DISTRIBUTION OF CEREBRAL ACTIVITY IN CHRONIC SCHIZOPHRENIA

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prior blood-transfusion in cadaverallograft rejection is controversiall Frozen cells are now commonly used in potential transplant recipients who require transfusions because removal of white blood-cells by freezing and washing eliminates antibody production against lymphocytes.2 However, Opelz and Terasaki have reported a poorer prognosis for renal cadaver allografts in patients who have either received no blood or only frozen cells compared with those who received whole blood or packed cells containing white blood-cells.1 These workers concluded THE role of

that the elimination of blood-transfusion or the use of frozen cells may be a move in the wrong direction. They imply that decreased exposure to blood lymphocyte antigens produces poorer graft survival by reducing the immune tolerance to HL-A antigens which results from exposure to these antigens from blood-transfusions. We suggest an alternative explanation-namely, that transfusion of certain blood derivatives (i.e., plasmaprotein fraction [P.P.F.] and albumin) may be causally related to poor graft survival. Unfortunately, information about transfusion of blood derivatives has not been published in reports from organ-transplant centres. However, Ness et al. have shown that, coincident with decreased use of blood-transfusion, there has been an increase in utilisation of blood derivatives.4 This change in transfusion practice among hxmodialysis programmes has resulted mainly from an attempt to decrease the antigenic stimuli for potential transplant recipients and to lower the risk of type B hepatitis. Most of the HL-A antigens found on lymphocytes are also present in serum, and in immunological activity the serum antigens seem identical to the cellular ones.5,6 Furthermore, serum HL-A antigens migrate on polyacrylamide gel as a single band in the region of /3]-globulins/ In the commercial production of plasma derivatives by the Cohn cold-ethanol precipitation technique, about 25 % of the &bgr;-globulin fraction distributes into Cohn fractions Iv-4 and v, from which P.P.F. is derived.8 Less than 3 % of 8globulin distributes into Cohn fraction v, from which albumin is prepared, thus lessening the likelihood that albumin is implicated in allograft rejection. Commercially available P.P.F. is produced from fractionation of plasma pooled from several thousand donors; thus, virtually all known HL-A antigens may be present in P.P.F. We suggest that increased use of P.P.F. in hxmodialysis and transplant programmes might result in decreased allograft survival rates due to prior sensitisation with HL-A antigens present in P.P.F. This might explain the discordant cadaver-graft survival-rates in different transplantation centres throughout the world. Furthermore, the practice of perfusing cadaver kidneys with cold cryoprecipitated human plasma at the time of transplantation may also play a major role in the poor cadaver-graft survival as compared with survival of living related donor grafts, since living donor grafts are not routinely perfused with this material. Evidence for the validity of this hypothesis can only be derived through epidemiological studies of P.P.F. utilisation in recipients of cadaver kidneys and

immunological analysis of host response to this plasma product. Requests for reprints should be addressed

to

C. P. P.

REFERENCES

Mannick, J. A. New Engl. J. Med. 1973, 288, 735. Huggins, C. E., Russell, P. S., Winn, H. J., Fuller, T. C., Beck, C. H., Jr. Transplant. Proc. 1973, 5, 809. 3. Opelz, G., Terasaki, P. I. Lancet, 1974, ii, 696. 4. Ness, P. M., Pennington, R. M. J. Am. med. Ass. 1974, 230, 247. 5. van Rood, J. J., van Leeuwen, A., van Santen, M. C. T. Nature, 1971, 226, 366. 6. Miyajima, T., Hirata, A. A., Terasaki, P. I. Tissue Antigens, 1973, 3,

1. 2.

251. 7. 8.

Billing, R. J., Terasaki, P. I. J. Immun. 1974, 112, 1124. Cohn, E. J., Strong, L. E., Hughes, W. L., Jr., Mulford, D. J., Ashworth, J. N., Melin, M., Taylor, H. L. J. Am. chem. Soc. 1949, 68, 459.

DISTRIBUTION OF CEREBRAL ACTIVITY IN CHRONIC SCHIZOPHRENIA DAVID H. INGVAR

Department of Clinical Neurophysiology, University Hospital, S-221 85 Lund, Sweden GÖRAN FRANZÉN

Department of Psychiatry II, Sankt Lars Hospital, S-220 06 Lund, Sweden

Summary with

blood-flow

of

regional cerebral patients normal mean hemisphere

Measurements

(R.C.B.F.)

show that

have is a shift in R.C.B.F. distribution that there but flows, so that high flows were relatively less common in frontal structures and relatively more common in postcentral structures. Since frontal structures control intentional behaviour while postcentral structures are concerned with perceptual processes (gnosis) schizophrenia may be thought of as a hypointentional, hypergnostic state; and this state may be caused by defective function of the non-specific mediothalamic frontocortical projection system.

