1280 most studies of this kind had been done on students in the USA, and the criticism could be made that results obtained on people who have had a very high protein intake throughout their lives cannot be applied to less privileged countries. To counter this criticism Scrimshaw, under the aegis of the United Nations University, organised a collaborative trial of nitrogen balance on habitual diets in a number of countries. The results did not show any important. differences,8 suggesting that the minimum protein requirement is not reduced in people who throughout their lives eat less protein than is customary in the USA. Nevertheless, there are other serious difficulties with the nitrogen balance method: the results obtained under the artificial conditions of a metabolic ward may not be valid in real life; nitrogen balance is extremely sensitive to energy intake9 and it is impossible to ensure that during the balance measurements the subjects are in exact energy balance; and, finally, the balance periods on different protein intakes are too short to allow for full adaptation. To get round these difficulties, a few studies have been made in which volunteers lived for 2-3 months, with full collection of excreta, on the minimum level of protein intake that had to be shown to be adequate in short-term balances. These experiments on the whole confirmed the validity of the short-term results. The average protein requirement, estimated in this way, is somewhat higher than that proposed by the previous committee.’ However, with almost all diets this higher protein intake will provide adequate amounts of the essential aminoacids for adults, so that no correction is needed for protein quality, except in the case of preschool children. This conclusion is in striking contrast to the attitudes of previous committees, which devoted much attention to aminoacid patterns and scores. These two changes-on the one hand, a higher requirement for total protein; on the other, abandonment of a correction for protein quality-tend to cancel out, so that estimates of the adult protein requirement on a normal diet are very much the same as they were ten years ago. There has also been little change for infants and children. Previous committees have totally neglected the question of the digestibility of protein. The new report emphasises that, both for adults and for children, a correction must be made for the relatively low digestibility of many vegetable proteins. Fortunately, extensive data on digestibility are available from FAO and other sources. The 1981 committee has followed traditional lines in its recommendations on the extra requirements for pregnancy and lactation. No attempt has been made to bridge the gap between the theoretical estimates and the much lower intakes actually observed in the third 8 Rand WM, et al, eds. Protein-energy requirements of developing countries: results of international research. Tokyo. United Nations University, 1983. 9 Food and Agriculture Organisation/World Health Organisation. Protein and energy requirements: a joint FAO/WHO memorandum. Bull WHO 1979; 57: 65-79. pIVU.UB...llVl1 W 11B...c:tll.1.1Y UaU.1B.." amu VV.1l.Ll awauvuavy successful lactation. This discrepancy has stimulated a successful lactation. This discrepancy has stimulated a collaborative programme to try to find out whether there are adaptive mechanisms that enable the lactating mother to utilise energy more efficiently." In general, the national and international committees that have considered man’s requirements for energy and nutrients have taken the line that they are making recommendations for people who are healthy. This is unrealistic for the third world, particularly for children exposed to repeated infections. The new report for the first time makes an attempt to tackle this issue and to give some guidelines on the extra needs of children who are underweight or repeatedly infected. The details will differ according to circumstances. Although an unusually rapid rate of growth requires a greater increase in the supply of protein than of energy, this does not make a case for high protein supplements, since the protein content of the child’s diet will seldom need to be greater than that of breast milk. In practice it may be more difficult to increase the intake of energy than of protein because of the low energy density of many of the paps given to children in tropical countries. It will be interesting to see in ten years time how far the present approaches and the figures derived from them have been useful, and how far the many uncertainties have stimulated further research. Much of the future research on this subject is likely to be epidemiological, perhaps involving interventions. After all, the only way to answer with certainty the question, "Is a person getting enough food?" is to provide some more and see if it improves function and quality of life. Post-haemorrhagic Ventricular Dilatation in Infants: Who and How to Treat FEW issues in neonatal medicine are more controversial than the management of post- haemorrhagic ventricular dilatation. The term post- haemorrhagic hydrocephalus, commonly used to describe enlargement of the ventricles following intracranial haemorrhage, confuses the issue by implying that the dilatation is due to obstruction. This may not be the case in many such infants and before debating the best method of treatment we should ask which type of ventricular dilatation requires active management. The incidence of post-haemorrhagic ventricular dilatation (PHVD), diagnosed by real-time ultrasound, 10. Prentice AM. Variations in maternal dietary intake, birth weight and breast milk output in the Gambia. In: Aebi H, Whitehead RG, eds Maternal nutrition during pregnancy and lactation. Bern: Hans Huber, 1980. 11. Durnin IVGA, McKillop FM, Grant S, Fitzgerald G. Is nutritional status endangered by virtually no extra intake during pregnancy? Lancet 1985; ii: 823-25.
