.84 0.014 Wood Betony 0.656 0.008 Valerian 0.579 0.006 Black Cohosh 0.555 0.013 *NKA = inhibition of Na, K-ATPase ouabain binding. †RIA = cross-reactivity to digoxin antibody in radioimmunoassay. Adapted from Longerich et al2 Figure 1. Emergen-cy room monitor strips. that stated, “Do not drive or operate machinery while using this product, as drowsiness may result.” Longerich and colleagues2 showed that many of the herbs used in teas contain digoxin-like “factors.” Like digoxin, these “factors” are cardioglycoside compounds, and they exert the same effect on the myocardium as does digoxin. Table 1 lists the digoxin activity equivalents for the herbs in the supplement described in this case study. Note that there is a difference between the amounts of digoxin-like “fac-tors” measured by the two methods. This suggests that while the measured amount of “digoxin” in this patient was 0.9 ng/mL, the effective amount of digoxin-like “factors” in the blood may have been much higher. Digoxin antibody immunoassays only detect those digoxin-like compounds with a chemical structure similar enough to digoxin to bind to the antibody. Such tests do not detect compounds with enough difference in the structure to avoid binding, but which still exhibit signifi-cant cardioglycoside activity. This activ-ity is measured by the ouabain Na,K-ATPase binding assay that detects those compounds, which will exert an effect on the digoxin receptor on the myocardi-um. The assay works by detecting the ability of compounds to displace radio-labeled ouabain from Na,K-ATPase and comparing it to the ability of digoxin to displace the ouabain from the Na,K-ATPase (the site of action for digoxin in the body). While the patient denied tak-ing any more pills than was suggested on the label, actual amounts consumed can-not be verified. The product the patient had taken was not available for further analysis. Therefore, we could evaluate neither the precise amounts of the specified herbs nor contamination of the product with other herbs. Over the past several years, some herbal supplements have come under increased scrutiny as a result of patient illnesses. A recent report describes digoxin toxicity in two patients taking an herbal supplement for cleansing of the bowel.3 The shipment of plantain used in the supplement was shown to be con-taminated with Digitalis lanata. A num-ber of other plants, including oleander (Nerium oleander, a cause of accidental poisoning in children), have been shown to contain cardiac glycosides.4 Further-more, an analysis of traditional Chinese medicines in California showed that 32% contained undeclared compounds.5 This case serves to remind us, as physi-cians, of the importance of discussing alternative medicines with patients. Our patients take a wide variety of herbal medications, including saw palmetto (Serenoa repens or Sabal serrulata) for prostate problems, ginkgo (Ginkgo bilo-ba) for dementia and memory problems, echinacea (Echinacea purpurea or Echi-nacea angustifolia) for immunostimula-tion, pleurisy root (Asclepias tuberosa, which also contains high quantities of digoxin-like compounds) for asthma, and so on. Furthermore, many patients take combination products that contain several different herbal compounds. All of these kinds of herbal supplements can poten-tially interact with medications that patients may be taking. Depending on the reliability of the source of the herbs, these supplements also may be contaminated with other plants that are not intended to be in the product. Such contamination can signif-icantly interfere with treatments we may be giving outpatients. Such contamina-tion also means the patient may be unknowingly receiving medicinal sub-stances that they do not need or want, such as digoxin or digoxin-like factors. We must remember to ask our patients not just what medicines they are taking, but also what dietary supplements they may be using. References 1. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the Unit-ed States, 1990-1997: results of a follow-up national survey. JAMA 1998;280:1569-1575. 2. Longerich L, Johnson E, Gault MH. Digox-in- like factors in herbal teas. Clin Invest Med 1993;16:210-218. 3. Slifman NR, Obermeyer WR, Aloi BK, et al. Contamination of botanical dietary supplements by Digitalis lanata. N Engl J Med 1998;339:806- 811. 4. Radford DJ, Gillies AD, Hinds JA, Duffy P. Naturally occurring cardiac glycosides. Med J Aust 1986;144:540-544. 5. Ko RJ. Adulterants in Asian patent medicines. N Engl J Med 1998;339:847. 446 • JAOA • Vol 101 • No 8 • August 2001 Scheinost • Case report
