EDITORIALS

situation where a buyer is in a singularly poor position to exercise sound judgment about the value of what is being bought. It is a dangerous precedent to cast aside a body of human experience, garnered over decades, which has determined that in a complex technologic society the consumer should be somehow protected from unbridled exploitation in matters beyond his or her technologic ken. Irrationality is for real, manipulation of mass psychology is for real. These are the disturbing truths that surface when one awakens from this Laetrile nightmare. -MSMW

Familial Mediterranean Fever- A Progress Report THE SPECIALTY CONFERENCE from the University of California, Los Angeles, on familial Mediterranean fever (FMF) in this issue deserves special comment for several reasons. rs,itdedenes renewed clinical interest and rekindled research effort in a rare disease that promises to shed no light on cancer, arteriosclerosis, diabetes, or any other bete noire scheduled for caging via a categorical center grant. Second, the individual contributions serve to contrast sharply a redefined knowledge of the clinical manifestations Of FMF (and their generally excellent response to an ageold nostrum) with our astonishing ignorance of the pathogenesis of the disease. Finally, there is the implicit suggestion that the "colchicine connection" may point talented sleuths in the proper investigative direction toward enlightenment concerning the underlying mechanism of FMF attacks. Regarding the clinical features, there is a growing awareness that the Israeli version of FMF is not the only one. As noted by the UCLA group, amyloidosis is extremely rare in their cohort of Armenian patients, and this is also true of Jewish patients seen in the United States.' Many of them are Ashkenazi, rather than Sephardic Jews-a fact that has uncertain relevance to their freedom from amyloid deposition. Arthritis and skin manifestations are considerably less common here than in Israel.'' The absence of a positive family history is probably more frequent among our sporadic

40

JULY 1977 *

127 *

1

cases, as compared with their endemic ones. Are we talking about the same disease? Decidedly yes -on the basis of its most important hallmarks: brief (1 to 3 days) and unpredictable attacks of abdominal pain and fever; rapid lysis to completely normal interval health, and the lack of an identifiable cause despite exhaustive diagnostic evaluation. Although it is premature to consider colchicine suppression a hallmark of the disease, its value to so many patients in the Mediterranean basin and in North America does support a unitarian concept of what is being called FMF in both regions. The widespread use of colchicine treatment has sparked a newer set of observations. Most patients receiving suppressive therapy of one to three pills per day describe incipient attacks that are completely aborted by a single additional dose. Approximately 15 percent of patients with FMF show minimal or no response to colchicine. (The reason

for this isInasparticular, cloudy asremission why most patients respond.) is less apt to do be achieved in children, even at adult dosage. An e f t y produce genetic damage appeared to be assuaged from offspring the Tel Hashomer a brief by reportnormal in seven "atgroup, risk" which described prgacethtwefoledhouheivy. Alas,tey havese chldvwith since obsered observed aa child with they have Alas, Down's syndrome born to a mother who mad. visedly Whethe continued thcuen colchicine to disc pregnant.5 ninut aonciion while drugetreecmont befo wil

nnedicontin

be

sufficiently

protective remains uncertain.

For

this reason, the program of prodrome-initiated colchicine treatment described by Wright and coworkers6 is an appropriate substitute for chronic prophylaxis in potential child-bearing patients whose attacks can be substantially aborted in this manner. The intimation that colchicine might reverse or prevent amyloidosis in FMF victims is based on very preliminary observations.4 If borne out, this would be mind boggling indeed, especially in view of the purported lack of relationship between amyloidosis and the frequency or severity of FMF attacks.3 Although it has been shown that colchicine pre-treatment can block casein-induced amyloidosis in mice,78 the dosage required to achieve this is approximately a third of the lethal dose in these animals. Finally, how might colchicine provide a clue to our understanding of the pathogenesis of FMF?

