2
1392 related to the quantity of sodium infused. Black and Williams suggest that these variations were due to the continuing loss of sodium and the varying water intake. They had the greatest difficulty in assessing whether or not sodium depletion was present: hyponatraemia was not a reliable guide-indeed, 2 patients who responded had serum-sodium values greater than 140 mEq. per litre. Black and Williams conclude that the administration of hypertonic sodium salts in small quantities is justified as a therapeutic test to exclude sodium depletion in patients with renal failure-even if they are critically ill or have severe hypertension. In fact, of their 14 patients with chronic renal disease, 5 benefited. They emphasise that, although hyponatraemia is sometimes found in sodium depletion, it is " not a function of sodium balance alone "; for the concentration of sodium in the plasma depends on the relative amounts of sodium, potassium, and water in the body.6-8 Moreover, it is possible that, as uraemia advances, water moves into the cells from the extra- cellular fluid 9; again, disease may cause a shift of sodium into the cells.6 These possibilities add to the difficulty of assessing the body’s content of sodium from the level in the plasma. Even in the presence of a normal body com- plement of sodium, hyponatraemia follows " stress "-e.g., trauma. 10 The more reliable tests of total body contents (estimation of total body-water, and extracellular and plasma volumes of exchangeable radiosodium or radio- potassium) are not everywhere available; they take so long that the results can often be only of retrospective interest. The decision to try the effect of hypertonic saline must therefore rest on clinical judgment. Improvement in the clinical state and a fall in the blood-urea level can be taken as signals for further infusions on succeeding days; for sodium depletion can cause vomiting 11 and thus continuing electrolyte loss. Black and Williams also found that hypertonic sodium salts led to improvement in patients who had been over- loaded with water; but there was evidence that they were short of sodium as well. Sodium salts are probably best avoided, except in emergency, in patients with acute or chronic renal failure who have had no sodium loss but who have been overloaded with water; for, in them, the therapy produces an additional abnormality-sodium excess. Pure water excess is best treated by fluid restriction; but, should this prove too slow in relieving symptoms, the use of an artificial kidney may be necessary; but the artificial kidney has to be used carefully lest, where there is pure water excess, sodium is removed with the water. Until more is known of the effects of ultrafiltration on sodium and water balance, hxmodialysis should be reserved for relieving symptoms and should not be used to attain chemical perfection with the attendant risk of sodium depletion. Black and Williams used two hypertonic sodium solutions-sodium chloride 5 g. per 100 ml. and sodium lactate 11 -2 g. per 100 ml. (so-called " molar lactate "). They gave 200 ml. intravenously in half to two hours; a good clinical response, with lowering of the blood-urea, was an indication for repeats at daily intervals. The only contraindication was congestive heart-failure. The serum- potassium level usually fell; potassium may therefore be 6. Merrill, J. P. The Treatment of Renal Failure. New York, 1955. 7. Wynn, V., Houghton, B. J. Quart. J. Med. 1957, 26, 375. 8. Edelman, I. S., Leibman, J., O’Meara, M. P., Birkenfield, L. W. J. clin. Invest. 1958, 37, 1236. 9. Hamburger, J., Mathé, G. in Ciba Foundation Symposium on the Kidney (edited by A. A. G. Lewis and G. E. W. Wolstenholme); p. 288. London, 1954. 10. Moore, F. D., Ball, M. R. The Metabolic Response to Surgery. Spring- field, Ill., 1954. 11. Marriott, H. L. Brit. med. J. 1947, i, 328. added with advantage, especially in patients receiving digitalis. 12 Black and Williams varied the proportion of lactate to chloride according to the depression of the plasma-bicarbonate level. Since most of these patients have renal impairment, it may be safer, in the first instance, to adjust the proportions so that the sodium/chloride ratio of the plasma will be returned to normal-i.e., 1-4:1-0." s This will avoid alkalosis and prevent the onset of tetany. The rapid clinical and biochemical response to hyper- tonic sodium infusions obtained by Black and Williams must mean that the patients had a sodium deficit without comparable water deficit. The improvement could be due to increased glomerular filtration or, more rarely, to lessening of renal cellular overhydration 2 13 ; but part of the improvement may have been due to reduction in the rate of protein breakdown,14 for McCance 15 16 showed that sodium depletion caused a negative nitrogen balance. Reduction in the volume of extracellular water, often found in sodium depletion, also causes a negative nitrogen balance.9 17 11 Over-correction of the sodium depletion must be avoided lest the rate of protein catabolism increase again. 19 These results with hypertonic sodium solutions are excellent, but the value of hxmodialysis must not be underestimated; for advanced urarmia also increases the rate of protein breakdown 20 and frequently overloads the renal reserve, even though the urinary output may exceed the 1-5 litres per day required to sustain life in chronic renal disease.21 In these circumstances, haemodialysis can rapidly reduce the rate of protein catabolism and, if the sodium depletion be corrected at the same time, the clinical znd biochemical improvement will be sustained. INFORMATION BOOKLETS FOR PATIENTS INFORMATION booklets issued by hospitals to their patients contribute to the right kind of health education- the teaching of common sense rather than self-diagnosis. King Edward’s Hospital Fund for London has investi- gated the use of such booklets by a sample group of hospitals. A questionary was sent to all the hospitals under one regional hospital board, and to thirty-three other hospital authorities in the United Kingdom; the hospitals were also asked for samples of any booklets they used. The results of this inquiry have now been reported. 22 60% of the sample group are found to issue booklets, as compared with 32% in 1953-a commendable step in the right direction. The patient’s need for information about admission to hospital has long been established. At the very least, these booklets prevent confusion about how and where to arrive for admission; the better ones, by creating a sympathetic rapport, may dispel fears and help the patient to prepare himself for the unfamiliar hospital world. Moreover, they may conceivably be of value in saving the doctor’s and nurse’s time, as well as in gaining the patient’s informed cooperation. On these grounds alone, 12. Lown, B., Salzberg, H., Enselberg, C. D., Weston, R. E. Proc. Soc. exp. Biol., N.Y. 1951, 76, 797. 13. Funck-Brentano, J. L. Cited by Hamburger, J., Mathé, G. in Ciba Foundation Symposium on the Kidney (edited by A. A. G. Lewis and G. E. W. Wolstenholme); p. 288. London, 1954. 14. Peters, J. P., Van Slyke, D. D. Quantitative Clinical Chemistry. London, 1946. 15. McCance, R. A. Proc. roy. Soc. B. 1936, 119, 245. 16. McCance, R. A. Lancet, 1936, i, 823. 17. Flear, C. T. G., Clarke, R. Clin. Sci. 1955, 14, 575. 18. McCance, R. A., Widdowson, E. M. Acta pœdiat., Stockh. 1957, 46, 337. 19. McCance, R. A., Morrison, A. B. Quart. J. exp. Physiol. 1956, 41, 365. 20. Parsons, F. M. in Modern Trends in Urology (edited by Sir Eric Riches). London, 1960. 21. Kelemen, W. A., Kolff, W. J. Arch. intern. Med. 1960, 106, 608. 22. Information Booklets for Patients; published by King Edward’s Hospital Fund, 34, King St., London, E.C.2. June, 1962. Pp. 24. Is.