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Transcript | Mein et al • Special communications JAOA • Vol 101 • No 8 • August 2001 • 441 Manual medicine covers a broad spectrum of techniques, including soft tissue treatment and high-velocity low-amplitude (HVLA) thrusting. In osteopathic terminology, these and many other manual medicine techniques as a whole are commonly referred to as osteo-pathic manipulative treatment (OMT).1 Although many osteopathic physicians take the variety of techniques for granted because of the rich heritage of their pro-fession, there remains ignorance of man-ual medicine diversity in the healthcare community at large, and this has led to serious shortcomings in current research methodology with regard to manipula-tion. Consequently, the role of manual medicine in the emerging medical paradigm is uncertain. Healthcare services that use manual medicine include osteopathic medicine, chiropractic, physical therapy, and mas-sage therapy. Specific types of practi-tioners often rely more often on certain techniques or sets of techniques than do other practitioners (for example, long-lever techniques with osteopathic physi-cians, HVLA adjustments with chiro-practors), but there remains considerable diversity within manual medicine–ori-ented professions and significant overlap between them. However, the research lit-erature often fails to reflect this diversity. For example, one recent study of treat-ments for low back pain refers simply to “chiropractic” in the abstract and throughout most of the article, as if a general set of modalities were being applied (the article only noted briefly that side-posture, HVLA adjustments were the only chiropractic modality used).2 Early osteopathic physicians used a variety of articular and nonarticular approaches to achieve their goal of nor-malizing blood flow. They used general mobilizations (the osteopathic “general treatment”), long- and short-lever manip-ulations of the entire musculoskeletal sys-tem, strain-counterstrain, and specific pressures (“stimulation” and “inhibi-tion”) to influence and regulate sympa-thetic nervous system functions. Also, drainage techniques were part of com-monly accepted practice.3 Early chiropractors, with the goal of normalizing nerve function by reducing the vertebral subluxation, were some-what more limited in their approach, rely-ing primarily on HVLA thrusts. As time has passed, chiropractors have added con-siderably to their body of therapeutic applications, broadening their range of manual articular techniques; adding man-ual reflex and muscle relaxation tech-niques; and incorporating nonmanual therapeutic modalities, such as electrical and thermal modes of therapy, bracing, casts, support, traction, and nutritional counseling—all of which have been ben-eficial. However, in their research approach to demonstrate the validity of manual medicine, chiropractors have focused almost entirely on the HVLA spinal adjustment, ignoring the diversity of other manual techniques with claims of effectiveness.4 Problematic research methodology Two well-publicized studies reported in leading medical journals illustrate the potential methodologic problems associ- Dr Mein is medical director at Meridian Institute, Virginia Beach, Virginia, where Mr McMillin is program director, Dr Richards is director of research, and Dr Nelson is a clinical researcher. Dr Greenman is professor emer-itus at Michigan State University College of Osteopathic Medicine, East Lansing, Mich. Correspondence to Eric A. Mein, MD, Meridian Institute, 1853 Old Donation Park-way, Suite 1, Virginia Beach, VA 23454. E-mail: meridian@meridianinstitute.com Manual medicine diversity: research pitfalls and the emerging medical paradigm ERIC A. MEIN, MD; PHILIP E. GREENMAN, DO; DAVID L. MCMILLIN, MA; DOUGLAS G. RICHARDS, PhD; CARL D. NELSON, DC Special communications Recent studies published in leading medical journals have concluded that chiropractic treatment is not particularly helpful for relieving asthma and migraine symptoms because even though study participants showed notable improvement in symptoms, those subjects who received sham manual medicine treatments also showed improvement. Yet the sham treatment received by control groups in these studies is reminiscent in many ways of traditional osteopathic manipulation. This seems to represent not only a failure to recognize the value of many manual medicine tech-niques but also an ignorance of the broad spectrum of manual medicine tech-niques used by various practitioners, from osteopathic physicians to chiropractors to physical therapists. Such blind spots compromise research methodology with regard to manual medicine studies, which could, in turn, diminish the role of manual medicine in clinical practice. Osteopathic manipulative treatment pro-vides an excellent model for recognizing and integrating the full range of manual medicine techniques into research and clinical applications because of the wide range of techniques employed. The potential exists for these techniques to contribute much to medical research and clinical practice—provided that osteopathic physicians and other manual medicine practitioners work to alleviate ignorance about the effica-cy of various forms of