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about half the cases. Fever was the only other con-sistent feature, and most patients were in good generalcondition despite their massive cervical lympha-denopathy. Lesions outside lymph-nodes were few.The patients, reported from so many different

centres, had been subjected to a variety of tests andexaminations, but most of these were unrevealing.Anaemia, normochromic in type (16 out of 24), andneutrophil leucocytosis (13 out of 19) were commonlyrecorded, but eosinophilia was seen in only 1 patient.The erythrocyte-sedimentation rate was raised in14 out of 15, and 13 of 16 had hyperglobulinaemiawith reversal of the albumin globulin ratio. Of the 5cases where immunoglobulin levels were determinedIgG was increased in all, IgA in 3, and IgM in 2.Serum-cholesterol was normal in 7 out of 7 cases, and

only a minority showed slight bone-marrow histio-cytosis. All sorts of serological, skin, and cultural testsand inoculations gave equivocal or negative results.The lymphadenopathy progressed for a long time butultimately tended to regress, little if at all influencedby the various treatments tried. Only 2 patients died,the youngest at 12 years of age with generalisedamyloidosis, the other at 25 years of a pseudomonaspneumonia.The matted lymph-nodes had yellow areas of

nodal tissue surrounded by bands of white fibroustissue. There was an apparent sequence of lesions,starting with dilatation of all sinuses and proliferationof cells in the sinuses. The proliferating cellsincluded histiocytes, often foamy and clumpedtogether, and multinucleate giant cells. While someexhibited mild degrees of atypia, mitoses, even in theatypical cases, were extraordinarily rare. But in

every case the histiocytes engulfed hxmatopoieticcells, lymphocytes, red blood-cells, and even plasmacells. Eosinophils were rarely seen and necrosis andgranulomas never. Special stains, apart from re-

vealing some neutral fat in the histiocytes, wereunhelpful and no organisms were ever detected.Electron microscopy so far has added little informa-tion, and ro abnormal fats were detected chemically.The contrast between the massiveness of the

lymphadenopathy and the good general condition ofthe patients is remarkable. The condition is pro-gressive or stable over some years, and then usuallysubsides; it is hard to say whether the amyloid andthe infection in the 2 necropsy cases were related tothe disease or were fortuitous. The cause is quiteunknown. No pathogen has been recovered, and thedisease does not resemble other conditions resultingfrom humoral or cellular-immunity deficiency or

from disorders of phagocytosis. It does not seem a

malignant process or to be related to other lympho-proliferative or haematoproliferative disorders. The

proliferating cells are histiocytes, not lymphocytesas in the condition described by CANALE and SMITH,44and the histiocytes are not so atypical as in the44. Canale, V. C., Smith, C. H. J Pediat. 1967, 70, 891.

malignant histiocytoses such as histiocytic medullaryreticulosis.45 In the familial hxmophagocytic histio-cytosis the phagocytosed elements are red blood-cells,not, as in this non-familial disease, lymphocytes,plasma cells, and red blood-cells. Clinically andhistologically it differs from the differentiated

histiocytoses of the eosinophilic-granuloma, Letterer-Siwe, and Hand-Schuller-Christian types. (Inpassing, it may be noted that the VOGELs have latelycast a coldly critical eye on the supposed unity ofthese conditions.46) One clue 42 is that the new

lymphoma seems to be more common in the lowersocioeconomic groups, in the tropics, in Blacks, andin Uganda, where the disease is seen with some

frequency 42 (4 cases in 6 months). The possiblerelevance of salmonellosis was suggested, though sero-logical tests were negative. Could there be confusionin Uganda between the new lymphoma’and histiocyticmedullary reticulosis-both seem to be especiallycommon in that country-or could they be related ?

It is clearly important to diagnose this condition,to differentiate it from more malign lymphomas, and,in view of the excellent prognosis, not to overtreat it.The quest is now on for more cases and for clues tothe aetiology.

