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WHO PAYS FOR TEXTBOOK ILLUSTRATIONS ?

A. HOLLMAN.

SIR,-I have recently written several chapters for multi-author textbooks and have been told, on submitting an accountfor the illustrations and typing, that the publishers will notmeet this cost. It is implied that any royalties I receive will besufficient payment, and this is admittedly a rational (ifunacceptable) situation.However, many authors of such chapters will have had their

illustrations and typing done by the institution in which theywork. This means that hospitals or medical schools will besubsidising the commercial publication of a textbook.

I believe that this is an undesirable state of affairs and I

suggest that publishers who commission a book should agreein advance to pay the full costs of preparation.

It would be interesting to hear the views on this subject ofdepartments of medical illustration, who undoubtedly do muchunpaid work on behalf of medical publishing firms.London W.5. A. HOLLMAN.

PNEUMOCYSTIS CARINII PNEUMONIA

SIR,-For more than a decade we have been interested inthe diagnosis and treatment of Pneumocystis carinii pneumonia,a disease affecting premature and feeble children.The clinical symptoms are failure to thrive, sometimes

appearance of foamy saliva in the mouth, feeding difficulties,tachypncea, and perioral cyanosis followed by pallor. Five

stages can be distinguished in the X-ray picture .1 2 The firstthree stages are seen during the period when there are slightclinical symptoms or none. At first an intensified pattern isseen in the peripheral parts of the lungs, perivascularly andperibronchially. In the second stage a fine network appears-an index of the progress of the disease. In the third stage thefine network-like shadow extends to the pleura, and theperipheral parts of the lungs may be emphysematous. Clinic-ally, at this stage, the infants are greyish and easily tire whenfed. In the fourth stage, the X-ray reveals oedema which dimsthe network contour, and the emphysema of the peripheralparts of the lungs becomes more pronounced. The diaphragmis depressed and the ribs are expanded. In this stage, andsometimes even in the third stage, the so-called " butterflyfigure " is visible. Tachypnoea is striking, with a rate of 60-70per minute, and the infants are slate-grey. In the fifth stage,the lungs are greatly expanded. Emphysematous blebs appear,from whose rupture pneumothorax may result. Clinically, thedyspnoea is severe, with a respiratory-rate of over 70, andhypercapnia and hypoxia are pronounced.

In the diagnosis of the disease we use with success the directdemonstration of P. carinii,3 which was first demonstrated byVanek et al. in the lungs of infants with interstitial pneumonia.These workers regard the microorganism as a protozoon,whereas others take it to be a fungus or virus. The presence ofP. carinii is an indication of the disease: it is best demonstrated,in our experience, most suitably in a smear of tracheal mucusobtained by aspiration through a laryngoscope.3 After stainingthe smear according to Gram-Weigert’s method, P. carinii canbe well demonstrated not only when X-ray and clinical changesare manifest but also 7-10 days earlier.From the case-histories of 1071 premature infants, using the

Hollerith technique,5 the incidence of the disease in ourmaterial was 18-1%. According to the data obtained bystatistical analysis, the factors that favoured the onset of thedisease were low birthweight, congenital malformations,duration of stay in hospital, and treatment with various anti-biotics, as well as with prednisolone and anabolic steroids;neonatal jaundice and exchange transfusions had no influenceon the occurrence of the pneumonia. " Agammaglobulinxmia "

-i.e., an antibody-deficiency syndrome-has not been demon-1. Waltner, K., Diósszilágyi, G., Páldy, L., Török, J., Koltay, M. Acta

med. hung. 1954, 5, 381.2. Fanconi, G., Wallgren, A. Lehrbuch der Padiatrie. Basle, 1961.3. T6th, Gy., Balogh, E., Bélay, M. Acta pœdiat. hung. 1966, 7, 25.4. Vanek, J., Jirovec, O., Lukec, J. Annls pœdiat. 1953, 180, 1.5. Kovács, Z., Veress, I., Márkus, V., Páldy, L. Mschr. Kinderheilk.