manipulation. (Key words: osteopathic manipulative treatment, chiropractic, research design, alternative medicine) ated with manual medicine diversity. One such example is a study that compared “active” and “simulated” chiropractic manipulation as adjunctive treatment for childhood asthma, conducted by Balon and others.5 The active treatment consisted of “manual contact with spinal or pelvic joints followed by high-velocity low-amplitude directional push often associ-ated with joint opening, creating a cavi-tation, or ‘pop.’” This treatment is a standard HVLA technique used by a wide variety of practitioners, such as osteo-pathic physicians, chiropractors, and phys-ical therapists. The simulated treatment involved the following parameters: (1) providing “soft-tissue massage and gentle palpation” to the spine, paraspinal muscles, and shoul-ders; (2) “turning the subject’s head from one side to the other”; (3) providing “a nondirectional push, or impulse” to the gluteal area with the subject lying on one side and then the other; (4) placing the subject in a prone position so that “a similar impulse was applied bilaterally to the scapulae”; (5) putting the subject in a supine position “with the head rotated slightly to each side, and an impulse applied to the external occipital protu-berance”; and (6) applying low-ampli-tude, low-velocity impulses “in all these nontherapeutic contacts, with adequate joint slack so that no joint opening or cavitation occurred.” Jongeward6 and Rossner7 have ques-tioned the appropriateness of such simu-lated treatment, noting that standard chi-ropractic practice can include soft tissue work. Another problem is that the simu-lated treatment bears a marked similari-ty to a traditional general osteopathic treatment.8,9,10(pp85-86) Balon and colleagues5 summarized the simulated treatment by stating, “Hence, the comparison of treatments was between active spinal manipulation as routinely performed by chiropractors and hands-on procedures without adjustments or manipulation.” Based on the conclu-sions of the researchers, it would seem they were unaware of the early osteo-pathic works addressing asthma8-10 and the more recent literature on OMT for respiratory conditions, particularly by Kuchera and Kuchera.11 The method-ologic limitations of the study by Balon and others with regard to manual medicine diversity have been noted.12 Balon and coworkers responded that they were unconvinced by the evidence sup-porting the efficacy of their “simulated treatment.”13 The results as reported by the re-searchers were “Symptoms of asthma and use of -agonists decreased and the quality of life increased in both groups, with no significant differences between the groups.” The conclusion was that “the addition of chiropractic spinal manipulation to usual medical care pro-vided no benefit.”5 Thus, the conclusion suggests an apparent failure of chiropractic to address systemic dysfunction, such as asthma. Although technically this conclusion is limited to HVLA spinal adjustments, the fallout will, for all practical purpose, prob-ably affect attitudes toward all types of manual medicine and manual medicine practitioners. The problem is that while the study is widely perceived as indicating a failure of manual medicine for the treat-ment of systemic dysfunction, it may instead be indicative that the subjects in both groups benefited—but from two distinct forms of manual medicine. Igno-rance (whether by lack of knowledge or by the choice to ignore the available infor-mation) has severely distorted the findings of this widely publicized study. This study is not the only example of such confusion. A similar study14 demon-strates a comparable ignorance of manual medicine diversity, duplicating the methodologic flaws, favorable outcomes, and unfounded conclusions of the study by Balon and others. The researchers in this study compared two forms of man-ual therapy for the treatment of tension headache. The experimental treatment consisted of standard HVLA chiropractic treatment and deep friction massage, plus trigger point therapy if indicated. The subjects receiving this intervention were designated as the “manipulation” group. The control group received deep friction massage plus low-power laser light (con-sidered not to be efficacious for tension headache). Thus, essentially, one form of manual medicine is again compared to another. The researchers observed that “by week 7, each group experienced sig-nificant reductions in mean daily headache hours...and mean number of analgesics per day.”14 Because both groups bene-fited equally, the authors concluded that “As an isolated intervention, spinal manipulation does not seem to have a positive effect on episodic tension-type headaches.”14 Both studies were reported in the mass media with the simplistic conclusion that chiropractic does not work for such con-ditions as childhood asthma and tension headache. The