schizophrenia

THE schizophrenic psychosis is characterised by symptoms which affect afferent and efferent functions of the central nervous system. On the afferent-perceptual side, overinclusion phenomena, leading to distortion of sensory messages, may be noted. On the efferent-behavioural side, there seems in general to be a defective synthesis of, or access to, normal programmes for locomotion, speech, and emotions. This may lead to derangement of movements and gestures, speech disturbances, and abnormal affective responses. The behavioural symptoms may progress into a state of ambivalence, severe indifference, autism, and different forms of catatonia. Even in advanced cases, however, a neurological examination is normal and wakefulness is retained. Schizophrenia, even in advanced forms, is not accompanied by any known alterations of the cerebral morphology.] The patients also have a normal level of mean cerebral oxygen uptake and blood-flow: Chronic schizophrenia thus seems to represent a genuine functional disorder-in striking contrast to

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many forms of organic dementia in Which there is loss of neurons and a decrease of the cerebral meta-

bolism and circulation.3 The functional disturbance

underlying schizophre-

nia could be caused by subtle alterations of the neuronal functions which have so far defied quantitative assessment, or it could be due to an abnormal distribution of cerebral activity which would not affect the total mean cerebral metabolism and blood-flow. We have found evidence for this second alternative.4,s5 The distribution of activity in the dominant cerebral hemisphere was measured in thirty-one patients (thirteen The women, eighteen men) with chronic schizophrenia. mean age was 39 years (17-72) and the mean duration of the disease was about 30 years. Many of the patients were severely ill, showing extreme autism and bizarre behaviour.

The measurements were made with the intra-arterial xenon clearance technique,6 using a 32-detector computeroperated device. Quantitative values were obtained of the R.C.B.F., expressed in ml. per 100 g. brain per minute. Since the cerebral flow normally mirrors the rate of oxidative neuronal metabolism, multiregional flow measurements picture the activity distribution in the hemisphere

measured.6 We confirmed that chronic schizophrenics had a normal hemisphere blood-flow (and oxygen uptake, measured in eight patients.) However, significant deviations from the normal distribution of the R.C.B.F., both at rest and during mental activation, could be shown. There was no evidence that the abnormal flow distribution was caused by circulatory or respiratory conditions, age, or drugs. In non-schizophrenics (controls) the resting distribution of blood-flow (activity) in the dominant hemisphere shows the highest flows, 10-30% above the hemisphere mean, in premotor and frontal regions. The lowest flows are found temporally and in parietal regions (see figure).7 In contrast, many of the schizophrenic patients, especially the most advanced cases, showed an almost reversed pattern with low flows in frontal regions and high flows postcentrally. When corresponding frontal regions were compared between the most psychotic schizophrenics and controls the difference was found to be significant 4·s In the most psychotic group, the intensity of the psychosis (rated by the Rockland-Pollin scale 8) showed a highly significant positive correlation to the mean hemisphere This finding has been blood-flow (r=0-81, p
Distribution of cerebral blood-flow

at rest

in relation to the

flow, in non-psychotic neurologically normal controls and in two groups of patients with chronic

hemisphere

mean

schizophrenia. The three diagrams are made up of superimposed plots of the flow distribution over the hemisphere in relation to individual hemisphere mean flows. The black circles are of five different sizes and denote flows 10, 15, 20, 25, or 30% above the hemisphere mean reference flow, empty circles corresponding values below the reference. Upper tharaw—R.c.B.p. distribution in ten neurologically and psychometrically normal male alcoholics with a mean age of 39. The mean hemisphere flow for these controls was 57 ml./100 g./ min (a normal value). Note the typical normal distribution of the R.C.B.F. with a striking preponderance of the highest flows in premotor and frontal regions, as well as over the anterior sylvian region. The lowest flows are concentrated to the temporal and parietal regions.

Lower two diagrams-Two groups of chronic schizophrenics with low degree of psychosis on the Rockland-Pollin (R.P.) scale (ten males, four females, mean age 35) and high R.P. Four patients scores (four males, nine females, mean age 64). (of the 31 examined) with intermediate scores have been excluded in this diagram.5 Both groups had a normal mean hemisphere blood-flow (54 and 53 ml./100 g./min, respectively). The flow distribution, however, was abnormal, and this is most clearly seen in the high R.P. score group where there were very few high flows in frontal structures but an increase in the number of high flows in postcentral structures. This reversal of the normal flow pattern (the " hypofrontal " pattern 4) can also be discerned in patients with low R.P. scores. Respiratory and circulatory conditions did not differ significantly between the groups and there was no evidence that the change in the C.B.F. distribution in the schizophrenics was caused by drugs or by age factors.4·’

