rheumatoid arthritis

1155

recognised by the Government who do not believe thatthese objects will be prejudiced ".

It is doubtful whether the new procedure will resultin any significant reduction in the total Government

expenditure on drugs under the National Health Service.Of a total estimated expenditure in the current financialyear of Ell 0 million, about El 4 million represents pur-chases by hospitals. Expenditure by hospitals on thedrugs specifically mentioned by the Ministry appears tobe about El million.1 The Government will no longerderive such benefit as it has had in the past from cheaperpurchases by individual hospital authorities from un-licensed foreign sources-a practice which the Govern-ment could hardly be expected to countenance-and,although the Government should get the benefit of lowerprices on the proposed central contracts, the compensa-tion (as yet undetermined in amount) to British patenteeswill have to be taken into account as well.

1. Times, May 18, 1961.2. Annals of Internal Medicine, 1960, 53, no. 7. 3. Duthie, J. J. R., Brown, P. E., Knox, J. D. E., Thompson, M. Ann.

rheum. Dis. 1957, 16, 411. See Lancet, 1958, i, 894.

RHEUMATOID ARTHRITIS

FROM time to time a group of American physicianssurvey recent work on the rheumatic diseases. Thethirteenth rheumatism review, 2 covering the period1956-58, deals with more than 4000 publications andlists almost 3500.

The longest section relates to the management ofrheumatoid arthritis; and, although the editors haveselected the material carefully, the reader is left with theimpression that the gain in knowledge has been small inproportion to the vast amount of research. The review

points to increased awareness of the hazards of long-termadministration of steroid hormones. Though there is nounanimity on the indications for steroid therapy, it is

generally agreed that such therapy should be consideredonly after trial of other methods. Treatment is based ona basic regimen of rest in the active stage of the disease,physiotherapy and reablement, overall social care, andcontinued administration of a more or less non-toxic

analgesic such as aspirin. The more potent and toxic

drugs should be reserved for patients who fail or ceaseto respond to other measures.Because the course of rheumatoid arthritis is variable

and unpredictable, clinical trials of new remedies mustnecessarily include many patients and be conducted overlengthy periods. The results may establish whether ornot the agent on trial has a beneficial effect; but, unlessall patients in the trial improve, the results cannot beexpected to yield prospective information about the

response of the individual patient. This serious limita-tion of clinical trials in rheumatoid arthritis seems to be

unavoidable; and probably until more is known about thenature and course of the disease much time will be spentin testing drug after drug.There may be a case for submitting to controlled trials

the various components of the basic regimen. Duthieet al. showed that the prognosis for patients admitted tohospital in the first year of the disease was better than forothers, and that the benefit was maintained over a periodof years. This suggests that early institution of the basicregimen may do more than control the disease temporarily.If this is so, then it is surely reasonable to examineeach component of the regimen in detail. Meanwhile, in

routine practice, this regimen should be applied as earlyas possible in the course of the disease, even if the patienthas to be admitted to hospital; and in addition a potentsuppressive drug such as corticotrophin may be adminis-tered for a limited period. Those reared in the strict

discipline of clinical trials may recoil at such a blunder-buss technique. But there will’ be plenty of clinicaltrials to read about in the fourteenth review, due at theend of this year.

1. Goddard, D. R. Anesthesiology, 1960, 21, 587.2. Fleischer, S. ibid. p. 597.3. Kinney, J. M. ibid. p. 615.4. Farhi, L. E., Rahn, H. ibid. p. 604.5. Farhi, L. E., Rahn, H. J. appl. Physiol. 1955, 7, 472.6. Nunn, J. F. Anesthesiology, 1960, 21, 620.

CARBON DIOXIDE

THE balance of carbon dioxide in the body is a

notoriously complex subject: neither the factors governingpCO2 nor the effects of changes in pCO2 are simple tounderstand, and it is difficult to find authoritative workon either topic. A symposium in Anesthesiology will bewelcomed by many who share an interest in this quiteremarkably active catabolite. It is perhaps appropriatethat this symposium should have been devised by anves-thetists, who undoubtedly see the most extreme departuresfrom normal carbon-dioxide balance, and who are them-selves the most important variable factor determining thepCO2 of their patients.The symposium opens with an account of the role of carbon

dioxide in the world as a whole.l Few students of the medical

aspects of carbon dioxide will not be intrigued to read of thegeological origin of carbon dioxide, and the part played by theoceans in the regulation of the atmospheric concentration.Subsequent more mundane chapters review the metabolic

production of carbon dioxide and its transport by the blood.2 3

In an important article Farhi and Rahn consider the dyna-mics of changes in carbon-dioxide stores within the body.This constitutes a development of their studies reported sixyears ago.5 They discuss the concept of many body stores inseries and parallel-all with different rates of carbon-dioxideproduction, different quantities and tensions of stored carbondioxide, different storage capacities, and different rates ofaccumulation and discharge when coming into equilibriumwith a changed arterial carbon-dioxide tension. They point outthat the rate at which the various stores come into equilibriumis not constant but may vary greatly, chiefly as a result ofchanges in the rate of blood-flow perfusing the particularstore. Identification and quantification of all the carbon-dioxide stores is a hopelessly difficult task, and Farhi and Rahnhave confined their attention to the five most important stores-alveolar gas, heart, brain, muscle, and remaining stores con-sidered together. Two important stores are not considered:bone and fat contain very large quantities of carbon dioxide,but they are thought to equilibrate so slowly that their influencewill be negligible in short and medium term changes. Thetime constants of alveolar gas, heart, and brain are calculatedto lie between one and three minutes, while for muscle a typicalvalue is thirty minutes-though this value can be varied betweenwide limits by changes in muscle blood-flow. With its largevolume of stored carbon dioxide, the muscle store is clearly amajor factor governing the time constant of the body as a whole.These findings, which have formed the basis for the construc-tion of an electrical analogue computor, will cause many toreconsider their views on the storage not only of carbon dioxidebut also of anaesthetic and other drugs.Nunn review the elimination of carbon dioxide by the

lungs-particularly under the conditions of anaesthesia. Thereis now a wealth of information on this subject, and most of themystery seems to have been stripped from the oft-discussedtopic of carbon-dioxide homocostasis.The next group of papers is concerned with the biological