design and outcome of the studies do not allow us to draw such conclusions, however. Perhaps a more accurate conclusion should have been that we do not know if HVLA adjust-ments are specifically helpful or not. Although the favorable outcomes could have resulted from chance or placebo effects, a reasonable person might also justifiably conclude that various forms of manual medicine can be helpful for these conditions. Kuchera15 recently dis-cussed in detail the mechanisms by which OMT could be used in treatment of headaches of various types. Ignorance of the diversity and validity of the full spec-trum of manual therapy applications con-founds the issue. More research is des-perately needed—research which seriously considers the full spectrum of manual medicine options from a variety of health-care professions. Developing an appropriate research methodology is a challenge. Consideration must be given not only to the diversity of potentially effective manual techniques, but to the difficulty of identifying a sim-ulated treatment with no physical effects. Even light stroking of the skin may have significant effects on physiology.16 In con-trast to randomized clinical trials of drugs, double-blind methodology is not possible with manual medicine research; the ther-apist is always aware of the technique being applied. Even blinding patients is problematic, particularly if they have pre-vious exposure to manual techniques. Rather than a treatment/placebo com-parison, perhaps the only possible com- 442 • JAOA • Vol 101 • No 8 • August 2001 Mein et al • Special communications parison will be between active treatment methods. This then raises the problem of individualization of treatment; even the study by Balon and others5 acknowledges that the therapists tailored their treat-ments to the needs of the individual patients. A wider discussion of the methodologic issues inherent in the study of manual therapy is necessary to counter the application of overly simplistic and inappropriate methodologies in studies of manual medicine and in the media coverage of such studies. Manual medicine and the emerging medical paradigm So what does this have to do with osteo-pathic medicine? It would seem that chi-ropractors and many members of the medical establishment involved in report-ing these studies are simply ignorant of the osteopathic medical perspective. While this type of misunderstanding is neither new nor surprising, it has tremendous implications for the future. We are in the midst of a medical rev-olution, and in this revolution, many questions are being asked about manual medicine and other techniques that are sometimes referred to as “alternative” medicine. What is the role of manual medicine in the emerging medical paradigm? Will manual medicine be lim-ited to relieving musculoskeletal pain? Will osteopathic manipulative treatment remain a self-contained system of healing? Is there a legitimate role for the full spec-trum of manipulative techniques in the treatment of systemic dysfunction? Osteopathic medicine has a great deal to offer. Because of its rich heritage of philosophy, research, and clinical tech-niques, the profession can influence the direction of healthcare in a positive man-ner. Osteopathic medicine has integrated the diversity of manual medicine tech-niques into its own system in the form of OMT. Thus, osteopathic medicine is the single best representative of manual medicine diversity currently available to researchers and clinicians. Another primary factor driving the current changes in healthcare is eco-nomics. Not only must treatment options be safe and efficacious, they must be cost-effective. The diversity of manual medicine techniques provides a variety of approach-es that could have significant cost-saving potential. This is particularly true for sim-ple regulatory techniques, as contrasted with corrective techniques. For example, inhibitive pressure and thoracic lymphatic pump applications can be easily adapted for application by lay persons and thera-pists. In a study on labor pain during con-tractions of gravid uterus at term, lumbar inhibitory pressure was shown to be effec-tive in reducing pain in a group of 175 women. This simple technique was applied by husbands and other family members, as well as by nurses and physi-cians. “Since back pressure in a high per-centage of cases was administered by the husband, this suggests that training of husbands in the proper technique would minimize staff time required in labor and delivery, as well as the need for medica-tion.” 17 Also, thoracic lymphatic pumping (TLP) has been shown to be at least as effective as incentive spirometry in pre-venting atelectasis in patients who have undergone cholecystectomy. In addition to its treatment efficacy, the authors noted that TLP costs were lower than those for incentive spirometry and that “the TLP treatment costs could be further reduced by training