Transcript
1280
most studies of this kind had been done on students inthe USA, and the criticism could be made that resultsobtained on people who have had a very high proteinintake throughout their lives cannot be applied to lessprivileged countries. To counter this criticismScrimshaw, under the aegis of the United NationsUniversity, organised a collaborative trial of nitrogenbalance on habitual diets in a number of countries. Theresults did not show any important. differences,8suggesting that the minimum protein requirement isnot reduced in people who throughout their lives eatless protein than is customary in the USA.Nevertheless, there are other serious difficulties with
the nitrogen balance method: the results obtainedunder the artificial conditions of a metabolic ward maynot be valid in real life; nitrogen balance is extremelysensitive to energy intake9 and it is impossible to ensurethat during the balance measurements the subjects arein exact energy balance; and, finally, the balance
periods on different protein intakes are too short toallow for full adaptation. To get round thesedifficulties, a few studies have been made in whichvolunteers lived for 2-3 months, with full collection ofexcreta, on the minimum level of protein intake thathad to be shown to be adequate in short-term balances.These experiments on the whole confirmed the validityof the short-term results.The average protein requirement, estimated in this
way, is somewhat higher than that proposed by theprevious committee.’ However, with almost all dietsthis higher protein intake will provide adequateamounts of the essential aminoacids for adults, so thatno correction is needed for protein quality, except inthe case of preschool children. This conclusion is instriking contrast to the attitudes of previouscommittees, which devoted much attention to
aminoacid patterns and scores. These two changes-onthe one hand, a higher requirement for total protein; onthe other, abandonment of a correction for proteinquality-tend to cancel out, so that estimates of theadult protein requirement on a normal diet are verymuch the same as they were ten years ago. There hasalso been little change for infants and children.Previous committees have totally neglected the
question of the digestibility of protein. The new reportemphasises that, both for adults and for children, acorrection must be made for the relatively low
digestibility of many vegetable proteins. Fortunately,extensive data on digestibility are available from FAOand other sources.The 1981 committee has followed traditional lines in
its recommendations on the extra requirements forpregnancy and lactation. No attempt has been made to
bridge the gap between the theoretical estimates andthe much lower intakes actually observed in the third
8 Rand WM, et al, eds. Protein-energy requirements of developing countries: results ofinternational research. Tokyo. United Nations University, 1983.
9 Food and Agriculture Organisation/World Health Organisation. Protein and energyrequirements: a joint FAO/WHO memorandum. Bull WHO 1979; 57: 65-79.
pIVU.UB...llVl1 W 11B...c:tll.1.1Y UaU.1B.." amu VV.1l.Ll awauvuavysuccessful lactation. This discrepancy has stimulated asuccessful lactation. This discrepancy has stimulated acollaborative programme to try to find out whetherthere are adaptive mechanisms that enable the lactatingmother to utilise energy more efficiently."
In general, the national and international committeesthat have considered man’s requirements for energyand nutrients have taken the line that they are makingrecommendations for people who are healthy. This isunrealistic for the third world, particularly for childrenexposed to repeated infections. The new report for thefirst time makes an attempt to tackle this issue and togive some guidelines on the extra needs of children whoare underweight or repeatedly infected. The detailswill differ according to circumstances. Although anunusually rapid rate of growth requires a greaterincrease in the supply of protein than of energy, thisdoes not make a case for high protein supplements,since the protein content of the child’s diet will seldomneed to be greater than that of breast milk. In practice itmay be more difficult to increase the intake of energythan of protein because of the low energy density ofmany of the paps given to children in tropicalcountries.
It will be interesting to see in ten years time how farthe present approaches and the figures derived fromthem have been useful, and how far the manyuncertainties have stimulated further research. Muchof the future research on this subject is likely to beepidemiological, perhaps involving interventions.After all, the only way to answer with certainty thequestion, "Is a person getting enough food?" is to
provide some more and see if it improves function andquality of life.
Post-haemorrhagic VentricularDilatation in Infants: Who and How to
Treat
FEW issues in neonatal medicine are more
controversial than the management of post-haemorrhagic ventricular dilatation. The term post-haemorrhagic hydrocephalus, commonly used to
describe enlargement of the ventricles followingintracranial haemorrhage, confuses the issue byimplying that the dilatation is due to obstruction. Thismay not be the case in many such infants and before
debating the best method of treatment we should askwhich type of ventricular dilatation requires activemanagement.The incidence of post-haemorrhagic ventricular
dilatation (PHVD), diagnosed by real-time ultrasound,
10. Prentice AM. Variations in maternal dietary intake, birth weight and breast milk outputin the Gambia. In: Aebi H, Whitehead RG, eds Maternal nutrition during
pregnancy and lactation. Bern: Hans Huber, 1980.11. Durnin IVGA, McKillop FM, Grant S, Fitzgerald G. Is nutritional status endangered
by virtually no extra intake during pregnancy? Lancet 1985; ii: 823-25.