INFORMATION BOOKLETS FOR PATIENTS

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related to the quantity of sodium infused. Black andWilliams suggest that these variations were due to thecontinuing loss of sodium and the varying water intake.They had the greatest difficulty in assessing whether or notsodium depletion was present: hyponatraemia was not areliable guide-indeed, 2 patients who responded hadserum-sodium values greater than 140 mEq. per litre.

Black and Williams conclude that the administration of

hypertonic sodium salts in small quantities is justified asa therapeutic test to exclude sodium depletion in patientswith renal failure-even if they are critically ill or havesevere hypertension. In fact, of their 14 patients withchronic renal disease, 5 benefited. They emphasise that,although hyponatraemia is sometimes found in sodium

depletion, it is " not a function of sodium balance alone ";for the concentration of sodium in the plasma depends onthe relative amounts of sodium, potassium, and water inthe body.6-8 Moreover, it is possible that, as uraemia

advances, water moves into the cells from the extra-

cellular fluid 9; again, disease may cause a shift of sodiuminto the cells.6 These possibilities add to the difficulty ofassessing the body’s content of sodium from the level inthe plasma. Even in the presence of a normal body com-plement of sodium, hyponatraemia follows " stress "-e.g.,trauma. 10 The more reliable tests of total body contents(estimation of total body-water, and extracellular and