HYPERCAPNIA IN BRONCHIAL ASTHMA

THE initial functional disturbance in an asthmaticattack is airway obstruction. The reduction inbronchial calibre that follows means that airwayclosure occurs sooner in expiration than normal; and,because the elastic forces keeping the bronchi patentduring expiration are greater at large lung volumes,the lungs are hyperinflated to enable tidal breathingto continue. 4’ Hyperinflation leads to an increase inthe work of breathing, and at this stage the patientexperiences difficulty with both inspiration and

expiration. It is with hyperinflation that importantchanges occur in the arterial blood-gas tensions .41There is a striking increase in ventilation/perfusionimbalance in the lung, leading to hypoxaemia, butdespite this (at least initially) alveolar ventilationincreases, producing hypocapnia and a mild respiratoryalkalosis.49,50 Nevertheless, as the attack intensifies,many of the narrow airways become plugged withviscid secretion. The work of breathing increasesabove the patient’s capacity to sustain high levels ofalveolar ventilation, and alveolar ventilation falls. Thelowered arterial carbon-dioxide tension (PaCO2) beginsto return to normal and the arterial oxygen tension

(PaO2) falls further, and as the situation becomesworse still the Pac02 begins to rise. Hypoxxmiainvariably becomes more severe with the rise in

PaCO2, and, because hypercapnia develops rapidly insevere asthma, homoeostatic mechanisms do not

adjust acid/base balance and there is uncompensatedrespiratory acidosis and acidaemia. How can hyper-45. Serck-Hanssen, A., Purchit, G. P. Br. J. Cancer, 1968, 22, 506.46. Vogel, J. M., Vogel, P. Semin. Hemat. 1972, 9, 394.47. Woolcock, A. J., Read, J. Lancet, 1965, ii, 1323.48. Palmer, K. N. V., Diament, M. L. ibid. 1968, i, 318.49. Palmer, K. N. V., Diament, M. L. ibid. 1967, ii, 383.50. McFadden, E. R., Lyons, H. A. New Engl. J. Med. 1968, 278, 1027.

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capnia be detected in the asthmatic attack ? The

patient will be obviously ill clinically, with unequivocalcentral cyanosis, tachycardia greater than 150 perminute, pulsus paradoxus, clinical evidence of severelung hyperinflation, and with retention of largeamounts of viscid bronchial secretion 51 but the

presence and degree of hypercapnia and its effect onacid-base balance and the extent of the hypoxsemia canonly be determined with certainty by measuringarterial blood-gas tensions-mandatory in all patientswith severe asthma. How should the severe asthmaticwith hypercapnia be treated ? With large doses ofcorticosteroids, bronchodilators, oxygen, antibiotics,physiotherapy (if the patient can cooperate), andcorrection of dehydration; but in many instancesthere is a latent period of some hours before thesemeasures become effective and the patient is in

danger of death from cardiac arrhythmias or asystole,exhaustion, or metabolic disturbances and hypoxsemiaunless given controlled mechanical ventilation. Sheehyand his colleagues 52 have lately reported their experi-ence in the management of seventy episodes of severeasthma in 46 patients in an acute-respiratory-careunit. In forty-two episodes the patients were hyper-capnic and in twenty-two episodes mechanical ventila-tion was required, most often because of failure torespond to intensive medical therapy within two hours,but also occasionally because of respiratory arrest.