a respiratory therapist to administer the treatment.”18 There is historical precedent for involv-ing lay persons and therapists in the less technical manual therapy applications. The early osteopathic physicians recog-nized a hierarchy of expertise with regard to technique. One early osteopathic text-book was specifically written with the lower end of this hierarchy in mind. In the preface to the second edition of his book, Eduard Goetz acknowledged the accessi-bility of simple manual medicine appli-cations when he wrote, “The mere read-ing of the book cannot possibly result in one’s becoming a full fledged osteopath. The intention is simply to impart sufficient knowledge of the mode of procedure to enable the careful reader to apply the treatment in his home in case of emer-gency and until such a time as a regular practicing osteopath can be called in should that be found necessary.”10 (For those interested in the work of Goetz and other early osteopathic physicians, some of their texts are now available on the Early American Manual Therapy Web site at www.meridianinstitute.com.) When considering the relatively low level of expertise required to perform deep friction massage and soft-tissue tech-niques, such as those used as control treat-ments in the previously discussed asth-ma and tension headache studies, one wonders if there might be a role for fam-ily members or massage therapists in treat-ing conditions like asthma and headache. Theoretically, the physician could become an educator, trainer, and supervisor of the treatment regimen for certain condi-tions. With the increased emphasis on home health and cost-effectiveness, this could be a workable model in the new medical paradigm—so long as issues of training and safety are addressed. Osteopathic medicine is now pre-sented with the opportunity to contribute to the broader emerging medical paradigm with regard to research into manual medicine and clinical applica-tions of manual techniques. Osteopath-ic physicians are in an excellent position to shape the new paradigm, but they also face the danger of sitting quietly on the sidelines while others determine the role of manual medicine in the evolving health-care system. References 1. Glossary of Osteopathic Terminology. Kirksville, Mo: Kirksville College of Osteopath-ic Medicine; 1990. 2. Cherkin DC, Deyo RA, Battie M, Street J, Barlow W. A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low-back pain. N Engl J Med 1998;339:1021-1029. 3. Mein EA, Richards DG, McMillin DL, McPart-land JM, Nelson CD. Physiologic regulation through manual therapy. Phys Med Rehab 2000;14:27-42. 4. Nelson CD, McMillin DL, Richards DG, Mein EA, Redwood D. Manual healing diversity and other challenges to chiropractic integration. J Manipulative Physiol Ther 2000;23:202-207. Mein et al • Special communications JAOA • Vol 101 • No 8 • August 2001 • 443 5. Balon J, Aker PD, Crowther ER, Danielson C, Cox PG, O’Shaughnessy D, et al. A com-parison of active and simulated chiropractic manipulation as adjunctive treatment for child-hood asthma. N Engl J Med 1998;339:1013- 1020. 6. Jongeward BV. Chiropractic manipulation for childhood asthma. N Engl J Med 1999; 340: 391-392. 7. Rossner A. Scratching where it itches: core issues in chiropractic research. Dynamic Chi-ropractic 1999;17:16,22. 8. Hazzard C. The Practice and Applied Ther-apeutics of Osteopathy. 3rd ed. Kirksville, Mo: Journal Printing Company; 1905: 75-80. 9. Barber ED. Osteopathy Complete. 4th ed. Kansas City, Mo: Hudson-Kimberly Publish-ing Co; 1898:60-68. 10. Goetz EW. A Manual of Osteopathy. 2nd ed. Cincinnati, Ohio: Nature’s Cure Co; 1909: 85-86. 11. Kuchera M, Kuchera WA. Osteopathic Considerations in Systemic Dysfunction. Kirksville, Mo: Kirksville College of Osteopath-ic Medicine; 1991. 12. Richards DG, Mein EA, Nelson CD. Chi-ropractic manipulation for childhood asthma. N Engl J Med 1999;340:391-392. 13. Balon J, Crowther ER, Sears MR. Chiro-practic manipulation for childhood asthma. N Engl J Med 1999;340:392. 14. Bove G, Nilsson N. Spinal manipulation in the treatment of episodic tension-type headache. JAMA 1998;280:1576-1579. 15. Kuchera ML. Osteopathic principles and practice/osteopathic manipulative treatment considerations in cephalgia. JAOA 1998;98(suppl):514-519. 16. Kurz I. Textbook of Dr. Vodder’s Manual Lymph Drainage. Vol 2. Brussels, Belgium: Haug International; 1986. 17. Guthrie RA. Lumbar inhibitory pressure for lumbar myalgia during contractions of the gravid uterus at term. JAOA 1980;80:264-266. 18. Sleszynski SL, Kelso AF. Comparison of thoracic manipulation with incentive spirometry in preventing postoperative atelectasis. JAOA 1993;93:834-845. 