plasma volumes of exchangeable radiosodium or radio-potassium) are not everywhere available; they take so longthat the results can often be only of retrospective interest.The decision to try the effect of hypertonic saline musttherefore rest on clinical judgment. Improvement in theclinical state and a fall in the blood-urea level can be takenas signals for further infusions on succeeding days;for sodium depletion can cause vomiting 11 and thus

continuing electrolyte loss.Black and Williams also found that hypertonic sodium

salts led to improvement in patients who had been over-loaded with water; but there was evidence that they wereshort of sodium as well. Sodium salts are probably bestavoided, except in emergency, in patients with acute orchronic renal failure who have had no sodium loss but whohave been overloaded with water; for, in them, the therapyproduces an additional abnormality-sodium excess. Purewater excess is best treated by fluid restriction; but, shouldthis prove too slow in relieving symptoms, the use of anartificial kidney may be necessary; but the artificial kidneyhas to be used carefully lest, where there is pure waterexcess, sodium is removed with the water. Until more isknown of the effects of ultrafiltration on sodium and waterbalance, hxmodialysis should be reserved for relievingsymptoms and should not be used to attain chemical

perfection with the attendant risk of sodium depletion.Black and Williams used two hypertonic sodium

solutions-sodium chloride 5 g. per 100 ml. and sodiumlactate 11 -2 g. per 100 ml. (so-called " molar lactate ").They gave 200 ml. intravenously in half to two hours;a good clinical response, with lowering of the blood-urea,was an indication for repeats at daily intervals. The onlycontraindication was congestive heart-failure. The serum-potassium level usually fell; potassium may therefore be6. Merrill, J. P. The Treatment of Renal Failure. New York, 1955.7. Wynn, V., Houghton, B. J. Quart. J. Med. 1957, 26, 375.8. Edelman, I. S., Leibman, J., O’Meara, M. P., Birkenfield, L. W. J. clin.

Invest. 1958, 37, 1236.9. Hamburger, J., Mathé, G. in Ciba Foundation Symposium on the

Kidney (edited by A. A. G. Lewis and G. E. W. Wolstenholme); p. 288.London, 1954.

10. Moore, F. D., Ball, M. R. The Metabolic Response to Surgery. Spring-field, Ill., 1954.

11. Marriott, H. L. Brit. med. J. 1947, i, 328.

added with advantage, especially in patients receivingdigitalis. 12 Black and Williams varied the proportion oflactate to chloride according to the depression of theplasma-bicarbonate level. Since most of these patientshave renal impairment, it may be safer, in the first instance,to adjust the proportions so that the sodium/chloride ratioof the plasma will be returned to normal-i.e., 1-4:1-0." sThis will avoid alkalosis and prevent the onset of tetany.The rapid clinical and biochemical response to hyper-

tonic sodium infusions obtained by Black and Williamsmust mean that the patients had a sodium deficit withoutcomparable water deficit. The improvement could be dueto increased glomerular filtration or, more rarely, to

lessening of renal cellular overhydration 2 13 ; but part ofthe improvement may have been due to reduction in therate of protein breakdown,14 for McCance 15 16 showedthat sodium depletion caused a negative nitrogen balance.Reduction in the volume of extracellular water, oftenfound in sodium depletion, also causes a negative nitrogenbalance.9 17 11 Over-correction of the sodium depletionmust be avoided lest the rate of protein catabolismincrease again. 19These results with hypertonic sodium solutions are

excellent, but the value of hxmodialysis must not beunderestimated; for advanced urarmia also increases therate of protein breakdown 20 and frequently overloads therenal reserve, even though the urinary output may exceedthe 1-5 litres per day required to sustain life in chronicrenal disease.21 In these circumstances, haemodialysis canrapidly reduce the rate of protein catabolism and, if thesodium depletion be corrected at the same time, theclinical znd biochemical improvement will be sustained.