2 of the ventilated patients died. A cuffed endo-tracheal tube was passed after local anaesthesia to thelarynx, when sedation with intravenous morphinewas given to allow control of ventilation. Respiratoryminute volume was adjusted to produce a gradualreduction in Paco2 of approximately 5 mm. Hg perhour. (Too rapid a fall in PaCO2 can lead to cardiacarrhythmias, hypotension, and seizures.) Powerfulventilators were required since pressures of 40-60 cm.of water or more were needed at the onset of ventila-tion. No patient was ventilated for less than twenty-four hours and the endotracheal tube was removed

only when the arterial blood-gas tensions were withinthe normal range, morphine had been discontinued,and the patient was awake and able to maintain anormal tidal volume for 15 minutes. Neuromuscular

blocking agents were not used. Levin and Dillon 53used the neuromuscular blocking agent pancuroniumbromide in 4 severe cases of asthma with hypercapniarequiring assisted ventilation. All their patientssurvived and they found pancuronium to be moreeffective than succinylcholine chloride; they prefer itto other neuromuscular blocking drugs such as

curare and its derivatives because pancuronium doesnot cause histamine release or important cardiovascularside-effects. They believe neuromuscular blockingagents are of value in severe asthma needing ventilationbecause accessory muscles are relaxed and oxygenconsumption thereby reduced, and also because lowerpressures are required during ventilation.Many of the deaths in severe asthma will be pre-

vented only if it is recognised that a raised or risingPaCO2 points to a severe medical emergency which is

51. Rebuck, A. S., Read, J. Am. J. Med. 1971, 51, 788.52. Sheehy, A. F., DiBenedetto, R., Lefrak, S., Lyons, H. A. Archs

intern. Med. 1972, 130, 37.53. Levin, N., Dillon, J. B. J. Am. med. Ass. 1972, 222, 1265.

often an indication for assisted ventilation. Thisserious condition requires the close cooperation ofboth physicians and anaesthetists.

THE PHARMACIST AND HIS SPECIALKNOWLEDGE

WITH increasing specialisation in medicine, therealisation is growing that health care depends on thecoordinated activity of a large team of people withdifferent training and skills. This is implicit in theNational Health Service Reorganisation Bill, whichseeks to bring all health needs of a community underthe responsibility of a single authority which will setits priorities and organise its services in the way bestsuited to each individual area. 1,2 The role of the

pharmacist in the health team is an important one,and clinicians will undoubtedly depend more andmore upon his specialist knowledge in the spheres ofbiological availability, drug formulation, and druginteraction. Two recent issues of the Drug andTherapeutics Bulletin have been devoted to this

subject .3,4 The first emphasises the help which thepharmacist can give in advising a doctor of possibleadverse drug reactions, including a history of drughypersensitivity, and by drawing attention to situa-tions where the choice of a prescribed preparation,dosage, frequency, timing, or method of administra-tion seem to be inappropriate to the age and conditionof the patient. All too often, unfortunately, doctorsfail to give full and clear instructions on their pre-scriptions, even in the case of dangerous drugs, andthis can result in problems for the pharmacist, whomust decide either to act on his own initiative andadvise the patient without reference to the prescriber,or first get in touch with the doctor concerned. Somedoctors appear to resent any suggestion of inter-ference by a pharmacist, and this has led to mis-understandings between professional colleagues whichcould have been avoided by better appreciation ofeach others’ responsibilities to patients.The second Bulletin deals with the presentation of

dispensed medicines, and how this can help or hindertheir best use. The traditional methods of dispensingmedicines in packs or bottles may well have contributedin many instances to their misuse and to accidentalpoisoning, and a strong case is made for functionallydesigned packs-particularly individual-dose packagingof drugs usually dispensed in relatively large numbersand which carry particular dangers of overdosage.

This is an area of patient care of special importanceto pharmacists, and in which their training makesthem particularly expert. It re-emphasises the

importance of area group meetings of doctors and

pharmacists to which we have referred more thanonce in the past,5, where free communication of

problems and ideas will undoubtedly lead to betterpatient care.

1. National Health Service Reorganisation: England. Cmnd. 5055.H.M. Stationery Office, 1972.

2. Lancet, 1972, ii, 1155.3. Drug Therap. Bull. 1972, 10, 97.4. ibid. p. 101.5. Lancet, 1971, i, 332.6. ibid. 1972, ii, 1298.