1281
has varied in three studies’-3 from 10% to 54% of high-risk infants. Of the 46 affected infants reported in thesestudies, only 7 (14%) were judged in need of a
ventricular shunt. Did the other infants have "arrested
hydrocephalus" or did the ventricles dilate because ofcerebral atrophy? Some workers have suggested thatventricular dilatation of any degree predisposes theinfant to a greater risk of subsequent handicap,presumably by a pressure effect,4 but there are few datato substantiate this. A Toronto investigations showedthat ventricular dilatation was as common in high-riskinfants without haemorrhage as in those who hadevidence of intracranial bleeding. They and others6,7have suggested that many cases of persistentventricular dilatation are due to cerebral atrophy. Themeasurement of cerebrospinal fluid (CSF) pressuremay help to differentiate the two groups.8,9The outlook for infants treated with ventricular
shunts for progressive ventricular dilatation is verypoor. Review of seven recent follow-up studies4,IO-I5 ininfants who had had shunts inserted after
intraventricular haemorrhage shows that only 9 of 50(18%) were neurodevelopmentally normal and mostwere severely handicapped. In survivors of non-
haemorrhagic congenital hydrocephalus the outcomeis much better, 52 of 92 (57%) being considerednormal. 16- 19 This type of crude comparison is only ofvalue in suggesting that poor outcome in the infantswith shunts inserted after haemorrage is multifactorial,and that an increase in CSF pressure due to ventricular
1 Ment LR, Duncan CC, Scott DT, Ehrenkranz RA. Post-hemorrhagic hydrocephalus.Low incidence in very low birth weight neonates with intraventricular hemorrhage.J Neurosurg 1984, 40: 343-47.
2 Levene MI, Starte DR. A longitudinal study of post-haemorrhagic ventriculardilatation in the newborn. Arch Dis Child 1981; 56: 905-10.
4 Palmer P, Dubowitz LMS, Levene MI, Dubowitz V. Developmental and neurologicalprogress of preterm infants with intraventricular haemorrhage and ventriculardilatation. Arch Dis Child 1982; 57: 748-53.
5. Flodmark O, Scotti G, Harwood-Nash DC. Clinical significance of ventriculomegaly inchildren who suffered perinatal asphyxia with or without intracranial hemorrhage:An 18 month follow-up study. J Comp Ass Tom 1981; 5: 663-73.
6. Stewart AL, Thorburn RJ, Hope PL, Goldsmith M, Lipscomb AP, Reynolds EOR.Ultrasound appearance of the brain in very preterm infants and neuro-
developmental outcome at 18 months of age. Arch Dis Child 1983; 58: 598-604.7. Graziani LJ, Pasto M, Stanley C, Steben J, Desai H, Desai S, Foy PM, Branca P,
Goldberg BB. Cranial ultrasound and clinical studies in preterm infants. J Pediatr1985; 106: 269-76.
8. Hill A, Volpe JJ. Normal pressure hydrocephalus in the newborn. Pediatris 1981; 68:623-29.
9. Kaiser AM, Whitelaw AG. Cerebrospinal fluid pressure during post-haemorrhagicventricular dilatation in newborn infants Arch Dis Child 1985; 60: 920-24.
10. Krishnamoorthy KS, Shannon DC, DeLong GR, Todres ID, Davis KR. Neurologicsequelae in the survivors of neonatal intraventricular hemorrhage. Pediatrics 1979;64: 233-37.
11. Chaplin ER, Goldstein GW, Myerberg DZ, Hunt JV, Tooley WH. Posthemorrhagichydrocephalus in the preterm infant. Pediatrics 1980; 65: 901-09.
12 Cooke RWI. Early prognosis of low birthweight infants treated for progressiveposthaemorrhagic hydrocephalus. Arch Dis Child 1983, 58: 410-14.
13 Liechty EA, Gilmour RL, Bryson CQ, Bull MJ Outcome of high-risk neonates withventriculomegaly. Deve Med Child Neurol 1983; 25: 162-68.