EDITORIALS

If there is any analogy to the gout story, our attention must surely be directed to the polymorphoniuclear leukocyte as a crucial intermediary in the evocation and perpetuation of the inflammatory attack. Polymorphs have not only been identified as the dominant cell in FMF effusions, but a tantalizing photograph has even shown inclusion bodies (phagocytosed what?) within them.3 The message for the investigator would seem clear: the material to be examined is probably not intravascular, but intraperitoneal, on occasion intrapleural, and rarely (in this country) intra-articular. But this is far easier said than done. It is an unusual FMF patient who is willing to discontinue taking colchicine, and a still rarer one willing to have peritoneal lavage done at the inception of his attack. (And how about the human experimentation committee?) But think of the potential yield to a hypothetical multidisciplinary group of investigators! There would be cells to examine by phase and electron microscopy for unusual ingestants, and supernatant to search for that elusive metabolite (the protagonist?) as well as the more fashionable mediators of inflammation such as products of complement activation, immune complexes and prostaglandins. Doubtless a lead would be gained, providing it was resolved to discount the inevitable viral particle or two that would peek out from an electron micrograph. By incubating harvested polymorphs, one might also learn whether the demonstration that they are unstable in certain unphysiological conditions is translatable to the in vivo, inflammatory milieu. A fanciful project? Perhaps. But to the extent that our understanding of the mechanism of gouty arthritis has emerged from a close look at what is occurring in joint fluid, so might one wish for some application of Sutton's law to the investigation of FMF. STEPHEN E. GOLDFINGER, MD

Harvard Medical School Boston REFERENCES

1. Siegal S: Familial paroxysmal polyserositis-Anlysis of fifty cases. Am J Med 36:893-918, Jun 1964 2. Schwabe AD, Peters RS: Familial Mediterranean fever in Armenians-Analysis of 100 cases. Medicine 53:453-462, Nov 1974 3. Sohar E, Gafni J, Pras M, et al: Familial Mediterranean fever -A survey of 470 cases and a review of the literature. Am J Med

43:227-253, Aug 1967 4. Zemer D, Pras M, Sohar E, et al: Colchicine in familial Mediterranean fever (Letter). N Eng J Med 294:170-171, Jan 15, 1976 5. Pras M: Personal communication, 1977 6. Wright DG, Wolff SM, Fausi AS, et al: Efficiency of intermittent colchicine therapy in familial Mediterranean fever. Ann Intern Med 86:162-165, Feb 1977 7. Shirama T. Cohen AS: Blockage of amyloid induction by colchicine in an animal model. J Exp Med 140:1102-1107, Oct 1974 8. Kedar I, Ravid M, Sohar E, et al: Colchicine inhibition of casein-induced amyloidosis in mice. Isr J Med Sci 10:787-789, Jul 1974

An Extended Role for Physician Extenders THERE IS NOTHING really new about the concept of physician extenders. Well-trained professionals and assistants of many kinds have long been extending the reach of physicians in their offices, in the care of their patients in hospitals, and in many other settings. Practicing physicians simply could not serve their patients or the public as well as they do without this kind of assistance. This has been a natural development. Perhaps it is now high time to give more consideration to a further role for physician extenders-a role that would enable physicians, or groups or clusters of physicians, to surmount geographic, cultural, language and even economic barriers to making mainstream medical and health care available to those segments of the citizenry who do not yet have adequate access to it. This could be a further extension of the natural role of physician extenders. Both the governmental (public) and the nongovernmental (private) sectors of our country have addressed these difficult problems over the years. So far the problems have not been very well resolved. In some ways they may even have been compounded. Private insurance for medical care solved some but not all the problems. Government funding of health care for the aged and the poor (Medicare and Medicaid) solved some but not all the problems-and unexpectedly created some new ones. For example, and really not all that surprising, the more dollars that were infused into the nation's health care system, the more the costs rose. The escalating costs are now becoming really frightening, and their control is about to take precedence over the basic purpose, which is to ensure that adequate (we used to say the best) care is available to persons who need it. Among the populations which are yet to be reached adequately are those who are "remote" from the existing health care system because of what have been called "barriers," as though these were purposely erected to prevent access. Of course

there

was no

such purpose. Rather the

THE WESTERN JOURNAL OF MEDICINE

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