1966, 114, 476.

strated in these patients. Correlation is not easily established,because the pneumonia manifests itself clinically mostly atabout the age of 3 months-i.e., in the period of physiologicalhypogammaglobulineemia. Using immunological methods forthe quantitation of the three major immunoglobulins (IgG,IgM, IgA), we found 6 that the immunoglobulin levels werealways within physiological limits in 43 patients, in none ofwhom was agammaglobulinsemia present. Even in the clinicallygravest cases a pronounced increase of the IgM (2pM)immunoglobulin could be demonstrated. Our data, thoughthey do not exclude the predisposing role of hypogamma-globulinsemia, show that the correlation between the antibody-deficiency syndromes and P. carinii pneumonia is not regularand is by no means characteristic. Other factors of the defencemechanism-e.g., the cellular defence system-may also playa significant part. This is supported by our studies showingdecreased phagocytic activity of the leucocytes of infants withthis disease. We found that the serum-cholinesterase, too,decreased when symptoms were pronounced. 8

We were the first to suggest the use of pentamidine.9 10 Thisis an aromatic diamidine which is equally efficacious in bothprotozoal and fungus diseases." From our experiments 12 wefound that pentamidine inhibits the growth of Candida albicansmore significantly than does ’ Solustibosan’ or ethylstibamine(’ Neostibosan ’). In 24 infants, in whom the diagnosis hadbeen confirmed by direct demonstration of the pneumocystisin the tracheal mucus, we examined the effect of pentamidineon the pathogen.13 From the 6th day of treatment, the signs ofdegeneration of the pneumocystis became more and morepronounced; by the 10th day the organisms had almost entirelydisintegrated, and later they could not be demonstrated at all.Concurrently, the clinical and X-ray changes also graduallysubsided. Judged by these findings, pentamidine seems toexert a direct effect destructive to the pathogen.Our method of treatment is to give 4 mg. per kg. pentamidine

daily, in one intramuscular injection, for 12-14 days. In verygrave cases the drug can be given intravenously. The 200 mg.phial of powder is dissolved in 4 ml. of distilled water; thedissolved drug may be used for about a week, if kept in arefrigerator. The clinical effect of the therapy appears mostly4-6 days after the first injection. In uncomplicated cases,contemporaneous administration of antibiotics is unnecessary;such complementary therapy is needed only when mixed,bacterial infection is present. Symptomatic treatment is byoxygen and Digitalis lanata glycoside (e.g., Isolanid’), whichis given intramuscularly 0-02 mg. per kg. 2-3 times on the firstday, or in less grave cases by mouth 0-03-0-06 mg. per kg.2-3 times daily (1-2 drops per kg. per day is usually sufficient),followed by a gradual withdrawal. The infant is not bathed, inorder to avoid unnecessary movement; food is given by gastrictube, and feeding by mouth is gradually tried only when theclinical state improves.By this method, 212 cases were treated between 1958 and

1962.10 The mortality decreased from the earlier 50% to

18-8 and 20% respectively in the first two years (1958 and 1959)and, owing to early treatment, to 2-3-3-5% in 1960-61. Sincethen the favourable effect of pentamidine in the treatment ofinterstitial pneumonia has been confirmed by Marshall et al.14and others.15-18 Robbins 15 has described folic-acid antagonism6. Koltay, M., Illyés, M. Acta pœdiat., Stockh. 1966, 55, 489.7. Ivády, Gy., Dux, E., Illyés, M. Z. Kinderheilk. 1961, 85, 378.8. Ivády, Gy., Eck, E., Kovács, Z. Dte GesundhWes. 1961, 16, 1625.9. Ivády, Gy., Paldy, L. Mschr. Kinderheilk. 1958, 106, 10.