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activity changes in the brain found in controls during men-

loss of the frontally dominant surface negative, so called expectancy response, as well as a disappearance Luria 11 has stressed that frontal structures house of recruiting responses. Finally, the blockade also causes an increase in the amplitude of evoked potenthe neuronal programmes (" melodies ") for control tials in primary and secondary projection areas. Such of intentional behaviour. Postcentral structures are, an experimentally produced syndrome appears in as is well known, mainly concerned with perceptual several ways to constitute a counterpart to the hypoUsing this attractively simple processes (gnosis). intentional and hypergnostic state which, as we sugconcept, one may interpret our results with the aid of two new terms. The specific abnormal R.C.B.F. distrigest, may underlie the behavioural and perceptual abnormalities in chronic schizophrenia. A further bution in schizophrenia suggests that this state might be termed hypointentional and hypergnostic, since brain study of the neuronal physiology and the humoral transmission of the non-specific frontocortical medioregions for intentional behaviour showed a low thalamic projection system in man therefore seems to and showed an those for activity, responsible gnosis be important for research on schizophrenia. abnormally high activity. We should further like to suggest that a hypointenREFERENCES tional and hypergnostic state could be caused by a 1. Rosenthal, R., Bigelow, L. B. Br. J. Psychiat. 1972, 121, 259. defective function of the non-specific mediothalamic 2. Kety, S. S., Woodford, R. B., Harmel, M. H., Freyhan, F. A., frontocortical projection systemp.13 which provides Appel, K. E., Schmidt, C. F. Am. J. Psychiat. 1948, 104, 765. 3. Ingvar, D. H., Gustafson, L. Acta neurol. scand. 1970, 46, suppl. 43, widespread activation of frontal structures, and also p. 42. exerts an inhibitory control upon afferent systems. 4. Ingvar, D. H., Franzén, G. Acta psychiat. scand. 1974, 50, 425. As shown in animal experiments, a permanent or 5. Franzén, G., Ingvar, D. H. Unpublished. 6. Lassen, N. A., Ingvar, D. H. Progr. nucl. Med. 1972, 1, 376. transient blockade of this system leads to a state 7. Ingvar, D. H., Schwartz, M. S. Brain, 1974, 97, 273. characterised by inattention, disinterest, and aimless 8. Rockland, L. H., Pollin, W. Archs gen. Psychiat. 1965, 12, 23. 9. Hoyer, S., Oesterreich, K. Personal communication. wandering about, as well as a general interference with 10. Risberg, J., Ingvar, D. H. Brain, 1973, 96, 737. the higher organisation of stimulus selection and 11. Luria, A. R. Higher Cortical Functions in Man. London, 1966. 12. Jasper, H. E.E.G. clin. Neurophysiol. 1949, 1, 405. response choice. This takes place without neuro13. Skinner, S. E., Lindsley, D. B. in Psychophysiology of the Frontal of or loss wakefulness. disturbance There is logical Lobes (edited by K. H. Pribram and A. R. Luria); p. 332. New also a series of electrophysiological changes, including York, 1973. a

tal effort.4,10

.

Methods and Devices A DEVICE TO PREVENT DISCONNECTION AT 3-WAY TAP JUNCTIONS

S. E. BARNES

Department of Pæediatrics, John Radcliffe Hospital, Headington, Oxford OX3 9DU M. L. CHISWICK St.

the nursing staff prevented these babies from bleeding such an extent as to be beyond resuscitation. One baby died 24 hours after the accident from an intraventricular

by

Mary’s Hospital, Manchester

to

CATHETERS are often connected to infusion or monitorlines by 3-way taps (fig. 1). Lately, we have encountered a series of accidents involving infants in a special-care baby unit in which there has been separation of these connections and subsequent haemorrhage or air embolism (see accompanying table). In babies or infants with small blood-volumes, such accidents can be fatal. All babies, except one who had an air embolus, were treated promptly with rapid transfusion of fresh blood from a previously matched member of staff. Only rapid discovery

ing

ACCIDENTS IN INFANTS INVOLVING DISCONNECTION OF

Fig. 1-Diagram of 3-way tap joining an intravenous (IV) or intra-arterial (I/A) catheter to infusion or transducer line.

3-WAY

TAPS

hoemorrhage. All the accidents except one involved junction A (fig. 1). We initially suspected that the tapered connection between the 3-way tap and infusion or transducer line (junction A) had not been correctly assembled, but we now feel that such a joint is inherently unsafe. Tapered joints between relatively hard or non-elastic materials are liable to sudden loosening if they are flexed repeatedly. For this reason they require a locking device such as the’Luer-Lok’, but this is not incorporated into infusion or transducer lines to connect them with the 3-way taps. Repeated bending and stretching of the joints may occur during normal manipulation of the 3-way tap and during handling of the patient or

equipment. In

addition, when

an

infusion pump is used, and the 3-

way tap is then positioned to sample blood, a considerable pressure builds up if the infusion pump is left on ; this

tends to weaken the joint between the 3-way tap and infusion line and allows separation to occur. The junction between the catheter and 3-way tap (junction B) is also of a tapered type, but here the end of the catheter taking part in the joint is flexible and elastic. Disruption by pulling and flexing is almost impossible, provided the catheter end is well forced on to the 3-way tap.