14 Allan WC, Dransfield DA, Tito AM. Ventricular dilation following periventricular-intraventricular hemorrhage. Outcome at one year. Pediatrics 1984; 73: 158-62.
15. Kreusser KL, Tarby TJ, Kovnar E, Taylor DA, Hill A, Volpe JJ. Serial lumbarpunctures for at least temporary amelioration of neonatal posthemorrhagichydrocephalus Pediatrics 1985; 75: 719-24
16 Lorber J The results of early treatment of extreme hydrocephalus Devel Med ChildNeurol 1968, 16: 21-29
17 Hagberg B, Naglo A-S. The conservative management of infantile hydrocephalus. ActaPoediatr Scand 1977; 61: 165-77.
18 Mealey J, Gilmour RL, Bubb ML. The prognosis of overt hydrocephalus at birth. JNeurosurg 1973, 39: 348-55.
19 McCullough DC, Balzer-Martin A. Current prognosis in overt neonatal
hydrocephalus. J Neurosurg 1982; 57: 378-83.
obstruction without associated haemorrhagic injurydoes not in itself necessarily cause brain damage.Cerebral atrophy probably contributes to post-haemorrhagic ventricular dilatation in a substantialnumber of infants.If we are unsure of who to treat and when, the
question of how to treat is even more difficult. Mostclinicians now try to avoid ventricular shunting,particularly in the first month of life, and the mainconservative methods of controlling ventriculardilatation are drugs and repeated lumbar puncturetaps. The aim is to win time for arachnoid granulationsto recanalise or for arachnoiditis at the base of the skullto organise so that CSF drainage returns to normal.Mantovani and colleagues2D compared daily lumbarpuncture taps with supportive treatment only, for
preventing hydrocephalus after intraventricular
haemorrhage. There was no difference between thegroups in eventual requirement for ventricular shunts,suggesting that not enough blood and fibrin could beremoved to prevent obstruction. Anwar et al,2 assessedthe benefits of serial lumbar punctures for preventingpost-haemorrhagic hydrocephalus in prematureinfants, likewise found no difference between thetreatment and control groups in the number of infants
needing shunts.Attempts have been made to treat established
ventricular dilatation by repeated lumbar puncturetaps.I5,22 Although the number of infants requiringventricular shunts was said to have been reduced bythis treatment, there was no control group in either
study. It is probable that, in most untreated infants,- ventricular dilatation ceases spontaneously, so
attempts to assess the efficacy of treatment without acontrol group (as in many studies) are largelyunhelpful.Medical management of infantile hydrocephalus has
been attempted with isosorbide,23,24 glycerol,z5 andacetazolamide .21,21 The first two act by an osmoticeffect, and acetazolamide probably reduces thesecretion of CSF by the choroid plexus. Shinnar et a 127claim that, in post-haemorrhagic "hydrocephalus",the combination of acetazolamide and frusemideaverted the need for a shunt in over half their
patients-but again the lack of a control group weakenstheir case. Furthermore, these two drugs seem to havelittle effect in arresting progressive ventricular
20. Mantovam JF, Pasternak JF, Mathew OP, Allan WC, Mills MT, Casper J, Volpe JJ.Failure of daily lumbar punctures to prevent the development of hydrocephalusfollowing intraventricular hemorrhage J Pediatr 1980; 97: 278-81.
21. Anwar M, Kadam S, Hiatt IM, Hegyi T Serial lumbar punctures in prevention of post-hemorrhagic hydrocephalus in preterm infants. J Pediatr 1985; 107: 446-50.
hemorrhagic hydrocephalus in low birth weight infants Treatment by serial lumbarpunctures. J Pediatr 1980; 97: 273-77.
23. Hayden PW, Foltz EL, Shurtleft DB. Effect of an oral osmotic agent on ventricularfluid pressure of hydrocephalic children. Pediatrics 1968, 41: 955-67.
24. Lorber J Isosorbide in treatment of infantile hydrocephalus. Arch Dis Child 1975; 50:431-36.
dilatation if used in the first two weeks of life.Acetazolamide may cause electrolyte or acid-basedisorders and infants receiving regular treatment
require careful supervision.The best management of post-haemorrhagic
ventricular dilatation remains in doubt. The very pooroutcome of infants receiving ventricular shunts maynot indicate that the operation is being done too late; itmay simply reflect the massive scale of the originalcerebral insult, of which hydrocephalus may be nomore than a paraphenomenon. Claims that lumbarpunctures or medical treatment avoid the need for
shunting carry little conviction. We need a wellcontrolled study in which medical treatment is
compared with lumbar punctures and possibly with notreatment at all.