444 • JAOA • Vol 101 • No 8 • August 2001 Mein et al • Special communications/Scheinost • Case report Use of herbs as dietary supplements has become common in the United States. According to a 1997 survey, 12.1% of the households interviewed were using herbal medicines.1 The out-of-pocket expense for these medicines was estimated at $5.1 billion. Unfortunately, many people do not know the possible side effects of these treatments. Too often, patients perceive that because herbal med-ications are “natural,” they are therefore safe to take without fear of side effects. This case presents an otherwise healthy young female who was taking an herbal supplement for emotional stress. She came to the emergency department because of chest pain, and subsequently became bradycardic and hypotensive. The patient was then found to have an elevated digox-in level. Report of case A 26-year-old woman presented to the emergency department via ambulance with chest pain of approximately 7 hours’ duration. The patient was a topless dancer who started having the chest pain while at work. The pain was described as a shooting pain that was “in her ribs” on the left side. She went home after work and continued to have pain, and it even-tually became severe enough that she decided to visit the hospital. She had no known drug allergies. The patient’s only medication was birth con-trol pills. Her past medical history was negative, and her past surgical history was negative. The social history was sig-nificant in that the patient reported tobac-co use (1 pack/day) and reported that she had ingested four alcoholic drinks over the course of her shift at work. The patient denied use of illicit drugs. Review of sys-tems was noncontributory. Physical examination was significant only for chest pain, which was repro-ducible to palpation over the left chest, superior to the breast, and approaching the left sternal border. The patient’s heart exhibited regular rate and rhythm with-out murmur. Her lungs were clear to aus-cultation. Vital signs included tempera-ture, 98.6 F; respirations, 16 breaths/min; heart rate, 76 beats/min; and blood pres-sure, 112/59 mm Hg. The rest of the examination was unremarkable. In the emergency department, the patient was given oxygen via nasal can-nula, and she was placed on a cardiac monitor—according to standard chest pain protocol. During the course of mon-itoring, her heart rate dropped to 39 beats/min and her blood pressure dropped Dr Scheinost is in private practice in Hender-son, Kentucky. Correspondence to Michael E. Scheinost, DO, PhD, Family Health Center, 110 Third Street, Suite 370, Henderson, KY 42420. E-mail: mikescheinost@pol.net Digoxin toxicity in a 26-year-old woman taking a herbal dietary supplement MICHAEL E. SCHEINOST, DO, PhD Case report Herbal dietary supplements are often considered by patients to be safe and free from side effects. The case described here shows digoxin toxicity in a patient taking a dietary supplement not normally considered to contain digoxin. In addition to highlighting the risks of herbal supplements, this case also demonstrates the con-cept that digoxin equivalents are not picked up by the standard digoxin assay. (Key words: digoxin, dietary supplements) to 59/36 mm Hg. The monitor showed an absence of P waves (Figure 1). The patient was placed in Trendelenburg’s position and infused with normal saline. Before a 12-lead EKG could be obtained, the patient’s heart rate and blood pressure returned to original baseline. Cardiac lab-oratory results and urine drug screen results were normal with the exception of a digoxin level of 0.9 ng/mL (normal ther-apeutic range, 0.5 to 2.0 ng/mL). Further discussion with the patient revealed that she had been under a great deal of stress recently and that she had been taking an herbal dietary supplement that contained skullcap herb (Scutellaria lateriflora), wood betony herb (Pedicularis canadensis), black cohosh root (Cimi-cifuga racemosa), hops flowers (Humulus lupulus), valerian root (Valeriana offici-nalis), and cayenne pepper fruit (Cap-sicum annuum). She denied taking any more than the indicated dosage of one to two capsules three times a day. Poison control center personnel suggested that the herbs in the patient’s supplement could cause bradycardia and hypotension. The recommendation was to observe the patient, provide supportive care, and to instruct her to stop taking the medica-tion. The patient was admitted to teleme-try for 24-hour observation. She was dis-charged in normal sinus rhythm and was lost to subsequent follow-up after this time. Comments Use of herbal dietary supplements in the United States has become a multibillion dollar industry.1 Because many of these products are listed as dietary supplements, no US Food and Drug Administration controls are exerted over the quality or quantity of herbs in any given product. Patients tend to see such products as harmless supplements and therefore rarely inform their physicians of herbal supple-ment use, unless specifically asked about such use. In this case, the patient was tak-ing an herbal supplement to help relieve her stress—as the product name suggest-ed the