10. Ivády, Gy., Páldy, L., Unger, G. ibid. 1963, 111, 297.11. Findlay, G. M. Recent Advances in Chemotherapy; vol. I. London,

1950.12. Ivády, Gy., Friedrich, E. Dte GesundhWes. 1960, 15, 1960.13. T6th, Gy., Balog, E., Bélay, M. Acta pœdiat. hung. 1966, 7, 339.14. Marshall, W. C., Weston, H. J., Bodian, M. Archs Dis. Childh. 1964,

39, 18.15. Robbins, J. B., Miller, R. H., Arean, V. M., Pearson, H. A. New Engl.

J. Med. 1965, 272, 708.16. Rodgers, T., Haggie, M. H. N. Lancet, 1964, i, 1042.17. Lörinczi, K., Mérth, J., Perényi, K. Gyermekgyógyászat, 1964, 15, 207.18. Patterson, J. H., Lindsey, I. L., Edwards, E. S. Pediatrics, Springfield,

1966, 38, 388.

617

as a side-effect of pentamidine in an 8-year-old girl withinterstitial pneumonia and hypogammaglobulinaemia. In our

patients we have not encountered any side-effect, apart frommild, occasional erythrocyturia and anaemia. From our

experience we believe that, if pentamidine is given in the earlystage of the illness, most patients can be saved.

GY. IVÁDYL. PÁLDYM. KOLTAYG. TÓTHZ. KOVÁCS.

Paul Heim Hospital for Children,Üllöi ut 86, Budapest 8,

and Radiology and Paediatrics Clinics,Szeged, Hungary.

NYSTATIN-RESISTANT CANDIDA STRAINS ?

E. DROUHET.

Mycology Laboratory,Pasteur Institute,

Paris.

SIR,-Elmes has stated: "a recent survey has revealed that 1 in5 strains of monilia are resistant to nystatin ".1 Unfortunately,he did not mention any details about the survey referred to, nordid he give any bibliographical reference to substantiate hisargument. In 1954 I published 2 data demonstrating that out of55 strains of candida isolated from different mycologicalconditions, none developed any level of resistance in patientstreated with nystatin, even after long-term therapy. OnDec. 1, 1966, I reported on resistance of fungi to antifungalantibiotics at a special session on microbial resistance held by theFrench Society for Microbiology. My conclusion, unanimouslyaccepted, was that no candida strain resistant to nystatin hasever been found in patients with candidal infection, even afterrelapses, with consequent recurrent or long-term administra-tion of this antibiotic.Any candida strain showing natural resistance to nystatin

and isolated from a patient, whether or not there has beenprevious nystatin administration, would be gratefully receivedin my laboratory. This strain would be of great help in carry-ing out research on the mechanism involved in resistance,which so far I have been unable to study owing to the lack ofany appropriate material available, to my knowledge.

It is, of course, worth mentioning that some authors 3 wereable to obtain in vitro some sub-strains of candida less sensitiveto nystatin than the parent wild strains. But this artificial andvery moderate loss of sensitivity has nothing to do with theidea that there could be natural resistance in one out of fivestrains currently isolated from patients or normal people.

OXYGEN BY FACE MASK AND NASAL CATHETER

SIR,-I was interested to read the results obtained byDr. Catterall and her colleagues (Feb. 25, p. 415), whencomparing the performance of nasal catheters and an oronasalmask in oxygen therapy, and those of Dr. Lal and Dr. Savidgelast week (p. 576) comparing the M.C. and B.L.B. masks.Dr. Catterall and her colleagues concluded that arterial-oxygentensions were higher when the M.C. mask was worn thanwhen Argyle nasal catheters were used. Studies carried outon ten consecutive patients admitted to this unit with acutemyocardial infarction indicate a similar picture.Each patient had a confirmed myocardial infarction