The Nobel Peace Prize
Two articles this week-by Dr Lown and Dr Pastore(p 1285) and by Dr Sidel (p 1287)-coincide, more orless intentionally, with the ceremony in Oslo on Dec 10at which the 1985 Nobel Peace Prize is to be awarded towhat might by called, in today’s title of mild disparage-ment, a pressure group: International Physicians forthe Prevention of Nuclear War (p 1289). The Lancetthereby seeks to mark the recognition by the Nobelcommittee of the group’s feat, over the past five years,in reminding the world and its leaders what peril andwhat medical inadequacy lie in the threat of nuclearwar. A "peace movement" generated by members ofthe medical profession is nothing new.’ Indeed, wordsof peace and exhortations about the stupidity ofviolence were no doubt exchanged among physiciansand those they lived with in Egypt and Greece long ago.This traditional medical voice of warning and protesthas been echoed, amidst an imminence of destructionin a degree inconceivable to ancient civilisations, byIPPNW and its affiliated bodies in the 1980s.The award of the Peace Prize has, of course,
generated a recurrence of criticism (some of it2
bordering on the hysterical) from those despondentswho see IPPNW as a dupe of the Soviet Union. Theycondemn Dr Lown, Dr Chazov, and other ofIPPNW’sleaders for failing to link their medical argumentsagainst nuclear war with protests directed at thoseGovernments who are held to oppress certain of theircitizens for failing to comply with the doctrines of apolitical establishment. Representing a view from theUnited States, Dr Lown and Dr Pastore (p 1285)mention some political points. IPPNW has alwaysinsisted that it "would not take a position on thespecific policies of any Government". As is reflected bythe bitterness in one3 of the responses to news of the
prize, IPPNW is thereby vulnerable to charges ofindifference to human rights. Another view might bethat it is defending the most fundamental of humanrights-to survive. Disquiet about human rights has
1. Humphrey J. Physicians’ peace movements Medicine and War 1985; 1: 87-99.2 Editorial. The Nobel Peace fraud Wall Street Journal Oct 14, 19853. Wynn A, Reddaway P What sort of peace do these men want? Times, Dec 3. 1985, p 14
prompted the idea of an alternative Nobel Prize
(p 1317). Which country, however, is so free and soperfect that it might not be the target of an"alternative" prize?Apart from issues of the right to dissent, the political
implications of the campaigns voiced by IPPNW andother professional bodies striving to deter the UnitedStates and the Soviet Union from self destruction andworld catastrophe are inescapable. If the medical
profession flinches from all conceivably political tonein a declaration of its fear of nuclear war and a forecastof damage, then its influence will be weakened. Therenewed cry of dismay, for which IPPNW has won thisdistinction in Oslo, must be sustained, politically orotherwise-as an act of professional conscience.
TREATMENT OF HAIRY CELL LEUKAEMIA
FIRST described by Bouroncle and her colleagues in 1958under the designation leukaemic reticuloendotheliosis,4hairy cell leukaemia (HCL) is an uncommon disorder,accounting for only some 1-2% of all leukaemias and
lymphomas.5 Although interesting clinical and
morphological variants occur,6-8 a reasonably distinctive
clinicopathological picture of HCL has now emerged,following the publication of several large series of cases.5,9.!lThe important features include splenomegaly, with little orno lymphadenopathy; and pancytopenia with the presence inthe blood of the distinctive mononuclear "hairy" cells, whichalso infiltrate the spleen and marrow in a characteristic way.l2Very often there is conspicuous reticulin fibrosis in the
marrow, which may be difficult to aspirate. The bloodcytopenias reflect both marrow failure and hypersplenism,and either mechanism may predominate, though neutropeniaresults, particularly, from marrow disease and
thrombocytopenia from splenic sequestration. Theanaemia is exacerbated by splenic pooling of red cells, often aconspicuous feature in HCL. 14The median survival of patients with HCL is 4-5 years,
but some 10% of cases have an indolent course and muchbetter prognosis: one of Bouroncle’s original patients wasrecently reported to have survived 30 years.I2 In one largestudy,1O those with a benign course were 10 years older thanthe 52-year median of the whole group. They had less
splenomegaly, fewer circulating hairy cells, and more
granulocytes than the others. These individuals may be
symptom-free and probably require no treatment at
diagnosis. When treatment of HCL was discussed in thesecolumns in 1982, splenectomy was believed to be the treat.ment of choice in symptomatic patients. 15 Several series have
4. Bouroncle BA, Wiseman BK, Doan CA. Leukemic reticuloendotheliosis. Blood 1958,13: 609-30.