supplement would do. The only warning on the product label was one Scheinost • Case report JAOA • Vol 101 • No 8 • August 2001 • 445 Table Digoxin-like “Factors” in Selected Herbs g Digoxin equivalents per 200 mL cup of tea Herb NKA* RIA† Cayenne 4.85 0.004 Hops 2.51 0.013 Skullcap 1.84 0.014 Wood Betony 0.656 0.008 Valerian 0.579 0.006 Black Cohosh 0.555 0.013 *NKA = inhibition of Na, K-ATPase ouabain binding. †RIA = cross-reactivity to digoxin antibody in radioimmunoassay. Adapted from Longerich et al2 Figure 1. Emergen-cy room monitor strips. that stated, “Do not drive or operate machinery while using this product, as drowsiness may result.” Longerich and colleagues2 showed that many of the herbs used in teas contain digoxin-like “factors.” Like digoxin, these “factors” are cardioglycoside compounds, and they exert the same effect on the myocardium as does digoxin. Table 1 lists the digoxin activity equivalents for the herbs in the supplement described in this case study. Note that there is a difference between the amounts of digoxin-like “fac-tors” measured by the two methods. This suggests that while the measured amount of “digoxin” in this patient was 0.9 ng/mL, the effective amount of digoxin-like “factors” in the blood may have been much higher. Digoxin antibody immunoassays only detect those digoxin-like compounds with a chemical structure similar enough to digoxin to bind to the antibody. Such tests do not detect compounds with enough difference in the structure to avoid binding, but which still exhibit signifi-cant cardioglycoside activity. This activ-ity is measured by the ouabain Na,K-ATPase binding assay that detects those compounds, which will exert an effect on the digoxin receptor on the myocardi-um. The assay works by detecting the ability of compounds to displace radio-labeled ouabain from Na,K-ATPase and comparing it to the ability of digoxin to displace the ouabain from the Na,K-ATPase (the site of action for digoxin in the body). While the patient denied tak-ing any more pills than was suggested on the label, actual amounts consumed can-not be verified. The product the patient had taken was not available for further analysis. Therefore, we could evaluate neither the precise amounts of the specified herbs nor contamination of the product with other herbs. Over the past several years, some herbal supplements have come under increased scrutiny as a result of patient illnesses. A recent report describes digoxin toxicity in two patients taking an herbal supplement for cleansing of the bowel.3 The shipment of plantain used in the supplement was shown to be con-taminated with Digitalis lanata. A num-ber of other plants, including oleander (Nerium oleander, a cause of accidental poisoning in children), have been shown to contain cardiac glycosides.4 Further-more, an analysis of traditional Chinese medicines in California showed that 32% contained undeclared compounds.5 This case serves to remind us, as physi-cians, of the importance of discussing alternative medicines with patients. Our patients take a wide variety of herbal medications, including saw palmetto (Serenoa repens or Sabal serrulata) for prostate problems, ginkgo (Ginkgo bilo-ba) for dementia and memory problems, echinacea (Echinacea purpurea or Echi-nacea angustifolia) for immunostimula-tion, pleurisy root (Asclepias tuberosa, which also contains high quantities of digoxin-like compounds) for asthma, and so on. Furthermore, many patients take combination products that contain several different herbal compounds. All of these kinds of herbal supplements can poten-tially interact with medications that patients may be taking. Depending on the reliability of the source of the herbs, these supplements also may be contaminated with other plants that are not intended to be in the product. Such contamination can signif-icantly interfere with treatments we may be giving outpatients. Such contamina-tion also means the patient may be unknowingly receiving medicinal sub-stances that they do not need or want, such as digoxin or digoxin-like factors. We must remember to ask our patients not just what medicines they are taking, but also what dietary supplements they may be using. References 1. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the Unit-ed States, 1990-1997: results of a follow-up national survey. JAMA 1998;280:1569-1575. 2. Longerich L, Johnson E, Gault MH. Digox-in- like factors in herbal teas. Clin Invest Med 1993;16:210-218. 3. Slifman NR, Obermeyer WR, Aloi BK, et al. Contamination of botanical dietary supplements by Digitalis lanata. N Engl J Med 1998;339:806- 811. 4. Radford DJ, Gillies AD, Hinds JA, Duffy P. Naturally occurring cardiac glycosides. Med J Aust 1986;144:540-544. 5. Ko RJ. Adulterants in Asian patent medicines. N Engl J Med 1998;339:847. 446 • JAOA • Vol 101 • No 8 • August 2001 Scheinost • Case report |
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