RHEUMATOID ARTHRITIS
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1155 recognised by the Government who do not believe that these objects will be prejudiced ". It is doubtful whether the new procedure will result in any significant reduction in the total Government expenditure on drugs under the National Health Service. Of a total estimated expenditure in the current financial year of Ell 0 million, about El 4 million represents pur- chases by hospitals. Expenditure by hospitals on the drugs specifically mentioned by the Ministry appears to be about El million.1 The Government will no longer derive such benefit as it has had in the past from cheaper purchases 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 lower prices on the proposed central contracts, the compensa- tion (as yet undetermined in amount) to British patentees will 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 physicians survey recent work on the rheumatic diseases. The thirteenth rheumatism review, 2 covering the period 1956-58, deals with more than 4000 publications and lists almost 3500. The longest section relates to the management of rheumatoid arthritis; and, although the editors have selected the material carefully, the reader is left with the impression that the gain in knowledge has been small in proportion to the vast amount of research. The review points to increased awareness of the hazards of long-term administration of steroid hormones. Though there is no unanimity on the indications for steroid therapy, it is generally agreed that such therapy should be considered only after trial of other methods. Treatment is based on a basic regimen of rest in the active stage of the disease, physiotherapy and reablement, overall social care, and continued 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 cease to respond to other measures. Because the course of rheumatoid arthritis is variable and unpredictable, clinical trials of new remedies must necessarily include many patients and be conducted over lengthy periods. The results may establish whether or not the agent on trial has a beneficial effect; but, unless all patients in the trial improve, the results cannot be expected 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 the nature and course of the disease much time will be spent in testing drug after drug. There may be a case for submitting to controlled trials the various components of the basic regimen. Duthie et al. showed that the prognosis for patients admitted to hospital in the first year of the disease was better than for others, and that the benefit was maintained over a period of years. This suggests that early institution of the basic regimen may do more than control the disease temporarily. If this is so, then it is surely reasonable to examine each component of the regimen in detail. Meanwhile, in routine practice, this regimen should be applied as early as possible in the course of the disease, even if the patient has to be admitted to hospital; and in addition a potent suppressive 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 clinical trials to read about in the fourteenth review, due at the end 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 governing pCO2 nor the effects of changes in pCO2 are simple to understand, and it is difficult to find authoritative work on either topic. A symposium in Anesthesiology will be welcomed by many who share an interest in this quite remarkably active catabolite. It is perhaps appropriate that this symposium should have been devised by anves- thetists, who undoubtedly see the most extreme departures from normal carbon-dioxide balance, and who are them- selves the most important variable factor determining the pCO2 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 the geological origin of carbon dioxide, and the part played by the oceans 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 six years ago.5 They discuss the concept of many body stores in series and parallel-all with different rates of carbon-dioxide production, different quantities and tensions of stored carbon dioxide, different storage capacities, and different rates of accumulation and discharge when coming into equilibrium with a changed arterial carbon-dioxide tension. They point out that the rate at which the various stores come into equilibrium is not constant but may vary greatly, chiefly as a result of changes in the rate of blood-flow perfusing the particular store. Identification and quantification of all the carbon- dioxide stores is a hopelessly difficult task, and Farhi and Rahn have 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 influence will be negligible in short and medium term changes. The time constants of alveolar gas, heart, and brain are calculated to lie between one and three minutes, while for muscle a typical value is thirty minutes-though this value can be varied between wide limits by changes in muscle blood-flow. With its large volume of stored carbon dioxide, the muscle store is clearly a major 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 to reconsider their views on the storage not only of carbon dioxide but also of anaesthetic and other drugs. Nunn review the elimination of carbon dioxide by the lungs-particularly under the conditions of anaesthesia. There is now a wealth of information on this subject, and most of the mystery seems to have been stripped from the oft-discussed topic of carbon-dioxide homocostasis. The next group of papers is concerned with the biological
Transcript of 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