INFORMATION BOOKLETS FOR PATIENTS

INFORMATION booklets issued by hospitals to their

patients contribute to the right kind of health education-the teaching of common sense rather than self-diagnosis.King Edward’s Hospital Fund for London has investi-gated the use of such booklets by a sample group ofhospitals. A questionary was sent to all the hospitals underone regional hospital board, and to thirty-three otherhospital authorities in the United Kingdom; the hospitalswere also asked for samples of any booklets they used.The results of this inquiry have now been reported. 22

60% of the sample group are found to issue booklets, ascompared with 32% in 1953-a commendable step in theright direction. The patient’s need for information aboutadmission to hospital has long been established. At the

very least, these booklets prevent confusion about howand where to arrive for admission; the better ones, bycreating a sympathetic rapport, may dispel fears and helpthe patient to prepare himself for the unfamiliar hospitalworld. Moreover, they may conceivably be of value insaving the doctor’s and nurse’s time, as well as in gainingthe patient’s informed cooperation. On these grounds alone,12. Lown, B., Salzberg, H., Enselberg, C. D., Weston, R. E. Proc. Soc. exp.

Biol., N.Y. 1951, 76, 797.13. Funck-Brentano, J. L. Cited by Hamburger, J., Mathé, G. in Ciba

Foundation Symposium on the Kidney (edited by A. A. G. Lewis andG. E. W. Wolstenholme); p. 288. London, 1954.

14. Peters, J. P., Van Slyke, D. D. Quantitative Clinical Chemistry.London, 1946.

15. McCance, R. A. Proc. roy. Soc. B. 1936, 119, 245.16. McCance, R. A. Lancet, 1936, i, 823.17. Flear, C. T. G., Clarke, R. Clin. Sci. 1955, 14, 575.18. McCance, R. A., Widdowson, E. M. Acta pœdiat., Stockh. 1957, 46, 337.19. McCance, R. A., Morrison, A. B. Quart. J. exp. Physiol. 1956, 41, 365.20. Parsons, F. M. in Modern Trends in Urology (edited by Sir Eric Riches).

London, 1960.21. Kelemen, W. A., Kolff, W. J. Arch. intern. Med. 1960, 106, 608.22. Information Booklets for Patients; published by King Edward’s Hospital

Fund, 34, King St., London, E.C.2. June, 1962. Pp. 24. Is.

1393

the small cost of their production-from ld. to 6d. depend-ing on size and printing facilities-seems entirely justifiable.The report finds that acute hospitals generally provide

the most information. Maternity and psediatric patientshave special needs. One booklet, produced by a privatecompany for maternity hospitals, is edited by a professorof obstetrics and discusses antenatal care and mothercraft

generally. Ten out of the eleven children’s hospitalsquestioned provide booklets for the parents of childrenadmitted. Only one issues information for the children.The University of Vancouver gives its child patients apicture book written by a child psychiatrist in collabora-tion with a professional writer. This book has alreadybeen responsible for a reduction in the number of childrenwho suffer from emotional disorders as a result of their

stay in hospital.The contents of various booklets are discussed in the

report, and actual quotations appear as an appendix. Theinformation varies from a sheet of brief instructions tobooklets showing good insight into the patient’s needs.The report does not examine the patient’s views, but itshould encourage more hospitals to use this means ofcommunication and reassurance, and to use it well.

DEMETHYLCHLORTETRACYCLINE AND

GASTRIC CANCER

DRUGS which are taken up selectively by tumours are ofinterest because of the possibilities of concentratingtherapeutic agents in the target tissue and also of diagnos-ing and delineating the tumour. Moore showed thatfluorescein given by mouth was retained by the gastro-intestinal tract, the brain, and the spine. It was also

selectively retained by tumour tissue, which was thendemonstrable by ultraviolet light; the tumour’s fluor-escence persisted for long periods, and the growthcould therefore be identified after one or two dayswhen the background fluorescence of normal tissue haddisappeared. Moore subsequently developed a techniquefor localising brain tumours 2 which was based on thisprinciple; he used fluorescein labelled with radioactiveiodine and mapped the resulting tissue radioactivity.Thus, he made use of the selective concentration offluorescein in rapidly growing tissues but ignored thedye’s fluorescent properties.