(characteristic electrocardiographic changes and serum-enzymeelevation) and on admission to the unit was classified accordingto the coronary prognostic index of Peel. Oxygen therapywas started immediately, using Argyle nasal catheters inserted3-4 cm. up each nostril. An arterial-blood sample was takenafter an hour of oxygen administration from an indwellingfemoral-artery nylon cannula, and Pao2 determined with a1. Elmes, P. C. Prescribers’ J. 1966, 6, 75.2. Drouhet, E. Annls Inst. Pasteur, Paris, 1955, 88, 298.3. Donovick, R. et al. in Therapy of Fungus Diseases; p. 211. Boston, 1955;

Stout, H. A., Pagano, J. F. Antibiotics A. 1955-56, p. 704; Littman,M. L. et al. ibid. 1957-58, p. 981; Hebeka, E. K., Solotorovsky, M.J. Bact. 1965, 89, 1533.

4. Peel, A. A. F., Semple, T., Wang, I., Lanchester, W. M. ,Dall, J. L. G.Br. Heart J. 1962, 24, 745.

ARTERIAL-OXYGEN TENSIONS WITH M.C. MASK AND ARGYLE NASAL

CATHETER IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

* Percentages indicate by how much the oxygen tension obtained with theM.C. mask exceeded that obtained with the catheter.

polarographic microelectrode (E.LL.). The nasal catheterswere then replaced by an M.C. mask and oxygen wasadministered at the same flow-rate (6 litres per minute); afurther arterial-blood sample was taken after an hour and thePao2 estimated. In each case any clinical evidence of pulmonarycongestion was recorded and a chest X-ray was taken forsigns of pulmonary oedema.The results in the accompanying table show that in all

cases the P a02 rose when oxygen was given by M.C. maskinstead of nasal catheters. The mean Pao, of patients receivingoxygen via nasal catheters was 82 mm. Hg, and this wasincreased to 106 mm. Hg when the catheters were replaced bythe M.C. mask. Five of the patients (nos. 1, 2, 5, 7, and 9)had clinical evidence of pulmonary congestion; the meanP a02 of these patients while receiving oxygen via nasalcatheters was 82 mm. Hg, rising to a mean of 106 mm. Hgon substituting the M.C. mask but keeping the oxygenflow-rate constant. The smallest increase in Pao2 (patientno. 5) was 3%; this patient had severe left-ventricular failureand segmental pulmonary collapse.

Myocardial infarction is often accompanied by a low

arterial-oxygen tension 5 6 and oxygen is now widelyadministered to patients with this condition. It is thus

important to use a method of administering oxygen which isefficacious and acceptable to the patient. Nasal catheters arewell tolerated by nearly all the patients admitted to this unit,including those in the trial. Unfortunately, though the M.C.mask produced significantly higher P a02 levels in the patientsstudied, even in the presence of pulmonary congestion, theyfound it uncomfortable if worn continuously for more thantwelve hours. Oxygen is administered continuously for at

least forty-eight hours to all patients in this unit and nasalcatheters are used routinely, the M.C. mask being reservedfor the more severely hypoxsemic patients.

C. J. WOODS.

Coronary Intensive Care Unit,Sefton General Hospital,

Smithdown Road, Liverpool 15.

FIRE-RISK WITH HYPERBARIC OXYGEN

SIR,-It seems clear from the articles by Flight LieutenantDenison and his colleagues and Mr. Purser and recentreports of accidents in America that the risks of fire in a hyper-baric-oxygen environment are substantial, and that, unlesscareful rethinking is undertaken on single-patient-chamberdesign we shall, sooner or later, be faced with a clinical re-enactment of the Apollo disaster.5. McNicol, M. W., Kirby, B. H., Bhoola, K. D., Everest, M. E., Price,

H. V., Freedman, S. F. Br. med. J. 1965, ii, 1270.6. Valentine, P. A., Fluck, D. C., Mounsey, J. P. D., Reid, D., Shillingford,

J. P., Steiner, R. E. Lancet, 1966, ii, 837.7. Denison, D. M., Ernsting, J., Cresswell, A. W. Lancet 1966, ii, 1404.8. Purser, P. R. ibid. p. 1405.