Interest in fluorescence then seems to have lapsed untilMilch et awl. observed that the tetracyclines are selectivelyconcentrated in tumour tissue and fluoresce character-

istically in ultraviolet light. Concentration of these sub-stances in bone had previously been noted 4 5 and thisproperty has since been used to demonstrate lesions duringoperation and before biopsy. 6

Klinger and Katz have applied this type of techniquein a more sophisticated, way to the diagnosis of gastriccarcinoma. They gave tetracycline for five days andwashed out the stomach after a further two days. In 17out of 18 cases of gastric carcinoma the gastric contentsfluoresced in ultraviolet light; in 41 control patients with-out gastric carcinoma no fluorescence was seen. Theseobservations have been confirmed and extended by Berkand Kantor.8 8 Using a similar technique with demethyl-1. Moore, G. E. Science, 1947, 106, 130.2. Moore, G. E. ibid. 1948, 107, 569.3. Milch, R. A., Rall, D. P., Tobie, J. E. J. nat Cancer Inst. 1957, 19, 79.4. André T. Acta. radiol. Stockh. 1956, suppl. 142.5. Loo, T. L., Titus, E. D., Rall, D. P. Science, 1957, 126, 253.6. McLeay, J. F., Walske, B. R. J. Bone Jt Surg. 1960, 42A, 940.7. Klinger, J., Katz, R. Gastroenterology, 1961, 41, 29.8. Berk, J. E., Kantor, S. M. J. Amer. med. Ass. 1962, 179, 997.

chlortetracycline, they obtained a positive reaction in 9cases of gastric carcinoma and in 2 cases of benigngastric ulcer; these results were later confirmed byhistological examination. 7 healthy subjects were examined,and 32 patients in whom various gastric disordershad been diagnosed by methods other than histological.Of these 39 there was fluorescence in only 2, and in 1 ofthese gastric carcinoma had been diagnosed; the otherpatient was thought to have a benign ulcer. In none of theothers was a neoplastic lesion suspected.These encouraging results will probably lead to a more

extensive survey of the use of fluorescent methods in the

diagnosis of malignant tumours. In organs other than thestomach, technical difficulties will be greater. Thesefluorescent compounds could possibly be labelled withradioactive isotopes in order to irradiate tumours 9;similarly, they might be used to concentrate cytotoxicgroups at the site of the growth. The results are alsorelevant theoretically to the concentrating mechanism intumour tissue 5 and to the study of carcinogenesis andspread; the malignant cell does not itself seem to bethe site of binding. 10 131 has also been found to be

selectively concentrated in gastric carcinomas.ll

THE LANCET BY AIR

NOT long ago a subscriber wrote saying that he wouldbe away for a year-but would we please continue tosend each weekly copy to his home so that he could gothrough them all when he got back. Though we applaudhis intentions, this is not at all our idea of how to enjoya weekly journal. A newspaper is something that belongsto the moment; and, though our own contents are notalways as evanescent as those of some lay contemporaries,we are certain that nothing we offer is so valuable as therapid give-and-take of information and opinion. Nowthat air mails go everywhere we shall not be satisfieduntil all our subscribers, however distant, have a chanceto read their journal, and write their letters of dissent orconfirmation, before the next issue appears in London.When this happens we shall know that we are reallydoing something to unite the medical world.At present The Lancet cannot be distributed in this

way to everybody abroad, because airmail rates are stillhigh and our subscription (E3 3s. both at home and

overseas) is low. But next week we are taking what wehope will prove to be a first step towards such distribu-tion. From July 7 all copies which go abroad but are notsent by the Post Office by air will be printed on thinnerpaper; and subscribers will be invited to take out anairmail subscription which will bring them The Lancetin a few days instead of (sometimes) many weeks. For

Canada, the United States, Australia, New Zealand,South Africa, India, Pakistan, Malaya, China, Japan, andsome other parts of Africa, the inclusive annual charge willbe E10 10s.; and for certain African countries (includingEgypt, Ethiopia, Sudan, Libya, and Morocco) and theMiddle East, it will be E8 8s.We sincerely hope that readers in distant countries will

think these charges worth paying in order to be broughtinto almost immediate contact with medical colleagueselsewhere, who increasingly (we are glad to say) makeuse of our pages for their announcements and theirdiscussions.9. Dunn, A. L., Eskelson, C. D., McLeay, J. F., Ogborn, R. E., Walske,

B. R. Proc. Soc. exp. Biol. N.Y. 1960, 104, 12.10. Vassar, P. S., Saunders, A. M., Culling, C. F. A. Arch. Path. (Lab. Med.)

1960, 69, 613.11. See Lancet, Feb. 24, 1962, p. 417.